Hindawi Publishing Corporation
`Emergency Medicine International
`Volume 2012, Article ID 476161, 5 pages
`doi:10.1155/2012/476161
`
`Research Article
`Prehospital Medication Administration: A Randomised Study
`Comparing Intranasal and Intravenous Routes
`
`Cian McDermott1 and Niamh C. Collins2
`
`1 Centre for Emergency Medical Science, University College Dublin, Dublin, Ireland
`2 Medical Advisory Group of the Pre-hospital Emergency Care Council in Ireland, Naas, Ireland
`
`Correspondence should be addressed to Cian McDermott, cianmcdermott@gmail.com
`
`Received 3 April 2012; Revised 5 June 2012; Accepted 11 June 2012
`
`Academic Editor: Oliver Flower
`
`Copyright © 2012 C. McDermott and N. C. Collins. This is an open access article distributed under the Creative Commons
`Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is
`properly cited.
`
`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.
`
`1. Introduction
`
`The mortality associated with opioid overdose has continued
`to increase globally in recent years. In 2009, the number of
`Irish drug-related deaths attributed to opioid intoxication
`rose by 20% [1], while in Europe, opioids were responsible
`for 75% of all drug-related deaths [2]. In the United States
`in 2007, there were 11,499 deaths resulting from opioid
`overdose [3]. The main cause of death is as a result of opioid-
`induced respiratory depression [4]. After the initiation of
`basic life support measures, naloxone is an opioid antagonist
`that is used to reverse respiratory depression and mental
`state changes. It is widely marketed under the brand name
`Narcan. The common routes of administration of naloxone
`are intravenous (IV), intraosseous (IO), intramuscular (IM),
`and subcutaneous. Intranasal (IN) administration is an
`alternative route for naloxone delivery [5].
`When a patient presents in opioid-induced cardiorespi-
`ratory arrest, immediate effective antagonism by naloxone
`
`reverses the opioid-induced side effects. Direct entry of
`naloxone into the systemic circulation is required and this
`is most reliably achieved with IV or IO medication admin-
`istration. Vascular access is often a major challenge when
`treating a patient with opioid overdose in the prehospital
`setting due to damage to veins from repeated drug use [6].
`Multiple attempts at intravenous cannulation may result in
`an increased risk of exposure to blood-borne infections,
`in a group of patients that have a high seroprevalence
`of blood-borne transmissible viral infections (hepatitis B,
`C, and human immunodeficiency virus) [6]. The rate of
`occupational blood exposures for prehospital providers is
`estimated to be in excess of 49,000 per annum, which
`includes over 10,000 cases of needlestick injuries [7].
`Most opioid overdoses occur in a prehospital setting,
`arising from unintentional self-poisoning [8]. Emergency
`medical services (EMS) providers are usually the patient’s
`first contact with the health service. In many jurisdictions
`worldwide, naloxone is used by EMS personnel to treat
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`opioid overdoses [9–13]. In Ireland, the prehospital emer-
`gency medical care system is regulated and governed by the
`Pre-Hospital Emergency Care Council [14]. EMS personnel
`(paramedics and advanced paramedics) are permitted to
`administer naloxone to treat a suspected opioid overdose
`in accordance with national clinical practice guidelines
`[15]. However, there is currently no provision for the use
`of IN naloxone in prehospital medicine in Ireland. The
`introduction of an alternative needle-free route of naloxone
`delivery that is fast acting, effective, and safe would be
`beneficial to patients and EMS providers.
`Intranasal administration of naloxone obviates the need
`for IV catheter placement in high-risk patients and could
`reduce some of these associated risks. The nasal route is pre-
`sented as an alternative for drug delivery since the rich vas-
`cular plexus of the nose offers a direct route for medication
`entry into the bloodstream [5, 8]. Also, especially relevant to
`prehospital clinical practice, the nasal cavity is a readily acces-
`sible and pain-free site for use in any emergency situation.
`While the bioavailability of IN naloxone reaches almost
`100% that of IV naloxone and achieves peak plasma
`concentration in 3 minutes in animal studies [16], there
`is a lack of human pharmacokinetic data. Previous studies
`have demonstrated that IN naloxone is effective and safe
`when used to treat an opioid overdose [9–11]. Several non-
`randomised pre-hospital studies have also shown that the
`overall time interval from patient contact to patient recovery
`is similar for IN and IV naloxone [12, 13].
`The primary aim of this study is to compare the time
`taken to administer a medication via the IN and IV routes. A
`secondary aim is to assess the end-user satisfaction for both
`routes in a cohort of advanced paramedic trainees.
`
`2. Methods
`
`2.1. Study Setting and Design. This was a randomised
`controlled trial that took place at the National Ambulance
`Services College in Dublin, Ireland. A class of 18 advanced
`paramedic trainees, registered with a University College
`Dublin training programme, were asked to participate in
`a classroom-based study that was used to simulate a real-
`life patient encounter of an opioid overdose. Standardised
`formal IV cannulation techniques had previously been
`taught using a mannequin and each trainee had completed
`a five-week hospital placement during which time super-
`vised IV cannulations were performed on patients. Each
`trainee also received formal instruction regarding the use
`of a mucosal atomizer device (MAD) to deliver intranasal
`medication. This is a single-use atomizer device with a
`luer-lock connector for delivery of a measured dose of IN
`medication via a syringe (Figure 1).
`Block randomisation was used to assign trainees equally
`to each study group—9 trainees were allocated to group A
`(IN) and the remainder was assigned to group B (IV).
`The study was designed to mirror a real-life patient
`encounter. A table was arranged at bed height with a
`mannequin for IN administration and a phlebotomy arm for
`IV cannulation (Figure 2). A standard advanced paramedic
`kit bag, containing the MAD, a 3 ml plastic syringe, a 21G
`
`Figure 1: Mucosal atomizer device for delivery of intranasal
`medication (reproduced with permission from Wolfe Tory Medical,
`Inc., USA).
`
`hypodermic needle, and a 20G IV cannula in a clear plastic
`pouch was placed beside the table. A clear glass vial, filled
`with 1 ml of saline solution was used for both groups.
`Trainees were instructed to administer the medication as per
`the route indicated at randomisation. A research assistant
`who was not involved in the study design or result interpre-
`tation recorded the time taken for each trainee to prepare
`the medication and prepare the route of administration (i.e.,
`insert a cannula or check the nose). The clock was started as
`the trainee opened the kit bag and stopped as the medication
`was delivered. Each trainee was permitted to complete the
`task once only.
`
`2.2. Outcome Measures. The primary outcome measure in
`this study was the time taken by trainees for completion of
`the task in group A (IN) and group B (IV) as detailed above.
`Practitioner satisfaction with each route of medication
`administration was the secondary outcome measure. Follow-
`ing completion of the procedure, each trainee was asked to
`fill out a 5-point Likert rating scale. This was used to measure
`the trainees’ satisfaction in terms of user-friendliness and
`safety of the procedure that they had been assigned to. A
`procedure was defined as “safe” if the trainee did not expect
`to encounter a blood exposures or needlestick injury while
`using that technique in a real-life scenario.
`
`2.3. Data Analysis. Descriptive statistical analysis was
`applied to the data in this study (mean, median, standard
`deviation and mean time difference with 95% confidence
`intervals, CI). The data was found to follow a normal
`distribution using the Anderson-Darling test;
`thus,
`the
`difference in mean times for both groups was compared
`using a two-tailed student’s t-test. A P-value < 0.05 was
`chosen as significant.
`
`3. Results
`
`18 advanced paramedic trainees participated in this study—
`15 males and 3 females. The mean age of participants was
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`Table 1: Advanced paramedic trainees shown by time taken for
`medication delivery.
`
`Trainee
`
`Group A
`IN (s)
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`12
`13
`14
`15
`16
`17
`18
`
`103.8
`103.4
`
`95.7
`82.3
`114.9
`
`95.3
`68.8
`62.3
`
`57.4
`
`Group B
`IV (s)
`185.4
`159.4
`240.6
`
`133.7
`231.6
`152.2
`
`186.2
`
`161
`153.4
`
`Eighty-nine percent (8 out of 9) of trainees from group A
`“strongly agreed” that the IN technique was both easy to use
`and safe to use. Most trainees from group B regarded the IV
`technique as easy to use but most “disagreed” (67%) that the
`technique was safe to use (Figures 3(a) and 3(b)). All trainees
`completed the study and no adverse incidents occurred.
`
`4. Discussion
`
`The findings of this study show that it is faster to deliver
`a medication via the IN route than the IV route when
`administered by a cohort of advanced paramedic trainees. To
`our knowledge, no study has yet attempted to quantify the
`actual time difference that occurs as a result of the route of
`administration used to deliver naloxone. In this study, the IN
`route was also preferred over the IV route, both in terms of
`ease of use and safety profile.
`Two randomised controlled trials have compared the
`time taken to achieve adequate patient response when using
`IN and IM naloxone [9, 10]. A positive clinical response in
`both of these studies was defined as the time taken to regain
`a respiratory rate of 10 breaths per minute. Patients in the
`initial study had a slower response when given IN naloxone
`(IN 8 minutes versus IM 6 minutes, P = 0.006) [10] while
`mean response times were similar in the more recent study
`(IN 8.0 minutes, IM 7.9 minutes, difference 0.1, 95% CI −1.3
`to 1.5) [9]. A more concentrated solution of IN naloxone was
`specifically manufactured for use in the later study—this was
`thought to account for the difference in response time for IN
`naloxone between these studies.
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`(a)
`
`(b)
`
`Figure 2: Materials used to carry out classroom-based study in the
`National Ambulance Services Centre.
`
`50.5 years and the age range was 32 years to 57 years. Table 1
`compares the route of medication administration and time
`taken for each advanced paramedic trainee.
`The mean time taken for group A to deliver medication
`via the IN route was 87.1 seconds. The standard deviation
`was 20.35 (range 57.4 to 114.9 seconds). The mean time
`taken for group B to insert a cannula and administer the
`medication IV was 178.2 seconds. The standard deviation
`was 36.71 (range 133.7 to 240.6 seconds). There was a
`difference in mean delivery times of 91.1 seconds (P ≤
`0.0001) with 95% CI ranging from 55.2 seconds to 126.9
`seconds. Thus, there was a statistically significant difference
`in the primary outcome measure in this study in favour of IN
`medication administration.
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`Emergency Medicine International
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`Group A
`
`Group B
`
`Easy
`Not easy
`
`(a)
`
`of patient intoxication [11]. However, advanced paramedic
`trainees in this study expressed a clear preference for the IN
`route.
`In the United States (US), in 2000, the Needlestick Safety
`and Prevention Act was enacted into federal law [17]. Under
`this new legislation, the Occupational Safety and Health
`Administration established requirements for all employers
`to reduce percutaneous injuries in at-risk employees from
`contaminated sharps by using safety-engineered medical
`devices [18]. Prior to this, the rate of needlestick injury was
`estimated at 378,000 to 756,000 incidents per annum [19].
`Since its introduction, there has been a steady decline in the
`annual rate of percutaneous injuries in the US, for example,
`in 2001, a reduction of almost 38% was reported amongst
`hospital employees [20]. The results of this study show that
`most advanced paramedic trainees perceived the IN route
`(89%) to be safer than the IV route of administration (33%).
`Thus, IN naloxone is proposed as one such needle-free
`initiative that may reduce exposure of EMS personnel to
`blood-borne viruses, when treating high-risk patients with
`an opioid overdose.
`
`Group A
`
`Group B
`
`5. Limitations
`
`0123456789
`
`0123456789
`
`Safe
`Not safe
`
`(b)
`
`Figure 3: (a) Advanced paramedic trainee response to question-
`naire regarding ease of use of IN or IV delivery. (b) Advanced
`paramedic trainee response to questionnaire regarding safety of use
`of IN or IV delivery.
`
`Additional nonrandomised studies have shown that
`the overall time intervals from initial patient contact by
`paramedics to patient clinical response (defined as an
`increase in respiratory rate and Glasgow Coma Score) were
`not prolonged when using IN naloxone compared with IV
`naloxone [12, 13]. The authors concluded that any delay in
`the clinical response to IN naloxone is compensated for by
`the time taken to establish IV access.
`A mean time difference of 91.1 seconds was recorded
`in this study with the 95% confidence interval ranging
`from 55.2 seconds to 126.9 seconds. A clinically significant
`difference in patient response times has previously been
`defined as 1 minute, based on respiratory depression and
`oxygen desaturation that may occur after this time [9]. Thus,
`the use of the IN route of delivery of naloxone to treat an
`opioid overdose may have an important impact on successful
`patient resuscitation in a real-life clinical scenario.
`The results of this study also concluded that there
`was high level of practitioner satisfaction among advanced
`paramedic-trainees in relation to the ease of use of the
`IN route of administration. In this cohort, 89% of users
`found the IN route easy to use. Paramedics in other studies
`perceived IN naloxone to be less effective than its parenteral
`counterpart [11]. It has been reported that there is a
`preference by paramedics toward one route of delivery or
`another based on personal experience and not on the level
`
`The limitations of this study include its small sample size
`(n = 18) and that it lacked blinding. The small sample size
`was due to the availability of advanced paramedic trainees
`that were enrolled in the teaching programme at the time of
`the study. Also, the participants were advanced paramedic
`trainees and may not yet have sufficient experience in IV
`cannulation techniques, which may have increased the time
`taken to gain IV access in some cases. Finally, this was a
`classroom-based study designed to simulate real-life events.
`In clinical practice, a field-based patient encounter may have
`other confounding patient and environmental variables that
`could potentially affect the outcomes.
`
`6. 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 an IV route of administration. The authors
`therefore, propose that this needle-free route of medication
`administration be employed more frequently when treating
`high-risk patients with an opioid overdose.
`
`Conflict of Interests
`
`The authors declare no conflict of interests.
`
`Acknowledgments
`
`The authors would like to thank the staff and students (class
`12) of the Centre for Emergency Medical Science, University
`College Dublin, Ireland and the National Ambulance Ser-
`vices College, Dublin, Ireland. We are also grateful to Niall
`McDermott, Centre of Business Analytics, University College
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`Dublin, Ireland and Niamh Cummins, Research Manager,
`Centre for Prehospital Research, Graduate Entry Medical
`School, University of Limerick, Ireland.
`
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