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.     

Are heroin overdose deaths related to patient release after prehospital treatment with naloxone?

Objective. Naloxone is frequently used by prehospital care providers to treat suspected heroin and opioid overdoses. The authors' EMS system has operated a policy of allowing these patients, once successfully treated, to sign out against medical advice (AMA) in the field. This study was performed to evaluate the safety of this practice. Methods. The authors retrospectively reviewed all 1996 San Diego County Medical Examiner's (ME'S) cases in which opioid overdoses contributed to the cause of death. The records of all patients who were found dead in public or private residences or died in emergency departments of reasons other than natural causes or progression of disease, are forwarded to the ME office. ME cases associated with opiate use as a cause of death were cross-compared with all patients who received naloxone by field paramedics and then refused transport. The charts were reviewed by dates, times, age, sex, location, and, when available, ethnicity. Results. There were 117 ME cases of opiate overdose deaths and 317 prehospital patients who received naloxone and refused further treatment. When compared by age, time, date, sex, location, and ethnicity, there was no case in which a patient was treated by paramedics with naloxone within 12 hours of being found dead of an opiate overdose. Conclusions. Giving naloxone to heroin overdoses in the field and then allowing the patients to sign out AMA resulted in no death in the one-year period studied. This study did not evaluate for return visits by paramedics nor whether patients were later taken to hospitals by private vehicles.     

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.     

Assessment for Deaths in Out-of-hospital Heroin Overdose Patients Treated with Naloxone Who Refuse Transport

Naloxone frequently is used to treat suspected heroin and opioid overdoses in the out-of-hospital setting. The authors' emergency medical services system has operated a policy of allowing these patients, when successfully treated, to sign out against medical advice (AMA) in the field. OBJECTIVES: To evaluate the safety of this AMA policy. METHODS: This is a retrospective review of out-of-hospital and medical examiner (ME) databases over a five-year period. The authors reviewed all ME cases in which opioid overdoses were listed as contributing to the cause of death. These cases were cross-compared with all patients who received naloxone by field paramedics and then refused transport. The charts were reviewed by dates, times, age, sex, location, and ethnicity when available. RESULTS: There were 998 out-of-hospital patients who received naloxone and refused further treatment and 601 ME cases of opioid overdose deaths. When compared by age, time, date, sex, location, and ethnicity, there were no cases in which a patient was treated by paramedics with naloxone within 12 hours of being found dead of an opioid overdose. CONCLUSIONS: Giving naloxone to patients with heroin overdoses in the field and then allowing them to sign out AMA resulted in no identifiable deaths within this study population.     

Out-of-hospital Treatment of Opioid Overdoses in an Urban Setting

Objectives : To investigate clinical outcomes in a cohort of opioid overdose patients treated in an out-of-hospital urban setting noted for a high prevalence of IV opioid use. Methods : A retrospective review was performed of presumed opioid overdoses that were managed in 1993 by the emergency medical services (EMS) system in a single-tiered, urban advanced life support (ALS) EMS system. Specifically. all patients administered naloxone by the county paramedics were reviewed. Those patients with at least 3 of 5 objective criteria of an opioid overdose [respiratory rate <6/min, pinpoint pupils, evidence of IV drug use, Glasgow Coma Scale (GCS) score <12, or cyanosis] were included. A response to naloxone was defined as improvement to a GCS 14 and a respiratory rate 10/min within 5 minutes of naloxone administration. ED dispositions of opioid-overdose patients brought to the county hospital were reviewed. All medical examiner's cases deemed to be opioid-overdose-related deaths by postmortem toxicologic levels also were reviewed. Results : There were 726 patients identified with presumed opioid overdoses. Most patients (609/726, 85.4%) had an initial pulse and blood pressure (BP). Most (94%) of this group responded to naloxone and all were transported. Of the remainder, 101 (14%) had obvious signs of death and 16 (2.2%) were in cardiopulmonary arrest without obvious signs of death. Of the patients in full arrest, 2 had return of spontaneous circulation but neither survived. Of the 609 patients who had initial BPs, 487 (80%) received naloxone IM (plus bag-valve-mask ventilation) and 122 (20%) received the drug IV. Responses to naloxone were similar; 94% IM vs 90% IV. Of 443 patients transported to the county hospital, 12 (2.7%) were admitted. The admitted patients had noncardiogenic pulmonary edema (n = 4). pneumonia (n = 2), other infections (n = 2), persistent respiratory depression (n = 2). and persistent alteration in mental status (n = 2). The patients with pulmonary edema were clinically obvious upon ED arrival. Hypotension was never noted and bradycardia was seen in only 2% of our presumed-opioid:overdose population. Conclusions : The majority of the opioid-overdose patients who had initial BPs responded readily to naloxone, with few patients requiring admission. Noncardiogenic pulmonary edema was uncommon and when present, hypoxia was evident upon arrival to the ED. Naloxone administered IM in conjunction with bag-valve-mask ventilation was effective in this patient population. The opioid-overdose patients in cardiopulmonary arrest did not survive.     

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.     

Improving Prehospital Protocol Adherence Using Bundled Educational Interventions

Background: Seizures and anaphylaxis are life-threatening conditions that require immediate treatment in the prehospital setting. There is variation in treatment of pediatric prehospital patients for both anaphylaxis and seizures. This educational study was done to improve compliance with pediatric prehospital protocols, educate prehospital providers and decrease variation in care. Objective: To improve the quality of care for children with seizures and anaphylaxis in the prehospital setting using a bundled, multifaceted educational intervention. Methods: Evidence-based pediatric prehospital guidelines for seizures and anaphylaxis were used to create a curriculum for the paramedics in the EMS system. The curriculum included in-person training, videos, distribution of decision support tools, and a targeted social media campaign to reinforce the evidence-based guidelines. Prehospital charts were reviewed for pediatric patients with a chief complaint of anaphylaxis or seizures who were transported by paramedics to one of ten hospitals, including three children's hospitals, for 8 months prior to the intervention and eight months following the intervention. The primary outcome for seizures was whether midazolam was given via the preferred intranasal (IN) or intramuscular (IM) routes. The primary outcome for anaphylaxis was whether IM epinephrine was given. Results: A total of 1,402 pediatric patients were transported for seizures by paramedics to during the study period. A total of 88 patients were actively seizing pre-intervention and 93 post-intervention. Of the actively seizing patients, 52 were given midazolam pre-intervention and 62 were given midazolam post-intervention. Pre-intervention, 29% (15/52) of the seizing patients received midazolam via the preferred IM or IN routes, compared to 74% (46/62) of the seizing patients post-intervention. A total of 45 patients with anaphylaxis were transported by paramedics, 30 pre-intervention and 15 post-intervention. Paramedics administered epinephrine to 17% (5/30) patients pre-intervention and 67% (10/15) patients post-intervention. Conclusion: The use of a bundled, multifaceted educational intervention including in-person training, decision support tools, and social media improved adherence to updated evidence-based pediatric prehospital protocols.     

NAEMSE Abstracts from the Prehospital Care Research Forum at UCLA

Abstract

We present a case of failed prehospital treatment of fentanyl induced apnea with intranasal (IN) naloxone. While IN administration of naloxone is becoming more common in both lay and pre-hospital settings, older EMS protocols utilized intravenous (IV) administration. Longer-acting, higher potency opioids, such as fentanyl, may not be as easily reversed as heroin, and studies evaluating IN administration in this population are lacking. In order to contribute to our understanding of the strengths and limitations of IN administration of naloxone, we present a case where it failed to restore ventilation. We also describe peer reviewed literature that supports the use of IV naloxone following heroin overdose and explore possible limitations of generalizing this literature to opioids other than heroin and to IN routes of administration.     

Appropriateness of intravenous cannulation by paramedics: A london study

Introduction. The number of patients undergoing intravenous (IV) cannulation by paramedics has increased dramatically over recent years in the UK. Treatment protocols for cannulation in the field are loosely defined. Variation in practice may lead to patients' receiving differential treatment according to customary practice, rather than according to their clinical conditions. Objectives. To explore variations in practice and assess level of appropriatenesss of IV cannulation by London Ambulance Service (LAS) paramedics; to revise treatment protocols and work toward clinical guidelines, if indicated by study findings. Methods. Skill usage data were analyzed for all LAS paramedics for 1995-96. All patients who were IV-cannulated and transported to three hospitals by LAS during March 1996 were identified. A panel of accident and emergency (A&E) and prehospital specialists judged each case for appropriateness. Results. Variation during the year was wide, with a range of 1 to 221 (mean 47) patients cannulated per paramedic, although the majority showed some consistency in frequency of skill usage. A sample of 183 cases was reviewed. The majority judged 149 (81.4%) to be appropriate, although there was considerable disagreement between reviewers (κ = 0.43, p < 0.001). Data suggested that those paramedics who cannulate more frequently cannulated less appropriately during the study period (lowest 30%: 73.9% appropriate; highest 30%: 45.8% appropriate, p = 0.05). Conclusion. Despite wide variation between paramedics, the panel judged overall appropriateness of cannulation to be high. The audit advisory group judged that new clinical guidelines might not achieve an improvement in practice and were not supported by study findings. It was recommended that variations be addressed through individual practice review. PREHOSPITAL EMERGENCY CARE 2000;4:156-163     

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.     

Midazolam for the treatment of out-of-hospital pediatric seizures

Objective. To assess the effectiveness and safety of intravenous (IV) and intramuscular (IM) midazolam in the treatment of pediatric seizures by paramedics. Methods. All cases in which paramedics treated patients under the age of 18 years with midazolam for seizures per county protocol were evaluated over a one-year period. Prehospital records were reviewed for treatment and reassessment, while the subgroup of patients who were transported to Children's Hospital were followed up for emergency department (ED) outcome. Results. Midazolam was administered to 86 pediatric patients with ages ranging from 2 months to 14 years for the treatment of seizures per county protocol. There were 54 IV doses and 32 IM doses delivered. Of the 86 patients, post-intervention reevaluation was documented for 74 patients (86%) representing 49 IV and 25 IM doses. Improvement was reported for 91% (67/74) of patients. Greater success was reported with IV drug administration (47/49, 96%) as compared with 80% (20/25) with IM administration (p < 0.05). Four patients (three treated IM and one IV) had respiratory compromise necessitating field airway management. All four patients had respiratory compromise documented prior to midazolam administration. Forty-four patients were treated at Children's Hospital. Seven were intubated in the ED after having been given additional medications for seizures. None were intubated on arrival and none were felt to require intubation secondary to midazolam-induced respiratory depression. Conclusion. Prehospital IV midazolam is an effective intervention for pediatric seizures, while IM midazolam was associated with a 20% failure rate, with both having minimal risk of respiratory compromise. PREHOSPITAL EMERGENCY CARE 2002;6:215-217     

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.     

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.     

Prehospital use of analgesia for suspected extremity fractures

Introduction. Pain and its control have been studied extensively in the emergency department. Numerous studies indicate that inadequate treatment of pain is common, despite the availability of myriad analgesics. It has been suggested that oligoanesthesia is also a common practice in the prehospital setting. Objective. To assess the use of prehospital analgesia in patients with suspected extremity fracture. Methods. Emergency medical services (EMS) call reports were reviewed for all patients with suspected extremity fractures treated from June 1997 to July 1998 in a midwestern community with a population base of 223,000. Data collected included demographic information, mechanism of injury, medications given, and field treatment. Standing orders for administration of analgesia were available and permitted paramedics to give either morphine sulfate or nitrous oxide per protocol. Results. The EMS call reports were analyzed for 1,073 patients with suspected extremity fractures. The mean patient age was 47 years. Accidental injuries comprised 86.5% of those reviewed. Suspected leg fractures were most common (20%), followed by hips (18%), arms (11%), knees (10%), ankles (9%), shoulders (7.2%), hands (5.5%), and wrists (5.3%). Multiple trauma and assorted broken digits accounted for the remaining 14%. The most common mechanisms of injury were: fall (43%), motor vehicle collision (21%), and human assault (10%). Intravenous lines were placed in 9.4% of patients; 17% received ice packs; 16% received bandage/dressings; 25% received air splints; and 19% were fully immobilized. Analgesia was administered to 18 patients (1.8%): 16 patients received nitrous oxide and two received morphine. Conclusion. Administration of analgesics to prehospital patients with suspected fractures was rare. Prehospital identification and treatment of pain for patients with musculoskeletal trauma could be improved. PREHOSPITAL EMERGENCY CARE 2000;4:205-208     

A PPROPRIATENESS OF I NTRAVENOUS C ANNULATION BY P ARAMEDICS : A L ONDON S TUDY

Introduction. The number of patients undergoing intravenous (IV) cannulation by paramedics has increased dramatically over recent years in the UK. Treatment protocols for cannulation in the field are loosely defined. Variation in practice may lead to patients' receiving differential treatment according to customary practice, rather than according to their clinical conditions. Objectives. To explore variations in practice and assess level of appropriatenesss of IV cannulation by London Ambulance Service (LAS) paramedics; to revise treatment protocols and work toward clinical guidelines, if indicated by study findings. Methods. Skill usage data were analyzed for all LAS paramedics for 1995–96. All patients who were IV-cannulated and transported to three hospitals by LAS during March 1996 were identified. A panel of accident and emergency (A&E) and prehospital specialists judged each case for appropriateness. Results. Variation during the year was wide, with a range of 1 to 221 (mean 47) patients cannulated per paramedic, although the majority showed some consistency in frequency of skill usage. A sample of 183 cases was reviewed. The majority judged 149 (81.4%) to be appropriate, although there was considerable disagreement between reviewers (κ = 0.43, p < 0.001). Data suggested that those paramedics who cannulate more frequently cannulated less appropriately during the study period (lowest 30%: 73.9% appropriate; highest 30%: 45.8% appropriate, p = 0.05). Conclusion. Despite wide variation between paramedics, the panel judged overall appropriateness of cannulation to be high. The audit advisory group judged that new clinical guidelines might not achieve an improvement in practice and were not supported by study findings. It was recommended that variations be addressed through individual practice review.