INTRANASAL ADMINISTRATION OF NALOXONE BY PARAMEDICS
`Erik D. Barton, MD, MS, Joseph Ramos, MD, Christopher Colwell, MD,
`Jeff Benson, EMT-P, Jeff Baily, EMT-P, William Dunn, EMT-P
`
`ABSTRACT
`Introduction. Naloxone is a medication that is frequently
`administered in the field by paramedics for suspected opi-
`oid overdoses. Most prehospital protocols, however, require
`this medication to be given to patients intravenously (IV) or
`intramuscularly (IM). Unfortunately, intravenous line place-
`ment may be problematic and time-consuming in chronic IV
`drug users. There may also be a delay in patient response to
`opioid reversal with IM absorption of naloxone. Addition-
`ally, routine use of needles in high-risk populations poses an
`increased risk of occupational blood exposures to para-
`medics. Objective. To prospectively test the effectiveness of
`intranasal (IN) naloxone administration by paramedics. This
`preliminary report summarizes the first month’s experience
`in the city of Denver. Methods. Naloxone was first adminis-
`tered to patients found unconscious in the field using a nasal
`mucosal atomizer device (MAD). Patients were then treated
`using standard prehospital protocols, which included IV
`line placement and medications, if they did not immediate-
`ly respond to IN naloxone. Time to patient response was
`recorded. Results. A total of 30 patients received IN nalox-
`one in the field over a one-month period. Of these, 11
`patients responded to either IN or IV naloxone. Ten (91%)
`patients responded to IN naloxone alone, with an average
`response time of 3.4 minutes. Seven patients (64%) did not
`require an IV in the field after response to IN naloxone.
`Conclusions. Intranasal naloxone may provide a safe, rapid,
`effective way to manage suspected opioid overdoses in the
`field. Use of this route may decrease paramedic exposures to
`blood-borne diseases. The addition of IN naloxone adminis-
`tration to prehospital protocols should be considered as an
`initial therapy for suspected opioid abusers. Key words:
`naloxone; opioid; overdose; paramedics; intranasal; drug
`abuse.
`PREHOSPITAL EMERGENCY CARE 2002;6:54–58
`
`Received April 24, 2001, from the Division of Emergency Medicine,
`University of Utah Health Sciences Center (EDB), Salt Lake City,
`Utah; the Department of Emergency Medicine, Denver Health
`Medical Center (JR, CC), Denver, Colorado; and the Denver Health
`Paramedic Division (CC, JB, JB, WD), Denver, Colorado. Revision
`received August 27, 2001; accepted for publication August 31, 2001.
`Presented at the First Mediterranean Emergency Medicine
`Congress, Stresa, Italy, September 2001; and the American College
`of Emergency Physicians Scientific Assembly Research Forum,
`Chicago, Ilinois, October 2001.
`Supported with Muscosal Atomizer Devices (MAD) supplied by
`Wolfe-Tory Medical, Inc., Salt Lake City, UT.
`Address correspondence and reprint requests to: Erik D. Barton,
`MD, MS, University of Utah Health Sciences Center, Division of
`Emergency Medicine, 1150 Moran Building, 175 North Medical
`Drive East, Salt Lake City, UT 84132. e-mail: <edbarton@worldnet.
`att.net>.
`
`When confronted with a patient suffering from a sus-
`pected opioid overdose, the drug of choice is naloxone
`(Narcan) given by intravenous (IV) or intramuscular
`(IM) route. Unfortunately, opioid addicts who inject
`drugs can often have limited peripheral venous
`access. Valuable time may be lost in trying to gain IV
`access if multiple attempts are required. Although the
`IM and subcutaneous (SQ) routes have been shown to
`be effective, they have a much slower rate of absorp-
`tion and typically require a much longer time period
`for the patient to respond.1,2 Additionally, emergency
`medical services (EMS) personnel are at risk for inad-
`vertent needlesticks when attempting to place IV lines
`or give IM or SQ injections in the field. These patients
`typically pose an increased risk of blood-borne dis-
`eases such as hepatitis B, hepatitis C, and HIV.
`Other routes of naloxone administration such as
`sublingual, intralingual, and submental injections also
`require the use of needles and have shown a delayed
`onset of action.3–5 Endotracheal administration of
`naloxone6,7 requires placement of an endotracheal
`tube, and nebulized naloxone is ineffective in revers-
`ing opioid effect.8
`Intranasal (IN) absorption of naloxone has been
`shown to be almost as rapid as the IV route with sim-
`
`FIGURE 1. The mucosal atomizer device (MAD) attached to a syringe
`showing the spray pattern of medication.
`
`54
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`Barton et al.
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`INTRANASAL ADMINISTRATION OF NALOXONE
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`55
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`ilar bioavailability in both animal and human mod-
`els.9–11 We are not aware, however, of any published
`data on the effectiveness of IN naloxone in opioid
`overdoses often observed in patients such as heroin
`addicts. Since EMS personnel encounter the majority
`of these patients in the field, we sought to evaluate the
`effectiveness of IN naloxone in a prospective prehos-
`pital study. This report summarizes our first month’s
`experience.
`
`METHODS
`
`Design
`This study was performed by the Denver Health
`Paramedic Division as a prospective evaluation of IN
`naloxone in all patients who presented with altered
`mental status (AMS), as “found down” (FD), or with
`suspected opioid overdose (OD). These patients
`would otherwise have an IV placed and receive IV
`naloxone (1–2 mg) by protocol. The preliminary study
`was performed from February 1 to February 28, 2001,
`as part of a Paramedic Division Quality Assurance
`Evaluation of IN naloxone. Institutional review board
`(IRB) approval was granted.
`
`Procedure
`Patients encountered by paramedics with AMS, FD, or
`OD were initially administered 2 mg of naloxone IN
`using a disposable Mucosal Atomizer Device (MAD;
`Wolfe-Tory Medical, Inc., Salt Lake City, UT) and
`syringe (Fig. 1). The IN naloxone dose was chosen
`because 2 mg is the initial IV dose mandated by the
`Denver Health Paramedic Protocol and bioavailabili-
`ties appears to be similar by the two routes.9–11 One
`milliliter of the 1-mg/mL solution was administered
`into each nares, for a total volume of 2 mL (Fig. 2).
`Paramedics were then instructed to continue to treat
`all patients as per standard protocols, including air-
`way management, IV line placement, and medica-
`tions, unless the patient responded and no further
`treatment was required. If a patient did not respond to
`IN naloxone within an appropriate time to establish
`an IV and an airway if necessary, then an IV dose of 2
`mg was administered. Times were recorded to the
`hour and minute on a study sheet (Fig. 3) by para-
`medic providers and included: time of initial patient
`encounter, IN naloxone administration, IV insertion,
`IV naloxone administration, and patient response.
`Additionally, paramedics were asked to report any
`obvious abnormalities noted in the patient’s nasal
`mucosa (such as bleeding, deformity, mucus) at the
`time of IN drug administration.
`
`Outcomes
`The rate of patient response to IN naloxone, defined as
`a significant improvement in level of consciousness as
`
`FIGURE 2. The mucosal atomizer device (MAD) being used for
`intranasal administraion of naloxone on a patient (paramedic vol-
`unteer).
`
`determined by paramedics, prior to IV insertion or to
`IV administration of a second dose of naloxone was
`measured. Additionally, the time of response to nalox-
`one was measured.
`
`RESULTS
`
`During the study period a total of 30 patients received
`IN naloxone using the MAD. A total of 13 patients
`(43%) responded to either naloxone by any route (n =
`11) or dextrose (n = 2) given by paramedics in the
`field. There were 11 patients with AMS listed as the
`indication for naloxone administration, seven patients
`with FD listed, and 12 patients with suspected OD list-
`ed. Of these, one patient responded to naloxone in the
`AMS group (9%), no patients responded in the FD
`group (0%), and ten patients responded in the OD
`group (83%).
`Of the 11 naloxone responders there were ten
`patients (91%) who responded to IN naloxone alone.
`The average time of response was 3.4 minutes (range
`2 to 6 minutes). One patient responded to IV naloxone
`and not to IN naloxone alone. Appropriate response
`occurred at 11 minutes after IN administration and the
`patient was noted to have a significant amount of epis-
`taxis. Seven of the 11 naloxone responders (64%) did
`not require IV placement in the field.
`DISCUSSION
`
`The use of IN drug administration has long been con-
`sidered a alternative route for a wide variety of med-
`ications. More importantly, IN administration of sev-
`eral medications used in the prehospital setting
`(atropine, dextrose, diazepam, epinephrine, glucagon,
`lidocaine, midazolam, morphine, naloxone, and nitro-
`glycerine (Table 1) has been studied to assess the effec-
`tiveness of this route of therapy.11–20 While effective in
`many circumstances, however, the IN route has yet to
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`PREHOSPITAL EMERGENCY CARE
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`JANUARY / MARCH 2002 VOLUME 6 / NUMBER 1
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`FIGURE 3. The paramedic recording sheet for the prehospital intranasal naloxone study.
`
`replace standard IV therapy in the vast majority of
`prehospital treatment protocols.
`The risk of occupational blood exposure to prehos-
`pital providers has been demonstrated to increase
`with more years of service. In fact, a risk as high as 25
`blood contacts per 1,000 EMS calls has been reported
`in the literature.21 While only about 2–5% of these are
`needlestick exposures, there is also significant risk
`with exposures to nonintact skin, mucous membranes,
`and eyes (from splashes).22 Routine use of IV lines and
`medications, especially in nontrauma patients, may
`account for the majority of these exposures. Similar
`risks have been observed in the hospital setting, and
`
`the response over the past several years has been to
`develop safer needle disposal systems as well as
`needle-less drug delivery IV lines. Unfortunately,
`these systems are unavailable or cumbersome to use
`in the prehospital setting. Consequently, the risk of
`paramedic needle exposures to blood-borne infectious
`diseases continues to pose a significant threat.
`Naloxone has been found to have almost 100%
`bioavailability through the nasal mucosa in animal
`models and in human opioid addicts.9–11 Subse-
`quently, IN naloxone has an onset of action and plas-
`ma level that make it indistinguishable from IV nalox-
`one.9 Though accepted as an alternative route of
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`Barton et al.
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`INTRANASAL ADMINISTRATION OF NALOXONE
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`57
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`administration, no studies have been previously
`reported using IN naloxone as an initial mode of treat-
`ment in overdose patients. We chose a staged protocol
`using the IN route first, followed by an IV dose if nec-
`essary. This was done to determine both the rate of
`response within a limited time period and the number
`of IV attempts that could be avoided in the field if the
`patient responded appropriately. Issues such as
`informed consent and blinded treatment protocols
`would be more difficult to perform in the prehospital
`setting for an appropriate comparison study.
`This study attempts to address the efficacy of IN
`naloxone by rapidly administering the IN drug upon
`initial patient evaluation. Standard prehospital treat-
`ment protocols were subsequently followed. The pur-
`pose of such a protocol was to assess the rate of
`response of patients given IN naloxone relative to sub-
`sequent IV line placement and need for repeat doses
`of IV medication. The results demonstrate a 91%
`response rate to the IN naloxone for all patients who
`responded to naloxone. This result strongly suggests
`that the IN route could be used successfully in a
`majority of patients to speed reversal of opioid intoxi-
`cation. With rapid administration and easy access to
`the nasal mucosa, the IN route may, in fact, reduce the
`duration of respiratory depression and decrease the
`number of prehospital intubations often seen in this
`patient population. Additionally, a significant number
`of patients in this study (64%) did not require IV
`placement in the field, which may be a safer practice
`when treating opioid abusers outside of the emer-
`gency department.
`The one patient in our series who did not respond to
`IN naloxone and subsequently responded to IV nalox-
`one was noted to have epistaxis. Physical factors such
`as nasal septum abnormalities, trauma, epistaxis,
`excessive mucus, and mucosal destruction from other
`intranasal drug use (i.e., cocaine) may have a signifi-
`cant effect on the rate and amount of absorption of IN
`medications. Drug abusers might be a population at
`higher risk for these nasal abnormalities for a variety
`of reasons. Additionally, paramedics should continue
`to use blood exposure precautions for external sources
`of bleeding, such as epistaxis, in these patients.
`Prospective evaluation of the nares to assess for any
`abnormalities may be required prior to the adminis-
`tration of IN naloxone. Further study will most likely
`elucidate what percentage of these patients will con-
`tinue to require IV naloxone.
`CONCLUSION
`
`Intranasal naloxone has been demonstrated to be a
`very easy route for drug administration in the field
`with a high patient response rate in this preliminary
`study. This method utilizes an inexpensive device that
`provides rapid administration of the medication with
`
`TABLE 1. Intranasal Medications Previously
`Studied* for Systemic Indications
`
`Indication
`
`Analgesia
`
`Antiemetics
`
`Antihypertensives
`
`Cardiac arrest/ACLS
`
`Drug overdose
`Headache therapy
`
`Hypoglycemia
`
`Sedation
`
`Seizures
`
`Miscellaneous
`
`Medications
`
`Fentanyl23
`Sufentanil24
`Buprenorphine25
`Meclizine26
`Metoclopramide27
`Angiotensin II28
`Hydralazine29
`Nifedipine30
`Nitroglycerine31
`Propranolol32
`Verapamil33
`Atropine34
`Epinephrine35
`Lidocaine36
`Naloxone10
`Butorphanol37
`Dihydroergotamine38
`Lidocaine39
`Sumatriptan40
`Dextrose41
`Glucagon42
`Diazepam43
`Ketamine44
`Midazolam45
`Diazepam46
`Midazolam47
`Gentamycin48
`Neostigmine49
`
`*For complete reference citations, see the reference list. ACLS = Advanced
`Cardiac Life Support.
`
`minimal risk of blood-borne exposure. Use of an IN
`naloxone protocol may promote a safer practice for
`paramedics while maintaining effective treatment for
`patients with opioid overdoses.
`
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