Therapeutic
Intranasal Drug DeliveryFeatured new articles related to intranasal drug delivery:
July-September 2012
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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.
BACKGROUND: In emergency medicine, the ability to
provide rapid, adequate pain control without high resource utilization
is ideal. In this study, the efficacy of intranasal sufentanil in
emergency department (ED) patients with acute distal extremity injury
was evaluated. METHODS: A nonrandomized, open-label dose trial to
determine safety and efficacy of intranasal sufentanil in patients with
a distal extremity injury who presented to the ED with moderate to
severe pain was conducted. Vital signs, pain scores, Ramsay sedation
score, and any side effects during a 30-minute observation period after
medication administration were recorded. Patients, nurses, and
physicians completed satisfaction surveys. RESULTS: Fifteen ED patients
with acute extremity injuries agreed to participate in the study and
received a dose of 0.5 mg/kg of sufentanil intranasally. The average
pain score decreased 4.3 points (from 7.8 to 3.5). Eight patients
reported a final pain score of #3. The most common side effect was mild
dysphoria. Patients, physicians, and nurses reported high average
satisfaction scores. CONCLUSION: Intranasal sufentanil resulted in a
significant clinical reduction in patients' reported pain without
serious side effects. This medication and administration route
demonstrated promise for potential use in the ED.
Web site Editorial comments:
Using sufentanil, an synthetic opiate 8-10 times more potent than fentanyl these authors very successfully reduced pain in adult patients suffering from orthopedic trauma. The mean drop in pain scores was 4.3 points (from 7.8 to 3.5) with over half the patients scores less than 3 (mild pain). Likert satisfaction score for patients were 4.5. Minimal sedation, rare drop in oxygen saturation and a fair amount of "loopy, fuzzy, floaty, whoozy" side effects were noted. The authors point out that sufentanil's potency, volume of delivery high therapeutic index and efficacy make it an ideal drug for nasal drug delivery in adults. As an aside we also use this therapy often for procedural pain control with mild sedation to I&D abscesses with very good results. It is also quite inexpensive as it is generic and there is very little nursing effort needed to provide this therapy. Again I advise pulse oximetry despite this research data - the elderly tend to drop their oxygen saturations into the 85-90% range frequently and within a few minutes of delivery.
Pubmed link: http://www.ncbi.nlm.nih.gov/pubmed/22941851
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Thakker, A. and P. Shanbag (2012). "A randomized
controlled trial of intranasal-midazolam versus intravenous-diazepam for
acute childhood seizures." J Neurol.
The
objective of this study is to compare the safety and efficacy of
midazolam given intranasally with diazepam given intravenously in the
treatment of acute childhood seizures. A randomized controlled study was
conducted in a pediatric emergency department in a tertiary general
hospital. Fifty children aged from 1 month to 12 years presenting with
acute seizures of at least 10 min duration were enrolled during a 12
month period. Intranasal midazolam (0.2 mg/kg) and intravenous diazepam
(0.3 mg/kg) were administered. The main outcome measures were interval
between arrival at hospital and starting treatment and interval between
arrival at hospital and cessation of seizures. Intranasal midazolam and
intravenous diazepam were equally effective. Overall 18 of 27 seizures
were controlled with midazolam and 15 of 23 with diazepam. The mean
interval between arrival at hospital and starting treatment was
significantly shorter in the midazolam group [3.37 min (SD 2.46)] as
compared to the diazepam group [14.13 min (SD 3.39)]. The mean interval
between cessation of seizures and arrival at hospital was significantly
shorter in the midazolam group [6.67 min (SD 3.12)] as compared to the
diazepam group [17.18 min (SD 5.09)]. The mean interval between control
of seizures and administration of the drug was shorter in the diazepam
group [2.67 min (SD 2.31)] as compared to the midazolam group [3.01 min
(SD 2.79)]. No significant side effects were observed in either group.
Seizures were controlled more quickly with intravenous diazepam than
with intranasal midazolam. Midazolam was as safe and effective as
diazepam. The overall interval between arrival at hospital and cessation
of seizures was shorter with intranasal midazolam than with intravenous
diazepam. The intranasal route can be possibly used not only in medical
centres, but with appropriate instruction by the parents of children
with acute seizures at home.
Web site Editorial comments:
Here is another randomized trial comparing intranasal midazolam to intravenous diazepam and showing clinical equivalency in terms of seizure cessation but much faster resolution of the seizure when the nasal drug is given – all due to no need for an IV line. The time differences may be clinically significant in terms of brain hypoxia and potential long term outcomes – 6.7 minutes versus 17.2 minutes. In this study the resolution rates for single dose therapy were only 65 to 66% - very similar to other studies conducted outside of wealthy western countries (this study is from India). This is probably due to the very high incidence of CNS infections which was 26% in this study. This study and the other recent RCT on the same topic (that of Javadzadeh) both reconfirm the efficacy, safety and rapid control of status epilepticus treated with intranasal midazolam. These authors as others feel this treatment should be exported to the families of these children to allow rapid control of the seizures at home.
Pubmed link: http://www.ncbi.nlm.nih.gov/pubmed/22983456
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Tsze,
D. S., D. W. Steele, et al. (2012). "Intranasal Ketamine for Procedural
Sedation in Pediatric Laceration Repair: A Preliminary Report."
Pediatr Emerg Care 28(8):
767-770.
OBJECTIVE: The objective of this study was to compare the efficacy of 3
doses of intranasal ketamine (INK) for sedation of children from 1 to 7
years old requiring laceration repair. METHODS: This was a randomized,
prospective, double-blind trial of children requiring sedation for
laceration repair. Patients with simple lacerations were randomized by
age to receive 3, 6, or 9 mg/kg INK. Adequacy and efficacy of sedation
were measured with the Ramsay sedation score and the Observational Scale
of Behavioral Distress-Revised. Serum ketamine and norketamine levels
were drawn during the procedure. Sedation duration and adverse events
were recorded. RESULTS: Of the 12 patients enrolled, 3 patients achieved
adequate sedation, all at the 9-mg/kg dose. The study was suspended at
that time as per predetermined criteria. CONCLUSIONS: Nine milligrams of
INK per kilogram produced a significantly higher proportion of
successful sedations than the 3- and 6-mg/kg doses.
Web site Editorial comments:
These study results are disappointing if not entirely expected based on prior data published over the last 20 years (visit section on IN sedation using ketamine at this part of the web site). The authors did not find reliable sedation nor high serum ketamine levels using intranasal ketamine in doses of 3 or 6 mg/kg even though the used the most potent formulation (100 mg/kg) they could get. Once they pushed the dose to 9 mg/kg it usually worked. There are multiple other studies with similar results confirming that 3 mg/kg of IN ketamine is not effective for sedation, 5-6 mg/kg gives adequate anxiolysis but not dissociative anesthesia 9which these authors sought) and 9-10 mg/kg fairly reliably provides dissociated conditions. As far back as 1988 it was noted that you could administer 6 mg/kg, wait 5-10 minutes and administer another 3 mg/kg if needed and dissociative anesthesia with nystagmus was achieved 98% of the time. In other words, intranasal titration is effective just as IV titration is effective. I suspect we need a few more larger trials using what is known to be an appropriate dose to determine if this indeed is reliable - volumes of drug may become an issue since the most concentrated form most of us can obtain is 100 mg/ml. Be aware that PAIN control requires far less drug - more in the range o f 1 mg/kg with little impact on cognitive function (visit the pain section of the site for more information on this topic).
Pubmed link: http://www.ncbi.nlm.nih.gov/pubmed/22858745
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Sibley, T., R. Jacobsen, et al. (2012). "Successful Administration of
Intranasal Glucagon in the Out-of-Hospital Environment." Prehosp
Emerg Care.
Abstract: We present a case of successful prehospital treatment of
hypoglycemia with intranasal (IN) glucagon. Episodes of hypoglycemia can
be of varying severity and often requires quick reversal to prevent
alteration in mental status or hypoglycemic coma. Glucagon has been
shown to be as effective as glucose for the treatment of hypoglycemia.
The inability to obtain intravenous (IV) access often impairs delivery
of this peptide and is therefore frequently given via the intramuscular
(IM) route. Intranasal administration of glucagon has been shown to be
as effective as the IV route and may be used for rapid correction of
hypoglycemic episodes where IV access is difficult or unavailable and IM
administration is undesirable. We describe the first documentation in
the peer-reviewed literature of the successful treatment and reversal of
an insulin-induced hypoglycemic episode with IN glucagon in the
prehospital setting. We also present a review of the literature
regarding this novel medication administration route.
Web site Editorial comments:
This article describes a case of a woman who was unconscious and had a blood sugar of 21. After 3 failed attempts they administered 1 mg of IN glucagon and she aroused fairly quickly. Repeat blood sugar as 116. Though this is really the first published EMS case describing successful use in IN glucagon, the authors provide an in-depth review of the other literature relating to intranasal and intramuscular glucagon. They conclude that the drug is effective intranasally but considerable more expensive than IV glucose. However in a setting such as BLS response or rural EMS response the benefits of IN glucagon in the hands of a BLS provider probably far outweigh the additional costs of accessing ALS care. Furthermore they provide evidence that the lay public would appreciate a nasal glucagon kit were it available – again justifying the cost to allow families to treat hypoglycemic spells.
Pubmed link: http://www.ncbi.nlm.nih.gov/pubmed/22971130
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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.
Web site Editorial comments:
Here is the first article showing nasal atomization use in newborns and
demonstrating safety and efficacy (as well as possible in this unique
setting). Prior to this publication the youngest reported age of nasal
atomized fentanyl was 3 months old.
Pubmed link: http://www.ncbi.nlm.nih.gov/pubmed/23017621
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Title:
Abstract
Web site Editorial comments:
Pubmed link:
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