IV vs SQ Naloxone, Wanger et al.
`
`293
`
`Intravenous vs Subcutaneous Naloxone for Out-of-
`hospital Management of Presumed Opioid Overdose
`Karen Wanger; MDCM, Laura Brough, BSc, EMA Il, Ian Macmillan, EMA II, Jim Goulding, MD.
`lain MacPhail, MD, MHSc, James M. Christenson, MD
`
`I ABSTRACT
`.....................................................................................................................................................
`Objective: To determine whether naloxone administered IV to out-of-hospital patients with suspected opioid
`overdose would have a more rapid therapeutic onset than naloxone given subcutaneously (SQ).
`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 2 1 0 breathdmin, and durations of bag-valve-mask
`ventilation. Subjects received either naloxone 0.4 mg IV (n = 74) or naloxone 0.8 mg SQ (n = 122). for
`respiratory depression of < l o breathdmin.
`Results: Mean interval from crew arrival to respiratory rate 2 1 0 breathdmin was 9.3 2 4.2 min for the IV
`group vs 9.6 & 4.58 min for the SQ group (95% CI of the difference -1.55. 1.00). Mean duration of bag-
`4.8 min for the SQ group. Cost of
`valve-mask ventilation was 8.1 & 6.0 min for the IV group vs 9.1
`materials for administering naloxone 0.4 mg IV was $12.30/patient, compared with $10.7O/patient for naloxone
`0.8 mg SQ.
`Conclusion: There was no clinical difference in the time interval to respiratory rate 2 10 breathdmin between
`naloxone 0.8 mg SQ and naloxone 0.4 mg IV for the out-of-hospital management of patients with suspected
`opioid overdose. The slower rate of absorption via the SQ route was offset by the delay in establishing an
`IV.
`Key words: opioid overdose; naloxone; respiratory depression; route of administration; EMS; emergency
`medical services; out-of-hospital.
`Acad. Emerg. Med. 1998; 51293-299.
`
`_+
`
`I Administration of an opioid antagonist has become an
`accepted part of the out-of-hospital management of opioid
`overdose.'-4 Acute opioid intoxication is characterized by
`drowsiness, euphoria, miosis, and respiratory depression.'
`In overdose, respiratory depression becomes profound
`enough to cause anoxia, leading to death. Prior to the
`
`..................................................................................
`
`From the British Columbia Ambulance Service, Vancouver; BC, Canada
`(KW. LB. IM, JG, JMC): St. Paul's Hospital, Vancouver, BC, Canada,
`Departmen1 of Emergency Medicine (Kw. JG. JMC): the Paramedic
`Academy, Justice Institute of British Columbia. Vancouver, BC, Canada
`(IMP): and the University of British Columbia, Vancouves BC, Canada
`(JMC, KW IMP, JG). Current aflliarion: Capital Health Region, vic-
`toria, BC, Canada, Department of Emergency Medicine (JG).
`
`Received: July 10, 1997; revision received: September 30, 1997: ac-
`cepted: October 5, 1997: updated: November 2, 1997.
`
`Prior presentation: SAEM annual meeting, Washington, DC, May 1997,
`and che Canadian Association of Emergency Physicians annual meet-
`ing, Halifax. Nova Scotia. Canada, May 1997.
`
`Address for correspondence and reprints: Karen Wanger, MDCM, Re-
`gional Medical Consultant, B. C. Ambulance Service, 1203-601 West
`Broadway, Vancouver, BC, V5Z 4C2, Canada. Far: 604-660-6702:
`e-mail: karen. wanger@moh.hnet. bc.ca
`
`1960s, treatment of opioid overdose consisted of airway
`support and oxygenation until the effect of the opioid
`wore off. For out-of-hospital caregivers, this necessitated
`continuous airway maintenance with bag-valve-mask or
`endotracheal intubation during transport.
`In 196 1, Dupont Pharmaceutical synthesized nalox-
`one, the first substance to act as a purely competitive an-
`tagonist at mu-receptor sites.' Its high lipid solubility al-
`lows naloxone to readily cross the blood-brain barrier.
`Via the IV route, onset of action is within 1-2 minutes.
`The distribution half-life is 20 minutes to 4 hours:-* and
`the drug is then metabolized by the liver to naloxone-3-
`glucuronide and excreted within 72
`Naloxone is absorbed not only IV, but also by IM,
`subcutaneous (SQ), endotracheal, sublingual, int;alingual,
`In routine use, IM or
`submental, and nasal
`SQ injections are acceptable alternate routes of adminis-
`tration if IV access is impossible, but generally have not
`been advocated for emergency situations due to an unpre-
`dictable absorption rate. Although one large, retrospective
`study of presumed out-of-hospital opioid overdoses found
`good response to IM naloxone use: animal studies have
`shown naloxone absorption to be delayed by up to 15
`minutes after IM or SQ inje~tion.~"'~
`
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`In emergency situations, IV administration of nalox-
`one is the route of choice because of its rapid onset. The
`ability of out-of-hospital caregivers to reverse the respi-
`ratory depression of opioids using IV naloxone has greatly
`decreased the duration of the hypoxic state during which
`the airway is at risk. Transport of patients at risk for re-
`spiratory depression from opioids has become easier and
`much less physically strenuous. However, venous access
`can be difficult or impossible to achieve in the chronic IV
`drug user.
`The skin of chronic users is characterized by repeated
`injection sites, resulting in “track marks,” ulcers, and
`sclerosis of veins. Abscesses and cellulitis commonly
`overlie venous access sites. The difficulty in obtaining ve-
`nous access in chronic IV drug users under emergency
`conditions in the field and the enhanced risk of occupa-
`tional blood ont tact'^-'^ with patients who have high risk
`factors for HIV seropositivity and hepatitis B suggest the
`need for an alternative to the IV route of administration.
`We conducted a study of naloxone administered IV vs
`SQ in patients with opioid overdose. The null hypothesis
`of this study was that there would be no difference in the
`time interval from arrival at the patient’s side to respira-
`tory rate 210 breathdmin when using either 0.4 mg IV
`naloxone or 0.8 mg SQ naloxone. Based on the literature,
`we expected that this time interval would be shorter for
`the IV route than for the SQ route. A secondary objective
`was to assess the ease of use of SQ vs IV naloxone in the
`out-of-hospital environment. The SQ route was chosen
`over the Ih4 route because the attendants were already
`trained in the administration of SQ injections of epineph-
`rine for the treatment of anaphylaxis.
`
`I METHODS
`
`Study Design: Prospective data were collected during a
`historical control period and after a protocol change from
`IV to SQ naloxone. Comparison with a historical control,
`rather than use of a concurrent randomized treatment de-
`sign, was the study design advised and approved by the
`University of British Columbia Ethics Committee. The
`Medical Advisory Committee of the British Columbia
`Ambulance Service approved the protocol change.
`
`Population and Setting: The study was conducted in
`the Greater Vancouver Regional District (GVRD) of Brit-
`ish Columbia, which has a population of approximately
`1.6 million. The primary receiving hospital was St. Paul’s
`Hospital, a 420-bed tertiary care facility situated in the
`downtown core of Vancouver, BC. The ED census is
`54,000 patient visits per year, and the unit provides care
`to the majority of IV drug users in the GVRD. Patients
`also were received at Vancouver General, Royal Colum-
`bian, Mount St. Joseph’s, and Burnaby General Hospitals
`in Vancouver, BC.
`
`Participants in the study were British Columbia Am-
`bulance Service (BCAS) attendants, who are trained to the
`EMA-I (basic life support), EMA-11 (IV), and advanced
`life support (ALS) levels. The province-wide BCAS is the
`largest geographic ambulance system in the world, with
`over 3,300 employees at more than 200 ambulance sta-
`tions. The 3-tiered system involves simultaneous dispatch
`of first responder, EMA, and ALS cars. Average ambu-
`lance response time for respiratory arrest in the partici-
`pating stations is 4-6 minutes. The study involved the 11
`ambulance stations that fall into the catchment area ser-
`vicing the most concentrated density of intravenous drug
`users.
`Subjects for the study were out-of-hospital patients
`with presumed opioid overdose who received naloxone.
`Inclusion criteria were all patients who fit the BCAS pro-
`tocol for suspected opioid overdose, which is: decreased
`level of consciousness, history suggestive of opioid use,
`and respiratory rate 4 0 breathdmin. Patients were ex-
`cluded if they were in cardiac arrest. Since the goal was
`to measure therapeutic response to naloxone, only those
`patients who met the criteria for suspected opioid over-
`dose and who received naloxone were entered into the
`study.
`
`Experimental Protocol: The standard protocol for man-
`agement of opioid overdose consisted of maintenance of
`ventilation and oxygenation via bag-valve-mask; obtain-
`ing a brief patient history and a baseline set of vital signs
`prior to establishment of a peripheral IV line of normal
`saline; and the administration of naloxone 0.4 mg IV. The
`protocol did not require that a base-station physician be
`consulted prior to administration of the first dose of nal-
`oxone. If, according to crew judgment, no improvement
`was observed over a period of 5 minutes, orders for an
`additional 0.4 mg of naloxone could be obtained from an
`emergency physician via telephone. The protocol also al-
`lowed for blood glucose determination and consideration
`of other contributing factors at that time. It has been the
`pattern of practice of the BCAS to use ventilatory assist
`and small doses of naloxone to support patients with re-
`spiratory rate <lo breathshin due to suspected opioid
`overdose. The intent is to prevent the complications of
`larger doses of naloxone while protecting the patients
`from the effects of hypoventilation.
`In addition to routine documentation, the attendants
`completed field data forms each time naloxone was given
`for suspected opioid overdose. They recorded the time of
`crew arrival at the patient’s side, IV initiation, drug ad-
`ministration, and start/stop of airway intervention. In ad-
`dition, they recorded the patient’s respiratory rate every 2
`minutes. The data form also captured subjective assess-
`ments of ease of use and risk of needlestick injury, and
`open-ended comments on any aspect of the protocol and
`the study.
`
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`IV vs SQ Naloxone, Wanger et al.
`
`295
`
`Data on ED length of stay, discharge diagnosis, and
`complications were obtained for those patients for whom
`identification obtained by paramedics could be cross-
`referenced with hospital records (a common problem in
`the IV drug user population).
`The study was conducted sequentially in 2 phases, IV
`and SQ. Funding support was limited to 3 months of data
`collection. To ensure the collection of adequate informa-
`tion on efficacy or potential problems with SQ naloxone,
`a 2-month experimental period followed a 1-month con-
`trol period.
`The IV phase was conducted over a 4-week period
`from June 1 to June 30, 1996. Data on response to the
`standard IV naloxone protocol were collected for consec-
`utive patients meeting the inclusion criteria. The SQ phase
`of the study was conducted from July 1 to September 1,
`1996. The standard protocol for presumed opioid overdose
`was changed for the 11 stations involved for the purposes
`of the study. The experimental protocol began with stan-
`dard airway management and obtaining history and vital
`signs. Patients were then given naloxone 0.8 mg SQ into
`the upper arm or thigh. If, according to crew judgment,
`no improvement was observed after 5 minutes, the crew
`defaulted to the IV phase protocol (IV rescue). An IV line
`was established and 0.4 mg naloxone was administered
`IV, followed by standard patient care.
`
`Analytical Methods and Sample Size Determinations:
`Field data forms were reviewed for appropriateness of ap-
`plication of the suspected overdose protocol, drug com-
`binations used by the patient, initial and every 5 minute
`vital signs, dose and route of administration of naloxone,
`duration of basic airway intervention, total time with pa-
`tient until spontaneous ventilation 2 10 breathdmin, and
`total time from drug administration to spontaneous ven-
`tilation. The primary outcome of interest was the time
`interval from arrival at the patient’s side until the respi-
`ratory rate was 2 1 0 breathdmin. It was determined prior
`to commencement of the study that a 2-minute difference
`between the IV and SQ groups for the primary outcome
`would be considered clinically significant (based on a
`25% difference in documented response time).
`Data were analyzed using SPSS (V.7.0, SPSS Inc..
`Chicago, IL). Comparisons of mean time intervals were
`done using the unpaired t-test and verified with nonpara-
`metric testing. Power calculations using the results from
`the control arm of the study were performed using an a
`= 0.05, power = 0.90, A = 2.0 minutes, and SD = 4.18.
`Based on these calculations, a sample size of 184 (92 per
`arm) was required.
`Since there is no capability for our ambulance crews
`to monitor respiration continuously, the every-2-minute
`recordings were considered to be the smallest feasible in-
`terval for manual recording. For analysis, the intervals
`were treated as continuous variables.
`
`I TABLE 1
`Subject Populations in the IV and SQ Naloxone
`Groups
`..............................................................................
`
`Age (mean)
`
`Gender
`Men
`Women
`Unknown
`
`Initial respiratory
`rate (mean)
`
`Initial Glasgow
`Coma Scale
`score (mean)
`
`Initial systolic
`blood pressure
`(mean)
`
`Initial heart rate
`(mean)
`
`Initial respiratory
`rate = 0
`
`36 yr
`
`33 yr
`
`58 (78.4%)
`12 (16.2%)
`4 (5.4%)
`
`97 (79.5%)
`17 (13.9%)
`8 (6.6%)
`
`2.2 breathdmin
`
`2.9 breathdmin
`
`4.1
`
`4.6
`
`141.8 mm Hg
`
`144.5 mm Hg
`
`101.5 beats/min
`
`102.3 beatdmin
`
`39 (53%)
`
`68 (56%)
`
`I RESULTS
`..............................................................................
`
`The total number of subjects enrolled in the study over
`the 12-week period was 222, 83 of whom were in the IV
`naloxone phase, and 139 in the SQ phase. Of these, 9 of
`the IV group and 17 of the SQ group were excluded due
`to inappropriate use of the protocol (respiratory rate 210
`breathdmin prior to naloxone administration) (n = 25) or
`insufficient data (n = 1).
`Data concerning age, gender, initial respiratory rate,
`heart rate, and blood pressure (BP), and initial Glasgow
`Coma Scale score are shown in Table 1. A post-hoc power
`analysis was performed and confirmed the adequacy of
`our sample size.
`A summary of calculated time intervals is shown in
`Tables 2 and 3. Figures 1 and 2 are graphic representations
`of the primary outcome (time interval from arrival at pa-
`tient’s side to respiratory rate 2 1 0 breathdmin).
`The number of patients requiring at least 2 doses of nal-
`oxone prior to hospital arrival was 26 out of 74 (35%) in
`the IV group and 18 out of 122 (15%) in the SQ group.
`Sixteen of the 18 patients in the SQ group requiring a second
`dose were given the second dose via the IV route (IV rescue,
`0.4 mg naloxone IV), while 2 received a second dose of 0.8
`mg SQ. All patients were included in the analysis.
`One patient in each of the 2 study groups had an initial
`BP of c90 mm Hg. The patient in the SQ group responded
`well to one dose of SQ naloxone. The patient in the IV
`group required a second dose.
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`10
`
`9
`
`8
`
`7
`
`6
`
`5
`
`
`
`.-
`E
`E
`F
`
`8.55
`
`Iarplratory Rate 210
`
`7
`27
`
`3.76 +I-3.13
`
`T h e inbml from
`adminbtnllon of
`drug to respiratory
`nteC10
`
`5.53+1-3.94
`
`/
`Admlnistratlon /
`
`Time of
`
`Drug
`
`4
`
`3
`
`2
`
`1
`
`0
`
`Timm lntmml from
`arrinl at patienrs ride
`to administration d
`drug
`GJ
`
`IV
`
`SQ
`I FIGURE 1. Comparison of time intervals (group mean t SD) from
`arrival at patient’s side to respiratory rate 210 breathdmin for patients
`receiving naloxone 0.4 mg IV vs naloxone 0.8 mg subcutaneous (SQ)
`in the out-of-hospital setting.
`
`In their anecdotal comments, the attendants indicated
`that they preferred the SQ to the IV route. Reasons given
`included less spillage of blood compared with IV initia-
`tion; perceived reduced risk of needlestick injury with the
`use of spring-loaded safety needles; and the impression
`that emergence was more gradual, resulting in less vio-
`lence and aggression at the scene.
`ED data were available for only 110 (56%) patients
`overall (58% of the IV and 55% of the SQ subjects). Of
`those for whom data were available, the ED final diag-
`nosis for almost all patients was heroin overdose. Of the
`SQ group, one patient was admitted with a diagnosis
`of pneumonia, and one patient had rhabdomyolysis
`diagnosed, but was subsequently released. Of the IV
`group, one patient was diagnosed as having pneumonia,
`and one as having “vomiting.” Neither patient was ad-
`mitted to hospital. The mean duration of stay in the ED
`was 3.3 hours for the N group, and 3.5 hours for the SQ
`group.
`The cost of materials to administer naloxone via the
`IV route is $12.30 Canadian (0.4 mg naloxone, needle/
`syringe, IV catheter, IV tubing, and normal saline 250-mL
`bag), compared with $10.70 Canadian for the SQ route
`(0.8 mg naloxone plus needlehyringe). These are actual
`costs to the BCAS based on bulk pricing from the BCAS
`distributor. This difference increases to an average of
`$2.20 per patient if the need for additional naloxone (35%
`of the IV group-0.4 mg naloxone; vs 15% of the SQ
`group-IV
`tube, catheter, second syringe, and 0.4 mg nal-
`oxone) is taken into consideration.
`
`I ’ DISCUSSION
`..............................................................................
`It has been previously established that paramedical per-
`sonnel involved in out-of-hospital care have an increased
`risk of exposure to blood-borne disease (HIV and hepatitis
`
`B) due to occupational blood c~ntact.’~’*~ Procedures that
`contribute to the risk of percutaneous exposure include
`wound care, IV starts, and syringe handling.” Despite the
`use of gloves and universal precautions, blood contact still
`
`I TABLE 2 Time Intervals for Patients Receiving Naloxone 0.4 mg IV vs Naloxone 0.8 mg SQ in the Out-of-hospital Setting
`....................................................................................................................................................................
`IV
`SQ
`(n = 74)
`(n = 122)
`5.7 2 3.8 min
`4.0 5 3.0 min
`
`p-value
`0.002
`
`95% CI of
`the Difference
`0.6, 2.7
`
`Time interval from arrival at patient’s side to
`drug administration
`
`’
`
`Time interval from drug administration to res-
`piratory rate 210 breathslmin
`
`Time interval from arrival at patient’s side to
`respiratory rate 2 10 breathslmin
`
`Duration of bag-valve-mask ventilation
`
`3.8 t 3.1 min
`
`5.5 t 3.9 min
`
`9.3 t 4.2 rnin
`
`8.1 * 6.0 min
`
`9.6 t 4.6 min
`
`9.1 * 4.8 rnin
`
`0.001
`
`0.67
`
`-2.7, 0.8
`
`-1.6, 1.0
`
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`IV vs SQ Naloxone, Wanger et al.
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`_____
`
`297
`
`occurs during patient treatment in a considerable number
`of cases.”
`The risk of HIV exposure is dependent on the preva-
`lence of the pathogen in the patient population, the nature
`and frequency of blood contact, and the risk of infection
`transmission for a single blood contact. It has been esti-
`mated that the risk of HIV seropositivity among IV drug
`users ranges from 6.7% to 18.7%. depending on the area
`surveyed.’’*23 The patient population at highest risk for
`seropositivity is 15-44-year-old males, the same popula-
`tion at highest risk for opioid overd~se.’~-’~ The Centre
`for Disease Control in British Columbia estimates that the
`number of IV drug users infected with HIV was approx-
`imately 1,500 at the end of 1997.
`British Columbia has been experiencing an increase in
`IV drug use. In 1996 there were 125 deaths attributed to
`unintended overdose of illicit drugs in Vancouver, com-
`pared with 67 in 1991.24 Opioids, primarily heroin, ac-
`count for 54.8% of overdose deaths.= The prevalence of
`
`I TABLE 3
`Time Intervals for Patients in the Naloxone 0.8 mg
`SQ Group Who Received IV Rescue (n = 16)
`..............................................................................
`
`Time interval from arrival at patient’s side to
`breaths/min
`respiratory rate
`
`13.1 5 4.5 min
`
`Duration of bag-valve-mask ventilation
`
`14.3 5 5.5 min
`
`synthetic opioids (e.g., pentazocine, fentanyl) in Vancou-
`ver, BC, is much lower than in most large U.S. cities.
`This increase in illicit drug use, along with the risk of
`blood-borne infection, reinforces the need for an alterna-
`tive to the IV route of naloxone administration for the
`treatment of patients with suspected opioid overdose in
`the out-of-hospital setting. A small pilot study performed
`in Vancouver in 1995 indicated that naloxone 0.4 mg
`given SQ was ineffective, but 0.8 mg SQ produced a good
`response. These results encouraged us to repeat the study
`on a larger scale using naloxone 0.8 mg SQ.
`
`.
`
`. . ..
`
`l o
`
`5
`
`...........
`.... ..
`......
`.... .
`
`- h
`
`I
`
`m m m m m a r n m m m m
`
`a
`
`. .
`am.. ......
`......
`.........
`....
`............
`..............
`........
`.....
`............
`.....
`
`w m m m m
`
`. a .
`
`d
`
`i
`
`a
`
`n
`
`
`
`0
`
`SQ
`I V
`I FIGURE 2. Actual vs median time intervals from arrival at patient’s side to respiratory rate 210 breathdmin for patients receiving naloxone
`0.4 mg IV vs naloxone 0.8 mg SQ in the out-of-hospital setting.
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`Our study indicated that there was no advantage to the
`use of IV naloxone over the SQ route. The interval from
`crew arrival at the patient’s side to respiratory rate 2 1 0
`breathdmin was 17 seconds shorter for the IV group vs
`the SQ group, and there was 4-minute difference in du-
`ration of basic airway intervention (bag-valve-mask ven-
`tilation) between the IV and SQ groups.
`A comparatively large number of patients in the IV
`group (34%) required a second dose of naloxone. Al-
`though it is possible that there was a change in the purity
`of heroin on the street during the course of the study, we
`have no direct evidence that this was so. It is also possible
`that naloxone has a shorter duration of action when given
`IV vs SQ.
`On a subjective basis, attendants preferred the SQ to
`the IV route due to perceptions that there was less spillage
`of blood, lower risk of needlestick injury, and less vio-
`lence and aggression at the scene due to more gradual
`emergence from the overdose. There were anecdotal re-
`ports that more patients in the SQ group attempted to
`refuse hospital transport, but this was not documented.
`It is important to note that the onset of action from
`the time of naloxone administration is faster via the IV
`route (Fig. 1). Although SQ naloxone is an acceptable
`alternative to IV naloxone for patients with suspected
`opioid overdose who are hemodynamically stable, patients
`who are hemodynamically unstable or are otherwise crit-
`ically ill should have IV access established when possible
`and receive naloxone by that route.
`The materials needed to administer naloxone 0.8 mg
`SQ cost $1.60 Canadian less per patient than the materials
`needed to administer naloxone 0.4 mg IV. Although a
`small proportion of patients (15%) required an IV in ad-
`dition to SQ naloxone, the average cost per patient is still
`less than that for naloxone administered via the IV route
`alone.
`
`I LIMITATIONS AND FUTURE QUESTIONS
`..............................................................................
`The study was limited by the sequential, rather than ran-
`domized, nature of the design. The sequential design was
`necessary because the Ethics Review Committee would
`not approve a randomized design without the use of in-
`formed consent, which was precluded by the level of con-
`sciousness of the subjects. As a result, we are unable to
`ensure that the purity of the drugs in use on the street was
`consistent during all phases of the study.
`As with other out-of-hospital studies, there was no
`possibility of obtaining an objective diagnosis of opioid
`overdose prior to including subjects in the study. It is pos-
`sible that patients with no response or partial response to
`naloxone were actually misdiagnosed or had another di-
`agnosis in addition to opioid overdose. Toxicology screens
`are not feasible prior to the administration of naloxone for
`presumed opioid overdose in the out-of-hospital setting.
`
`However, it is standard clinical practice to initiate the nal-
`oxone protocol without this determination, and the pur-
`pose of this study was to evaluate the performance of SQ
`naloxone where IV naloxone would have been given rou-
`tinely.
`The authors recognize that there may be a difference
`in patient care between the period leading up to the study
`and the study period itself. Because data collections were
`identical during the 2 arms of the study, we believe that
`a change in clinical practice by paramedics due to partic-
`ipation in the study is unlikely.
`The dose of naloxone normally suggested in the lit-
`erature is 2.0 mg IV.’ However, the standard dose of nal-
`oxone used in the out-of-hospital setting in Vancouver has
`been 0.4 mg IV because the prevalence of synthetic
`opioids (e.g., pentazocine, fentanyl) in Vancouver is much
`lower than that in most large U.S. cities. Heroin is the
`most commonly used street opioid in Vancouver, BC.
`Thus it may be difficult to extrapolate our dosing regimen
`to areas in which there are different patterns of drug use.
`It should be emphasized that ED data were available
`for only 56% of patients. Although the outcome at hospital
`discharge was not a focus of this study, it would be useful
`to perform a follow-up study that provided this informa-
`tion.
`The favorable results of this study suggest the need
`for prospective, randomized comparison of IV vs SQ and/
`or other routes of administration of naloxone.
`
`I CONCLUSION
`..............................................................................
`We cannot reject the null hypothesis of this study, i.e.,
`that there would be no difference in the time interval from
`arrival at the patient’s side to a respiratory rate 210
`breathdmin between 0.4 mg IV naloxone and 0.8 mg SQ
`naloxone. Despite laboratory data suggesting that absorp-
`tion of SQ naloxone is delayed by up to ‘15 minutes, this
`was not borne out by our field data. We conclude that the
`SQ route is an acceptable alternative to the IV route for
`the administration of naloxone in the out-of-hospital set-
`ting when IV access cannot be easily established.
`
`The authors gratefully acknowledge the contributions and support of
`Jeff Freeman MD, the paramedics of British Columbia Ambulance Sta-
`tions 241. 242. 243, 244. 245, 246. 247. 248, 258, 260. and 261. the
`Medical Research Council of Canadduniversity of British Columbia
`Summer Student Research Bursary Program, Susak Management As-
`sociates, the Paramedic Academy, Justice Institute of British Columbia,
`and the St. Paul’s Hospital Emergency Research Group. Supported by
`the Medical Research CounciVUniversity of British Columbia Summer
`Student Research Bursary Program.
`
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