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
Akers, J. L., R. N. Hansen, et al. (2017). "Implementing take-home
naloxone in an urban community pharmacy." J Am Pharm Assoc (2003)
57(2S): S161-S167.
OBJECTIVE: Morbidity and mortality associated with opioid use
have increased across the nation, growing into what can only be
described as an epidemic. SETTING: In Washington State between 2002 and
2004, the statewide death rate attributed to any opioid was 6.6 per
100,000 people, but between 2011 and 2013 it increased to 8.6 per
100,000 people. Pharmacies provide a unique access point for harm
reduction services to patients due to their ease of accessibility in the
community. PRACTICE DESCRIPTION: In development of a take-home naloxone
(THN) program, there were multiple areas that needed to be considered.
These included product selection, collaborative practice agreements,
training format and materials, managing patient and provider
expectations, partnerships, and community perception of the service.
PRACTICE INNOVATION: Initial demographics from our experience of people
obtaining THN showed a significant difference in the median age from
other available programs in the area (57 years vs. 34, 35, and 31).
These people tended to be bystanders, instead of end users of opioids,
which led to redirecting marketing of our program. We provided community
and group trainings for various organizations around the greater Seattle
area. We have trained approximately 1400 unique individuals on how to
recognize and respond to an opioid overdose, and how to administer
naloxone. EVALUATION: One organization reports 20 successful overdose
rescues from 99 kits (100% intranasal route) dispensed by our pharmacy
(20.2% rescue rate). RESULTS: Since 2012 when our THN program began, we
have seen growth of these programs across the state. Based on data
through 2015, deaths from heroin in King County have decreased for the
first time in the last 7 years, and the number of people seeking
treatment for heroin addiction has increased. CONCLUSION: Take-home
naloxone programs can be successfully implemented into community
pharmacies to increase access and awareness of opioid overdose
recognition and response.
OBJECTIVE: Naloxone hydrochloride, an opioid antagonist, has been approved
as a concentrated 4 mg dose intranasal formulation for the emergency
treatment of known or suspected opioid overdose. This new formulation is
easier to use and contains a higher dose of naloxone compared with
earlier, unapproved kits. A survey of first responders and
community-based organizations was conducted to understand initial
real-world experiences with this new formulation for opioid overdose
reversal. METHODS: In August 2016, 152 US organizations known to have
received units of the approved 4 mg dose/unit naloxone nasal spray (Narcan((R))(1)
nasal spray 4 mg; NNS) were surveyed regarding experiences using this
formulation and availability of recorded data on these cases.
Descriptive statistics were calculated based on the number of responses
received for each item. RESULTS: Eight first-responder or
community-based organizations provided case report data on 261 attempted
overdose reversals using NNS, with survival reported for 245 cases.
Successful overdose reversals were reported in 98.8% (242/245) of cases;
most cases (73.5%; 125/170) reported a time to response of </=5 minutes
after NNS administration. Heroin was the substance reportedly involved
in a majority (95.4%; 165/173) of these cases; fentanyl was reported to
be involved in 5.2% (9/173) of the cases. Many reversals (97.6%;
248/254) involved administration of </=2 units of NNS. Three deaths were
reported (NNS was reported to have been administered too late for two
cases [the individuals were deceased prior to NNS administration];
details were not provided for the third case). The most commonly
reported observed events were "withdrawal" (14.3%; 28/196); "nausea",
"vomiting", or "gagging/retching" (10.2%; 20/196); and "irritability" or
"anger" (8.7%; 17/196). CONCLUSION: This survey of data provided by
first-responder and community-based organizations indicated that NNS was
successful at reversing the effects of opioid overdose in most reported
cases.
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.
Bailey, A. M. and D. P. Wermeling (2014). "Naloxone for Opioid
Overdose Prevention: Pharmacists' Role in Community-Based Practice
Settings." Ann Pharmacother.
Baker, J. L., G. D. Kelen, et al. (1987).
"Unsuspected human immunodeficiency virus in critically ill emergency
patients." Jama 257(19): 2609-11.
Bakhireva, L. N., A. Bautista, et al. (2018). "Barriers and facilitators
to dispensing of intranasal naloxone by pharmacists." Subst Abus
39(3): 331-341.
Barry, T., J. Klimas, et al. (2017). "Opiate addiction and overdose:
experiences, attitudes, and appetite for community naloxone provision."
Br J Gen Pract 67(657):
e267-e273.
BACKGROUND: More than 200 opiate overdose deaths occur annually
in Ireland. Overdose prevention and management, including naloxone
prescription, should be a priority for healthcare services. Naloxone is
an effective overdose treatment and is now being considered for wider
lay use. AIM: To establish GPs' views and experiences of opiate
addiction, overdose care, and naloxone provision. DESIGN AND SETTING: An
anonymous postal survey to GPs affiliated with the Department of
Academic General Practice, University College Dublin, Ireland. METHOD: A
total of 714 GPs were invited to complete an anonymous postal survey.
Results were compared with a parallel GP trainee survey. RESULTS: A
total of 448/714 (62.7%) GPs responded. Approximately one-third of GPs
were based in urban, rural, and mixed areas. Over 75% of GPs who
responded had patients who used illicit opiates, and 25% prescribed
methadone. Two-thirds of GPs were in favour of increased naloxone
availability in the community; almost one-third would take part in such
a scheme. A higher proportion of GP trainees had used naloxone to treat
opiate overdose than qualified GPs. In addition, a higher proportion of
GP trainees were willing to be involved in naloxone distribution than
qualified GPs. Intranasal naloxone was much preferred to single
(P<0.001) or multiple dose (P<0.001) intramuscular naloxone. Few GPs
objected to wider naloxone availability, with 66.1% (n = 292) being in
favour. CONCLUSION: GPs report extensive contact with people who have
opiate use disorders but provide limited opiate agonist treatment. They
support wider availability of naloxone and would participate in its
expansion. Development and evaluation of an implementation strategy to
support GP-based distribution is urgently needed.
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.
Behar, E., G. M. Santos, et al. (2015). "Brief overdose
education is sufficient for naloxone distribution to opioid users."
Drug Alcohol Depend 148:
209-212.
BACKGROUND: While drug
users are frequently equipped with naloxone for lay opioid overdose
reversal, the amount of education needed to ensure knowledge of
indications and administration is unknown. METHODS: We administered four
instruments, assessing comfort and knowledge around opioid overdose and
naloxone administration, to opioid users receiving naloxone for the
first time (N=60) and upon returning for a refill (N=54) at community
distribution programs. Participants completed the instruments prior to
receiving naloxone; first-time recipients repeated the instruments
immediately after the standardized 5-10min education. RESULTS: Comfort
with recognition of, response to, and administration of naloxone for an
overdose event significantly increased after brief education among
first-time recipients (p<0.05). Knowledge of appropriate responses to
opioid overdose was high across all assessments; 96% of participants
could identify at least one acceptable action to assess and one
acceptable action to care for an opioid overdose. Facility with naloxone
administration was high across all assessments and significantly
increased for intranasal administration after education for first-time
recipients (p<0.001). First-time recipients (before and after education)
and refillers demonstrated a high level of knowledge on the Brief
Overdose Recognition and Response Assessment, correctly identifying a
mean of 13.7 out of 16 overdose scenarios. CONCLUSIONS: Opioid users
seeking naloxone in San Francisco have a high level of baseline
knowledge around recognizing and responding to opioid overdose and those
returning for refills retain that knowledge. Brief education is
sufficient to improve comfort and facility in recognizing and managing
overdose.
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.
Chang, G., M. Davids, et al. (2017). "Overdose education and naloxone
distribution for veterans with opioid use disorder: Results from a pilot
initiative." J Addict Dis
36(4): 217-221.
Patients with
opioid use disorder are at a high risk of overdose. To minimize that
risk, a program offering intranasal naloxone rescue kits was piloted at
a Veterans Administration Hospital. The purpose of this study was to
characterize veterans who accepted these potentially lifesaving kits.
Retrospective medical chart review of 158 veterans with opioid use
disorder receiving treatment on either the inpatient psychiatry
detoxification units or outpatient methadone maintenance setting who
were offered overdose education and naloxone rescue kits. One hundred
and ten of 158 veterans (70%) accepted overdose education and naloxone
rescue. Overall, they had a mean age of 39.1 years and averaged 12.7
years of opioid use. In the prior month, they averaged 14.3 days of
heroin use; they used alone 48.5% of the time. They estimated an average
of 2.8 accidental overdoses over their lifetimes. There were few
significant differences between those who accepted and those who
declined with regard to demographic and clinical variables. However,
significantly higher percentages of outpatients accepted overdose
education and naloxone rescue compared to inpatients (89% versus 63%, p
= 0.003, Chi-square); the odds of acceptance were increased four-fold
when offered to outpatients. Outpatients were nearly a decade older,
with more years of opioid use (19.0 versus 11.0), but with less
utilization of inpatient services in the prior year (all p < 0.05). The
main finding was that 70% of veterans accepted overdose education and
naloxone rescue, but significantly higher proportions of outpatients
were more receptive than inpatients (89% versus 63%, p = 0.003). Efforts
to increase overdose education and naloxone rescue acceptance in all
settings are encouraged.
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.
Davis, C. S., S. Ruiz, et al. (2014). "Expanded access to naloxone among
firefighters, police officers, and emergency medical technicians in
Massachusetts." Am J Public Health
104(8): e7-9.
Naloxone is a medication that reverses respiratory
depression from opioid overdose if given in time. Paramedics routinely
administer naloxone to opioid overdose victims in the prehospital
setting, and many states are moving to increase access to the
medication. Several jurisdictions have expanded naloxone administration
authority to nonparamedic first responders, and others are considering
that step. We report here on policy change in Massachusetts, where
several communities have equipped emergency medical technicians, law
enforcement officers, and firefighters with naloxone.
Dahlem, C. H., M. J. Horstman, et al. (2015). "Development and
implementation of intranasal naloxone opioid overdose response protocol
at a homeless health clinic." J Am Assoc Nurse Pract.
PURPOSE: To describe the development, implementation, and
preliminary evaluation of Opioid Overdose Response Protocol using
intranasal (IN) naloxone in a homeless shelter. DATA SOURCES: Opioid
Overdose Response Protocol and training curriculum were developed using
the Massachusetts Department of Public Health Opioid Overdose Education
and Naloxone Distribution (OEND) flow chart, the American Heart
Association (AHA) simplified adult basic life support algorithm, and
resources through Harms Reduction Coalition. CONCLUSIONS: Intranasal
naloxone offers a safe and effective method for opioid reversal. To
combat the rising incidence of opioid overdose, IN naloxone should be
made available at homeless shelters and other facilities with high
frequency of opioid overdose, including the training of appropriate
staff. This project has demonstrated the effective training and
implementation of an Opioid Overdose Response Protocol, based on
feedback received from cardiopulmonary resuscitation (CPR) trained
nonhealthcare staff. Nurse practitioners (NPs), with our focus on
patient care, prevention, and education, are well suited to the
deployment of this life-saving protocol. IMPLICATIONS FOR PRACTICE: NPs
are in critical positions to integrate opioid overdose prevention
education and provide naloxone rescue kits in clinical practices.
Dietze, P., M. Jauncey, et al. (2019). "Effect of Intranasal vs
Intramuscular Naloxone on Opioid Overdose: A Randomized Clinical Trial."
JAMA Netw Open 2(11):
e1914977.
Importance: Previous unblinded clinical trials
suggested that the intranasal route of naloxone hydrochloride was
inferior to the widely used intramuscular route for the reversal of
opioid overdose. Objective: To test whether a dose of naloxone
administered intranasally is as effective as the same dose of
intramuscularly administered naloxone in reversing opioid overdose.
Design, Setting, and Participants: A double-blind, double-dummy
randomized clinical trial was conducted at the Uniting Medically
Supervised Injecting Centre in Sydney, Australia. Clients of the center
were recruited to participate from February 1, 2012, to January 3, 2017.
Eligible clients were aged 18 years or older with a history of injecting
drug use (n = 197). Intention-to-treat analysis was performed for all
participants who received both intranasal and intramuscular modes of
treatment (active or placebo). Interventions: Clients were randomized to
receive 1 of 2 treatments: (1) intranasal administration of naloxone
hydrochloride 800 mug per 1 mL and intramuscular administration of
placebo 1 mL or (2) intramuscular administration of naloxone
hydrochloride 800 mug per 1 mL and intranasal administration of placebo
1 mL. Main Outcomes and Measures: The primary outcome measure was the
need for a rescue dose of intramuscular naloxone hydrochloride (800 mug)
10 minutes after the initial treatment. Secondary outcome measures
included time to adequate respiratory rate greater than or equal to 10
breaths per minute and time to Glasgow Coma Scale score greater than or
equal to 13. Results: A total of 197 clients (173 [87.8%] male; mean
[SD] age, 34.0 [7.82] years) completed the trial, of whom 93 (47.2%)
were randomized to intramuscular naloxone dose and 104 (52.8%) to
intranasal naloxone dose. Clients randomized to intramuscular naloxone
administration were less likely to require a rescue dose of naloxone
compared with clients randomized to intranasal naloxone administration
(8 [8.6%] vs 24 [23.1%]; odds ratio, 0.35; 95% CI, 0.15-0.66; P = .002).
A 65% increase in hazard (hazard ratio, 1.65; 95% CI, 1.21-2.25; P =
.002) for time to respiratory rate of at least 10 and an 81% increase in
hazard (hazard ratio, 1.81; 95% CI, 1.28-2.56; P = .001) for time to
Glasgow Coma Scale score of at least 13 were observed for the group
receiving intranasal naloxone compared with the group receiving
intramuscular naloxone. No major adverse events were reported for either
group. Conclusions and Relevance: This trial showed that intranasally
administered naloxone in a supervised injecting facility can reverse
opioid overdose but not as efficiently as intramuscularly administered
naloxone can, findings that largely replicate those of previous
unblinded clinical trials. These results suggest that determining the
optimal dose and concentration of intranasal naloxone to respond to
opioid overdose in real-world conditions is an international priority.
Trial Registration: anzctr.org.au Identifier: ACTRN12611000852954.
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.
Doe-Simkins, M., E. Quinn, et al. (2014). "Overdose rescues by trained
and untrained participants and change in opioid use among
substance-using participants in overdose education and naloxone
distribution programs: a retrospective cohort study." BMC Public
Health 14: 297.
Dunn, K. E., F. S. Barrett, et al. (2018). "Naloxone formulation for
overdose reversal preference among patients receiving opioids for pain
management." Addict Behav
86: 56-60.
Dwyer, K., A. Y. Walley, et al. (2015). "Opioid education and nasal
naloxone rescue kits in the emergency department." West J Emerg Med
16(3): 381-384.
INTRODUCTION: Emergency departments (EDs) may be high-yield
venues to address opioid deaths with education on both overdose
prevention and appropriate actions in a witnessed overdose. In addition,
the ED has the potential to equip patients with nasal naloxone kits as
part of this effort. We evaluated the feasibility of an ED-based
overdose prevention program and described the overdose risk knowledge,
opioid use, overdoses, and overdose responses among participants who
received overdose education and naloxone rescue kits (OEN) and
participants who received overdose education only (OE). METHODS: Program
participants were surveyed by telephone after their ED visit about their
substance use, overdose risk knowledge, history of witnessed and
personal overdoses, and actions in a witnessed overdose including use of
naloxone. RESULTS: A total of 415 ED patients received OE or OEN between
January 1, 2011 and February 28, 2012. Among those, 51 (12%) completed
the survey; 37 (73%) of those received a naloxone kit, and 14 (27%)
received OE only. Past 30-day opioid use was reported by 35% OEN and 36%
OE, and an overdose was reported by 19% OEN and 29% OE. Among 53%
(27/51) of participants who witnessed another individual experiencing an
overdose, 95% OEN and 88% OE stayed with victim, 74% OEN and 38% OE
called 911, 26% OEN and 25% OE performed rescue breathing, and 32% OEN
(n=6) used a naloxone kit to reverse the overdose. We did not detect
statistically significant differences between OEN and OE-only groups in
opioid use, overdose or response to a witnessed overdose. CONCLUSION:
This is the first study to demonstrate the feasibility of ED-based
opioid overdose prevention education and naloxone distribution to
trained laypersons, patients and their social network. The program
reached a high-risk population that commonly witnessed overdoses and
that called for help and used naloxone, when available, to rescue
people. While the study was retrospective with a low response rate, it
provides preliminary data for larger, prospective studies of ED-based
overdose prevention programs.
Eggleston, W., C. Podolak, et al. (2018). "A randomized usability
assessment of simulated naloxone administration by community members."
Addiction 113(12):
2300-2304.
BACKGROUND AND AIMS: Expanded access to naloxone has been identified as a
key intervention for reducing opioid-related morbidity and mortality. It
is not known which naloxone device will result in rapid, successful
administration when administered by community members. The aims of this
study were to estimate and compare (1) the rate of successful
administration and (2) time to successful administration for single-step
nasal spray, multi-step atomized nasal spray and intramuscular simulated
naloxone by community members. DESIGN: A prospective, single-site,
open-label, randomized usability assessment of simulated naloxone
administration in a convenience sample of community members.
Participants were randomized to single-step nasal spray (SP), multi-step
atomized nasal spray (AT) or intramuscular simulated (IM) naloxone and
asked to administer the simulated medication to a mannequin after
completing a 2-minute training video. SETTING: New York, USA at a state
fair that attracts between 60 000 and 120 000 individuals daily.
PARTICIPANTS: A total of 138 participants completed the study over a
2-day period in September 2016. All participants were at least 18 years
of age and had no prior naloxone training. MEASUREMENTS: The rate of
successful administration and time to successful administration were
recorded for each device. FINDINGS: The SP device (100%; P < 0.001) had
a higher rate of success compared with the IM device (69.6%). Although
success differed between the AT (89.1%) device and IM device, as well as
the AT device and SP device, these differences were not significant. The
SP device also had a shorter median time to successful administration
(34.3 sec) compared with the IM (99.9 sec; P < 0.001) and AT (110.3; P <
0.001) devices. CONCLUSIONS: After video training, community members are
able to (1) administer single-step nasal spray naloxone with a higher
rate of success than intramuscular naloxone in a simulated overdose
setting and (2) administer single-step nasal spray naloxone more rapidly
than both intramuscular and multi-step atomized nasal spray naloxone.
Fareed, A., A. M. Buchanan-Cummings, et al. (2015). "Reversal of
overdose on fentanyl being illicitly sold as heroin with naloxone nasal
spray: A case report." Am J Addict
24(5): 388-390.
BACKGROUND: This is a case report describing a reversal of
fentanyl overdose with naloxone nasal spray. The patient was not aware
that he overdosed on fentanyl being sold as heroin. METHODS: The
Veterans Health Administration (VHA) has implemented an initiative to
provide education for veterans, their families, friends and significant
others about opioid overdose and use of naloxone reversal kits. The
Atlanta VA Medical Center adopted this program to reduce the risk of
opioid overdose in high risk patients. RESULTS: Over the past year, we
provided educational sessions for 63 veterans and their families. We
also prescribed 41 naloxone kits. We have received three reports of
opioid overdose reversal with use of naloxone kits prescribed by the
Atlanta VA Medical Center. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: The
authors recommend that public health administrators and policy makers
advocate for the implementation of these programs to reduce the rising
number of overdose death in the United States and worldwide. (Am J
Addict 2015;24:388 -390).
Fisher, R., D. O'Donnell, et al. (2016). "Police Officers Can
Safely and Effectively Administer Intranasal Naloxone."
Prehosp Emerg Care: 1-6.
INTRODUCTION: Opioid overdose rates continue to rise at an alarming rate.
One method used to combat this epidemic is the administration of
naloxone by law enforcement. Many cities have implemented police
naloxone administration programs, but there is a minimal amount of
research examining this policy. The following study examines data over
18 months, after implementation of a police naloxone program in an urban
setting. We describe the most common indications and outcomes of
naloxone administration as well as examine the incidence of arrest,
immediate detention, or voluntary transport to the hospital. In doing
so, this study seeks to describe the clinical factors surrounding police
use of naloxone, and the effects of police administration. METHODS: All
police officer administrations were queried from April 2014 through
September 2015 (n = 126). For each incident we collected the indication,
response, and disposition of the patient that was recorded on a
"sick-injured civilian" report that officers were required to complete
after administration of naloxone. All of the relevant information was
abstracted from this report into an electronic data collection form that
was then input into SPSS for analysis. RESULTS: The most common
indication for administration was unconscious/unresponsive (n = 117;
92.9%) followed by slowed breathing (n = 72; 57.1%), appeared blue (n =
63; 50.0%) and not breathing (n = 41; 32.5%). After administration of
naloxone the majority of patients regained consciousness (n = 82; 65.1%)
followed by began to breath (n = 71; 56.3%). However, in 17.5% (n = 22)
of the cases "Nothing" happened when naloxone was administered. The
majority of patients were transported voluntarily to the hospital (n =
122; 96.8%). Lastly, there was only one report where the patient became
combative. CONCLUSION: Our study shows that police officers trained in
naloxone administration can correctly recognize symptoms of opioid
overdose, and can appropriately administer naloxone without significant
adverse effects or outcomes. Furthermore, the administration of police
naloxone does not result in a significant incidence of combativeness or
need for scene escalations such as immediate detention. Further research
is needed to investigate the impact of police naloxone; specifically,
comparing outcomes of police delivery to EMS alone, as well as the
impact on rural opioid overdoses.
Frauger, E., F. Kheloufi, et al. (2018). "[Interest of take-home
naloxone for opioid overdose]." Therapie
73(6): 511-520.
Galea, S., N. Worthington, et al. (2006). "Provision of naloxone to
injection drug users as an overdose prevention strategy: early evidence
from a pilot study in New York City." Addict Behav
31(5): 907-912.
INTRODUCTION: Naloxone, an opiate antagonist that can
avert opiate overdose morality, has long been prescribed to drug users
in Europe and in a few US cities. However, there has been little
documented evidence of naloxone distribution programs and their
feasibility in the peer reviewed literature in the US. METHODS: A pilot
overdose prevention and reversal program was implemented in a New York
City syringe exchange program. We assessed demographics, drug use, and
overdose history, experience, and behavior at baseline, when
participants returned for prescription refills, and 3 months after
baseline assessment. RESULTS: 25 participants were recruited. 22 (88%)
participants were successfully followed-up in the first 3 months; of
these, 11 (50%) participants reported witnessing a total of 26 overdoses
during the follow-up period. Among 17 most-recent overdoses witnessed,
naloxone was administered 10 times; all persons who had naloxone
administered lived. DISCUSSION: Naloxone administration by injection
drug users is feasible as part of a comprehensive overdose prevention
strategy and may be a practicable way to reduce overdose deaths on a
larger scale.
Green, T. C., M. Ray, et
al. (2014). "Two cases of intranasal naloxone self-administration in
opioid overdose." Subst Abus
35(2): 129-132.
ABSTRACT. Background:
Overdose is a leading cause of death for former prisoners, exacting its
greatest toll during the first 2 weeks post release. Protective effects
have been observed with training individuals at high risk of overdose
and prescribing them naloxone, an opioid antagonist that reverses the
effects of the opioid-induced respiratory depression that causes death.
Cases: The authors report 2 people with opiate use histories who
self-administered intranasal naloxone to treat their own heroin
overdoses following release from prison. Patient A is a 34-year-old
male, who reported having experienced an overdose on heroin the day
after he was released from incarceration. Patient B is a 29-year-old
female, who reported an overdose on her first injection of heroin, 17
days post release from incarceration. Both patients self-administered
the medication but were assisted at some point during the injury by a
witness whom they had personally instructed in how to prepare and
administer the medication. Neither patient experienced withdrawal
symptoms following exposure to naloxone. Discussion: Self-administration
of naloxone should not be a goal of overdose death prevention training.
A safer, more reliable approach is to prescribe naloxone to at-risk
patients and train and also equip members of their household and social
or drug-using networks in overdose prevention and response.
Importance: Despite the increasingly important role of
pharmacies in the implementation of naloxone access laws, there is
limited information on the impact of such laws at the local level.
Objective: To evaluate the availability (with or without a prescription)
and cost of naloxone nasal spray at pharmacies in Philadelphia,
Pennsylvania, following a statewide standing order enacted in
Pennsylvania in August 2015 to allow pharmacies to dispense naloxone
without a prescription. Design, Setting, and Participants: A survey
study was conducted by telephone of all pharmacies in Philadelphia
between February and August 2017. Pharmacies were geocoded and linked
with the American Community Survey (2011-2015) to obtain information on
the demographic characteristics of census tracts and the Medical
Examiner's Office of the Philadelphia Department of Public Health to
derive information on the number of opioid overdose deaths per 100000
people for each planning district. Data were analyzed from March 2018 to
February 2019. Main Outcomes and Measures: Availability and
out-of-pocket cost of naloxone nasal spray (with or without a
prescription) at Philadelphia pharmacies overall and by pharmacy and
neighborhood characteristics. Results: Of 454 eligible pharmacies, 418
were surveyed (92.1% response rate). One in 3 pharmacies (34.2%) had
naloxone nasal spray in stock; of these, 61.5% indicated it was
available without a prescription. There were significant differences in
the availability of naloxone by pharmacy type and neighborhood
characteristics. Naloxone was both more likely to be in stock (45.9% vs
27.8%; difference, 18.0%; 95% CI, 8.3%-27.8%; P < .001) and available
without a prescription (80.6% vs 42.2%; difference, 38.4%; 95% CI,
23.0%-53.8%; P < .001) in chain stores than in independent stores.
Naloxone was also less likely to be available in planning districts with
very elevated rates of opioid overdose death (>/=50 per 100000 people)
compared with those with lower rates (31.1% vs 38.5%). The median (interquartile
range) out-of-pocket cost among pharmacies offering naloxone without a
prescription was $145 ($119-$150); costs were greatest in independent
pharmacies and planning districts with elevated rates of opioid overdose
death. Conclusions and Relevance: Despite the implementation of a
statewide standing order in Pennsylvania more than 3 years prior to this
study, only one-third of Philadelphia pharmacies carried naloxone nasal
spray and many also required a physician's prescription. Efforts to
strengthen the implementation of naloxone access laws and better ensure
naloxone supply at local pharmacies are warranted, especially in
localities with the highest rates of overdose death.
Gulec, N., J. Lahey, et al. (2017). "Basic and Advanced EMS
Providers Are Equally Effective in Naloxone Administration for Opioid
Overdose in Northern New England." Prehosp Emerg
Care: 1-7.
Gulec, N., J. Lahey, et al. (2018). "Basic and Advanced EMS Providers
Are Equally Effective in Naloxone Administration for Opioid Overdose in
Northern New England." Prehosp Emerg Care
22(2): 163-169.
OBJECTIVE: Overdose mortality from illicit and prescription
opioids has reached epidemic proportions in the United States,
especially in rural areas. Naloxone is a safe and effective agent that
has been shown to successfully reverse the effects of opioid overdose in
the prehospital setting. The National EMS Scope of Practice Model
currently only recommends advanced life support (ALS) providers to
administer naloxone; however, some individual states have expanded this
scope of practice to include intranasal (IN) administration of naloxone
by basic life support (BLS) providers, including the Northern New
England states. This study compares the effectiveness and
appropriateness of naloxone administration between BLS and ALS
providers. METHODS: All Vermont, New Hampshire, and Maine EMS patient
encounters between April 1, 2014 and December 31, 2016 where naloxone
was administered were examined and 3,219 patients were identified. The
proportion of successful reversals of opioid overdose, based on
improvement in the Glasgow Coma Scale (GCS), respiratory rate (RR), and
provider global assessment (GA) of response to medication was compared
between BLS and ALS providers using a Chi-Squared statistic, Fisher's
exact or Wilcoxon rank-sum test. RESULTS: There was no significant
difference in the percent improvement in GCS between BLS and ALS (64%
and 64% P = 0.94). There was no significant difference in the percentage
of improvement in RR between BLS and ALS (45% and 48% P = 0.43). There
was a significant difference in the percentage of improvement of GA
between BLS and ALS (80% and 67% P < 0.001). There was no significant
difference in determining appropriate cases to administer naloxone where
RR < 12 and GCS < 15 between BLS and ALS (42% and 43% P = 0.94).
CONCLUSIONS: BLS providers were as effective as ALS providers in
improving patient outcome measures after naloxone administration and in
identifying patients for whom administration of naloxone is appropriate.
These findings support expanding the National EMS Scope of Practice
Model to include BLS administration of intranasal naloxone for suspected
opioid overdoses.
Hammett, T. M., S. Phan, et al. (2014). "Pharmacies as providers of
expanded health services for people who inject drugs: a review of laws,
policies, and barriers in six countries." BMC Health Serv Res
14: 261.
Heavey, S. C., A. M. Delmerico, et al. (2018). "Descriptive Epidemiology
for Community-wide Naloxone Administration by Police Officers and
Firefighters Responding to Opioid Overdose." J Community Health
43(2): 304-311.
Recently implemented New York State policy allows police and fire
to administer intranasal naloxone when responding to opioid overdoses.
This work describes the geographic distribution of naloxone
administration (NlxnA) by police and fire when responding to opioid
overdoses in Erie County, NY, an area of approximately 920,000 people
including the City of Buffalo. Data are from opioid overdose reports (N
= 800) filed with the Erie County Department of Health (July 2014-June
2016) by police/fire and include the overdose ZIP code, reported drug(s)
used, and NlxnA. ZIP code data were geocoded and mapped to examine
spatial patterns of NlxnA. The highest NlxnA rates (range: 0.01-84.3 per
10,000 population) were concentrated within the city and first-ring
suburbs. Within 3 min 27.3% responded to NlxnA and 81.6% survived the
overdose. The average individual was male (70.3%) and 31.4 years old (SD
= 10.3). Further work is needed to better understand NlxnA and overdose,
including exploring how the neighborhood environment creates a context
for drug use, and how this context influences naloxone use and overdose
experiences.
Han, J. K., L. G. Hill, et al. (2017). "Naloxone Counseling for Harm
Reduction and Patient Engagement." Fam Med
49(9): 730-733.
BACKGROUND AND OBJECTIVES: The United States is experiencing an
epidemic of opioid-related deaths. Naloxone, the drug of choice for
reversing acute opioid overdose, is not routinely prescribed for
outpatient use. The aims of this project were to improve naloxone
awareness, increase naloxone prescribing, and prevent opioid overdoses.
METHODS: A naloxone counseling intervention was implemented in three
family health centers by an interprofessional team of providers
including family medicine physicians, clinical pharmacists, and social
workers. An outreach letter was designed with provider input, an
electronic order set was developed to facilitate prescribing, and
intranasal naloxone kits were assembled for free dispensing. Providers
and staff received education about opioid overdose and naloxone
prescribing. Faculty and resident physicians were surveyed before and
after the intervention to assess their attitudes. Patients who received
naloxone kits were surveyed to assess their attitudes and use of opioids
and naloxone. RESULTS: Over 16 months, 71 outreach letters were
distributed and 97 naloxone kits were dispensed. The majority of kits
were prescribed for illicit opioid use. Faculty and resident physician
surveys indicated improved knowledge about naloxone prescribing, and
increased professional satisfaction caring for patients requesting
opioids. Surveyed patients endorsed high levels of comfort discussing
opioid use with their primary care physician. Five successful opioid
overdose reversals were reported. CONCLUSIONS: An interprofessional
naloxone counseling intervention engaged patients in opioid use
discussions, increased provider satisfaction, and reversed overdoses.
Improving naloxone access is an essential component of comprehensive
overdose prevention programs that encourage responsible opioid
prescribing and use.
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.
Klebacher, R., M. I. Harris, et al. (2017). "Incidence of Naloxone
Redosing in the Age of the New Opioid Epidemic."
Prehosp Emerg Care: 1-6.
STUDY OBJECTIVE: Naloxone, an opioid-antagonist deliverable by an
intra-nasal route, has become widely available and utilized by law
enforcement officers as well as basic life support (BLS) providers in
the prehospital setting. This study aimed to determine the frequency of
repeat naloxone dosing in suspected narcotic overdose (OD) patients and
identify patient characteristics. METHODS: A retrospective chart review
of patients over 17 years of age with suspected opioid overdose, treated
with an initial intranasal (IN) dose of naloxone and subsequently
managed by paramedics, was performed from April 2014 to June 2016.
Demographic data was analyzed using descriptive statistics to identify
those aspects of the history, physical exam findings. Results: A sample
size of 2166 patients with suspected opioid OD received naloxone from
first responders. No patients who achieved GCS 15 after treatment
required redosing; 195 (9%) received two doses and 53 patients received
three doses of naloxone by advanced life support. Patients were
primarily male (75.4%), Caucasian (88.2%), with a mean age of 36.4
years. A total of 76.7% of patients were found in the home, 23.1% had a
suspected mixed ingestion, and 27.2% had a previous OD. Two percent of
all patients required a third dose of naloxone. CONCLUSION: In this
prehospital study, we confirmed that intranasal naloxone is effective in
reversing suspected opioid toxicity. Nine percent of patients required
two or more doses of naloxone to achieve clinical reversal of suspected
opioid toxicity. Two percent of patients received a third dose of
naloxone.
Kobayashi, L., T. C. Green, et al. (2017). "Patient Simulation for
Assessment of Layperson Management of Opioid Overdose With Intranasal
Naloxone in a Recently Released Prisoner Cohort." Simul Healthc
12(1): 22-27.
INTRODUCTION: Investigators applied simulation to an experimental
program that educated, trained, and assessed at-risk, volunteering
prisoners on opioid overdose (OD) prevention, recognition, and layperson
management with intranasal (IN) naloxone. METHODS: Consenting inmates
were assessed for OD-related experience and knowledge then exposed
on-site to standardized didactics and educational DVD (without
simulation). Subjects were provided with IN naloxone kits at time of
release and scheduled for postrelease assessment. At follow-up, the
subjects were evaluated for their performance of layperson opioid OD
resuscitative skills during video-recorded simulations. Two
investigators independently scored each subject's resuscitative actions
with a 21-item checklist; post hoc video reviews were separately
completed to adjudicate subjects' interactions for overall benefit or
harm. RESULTS: One hundred three prisoners completed the baseline
assessment and study intervention and then were prescribed IN naloxone
kits. One-month follow-up and simulation data were available for 85
subjects (82.5% of trained recruits) who had been released and resided
in the community. Subjects' simulation checklist median score was 12.0 (interquartile
range, 11.0-15.0) of 21 total indicated actions. Forty-four participants
(51.8%) correctly administered naloxone; 16 additional subjects (18.8%)
suboptimally administered naloxone. Nonindicated actions, primarily
chest compressions, were observed in 49.4% of simulations. Simulated
resuscitative actions by 80 subjects (94.1%) were determined post hoc to
be beneficial overall for patients overdosing on opioids. CONCLUSIONS:
As part of an opioid OD prevention research program for at-risk inmates,
investigators applied simulation to 1-month follow-up assessments of
knowledge retention and skills acquisition in postrelease participants.
Simulation supplemented traditional research tools for investigation of
layperson OD management.
Krieter, P., N. Chiang, et al. (2016). "Pharmacokinetic
Properties and Human Use Characteristics of an FDA-Approved Intranasal
Naloxone Product for the Treatment of Opioid Overdose." J Clin
Pharmacol 56(10): 1243-1253.
Parenteral naloxone has been approved to treat opiate overdose for over 4
decades. Intranasal naloxone, administered "off label" using improvised
devices, has been widely used by both first responders and the lay
public to treat overdose. However, these improvised devices require
training for effective use, and the recommended volumes (2 to 4 mL)
exceed those considered optimum for intranasal administration. The
present study compared the pharmacokinetic properties of intranasal
naloxone (2 to 8 mg) delivered in low volumes (0.1 to 0.2 mL) using an
Aptar Unit-Dose device to an approved (0.4 mg) intramuscular dose. A
parallel study assessed the ease of use of this device in a simulated
overdose situation. All doses of intranasal naloxone resulted in plasma
concentrations and areas under the curve greater than those observed
following the intramuscular dose; the time to reach maximum plasma
concentrations was not different following intranasal and intramuscular
administration. Plasma concentrations of naloxone were dose proportional
between 2 and 8 mg and independent of whether drug was administered to 1
or both nostrils. In a study using individuals representative of the
general population, >90% were able to perform both critical tasks
(inserting nozzle into a nostril and pressing plunger) needed to deliver
a simulated dose of naloxone without prior training. Based on both
pharmacokinetic and human use studies, a 4-mg dose delivered in a single
device (0.1 mL) was selected as the final product. This product can be
used by first responders and the lay public, providing an important and
potentially life-saving intervention for victims of an opioid overdose.
Krieter, P. A., C. N. Chiang, et al. (2019). "Comparison of the
Pharmacokinetic Properties of Naloxone Following the Use of FDA-Approved
Intranasal and Intramuscular Devices Versus a Common Improvised Nasal
Naloxone Device." J Clin Pharmacol
59(8): 1078-1084.
For more than a decade, first responders and the
general public have been able to treat suspected opioid overdoses using
an improvised nasal naloxone device (INND) constructed from a prefilled
syringe containing 2 mg of naloxone (1 mg/mL) attached to a mucosal
atomization device. In recent years, the U.S. Food and Drug
Administration (FDA)-approved Ezvio, an autoinjector that delivers 2 mg
by intramuscular injection and Narcan nasal spray (2- and 4-mg
strengths; 0.1 mL/dose) for the emergency treatment of a known or
suspected opioid overdose. The present study was conducted to compare
the pharmacokinetics of naloxone using the FDA-approved devices (each
administered once) and either 1 or 2 administrations using the INND.
When naloxone was administered twice using the improvised device, the
doses were separated by 2 minutes. The highest maximum plasma
concentration was achieved using the 4-mg FDA-approved spray. The
highest exposures at 5 minutes postdose, based on AUC values, were after
administration with the autoinjector and the 4-mg FDA-approved spray; at
10, 15, and 20 minutes postdose, the latter yielded the greatest
exposure. Even after 2 administrations, the INND failed to achieve
naloxone plasma levels comparable to the FDA-approved devices at any
time. The ease of use and higher plasma concentrations achieved using
the 4-mg FDA-approved spray, compared with the INND, should be
considered when deciding which naloxone device to use.
Lenton, S., P. Dietze, et al. (2014). "Working together:
Expanding the availability of naloxone for peer administration to
prevent opioid overdose deaths in the Australian Capital Territory and
beyond." Drug Alcohol Rev.
ISSUE: Since the mid-1990s, there have been calls to make naloxone, a
prescription-only medicine in many countries, available to heroin and
other opioid users and their peers and family members to prevent
overdose deaths. CONTEXT: In Australia there were calls for a trial of
peer naloxone in 2000, yet at the end of that year, heroin availability
and harm rapidly declined, and a trial did not proceed. In other
countries, a number of peer naloxone programs have been successfully
implemented. Although a controlled trial had not been conducted,
evidence of program implementation demonstrated that trained injecting
drug-using peers and others could successfully administer naloxone to
reverse heroin overdose, with few, if any, adverse effects. APPROACH: In
2009 Australian drug researchers advocated the broader availability of
naloxone for peer administration in cases of opioid overdose.
Industrious local advocacy and program development work by a number of
stakeholders, notably by the Canberra Alliance for Harm Minimisation and
Advocacy, a drug user organisation, contributed to the rollout of
Australia's first prescription naloxone program in the Australian
Capital Territory (ACT). Over the subsequent 18 months, prescription
naloxone programs were commenced in four other Australian states.
IMPLICATIONS: The development of Australia's first take-home naloxone
program in the ACT has been an 'ice-breaker' for development of other
Australian programs. Issues to be addressed to facilitate future
scale-up of naloxone programs concern scheduling and cost, legal
protections for lay administration, prescribing as a barrier to
scale-up; intranasal administration, administration by service providers
and collaboration between stakeholders.
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.
Madah-Amiri, D., L. Gjersing, et al. (2019). "Naloxone distribution and
possession following a large-scale naloxone programme." Addiction
114(1): 92-100.
Mahonski, S. G., J. B. Leonard, et al. (2019). "Prepacked naloxone
administration for suspected opioid overdose in the era of illicitly
manufactured fentanyl: a retrospective study of regional poison center
data." Clin Toxicol (Phila):
1-7.
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.
McDonald, R., O. Danielsson Glende, et al. (2018). "International patent
applications for non-injectable naloxone for opioid overdose reversal:
Exploratory search and retrieve analysis of the PatentScope database."
Drug Alcohol Rev 37(2):
205-215.
McDonald, R., U. Lorch, et al. (2018). "Pharmacokinetics of concentrated
naloxone nasal spray for opioid overdose reversal: Phase I healthy
volunteer study." Addiction
113(3): 484-493.
Open access:
https://onlinelibrary.wiley.com/doi/epdf/10.1111/add.14033
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.
Neale, J., C. Brown, et al. (2018). "How competent are people
who use opioids at responding to overdoses? Qualitative analyses of
actions and decisions taken during overdose emergencies."
Addiction.
BACKGROUND AND AIMS: Providing take-home naloxone (THN) to people who use opioids is an increasingly common strategy for reversing opioid overdose. However, implementation is hindered by doubts regarding the ability of people who use opioids to administer naloxone and respond appropriately to overdoses. We aimed to increase understanding of the competencies required and demonstrated by opioid users who had recently participated in a THN programme and were subsequently confronted with an overdose emergency. DESIGN: Qualitative study designed to supplement findings from a randomized controlled trial of overdose education and naloxone distribution. Interviews were audio-recorded, transcribed, systematically coded and analysed via Iterative Categorization. SETTING: New York City, USA. PARTICIPANTS: Thirty-nine people who used opioids (32 men, 7 women; aged 22-58 years). INTERVENTION: Trial participants received brief or extended overdose training and injectable or nasal naloxone. MEASUREMENTS: The systematic coding frame comprised deductive codes based on the topic guide and more inductive codes emerging from the data. FINDINGS: In 38 of 39 cases the victim was successfully resuscitated; the outcome of one overdose intervention was unknown. Analyses revealed five core overdose response 'tasks': (1) overdose identification; (2) mobilizing support; (3) following basic first aid instructions; (4) naloxone administration; and (5) post-resuscitation management. These tasks comprised actions and decisions that were themselves affected by diverse cognitive, emotional, experiential, interpersonal and social factors over which lay responders often had little control. Despite this, participants demonstrated high levels of competency. They had acquired new skills and knowledge through training and brought critical 'insider' understanding to overdose events and the resuscitation actions which they applied. CONCLUSIONS: People who use opioids can be trained to respond appropriately to opioid overdoses and thus to save their peers' lives. Overdose response requires both practical competency (e.g. skills and knowledge in administering basic first aid and naloxone) and social competency (e.g. willingness to help others, having the confidence to be authoritative and make decisions, communicating effectively and demonstrating compassion and care to victims post-resuscitation).
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)
Pietrusza, L. M., K. R. Puskar, et al. (2018). "Evaluation of an Opiate
Overdose Educational Intervention and Naloxone Prescribing Program in
Homeless Adults Who Use Opiates." J Addict Nurs
29(3): 188-195.
Pruyn, S., J. Frey, et al. (2019). "Quality Assessment of Expired
Naloxone Products from First-Responders' Supplies." Prehosp Emerg
Care 23(5):
647-653.
Objective: Naloxone is an opioid receptor antagonist
that reverses life-threatening effects of opioid overdose. Since the
1970s, naloxone products have been developed as injectable solutions,
and more recently as nasal sprays. Naloxone products have saved many
lives in emergency settings. These products are routinely carried by
public safety first-responders including fire fighters (FF), law
enforcement officers (LEO), and emergency medical services (EMS). Now,
they are also distributed through community access programs to the
public. While public safety medications are monitored, those publically
distributed are not, so expired products can be possibly found on-hand
in an emergency. This study analyzed the quality and stability of
expired Naloxone HCl Solutions for Injection, to assess their remaining
efficacies and potential risks. Methods: The samples were collected from
EMS or law enforcement training supplies and expired returns, with
expiration dates ranging from 1990 to 2018. Using standardized
techniques, the remaining naloxone was quantified, and the main
degradation products, nornaloxone (also known as noroxymorphone) and
other possible species, were monitored and quantified systematically.
Results: Most tested samples were found containing more than 90% of
labeled naloxone, including those stored for nearly 30 years. The
naloxone degradation was slow, but generally correlated with storage
time length. There was no significant amount of degradation products
detected across all samples. Nornaloxone was detected from some older
samples, but all less than 1%. Therefore, although it is an opioid
agonist, the risk caused by nornaloxone should be low. Conclusion: This
quality assessment demonstrates that expired naloxone products may still
meet USP standards, even after many years. Further pharmaceutical,
clinical, and regulatory investigation should be conducted to confirm
our findings, especially for new naloxone products with different
formulations and routes of administration. Extending the shelf-life of
naloxone products may have important financial and public health
consequences in addressing future drug shortages and meeting the needs
for this critical drug.
Rando, J., D. Broering, et al. (2015). "Intranasal naloxone
administration by police first responders is associated with decreased
opioid overdose deaths." Am J Emerg Med.
OBJECTIVE: This study sought to answer the question, "Can police
officers administer intranasal naloxone to drug overdose victims to
decrease the opioid overdose death rate?" METHODS: This prospective
interventional study was conducted in Lorain County, OH, from January
2011 to October 2014. Starting October 2013, trained police officers
administered naloxone to suspected opioid overdose victims through a
police officer naloxone prescription program (NPP). Those found by the
county coroner to be positive for opioids at the time of death and those
who received naloxone from police officers were included in this study.
The rate of change in the total number of opioid-related deaths in
Lorain County per quarter year, before and after initiation of the NPP,
and the trend in the survival rate of overdose victims who were given
naloxone were analyzed by linear regression. Significance was
established a priori at P < .05. RESULTS: Data from 247 individuals were
eligible for study inclusion. Opioid overdose deaths increased
significantly before initiation of the police officer NPP with average
deaths per quarter of 5.5 for 2011, 15.3 for 2012, and 16.3 for the
first 9 months of 2013. After initiation of the police officer NPP, the
number of opioid overdose deaths decreased each quarter with an overall
average of 13.4. Of the 67 participants who received naloxone by police
officers, 52 (77.6%) survived, and 8 (11.9%) were lost to follow-up.
CONCLUSIONS: Intranasal naloxone administration by police first
responders is associated with decreased deaths in opioid overdose
victims.
Ray B, O'Donnell D, Kahre K. Police officer attitudes towards intranasal naloxone training. Drug Alcohol Depend 2015;146:107-10.
Richert, T. (2015). "Wasted, overdosed, or beyond saving -
To act or not to act? Heroin users' views, assessments, and responses to
witnessed overdoses in Malmo, Sweden." Int J Drug Policy
26(1): 92-99.
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.
Rosenberg, M., G. Chai, et al. (2018). "Trends and economic drivers for
United States naloxone pricing, January 2006 to February 2017."
Addict Behav 86:
86-89.
Anecdotal evidence indicates that naloxone prices have risen in recent years, but limited research has examined the magnitude of these increases and potential causes. We contribute nationally representative evidence to help answer each of these questions, including wholesale pricing data from a proprietary drug sales database spanning January 2006 to February 2017. We find that all formulations of naloxone increased in price since 2006 except for Narcan Nasal Spray. These cumulative increases totaled 2281% for the 0.4 MG single-dose products, 244% for the 2 MG single-dose products, 3797% for the 4 MG multi-dose products, and 469% for the 0.4 MG Evzio auto-injector. We believe that increased demand for naloxone from the opioid epidemic may explain the more gradual price increases for the 0.4 MG single-dose and 4 MG multi-dose products prior to 2012. On the other hand, we believe that the sudden, sustained prices increases occurring for all of the products since 2012 may be the result of a drug shortage for the 0.4 MG single-dose products and the fact that each naloxone product has historically been sold by only a single competitor.
Sabzghabaee, A. M., N. Eizadi-Mood, et al. (2014). "Naloxone therapy in
opioid overdose patients: intranasal or intravenous? A randomized
clinical trial." Arch Med Sci
10(2): 309-314.
INTRODUCTION: This study was designed to compare the
effects of intranasal (IN) and intravenous (IV) administration of
naloxone in patients who had overdosed on opioids. MATERIAL AND METHODS:
This randomized clinical trial study was conducted in the Department of
Poisoning Emergencies at Noor and Ali Asghar (PBUH) University Hospital.
One hundred opioid overdose patients were assigned by random allocation
software into two study groups (n = 50). Both groups received 0.4 mg
naloxone: one group IN and the other IV. Outcomes included change in the
level of consciousness (measured using a descriptive scale and the
Glasgow Coma Scale (GCS)), time to response, vital signs (blood
pressure, heart rate and respiratory rate), arterial blood O2 saturation
before and after naloxone administration, side-effects (agitation) and
length of hospital stay. RESULTS: Patients who had been administered IN
naloxone demonstrated significantly higher levels of consciousness than
those in the IV group using both descriptive and GCS scales (p < 0.001).
There was a significant difference in the heart rate between IN and IV
groups (p = 0.003). However, blood pressure, respiratory rate and
arterial O2 saturation were not significantly different between the two
groups after naloxone administration (p = 0.18, p = 0.17, p = 0.32).
There was also no significant difference in the length of hospital stay
between the two groups (p = 0.14). CONCLUSIONS: Intranasal naloxone is
as effective as IV naloxone in reversing both respiratory depression and
depressive effects on the central nervous system caused by opioid
overdose.
Samuels, E. (2014). "Emergency department naloxone distribution: a rhode
island department of health, recovery community, and emergency
department partnership to reduce opioid overdose deaths." R I Med J
(2013) 97(10):
38-39.
In response to increasing rates of opioid overdose deaths in Rhode Island (RI, the RI Department of Health, RI emergency physicians, and Anchor Community Recovery Center designed an emergency department (ED) naloxone distribution and peer-recovery coach program for people at risk of opioid overdose. ED patients at risk for overdose are offered a take home naloxone kit, patient education video, and, when available, an Anchor peer recovery coach to provide recovery support and referral to treatment. In August 2014, the program launched at Kent, Miriam, and Rhode Island Hospital Emergency Departments. [Full text available at http://rimed.org/rimedicaljournal-2014-10.asp, free with no login].
Seal, K. H., M. Downing, et al. (2003). "Attitudes about prescribing
take-home naloxone to injection drug users for the management of heroin
overdose: a survey of street-recruited injectors in the San Francisco
Bay Area." J Urban Health
80(2): 291-301.
Naloxone, an injectable opiate antagonist, can
immediately reverse an opiate overdose and prevent overdose death. We
sought to determine injection drug users' (IDUs) attitudes about being
prescribed take-home naloxone. During November 1999 to February 2000, we
surveyed 82 street-recruited IDUs from the San Francisco Bay Area of
California who had experienced one or more heroin overdose events. We
used a questionnaire that included structured and open-ended questions.
Most respondents (89%) had witnessed an overdose, and 90% reported
initially attempting lay remedies in an effort to help companions
survive. Only 51% reported soliciting emergency assistance (calling 911)
for the last witnessed overdose, with most hesitating due to fear of
police involvement. Of IDUs surveyed, 87% were strongly in favor of
participating in an overdose management training program to receive
take-home naloxone and training in resuscitation techniques.
Nevertheless, respondents expressed a variety of concerning attitudes.
If provided naloxone, 35% predicted that they might feel comfortable
using greater amounts of heroin, 62% might be less inclined to call 911
for an overdose, 30% might leave an overdose victim after naloxone
resuscitation, and 46% might not be able to dissuade the victim from
using heroin again to alleviate withdrawal symptoms induced by naloxone.
Prescribing take-home naloxone to IDUs with training in its use and in
resuscitation techniques may represent a life-saving, peer-based adjunct
to accessing emergency services. Nevertheless, strategies for overcoming
potential risks associated with the use of take-home naloxone would need
to be emphasized in an overdose management training program.
Seal, K. H., R. Thawley, et al. (2005). "Naloxone distribution and
cardiopulmonary resuscitation training for injection drug users to
prevent heroin overdose death: a pilot intervention study." J Urban
Health 82(2):
303-311.
Fatal heroin overdose has become a leading cause of death among injection drug users (IDUs). Several recent feasibility studies have concluded that naloxone distribution programs for heroin injectors should be implemented to decrease heroin over-dose deaths, but there have been no prospective trials of such programs in North America. This pilot study was undertaken to investigate the safety and feasibility of training injection drug using partners to perform cardiopulmonary resuscitation (CPR) and administer naloxone in the event of heroin overdose. During May and June 2001, 24 IDUs (12 pairs of injection partners) were recruited from street settings in San Francisco. Participants took part in 8-hour training in heroin overdose prevention, CPR, and the use of naloxone. Following the intervention, participants were prospectively followed for 6 months to determine the number and outcomes of witnessed heroin overdoses, outcomes of participant interventions, and changes in participants' knowledge of overdose and drug use behavior. Study participants witnessed 20 heroin overdose events during 6 months follow-up. They performed CPR in 16 (80%) events, administered naloxone in 15 (75%) and did one or the other in 19 (95%). All overdose victims survived. Knowledge about heroin overdose management increased, whereas heroin use decreased. IDUs can be trained to respond to heroin overdose emergencies by performing CPR and administering naloxone. Future research is needed to evaluate the effectiveness of this peer intervention to prevent fatal heroin overdose.
Skulberg, A. K., A. Asberg, et al. (2019). "Pharmacokinetics of a novel,
approved, 1.4-mg intranasal naloxone formulation for reversal of opioid
overdose-a randomized controlled trial." Addiction
114(5): 859-867.
BACKGROUND AND AIMS: Intranasal (i.n.) naloxone is an
established treatment for opioid overdose. Anyone likely to witness an
overdose should have access to the antidote. We aimed to determine
whether an i.n. formulation delivering 1.4 mg naloxone hydrochloride
would achieve systemic exposure comparable to that of 0.8 mg
intramuscular (i.m.) naloxone. DESIGN: Open, randomized four-way
cross-over trial. SETTING: Clinical Trials Units in St Olav's Hospital,
Trondheim and Rikshospitalet, Oslo, Norway. PARTICIPANTS: Twenty-two
healthy human volunteers, 10 women, median age = 25.8 years.
INTERVENTION AND COMPARATOR: One and two doses of i.n. 1.4 mg naloxone
compared with i.m. 0.8 mg and intravenous (i.v.) 0.4 mg naloxone.
MEASUREMENTS: Quantification of plasma naloxone was performed by liquid
chromatography tandem mass spectrometry. Pharmacokinetic non-compartment
analyses were used for the main analyses. A non-parametric
pharmacokinetic population model was developed for Monte Carlo
simulations of different dosing scenarios. FINDINGS: Area under the
curve from administration to last measured concentration (AUC0-last )
for i.n. 1.4 mg and i.m. 0.8 mg were 2.62 +/- 0.94 and 3.09 +/- 0.64 h x
ng/ml, respectively (P = 0.33). Maximum concentration (Cmax ) was 2.36
+/- 0.68 ng/ml for i.n. 1.4 mg and 3.73 +/- 3.34 for i.m. 0.8 mg (P =
0.72). Two i.n. doses showed dose linearity and achieved a Cmax of 4.18
+/- 1.53 ng/ml. Tmax was reached after 20.2 +/- 9.4 minutes for i.n. 1.4
mg and 13.6 +/- 15.4 minutes for i.m. 0.8 mg (P = 0.098). The absolute
bioavailability for i.n. 1.4 mg was 0.49 (+/-0.24), while the relative
i.n./i.m. bioavailability was 0.52 (+/-0.25). CONCLUSION: Intranasal 1.4
mg naloxone provides adequate systemic concentrations to treat opioid
overdose compared with intramuscular 0.8 mg, without statistical
difference on maximum plasma concentration, time to maximum plasma
concentration or area under the curve. Simulations support its
appropriateness both as peer administered antidote and for titration of
treatment by professionals.
Smart, R., C. K. Geiger, et al. (2019). "An Observational Study of
Retail Pharmacy Naloxone Prescriptions: Differences Across Provider
Specialties and Patient Populations." J Gen Intern
Med.
BACKGROUND: Despite exponential growth in
pharmacy-dispensed naloxone, little information is available regarding
variation in naloxone prescribing pattern across specialty groups,
regions, and patient populations. OBJECTIVE: Explore variation in
pharmacy-dispensed naloxone by prescriber specialty and patient
characteristics. DESIGN: Cross-sectional analysis of the 2016 national
retail pharmacy naloxone prescription claims from the IQVIA Real
Longitudinal Prescriptions database. PARTICIPANTS: Naloxone prescribers
and individuals filling naloxone prescriptions. MAIN MEASURES:
Descriptive statistics assess differences across prescriber specialty
groups in number of naloxone prescribers, patient and prescription
characteristics, and geographic variation in naloxone dispensation and
naloxone market share across prescriber specialty groups or formulation.
KEY RESULTS: In 2016, 100,958 naloxone prescriptions written by 14,026
prescribers were filled by 88,735 patients. Primary care physicians
accounted for the largest share of naloxone prescribers (45.9%); pain
and anesthesia physicians and non-physicians prescribed to significantly
greater numbers of patients (means of 10 and 8, respectively). While
responsible for a relatively small share of naloxone dispensed (6.1%),
psychiatrists and addiction specialists disproportionately served
younger individuals, accounting for 49.5% of all prescriptions for
individuals aged 35 and younger. Naloxone fill rates differed greatly
across geographic regions, with the highest per capita rates in New
England and the most concentrated prescribing in the West South Central
and South Atlantic regions, where naloxone prescribers had the highest
average numbers of patients (9.7 and 7.9, respectively). The South
Atlantic and West South Central also had naloxone markets dominated by
the Evzio(R) auto-injector, responsible for 50.3% and 43.8% of all
naloxone dispensed in the regions; in contrast, New England's naloxone
market was predominantly comprised of generic formulations (48.8%) and
Narcan(R) nasal spray (45.4%). CONCLUSIONS: Our findings reflect a need
to better understand barriers to uptake of naloxone prescribing behavior
among physicians and other prescribers to ensure individuals have
adequate opportunity to receive naloxone from their treating clinicians.
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.
Strang, J., R. McDonald, et al. (2016). "Clinical provision of
improvised nasal naloxone without experimental testing and without
regulatory approval: imaginative shortcut or dangerous bypass of
essential safety procedures?" Addiction 111(4): 574-582.
CONTEXT: Take-home naloxone is increasingly provided to prevent heroin
overdose deaths. Naloxone 0.4-2.0 mg is licensed for use by injection.
Some clinicians supply improvised nasal naloxone kits (outside licensed
approval). Is this acceptable? AIMS: (1) To consider provision of
improvised nasal naloxone in clinical practice and (2) to search for
evidence for pharmacokinetics and effectiveness (versus injection).
METHODS: (1) To document existing nasal naloxone schemes and published
evidence of pharmacokinetics (systematic search of the CINAHL, Cochrane,
EMBASE and MEDLINE databases and 18 records included in narrative
synthesis). (2) To analyse ongoing studies investigating nasal naloxone
(WHO International Clinical Trials Registry Platform and US NIH RePORT
databases). FINDINGS: (1) Multiple studies report overdose reversals
following administration of improvised intranasal naloxone. (2) Overdose
reversal after nasal naloxone is frequent but may not always occur. (3)
Until late 2015, the only commercially available naloxone concentrations
were 0.4 mg/ml and 2 mg/2 ml. Nasal medications are typically 0.05-0.25
ml of fluid per nostril. The only published study of pharmacokinetics
and bioavailability finds that nasal naloxone has poor bioavailability.
QUESTIONS FOR DEBATE: (1) Why are pharmacokinetics and bioavailability
data for nasal naloxone not available before incorporation into standard
clinical practice? (2) Does nasal naloxone have the potential to become
a reliable clinical formulation? (3) What pre-clinical and clinical
studies should precede utilization of novel naloxone formulations as
standard emergency medications? CONCLUSIONS: The addictions treatment
field has rushed prematurely into the use of improvised nasal naloxone
kits. Evidence of adequate bioavailability and acceptable
pharmacokinetic curves are vital preliminary steps, especially when
effective approved formulations exist.
Strang, J., R. McDonald, et al. (2019). "Take-Home Naloxone for the
Emergency Interim Management of Opioid Overdose: The Public Health
Application of an Emergency Medicine." Drugs
79(13): 1395-1418.
Naloxone is a well-established essential medicine for
the treatment of life-threatening heroin/opioid overdose in emergency
medicine. Over two decades, the concept of 'take-home naloxone' has
evolved, comprising pre-provision of an emergency supply to laypersons
likely to witness an opioid overdose (e.g. peers and family members of
people who use opioids as well as non-medical personnel), with the
recommendation to administer the naloxone to the overdose victim as
interim care while awaiting an ambulance. There is an urgent need for
more widespread naloxone access considering the growing problem of
opioid overdose deaths, accounting for more than 100,000 deaths
worldwide annually. Rises in mortality are particularly sharp in North
America, where the ongoing prescription opioid problem is now overlaid
with a rapid growth in overdose deaths from heroin and illicit fentanyl.
Using opioids alone is dangerous, and the mortality risk is clustered at
certain times and contexts, including on prison release and discharge
from hospital and residential care. The provision of take-home naloxone
has required the introduction of new legislation and new naloxone
products. These include pre-filled syringes and auto-injectors and,
crucially, new concentrated nasal sprays (four formulations recently
approved in different countries) with speed of onset comparable to
intramuscular naloxone and relative bioavailability of approximately
40-50%. Choosing the right naloxone dose in the fentanyl era is a matter
of ongoing debate, but the safety margin of the approved nasal sprays is
superior to improvised nasal kits. New legislation in different
countries permits over-the-counter sales or other prescription-free
methods of provision. However, access remains uneven with take-home
naloxone still not provided in many countries and communities, and with
ongoing barriers contributing to implementation inertia. Take-home
naloxone is an important component of the response to the global
overdose problem, but greater commitment to implementation will be
essential, alongside improved affordable products, if a greater impact
is to be achieved.
Tippey, K. G., M. Yovanoff, et al. (2019). "Comparative Human Factors
Evaluation of Two Nasal Naloxone Administration Devices: NARCAN((R))
Nasal Spray and Naloxone Prefilled Syringe with Nasal Atomizer." Pain
Ther 8(1): 89-98.
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.
Vanky, E., L. Hellmundt, et al. (2017). "Pharmacokinetics after a single
dose of naloxone administered as a nasal spray in healthy volunteers."
Acta Anaesthesiol Scand
61(6): 636-640.
BACKGROUND: There is increasing interest in the use of intranasal
naloxone to reverse adverse opioid effects during management of
procedural pain in children and in adults after overdose. There are
limited data on the pharmacokinetics of intranasal naloxone so in this
study we aimed to detail the pharmacokinetic profile of the commercially
marketed injectable solution of naloxone 0.4 mg/ml when administered as
an intranasal spray. METHODS: Twenty healthy volunteers received
naloxone as an intranasal spray at a dose of 10 mug/kg. Venous blood
sampling was carried out for 90 min after administration to determine
the time profile of the plasma concentrations of using tandem mass
spectrometry. Pharmacokinetic parameters were calculated using a
one-compartment model. RESULTS: Median time to maximum naloxone
concentration (Tmax) was 14.5 (95% CI: 9.0-16.5) min, mean maximum
naloxone concentration (Cmax) was 1.09 +/- 0.56 ng/ml and mean AUC0-90
min was 37.1 +/- 15.0 ng*min/ml. Elimination half-life estimated from
the median concentration data was 28.2 min. CONCLUSION: Our results show
a faster uptake of intranasal naloxone to maximum concentration compared
with previous studies although with a marked variation in maximum
concentration. The findings are consistent with our clinical experience
of the time profile for reversing the effects of sufentanil sedation in
children.
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.
Wagner, K. D., P. J. Davidson, et al. (2014). ""I felt like a
superhero": the experience of responding to drug overdose among
individuals trained in overdose prevention." Int J Drug Policy
25(1): 157-165.
BACKGROUND: Overdose prevention programs (OPPs) train
people who inject drugs and other community members to prevent,
recognise and respond to opioid overdose. However, little is known about
the experience of taking up the role of an "overdose responder" for the
participants. METHODS: We present findings from qualitative interviews
with 30 participants from two OPPs in Los Angeles, CA, USA from 2010 to
2011 who had responded to at least one overdose since being trained in
overdose prevention and response. RESULTS: Being trained by an OPP and
responding to overdoses had both positive and negative effects for
trained "responders". Positive effects include an increased sense of
control and confidence, feelings of heroism and pride, and a recognition
and appreciation of one's expertise. Negative effects include a sense of
burden, regret, fear, and anger, which sometimes led to cutting social
ties, but might also be mitigated by the increased empowerment
associated with the positive effects. CONCLUSION: Findings suggest that
becoming an overdose responder can involve taking up a new social role
that has positive effects, but also confers some stress that may require
additional support. OPPs should provide flexible opportunities for
social support to individuals making the transition to this new and
critical social role. Equipping individuals with the skills, technology,
and support they need to respond to drug overdose has the potential to
confer both individual and community-wide benefits.
Wagner, K. D., T. W. Valente, et al. (2010). "Evaluation of an overdose
prevention and response training programme for injection drug users in
the Skid Row area of Los Angeles, CA." Int J Drug Policy
21(3): 186-193.
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.
Weiner, S. G., P. M. Mitchell, et al. (2017). "Use of Intranasal
Naloxone by Basic Life Support Providers." Prehosp Emerg Care
21(3): 322-326.
STUDY OBJECTIVES: Intranasal delivery of naloxone to reverse the
effects of opioid overdose by Advanced Life Support (ALS) providers has
been studied in several prehospital settings. In 2006, in response to
the increase in opioid-related overdoses, a special waiver from the
state allowed administration of intranasal naloxone by Basic Life
Support (BLS) providers in our city. This study aimed to determine: 1)
if patients who received a 2-mg dose of nasal naloxone administered by
BLS required repeat dosing while in the emergency department (ED), and
2) the disposition of these patients. METHODS: This was a retrospective
review of patients transported by an inner-city municipal ambulance
service to one of three academic medical centers. We included patients
aged 18 and older that were transported by ambulance between 1/1/2006
and 12/12/2012 and who received intranasal naloxone by BLS providers as
per a state approved protocol. Site investigators matched EMS run data
to patients from each hospital's EMR and performed a chart review to
confirm that the patient was correctly identified and to record the
outcomes of interest. Descriptive statistics were then generated.
RESULTS: A total of 793 patients received nasal naloxone by BLS and were
transported to three hospitals. ALS intervened and transported 116
(14.6%) patients, and 11 (1.4%) were intubated in the field. There were
724 (91.3%) patients successfully matched to an ED chart. Hospital A
received 336 (46.4%) patients, Hospital B received 210 (29.0%) patients,
and Hospital C received 178 (24.6%) patients. Mean age was 36.2 (SD
10.5) years and 522 (72.1%) were male; 702 (97.1%) were reported to have
abused heroin while 21 (2.9%) used other opioids. Nasal naloxone had an
effect per the prehospital record in 689 (95.2%) patients. An additional
naloxone dose was given in the ED to 64 (8.8%) patients. ED dispositions
were: 507 (70.0%) discharged, 105 (14.5%) admitted, and 112 (15.5%)
other (e.g., left against medical advice, left without being seen, or
transferred). CONCLUSIONS: Only a small percentage of patients receiving
prehospital administration of nasal naloxone by BLS providers required
additional doses of naloxone in the ED and the majority of patients were
discharged.
Wermeling, D. P. (2010). "Opioid harm reduction strategies: focus on expanded access to intranasal naloxone." Pharmacotherapy 30(7): 627-631.
Wermeling, D. P. (2015). "Review of naloxone safety for
opioid overdose: practical considerations for new technology and
expanded public access." Ther Adv Drug Saf
6(1): 20-31.
Opioid overdose and mortality have increased at an alarming rate prompting new public health initiatives to reduce drug poisoning. One initiative is to expand access to the opioid antidote naloxone. Naloxone has a long history of safe and effective use by organized healthcare systems and providers in the treatment of opioid overdose by paramedics/emergency medicine technicians, emergency medicine physicians and anesthesiologists. The safety of naloxone in a prehospital setting administered by nonhealthcare professionals has not been formally established but will likely parallel medically supervised experiences. Naloxone dose and route of administration can produce variable intensity of potential adverse reactions and opioid withdrawal symptoms: intravenous administration and higher doses produce more adverse events and more severe withdrawal symptoms in those individuals who are opioid dependent. More serious adverse reactions after naloxone administration occur rarely and may be confounded by the effects of other co-intoxicants and the effects of prolonged hypoxia. One component of the new opioid harm reduction initiative is to expand naloxone access to high-risk individuals (addicts, abusers, or patients taking high-dose or extended-release opioids for pain) and their close family or household contacts. Patients or their close contacts receive a naloxone prescription to have the medication on their person or in the home for use during an emergency. Contacts are trained on overdose recognition, rescue breathing and administration of naloxone by intramuscular injection or nasal spraying of the injection prior to the arrival of emergency medical personnel. The safety profile of naloxone in traditional medical use must be considered in this new context of outpatient prescribing, dispensing and treatment of overdose prior to paramedic arrival. New naloxone delivery products are being developed for this prehospital application of naloxone in treatment of opioid overdose and prevention of opioid-induced mortality.
Williams, K., E. S. Lang, et al. (2019). "Evidence-Based Guidelines
for EMS Administration of Naloxone." Prehosp Emerg Care
23(6): 749-763.
The opioid crisis is a growing concern for Americans,
and it has become the leading cause of injury-related death in the
United States. An adjunct to respiratory support that can reduce this
high mortality rate is the administration of naloxone by Emergency
Medical Services (EMS) practitioners for patients with suspected opioid
overdose. However, clear evidence-based guidelines to direct EMS use of
naloxone for opioid overdose have not been developed. Leveraging the
recent Agency for Healthcare Research and Quality (AHRQ) systematic
review on the EMS administration of naloxone for opioid poisonings,
federal partners determined the need for a clinical practice guideline
for EMS practitioners faced with suspected opioid poisoning. Project
funding was provided by the National Highway Traffic Safety
Administration, Office of EMS, (NHTSA OEMS), and the Health Resources
and Services Administration, Maternal and Child Health Bureau's EMS for
Children Program (EMSC). The objectives of this project were to develop
and disseminate an evidence-based guideline and model protocol for
administration of naloxone by EMS practitioners to persons with
suspected opioid overdose. We have four recommendations relating to
route of administration, all conditional, and all supported by low or
very low certainty of evidence. We recommend the intravenous route of
administration to facilitate titration of dose, and disfavor the
intramuscular route due to difficulty with titration, slower time to
clinical effect, and potential exposure to needles. We equally recommend
the intranasal and intravenous routes of administration, while noting
there are variables which will determine which route is best for each
patient. Where we are unable to make recommendations due to evidence
limitations (dosing, titration, timing, and transport) we offer
technical remarks. Limitations of our work include the introduction of
novel synthetic opioids after many of the reviewed papers were produced,
which may affect the dose of naloxone required for effect, high risk of
bias and imprecision in the reviewed papers, and the introduction of new
naloxone administration devices since many of the reviewed papers were
published. Future research should be conducted to evaluate new devices
and address the introduction of synthetic opioids.
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.
Wu, C., T. Brown, et al. (2019). "Access to naloxone at community
pharmacies under the Massachusetts statewide standing order."
J Am Pharm Assoc (2003).
OBJECTIVE: This study aimed to evaluate access to, and
barriers to accessing, naloxone at community pharmacies throughout
Massachusetts following implementation of new legislation that requires
all community pharmacies to maintain a sufficient supply for dispensing
under a statewide standing order. DESIGN: From September 2018 through
January 2019, we conducted a cross-sectional telephone-based survey of
Massachusetts pharmacies by having an interviewer pose as a customer
seeking naloxone. SETTING AND PARTICIPANTS: Community pharmacies were
identified from a list of all actively licensed pharmacies provided by
the Massachusetts Department of Public Health and one-half were randomly
selected for inclusion. Pharmacies that were permanently closed,
duplicated on the list, or closed to the general public were excluded
from analysis. OUTCOME MEASURES: Rates of stocked naloxone, perceived
need for identification or prescription, and pricing. RESULTS: Of the
524 pharmacies surveyed, 97.7% (n = 512) reported routinely stocking
naloxone. Of those, 90.4% (n = 463) had naloxone in stock on the day of
contact. Most pharmacies with naloxone in stock did not require a
prescription (96.1%; n = 445); at these pharmacies, personal
identification was required by 38.9% (n = 180). The average
out-of-pocket naloxone nasal spray price was $128.34 +/- $40.75.
CONCLUSION: Nearly all Massachusetts community pharmacies routinely
stock naloxone as required by state law; however, barriers remain
regarding perceived need for identification and high out-of-pocket
costs.