Therapeutic
Intranasal Drug DeliveryIntranasal naloxone (Narcan) for the treatment of heroin and other opiate overdoses - abstracted references:
(1999) NIOSH Alert: Preventing needlestick
injuries in health care settings. National Institute for Occupational
Safety and Health Volume,
DOI: http://www.cdc.gov/niosh/2000-108.html#1
Baca, C. T. and K. J. Grant (2005). "Take-home
naloxone to reduce heroin death." Addiction 100(12): 1823-31.
BACKGROUND: This paper reviews the relevant literature related to
the distribution of take-home naloxone. METHODS: A Medline search was
conducted on articles published between January 1990 and June 2004 to
identify scientific literature relevant to this subject. Those
publications were reviewed, and from them other literature was
identified and reviewed. RESULTS: The prevalence, pathophysiology and
circumstances of heroin overdose, and also bystander response are
included in this review. Naloxone peer distribution has been instituted
to varying degrees in the United States, Italy, Spain, Germany and the
United Kingdom. CONCLUSION: At this point the evidence supporting
naloxone distribution is primarily anecdotal, although promising.
Although the distribution of naloxone holds promise for further reducing
heroin overdose mortality, problems remain. Naloxone alone may be
insufficient in some cases to revive the victim, and cardiopulmonary
resuscitation (CPR), especially rescue breathing, may also be needed. A
second dose of naloxone might be necessary. Complications following
resuscitation from overdose may infrequently need in-hospital care.
Mortality from injecting without anyone else present will be unaffected
by take-home naloxone. Take-home naloxone should be studied in a
rigorous scientific manner.
Baker, J. L., G. D. Kelen, et al. (1987).
"Unsuspected human immunodeficiency virus in critically ill emergency
patients." Jama 257(19): 2609-11.
Barton, Ed, et al. (2005). "Efficacy of
intranasal naloxone as a needleless alternative for treatment of opioid
overdose in the prehospital setting." J Emerg Med 29(3): 265-71.
Prehospital providers are at increased risk for blood-borne
exposure and disease due to the nature of their environment. The use if
intranasal (i.n.) medications in high-risk populations may limit this
risk of exposure. To determine the efficacy of i.n. naloxone in the
treatment of suspected opiate overdose patients in the prehospital
setting, a prospective, nonrandomized trial of administering i.n.
naloxone by paramedics to patients with suspected opiate overdoses over
a 6-month period was performed. All adult patients encountered in the
prehospital setting as suspected opiate overdose (OD), found down (FD),
or with altered mental status (AMS) who met the criteria for naloxone
administration were included in the study. i.n. naloxone (2 mg) was
administered immediately upon patient contact and before i.v. insertion
and administration of i.v. naloxone (2 mg). Patients were then treated
by EMS protocol. The main outcome measures were: time of i.n. naloxone
administration, time of i.v. naloxone administration, time of
appropriate patient response as reported by paramedics. Ninety-five
patients received i.n. naloxone and were included in the study. A total
of 52 patients responded to naloxone by either i.n. or i.v., with 43
(83%) responding to i.n. naloxone alone. Seven patients (16%) in this
group required further doses of i.v. naloxone. In conclusion, i.n.
naloxone is a novel alternative method for drug administration in
high-risk patients in the prehospital setting with good overall
effectiveness. The use of this route is further discussed in relation to
efficacy of treatment and minimizing the risk of blood-borne exposures
to EMS personnel.
Belz, D., J. Lieb, et al. (2006). "Naloxone use
in a tiered-response emergency medical services system." Prehosp
Emerg Care 10(4): 468-71.
OBJECTIVE: To examine the delivery and effect of naloxone for
opioid overdose in a tiered-response emergency medical services (EMS)
system and to ascertain how much time could be saved if the first
arriving emergency medical technicians (EMTs) could have administered
intranasal naloxone. METHODS: This was case series of all EMS-treated
overdose patients who received naloxone by paramedics in a two-tiered
EMS system during 2004. The system dispatches basic life support-trained
fire fighter-EMTs and/or advanced life support-trained paramedics
depending on the severity of cases. Main outcomes were geographic
distribution of naloxone-treated overdose, severity of cases, response
to naloxone, and time interval between arrival of EMTs and arrival of
paramedics at the scene. RESULTS: There were 164 patients who received
naloxone for suspected overdose. There were 75 patients (46%) initially
unresponsive to painful stimulus. Respiratory rate was <10 breaths/min
in 79 (48%). Death occurred in 36 (22%) at the scene or during
transport. A full or partial response to naloxone occurred in 119 (73%).
Recognized adverse reactions were limited to agitation/combativeness in
25 (15%) and emesis in six (4%). Average EMT arrival time was 5.9
minutes. Average paramedic arrival time was 11.6 minutes in most cases
and 16.1 minutes in 46 cases (28%) in which paramedics were requested by
EMTs at the scene. CONCLUSIONS: There is potential for significantly
earlier delivery of naloxone to patients in opioid overdose if EMTs
could deliver intranasal naloxone. A pilot study training and
authorizing EMTs to administer intranasal naloxone in suspected opioid
overdose is warranted.
Coffin, P. O. and S. D. Sullivan
(2013). "Cost-effectiveness of distributing naloxone to heroin users for
lay overdose reversal." Ann Intern Med 158(1): 1-9.
BACKGROUND: Opioid overdose is a leading cause of
accidental death in the United States. OBJECTIVE: To estimate the
cost-effectiveness of distributing naloxone, an opioid antagonist, to
heroin users for use at witnessed overdoses. DESIGN: Integrated Markov
and decision analytic model using deterministic and probabilistic
analyses and incorporating recurrent overdoses and a secondary analysis
assuming heroin users are a net cost to society. DATA SOURCES: Published
literature calibrated to epidemiologic data. TARGET POPULATION:
Hypothetical 21-year-old novice U.S. heroin user and more experienced
users with scenario analyses. TIME HORIZON: Lifetime. PERSPECTIVE:
Societal. INTERVENTION: Naloxone distribution for lay administration.
OUTCOME MEASURES: Overdose deaths prevented and incremental
cost-effectiveness ratio (ICER). RESULTS OF BASE-CASE ANALYSIS: In the
probabilistic analysis, 6% of overdose deaths were prevented with
naloxone distribution; 1 death was prevented for every 227 naloxone kits
distributed (95% CI, 71 to 716). Naloxone distribution increased costs
by $53 (CI, $3 to $156) and quality-adjusted life-years by 0.119 (CI,
0.017 to 0.378) for an ICER of $438 (CI, $48 to $1706). RESULTS OF
SENSITIVITY ANALYSIS: Naloxone distribution was cost-effective in all
deterministic and probabilistic sensitivity and scenario analyses, and
it was cost-saving if it resulted in fewer overdoses or emergency
medical service activations. In a "worst-case scenario" where overdose
was rarely witnessed and naloxone was rarely used, minimally effective,
and expensive, the ICER was $14 000. If national drug-related
expenditures were applied to heroin users, the ICER was $2429.
LIMITATION: Limited sources of controlled data resulted in wide CIs.
CONCLUSION: Naloxone distribution to heroin users is likely to reduce
overdose deaths and is cost-effective, even under markedly conservative
assumptions. PRIMARY FUNDING SOURCE: National Institute of Allergy and
Infectious Diseases.
Doe-Simkins, M., A. Y. Walley, et al. (2009). "Saved by the nose: bystander-administered intranasal naloxone hydrochloride for opioid overdose." Am J Public Health 99(5): 788-91.
Administering naloxone hydrochloride (naloxone) during an opioid overdose reverses the overdose and can prevent death. Although typically delivered via intramuscular or intravenous injection, naloxone may be delivered via intranasal spray device. In August 2006, the Boston Public Health Commission passed a public health regulation that authorized an opioid overdose prevention program that included intranasal naloxone education and distribution of the spray to potential bystanders. Participants were taught by trained nonmedical needle exchange staff. After 15 months, the program provided training and intranasal naloxone to 385 participants who reported 74 successful overdose reversals. Problems with intranasal naloxone were uncommon. Overdose prevention education with distribution of intranasal naloxone is a feasible public health intervention to address opioid overdose.Hussain, A., R. Kimura, et al. (1984). "Nasal
absorption of naloxone and
buprenorphine in rats." Int J Pharm 21: 233-237.
These authors measured bioavailabillity of naloxone via the IV
and the intranasal route in rats and found that the peak levels of
naloxone were similar and the bioavailability of naloxone intranasally
was 100% (the same) of that available IV.
Kelen, G. D., G. B. Green, et al. (1992).
"Hepatitis B and hepatitis C in emergency department patients." N
Engl J Med 326(21): 1399-404.
Kelly, Am, et al. (2005). "Randomised trial of
intranasal versus intramuscular naloxone in prehospital treatment for
suspected opioid overdose." Med J Aust 182(1): 24-7.
OBJECTIVE: To determine the effectiveness of intranasal (IN)
naloxone compared with intramuscular (IM) naloxone for treatment of
respiratory depression due to suspected opiate overdose in the
prehospital setting. DESIGN: Prospective, randomised, unblinded trial of
either 2 mg naloxone injected intramuscularly or 2 mg naloxone delivered
intranasally with a mucosal atomiser. PARTICIPANTS AND SETTING: 155
patients (71 IM and 84 IN) requiring treatment for suspected opiate
overdose and attended by paramedics of the Metropolitan Ambulance
Service (MAS) and Rural Ambulance Victoria (RAV) in Victoria. MAIN
OUTCOME MEASURES: Response time to regain a respiratory rate greater
than 10 per minute. Secondary outcome measures were proportion of
patients with respiratory rate greater than 10 per minute at 8 minutes
and/or a GCS score over 11 at 8 minutes; proportion requiring rescue
naloxone; rate of adverse events; proportion of the IN group for whom IN
naloxone alone was sufficient treatment. RESULTS: The IM group had more
rapid response than the IN group, and were more likely to have more than
10 spontaneous respirations per minute within 8 minutes (82% v 63%; P =
0.0173). There was no statistically significant difference between the
IM and IN groups for needing rescue naloxone (13% [IM group] v 26% [IN
group]; P = 0.0558). There were no major adverse events. For patients
treated with IN naloxone, this was sufficient to reverse opiate toxicity
in 74%. CONCLUSION: IN naloxone is effective in treating opiate-induced
respiratory depression, but is not as effective as IM naloxone. IN
delivery of naxolone could reduce the risk of needlestick injury to
ambulance officers and, being relatively safe to make more widely
available, could increase access to life-saving treatment in the
community.
Kerr, D., A. M. Kelly, et al. (2009). "Randomized
controlled trial comparing the effectiveness and safety of intranasal
and intramuscular naloxone for the treatment of suspected heroin
overdose." Addiction 104(12): 2067-74.
Loimer, N., P. Hofmann, et al. (1994). "Nasal
administration of naloxone is as effective as the intravenous route in
opiate addicts." Int J Addict 29(6): 819-27.
Naloxone is used intravenously in opiate addiction in emergency
cases, in rapid opiate detoxification, and as a diagnostic tool. This is
a study comparing the efficacy of intranasal naloxone to other routes
(intravenous/intramuscular) in 17 opiate-dependent patients. The nasal
drug administration of naloxone was found to be as effective as the
intravenous route. The nasal drug application offers a wide margin of
safety for patients and medical staff, especially in emergency
situations in regard to infection risks associated with vessel puncture.
Marcus, R., D. H. Culver, et al. (1993). "Risk
of human immunodeficiency virus infection among emergency department
workers." Am J Med 94(4): 363-70.
PURPOSE: To estimate (1) the prevalence of human immunodeficiency
virus (HIV) infection in emergency department (ED) patients, (2) the
frequency of blood contact (BC) in ED workers (EDWs), (3) the efficacy
of gloves in preventing BC, and (4) the risk of HIV infection in EDWs
due to BC. PATIENTS AND METHODS: We conducted an 8-month study in three
pairs of inner-city and suburban hospital EDs in high AIDS incidence
areas in the United States. At each hospital, blood specimens from
approximately 3,400 ED patients were tested for HIV antibody. Observers
monitored BC and glove use by EDWs. RESULTS: HIV seroprevalence was 4.1
to 8.9 per 100 patient visits in the 3 inner-city EDs, 6.1 in 1 suburban
ED, and 0.2 and 0.7 in the other 2 suburban EDs. The HIV infection
status of 69% of the infected patients was unknown to ED staff.
Seroprevalence rates were highest among patients aged 15 to 44 years,
males, blacks and Hispanics, and patients with pneumonia. BC was
observed in 379 (3.9%) of 9,793 procedures; 362 (95%) of the BCs were on
skin, 11 (3%) were on mucous membranes, and 6 (2%) were percutaneous.
Overall procedure-adjusted skin BC rates were 11.2 BCs per 100
procedures for ungloved workers and 1.3 for gloved EDWs (relative risk =
8.8; 95% confidence interval = 7.3 to 10.3). In the high HIV
seroprevalence EDs studied, 1 in every 40 full-time ED physicians or
nurses can expect an HIV-positive percutaneous BC annually; in the low
HIV seroprevalence EDs studied, 1 in every 575. The annual occupational
risk of HIV infection for an individual ED physician or nurse from
performing procedures observed in this study is estimated as 0.008% to
0.026% (1 in 13,100 to 1 in 3,800) in a high HIV seroprevalence area and
0.0005% to 0.002% (1 in 187,000 to 1 in 55,000) in a low HIV
seroprevalence area. CONCLUSIONS: In both inner-city and suburban EDs,
patient HIV seroprevalence varies with patient demographics and clinical
presentation; the infection status of most HIV-positive patients is
unknown to ED staff. The risk to an EDW of occupationally acquiring HIV
infection varies by ED location and the nature and frequency of BC; this
risk can be reduced by adherence to universal precautions.
Marcus, R., P. U. Srivastava, et al. (1995).
"Occupational blood contact among prehospital providers." Ann Emerg
Med 25(6): 776-9.
STUDY OBJECTIVE: To assess the nature and frequency of blood
contact (BC) among emergency medical service (EMS) workers. DESIGN:
During an 8-month period, we interviewed EMS workers returning from
emergency transport calls on a sample of shifts. We simultaneously
conducted an HIV seroprevalence survey among EMS-transported patients at
receiving hospitals served by these workers. SETTING: Three US cities
with high AIDS incidence. PARTICIPANTS: EMS workers. RESULTS: During 165
shifts, 2,472 patients were attended. Sixty-two BCs (1 needlestick and
61 skin contacts) were reported. Individual EMS workers had a mean of
1.25 BCs, including .02 percutaneous exposures, per 100 patients
attended. The estimated annual frequency of BC for an EMS worker at the
study sites was 12.3, including .2 percutaneous exposures. For 93.5% of
the BCs, the HIV serostatus of the source patients was unknown to the
EMS worker. HIV seroprevalences among EMS-transported patients at the
three receiving hospital emergency departments were 8.3, 7.7, and 4.1
per 100 patients; the highest rates were among male patients 15 to 44
years old who presented with pneumonia. CONCLUSION: EMS personnel
regularly experience BCs, most of which are skin contacts. Because the
HIV serostatus of the patient is usually unknown, EMS workers should
practice universal precautions. Postexposure management should include a
mechanism for voluntary HIV counseling and testing of the patient after
transport and transmittal of the results to the EMS.
Martin, T. G. (2003). "Take home naloxone:
feasability, safety and efficacy." J Toxicol Clin Toxicol 41(4):
415-416.
Fatal and nonfatal opiate overdose (OD) occur at a high or
increasing higher rate in many parts of the world. Unintentional fatal
opiate OD in opiate abusers is usually due to heroin but sometimes also
methadone and buprenorphine. Sedative hypnotic coingestants especially
ethanol or benzodiazepines, reduced tolerance from voluntary or forced
abstinence (jail) and increased purity contribute to increase
opiate-related mortality. Opiate abusers who witness an OD may not
summon EMS because they don¹t trust them and fear police who often
respond with them. Police may arrest and charge opiate abusers for
outstanding warrants, possession, or murder if they supplied or injected
the illicit substances1. EMS staff may transport users to the hospital
involuntarily and/or give larger than necessary doses of naloxone to
ensure a rapid reversal and less risk of renarcotization. Opiate abusers
often attempt ineffective street remedies before summoning help. Take
home naloxone was first suggested by Strang in 1992 to minimize the harm
from opiate misuse2. To be feasible, take home naloxone programs must be
acceptable to opiate abusers and prescribing physicians, affordable,
easily teachable and applicable at opiate OD scenes. Most opiate abusers
would favor taking home naloxone, would keep it in their home and use it
if it were available3. The legal risk for U.S. physicians who prescribe
naloxone for laypersons was judged to be low for those who act in good
faith, in the course of professional practice and for a legitimate
medical purpose1. Take home naloxone programs are feasible. Dispensing
naloxone should be preceded by education that includes the purpose of
naloxone use, potential adverse effects, recognizing serious opiate OD,
indications for and technique of use, summoning EMS, reporting outcome
and getting more naloxone. The education program should be designed for
naloxone use on a fellow opiate abuser or by friends or family on the
recipient. Mouth-to-mouth or cardiopulmonary resuscitation instructions
are optional. Recipients should be taught to suspect a serious OD if
heroin or other opiate has been used within the past 3h and the user is
blue, unresponsive to vigorous stimulation, or cannot maintain arousal
without constant or frequent stimulation. Naloxone is indicated for
opiate OD who is unresponsive to vigorous stimulation. EMS should be
summoned whenever naloxone is given, when arousal cannot be maintained
without constant or frequent stimulation or when ³nodding off² is
occurring and a responsible observer cannot remain present. The optimal
route for layperson naloxone would be easy to learn and perform, with
minimal risk of injury to the victim and rescuer, facilitates rapid
onset of arousal but not abrupt withdrawal and needs little to no
special equipment. The IM, SQ and intranasal (IN) routes appear to have
the most attractive risk benefit and cost considerations. The IN route
requires a special aerosol-generating device. The duration of action of
IV naloxone was found to be substantially less than combined IV/IM
naloxone (90 vs >360 min, respectively) in reversing morphineinduced
respiratory depression4. In a comparison of SQ vs IV naloxone, the
overall time to arousal was nearly identical (9.6 vs 9.3 min,
respectively) with the slightly longer onset of action for SQ balanced
by the slightly longer time required start the IV5. The IM and SQ routes
could be considered as Œinjected¹ routes and taught as a deep injection.
For the Œinjected¹ route (SQ or IM), 0.8 to 1.0 mg and for the IN route
2mg are the recommended initial doses. The risks and benefits of take
home naloxone programs must be carefully considered. Arousal of heroin
OD victims from layperson naloxone use could result in a larger
proportion of victims leaving the scene prior to EMS arrival or against
medical advice (AMA) afterwards. Because naloxone appears to have a
shorter duration of effect than heroin, serious renarcotization may
occur. The SQ, IM, or IN routes lead to slower absorption and a reduced
risk of renarcotization. Abrupt reversal of CNS depression without prior
correction of hypoxia and hypercarbia may result in greater
catecholamine levels and risks of adverse sequela. Naloxone can
precipitate acute withdrawal resulting in combative or agitated
behavior. The slower onset and less severe withdrawal from IM, SQ and IN
routes lower the risk of adverse reactions to naloxone. While there is
concern that lowering the risk of death will remove an important
deterrent, many believe that opiate abuse is not deterred by risk of
bodily harm or death. Many experts believe that naloxone misuse by
opiate abusers is very unlikely to occur and early evidence from
feasibility trials substantiate this belief6. The sooner that the
respiratory failure is corrected the less likely it will cause pulmonary
edema, hypoxic encephalopathy or death. There are scant published data
available to judge its efficacy or safety. In Berlin, naloxone,
supplies, and instructions were dispensed to 124 opiate abusers. They
reported that 22 users gave naloxone on 27 occasions; IM on 14 (48%), IV
on 13 (45%) and SQ on 2 (7%). Naloxone use appeared to be appropriate in
26 (90%), of dubious benefit in 2 (7%) and inappropriate (cocaine OD) on
1 (4%) occasion7. In Jersey, a minijet prefilled with naloxone along and
training were given to 101opiate abusers resulting in 5 successful
resuscitations7. In Chicago, naloxone has been distributed to over 550
opiate abusers with 52 successful uses reported8. In Can Tunis, Spain,
naloxone is being provided along with brieftraining and 60 successful
cases have been reported9. There are many challenges in designing a
trial to determine the effectiveness of take home naloxone programs.
Since naloxone use in these circumstances is a life-saving therapy, it
would be unethical to randomize therapy between naloxone and a placebo
treatment. These challenges must be overcome and higher-quality data
provided before the effectiveness and safety of take home naloxone
programs can be assessed. References: 1. Burris S, Norland J, Edlin BR.
Legal aspects of providing naloxone to heroin users in the United
States. Int J Drug Policy 2001;12:237248. 2. Strang J, Farrell M. Harm
minimisation for drug misusers. BMJ 1992;304:11278. 3. Strang J, Powis
B, Best D et al. Preventing opiate overdose fatalities with take-home
naloxone: pre-launch study of possible impact and acceptability.
Addiction 1999;94:199204. 4. Longnecker DE, Grazis PA, Eggers GWN.
Naloxone for antagonism of morphine-induced respiratory depression.
Anesth Analg 1973;52:447453. 5. Wanger K, Brough L, Macmillan I et al.
Intravenous vs. subcutaneous naloxone for out-of-hospital management of
presumed opioid overdose. Acad Emerg Med 1998;5:293299. 6. Darke S, Hall
W. The distribution of naloxone to heroin users. Addiction
1997;92:11959. 7. Dettmer K, Saunders B, Strang J. Take home naloxone
and the prevention of deaths from opiate overdose: two pilot schemes.
BMJ 2001;322:8956. 8. Bigg D. Data on take home naloxone are unclear but
not condemnatory. (Editorial) BMJ 2002;324:678. 9. Trujols J. Take home
naloxone: Life-saving intervention, medico-legal concern and heroin
user¹s competence. (Editorial) BMJ.COM Rapid Responses 13 May 2001.
Merlin M.A., Saybolt M., Kapitanyan R, et al (2009) "Intranasal naloxone delivery is an alternative to intravenoius naloxone for opioid overdoses." Am J Emerg Med - published online Oct 2009, pending journal publication
Introduction -
This study proposes that intranasal (IN) naloxone
administration is preferable to intravenous (IV) naloxone by emergency
medical services for opioid overdoses. Our study attempts to establish
that IN naloxone is as effective as IV naloxone but without the risk of
needle exposure. We also attempt to validate the use of the Glasgow Coma
Scale (GCS) in opioid intoxication. Methods -
A retrospective chart review of
prehospital advanced life support patients was performed on confirmed
opioid overdose patients. Initial and final unassisted respiratory rates
(RR) and GCS, recorded by paramedics, were used as indicators of
naloxone effectiveness. The median changes in RR and GCS were
determined. Results-Three
hundred forty-four patients who received naloxone by paramedics from
January 1, 2005, until December 31, 2007, were evaluated. Of confirmed
opioid overdoses, change in RR was 6 for the IV group and 4 for the IN
group (P = .08). Change in GCS was 4 for the IV group and 3 for
the IN group (P = .19). Correlations between RR and GCS for
initial, final, and change were significant at the 0.01 level (ρ
= 0.577, 0.462, 0.568, respectively). Conclusion:
Intranasal naloxone is statistically as effective as IV naloxone at
reversing the effects of opioid overdose. The IV and IN groups had
similar average increases in RR and GCS. Based on our results, IN
naloxone is a viable alternative to IV naloxone while posing less risk
of needle stick injury. Additionally, we demonstrated that GCS is
correlated with RR in opioid intoxication.
McDermott, C. and N. C. Collins (2012). "Prehospital medication
administration: a randomised study comparing intranasal and intravenous
routes." Emerg Med Int
2012: 476161.
Introduction. Opioid overdose is an ever-increasing problem globally.
Recent studies have demonstrated that intranasal (IN) naloxone is a safe
and effective alternative to traditional routes of naloxone
administration for reversal of opioid overdose. Aims. This randomised
controlled trial aimed to compare the time taken to deliver intranasal
medication with that of intravenous (IV) medication by advanced
paramedic trainees. Methods. 18 advanced paramedic trainees administered
either an IN or IV medication to a mannequin model in a classroom-based
setting. The time taken for medication delivery was compared. End-user
satisfaction was assessed using a 5-point questionnaire regarding ease
of use and safety for both routes. Results. The mean time taken for the
IN and IV group was 87.1 seconds and 178.2 seconds respectively. The
difference in mean time taken was 91.1 seconds (95% confidence interval
55.2 seconds to 126.9 seconds, P </= 0.0001). 89% of advanced paramedic
trainees reported that the IN route was easier and safer to use than the
IV route. Conclusion. This study demonstrates that, amongst advanced
paramedic trainees, the IN route of medication administration is
significantly faster, better accepted and perceived to be safer than
using the IV route. Thus, IN medication administration could be
considered more frequently when administering emergency medications in a
pre-hospital setting.
Osterwalder, J. J. (1995). "Patients intoxicated
with heroin or heroin mixtures: how long should they be monitored?"
Eur J Emerg Med 2(2): 97-101.
Our investigation was carried out in subjects intoxicated with
heroin or heroin mixtures to find out the time interval during which
delayed life-threatening complications become manifest, such as
pulmonary oedema or relapse into respiratory depression or coma after
naloxone treatment. We studied prospectively all drug intoxications
between 1991 and 1992. Of the 538 intoxications, we assessed in detail
160 outpatients who lived within the catchment area of our hospital. The
outcome variables studied were (1) rehospitalization for pulmonary
oedema, (2) relapse into coma, and/or (3) death and cause within 24 h
after release from hospital. Deaths occurring outside our hospital have
to be reported, as decreed by law, to the Institute for Forensic
Medicine. The results of our investigation showed no rehospitalization
owing to pulmonary oedema or coma, but one death, outside the hospital,
owing to delayed pulmonary oedema. This delayed complication had an
incidence of 0.6% (95% confidence interval 0-3.8%). A reintoxication
could be excluded in this patient. Based on reliable report, the
pulmonary oedema occurred between approximately 2 1/4 and 8 1/4 hours
after intoxication. In the literature, only two cases of delayed
pulmonary oedema have been reported with reliable time statements (4 and
6 h after hospitalization). We therefore conclude that surveillance for
at least 8 h is essential after successful treatment to exclude delayed
pulmonary oedema in patients intoxicated with heroin or heroin mixtures.
Parkin, J. M., M. Murphy, et al. (2000).
"Tolerability and side-effects of post-exposure prophylaxis for HIV
infection." Lancet 355(9205): 722-3.
A study of HIV post-exposure prophylaxis in 28 recipients showed
that indinavir-containing regimens were poorly tolerated. This finding
has implications for compliance and efficacy of the currently
recommended combinations.
Pepe, P. E., F. B. Hollinger, et al. (1986).
"Viral hepatitis risk in urban emergency medical services personnel."
Ann Emerg Med 15(4): 454-7.
Houston has large groups of people known to be at high risk for
hepatitis B virus (HBV) infection. Emergency medical services (EMS)
personnel are continuously exposed to blood from these high-risk
individuals. We sought to determine the prevalence of HBV infection in
the city's EMS personnel. Of the 350 Houston firefighters assigned to
EMS, 344 were surveyed by questionnaire and a blood specimen was
obtained. Each sample was assayed by radio-immunoassay or enzyme-linked
immunoassay for hepatitis A antibody (anti-HAV), hepatitis B surface
antigen (HBsAg), and antibodies to HBsAg (anti-HBs) and hepatitis B core
antigen (anti-HBc). A history of hepatitis was reported by 19 persons,
17 of whom had serologic evidence of infection with HAV (56%), HBV
(26%), or both diseases (11%). The anti-HAV prevalence was 16% (12% in
whites and 35% in nonwhites; P less than .001). No correlation was
observed with years of occupational exposure. Of the 338 personnel
evaluated for HBV seromarkers (six HBsAg-vaccinated subjects were
excluded), 13% were positive; 0.6% had an active infection as determined
by the presence of both HBsAg and anti-HBc; 6.8% were both anti-HBs and
anti-HBc positive; 0.9% were positive for anti-HBc alone; and 4.7% of
the sera contained only anti-HBs (all with geometric mean antibody
levels of less than or equal to 13 mlU/mL). The 28 individuals (8.3%)
whose sera contained anti-HBc were classified as cases of previous or
concurrent HBV infection. A strong correlation (P less than .004) was
observed between HBV infection and years of work exposure in EMS
regardless of job description (paramedic versus emergency medical
technician).(ABSTRACT TRUNCATED AT 250 WORDS)
Robertson, T. M., G. W. Hendey, et al. (2009). "Intranasal naloxone is a viable alternative to intravenous naloxone for prehospital narcotic overdose." Prehosp Emerg Care 13(4): 512-5.
OBJECTIVE: To compare the prehospital time intervals from patient contact and medication administration to clinical response for intranasal (IN) versus intravenous (IV) naloxone in patients with suspected narcotic overdose. METHODS: This was a retrospective review of emergency medical services (EMS) and hospital records, before and after implementation of a protocol for administration of intranasal naloxone by the Central California EMS Agency. We included patients with suspected narcotic overdose treated in the prehospital setting over 17 months, between March 2003 and July 2004. Paramedics documented dose, route of administration, and positive response times using an electronic record. Clinical response was defined as an increase in respiratory rate (breaths/min) or Glasgow Coma Scale score of at least 6. Main outcome variables included time from medication to clinical response and time from patient contact to clinical response. Secondary variables included numbers of doses administered and rescue doses given by an alternate route. Between-group comparisons were accomplished using t-tests and chi-square tests as appropriate. RESULTS: One hundred fifty-four patients met the inclusion criteria, including 104 treated with IV and 50 treated with IN naloxone. Clinical response was noted in 33 (66%) and 58 (56%) of the IN and IV groups, respectively (p = 0.3). The mean time between naloxone administration and clinical response was longer for the IN group (12.9 vs. 8.1 min, p = 0.02). However, the mean times from patient contact to clinical response were not significantly different between the IN and IV groups (20.3 vs. 20.7 min, p = 0.9). More patients in the IN group received two doses of naloxone (34% vs. 18%, p = 0.05), and three patients in the IN group received a subsequent dose of IV or IM naloxone. CONCLUSIONS: The time from dose administration to clinical response for naloxone was longer for the IN route, but the overall time from patient contact to response was the same for the IV and IN routes. Given the difficulty and potential hazards in obtaining IV access in many patients with narcotic overdose, IN naloxone appears to be a useful and potentially safer alternative.
Smith, D. A., L. Leake, et al. (1992). "Is
admission after intravenous heroin overdose necessary?" Ann Emerg Med
21(11): 1326-30.
STUDY OBJECTIVES: To investigate the time of onset and incidence
of complications in patients presenting to the emergency department with
an IV heroin overdose and the need for routine admission of such
patients. METHODS: A retrospective chart review of hospital and
emergency medical service records of 124 patient visits involving IV
heroin overdose over a five-month period. We also reviewed the death
certificates of 115 persons having succumbed to a narcotic overdose over
a 44-month period and compared these with our hospital records. SETTING:
Urban county hospital. TYPE OF PARTICIPANTS: Patients presenting to the
ED with an IV heroin overdose. RESULTS: There were five deaths in the
ED, 12 hospital admissions, and 107 patients who were discharged home.
Neither delayed onset of pulmonary edema nor recurrence of respiratory
depression was observed. Of the 115 persons having succumbed to a
narcotic overdose, eight had been seen previously at our hospital for a
heroin overdose. There is no evidence that any of these eight deaths
would have been prevented by a 24-hour hospital observation period.
CONCLUSION: Complications arising from an IV overdose of heroin are
usually evident on arrival in the ED or shortly thereafter. On
retrospective review we have found no evidence that admission to the
hospital and 24 hours of observation are of benefit to patients who are
awake, alert, and lacking evidence of pulmonary complications after an
IV heroin overdose.
Unick GJ, Rosenblum D, Mars S, Ciccarone D (2013) Intertwined Epidemics: National Demographic Trends in Hospitalizations for Heroin- and Opioid-Related Overdoses, 1993–2009. PLoS ONE 8(2): e54496. doi:10.1371/journal.pone.0054496
The historical patterns of opiate use show that sources and methods of access greatly influence who is at risk. Today, there is evidence that an enormous increase in the availability of prescription opiates is fuelling a rise in addiction nationally, drawing in new initiates to these drugs and changing the geography of opiate overdoses. Recent efforts at supply-based reductions in prescription opiates may reduce harm, but addicted individuals may switch to other opiates such as heroin. In this analysis, we test the hypothesis that changes in the rates of Prescription Opiate Overdoses (POD) are correlated with changes in the rate of heroin overdoses (HOD). ICD9 codes from the Nationwide Inpatient Sample and population data from the Census were used to estimate overall and demographic specific rates of POD and HOD hospital admissions between 1993 and 2009. Regression models were used to test for linear trends and lagged negative binomial regression models were used to model the interrelationship between POD and HOD hospital admissions. Findings show that whites, women, and middle-aged individuals had the largest increase in POD and HOD rates over the study period and that HOD rates have increased in since 2007. The lagged models show that increases in a hospitals POD predict an increase in the subsequent years HOD admissions by a factor of 1.26 (p
,0.001) and that each increase in HOD admissions increase the subsequent years POD by a factor of 1.57 (p,0.001). Our hypothesis of fungibility between prescription opiates and heroin was supported by these analyses. These findings suggest that focusing on supply-based interventions may simply lead to a shift in use to heroin rather minimizing the reduction in harm. The alternative approach of using drug abuse prevention resources on treatment and demand-side reduction is likely to be more productive at reducing opiate abuse related harm.
Valenzuela, T. D., E. W. Hook, 3rd, et al.
(1985). "Occupational exposure to hepatitis B in paramedics." Arch
Intern Med 145(11): 1976-7.
To determine their occupational risk for hepatitis B infection,
59 Seattle paramedics were tested for hepatitis B serum markers.
Evidence of antibody to hepatitis B surface antigen (anti-HBs) or
antibody to hepatitis B core antigen (anti-HBc) was found in 25%, a rate
five times that of a similar Seattle population. Seropositivity did not
correlate with age, race, clinical history, or length of service. Of the
15 paramedics with seropositivity to hepatitis B virus six initially had
low titers of either anti-HBs or anti-HBc. Four of the six demonstrated
persistent low-grade seropositivity on retesting. Paramedics are at
increased risk of hepatitis B infection. The high frequency of low-titer
anti-HBs suggests that frequent low-level exposure to hepatitis B virus
occurs in this population; hepatitis B vaccine should be strongly
considered for paramedics.
Vilke, G. M., J. Buchanan, et al. (1999). "Are
heroin overdose deaths related to patient release after prehospital
treatment with naloxone?" Prehosp Emerg Care 3(3): 183-6.
OBJECTIVE: Naloxone is frequently used by prehospital care
providers to treat suspected heroin and opioid overdoses. The authors'
EMS system has operated a policy of allowing these patients, once
successfully treated, to sign out against medical advice (AMA) in the
field. This study was performed to evaluate the safety of this practice.
METHODS: The authors retrospectively reviewed all 1996 San Diego County
Medical Examiner's (ME's) cases in which opioid overdoses contributed to
the cause of death. The records of all patients who were found dead in
public or private residences or died in emergency departments of reasons
other than natural causes or progression of disease, are forwarded to
the ME office. ME cases associated with opiate use as a cause of death
were cross-compared with all patients who received naloxone by field
paramedics and then refused transport. The charts were reviewed by
dates, times, age, sex, location, and, when available, ethnicity.
RESULTS: There were 117 ME cases of opiate overdose deaths and 317
prehospital patients who received naloxone and refused further
treatment. When compared by age, time, date, sex, location, and
ethnicity, there was no case in which a patient was treated by
paramedics with naloxone within 12 hours of being found dead of an
opiate overdose. CONCLUSIONS: Giving naloxone to heroin overdoses in the
field and then allowing the patients to sign out AMA resulted in no
death in the one-year period studied. This study did not evaluate for
return visits by paramedics nor whether patients were later taken to
hospitals by private vehicles.
Walley, A. Y., M. Doe-Simkins, et al. (2012). "Opioid overdose
prevention with intranasal naloxone among people who take methadone."
J Subst Abuse Treat.
Overdose education and naloxone distribution (OEND) is an intervention
that addresses overdose, but has not been studied among people who take
methadone, a drug involved in increasing numbers of overdoses. This
study describes the implementation of OEND among people taking methadone
in the previous 30days in various settings in Massachusetts. From 2008
to 2010, 1553 participants received OEND who had taken methadone in the
past 30days. Settings included inpatient detoxification (47%), HIV
prevention programs (25%), methadone maintenance treatment programs
(MMTP) (17%), and other settings (11%). Previous overdose, recent
inpatient detoxification and incarceration, and polysubstance use were
overdose risks factors common among all groups. Participants reported 92
overdose rescues. OEND programs are public health interventions that
address overdose risk among people who take methadone and their social
networks. OEND programs can be implemented in MMTPs, detoxification
programs, and HIV prevention programs.
Wanger, K., L. Brough, et al. (1998).
"Intravenous vs subcutaneous naloxone for out-of-hospital management of
presumed opioid overdose." Acad Emerg Med 5(4): 293-9.
OBJECTIVE: To determine whether naloxone administered i.v. to
out-of- hospital patients with suspected opioid overdose would have a
more rapid therapeutic onset than naloxone given subcutaneously (s.q.).
METHODS: A prospective, sequential, observational cohort study of 196
consecutive patients with suspected opioid overdose was conducted in an
urban out-of-hospital setting, comparing time intervals from arrival at
the patient's side to development of a respiratory rate > or =10
breaths/min, and durations of bag-valve-mask ventilation. Subjects
received either naloxone 0.4 mg i.v. (n = 74) or naloxone 0.8 mg s.q. (n
= 122), for respiratory depression of or =10 breaths/min was 9.3 +/- 4.2
min for the i.v. group vs 9.6 +/- 4.58 min for the s.q. group (95% CI of
the difference -1.55, 1.00). Mean duration of bag- valve-mask
ventilation was 8.1 +/- 6.0 min for the i.v. group vs 9.1 +/- 4.8 min
for the s.q. group. Cost of materials for administering naloxone 0.4 mg
i.v. was $12.30/patient, compared with $10.70/patient for naloxone 0.8
mg s.q. CONCLUSION: There was no clinical difference in the time
interval to respiratory rate > or =10 breaths/min between naloxone 0.8
mg s.q. and naloxone 0.4 mg i.v. for the out-of-hospital management of
patients with suspected opioid overdose. The slower rate of absorption
via the s.q. route was offset by the delay in establishing an i.v.
Wermeling, D. P. (2010). "Opioid harm reduction strategies: focus on expanded access to intranasal naloxone." Pharmacotherapy 30(7): 627-631.
Wolfe, T. R. and E. D. Barton (2003). "Reducing
needlestick risk: Nasal drug delivery in EMS." J Emerg Med Serv JEMS
28(12): 52-63.