Prehospital Emergency Care
`
`ISSN: 1090-3127 (Print) 1545-0066 (Online) Journal homepage: https://www.tandfonline.com/loi/ipec20
`
`Naloxone Use in a Tiered-Response Emergency
`Medical Services System
`
`Daniel Belz, Jacob Lieb, Tom Rea & Mickey S. Eisenberg
`
`To cite this article: Daniel Belz, Jacob Lieb, Tom Rea & Mickey S. Eisenberg (2006) Naloxone
`Use in a Tiered-Response Emergency Medical Services System, Prehospital Emergency Care,
`10:4, 468-471, DOI: 10.1080/10903120600885134
`To link to this article: https://doi.org/10.1080/10903120600885134
`
`Published online: 02 Jul 2009.
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`NALOXONE USE IN A TIERED-RESPONSE EMERGENCY
`MEDICAL SERVICES SYSTEM
`Daniel Belz, BA, Jacob Lieb, BS, Tom Rea, MD, MPH, Mickey S. Eisenberg, MD, PhD
`
`ABSTRACT
`
`Objective. To examine the delivery and effect of naloxone
`for opioid overdose in a tiered-response emergency medi-
`cal services (EMS) system and to ascertain how much time
`could be saved if the first arriving emergency medical tech-
`nicians (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 ba-
`sic life support–trained fire fighter–EMTs and/or advanced
`life support–trained paramedics depending on the sever-
`ity 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 ar-
`rival of paramedics at the scene. Results. There were 164 pa-
`tients who received naloxone for suspected overdose. There
`were 75 patients (46%) initially unresponsive to painful stim-
`ulus. Respiratory rate was <10 breaths/min in 79 (48%).
`Death occurred in 36 (22%) at the scene or during trans-
`port. A full or partial response to naloxone occurred in 119
`(73%). Recognized adverse reactions were limited to agita-
`tion/combativeness in 25 (15%) and emesis in six (4%). Aver-
`age EMT arrival time was 5.9 minutes. Average paramedic ar-
`rival 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 train-
`ing and authorizing EMTs to administer intranasal nalox-
`one in suspected opioid overdose is warranted. Key words:
`emergency medical technician; heroin; naloxone; Narcan;
`overdose; opioid; opiate.
`
`PREHOSPITAL EMERGENCY CARE 2006;10:468–471
`
`INTRODUCTION
`Basic emergency medical technicians (EMTs) are usu-
`ally the first care providers to arrive on the scene
`
`Received March 17, 2006, from the Department of Medicine, School
`of Medicine, University of Washington, Seattle, WA (DB, JL); and
`Emergency Medical Services Division, Public Health Seattle and King
`County, Seattle, WA (TR, MSE). Revision received June 13, 2006; ac-
`cepted for publication June 16, 2006.
`Address correspondence requests to: Mickey S. Eisenberg, MD, PhD,
`Emergency Medical Services Division, Public Health Seattle and King
`County, 999 Third Avenue, Suite 700, Seattle, WA 98104. e-mail:
`<gingy@u.washington.edu>.
`doi: 10.1080/10903120600885134
`
`468
`
`in cases of opioid overdose in most communities.
`States set their own individual standards governing the
`specific treatments EMTs are allowed to provide. In gen-
`eral, states restrict EMTs from obtaining intravenous
`access or administering parenteral pharmacotherapies
`(an exception is subcutaneous epinephrine for anaphy-
`laxis, which is authorized in many states). Intravenous
`and intramuscular naloxone have been shown to be safe
`and effective for the treatment of acute heroin overdose
`by advanced life support paramedics in the prehospi-
`tal setting and are the treatment of choice for suspected
`narcotic overdose.1 More recently, it has been shown
`that the intranasal route can be a safe, simple, and ef-
`fective mode of administering naloxone in opioid over-
`dose patients.2,3 This opens the possibility for EMTs
`to administer naloxone without penetrating the skin if
`authorized to do so. Our study sought to examine how
`much time could be saved if basic EMTs could provide
`naloxone to patients with suspected opioid overdose in
`the prehospital setting.
`
`METHODS
`Study Design, Setting, and Participants
`The investigation was a case series of all emergency
`medical services (EMS)-treated cases of opioid over-
`dose in King County, Washington, in which naloxone
`was administered by paramedics during 2004. Twenty-
`five fire departments and four paramedic agencies pro-
`vide EMS response and transport for the county, which
`includes urban, suburban, and rural areas and has a
`population greater than 1,200,000 (excluding Seattle).
`King County had an annual call volume of 27,627 ad-
`vanced life support calls and 98,070 basic life support
`calls in 2004. The study was approved by the University
`of Washington Human Subjects Committee.
`
`EMS System
`King County is served by a two-tiered EMS system that
`is activated by calling 9-1-1 and speaking with an emer-
`gency medical dispatcher. The first tier consists of fire
`fighter-EMTs who are trained in basic life support and
`defibrillation. The second tier consists of paramedics
`who are trained in advance life support. Dispatchers
`use protocols, established by the county medical direc-
`tor, called “criteria-based dispatch” and depending on
`the severity of the case may 1) dispatch EMT responders
`only, 2) dispatch EMTs and paramedics simultaneously,
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`Belz et al. NALOXONE BY EMTS
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`469
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`3) upgrade the call to paramedic level when more infor-
`mation becomes available, or 4) dispatch paramedics in
`response to an EMT request from the scene.4
`
`Data Collection, Measurement, and
`Analysis
`The first- and second-tier personnel separately com-
`plete medical report forms for all cases. Information
`is then entered into a computerized database. Using
`the database, we identified 719 cases coded as an in-
`tentional or accidental drug overdose that occurred
`during 2004. These were reviewed for use of nalox-
`one by paramedics, which took place in 164 cases. The
`164 paramedic records were manually reviewed for ad-
`ditional data that could be abstracted and combined
`with information available in the computer database.
`Of primary interest were the type of paramedic re-
`sponse (simultaneous with EMTs, upgraded by dis-
`patcher, or requested by EMTs at the scene), EMT call-
`to-arrival time, paramedic call-to-arrival time, and the
`time interval between EMT and paramedic arrival. Sec-
`ondarily we collected data on the age and gender of
`patients, alert/verbal/pain/unresponsive score, respi-
`ratory effort, initial respiratory rate, patient mortality,
`pupil size and reactivity, historical evidence of opi-
`oid use, number of naloxone doses and route, endo-
`tracheal intubation, response to naloxone, respiratory
`rate before and after administration of naloxone, pulse
`oximetry before and after administration of naloxone,
`systolic blood pressures before and after administration
`of naloxone, and violent response to naloxone (vomit-
`ing, agitation, or combativeness). These secondary data
`were used to assess accurateness of assessment, ef-
`fectiveness of resuscitation, and adverse responses to
`treatment.
`
`RESULTS
`There were 164 patients who received naloxone by
`paramedics. Age ranged from 14 to 86 years, with a
`median age of 43 years. The age distribution was bi-
`modal, with a large peak centered on the median age
`and a much smaller peak for patients in their 80s. Males
`patients accounted for 52% of cases. There was variabil-
`ity in the number of cases across fire departments, as
`shown in Figure 1. Wide variability among departments
`remained even when adjusting for population.
`
`Tiered Response
`Paramedics were dispatched simultaneously with
`EMTs in 69 cases (42%). Paramedics were dispatched
`later due to more information in 39 cases (24%), and
`paramedics were dispatched in response to EMT re-
`quest from the scene in 46 cases (28%). For the 69 cases
`
`with simultaneous dispatch, the average EMT time to
`arrival from call received was 5.9 minutes and the av-
`erage paramedic time to arrival from call received was
`11.6 minutes. However, the average paramedic time to
`arrival (from the time of the call to the dispatch cen-
`ter) was 16.1 minutes when paramedics were requested
`by EMTs. This longer time is due to the extra time re-
`quired for the EMTs to arrive at the scene and then
`request paramedics. The average difference between
`EMT and paramedic arrival when they were requested
`by EMTs was 10.2 minutes, and the longest interval
`between EMT and paramedic arrival for a case was
`22.4 minutes. In the King County EMS system, EMTs
`generally wait at the scene for paramedic arrival if ad-
`vanced life support assistance is required. When it is
`known that the paramedics will be delayed beyond
`15 minutes, they may choose to rendezvous with the
`paramedics.
`
`Initial Assessment of Patients
`On the AVPU scale (Alert, response to Verbal stimuli,
`response to Pain, Unresponsive), 13 patients (8%) were
`alert (able to answer at least one orientation question
`correctly), 33 (20%) responded to verbal stimulus alone,
`43 (26%) responded only to painful stimulus, and 75
`(46%) had no response to verbal or painful stimulus. Ini-
`tial respiratory effort was categorized by paramedics as
`normal in 37 (23%), labored or shallow in 40 (24%), and
`<10 breaths/min or absent in 79 (48%). Miotic pupils
`(defined as pupils ≤2 mm, or 3 mm with poor light
`reactivity) were present in 134 patients (82%). Histori-
`cal or situational evidence suggesting an opioid as the
`agent of overdose was found in 128 (78%). This evi-
`dence included a history of opioid abuse, admission
`of opioid use by the patient or acquaintances at the
`scene, needle track marks, or presence of opioid para-
`phernalia.
`
`Administration of Pharmacotherapy
`A single dose of naloxone was given in 111 cases (68%),
`two doses were given in 51 (31%), and three doses were
`given in only two (1%). The route of administration was
`solely intravenous in 108 (66%), a combination of intra-
`venous and intramuscular in 29 (17%), solely intramus-
`cular in 18 (11%), solely intranasal in two (1%), and a
`combination of intramuscular and intranasal in one. In-
`travenous access that was impossible or extremely dif-
`ficult to attain was noted in nine cases (5%). The most
`frequent initial dose was 1 mg but ranged from 0.2 to
`2 mg. The total dosage ranged from 0.2 to 4 mg.
`
`Response to Therapy
`The response to naloxone was subjectively graded as
`falling into one of four categories: full response (alert
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`470
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`PREHOSPITAL EMERGENCY CARE OCTOBER / DECEMBER 2006 VOLUME 10 / NUMBER 4
`
`FIGURE 1. Frequency of naloxone administration by paramedics in suspected overdose during 2004, by fire department.
`
`mental status, normal respiratory rate), partial response
`(improvement in mental status or respiratory rate), no
`response, or unknown. A full response to naloxone oc-
`curred in 78 patients (48%), a partial response occurred
`in 41 (25%), no response occurred in 24 (15%), and re-
`sponse to naloxone was unrecorded in 21 (13%).
`Systolic blood pressure increased from an average of
`123 mm Hg before administration of naloxone to an av-
`erage of 127 mm Hg after administration of naloxone.
`The range of systolic pressure pretreatment was unmea-
`surable through 230 mm Hg, and the range posttreat-
`ment was 68–192 mm Hg. Respiratory rate increased
`from an average of 11 breaths/min before administra-
`tion of naloxone to 18 breaths/min after administration
`of naloxone. The latter respiratory rate does not include
`intubated patients. Intubation was performed in 36
`cases (22%). The range of respiratory rate changed from
`0 to 40 breaths/min before administration of nalox-
`one to 8–40 breaths/min after administraion of nalox-
`one. Arterial hemoglobin saturation (SpO2) increased
`from an average of 90% with a range of 35%–100%
`before administration of naloxone to an average of
`97% with a range of 70%–100% after administration of
`naloxone. (This included all patients for which SpO2
`data were available, including those receiving oxy-
`gen therapy and intubated patients.) Thirty-six patients
`(22%) were known to have died at the scene or during
`transport.
`
`Adverse Reactions
`Naloxone-associated violence, such as agitation, com-
`bativeness, or vomiting, occurred in 25 cases (15%). No
`violence occurred in 127 cases (77%), and it could not
`be determined whether violence occurred in 12 cases
`(7%). The 25 cases associated with posttreatment vio-
`lence were made up of agitation/combativeness in 21
`cases (13%) and vomiting in six cases (4%). In all cases
`of vomiting, the patient was either alert posttreatment
`or had an intact gagreflex documented.
`
`DISCUSSION
`The cause of death in opioid overdose is most com-
`monly secondary to an inability to maintain air-
`way patency, diminished ventilatory drive, and/or
`anaphylaxis.5 After ensuring an adequate airway
`and initiating respiratory and cardiovascular support,
`naloxone is the drug of choice for management of opi-
`oid overdose and can frequently obviate the need for
`endotracheal intubation.5
`Recognition of the benefits of early naloxone admin-
`istration in opioid overdose has led to programs that
`supply naloxone to opioid abusers for use in the event
`of an overdose.6 These programs have been criticized
`for possibly postponing access to care.7 Authorizing
`EMTs to administer naloxone may be an option for
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`Belz et al. NALOXONE BY EMTS
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`471
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`making naloxone more readily available where and
`when it is needed without the possible downsides of
`a community-based approach.
`Serious overdose cases are sometimes hard for the
`dispatcher to identify, thus leading to a request from
`the scene for paramedics rather than them being dis-
`patched initially. This is often the case because the call
`may come from a third party or be misidentified as
`some other condition (e.g., fainting or sick unknown).
`In 46 cases (28%) in our series, the emergency dispatcher
`was unable to recognize the case as one involving opi-
`oid overdose and as a result initially dispatched only
`EMTs to the scene. Once EMTs arrived they requested
`paramedics, resulting in additional time for paramedics
`to arrive. This interval of continued respiratory depres-
`sion may be clinically deleterious due to the risk of aci-
`dosis, hypoxemia, and aspiration.
`EMTs are not trained to intubate or provide par-
`enteral medications. They are trained to provide bag-
`valve-mask respiratory support. However, bag-valve
`masking by EMTs and other relatively inexperienced
`operators has been associated with inadequate minute
`ventilation and significant amounts of air entering
`the stomach.8 Intranasal naloxone could thus provide
`EMTs with a needed tool to improve respiratory func-
`tion in opioid overdose.
`No serious side effects of naloxone were recognized
`in our series. Training to manage the agitation and
`combativeness seen in 15% of our cases would need
`to be part of any program training EMTs to adminis-
`ter naloxone. However, nasal administration compared
`with parenteral administration has been shown to have
`a lower incidence of agitation in one series, possibly due
`to slower absorption.2
`A fair number of life-threatening overdoses were
`demonstrated in the study area (approximately one ev-
`ery other day), with more frequent occurrence in some
`communities. More than half (83 of 164) of the opiate
`overdoses requiring naloxone administration occurred
`in six fire districts (Figure 1). Any pilot program to
`train EMTs to administer intranasal naloxone should
`clearly occur in communities with a high incidence of
`opioid overdose. Authorization of administration in a
`few high-incidence communities may thus be more ap-
`propriate than throughout an entire region or state.
`Our study is limited by its retrospective nature and
`the use of records completed in an emergent setting. It
`is possible that EMS providers did not accurately assess
`some of the findings. Errors may have been made when
`recording data, and records occasionally had missing
`
`data. Coding errors could also be present. The author
`who conducted data abstraction and subjective grading
`was not blinded to the route of naloxone administra-
`tion. Responses seen after administration of naloxone
`were probably influenced positively by other compo-
`nents of the resuscitative effort.
`
`CONCLUSIONS
`The issue of whether EMTs should be authorized to ad-
`minister naloxone in a tiered-response system involves
`many considerations. Our study cannot speak to all of
`these. However, we believe the simplicity, efficacy, and
`safety of intranasal naloxone administration2,3, the fre-
`quency and distribution of opioid overdose in our com-
`munity, and the time factors associated with the arrival
`of EMTs and paramedics argue for a pilot project to
`train EMTs to administer intranasal naloxone in sus-
`pected opioid overdose.
`
`The authors thanks Linda Becker for her assistance with the develop-
`ment of the database; Dan Henwood for helping identify cases; Tom
`Gudmestad for editorial review; the emergency medical dispatchers,
`EMT fire fighters, and paramedics of King County, Washington, for
`their ongoing commitment to care; and Tom Hearne, PhD, for pro-
`viding administrative support.
`
`References
`
`1. Buajordet I, Naess AC, Jacobsen D, Brors O. Adverse events after
`naloxone treatment of episodes of suspected acute opioid over-
`dose. Eur J Emerg Med. 2004;11:19–23.
`2. Barton ED, Colwell CB, Wolfe T, et al. Efficacy of intranasal nalox-
`one as a needleless alternative for treatment of opioid overdose in
`the prehospital setting. Emerg Med. 2005;29:265–71.
`3. Kelly AM, Kerr D, Dietze P, Patrick I, Walker T, Koutsogiannis Z.
`Randomised trial of intranasal versus intramuscular naloxone in
`prehospital treatment for suspected opioid overdose. Med J Aust.
`2005;182:24–7.
`4. Culley LL, Henwood DK, Clark JJ, Eisenberg MS, Horton C: In-
`creasing the efficiency of emergency medical services by using
`criteria based dispatch. Ann Emerg Med. 1994;24:867–72.
`5. Weaver MF. Heroin and other opioids. In UpToDate. (www.
`uptodate.com) Accessed August 15, 2006.
`6. Sporer KA. Strategies for preventing heroin overdose. BMJ.
`2003;326:442–4.
`7. Ashworth AJ, Kidd A. Take home naloxone for opiate addicts.
`Apparent advantages may be balanced by hidden harms. BMJ.
`2001;323:935.
`8. Wenzel V, Idris AH, Dorges V, et al. The respiratory system dur-
`ing resuscitation: a review of the history, risk of infection dur-
`ing assisted ventilation, respiratory mechanics, and ventilation
`strategies for patients with an unprotected airway. Resuscitation.
`2001;49:123–134.
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