Therapeutic
Intranasal Drug DeliveryIntranasal opiates (fentanyl, sufentanil, morphine) and ketamine for the treatment of acute, chronic and breakthrough pain - abstracted references:
(1988). "Sedation, analgesia, and intranasal
sufentanil." Lancet 2(8601): 24.
(2003). "Intranasal delivery of morphine may offer
better effects." Clin J Oncol Nurs 7(4): 377.
(2006). "Intranasal morphine for postoperative pain."
J Pain Palliat Care Pharmacother 20(2): 93-4.
Abdell-Ghaffar, H. and M. A. M. Salem (2012). "Safety and Analgesic
efficacy of Pre-emptive Intranasal Ketamine versus Intranasal fentanyl
in patients undergoing endoscopic nasal surgery." Journal Am Sci
8(3): 430-436.
Objectives: No clinical
studies investigated
nasal mucosal coverage
and nasal integrity
as local causative
factors for
inter-individual
variation in
clinical effects
commonly reported
with intranasal
opioid
administration. Moreover,
most of published clinical trails investigated the use of intranasal
analgesic medications in extranasal painful
settings. The purpose of this study was to demonstrate safety and
analgesic efficacy of pre-emptive intranasal ketamine
(non-opioid) vs.
intranasal fentanyl
(opioid) in
patients undergoing
endoscopic nasal
surgery. Methods: 60
adult normotensive
patients were
randomly assigned
to receive
intranasal
administration of
either 1.5mg/kg
ketamine 50mg/ml (INK
group, n=20) or 1.5µg/kg fentanyl 50µg/ml (INF group, n=20), or saline
(placebo group, n=20) 30 min.
before induction of general anesthesia. Assessment parameters
included; hemodynamics, postoperative pain, sedation
and adverse effects. Results: Intranasal fentanyl significantly
attenuated hemodynamic changes in SBP, DBP and HR at
1, 3,
5 and
7min. after
intubation. INK
and INF
significantly
prolonged time
to first
analgesic request
(253.74±25.01min. P<0.000 vs. 233.80±24.57min, P<0.000), compared
with placebo (120.71±24.64min.). Diclofenac
consumption was
significantly reduced
in INK
(85.32±10.31mg) and
INF (81.42±8.48mg)
compared with
placebo
(150.00±0.00mg). VAS scores were significantly lower with INK and INF in
first 4h postoperative (P<0.000) with a
trend towards
lower values
at all
recorded time
points. Incidence
of adverse
effects was
higher in INK,
While the
surgeon (P<0.000) and patient (P<0.000) satisfaction indices were
higher with INF. Conclusion: Intranasal ketamine or
intranasal fentanyl
enhanced
postoperative analgesia
after endoscopic
nasal surgery.
Psychomimetic side
effects of
ketamine still occur with intranasal administration and the
clinical goal of ketamine must be defined.
Abrams, R., J. E. Morrison, et al. (1993). "Safety
and effectiveness of intranasal administration of sedative medications
(ketamine, midazolam, or sufentanil) for urgent brief pediatric dental
procedures." Anesth Prog 40(3): 63-6.
Thirty children presenting to the dental clinic of a
pediatric hospital who required brief but urgent dental care, and who
could not be satisfactorily examined or treated, were administered one
of three medications--ketamine (Ketalar), 3 mg/kg; midazolam (Versed),
0.4 mg/kg; or sufentanil (Sufenta), 1.5 or 1.0
micrograms/kg--intranasally in a randomized, double-blinded protocol.
The patients were brought to the day surgery area following appropriate
fasting and administered one of the medications diluted in a dose of 0.1
mL/kg normal saline while sitting in a nurse's arms. Cardiorespiratory
monitors were applied when tolerated, and the child was placed on the
operating room table. Each child was injected locally with up to one
dental cartridge of 2% lidocaine with 1:100,000 epinephrine before
dental extractions. A sedation score was recorded using a scale where 1
= hysterical/untreatable, 5 = ideal sedation, and 10 = obtunded and
desaturated, requiring airway management assistance. Midazolam
administration resulted in acceptable sedation (mean score: 4) with no
desaturations below 90% as measured by pulse oximetry and a mean
recovery room observation time of only 3 +/- 2 min (+/- SD). Ketamine
also had a mean sedation score of 4 and a short recovery period (7 +/- 7
min); however, two children experienced brief desaturations. Sufentanil
at 1.5 micrograms/kg was noted to produce much more heavily sedated
children (mean score 7), with a high incidence of significant oximetry
desaturation (80%) and prolonged recovery room duration (58 +/- 40 min).
Use of 1.0 microgram/kg sufentanil resulted in no desaturations, less
sedation (mean score 4), and a brief recovery time (7 +/- 13
min).(ABSTRACT TRUNCATED AT 250 WORDS)
Adelgais, K. M., A. Brent, et al. (2017). "Intranasal Fentanyl and
Quality of Pediatric Acute Care." J Emerg Med.
BACKGROUND: Changes in the manner in which medications can be
delivered can have significant effects on the quality of care in the
acute care setting. OBJECTIVE: The objective of this study was to
evaluate the change in three Institute of Medicine quality indicators
(timeliness, safety, and effectiveness) in the pediatric emergency
department (ED) after the introduction of the Mucosal Atomizer Device
Nasal (MADn) for opioid analgesia. METHODS: This was a retrospective
review of patients receiving opioid analgesia for certain conditions
over a 5-year period. We compared patients receiving intravenous opioid
(IVO) to those receiving intranasal fentanyl (INF). Timeliness outcomes
include time from medication order to administration, time from dose to
discharge, overall time to analgesia, and ED length of stay.
Effectiveness outcomes include change in pain score and frequency of
repeat dosing. Safety outcomes were the frequency of reversal agent
administration or a documented oxygen desaturation of < 90%. Sensitivity
analyses were performed to evaluate the effect of moderate sedation on
all three outcomes. RESULTS: During the study period, 1702 patients
received opioid analgesia, 744 before and 958 after MADn introduction,
of whom, 233 (24%) received INF. After MADn introduction, patients
receiving INF had a shorter time to discharge from dose (109 vs. 203
min; p < 0.05) and shorter ED length of stay (168 vs. 267 min; p <
0.05). There was no difference in pain score reduction; however, repeat
dosing was less frequent for patients receiving INF (16% vs. 27%). There
was no use of reversal medication and no difference in the frequency of
oxygen desaturations. When patients undergoing moderate sedation were
removed from the analysis, there was no difference in the direction of
findings for all three outcomes. CONCLUSIONS: INF is associated with
improved timeliness and equivalent effectiveness and safety when
compared to IVO in the setting of the pediatric ED.
Afridi, S. K., N. J. Giffin, et al. (2013). "A randomized controlled trial of intranasal ketamine in migraine with prolonged aura." Neurology 80(7): 642-647.
OBJECTIVE: The aim of our study was to test the hypothesis that ketamine
would affect aura in a randomized controlled double-blind trial, and
thus to provide direct evidence for the role of glutamatergic
transmission in human aura. METHODS: We performed a double-blinded,
randomized parallel-group controlled study investigating the effect of
25 mg intranasal ketamine on migraine with prolonged aura in 30
migraineurs using 2 mg intranasal midazolam as an active control. Each
subject recorded data from 3 episodes of migraine. RESULTS: Eighteen
subjects completed the study. Ketamine reduced the severity (p = 0.032)
but not duration of aura in this group, whereas midazolam had no effect.
CONCLUSIONS: These data provide translational evidence for the potential
importance of glutamatergic mechanisms in migraine aura and offer a
pharmacologic parallel between animal experimental work on cortical
spreading depression and the clinical problem. CLASSIFICATION OF
EVIDENCE: This study provides class III evidence that intranasal
ketamine is effective in reducing aura severity in patients with
migraine with prolonged aura.
Background: Vaso-occlusive
episodes (VOE) are the leading cause of hospitalizations & emergency
department (ED) visits in sickle cell disease (SCD), & are associated
with increased mortality. Intranasal fentanyl (INF) provides rapid &
powerful parenteral analgesia, with an onset of action of 5-10 minutes,
& peak effect in 30 minutes. INF is a safe & effective method of
pain management for children in the ED & other settings, yet it is
underutilized in SCD.
Objective: To
study the impact of the addition of INF to standard ED management
for SCD VOE on time to parenteral opioid, pain scores, ED length of stay
(LOS) & admission rate.
Methods: This
quality improvement initiative was conducted at a tertiary pediatric ED
at Children's Healthcare of Atlanta from November 2013-May 2014.
Patients with all genotypes of SCD ages ≥2 years old who presented with
VOE & pain score >6/10 were offered INF within 15 minutes of triage. 2
INF doses (1.5mcg/kg/dose; max 100mcg/dose) were given 5 minutes apart.
Patients then continued on institutional standard protocol treatment for
VOE (±PO hydrocodone, ±IV ketorolac, & ± IV morphine or IV hydromorphone).
Pain scores were documented at frequent intervals by nursing staff.
Patient/parent satisfaction data were obtained using a satisfaction
questionnaire. Outcomes included: Time from arrival to 1st parenteral
opioid, pain scores, ED LOS (time from arrival to disposition),
admission rates & patient/parent satisfaction. We compared patients in
this study to those who did not receive INF during the study period
(n=48) & historical controls from Jan-Dec 2012 (n=231) for the 1st three
outcomes.
Results: 248
visits for VOE met inclusion criteria, of whom 228 received parenteral
opioids (92%) & 180/228 (79 %) received INF. Mean age was 11.7±4.5
years. The majority were female (56%), 65% HbSS, 14% HbSC & 21% had
other genotype. 48 patients did not receive INF; 36 were not
offered INF without explanation for protocol deviation &12 patients
refused. They had similar gender & Hb genotype, but were older than INF+
patients (13.5±4.0 years, p=0.01). The mean time from
arrival to 1st parenteral
opioid decreased significantly in the INF+ group compared to historical
controls, and was remarkably shorter than those not treated with INF.
There was minimal difference in LOS between INF+ group & historical
controls, but LOS was shorter in the group that did not receive INF. Admission rates were
significantly higher in those who did not receive INF when compared to
those treated with INF & historical controls.
(See Table 1)
Table 1
|
|
INF+
(n =180) |
INF-
(n =48) |
Historical Data (n=231) |
P-value |
|
Time to 1st Parenteral
Opioid (minutes) |
29 ±15 |
77 ±44 |
35±18 |
p < 0.0001 |
|
LOS (minutes) |
215± 86 |
197± 67 |
231±95 |
p = 0.028 |
|
Admission Rate (%) |
48% |
71% |
45% |
p = 0.004 |
Mean baseline pain score was 8.5±1.5, 1st reassessment pain score after
INF was 7.8±2.4 & last ED pain score prior to disposition was 5.5±3.4.
Pain scores were similar in all groups. 98 families completed the
patient satisfaction questionnaire, 79 (81%) of whom received INF. 65%
of patients who received INF were satisfied & would like to receive the
treatment again in the ED. Conclusions: The
addition of INF to the management of SCD VOE significantly improved time
to receipt of 1st parenteral
analgesia & was well tolerated. Admission rates were significantly
higher in patients who did not receive INF during our study period. The
associated delay in time to receipt of 1st parenteral
analgesia may have contributed to the increased admission rate. However,
causality of INF on admission rates cannot be determined without further
study. INF did not impact ED LOS compared to historical controls,
however rapid admission turn-around time likely decreased LOS in the
INF- group. INF is a safe & effective strategy to provide rapid pain
relief in children with SCD &
VOE.
Disclosures: Off
Label Use: Intranasal
Fentanyl (INF). Widely accepted as off label use in pediatric ED's and a
variety of other clinical settings for the management of pain. It is a
synthetic narcotic analgesic with a rapid onset and short duration of
action. Current evidence suggests that INF is a safe and effective
method of pain management for children in a variety of clinical
settings..
Akinsola, B., R. Hagbom, et al. (2018). "Impact of Intranasal
Fentanyl in Nurse Initiated Protocols for Sickle Cell Vaso-occlusive
Pain Episodes in a Pediatric Emergency Department."
Am J Hematol.
Ali, S. and T. P. Klassen (2007). "Intranasal
fentanyl and intravenous morphine did not differ for pain relief in
children with closed long-bone fractures." Evid Based Med 12(6):
176.
Andolfatto, G., E. Willman, et al. (2013). "Intranasal Ketamine for
Analgesia in the Emergency Department: A Prospective Observational
Series." Acad Emerg Med
20(10): 1050-1054.
OBJECTIVES: The objective was to examine the
feasibility, effectiveness, and adverse effect profile of intranasal
ketamine for analgesia in emergency department (ED) patients. METHODS:
This was a prospective observational study examining a convenience
sample of patients aged older than 6 years experiencing moderate or
severe pain, defined as a visual analog scale (VAS) score of 50 mm or
greater. Patients received 0.5 to 0.75 mg/kg intranasal ketamine. Pain
scores were recorded on a standard 100-mm VAS by trained investigators
at baseline, then every 5 minutes for 30 minutes, and then every 10
minutes for an additional 30 minutes. The primary outcome was the number
and proportion of patients experiencing clinically significant
reductions in VAS pain scores, defined as VAS reductions of 13 mm or
more, within 30 minutes. Secondary outcomes included the median
reduction in VAS, the median time required to achieve a 13 mm reduction
in VAS, vital sign changes, and adverse events. Continuous data are
reported with medians and interquartile ranges (IQRs). The Wilcoxon
signed-ranks test was used to assess changes in VAS scores. Adverse
effects are reported with proportions and 95% confidence intervals
(CIs). RESULTS: Forty patients were enrolled with a median age of 47
years (IQR = 36 to 57 years; range = 11 to 79 years) for primarily
orthopedic injuries. A reduction in VAS of 13 mm or more within 30
minutes was achieved in 35 patients (88%). The median change in VAS at
30 minutes was 34 mm (44%). Median time required to achieve a 13 mm VAS
reduction was 9.5 minutes (IQR = 5 to 13 minutes; range = 5 to 25
minutes). No serious adverse effects occurred. Minor adverse effects
included dizziness (21 patients, 53%; 95% CI = 38% to 67%), feeling of
unreality (14 patients, 35%; 95% CI = 22% to 50%), nausea (four
patients, 10%; 95% CI = 4% to 23%), mood change (three patients, 8%; 95%
CI = 3% to 20%), and changes in hearing (one patient, 3%; 95% CI = 0% to
13%). All adverse effects were transient and none required intervention.
There were no changes in vital signs requiring clinical intervention.
CONCLUSIONS: Intranasal ketamine reduced VAS pain scores to a clinically
significant degree in 88% of ED patients in this series. Adverse effects
were minor and transient. Intranasal ketamine may have a role in the
provision of effective, expeditious analgesia to ED patients.
Andolfatto, G., K. Innes, et al. (2019). "Prehospital Analgesia With
Intranasal Ketamine (PAIN-K): A Randomized Double-Blind Trial in
Adults." Ann Emerg Med
74(2): 241-250.
STUDY OBJECTIVE: We compare intranasal ketamine with intranasal placebo in
providing pain reduction at 30 minutes when added to usual paramedic
care with nitrous oxide. METHODS: This was a randomized double-blind
study of out-of-hospital patients with acute pain who reported a verbal
numeric rating scale (VNRS) pain score greater than or equal to 5.
Exclusion criteria were younger than 18 years, known ketamine
intolerance, nontraumatic chest pain, altered mental status, pregnancy,
and nasal occlusion. Patients received usual paramedic care and were
randomized to receive either intranasal ketamine or intranasal saline
solution at 0.75 mg/kg. The primary outcome was the proportion of
patients with VNRS score reduction greater than or equal to 2 at 30
minutes. Secondary outcomes were pain reduction at 15 minutes,
patient-reported comfort, satisfaction scores, nitrous oxide
consumption, and incidence of adverse events. RESULTS: One hundred
twenty subjects were enrolled. Seventy-six percent of intranasal
ketamine patients versus 41% of placebo patients reported a greater than
or equal to 2-point VNRS reduction at 30 minutes (difference 35%; 95%
confidence interval 17% to 51%). Median VNRS reduction at 15 minutes was
2.0 and 1.0 and at 30 minutes was 3.0 and 1.0 for ketamine and placebo,
respectively. Improved comfort at 15 and 30 minutes was reported for 75%
versus 57% and 61% versus 46% of ketamine and placebo patients,
respectively. Sixty-two percent of patients (95% confidence interval 49%
to 73%) versus 20% (95% confidence interval 12% to 32%) reported adverse
events with ketamine and placebo, respectively. Adverse events were
minor, with no patients requiring physical or medical intervention.
CONCLUSION: Added to nitrous oxide, intranasal ketamine provides
clinically significant pain reduction and improved comfort compared with
intranasal placebo, with more minor adverse events.
Arnautovic, T., K. Sommese, et al. (2018). "Evaluating the
Implementation Barriers of an Intranasal Fentanyl Pain Pathway for
Pediatric Long-Bone Fractures." Pediatr Emerg Care
34(7): 473-478.
OBJECTIVES: This study aimed to assess physician comfort, knowledge, and
implementation barriers regarding the use of intranasal fentanyl (INF)
for pain management in patients with long-bone fractures in a pediatric
emergency department (ED) with an INF pain pathway. METHODS: A
retrospective chart review was conducted of patients, 3 to 21 years old,
in our ED with an International Classification of Diseases-9th Revision
code for a long-bone fracture from September 1, 2013, to August 31,
2015. Patients were divided into 4 groups: (1) received INF on the
pathway appropriately; (2) "missed opportunities" to receive INF,
defined as either INF was ordered and then subsequently canceled (for
pain ratings, >/=6/10), or INF was ordered, cancelled, and intravenous
(IV) morphine given, or INF was not ordered and a peripheral IV line was
placed to give IV morphine as first-line medication; (3) peripheral IV
established upon ED arrival; (4) no pain medication required.
Additionally, a survey regarding practice habits for pain management was
completed to evaluate physician barriers to utilization of the pathway.
RESULTS: A total of 1374 patients met the inclusion criteria. Missed
opportunities were identified 41% of the time. Neither younger patient
age nor more years of physician experience in the ED were associated
with increased rates of missed opportunities. The survey (95% response
rate) revealed greater comfort with and preference for IV morphine over
INF. CONCLUSIONS: The high rate of missed opportunities, despite the
implementation of an INF pain pathway, indicates the need for further
exploration of the barriers to utilization of the INF pain pathway.
Banala, S. R., O. K. Khattab, et al. (2020). "Intranasal
fentanyl spray versus intravenous opioids for the treatment of severe
pain in patients with cancer in the emergency department setting: A
randomized controlled trial." PLoS One 15(7): e0235461.
OBJECTIVE: Intranasal fentanyl (INF) quickly and noninvasively relieves severe pain, whereas intravenous hydromorphone (IVH) reliably treats severe cancer pain but requires vascular access. The trial evaluated the efficacy of INF relative to IVH for treating cancer patients with severe pain in an emergency department (ED) setting. METHODS: We randomized 82 patients from a comprehensive cancer center ED to receive INF (n = 42) or IVH (n = 40). Eligible patients reported severe pain at randomization (>/=7, scale: 0 "none" to 10 "worst pain"). We conducted non-inferiority comparisons (non-inferiority margin = 0.9) of pain change from treatment initiation (T0) to one hour later (T60). T0 pain ratings were unavailable; therefore, we estimated T0 pain by comparing 1) T60 ratings, assuming similar group T0 ratings; 2) pain change, estimating T0 pain = randomization ratings, and 3) pain change, with T0 pain = 10 (IVH group) or T0 pain = randomization rating (INF group). RESULTS: At T60, the upper 90% confidence limit (CL) of the mean log-transformed pain ratings for the INF group exceeded the mean IVH group rating by 0.16 points (>pain). Substituting randomization ratings for T0 pain, the lower 90% CL of mean pain change in the INF group extended 0.32 points below (<pain relief) mean change in the IVH group. Finally, assuming all subjects in the IVH group had maximum pain at T0 and that T0 pain for the INF group remained unchanged from randomization, the lower bound of the 90% CL for mean pain decrease in the INF group extended 1.37 points below (<pain relief) mean decrease in the IVH group. Time (minutes) from randomization until T0 was longer for the IVH (Median 23, IQR 12) versus INF (Median 15, IQR 11) group (P<0.001). CONCLUSIONS: Two of three analyses supported non-inferiority of INF versus IVH, while one analysis was inconclusive. Compared to IVH, INF had the advantage of shorter time to administration. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02459964.
Bates, B. A., S. A. Schutzman, et al. (1994). "A
comparison of intranasal sufentanil and midazolam to intramuscular
meperidine, promethazine, and chlorpromazine for conscious sedation in
children." Ann Emerg Med 24(4): 646-51.
STUDY OBJECTIVE: To compare intranasal sufentanil and midazolam
(IN-SM) with intramuscular meperidine, promethazine, and chlorpromazine
(IM-MPC) for sedation in children. DESIGN: Single-blind, randomized,
controlled study. SETTING: Urban children's emergency department.
PARTICIPANTS: A convenience sample of children aged 1 to 4 years
requiring suturing. INTERVENTIONS: IN-SM or IM-MPC. RESULTS: Vital
signs, O2 saturation, and anxiety and pain scores were recorded. A
6-point scale was used to assess response to medication, and a 12-point
recovery score was used to determine readiness for discharge. Both
groups were similar in age and sex distribution. There were no
significant adverse effects in either group. Patients tolerated the IN
regimen better than the IM regimen. Behavioral scores were lower during
repair than at baseline within each group; however, they were not
different between groups. Time to discharge was longer and recovery
scores were lower (worse) among the IM-MPC group. CONCLUSION: IN-SM is
as effective as IM-MPC for sedation in children.
Bayrak, F., I. Gunday, et al. (2007). "A comparison
of oral midazolam, oral tramadol, and intranasal sufentanil
premedication in pediatric patients." J Opioid Manag 3(2): 74-8.
BACKGROUND: This study was designed to evaluate the efficacy and
safety of oral midazolam, tramadol drops, and intranasal sufentanil for
premedication of pediatric patients. METHODS: Sixty children, three to
10 years of age, who were designated as American Society of
Anesthesiologists physical status 1 and who were undergoing
adenotonsillectomy as inpatients were randomized to receive a dosage of
0.5 mg/kg (total of 4 ml) midazolam in cherry juice (n=20, Group M), 3
mg/kg tramadol drops (n=20, Group T), or 2 microg/kg intranasal
sufentanil (n=20, Group S). Clinical responses (sedation, anxiolysis,
cooperation) and adverse effects (respiratory, hemodynamic, etc.) were
recorded. Safety was assessed by continuous oxygen saturation monitoring
and observation. Vital signs (blood pressure, pulse, oxygen saturation,
respiratory rate) were recorded before drug administration (baseline)
and then every 10 minutes until the induction of anesthesia. RESULTS:
Mean blood pressure decreased significantly after five minutes of
intranasal sufentanil administration relative to Groups M (p < 0.01) and
T (p < 0.05), whereas heart rate remained unchanged. Oxygen saturation
and respiratory rate decreased significantly after 20 and 30 minutes of
intranasal sufentanil administration relative to Groups M and T (p <
0.05). Anxiety scores showed rates of 45 percent in Group M, 5 percent
in Group T, and 40 percent in Group S. Anxiety scores in Groups M and S
were better than those of Group T (p < 0.01). Cooperation scores for
face-mask acceptance showed rates of 85 percent in Group M, 45 percent
in Group T, and 85 percent in Group S (p < 0.01). CONCLUSION: Intranasal
sufentanil and oral midazolam are more appropriate premedication options
than tramadol drops in children.
Belkouch, A., S. Zidouh, et al. (2015). "Does intranasal fentanyl
provide efficient analgesia for renal colic in adults?" Pan Afr Med J
20: 407.
INTRODUCTION: Intranasal fentanyl provides rapid and powerful
analgesia which is particularly interesting in patients without
intravenous access. We propose to use it for analgesia in adults
presenting renal colics. METHODS: A prospective study was conducted from
the 2nd January to February 2013 in our emergency department. Patients
aged up to 18 years old who presented with renal colic were included in
this audit. Patients were excluded if they had loss of consciousness,
cognitive impairment, acute or chronic nasal problems. A formal written
consent was obtained from patients. The research team was alerted by
medical and nursing staff. A member of the research team would check
with medical or nursing staff whether administration of Intra nasal (IN)
fentanyl was required. It was administered at a pre-calculated dose of
1.5 mg/kg and 50 mg/ml concentration was used. Data was prospectively
collected by one of the researchers at various intervals during the
patient's presentation and recorded on a pre-formatted data sheet. Pain
scores were collected at 5, 15, 30, 45 and 60 minutes following IN
fentanyl using a visual analogue scale pain. Observations routinely
collected for patients receiving IV opiates and any adverse events were
also recorded. RESULTS: 23 eligible patients were enrolled; median age
was 51,3 years. 47,8% were women and the mean weight was 73 kg. Median
dose of IN fentanyl was 106 mug. Two patients have required morphinic
analgesia despite having received adapted dose of IN fentanyl. The
initial pain scores before IN fentanyl were high with a median of 82,2
mm (59-100). Five minutes after IN fentanyl administration the median
pain score dropped to 48 mm(36-63) and achieved the lowest score of
8mm(0-22) at 30 min. Pain scores were significantly lower at 5 min (P <
0.001) and at all subsequent time points (P < 0.001). No side effects
were recorded. CONCLUSION: Intranasal fentanyl seems to be efficient for
analgesia in adult patients with renal colic.
Bendall, J. C., P. M. Simpson, et al. (2011). "Effectiveness of Prehospital Morphine, Fentanyl, and Methoxyflurane in Pediatric Patients." Prehosp Emerg Care.
Abstract: Objectives. To compare the effectiveness of intravenous morphine, intranasal (IN) fentanyl, and inhaled methoxyflurane for managing moderate to severe pain in pediatric patients in the out-of-hospital setting. Methods. We conducted a retrospective comparative study of 3,312 pediatric patients aged between 5 and 15 years who had moderate to severe pain (pain score over 5) and who received intravenous morphine, IN fentanyl, or inhaled methoxyflurane, either alone or in combination, between January 1, 2004, and November 30, 2006. Multivariate logistic regression was used to analyze data extracted from a clinical database containing routinely entered information from patient health care records. The primary outcome measure was effective analgesia, defined as a reduction in pain severity of over 30% of initial pain score using an 11-point verbal numeric rating scale. Results. Effective analgesia was achieved in 82.5% of cases overall. All analgesic agents were effective in the majority of patients (87.5%, 89.5%, and 78.3% for morphine, fentanyl, and methoxyflurane, respectively). There was evidence that methoxyflurane was less effective than both morphine (odds ratio [OR] 0.52; 95% confidence interval [CI] 0.36-0.74) and fentanyl (OR 0.43; 95% CI 0.29-0.62; p < 0.0001). There was no clinical or statistical evidence of difference in the effectiveness of fentanyl and morphine in this population (OR 1.22; 95% CI 0.74-2.01). There was no evidence that combination analgesia was better than either fentanyl or morphine alone. Conclusion. Intranasal fentanyl and intravenous morphine are equally effective analgesic agents in pediatric patients with moderate to severe acute pain in the out-of-hospital setting. Methoxyflurane is less effective in comparison with both morphine and fentanyl, but is an effective analgesic in the majority of children.
Benish, T., D. Villalobos, et al. (2019). "The THINK (Treatment of
Headache with Intranasal Ketamine) Trial: A Randomized Controlled Trial
Comparing Intranasal Ketamine with Intravenous Metoclopramide." J
Emerg Med 56(3):
248-257 e241.
BACKGROUND: Headache is a common chief complaint in the emergency
department (ED) setting. OBJECTIVES: To compare analgesia with
metoclopramide and diphenhydramine vs. intranasal ketamine among ED
patients with primary headache. METHODS: We enrolled a convenience
sample of adults with a primary headache in a randomized, single-blind,
placebo-controlled trial. We randomized patients to either a control arm
(intravenous metoclopramide and diphenhydramine) or intranasal ketamine.
The primary outcome was change in pain 0-100 mm visual analog scale
(VAS) score measured at study start and 30 min post completion of
initial medication administration. Secondary outcomes included side
effects, hospital admission, and return to care within 48-72 h. RESULTS:
All 53 enrolled subjects completed the study, 26 of whom were allocated
to the control arm and 27 to intranasal ketamine. The mean change in
pain VAS score at 30 min post intervention was 22.2 mm in the control
arm vs. 29.0 in the intranasal ketamine arm (effect size difference 6.8
mm, 95% confidence interval -5.8-19.4). The incidence of reported side
effects was 65.4% in the control arm vs. 66.7% in the ketamine arm.
Three patients (11.5%) allocated to the control arm required admission
for headache pain control vs. 1 patient (3.7%) in the intranasal
ketamine arm. Three (11.5%) additional patients in the control arm
returned to the ED within 48-72 h for headache pain vs. none in the
ketamine arm. CONCLUSIONS: In this small randomized study, intranasal
ketamine was not superior to standard therapy among ED patients with
primary headache syndromes.
Blancher, M., M. Maignan, et al. (2019). "Intranasal sufentanil versus
intravenous morphine for acute severe trauma pain: A double-blind
randomized non-inferiority study." PLoS Med
16(7): e1002849.
Borland, M., I. Jacobs, et al. (2007). "A randomized
controlled trial comparing intranasal fentanyl to intravenous morphine
for managing acute pain in children in the emergency department." Ann
Emerg Med 49(3): 335-40.
STUDY OBJECTIVE: We compare the efficacy of intranasal fentanyl
versus intravenous morphine in a pediatric population presenting to an
emergency department (ED) with acute long-bone fractures. METHODS: We
conducted a prospective, randomized, double-blind, placebo-controlled,
clinical trial in a tertiary pediatric ED between September 2001 and
January 2005. A convenience sample of children aged 7 to 15 years with
clinically deformed closed long-bone fractures was included to receive
either active intravenous morphine (10 mg/mL) and intranasal placebo or
active intranasal concentrated fentanyl (150 microg/mL) and intravenous
placebo. Exclusion criteria were narcotic analgesia within 4 hours of
arrival, significant head injury, allergy to opiates, nasal blockage, or
inability to perform pain scoring. Pain scores were rated by using a
100-mm visual analog scale at 0, 5, 10, 20, and 30 minutes. Routine
clinical observations and adverse events were recorded. RESULTS:
Sixty-seven children were enrolled (mean age 10.9 years [SD 2.4]).
Fractures were radius or ulna 53 (79.1%), humerus 9 (13.4%), tibia or
fibula 4 (6.0%), and femur 1 (1.5%). Thirty-four children received
intravenous (i.v.) morphine and 33 received intranasal fentanyl.
Statistically significant differences in visual analog scale scores were
not observed between the 2 treatment arms either preanalgesia or at 5,
10, 20, or 30 minutes postanalgesia (P=.333). At 10 minutes, the
difference in mean visual analog scale between the morphine and fentanyl
groups was -5 mm (95% confidence interval -16 to 7 mm). Reductions in
combined pain scores occurred at 5 minutes (20 mm; P=.000), 10 minutes
(4 mm; P=.012), and 20 minutes (8 mm; P=.000) postanalgesia. The mean
total INF dose was 1.7 microg/kg, and the mean total i.v. morphine dose
was 0.11 mg/kg. There were no serious adverse events. CONCLUSION:
Intranasal fentanyl delivered as 150 microg/mL at a dose of 1.7 microg/kg
was shown to be an effective analgesic in children aged 7 to 15 years
presenting to an ED with an acute fracture when compared to intravenous
morphine at 0.1 mg/kg.
Borland, M. L., I. Jacobs, et al. (2002). "Intranasal
fentanyl reduces acute pain in children in the emergency department: a
safety and efficacy study." Emerg Med (Fremantle) 14(3): 275-80.
INTRODUCTION: Provision of rapid, painless and effective
analgesia to children remains problematic in the prehospital and
emergency setting. Intranasal fentanyl has the potential to eliminate
many of the problems of narcotic administration in children. The aim of
this study, conducted in a tertiary paediatric emergency department was
to evaluate the safety and efficacy of intranasal fentanyl in children.
METHODS: Children in acute pain aged between three and 12 years
inclusive were enrolled on presentation to the emergency department.
Routine observations and pain scoring by the child and caregiver was
undertaken prior to the child receiving fentanyl (20 micrograms for 3-7
year olds and 40 micrograms for 8-12 year olds) and at intervals of 5
min for 30 min Additional fentanyl at the dose of 20 micrograms was
given 5 minutely as required. Caregivers and older children used a
visual analogue scale (VAS) and the younger children used the Wong-Baker
faces scale (WBS). RESULTS: Forty five children were enrolled with a
mean age of 8.0 years. The median dose of fentanyl administered was 1.5
micrograms/kg. Mean pain score in 32 children using the VAS was 62.3 mm
(95% confidence interval 53.2-69.4 mm) at presentation and reduced at 10
min to 44.6 mm (95% confidence interval 36.2-53.1 mm). In 16 children
using WBS the initial mean reading was 4.0 (95% confidence interval
3.3-4.7) and reduced to 2.2 (95% confidence interval 1.3-3.1) at 10 min.
Caregiver pain scores showed a mean preintervention pain score of 64.9
mm (95% confidence interval 57.7-72.2 mm) with a significant reduction
at 10 min to 41.7 mm (95% confidence interval 34.7-48.6 mm). There was
no significant alteration in pulse rate, respiratory rate, and blood
pressure or oxygen saturations. There were no negative side-effects.
CONCLUSIONS: Early and significant reduction in pain (compared to
baseline assessments) was achieved in children using intranasal fentanyl
by 10 min and sustained throughout the 30 min of observations. This
raises the possibility of using intranasal fentanyl in children in the
prehospital setting as well as a role for this form of analgesia as
triage nurse-initiated administration in the emergency department.
Borland, M. L., L. J. Clark, et al. (2008). "Comparative review of the clinical use of intranasal fentanyl versus morphine in a paediatric emergency department." Emerg Med Australas 20(6): 515-20.
OBJECTIVES: Comparison of intranasal fentanyl (INF) and parenteral morphine in children in an ED. Primary objective was to compare time to analgesia from presentation, with secondary objectives to assess patient profiles, specifics of opiate analgesics used plus rate of i.v. access for analgesia alone. SETTING: Tertiary paediatric ED. METHODS: Retrospective review of case notes identified through controlled drug register. Patients who received INF and/or parenteral morphine between 1 January and 31 March 2005 (before introduction of fentanyl) and in corresponding months in 2006 and 2007 were included. RESULTS: A total of 617 patients were included. Geometric mean time to analgesia was statistically different for INF versus morphine in 2006 (31.2 min, SD 2.6 vs 55.6 min, SD 2.4) and in 2007 (23.7 min, SD 2.8 vs 53.1 min, SD 3.1) (both P < 0.000). Mean initial dose of INF in 2007 was 1.46 mg/kg (SD 0.11) compared with 1.32 mg/kg (SD 0.36) in 2006. Mean total dose in 2007 was 2.14 mg/kg (SD 0.93), increased from 1.60 mg/kg (SD 0.56) in 2006. INF was used most commonly for fractures and morphine for abdominal pain. The i.v. access for opiate analgesia decreased from 161/161 (100%) in 2005 to 99/237 (41.8%) in 2007. CONCLUSION: Use of INF in our paediatric ED setting was associated with a significantly reduced time to analgesia for patients requiring immediate analgesia compared with parenteral morphine. Since the introduction of an INF protocol to our department in mid-2005, INF use has increased, with a corresponding decrease in the use of morphine and a reduction in i.v. access for analgesia.Borland, M., S. Milsom, et al. (2011). "Equivalency of two concentrations of fentanyl administered by the intranasal route for acute analgesia in children in a paediatric emergency department: A randomized controlled trial." Emerg Med Australas 23(2): 202-208.
Objective: Intranasal fentanyl's (INF) effectiveness is established using highly concentrated INF (HINF). Standard concentration INF (SINF) is more widely available. We aimed to illustrate the equivalence of SINF to HINF. Methods: Double-blinded randomized controlled trial was used within a children's hospital ED. Children aged 3-15 years with fractures were randomized to SINF or HINF. Outcome measures included pain scores at time zero and every 10 min until 30 min. Additional analgesic agents were noted. Results: Data in 189 children (91 HINF, 98 SINF) were obtained. Pre-analgesia median VAS was 80.0 mm (interquartile range [IQR] 60.0-95.5) in SINF, 77.5 mm (IQR 60.0-100) in HINF. At 10 min median VAS was 49.5 mm (IQR 26.5-68.5) and 43.0 mm (IQR 15.2-66.0), respectively, at 20 min 27.5 mm (IQR 18.5-56.5) and 35.0 mm (IQR 9.0-57.0) and at 30 min 20.0 mm (IQR 10.0-46.0) and 21.5 mm (IQR 4.75-51.0). Each agent demonstrated significant decrease in pain scores (median decrease 40 mm, P = 0.000). Additional analgesia was given in 67 (42 SINF, 25 HINF) (P = 0.028). The decrease in pain scores between children < and >/=50 kg in SINF was significant both overall (P = 0.005) and between 10 and 20 min (P = 0.003). There was no difference in HINF at any time by weight. Conclusions: The two concentrations of INF were equivalent in reducing pain, with a trend to increased oral additional agents in the more dilute solution. The widespread use of this readily available analgesic in the standard concentration can be supported, particularly in patients <50 kg.
Bouida, W., K. Bel Haj Ali, et al. (2020). "Effect on Opioids
Requirement of Early Administration of Intranasal Ketamine for Acute
Traumatic Pain." Clin J Pain 36(6): 458-462.
Brown, C., J. Moodie, et al. (2009). "Intranasal
ketorolac for postoperative pain: a phase 3, double-blind, randomized
study." Pain Med 10(6): 1106-1114.
OBJECTIVE: Analgesic efficacy and tolerability of intranasal (IN) ketorolac was evaluated in postoperative patients in a randomized, double-blind, placebo-controlled study. METHODS: Patients received IN ketorolac (30 mg) or placebo three times daily for up to 5 days, with access to morphine by patient controlled analgesia (PCA). Patients in a single-dose phase were removed from PCA 3 hours prior to the first study dose the day after surgery, and received a single IN ketorolac or placebo dose when visual analog scale scores were > or =40. RESULTS: Three hundred patients (N = 199 ketorolac, N = 101 placebo) were enrolled following primarily hysterectomies (135/300, 45%) and hip replacements (100/300, 33%); 189 (N = 115 ketorolac, N = 74 placebo) entered the single-dose phase. Mean age was 52 years (range 19-81) and 69% of patients were women. The primary efficacy endpoint, the single-dose summed pain intensity difference score at 6 hours, was significantly higher in the ketorolac group compared with placebo (83.3 vs 37.2, P < 0.007), indicating greater pain reduction with ketorolac. Morphine use was reduced by 34% in the ketorolac group compared with the placebo group. The incidence of adverse events ( approximately 98%) was similar in the two groups. The most common adverse events in both groups were nausea and vomiting. There was a trend in the ketorolac group for a lower incidence of opioid-related side effects such as constipation and pruritus. Nasal irritation occurred more frequently with ketorolac vs placebo (24% vs 2%). CONCLUSION: IN ketorolac was well tolerated and effective in treating moderate-to-severe postoperative pain in inpatients; the convenience of IN dosing suggests that its usefulness in the ambulatory care setting should be evaluated.
Carr, D. B., L. C. Goudas, et al. (2004). "Safety and efficacy of intranasal ketamine for the treatment of breakthrough pain in patients with chronic pain: a randomized, double-blind, placebo-controlled, crossover study." Pain 108(1-2): 17-27.
Few placebo-controlled trials have investigated the treatment of breakthrough pain (BTP) in patients with chronic pain. We evaluated the efficacy and safety of intranasal ketamine for BTP in a randomized, double-blind, placebo-controlled, crossover trial. Twenty patients with chronic pain and at least two spontaneous BTP episodes daily self-administered up to five doses of intranasal ketamine or placebo at the onset of a spontaneous BTP episode (pain intensity > or =5 on a 0-10 scale). Two BTP episodes at least 48 h apart were treated with either ketamine or placebo. Patients reported significantly lower BTP intensity following intranasal ketamine than after placebo (P < 0.0001) with pain relief within 10 min of dosing and lasting for up to 60 min. No patient in the ketamine group required his/her usual rescue medication to treat the BTP episode, while seven out of 20 (35%) patients in placebo group did (P = 0.0135). Intranasal ketamine was well tolerated with no serious adverse events. After ketamine administration, four patients reported a transient change in taste, one patient reported rhinorrhea, one patient reported nasal passage irritation, and two patients experienced transient elevation in blood pressure. A side effect questionnaire administered 60 min and 24 h after drug or placebo administration elicited no reports of auditory or visual hallucinations. These data suggest that intranasal administration of ketamine provides rapid, safe and effective relief for BTP.
Chew, K. S. and A. H. Shaharudin (2016). "An open-label
randomised controlled trial on the efficacy of adding intranasal
fentanyl to intravenous tramadol in patients with moderate to severe
pain following acute musculoskeletal injuries." Singapore Med J.
INTRODUCTION: The use of intranasal fentanyl as an alternative
type of analgesia has been shown to be effective in paediatric
populations and prehospital settings. Studies on the use of intranasal
fentanyl in adult patients in emergency settings are limited. METHODS:
An open-label study was conducted to evaluate the effectiveness of the
addition of 1.5 mcg/kg intranasal fentanyl to 2 mg/kg intravenous
tramadol (fentanyl + tramadol arm, n = 10) as compared to the
administration of 2 mg/kg intravenous tramadol alone (tramadol-only arm,
n = 10) in adult patients with moderate to severe pain due to acute
musculoskeletal injuries. RESULTS: When analysed using the independent
t-test, the difference the between the mean visual analog scale scores
pre-intervention and ten-minute post-intervention was 29.8 +/- 8.4 mm in
the fentanyl + tramadol arm and 19.6 +/- 9.7 mm in the tramadol-only arm
(t[18] = 2.515, p = 0.022, 95% confidence interval 1.68-18.72 mm). A
statistically significant, albeit transient, reduction in the ten-minute
post-intervention mean arterial pressure was noted in the fentanyl +
tramadol arm as compared to the tramadol-only arm (13.35 mmHg vs. 7.65
mmHg; using Mann-Whitney U test with U-value = 21.5, p = 0.029, r =
0.48). There was a higher incidence of transient dizziness ten minutes
after intervention among the patients in the fentanyl + tramadol arm.
CONCLUSION: Although effective, intranasal fentanyl may not be
appropriate for routine use in adult patients as it may result in a
significant reduction in blood pressure.
Christensen, K., E. Rogers, et al. (2007). "Safety and efficacy of
intranasal ketamine for acute postoperative pain." Acute pain
9: 183-192.
Background: Subanaesthetic doses of ketamine are analgesic.
Intranasal administration offers a non-invasive route for systemic drug
delivery. We evaluated the safety and analgesic efficacy of intranasal
ketamine in treating moderate-to-severe, acute postoperative pain in the
molar extraction model. Methods: Intranasal ketamine (10mg, 30mg, and
50mg) and placebo were evaluated in a randomised, double-blind,
single-dose, parallel study in 40 patients undergoing removal of 2—4
impacted third molars. Analgesic efficacy was assessed over a 3 h period
following drug administration. Safety was evaluated through adverse
event reporting, vital signs, pulse oximetry, nasal assessments, and a
standard dissociative side effects questionnaire. Results: Ketamine
delivered intranasally was well tolerated. Statistically significant
analgesia, superior to placebo, was observed with the highest dose
tested, 50mg, over a 3 h period. Rapid onset of analgesia was reported
(<10min), and meaningful pain relief was achieved within 15min of the
50mg dose. The majority of adverse events were mild/weak and transient.
No untoward effects were observed on vital signs, pulse oximetry, and
nasal examination. At the doses tested, no significant dissociative
effects were evident using the Side Effects Rating Scale for
Dissociative Anaesthetics. Conclusion: Intranasal ketaminemay offer a
safe, nonopioid, well-tolerated, needle-free analgesic with efficacy in
moderate-to-severe acute pain.
Christrup, L. L., D. Foster, et al. (2008).
"Pharmacokinetics, efficacy, and tolerability of fentanyl following
intranasal versus intravenous administration in adults undergoing
third-molar extraction: A randomized, double-blind, double-dummy,
two-way, crossover study." Clin Ther 30(3): 469-81.
Objective: The aim of this study was to compare the
pharmacokinetic profile, as well as the efficacy and tolerability, of IN
and IV administration of fentanyl in acute, episodic pain in patients
undergoing third-molar extraction. Methods: In this randomized,
double-blind, double-dummy, 2-way, crossover study, patients were
randomized to receive 1 of 4 doses (75, 100, 150, or 200 mug) by both
the IN and IV routes in random order, after each of 2 separate molar
extractions (interval, >/=1 week). Venous blood samples were obtained
for quantification of plasma fentanyl concentrations before and at 1, 3,
5, 7, 9, 12, 15, 25, 40, 60, 90, 120, and 180 minutes after
administration. Pain scores (on an 11-point numeric rating scale) were
recorded before and at 15, 30, 45, 60, 75, 90, 105, 120, 150, 180, 210,
and 240 minutes. Patients indicated the times at which they perceived
meaningful pain relief (onset of action) and at which analgesia ended
(duration of effect), after which they were able to use rescue
medication (time to rescue medication use). Results: A total of 24
patients were enrolled (in all, 47 extractions) (46% male; mean age,
24.1 years; 94% white, 6% Asian). Mean T(max) values were 12.8 and 6.0
minutes (P < 0.001), times to onset of analgesia were 7 and 2 minutes (P
< 0.001), and durations of effect were 56 and 59 minutes after IN and IV
administration (P = NS), respectively. Differences in the onsets and
durations of analgesia after IN and IV administration of single doses
were not significantly different, and neither was the difference in
overall analgesia, with pain scores returning to near-predose values at
statistically similar times after dosing. Duration of effect was
directly related to IN fentanyl dose, with significantly less use of
rescue medication after IN than after IV administration (P < 0.005). The
IN and IV formulations were both well tolerated, with similar numbers of
nasally related adverse events recorded for both routes of
administration. Conclusions: Onsets and durations of analgesia were not
significantly different between single doses of IN and IV fentanyl in
these adults undergoing third-molar extraction. Both IN and IV
administration were generally well tolerated.
Cleary, J. F. (1997). "Pharmacokinetic and
pharmacodynamic issues in the treatment of breakthrough pain." Semin
Oncol 24(5 Suppl 16): S16-13-9.
The primary objective of the present study was to determine the effectiveness of intranasal fentanyl analgesia in children aged 1-3 years with acute moderate to severe pain presenting to the ED. We also aimed to gather information on the safety and acceptability of intranasal fentanyl in this age group. Two paediatric ED enrolled children aged 1-3 years, with acute moderate or severe pain. Intranasal fentanyl was administered (1.5 microg/kg) via a mucosal atomiser device using a 50 microg/mL solution of fentanyl. Physiological parameters (heart rate, respiratory rate, oxygen saturations and level of consciousness) were measured at regular intervals. Objective pain assessment was completed using the Faces, Legs, Arms, Cry, Consolability (FLACC) score. Forty-six children presenting with acute moderate to severe pain were included. The median FLACC score before intranasal fentanyl administration was 8 (interquartile range [IQR] 5-10), decreasing to 2 (IQR 0-4) 10 min post fentanyl (P < 0.0001) and 0 (IQR 0-2) 30 min post fentanyl (P < 0.0001). A clinically significant decrease in FLACC scores was seen in 93% of children 10 min post fentanyl administration and 98% of children 30 min post fentanyl. Intranasal fentanyl delivery using a mucosal atomiser was well tolerated by all children. There were no adverse drug reactions or adverse events detected. Intranasal fentanyl is an effective, safe and well-tolerated mode of analgesia for children aged 1-3 years with moderate to severe pain.
Dale, O., R. Hjortkjaer, et al. (2002). "Nasal
administration of opioids for pain management in adults." Acta
Anaesthesiol Scand 46(7): 759-70.
BACKGROUND: Nasal administration of opioids may be an alternative route to intravenous, subcutaneous, oral transmucosal, oral or rectal administration in some patients. Key features may be self-administration, combined with rapid onset of action. The aim of this paper is to evaluate the present base of knowledge on this topic. METHODS: The review is based on human studies found in Medline or in the reference list of these papers. The physiology of the nasal mucosa and some pharmaceutical aspects of nasal administration are described. The design of each study is described, but not systematically evaluated. RESULTS: Pharmacokinetic studies in volunteers are reported for fentanyl, alfentanil, sufentanil, butorphanol, oxycodone and buprenorphine. Mean times for achieving maximum serum concentrations vary from 5 to 50 min, while mean figures for bioavailability vary from 46 to 71%. Fentanyl, pethidine and butorphanol have been studied for postoperative pain. Mean onset times vary from 12 to 22 min and times to peak effect from 24 to 60 min. There is considerable interindividual variation in pharmacokinetics and clinical outcome. This may partly be due to lack of optimization of nasal formulations. Patient-controlled nasal analgesia is an effective alternative to intravenous PCA. Adverse effects are mainly those related to the opioids themselves, rather than to nasal administration. Some experience with nasal opioids in outpatients and for chronic pain has also been reported. CONCLUSION: Nasal administration of opioids has promising features, but is still in its infancy. Adequately designed clinical studies are needed. Improvements of nasal sprayer devices and opioid formulations may improve clinical outcome.
Dewhirst, E., G. Fedel, et al. (2014). "Pain management following
myringotomy and tube placement: intranasal dexmedetomidine versus
intranasal fentanyl." Int J Pediatr Otorhinolaryngol
78(7): 1090-1094.
PURPOSE: Despite the brevity of the procedure, bilateral myringotomy and
tympanostomy tube placement (BMT) can result in significant
postoperative pain and discomfort. As the procedure is frequently
performed without intravenous access, non-parenteral routes of
administration are frequently used for analgesia. The current study
prospectively compares the efficacy of intranasal (IN) dexmedetomidine
with IN fentanyl for children undergoing BMT. METHODS: This prospective,
double-blinded, randomized clinical trial included pediatric patients
undergoing BMT. The patients were randomized to receive either IN
dexmedetomidine (1 mug/kg) or fentanyl (2 mug/kg) after the induction of
general anesthesia with sevoflurane. All patients received rectal
acetaminophen (40 mg/kg) and the first 50 patients also received
premedication with oral midazolam. Postoperative pain and recovery were
assessed using pediatric pain and recovery scales, and any adverse
effects were monitored for. RESULTS: The study cohort included 100
patients who ranged in age from 1 to 7.7 years and in weight from 8.6 to
37.4 kg. They were divided into 4 groups with 25 patients in each group:
(1) midazolam premedication+IN dexmedetomidine; (2) midazolam
premedication+IN fentanyl; (3) no premedication+IN dexmedetomidine; and
(4) no premedication+IN fentanyl. Pain scores were comparable when
comparing groups 2, 3 and 4, but were higher in group 1 (midazolam
premedication with IN dexmedetomidine). There was no difference in total
time in the post-anesthesia care unit (PACU) or time from arrival in the
PACU until hospital discharge between the 4 groups. The heart rate (HR)
was significantly lower in group 3 when compared to the other groups at
several different times after arrival to the PACU. No clinically
significant difference was noted in blood pressure. CONCLUSION:
Following BMT, when no premedication is administered, there was no
clinical advantage when comparing IN dexmedetomidine (1 mug/kg) to IN
fentanyl (2 mug/kg). The addition of oral midazolam as a premedication
worsened the outcome measures particularly for children receiving IN
dexmedetomidine.
Dolatabadi, A. A., M. Shojaee, et al. (2015). "Intranasal sufentanil
versus intravenous morphine sulfate in pain management of patients with
extremity trauma." Iranian Journal of Emergency Medicine
3(2): 116-121.
Introduction: Pain is one of the most common complaints of
patients referred to emergency department (ED) and its control is one of
the most important responsibilities of the physicians. The present study
was designed, aiming to compare the efficiency of intranasal sufentanil
and intravenous (IV) morphine sulfate in controlling extremity trauma
patients' pain in ED. Methods: In the present clinical trial, extremity
trauma cases referred to the ED of Imam Hossein Hospital, Tehran, Iran,
from October 2014 to March 2015 were randomly divided into 2 groups
treated with intranasal sufentanil (0.3 μg/kg) and IV morphine sulfate
(0.1 mg/kg) single-doses. Demographic data and information regarding the
quality of pain control such as pain severity before intervention and
15, 30, and 60 minutes after intervention, and probable side effects
were gathered using a checklist and compared between the 2 groups.
Results: 88 patients with the mean age of 35.5 ± 14.8 years were
included in the study (81.8% male). 44 patients received IV morphine
sulfate and 44 got intranasal sufentanil. No significant difference was
detected between the 2 groups regarding baseline characteristics. In
addition, there was no significant difference in the groups regarding
pain relief at different studied times (p = 0.12; F = 2.46; df: 1, 86).
Success rate of the drugs also did not differ significantly at different
studied times (p = 0.52). No significant difference was seen between the
groups regarding side effects (p = 0.24). Conclusion: Based on the
results of this study, it seems that intranasal sufentanil has a similar
effect to IV morphine sulfate in rapid, efficient, and non-invasive pain
control in patients with traumatic extremity injuries.
Dooris, B., C. Reid, et al. (2001). "Intranasal
diamorphine in adults." Emerg Med J 18(5): 412-3.
Elitsur, R., A. Hollenbeck, et al. (2019). "Efficacy and cost savings
with the use of a minimal sedation / anxiolysis protocol for intra-articular
corticosteroid injections in children with juvenile idiopathic
arthritis: a retrospective review of prospectively collected data."
Pediatr Rheumatol Online J
17(1): 11.
Ellerton, J. A., M. Greene, et al. (2013). "The use of analgesia in
mountain rescue casualties with moderate or severe pain."
Emerg Med J.
OBJECTIVES: To assess the effectiveness of analgesia used in mountain
rescue (MR) in casualties with moderate or severe pain. To determine if
a verbal numeric pain score is practical in this environment. To
describe the analgesic strategies used by MR. DESIGN: Prospective,
descriptive study. SETTING: Fifty-one MR teams in England and Wales. The
study period was 1 September 2008 to 31 August 2010. PARTICIPANTS: 92 MR
casualties with a pain score of 4/10 or greater. MAIN OUTCOME: 38% of
casualties achieved a pain reduction of 50% or greater in their initial
score at 15 min and 60.2% had achieved this at handover. RESULTS: The
initial pain score was 8 (median), reducing to 5 at 15 min and 3 at
handover. The mean pain reduction was 2.5+/-2.4 at 15 min and 3.9+/-2.5
at handover. 80 casualties (87%) were treated with an opioid and seven
had two different opioids administered. Seven main strategies were
identified in which the principal agent was entonox, intramuscular
opioid, oral analgesia, fentanyl lozenge, intranasal or intravenous
opioid. The choice of strategy varied with the skills of the casualty
carer. CONCLUSIONS: Pain should be assessed using a pain score. When
possible, intravenous opioid is the gold standard to achieve early and
continuing pain control in patients with moderate or severe pain.
Entonox and oral analgesics, as sole agents, have limited use in
moderate or severe pain. Intranasal opioid and fentanyl lozenge are
effective, and appropriate in MR. Research priorities include
bioavailability in different environmental conditions and patient's
satisfaction with their pain management.
Etteri, M. and A. Bellone (2012).
"Intranasal Fentanyl for analgesia in adults with acute renal colic."
Emergency Care Journal 8(2): 13-18.
Objectives: The usual treatment of pain in acute renal colic is analgesic
in intravenous (IV) route. We tried a rapid, non painful, non-invasive
route of administration using intranasal fentanyl versus IV standard
treatment (non steroidal anti-inflammatory drug (NSAIDs) plus morphine)
for the relief of pain in renal colic presenting to an Emergency
Department (ED). Methods: We conducted a prospective non-blinded
randomized clinical trial. A sample of 63 adult patients with clinical
diagnosis of acute renal colic was included to receive either
intravenous morphine (5 mg) plus ketorolac (30 mg) or intranasal
fentanyl (3 µg/kg). Pain score were rated by using a 10 cm visual
analogue scale at 0,30 and 60 minutes after the treatment. Primary
outcome was pain reduction. Secondary outcomes were adverse events and
rescue treatment. Results: Sixty-three patients were enrolled. Thirty
patients received nasal fentanyl and thirty-three received intravenous
morphine plus ketorolac. Morphine-ketorolac therapy was statistically
significant more effective than nasal fentanyl therapy in visual analog
scores at 30 minutes: the difference in mean visual analog scale between
the two groups was 1.74 cm (95% confidence interval 0.29 to 3.2;
P=0.018) at 30 minutes. There were not statistically significant
differences between the two groups at 60 minutes. There were no
significant differences between the groups with regard to secondary
outcomes (adverse events and rescue treatment). Conclusions: A
combination of intravenous morphine plus ketorolac offers pain relief
superior to nasal fentanyl treatment for ED patients with acute renal
colic
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Eva, G. (2001). "Nasal diamorphine in children with
clinical fractures. Patients should be told what to do when analgesia
wears off." Bmj 322(7298): 1367-8.
Farnia, M. R., A. Jalali, et al. (2017). "Comparison of intranasal
ketamine versus IV morphine in reducing pain in patients with renal
colic." Am J Emerg Med
35(3): 434-437.
BACKGROUND: Various drugs have been used to relieve abdominal
pain in patients with renal colic. Ketamine is a popular choice as an
analgesic. OBJECTIVE: To compare the effectiveness of intranasal (IN)
ketamine versus intravenous (IV) morphine in reducing pain in patients
with renal colic. METHODS: A randomized double-blind controlled trial
was performed in 53 patients with renal colic recruited from the
emergency department (ED) in 2015. Finally, 40 patients were enrolled in
this study. Patients in the ketamine group received IN ketamine 1 mg/kg
and IV placebo while patients in the control group received IV morphine
0.1mg/kg and IN placebo. Our goal was to assess visual analogue scale
(VAS) changes between the 2 groups. Patients' VAS scores were reported
before and 5, 15, 30min after drug injection. RESULTS: Before drug
administration, the mean+/-SD VAS score was 7.40+/-1.18 in the morphine
group (group A) and 8.35+/-1.30 in the ketamine group (group B)
(P-value=0.021). After adjustment by the appropriate analysis, the
mean+/-SD VAS score in group (A) and (B) at 5min were (6.07+/-0.47 vs
6.87+/-0.47; mean difference -0.79, 95% confidence interval (CI) -1.48
to -1.04) (P-value=0.025), at 15 and 30min, the mean+/-SD VAS score in
group (A) and (B) were (5.24+/-0.49 vs 5.60+/-0.49; mean difference
-0.36, 95% CI -1.08 to 0.34) and (4.02+/-0.59 vs 4.17+/-0.59; mean
difference -0.15, 95% CI -1.02 to 0.71) (P-value=0.304 and 0.719)
respectively. CONCLUSIONS: IN ketamine may be effective in decreasing
pain in renal colic.
Purpose:
A painful vaso-occlusive crisis (VOC) is the most common indication
for patients with sickle cell disease (SSD) to seek emergency care. The
mainstay of treatment for VOC is aggressive intravenous analgesia with
opiates and hydration. However, there is often a delay in establishing
intravenous access and providing initial analgesia to these patients.
Intranasal fentanyl (INF) has been shown to be safe and effective in
providing prompt analgesia to children with other painful conditions in
the ED and prehospital setting. Our objective was to determine if
children with a VOC who receive initial treatment with INF compared to
placebo achieve a greater decrease in pain score 20 minutes after study
drug administration.
Methods:
This was a randomized, double-blind, placebo-controlled trial. Children
with SSD ages 3-20 years not taking daily opiates were eligible for the
study and were pre-consented for inclusion at a previous healthcare
encounter. Upon presentation to the ED, consented subjects with a pain
score ≥6 were randomized to receive a single 2ug/kg (max 100ug) dose of
INF or an equivalent volume of intranasal saline. Pain scores were
obtained using the Wong-Baker FACES pain scale prior to study drug
administration and at 10, 20 and 30 minutes afterwards. Additional
analgesic medication was given per standard ED care. Demographic data,
information related to the ED visit and adverse events were collected.
Pain scores were analyzed using medians with interquartile ranges and
the Mann-Whitney U test was used to compare changes in pain scores
between groups.
Results:
Forty-nine patients completed the study (24 INF, 25 placebo). The two
groups were similar with respect to mean age and median initial pain
score [INF 10 (IQR 8-10), placebo 9 (IQR 8-10) p=0.38). A greater
percentage of subjects who received INF were female (54% vs 24%,
(<0.05)]. Patients who received INF had a statistically significant
decrease in median pain score at 20 minutes compared to placebo [2 (IQR
0.5-4) vs. 1 (IQR 0-2), p=0.048], but not at 10 or 30 minutes. Except
for one subject in the placebo group, no other subjects received any
additional analgesics prior to 20 minutes. There was no difference in
the percentage of subjects who received additional analgesics prior to
30 minutes. There was no difference in admission rate between groups.
There were no serious adverse events in either group.
Conclusion:
Children who received INF had a statistically significant greater
decrease in pain score at 20 minutes compared to those who received
placebo. Further studies should evaluate how to best incorporate
intranasal fentanyl into the emergency care of a child with a painful
VOC.
Fein, D. M., J. R. Avner, et al. (2017). "Intranasal fentanyl for
initial treatment of vaso-occlusive crisis in sickle cell disease."
Pediatr Blood Cancer 64(6).
BACKGROUND: Analgesia administration for children with vaso-occlusive
crises is often delayed in the emergency department. Intranasal fentanyl
(INF) has been shown to be safe and effective in providing rapid
analgesia for other painful conditions. Our objective was to determine
if children with a vaso-occlusive crisis (VOC) who received initial
treatment with INF compared to placebo achieved a greater decrease in
pain score after 20 min. PROCEDURE: This was a randomized, double-blind,
placebo-controlled trial. Children with sickle cell disease, 3-20 years
old, not taking daily opiates were eligible for the study. Subjects who
presented to the emergency department with a pain score >/=6 were
randomized to either a single dose of INF (2 mug/kg, maximum 100 mug) or
an equivalent volume of intranasal saline. Pain scores were obtained
using a modified Wong-Baker FACES pain scale prior to the administration
of study drug and at 10, 20, and 30 min afterward. Additional analgesic
medication was given per standard protocol. RESULTS: Forty-nine subjects
completed the study (24 fentanyl and 25 placebo). Subjects who received
INF had a greater decrease in median pain score at 20 min compared to
placebo (2 [interquartile range, (IQR) 0.5-4] vs. 1 [IQR 0-2], P =
0.048), but not at 10 or 30 min. There were no serious adverse events in
either group. CONCLUSION: Children who received INF had a greater
decrease in pain score at 20 min compared to those who received placebo.
Further studies should evaluate how to best incorporate INF into the
emergency care of a child with a VOC.
Fenster, D. B., P. S. Dayan, et al. (2018). "Randomized Trial of
Intranasal Fentanyl Versus Intravenous Morphine for Abscess Incision and
Drainage." Pediatr Emerg Care
34(9): 607-612.
OBJECTIVES: Abscess incision and drainage (I&D) are painful and
distressing procedures in children. Intranasal (IN) fentanyl is an
effective analgesic for reducing symptomatic pain associate with
fractures and burns but has not been studied for reducing procedural
pain during abscess I&D. Our objective was to compare the analgesic
efficacy of IN fentanyl with intravenous (IV) morphine for abscess I&D
in children. METHODS: We performed a randomized noninferiority trial in
children aged 4 to 18 years undergoing abscess I&D in a pediatric
emergency department. Patients received IN fentanyl (2 mug/kg; maximum,
100 mug) or IV morphine (0.1 mg/kg; maximum, 8 mg). The primary outcome,
determined independently by blinded assessors, was the Observational
Scale of Behavioral Distress-Revised (OSBD-R). The prestated margin of
noninferiority (Delta) was 1.80. Secondary outcomes included
self-reported pain, treatment failure, and patient and parental
satisfaction. RESULTS: We enrolled 20 children (median age, 15.4 years),
10 in each group. The difference between total OSBD-R scores was -13.45
(95% confidence interval, -24.24 to -2.67), favoring IN fentanyl.There
was less self-reported pain in patients who received IN fentanyl
immediately after the procedure. Four patients (40%) receiving IV
morphine had treatment failures and required moderate sedation or had
the procedure terminated. More patients who received IN fentanyl were
satisfied with the analgesic administered compared with those who
received IV morphine. CONCLUSIONS: In a small sample of children aged 4
to 18 years undergoing abscess I&D, IN fentanyl was noninferior, and
potentially superior, to IV morphine for reducing procedural pain and
distress.
Finkel, J. C., I. T. Cohen, et al. (2001). "The
effect of intranasal fentanyl on the emergence characteristics after
sevoflurane anesthesia in children undergoing surgery for bilateral
myringotomy tube placement." Anesth Analg 92(5): 1164-8.
Children undergoing placement of bilateral myringotomy tubes
(BMT) often exhibit pain-related behavior (agitation) in the
postanesthesia care unit. We compared the emergence and recovery
profiles of pediatric patients who received sevoflurane with or without
supplementary intranasal fentanyl for BMT surgery. By using a
prospective, double-blinded design, 150 children 6 mo to 5 yr of age,
scheduled for routine BMT surgery, were anesthetized with sevoflurane
(2%-3%) in a 60% N(2)O/O(2) gas mixture. Patients were randomized to
receive equal volumes of intranasal saline (Control), 1 microg/kg
fentanyl or 2 microg/kg fentanyl. A blinded observer evaluated each
patient using a previously described 4-point agitation scale and the
Steward recovery scale. Response to parental presence was observed after
a score of six (full recovery) was achieved on the Steward recovery
scale. There were no significant differences among the three groups
regarding age, weight, surgeon, duration of anesthesia, or ear
condition. Recovery times and emergence characteristic scores were not
statistically different. Agitation scores were significantly reduced in
the 2-microg/kg Fentanyl group as compared with the Control group (P =
0.012). Fentanyl 2 microg/kg is recommended to reduce the incidence of
agitation seen in these patients. IMPLICATIONS: We examined the use of
nasally administered fentanyl for the relief of agitation or discomfort
after placement of bilateral myringotomy tubes in 150 children ages 6 mo
to 5 yr using a prospective, double-blinded design. Fentanyl 2 microg/kg
was found to reduce the incidence of agitation in these patients.
Finn, J., J. Wright, et al. (2004). "A randomised
crossover trial of patient controlled intranasal fentanyl and oral
morphine for procedural wound care in adult patients with burns."
Burns 30(3): 262-8.
This study sought to compare the analgesic efficacy and safety of
patient controlled intra-nasal (PCIN) fentanyl with oral morphine for
procedural wound care in burns patients. A randomised double-blind
placebo controlled, two period, two-treatment crossover trial was
conducted within the Burns Unit of a major teaching hospital in Perth,
Western Australia. Patients requiring identical wound care procedures on
two consecutive mornings (and not prescribed intravenous analgesia) were
randomised to receive either PCIN fentanyl with oral placebo or oral
morphine with intranasal placebo on 1 day, followed by the alternate
active drug on the following day. Twenty-six patients (22 males), aged
between 18 and 69 years (35.5 +/- 12.4 years), with total body surface
burns (TBSA) range 1-25% (6.9 +/- 4.5), indicated their level of pain on
a 10 point (0-10) numeric scale at various time periods before, during
and after the procedure. A mean total dose of 1.48 +/- 0.57 microg/kg of
PCIN fentanyl and 0.35 +/- 0.12 mg/kg of oral morphine was administered.
No statistically significant difference was found between the pain
scores recorded for patients during the procedure with PCIN fentanyl
compared to that with oral morphine (mean difference = -0.75, 95% CI =
-1.97 to 0.47, P = 0.22). Two patients experienced hypotension during
the procedure--both had received active oral morphine. No patients
experienced respiratory depression or a significant drop in oxygen
saturation. There were four episodes (in three patients) where 'rescue
analgesia' for severe pain was required--two episodes involving oral
morphine and two involving PCIN fentanyl. It was concluded that PCIN
fentanyl is similar in efficacy and safety to oral morphine for relief
of procedural wound care pain in burns patients.
Fleet, J., I. Belan, et al. (2015). "A comparison of fentanyl with pethidine for pain relief during childbirth: a randomised controlled trial." BJOG 122(7): 983-992.
Fleet, J. A., M. Jones, et al. (2017). "Taking the alternative route:
Women's experience of intranasal fentanyl, subcutaneous fentanyl or
intramuscular pethidine for labour analgesia." Midwifery
53: 15-19.
OBJECTIVE: To compare women's experience of receiving either
intranasal fentanyl, subcutaneous fentanyl or intramuscular pethidine
for labour analgesia. DESIGN: A content analysis was undertaken as part
of the third phase of a larger randomised controlled trial, using the
per-protocol dataset to examine women's experiences of treatment
received. Healthy women birthing at term, who received intranasal
fentanyl (n=41), subcutaneous fentanyl (n=37) and/or intramuscular
pethidine (n=38) for labour analgesia, were contacted at 6 weeks
postpartum to complete a phone questionnaire. SETTING: A tertiary and
regional maternity unit in South Australia. FINDINGS: Over 80% of women
who received intranasal or subcutaneous fentanyl reported that they
would use the treatment again compared to 44.8% of women who had
received pethidine (self-administered intranasal fentanyl provided more
expressive responses emphasising the route provided a strong sense of
control and enablement. KEY CONCLUSIONS: Route of administration
influenced the women's experience, more women who self-administered
intranasal fentanyl reported positive emotional responses, with women
reporting increased autonomy and satisfaction. Whereas, women who relied
on the midwife to administer subcutaneous fentanyl or intramuscular
pethidine, were more often focused on the physical effect of the drug.
Pethidine was the least preferred option due to adverse effects.
IMPLICATIONS FOR PRACTICE: For women requesting parenteral analgesia,
fentanyl administered by less invasive routes offers women additional
options that may better meet their emotional, cognitive and physical
needs than the current practice of administering intramuscular pethidine.
Flood, P. and D. Daniel (2004). "Intranasal nicotine
for postoperative pain treatment." Anesthesiology 101(6):
1417-21.
BACKGROUND: Despite pharmacological treatment, 70-80% of patients
report moderate to severe pain after surgery. Because nicotine has been
reported to have analgesic properties in animal and human volunteer
studies, the authors assessed the analgesic efficacy of a single 3 mg
dose of nicotine nasal spray administered before emergence from general
anesthesia. METHODS: The authors conducted a randomized, double blind,
placebo controlled trial of 20 healthy women (mean age 45 (SD 8) yr) who
were to undergo uterine surgery through a low transverse incision. After
the conclusion of surgery but before emergence from general anesthesia,
the anesthesiologist administered either nicotine nasal spray or a
placebo. Numerical analog pain score and morphine utilization and
hemodynamic values were measured for 24 h. RESULTS: The patients treated
with nicotine reported lower pain scores during the first hour after
surgery (peak numerical analog score, 7.6 (SD 1.4) versus 5.3 (SD 1.6);
P < 0.001) and used half the amount of morphine as the control group (12
(SD 6) versus 6 (SD 5) mg; P < 0.05). Patients who received nicotine
still reported less pain than those in the control group 24 h after
surgery (1.5 (SD 0.5) versus 4.9 (SD 1.4); P < 0.01). Systolic blood
pressure was lower in the group that received nicotine (105 (SD 3)
versus 122 (SD 3); P < 0.001), but there was no difference in diastolic
blood pressure or heart rate. CONCLUSIONS: Treatment with a single dose
of nicotine immediately before emergence from anesthesia was associated
with significantly lower reported pain scores during the first day after
surgery. The decreased pain was associated with a reduction in morphine
utilization and the analgesic effect of nicotine was not associated with
hypertension or tachycardia.
Frey, T. M., T. A. Florin, et al. (2019). "Effect of Intranasal Ketamine
vs Fentanyl on Pain Reduction for Extremity Injuries in Children: The
PRIME Randomized Clinical Trial." JAMA Pediatr
173(2): 140-146.
Importance: Timely analgesia is critical for children with injuries
presenting to the emergency department, yet pain control efforts are
often inadequate. Intranasal administration of pain medications provides
rapid analgesia with minimal discomfort. Opioids are historically used
for significant pain from traumatic injuries but have concerning adverse
effects. Intranasal ketamine may provide an effective alternative.
Objective: To determine whether intranasal ketamine is noninferior to
intranasal fentanyl for pain reduction in children presenting with acute
extremity injuries. Design, Setting, and Participants: The Pain
Reduction With Intranasal Medications for Extremity Injuries (PRIME)
trial was a double-blind, randomized, active-control, noninferiority
trial in a pediatric, tertiary, level 1 trauma center. Participants were
children aged 8 to 17 years presenting to the emergency department with
moderate to severe pain due to traumatic limb injuries between March
2016 and February 2017. Analyses were intention to treat and began in
May 2017. Interventions: Intranasal ketamine (1.5 mg/kg) or intranasal
fentanyl (2 microg/kg). Main Outcomes and Measures: The primary outcome
was reduction in visual analog scale pain score 30 minutes after
intervention. The noninferiority margin for this outcome was 10.
Results: Of 90 children enrolled, 45 (50%) were allocated to ketamine
(mean [SD] age, 11.8 [2.6] years; 26 boys [59%]) and 45 (50%) to
fentanyl (mean [SD] age, 12.2 [2.3] years; 31 boys [74%]). Thirty
minutes after medication, the mean visual analog scale reduction was
30.6 mm (95% CI, 25.4-35.8) for ketamine and 31.9 mm (95% CI, 26.6-37.2)
for fentanyl. Ketamine was noninferior to fentanyl for pain reduction
based on a 1-sided test of group difference less than the noninferiority
margin, as the CIs crossed 0 but did not cross the prespecified
noninferiority margin (difference in mean pain reduction between groups,
1.3; 90% CI, -6.2 to 8.7). The risk of adverse events was higher in the
ketamine group (relative risk, 2.5; 95% CI, 1.5-4.0), but all events
were minor and transient. Rescue analgesia was similar between groups
(relative risk, 0.89; 95% CI, 0.5-1.6). Conclusions and Relevance:
Ketamine provides effective analgesia that is noninferior to fentanyl,
although participants who received ketamine had an increase in adverse
events that were minor and transient. Intranasal ketamine may be an
appropriate alternative to intranasal fentanyl for pain associated with
acute extremity injuries. Ketamine should be considered for pediatric
pain management in the emergency setting, especially when opioids are
associated with increased risk. Trial Registration: ClinicalTrials.gov
Identifier: NCT02778880.
Galinkin, J. L., L. M. Fazi, et al. (2000). "Use of
intranasal fentanyl in children undergoing myringotomy and tube
placement during halothane and sevoflurane anesthesia."
Anesthesiology 93(6): 1378-83.
BACKGROUND: Many children are restless, disoriented, and
inconsolable immediately after bilateral myringotomy and tympanosotomy
tube placement (BMT). Rapid emergence from sevoflurane anesthesia and
postoperative pain may increase emergence agitation. The authors first
determined serum fentanyl concentrations in a two-phase study of
intranasal fentanyl. The second phase was a prospective,
placebo-controlled, double-blind study to determine the efficacy of
intranasal fentanyl in reducing emergence agitation after sevoflurane or
halothane anesthesia. METHODS: In phase 1, 26 children with American
Society of Anesthesiologists (ASA) physical status I or II who were
scheduled for BMT received intranasal fentanyl, 2 microg/kg, during a
standardized anesthetic. Serum fentanyl concentrations in blood samples
drawn at emergence and at postanesthesia care unit (PACU) discharge were
determined by radioimmunoassay. In phase 2, 265 children with ASA
physical status I or II were randomized to receive sevoflurane or
halothane anesthesia along with either intranasal fentanyl (2 microg/kg)
or saline. Postoperative agitation, Children's Hospital of Eastern
Ontario Pain Scale (CHEOPS) scores, and satisfaction of PACU nurses and
parents with the anesthetic technique were evaluated. RESULTS: In phase
1, the mean fentanyl concentrations at 10 +/- 4 min (mean +/- SD) and 34
+/- 9 min after administering intranasal fentanyl were 0.80 +/- 0.28 and
0.64 +/- 0.25 ng/ml, respectively. In phase 2, the incidence of severe
agitation, highest CHEOPS scores, and heart rate in the PACU were
decreased with intranasal fentanyl. There were no differences between
sevoflurane and halothane in these measures and in times to hospital
discharge. The incidence of postoperative vomiting, hypoxemia, and slow
respiratory rates were not increased with fentanyl. CONCLUSIONS: Serum
fentanyl concentrations after intranasal administration exceed the
minimum effective steady state concentration for analgesia in adults.
The use of intranasal fentanyl during halothane or sevoflurane
anesthesia for BMT is associated with diminished postoperative agitation
without an increase in vomiting, hypoxemia, or discharge times.
Good, P., K. Jackson, et al. (2009). "Intranasal sufentanil for cancer-associated breakthrough pain." Palliat Med 23(1): 54-8.
The objective of this study was to demonstrate the efficacy, safety and patient acceptability of the use of intranasal sufentanil for cancer-associated breakthrough pain. This was a prospective, open label, observational study of patients in three inpatient palliative care units in Australia. Patients on opioids with cancer-associated breakthrough pain and clinical evidence of opioid responsiveness to their breakthrough pain were given intranasal (IN) Sufentanil via a GO Medical patient controlled IN analgesia device. The main outcome measures were pain scores, need to revert to previous breakthrough opioid after 30 min, number of patients who chose to continue using IN sufentanil, and adverse effects. There were 64 episodes of use of IN sufentanil for breakthrough pain in 30 patients. There was a significant reduction in pain scores at 15 (P < 0.0001) and 30 min (P < 0.0001). In only 4/64 (6%) episodes of breakthrough pain did the participants choose to revert to their prestudy breakthrough medication. Twenty-three patients (77%) rated IN sufentanil as better than their prestudy breakthrough medication. The incidence of adverse effects was low and most were mild. Our study showed that IN sufentanil can provide relatively rapid onset, intense but relatively short lasting analgesia and in the palliative care setting it is an effective, practical, and safe option for breakthrough pain.
Goudas, L. C., D. B. Carr, et al. (2002). "Efficacy and
safety of intranasal ketamine for the management of breakthrough pain in
chronic pain. A randomized, double-blind, placebo-controlled, cross-over
trial." American Society of Clinical Oncology Meeting
Abstract No:
450.
Breakthrough Pain (BTP) is common (prevalence: 19% to 93%) among
chronic pain patients, however few placebo-controlled trials have
investigated BTP in these patients. Breakthrough pain management
typically involves dosage increases of round-the-clock opioids and/or
supplemental rescue doses of short-acting opioids or fixed-dose mixtures
with NSAIDs. These medications have a relatively slow onset of action,
rendering them inadequate in treating severe, paroxysmal BTP. The large
surface area and local vascularity of the nasal mucosa offers an ideal
route for rapid delivery of drugs into the systemic circulation. To
evaluate the efficacy and safety of intranasal ketamine HCl, we
performed a randomized, double-blind, placebo-controlled, cross-over
trial in 20 patients suffering from chronic pain. Patients experiencing
at least 2 BTP episodes daily were randomized to receive ketamine and
placebo intranasally. Patients self-administered up to 5 fixed doses (10
mg each, up to 50 mg per episode) of drug or placebo at the onset of BTP
(intensity of BTP > 5 on a 0 to 10 numeric scale). Two BTP episodes,
each on a separate day, were treated with either ketamine or placebo.
Patients reported significantly lower intensity of their BTP episode
following intranasal ketamine as compared to placebo (p<0.0001). Onset
of pain relief occurred within 5 minutes of dosing with ketamine and
lasted up to 60 minutes. No patient in the ketamine group required
his/her regular rescue medication, while 7/20 (35%) in the placebo group
did (p=0.0135). Intranasal ketamine was well-tolerated with no serious
adverse events reported. In the ketamine group, there were 4 reports of
change in taste (20%), and one report each of rhinorrhea (5%), throat
irritation (5%), and nasal irritation (5%). Some patients (20%) reported
varying degrees of dizziness and a feeling of unreality, resolving
within 60 minutes. No patients reported hallucinations. These data
suggest that intranasal ketamine provides rapid, safe, and effective
relief for breakthrough pain that may reduce the need for short-acting
opioids.
Grant, G. M. and D. R. Mehlisch (2010).
"Intranasal ketorolac for pain secondary to third molar impaction
surgery: a randomized, double-blind, placebo-controlled trial." J
Oral Maxillofac Surg 68(5): 1025-1031.
PURPOSE: This randomized, double-blind, placebo-controlled study evaluated the efficacy and safety of intranasal (IN) ketorolac in patients who had third molar extraction surgery with bony impactions. MATERIALS AND METHODS: After surgery, patients were randomly assigned to receive IN ketorolac 31.5 mg (n = 40) or IN placebo (n = 40). Safety was assessed from spontaneously reported adverse events and measurement of vital signs. Efficacy assessments included pain intensity, which was measured on a 0- to 100-mm visual analog scale, total pain relief, and global pain evaluation up to 8 hours after dosing or until patients required rescue analgesia. The primary efficacy variable was the summed pain intensity difference score over the first 8 hours after dosing. RESULTS: Summed pain intensity difference values +/- SE were significantly higher (indicating better analgesia) in the ketorolac group compared with placebo (136.7 +/- 33.0 vs -105.2 +/- 29.1, P < .001). Total pain relief scores were significantly higher (P < .001) in the ketorolac group compared with placebo at all times. A larger proportion of subjects in the ketorolac group reported good, very good, or excellent pain control compared with the control group (60% vs 13%). Times to perceptible (21.5 minutes) and meaningful (66.0 minutes) pain relief were significantly shorter and the time to rescue analgesic use was significantly longer in the ketorolac group (P < .001). Eight patients in the placebo group and 3 in the ketorolac group had adverse events, none of which was serious. The 3 events in the ketorolac group were reports of mild headache. CONCLUSION: A single IN ketorolac 31.5 mg dose was well tolerated and provided rapid and effective pain relief in oral surgery patients for a period up to 8 hours.
Graudins, A., R. Meek, et al. (2015). "The PICHFORK (Pain in Children
Fentanyl or Ketamine) trial: a randomized controlled trial comparing
intranasal ketamine and fentanyl for the relief of moderate to severe
pain in children with limb injuries." Ann Emerg Med
65(3): 248-254 e241.
STUDY OBJECTIVE: We compare the analgesic effectiveness of
intranasal fentanyl and ketamine in children. METHODS: This was a
double-blind, randomized, controlled trial comparing fentanyl at 1.5
mug/kg with ketamine at 1 mg/kg in children aged 3 to 13 years and
weighing less than 50 kg, with isolated limb injury and pain of more
than 6 of 10 at triage. The sample size was 40 in each arm. Subjects
were coadministered oral ibuprofen at 10 mg/kg. The primary outcome was
median pain rating reduction at 30 minutes. Secondary outcomes were pain
rating reduction at 15 and 60 minutes, subjective improvement and
satisfaction, University of Michigan Sedation Score, adverse events, and
rescue analgesia. RESULTS: Eighty children enrolled, and 73 were
available for analysis: 37 fentanyl and 36 ketamine. Median age was 8
years; 63% were male children; median baseline pain rating was 80 mm. At
30 minutes, median reductions for ketamine and fentanyl were 45 and 40
mm, respectively (difference 5 mm; 95% confidence interval [CI] -10 to
20 mm). Reductions exceeded 20 mm for ketamine and fentanyl in 82% and
79% of patients, respectively (difference 3%; 95% CI -22% to 16%). Pain
rating reduction was maintained to 60 minutes in both groups.
Satisfaction was reported for ketamine and fentanyl by 83% and 72% of
patients, respectively (difference 11%; 95% CI -9% to 30%). Adverse
events, mainly mild, were reported for ketamine and fentanyl by 78% and
40% of patients, respectively (difference 38%; 95% CI -58% to 16%).
Three ketamine patients had a moderate degree of sedation by University
of Michigan Sedation Score. CONCLUSION: Intranasal fentanyl and ketamine
were associated with similar pain reduction in children with moderate to
severe pain from limb injury. Ketamine was associated with more minor
adverse events.
Guthrie, A. M., R. A. Baum, et al. (2019). "Use of Intranasal
Ketamine in Pediatric Patients in the Emergency Department."
Pediatr Emerg Care.
OBJECTIVES: Ketamine is a safe and widely used sedative and analgesic in
the pediatric emergency department (ED). The use of intranasal (IN)
ketamine in exchange for the administration of intravenous sedatives or
analgesics for procedural sedation in pediatric patients is not
commonplace. The goal of this study was to evaluate provider perceptions
and patient outcomes at varying doses of IN ketamine for anxiolysis,
agitation, or analgesia. METHODS: From January 2018 to May 2018, we
performed a prospective survey and chart review of pediatric patients
receiving IN ketamine. The primary outcome was to determine provider
satisfaction with using IN ketamine. Secondary objectives included
comparing outcomes stratified by dose, adverse events, assessing for
treatment failure, and ED length of stay (LOS). As a secondary
comparison, patients receiving IN ketamine whom otherwise would have
required procedural sedation with intravenous sedatives or analgesics
were placed into a subgroup. This subgroup of patients was compared with
a cohort who received intravenous sedatives or analgesics for procedural
sedation during a similar period the preceding year (January 2017 to
June 2017). RESULTS: Of the 196 cases, 100% of the providers were
comfortable using IN ketamine. The median overall provider satisfaction
was 90 out of 100, the perception of patient comfort was 75 out of 100,
and perceived patient comfort was maximized when using doses between 3
and 5 mg/kg. There were 15 (7.7%) patients who experienced ketamine
treatment failure. Overall, the rate of adverse events was 6%, but were
considered minor [nausea (n = 3; 1.5%), dizziness (n = 2; 1%), and
drowsiness (n = 2; 1%)]. No patients required respiratory support or
intubation. The mean LOS was 237.9 minutes, compared with those who
underwent procedural sedation with an LOS of 332.4 minutes (P < 0.001).
CONCLUSIONS: This study demonstrates that IN ketamine was able to
provide safe and successful analgesia and anxiolysis in pediatric
patients in an ED setting. In addition, providers expressed a high
degree of satisfaction with using IN ketamine (90 out of 100) in
addition to a high degree of patient comfort during the procedure (75
out of 100). Intranasal ketamine provides an alternative to intravenous
medication normally requiring more resource-intensive monitoring.
Procedural sedations are resource and time intensive activities that
increase ED LOS. Intranasal ketamine used for anxiolysis and analgesia
offers the benefits of freeing up resources of staff and monitoring
while enhancing overall throughput through a pediatric ED.
Hallas, P. and J. Cordtz (2017). "Fracture reduction in the ED and
intranasal fentanyl 50mcg/ml in children." Am J
Emerg Med.
Hallett, A., F. O'Higgins, et al. (2000).
"Patient-controlled intranasal diamorphine for postoperative pain: an
acceptability study." Anaesthesia 55(6): 532-9.
A patient acceptability study was conducted using
patient-controlled intranasal diamorphine. Patients undergoing
nonemergency orthopaedic or gynaecological surgery self-administered
intranasal diamorphine for 24 h postoperatively. Pain, pain relief,
sedation, respiratory rate, nausea and vomiting were assessed regularly.
After 24 h, patients and their attending nurses completed a
questionnaire assessing satisfaction and practical aspects of the
technique. Satisfaction was reported as good or complete by 69% of
patients and 69% of nurses. Pain relief was assessed as better than
expected by 45% of patients and better than normal by 50% of nurses.
Seventy-nine per cent of patients would be pleased to use
patient-controlled intranasal diamorphine again and 89% of nurses would
be happy for their patients to use it again. Sedation was uncommon and
mild and there were no episodes of significant respiratory depression.
Fifty-three per cent of patients reported no nausea and 74% did not
vomit at any stage. There were seven withdrawals, four due to problems
with the device and three due to therapeutic problems. The nasal spray
may need modification to improve reliability. However, we found
patient-controlled intranasal analgesia an effective technique, which
was well tolerated by patients and nurses and was without unpleasant
side-effects. Further work to determine how it performs compared with
intramuscular or intravenous analgesia is now needed.
Han, M., H. Wang, et al. (2009). "Intranasal instillation of sufentanil reduces myoclonus induced by etomidate." Anhui Medical and Pharm J.
Aim To investigate the effects of intranasal sufentanil reducing myoclonus induced by etomidate. Methods Eighty ASA class I or Ⅱ patients aged 32 to 70 years weighing 50 to 85 kg without neuromuscular disorders who were undergoing elective surgery were randomly divided into two groups: Group A received intranasal instillation of sufentanil 0.2 μg·kg-1,which was diluted to 1 ml. Group B received intranasal instillation of normal saline l ml, After 2 min, two groups were injected etomidate 0.3 mg·kg-1.MBP,HR,SPO2 and RR were recorded before intranasal instillation of sufentanil(T0),at 1 min(T1) and 2 min(T2)after intranasal instillation of sufentanil. Myoclonus was observed and graded. Results The incidence of myoclonus was significantly lower in group A than that in group B(P0.01).There was no significant difference in MBP, HR, SPO2 and RR at all time points between group A and group B. Conclusion Intranasal instillation of sufentanil 0.2 μg·kg-1 can reduce myoclonus induced by etomidate.
Harlos, M. (2002). "Palliative Care Incident Pain and
Incident Dyspnea Protocol." Internet public domain protocol:
http://palliative.info/incidentpain.htm.
This is a protocol for transmucosal (sublingual and intranasal)
fentanyl and sufentanil to treat pain and dyspnea in hospice setting.
Harlos, M. S., S. Stenekes, et al. (2012). "Intranasal Fentanyl
in the Palliative Care of Newborns and Infants." J
Pain Symptom Manage.
CONTEXT: Perinatal palliative care is an area of increasing focus among
clinicians supporting newborns and their families. Although not every
newborn will survive the neonatal period, assuring their comfort and
quality of life remains an imperative for their care providers. It can
be challenging to administer medications such as opioids in a minimally
invasive yet effective manner. OBJECTIVES: To describe the experience
using intranasal (IN) fentanyl in the management of distress in a case
series of 11 dying neonates. METHODS: A retrospective chart review was
undertaken of 58 consecutive referrals of newborns and infants aged six
months or younger between November 2006 and July 2010 to the Winnipeg
Regional Health Authority Pediatric Palliative Care Service to determine
how often IN fentanyl was used and review documented responses after the
medication. RESULTS: Of 58 referrals, IN fentanyl was used in 11
patients, in all cases for concerns regarding respiratory distress.
Chart documentation indicated that fentanyl was tolerated well, with no
circumstances of drug-related apnea and no occurrences of chest wall
rigidity. In most cases, labored breathing and restlessness settled
after medication administration. The average time from administration of
the last dose of fentanyl until death was 61 minutes. CONCLUSION: We
found IN fentanyl, which can be administered in a variety of care
settings, to be a minimally invasive means of palliating distress in
dying newborns and infants. No adverse events related to its use were
noted.
Haynes, G., N. H. Brahen, et al. (1993). "Plasma
sufentanil concentration after intranasal administration to paediatric
outpatients." Can J Anaesth 40(3): 286.
Heard, C., P. Creighton, et al. (2009). "Intranasal flumazenil and naloxone to reverse over-sedation in a child undergoing dental restorations." Paediatr Anaesth 19(8): 795-7; discussion 798-9.
We describe a 3-year-old child who became over-sedated after receiving intranasal (IN) midazolam (0.53 mg.kg(-1)) and IN sufentanil (1 mcg.kg(-1)) for dental restorations in the dental office. Desaturation was attributed to laryngospasm, which was managed with positive pressure ventilation and oxygen. The sedation was reversed with a combination of IN flumazenil and naloxone.
Helmers, J. H., H. Noorduin, et al. (1989).
"Comparison of intravenous and intranasal sufentanil absorption and
sedation." Can J Anaesth 36(5): 494-7.
The absorption and sedation following an intranasal dose of
sufentanil were evaluated and compared with those of the same dose given
intravenously. Sixteen adult patients scheduled for elective surgery
were randomly allocated to receive as premedication 15 micrograms
sufentanil either intravenously or intranasally. Before administration
and at fixed time intervals thereafter, the degree of sedation was
assessed, vital signs were recorded and venous blood samples were taken
for the determination of sufentanil plasma concentrations. Peroperative
sedation of rapid onset and limited duration was seen in both groups.
However, the onset of sedation was more rapid after intravenous
injection. At 10 min, all patients in the IV group were sedated versus
only two in the intranasal group (P less than 0.01). No significant
intergroup differences in sedation were seen at 20 to 60 min. This
clinical effect is in agreement with the measured plasma levels, which
were significantly lower after intranasal application at 5 and 10 min,
being 36 and 56 per cent of those after IV dosing, respectively. From 30
min, plasma concentrations were virtually identical for the two routes
of administration. The AUC0-120 min after intranasal dosing was 78 per
cent of that after intravenous injection. Intranasal dosing induced no
clinically significant changes in vital signs, whereas after IV
sufentanil, a clinically significant decrease in PaO2 was seen at 5 min.
The results of this study show that sufentanil, when administered
intranasally, is rapidly and effectively absorbed from the human nasal
mucosa, so that this route may be an attractive alternative for a
premedicant, avoiding the discomfort of an intravenous or intramuscular
injection.
Henderson, J. M., D. A. Brodsky, et al. (1988).
"Pre-induction of anesthesia in pediatric patients with nasally
administered sufentanil." Anesthesiology 68(5): 671-5.
To evaluate nasally administered sufentanil, 1.5-4.5
micrograms/kg, for pre-induction (i.e., pre-medication/induction) of
anesthesia in pediatric patients, the authors studied ASA PS 1 or 2
patients scheduled for elective surgery. Eighty children, ages 6 months
to 7 yr, were randomized to receive sufentanil (1.5, 3.0, or 4.5
micrograms/kg) or placebo (normal saline, 0.03 ml/kg) nasally over 15-20
s. Induction of anesthesia was completed with 5% halothane and O2 via
facemask. After tracheal intubation, anesthesia was maintained with N2O
(60-70%) and halothane, as clinically indicated. A blinded observer
remained with the child from prior to drug administration until
discharge from the recovery room. Patients given sufentanil were more
likely to separate willingly from their parents and be judged as calm at
or before 10 min compared to those given saline. Ventilatory compliance
during induction of anesthesia decreased markedly in 25% of subjects
given sufentanil, 4.5 micrograms/kg. Subjects given sufentanil moved or
coughed less during tracheal intubation and required less halothane
compared to those given placebo. During recovery, patients given
sufentanil cried less and fewer needed analgesics; recovery times were
similar for all groups. However, patients given sufentanil, 4.5
micrograms/kg, had a higher incidence of vomiting in the recovery room
and during the first postoperative day. The authors conclude that
nasally administered sufentanil, 1.5 or 3.0 micrograms/kg, facilitates
separation of children from parents, has minimal side effects, may
improve intubating conditions, and can provide postoperative analgesia.
Henderson, J. M. and D. M. Fisher (1990). "Intranasal
sufentanil." Can J Anaesth 37(3): 387.
Heniff, M. S., G. P. Moore, et al. (1997). "Comparison of routes of flumazenil administration to reverse midazolam-induced respiratory depression in a canine model." Acad Emerg Med 4(12): 1115-8.
OBJECTIVE: To determine whether flumazenil, a drug used to reverse benzodiazepine-induced respiratory depression and approved only for i.v. use, is effective by alternative routes. METHODS: A randomized, controlled, nonblinded, crossover canine trial was performed to evaluate reversal of midazolam-induced respiratory depression by flumazenil when administered by alternative routes. Mongrel dogs were sedated with thiopental 19 mg/kg i.v., then tracheally intubated. With the dogs spontaneously breathing, tidal volume, end-tidal CO2, and O2 saturation were observed until a stable baseline was achieved. Incremental doses of midazolam were administered until respiratory depression (30% decline in tidal volume, 10% decrease in O2 saturation, and 15% increase in end-tidal CO2) occurred. Flumazenil was administered by a randomly selected route [0.2 mg followed 1 minute later by 0.3 mg i.v., sublingual (s.l.) or intramuscular (i.m.); or 1 mg followed 1 minute later by 1.5 mg per rectum (PR)]. Time to return to baseline respiratory functions was recorded ("time to reversal"). Each of 10 dogs was studied using all 4 routes of flumazenil administration with a washout period of at least 7 days. An additional dog served as a control (no flumazenil). RESULTS: The control time to reversal was 1,620 seconds. The i.v. route was significantly faster (mean 120 +/- 24.5 sec) than the other 3 routes (p < 0.005). The SL route was the second fastest (mean 262 +/- 94.5 sec), the IM route was the third fastest (mean 310 +/- 133.7 sec) and the PR route was the s;owest (mean 342 +/- 84.4 sec). The SL, IM, and PR routes did not differ significantly from one another. CONCLUSIONS: Flumazenil administered by all 4 routes reversed midazolam-induced respiratory depression in a dog model. For the selected dosages used, the i.v. route was significantly faster than all 3 other routes, and SL was the second fastest.
Hippard, H. K., K. Govindan,
et al. (2012). "Postoperative analgesic and behavioral effects of
intranasal fentanyl, intravenous morphine, and intramuscular morphine in
pediatric patients undergoing bilateral myringotomy and placement of
ventilating tubes." Anesth Analg
115(2): 356-363.
BACKGROUND: Bilateral myringotomy and placement of ventilating
tubes (BMT) is one of the most common pediatric surgical procedures in
the United States. Many children who undergo BMT develop behavioral
changes in the postanesthesia care unit (PACU) and require rescue pain
medication. The incidence of these changes is lower in children
receiving intraoperative opioids by the nasal, IM, or IV route compared
with placebo. However, there are no data to indicate which route of
administration is better. Our study was designed to compare the
immediate postoperative analgesic and behavioral effects of 3 frequently
used intraoperative techniques of postoperative pain control for
patients undergoing BMT under general anesthesia. METHODS: One hundred
seventy-one ASA physical status I and II children scheduled for BMT were
randomized into 1 of 3 groups: group 1-nasal fentanyl 2 mug/kg with IV
and IM saline placebo; group 2-IV morphine 0.1 mg/kg with nasal and IM
placebo; or group 3-IM morphine 0.1 mg/kg with nasal and IV placebo. All
subjects received a standardized general anesthetic with sevoflurane,
N(2)O, and O(2) and similar postoperative care. The primary end point of
the study was the pain scores measured by the Faces, Legs, Activity,
Cry, and Consolability (FLACC) scale in the PACU. RESULTS: There were no
significant differences in peak FLACC pain among the 3 groups (mean [95%
CI] 2.0 [1.2-2.8] for intranasal fentanyl, 2.7 [1.7-3.6] for IV
morphine, and 2.9 [2.1-3.7] for IM morphine, respectively). There were
no differences in the scores on the Pediatric Anesthesia Emergence
Delirium (PAED) scale, incidence of postoperative emergence delirium
(PAED score >/=12), emesis, perioperative hypoxemia, or need for airway
intervention, and postoperative rescue analgesia. There were also no
differences in the duration of PACU stay or parental satisfaction among
the groups. CONCLUSION: In this double-blind, double-dummy study, there
was no difference in the efficacy of intranasal fentanyl, IM and IV
morphine in controlling postoperative pain and emergence delirium in
children undergoing BMT placement. The IM route is the simplest and
avoids the potential for delays to establish vascular access for IV
therapy and the risks of laryngospasm if intranasal drugs pass through
the posterior nasopharynx and irritate the vocal cords.
Hoeffe, J., E. Doyon Trottier, et al. (2017). "Intranasal fentanyl and
inhaled nitrous oxide for fracture reduction: The FAN observational
study." Am J Emerg Med
35(5): 710-715.
INTRODUCTION: Procedural sedation and analgesia (PSA) are
frequently used for fracture reduction in pediatric emergency
departments (ED). Combining intranasal (IN) fentanyl with inhalation of
nitrous oxide (N2O) allow for short recovery time and obviates painful
and time-consuming IV access insertions. METHODS: We performed a
bicentric, prospective, observational cohort study. Patients aged
4-18years were included if they received combined PSA with IN fentanyl
and N2O for the reduction of mildly/moderately displaced fracture or of
dislocation. Facial Pain Scale Revised (FPS-R) and Face, Leg, Activity,
Cry, Consolability (FLACC) scores were used to evaluate pain and anxiety
before, during and after procedure. University of Michigan Sedation
Score (UMSS), adverse events, detailed side effects and satisfaction of
patients, parents and medical staff were recorded at discharge. A follow
up telephone call was made after 24-72h. RESULTS: 90 patients were
included. There was no difference in FPS-R during the procedure (median
score 2 versus 2), but the FLACC score was significantly higher as
compared to before (median score 4 versus 0, Delta 2, 95% CI 0, 2).
Median UMSS was 1 (95% CI 1, 2). We recorded no serious adverse events.
Rate of vomiting was 12% (11/84). Satisfaction was high among
participants responding to this question 85/88 (97%) of parents, 74/83
(89%) of patients and 82/85 (96%) of physicians would want the same
sedation again. CONCLUSION: PSA with IN fentanyl and N2O is effective
and safe for the reduction of mildly/moderately displaced fracture or
dislocation, and has a high satisfaction rate.
Holdgate, A., A. Cao, et al. "The Implementation of Intranasal Fentanyl for Children in a Mixed Adult and Pediatric Emergency Department Reduces Time to Analgesic Administration." Acad Emerg Med, 2010; 17:1-4.
ACADEMIC EMERGENCY MEDICINE 2010; 17:1-4 (c) 2010 by the Society for Academic Emergency Medicine Abstract Objectives: The objective was to determine whether the introduction of intranasal (IN) fentanyl for children with acute pain would reduce the time to analgesic administration in a mixed adult and pediatric emergency department (ED). Methods: A protocol for IN fentanyl (1.5 mug/kg) for children age 1-15 years presenting with acute pain was introduced to the department. All children who received intravenous (IV) morphine in the 7 months prior to the introduction of the protocol and either IV morphine or IN fentanyl in the 7 months after the introduction of the protocol were identified from drug registers. Time to analgesic administration, time to see a doctor, and the ages of patients were compared between the periods before and after the introduction of IN fentanyl. Results: Following implementation, 81 patients received IN fentanyl and 37 received IV morphine, compared to 63 patients receiving morphine in the previous 7 months. The median time to analgesic administration for IN fentanyl was significantly shorter than for morphine (32 minutes vs. 63 minutes, p = 0.001). Children receiving fentanyl were significantly younger than those receiving morphine (median = 8.5 years vs. 12 years, p < 0.001). Conclusions: This study demonstrates that children treated with IN fentanyl received analgesic medication faster than those treated with IV morphine in a mixed ED. Younger children were more likely to receive opioid analgesia following the introduction of fentanyl.
Huge, V., M. Lauchart, et al. (2009). "Effects of low-dose intranasal (S)-ketamine in patients with neuropathic pain." Eur J Pain.
BACKGROUND: NMDA receptors are involved in the development and maintenance of neuropathic pain. We evaluated the efficacy and safety of intranasal (S)-ketamine, one of the most potent clinically available NMDA receptor antagonists. METHODS: Sixteen patients with neuropathic pain of various origins were randomized into two treatment groups: (S)-ketamine 0.2mg/kg (group 1); (S)-ketamine 0.4mg/kg (group 2). Plasma concentrations of (S)-ketamine and (S)-norketamine were measured over 6h by High Performance Liquid Chromatography combined with mass spectrometry. Quantitative sensory testing (QST) was conducted before, during and after treatment. Side effects and amount of pain reduction were recorded. RESULTS: Intranasal (S)-ketamine administration lead to peak plasma concentrations of 27.7+/-5.9ng/ml at 10+/-6.3min (group 1) and 34.3+/-22.2ng/ml at 13.8+/-4.8min after application (group 2). Maximal plasma concentrations of (S)-norketamine were 18.3+/-14.9ng/ml at 81+/-59min (group 1) and 34.3+/-5.5ng/ml at 75+/-40min (group 2). Pain scores decreased significantly in both groups with minimal pain at 60min after drug administration (70+/-10% and 61+/-13% of initial pain in groups 1 and 2). The time course of pain decrease was significantly correlated with plasma concentrations of (S)-ketamine and (S)-norketamine (partial correlations: (S)-norketamine: -0.90 and -0.86; (S)-ketamine: -0.72 and -0.71 for group 1 and group 2, respectively). Higher dosing elicited significantly more side effects. Intranasal (S)-ketamine had no significant impact on thermal or mechanical detection and pain thresholds in normal or symptomatic skin areas. CONCLUSIONS: Intranasal administration of low dose (S)-ketamine rapidly induces adequate plasma concentrations of (S)-ketamine and subsequently of its metabolite (S)-norketamine. The time course of analgesia correlated with plasma concentrations.
Illum, L., S. S. Davis, et al. (1996). "Nasal
administration of morphine-6-glucuronide in sheep--a pharmacokinetic
study." Biopharm Drug Dispos 17(8): 717-24.
The pharmacokinetics of morphine-6-glucuronide (M6G) after both
intravenous dosing and nasal administration were studied in sheep. The
nasal formulation consisted of M6G in combination with an absorption
promoting delivery system in the form of chitosan. The mean half-life of
M6G after intravenous administration was 51.0 +/- 8.2 min and that after
intranasal dosing was 45.0 +/- 5.5 min. M6G clearance and volume of
distribution were 5.4 +/- 1.5 mL min-1 kg-1 and 0.4 +/- 0.1 L kg-1
respectively. The plasma profile after nasal administration demonstrated
rapid absorption of M6G. The bioavailability of M6G in the chitosan
formulation was found to be 31.4%. These results suggest that M6G
administered in combination with the chitosan delivery system may be
considered as a suitable non-parenteral means of administering this
analgesic.
Illum, L., P. Watts, et al. (2002). "Intranasal
delivery of morphine." J Pharmacol Exp Ther 301(1): 391-400.
Morphine administered nasally to humans as a simple solution is
only absorbed to a limited degree, with a bioavailability of the order
of 10% compared with intravenous administration. This article describes
the development of novel nasal morphine formulations based on chitosan,
which, in the sheep model, provide a highly increased absorption with a
5- to 6-fold increase in bioavailability over simple morphine solutions.
The chitosan-morphine nasal formulations have been tested in healthy
volunteers in comparison with a slow i.v. infusion (over 30 min) of
morphine. The results show that the nasal formulation was rapidly
absorbed with a T(max) of 15 min or less and a bioavailability of nearly
60%. The shape of the plasma profile for nasal delivery of the chitosan-morphine
formulation was similar to the one obtained for the slow i.v.
administration of morphine. Furthermore, the metabolite profile obtained
after the nasal administration of the chitosan- morphine nasal
formulation was essentially identical to the one obtained for morphine
administered by the intravenous route. The levels of both
morphine-6-glucuronide and morphine-3-glucuronide were only about 25% of
that found after oral administration of morphine. It is concluded that a
properly designed nasal morphine formulation (such as one with chitosan)
can result in a non-injectable opioid product capable of offering
patients rapid and efficient pain relief.
Jackson, K., M. Ashby, et al. (2002). "Pilot dose
finding study of intranasal sufentanil for breakthrough and incident
cancer-associated pain." J Pain Symptom Manage 23(6): 450-2.
Jacobs, I. (2002). "A pilot study of prehospital
intranasal fentanyl." Prehosp Emerg Care 6(6): 157-158 (abstract
#47).
Johansson, J., J. Sjoberg, et al. (2013). "Prehospital analgesia using
nasal administration of S-ketamine--a case series." Scand J Trauma
Resusc Emerg Med 21:
38.
Karl, H. W., A. T. Keifer, et al. (1992). "Comparison
of the safety and efficacy of intranasal midazolam or sufentanil for
preinduction of anesthesia in pediatric patients." Anesthesiology
76(2): 209-15.
Nasal administration of sufentanil or midazolam is effective for
preinduction of pediatric patients, but there are no data on which to
base a choice between them. This blinded randomized study compares
behavioral and physiologic responses to sedation with one of these
medications followed by inhalation or intravenous induction. Ninety-five
patients aged 0.5-10 yr scheduled for elective surgery were stratified
by age: 30 infants 0.5-2 yr, 38 preschoolers 2.1-5 yr, and 27 school-age
children 5.1-10 yr. They were randomized to receive 0.04 ml/kg of
midazolam (0.2 mg/kg) or sufentanil (2 micrograms/kg). Hemoglobin oxygen
saturation by pulse oximetry (SpO2) and sedation score were recorded
prior to drug administration, at 2.5-min intervals for 10 min, at
separation, and during induction with graded halothane in oxygen.
Intubation was performed under deep halothane or 3 mg/kg of thiopental
and 0.1 mg/kg of pancuronium. Chest wall compliance was assessed
qualitatively in all patients prior to intubation. To assess the effects
of a mild standardized stress on unpremedicated patients, 75 of the
children with parents present were scored before and after oximeter
probe placement: of these, in 63% the sedation score did not change; 33%
appeared more anxious; and only 4% seemed reassured. Children of all
ages reacted negatively to physicians, and 23% were crying prior to
administration of drugs. Sufentanil appeared less unpleasant to receive
than midazolam: children cried 46 +/- 100 versus 76 +/- 73 s (P less
than 0.05), respectively, but by 7.5 min, no child was crying. Median
behavior scores at maximum anxiolysis were not different, but response
to sufentanil was more variable.(ABSTRACT TRUNCATED AT 250 WORDS)
Karlsen, A. P., D. M. Pedersen, et al. (2014). "Safety of intranasal
fentanyl in the out-of-hospital setting: a prospective observational
study." Ann Emerg Med
63(6): 699-703.
STUDY OBJECTIVE: Initial out-of-hospital analgesia is sometimes hampered by
difficulties in achieving intravenous access or lack of skills in
administering intravenous opioids. We study the safety profile and
apparent analgesic effect of intranasal fentanyl in the out-of-hospital
setting. METHODS: In this prospective observational study, we
administered intranasal fentanyl in the out-of-hospital setting to
adults and children older than 8 years with severe pain resulting from
orthopedic conditions, abdominal pain, or acute coronary syndrome
refractory to nitroglycerin spray. Patients received 1 to 3 doses of
either 50 or 100 mug, and the ambulance crew recorded adverse effects
and numeric rating scale (0 to 10) pain scores before and after
treatment. RESULTS: Our 903 evaluable patients received a mean
cumulative fentanyl dose of 114 mug (range 50 to 300 mug). There were no
serious adverse effects and no use of naloxone. Thirty-six patients (4%)
experienced mild adverse effects: mild hypotension, nausea, vomiting,
vertigo, abdominal pain, rash, or decrease of Glasgow Coma Scale score
to 14. The median reduction in pain score was 3 (interquartile range 2
to 5) after fentanyl administration. CONCLUSION: The out-of-hospital
administration of intranasal fentanyl in doses of 50 to 100 mug is safe
and appears effective.
Kaube, H., J. Herzog, et al. (2000). "Aura in some patients
with familial hemiplegic migraine can be stopped by intranasal
ketamine." Neurology
55(1): 139-141.
Migraine aura is probably caused by cortical-spreading
depression. No treatment for acute and severe migraine aura has been
described previously. The effect of ketamine (25 mg intranasally) was
studied in 11 patients with severe, disabling auras resulting from
familial hemiplegic migraine. In five patients ketamine reproducibly
reduced the severity and duration of the neurologic deficits, whereas in
the remaining six patients no beneficial effect was seen. Ketamine
offers, for the first time, a possible treatment option for severe and
prolonged aura.
Kavanagh, P. L., P. G. Sprinz, et al. (2015). "Improving the Management
of Vaso-Occlusive Episodes in the Pediatric Emergency Department."
Pediatrics 136(4):
e1016-1025.
Kelly, G. S., R. W. Stewart, et al. (2018). "Intranasal fentanyl
improves time to analgesic delivery in sickle cell pain crises."
Am J Emerg Med 36(7):
1305-1307.
Kendall, J. M. and V. S. Latter (2003). "Intranasal
diamorphine as an alternative to intramuscular morphine: pharmacokinetic
and pharmacodynamic aspects." Clin Pharmacokinet 42(6): 501-13.
Diamorphine is a semisynthetic derivative of morphine that is
currently licensed for use in the treatment of moderate to severe acute
pain, administered by the intramuscular, intravenous or subcutaneous
routes. It is highly water-soluble and has a number of properties that
render it suitable for administration via the nasal route.
Administration via the intranasal route is well described for other
drugs, but has only recently been evaluated in a clinical setting for
diamorphine. A well-tolerated and rapidly effective analgesic agent has
proven elusive in the paediatric setting. The pharmacokinetic profile of
intranasal diamorphine in adults has been systematically studied. It is
rapidly and dose-dependently absorbed as a dry powder, with peak plasma
concentrations occurring within 5 minutes, and has a similar
pharmacokinetic profile to that of intramuscular diamorphine. It is
rapidly converted to 6-acetylmorphine (peak concentrations within 5-10
minutes) and thence to morphine (peak concentrations within 1 hour). The
pharmacodynamic properties of intranasal diamorphine have also been
studied in comparison with intramuscular diamorphine. Intranasal and
intramuscular administration of diamorphine resulted in similar
physiological responses (including pupil diameter, respiration rate and
temperature). Changes in behavioural measures (including euphoria,
sedation and dysphoria) were also similar. Intranasal administration of
diamorphine, therefore, produces the expected drug effects on the same
timescale and of the same magnitude as intramuscular injection.
Intranasal diamorphine has been clinically evaluated in a randomised
controlled trial versus intramuscular morphine in the setting of acute
orthopaedic pain in children with fractures. Intranasal diamorphine
provided the same overall degree of pain relief as intramuscular
morphine, but with a quicker onset of action. It was found to be well
tolerated with an acceptable safety profile. It has also been studied in
the setting of patient-controlled analgesia for postoperative pain in
adults, with encouraging results. The pharmacokinetic and
pharmacodynamic properties of intranasal diamorphine, and particularly
the ability to administer it without a needle (and therefore reduce the
incidence of transmissible infection), have made this a popular route
for abuse amongst opioid addicts. In this setting, however, the
intranasal route is not free from adverse events, including deaths. The
primary clinical need in the paediatric population is for a well
tolerated, effective and expedient analgesic agent that is safe to use;
intranasal diamorphine has pharmacokinetic properties that would make it
suitable for such a clinical indication and, in clinical evaluations to
date, appears to be promising.
Kendall, J. M., B. C. Reeves, et al. (2001).
"Multicentre randomised controlled trial of nasal diamorphine for
analgesia in children and teenagers with clinical fractures." Bmj
322(7281): 261-5.
OBJECTIVE: To compare the effectiveness of nasal diamorphine
spray with intramuscular morphine for analgesia in children and
teenagers with acute pain due to a clinical fracture, and to describe
the safety profile of the spray. DESIGN: Multicentre randomised
controlled trial. SETTING: Emergency departments in eight UK hospitals.
PARTICIPANTS: Patients aged between 3 and 16 years presenting with a
clinical fracture of an upper or lower limb. MAIN OUTCOME MEASURES:
Patients' reported pain using the Wong Baker face pain scale, ratings of
reaction to treatment of the patients and acceptability of treatment by
staff and parents, and adverse events. RESULTS: 404 eligible patients
completed the trial (204 patients given nasal diamorphine spray and 200
given intramuscular morphine). Onset of pain relief was faster in the
spray group than in the intramuscular group, with lower pain scores in
the spray group at 5, 10, and 20 minutes after treatment but no
difference between the groups after 30 minutes. 80% of patients given
the spray showed no obvious discomfort compared with 9% given
intramuscular morphine (difference 71%, 95% confidence interval 65% to
78%). Treatment administration was judged acceptable by staff and
parents, respectively, for 98% (199 of 203) and 97% (186 of 192) of
patients in the spray group compared with 32% (64 of 199) and 72% (142
of 197) in the intramuscular group. No serious adverse events occurred
in the spray group, and the frequencies of all adverse events were
similar in both groups (spray 24.1% v intramuscular morphine 18.5%;
difference 5.6%, -2.3% to 13.6%). CONCLUSION: Nasal diamorphine spray
should be the preferred method of pain relief in children and teenagers
presenting to emergency departments in acute pain with clinical
fractures. The diamorphine spray should be used in place of
intramuscular morphine.
Kendall, J., I. Maconochie, et al. (2014). "A novel multipatient
intranasal diamorphine spray for use in acute pain in children:
pharmacovigilance data from an observational study."
Emerg Med J.
OBJECTIVES: To establish the safety of an intranasal diamorphine (IND)
spray in children. DESIGN: An open-label, single-dose pharmacovigilance
trial. SETTING: Emergency departments in eight UK hospitals.
PARTICIPANTS: Children aged 2-16 years with a fracture or other trauma.
OUTCOME MEASURES: Adverse events (AE) specifically related to nasal
irritation, respiratory and central nervous system depression. RESULTS:
226 patients received 0.1 mg/kg IND. No serious or severe AEs occurred.
The incidence of treatment-emergent AEs (TEAEs) was 26.5% (95% CI 20.9%
to 32.8%), 93% being mild. 89% were related to treatment, all being
known effects of the drug or route of administration except for three
events in two patients. 20.4% (95% CI 15.3% to 26.2%) patients reported
nasal irritation, all mild except one moderate and one 'unknown'
severity. No respiratory depression was reported. Three AEs related to
reduced Glasgow Coma Score (GCS) occurred, all mild. CONCLUSIONS: There
were no safety concerns raised during the conduct of the study. In
addition to expected side effects, IND can cause mild nasal irritation
in a proportion of patients. EUROPEAN UNION DRUG REGULATING AUTHORITIES
CLINICAL TRIAL NO: 2009-014982-16.
Kerr, D., D. Taylor, et al. (2015). "Patient-controlled intranasal
fentanyl analgesia: a pilot study to assess practicality and
tolerability during childbirth." Int J Obstet Anesth
24(2): 117-123.
BACKGROUND: Intranasal administration of fentanyl is a
non-invasive method of analgesic delivery which has been shown to be
effective. This pilot study aimed to assess the practicality and
tolerability of patient-controlled intranasal fentanyl for relieving
pain during childbirth. METHODS: This prospective, non-randomised,
clinical trial recruited women with a singleton pregnancy during
November 2009 to October 2011. Exclusion criteria included respiratory
disease, gestation <37weeks and pregnancy complications. The device
administered fentanyl 54mug per spray, incorporating a 3-min lock-out.
Data collected included demographics, dose, additional analgesia,
adverse events, pain relief and delivery outcomes. Follow-up data were
obtained within 48h regarding tolerability of the device. RESULTS: The
final sample included 32 women: mean age was 28.7years and gestation
39.8weeks. Mean fentanyl dose was 734mug and duration of use was 3.5h.
Most women (78.2%) reported satisfactory to excellent pain relief using
the nasal device. Four neonates (12.5%) required bag-mask ventilation at
birth: three had adequate respiration within 5min and one required
short-term observation in the special-care nursery. For all items, there
was a trend towards an adverse outcome, including neonatal respiratory
support, as the dose of fentanyl increased. On follow-up, 84.4% reported
they would use intranasal fentanyl for their next childbirth experience.
CONCLUSIONS: Patient-controlled intranasal fentanyl provides an
acceptable level of analgesia during childbirth. It may, however,
increase the risk of neonatal respiratory depression. Future, randomised
studies should evaluate the safety and efficacy of patient-controlled
intranasal fentanyl compared with existing analgesia options.
Kim, K. S., N. K. Yeo, et al. (2018). "Effect of Fentanyl Nasal Packing
Treatment on Patients With Acute Postoperative Pain After Nasal
Operation: A Randomized Double-Blind Controlled Trial." Ann Otol
Rhinol Laryngol 127(5): 297-305.
PURPOSE: Nasal packing is an option for bleeding control after endoscopic
sinus surgery and septoplasty. Although new packing materials have been
developed, patients still suffer from pain and require additional
analgesics treatments. In this study, a prospective, randomized, and
double-blind controlled trial was designed to evaluate the effect of
fentanyl-soaked packing on pain after endoscopic sinus surgery and
septoplasty. METHODS: One hundred fifty-two patients who underwent nasal
surgeries due to chronic rhinosinusitis or nasal septal deviation were
enrolled in this study. At the end of operation, 50 mcg fentanyl-soaked
biodegradable synthetic polyurethane foams packing Nasopore or Merocel
were applied to a group of 79 patients, and saline-soaked ones were
applied to another group of 73 patients. To evaluate the influence of
fentanyl on postoperative nasal pain, patients' conditions were assessed
via means of Numeric Rating Scale, patient satisfaction, and Ramsay
Sedation Scale. In addition, symptoms of headache or sore throat and any
signs of cardiopulmonary-relevant indicators were monitored. RESULTS:
The fentanyl group had significantly decreased Numeric Rating Scale and
increased patient satisfaction in every operation type for the majority
of postoperative time periods ( P < .05) with reduced postoperative
headache and sore throat compared to the control group. The fentanyl
group showed a higher score on Ramsay Sedation Scale than the control
group ( P < .05 in group including endoscopic sinus surgery). There were
no significant differences in cardiopulmonary-relevant indicators
between the 2 groups ( P > .05). CONCLUSION: Fentanyl group showed
significantly reduced postoperative pain without serious adverse
effects. We suggest that topical fentanyl application to nasal packs can
be a useful method to reduce pain during the early postoperative period
after endoscopic sinus surgery and septoplasty.
Ku, L. C., C. Simmons, et al. (2019). "Intranasal midazolam and fentanyl
for procedural sedation and analgesia in infants in the neonatal
intensive care unit." J Neonatal Perinatal Med
12(2): 143-148.
BACKGROUND: The intranasal route is a minimally invasive method for rapidly delivering midazolam and fentanyl to provide short-term analgesia and sedation in infants. However, intranasal use of midazolam and fentanyl is not labeled for infants and safety data are sparse. The objective of this study is to evaluate the safety of intranasal midazolam and intranasal fentanyl in infants admitted to the Neonatal Intensive Care Unit (NICU). METHODS: We retrospectively identified all infants receiving intranasal midazolam or fentanyl in the NICU from 2009 to 2015. We recorded indication for use and vital signs and determined the proportion of infants experiencing the following adverse events: death within 24 hours, hypotension, bradycardia, worsening respiratory status, and chest wall rigidity. Vital signs 4 hours before and after each dose were compared using the Wilcoxon signed-rank test. RESULTS: We identified 17 infants (gestational ages 23- 41 weeks) receiving 25 intranasal doses. None of the infants died or developed hypotension, bradycardia, or chest wall rigidity. Intranasal delivery was most commonly used for sedation during magnetic resonance imaging studies. Other indications include analgesia or sedation for retinopathy of prematurity surgery, intubation, and peripherally inserted central catheter placement. One infant receiving intranasal midazolam experienced worsening respiratory status. Vital signs before and after dosing were not significantly different. CONCLUSIONS: Intranasal midazolam and fentanyl use in term and preterm infants appeared safe and well-tolerated in this small cohort of infants. Larger, prospective studies evaluating the safety and efficacy of intranasal midazolam and fentanyl use in infants are warranted.
Kress, H. G., A. Oronska, et al. (2009). "Efficacy and tolerability of intranasal fentanyl spray 50 to 200 microg for breakthrough pain in patients with cancer: a phase III, multinational, randomized, double-blind, placebo-controlled, crossover trial with a 10-month, open-label extension treatment period." Clin Ther 31(6): 1177-91.
OBJECTIVE: This trial investigated the efficacy and long-term tolerability of intranasal fentanyl spray (INFS) 50 to 200 microg in the treatment of breakthrough pain in opioid-tolerant patients with cancer. METHODS: This Phase III, double-blind, randomized, placebo-controlled, crossover trial was conducted at pain centers, anesthesiology departments, palliative care units, and oncology clinics in Austria, Denmark, France, Germany, and Poland. Eligible patients were adults with cancer receiving a stable dose of long-term opioid treatment for the control of background pain. Patients were treated at home with their effective dose of INFS (50, 100, or 200 microg) or inactive spray (placebo) in a randomized sequence for 3 weeks, followed by a 10-month, open-label tolerability phase during which they received their effective dose of INFS. Throughout the study, patients were allowed to use their usual rescue medication, which was recorded in patient diaries. The primary efficacy end point was the pain intensity difference at 10 minutes after study drug administration (PID(10)), as assessed using an 11-point numeric rating scale (0 = no pain to 10 = worst pain imaginable). An effect size of 0.5 for PID was considered clinically relevant. The rate of response, defined as PID(10) >2, was also assessed. Adverse events (AEs) were recorded in patient diaries during the efficacy period and reported in monthly clinic visits and follow-up weekly telephone contacts during the extension period. RESULTS: In all, 120 patients were enrolled and achieved an effective dose; 113 were randomized and 111 were included in the intent-to-treat analysis set (56 men, 55 women; mean [SD] age, 60.6 [9.45] years; mean weight, 70.3 kg [men] and 65.3 kg [women]; white race, 107 [96.4%]; INFS 50 microg, 18; INFS 100 microg, 48; INFS 200 microg, 45; placebo, 110). PID(10) with INFS was 2-fold that with placebo (adjusted means, 2.36 vs 1.10; adjusted difference, 1.26 [greater than the clinically relevant difference of 0.5]; P < 0.001). Additional analysis revealed that the mean response rate with all 3 doses of INFS was 51.1% versus 20.9% with placebo. The prevalence of AEs was 22/111 (19.8%) during the efficacy period, during which the most frequently reported AEs were nausea (5 [4.5%]) and vertigo (2 [1.8%]). No serious AEs were considered related to the study drugs. In all, 108 patients entered the extension period, with a mean duration of exposure to INFS of 134.9 days. Progression of underlying malignant disease was the most common AE reported during this period (55 [50.9%]); this event was not considered treatment related. CONCLUSIONS: In these opioid-tolerant patients with cancer, INFS at doses of 50, 100, and 200 microg was associated with an onset of activity at 10 minutes and effective treatment of breakthrough pain compared with placebo. All doses were generally well tolerated and clinically efficacious.
Kronenberg and Rh (2002). "Ketamine as an analgesic:
parenteral, oral, rectal, subcutaneous, transdermal and intranasal
administration." J Pain Palliat Care Pharmacother
16(3): 27-35.
Ketamine is a parenteral anesthetic agent that provides analgesic
activity at sub-anesthetic doses. It is an N-methyl-D-aspartate (NMDA)
receptor antagonist with opioid receptor activity. Controlled studies
and case reports on ketamine demonstrate efficacy in neuropathic and
nociceptive pain. Because ketamine is a phencyclidine analogue, it has
some of the psychological adverse effects found with that hallucinogen,
especially in adults. Therefore, ketamine is not routinely used as an
anesthetic in adult patients. It is a frequently used veterinary
anesthetic, and is used more frequently in children than in adults. The
psychotomimetic effects have prompted the DEA to classify ketamine as a
Schedule III Controlled Substance. A review of the literature documents
the analgesic use of ketamine by anesthesiologists and pain specialists
in patients who have been refractory to standard analgesic medication
regimens. Most reports demonstrate no or mild psychotomimetic effects
when ketamine is dosed at sub-anesthetic doses. Patients who respond to
ketamine tend to demonstrate dramatic pain relief that obviates the
desire to stop treatment due to psychotomimetic effects (including
hallucinations and extracorporeal experiences). Ketamine is approved by
the FDA for intravenous and intramuscular administration. Use of this
drug by the oral, intranasal, transdermal, rectal, and subcutaneous
routes has been reported with analgesic efficacy in treating nociceptive
and neuropathic pain. Ketamine also has been reported to produce opioid
dose sparing and good patient acceptance. A transdermal formulation is
currently under patent review in Brazil and an intranasal formulation is
currently undergoing phase I/II clinical trials.
Kurien, T., K. R. Price, et al. (2016). "Manipulation and
reduction of paediatric fractures of the distal radius and forearm using
intranasal diamorphine and 50% oxygen and nitrous oxide in the emergency
department: a 2.5-year study." Bone Joint J 98-B(1): 131-136.
A retrospective study was performed in 100 children aged between two and 16
years, with a dorsally angulated stable fracture of the distal radius or
forearm, who were treated with manipulation in the emergency department
(ED) using intranasal diamorphine and 50% oxygen and nitrous oxide. Pre-
and post-manipulation radiographs, the final radiographs and the
clinical notes were reviewed. A successful reduction was achieved in 90
fractures (90%) and only three children (3%) required remanipulation and
Kirschner wire fixation or internal fixation. The use of Entonox and
intranasal diamorphine is safe and effective for the closed reduction of
a stable paediatric fracture of the distal radius and forearm in the ED.
By facilitating discharge on the same day, there is a substantial cost
benefit to families and the NHS and we recommend this method. TAKE HOME
MESSAGE: Simple easily reducible fractures of the distal radius and
forearm in children can be successfully and safely treated in the ED
using this approach, thus avoiding theatre admission and costly hospital
stay.
Lemoel, F., J. Contenti, et al. (2019). "Intranasal sufentanil given in
the emergency department triage zone for severe acute traumatic pain: a
randomized double-blind controlled trial." Intern Emerg Med
14(4): 571-579.
Liang, P., C. Zhou, et al. (2014). "Single-dose sufentanil or fentanyl
reduces agitation after sevoflurane anesthesia in children undergoing
ophthalmology surgery." Pak J Med Sci
30(5): 1059-1063.
OBJECTIVES: The trail investigated the effect of small dose sufentanil or fentanyl administrated before the end of surgery in reducing the incidence of emergence agitation after anesthesia with sevoflurane in preschool children undergoing ophthalmology surgery, and the incidence of emergence agitation of sevoflurane anesthesia. METHODS: From September 2011 to January 2012 January, ninety ASA I-II children, aged from 3-7 years, undergoing ophthalmology surgery in West China Hospital, were randomly assigned to three groups to receive intravenous saline, sufentanil 0.1mug/kg or fentanyl 1mug/kg at 20 minutes before the end of the surgery. Children were scored by scoring system for emergence agitation (SSEA), Children's and Infants' Postoperative Pain Scale (CHIPPS) score. RESULTS: The incidence of agitation was 30% in sufentanil group, 36.67% in fentanyl group, and 63.33% in control group. The incidence of sever agitation (SSEA score>/=3) was 6.67% in sufentanil group, 23.37% in fentanyl group, and 36.67% in control group. The agitation and pain scores in sufentanil group and fentanyl group were better than those in control group (P<0.05). There was no difference among three groups about time to extubation. CONCLUSIONS: We conclude that the incidence of emergence agitation after sevoflurane anesthesia in children undergoing ophthalmology surgery is up to 63.33%. The single dose of sufentanil or fentanyl can reduce the emergence agitation in children anesthesized with sevoflurane, with no adverse effects. The effect of sufentanil is better than fentanyl.
Lord, B., P. A. Jennings, et al. (2019). "Effects of the Introduction of
Intranasal Fentanyl on Reduction of Pain Severity Score in Children: An
Interrupted Time-Series Analysis." Pediatr Emerg Care
35(11): 749-754.
OBJECTIVES: Children are at risk of inadequate analgesia due to paramedics'
inexperience in assessing children and challenges in administering
analgesics when the patient is distressed and uncooperative. This study
reports on the outcome of a change to practice guidelines that added
intranasal fentanyl and intramuscular morphine within a large statewide
ambulance service. METHODS: This retrospective study included patients
younger than 15 years treated by paramedics between January 2008 and
December 2011. The primary outcome of interest was the proportion of
patients having a 2/10 or greater reduction in pain severity score using
an 11-point Verbal Numeric Rating Scale before and after the
intervention. Segmented regression analysis was used to estimate the
effect of the intervention over time. A multiple regression model
calculated odds ratios with 95% confidence intervals. RESULTS: A total
of 92,378 children were transported by paramedics during the study
period, with 9833 cases included in the analysis. The median age was 11
years; 61.6% were male. Before the intervention, 88.1% (n = 3114) of
children receiving analgesia had a reduction of pain severity of 2 or
more points, with 94.2% (n = 5933) achieving this benchmark after
intervention (P < 0.0001). The odds of a reduction in pain of 2 or more
points increased by 1.01 per month immediately before the intervention
and 2.33 after intervention (<0.0001). CONCLUSIONS: This large study of
a system-wide clinical practice guideline change has demonstrated a
significant improvement in the outcome of interest. However, a
proportion of children with moderate to severe pain did not receive
analgesia.
Lundeberg, S. and J. A. Roelofse (2010). "Aspects of pharmacokinetics and pharmacodynamics of sufentanil in pediatric practice." Paediatr Anaesth.
Sufentanil is a potent synthetic opioid. Like other opioids, sufentanil creates a stable hemodynamic environment in cardiovascularly compromised pediatric patients. Clearance, expressed as per kilogram, is increased in children compared to adults. The P450 CYP3A4 enzyme is responsible for the major metabolic N-dealkylation pathway. Enzyme activity is reduced in neonates but the maturation of sufentanil clearance is not described. The free active fraction is affected by age because of the reduced alpha(1) -acid glycoprotein plasma concentrations in neonates. Intranasal administration of sufentanil is a possible option for premedication, procedural sedation and analgesia in children, as this option has been found to be safe and effective. Studies concerning the pharmacokinetics and dynamics of sufentanil administered as a bolus or continuous infusion in children are few.
Malinovsky, J. M., C. Lejus, et al. (1993). "Plasma
concentrations of midazolam after i.v., nasal or rectal administration
in children." Br J Anaesth 70(6): 617-20.
Midazolam is used frequently for premedication in children,
preferably by non-parenteral administration. We have compared plasma
concentrations of midazolam after nasal, rectal and i.v. administration
in 45 children (aged 2-9 yr; weight 10-30 kg) undergoing minor
urological surgery. General anaesthesia consisted of spontaneous
respiration of halothane and nitrous oxide in oxygen via a face mask.
After administration of atropine and fentanyl i.v., children were
allocated randomly to receive midazolam 0.2 mg kg-1 by the nasal, rectal
or i.v. route. In the nasal group, children received 50% of the dose of
midazolam in each nostril. In the rectal group, midazolam was given
rectally via a cannula. Venous blood samples were obtained before and up
to 360 min after administration of the drug. Plasma concentrations of
midazolam were measured by gas chromatography and electron capture
detection. After nasal and rectal administration, midazolam Cmax was 182
(SD 57) ng ml-1 within 12.6 (5.9) min, and 48 (16) ng ml-1 within 12.1
(6.4) min, respectively. Rectal administration resulted in smaller
plasma concentrations. In the nasal group, a plasma concentration of
midazolam 100 ng ml-1 occurred at about 6 min. After 45 min, the
concentration curves after i.v. and nasal midazolam were similar.
Manjushree, R., A. Lahiri, et al. (2002). "Intranasal
fentanyl provides adequate postoperative analgesia in pediatric
patients." Can J Anaesth 49(2): 190-3.
PURPOSE: To evaluate intranasally administered fentanyl for
postoperative analgesia in pediatric patients. METHODS: Thirty-two
children aged four to eight years, ASA physical status I and II were
included in this prospective randomized controlled study. In the
postoperative care unit, patients were allocated to receive fentanyl,
using a double-blind study design, either intranasally (Group I) or
intravenously (Group II) in small titrated doses until they became pain
free or side effects appeared which prohibited continuation of the drug.
RESULTS: Satisfactory analgesia was achieved in both groups, though the
required drug dosage was higher in the intranasal group (1.43 +/- 0.39
microg.kg(-1)). Onset of analgesia tended to be slower via the
intranasal route compared to the iv route (13 +/- 4.5 vs 8.3 +/- 3.08
min; P=not significant). Side effects observed in this series were
within an acceptable range and similar for both modalities. CONCLUSION:
The intranasal route provides a good alternative for administration of
fentanyl in pediatric surgical patients.
Maroli, S., H. P. Srinath, et al. (2014). "Sniffing out pain: An in vivo
intranasal study of analgesic efficacy." J Int Oral Health
6(1): 66-71.
Mathieu, Cnudde, et al. (2006). "Intranasal
sufentanil is effective for postoperative analgesia in adults." Can J
Anaesth 53(1): 60-6.
PURPOSES: The aim of this prospective, randomized, double-blind
study was to compare two doses of intranasal sufentanil for
postoperative analgesia, titrated according to individual requirements
based upon a numeric rating scale (NRS) from 0 to 10 for pain. METHODS:
Forty patients, American Society of Anesthesiologists physical status
I-II, scheduled for herniorrhaphy or hemorrhoidectomy under general
anesthesia, were included when postoperative NRS was > 3. Nurses used a
nasal puff device delivering a constant volume. Patients were randomized
into two groups: Group A patients received a dose of 0.025 microg x
kg(-1) /puff, Group B patients a dose of 0.05 microg x kg(-1) /puff.
Puffs were administered as often as needed to obtain NRS < or = 3, with
an interval time of five minutes. Hemodynamic, respiratory measures and
sedation were recorded every five minutes.Results: The probability of
persistence of pain in Group B was consistently lower than in Group A.
After 20 min, 20% of the patients had a NRS score > 3 in Group B, as
opposed to 60% in Group A. At 60 min, no patient had a NRS > 3 in Group
B, whereas there was a probability of 20% to record a NRS > 3 for Group
A. Hemodynamic, respiratory parameters and sedation remained stable with
no intergroup differences. CONCLUSIONS: Nasal administration of 0.050
microg x kg(-1) /puff sufentanil allowed a NRS < 4 to be attained within
one hour in all patients, with efficacy achieved after 20 min. These
findings suggest that the intranasal route is an effective mode of
sufentanil administration for immediate postoperative analgesia in adult
patients.
McAleer, S. D., O. Majid, et al. (2007).
"Pharmacokinetics and safety of ketorolac following single intranasal
and intramuscular administration in healthy volunteers." J Clin
Pharmacol 47(1): 13-18.
McHale, B., C. D. Badenhorst, et al. (2018). "Do children undergoing
bilateral myringotomy with placement of ventilating tubes benefit from
pre-operative analgesia? A double-blinded, randomised,
placebo-controlled trial." J Laryngol Otol
132(8): 685-692.
OBJECTIVE: A double-blinded, randomised, placebo-controlled trial was conducted to determine whether routine pre-operative analgesia is beneficial in reducing post-operative ear pain following bilateral myringotomy and tube placement. METHODS: Forty-five children (aged 3-15 years) were randomised to receive either pre-operative analgesics (paracetamol and ibuprofen) (n = 21) or placebo (n = 24). All children underwent sevoflurane gas induction with intranasal fentanyl (2 mcg/kg) to reduce the incidence of emergence agitation. Post-operative pain scores were measured using the Wong-Baker Faces Pain Rating Scale. Median pain scores taken 90 minutes post-surgery, and the highest pain score recorded prior to 90 minutes, were analysed. RESULTS: There were no statistical differences between the median pain scores at 90 minutes or subsequent need for rescue analgesia. Emergence agitation did not occur in any child. Inadvertent ear trauma, use of an intravenous cannula or airway adjunct did not affect pain scores. CONCLUSION: Routine pre-operative analgesia does not reduce pain scores in the early post-operative period. Simple analgesics are effective for rescue analgesia in the minority of cases.
McLean, A. R., D. A. Braude, et al. (2009). "Intranasal fentanyl for analgesia in injured patients at a ski resort (abstract)." Wilderness Medical Journal 21(1): 68-69.
Introduction: Intranasal fentanyl has been shown to be a safe, effective mode of analgesic administration in prehospital, emergency department, and postoperative patients. We evaluated the use of intranasal fentanyl for initial analgesia in injured patients at a ski resort. Methods: We retrospectively reviewed the charts of 46 injured adult and pediatric patients treated with intranasal fentanyl during the 2007–2008 winter ski season. Patients were treated with fentanyl according to online MCEP-approved doses (approximate dose 1.4 μg/kg), using 50 μg/mL concentration fentanyl administered with a MAD Nasal (Wolfe Tory Medical Inc, Salt Lake City, UT) mucosal atomizing device. Doses were administered in 1/6 dose increments in alternating nares. Pain scores were recorded at 0, 2, 5, and 10 minutes using a verbally administered numerical rating scale of 0 through 10. Results: Data analysis was performed using results from 42 of the 46 patients: 5 pediatric and 37 adult. Four patients were excluded due to incomplete data. Thirty-four patients were initially treated on-slope and 8 patients were initially treated in the clinic. Average weight-based dosage for intranasal fentanyl was 1.4 μg/kg (95% confidence interval [CI]: 1.3–1.5 μg/kg; n = 42). The mean baseline pain score for all patients was 8.2 (95% CI: 7.7–8.7; n = 42). Pain scores were significantly reduced after treatment with fentanyl. Mean pain score reduction at 2 minutes was −1.4 (95% CI: −2.0 to −0.96; n = 41); at 5 minutes, −2.8 (95% CI: −3.5 to −2.1; n=42); at 10 minutes, −2.8 (95% CI: −3.7 to −1.9; n = 29). No significant complications were noted. Conclusion: Intranasal fentanyl provides effective analgesia in acutely injured patients and is a good option for patients in whom immediate intravenous access is complicated by environmental, anatomic, or resource limitations. The potential application for search-and-rescue and other austere medicine situations is widespread.
Middleton, P. M., P. M. Simpson, et al. (2010).
"Effectiveness of morphine, fentanyl, and methoxyflurane in the
prehospital setting." Prehosp Emerg Care 14(4): 439-447.
OBJECTIVE: To compare the effectiveness of intravenous (IV) morphine, intranasal (IN) fentanyl, and inhaled methoxyflurane when administered by paramedics to patients with moderate to severe pain. METHODS: We conducted a retrospective comparative study of adult patients with moderate to severe pain treated by paramedics from the Ambulance Service of New South Wales who received IV morphine, IN fentanyl, or inhaled methoxyflurane either alone or in combination between January 1, 2004, and November 30, 2006. We used multivariate logistic regression to analyze data extracted from a clinical database containing routinely entered information from patient health care records. The primary outcome measure was effective analgesia, defined as a reduction in pain severity of > or = 30% of initial pain score using an 11-point verbal numeric rating scale (VNRS-11). RESULTS: The study population comprised 52,046 patients aged between 16 and 100 years with VNRS-11 scores of > or = 5. All analgesic agents were effective in the majority of patients (81.8%, 80.0%, and 59.1% for morphine, fentanyl, and methoxyflurane, respectively). There was very strong evidence that methoxyflurane was inferior to both morphine and fentanyl (p < 0.0001). There was strong evidence that morphine was more effective than fentanyl (p = 0.002). There was no evidence that combination analgesia was better than either fentanyl or morphine alone. CONCLUSION: Inhaled methoxyflurane, IN fentanyl, and IV morphine are all effective analgesic agents in the out-of-hospital setting. Morphine and fentanyl are significantly more effective analgesic agents than methoxyflurane. Morphine appears to be more effective than IN fentanyl; however, the benefit of IV morphine may be offset to some degree by the ability to administer IN fentanyl without the need for IV access.
Miguez, M. C., C. Ferrero, et al. (2019). "Retrospective
Comparison of Intranasal Fentanyl and Inhaled Nitrous Oxide to
Intravenous Ketamine and Midazolam for Painful Orthopedic Procedures in
a Pediatric Emergency Department." Pediatr Emerg
Care.
OBJECTIVES: To compare the efficacy and adverse events of 2 pharmacological strategies: intranasal fentanyl and nitrous oxide (FN) inhaled against intravenous ketamine and midazolam (KM) as procedural sedation and analgesia (PSA) in painful orthopedic procedures in the pediatric emergency department (ED). METHODS: This is an observational retrospective cohort study. Patients were included that submitted to PSA for carrying out a painful orthopedic procedure in the ED of a tertiary hospital over a period of 2 years. The main outcome variable was efficacy and adverse events of the PSA procedure. RESULTS: Eighty-three patients were included. Fifty-two patients received FN and 31 KM. The PSA strategy was considered efficacious in 82.7% of the patients in the KM group and 80.6% in the FN cohort. No differences between both strategies were found (P = 0.815). Seventeen children showed early adverse events, 2 in the FN cohort and 15 in the KM group (relative risk of the KM strategy, 23.48; 95% confidence interval (CI), 3.24-169.99). The average of satisfaction obtained by the families was of 10 (CI, 10-10) in the KM cohort and of 9 (CI, 8-9.5) in the FN group (P = 0.152). The length of stay in the ED was longer in the KM cohort (P < 0.001). Hospital admission rate differences were not statistically different (9.6% vs 22.6%, P = 0.144) in the KM versus FN cohort. CONCLUSIONS: Both PSA strategies presented similar efficacy. The FN strategy was associated with a lower risk of adverse events and shorter ED length of stay than KM in this ED setting.
Mitchell, Tb, et al. (2006). "Feasibility and
acceptability of an intranasal diamorphine spray as an alternative to
injectable diamorphine for maintenance treatment." Eur Addict Res
12(2): 91-5.
An intranasal (IN) diamorphine spray was investigated as a
possible alternative to injectable diamorphine for maintenance
treatment. Plasma morphine and 6-monoacetylmorphine (6MAM)
concentrations and pharmacodynamic responses were measured for 4 h
following intravenous (IV) and IN administration of 40 mg diamorphine in
4 patients prescribed injectable diamorphine. The two routes were
primarily differentiated by the significantly greater speed and
magnitude of peak plasma morphine and 6MAM concentrations for IV versus
IN diamorphine. Beyond this initial peak, mean ratings suggested that
withdrawal suppression and positive effects were at least as strong for
IN compared to IV administration. All subjects gave favourable
appraisals of the IN diamorphine spray, citing advantages including ease
of use, the avoidance of needle hazards, and reduced stigma. IN
administration may be an alternative or supplementary form of
diamorphine maintenance and deserves serious further investigation.
Moksnes, K., O. M. Fredheim, et al. (2008). "Early
pharmacokinetics of nasal fentanyl: is there a significant arterio-venous
difference?" Eur J Clin Pharmacol.
OBJECTIVE: We have investigated the arterio-venous difference in
the pharmacokinetics of 50 mug fentanyl during the first hour following
nasal administration and documented its tolerability in opioid-naive
middle-aged to elderly patients. METHODS: Twelve male patients (range in
age 47-84 years) scheduled for transurethral resection of the prostate
gland received a 100-mul dose of 50 mug fentanyl base as a fentanyl
citrate formulation in one nostril. Simultaneous arterial and venous
blood samples for analyses of fentanyl were drawn at baseline and at 1,
3, 5, 7, 9, 13, 15, 20, 25, 35, 45 and 60 min after drug administration.
Vital signs, sedation and symptoms of local irritation were recorded.
RESULTS: The arterial C(max) (maximum serum concentration) of 0.83 ng/ml
was nearly twofold higher than the venous C(max) of 0.47 ng/ml, and the
arterial T(max) (time to maximum serum concentration) of 7.0 min was
about 5 min shorter than the venous T(max) of 11.6 min. The arterial
AUC(0-60) (area under the curve from 0 to 60 min after administration)
of 21 min*ng/ml was approximately 30% larger than the venous AUC(0-60)
of 15 min*ng/ml (all p values </= 0.005). Venous T(max) and C(max) did
not predict the corresponding arterial values. No significant adverse
events were observed. CONCLUSION: A significant arterio-venous
difference was present after intranasal administration of fentanyl. The
short arterial T(max) complies with its rapid onset of action. The use
of venous concentrations for the prediction of onset time of analgesia
should be discouraged. A 50-mug dose of nasal fentanyl was well
tolerated by opioid-naive middle-aged to elderly male patients.
Moodie, J. E., C. R. Brown, et al. (2008). "The safety and analgesic efficacy of intranasal ketorolac in patients with postoperative pain." Anesth Analg 107(6): 2025-31.
BACKGROUND: We evaluated the safety and efficacy of multiple doses of intranasal ketorolac tromethamine (ketorolac) for postoperative pain. METHODS: This was a double-blind, placebo-controlled study in patients undergoing major surgery who were randomized to receive intranasal ketorolac, 10 mg or 31.5 mg, [DOSAGE ERROR CORRECTED]or placebo every 8 h for 40 h. After surgery, patients with pain intensity of at least 40 on a 100-mm visual analog scale were assessed at 30 min and at 1, 2, 3, 4, 5, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48 h after receiving the study drug. Patient-controlled i.v. morphine provided supplemental analgesia. RESULTS: Among 127 patients enrolled, morphine use during the first 24 h was significantly less in patients receiving 31.5 mg [DOSAGE ERROR CORRECTED] of ketorolac (37.8 mg) than in the placebo group (56.5 mg) and in the 10-mg ketorolac group (54.3 mg). Over 48 h, the 31.5-mg ketorolac [DOSAGE ERROR CORRECTED] group used significantly less morphine than the placebo group. Summed pain intensity differences at 4 and 6 h significantly favored the 31.5-mg ketorolac [DOSAGE ERROR CORRECTED]group over the other groups. The rates of pyrexia and tachycardia were significantly lower in the ketorolac 31.5-mg [DOSAGE ERROR CORRECTED]group than in the placebo group. Other adverse events were reported with similar frequency in all treatment groups and most were considered unrelated to treatment. CONCLUSION: Thirty milligrams of intranasal ketorolac demonstrated significant analgesic efficacy compared to 10 mg of intranasal ketorolac and placebo.
Mozafari, J., M. Maleki Verki, et al. (2019). "Comparing
intranasal ketamine with intravenous fentanyl in reducing pain in
patients with renal colic: A double-blind randomized clinical trial."
Am J Emerg Med.
BACKGROUND: Kidney stones are a fairly common problem that manifests itself as symptoms of acute abdominal and flank pains in patients presenting to emergency departments. OBJECTIVE: The present study was conducted to compare the analgesic effect of intravenous fentanyl with that of intranasal ketamine in renal colic patients. METHODS: One mg/kg of intranasal ketamine was administered in the first group, and one mug/kg of intravenous fentanyl in the second group. The pain severity was measured in the patients in terms of a visual analogue scale (VAS) score at the beginning of the study and at minutes 5, 15 and 30, and the medication side-effects were evaluated and recorded. RESULTS: A total of 130 patients were ultimately assessed in two groups of 65. In the ketamine group, the mean severity of pain was 8.72+/-1.52 at the beginning of the study (P<0.001), 5.5+/-2.97 at minute 5 (P<0.001), 3.38+/-3.35 at minute 15 (P=0.004) and 2.53+/-3.41 at minute 30 (P=0.449). In the fentanyl group, this severity was 9.66+/-88.8 in the beginning of the study (P<0.001), 7.27+/-1.37 at minute 5 (P<0.001), 4.61+/-1.5 at minute 15 (P=0.004) and 1.24+/-1.25 at minute 30 (P=0.449). The general prevalence of the medication side-effects was 10 (15.4%) in the ketamine group and 1 (1.5%) in the fentanyl group (P=0.009). CONCLUSIONS: Ketamine was found to be less effective than fentanyl in controlling renal colic-induced pain, and to be associated with a higher prevalence of side-effects; nevertheless, ketamine can be effective in controlling this pain in conjunction with other medications.
Mudd, S. (2011). "Intranasal Fentanyl for Pain Management in Children: A Systematic Review of the Literature." J Pediatr Health Care 25(5): 316-322.
Intranasally administered fentanyl (INF) has been studied as an alternate route of delivery for pain relief in children. The purpose of this systematic review is to evaluate the available research evidence on the use of INF in the pediatric population. A search was conducted of PubMed, ISI, Scopus, Popline, CINAHL, and Embase for research studies evaluating INF in this population (0-18 years of age). The studies were graded on the strength of the evidence and the results reviewed. All of the reviewed studies showed similar or improved pain scores when compared with other opioids and administration methods. No severe adverse outcomes were reported. Current evidence suggests that INF is a safe and effective method of pain management for children in a variety of clinical settings.
Murphy, A., R. O'Sullivan, et al. (2014). "Intranasal fentanyl for the
management of acute pain in children." Cochrane Database Syst Rev
10: CD009942.\
BACKGROUND: Pain is the most common symptom in the emergency setting; however, timely management of acute pain in children continues to be suboptimal. Intranasal drug delivery has emerged as an alternative method of achieving quicker drug delivery without adding to the distress of a child by inserting an intravenous cannula. OBJECTIVES: We identified and evaluated all randomized controlled trials (RCTs) and quasi-randomized trials to assess the effects of intranasal fentanyl (INF) versus alternative analgesic interventions in children with acute pain, with respect to reduction in pain score, occurrence of adverse events, patient tolerability, use of "rescue analgesia," patient/parental satisfaction and patient mortality. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2014, Issue 1); MEDLINE (Ovid SP, from 1995 to January 2014); EMBASE (Ovid SP, from 1995 to January 2014); the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (EBSCO Host, from 1995 to January 2014); the Latin American and Caribbean Health Science Information Database (LILACS) (BIREME, from 1995 to January 2014); Commonwealth Agricultural Bureaux (CAB) Abstracts (from 1995 to January 2014); the Institute for Scientific Information (ISI) Web of Science (from 1995 to January 2014); BIOSIS Previews (from 1995 to January 2014); the China National Knowledge Infrastructure (CNKI) (from 1995 to January 2014); International Standard Randomized Controlled Trial Number (ISRCTN) (from 1995 to January 2014); ClinicalTrials.gov (from 1995 to January 2014); and the International Clinical Trials Registry Platform (ICTRP) (to January 2014). SELECTION CRITERIA: We included RCTs comparing INF versus any other pharmacological/non-pharmacological intervention for the treatment of children in acute pain (aged < 18 years). DATA COLLECTION AND ANALYSIS: Two independent review authors assessed each title and abstract for relevance. Full copies of all studies that met the inclusion criteria were retrieved for further assessment. Mean difference (MD), odds ratio (OR) and 95% confidence interval (CI) were used to measure effect sizes. Two review authors independently assessed and rated the methodological quality of each trial using the tool of The Cochrane Collaboration to assess risk of bias, as per Chapter 8 of the Cochrane Handbook for Systematic Reviews of Interventions. MAIN RESULTS: Three studies (313 participants) met the inclusion criteria. One study compared INF versus intramuscular morphine (IMM); another study compared INF versus intravenous morphine (IVM); and another study compared standard concentration INF (SINF) versus high concentration INF (HINF). All three studies reported a reduction in pain score following INF administration. INF produced a greater reduction in pain score at 10 minutes post administration when compared with IMM (INF group pain score: 1/5 vs IMM group pain score: 2/5; P value 0.014). No other statistically significant differences in pain scores were reported at any other time point. When INF was compared with IVM and HINF, no statistically significant differences in pain scores were noted between treatment arms, before analgesia or at 5, 10, 20 and 30 minutes post analgesia. Specifically, when INF was compared with IVM, both agents were seen to produce a statistically significant reduction in pain score up to 20 minutes post analgesia. No further reduction in pain score was noted after this time. When SINF was compared with HINF, a statistically and clinically significant reduction in pain scores over study time was observed (median decrease for both groups 40 mm, P value 0.000). No adverse events (e.g. opiate toxicity, death) were reported in any study following INF administration. One study described better patient tolerance to INF compared with IMM, which achieved statistical significance. The other studies described reports of a "bad taste" and vomiting with INF. Overall the risk of bias in all studies was considered low. AUTHORS' CONCLUSIONS: INF may be an effective analgesic for the treatment of patients with acute moderate to severe pain, and its administration appears to cause minimal distress to children. However, this review of published studies does not allow any definitive conclusions regarding whether INF is superior, non-inferior or equivalent to intramuscular or intravenous morphine. Limitations of this review include the following: few eligible studies for inclusion (three); no study examined the use of INF in children younger than three years of age; no study included children with pain from a "medical" cause (e.g. abdominal pain seen in appendicitis); and all eligible studies were conducted in Australia. Consequently, the findings may not be generalizable to other healthcare settings, to children younger than three years of age and to those with pain from a "medical" cause.
Murphy, A. P., M. Hughes, et al. (2016). "Intranasal fentanyl
for the prehospital management of acute pain in children."
Eur J Emerg Med.
INTRODUCTION: Acute pain is the most common symptom in the emergency
setting and its optimal management continues to challenge prehospital
emergency care practitioners, particularly in the paediatric population.
Difficulty in establishing vascular access and fear of opiate
administration to small children are recognized reasons for
oligoanalgesia. Intranasal fentanyl (INF) has been shown to be as safe
and effective as intravenous morphine in the treatment of severe pain in
children in the Emergency Department setting. AIM: This study aimed to
describe the clinical efficacy and safety of INF when administered by
advanced paramedics in the prehospital treatment of acute severe pain in
children. METHODS: A 1-year prospective cross-sectional study was
carried out of children (>1 year, <16 years) who received INF as part of
the prehospital treatment of acute pain by the statutory national
emergency medical services in Ireland. RESULTS: Ninety-four children
were included in the final analysis [median age 11 years (interquartile
range 7-13)]; 53% were males and trauma was implicated in 86% of cases.
A clinically effective reduction in the pain score was found in 78
children [83% (95% confidence interval: 74-89%)]. The median initial
pain rating score was 10. Pain assessment at 10 min after INF
administration indicated a median pain rating of 5 (interquartile range
2-7). No patient developed an adverse event as a result of INF.
DISCUSSION: INF at a dose of 1.5 microg/kg appears to be a safe and
effective analgesic in the prehospital management of acute severe pain
in children and may be an attractive alternative to both oral and
intravenous opiates.
Myrick, R., S. Blakemore, et al. (2020). "Outpatient pain
clinic and intranasal fentanyl to improve sickle cell disease outcomes."
Pediatr Blood Cancer 67(10): e28648.
Nave, R., H. Schmitt, and L. Popper, Faster absorption and higher systemic bioavailability of intranasal fentanyl spray compared to oral transmucosal fentanyl citrate in healthy subjects. Drug Deliv, 2013.
Context: Intranasal
fentanyl spray (INFS) was developed for the treatment of breakthrough
pain in cancer patients using an alternative route of administration.
Objective: The aim of this clinical study was to investigate the
pharmacokinetic (PK) profile and bioavailability of INFS in healthy
subjects compared to oral transmucosal fentanyl citrate (OTFC).
Materials and methods: In a randomized, single-center, open-label,
two-way crossover PK study, 24 subjects (12 male, 12 female, mean age
25.2 years) received INFS (single-dose delivery system 200 mug/100 mul)
and OTFC (buccal lozenge, 200 microg). Naltrexone was given to prevent
potential adverse reactions. Frequent plasma samples were taken up to 96
h and analyzed by LC-MS/MS with a lower limit of quantitation of 25
pg/ml. Primary PK parameter was the area under the fentanyl plasma
concentration-time curve (AUC0-inf). Results: Compared to OTFC, a much
faster absorption rate was observed for INFS which was supported by the
much earlier appearance of detectable fentanyl plasma levels and a
shorter Tmax. At 15 min post-dose, the mean plasma fentanyl levels
reached 602 pg/ml for INFS and 29 pg/ml for OTFC. Significantly higher
Cmax and AUC values were obtained with INFS compared to OTFC. Although
administered for 15 min, consumption of OTFC was incomplete in many
incidences ( approximately 70%) upon visual inspection. No safety
concerns were identified for fentanyl administration in combination with
oral naltrexone. Discussion and conclusion: One dose of INFS gives
significantly higher plasma fentanyl levels and significantly higher
bioavailability than OTFC based on dose-normalized AUC.
Nazemian, N., M. Torabi, et al. (2020). "Atomized intranasal
vs intravenous fentanyl in severe renal colic pain management: A
randomized single-blinded clinical trial." Am J Emerg Med 38(8):
1635-1640.
OBJECTIVES: Renal colic is one of the most common painful disorders in
patients referred to the emergency department. The main purpose of this
study was to compare the efficiency of two methods of intravenous (IVF)
and intranasal (INF) fentanyl administration in pain management in
patients with severe renal colic. MATERIALS & METHODS: This was a
single-blind randomized clinical trial performed on patients with severe
renal colic. The severity of pain was >/=8 based on the Numerical Rating
Scale (NRS). The efficacy of pain management was compared within and
between the IVF (intramuscular Ketorolac + intravenous fentanyl) and INF
(intramuscular Ketorolac + intranasal fentanyl) groups at different
times points. Oral consent was obtained from all the patients. RESULTS:
Of 220 individuals, 96 (43.60%) were women and 124 (56.40%) were men.
There were no significant differences between the two groups regarding
the baseline pain severity, age, sex, history of urolithiasis and body
mass index (BMI). The pain severity showed a significant reducing trend
in both groups (p<0.0001). There was also a significant difference
comparing the mean pain severity between groups at different times
(p<0.0001). In each group, the severity of pain showed significant
reduction compared with its prior measurement (P<0.0001). CONCLUSION:
Fentanyl is highly effective in controlling pain in patients with severe
renal colic referring to the emergency department. Intranasal
administration of fentanyl combination with ketorolac can be an
appropriate, non-invasive, easy-to-use and fast alternative to the
intravenous method to manage pain in these patients.
Nejati, A., M. Jalili, et al. (2019). "Intranasal ketamine reduces pain
of digital nerve block; a double blind randomized clinical trial." Am
J Emerg Med 37(9):
1622-1626.
BACKGROUND: Low dose ketamine can be used as analgesic in acute pain
management in the emergency department (ED). OBJECTIVE: Efficacy of IN
ketamine in acute pain management in the ED. METHOD: This is a double
blind randomized clinical trial on patients older than 15years who
needed digital nerve block (DNB). Participants randomly received IN
Ketamine (1ml=50mg) or placebo (normal saline, 1ml) 5min before DNB. In
both groups, patients' pain score was recorded by visual analogue score
(VAS) at baseline, after DNB and 45min after completion of DNB. Adverse
effects of ketamine and changes in vital signs were also recorded and
compared with placebo group. RESULTS: A total number of 100 patients
were enrolled in the study with the median (IQR) age of 36.5 (26) years,
including 65 men and 35 women. IN ketamine resulted in less pain
compared to placebo after performing DNB and 45min after the procedure.
Median (IQR) basic VAS score was 50 (15) in ketamine group, and 49 (27)
in control group. Median (IQR) block pain VAS score was 28.5 (19) in
ketamine group and 47.5 (31) in control group. Median (IQR) procedural
pain VAS score was 21.5 (16) in ketamine group and 43.5 (29) in control
group. Only 7 patients had adverse effects in either group. CONCLUSION:
The findings of this study suggest that IN ketamine can be effective in
reducing pain in patients with acute pain, without adding significant
side effects.
Nemeth, M., N. Jacobsen, et al. (2019). "Intranasal Analgesia
and Sedation in Pediatric Emergency Care-A Prospective Observational
Study on the Implementation of an Institutional Protocol in a Tertiary
Children's Hospital." Pediatr Emerg Care.
OBJECTIVES: Children presenting with acute traumatic pain or in
need of therapeutic or diagnostic procedures require rapid and effective
analgesia and/or sedation. Intranasal administration (INA) promises to
be a reliable, minimally invasive delivery route. However, INA is still
underused in Germany. We hence developed a protocol for acute pain
therapy (APT) and urgent analgesia and/or sedation (UAS). Our aim was to
evaluate the effectiveness and safety of our protocol. METHODS: We
performed a prospective observational study in a tertiary children's
hospital in Germany. Pediatric patients aged 0 to 17 years requiring APT
or UAS were included. Fentanyl, s-ketamine, midazolam, or combinations
were delivered according to protocol. Primary outcome variables included
quality of analgesia and/or sedation as measured on age-appropriate
scales and time to onset of drug action. Secondary outcomes were adverse
events and serious adverse events. RESULTS: One hundred pediatric
patients aged 0.3 to 16 years were enrolled, 34 for APT and 66 for UAS.
The median time onset of drug action was 5 minutes (ranging from 2 to 15
minutes). Fentanyl was most frequently used for APT (n = 19). Pain
scores decreased by a median of 4 points (range, 0-10; P < 0.0001). For
UAS, s-ketamine/midazolam was most frequently used (n = 25). Sedation
score indicated minimal sedation in most cases. Overall success rate
after the first attempt was 82%. Adverse events consisted of nasal
burning (n = 2) and vomiting (n = 2). No serious adverse events were
recorded. CONCLUSIONS: A fentanyl-, s-ketamine-, and midazolam-based INA
protocol was effective and safe for APT and UAS. It should then be
considered where intravenous access is impossible or inappropriate.
Nielsen, B. N., S. M. Friis, et al. (2014). "Intranasal
sufentanil/ketamine analgesia in children." Paediatr Anaesth
24(2): 170-180.
BACKGROUND: The management of procedural pain in children ranges from
physical restraint to pharmacological interventions. Pediatric
formulations that permit accurate dosing, are accepted by children and a
have a rapid onset of analgesia are lacking. OBJECTIVES: To investigate
a pediatric formulation of intranasal sufentanil 0.5 mcg.kg(-1) and
ketamine 0.5 mg.kg(-1) for procedural pain and to characterize the
pharmacokinetic (PK) profile. METHODS: Fifty children (>/=10 kg)
scheduled for a painful procedure were included in this prospective
nonrandomized open-label clinical trial. Thirteen of these children had
central venous access for drug assay sampling; enabling a compartmental
PK analysis using nonlinear mixed-effects models. Pain intensity before
and during the procedure was measured using age-appropriate pain scales.
Heart rate, oxygen saturation and sedation were recorded. RESULTS:
Children had a mean age of 8.8 (sd 4.9) years and weight 35.2 (sd 20.1)
kg. Sufentanil/ketamine nasal spray was effective (procedural pain
intensity scores </=5 (0-10)) in 78% of the painful procedures. The
spray was well accepted by 94% of the children. Oxygen saturation and
heart rate remained stable, and sedation was minimal. The
bioavailability of sufentanil and ketamine was 24.6% and 35.8%,
respectively. Maximum plasma concentration (Cmax) of sufentanil was
0.042 mcg.l(-1) (coefficient of variation (CV) 12.9%) at 13.8 min (CV
12.4%) (Tmax). Cmax for ketamine was 0.102 mg.l(-1) (CV 10.8%), and Tmax
was 8.5 min (CV 17.3%). CONCLUSION: Sufentanil/ketamine nasal spray
provided rapid onset of analgesia for a variety of painful procedures
with few adverse effects and has promising features for use in pediatric
procedural pain management.
O'Donnell, D. P., L. C. Schafer, et al. (2013). "Effect of Introducing
the Mucosal Atomization Device for Fentanyl Use in Out-of-Hospital
Pediatric Trauma Patients." Prehosp Disaster Med
28(5): 520-522.
Background: Pain associated with pediatric trauma is
often under-assessed and under-treated in the out-of-hospital setting.
Administering an opioid such as fentanyl via the intranasal route is a
safe and efficacious alternative to traditional routes of analgesic
delivery and could potentially improve pain management in pediatric
trauma patients. Objective: We sought to examine the effect of
introducing the Mucosal Atomization Device (MAD) on analgesia
administration as an alternative to intravenous fentanyl delivery in
pediatric trauma patients. We hypothesized that the introduction of the
MADwould increase the administration of fentanyl in pediatric trauma
patients. Methods: We utilized a two-group design (pre-MAD and post-MAD)
to study 946pediatric trauma patients (age < 16) transported by a large,
urban EMS agency to one of eight hospitals in the county. Two emergency
medicine physicians independently determined whether the patient met
criteria for pain medication receipt and a third reviewer resolved any
disagreements. We then compared the rates of fentanyl administration in
both groups. Results: There
was no statistically significant difference in fentanyl administration
between the pre-MAD (30.4%) and post-MAD groups (37.8%) (p = 0.238). A
subgroup analysis showed that age and mechanism of injury were stronger
predictors of fentanyl administration. Conclusion: Contrary to our
hypothesis, the addition of the MAD device did not increase fentanyl
administration in pediatric trauma patients. Future research is needed
to address the barriers to analgesia administration in pediatric trauma
patients
O'Neil, Paech, et al. (1997). "Preliminary clinical
use of a patient-controlled intranasal analgesia (PCINA) device."
Anaesth Intensive Care 25(4): 408-12.
Oliver, F. M., T. W. Sweatman, et al. (2000). "Comparative pharmacokinetics of submucosal vs. intravenous flumazenil (Romazicon) in an animal model." Pediatr Dent 22(6): 489-93.
PURPOSE: This study was performed to determine the bioavailability and local tissue toxicological safety of flumazenil (Romazicon) when administered by oral submucosal (SM) as opposed to intravenous (i.v.) injection. METHODS: Six dogs each received SM flumazenil (0.2 mg), and their serum was collected at predetermined time intervals (0-2 h) and frozen (-70 degrees C). Seven days later, the dogs received an identical dose of i.v. flumazenil, and serum samples were again collected, as above. Comparative quantitation of flumazenil levels (i.v. vs. SM) was made using a sensitive HPLC assay (UV detection). Direct/local drug toxicity was visually scored by unbiased raters of color photographs (test and control mucosa) taken at 1, 2, and 7 days following SM flumazenil injection. An oral pathologist examined slides processed from control and treatment tissues (hematoxylin and eosin staining) taken (punch biopsy) 1 week following SM injection to compare with direct clinical scores. RESULTS: Serum flumazenil levels reached a plateau (8.5 +/- 1.5 ng/mL, mean +/- SD) within 4 min of SM drug injection and declined thereafter to -2 ng/mL by 2 h. Bioavailability of SM flumazenil was 101 +/- 14%, based upon measuring the area under the serum concentration-time curves over 1.5 h (AUC 0-1.5 h, SM vs. i.v. drug). Thus, serum drug levels following SM drug administration were broadly comparable to those obtained during the elimination phase of corresponding i.v. drug delivery. Regarding drug tissue toxicity, no evidence of direct drug toxicity was observed by unbiased raters of color photographs (test and control mucosa) taken at 1, 2, and 7 days following SM flumazenil injection. Following pathologic review, no difference was seen in the degree of inflammation between treatment and control tissue. CONCLUSION: At the quantity and concentration used, SM drug flumazenil administration appears to be both a safe and a viable alternative to bolus i.v. drug delivery and worthy of further investigation.
Paech, M. J., C. B. Lim, et al. (2003). "A new
formulation of nasal fentanyl spray for postoperative analgesia: a pilot
study." Anaesthesia 58(8): 740-4.
Twenty-four gynaecological patients receiving postoperative
patient-controlled analgesia were enrolled in an open cross-over pilot
study evaluating two new formulations of nasal fentanyl spray. The
primary outcome was the bioavailability of nasal fentanyl in comparison
with intravenous fentanyl. This manuscript describes the clinical
outcomes of quality of postoperative analgesia and patient
acceptability. There were 21 complete data sets for both sequences of
the cross-over design. In randomised order, patients received
approximately 50 microg of fentanyl in a single dose by intranasal and
intravenous administration, but separated by at least 2 h. Analgesia was
of rapid onset (within 5 min) and similar quality. There was no
significant difference in side-effects. Four patients experienced mild
nasal stinging and although 10 (42%) preferred intravenous
administration, seven (29%) preferred intranasal and six (25%) had no
preference. We conclude that these formulations of fentanyl, delivered
as nasal spray, have potential clinical utility.
Page, N. and V. Nirabhawane (2018). "Intranasal Ketamine for the
Management of Incidental Pain during Wound Dressing in Cancer Patients:
A Pilot Study." Indian J Palliat Care
24(1): 58-60.
Introduction: Cancer wounds need regular dressing; else they develop infection, foul odor, and in extreme cases, maggots. Patients resist dressing due to the severe incidental pain during dressing. Intranasal ketamine was tried as an analgesic to reduce this incidental pain. Materials and Methods: Twenty patients with wounds requiring regular dressing were selected; these patients had a basal pain score of 4/10 and incidental pain score of 7/10 during four consecutive dressings. Ketamine 0.5 mg/kg was administered transmucosally 10 min before dressing, and pain scores, hemodynamic parameters, and sedation were recorded for up to 2 h in six consecutive dressings. Results: Ketamine produced a significant reduction in incidental pain without any hemodynamic changes or sedation. Conclusion: Ketamine appears to be a safe and effective analgesic when used intranasally for incidental pain.
Paquin, H., E. D. Trottier, et al. (2020). "Evaluation of a
clinical protocol using intranasal fentanyl for treatment of vaso-occlusive
crisis in sickle cell patients in the emergency department." Paediatr
Child Health 25(5): 293-299.
Background: Vaso-occlusive crisis (VOC) is one of the most frequent causes of emergency visits and admission in children with sickle cell disease (SCD). Objectives: This study aims to evaluate whether the use of a new pain management pathway using intranasal (IN) fentanyl from triage leads to improved care, translated by a decrease in time to first opiate dose. Methods: We performed a retrospective chart review of patients with SCD who presented to the emergency department (ED) with VOC, in the period pre- (52 patients) and post- (44 patients) implementation period of the protocol. Time to first opiate was the primary outcome and was evaluated pre- and postimplementation. Patients received a first opiate dose within 52.3 minutes of registration (interquantile range [IQR] 30.6, 74.6), corresponding to a 41.4-minute reduction in the opiate administration time (95% confidence interval [CI] -56.1, -27.9). There was also a 43% increase in the number of patients treated with a nonintravenous (IV) opiate as first opiate dose (95% CI 26, 57). In patients who were discharged from the ED, there was a 49% decrease in the number of IV line insertions (95% CI -67, -22). There was no difference in the hospitalization rates (difference of 6 [95% CI -13, 25]). Conclusions: This study validates the use of our protocol using IN fentanyl as first treatment of VOC in the ED by significantly reducing the time to first opiate dose and the number of IVs.
Parvizrad, R., A. Pakniyat, et al. (2017). "Comparing the analgesic
effect of intranasal with intravenous ketamine in isolated orthopedic
trauma: A randomized clinical trial." Turk J Emerg Med
17(3): 99-103.
OBJECTIVES: Ketamine is commonly used in anesthetic and sedation
before surgical procedures and acts as an analgesic in smaller doses.
The aim of this study was to assess the effects of intranasal (IN)
ketamine in patients with moderate to severe limb trauma (visual analog
scale (VAS) > 60 mm). METHODS: In a triple-blind randomized controlled
clinical trial; 154 patients with isolated orthopedic trauma and visual
analog scale (VAS) >/=60 mm were included on the basis of inclusion and
exclusion criteria. Patients were divided into two groups of ketamine-IN
(0.4 mg/kg IN ketamine and an equal volume of placebo saline
intravenously (IV)) and ketamine-IV (0.2 mg/kg ketamine IV with 0.5 ml
saline IN) on the basis of balanced block randomization method. At 5,
10, 20, and 30 min, patients were assessed for VAS measurement and
adverse events. Repeated measure ANOVA, independent t-test and chi
square test were employed. The level of statistical significance was
considered to be less than 0.05. RESULTS: Mean VAS in IN ketamine and IV
group at minute 30 was 31.50 +/- 13.40 and 29.35 +/- 11.73,
respectively. At minute 30, 31 patients (20.39%) required a low-dose of
morphine as rescue analgesia (P = 0.427). The results showed that mean
change score of VAS (difference of time 0 and time 30) in IN ketamine
and IV ketamine VAS were 43.8 (95% confidence interval: 41.1-46.5) and
46.4 (95% confidence interval: 42.8-50.1) and there is no difference
between two groups in case of score change of VAS (P = 0.245). Adverse
events in nasal and intravenous ketamine in both groups were mild and
transient. CONCLUSION: IN ketamine is associated with few side effects
and appropriate analgesic effects in isolated orthopedic trauma
patients, and it may be used in cases where there is no need for
venipuncture of peripheral vessels, especially in crowded EDs.
Pestieau, S. R., Z. M. Quezado, et al. (2011). "The effect of
dexmedetomidine during myringotomy and pressure-equalizing tube
placement in children." Paediatr Anaesth
21(11): 1128-1135.
BACKGROUND: Bilateral myringotomy (BMT) is a commonly performed
otolaryngologic procedure in children. OBJECTIVES: To examine the
effects of intranasal dexmedetomidine, an alpha(2)-adrenoceptor agonist,
on time-averaged pain scores, pain control, need for rescue analgesia,
and agitation scores in children undergoing BMT. METHODS: We designed a
trial to enroll 160 children randomized to one of four groups: two study
groups, dexmedetomidine (1 or 2 mug.kg(-1)), or two control groups
representing our institutional standards of practice (intranasal
fentanyl-2 mug.kg(-1) or acetaminophen as needed postoperatively).
RESULTS: After 101 children were enrolled, patient caregivers observed
that some enrollees were excessively sedated and required prolonged
postanesthesia care unit (PACU) stay. This observation led to an
unplanned interim analysis and early trial termination. After data were
collected, severe nonnormality of pain and agitation scores necessitated
a switch of the outcome to assess repeated measurements of the
proportion of patients with pain, severe pain, and agitation.
Demographics, time to emergence, and agitation were similar among all
groups. The risk of requiring acetaminophen rescue (P < 0.0001) and
proportion of patients having pain (P = 0.016) was significantly higher
in one control group (rescue analgesia only) compared with fentanyl or
dexmedetomidine groups. Importantly, length of stay in the PACU was
significantly longer in dexmedetomidine-2 mug.kg(-1)-treated compared
with dexmedetomidine-1 mug.kg(-1)-treated, fentanyl-treated, or the
control group, P = 0.0037. CONCLUSIONS: In this trial, we were unable to
answer the original question as to the role of dexmedetomidine on
time-averaged pain and agitation scores after BMT. However, our findings
clearly demonstrate that in children undergoing BMT, at higher doses,
dexmedetomidine significantly prolongs length of stay in the PACU.
Phillips, M. L., B. C. Willis, et al. (2016). "Bimodal analgesia vs
fentanyl in pediatric patients undergoing bilateral myringotomy and
tympanostomy tube placement: a propensity matched cohort study." J
Clin Anesth 32:
162-168.
STUDY OBJECTIVE: Bilateral myringotomy and tympanostomy tube placement
(BMT) is one of the most frequently performed pediatric outpatient
procedures with 667,000 children receiving tympanostomy tubes annually.
Because of this high volume, discovering the ideal analgesic regimen may
lead to decreased overall postanesthesia care unit (PACU) costs while
increasing patient and parent satisfaction. The purpose of this study is
to determine if there is any benefit in supplementing intranasal (IN)
fentanyl with intramuscular (IM) ketorolac with regard to immediate
recovery characteristics. DESIGN: Retrospective, cohort study. SETTING:
University-affiliated teaching hospital. PATIENTS: One thousand one
hundred forty American Society of Anesthesiologists physical status 1
and 2 pediatric patients scheduled for BMT. INTERVENTIONS: No
interventions were performed. MEASUREMENTS: A propensity matched cohort
of pediatric patients who underwent BMT at Vanderbilt Children's
Hospital from 2011 to 2014 was analyzed. The authors compared PACU
recovery time, rescue analgesic administration, maximal PACU pain
scores, and maximal PACU agitation scores between subgroups of patients
given either IN fentanyl and IM ketorolac or IN fentanyl alone
intraoperatively. MAIN RESULTS: After adjusting for patient demographics
and fentanyl dose, the fentanyl/ketorolac group received rescue
analgesics 4.7% (95% confidence interval [CI], 2.0%-7.5%) less often,
displayed moderate to severe pain 4.7% (95% CI, 1.5%-8.0%) less often,
and experienced emergence agitation 3.6% (95% CI, 1.5%-5.8%) less often
than patients in the fentanyl-only group. This corresponded to a
relative risk reduction of 127%, 76%, and 200%, respectively.
CONCLUSIONS: Based on our retrospective analysis, adding IM ketorolac to
IN fentanyl may be beneficial to pediatric patients undergoing BMT.
However, these results should be confirmed with a prospective,
double-blinded, randomized study.
Pouraghaei, M., P. Moharamzadeh, et al. (2020). "Intranasal
ketamine versus intravenous morphine for pain management in patients
with renal colic: a double-blind, randomized, controlled trial."
World J Urol.
BACKGROUND: Urinary stones are a common urologic problem that can be manifested as an intense pain, known as renal colic. Pain control is an important intervention for the emergency treatment of renal colic patients. Intranasal ketamine can form a crucial part of such interventions by offering a new route for a widely-used analgesic drug. METHODS: In a double-blind, randomized, clinical trial, adults with renal colic admitted to a tertiary hospital emergency department were examined. The intervention group received 1 mg/kg intranasal (IN) ketamine and 1 ml of saline as a placebo. The control group received 0.1 mg/kg intravenous (IV) morphine and four puffs of saline as the placebo. The pain score was measured on the Numerical Rating Scale (NRS) 0, 15, 30 and 60 min after the drug administration. RESULTS: A total of 184 patients enrolled in this study in two parallel groups. The two groups did not differ significantly in terms of pain intensity at the time of their referral (P = 0.489), 15 min post-dose (P = 0.204), 30 min post-dose (P = 0.978) and 60 min post-dose (P = 0.648). CONCLUSION: IN ketamine is as effective as IV morphine for pain control in renal colic patients. No remarkable side-effects were observed for IN ketamine use in these patients.
Quadir, M., H. Zia, et al. (2000). "Development
and evaluation of nasal formulations of ketorolac." Drug Deliv
7(4): 223-229.
Ketorolac tromethamine is a potent non-narcotic analgesic with moderate anti-inflammatory activity. Clinical studies indicate that ketorolac has a single dose efficacy greater than morphine for postoperative pain and has excellent applicability in the emergency treatment of pain. Due to incomplete oral absorption of ketorolac, several approaches have been tried to develop a nonoral formulation in addition to injections, especially for the treatment of migraine headache. The aim of our study was to develop a nasal formulation of ketorolac with a dose equivalent to the oral formulation. A series of spray and lyophilized powder formulations of ketorolac were administered into the nasal cavity of rabbits, and their pharmacokinetics profiles were assessed. The spray and powder formulations were compared through their pharmacokinetics parameters and absolute bioavailability. Drug plasma concentration was determined using solid phase extraction, followed by an HPLC analysis. Nasal spray formulations were significantly better absorbed than powder formulations. A nasal spray formulation of ketorolac tromethamine showed the highest absorption with an absolute bioavailability of 91%. Within 30 min of administration, the plasma concentration was comparable to that resulting from an intravenous injection. The absolute bioavailability of a solution of ketorolac acid was 70%. Apparently, the dissolution of ketorolac acid into the mucous layer limits its absorption. There were no significant differences in absorption between different powder formulations. Even the reduction of particle size from 123 microm to 63 microm did not indicate better absorption of ketorolac tromethamine from powder formulations. Interestingly, the absolute bioavailability of ketorolac tromethamine from a powder formulation is only 38%, indicating that the drug may not be totally released from the polymer matrix before it is removed from nasal epithelium by mucociliary clearance.
Quinn, K., S. Kriss, et al. (2018). "Analgesic Efficacy of
Intranasal Ketamine Versus Intranasal Fentanyl for Moderate to Severe
Pain in Children: A Prospective, Randomized, Double-Blind Study."
Pediatr Emerg Care.
PURPOSE: This study aimed to compare analgesic efficacy of intranasal (IN) ketamine to IN fentanyl for moderate to severe pain in children in a pediatric emergency department. METHODS: A prospective, randomized, double-blinded, noninferiority study evaluating children aged 3 to 17 years in a pediatric emergency department with acute moderate to severe pain was conducted. Patients received either 1 mg/kg of IN ketamine or 1.5 mug/kg of IN fentanyl and were evaluated after 10, 20, 30, and 60 minutes. The primary outcome was the degree of pain reduction after 20 minutes. RESULTS: Twenty-two patients were enrolled (11 in each group). Underlying pain conditions represented were musculoskeletal injury (73%) and abdominal pain (27%). At 20 minutes after analgesia, there was no significant difference in pain scores between the fentanyl (median, 2; range, 0-8) and ketamine groups (median, 4; range, 0-7; P = 0.20). The ketamine group showed a significantly greater rate of adverse effects, 73% versus 9% (P = 0.002), and throughout the course of the study period, 7 patients in the ketamine group (64%) group showed some degree of sedation versus no one in the fentanyl group (P = 0.004). CONCLUSIONS: There was insufficient power to support the analgesic noninferiority of IN ketamine at a dose of 1 mg/kg compared with IN fentanyl at a dose of 1.5 mug/kg in children experiencing painful conditions at 20 minutes after administration. Intranasal ketamine was found to be inferior to IN fentanyl in relieving pain at 10 minutes and was found to have significantly greater rates of sedation and dizziness.
Ralley, F. E. (1989). "Intranasal opiates: old route
for new drugs." Can J Anaesth 36(5): 491-3.
Rampersad, S., N. Jimenez, et al. (2010). "Two-agent analgesia versus acetaminophen in children having bilateral myringotomies and tubes surgery." Paediatr Anaesth 20(11): 1028-1035.
OBJECTIVES: The objective of this study was to determine whether the incidence of emergence agitation (EA) can be reduced by adding an additional, faster onset, non-IV analgesic, intranasal fentanyl or intramuscular (im) ketorolac to rectal acetaminophen. AIM: To compare the incidence of EA after analgesia with two agents vs acetaminophen alone in pediatric patients after bilateral myringotomy procedures (BM&T). BACKGROUND: Anesthesia for BM&T is usually performed with volatile anesthetics as a single agent without securing intravenous access. The anesthetic agent most commonly used is sevoflurane; however, EA has been reported in up to 67% of patients. Emergence agitation is distressing for parents, can impair the ability of nursing staff to adequately monitor the child, and can result in a child injuring him/herself if it is severe. METHODS/MATERIALS: A standardized anesthetic was used with oral midazolam premedication and sevoflurane for induction, and maintenance of anesthesia. All patients received 40 mg.kg(-1) rectal acetaminophen, group 1 received acetaminophen alone, group 2 received acetaminophen and 1 mcg.kg(-1) of intranasal fentanyl, and group 3 received acetaminophen and 1 mg.kg(-1) of intramuscular ketorolac. Incidence of EA was compared using chi-square test between the acetaminophen group alone vs the two-agent analgesia groups combined. Results: There were no differences in demographic and clinical characteristics between the two groups. There were no statistically significant differences between the three groups for the incidence of EA at any time point during recovery from anesthesia nor were there any significant differences in pain scores or side effects. No significant side effects because of the administration of a second analgesic agent were reported. CONCLUSIONS: We conclude that two-agent analgesia is not superior to acetaminophen alone for decreasing the incidence of EA after inhalation anesthesia with sevoflurane for BM&T surgery. Our overall incidence of EA was low compared to previous studies, which could potentially have decreased our ability to detect differences between groups.
Regan, L., A. R. Chapman,
et al. (2012). "Nose and vein, speed and pain: comparing the use of
intranasal diamorphine and intravenous morphine in a Scottish paediatric
emergency department." Emerg Med J.
Background: Urgent analgesia is essential for all children who
present in severe pain, but difficulties in obtaining venous access can
delay the use of adequate opiate analgesia. Intranasal diamorphine (IND)
is now in use in around 60% of emergency departments and is the
preferred choice of analgesia as reported by both parents and healthcare
professionals. While IND has similar efficacy to intramuscular morphine
in children, no study has compared its use against the current gold
standard, intravenous morphine (IVM).Methods: IND was introduced to the
Royal Aberdeen Children's Hospital on 24 December 2009. A retrospective
case series was constructed to compare its clinical performance with its
predecessor IVM. Three unexplored factors were investigated: time to
opiate analgesia, the requirement for further analgesia when still in
the emergency department and the effect of simple coanalgesia (eg,
paracetamol/ibuprofen) on these requirements.Results297 patients were
eligible for the study (147 IND, 150 IVM) over a 28-month period. There
was a non-significant trend to a longer median time to administration of
analgesia in patients receiving IND (p=0.170). Patients who received IND
were less likely to require further analgesia (p<0.001). Both groups
were less likely to require further analgesia when simple coanalgesia
was given (p=0.049).Conclusion: The authors found no significant
difference in time to administration of analgesia between agents, but a
learning curve has been identified. Sustained effort should be placed on
the use of simple coanalgesia. The clinical performance of IND compares
favourably with IVM in children with severe pain, and it remains an
appropriate preferred agent.
Reid, C., R. Hatton, et al. (2011). "Case report: prehospital use of intranasal ketamine for paediatric burn injury." Emerg Med J 28(4): 328-329.
In this study, the administration of an intravenous ketamine formulation to the nasal mucosa of a paediatric burn victim is described in the prehospital environment. Effective analgesia was achieved without the need for vascular or osseous access. Intranasal ketamine has been previously described for chronic pain and anaesthetic premedication. This case highlights its potential as an option for prehospital analgesia.
Reynolds, S. L., K. K. Bryant, et al. (2017). "Randomized
Controlled Feasibility Trial of Intranasal Ketamine Compared to
Intranasal Fentanyl for Analgesia in Children with Suspected Extremity
Fractures." Acad Emerg Med.
OBJECTIVE: We compared the tolerability and efficacy of
intranasal sub-dissociative ketamine to intranasal fentanyl for
analgesia of children with acute traumatic pain and investigated the
feasibility of a larger non-inferiority trial that could investigate the
potential opioid sparing effects of intranasal ketamine. METHODS: This
randomized controlled trial compared intranasal ketamine 1 mg/kg to
intranasal fentanyl 1.5 mug/kg in children 4-17 years old with acute
pain from suspected, isolated extremity fractures presenting to an urban
level II pediatric trauma center from December 2015 to November 2016.
Patients, parents, treating physicians, and outcome assessors were
blinded to group allocation. The primary outcome, a tolerability
measure, was the frequency of cumulative side effects and adverse events
within 60 minutes of drug administration. The secondary outcomes
included the difference in mean pain score reduction at 20 minutes, the
proportion of patients achieving a clinically significant reduction in
pain in 20 minutes, total dose of opioid pain medication in morphine
equivalents/kg/hour (excluding study drug) required during the emergency
department (ED) stay, and the feasibility of enrolling children
presenting to the ED in acute pain into a randomized trial conducted
under US regulations. All patients were monitored until 6 hours after
their last dose of study drug, or until admission to the hospital ward
or operating room. RESULTS: Of 629 patients screened, 87 received the
study drug and 82 had complete data for the primary outcome (41 patients
in each group). The median age (interquartile range) was 8 (3) years and
62% were male. Baseline pain scores were similar among patients
randomized to receive ketamine (73 +/- 26) and fentanyl (69 +/- 26)
[mean difference (95% CI): 4 (-7 to 15)]. The cumulative number of side
effects was 2.2 times higher in the ketamine group, but there were no
serious adverse events and no patients in either group required
intervention. The most common side effects of ketamine were bad taste in
the mouth (37; 90.2%), dizziness (30; 73.2%), and sleepiness (19;
46.3%). The most common side effects of fentanyl were sleepiness (15;
36.6%), bad taste in the mouth (9; 22%), and itchy nose (9; 22%). No
patients experienced respiratory side effects. At 20 minutes, the mean
pain scale score reduction was 44 +/- 36 for ketamine and 35 +/- 29 for
fentanyl [mean difference: 9 (95% CI: -4 to 23)]. Procedural sedation
with ketamine occurred in 28 ketamine patients (65%) and 25 fentanyl
patients (57%) prior to completing the study. CONCLUSIONS: Intranasal
ketamine was associated with more minor side effects than intranasal
fentanyl. Pain relief at 20 minutes was similar between groups. Our data
support the feasibility of a larger, non-inferiority trial to more
rigorously evaluate the safety, efficacy, and potential opioid sparing
benefits of intranasal ketamine analgesia for children with acute pain.
This article is protected by copyright. All rights reserved.
Riediger, C., M. Haschke, et al. (2015). "The analgesic effect of
combined treatment with intranasal
S-ketamine and intranasal midazolam compared with morphine
patient-controlled analgesia in spinal surgery patients: a
pilot study." J Pain Res
8: 87-94.
OBJECTIVES: Ketamine is a
well-known analgesic and dose-dependent anesthetic used in emergency and
disaster medicine. Recently, a new formulation of S-ketamine, as an
intranasal spray, was developed and tested in our institution in healthy
volunteers. The authors investigated the effect of intranasal S-ketamine
spray combined with midazolam intranasal spray in postoperative spinal
surgery patients. MATERIALS AND METHODS: In this prospective,
computer-randomized, double-blinded noninferiority study in spinal
surgery patients, the effects of intranasal S-ketamine and midazolam
were compared with standard morphine patient-controlled analgesia (PCA).
The primary end point was the numeric rating scale pain score 24 hours
after surgery. RESULTS: Twenty-two patients finished this study, eleven
in each group. There were similar numeric rating scale scores in the
morphine PCA and the S-ketamine-PCA groups at 1, 2, 4, 24, 48, and 72
hours after surgery during rest as well as in motion. There were no
differences in the satisfaction scores at any time between the groups.
The number of bolus demands and deliveries was not significantly
different. DISCUSSION: In our study, we found that an S-ketamine
intranasal spray combined with intra-nasal midazolam was similar in
effectiveness, satisfaction, number of demands/deliveries of S-ketamine
and morphine, and number/severity of adverse events compared with
standard intravenous PCA with morphine. S-ketamine can be regarded as an
effective alternative for a traditional intravenous morphine PCA in the
postoperative setting.
Rickard, C., P. O'Meara, et al. (2007). "A randomized
controlled trial of intranasal fentanyl vs intravenous morphine for
analgesia in the prehospital setting." Am J Emerg Med 25(8):
911-7.
STUDY OBJECTIVE: The objective of the study was to compare intranasal fentanyl (INF) with intravenous morphine (IVM) for prehospital analgesia. METHODS: This was a randomized, controlled, open-label trial. Consecutive adult patients (n = 258) requiring analgesia (Verbal Rating Score [VRS] >2/10 noncardiac or >5/10 cardiac) were recruited. Patients received INF 180 mug +/- 2 doses of 60 mug at > or =5-minute intervals or IVM 2.5 to 5 mg +/- 2 doses of 2.5 to 5 mg at > or =5-minute intervals. The end point was the difference in baseline/destination VRS. RESULTS: Groups were equivalent (P = not significant) for baseline VRS [mean (SD): INF 8.3 (1.7), IVM 8.1 (1.6)] and minutes to destination [mean (SD): INF 27.2 (15.5), IVM 30.6 (19.1)]. Patients had a mean (95% confidence interval) VRS reduction as follows: INF 4.22 (3.74-4.71), IVM 3.57 (3.10-4.03); P = .08. Higher baseline VRS (P < .001), no methoxyflurane use (P < .01), and back pain (P = .02) predicted VRS reduction. Safety and acceptability were comparable. CONCLUSIONS: There was no significant difference in the effectiveness of INF and IVM for prehospital analgesia.
Riediger, C., M. Haschke, et al. (2015). "The analgesic effect of
combined treatment with intranasal S-ketamine and intranasal midazolam
compared with morphine patient-controlled analgesia in spinal surgery
patients: a pilot study." J Pain Res
8: 87-94.
OBJECTIVES: Ketamine is a well-known analgesic and dose-dependent
anesthetic used in emergency and disaster medicine. Recently, a new
formulation of S-ketamine, as an intranasal spray, was developed and
tested in our institution in healthy volunteers. The authors
investigated the effect of intranasal S-ketamine spray combined with
midazolam intranasal spray in postoperative spinal surgery patients.
MATERIALS AND METHODS: In this prospective, computer-randomized,
double-blinded noninferiority study in spinal surgery patients, the
effects of intranasal S-ketamine and midazolam were compared with
standard morphine patient-controlled analgesia (PCA). The primary end
point was the numeric rating scale pain score 24 hours after surgery.
RESULTS: Twenty-two patients finished this study, eleven in each group.
There were similar numeric rating scale scores in the morphine PCA and
the S-ketamine-PCA groups at 1, 2, 4, 24, 48, and 72 hours after surgery
during rest as well as in motion. There were no differences in the
satisfaction scores at any time between the groups. The number of bolus
demands and deliveries was not significantly different. DISCUSSION: In
our study, we found that an S-ketamine intranasal spray combined with
intra-nasal midazolam was similar in effectiveness, satisfaction, number
of demands/deliveries of S-ketamine and morphine, and number/severity of
adverse events compared with standard intravenous PCA with morphine.
S-ketamine can be regarded as an effective alternative for a traditional
intravenous morphine PCA in the postoperative setting.
Roelofse, Ja, et al. (2004). "Intranasal
sufentanil/midazolam versus ketamine/midazolam for analgesia/sedation in
the pediatric population prior to undergoing multiple dental extractions
under general anesthesia: a prospective, double-blind, randomized
comparison." Anesth Prog 51(4): 114-21.
This article details a double-blind, randomized study evaluating
the efficacy and safety of intranasal sufentanil and intranasal
midazolam (S/M) when compared with intranasal ketamine and intranasal
midazolam (K/M) for sedation and analgesia in pediatric patients
undergoing dental surgery. Fifty healthy ASA status 1 children aged 5-7
years, weighing 15-20 kg, and having 6 or more teeth extracted, were
randomly allocated to 2 groups of 25 patients each (n = 50). In the S/M
group, 25 children received intranasal sufentanil 20 microg, and
intranasal midazolam 0.3 mg/kg 20 minutes before the induction of
anesthesia. In the K/M group, 25 children received intranasal ketamine 5
mg/kg and intranasal midazolam 0.3 mg/kg 20 minutes before the induction
of anesthesia. Sevoflurane in nitrous oxide and oxygen was used for
induction and maintenance of anesthesia. This study demonstrated the
safety and efficacy of both methods with ease of administration,
combined with a rapid onset of action. Both groups were equally sedated.
A smooth mask induction of anesthesia was experienced in the majority of
children. Effective postoperative analgesia for multiple dental
extractions was provided. The intranasal administration of drugs for
sedation and analgesia has some promising features in preschool children
undergoing multiple dental extractions.
Saunders, M., K. Adelgais, et al. (2007). "Use
of Intranasal Fentanyl for the Relief of Orthopedic Trauma Pain."
Pediatric Emergency Medicine data base:
http://www.pemdatabase.org/PAS2007.html.
BACKGROUND: Pediatric patients with painful orthopedic injuries often do not receive analgesia, due to NPO status and the invasive nature of IV placement. Intranasal fentanyl administration provides adequate and rapid analgesia, but has not been studied objectively for painful orthopedic injuries. OBJECTIVE: To prospectively evaluate the use of intranasal fentanyl as analgesia for painful pediatric orthopedic injuries. DESIGN/METHODS: We conducted a prospective interventional trial on a convenience sample of patients 3-18 years with painful orthopedic trauma. Eligible patients with pain scores greater than 3 faces on the Wong-Baker Faces (WBS) for 3-8 years or greater than 40mm on a Visual Analog Scale (VAS) for 9-18 years were enrolled. Fentanyl (2 mcg/kg, 100 mcg maximum) was administered intranasally using a syringe-tip atomization device. Pain scores and vital signs were obtained at baseline and at 10, 20, and 30 minutes after fentanyl administration. Satisfaction surveys were then completed using a 100mm VAS. The change in pain score was the primary outcome. RESULTS: 81 patients were enrolled (28 in the VAS group and 53 in the WBS group). The mean patient age was 7.9 years and 60% were male. The fracture types included forearm (47%; 32% required reduction), supracondylar (21%), clavicle (8%), tibia/fibula (6%), and other (18%). Pain scores after intranasal fentanyl administration are shown in Tables 1 and 2. Mean satisfaction scores were 78.6 (95% CI: 73.9-83.3) for providers, 74.3 (95% CI: 69.3-79.3) for parents, and 61.6 (95% CI: 53.4-69.8) for patients. No adverse events were recorded. CONCLUSIONS: Intranasal fentanyl at a dose of 2 mcg/kg is an effective method for providing analgesia to pediatric patients with moderate to severe pain due to orthopedic trauma.
Schacherer, N. M., D. E. Ramirez, et al. (2015). "Expedited
Delivery of Pain Medication for Long-Bone Fractures Using an Intranasal
Fentanyl Clinical Pathway." Pediatr Emerg Care.
OBJECTIVE: This study aims to determine whether a pathway
designed to facilitate the use of intranasal (IN) fentanyl for long-bone
fractures will expedite the delivery of pain medication, decrease the
total length of emergency department (ED) stay, and provide faster
analgesia compared with intravenous (IV) morphine. METHODS: A pain
pathway for IN fentanyl in long-bone fractures was instituted in our ED
in July 2011. We performed a retrospective and prospective chart review
of patients aged 3 to 21 years who presented to the ED with a clinically
suspected long-bone fracture and either received IV morphine or were
placed on IN fentanyl pain pathway. RESULTS: A total of 94 patients met
our inclusion criteria; 71 received IV morphine, and 23 received IN
fentanyl, per pathway protocol. The mean length of time to pain
medication administration was statistically significantly faster for IN
fentanyl (37 minutes) than for IV morphine (62 minutes) (P = 0.002). The
mean total length of stay for patients who received IN fentanyl versus
patients who received IV morphine was not statistically significantly
different after excluding patients who needed reduction or surgery.
Effectiveness of pain control was not statistically significantly
different between the IN fentanyl group and the IV morphine group.
CONCLUSIONS: Use of the IN fentanyl pain pathway significantly decreases
time to pain medication administration in pediatric patients with
suspected long-bone fractures.
Scheepers, L. D., C. J. Montgomery, et al. (2000). "Plasma concentration of flumazenil following intranasal administration in children." Can J Anaesth 47(2): 120-4.
PURPOSE: A pharmacokinetic study in children to determine plasma flumazenil concentrations after the intranasal administration of 40 microg x kg(-1). METHODS: Following institutional approval and informed written consent, 11 ASA physical status I-II patients, aged two to six years, undergoing general anesthesia for dental surgery were recruited. After induction, 40 microg x kg(-1) flumazenil Anexate, Roche, 0.1 mg x mL(-1) (0.4 mL x kg(-1))) were administered via a syringe as drops, prior to nasal intubation. Venous plasma samples were drawn prior to administration of flumazenil (t = 0), and then at 2, 4, 6, 8, 10, 15, 20, 30, 40, 60, and 120 min thereafter. The plasma samples were immediately processed by the on-site laboratory and then stored at -70 degrees C, before batch analysis via high performance liquid chromatography assay. Pharmacokinetic data calculations were performed using WinNonLin software (Scientific Consulting Inc.). RESULTS: Eleven patients were studied, but data for one patient were discarded due to insufficient sampling. The median age was 4.3 yr (range 3 to 6), with a median weight of 18.9 kg (range 14.9 to 22.2). There were seven boys and three girls. Mean Cmax was 67.8 ng x mL(-1) (SD 41.9), with Tmax at two minutes. The calculated half-life was 122 min (SD 99). CONCLUSION: The mean plasma concentrations of flumazenil attained were similar to those reported after intravenous administration, and may be sufficient to antagonize the side-effects of benzodiazepines. This route of administration may be useful when the intravenous route is not readily available.
Scheier, E., A. Siman, et al. (2017). "Intranasal ketamine proved
feasible for pain control in paediatric care and parental support was
high." Acta Paediatr
106(10): 1702.
Schoolman-Anderson, K., R. D. Lane, et al. (2018). "Pediatric emergency department triage-based pain guideline utilizing intranasal fentanyl: Effect of implementation." Am J Emerg Med 36(9): 1603-1607
BACKGROUND: Pain management guidelines in the emergency department (ED) may reduce time to analgesia administration (TTA). Intranasal fentanyl (INF) is a safe and effective alternative to intravenous opiates. The effect of an ED pain management guideline providing standing orders for nurse-initiated administration of intranasal fentanyl (INF) is not known. The objective of this study was to determine the impact of a pediatric ED triage-based pain protocol utilizing intranasal fentanyl (INF) on time to analgesia administration (TTA) and patient and parent satisfaction. METHODS: This was a prospective study of patients 3-17years with an isolated orthopedic injury presenting to a pediatric ED before and after instituting a triage-based pain guideline allowing for administration of INF by triage nurses. Our primary outcome was median TTA and secondary outcomes included the proportion of patients who received INF for pain, had unnecessary IV placement, and patient and parent satisfaction. RESULTS: We enrolled 132 patients; 72 pre-guideline, 60 post-guideline. Demographics were similar between groups. Median TTA was not different between groups (34.5min vs. 33min, p=.7). Utilization of INF increased from 41% pre-guideline to 60% post-guideline (p=.01) and unnecessary IV placement decreased from 24% to 0% (p=.002). Patients and parents preferred the IN route for analgesia administration. CONCLUSION: A triage-based pain protocol utilizing INF did not reduce TTA, but did result in increased INF use, decreased unnecessary IV placement, and was preferred by patients and parents to IV medication. INF is a viable analgesia alternative for children with isolated extremity injuries.
Schwagmeier, R., T. Oelmann, et al. (1996). "[Patient
acceptance of patient-controlled intranasal analgesia (PCINA)]."
Anaesthesist 45(3): 231-4.
Patient-controlled intravenous analgesia (i.v.-PCA) represents
the gold standard in the management of acute postoperative pain.
However, in many countries i.v.-PCA is rarely used. Recent clinical
studies demonstrated that intranasal fentanyl titration provides a rapid
and safe form and pain management. In the present study we investigated
patients' acceptance and assessment of patient-controlled intranasal
analgesia (PCINA) and compared it to intravenous PCA and the customarily
prescribed pain therapy. MATERIAL AND METHODS: After approval by the
local ethics committee and written informed consent, 79 ASA physical
status I or II patients were investigated on the first postoperative day
following orthopaedic surgery. The patients were allocated either to the
PCINA group (a maximum of 0.025 mg fentanyl over 6 min), to the i.v.-PCA
group (0.025 mg fentanyl bolus, lockout interval 6 min) or to a group of
patients who received the customarily prescribed pain management.
Following the 8-h investigation period, the patients were questioned
regarding their satisfaction with the pain therapy using a 6-point
rating scale (ranging from 1 = very good to 6 = not acceptable). The
patients were furthermore asked to name the advantages and disadvantages
of their pain management. RESULTS: Three patients in the i.v.-PCA group
had to be excluded due to pain at the injection site and one patient in
the PCINA group because of a surgical complication. Seventy-five
patients were finally included, 25 patients per group. No statistically
significant intergroup differences regarding age, weight, height and
initial pain intensity (evaluated by a 101-point numeric rating scale)
were demonstrated. The patients' satisfaction with the mode of pain
management was significantly higher in the PCINA (median "good")
and in the i.v.-PCA group (median "good") than in the group
who received the customarily prescribed pain management (median "satisfactory").
This difference was statistically significant (P = 0.0001). No
statistically significant difference was demonstrated between the PCINA
and i.v.-PCA groups. The patients in the PCINA and in the i.v.-PCA group
stated as main advantages the rapid onset of action and good pain relief
(n = 25 and n = 25, respectively), as well as their independence from
the doctor or nurse (n = 12 and n = 13). The main disadvantages were
pain on injection in the i.v.-PCA group and too frequent fentanyl
administrations in the PCINA group (n = 6). DISCUSSION: The results
demonstrate that the patients' satisfaction with PCINA is comparable to
that with i.v.-PCA. Both PCINA and i.v.-PCA were assessed as superior to
the customarily prescribed pain management (P = 0.0001). Patients'
acceptance of a given form of pain management is mainly related to its
efficiency. However, side effects such as pain on injection with i.v.-PCA,
or frequent opioid administration with PCINA, must be considered when
assessing a method of pain control. Patients' global assessment includes
both efficiency and side effects. PCINA represents an interesting
alternative non-invasive method for postoperative pain management.
Shrestha, R., S. Pant, et al. (2016). "Intranasal ketamine for the
treatment of patients with acute pain in the emergency department."
World J Emerg Med 7(1):
19-24.
BACKGROUND: Pain in the emergency department (ED) is common but
undertreated. The objective of this study was to examine the efficacy
and safety of intranasal (IN) ketamine used as an analgesic for patients
with acute injury with moderate to severe pain. METHODS: This study was
a cross sectional, observational study of patients more than 8 years old
experiencing moderate to severe pain [visual analog score (VAS) >50 mm].
The initial dose of IN ketamine was 0.7 mg/kg with an additional dose of
0.3 mg/kg if VAS was more than 50 mm after 15 minutes. Pain scores and
vital signs were recorded at 0, 15, 30 and 60 minutes. Side-effects,
sedation level and patient's satisfaction were also recorded. The
primary outcome was the number of patients achieving >/= 20 mm
reductions in VAS at 15 minutes. Other secondary outcome measures were
median reduction in VAS at 15, 30 and 60 minutes, changes of vital
signs, adverse events, satisfaction of patients, and need for additional
ketamine. RESULTS: Thirty-four patients with a median age of 29.5 years
(IQR 17.5-38) were enrolled, and they had an initial median VAS of 80 mm
(IQR 67-90). The VAS decreased more than 20 mm at 15 minutes in 27 (80%)
patients. The reduction of VAS from baseline to 40 mm (IQR 20-40), 20 mm
(IQR 14-20) and 20 mm (IQR 10-20) respectively at 15, 30 and 60 minutes
(P<0.001). No critical changes of vital signs were noted and adverse
effects were mild and transient. CONCLUSION: This study showed that IN
ketamine is an analgesic choice for patients with acute injury in
moderate to severe pain in an overcrowded and resource limited ED.
Sindhur, M., H. Balasubramanian, et al. (2020). "Intranasal
fentanyl for pain management during screening for retinopathy of
prematurity in preterm infants: a randomized controlled trial." J
Perinatol 40(6): 881-887.
OBJECTIVE: To study the efficacy of intranasal fentanyl as an adjunct for pain management during screening for retinopathy of prematurity (ROP) in preterm infants. STUDY DESIGN: In this single center, double blinded, randomized controlled trial, preterm neonates between 30 and 34 weeks postmenstrual age received either intranasal fentanyl (2 mcg/kg) or intranasal normal saline through a mucosal atomization device 5 min prior to the first ROP-screening examination. Both the groups received standard pain relief strategies (oral sucrose, 0.5% proparacaine eye drops and physical containment). The primary outcome was premature infant pain profile-revised (PIPP-R) score during the screening. RESULTS: A total of 111 infants were enrolled. PIPP-R score during the retinal examination was significantly lower in the fentanyl group (8.3 versus 11.5, mean difference: 3.2 (2.46-4.06), P < 0.001). There was no significant difference in the incidence of adverse effects. CONCLUSION: Intranasal fentanyl significantly reduced the pain associated with retinal examination without increasing the risk of respiratory depression. Large RCTs are required to verify the efficacy and safety of intranasal fentanyl for acute procedural pain in neonates. CLINICAL TRIAL REGISTRATION: CTRI/2017/12/011016.
Sin, B., I. Jeffrey, et al. (2019). "Intranasal Sufentanil Versus
Intravenous Morphine for Acute Pain in the Emergency Department: A
Randomized Pilot Trial." J Emerg Med
56(3): 301-307.
BACKGROUND: Patients in the United States frequently seek medical attention in the emergency department (ED) to address their pain. The intranasal (i.n.) route provides a safe, effective, and painless alternative method of drug administration. Sufentanil is an inexpensive synthetic opioid with a high therapeutic index and rapid onset of action, making it an attractive agent for management of acute pain in the ED. OBJECTIVE: The objective of our study was to evaluate the safety and efficacy of i.n. sufentanil as the primary analgesic for acute pain in the ED. METHODS: This was a single-center, prospective, randomized, double-blind, double-dummy, controlled trial that evaluated the use of i.n. sufentanil 0.7 mug/kg via mucosal atomizer device vs. intravenous morphine 0.1 mg/kg in adult patients who presented to the ED with acute pain. The primary outcome was patient's pain score at 10 min after administration of intervention. Secondary outcomes were adverse events, the need for rescue analgesia, and patient satisfaction after treatment. RESULTS: Thirty patients were enrolled in each group. There was no significant difference in pain scores at 10 min after administration of intervention (sufentanil: 2.0, interquartile range = 2.0-3.3 vs. morphine: 3.0, interquartile range = 2.0-5.3, p = 0.198). No serious adverse events were reported. Rescue analgesia was not requested in either group. No significant difference in median satisfaction scores was found. CONCLUSION: The use of i.n. sufentanil at 0.7 mug/kg/dose resulted in rapid and safe analgesia with comparable efficacy to i.v. morphine for up to 30 min in patients who presented with acute pain in the ED.
Singh, R., A. Pareek, et al. (2016). "Post-operative analgesic efficacy
of fentanyl via different routes – A comparative study of nebulisation,
intranasal and intravenous routes." IAIM
3(6): 16-22.
Background: Pain is main post operative adverse outcomes causing patient
distress, prolonging hospital stay, and increasing the incidence of
admissions after surgery. Study was done to assess and compare the
post-operative analgesic effects of fentanyl via nebulisation,
intranasal and intravenous routes to provide better analgesia,
anxiolysis and sedation to the patient. Materials and methods: After
approval from ethical committee of SPMC, Bikaner and written informed
valid consent from patients, sixty patients of either sex belonging to
ASA class I and II, were randomised into three group (Group I -
Nebulised Fentanyl, Group II - Intranasal Fentanyl, Group III -
Intravenous Fentanyl). With all aseptic precaution, subarachnoid block
was instilated via 23/25 gauze spinal needle by injecting sufficient
dose of bupivacaine heavy 5% to achieve an adequate sensory and motor
block for the proposed surgery. When patient complained pain 1st time,
fentanyl was given via nebulisation in group I, intranasal in group II,
and intravenous in group III with dose 4 mcg/kg, 1.5 mcg/kg, 2 mcg/kg
respectively. Patients were assessed for pain by VAS score. For
statistical data, SPSS 10.0 software was used. Results: In present
study, Ramsay sedation score, patient satisfaction score and duration of
analgesia was better in group II as compared to group I and III. Group
III had lesser time of onset of analgesia in comparison to group II and
I respectively.
Singla, N., S. Singla, et al. (2010).
"Intranasal ketorolac for acute postoperative pain." Curr Med Res
Opin 26(8): 1915-1923.
BACKGROUND: Efficacy and tolerability of intranasal ketorolac (SPRIX(R)) was assessed in abdominal surgery patients. METHODS: Adult patients were randomly assigned to receive ketorolac 31.5 mg (n = 214) or placebo (n = 107) every 6 hr after surgery for 48 hr, then up to 4 times/day for up to 5 days. Morphine sulfate via patient controlled analgesia was available in both groups as needed. RESULTS: Least square mean 6 hr summed pain intensity difference scores were significantly greater in the ketorolac group indicating better analgesic efficacy compared to placebo (117.4 vs. 89.9, p = 0.032; difference 27.6, 95% CI 2.5-52.7). Pain intensity difference indicated significantly better pain relief in the ketorolac group at 20 min after the first dose (p = 0.01). Morphine use over 48 hr decreased 26% in the ketorolac group compared to placebo (p = 0.004). Day 1 global pain control scores were significantly higher in the ketorolac group compared to placebo (p = 0.009). Quality of analgesia was rated significantly higher (p = 0.009) in the ketorolac group by 20 min after first dose. Adverse event and serious adverse event incidences were similar in both groups. Rhinalgia and nasal irritation, generally mild and transient in nature, occurred more frequently in the ketorolac group. CONCLUSION: Intranasal ketorolac was well tolerated and provided effective pain relief within 20 minutes with reduced opioid analgesia use. While IN ketorolac was assessed in an inpatient, conventional surgery setting in this study, IN ketorolac use may have more relevance for use in outpatient settings and ambulatory surgery or fast-track surgical procedures.
Skopp, G., B. Ganssmann, et al. (1997). "Plasma
concentrations of heroin and morphine-related metabolites after
intranasal and intramuscular administration." J Anal Toxicol
21(2): 105-11.
The disposition of heroin and its metabolites was investigated in
four healthy male volunteers following intranasal administration of 6
and 12 mg heroin hydrochloride. In addition, two doses of 6 mg heroin
hydrochloride were injected intramuscularly for comparison of
pharmacokinetic parameters. Serum samples were analyzed for heroin,
6-acetylmorphine, and morphine by solid-phase extraction-gas
chromatography-mass spectrometry. The concentration of morphine
glucuronides was determined by high-performance liquid chromatography
based on the native fluorescence of the conjugates. Major findings were
rapidly rising and declining terminal phases for heroin and
6-acetylmorphine and slowly declining phases of morphine and metabolites
after both routes of administration. The area under the curve values of
morphine-3-glucuronide depended on dose but not on route of
administration. The apparent terminal half-lives of
morphine-3-glucuronide ranged from 2.2 to 5.2 h for intranasally
administered heroin and were 3.0 and 1.7 h for the intramuscularly
applied drug. A mean morphine-3-glucuronide-heroin area-under-curve
ratio of 93 for the intranasal route as compared with 38 for the
intramuscular route demonstrated that circulating amounts of heroin were
about half the size after intranasal administration of the same dose.
Sokoloff, C., R. Daoust, et al. (2014). "Is adequate pain relief and
time to analgesia associated with emergency department length of stay? A
retrospective study." BMJ Open
4(3): e004288.
Steenblik, J., M. Goodman, et al. (2012). "Intranasal sufentanil
for the treatment of acute pain in a winter resort clinic."
Am J Emerg Med.
INTRODUCTION: Painful extremity injuries are common patient
complaints in resort clinics, urgent care clinics, and emergency
departments. We hypothesized that intranasal (IN) sufentanil could
provide rapid, noninvasive, effective pain relief to patients presenting
with acute extremity injuries. METHODS: This was an unblinded,
nonrandomized, observational study that enrolled a convenience sample of
patients presenting to a university-affiliated ski clinic with acute
moderate to severe pain associated with a traumatic injury between the
months of January and March 2011. Patients were excluded if they
reported an allergy to sufentanil or had hypoxia, significant head
injury, or hypotension. Nurses administered IN sufentanil using an IN
atomizer device. The nurse recorded patient-reported pain scores (0-10
scale) on arrival and at 10, 20, and 30 minutes after administration of
sufentanil. RESULTS: During the study period, 40 patients were enrolled;
75% were men. The average age was 32 years (range, 16-60 years). The
average dose of sufentanil was 37.7 mug. Five patients (12.5%) were
given additional IN analgesia. Average pain on arrival was 9 (on a
10-point scale), and the mean reduction in pain scores was 4.7 (95%
confidence interval [CI], 3.67-5.57) at 10 minutes, 5.79 (95% CI,
4.81-6.77) at 20 minutes, and 5.74 (95% CI, 4.72-6.76) at 30 minutes.
CONCLUSION: In this limited observational trial, IN sufentanil provided
rapid, safe, and noninvasive pain relief to patients presenting with
acute traumatic extremity injuries. Given the ease of administration,
this may serve as a viable option for use in other settings, such as
urgent care clinics and emergency departments.
Stephen, R., E. Lingenfelter, et al. (2012). "Intranasal sufentanil
provides adequate analgesia for emergency department patients with
extremity injuries." J Opioid Manag
8(4): 237-241.
Stoker, D. G., K. R. Reber, et al. (2008). "Analgesic
efficacy and safety of morphine-chitosan nasal solution in patients with
moderate to severe pain following orthopedic surgery." Pain Med
9(1): 3-12.
Introduction. Parenteral opioids are the standard of care for
treating moderate to severe postsurgical pain. This randomized,
double-blind, dose-ranging study compared the safety and efficacy of
intranasal (IN) morphine with intravenous (IV) morphine and placebo.
Methods. In total, 187 postbunionectomy patients with moderate to severe
pain were randomized to receive IN morphine 3.75 mg, 7.5 mg, 15 mg, or
30 mg, IV morphine 7.5 mg, or placebo in the single-dose phase and IN
morphine 7.5 mg or 15 mg thereafter. The primary outcome was a
dose-response assessment for total pain relief based upon visual analog
scales. Secondary endpoints included pain intensity, pain relief,
patient global evaluation, and time to rescue medication. Safety
assessments included adverse events and nasal examination. Results. A
statistically significant linear dose response was observed over the IN
morphine dose range for 4-hour total pain relief. Patients reported
statistically significant pain relief and pain intensity differences
following IV morphine and IN morphine at doses of 7.5 mg and greater
within 30 minutes postdose, compared with placebo. Median times to
rescue medication were 124 and 140 minutes for IN morphine 7.5 mg and 15
mg dosage groups, respectively, and 130 minutes for IV morphine. Local
adverse events associated with IN morphine were transient and mostly
mild (bad taste, nasal congestion, throat irritation, and sneezing).
Systemic adverse events, regardless of route of administration, were
dose-related and consistent with expected opioid effects. Conclusions.
By multiple measures of pain intensity and pain relief, IN morphine
provides sustained analgesia in postsurgical patients and thus may offer
a safe and less invasive alternative to IV morphine.
Striebel, H. W., B. Bonillo, et al. (1995).
"Self-administered intranasal meperidine for postoperative pain
management." Can J Anaesth 42(4): 287-91.
Recent studies have demonstrated that intranasal is comparable to
intravenous opioid titration in its pain-relieving effect. In these
studies, however, the intranasal opioid titration was performed by the
investigator, and the treatment period was two hours or less. The
purpose of this randomized, prospective study was to investigate whether
intranasal opioid administration by the patients themselves for a
prolonged postoperative period may be regarded as a therapeutic
alternative for postoperative pain management. Forty-four orthopaedic
patients were studied over a 12-hr period on the first day after
surgery. Twenty-two had free access to intranasal meperidine (nasal
group) and were allowed to administer six intranasal puffs (27 mg per
dose). The next self-administration was only permitted after a delay of
at least ten minutes. Another 22 patients received intermittent
subcutaneous meperidine injections (25 or 50 mg) on request (sc group).
Pain intensity was recorded at 30-min intervals with the aid of the
101-point numerical rating scale. The pain score was lower in the nasal
than in the sc group at the 30, 150 to 330, 420 to 480 and 540 to 600
min measuring points (P = < 0.05). The meperidine requirement was
112.9 +/- 81.3 mg in the nasal and 103.4 +/- 41.5 mg in the sc group
(NS). Two patients in each group complained of nausea and vomiting.
Thirteen of the 21 nasal and nine of the 15 sc patients who completed
the final questionnaire rated the pain management as excellent or good
(NS).(ABSTRACT TRUNCATED AT 250 WORDS)
Striebel, H. W., D. Koenigs, et al. (1992).
"Postoperative pain management by intranasal demand-adapted fentanyl
titration." Anesthesiology 77(2): 281-5.
The aim of the present study was to investigate whether
intranasal administration of fentanyl allows a demand-adapted
postoperative opioid titration. Forty-two patients who had undergone
surgery for lumbar intervertebral disk protrusion were included in a
prospective randomized double-blind study. When complaining about
intense pain, 22 patients received six sprays of fentanyl (0.027 mg)
intranasally and 6 ml sodium chloride 0.9% intravenously and 20 patients
received six sprays of sodium chloride 0.9% intranasally and 6 ml of a
diluted fentanyl solution (0.027 mg) intravenously. In both groups,
these doses were repeated every 5 min until the patients were free of
pain or refused further analgesic. Before the beginning of opioid
titration and then every 10 min for at least 1 h, pain was evaluated
with the aid of a 101-point numerical rating scale and a verbal rating
scale. Blood pressure, heart rate, arterial hemoglobin oxygen
saturation, respiratory rate, and side effects were recorded. All
patients were satisfied with the pain reduction achieved. The total
fentanyl dose was 0.073 mg (range 0.027-0.162) in the intravenous group
and 0.11 mg (range 0.027-0.243) in the intranasal group. The onset of
action after intranasal application was nearly as fast as after
intravenous titration. The pain reduction achieved was comparable in
both groups. Only at the (10-), 20- and 30-min measurement points was
the pain intensity significantly lower in the intravenous than in the
intranasal group. One patient of the intravenous group showed a decrease
in arterial hemoglobin oxygen saturation to less than 90%. Other serious
side effects were not observed.(ABSTRACT TRUNCATED AT 250 WORDS)
Striebel, H. W., T. Olmann, et al. (1996).
"Patient-controlled intranasal analgesia (PCINA) for the management of
postoperative pain: a pilot study." J Clin Anesth 8(1): 4-8.
STUDY OBJECTIVE: To compare patient-controlled intranasal
analgesia (PCINA) for post-operative pain management with ward-provided
pain therapy. DESIGN: Randomized, prospective pilot study. SETTING:
University medical center. PATIENTS: 20 ASA status I and II orthopedic
patients. INTERVENTIONS: On the first postoperative day, 20 patients
were randomized to receive either PCINA for 4 hours followed by 5 hours
of ward-provided pain therapy (Group 1; n = 10) or ward-provided pain
therapy for 5 hours followed by 4 hours of PCINA (Group 2; n = 10). The
PCINA device used permits self-administration up to a maximum 0.025 mg
dose of fentanyl every 6 minutes. Pain intensity (101-point numerical
rating scale) and vital signs, as well as possible side effects, were
registered at 30-minute intervals. MEASUREMENTS AND MAIN RESULTS: Within
30 minutes after the start of PCINA, pain intensity had decreased
significantly in both groups. At the 60, 150, 210, 240, 270, 390, 420,
and 480 minute measuring points, there was a significant intergroup
difference in pain intensity, the level being significantly lower in the
PCINA period. The handling of the PCINA device presented no problem to
any patient. The PCINA fentanyl requirement was 0.415 +/- 0.083 mg
(Group 1) and 0.408 +/- 0.06 mg (Group 2), respectively (NS). The
ward-provided pain therapy included pethidine, tramadol, metamizole,
acetaminophen, codeine, and diclofenac alone or in combination. Patient
satisfaction was greater with PCINA than with ward-provided pain therapy
(p < 0.0005). CONCLUSIONS: PCINA provides an adequate, noninvasive
mode of postoperative pain management. The PCINA device is easy to
handle and offers new perspectives in the management of postoperative
pain.
Striebel, H. W., J. Pommerening, et al. (1993).
"Intranasal fentanyl titration for postoperative pain management in an
unselected population." Anaesthesia 48(9): 753-7.
A randomized, double-blind study was undertaken to investigate
the suitability of intranasally administered fentanyl for postoperative
pain management under routine conditions in an unselected population.
For postoperative pain relief, patients received either 0.027 mg
fentanyl intranasally and sodium chloride 0.9% intravenously (intranasal
group, n = 53) or sodium chloride 0.9% intranasally and 0.027 mg
fentanyl intravenously (intravenous group, n = 59). These doses were
repeated every 5 min until the patients were free of pain or refused
further analgesia. Pain severity was evaluated before beginning opioid
titration and 5, 10, 15, 20, 30, 40, 50, 60, 70 and 80 min thereafter.
Adequate pain relief was achieved in 52 of 53 patients in the intranasal
and in all patients in the intravenous group. Pain intensities evaluated
on a 101-point numerical rating scale as well as on a verbal rating
scale decreased significantly in both study groups within 5 min. At the
15 min measurement point, numerical rating scale pain intensity and at
the 10 and 20 min point, verbal rating scale pain intensity was
significantly lower in the intravenous group. The incidence of side
effects was low in both groups and no patient complained of intranasal
pain. Intranasally administered fentanyl would appear to be suitable for
the management of postoperative pain.
Striebel, W. H., J. Malewicz, et al. (1993).
"Intranasal meperidine titration for postoperative pain relief."
Anesth Analg 76(5): 1047-51.
A prospective, randomized, double-blind study investigating the
efficacy of intranasal meperidine as compared with intravenous (i.v.)
administration for postoperative pain relief is described. The study was
limited to the initial titration of pain relief during a 2-h period
immediately after surgery. Sixty women having undergone a hysterectomy
were studied. Initially and when complaining of a pain intensity > or =
40 on the 101-point numerical rating scale (NRS), 30 patients received 6
sprays (27 mg) meperidine intranasally and simultaneously 6 mL NaCl 0.9%
i.v. (nasal group); another 30 patients received 6 sprays of NaCl 0.9%
intranasally and 6 mL of a diluted meperidine solution (27 mg) i.v.
(intravenous group). Patients already having a pain reduction < 40 on
the 101-point NRS, received half of the above dose. Meperidine was
repeated every 5 min until the patients were pain free or refused
further analgesic. Before the onset of meperidine titration and at 5- to
10-min intervals for 2 h thereafter, pain was evaluated with a 101-
point NRS and a verbal rating scale. Within 20 and 35 min the pain
scores evaluated by the NRS and verbal rating scale decreased in the
intravenous and nasal group to a median of zero. The total dose of
meperidine was 76.5 mg (range, 40.5-135.0) in the intravenous group and
104.4 mg (range, 27-135.0) in the nasal group (P < 0.05). One patient in
each group showed a brief decrease in arterial hemoglobin oxygen
saturation to < 90%. No patient complained of pain or burning in the
nose.(ABSTRACT TRUNCATED AT 250 WORDS)
Tanguay, A., J. Lebon, et al. (2020). "Intranasal Fentanyl
versus Subcutaneous Fentanyl for Pain Management in Prehospital Patients
with Acute Pain: A Retrospective Analysis." Prehosp Emerg Care
24(6): 760-768.
Objective: Retrospective analysis evaluating and comparing the feasibility, effectiveness and safety of intranasal fentanyl (INF) and subcutaneous fentanyl (SCF) for pain management of patients with acute severe pain in a rural/suburban Emergency Medical Services (EMS) system. Methods: Pre- and post-pain management data of all patients (aged >/=14 years) who were transported to the emergency department (January 2015-August 2017) were extracted from EMS and online medical control center records, and compared for groups receiving INF or SCF. Kaplan-Meier analysis and the log-rank test were used to describe and compare the percentage of patients in both groups who experienced relief according to their clinically significant pain relief score. Subgroup analysis was performed by patient age (<70 years, >/=70 years). Results: 94.6% (SCF = 94.8%; INF = 94.4%) of patients successfully received fentanyl and 82.7% (SCF = 81.2%; INF = 84.0%) had complete data and were included in the analysis. No difference was observed in time to administration or in the effectiveness of INF and SCF, and neither route of administration resulted in major adverse events that required intervention by paramedics. Upon subgroup analysis, INF patients >/=70 years were more likely to experience relief compared to those <70 years. Conclusion: This retrospective analysis of prehospital patients in the Chaudiere-Appalaches EMS system demonstrates that both IN and SC are feasible, effective and safe routes for administering fentanyl. The observed effects of INF were found to be greater among patients >/=70 years. Further research is required to compare these routes with more conventional methods of pain management.
Telfer, P. T., C. Lahoz, et al. (2009). "Intranasal diamorphine for acute sickle cell pain." Arch Dis Child.
The painful crisis is the commonest acute presentation of sickle cell disease (SCD), yet effective pain control in hospital is often delayed, inadequate and dependent on injected opiates. Intranasal diamorphine (IND) has been used in paediatric emergency departments for management of acute pain associated with fractures, but the analgesic effect is short-lived. We evaluated its efficacy and safety when given in combination with intravenous or oral morphine for rapid analgesia for children presenting to our emergency department with painful crisis of SCD. In phase one, nine patients received IND plus intravenous morphine. In phase two, thirteen received IND plus oral morphine. There was a rapid improvement in pain score, the proportions in severe pain at t=0,15,30 and 120 minutes in Phase 1 were 78%, 11%, 0% and 11%; in Phase 2 , 77%, 30%,15% and 0%. There were no serious side effects and questionnaire scores indicated that children found IND effective and acceptable. IND can be recommended for acute control of sickle pain in children presenting to hospital.
Telfer, P., N. Bahal, et al. (2014). "Management of the acute painful
crisis in sickle cell disease- a re-evaluation of the use of opioids in
adult patients." Br J Haematol
166(2): 157-164.
Management of the acute painful crisis (APC) of sickle cell disease (SCD)
remains unsatisfactory despite advances in the understanding and
management of acute pain in other clinical settings. One reason for this
is an unsophisticated approach to the use of opioid analgesics for pain
management. This applies to haematologists who are responsible for
developing acute sickle pain management protocols for their patients,
and to health care staff in the acute care setting. The objective of
this article is to evaluate the evidence for use of opioids in APC
management. We have highlighted the possibilities for improving
management by using alternatives to morphine, and intranasal (IN) or
transmucosal routes of administration for rapid onset of analgesia in
the emergency department (ED). We suggest how experience gained in
managing acute sickle pain in children could be extrapolated to
adolescents and young adults. We have also questioned whether patients
given strong opioids in the acute setting are being safely monitored and
what resources are required to ensure efficacy, safety and patient
satisfaction. We also identify aspects of care where there are
significant differences of opinion, which require further study by
randomized controlled trial.
Thomas, S. H. (2007). "Fentanyl in the prehospital
setting." Am J Emerg Med 25(7): 842-3.
Toussaint, S., J. Maidl, et al. (2000).
"Patient-controlled intranasal analgesia: effective alternative to
intravenous PCA for postoperative pain relief." Can J Anaesth
47(4): 299-302.
PURPOSE: To investigate whether the nasal route for fentanyl
administration in patient-controlled analgesia (PCA) provides as
effective postoperative analgesia as intravenous PCA. METHODS:
Patient-controlled intranasal or intravenous analgesia with fentanyl was
investigated in 48 patients (ASA I-III) on the day of surgery
(orthopedic, abdominal or thyroid) in a prospective, randomized,
double-blind, double-dummy study. Fentanyl was given in a bolus of 25
microg for intranasal and 17.5 microg for i.v. PCA, lockout interval six
minutes. The first requested dose was doubled in both groups. Pain
intensity (101-point numerical rating scale) and vital parameters were
observed at 11 measurement points during the 240 min study. Patients
were asked for side effects at every measurement point and for their
satisfaction at the end of the study by the same investigator (J.M.).
RESULTS: Onset of analgesia, the first reduction in pain intensity on
the numerical rating scale, was 21 +/- 11 min (range 15-45 min) in
intranasal and 22 +/- 16 min (range 15-90 min) in i.v. PCA. Pain
intensity was reduced from 55 +/- 11 to 11 +/- 10 in the intranasal
group and from 53 +/- 8 to 11 +/- 6 in the i.v. PCA group. Vital
parameters remained stable and side effects were comparable in both
groups. The judgement "excellent" or "good" was
given by 21 of 23 patients treated intranasally and 24 of 25 patients
treated intravenously. CONCLUSION: Intranasal PCA with fentanyl was an
effective alternative to i.v. PCA in postoperative patients.
Tsze, D. S., Y. M. Vitberg, et al. (2014). "Treatment of tetralogy of
Fallot hypoxic spell with intranasal fentanyl." Pediatrics
134(1): e266-269.
Turner, A. L., S. Shandley, et al. (2020). "Intranasal
Ketamine for Abortive Migraine Therapy in Pediatric Patients: A
Single-Center Review." Pediatr Neurol 104: 46-53.
BACKGROUND: Ketamine has recently emerged as a promising therapeutic
alternative for abortive migraine therapy, likely secondary to
N-methyl-d-aspartate antagonism. Most reports examine adults and the
intravenous route. Fewer utilize intranasal administration or pediatric
populations. Given the limited evidence for intranasal ketamine in
pediatric migraine populations, we retrospectively reviewed our
experience to further characterize safety and efficacy of intranasal
ketamine in this population. METHODS: A retrospective review in a
free-standing, pediatric medical center was performed examining the
utilization of intranasal ketamine at 0.1 to 0.2 mg/kg/dose up to five
doses in pediatric migraineurs. Pain scores (scale = 0 to 10) were
recorded at baseline and after each dose. Response was characterized as
pain score reduction to 0 to -3 and/or reduction of at least 50%.
RESULTS: Twenty-five encounters (25 of 34; 73.5%) were responders (mean
pain score reduction of -7.2 from admission to treatment completion).
Overall pain reduction from admission to discharge in the entire study
population was 66.1%. Side effects were mild and transient. CONCLUSIONS:
Our experience with intranasal ketamine has promising outcomes in both
pain relief and side effect minimization. When other therapeutic options
are unavailable, practitioners should consider intranasal ketamine.
Ueda, W. (2001). "Rhinorrhea by nasal fentanyl."
Anesthesiology 95(3): 812-3.
Vercauteren, M., E. Boeckx, et al. (1988).
"Intranasal sufentanil for pre-operative sedation." Anaesthesia
43(4): 270-3.
Sufentanil, a short-acting and potent narcotic agent, was studied
as a premedicant administered by the nasal route. A total dose of 5
micrograms appeared to be too low, while either 10 or 20 micrograms was
very effective in producing sedation. Side effects were minor. There
appeared to be no differences between nose drops and spray. In a further
study, sufentanil nose drops were compared with saline 0.9% in a
double-blind fashion. Sedation of rapid onset but of limited duration
was observed in the majority of patients who received sufentanil.
Ward, M., G. Minto, et al. (2002). "A comparison of
patient-controlled analgesia administered by the intravenous or
intranasal route during the early postoperative period." Anaesthesia
57(1): 48-52.
Intranasal administration of lipophilic opioids has been shown to
be an effective method of administration which is devoid of major side-
effects. Whether it is as effective as intravenous administration for
patient-controlled analgesia (PCA) has been investigated for fentanyl
and pethidine, but not for diamorphine. This study reports a randomised
controlled trial designed to compare the effectiveness of diamorphine
administered as PCA utilising either the intranasal or intravenous
routes. We investigated 52 consecutive patients undergoing primary lower
limb joint replacement surgery. Patients were randomly allocated to
receive PCA diamorphine, administered either intravenously (0.5 mg
bolus, 3 min lockout) or intranasally (1.0 mg bolus, 3 min lockout).
Pain was assessed using a Visual Analogue Score (VAS) at rest and on
movement on five occasions over the first 36 h postoperatively. The
results demonstrated that patients in the intranasal PCA group had
significantly higher VAS scores than the intravenous group, both at rest
(intranasal median 35.5 vs. intravenous median 20; p = 0.030) and on
movement (intranasal median 64 vs. intravenous median 50; p = 0.016).
However, significantly fewer patients in the intranasal group compared
with the intravenous group suffered episodes of vomiting (intranasal
0/24 vs. intravenous 6/24 patients; p = 0.022). We suggest that if a
maximal reduction in pain score is considered the goal of PCA
management, the intravenous route is preferable to the intranasal route.
Westin, Ue, et al. (2006). "Direct nose-to-brain
transfer of morphine after nasal administration to rats." Pharm Res
23(3): 565-72.
PURPOSE: The aim of this study was to quantify the olfactory
transfer of morphine to the brain hemispheres by comparing brain tissue
and plasma morphine levels after nasal administration with those after
intravenous administration. METHODS: Morphine (1.0 mg/kg body weight)
was administered via the right nostril or intravenously as a 15-min
constant-rate infusion to male rats. The content of morphine and its
metabolite morphine-3-glucuronide in samples of the olfactory bulbs,
brain hemispheres, and plasma was assessed using high-performance liquid
chromatography, and the areas under the concentration-time curves (AUC)
were calculated. RESULTS: At both 5 and 15 min after administration,
brain hemisphere morphine concentrations after nasal administration were
similar to those after i.v. administration of the same dose, despite
lower plasma concentrations after nasal administration. The brain
hemispheres/plasma morphine AUC ratios for the 0-5 min period were thus
approximately 3 and 0.1 after nasal and i.v. administration,
respectively, demonstrating a statistically significant early
distribution advantage of morphine to the brain hemispheres via the
nasal route. CONCLUSION: Morphine is transferred via olfactory pathways
to the brain hemispheres, and drug transfer via this route significantly
contributes to the early high brain concentrations after nasal
administration to rats.
Williams, J. M., S. Schuman, et al. (2019). "Intranasal Fentanyl
and Midazolam for Procedural Analgesia and Anxiolysis in Pediatric
Urgent Care Centers." Pediatr Emerg Care.
OBJECTIVES: Intranasal fentanyl and midazolam use is increasing in the
acute care setting for analgesia and anxiolysis, but there is a lack of
literature demonstrating their use, alone or in combination, at
pediatric urgent care centers. METHODS: This retrospective study
investigated intranasal fentanyl and midazolam use at an urgent care
center located within Le Bonheur Children's Hospital and 2 affiliated
off-site centers from September 22, 2011, to December 30, 2015. Data
collected included patient demographics, initial fentanyl dose, initial
midazolam dose, type of procedure, and serious adverse drug reactions.
RESULTS: Of the 490 patients who met the inclusion criteria, 143
patients received intranasal fentanyl alone, 92 received intranasal
midazolam alone, and 255 received fentanyl in combination with
midazolam. The overall patient population was 50% male with a median
(range) age of 4.5 (0.2-17.9) years, and most patients were black at
57.1%. The median (range) initial intranasal fentanyl dose was 2.02
(0.99-4.22) mug/kg, and the median initial (range) intranasal midazolam
dose was 0.19 (0.07-0.42) mg/kg. In cases where fentanyl and midazolam
were administered in combination, the median (range) initial fentanyl
dose was 2.23 (0.6-4.98) mug/kg and median (range) initial midazolam
dose was 0.2 (0.03-0.45) mg/kg. There were no serious adverse drug
reactions reported. CONCLUSIONS: Intranasal fentanyl and midazolam when
administrated alone and in combination can provide analgesia and
anxiolysis for minor procedures in pediatric patients treated in the
urgent care setting.
Wilson, J. A., J. M. Kendall, et al. (1997).
"Intranasal diamorphine for paediatric analgesia: assessment of safety
and efficacy." J Accid Emerg Med 14(2): 70-2.
OBJECTIVE: To evaluate the safety and efficacy of intranasal
diamorphine as an analgesic for use in children in accident and
emergency (A&E). METHODS: A prospective, randomised clinical trial
with consecutive recruitment of patients aged between 3 and 16 years
with clinically suspected limb fractures. One group received 0.1 mg/kg
intranasal diamorphine, and the other group received 0.2 mg/kg
intramuscular morphine. At 0, 5, 10, 20, and 30 minutes pain scores,
Glasgow coma score, and peripheral oxygen saturations were recorded;
parental acceptability was assessed at 30 minutes. RESULTS: 58 children
were recruited, with complete data collection in 51 (88%); the median
summed decrease in pain score was better for intranasal diamorphine than
intramuscular morphine (9 v 8), though this was not significant (P =
0.4, Mann-Whitney U test). The episode was recorded as "acceptable"
in all parents whose child received intranasal diamorphine, compared
with only 55% of parents in the intramuscular morphine group (P <
0.0001, Fisher's exact test). There was no incidence of decreased
peripheral oxygen saturation or depression in the level of consciousness
in any patient. CONCLUSIONS: Intranasal diamorphine is an effective,
safe, and acceptable method of analgesia for children requiring opiates
in the A & E department.
Wolfe, T. (2007). "Intranasal fentanyl for acute
pain: techniques to enhance efficacy." Ann Emerg Med 49(5):
721-2.
Wong, P., F. D. Chadwick, et al. (2003). "Intranasal
fentanyl for postoperative analgesia after elective Caesarean section."
Anaesthesia 58(8): 818-9.
Yeaman, F., E.
Oakley, et al. (2013). "Sub-dissociative dose intranasal ketamine for
limb injury pain in children in the emergency department: A pilot
study." Emerg Med Australas 25(2): 161-167.
OBJECTIVE: The present study aims to conduct a pilot study examining the
effectiveness of intranasal (IN) ketamine as an analgesic for children
in the ED. METHODS: The present study used an observational study on a
convenience sample of paediatric ED patients aged 3-13 years, with
moderate to severe (>/=6/10) pain from isolated limb injury. IN ketamine
was administered at enrolment, with a supplementary dose after 15 min,
if required. Primary outcome was change in median pain rating at 30 min.
Secondary outcomes included change in median pain rating at 60 min,
patient/parent satisfaction, need for additional analgesia and adverse
events being reported. RESULTS: For the 28 children included in the
primary analysis, median age was 9 years (interquartile range [IQR]
6-10). Twenty-three (82.1%) were male. Eighteen (64%) received only one
dose of IN ketamine (mean dose 0.84 mg/kg), whereas 10 (36%) required a
second dose at 15 min (mean for second dose 0.54 mg/kg). The total mean
dose for all patients was 1.0 mg/kg (95% CI: 0.92-1.14). The median pain
rating decreased from 74.5 mm (IQR 60-85) to 30 mm (IQR 12-51.5) at 30
min (P < 0.001, Mann-Whitney). For the 24 children who contributed data
at 60 min, the median pain rating was 25 mm (IQR 4-44). Twenty (83%)
subjects were satisfied with their analgesia. Eight (33%) were given
additional opioid analgesia and the 28 reported adverse events were all
transient and mild. CONCLUSIONS: In this population, an average dose of
1.0 mg/kg IN ketamine provided adequate analgesia by 30 min for most
patients.
Yenigun, A., S. Yilmaz, et al. (2018). "Demonstration of analgesic
effect of intranasal ketamine and intranasal fentanyl for postoperative
pain after pediatric tonsillectomy." Int J Pediatr Otorhinolaryngol
104: 182-185.
OBJECTIVE: Tonsillectomy is one of the oldest and most commonly performed surgical procedure in otolaryngology. Postoperative pain management is still an unsolved problem. In this study, our aim is to demonstrate the efficacy of intranasal ketamine and intranasal fentanyl for postoperative pain relief after tonsillectomy in children. MATERIAL AND METHOD: This randomized-controlled study was conducted to evaluate the effects of intranasal ketamine and intranasal fentanyl in children undergoing tonsillectomy. Tonsillectomy performed in 63 children were randomized into three groups. Group I received: Intravenous paracetamol (10 mg/kg), Group II received intranasal ketamine (1.5 mg/kg ketamine), Group III received intranasal fentanyl (1.5 mcg/kg). The Children's Hospital of Eastern Ontario Pain Scale (CHEOPS) and Wilson sedation scale scores were recorded at 15, 30, 60 min, 2 h, 6hr, 12 h and 24 h postoperatively. Patients were interviewed on the day after surgery to assess the postoperative pain, nightmares, hallucinations, nausea, vomiting and bleeding. RESULTS: Intranasal ketamine and intranasal fentanyl provided significantly stronger analgesic affects compared to intravenous paracetamol administration at postoperative 15, 30, 60 min and at 2, 6, 12 and 24 h in CHEOPS (p < 0.05). Sedative effects were observed in three patients in the intranasal ketamine administration group. No such sedative effect was seen in the groups that received intranasal fentanyl and intravenous paracetamol in Wilson Sedation Scale (p < 0.05). Cognitive impairment, constipation, nausea, vomiting and bleeding were not observed in any of the groups. CONCLUSION: This study showed that either intranasal ketamine and intranasal fentanyl were more effective than paracetamol for postoperative analgesia after pediatric tonsillectomy. Sedative effects were observed in three patients with the group of intranasal ketamine. There was no significant difference in the efficacy of IN Ketamine and IN Fentanyl for post-tonsillectomy pain.
Zedie, N., D. W. Amory, et al. (1996). "Comparison of
intranasal midazolam and sufentanil premedication in pediatric
outpatients." Clin Pharmacol Ther 59(3): 341-8.
BACKGROUND: Intranasally administered midazolam was compared with
sufentanil as a premedicant for 60 patients, aged 1/2 to 6 years,
undergoing outpatient surgery of 2 hours or less. METHODS: Thirty
minutes before anesthetic induction (halothane in 50% nitrous
oxide/oxygen), patients were randomly assigned to receive either
intranasal midazolam (0.2 mg/kg) or sufentanil (2 microg/kg). A "blinded"
observer evaluated preoperative emotional state, response to
premedication, induction, and emergence from anesthesia and side
effects. RESULTS: Children who had not previously cried were more likely
to cry when midazolam was administered compared with sufentanil (71%
versus 20%, p = 0.0031). Of 31 midazolam patients, 20 experienced nasal
irritation. Approximately 15 to 20 minutes after drug administration,
most patients in both groups could be comfortably separated from their
parents. The sufentanil group appeared to be more sedated and more
cooperative during induction of anesthesia. Vital signs and oxygen
saturation did not change significantly with either medication before or
after surgery, although two sufentanil patients had a moderate reduction
in ventilatory compliance after anesthetic induction. Sufentanil was
associated with more nausea and vomiting than midazolam (34% versus 6%,
p < 0.02). CONCLUSION: Both intranasal midazolam and sufentanil
provide rapid, safe, and effective sedation in small children before
anesthesia for ambulatory surgery. Sufentanil provided somewhat better
conditions for induction and emergence. Midazolam causes more nasal
irritation during instillation, and sufentanil causes more postoperative
nausea and vomiting. Both drugs enabled patients to be separated from
their parents with a minimum of distress. Patients in the midazolam
group were discharged approximately 40 minutes earlier (p <0.005).
Zeppetella, G. (2000). "An assessment of the safety,
eff icacy, and acceptability of intranasal fentanyl citrate in the
management of cancer-related breakthrough pain. A pilot study." J
Pain Symptom Manage 20(4): 253-8.
The effects of intranasal fentanyl citrate (INFC) were assessed
in 12 hospice inpatients with cancer-related breakthrough pain. Patients
received 20 &mgr;g of fentanyl citrate and were asked to rate their
pain using a visual analogue scale (VAS) before INFC, then after 3, 5,
10, 15, 30, 45, and 60 minutes. Eight patients (66%) had reductions in
pain scores, four within 5 minutes and seven within 10 minutes of taking
INFC. Ratings for INFC were very good (5 = 42%), good (3 = 25%),
moderate (1 = 8%), and bad (3 = 25%). In comparison to oral morphine,
INFC was better (6 = 50%), the same (3 = 25%), or worse (3 = 25%). Nine
patients (75%) said they would continue to use INFC. Of the three
patients who did not experience a positive result, two were taking
relatively higher baseline opioid doses and one was found to have a
fracture. No systemic adverse events were noted; two patients reported
nasal itching or discomfort on first use that disappeared with repeated
use. Intranasal fentanyl citrate appears safe and well tolerated by
these patients. Randomized placebo-controlled and dose-ranging studies
are required to confirm these findings.
Zeppetella, G. (2000). "Nebulized and intranasal
fentanyl in the management of cancer-related breakthrough pain."
Palliat Med 14(1): 57-8.