01Approach to the Critical Patient/attcp63

Immediate priorities

›Life-threatening presentation triggers

›Respiratory rate <12/min or apnea — immediate BVM ventilation before naloxone

›Airway opening — head-tilt/chin-lift or jaw thrust

›Suction secretions if gurgling present

›BVM ventilation with supplemental O2 prevents cardiac arrest in most cases

›Unresponsiveness or GCS <8

›Sternal rub or nailbed pressure to assess depth

›If no response, proceed to airway management before naloxone

›Cyanosis or SpO2 <90%

›Supplemental O2 immediately

›Escalate to BVM if not improving within 60 seconds

›Cardiac arrest

›High-quality CPR takes priority over naloxone administration

›AHA 2023 Focused Update: defibrillation for shockable rhythms; naloxone adjunct only

›Naloxone administration

›IV route preferred for fastest onset

›0.4 to 2 mg IV every 2 to 3 minutes until RR >=10/min

›In opioid-dependent patients titrate from 0.04 to 0.1 mg IV to avoid precipitated withdrawal

›Intranasal route if no IV access

›2 to 4 mg IN; repeat after 3 minutes if no response

›Bioavailability lower than IV; delayed onset 3 to 5 minutes

›Intramuscular route

›0.4 mg IM; repeat after 3 minutes

›If no response after 10 mg IV naloxone, reassess diagnosis — coingestants or structural pathology likely

›Airway decision tree

›Jaw thrust and airway adjunct first

›Nasopharyngeal airway for semiconscious patients

›Oropharyngeal airway only if unresponsive without gag

›Rapid sequence intubation if naloxone fails

›Wooden chest syndrome from fentanyl analogs requires intubation and neuromuscular blockade

›Succinylcholine 1.5 mg/kg IV or rocuronium 1.2 mg/kg IV for RSI

Monitoring and targets

›Continuous monitoring parameters

›SpO2 — target >=95%; do not rely on SpO2 alone as it may be normal on O2 despite hypercapnia

›End-tidal CO2 (ETCO2) preferred to detect hypercapnia early

›Normal ETCO2 35 to 45 mmHg; rising ETCO2 indicates worsening ventilation

›Respiratory rate — target >=10 breaths/min after naloxone

›Monitor every 15 minutes for resedation

›Recurrent respiratory depression occurs in up to 72% treated with titrated low-dose IV naloxone

›Cardiac monitoring

›QTc prolongation — methadone overdose risk for torsades de pointes

›Wide QRS — coingestant (TCA, sodium channel blocker)

›Bradycardia — expected with opioid toxicity; treat if hemodynamically significant

›Escalation triggers

›Recurrent respiratory depression after naloxone — initiate naloxone infusion

›Two-thirds of effective bolus dose per hour in 500 mL NS (0.004 mg/mL)

›Titrate to respiratory rate target

›Pulmonary edema after naloxone reversal — positive pressure ventilation

›CPAP 5 to 10 cmH2O for alert patients

›Intubation if obtunded with pulmonary edema

›Hemodynamic instability — IV fluid resuscitation followed by vasopressors if needed

›Norepinephrine 0.01 to 0.1 mcg/kg/min if shock unresponsive to fluids

Consult and team triggers

›Immediate consultation indications

›Toxicology or Poison Control — refractory cases, unknown substance, body packing

›No response after 10 mg naloxone

›Suspected synthetic opioid fentanyl analog

›Anesthesia or critical care — failed airway or wooden chest syndrome

›Fentanyl-induced rigidity requires neuromuscular blockade

›High-level airway skill required for rigid chest intubation

›Psychiatry — confirmed intentional overdose

›Section or psychiatric hold evaluation

›Addiction medicine — initiation of medications for opioid use disorder

›Buprenorphine initiation from ED when appropriate

›Methadone maintenance coordination

02History/hx53

Substance and exposure details

›Opioid type and formulation

›Heroin or illicit fentanyl — rapid onset, unpredictable potency

›Illicit fentanyl 50 to 100 times more potent than morphine

›Fentanyl analogs (carfentanil) may be thousands of times more potent

›Prescription opioids — type determines toxicity duration

›Short-acting: oxycodone, hydrocodone, morphine IR, codeine

›Long-acting: oxycodone ER, morphine ER, methadone, fentanyl patch, buprenorphine

›Methadone — prolonged half-life 24 to 36 hours; QTc prolongation risk

›Route of administration

›Intravenous injection

›Fastest onset; highest bioavailability

›Injection site complications: abscess, endocarditis risk

›Intranasal insufflation

›Oral ingestion

›Extended-release formulations — delayed peak toxicity up to 12 hours

›Transdermal patch

›Patches may remain on skin; check axillae, perineum, scrotum, oropharynx

›Smoking or inhalation

›Time of last use and estimated quantity

›Time determines expected resedation risk window

›Quantity relative to usual tolerance

Coingestants and medications

›Potentiating coingestants — not reversed by naloxone

›Benzodiazepines — most common coingestant in fatal overdoses

›Alcohol — additive respiratory depression; most opioid deaths involve coingestants

›Gabapentinoids (gabapentin, pregabalin) — dose-dependent respiratory depression

›Muscle relaxants and sedative-hypnotics

03Physical Exam/exam45

Vital signs

›Respiratory assessment

›Respiratory rate <12/min — hallmark of opioid toxicity

›Apnea most critical finding requiring immediate intervention

›Bradypnea with normal SpO2 can be falsely reassuring

›SpO2 — may be normal on supplemental O2 despite dangerous hypercapnia

›ETCO2 monitoring superior to SpO2 for detecting hypoventilation

›Heart rate — bradycardia expected with opioid toxicity

›Blood pressure — hypotension suggests hemodynamic compromise or coingestant

›Temperature — hypothermia from prolonged unresponsive state in cool environment

Neurologic and pupillary exam

›Level of consciousness

›Glasgow Coma Scale — scoring eye, verbal, motor components

›GCS <=8 indicates high aspiration risk

›Serial GCS monitoring for clinical trajectory

›Response to sternal rub or nailbed pressure

›No response indicates deep CNS depression

›Muscle tone assessment

›Flaccidity — typical of opioid CNS depression

›Rigidity — wooden chest syndrome from fentanyl analogs

›Pupillary exam

›Pinpoint miosis — classic finding in opioid toxicity

›Bilateral miosis differentiates from structural pontine lesion

›Mydriasis — indicates severe hypoxia overriding miotic effect

›Also seen with meperidine, tramadol, propoxyphene overdose

›Absence of miosis does NOT rule out opioid toxicity

Airway and respiratory exam

›Airway patency

04Differential Diagnosis/ddx35

Life-threatening mimics

›CNS and metabolic causes

›Hypoglycemia — ICD-10 E11.641; immediate point-of-care glucose

›Glucose <3.9 mmol/l mimics opioid-induced coma

›Responds to dextrose, not naloxone

›Stroke or intracranial hemorrhage — ICD-10 I64

›Focal neurologic deficits, asymmetric findings

›Sudden onset without substance exposure history

›Hypertensive encephalopathy — ICD-10 I67.4

›Severely elevated BP, headache, papilledema

›Meningitis or encephalitis — ICD-10 G03.9

›Fever, nuchal rigidity, photophobia

›Petechiae for meningococcal disease

›Toxic causes

›Benzodiazepine or sedative-hypnotic overdose — ICD-10 T42.4

›Similar CNS depression without miosis

›No response to naloxone

›Alcohol intoxication — ICD-10 F10.229

›Odor of ethanol; absent miosis; no naloxone response

›Carbon monoxide poisoning — ICD-10 T58

›Environmental exposure history; cherry-red skin

›CoHb on co-oximetry

›TCA or sodium channel blocker overdose — ICD-10 T43.011

›Wide QRS on ECG; hypotension; seizures

›Mixed overdose — ICD-10 T40.601

›Most common real-world scenario; partial naloxone response suggests coingestants

Other causes of altered consciousness

›Postictal state — ICD-10 G40.909

05Laboratory Tests/lt39

Point-of-care and emergency tests

›Immediate bedside testing

›Point-of-care glucose — rule out hypoglycemia immediately

›Target >3.9 mmol/l; treat if <3.9 mmol/l with D50W 25 mL IV

›Arterial blood gas or venous blood gas

›Respiratory acidosis: elevated pCO2, decreased pH, normal HCO3

›Hypoxemia: PaO2 <60 mmHg on room air

›pCO2 >50 mmHg indicates significant hypoventilation requiring intervention

›Urine drug screen

›Standard immunoassay does NOT detect fentanyl or most synthetic opioids

›False positives: quinolones, rifampin (opiate screen); dextromethorphan (PCP screen)

›Clinical diagnosis should not be excluded based on negative UDS

Core laboratory panel

›Metabolic and organ function tests

›Basic metabolic panel

›Electrolytes — hyponatremia in chronic opioid users

›Renal function — creatinine elevation affects opioid clearance

›Glucose confirmation

›Hepatic function panel

›Hepatic disease impairs opioid metabolism

›Elevated transaminases with acetaminophen coingestion

›Serum acetaminophen level — rule out coingestion in all overdoses

›Obtain at 4 hours post-ingestion for Rumack-Matthew nomogram

›Serum salicylate level — rule out coingestion

›Serum ethanol level

›Even low levels synergize with opioids to cause respiratory depression

›Lactate — if concern for shock, prolonged hypoxia, or coingestant

›Lactate >=2 mmol/l indicates tissue hypoperfusion

06Diagnostic Tests/dt59

Scoring Systems

›Opioid overdose severity assessment

›No validated emergency department-specific severity score widely adopted

›Severity stratified clinically: mild (drowsy, RR >12), moderate (obtunded, RR 8 to 12), severe (apneic, cyanotic, pulseless)

›COWS (Clinical Opioid Withdrawal Scale) — for withdrawal after naloxone

›Score 0 to 5: mild withdrawal

›Score 13 to 24: moderate withdrawal requiring treatment

›Score >=25: severe withdrawal requiring aggressive management

›ORT (Opioid Risk Tool) — predicts overdose risk in chronic pain patients

›Score >=8: high risk for opioid-related adverse events

›Validated in chronic pain population, not acute overdose

›Revised STRATIFY tool — post-overdose risk stratification for discharge

›Factors: long-acting opioid, requiring intubation, coingestants, cardiac arrest

›High-risk factors mandate hospital admission

MRI

›MRI head — indications in opioid toxicity

›Toxic leukoencephalopathy — delayed presentation hours to weeks post-overdose

›DWI sequence: restricted diffusion in white matter

›T2/FLAIR: bilateral symmetric periventricular hyperintensity

›Associated with heroin inhalation (chasing the dragon) and hypoxic-ischemic injury

›Ischemic stroke or anoxic brain injury — post-cardiac arrest evaluation

›DWI-ADC mismatch identifies early ischemia

›Global anoxic injury: diffuse cortical ribbon sign

›Not first-line in acute opioid overdose; CT preferred initially

›MRI brain reserved for persistent altered consciousness after naloxone reversal

›MRI spine — if concern for epidural abscess from injection drug use

›T2 hyperintensity in spinal cord or epidural collection

›Gadolinium contrast for enhancement of abscess wall

07Disposition/dispo36

ICU or monitored admission criteria

›High-acuity admission indications

›Long-acting or extended-release opioid ingestion

›Methadone half-life 24 to 36 hours — sustained risk

›Fentanyl patch removal does not immediately stop absorption

›Extended-release opioid formulations — monitoring for 12 to 24 hours

›Recurrent respiratory depression requiring naloxone infusion

›Indicates opioid duration exceeds naloxone duration

›Required intubation or ongoing ventilatory support

›Significant pulmonary edema — ICU monitoring for ARDS progression

›Cardiac arrest survivors — targeted temperature management protocol

›Significant coingestant requiring monitoring

›TCA overdose, methadone + QTc, significant alcohol with electrolyte derangement

›Intentional overdose — psychiatric hold and psychiatric evaluation

›Unknown or mixed substances with prolonged effect expected

Observation unit criteria

›Appropriate for observation unit or ED observation

›Short-acting opioid ingestion (heroin, fentanyl) with clear response to naloxone

›Minimum 1 hour observation after last naloxone dose

›Willman et al. 2017: heroin overdose patients with normal mental status and vitals after naloxone rarely require hospital admission

›Absence of high-risk coingestants

›GCS 15 with ambulation normal after observation

Discharge criteria

›Safe discharge requirements

›Short-acting opioid confirmed or strongly suspected

›Heroin, illicit fentanyl — observation 1 to 2 hours after naloxone

›Extended-release: do not discharge within 4 to 6 hours minimum

›Normal vital signs including respiratory rate >=12/min

08Treatment/t93

Airway and ventilation

›Initial airway management sequence

›Airway positioning

›Head-tilt/chin-lift for unconscious patient without C-spine concern

›Jaw thrust for suspected C-spine injury

›Airway adjuncts

›Nasopharyngeal airway — 7 to 8 mm for adults; well tolerated in semiconscious patients

›Oropharyngeal airway — only when no gag reflex present

›Bag-valve-mask ventilation

›Two-person technique preferred for optimal seal

›Rate 10 to 12 breaths/min in adults

›Tidal volume 6 to 8 mL/kg ideal body weight

›Definitive airway — rapid sequence intubation

›Indications for RSI

›Failure to respond to naloxone with ongoing apnea

›Wooden chest syndrome from fentanyl analogs

›Severe pulmonary edema with deteriorating consciousness

›Aspiration with inability to protect airway

›RSI medications

›Ketamine 1 to 2 mg/kg IV — preferred induction agent; maintains airway reflexes

›Succinylcholine 1.5 mg/kg IV — first-line paralytic if no contraindications

›Rocuronium 1.2 mg/kg IV — alternative if succinylcholine contraindicated

›Sugammadex 16 mg/kg IV available for rocuronium reversal

›Post-intubation ventilation targets

›Tidal volume 6 mL/kg ideal body weight

›PEEP 5 cmH2O initial; titrate for pulmonary edema

›FiO2 titrated to SpO2 94 to 98%

Naloxone — antidote therapy

›Naloxone dosing by route

›Intravenous naloxone

›0.4 to 2 mg IV initial dose; repeat every 2 to 3 minutes

›Opioid-dependent patient: titrate from 0.04 to 0.1 mg IV to minimize precipitated withdrawal

›Goal: RR >=10 to 12 breaths/min without full reversal of analgesia

›Onset 1 to 2 minutes; duration 30 to 90 minutes

›Intranasal naloxone

›2 to 4 mg IN initial dose; repeat after 3 minutes if no response

›AHA 2025 guidelines: 8 mg IN dose associated with more severe withdrawal without survival benefit over 4 mg dose

›Onset 3 to 5 minutes

›Intramuscular naloxone

›0.4 mg IM; repeat after 3 minutes

›Onset 3 to 5 minutes; useful when IV access unavailable

›Auto-injector (Evzio) or prefilled syringe for community settings

›0.4 mg or 2 mg formulations available

›Naloxone infusion — for resedation or long-acting opioid ingestion

›Prepare 2 mg naloxone in 500 mL NS (concentration 0.004 mg/mL)

›Starting rate: two-thirds of effective reversal bolus dose per hour

›Titrate to respiratory rate >=12/min

›Reassess every 30 minutes for response and withdrawal

›Indications for infusion

›Recurrent respiratory depression after repeated bolus doses

›Long-acting opioid ingestion (methadone, extended-release oxycodone)

›Confirmed or suspected high-potency synthetic opioid

›Naloxone — cautions and limitations

›Duration shorter than most opioids — resedation is expected

›Patients must be monitored for at least 1 hour after last dose

›Precipitated opioid withdrawal — agitation, tachycardia, vomiting, hypertension

›Life-threatening in patients with severe dependence

›Supportive care: antiemetics, benzodiazepines for severe agitation

›Does NOT reverse benzodiazepines, alcohol, or gabapentinoids

Supportive care

›Pulmonary edema management

›Positive pressure ventilation first-line

›CPAP 5 to 10 cmH2O if alert and protecting airway

›Intubation with PEEP if obtunded or deteriorating

›Diuretics — low evidence for opioid-induced non-cardiogenic pulmonary edema

›Use cautiously if concurrent cardiogenic component suspected

›Activated charcoal — narrow indication

›Oral opioid ingestion within 1 hour AND protected airway

›Dose 1 g/kg up to 50 g PO or via NG tube

›Contraindicated if altered consciousness without intubation

›Aspiration management

›If aspiration witnessed or suspected

›Suction oropharynx immediately

›Upright positioning when hemodynamically stable

›Antibiotics only if signs of pneumonia develop (fever, infiltrate, leukocytosis)

›Fentanyl patch removal

›Systematic full-body search for transdermal patches

›Check axillae, groin, perineum, scrotum, oropharyngeal mucosa

›Removal does not immediately stop absorption — reservoir in skin

Harm reduction and secondary prevention

›Take-home naloxone at discharge

›Prescribe to patient and close contacts or companions

›Naloxone nasal spray 4 mg — preferred for ease of administration

›Provide education on signs of overdose and administration technique

›ACEP and AHA support universal naloxone prescribing at discharge (Class I recommendation)

›Buprenorphine initiation from ED

›Offer initiation of buprenorphine/naloxone for opioid use disorder

›Low-dose induction or standard induction protocols

›JAMA 2026: buprenorphine from ED reduces subsequent overdose risk

›Target COWS >=8 before full induction to avoid precipitated withdrawal

›Starting dose 4 to 8 mg SL; observe 1 hour; repeat 4 mg if tolerated

›Bridge prescription — provide 7 to 14 day supply pending outpatient linkage

›Harm reduction counseling

›Avoid using alone without monitor

›Fentanyl test strips — before using any illicit substance

›Start with small test dose — loss of tolerance risk after abstinence period

›Naloxone always within reach

09Special Populations/sp58

Pregnancy

›Maternal opioid toxicity

›Physiologic changes affecting presentation

›Increased respiratory tidal volume in pregnancy may partially offset respiratory depression

›Delayed gastric emptying increases risk of aspiration

›Supine hypotension — left lateral decubitus positioning

›Fetal monitoring

›Fetal heart rate monitoring after maternal stabilization

›Maternal opioid toxicity causes fetal bradycardia and hypoxia

›Obstetrics consultation immediately

›Naloxone in pregnancy

›Naloxone safe in pregnancy — no evidence of fetal harm

›Maternal naloxone administration crosses placenta

›Can precipitate fetal opioid withdrawal — neonatal abstinence syndrome (NAS)

›Balance maternal respiratory depression risk against precipitated fetal withdrawal

›Neonatal opioid withdrawal syndrome (NOWS) — monitor neonate if maternal opioid use

›Finnegan Neonatal Abstinence Scoring Tool for severity

›Methadone or morphine for neonatal withdrawal

›Opioid use disorder treatment in pregnancy

›Methadone or buprenorphine — both FDA Category-acceptable for pregnancy

›Do not discontinue opioid agonist therapy abruptly — withdrawal can cause fetal distress

›Buprenorphine preferred over methadone for initiation in pregnancy by many guidelines

Geriatric

›Altered pharmacokinetics in older adults

›Reduced renal clearance — opioid metabolite accumulation

›Morphine-6-glucuronide accumulates in renal impairment

›Lower initial doses and longer dosing intervals required

›Reduced hepatic first-pass metabolism — higher bioavailability of oral opioids

›Decreased protein binding — higher free drug fraction

›Reduced respiratory reserve — lower threshold for respiratory failure

›Baseline SpO2 may be 92 to 94% without supplemental O2

›Naloxone in older adults

›Same dosing — titrate carefully to avoid cardiovascular stress from precipitated withdrawal

›Acute withdrawal: hypertension, tachycardia — risk of MI or stroke in high-risk patients

›Higher risk of aspiration — age-related dysphagia and decreased gag reflex

›Polypharmacy context

›Drug interactions more common — CYP3A4 inhibitors and opioids frequently co-prescribed

›Benzodiazepine coprescription — particularly high-risk combination

›BEERS criteria: avoid opioids with benzodiazepines in elderly patients

Pediatrics

›Neonatal opioid withdrawal (NOWS/NAS)

›Presentation — 24 to 72 hours after birth (methadone/buprenorphine exposed neonates may present later)

›Tremors, high-pitched cry, seizures, poor feeding, sweating

›Finnegan Neonatal Abstinence Scoring Tool — score >=8 indicates pharmacologic treatment

›Treatment

›Morphine 0.03 to 0.1 mg/kg/dose PO every 3 to 4 hours

›Non-pharmacologic: swaddling, low-stimulation environment, breastfeeding if eligible

›Pediatric opioid overdose

›Accidental ingestion — age <6 years most vulnerable

›Single methadone tablet 5 to 10 mg can be fatal in a toddler

›Extended-release opioid delayed toxicity — observe minimum 4 to 6 hours

›Naloxone dosing in children

›Children <20 kg: 0.01 mg/kg IV; may repeat every 2 to 3 minutes

›Children >=20 kg: 0.4 to 2 mg IV; same as adult dosing

›Intranasal: 0.1 mg/kg up to 2 mg per nostril

›JAMA Pediatrics 2026 (Ball et al.): buprenorphine safe and effective for adolescent opioid overdose and OUD

›Adolescent opioid use

›Fentanyl-laced counterfeit pills primary risk — may not know they are using opioids

›"Rainbow fentanyl" and candy-colored pills targeting youth

›Buprenorphine initiation recommended in adolescents >=16 years with OUD

›JAMA Pediatrics 2026: naloxone and buprenorphine treatment reduces mortality

10Background/b77

Epidemiology

›Opioid overdose burden — United States and North America

›Opioid-related mortality has increased dramatically since 1999

›Third wave of opioid crisis driven by illicit fentanyl since 2013

›Fourth wave (2019 onward): polysubstance use — fentanyl + stimulants

›Annual US opioid overdose deaths approximately 80,000 to 82,000 (2023 CDC data)

›Illicit synthetic opioids account for >75% of opioid overdose deaths

›Fentanyl-involved deaths increased 7.5-fold from 2010 to 2019

›Demographics

›Ages 25 to 54 years disproportionately affected

›Male sex at higher risk — approximately 2:1 ratio

›Indigenous populations disproportionately affected in Canada and United States

›Emergency department presentation data

›Opioid-related ED visits exceed 1.6 million per year in the United States

›5 to 10% require ICU-level care

›30-day mortality after opioid-associated cardiac arrest: 35 to 40%

›Out-of-hospital cardiac arrest

›Opioid-associated OHCA typically asphyxial — younger patients with better neurologic outcomes than cardiac-cause OHCA

›AHA 2021 Scientific Statement: opioid OHCA survival may be higher than non-opioid OHCA

Pathophysiology

›Opioid receptor pharmacology

›Mu-opioid receptor (MOR) — primary mediator of analgesia and respiratory depression

›Located in brainstem: pre-Botzinger complex (respiratory rhythm generator)

›Activation causes inhibition of respiratory pacemaker neurons

›Kappa-opioid receptor — contributes to sedation and analgesia

›Delta-opioid receptor — analgesia, mood modulation

›G-protein coupled receptors — activation reduces cAMP, opens K+ channels, closes Ca2+ channels

›Net effect: decreased neuronal excitability and neurotransmitter release

›Respiratory depression mechanism

›Brainstem respiratory center suppression

›Reduced response to hypercarbia and hypoxia — hypercapnic ventilatory response blunted

›Loss of hypoxic arousal response — patients do not wake when hypoxic

›Fentanyl-specific rapid respiratory depression

›Onset within 30 to 90 seconds IV; 5 to 20 minutes intranasal

›Noradrenergic mechanisms contribute to fentanyl rapid death — Torralva and Janowsky 2019

›Wooden chest syndrome (glottis and thoracic rigidity)

›Mu-receptor activation in brainstem and spinal cord causes centrally-mediated rigidity

›Prevents chest expansion for BVM ventilation

›Prevalence higher with high-dose synthetic fentanyl analogs

›Cardiovascular effects

›Bradycardia — central vagotonic effect and peripheral vasodilation

›Hypotension — histamine release (morphine), vasodilation, reduced sympathetic tone

›Pulmonary edema — mechanism not fully elucidated

›Possible negative pressure pulmonary edema (upper airway obstruction → attempted inspiration)

›Neurogenic pulmonary edema from catecholamine surge

›Direct opioid effect on pulmonary capillary permeability

›Toxic leukoencephalopathy

›Delayed complication — onset hours to weeks post-overdose

›Associated with heroin inhalation (chasing the dragon)

›Mitochondrial dysfunction from hypoxic injury to white matter

›Spongiform changes in white matter on MRI DWI

Therapeutic Considerations

›Naloxone pharmacology and evidence

›Competitive mu-opioid antagonist with 100x higher affinity than most opioids

›Rapid displacement of opioid from receptor — onset 1 to 2 minutes IV

›Duration 30 to 90 minutes — substantially shorter than most opioids

›Titrated dosing philosophy

›Goal is restoration of adequate spontaneous ventilation, not full reversal

›Full reversal in opioid-dependent patients precipitates severe withdrawal

›AHA 2023 Focused Update: titrate to RR >=10/min, not to consciousness

›High-dose naloxone for fentanyl analogs

›Carfentanil and ultra-potent analogs may require 10 mg or more

›Multiple sequential doses acceptable — AHA 2023 supports this approach

›Opioid use disorder treatment from ED

›Buprenorphine/naloxone — best evidence for long-term outcomes

›D'Onofrio et al. JAMA 2015: ED-initiated buprenorphine doubles 30-day engagement in treatment

›Harris et al. JAMA 2026: buprenorphine reduces all-cause mortality in OUD

›Low-dose buprenorphine induction (Bernese method) allows initiation without withdrawal

›Methadone — only via licensed opioid treatment programs

›Cannot be initiated from ED for OUD (can be dosed for pain)

›Naltrexone — requires full opioid detoxification before initiation

›Extended-release injectable (Vivitrol) 380 mg IM monthly after opioid-free period

›Fentanyl-specific management considerations

›Illicit fentanyl in the drug supply — present in heroin, counterfeit pills, cocaine, methamphetamine

›PCSS 2023 Guidance: assume fentanyl present in all illicit substance use

›Unpredictable potency — hotspots within a single supply can vary 100-fold

›Higher naloxone doses required than for heroin

›AHA 2023: 2 mg IV initial dose reasonable for suspected fentanyl

›Community first responders: 4 mg IN (not 2 mg) as first dose

›Resedation more common — infusion more frequently needed than with heroin

11Patient Discharge Instructions/pdi32

copy discharge instructions

›What happened to you today

›You had an overdose from opioid medications or drugs such as heroin, fentanyl, or painkillers

›Opioids slowed your breathing to a dangerous level

›You were given a medicine called naloxone (Narcan) to reverse the overdose

›Warning signs — return to the emergency department immediately if

›You feel very sleepy and cannot be woken up

›This could mean the opioid is still affecting you

›Your breathing becomes slow, shallow, or stops

›Your lips or fingernails turn blue

›You lose consciousness again

›Chest pain or difficulty breathing

›Confusion or inability to think clearly

›Vomiting that will not stop

›Your take-home naloxone (Narcan)

›You have been given a prescription for naloxone — fill it and keep it with you at all times

›Give it to a family member or friend who is around you

›Naloxone nasal spray — insert into one nostril and press plunger firmly

›Repeat in the other nostril after 2 to 3 minutes if no response

›Call 911 immediately and continue rescue breathing while waiting

›The naloxone will wear off before the drug does — you need emergency services

›Risk of another overdose

›After a period of not using (jail, hospital, detox), your tolerance is much lower

›You can overdose on an amount that would have been safe before

›Fentanyl is now in almost all street drugs — including pills, cocaine, and methamphetamine

›Use fentanyl test strips before using any substance

›Start with a very small test amount

›Never use alone — have someone with you who has naloxone

12References/r27

Guidelines and key sources

›AHA 2025 Guidelines for CPR and Emergency Cardiovascular Care

›Cao D, Arens AM, Chow SL, et al. Part 10: Adult and Pediatric Special Circumstances of Resuscitation. Circulation. 2025.

›Opioid overdose — naloxone dosing, airway priority, cardiac arrest management

›AHA 2023 Focused Update on Poisoning and Cardiac Arrest

›Lavonas EJ, Akpunonu PD, Arens AM, et al. Circulation. 2023.

›Naloxone 2 mg IV initial dose for suspected fentanyl; repeat dosing protocols

›Reaffirms CPR priority over naloxone in cardiac arrest

›Boyer EW. Management of Opioid Analgesic Overdose. NEJM. 2012

›Comprehensive framework for opioid overdose assessment and treatment

›Resedation rates, naloxone infusion protocols, disposition criteria

Landmark trials and society statements

›Harris MTH, Weinstein ZM, Walley AY. Medications for Opioid Use Disorder, Opioid Withdrawal, and Opioid Overdose. JAMA. 2026.

›Buprenorphine, methadone, naltrexone — comparative effectiveness and mortality data

›Buprenorphine significantly reduces all-cause mortality in OUD

›AHA Scientific Statement: Opioid-Associated Out-of-Hospital Cardiac Arrest. Circulation. 2021.

›Dezfulian C, Orkin AM, Maron BA, et al.

›Opioid OHCA distinctive features — asphyxial arrest, younger age, better neurologic recovery

›Ball A, Buresh C, Hadland SE. Naloxone and Buprenorphine Treatment for Adolescent Opioid Overdose and OUD. JAMA Pediatrics. 2026.

›Evidence for buprenorphine initiation and naloxone in adolescents

›Willman MW, Liss DB, Schwarz ES, Mullins ME. Do Heroin Overdose Patients Require Observation After Receiving Naloxone? Clinical Toxicology. 2017.

›1-hour observation after last naloxone dose sufficient for heroin overdose without high-risk features

›PCSS Guidance: Buprenorphine in the Age of Fentanyl. AAAP/ASAM. 2023.

›Low-dose buprenorphine induction protocols for fentanyl-involved OUD

›Bernese method — stepwise microdosing to avoid precipitated withdrawal

›Torralva R, Janowsky A. Noradrenergic Mechanisms in Fentanyl-Mediated Rapid Death. J Pharmacol Exp Ther. 2019.

›Noradrenergic mechanisms explain why fentanyl causes more rapid death than heroin

›Lo-Ciganic WH, et al. Machine-Learning Algorithms for Predicting Opioid Overdose Risk. JAMA Network Open. 2019.

Evidence & Review

Evidence & Review