Intranasal Naloxone Is a Viable Alternative to Intravenous Naloxone for Prehospital Narcotic Overdose

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.     

Naloxone Use in a Tiered-Response Emergency Medical Services System

Objective. To examine the delivery andeffect of naloxone for opioid overdose in a tiered-response emergency medical services (EMS) system andto 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, andtime interval between arrival of EMTs andarrival 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%) andemesis in six (4%). Average EMT arrival time was 5.9 minutes. Average paramedic arrival time was 11.6 minutes in most cases and16.1 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 andauthorizing EMTs to administer intranasal naloxone in suspected opioid overdose is warranted.     

Efficacy of intranasal naloxone as a needleless alternative for treatment of opioid overdose in the prehospital setting

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.     

Measuring a Crisis: Questioning the Use of Naloxone Administrations as a Marker for Opioid Overdoses in a Large U.S. EMS System

Objective: The United States is currently experiencing a public health crisis of opioid overdoses. To determine where resources may be most needed, many public health officials utilize naloxone administration by EMS as an easily-measured surrogate marker for opioid overdoses in a community. Our objective was to evaluate whether naloxone administration by EMS accurately represents EMS calls for opioid overdose. We hypothesize that naloxone administration underestimates opioid overdose. Methods: We conducted a chart review of suspected overdose patients and any patients administered naloxone in Wake County, North Carolina, from January 2013 to December 2015. Patient care report narratives and other relevant data were extracted from electronic patient care records and the resultant database was analyzed by two EMS physicians. Cases were divided into categories including “known opioid use,” “presumed opioid use,” “no known opioid,” “altered mental status,” “cardiac arrest with known opioid use,” “cardiac arrest with no known opioid use,” or “suspected alcohol intoxication,” and then further separated based on whether naloxone was administered. Patient categories were compared by patient demographics and incident year. Using the chart review classification as the gold standard, we calculated the sensitivity and positive predictive value (PPV) of naloxone administration for opioid overdose. Results: A total of 4,758 overdose cases from years 2013–15 were identified. During the same period, 1,351 patients were administered naloxone. Of the 1,431 patients with known or presumed opioid use, 57% (810 patients) received naloxone and 43% (621 patients) did not. The sensitivity of naloxone administration for the identification of patients with known or presumed opioid use was 57% (95% CI: 54%–59%) and the PPV was 60% (95% CI: 57%–63%). Conclusion: Among patients receiving care in this large urban EMS system in the United States, the overall sensitivity and positive predictive value for naloxone administration for identifying opioid overdoses was low. Better methods of identifying opioid overdose trends are needed to accurately characterize the burden of opioid overdose within and among communities.     

Comparison of lower-dose versus higher-dose intravenous naloxone on time to recurrence of opioid toxicity in the emergency department

Introduction: The initial dose of naloxone administered to patients who present to the emergency department (ED) with opioid overdose is highly variable. The objective of this study was to determine if the initial dose of intravenous (IV) naloxone given to these patients was associated with the time to recurrence of opioid toxicity.

Methods: This was a multicenter retrospective cohort study, conducted at two academic EDs in the United States. Consecutive adults who had a positive response to naloxone for opioid overdose in the ED were included. Patients were categorized into two groups based on initial IV naloxone dose administered: 0.4?mg (lower-dose) or 1–2?mg (higher-dose). The main outcome measure was the time to recurrence of opioid toxicity requiring a second dose of naloxone. Secondary outcomes included the need for naloxone continuous infusion and adverse events.

Results: The study included 84 patients with 42 patients receiving lower-dose and 42 patients receiving higher-dose naloxone. Median time to re-dose of naloxone was similar between the lower-dose (72 [IQR 46–139] minutes) and higher-dose (70 [IQR 44–126] minutes) groups (p=.810). There were 12 patients (29%) in the lower-dose group and 17 patients (41%) in the higher-dose group who subsequently required continuous infusions (p=.359). The proportion of patients with adverse events was similar between lower-dose and higher-dose groups (31% versus 41%, p=.495). There was no difference in the incidence of specific withdrawal related adverse effects.

Conclusions: The initial dose of naloxone given to patients in the ED does not influence the time to recurrence of opioid toxicity.     

Intranasal administration of naloxone by paramedics

Introduction. Naloxone is a medication that is frequently administered in the field by paramedics for suspected opioid overdoses. Most prehospital protocols, however, require this medication to be given to patients intravenously (IV) or intramuscularly (IM). Unfortunately, intravenous line placement 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. Additionally, routine use of needles in high-risk populations poses an increased risk of occupational blood exposures to paramedics. 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 administered 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 immediately respond to IN naloxone. Time to patient response was recorded. Results. A total of 30 patients received IN naloxone 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 administration to prehospital protocols should be considered as an initial therapy for suspected opioid abusers. PREHOSPITAL EMERGENCY CARE 2002;6:54-58     

Feasibility of Bystander Administration of Public-Access Naloxone for Opioid Overdose

Objective: Pre-stationing naloxone, a competitive antagonist that can reverse the effects of opioid overdose, in public spaces may expedite antidote delivery. Our study aimed to determine the feasibility of bystander-assisted overdose treatment using pre-stationed naloxone. Methods: Convenience sample of bystanders in Cambridge, Massachusetts in April 2017. Subjects assisted a simulated patient described as unconscious. Subjects interacted with simulated EMS dispatch to locate a nearby box, unlock it, and administer naloxone. Results: Fifty participants completed the simulation. Median time from simulated ambulance dispatch to naloxone administration was 189 seconds, and from arrival at patient side to administration 61 seconds. All but one participant (98.0%) correctly administered naloxone. Subjects' comfort with administration and willingness to provide medical care increased from before to after the trial. Comfort in administering naloxone varied significantly with level of previous training prior to, but not following, study participation. Conclusions: Bystanders are willing and able to access pre-stationed naloxone and administer it to a simulated patient in a public space. Public access naloxone stations may be a useful tool to reduce time to naloxone administration, particularly in areas where opioid overdoses are clustered.     

Suspected opioid-related emergency medical services encounters in a rural state, 1997-2002

Introduction

News organizations and governmental agencies have reported substantial increases in the number of opioid-related overdose cases in recent years.

Objective

To describe the utilization of emergency medical services (EMS) for suspected opioid-related overdose cases in a rural state during the period 1997 through 2002.

Methods

Statewide EMS records were reviewed for 1997 through 2002. Data reviewed included prehospital diagnosis and medications given to all patients by prehospital providers. For cases with a prehospital diagnosis of poisoning or overdose, data reviewed included medications given to patients by prehospital providers, pupil size, and respiratory rate. All records were reviewed in a defined sequence.

Results

The study period encompassed 1,175,781 patient encounters. Poisoning or overdose patients accounted for 19,808 (1.7%) encounters. Naloxone was administered by the EMS provider to 2,668 (0.2%) patients. For all poisoning or overdose patients, 1,308 (6.6%) had miotic pupils, 450 (2.2%) had a respiratory rate of <12 breaths/min, and 1,569 (7.9%) received naloxone. During the investigation period, total EMS patient encounters increased 25%, while patients with a complaint of poisoning or overdose increased 47%. The incidences of EMS overdose patients with miotic pupils, respiratory rate <10 breaths/min, and naloxone administration increased 167%, 295%, and 154%, respectively.

Conclusion

In this rural state, prehospital patients with findings suspicious for opioid overdose disproportionately outpaced the growth of all EMS encounters as well as general overdose encounters during the defined investigation period.     

Intranasal naloxone delivery is an alternative to intravenous naloxone for opioid overdoses

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.     

Do heroin overdose patients require observation after receiving naloxone?

Context: Heroin use in the US has exploded in recent years, and heroin overdoses requiring naloxone are very common. After awakening, some heroin users refuse further treatment or transport to the hospital. These patients may be at risk for recurrent respiratory depression or pulmonary edema. In those transported to the emergency department, the duration of the observation period is controversial. Additionally, non-medical first responders and lay bystanders can administer naloxone for heroin and opioid overdoses. There are concerns about the outcomes and safety of this practice as well.

Objectives: To search the medical literature related to the following questions: (1) What are the medical risks to a heroin user who refuses ambulance transport after naloxone? (2) If the heroin user is treated in the emergency department with naloxone, how long must they be observed prior to discharge? (3) How effective in heroin users is naloxone administered by first responders and bystanders? Are there risks associated with naloxone distribution programs?

Methods: We searched PubMed and GoogleScholar with search terms related to each of the questions listed above. The search was limited to English language and excluded patents and citations. The search was last updated on September 31, 2016. The articles found were reviewed for relevance to our objective questions. Eight out of 1020 citations were relevant to the first 2 questions, 5 of 707 were relevant to the third question and 15 of 287 were relevant to the fourth question. In the prehospital environment, does a heroin user revived with naloxone always require ambulance transport and what are the medical risks if ambulance transport is refused after naloxone? The eight articles were all observational studies done either prospectively or retrospectively. Two studies focused on heroin overdoses and included 1069 patients not transported to the hospital. No deaths occurred in this group. In counting the patients from all eight studies, some of which included non-heroin opioid overdoses, there were 5443 patients treated without transport and four deaths from rebound opioid toxicity. The number needed to transport to save one life (NNT) is 1361. Adverse effects were mostly related to opioid withdrawal. If a heroin user is treated in the ED, how long must the patient stay under observation before being safe for discharge? Five articles addressing the duration of ED observation required for patients treated with naloxone for opioid overdoses. Although a wide range of observation durations were reported, one study supported observing patients for one hour. If after this period the patient mobilizes as usual, has normal vital signs, and a Glasgow Coma Scale of 15, they can be discharged safely. What are the likely risks in heroin users following naloxone use by lay bystanders or first responders? Of the 15 relevant papers, a systematic review reported a 100% survival rate in eleven studies and a range of 96–99% survival in the remaining four. Two other studies suffered from poor follow-up and had lower success rates of 83% and 89%. Few if any risks were associated with opioid overdose prevention programs in which lay people were trained to administer naloxone.

Conclusions: Patients revived with naloxone after heroin overdose may be safely released without transport to the hospital if they have normal mentation and vital signs. In the absence of co-intoxicants and further opioid use there is very low risk of death from rebound opioid toxicity. For those patients treated in the ED for opioid overdose, an observation period of one hour is sufficient if they ambulate as usual, have normal vital signs and a Glasgow Coma Scale of 15. Patients suffering opioid toxicity can be administered naloxone safely by first responders and trained lay people. Programs that train these individuals are likely safe and beneficial, however further research is necessary.     

Retrospective Review of Need for Delayed Naloxone or Oxygen in Emergency Department Patients Receiving Naloxone for Heroin Reversal

BackgroundEmergency departments (EDs) are experiencing an increasing number of heroin overdose visits. Currently, there is no generally agreed upon ED observation period for heroin overdose patients who receive naloxone.ObjectivesWe aimed to determine the safety of a 2-h observation period for heroin overdose patients who receive naloxone.MethodsWe performed a chart review of all patients who presented with any opioid-related complaint between 2009 and 2014 to our urban academic trauma center. Subset analysis of patients with isolated heroin overdose who received naloxone was performed, with the intent of excluding patients intoxicated with long-acting/enteral opioids. The primary outcome was the number of patients who required delayed intervention—specifically, additional naloxone or supplemental oxygen.ResultsBetween 2009 and 2014, we recorded 806 visits to our ED for heroin use after receiving naloxone. Twenty-nine patients (3.6%) received a repeat dose of naloxone, and 17 patients (2%) received oxygen ≥2 h after initial naloxone administration. Our 2-h intervention rate was 4.6% (N = 37). This decreased to 1.9% (N = 15) after 3 h and 0.9% (N = 7) after 4 h. Patients with polysubstance use were more likely to receive repeat naloxone (p < 0.01), but not oxygen (p = 0.10). Preexisting cardiopulmonary conditions did not correlate with a need for supplemental oxygen (p = 0.24) or repeat naloxone (p = 0.30).ConclusionsA 2-h ED observation period for heroin overdose patients reversed with naloxone resulted in a delayed intervention rate of 5%. Clinicians may consider a 3-h observation period, with extra scrutiny in polysubstance abuse.     

Intravenous vs Subcutaneous Naloxone for Out-of-hospital Management of Presumed Opioid Overdose

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 ≥10 breaths/min, 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 <10 breaths/min.
Results : Mean interval from crew arrival to respiratory rate ≥ 10 breaths/min was 9.3 ± 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-valve-mask ventilation was 8.1 ± 6.0 min for the IV group vs 9.1 ± 4.8 min for the SQ group. Cost of materials for administering naloxone 0.4 mg IV was $12.30/patient, compared with $10.70/patient for naloxone 0.8 mg SQ.
Conclusion : There was no clinical difference in the time interval to respiratory rate ≥10 breaths/min 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.     

Is a Prehospital Treat and Release Protocol for Opioid Overdose Safe?

Background

The current standards for domestic emergency medical services suggest that all patients suspected of opioid overdose be transported to the emergency department for evaluation and treatment. This includes patients who improve after naloxone administration in the field because of concerns for rebound toxicity. However, various emergency medical services systems release such patients at the scene after a 15- to 20-min observation period as long as they return to their baseline.