Intranasal 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.Compton, W. M., N. D. Volkow, et al. (2013). "Expanded access to opioid overdose intervention: research, practice, and policy needs." Ann Intern Med 158(1): 65-66.
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.AIMS: Traditionally, the opiate antagonist naloxone has been administered parenterally; however, intranasal (i.n.) administration has the potential to reduce the risk of needlestick injury. This is important when working with populations known to have a high prevalence of blood-borne viruses. Preliminary research suggests that i.n. administration might be effective, but suboptimal naloxone solutions were used. This study compared the effectiveness of concentrated (2 mg/ml) i.n. naloxone to intramuscular (i.m.) naloxone for suspected opiate overdose. METHODS: This randomized controlled trial included patients treated for suspected opiate overdose in the pre-hospital setting. Patients received 2 mg of either i.n. or i.m. naloxone. The primary outcome was the proportion of patients who responded within 10 minutes of naloxone treatment. Secondary outcomes included time to adequate response and requirement for supplementary naloxone. Data were analysed using multivariate statistical techniques. RESULTS: A total of 172 patients were enrolled into the study. Median age was 29 years and 74% were male. Rates of response within 10 minutes were similar: i.n. naloxone (60/83, 72.3%) compared with i.m. naloxone (69/89, 77.5%) [difference: -5.2%, 95% confidence interval (CI) -18.2 to 7.7]. No difference was observed in mean response time (i.n.: 8.0, i.m.: 7.9 minutes; difference 0.1, 95% CI -1.3 to 1.5). Supplementary naloxone was administered to fewer patients who received i.m. naloxone (i.n.: 18.1%; i.m.: 4.5%) (difference: 13.6%, 95% CI 4.2-22.9). CONCLUSIONS: Concentrated intranasal naloxone reversed heroin overdose successfully in 82% of patients. Time to adequate response was the same for both routes, suggesting that the i.n. route of administration is of similar effectiveness to the i.m. route as a first-line treatment for heroin overdose.
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.