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.     

Opioid Toxicity Recurrence After an Initial Response to Naloxone

Abstract

Objective: To determine the frequency and potential predictors of opioid toxicity recurrence after a response to naloxone in adult Emergency Department patients. Methods: A retrospective case-control study of naloxone-treated patients with opioid toxicity over an 8-year period. Both the patient response to naloxone and recurrence of opioid toxicity was determined by an expert Delphi Panel. The frequency of opioid toxicity recurrence was compared by the duration of opioid effect, the route of opioid exposure, and the presence of other CNS depressant drugs. Results: Ninety of 221 (41%) cases with a discharge diagnosis of opioid toxicity were treated with naloxone; six patients were excluded because of a lack of toxicity. There was a response to naloxone in 50% of the 84 cases, and recurrence of toxicity in 31% (95% CI 17–45%) of naloxone responders. The most common opioids were codeine, heroin, propoxyphene, and oxycodone/hydrocodone. Recurrence of toxicity was more common with long-acting opioids (p = 0.04), and was not associated with the route of opioid exposure (p = 0.42), or presence of ethanol and other CNS depressants (p ± 0.87). Conclusion: Opioid toxicity recurrence after a response to naloxone occurred in approximately 1/3 of adult Emergency Department opioid overdose cases. Recurrence was more common with long-acting opioids and was not associated with the route of opioid exposure. Other clinically useful predictors of toxicity recurrence were not identified.     

Do Co‐intoxicants Increase Adverse Event Rates in the First 24 Hours in Patients Resuscitated from Acute Opioid Overdose?

Abstract

Background:?Patients frequently arrive in emergency departments (EDs) after being resuscitated from opioid overdose. Autopsy studies suggest that multidrug intoxication is a major risk factor for adverse outcomes after acute heroin overdose in patients. If this is true, there may be high‐risk drug combinations that identify patients who require more intensive monitoring and prolonged observation. Our objective was to determine the impact of co‐intoxication with alcohol, cocaine, or CNS depressant drugs on short‐term adverse event rates in patients resuscitated from acute opioid overdose. Methods:?Data were extracted from the database of a prospective opioid overdose cohort study conducted between May 1997 and 1999. Patients were prospectively enrolled if they received naloxone for presumed opioid overdose. Investigators gathered clinical, demographic, and other predictor variables, including co‐intoxicants used. Patients were followed to identify prespecified adverse outcome events occurring within 24 h, and multiple logistic regression was used to determine the association of concomitant drug use on short‐term adverse event rates. Results:?Of 1155 patients studied, 58 (5%) had pure opioid overdose and 922 (80%) reported co‐intoxicants, including alcohol, cocaine, and CNS depressants. Overall, out of 1056 patients with known outcome status there were 123 major adverse events (11.6%) and 194 minor adverse events (18.4%). After adjustment for age, gender, HIV status, cardiovascular disease, pulmonary disease and diabetes, we found that coadministration of alcohol, cocaine, or CNS depressants, alone or in combination, was not associated with increased risk of death or adverse events during the 24 h follow‐up period. Conclusion:?In patients resuscitated from acute opioid overdose, short‐term outcomes are similar for patients with pure opioid overdose and multidrug intoxications. A history of cointoxication cannot be used to identify high‐risk patients who require more intensive ED monitoring or prolonged observation.     

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.     

The changing epidemiology of opioid overdose in Baltimore,Maryland, 2012–2017: insights from emergency medical services

IntroductionAn estimated 100,306 people died from an overdose from May 2020 to April 2021. Emergency Medical Services (EMS) are often the first responder to opioid overdose, and EMS encounter records can provide granular epidemiologic data on opioid overdose. This study describes the demographic, temporal, and geographic epidemiology of suspected opioid overdose in Baltimore City using data from Baltimore City Fire Department EMS encounters with the administration of the opioid antagonist naloxone.MethodThe present analyses used patient encounter data from 2012 to 2017 from the Baltimore City Fire Department, the city’s primary provider of EMS services. The analytic sample included patient encounters within the city that involved naloxone administration to patients 15 years of age or older (n = 20,592). Negative binomial regression was used to calculate the incidence rates based on demographic characteristics, year, and census tract. Choropleth maps were used to show the geographic distribution of overdose incidence across census tracts in 2013, 2015, and 2017.ResultsFrom 2012 to 2017, the annual number of EMS encounters with naloxone administrations approximately doubled every 2 years, and the temporal pattern of naloxone administration was similar to the pattern of fatal opioid-related overdoses. For most census tracts, incidence rates significantly increased over time. Population-based incidence of naloxone administration varied significantly by socio-demographic characteristics. Males, non-whites, and those 25–69 years of age had the highest incidence rates.ConclusionThe incidence of naloxone administration increased dramatically over the study period. Despite significant cross-sectional variation in incidence across demographically and geographically defined groups, there were significant proportional increases in incidence rates, consistent with fatal overdose rates over the period. This study demonstrated the value of EMS data for understanding the local epidemiology of opioid-related overdose.

Key Messages

• Patterns of EMS encounters with naloxone administration appear to be an excellent proxy for patterns of opioid-related overdoses based on the consistency of fatal overdose rates over time.
• EMS plays a central role in preventing fatal opioid-related overdoses through the administration of naloxone, provision of other emergency services, and transportation to medical facilities.
• EMS encounters with naloxone administration could also be used to evaluate the impact of overdose prevention interventions and public health services.

     

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.     

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.     

Fentanyl-contaminated cocaine outbreak with laboratory confirmation in New York City in 2019

BackgroundIllicitly manufactured fentanyl and fentanyl analogues (IMFs) are being increasingly suspected in overdose deaths. However, few prior outbreaks have been reported thus far of patients with laboratory-confirmed IMF toxicity after reporting intent to use only nonopioid substances. Herein we report a case series of nine patients without opioid use disorder who presented to two urban emergency departments (EDs) with opioid toxicity after insufflating a substance they believed to be cocaine.Case reportsOver a period of under three hours, nine patients from five discrete locations were brought to two affiliated urban academic EDs. All patients denied prior illicit opioid use. All patients endorsed insufflating cocaine shortly prior to ED presentation. Soon after exposure, all developed lightheadedness and/or respiratory depression. Seven patients received naloxone en route to the hospital; all had improvement in respiratory function by arrival to the ED. None of the patients required any additional naloxone administration in the ED. All nine patients were discharged home after observation.Blood +/− urine samples were obtained from eight patients. All patients who provided specimens tested positive for cocaine metabolites and had quantifiable IMF concentrations, as well as several detectable fentanyl derivatives, analogues, and synthetic opioid manufacturing intermediates.DiscussionIMF-contamination of illicit drugs remains a public health concern that does not appear to be restricted to heroin. This confirmed outbreak demonstrates that providers should elevate their level of suspicion for concomitant unintentional IMF exposure even in cases of non-opioid drug intoxication. Responsive public health apparatuses must prepare for future IMF-contamination outbreaks.     

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.     

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.     

Epidemiology of Emergency Department Visits for Opioid Overdose: A Population-Based Study

ObjectivesTo evaluate the rate of emergency department (ED) visits for opioid overdose and to examine whether frequent ED visits for opioid overdose are associated with more hospitalizations, near-fatal events, and health care spending.Patients and MethodsRetrospective cohort study of adults with at least 1 ED visit for opioid overdose between January 1, 2010, and December 31, 2011, derived from population-based data of State Emergency Department Databases and State Inpatient Databases for 2 large and diverse states: California and Florida. Main outcome measures were hospitalizations for opioid overdose, near-fatal events (overdose involving mechanical ventilation), and hospital charges during the year after the first ED visit.ResultsThe analytic cohort comprised 19,831 unique patients with 21,609 ED visits for opioid overdose. During a 1-year period, 7% (95% CI, 7%-7%; n=1389 patients) of the patients had frequent (2 or more) ED visits, accounting for 15% (95% CI, 14%-15%; n=3167) of all opioid overdose ED visits. Middle age, male sex, public insurance, lower household income, and comorbidities (such as chronic pulmonary disease and neurological diseases) were associated with frequent ED visits (all P<.01). Overall, 53% (95% CI, 52%-54%; n=11,412) of the ED visits for opioid overdose resulted in hospitalizations; patients with frequent ED visits for opioid overdose had a higher likelihood of hospitalization (adjusted odds ratio, 3.98; 95% CI, 3.38-4.69). In addition, 10.0% (95% CI, 10%-10%; n=2161) of the ED visits led to near-fatal events; patients with frequent ED visits had a higher likelihood of a near-fatal event (adjusted odds ratio, 2.27; 95% CI, 1.96-2.66). Total charges in Florida were $208 million (95% CI, $200-$219 million).ConclusionIn this population-based cohort, we found that frequent ED visits for opioid overdose were associated with a higher likelihood of future hospitalizations and near-fatal events.     

Use and efficacy of nebulized naloxone in patients with suspected opioid intoxication

ObjectiveTo describe the use and efficacy of nebulized naloxone in patients with suspected opioid intoxication.MethodsThis was an observational study conducted at an inner city emergency department. Patients were eligible if they had self-reported or suspected opioid intoxication and a spontaneous respiratory rate ≥ 6 breaths/minute. Nebulized naloxone (2 mg in 3 mL normal saline) was administered through a standard face mask at the discretion of the treating physician. Structured data collection included demographics, vital signs pre and post naloxone administration and adverse events. The primary outcome was level of consciousness, which was recorded pre and 15 minutes postnaloxone administration using the Glasgow Coma Scale (GCS) and the Richmond Agitation Sedation Scale (RASS).ResultsOf the 73 patients who presented with suspected opioid intoxication and were given naloxone over the study period, 26 were initially treated with nebulized naloxone. After nebulized naloxone administration, median GCS improved from 11 [interquartile range (IQR) 3.5] to 13 (IQR, 2.5), P = .001. Median RASS improved from ? 3.0 (IQR, ? 1.0) to ? 2.0 (IQR, ? 1.5), P < .0001. Need for supplemental oxygen decreased from 81% to 50%, P = .03. Vital signs did not differ pre/post therapy. There were few adverse effects from nebulized naloxone administration: 12% experienced moderate-severe agitation, 8% were diaphoretic and none vomited. Eleven required subsequent administrations of naloxone, nine of whom self-reported using either heroin, methadone or both. Of these, 5 underwent urine drug screening and all 5 tested positive for either opiates or methadone.ConclusionsNebulized naloxone was well-tolerated and led to a reduction in the need for supplemental oxygen as well as improved median GCS and RASS scores in patients with suspected opioid intoxication.     

Early Discharge of Patients with Presumed Opioid Overdose: Development of a Clinical Prediction Rule

OBJECTIVE: To develop a clinical prediction rule to identify patients who can be safely discharged one hour after the administration of naloxone for presumed opioid overdose. METHODS: Patients who received naloxone for known or presumed opioid overdose were formally evaluated one hour later for multiple potential predictor variables. Patients were classified into two groups: those with adverse events within 24 hours and those without. Using classification and regression tree methodology, a decision rule was developed to predict safe discharge. RESULTS: Clinical findings from 573 patients allowed us to develop a clinical prediction rule with a sensitivity of 99% (95% CI = 96% to 100%) and a specificity of 40% (95% CI = 36% to 45%). Patients with presumed opioid overdose can be safely discharged one hour after naloxone administration if they: 1) can mobilize as usual; 2) have oxygen saturation on room air of >92%; 3) have a respiratory rate >10 breaths/min and <20 breaths/min; 4) have a temperature of >35.0 degrees C and <37.5 degrees C; 5) have a heart rate >50 beats/min and <100 beats/min; and 6) have a Glasgow Coma Scale score of 15. CONCLUSIONS: This prediction rule for safe early discharge of patients with presumed opioid overdose performs well in this derivation set but requires validation followed by confirmation of safe implementation.