Acute Intoxication, Withdrawal, and Overdose

Naloxone dosing, alcohol withdrawal, benzodiazepine withdrawal, and buprenorphine precipitated withdrawal.

Opioid Overdose

First priority: BVM ventilation

Support respirations while preparing naloxone. Do not delay bag-valve-mask ventilation. WikEM Opioid toxicity

Naloxone dosing by route

Route	Dose	Onset	Duration	Notes
IV/IM/IO (apneic or near-apneic)	2 mg IV	1-2 min	20-90 min	May start 0.4 mg and rapidly escalate
IV (opioid-naive, mild-mod respiratory depression)	0.4 mg IV	1-2 min	20-90 min	—
IV (opioid-dependent, mild-mod)	0.04-0.05 mg IV (“push-dose”)	1-2 min	20-90 min	Titrate to respiratory effort, NOT consciousness — minimizes precipitated withdrawal
Intranasal (IN)	4 mg IN (one spray, one nostril)	3-5 min	20-90 min	OTC since March 2023. Repeat in other nostril q2-3 min
IN (higher-dose)	8 mg IN (Kloxxado)	3-5 min	20-90 min	FDA-approved alternative
IM	0.4 mg IM	3-5 min	20-90 min	Repeat q2-5 min if no IV access
Continuous infusion	2/3 of wake-up dose per hour	—	—	Give additional half-bolus 15 min after starting infusion. Titrate to respiratory effort

Key points:

If no response after 10 mg total, strongly reconsider the diagnosis.
Naloxone duration (20-90 min) is shorter than most opioids — redosing is expected.
“Wooden chest syndrome” (fentanyl-induced chest wall rigidity) may impair BVM; treat with naloxone, if ineffective consider NMB plus intubation.

Fentanyl considerations

Fentanyl overdoses frequently require higher initial doses (2-4 mg) and repeated dosing due to rapid redistribution and short naloxone duration relative to fentanyl’s duration.

Xylazine (“tranq”)

Alpha-2 agonist adulterant; not reversed by naloxone. Suspect when patient does not respond to adequate naloxone. Management is supportive: airway, atropine for symptomatic bradycardia, IV fluids for hypotension. Associated with necrotic skin ulcerations at injection sites.

Disposition after overdose

Opioid type	Observation period
Heroin / short-acting	1-2 h after last naloxone dose if ambulatory, O2 sat above 92%, RR at least 10, HR above 50, GCS 15
Methadone	12-24 h (half-life up to 60 h; recurrent respiratory depression risk)
Extended-release (OxyContin, fentanyl patch)	At least 12 h

Take-home naloxone

Every patient discharged after overdose should receive take-home naloxone (OTC Narcan 4 mg IN). No prescription needed. Counsel patient and family on recognition of overdose signs and administration technique.

Alcohol Withdrawal

See the full alcohol withdrawal protocol (including CIWA-Ar thresholds, tiered benzodiazepine dosing, phenobarbital role, and ICU-level management) in the Overnight Cross-Cover Quick Reference.

Abridged CIWA-Ar thresholds

Score	Severity	Action
Below 8	None to mild	Supportive care; typically no medication needed
8-10 (or 8-19)	Mild to moderate	Begin symptom-triggered benzodiazepines
At least 19 (or at least 20)	Severe / DTs risk	ICU-level care; aggressive benzodiazepine therapy

Benzodiazepine dosing by severity

Severity	First-line	Notes
Mild (CIWA below 10)	Chlordiazepoxide 25-50 mg PO q6h or lorazepam 1-2 mg PO/IV q4-6h PRN	Symptom-triggered
Moderate (CIWA 10-18)	Lorazepam 2-4 mg PO/IV q1-2h or diazepam 5-10 mg PO/IV q1-2h	Long-acting agents preferred for front-loading per ASAM
Severe (CIWA at least 19 / DTs)	Diazepam 10-20 mg IV q10-15 min (front-loading) or lorazepam 2-4 mg IV q10-15 min until calm	No defined ceiling with benzodiazepine front-loading

Key principles:

Long-acting benzodiazepines (diazepam, chlordiazepoxide) preferred for front-loading — less breakthrough withdrawal, smoother taper.
Lorazepam/oxazepam preferred in advanced liver disease (no active metabolites, glucuronidation).
Diazepam avoid in severe hepatic impairment (active metabolites accumulate, encephalopathy risk).
Symptom-triggered therapy is as effective as fixed-dose but with more rapid detox.

Phenobarbital role

Setting	Dose	Notes
Adjunct (severe/refractory)	10 mg/kg IV in 100 mL NS over 30 min	Reduces benzodiazepine requirements and ICU admissions
Benzodiazepine-refractory	130-260 mg IV q15-20 min (after equivalent of 200 mg diazepam)	Second-line rescue
Oral (mild-moderate, experienced clinicians)	65-130 mg PO/IV	Narrow therapeutic window — only in highly supervised settings

Cautions: respiratory depression, over-sedation, bradycardia, hypotension, Stevens-Johnson syndrome (rare). Propylene glycol diluent can cause hyperosmolar AGMA if given as drip at least 48 h.

Thiamine before glucose

Phase	Dose	Duration
Acute (inpatient)	Thiamine 200-500 mg IV TID	3-5 days
Maintenance	Thiamine 100 mg PO daily	Indefinite while at risk
Nutritional adjuncts	Folate 1 mg PO daily, multivitamin, Mg/K/PO4 repletion	—

Critical: Give thiamine BEFORE glucose — glucose administration without thiamine can precipitate Wernicke encephalopathy in thiamine-deficient patients. The “banana bag” is not routinely required for most chronic alcoholics. WikEM Ethanol withdrawal

Benzodiazepine Withdrawal

Risk stratification

Clinically similar to alcohol withdrawal (shared GABA/NMDA receptor mechanisms).
Onset: several days to up to 3 weeks after last dose (depends on half-life of the specific benzodiazepine).
Higher risk with: high doses, prolonged use, short-acting agents (alprazolam, triazolam).
Psychosis is more common than in alcohol withdrawal.

Clinical features

Autonomic hyperactivity (diaphoresis, tachycardia, hyperthermia)
Nausea/vomiting
Tremulousness, psychomotor agitation
Anxiety, insomnia, irritability
Psychosis (more common than alcohol withdrawal)
Seizures — treat with benzodiazepines (NOT phenytoin — same principle as alcohol withdrawal)

Seizure prevention and management

Same first-line agents as alcohol withdrawal: long-acting benzodiazepines (diazepam or chlordiazepoxide). Mild cases that can tolerate PO: chlordiazepoxide taper. Moderate/severe: IV diazepam. Do NOT use phenytoin/fosphenytoin for withdrawal seizures — they are GABA-mediated, not driven by kindling of excitatory pathways. WikEM Benzodiazepine withdrawal

Diazepam-equivalent conversion

Benzodiazepine	Multiply dose by	Example
Triazolam	x 20	0.25 mg triazolam = 5 mg diazepam
Alprazolam	x 10	0.5 mg alprazolam = 5 mg diazepam
Lorazepam	x 5	2 mg lorazepam = 10 mg diazepam

Taper strategy

Convert total daily dose to diazepam equivalents.
Decrease by 25% in week 1.
Decrease by 25% in week 2.
Then decrease by 12.5% for each subsequent week.

Admission criteria: multiple seizures, uncontrolled autonomic hyperstimulation, decreased level of consciousness. Consider neurology consult if patient was on benzodiazepines for seizure control.

Buprenorphine Precipitated Withdrawal

Mechanism

Buprenorphine is a partial mu agonist; it can precipitate florid withdrawal if given while the patient still has full agonists on board. WikEM Opioid toxicity

COWS threshold

COWS score at least 8-12 (preferably above 10) required before first dose. Do NOT rely on “time since last use” — patients may misreport and metabolism varies.

Avoidance strategy

For opioid overdose in a patient with OUD: use push-dose naloxone (0.04-0.05 mg IV) titrated to respiratory effort, NOT consciousness, to minimize precipitated withdrawal.
Confirm COWS score before initiating buprenorphine.

Induction dosing

Standard ED initiation: buprenorphine/naloxone 4 mg/1 mg SL, repeat q1-2h PRN (typical day-1 total 8-16 mg). No X-waiver required since MAT Act 2023.

References

WikEM Opioid toxicity
WikEM Ethanol withdrawal
WikEM Benzodiazepine withdrawal
ASAM Clinical Practice Guideline on Alcohol Withdrawal Management
Substance Use Guidelines — society guidelines, SAMHSA TIPs, and screening tools