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`(cid:176) FIELD ACTION REPORT (cid:176)(cid:176) FIELD ACTION REPORT (cid:176)
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`Saved by the Nose: Bystander-Administered Intranasal
`Naloxone Hydrochloride for Opioid Overdose
`
`| Maya Doe-Simkins, MPH, Alexander Y. Walley, MD, MSc, Andy Epstein, RN, MPH, and Peter Moyer, MD, MPH
`
`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. Prob-
`lems with intranasal naloxone were uncommon. Overdose prevention education with distribution of
`intranasal naloxone is a feasible public health intervention to address opioid overdose. Am J Public
`Health. 2009;99:788–791. doi:10.2105/AJPH.2008.146647.
`
`KEY FINDINGS
`■ Needle-exchange partici-
`pants have experienced and
`witnessed high rates of over-
`doses.
`■ Needle-exchange participants
`can successfully recognize an
`overdose and use intranasal
`naloxone to reverse potentially
`fatal opioid overdoses.
`■ With the support and regula-
`tion of the local public health
`authority, overdose prevention
`programs can provide training
`and distribute intranasal nalox-
`one without a direct clinical
`health care provider–patient
`encounter.
`■ Overdose prevention programs
`that include the distribution of
`intranasal naloxone by non-
`medical personnel are feasible
`for city public health depart-
`ments.
`
`RATES OF OPIOID OVERDOSE
`have increased since the early
`1990s because of lower-cost,
`higher-purity heroin and pre-
`scription opioid abuse.1–5 In Mas-
`sachusetts, from 1990 to 2006,
`annual opioid overdose–related
`fatalities increased over 6-fold,
`from 94 to 637.6,7 In response,
`the Boston Public Health
`Commission (BPHC) passed a
`regulation that authorized the
`development of an overdose pre-
`vention program with naloxone
`distribution through its mobile
`needle-exchange program. This
`program is innovative, because
`it includes the distribution of
`intranasal naloxone by trained,
`nonmedical public health
`workers to potential overdose
`bystanders for administration
`to overdose victims. Legal and
`regulatory barriers to implemen-
`tation are detailed in the box on
`page 791.
`Naloxone, an opioid antago-
`nist, reverses opioid overdose by
`displacing opioid agonists, such
`as heroin or oxycodone, from
`
`opioid receptors. It is the stan-
`dard treatment used by medical
`personnel. It has no abuse po-
`tential, and its only contraindica-
`tion is a prior allergic reaction,
`which is rare.8 Although typically
`administered intravenously or
`intramuscularly, it can be admin-
`istered intranasally.9–13 Strong
`interest in overdose prevention
`training and access to naloxone
`exists among potential overdose
`bystanders, including family
`members14 and drug-using part-
`ners.15 Overdose prevention pro-
`grams with naloxone distribution
`that train and distribute naloxone
`to people who are likely to wit-
`ness an overdose have been
`successfully implemented in
`several communities, includ-
`ing Chicago,16,17 New York,18,19
`San Francisco,20 Baltimore,15,21
`and New Mexico.8 A 6-program
`study demonstrated that trained
`bystanders were similarly skilled
`as medical experts in recog-
`nizing opioid overdose situa-
`tions, and when naloxone was
`indicated.22
`
`The BPHC started an overdose
`prevention program with intra-
`nasal naloxone distribution as a
`result of the successful experience
`of the city’s emergency medical
`services use of the nasal spray
`as a prehospital treatment for
`opioid overdose; the concept was
`also seen as an attractive option
`because intranasal delivery of the
`drug eliminates the risks of needle-
`stick injuries and needle disposal.
`BPHC implemented the program
`through the needle-exchange
`program because program partici-
`pants were considered particularly
`likely to witness overdoses.
`
`PROGRAM CURRICULUM
`
`All participating needle-exchange
`program staff—2 nurses and
`4 nonmedical public health
`workers—completed 8 hours of
`didactic training, a knowledge
`test, and at least 4 supervised
`bystander-training sessions. Both
`the staff training and bystander
`training were adapted from exist-
`ing program curricula from other
`cities that primarily used needle-
`based naloxone.8,14,17–21
`The 15-minute bystander
`training included techniques in
`overdose prevention. Staff com-
`pleted a checklist (available as a
`supplement to the online article
`at http://www.ajph.org) to ensure
`participant comprehension. Over-
`dose prevention kits included
`instructions; 2 luer-lock, prefilled
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`syringes with 2 mg/2 mL nalox-
`one hydrochloride; and the mu-
`cosal atomization device. Partici-
`pants were instructed to deliver 1
`mL (1 mg) to each nostril of the
`overdose victim. Because most
`opioid agonists have a longer half-
`life than naloxone, if overdose
`symptoms returned, victims could
`be treated with the second dose.
`
`DATA COLLECTION AND
`ANALYSIS
`
`From September 2006 to De-
`cember 2007, during each by-
`stander training, staff completed
`an enrollment form, recording
`respondents’ demographics and
`overdose risk factors. When par-
`ticipants returned to the needle-
`exchange program, staff com-
`pleted a form detailing overdoses
`witnessed, use of naloxone, and
`whether additional doses were
`needed. Data were maintained
`in a Microsoft Access 2003 data-
`base (Microsoft Corp, Redmond,
`WA). We compared enrollment
`data from participants who re-
`ported overdose reversals with
`those who did not with the t test
`of means and the (cid:114)2 or Fisher
`exact test. We used SAS version
`9.1 (SAS Institute, Cary, NC) for
`all tests of comparison.
`
`DISCUSSION AND
`EVALUATION
`
`Over 15 months, the program
`provided education and intra-
`nasal naloxone to 385 poten-
`tial bystanders. At enrollment
`(Table 1), heroin was the most
`frequently used drug, followed
`by cocaine, methadone, benzo-
`diazepines, and alcohol. Opioids
`were used on a mean of 24.1
`of the last 30 days. Cocaine was
`the drug used most commonly in
`combination with heroin. Among
`224 (64%) who reported a
`
`previous overdose, the median
`number of lifetime overdoses was
`2, and among the 303 (92%)
`who had witnessed an overdose,
`the median number of lifetime
`witnessed overdoses was 5.
`Follow-up contact was made
`at least once with 278 (72%)
`participants, 222 of whom re-
`ported no overdoses witnessed
`and no need for additional doses
`of naloxone. Among the 57
`participants who requested addi-
`tional doses, 7 had the naloxone
`lost, stolen, or confiscated, and
`50 administered naloxone while
`observing an overdose (Figure
`1). Among the 50 participants
`(13%) who reported revers-
`ing an overdose, 74 successful
`reversals were reported. Except
`for mean age (43 vs 39 years;
`P < .05), there were no signifi-
`cant differences between those
`participants who reported revers-
`ing an overdose and those who
`did not (data not shown). Emer-
`gency medical personnel were
`involved in 21 of the 74 (28%)
`reported overdoses and were not
`involved in 39 (53%) reported
`overdoses. Involvement by emer-
`gency medical personnel was not
`reported in the remainder (data
`available as a supplement to the
`online article at http://www.ajph.
`org). Two previous studies of
`naloxone distribution programs
`have reported similar rates of
`emergency medical personnel in-
`volvement (10% to 31%).20,23
`Among follow-up contacts,
`problems were uncommon.
`During 4 overdoses, bystanders
`could not connect the mucosal
`atomization device to the sy-
`ringe, although each resulted in
`successful reversal. Two admin-
`istered naloxone nasally directly
`from the syringe, 1 injected the
`naloxone intramuscularly, and
`1 did not administer naloxone,
`but delivered rescue breathing
`
`May 2009, Vol 99, No. 5 | American Journal of Public Health
`
`TABLE 1—Selected Characteristics of Participants (N = 385)
`in an Overdose Prevention Program With Intranasal Naloxone
`Distribution: Boston, MA, September 2006–December 2007
`
`Sample Total
`
`No. (%) or Mean ±SD
`
`Age, y
`Women
`Race/Ethnicity
`White
`Hispanic
`Black
`Other
`HIV status
`Positive
`Negative
`HCV status
`Positive
`Negative
`Days opioids used
`Substance used in the last 30 d
`Heroin
`Methadone
`Buprenorphine
`Other opioids
`Cocaine
`Benzodiazepines
`Alcohol
`Heroin and cocaine
`Heroin and benzos
`Heroin and alcohol
`Heroin, benzos, alcohol
`Clonodine
`History of nonfatal overdose
`Had a nonfatal overdose
`Nonfatal overdoses experienced, median
`(interquartile range)
`Nonfatal overdose treated with naloxone
`Lifetime witnessed overdose
`Had witnessed an overdose
`Overdoses witnessed, median
` (interquartile range)
`
`
`
`
`
`377
`381
`374
`
`219
`
`246
`
`351
`385
`
`
`
`349
`
`329
`
`39.6 ± 11
`129 (34)
`
`245 (66)
` 81 (22)
` 45 (12)
` 3 (1)
`
` 26 (12)
`193 (88)
`
`159 (65)
` 87 (35)
`24.1 ± 10.7
`
`273 (71)
`149 (39)
`11 (3)
` 60 (16)
`155 (40)
`118 (31)
` 88 (23)
`125 (33)
` 98 (26)
` 69 (18)
`35 (9)
`26 (7)
`
`225 (65)
`
` 2 (1–5)
`
` 146 (69)a
`
`303 (92)
`
` 5 (3–15)
`
`aThe percentage represents the percentage of respondents who had a nonfatal overdose and
`answered the question about whether naloxone had been used (n = 212).
`
`and physical stimulation until
`Boston Emergency Medical Ser-
`vices arrived. Two bystanders
`reported that naloxone induced
`withdrawal symptoms, but, in
`both cases, the victim did not
`use additional opioids to allevi-
`ate symptoms. Two bystanders
`observed the naloxone wearing
`off: 1 readministered it after 90
`minutes, and 1 reported that the
`
`victim became resedated after
`20 minutes, when Boston
`Emergency Medical Services
`assumed care. Two people had
`naloxone confiscated at a home-
`less shelter, 1 reported being
`expelled from a residential drug
`treatment program for having
`the substance, and 3 reported
`negative interactions with
`emergency medical personnel,
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`Received OD prevention and management training
`385 participants
`
`Follow-up contact
`no replacement doses
`no OD reversal reported
`222 participants
`
`Follow-up contact
`replacement doses
`57 participants
`
`No follow-up contact
`no replacement doses
`106 participants
`
`Replacement doses
`no OD reversal reported
`7 participants
`
`Replacement doses
`OD reversal(s) reported
`50 participants
`
`Reported 1 OD reversal
`32 participants
`
`Reported 2 OD reversals
`13 participants
`
`Reported 3 OD reversals
`4 participants
`
`Reported 4 OD reversals
`1 participant
`
`FIGURE 1—Flow chart of follow-up of 385 potential bystanders who received overdose (OD) prevention and
`management training: Boston, MA, September 2006–December 2007.
`
`none of which resulted in
`arrest (8 reported positive
`interactions).
`Of the 74 reported reversals,
`4 reports were of bystanders not
`initially enrolled in the program
`who used intranasal naloxone
`obtained from peers who were
`enrolled. Thus, there was some
`peer-to-peer overdose knowledge
`and skill transfer beyond the
`program.
`The BPHC overdose-prevention
`naloxone distribution program was
`implemented without substantial
`additional funding. Space, printing
`costs, and staff time were provided
`by the existing needle-exchange
`program. Naloxone kits cost ap-
`proximately $25.
`
`NEXT STEPS
`
`The BPHC naloxone distribution
`program is a feasible, successful
`program that includes distribution
`of intranasal naloxone by non-
`medical staff. The Massachusetts
`
`Department of Public Health has
`identified overdose prevention as
`a major focus area for new pub-
`lic health initiatives and has ex-
`panded the program to 5 addi-
`tional sites that target needle-
`exchange participants, staff at
`substance abuse treatment pro-
`grams, homeless shelters, and
`families and friends of opioid
`users.
`
`About the Authors
`At the time of the study, Maya Doe-
`Simkins was with the Boston Public Health
`Commission AHOPE Needle Exchange
`program, Boston, MA. Alexander Y. Wal-
`ley is with the Boston University School of
`Medicine, Boston, and the Massachusetts
`Department of Public Health’s overdose-
`prevention pilot program, Boston. Andy
`Epstein is with the Massachusetts De-
`partment of Public Health, Boston. Peter
`Moyer is with the Department of Emer-
`gency Medicine, Boston University School
`of Medicine, Boston, and Boston Emer-
`gency Medical Services, Boston Police and
`Fire Departments, Boston.
`Requests for reprints should be sent
`to Alexander Y. Walley, MD, Section of
`General Internal Medicine, Boston Medical
`Center, 801 Massachusetts Ave, 2nd Floor,
`
`Boston, MA 02118 (e-mail: awalley@
`bu.edu).
`This article was accepted September
`2, 2008.
`
`Contributors
`M. Doe-Simkins and A. Y. Walley, as
`co-first authors, jointly wrote the first
`draft and led subsequent revisions of
`the article. M. Doe-Simkins managed
`the data collection and assembly of
`the dataset and was a lead trainer
`of participants and other staff.
`A. Y. Walley performed the data
`analysis and led the institutional
`review board application. A. Epstein led
`the development and implementation of
`the project. P. Moyer provided medical
`supervision and direction. All authors
`helped to conceptualize ideas, develop
`the project, interpret findings, and re-
`view drafts of the article.
`
`Acknowledgments
`This project would not have been
`possible without the AHOPE needle-
`exchange staff and the administration
`of the Boston Public Health Commis-
`sion (BPHC). The program benefited
`from ongoing input and feedback
`from the participants. We would like
`to specifically thank John Auerbach,
`former director of BPHC, and current
`Commissioner of Health, Adam Butler,
`a lead trainer and manager of the
`AHOPE needle-exchange program, and
`
`John Townsend, General Counsel of
`the BPHC.
`
`Human Participant Protection
`This study was approved as an exempt
`study by the Boston University Medical
`Center institutional review board.
`
`References
`1. Paulozzi LJ, Budnitz DS, Xi Y. In-
`creasing deaths from opioid analgesics
`in the United States. Pharmacoepidemiol
`Drug Saf. 2006;15:618–627.
`2. Centers for Disease Control and
`Prevention. Unintentional opiate over-
`dose deaths—King County, Washington,
`1990–1999. MMWR Morb Mortal
`Wkly Rep. 2000;49:636–640.
`3. Centers for Disease Control
`and Prevention. Heroin overdose
`deaths—Multnomah County, Oregon,
`1993-1999. MMWR Morb Mortal Wkly
`Rep. 2000;49:633–636.
`4. Shah NG, Lathrop SL, Reichard
`RR, Landen MG. Unintentional
`drug overdose death trends in New
`Mexico, USA, 1990–2005: combina-
`tions of heroin, cocaine, prescrip-
`tion opioids and alcohol. Addiction.
`2008;103:126–136.
`5. Paulozzi LJ. Opioid analgesic involve-
`ment in drug abuse deaths in American
`metropolitan areas. Am J Public Health.
`2006;96:1755–1757.
`6. Fernandez W, Hackman H, McK-
`eown L, Anderson T, Hume B. Trends
`in opioid-related fatal overdoses in Mas-
`sachusetts, 1990–2003. J Subst Abuse
`Treat. 2006;31:151–156.
`7. Massachusetts Department of
`Public Health Bureau of Substance
`Abuse Services. Fatal opioid overdose
`trends continue. Prevention News [se-
`rial online]. 2008;2. Available at:
`http://170.63.97.68/Eeohhs2/docs/
`dph/substance_abuse/prevention_
`newsletter_2008spring.rtf. Accessed
`September 21, 2008.
`8. Baca CT, Grant KJ. Take-home nalox-
`one to reduce heroin death. Addiction.
`2005;100:1823–1831.
`9. Ashton H, Hassan Z. Intranasal
`naloxone in suspected opioid overdose.
`Emerg Med J. 2006;23:221–223.
`10. Barton ED, Colwell CB, Wolfe T, et
`al. Efficacy of intranasal naloxone as a
`needleless alternative for treatment of
`opioid overdose in the prehospital set-
`ting. J Emerg Med. 2005;29:265–271.
`11. Kelly AM, Kerr D, Dietze P, Patrick
`I, Walker T, Koutso giannis Z. Ran-
`domised trial of intranasal versus intra-
`muscular naloxone in prehospital treat-
`ment for suspected opioid overdose.
`Med J Aust. 2005;182:24–27.
`
`790 | Field Action Report | Peer Reviewed | Doe-Simkins et al.
`
`American Journal of Public Health | May 2009, Vol 99, No.5
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`(cid:176) FIELD ACTION REPORT (cid:176)
`
`evaluation of six overdose training
`and naloxone distribution programs
`in the United States. Addiction.
`2008;103:979–989.
`
`23. Dettmer K, Saunders B,
`Strang J. Take home naloxone and
`the prevention of deaths from
`opiate overdose: two pilot schemes.
`
`BMJ. 2001;322(7291): 895–
`896.
`
`24. Davis JE. Self-injectable epinephrine
`for allergic emergencies. J Emerg Med.
`2008. Epub ahead of print January
`31, 2008. Available at: http://www.
`sciencedirect.com. Accessed September
`21, 2008.
`
`25. Sporer KA, Kral AH. Prescription
`naloxone: a novel approach to heroin
`overdose prevention. Ann Emerg Med.
`2007;49(2):172–177.
`
`26. Burris S, Norland J, Edlin BR. Legal
`aspects of providing naloxone to heroin
`users in the United States. Int J Drug
`Policy. 2001;12:237–248.
`
`Legal and Regulatory Barriers to Implementing an Overdose Prevention Program
`With Intranasal Naloxone Distribution by Nonmedical Personnel
`
`Barrier
`
`Nonmedical personnel are
`not authorized to distribute
`prescription medication
`and are not authorized to
`administer a prescription
`medication to a person who
`has not been prescribed the
`medication.
`
`Intranasal delivery of
`naloxone is an off-label
`method.
`
`Response
`• The standard of care for the use of naloxone has for decades included use by
`prehospital personnel in nonclinical settings operating under standing orders
`from physicians who are neither on-site nor directly supervising.
`• Other life saving prescription medications, such as epinephrine injectors
`for anaphylactic shock,24 and other devices, such as automated external
`defibrillators, are used by bystanders and nonmedical personnel.
`• Other states, such as New Mexico, New York and Connecticut, have addressed
`
`this by passing laws that limit the liability of medical and nonmedical personnel
`who administer and distribute potentially lifesaving medication.25
`
`• A study of 6 programs that train bystanders to recognize and respond to opioid
`
`overdose by using naloxone has demonstrated that trained potential bystanders
`are similarly skilled as medical experts in recognizing opioid overdose situations
`and when naloxone is indicated.22
`
`• A local public health regulation was passed by BPHC, the City of Boston’s board
`
`of health, identifying the overdose-prevention naloxone distribution program as
`an official public health program and assuming liability for the work of medical
`and non-medical personnel involved in the program.
`
`• Under the medical license of the Medical Director of Boston Emergency Medical
`
`Services, potential bystanders received a standard curriculum about overdose
`prevention with instructions and demonstration of how to properly use the
`medication. Receipt of this curriculum was documented by BPHC staff.
`
`explicitly prohibited by law.25,26
`
`• Prescriptions drugs may be and are routinely given for any indication not
`• While no large scale randomized clinical trials have been conducted, intranasal
`naloxone has been evaluated in several research studies, with little evidence
`of adverse events.9–13 A small randomized trial comparing intranasal with
`intramuscular delivery of naloxone used by emergency personnel demonstrated
`that intranasal delivery had a longer time to clinical response
`(8 minutes vs 6 minutes), but less agitation or irritation (2% vs 13%).11
`
`• Intranasal naloxone is a first-line treatment for opioid overdose among
`
`emergency medical personnel in the local Boston community.
`
`12. Loimer N, Hofmann P, Chaudhry
`HR. Nasal administration of nalox-
`one is as effective as the intravenous
`route in opiate addicts. Int J Addict.
`1994;29:819–827.
`
`13. Barton ED, Ramos J, Colwell
`C, Benson J, Baily J, Dunn W. In-
`tranasal administration of naloxone
`by paramedics. Prehosp Emerg Care.
`2002;6:54–58.
`
`14. Strang J, Manning V, Mayet S,
`et al. Family carers and the prevention
`of heroin overdose deaths: Unmet train-
`ing need and overlooked intervention
`opportunity of resuscitation training and
`supply of naloxone. Drugs Educ Prev
`Policy; 2008;15:211–218.
`
`15. Sherman SG, Gann DS, Tobin KE,
`Latkin CA, Welsh C, Bielenson P. “The
`life they save may be mine”: diffusion
`of overdose prevention information
`from a city sponsored programme
`[published online ahead of print May
`23, 3008]. Int J Drug Policy. PMID:
`18502635.
`
`16. Bigg D. Data on take home nalox-
`one are unclear but not condemnatory.
`BMJ. 2002;324:678.
`
`17. Maxwell S, Bigg D, Stanczykiewicz
`K, Carlberg-Racich S. Prescribing nalox-
`one to actively injecting heroin users:
`a program to reduce heroin overdose
`deaths. J Addict Dis. 2006;25:89–96.
`
`18. Galea S, Worthington N, Piper
`TM, Nandi VV, Curtis M, Rosenthal
`DM. Provision of naloxone to injection
`drug users as an overdose prevention
`strategy: early evidence from a pilot
`study in New York City. Addict Behav.
`2006;31:907–912.
`
`19. Piper TM, Rudenstine S, Stancliff
`S, et al. Overdose prevention for injec-
`tion drug users: lessons learned from
`naloxone training and distribution pro-
`grams in New York City. Harm Reduct
`J. 2007;4:3.
`
`20. Seal KH, Thawley R, Gee L, et al.
`Naloxone distribution and cardiopulmo-
`nary resuscitation training for injection
`drug users to prevent heroin overdose
`death: a pilot intervention study. J
`Urban Health. 2005;82:303–311.
`
`21. Tobin KE, Sherman SG, Beilenson
`P, Welsh C, Latkin CA. Evaluation of
`the Staying Alive programme: training
`injection drug users to properly admin-
`ister naloxone and save lives [published
`online ahead of print April 21, 2008].
`Int J Drug Policy. PMID: 18434126.
`
`22. Green TC, Heimer R, Grau LE.
`Distinguishing signs of opioid overdose
`and indication for naloxone: an
`
`May 2009, Vol 99, No. 5 | American Journal of Public Health
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