Substance Use — Alcohol

101. Alcohol Withdrawal

CNS hyperexcitability on cessation/reduction · mild → severe → DTs · withdrawal seizures · benzodiazepines are the backbone · thiamine before glucose · Super Compact

Sx: timeline matters — mild (6–12h): tremor, anxiety, insomnia, headache, palpitations, GI upset · alcoholic hallucinosis (12–24h): visual/tactile/auditory hallucinations with intact sensorium · withdrawal seizures (6–48h): generalized tonic-clonic, usually single/brief · DTs (48–96h): delirium, agitation, fluctuating sensorium, autonomic storm (fever, tachycardia, HTN, diaphoresis) — mortality if untreated (DTs = altered sensorium + autonomic instability; distinct from earlier hallucinosis where sensorium is clear)

Neg: denies other cause of AMS/seizure unexamined (hypoglycemia, head trauma/subdural, infection/sepsis, hepatic encephalopathy, electrolytes — check) · denies that benzos withheld for fear of sedation in true withdrawal · denies missed Wernicke (give thiamine) · denies concurrent benzo/opioid withdrawal

SHx: quantity/duration of use, time of last drink, prior withdrawal/DTs/seizures (predicts severity — kindling), prior detox/ICU admissions · co-ingestants, benzo use · malnutrition · liver disease · social supports

Etiology: chronic alcohol enhances inhibitory GABA + suppresses excitatory glutamate/NMDA → abrupt cessation removes GABA tone and unmasks glutamate excess → CNS hyperexcitability + autonomic hyperactivity · severity driven by use intensity and prior episodes (kindling — each withdrawal worsens the next)

RF: heavy/prolonged use · prior DTs or withdrawal seizures (strongest predictor) · concurrent illness/infection · older age · abnormal LFTs/electrolytes · high initial CIWA

Data: CIWA-Ar score (severity + symptom-triggered dosing) · fingerstick glucose · BMP, magnesium, phosphate, calcium (often depleted — replace; hypoMg lowers seizure threshold) · LFTs, lipase · CBC · consider head CT, LP, cultures, ammonia if AMS atypical/not fitting · ECG (QT, ischemia) · ethanol level (correlate with state) · urine tox (co-ingestants)

DDx: DTs (AMS + autonomic storm, 48–96h) vs alcoholic hallucinosis (clear sensorium) · sepsis/infection · hepatic encephalopathy (asterixis, ↑ammonia) · benzo/sedative withdrawal · intracranial process (trauma, bleed) · Wernicke (ophthalmoplegia, ataxia, confusion)

Home Meds: hold sedating/QT meds as appropriate · reconcile home benzos (don't abruptly stop) · thiamine, folate, multivitamin · address hepatic dosing

Plan

CONSULT: ICU (DTs, refractory/high benzo requirements, airway risk) · Addiction Medicine / Psychiatry (relapse prevention, MAT) · Neurology (atypical/recurrent seizures)

– THIAMINE FIRST — before any glucose: thiamine 100–500 mg IV (higher dose, e.g. 500 mg IV q8h × ≥3 days, if Wernicke suspected — ophthalmoplegia/ataxia/confusion); giving glucose before thiamine can precipitate Wernicke encephalopathy in the depleted; add folate + multivitamin
– Benzodiazepines — the backbone (GABA agonists):
  • Symptom-triggered (preferred) by CIWA-Ar: e.g. diazepam 5–10 mg IV/PO, or lorazepam 2–4 mg IV/PO, or chlordiazepoxide 25–100 mg PO, dosed when CIWA ≥8–10, reassessed q1h — titrate to light sedation/symptom control
  • Use LORAZEPAM (or oxazepam) in significant liver disease/elderly (no active metabolites, hepatic-independent metabolism); diazepam/chlordiazepoxide are long-acting (smoother taper) but accumulate in liver failure
  • Front-loading for severe (e.g. diazepam 10–20 mg q1–2h until calm) achieves rapid control with self-taper
– Withdrawal seizures: usually self-limited; benzodiazepines treat and prevent recurrence (lorazepam 2–4 mg IV) — phenytoin does NOT prevent alcohol withdrawal seizures; if status → standard status protocol; investigate other causes if focal/atypical/recurrent
– Delirium tremens (emergency): aggressive escalating IV benzodiazepines (e.g. diazepam 10 mg → 20 mg IV q5–10min, or lorazepam boluses/infusion, titrated to light sedation); ICU; add phenobarbital (adjunct/benzo-sparing) or dexmedetomidine/propofol (adjuncts — not monotherapy, don't treat the GABA deficit alone) for refractory/benzo-resistant; treat autonomic instability, protect airway, supportive care
– Replete electrolytes: magnesium (1–2 g IV — also raises seizure threshold), potassium, phosphate (refeeding risk), correct hypoglycemia (after thiamine)
– Supportive: IV fluids (often volume-depleted), calm environment, monitor vitals/CIWA, fall/aspiration precautions, treat coexisting illness/infection
– Thiamine before glucose, every time — a glucose load in a thiamine-depleted alcoholic can tip them into Wernicke. Then benzodiazepines are the whole game: dose them to the symptoms (CIWA), don't be timid in DTs, and reach for phenobarbital or dexmedetomidine as adjuncts when benzo requirements escalate — but never as substitutes, because only the GABA agonists fix the underlying deficit.
– PT/OT: mobilize when safe; fall precautions throughout
– Trend: CIWA-Ar serially, vitals (HR/BP/temp), mental status, glucose, electrolytes (Mg/K/Phos), benzo requirements (rising → escalate/ICU), seizure activity
– Escalation triggers: DTs, escalating/refractory benzo needs, seizures/status, airway compromise, or autonomic instability → ICU + aggressive benzos ± phenobarbital/dexmedetomidine; atypical course → reinvestigate (CT/LP/cultures)
– Discharge checklist: withdrawal resolved + stable off escalating benzos (with appropriate taper if applicable); thiamine/folate/vitamins continued; electrolytes normalized; MAT offered (naltrexone, acamprosate, disulfiram) + addiction/counseling referral; relapse-prevention plan; outpatient follow-up; return precautions (tremor, hallucinations, seizures, confusion)

101. Alcohol Withdrawal

complete reference · mild + severe + delirium tremens + withdrawal seizures · CIWA-driven benzodiazepines · thiamine before glucose · Full Card

Symptoms / Associated Sx

• The timeline is diagnostic: mild withdrawal (6–12 hours) brings tremor, anxiety, insomnia, headache, palpitations, and GI upset

• Alcoholic hallucinosis (12–24 hours): visual, tactile, or auditory hallucinations with an intact, clear sensorium

• Withdrawal seizures (6–48 hours): generalized tonic-clonic seizures, usually single and brief

• Delirium tremens (48–96 hours): delirium, agitation, a fluctuating sensorium, and an autonomic storm (fever, tachycardia, hypertension, diaphoresis) — carrying significant mortality if untreated

• DTs are distinguished by an altered sensorium with autonomic instability, unlike earlier hallucinosis where the sensorium remains clear

Neg

• Pt denies an unexamined alternative cause of altered mental status or seizure (hypoglycemia, head trauma/subdural hematoma, infection/sepsis, hepatic encephalopathy, electrolyte derangement)

• Pt denies that benzodiazepines were withheld for fear of sedation in genuine withdrawal

• Pt denies a missed Wernicke encephalopathy (give thiamine) and denies concurrent benzodiazepine or opioid withdrawal

Social History (SHx)

• Quantity and duration of use, and the time of the last drink

• Prior withdrawal, DTs, or withdrawal seizures (the strongest predictor of severity, via kindling), and prior detox or ICU admissions

• Co-ingestants and benzodiazepine use

• Malnutrition, liver disease, and social supports

Main Etiology

• Chronic alcohol enhances inhibitory GABA tone and suppresses excitatory glutamate/NMDA signaling; abrupt cessation removes the GABA tone and unmasks a relative glutamate excess

• The result is CNS hyperexcitability with autonomic hyperactivity

• Severity is driven by the intensity of use and the number of prior episodes — the kindling phenomenon, in which each withdrawal worsens the next

RF

• Modifiable: ongoing heavy use, nutritional and electrolyte status, treatment of concurrent illness

• Non-modifiable: prior DTs or withdrawal seizures (the strongest predictor), older age, and chronic liver disease

Data

• CIWA-Ar score (quantifies severity and drives symptom-triggered dosing)

• Fingerstick glucose

• BMP, magnesium, phosphate, and calcium (often depleted — replace; hypomagnesemia lowers the seizure threshold)

• LFTs, lipase, and CBC

• Consider head CT, lumbar puncture, cultures, and ammonia (if the altered mental status is atypical or does not fit withdrawal)

• ECG (QT, ischemia); ethanol level (correlated with clinical state); urine toxicology (co-ingestants)

DDx

Delirium tremens (altered mental status with autonomic storm, 48–96 hours) versus alcoholic hallucinosis (clear sensorium) · sepsis or infection · hepatic encephalopathy (asterixis, elevated ammonia) · benzodiazepine or sedative withdrawal · an intracranial process (trauma, hemorrhage) · Wernicke encephalopathy (ophthalmoplegia, ataxia, confusion)

Home Meds

• Hold: sedating and QT-prolonging medications as appropriate

• Reconcile: home benzodiazepines (do not abruptly discontinue)

• Give: thiamine, folate, and a multivitamin; account for hepatic dosing

Plan

CONSULT: ICU (delirium tremens, refractory or high benzodiazepine requirements, airway risk) · Addiction Medicine/Psychiatry (relapse prevention, medication-assisted treatment) · Neurology (atypical or recurrent seizures)

• Thiamine first — before any glucose: thiamine 100–500 mg IV (higher dosing, such as 500 mg IV every 8 hours for at least 3 days, if Wernicke is suspected — ophthalmoplegia, ataxia, confusion), since glucose given before thiamine can precipitate Wernicke encephalopathy in the depleted patient; add folate and a multivitamin

• Benzodiazepines — the backbone (GABA agonists):

• • Symptom-triggered dosing (preferred) by CIWA-Ar: diazepam 5–10 mg IV/PO, lorazepam 2–4 mg IV/PO, or chlordiazepoxide 25–100 mg PO, given when CIWA is ≥8–10 and reassessed hourly, titrated to light sedation and symptom control

• • Use lorazepam or oxazepam in significant liver disease or the elderly (no active metabolites, hepatic-independent metabolism); diazepam and chlordiazepoxide are long-acting for a smoother self-taper but accumulate in liver failure

• • Front-loading for severe withdrawal (e.g. diazepam 10–20 mg every 1–2 hours until calm) achieves rapid control with a built-in self-taper

• Withdrawal seizures: usually self-limited; benzodiazepines both treat and prevent recurrence (lorazepam 2–4 mg IV) — phenytoin does not prevent alcohol withdrawal seizures; manage status epilepticus per the standard protocol; and investigate other causes if the seizure is focal, atypical, or recurrent

• Delirium tremens (an emergency): aggressive escalating IV benzodiazepines (diazepam 10 mg then 20 mg IV every 5–10 minutes, or lorazepam boluses/infusion, titrated to light sedation) with ICU care; add phenobarbital as a benzodiazepine-sparing adjunct, or dexmedetomidine/propofol as adjuncts (not monotherapy, since they don't address the GABA deficit alone) for refractory or benzodiazepine-resistant cases; treat autonomic instability, protect the airway, and provide supportive care

• Replete electrolytes: magnesium (1–2 g IV, which also raises the seizure threshold), potassium, and phosphate (refeeding risk), and correct hypoglycemia after thiamine

• Supportive care: IV fluids (patients are often volume-depleted), a calm environment, monitoring of vitals and CIWA, fall and aspiration precautions, and treatment of any coexisting illness or infection

• PT/OT: mobilize when safe, with fall precautions throughout

• Trend: serial CIWA-Ar, vitals (heart rate, blood pressure, temperature), mental status, glucose, electrolytes (magnesium, potassium, phosphate), benzodiazepine requirements (rising needs warrant escalation/ICU), and seizure activity

• Escalation triggers: delirium tremens, escalating or refractory benzodiazepine needs, seizures or status epilepticus, airway compromise, or autonomic instability → ICU with aggressive benzodiazepines and phenobarbital/dexmedetomidine; an atypical course → reinvestigate with CT, LP, and cultures

• Discharge checklist: withdrawal resolved and stable off escalating benzodiazepines (with an appropriate taper if applicable); thiamine, folate, and vitamins continued; electrolytes normalized; medication-assisted treatment offered (naltrexone, acamprosate, disulfiram) with an addiction/counseling referral; a relapse-prevention plan; outpatient follow-up; return precautions for tremor, hallucinations, seizures, or confusion

Red Flags

• Delirium tremens (altered sensorium with autonomic storm) → ICU and aggressive escalating benzodiazepines; significant mortality if undertreated

• Escalating or refractory benzodiazepine requirements → ICU with phenobarbital or dexmedetomidine adjuncts

• Withdrawal seizures progressing to status epilepticus → standard status protocol

• Focal, atypical, or recurrent seizures, or an altered mental status not fitting withdrawal → image and reinvestigate (subdural, infection, metabolic)

• Suspected Wernicke encephalopathy → high-dose IV thiamine before glucose

Senior IM Resident Pearls

• Thiamine before glucose, every time. A glucose load in a thiamine-depleted alcoholic can precipitate Wernicke encephalopathy — give the thiamine first.

• Dose benzodiazepines to the symptoms, not the clock. Symptom-triggered CIWA-based dosing outperforms fixed schedules and avoids both under- and over-sedation.

• Prior DTs or withdrawal seizures is the strongest predictor. Kindling means each episode is worse than the last — escalate vigilance in a patient with that history.

• Phenytoin doesn't work for alcohol withdrawal seizures. Benzodiazepines treat and prevent them; reserve anticonvulsant workup for focal or atypical features.

• Reach for phenobarbital or dexmedetomidine as adjuncts, not substitutes. In escalating DTs they help, but only the GABA agonists address the underlying deficit — dexmedetomidine controls autonomic signs while masking worsening delirium.

• Choose lorazepam in liver disease. It lacks active metabolites and isn't dependent on hepatic oxidation, so it won't accumulate the way diazepam or chlordiazepoxide do.

• Common mistake: attributing all altered mental status to withdrawal — the alcoholic patient is also at high risk for subdural hematoma, infection, and hepatic encephalopathy; keep the differential open.

Substance Use — Alcohol

102. Alcohol Intoxication

acute ethanol CNS depression · falls/trauma · altered mental status · mostly supportive — but never assume alcohol explains all the AMS · Super Compact

Sx: dose-dependent CNS depression — slurred speech, ataxia, incoordination, disinhibition, nystagmus, impaired judgment → drowsiness, stupor → coma, respiratory depression, loss of airway reflexes (aspiration risk) at high levels · nausea/vomiting · hypothermia, hypoglycemia (esp in children/malnourished) (tolerance varies enormously — a chronic user may be talking at a level that would obtund a naive drinker; the level doesn't always match the exam)

Neg: denies that intoxication explains ALL the AMS (rule out: head trauma/subdural — common with falls, hypoglycemia, co-ingestants, toxic alcohols, infection/sepsis, postictal, Wernicke, hepatic encephalopathy) · denies missed trauma from a fall · denies unexamined depressed airway · denies that a level rising or not clearing as expected was ignored

SHx: pattern/quantity of use, chronic vs binge · co-ingestants (benzos, opioids — synergistic depression) · prior trauma/falls · liver disease · the circumstances (found down, witnessed fall, assault)

Etiology: ethanol potentiates GABA and inhibits NMDA/glutamate → dose-dependent CNS and respiratory depression · metabolized at a relatively fixed rate (~roughly 15–20 mg/dL/h, faster in chronic users) — so clinical clearance is largely time + supportive care · danger from airway compromise, aspiration, trauma, hypoglycemia, and co-ingestants

RF: binge drinking · co-ingestion of other CNS depressants · falls/trauma risk · malnutrition (hypoglycemia) · extremes of age · naïve drinker (low tolerance)

Data: fingerstick glucose (always — treatable, mimics intoxication) · ethanol level (correlate with mental status — discordance demands a search for another cause) · low threshold for non-contrast head CT (any fall, focal deficit, not improving as expected, anticoagulated) · BMP, magnesium, LFTs · osmolar gap / consider toxic alcohols if acidosis or level doesn't fit · urine tox + acetaminophen/salicylate if intentional/co-ingestion suspected · ABG if depressed respirations

DDx: isolated ethanol intoxication (improving with time, level fits) · head injury/subdural (fall, focal, not clearing) · hypoglycemia · co-ingestant/toxic alcohol (osmolar/anion gap) · sepsis/infection · postictal · hepatic encephalopathy · Wernicke

Home Meds: hold sedating meds while intoxicated · thiamine · resume home meds when sober/safe · reconcile with care if liver disease

Plan

CONSULT: Trauma/Neurosurgery (significant head injury/bleed) · ICU (airway compromise, severe co-ingestion) · Addiction/Psychiatry (AUD, intentional ingestion, suicidality screen)

– Airway/breathing first: assess airway protection and respiratory drive — position to prevent aspiration, suction, supplemental O2; intubate if unable to protect airway / significant respiratory depression; continuous monitoring (pulse ox, capnography if obtunded)
– Check and treat glucose: fingerstick immediately; dextrose for hypoglycemia — but give thiamine first/with it (thiamine 100 mg IV) to avoid precipitating Wernicke in the depleted
– Supportive care is the mainstay: IV fluids if depleted, antiemetics, warming if hypothermic, fall precautions, frequent neuro checks, monitor until clinically sober (clearance is largely time) — no role for routine "banana bag" beyond thiamine/glucose/electrolyte correction; no proven benefit to fluids accelerating clearance
– EVALUATE FOR TRAUMA + alternative causes (the key cognitive step): examine head-to-toe for injury; low threshold for head CT (fall, focal deficit, anticoagulation, or failure to improve on the expected trajectory); reassess serially — if mental status isn't improving as the level falls, the alcohol is NOT the whole story → broaden (CT, labs, infection workup, co-ingestants, toxic alcohols)
– Manage co-ingestions: if opioids suspected → naloxone; if intentional → acetaminophen + salicylate levels, toxic-alcohol workup, psychiatric evaluation once sober
– Replete electrolytes (magnesium, potassium, phosphate) and give thiamine/folate in the chronic user; watch for evolving withdrawal as the level falls
– The central discipline here is to never let "he's just drunk" close the workup. Intoxicated patients fall and hit their heads, take other drugs, get infected, and go hypoglycemic. Check a glucose, have a low threshold for a head CT, and if the sensorium doesn't track the falling ethanol level, go looking for the real reason.
– PT/OT: assess gait/safety before discharge; fall precautions
– Trend: mental status vs ethanol level (should improve together), airway/respiratory status, glucose, vitals, evolving withdrawal signs
– Escalation triggers: airway compromise/respiratory depression → ICU/intubation; head bleed → neurosurgery; AMS not clearing with falling level → urgent reinvestigation; emerging withdrawal → treat per withdrawal pathway
– Discharge checklist: clinically sober + safe gait + injuries excluded/addressed; glucose/electrolytes corrected; screen for AUD + suicidality (if intentional); MAT + addiction referral offered; thiamine/vitamins; safe disposition (not discharged while impaired); return precautions (worsening headache/vomiting, confusion, weakness — possible delayed bleed)

102. Alcohol Intoxication

complete reference · acute intoxication + falls/trauma + altered mental status · supportive care + exclude mimics · Full Card

Symptoms / Associated Sx

• Dose-dependent CNS depression: slurred speech, ataxia, incoordination, disinhibition, nystagmus, and impaired judgment, progressing to drowsiness and stupor

• At high levels: coma, respiratory depression, and loss of airway reflexes with aspiration risk

• Nausea and vomiting; hypothermia and hypoglycemia (especially in children and the malnourished)

• Tolerance varies enormously — a chronic user may be conversant at a level that would obtund a naïve drinker, so the measured level does not always match the exam

Neg

• Pt denies that intoxication explains all of the altered mental status — exclude head trauma/subdural hematoma (common with falls), hypoglycemia, co-ingestants, toxic alcohols, infection/sepsis, a postictal state, Wernicke encephalopathy, and hepatic encephalopathy

• Pt denies missed trauma from a fall and denies an unexamined depressed airway

• Pt denies that a level which is rising, or not clearing as expected, was overlooked

Social History (SHx)

• Pattern and quantity of use, chronic versus binge

• Co-ingestants (benzodiazepines, opioids — synergistic depression)

• Prior trauma or falls and liver disease

• The circumstances (found down, a witnessed fall, assault)

Main Etiology

• Ethanol potentiates GABA and inhibits NMDA/glutamate signaling, producing dose-dependent CNS and respiratory depression

• It is metabolized at a relatively fixed rate (roughly 15–20 mg/dL/h, faster in chronic users), so clinical clearance is largely a matter of time plus supportive care

• The danger comes from airway compromise, aspiration, trauma, hypoglycemia, and co-ingestants rather than the ethanol alone

RF

• Modifiable: binge drinking, co-ingestion of other CNS depressants, fall/trauma exposure

• Non-modifiable: extremes of age, malnutrition, and low tolerance in the naïve drinker

Data

• Fingerstick glucose (always — a treatable condition that mimics intoxication)

• Ethanol level (correlated with mental status; discordance demands a search for another cause)

• A low threshold for non-contrast head CT (any fall, focal deficit, failure to improve as expected, or anticoagulation)

• BMP, magnesium, and LFTs

• Osmolar gap and consideration of toxic alcohols (if there is an acidosis or the level doesn't fit the picture)

• Urine toxicology with acetaminophen and salicylate levels if an intentional or co-ingestion is suspected; an ABG if respirations are depressed

DDx

Isolated ethanol intoxication (improving over time, with a level that fits the exam) · head injury or subdural hematoma (a fall, focal findings, not clearing) · hypoglycemia · a co-ingestant or toxic alcohol (osmolar or anion gap) · sepsis/infection · a postictal state · hepatic encephalopathy · Wernicke encephalopathy

Home Meds

• Hold: sedating medications while intoxicated

• Give: thiamine

• Resume home medications when sober and safe, reconciling carefully in liver disease

Plan

CONSULT: Trauma/Neurosurgery (significant head injury or intracranial bleed) · ICU (airway compromise, severe co-ingestion) · Addiction/Psychiatry (alcohol use disorder, intentional ingestion, suicidality screen)

• Airway and breathing first: assess airway protection and respiratory drive — position to prevent aspiration, suction, and provide supplemental oxygen; intubate if the patient cannot protect the airway or has significant respiratory depression; and monitor continuously (pulse oximetry, capnography if obtunded)

• Check and treat the glucose: obtain a fingerstick immediately and give dextrose for hypoglycemia — but give thiamine first or concurrently (thiamine 100 mg IV) to avoid precipitating Wernicke encephalopathy in a depleted patient

• Supportive care is the mainstay: IV fluids if depleted, antiemetics, warming if hypothermic, fall precautions, frequent neurologic checks, and monitoring until clinically sober (clearance is largely a function of time) — there is no role for a routine "banana bag" beyond thiamine, glucose, and electrolyte correction, and no proven benefit of fluids in accelerating clearance

• Evaluate for trauma and alternative causes (the key cognitive step): examine head-to-toe for injury, maintain a low threshold for head CT (a fall, focal deficit, anticoagulation, or failure to improve on the expected trajectory), and reassess serially — if the mental status is not improving as the level falls, the alcohol is not the whole story, and the workup should broaden to CT, labs, an infection workup, co-ingestants, and toxic alcohols

• Manage co-ingestions: give naloxone if opioids are suspected; for an intentional ingestion, check acetaminophen and salicylate levels, pursue a toxic-alcohol workup, and arrange a psychiatric evaluation once sober

• Replete electrolytes (magnesium, potassium, phosphate) and give thiamine and folate in the chronic user, watching for evolving withdrawal as the level falls

• PT/OT: assess gait and safety before discharge, with fall precautions

• Trend: mental status against the ethanol level (they should improve together), airway and respiratory status, glucose, vitals, and any evolving withdrawal signs

• Escalation triggers: airway compromise or respiratory depression → ICU/intubation; an intracranial bleed → neurosurgery; altered mental status not clearing with a falling level → urgent reinvestigation; emerging withdrawal → treat per the withdrawal pathway

• Discharge checklist: clinically sober with a safe gait and injuries excluded or addressed; glucose and electrolytes corrected; screening for alcohol use disorder and suicidality (if intentional); medication-assisted treatment and an addiction referral offered; thiamine and vitamins; a safe disposition (not discharged while impaired); return precautions for worsening headache or vomiting, confusion, or weakness suggesting a delayed bleed

Red Flags

• Inability to protect the airway or significant respiratory depression → intubation and ICU care

• Altered mental status not improving as the ethanol level falls → the alcohol is not the whole story; reinvestigate urgently

• Any fall, focal deficit, or anticoagulation → low threshold for head CT to exclude a subdural hematoma

• Hypoglycemia masquerading as intoxication → check and treat the glucose (with thiamine first)

• Intentional ingestion → screen for co-ingestants (acetaminophen, salicylate, toxic alcohols) and suicidality

Senior IM Resident Pearls

• "He's just drunk" must never close the workup. Intoxicated patients fall, take other drugs, get infected, and go hypoglycemic — keep looking.

• The level should track the exam. If the sensorium doesn't improve as the ethanol level falls, go hunting for the real cause (bleed, infection, co-ingestant, toxic alcohol).

• Always check a glucose. Hypoglycemia perfectly mimics intoxication and is instantly treatable — and give thiamine before or with the dextrose.

• The intoxicated head is a high-risk head. Falls plus blunted pain perception plus possible anticoagulation make the threshold for CT low.

• Watch for the handoff to withdrawal. As the level falls in a chronic heavy user, withdrawal can emerge — anticipate it rather than be surprised.

• Supportive care, not magic fluids. No infusion meaningfully speeds ethanol clearance; the job is airway protection, glucose, and serial reassessment.

• Common mistake: discharging an "intoxicated" patient who was actually bleeding intracranially or hypoglycemic — document a clearing sensorium and a safe gait before disposition.

Toxicology — Opioids

103. Opioid Overdose

the classic triad: CNS depression + respiratory depression + miosis · heroin / fentanyl / prescription · naloxone is the antidote, airway is the priority · Super Compact

Sx: classic triad — depressed mental status + respiratory depression (↓rate, the killer) + pinpoint pupils (miosis) · ↓RR/apnea, hypoxia, cyanosis, bradypnea, hypopnea → coma; bradycardia, hypotension; fentanyl: rapid onset, "wooden chest" rigidity, very high potency (small amounts lethal); can cause non-cardiogenic pulmonary edema · (miosis may be absent with co-ingestants, hypoxia, or certain opioids — meperidine/tramadol; don't exclude OD on pupils alone — respiratory rate is the vital sign that matters)

Neg: denies co-ingestants altering picture (stimulants, benzos — mixed) · denies that miosis is required to diagnose (hypoxia/co-ingestant can dilate) · denies missed anoxic brain injury from prolonged hypoxia · denies that a single naloxone dose rules out OD (may need repeat/infusion, esp long-acting/fentanyl)

SHx: opioid type/route (IV heroin, illicit fentanyl, prescription oxycodone/methadone), known use disorder, MAT (methadone/buprenorphine), prior overdoses/naloxone use · access to fentanyl (contaminated supply) · co-use of benzos/alcohol · pain prescriptions

Etiology: opioid agonism at mu receptors → dose-dependent CNS + brainstem respiratory depression (blunted CO2 response) → hypoventilation, hypoxia, death · fentanyl/analogues: extreme potency + rapid onset + chest-wall rigidity make even tiny exposures lethal and may need higher/repeat naloxone · long-acting agents (methadone, ER formulations) → prolonged toxicity outlasting naloxone

RF: opioid use disorder/IV use · illicit fentanyl-contaminated supply · concurrent sedatives (benzos, alcohol) · loss of tolerance (post-incarceration/abstinence/detox) · high-dose prescriptions · renal/hepatic impairment

Data: clinical diagnosis (triad) + response to naloxone · pulse oximetry + capnography/RR (the priority monitor) · ABG (hypercapnia/hypoxia) · fingerstick glucose (AMS) · ECG (methadone → ↑QT/torsades; co-ingestants) · CXR (aspiration/pulmonary edema) · acetaminophen + salicylate levels (combination products, intentional) · urine tox (may miss fentanyl/synthetics on standard panels) · CK (rhabdo if down long)

DDx: opioid OD (triad + naloxone response) · other sedative OD (benzo, alcohol — no miosis/naloxone response) · clonidine/imidazoline (can mimic) · pontine stroke (miosis + AMS) · hypoglycemia · hypercapnic/hypoxic encephalopathy · co-ingestant mixed picture

Home Meds: reconcile opioids, methadone, buprenorphine · hold all opioids/sedatives during acute management · review QT meds (methadone) · plan MAT continuation/initiation

Plan

CONSULT: ICU (intubation, naloxone infusion, prolonged/severe) · Toxicology/Poison Control 1-800-222-1222 · Addiction Medicine (MAT initiation, OUD) · Psychiatry (intentional)

– AIRWAY + BREATHING FIRST (this is what kills): support ventilation immediately — bag-valve-mask with 100% O2 for apnea/severe hypoventilation while preparing naloxone; this oxygenation is more urgent than the antidote
– NALOXONE (the antidote) — titrate to ADEQUATE VENTILATION, not full arousal: 0.04–0.4 mg IV (start low in known opioid-dependent to avoid precipitating florid withdrawal), repeat/escalate q2–3 min (up to ~2 mg, then consider higher cumulative doses up to ~10 mg for fentanyl/synthetics); IM/intranasal (e.g. 4 mg IN) if no IV access; goal is restoring respiratory drive (RR ≥ ~10–12), not complete reversal of analgesia/consciousness (over-reversal → agitation, withdrawal, vomiting/aspiration, sympathetic surge, pulmonary edema)
– Anticipate re-sedation — naloxone is SHORT-acting (~30–90 min): opioids (esp methadone, ER products, large fentanyl loads) outlast it → observe several hours; for recurrent depression start a naloxone infusion (~⅔ of the effective waking bolus per hour, titrated); never discharge immediately after a single bolus for a long-acting agent
– If intubation needed (failure to maintain ventilation/protect airway, or to avoid repeated naloxone in some cases) → ICU
– Supportive + workup: treat hypoglycemia (after glucose check), manage non-cardiogenic pulmonary edema supportively, treat aspiration, fluids; check acetaminophen/salicylate if combination product or intentional; ECG for methadone QT; CK if prolonged down-time (rhabdo)
– Transition to recovery/MAT: once stable, offer buprenorphine or methadone initiation and naltrexone counseling; prescribe take-home naloxone + train the patient/family; harm-reduction counseling
– Two rules save lives: ventilate before you reverse (oxygen is more urgent than naloxone), and titrate naloxone to breathing, not to full wakefulness — blasting an opioid-dependent patient awake trades a treatable airway problem for combative withdrawal and aspiration. And remember naloxone wears off before the opioid does, so the patient who looks fixed can re-arrest — observe, and infuse if needed.
– PT/OT: per status once stable
– Trend: RR + oxygenation + capnography (the key), mental status, recurrence of depression (re-sedation), naloxone requirement, ECG (methadone), CK, glucose
– Escalation triggers: apnea/failure to ventilate → BVM + intubation + ICU; recurrent depression → naloxone infusion + ICU; massive/fentanyl exposure needing escalating doses → ICU; QT/torsades (methadone) → cardiology/ICU
– Discharge checklist: sustained adequate ventilation off naloxone for an appropriate observation period (longer for long-acting agents); take-home naloxone prescribed + education; MAT initiated or referral arranged; suicidality screen if intentional; harm-reduction + addiction follow-up; return precautions (re-sedation, breathing difficulty, recurrence)

103. Opioid Overdose

complete reference · heroin + fentanyl + prescription opioids + respiratory depression · ventilate then naloxone · Full Card

Symptoms / Associated Sx

• The classic triad of depressed mental status, respiratory depression (a reduced rate — the lethal feature), and pinpoint pupils (miosis)

• Reduced respiratory rate or apnea, hypoxia, cyanosis, and progression to coma; bradycardia and hypotension

• Fentanyl is distinguished by rapid onset, "wooden chest" rigidity, and extreme potency such that small amounts are lethal; it can also cause non-cardiogenic pulmonary edema

• Miosis may be absent with co-ingestants, hypoxia, or certain opioids (meperidine, tramadol) — overdose should not be excluded on pupils alone, since the respiratory rate is the vital sign that matters

Neg

• Pt denies co-ingestants that alter the picture (stimulants, benzodiazepines — a mixed presentation)

• Pt denies that miosis is required for the diagnosis (hypoxia or a co-ingestant can dilate the pupils)

• Pt denies a missed anoxic brain injury from prolonged hypoxia and denies that a single naloxone dose rules out overdose (repeat dosing or an infusion may be needed, especially for long-acting agents or fentanyl)

Social History (SHx)

• Opioid type and route (IV heroin, illicit fentanyl, prescription oxycodone or methadone), a known use disorder, and any medication-assisted treatment (methadone, buprenorphine)

• Prior overdoses and naloxone use

• Access to a fentanyl-contaminated supply and co-use of benzodiazepines or alcohol

• Pain prescriptions

Main Etiology

• Opioid agonism at mu receptors produces dose-dependent CNS and brainstem respiratory depression (a blunted CO2 response), causing hypoventilation, hypoxia, and death

• Fentanyl and its analogues combine extreme potency, rapid onset, and chest-wall rigidity, making even tiny exposures lethal and sometimes requiring higher or repeated naloxone doses

• Long-acting agents (methadone, extended-release formulations) produce prolonged toxicity that outlasts naloxone

RF

• Modifiable: concurrent sedatives, access to a contaminated supply, dose of prescribed opioids

• Non-modifiable: opioid use disorder, loss of tolerance after abstinence/incarceration/detox, and renal or hepatic impairment

Data

• Clinical diagnosis (the triad) with the response to naloxone

• Pulse oximetry with capnography and respiratory rate (the priority monitor)

• ABG (hypercapnia, hypoxia); fingerstick glucose (altered mental status)

• ECG (methadone causes QT prolongation and torsades; assess for co-ingestants)

• CXR (aspiration, pulmonary edema)

• Acetaminophen and salicylate levels (combination products, intentional ingestion)

• Urine toxicology (standard panels may miss fentanyl and synthetics); CK if the patient was down for a prolonged period (rhabdomyolysis)

DDx

Opioid overdose (the triad with a naloxone response) · another sedative overdose (benzodiazepine, alcohol — without miosis or a naloxone response) · clonidine or other imidazoline (can mimic it) · pontine stroke (miosis with altered mental status) · hypoglycemia · hypercapnic or hypoxic encephalopathy · a mixed co-ingestant picture

Home Meds

• Reconcile: opioids, methadone, and buprenorphine

• Hold: all opioids and sedatives during acute management

• Review: QT-prolonging medications (methadone); plan medication-assisted treatment continuation or initiation

Plan

CONSULT: ICU (intubation, naloxone infusion, prolonged or severe cases) · Toxicology/Poison Control (1-800-222-1222) · Addiction Medicine (MAT initiation, opioid use disorder) · Psychiatry (intentional ingestion)

• Airway and breathing first (this is what kills): support ventilation immediately with bag-valve-mask and 100% oxygen for apnea or severe hypoventilation while preparing naloxone — this oxygenation is more urgent than the antidote

• Naloxone (the antidote) — titrate to adequate ventilation, not full arousal: 0.04–0.4 mg IV (start low in a known opioid-dependent patient to avoid precipitating florid withdrawal), repeated and escalated every 2–3 minutes (up to ~2 mg, then higher cumulative doses up to ~10 mg for fentanyl or synthetics); give IM or intranasal (e.g. 4 mg IN) if there is no IV access; the goal is restoring respiratory drive (a rate of about 10–12) rather than fully reversing analgesia or consciousness, since over-reversal causes agitation, withdrawal, vomiting with aspiration, a sympathetic surge, and pulmonary edema

• Anticipate re-sedation — naloxone is short-acting (~30–90 minutes): opioids (especially methadone, ER products, and large fentanyl loads) outlast it, so observe for several hours; for recurrent depression start a naloxone infusion (approximately two-thirds of the effective waking bolus per hour, titrated); and never discharge immediately after a single bolus for a long-acting agent

• Intubate if needed (failure to maintain ventilation or protect the airway) and admit to the ICU

• Supportive care and workup: treat hypoglycemia (after a glucose check), manage non-cardiogenic pulmonary edema and aspiration supportively, and give fluids; check acetaminophen and salicylate levels for combination products or intentional ingestion; obtain an ECG for methadone-related QT prolongation; and check CK after a prolonged down-time

• Transition to recovery/MAT: once stable, offer buprenorphine or methadone initiation and naltrexone counseling; prescribe take-home naloxone and train the patient and family; and provide harm-reduction counseling

• PT/OT: as appropriate once stable

• Trend: respiratory rate, oxygenation, and capnography (the key parameters), mental status, recurrence of depression (re-sedation), naloxone requirement, the ECG (methadone), CK, and glucose

• Escalation triggers: apnea or failure to ventilate → bag-valve-mask, intubation, and ICU; recurrent depression → naloxone infusion and ICU; a massive or fentanyl exposure needing escalating doses → ICU; QT prolongation or torsades (methadone) → cardiology/ICU

• Discharge checklist: sustained adequate ventilation off naloxone for an appropriate observation period (longer for long-acting agents); take-home naloxone prescribed with education; MAT initiated or a referral arranged; a suicidality screen if intentional; harm-reduction and addiction follow-up; return precautions for re-sedation, breathing difficulty, or recurrence

Red Flags

• Apnea or failure to ventilate → bag-valve-mask oxygenation immediately, before or alongside naloxone

• Re-sedation after initial reversal → naloxone is shorter-acting than the opioid; observe and start an infusion

• Fentanyl or synthetic exposure needing escalating naloxone doses → ICU monitoring

• Methadone overdose → QT prolongation and torsades risk

• Non-cardiogenic pulmonary edema after reversal → supportive respiratory care

Senior IM Resident Pearls

• Ventilate before you reverse. Oxygen via bag-valve-mask is more urgent than naloxone — the hypoxia kills, and you can support breathing while the antidote is drawn up.

• Titrate naloxone to breathing, not to wakefulness. Blasting a dependent patient fully awake trades a treatable airway problem for combative withdrawal, vomiting, and aspiration.

• Naloxone wears off before the opioid does. A patient who looks fixed can re-arrest — observe for hours and use an infusion for long-acting agents or large fentanyl loads.

• Don't exclude overdose on the pupils. Miosis can be absent with hypoxia or co-ingestants; the respiratory rate is the diagnostic vital sign.

• Methadone is a QT drug. Get an ECG and watch for torsades, especially with other QT-prolonging agents on board.

• Every overdose is an MAT opportunity. Offer buprenorphine or methadone, prescribe take-home naloxone, and engage addiction services before discharge — it reduces mortality.

• Common mistake: discharging a methadone or ER-opioid overdose after a single naloxone bolus — the toxicity outlasts the antidote and the patient re-sedates at home.

Substance Use — Opioids

104. Opioid Withdrawal

flu-like, miserable but rarely life-threatening · heroin / fentanyl / methadone / buprenorphine transitions · COWS-guided · buprenorphine induction is the key skill · Super Compact

Sx: opposite of intoxication — anxiety, restlessness, drug craving, yawning, lacrimation, rhinorrhea, sweating, mydriasis (dilated pupils), piloerection ("cold turkey"), myalgias/arthralgias, abdominal cramps, nausea/vomiting/diarrhea, tachycardia, hypertension, dilated pupils · (uncomfortable and dysphoric but rarely fatal in adults — the danger is in dehydration, complications, and untreated suffering driving relapse/AMA; can be life-threatening in neonates)

Neg: denies that this is dangerous like alcohol/benzo withdrawal (usually not — but treat the suffering) · denies missed dehydration/electrolyte loss from vomiting/diarrhea · denies precipitated withdrawal risk from premature buprenorphine/naloxone (timing matters) · denies co-occurring sedative withdrawal masked

SHx: opioid type/route/last use (fentanyl — shorter half-life, faster but stored in fat → variable/prolonged; methadone — long half-life, delayed/prolonged withdrawal), MAT history (methadone/buprenorphine), prior withdrawal/treatment, pregnancy (don't withdraw — maintain MAT), pain conditions

Etiology: physiologic dependence → abrupt cessation/reduction or antagonist exposure (naloxone, or buprenorphine given too early) removes mu-opioid tone → noradrenergic/autonomic rebound (locus coeruleus hyperactivity) + the somatic/GI symptom complex · timing/severity depend on the agent's half-life (short-acting heroin: 6–12h onset; methadone: 24–48h, prolonged)

RF: abrupt cessation/incarceration · antagonist administration (naloxone reversal) · premature buprenorphine induction (precipitated withdrawal) · long-acting agents (protracted course) · inadequate MAT dosing

Data: COWS (Clinical Opiate Withdrawal Scale) — grade severity, time buprenorphine induction · clinical diagnosis · BMP (losses from vomiting/diarrhea) · fingerstick glucose · pregnancy test (women) · urine tox (corroborate; may miss fentanyl/synthetics) · consider ECG (methadone QT) · assess hydration

DDx: opioid withdrawal (mydriasis, GI Sx, COWS, recent cessation) · precipitated withdrawal (after buprenorphine/naloxone, abrupt severe) · sympathomimetic/stimulant state · sedative withdrawal · gastroenteritis/sepsis · serotonin syndrome (if clonus/hyperthermia) · anxiety disorder

Home Meds: continue MAT (methadone/buprenorphine) — do not stop in maintenance patients (verify dose with clinic/PDMP) · reconcile opioids · maintain MAT in pregnancy

Plan

CONSULT: Addiction Medicine (MAT induction/continuation, OUD — primary) · OB (pregnant — maintain MAT, never withdraw) · Psychiatry (co-occurring)

– Grade with COWS and treat the suffering (untreated withdrawal drives AMA and relapse/overdose)
– Buprenorphine (preferred — both treatment and the bridge to MAT): partial mu-agonist; induce when in MODERATE withdrawal (COWS ≥8–12) and after an adequate opioid-free interval to avoid precipitated withdrawal (it displaces full agonists from the receptor) — typically ~6–12h after short-acting opioids, longer after methadone, and with fentanyl the timing is trickier (fat storage); start ~2–4 mg SL, reassess in 1–2h, titrate (e.g. to 8–16 mg day 1); manage to a maintenance dose
– Methadone (alternative, in appropriate settings/licensed programs or inpatient for withdrawal): full agonist, long-acting; start conservatively, titrate (caution: QT, respiratory depression, accumulation)
– Symptomatic/adjunctive (if not using or bridging to opioid agonist):
  • Clonidine (alpha-2 agonist — blunts autonomic/noradrenergic symptoms; watch hypotension) or lofexidine
  • Antiemetics (ondansetron), antidiarrheals (loperamide), antispasmodics (dicyclomine), NSAIDs/acetaminophen for myalgias, hydroxyzine for anxiety/sleep
– Precipitated withdrawal management (abrupt severe withdrawal after buprenorphine/naloxone): supportive + more buprenorphine (high-dose can override) per addiction guidance; comfort meds; don't abandon induction
– Supportive: IV fluids + electrolyte repletion for vomiting/diarrhea losses, monitor hydration
– Engage in care: link to ongoing MAT (this admission is a high-value opportunity), counseling, harm reduction, take-home naloxone
– Opioid withdrawal rarely kills an adult, but treating it well is what keeps the patient in the hospital and in treatment instead of leaving to use again at a now-reduced tolerance — a deadly combination. The single technical skill that matters is buprenorphine timing: induce in moderate withdrawal, not early, or you precipitate the very withdrawal you're trying to treat.
– PT/OT: as needed
– Trend: COWS serially, hydration/electrolytes, response to buprenorphine/symptomatic meds, BP (clonidine), precipitated withdrawal, engagement
– Escalation triggers: precipitated withdrawal → addiction guidance + higher-dose buprenorphine/supportive; severe dehydration → IV resuscitation; pregnancy → OB + maintain MAT; co-occurring sedative withdrawal → treat that pathway
– Discharge checklist: MAT continued/initiated with a confirmed outpatient plan + first dose/prescription bridge; symptoms controlled + hydrated; take-home naloxone + education; addiction/counseling linkage; warn re loss of tolerance + overdose risk if relapse; OB follow-up if pregnant; return precautions (severe vomiting/dehydration, inability to keep meds down, relapse)

104. Opioid Withdrawal

complete reference · heroin + fentanyl + methadone + buprenorphine transitions · COWS-guided, buprenorphine induction · Full Card

Symptoms / Associated Sx

• Essentially the opposite of intoxication: anxiety, restlessness, and drug craving

• Yawning, lacrimation, rhinorrhea, sweating, mydriasis (dilated pupils), and piloerection ("cold turkey")

• Myalgias and arthralgias, abdominal cramps, and nausea, vomiting, and diarrhea

• Tachycardia and hypertension

• Uncomfortable and dysphoric but rarely fatal in adults — the danger lies in dehydration, complications, and untreated suffering driving the patient to leave and relapse; it can, however, be life-threatening in neonates

Neg

• Pt denies that this is dangerous in the way alcohol or benzodiazepine withdrawal is (usually not, though the suffering still warrants treatment)

• Pt denies missed dehydration or electrolyte loss from vomiting and diarrhea

• Pt denies a precipitated-withdrawal risk from premature buprenorphine or naloxone (timing matters) and denies a masked co-occurring sedative withdrawal

Social History (SHx)

• Opioid type, route, and last use (fentanyl has a short half-life but is stored in fat, giving a variable and sometimes prolonged course; methadone has a long half-life with delayed, prolonged withdrawal)

• Medication-assisted treatment history (methadone, buprenorphine) and prior withdrawal or treatment

• Pregnancy (do not withdraw — maintain MAT)

• Pain conditions

Main Etiology

• Physiologic dependence means that abrupt cessation or reduction, or antagonist exposure (naloxone, or buprenorphine given too early), removes mu-opioid tone

• This produces a noradrenergic and autonomic rebound (locus coeruleus hyperactivity) with the characteristic somatic and GI symptom complex

• The timing and severity depend on the agent's half-life — short-acting heroin causes onset at 6–12 hours, while methadone causes onset at 24–48 hours with a prolonged course

RF

• Modifiable: timing of buprenorphine induction, adequacy of MAT dosing

• Non-modifiable: abrupt cessation (incarceration), antagonist administration during reversal, and the use of long-acting agents

Data

• COWS (Clinical Opiate Withdrawal Scale) (grades severity and times buprenorphine induction)

• Clinical diagnosis

• BMP (losses from vomiting and diarrhea); fingerstick glucose

• Pregnancy test in women

• Urine toxicology (corroborative; may miss fentanyl and synthetics); consider an ECG (methadone QT); and assess hydration

DDx

Opioid withdrawal (mydriasis, GI symptoms, an elevated COWS, recent cessation) · precipitated withdrawal (abrupt and severe after buprenorphine or naloxone) · a sympathomimetic/stimulant state · sedative withdrawal · gastroenteritis or sepsis · serotonin syndrome (if clonus or hyperthermia) · an anxiety disorder

Home Meds

• Continue MAT (methadone, buprenorphine) — do not stop it in maintenance patients (verify the dose with the clinic or PDMP)

• Reconcile: opioids

• Maintain MAT in pregnancy

Plan

CONSULT: Addiction Medicine (MAT induction or continuation, opioid use disorder — primary) · Obstetrics (pregnant patients — maintain MAT, never withdraw) · Psychiatry (co-occurring conditions)

• Grade with COWS and treat the suffering, since untreated withdrawal drives patients to leave against advice and relapse with overdose risk

• Buprenorphine (preferred — both treatment and the bridge to MAT): a partial mu-agonist induced when the patient is in moderate withdrawal (COWS ≥8–12) and after an adequate opioid-free interval to avoid precipitated withdrawal (it displaces full agonists from the receptor) — typically about 6–12 hours after short-acting opioids, longer after methadone, and trickier to time with fentanyl due to fat storage — starting at ~2–4 mg sublingually, reassessing in 1–2 hours, and titrating (e.g. to 8–16 mg on day 1) toward a maintenance dose

• Methadone (an alternative in appropriate, licensed settings or inpatient for withdrawal): a long-acting full agonist started conservatively and titrated, with caution for QT prolongation, respiratory depression, and accumulation

• Symptomatic and adjunctive therapy (if not using or bridging to an opioid agonist):

• • Clonidine (an alpha-2 agonist that blunts the autonomic and noradrenergic symptoms; watch for hypotension) or lofexidine

• • Antiemetics (ondansetron), antidiarrheals (loperamide), antispasmodics (dicyclomine), NSAIDs or acetaminophen for myalgias, and hydroxyzine for anxiety and sleep

• Precipitated withdrawal management (abrupt severe withdrawal after buprenorphine or naloxone): supportive care plus additional buprenorphine (high doses can override it) per addiction guidance, comfort medications, and not abandoning the induction

• Supportive care: IV fluids and electrolyte repletion for vomiting and diarrhea losses, with monitoring of hydration

• Engage in care: link to ongoing MAT (this admission is a high-value opportunity), counseling, harm reduction, and take-home naloxone

• PT/OT: as needed

• Trend: serial COWS, hydration and electrolytes, the response to buprenorphine and symptomatic medications, blood pressure (on clonidine), any precipitated withdrawal, and engagement in care

• Escalation triggers: precipitated withdrawal → addiction guidance with higher-dose buprenorphine and supportive care; severe dehydration → IV resuscitation; pregnancy → obstetrics and maintenance of MAT; a co-occurring sedative withdrawal → treat that pathway

• Discharge checklist: MAT continued or initiated with a confirmed outpatient plan and a first dose or prescription bridge; symptoms controlled and the patient hydrated; take-home naloxone with education; addiction and counseling linkage; counseling on loss of tolerance and overdose risk if relapse occurs; obstetric follow-up if pregnant; return precautions for severe vomiting or dehydration, inability to keep medications down, or relapse

Red Flags

• Precipitated withdrawal after buprenorphine or naloxone → severe, abrupt symptoms requiring addiction guidance and supportive care

• Severe dehydration from vomiting and diarrhea → IV resuscitation and electrolyte repletion

• Pregnancy → never withdraw; maintain MAT, as withdrawal risks the fetus

• Patient leaving against advice → high relapse and overdose risk at reduced tolerance; treat symptoms aggressively to retain in care

• Neonatal withdrawal → potentially life-threatening, unlike the adult course

Senior IM Resident Pearls

• Withdrawal rarely kills an adult, but treating it well saves lives. Good symptom control keeps the patient in the hospital and in treatment rather than leaving to use at a now-reduced tolerance — a deadly combination.

• Buprenorphine timing is the whole skill. Induce in moderate withdrawal (COWS ≥8–12), not early — give it too soon and you precipitate the very withdrawal you're treating.

• Fentanyl complicates the timing. Its fat storage makes the opioid-free window less predictable, so induction can be trickier and may need a more cautious or alternative approach.

• Never withdraw a pregnant patient. Maintain methadone or buprenorphine — withdrawal endangers the fetus, and MAT is the standard of care.

• Clonidine covers the autonomic symptoms when you're not using an opioid agonist, but watch the blood pressure and don't expect it to touch the craving.

• This admission is a treatment opportunity. Start MAT, prescribe naloxone, and connect to addiction services — engagement during a hospitalization meaningfully reduces mortality.

• Common mistake: giving buprenorphine or naloxone too early and precipitating florid withdrawal — confirm adequate withdrawal severity and an opioid-free interval before induction.

Toxicology — Iatrogenic / CNS

105. Medication-Induced Encephalopathy

altered mental status from drugs · polypharmacy / gabapentin / baclofen / opioids / sedatives · the diagnosis is "what did we give them" · renal/hepatic accumulation is the trap · Super Compact

Sx: altered mental status on a spectrum — sedation, confusion, inattention, drowsiness, slurred speech, ataxia, myoclonus/asterixis → stupor/coma · fluctuating; often insidious and multifactorial, especially in elderly · may have agent-specific signs (opioids: miosis + ↓RR; baclofen: hypotonia/coma + withdrawal risk; gabapentinoids: ataxia/sedation) (the clue is the temporal link to a new drug, a dose increase, or worsening organ function — "what changed in the med list?")

Neg: denies that non-drug causes were skipped (infection/sepsis, metabolic — Na/glucose/Ca, hypoxia/hypercarbia, uremia, hepatic, stroke, seizure/postictal, thiamine) · denies missed renal/hepatic accumulation of a renally-cleared drug · denies unexamined drug-drug interaction · denies missed withdrawal (baclofen, benzo) mimicking

SHx: full medication reconciliation (the core) — recent additions/dose changes, OTC/herbals, accidental double-dosing · renal/hepatic function changes (accumulation) · age/frailty · polypharmacy count · prior similar episodes

Etiology: CNS-active drug effect, accumulation, or interaction → encephalopathy · common culprits: opioids (sedation ± respiratory depression), benzodiazepines/sedative-hypnotics (Z-drugs), gabapentin/pregabalin (renally cleared → accumulate in CKD/AKI — a very common missed cause), baclofen (renally cleared → accumulation → coma; abrupt stop → severe withdrawal), anticholinergics, antipsychotics, lithium, antiepileptics, muscle relaxants · amplified by polypharmacy, organ dysfunction, and age

RF: elderly/frail · polypharmacy · renal or hepatic impairment (accumulation) · recent med changes/hospital additions · drug-drug interactions · low body weight

Data: medication review + timeline (the key "test") · rule out other causes: BMP (Na, glucose, Ca, renal fxn), LFTs/ammonia, CBC + cultures/infection workup, TSH, fingerstick glucose, ABG (CO2/O2), B12/thiamine if indicated · drug levels where available (digoxin, lithium, valproate, certain AEDs) · head CT (focal deficit, trauma, not explained) · consider EEG (nonconvulsive status), urine tox · review renal dosing of all agents

DDx: drug-induced (temporal link, culprit identified, improves on withdrawal) · metabolic encephalopathy (Na/glucose/Ca/uremia/hepatic) · infection/sepsis/delirium · hypoxic-hypercarbic · structural (stroke/bleed) · nonconvulsive status · withdrawal syndrome

Home Meds: STOP/reduce the culprit(s) · renally/hepatically dose-adjust everything · deprescribe nonessential CNS-active drugs · do NOT abruptly stop baclofen or benzos (withdrawal) — taper

Plan

CONSULT: Pharmacy (med review, renal dosing, interactions — high yield) · Nephrology (accumulation, dialysis for select agents) · Neurology (atypical/persistent, EEG) · Geriatrics (elderly polypharmacy) · Toxicology/Poison Control

– Identify and remove the offending agent(s) — the central intervention: reconcile meds, map the timeline against symptom onset and organ-function changes, stop or reduce the culprit, and adjust dosing for renal/hepatic function
– Exclude the dangerous mimics in parallel — check glucose, sodium, calcium, renal function, ammonia, oxygenation/CO2, infection; image if focal/unexplained; EEG if nonconvulsive status suspected (don't anchor on "it's the meds" and miss sepsis or a bleed)
– Agent-specific management:
  • Opioids: hold; naloxone if respiratory depression (titrate to ventilation — 0.04–0.4 mg IV, repeat); support airway
  • Benzodiazepines/Z-drugs: supportive; flumazenil generally AVOIDED (seizure risk, esp chronic use/mixed/TCA co-ingestion); time + supportive care
  • Gabapentin/pregabalin: hold/reduce, renally dose; supportive — accumulates in renal impairment; dialysis can remove in severe toxicity/renal failure
  • Baclofen: hold if toxic but taper rather than abruptly stop chronic baclofen (abrupt withdrawal → agitation, seizures, rigidity, fever — can mimic NMS/serotonin syndrome); supportive, dialysis for severe toxicity in renal failure
  • Lithium/digoxin/valproate: check levels, hold, specific management (dialysis for lithium; Digibind for digoxin — see relevant pathways)
– Supportive care: airway protection, monitoring, fall/aspiration precautions, IV fluids, treat agitation non-pharmacologically where possible (avoid adding more CNS-active drugs)
– The highest-yield move is a careful medication reconciliation with a timeline: nearly every case ties to a new drug, a dose bump, or a renally-cleared agent accumulating as the kidneys declined — gabapentin and baclofen are the classic stealth culprits in CKD. But never let "it's the meds" stop you from checking a glucose, a sodium, and for infection, because those mimics are common and lethal.
– PT/OT: cognitive/functional assessment as it clears; fall precautions
– Trend: mental status as culprit withdrawn (should improve — confirms diagnosis), renal/hepatic function, drug levels, vitals, exclusion of other causes
– Escalation triggers: respiratory depression/airway → ICU + naloxone/support; severe gabapentinoid/baclofen/lithium toxicity in renal failure → nephrology/dialysis; not improving off culprit → reinvestigate mimics; baclofen withdrawal → reinstate + taper
– Discharge checklist: culprit removed/adjusted + mental status recovered; medication list deprescribed/simplified with renal dosing; clear documentation of the offending agent (avoid re-prescription); pharmacy/geriatric med review; caregiver education; outpatient follow-up + cognitive reassessment; return precautions (confusion, excessive drowsiness, falls)

105. Medication-Induced Encephalopathy

complete reference · polypharmacy + gabapentin + baclofen + opioids + sedatives · reconcile, remove, renally dose · Full Card

Symptoms / Associated Sx

• Altered mental status on a spectrum: sedation, confusion, inattention, drowsiness, slurred speech, ataxia, myoclonus or asterixis, progressing to stupor and coma

• Often fluctuating, insidious, and multifactorial, especially in the elderly

• Agent-specific signs may appear (opioids: miosis with a reduced respiratory rate; baclofen: hypotonia and coma with withdrawal risk; gabapentinoids: ataxia and sedation)

• The clue is the temporal link to a new drug, a dose increase, or worsening organ function — ask what changed in the medication list

Neg

• Pt denies that non-drug causes were skipped (infection/sepsis, metabolic derangement of sodium/glucose/calcium, hypoxia/hypercarbia, uremia, hepatic failure, stroke, a postictal state, thiamine deficiency)

• Pt denies a missed renal or hepatic accumulation of a renally-cleared drug

• Pt denies an unexamined drug-drug interaction and denies a missed withdrawal syndrome (baclofen, benzodiazepine) mimicking the picture

Social History (SHx)

• A full medication reconciliation is the core — recent additions and dose changes, OTC and herbal products, and accidental double-dosing

• Changes in renal or hepatic function (causing accumulation)

• Age and frailty, and the polypharmacy count

• Prior similar episodes

Main Etiology

• A CNS-active drug effect, drug accumulation, or drug-drug interaction producing encephalopathy

• Common culprits: opioids (sedation with or without respiratory depression), benzodiazepines and sedative-hypnotics (Z-drugs), gabapentin and pregabalin (renally cleared, accumulating in CKD/AKI — a very common missed cause), baclofen (renally cleared, accumulating to coma, with abrupt cessation causing severe withdrawal), anticholinergics, antipsychotics, lithium, antiepileptics, and muscle relaxants

• Amplified by polypharmacy, organ dysfunction, and advanced age

RF

• Modifiable: polypharmacy, drug-drug interactions, and dosing relative to renal/hepatic function

• Non-modifiable: advanced age and frailty, organ impairment, and low body weight

Data

• Medication review with a timeline (the key diagnostic step)

• Rule out other causes: BMP (sodium, glucose, calcium, renal function), LFTs and ammonia, CBC with cultures and an infection workup, TSH, fingerstick glucose, ABG (CO2, O2), and B12/thiamine if indicated

• Drug levels where available (digoxin, lithium, valproate, certain antiepileptics)

• Head CT (focal deficit, trauma, or an otherwise unexplained picture)

• Consider EEG (nonconvulsive status) and urine toxicology; review the renal dosing of every agent

DDx

Drug-induced encephalopathy (a temporal link, an identified culprit, improvement on withdrawal) · metabolic encephalopathy (sodium, glucose, calcium, uremia, hepatic) · infection/sepsis or delirium · hypoxic-hypercarbic encephalopathy · a structural cause (stroke, hemorrhage) · nonconvulsive status epilepticus · a withdrawal syndrome

Home Meds

• Stop/reduce the culprit medication(s)

• Dose-adjust everything for renal and hepatic function; deprescribe nonessential CNS-active drugs

• Do not abruptly stop baclofen or benzodiazepines (withdrawal risk) — taper instead

Plan

CONSULT: Pharmacy (medication review, renal dosing, interactions — high yield) · Nephrology (accumulation, dialysis for select agents) · Neurology (atypical or persistent cases, EEG) · Geriatrics (elderly polypharmacy) · Toxicology/Poison Control

• Identify and remove the offending agent(s) — the central intervention: reconcile the medications, map the timeline against symptom onset and organ-function changes, stop or reduce the culprit, and adjust dosing for renal and hepatic function

• Exclude the dangerous mimics in parallel: check glucose, sodium, calcium, renal function, ammonia, oxygenation and CO2, and for infection; image if there are focal or unexplained features; and obtain an EEG if nonconvulsive status is suspected — do not anchor on "it's the medications" and miss sepsis or a bleed

• Agent-specific management:

• • Opioids: hold them; give naloxone for respiratory depression (titrated to ventilation — 0.04–0.4 mg IV, repeated) and support the airway

• • Benzodiazepines/Z-drugs: supportive care; flumazenil is generally avoided (seizure risk, especially with chronic use, mixed ingestions, or TCA co-ingestion) — time and supportive care are the treatment

• • Gabapentin/pregabalin: hold or reduce and renally dose; supportive care, since these accumulate in renal impairment, and dialysis can remove them in severe toxicity or renal failure

• • Baclofen: hold if toxic, but taper rather than abruptly stop chronic baclofen (abrupt withdrawal causes agitation, seizures, rigidity, and fever that can mimic NMS or serotonin syndrome); supportive care, with dialysis for severe toxicity in renal failure

• • Lithium, digoxin, valproate: check levels and hold, with specific management (dialysis for lithium, digoxin-specific antibody fragments for digoxin)

• Supportive care: airway protection, monitoring, fall and aspiration precautions, IV fluids, and non-pharmacologic management of agitation where possible (avoid adding more CNS-active drugs)

• PT/OT: cognitive and functional assessment as the encephalopathy clears, with fall precautions

• Trend: mental status as the culprit is withdrawn (improvement confirms the diagnosis), renal and hepatic function, drug levels, vitals, and the exclusion of other causes

• Escalation triggers: respiratory depression or airway compromise → ICU with naloxone and support; severe gabapentinoid, baclofen, or lithium toxicity in renal failure → nephrology and dialysis; failure to improve off the culprit → reinvestigate the mimics; baclofen withdrawal → reinstate and taper

• Discharge checklist: the culprit removed or adjusted with mental status recovered; a deprescribed and simplified medication list with renal dosing; clear documentation of the offending agent to prevent re-prescription; a pharmacy or geriatric medication review; caregiver education; outpatient follow-up with cognitive reassessment; return precautions for confusion, excessive drowsiness, or falls

Red Flags

• Respiratory depression (opioids, combined CNS depressants) → airway support, naloxone, and ICU

• A renally-cleared agent (gabapentin, baclofen, lithium) accumulating as renal function declines → consider dialysis

• Abrupt discontinuation of chronic baclofen or a benzodiazepine → a severe withdrawal syndrome that can mimic NMS or serotonin syndrome

• Failure to improve after removing the suspected culprit → an unrecognized mimic (sepsis, metabolic, structural)

• Nonconvulsive status epilepticus masquerading as drug sedation → EEG

Senior IM Resident Pearls

• The medication reconciliation is the test. Map a timeline of new drugs, dose changes, and organ-function trends against the symptom onset — the culprit usually announces itself.

• Gabapentin and baclofen are the stealth culprits in CKD. Both are renally cleared and quietly accumulate as the kidneys decline, causing an encephalopathy that's easy to miss.

• Don't anchor — check a glucose, sodium, and for infection. "It's the meds" is a comfortable but dangerous conclusion if you haven't excluded the common, lethal mimics.

• Confirm the diagnosis by withdrawal. Improvement after stopping the suspected agent both treats and confirms — persistent encephalopathy means you have the wrong cause.

• Avoid flumazenil. In chronic benzodiazepine use or a mixed ingestion it can precipitate seizures — supportive care is almost always the right call.

• Taper baclofen, don't yank it. Abrupt cessation triggers a severe, sometimes life-threatening withdrawal with rigidity and fever that mimics NMS.

• Common mistake: restarting the offending drug at discharge because it wasn't clearly flagged — document the culprit prominently to prevent the bounce-back.

Substance Use — Sedative-Hypnotics

106. Benzodiazepine Withdrawal

a GABA-withdrawal syndrome like alcohol's — and just as dangerous · anxiety / tremor / seizures / delirium · long-acting benzo taper is the treatment · Super Compact

Sx: mirrors alcohol withdrawal (shared GABA mechanism) — anxiety, agitation, insomnia, tremor, sweating, palpitations, tachycardia, hypertension, sensory hypersensitivity (photophobia, hyperacusis) · severe: seizures, delirium, psychosis, autonomic instability/hyperthermia (DT-like) · onset depends on half-life — short-acting (alprazolam, lorazepam): 1–2 days; long-acting (diazepam, clonazepam): delayed, up to a week+ · (this is a potentially LIFE-THREATENING withdrawal — do not underestimate it the way opioid withdrawal can be; protracted symptoms common)

Neg: denies that this was treated like benign opioid withdrawal (benzo withdrawal can kill — seizures, status, DT-like delirium) · denies concurrent alcohol withdrawal masked · denies missed other AMS/seizure cause · denies that abrupt cessation (iatrogenic — meds held on admission) was overlooked as the trigger

SHx: benzodiazepine type/dose/duration (chronic high-dose = highest risk), Z-drugs (zolpidem etc.), reason for use, last dose, prior withdrawal/seizures · concurrent alcohol/opioid use · abrupt stop (ran out, admitted and held) · barbiturate use

Etiology: chronic benzodiazepine use upregulates the system around enhanced GABA-A inhibition; abrupt cessation/reduction → loss of inhibitory tone → CNS hyperexcitability (same pathophysiology as alcohol withdrawal) → anxiety/tremor → seizures/delirium · severity scales with dose, duration, potency, and abruptness; often iatrogenic when home benzos are stopped on admission

RF: high-dose/long-duration use · short-acting/high-potency agents (alprazolam) · abrupt cessation · concurrent alcohol use disorder · prior withdrawal seizures · older age · polypharmacy

Data: clinical diagnosis + medication/use history (last dose, dose, duration) · fingerstick glucose, BMP, magnesium · rule out concurrent causes (infection, structural, metabolic) as for any AMS/seizure · ECG · urine tox (corroborate; standard panels may miss clonazepam/alprazolam) · assess for concurrent alcohol withdrawal (overlapping)

DDx: benzodiazepine withdrawal (cessation history, GABA-withdrawal picture) · alcohol withdrawal (coexisting/identical) · barbiturate withdrawal · sympathomimetic/serotonin syndrome · anxiety/agitated delirium · infection/sepsis · primary seizure disorder

Home Meds: reinstate the home benzodiazepine (or equivalent) — do NOT continue abrupt cessation · convert to a long-acting agent for a controlled taper · reconcile concurrent sedatives/alcohol

Plan

CONSULT: ICU (seizures/status, severe delirium, autonomic instability) · Psychiatry/Addiction (taper planning, dependence, dual use) · Neurology (recurrent/atypical seizures)

– Treat with benzodiazepines — reinstate and taper (the mainstay): restart an adequate benzodiazepine dose to control symptoms, ideally converting to a long-acting agent (diazepam or clonazepam) for a smooth, gradual taper (e.g. reduce ~10–25% every few days–week, individualized) — abrupt is dangerous, slow is safe; symptom-triggered or fixed-dose depending on severity
– Severe withdrawal / seizures / delirium (emergency, treat like severe alcohol withdrawal): aggressive IV benzodiazepines (e.g. lorazepam 2–4 mg IV or diazepam 5–10 mg IV, repeat/titrate to control); add phenobarbital (cross-tolerant, benzo-sparing — useful in refractory/benzo-resistant cases) for escalating requirements; ICU; treat status epilepticus per protocol; airway protection/supportive care for autonomic instability
– Phenobarbital is a valuable adjunct/alternative (acts at the GABA-A receptor, long-acting, useful for refractory withdrawal) — dosed/titrated carefully (respiratory depression)
– Adjuncts: consider anticonvulsants (carbamazepine, gabapentin) for adjunctive symptom control in milder cases per addiction guidance; treat anxiety/insomnia supportively
– Replete electrolytes (magnesium, glucose) and rule out/treat concurrent causes and concurrent alcohol withdrawal (very common overlap — cover both)
– Supportive: calm low-stimulation environment, monitor vitals/mental status/seizure activity, fall/aspiration precautions, IV fluids
– Treat benzodiazepine withdrawal with the same seriousness as alcohol withdrawal — it shares the GABA mechanism and can produce seizures, status, and a DT-like delirium that kills. A common iatrogenic version: a patient on chronic benzos gets admitted, the home benzo is held, and they seize on day two or three. Reinstate, convert to a long-acting agent, and taper slowly — never abruptly.
– PT/OT: as tolerated; fall precautions
– Trend: withdrawal symptoms/severity, vitals, mental status, seizure activity, benzo/phenobarbital requirements (rising → escalate/ICU), response to taper
– Escalation triggers: seizures/status, severe delirium, or autonomic instability → ICU + aggressive benzos ± phenobarbital; refractory requirements → phenobarbital/ICU; concurrent severe alcohol withdrawal → cover both pathways
– Discharge checklist: stable on a controlled taper with a clear outpatient taper plan + prescriber; symptoms controlled; education that abrupt cessation is dangerous; psychiatry/addiction follow-up; address underlying anxiety/insomnia non-benzo where possible; return precautions (worsening anxiety/tremor, seizures, confusion)

106. Benzodiazepine Withdrawal

complete reference · anxiety + tremor + seizures + delirium · reinstate, convert to long-acting, taper slowly · Full Card

Symptoms / Associated Sx

• Mirrors alcohol withdrawal through the shared GABA mechanism: anxiety, agitation, insomnia, tremor, sweating, palpitations, tachycardia, hypertension, and sensory hypersensitivity (photophobia, hyperacusis)

• Severe withdrawal brings seizures, delirium, psychosis, and autonomic instability with hyperthermia (a DT-like picture)

• Onset depends on the half-life — short-acting agents (alprazolam, lorazepam) at 1–2 days, long-acting agents (diazepam, clonazepam) delayed up to a week or more

• This is a potentially life-threatening withdrawal that should not be underestimated the way opioid withdrawal can be, and protracted symptoms are common

Neg

• Pt denies that this was treated as a benign syndrome like opioid withdrawal — benzodiazepine withdrawal can be fatal through seizures, status, and a DT-like delirium

• Pt denies a masked concurrent alcohol withdrawal and denies a missed alternative cause of altered mental status or seizure

• Pt denies that abrupt cessation (often iatrogenic, when home medications are held on admission) was overlooked as the trigger

Social History (SHx)

• Benzodiazepine type, dose, and duration (chronic high-dose use carries the highest risk), Z-drug use, the reason for use, and the last dose

• Prior withdrawal or seizures

• Concurrent alcohol or opioid use

• Abrupt cessation (ran out, or admitted and the medication held); barbiturate use

Main Etiology

• Chronic benzodiazepine use produces adaptive changes around enhanced GABA-A inhibition; abrupt cessation or reduction removes the inhibitory tone

• The result is CNS hyperexcitability — the same pathophysiology as alcohol withdrawal — progressing from anxiety and tremor to seizures and delirium

• Severity scales with dose, duration, potency, and the abruptness of cessation, and the syndrome is often iatrogenic when home benzodiazepines are stopped on admission

RF

• Modifiable: abruptness of cessation, recognition of dependence, concurrent alcohol use

• Non-modifiable: high-dose long-duration use, high-potency short-acting agents, prior withdrawal seizures, older age, and polypharmacy

Data

• Clinical diagnosis with the medication and use history (last dose, dose, duration)

• Fingerstick glucose, BMP, and magnesium

• Rule out concurrent causes (infection, structural, metabolic) as for any altered mental status or seizure

• ECG; urine toxicology (corroborative; standard panels may miss clonazepam and alprazolam)

• Assess for a concurrent, overlapping alcohol withdrawal

DDx

Benzodiazepine withdrawal (a cessation history with a GABA-withdrawal picture) · alcohol withdrawal (coexisting or identical) · barbiturate withdrawal · a sympathomimetic or serotonin syndrome · anxiety or agitated delirium · infection/sepsis · a primary seizure disorder

Home Meds

• Reinstate the home benzodiazepine or an equivalent — do not continue abrupt cessation

• Convert to a long-acting agent for a controlled taper

• Reconcile concurrent sedatives and alcohol

Plan

CONSULT: ICU (seizures or status, severe delirium, autonomic instability) · Psychiatry/Addiction (taper planning, dependence, dual use) · Neurology (recurrent or atypical seizures)

• Treat with benzodiazepines — reinstate and taper (the mainstay): restart an adequate dose to control symptoms, ideally converting to a long-acting agent (diazepam or clonazepam) for a smooth, gradual taper (reducing roughly 10–25% every few days to a week, individualized) — abrupt cessation is dangerous and a slow taper is safe; use symptom-triggered or fixed-dose schedules depending on severity

• Severe withdrawal, seizures, or delirium (an emergency, treated like severe alcohol withdrawal): aggressive IV benzodiazepines (lorazepam 2–4 mg IV or diazepam 5–10 mg IV, repeated and titrated to control); add phenobarbital (cross-tolerant and benzodiazepine-sparing, useful in refractory or benzodiazepine-resistant cases) for escalating requirements; ICU care; status epilepticus managed per protocol; and airway protection with supportive care for autonomic instability

• Phenobarbital is a valuable adjunct or alternative (acting at the GABA-A receptor, long-acting, and useful for refractory withdrawal), dosed and titrated carefully given the respiratory-depression risk

• Adjuncts: consider anticonvulsants (carbamazepine, gabapentin) for adjunctive symptom control in milder cases per addiction guidance, and treat anxiety and insomnia supportively

• Replete electrolytes (magnesium, glucose) and rule out or treat concurrent causes and a concurrent alcohol withdrawal (a very common overlap — cover both)

• Supportive care: a calm, low-stimulation environment, monitoring of vitals, mental status, and seizure activity, fall and aspiration precautions, and IV fluids

• PT/OT: as tolerated, with fall precautions

• Trend: withdrawal symptoms and severity, vitals, mental status, seizure activity, benzodiazepine and phenobarbital requirements (rising needs warrant escalation/ICU), and the response to the taper

• Escalation triggers: seizures or status, severe delirium, or autonomic instability → ICU with aggressive benzodiazepines and phenobarbital; refractory requirements → phenobarbital and ICU; a concurrent severe alcohol withdrawal → cover both pathways

• Discharge checklist: stable on a controlled taper with a clear outpatient taper plan and prescriber; symptoms controlled; education that abrupt cessation is dangerous; psychiatry/addiction follow-up; non-benzodiazepine management of the underlying anxiety or insomnia where possible; return precautions for worsening anxiety or tremor, seizures, or confusion

Red Flags

• Seizures or status epilepticus → ICU and aggressive benzodiazepines with phenobarbital

• DT-like delirium with autonomic instability and hyperthermia → ICU and supportive care; carries real mortality

• Iatrogenic abrupt cessation of chronic home benzodiazepines on admission → a preventable, dangerous trigger

• Concurrent alcohol withdrawal → additive risk; treat both

• Escalating, refractory medication requirements → phenobarbital and ICU

Senior IM Resident Pearls

• Treat it as seriously as alcohol withdrawal. Same GABA mechanism, same capacity for seizures, status, and a lethal delirium — never dismiss it as merely uncomfortable.

• Beware the iatrogenic case. A patient on chronic benzodiazepines whose home dose is held on admission can seize on day two or three — reconcile and reinstate.

• Convert to long-acting and taper slowly. Diazepam or clonazepam give a smoother, safer taper than continuing a short-acting, high-potency agent like alprazolam.

• Phenobarbital is the refractory-case tool. Cross-tolerant and benzodiazepine-sparing, it's invaluable when requirements escalate — but respect its respiratory-depression risk.

• Look for the alcohol overlap. Many patients withdraw from both simultaneously; a regimen that covers one usually needs to cover the other.

• Short-acting, high-potency agents withdraw hardest. Alprazolam dependence is notoriously difficult — anticipate a more severe, abrupt course.

• Common mistake: abruptly stopping a home benzodiazepine "because the patient is sedated" without a taper plan — that decision can precipitate the seizure you then have to treat.

Toxicology — Sedative-Hypnotics

107. Benzodiazepine Overdose

CNS depression, usually benign alone · sedation / respiratory depression / mixed ingestions · supportive care is the answer · flumazenil is usually the WRONG move · Super Compact

Sx: CNS depression — sedation, drowsiness, slurred speech, ataxia, confusion → stupor; usually preserved vitals and only mild respiratory depression when taken ALONE (oral pure-benzo overdose is rarely fatal) · the danger is co-ingestion — with opioids, alcohol, or other sedatives → synergistic respiratory depression, coma, death; or IV/ultra-potent agents · (a deeply obtunded or apneic "benzo overdose" usually means a co-ingestant — benzodiazepines alone seldom do that orally)

Neg: denies that it's a pure single-agent ingestion without checking (assume mixed — get acetaminophen/salicylate/co-ingestant levels) · denies missed opioid component (respiratory depression + miosis) · denies that flumazenil was given to a chronic user/unknown co-ingestion (seizure precipitation) · denies missed airway compromise

SHx: agent/dose/intent (intentional vs accidental), co-ingestants (opioids, alcohol, TCAs, acetaminophen), chronic benzo/sedative use or dependence (flumazenil contraindication), prior overdoses/psychiatric history, access to pills

Etiology: excessive GABA-A potentiation → CNS depression · oral benzodiazepines alone have a wide therapeutic index and rarely cause fatal respiratory depression; lethality comes from synergy with other CNS depressants (opioids, alcohol, barbiturates) or with very potent/IV routes · the clinical danger is airway/ventilation, especially in mixed ingestions

RF: co-ingestion of opioids/alcohol/other sedatives · intentional overdose · elderly/comorbid (respiratory reserve) · chronic dependence (withdrawal/flumazenil risk) · IV or high-potency agents

Data: clinical assessment of airway/breathing + pulse ox/capnography · fingerstick glucose · acetaminophen + salicylate levels + ECG (TCA — wide QRS) in any intentional/unknown ingestion · ABG if depressed respirations · urine tox (may miss clonazepam/alprazolam; confirmatory not necessary to treat) · co-ingestant workup; consider why obtunded if out of proportion (search for the real culprit)

DDx: benzodiazepine overdose (sedation, stable vitals if isolated) · opioid overdose (miosis, ↓RR, naloxone response) · alcohol/other sedative · mixed ingestion (deep depression) · TCA (wide QRS, anticholinergic) · metabolic/structural AMS

Home Meds: hold sedatives during acute care · reconcile co-ingestants · for chronic users, plan to avoid abrupt cessation (withdrawal) after recovery · psychiatric med review if intentional

Plan

CONSULT: ICU (respiratory depression/airway, mixed severe ingestion) · Toxicology/Poison Control 1-800-222-1222 · Psychiatry (intentional/suicidality)

– SUPPORTIVE CARE IS THE MAINSTAY: the great majority of isolated oral benzodiazepine overdoses do well with observation, airway monitoring, and supplemental O2 — protect the airway and support ventilation (BVM, intubation) if needed; continuous pulse ox/capnography; IV fluids; let it metabolize
– FLUMAZENIL — generally AVOID (this is the key teaching point): the benzodiazepine antagonist can precipitate seizures (and benzo withdrawal) in chronic/dependent users, and is dangerous in mixed ingestions — especially with TCAs or other proconvulsants, where it can unmask seizures and arrhythmias; do NOT use empirically in an undifferentiated overdose; reserve for very select cases (e.g. a benzodiazepine-naïve patient, iatrogenic procedural oversedation, no co-ingestants, no seizure/dependence history) and discuss with toxicology — the risks usually outweigh the benefits
– Evaluate and treat co-ingestants (where the real risk lies): naloxone if opioid component (respiratory depression), acetaminophen + salicylate levels + NAC if indicated, ECG for TCA (wide QRS → sodium bicarbonate), alcohol/toxic-alcohol assessment — the mixed ingestion drives morbidity
– Decontamination: activated charcoal only in select early presentations with intact/protected airway (often not indicated; aspiration risk in the sedated — usually avoided)
– Supportive: glucose check/treat, monitor until clearing, fall/aspiration precautions, watch for emerging withdrawal in chronic users as it clears
– Two rules: a pure oral benzodiazepine overdose is usually a "watch, support the airway, and wait" problem — and flumazenil is almost always the wrong move. Giving it to a chronic user or a mixed ingestion can convert a stable, sleepy patient into one having seizures you can no longer treat with benzodiazepines. If the patient is more obtunded than a benzo alone explains, find the co-ingestant.
– PT/OT: assess before discharge
– Trend: airway/respiratory status + capnography, mental status (clearing), co-ingestant workup/levels, ECG (TCA), glucose, emerging withdrawal
– Escalation triggers: respiratory depression/airway compromise → ICU/intubation; significant co-ingestion (opioid, TCA, acetaminophen, toxic alcohol) → manage that pathway + ICU; deeper-than-expected depression → hunt for the co-ingestant
– Discharge checklist: clinically recovered + airway-safe + co-ingestants excluded/treated; psychiatric evaluation + suicidality risk assessment if intentional; avoid abrupt benzo cessation plan for dependent patients; addiction/psychiatry referral; counsel on combining sedatives; return precautions (excessive drowsiness, breathing difficulty, confusion)

107. Benzodiazepine Overdose

complete reference · sedation + respiratory depression + mixed ingestions · supportive care, avoid flumazenil · Full Card

Symptoms / Associated Sx

• CNS depression: sedation, drowsiness, slurred speech, ataxia, and confusion, progressing to stupor

• When taken alone, vitals are usually preserved with only mild respiratory depression — a pure oral benzodiazepine overdose is rarely fatal

• The danger is co-ingestion — with opioids, alcohol, or other sedatives, producing synergistic respiratory depression, coma, and death — or ultra-potent/IV agents

• A deeply obtunded or apneic "benzodiazepine overdose" usually signals a co-ingestant, since benzodiazepines alone seldom cause that orally

Neg

• Pt denies that it is assumed to be a pure single-agent ingestion without checking — assume a mixed ingestion and obtain acetaminophen, salicylate, and co-ingestant levels

• Pt denies a missed opioid component (respiratory depression with miosis)

• Pt denies that flumazenil was given to a chronic user or an unknown co-ingestion (seizure precipitation) and denies a missed airway compromise

Social History (SHx)

• Agent, dose, and intent (intentional versus accidental)

• Co-ingestants (opioids, alcohol, TCAs, acetaminophen)

• Chronic benzodiazepine or sedative use or dependence (a flumazenil contraindication)

• Prior overdoses and psychiatric history; access to pills

Main Etiology

• Excessive GABA-A potentiation produces CNS depression

• Oral benzodiazepines alone have a wide therapeutic index and rarely cause fatal respiratory depression

• Lethality comes from synergy with other CNS depressants (opioids, alcohol, barbiturates) or from very potent agents and the IV route

• The clinical danger is airway and ventilation, particularly in mixed ingestions

RF

• Modifiable: co-ingestion of other CNS depressants, the route and potency used

• Non-modifiable: older age and comorbidity (reduced respiratory reserve), chronic dependence, and intentional overdose

Data

• Clinical assessment of airway and breathing with pulse oximetry and capnography

• Fingerstick glucose

• Acetaminophen and salicylate levels with an ECG (for TCA — a wide QRS) in any intentional or unknown ingestion

• ABG if respirations are depressed

• Urine toxicology (may miss clonazepam and alprazolam; confirmation is not required to treat); a co-ingestant workup; and consideration of why the patient is obtunded if it is out of proportion to a benzodiazepine alone

DDx

Benzodiazepine overdose (sedation with stable vitals if isolated) · opioid overdose (miosis, reduced respiratory rate, naloxone response) · alcohol or other sedative · a mixed ingestion (deep depression) · TCA overdose (wide QRS, anticholinergic features) · a metabolic or structural cause of altered mental status

Home Meds

• Hold: sedatives during acute care

• Reconcile: co-ingestants

• Plan to avoid abrupt cessation in chronic users after recovery (withdrawal); review psychiatric medications if the ingestion was intentional

Plan

CONSULT: ICU (respiratory depression or airway compromise, severe mixed ingestion) · Toxicology/Poison Control (1-800-222-1222) · Psychiatry (intentional ingestion, suicidality)

• Supportive care is the mainstay: the great majority of isolated oral benzodiazepine overdoses do well with observation, airway monitoring, and supplemental oxygen — protect the airway and support ventilation (bag-valve-mask, intubation) if needed, with continuous pulse oximetry and capnography, IV fluids, and time to metabolize

• Flumazenil — generally avoid (the key teaching point): the benzodiazepine antagonist can precipitate seizures and benzodiazepine withdrawal in chronic or dependent users and is dangerous in mixed ingestions — especially with TCAs or other proconvulsants, where it can unmask seizures and arrhythmias — so it should not be used empirically in an undifferentiated overdose; reserve it for very select cases (a benzodiazepine-naïve patient, iatrogenic procedural oversedation, no co-ingestants, no seizure or dependence history) and discuss with toxicology, since the risks usually outweigh the benefits

• Evaluate and treat co-ingestants (where the real risk lies): naloxone for an opioid component (respiratory depression); acetaminophen and salicylate levels with NAC if indicated; an ECG for TCA toxicity (a wide QRS treated with sodium bicarbonate); and assessment for alcohol or toxic alcohols — the mixed ingestion drives the morbidity

• Decontamination: activated charcoal only in select early presentations with an intact or protected airway (often not indicated, given the aspiration risk in a sedated patient — usually avoided)

• Supportive care: check and treat glucose, monitor until clearing, observe fall and aspiration precautions, and watch for emerging withdrawal in chronic users as the drug clears

• PT/OT: assess before discharge

• Trend: airway and respiratory status with capnography, mental status (clearing), the co-ingestant workup and levels, the ECG (TCA), glucose, and any emerging withdrawal

• Escalation triggers: respiratory depression or airway compromise → ICU/intubation; a significant co-ingestion (opioid, TCA, acetaminophen, toxic alcohol) → manage that pathway with ICU care; a depression deeper than a benzodiazepine alone explains → hunt for the co-ingestant

• Discharge checklist: clinically recovered, airway-safe, and co-ingestants excluded or treated; a psychiatric evaluation and suicidality risk assessment if intentional; a plan to avoid abrupt benzodiazepine cessation in dependent patients; addiction/psychiatry referral; counseling on combining sedatives; return precautions for excessive drowsiness, breathing difficulty, or confusion

Red Flags

• Respiratory depression or apnea → almost always a co-ingestion; support ventilation and search for the other agent

• Flumazenil given to a chronic user or mixed ingestion → precipitated seizures that are then hard to treat

• Wide QRS on ECG → TCA co-ingestion → sodium bicarbonate

• Miosis with respiratory depression → opioid co-ingestion → naloxone

• Obtundation out of proportion to a benzodiazepine → an occult co-ingestant or alternative diagnosis

Senior IM Resident Pearls

• Isolated oral benzodiazepine overdose is a "watch and support" problem. The wide therapeutic index means observation, airway monitoring, and time usually suffice.

• Flumazenil is almost always the wrong move. It can convert a stable, sleepy patient into one having seizures you can no longer abort with benzodiazepines — reserve it for rare, well-defined situations and call toxicology.

• Deep depression means a co-ingestant. If the patient is more obtunded than a benzodiazepine alone explains, the opioid, alcohol, or TCA on board is the real problem.

• Always screen the intentional overdose broadly. Acetaminophen, salicylate, and an ECG for TCA are mandatory — the benzodiazepine may be the least of the patient's problems.

• Charcoal is rarely the answer in the sedated patient. The aspiration risk usually outweighs any benefit once the airway is at risk.

• Anticipate withdrawal on the back end. A chronic user who overdosed will withdraw as the drug clears — plan a taper rather than abrupt cessation.

• Common mistake: reaching for flumazenil to "wake the patient up" — it's a setup for refractory seizures in exactly the population most likely to overdose.

Toxicology — Stimulants

108. Cocaine Toxicity

sympathomimetic + sodium-channel blockade · chest pain / hypertensive emergency / arrhythmias / stroke · benzodiazepines first · AVOID beta-blockers (unopposed alpha) · Super Compact

Sx: sympathomimetic storm — agitation, euphoria, anxiety, tachycardia, hypertension, hyperthermia, diaphoresis, mydriasis · chest pain (ACS/coronary vasospasm/MI — even in young, normal coronaries), arrhythmias (wide-complex from Na-channel blockade, VT/VF, brady at high doses), hypertensive emergency, stroke (ischemic + hemorrhagic), seizures, aortic dissection, agitated delirium, rhabdomyolysis · (young patient + chest pain or stroke + sympathetic signs → think cocaine; the dual mechanism — catecholamine excess AND sodium-channel blockade — shapes treatment)

Neg: denies that a beta-blocker was given (unopposed alpha → worse HTN/vasospasm — avoid) · denies missed ACS/dissection/ICH in a chest-pain or neuro presentation · denies missed hyperthermia (a lethal/under-recognized complication) · denies co-ingestants (levamisole-cut, opioids, alcohol)

SHx: route/amount/timing (smoked crack, IV, insufflated), chronic vs binge, "body packer/stuffer" (concealed packets → massive delayed toxicity), co-use (alcohol → cocaethylene, more cardiotoxic; opioids = "speedball"), cardiac/neuro history

Etiology: blocks reuptake of norepinephrine, dopamine, serotonin → catecholamine excess → vasoconstriction, ↑HR/BP, hyperthermia, CNS stimulation · also blocks fast sodium channels (local-anesthetic effect) → wide QRS, arrhythmias · vasospasm + prothrombotic + ↑demand → MI, stroke; accelerated atherosclerosis with chronic use

RF: high dose/binge · concurrent alcohol (cocaethylene) · body packing/stuffing · underlying CAD · chronic use · co-stimulants

Data: ECG (ischemia/STEMI, wide QRS, QT, arrhythmia) + serial troponins (chest pain) · core temperature (hyperthermia — check actively) · BMP, CK (rhabdo), renal function · head CT (neuro signs/severe HTN → stroke/ICH); CTA if dissection suspected (chest/back pain, pulse differential) · CXR · urine tox (confirms; cocaine metabolites) · glucose · acetaminophen/salicylate if intentional

DDx: cocaine toxicity (sympathomimetic + Na-block, urine tox) · other sympathomimetic (meth/amphetamine, synthetic stimulants) · serotonin syndrome/NMS (clonus/rigidity) · thyroid storm · anticholinergic (dry skin vs diaphoretic) · sepsis · primary ACS/stroke/dissection

Home Meds: hold sympathomimetics/stimulants · avoid non-selective beta-blockers acutely · manage home cardiac meds per situation · review QT agents

Plan

CONSULT: Cardiology (ACS/MI, arrhythmia) · ICU (severe — hyperthermia, agitation, instability, dissection) · Neurology/Neurosurgery (stroke/ICH) · Toxicology/Poison Control · Surgery (dissection, body packing)

– BENZODIAZEPINES are first-line for almost everything (agitation, tachycardia, hypertension, chest pain, seizures): diazepam 5–10 mg IV or lorazepam 2–4 mg IV, titrated/repeated — they reduce central sympathetic outflow, lowering HR/BP, calming agitation, treating seizures, and easing cardiac demand; the cornerstone
– AVOID beta-blockers acutely (key pitfall): beta-blockade leaves unopposed alpha-adrenergic stimulation → worsening vasoconstriction, hypertension, and coronary vasospasm; do not give in acute cocaine toxicity (controversial for some agents, but standard teaching = avoid)
– Chest pain / ACS: benzodiazepines + aspirin, nitroglycerin (vasospasm), and consider phentolamine (alpha-blocker) or CCB for refractory hypertension/vasospasm; serial ECG/troponin; cath/PCI for true STEMI/refractory ischemia per cardiology; heparin per ACS
– Hypertensive emergency: benzodiazepines first; if persistent → nitroglycerin, nitroprusside, or phentolamine (alpha-blocker) — titratable, avoid beta-blockers
– Arrhythmias: wide-complex (Na-channel blockade) → sodium bicarbonate 1–2 mEq/kg IV bolus (narrows QRS); standard ACLS for VT/VF (avoid pure beta-blockers); benzodiazepines for sinus tachycardia
– Hyperthermia (life-threatening): aggressive external cooling + benzodiazepines/sedation (treat the agitation driving it); intubation/paralysis for extreme cases; this is a leading cause of death — don't miss it
– Stroke/ICH: emergent imaging + stroke/neurosurgery pathway; control BP
– Rhabdomyolysis: IV fluids, monitor CK/renal function/K
– Body packers: whole-bowel irrigation, surgery if obstruction/rupture (do not endoscopically retrieve — rupture risk)
– Two anchors: benzodiazepines are the answer to almost everything cocaine throws at you (they calm the sympathetic storm at its source), and you avoid beta-blockers because blocking beta leaves alpha unopposed and worsens the vasospasm. Add sodium bicarbonate for the wide QRS, and actively check a temperature — hyperthermia is a quiet killer here.
– PT/OT: once stable
– Trend: ECG/troponin, BP/HR, core temp, CK/renal function, mental status/agitation, neuro exam, response to benzodiazepines
– Escalation triggers: MI/refractory ischemia → cath lab; severe hyperthermia/agitation/instability → ICU + aggressive cooling/sedation; stroke/ICH/dissection → emergent specialty + imaging; wide-complex arrhythmia → bicarbonate + ICU
– Discharge checklist: toxicity resolved + cardiac/neuro complications excluded/treated; addiction referral + counseling; cardiovascular risk counseling (cocaine + recurrent ACS risk); rhabdo/renal resolved; psychiatry if intentional; return precautions (chest pain, neuro symptoms, palpitations, severe agitation)

108. Cocaine Toxicity

complete reference · chest pain + hypertensive emergency + arrhythmias + stroke · benzodiazepines first, avoid beta-blockers · Full Card

Symptoms / Associated Sx

• A sympathomimetic storm: agitation, euphoria, anxiety, tachycardia, hypertension, hyperthermia, diaphoresis, and mydriasis

• Chest pain from ACS, coronary vasospasm, or MI — even in young patients with normal coronaries

• Arrhythmias (wide-complex from sodium-channel blockade, VT/VF, bradycardia at high doses), hypertensive emergency, stroke (ischemic and hemorrhagic), seizures, and aortic dissection

• Agitated delirium and rhabdomyolysis

• A young patient with chest pain or stroke plus sympathetic signs should prompt thought of cocaine; the dual mechanism — catecholamine excess and sodium-channel blockade — shapes treatment

Neg

• Pt denies that a beta-blocker was given (unopposed alpha stimulation worsens hypertension and vasospasm — avoid)

• Pt denies a missed ACS, dissection, or intracranial hemorrhage in a chest-pain or neurologic presentation

• Pt denies a missed hyperthermia (a lethal, under-recognized complication) and denies co-ingestants (levamisole-cut cocaine, opioids, alcohol)

Social History (SHx)

• Route, amount, and timing (smoked crack, IV, insufflated), and chronic versus binge use

• Body packing or stuffing (concealed packets causing massive delayed toxicity)

• Co-use with alcohol (forming cocaethylene, which is more cardiotoxic) or opioids (a "speedball")

• Cardiac and neurologic history

Main Etiology

• Cocaine blocks reuptake of norepinephrine, dopamine, and serotonin, producing catecholamine excess with vasoconstriction, tachycardia, hypertension, hyperthermia, and CNS stimulation

• It also blocks fast sodium channels (a local-anesthetic effect), causing a wide QRS and arrhythmias

• Vasospasm, a prothrombotic state, and increased myocardial demand cause MI and stroke, with accelerated atherosclerosis in chronic use

RF

• Modifiable: dose and binge pattern, concurrent alcohol use, body packing/stuffing

• Non-modifiable: underlying coronary disease and the effects of chronic use

Data

• ECG (ischemia/STEMI, wide QRS, QT, arrhythmia) with serial troponins (for chest pain)

• Core temperature (check actively for hyperthermia)

• BMP, CK (rhabdomyolysis), and renal function

• Head CT (neurologic signs or severe hypertension — stroke or ICH); CTA if dissection is suspected (chest/back pain, a pulse differential)

• CXR; urine toxicology (confirms cocaine metabolites); glucose; and acetaminophen/salicylate levels if intentional

DDx

Cocaine toxicity (sympathomimetic features with sodium-channel blockade, confirmed on urine toxicology) · another sympathomimetic (methamphetamine, amphetamine, synthetic stimulants) · serotonin syndrome or NMS (clonus, rigidity) · thyroid storm · anticholinergic toxicity (dry skin versus the diaphoresis of cocaine) · sepsis · a primary ACS, stroke, or dissection

Home Meds

• Hold: sympathomimetics and stimulants

• Avoid: non-selective beta-blockers acutely

• Manage: home cardiac medications per the situation; review QT-prolonging agents

Plan

CONSULT: Cardiology (ACS/MI, arrhythmia) · ICU (severe — hyperthermia, agitation, instability, dissection) · Neurology/Neurosurgery (stroke, ICH) · Toxicology/Poison Control · Surgery (dissection, body packing)

• Benzodiazepines are first-line for almost everything (agitation, tachycardia, hypertension, chest pain, seizures): diazepam 5–10 mg IV or lorazepam 2–4 mg IV, titrated and repeated — they reduce central sympathetic outflow, lowering heart rate and blood pressure, calming agitation, treating seizures, and easing cardiac demand; they are the cornerstone

• Avoid beta-blockers acutely (the key pitfall): beta-blockade leaves unopposed alpha-adrenergic stimulation, worsening vasoconstriction, hypertension, and coronary vasospasm — standard teaching is to avoid them in acute cocaine toxicity

• Chest pain / ACS: benzodiazepines plus aspirin, nitroglycerin (for vasospasm), and consideration of phentolamine (an alpha-blocker) or a calcium channel blocker for refractory hypertension or vasospasm; serial ECGs and troponins; and catheterization/PCI for a true STEMI or refractory ischemia per cardiology, with heparin per the ACS pathway

• Hypertensive emergency: benzodiazepines first, and if persistent, nitroglycerin, nitroprusside, or phentolamine — all titratable, while avoiding beta-blockers

• Arrhythmias: a wide-complex rhythm from sodium-channel blockade is treated with sodium bicarbonate 1–2 mEq/kg IV bolus (which narrows the QRS); standard ACLS for VT/VF (avoiding pure beta-blockers); and benzodiazepines for sinus tachycardia

• Hyperthermia (life-threatening): aggressive external cooling with benzodiazepines/sedation (treating the agitation that drives it), and intubation with paralysis in extreme cases — a leading cause of death that must not be missed

• Stroke/ICH: emergent imaging and the stroke/neurosurgery pathway, with blood pressure control

• Rhabdomyolysis: IV fluids with monitoring of CK, renal function, and potassium

• Body packers: whole-bowel irrigation, and surgery for obstruction or rupture (avoid endoscopic retrieval given the rupture risk)

• PT/OT: once stable

• Trend: the ECG and troponin, blood pressure and heart rate, core temperature, CK and renal function, mental status and agitation, the neurologic exam, and the response to benzodiazepines

• Escalation triggers: MI or refractory ischemia → catheterization lab; severe hyperthermia, agitation, or instability → ICU with aggressive cooling and sedation; stroke, ICH, or dissection → emergent specialty care and imaging; a wide-complex arrhythmia → bicarbonate and ICU

• Discharge checklist: toxicity resolved with cardiac and neurologic complications excluded or treated; an addiction referral and counseling; cardiovascular risk counseling (cocaine and recurrent ACS risk); resolution of rhabdomyolysis and renal injury; psychiatry if intentional; return precautions for chest pain, neurologic symptoms, palpitations, or severe agitation

Red Flags

• Chest pain with ischemia → cocaine-associated MI even in the young; treat and involve cardiology, avoiding beta-blockers

• Hyperthermia → a leading cause of death; cool aggressively and sedate

• Wide-complex arrhythmia → sodium-channel blockade → sodium bicarbonate

• Focal neurologic deficit or severe hypertension → stroke or intracranial hemorrhage → emergent imaging

• Tearing chest/back pain with a pulse differential → aortic dissection → CTA and surgery

Senior IM Resident Pearls

• Benzodiazepines are the answer to almost everything. They calm the sympathetic storm at its source, lowering heart rate, blood pressure, temperature, and agitation while treating seizures and cardiac demand.

• Avoid beta-blockers. Blocking beta leaves alpha unopposed and worsens the vasospasm and hypertension — the classic cocaine pitfall.

• Sodium bicarbonate for the wide QRS. The local-anesthetic sodium-channel blockade responds to bicarbonate just as TCA toxicity does.

• Actively check a temperature. Hyperthermia is a quiet killer in stimulant toxicity — it won't announce itself, so measure the core temperature and cool aggressively.

• Young chest pain is cocaine until proven otherwise. Vasospasm and a prothrombotic state cause MI in patients with pristine coronaries — and dissection is on the differential too.

• Cocaine plus alcohol makes cocaethylene, which is more cardiotoxic and longer-lasting — ask about co-use.

• Common mistake: giving metoprolol to a cocaine chest-pain patient — the unopposed alpha effect can worsen ischemia; reach for benzodiazepines and nitrates instead.

Toxicology — Stimulants

109. Methamphetamine Intoxication

prolonged sympathomimetic + psychosis · agitation / psychosis / severe hypertension / rhabdomyolysis · benzodiazepines first, same playbook as cocaine but longer · Super Compact

Sx: sympathomimetic + prominent psychiatric — severe agitation, aggression, psychosis (paranoia, hallucinations, delusions), excited delirium, hypervigilance · tachycardia, severe hypertension, hyperthermia, mydriasis, diaphoresis · rhabdomyolysis (agitation/hyperthermia/exertion), chest pain/ACS, arrhythmias, seizures, stroke (ischemic + hemorrhagic) · choreoathetoid movements, bruxism, skin picking · (vs cocaine: LONGER duration — hours, prolonged agitation/psychosis; psychosis and excited delirium are especially prominent)

Neg: denies that a beta-blocker was given (unopposed alpha — avoid, as in cocaine) · denies missed hyperthermia (lethal — check core temp) · denies missed rhabdomyolysis/renal injury · denies that psychosis was assumed primary without considering the stimulant · denies missed stroke/ACS · denies co-ingestants

SHx: route/amount/timing (smoked, IV, insufflated, oral — long action), chronic vs binge, "tweaking"/prolonged sleeplessness, co-use (opioids, alcohol), prior psychosis, manufacturing exposures · housing/social context

Etiology: methamphetamine drives release and blocks reuptake of norepinephrine, dopamine, serotonin → catecholamine excess + strong dopaminergic effect (psychosis) · longer half-life than cocaine → prolonged toxicity · complications from sympathetic overdrive (hyperthermia, HTN, arrhythmia, MI, stroke) and from agitation/hyperthermia (rhabdomyolysis, AKI, DIC, multi-organ failure in severe excited delirium)

RF: high dose/binge · chronic use · concurrent stimulants/sympathomimetics · underlying psychiatric/cardiac disease · dehydration/exertion (rhabdo, hyperthermia)

Data: core temperature (actively — hyperthermia kills) · ECG + troponin (ischemia, arrhythmia, QT) · CK + renal function + potassium (rhabdo), BMP, urinalysis (myoglobin) · head CT for neuro signs/severe HTN (stroke/ICH) · glucose · CXR · urine tox (amphetamines; false-positives common — correlate) · coags/CBC if severe (DIC) · acetaminophen/salicylate if intentional

DDx: methamphetamine intoxication (prolonged sympathomimetic + psychosis) · cocaine/other stimulant · synthetic cathinones ("bath salts") · serotonin syndrome/NMS (clonus/rigidity) · primary psychosis/mania · thyroid storm · anticholinergic (dry skin) · sepsis/CNS infection

Home Meds: hold stimulants/sympathomimetics · avoid beta-blockers acutely · hold/review serotonergic + QT agents · reconcile psychiatric meds

Plan

CONSULT: ICU (severe agitation/hyperthermia/instability/rhabdo) · Psychiatry (psychosis, agitation, dual diagnosis) · Cardiology (ACS/arrhythmia) · Neurology/Neurosurgery (stroke/ICH) · Toxicology/Poison Control · Nephrology (severe rhabdo/AKI)

– BENZODIAZEPINES are the cornerstone (agitation, tachycardia, hypertension, hyperthermia, seizures): diazepam 5–10 mg IV or lorazepam 2–4 mg IV, titrated/repeated to calm — control the agitation and you control most of the downstream physiology (HR, BP, temp); may need large cumulative doses
– Severe agitation / excited delirium (an emergency): escalate sedation aggressively — high-dose benzodiazepines ± antipsychotic adjunct (e.g. haloperidol or droperidol, or a second-generation agent — use with caution re QT/lowered seizure threshold/temperature regulation, NOT as monotherapy or first-line over benzos); ketamine is an option for extreme agitation; prepare for intubation if uncontrollable (protect against hyperthermia/rhabdo/acidosis death spiral) → ICU
– Hyperthermia (life-threatening): aggressive external/active cooling + deep sedation (and paralysis/intubation if needed); a leading cause of death in excited delirium — treat immediately, don't wait
– Severe hypertension: benzodiazepines first; if persistent → nitroglycerin, nitroprusside, or phentolamine (titratable, avoid beta-blockers)
– Chest pain/ACS: benzodiazepines + aspirin/nitrates; cardiology for true MI; avoid beta-blockers · wide-complex arrhythmia → sodium bicarbonate 1–2 mEq/kg IV
– Rhabdomyolysis: aggressive IV fluids, monitor CK/renal function/potassium, treat hyperkalemia, watch for AKI/compartment syndrome
– Psychosis: often resolves with sedation + time; antipsychotics for persistent psychosis; psychiatry; reassess (methamphetamine psychosis can be prolonged but usually clears — distinguish from primary disorder)
– Supportive: fluids, electrolytes, glucose, quiet environment, restraints only if needed for safety (chemical sedation preferred — physical restraints worsen rhabdo/hyperthermia)
– Same two anchors as cocaine — benzodiazepines first, no beta-blockers — but methamphetamine runs longer and hits the psyche harder, so expect prolonged agitation and psychosis and be ready to escalate sedation. The triad that kills is hyperthermia + rhabdomyolysis + acidosis in excited delirium: cool aggressively, sedate deeply, flood with fluids, and don't hesitate to intubate.
– PT/OT: once stable
– Trend: core temp, agitation/sedation level, BP/HR, ECG/troponin, CK/renal function/K, mental status/psychosis, neuro exam, urine output
– Escalation triggers: excited delirium/uncontrolled agitation/hyperthermia → ICU + deep sedation/intubation + cooling; severe rhabdo/AKI → nephrology/dialysis; MI/arrhythmia → cardiology; stroke/ICH → neuro/neurosurgery
– Discharge checklist: toxicity + agitation resolved, psychosis cleared or psychiatry-managed, rhabdo/renal resolved, cardiac/neuro complications excluded; addiction treatment referral + counseling (no FDA-approved MAT — behavioral/contingency management); psychiatry follow-up; CV risk counseling; return precautions (chest pain, neuro symptoms, severe agitation, dark urine)

109. Methamphetamine Intoxication

complete reference · agitation + psychosis + severe hypertension + rhabdomyolysis · benzodiazepines first, longer course than cocaine · Full Card

Symptoms / Associated Sx

• A sympathomimetic picture with prominent psychiatric features: severe agitation, aggression, psychosis (paranoia, hallucinations, delusions), excited delirium, and hypervigilance

• Tachycardia, severe hypertension, hyperthermia, mydriasis, and diaphoresis

• Rhabdomyolysis (from agitation, hyperthermia, and exertion), chest pain or ACS, arrhythmias, seizures, and stroke (ischemic and hemorrhagic)

• Choreoathetoid movements, bruxism, and skin picking

• Compared with cocaine, the duration is longer (hours, with prolonged agitation and psychosis), and the psychosis and excited delirium are especially prominent

Neg

• Pt denies that a beta-blocker was given (unopposed alpha stimulation — avoid, as in cocaine)

• Pt denies a missed hyperthermia (lethal — check the core temperature) and denies a missed rhabdomyolysis or renal injury

• Pt denies that psychosis was assumed to be primary without considering the stimulant, and denies a missed stroke, ACS, or co-ingestant

Social History (SHx)

• Route, amount, and timing (smoked, IV, insufflated, or oral — a long action), and chronic versus binge use

• "Tweaking" with prolonged sleeplessness

• Co-use with opioids or alcohol, prior psychosis, and any manufacturing exposures

• Housing and social context

Main Etiology

• Methamphetamine drives the release and blocks the reuptake of norepinephrine, dopamine, and serotonin, producing catecholamine excess with a strong dopaminergic effect that drives psychosis

• Its longer half-life than cocaine produces prolonged toxicity

• Complications arise from sympathetic overdrive (hyperthermia, hypertension, arrhythmia, MI, stroke) and from agitation and hyperthermia (rhabdomyolysis, AKI, DIC, and multi-organ failure in severe excited delirium)

RF

• Modifiable: dose and binge pattern, concurrent stimulant use, dehydration and exertion

• Non-modifiable: chronic use and underlying psychiatric or cardiac disease

Data

• Core temperature (check actively — hyperthermia kills)

• ECG with troponin (ischemia, arrhythmia, QT)

• CK, renal function, and potassium (rhabdomyolysis), BMP, and urinalysis (myoglobin)

• Head CT (neurologic signs or severe hypertension — stroke or ICH)

• Glucose; CXR; urine toxicology (amphetamines, though false positives are common — correlate); coagulation studies and CBC if severe (DIC); and acetaminophen/salicylate levels if intentional

DDx

Methamphetamine intoxication (a prolonged sympathomimetic picture with psychosis) · cocaine or another stimulant · synthetic cathinones ("bath salts") · serotonin syndrome or NMS (clonus, rigidity) · primary psychosis or mania · thyroid storm · anticholinergic toxicity (dry skin) · sepsis or a CNS infection

Home Meds

• Hold: stimulants and sympathomimetics

• Avoid: beta-blockers acutely

• Hold/review: serotonergic and QT-prolonging agents; reconcile psychiatric medications

Plan

CONSULT: ICU (severe agitation, hyperthermia, instability, rhabdomyolysis) · Psychiatry (psychosis, agitation, dual diagnosis) · Cardiology (ACS, arrhythmia) · Neurology/Neurosurgery (stroke, ICH) · Toxicology/Poison Control · Nephrology (severe rhabdomyolysis or AKI)

• Benzodiazepines are the cornerstone (agitation, tachycardia, hypertension, hyperthermia, seizures): diazepam 5–10 mg IV or lorazepam 2–4 mg IV, titrated and repeated to calm — controlling the agitation controls most of the downstream physiology (heart rate, blood pressure, temperature), and large cumulative doses may be needed

• Severe agitation or excited delirium (an emergency): escalate sedation aggressively with high-dose benzodiazepines, plus an antipsychotic adjunct (haloperidol, droperidol, or a second-generation agent — used cautiously given QT prolongation, a lowered seizure threshold, and impaired temperature regulation, and not as monotherapy or first-line over benzodiazepines); ketamine is an option for extreme agitation; and prepare for intubation if the patient is uncontrollable (to protect against the hyperthermia/rhabdomyolysis/acidosis death spiral), with ICU admission

• Hyperthermia (life-threatening): aggressive active cooling with deep sedation (and paralysis/intubation if needed) — a leading cause of death in excited delirium that must be treated immediately

• Severe hypertension: benzodiazepines first, and if persistent, nitroglycerin, nitroprusside, or phentolamine (titratable, avoiding beta-blockers)

• Chest pain/ACS: benzodiazepines with aspirin and nitrates, cardiology for a true MI, and avoidance of beta-blockers; a wide-complex arrhythmia is treated with sodium bicarbonate 1–2 mEq/kg IV

• Rhabdomyolysis: aggressive IV fluids with monitoring of CK, renal function, and potassium, treatment of hyperkalemia, and vigilance for AKI and compartment syndrome

• Psychosis: often resolves with sedation and time; antipsychotics for persistent psychosis, with psychiatry involvement and reassessment, since methamphetamine psychosis can be prolonged but usually clears (distinguish it from a primary disorder)

• Supportive care: fluids, electrolytes, glucose, a quiet environment, and restraints only if needed for safety (chemical sedation is preferred, since physical restraints worsen rhabdomyolysis and hyperthermia)

• PT/OT: once stable

• Trend: core temperature, agitation/sedation level, blood pressure and heart rate, ECG and troponin, CK, renal function, and potassium, mental status and psychosis, the neurologic exam, and urine output

• Escalation triggers: excited delirium, uncontrolled agitation, or hyperthermia → ICU with deep sedation/intubation and cooling; severe rhabdomyolysis or AKI → nephrology and dialysis; MI or arrhythmia → cardiology; stroke or ICH → neurology/neurosurgery

• Discharge checklist: toxicity and agitation resolved, psychosis cleared or managed by psychiatry, rhabdomyolysis and renal injury resolved, and cardiac/neurologic complications excluded; an addiction treatment referral and counseling (no FDA-approved medication-assisted treatment exists — behavioral and contingency management are used); psychiatry follow-up; cardiovascular risk counseling; return precautions for chest pain, neurologic symptoms, severe agitation, or dark urine

Red Flags

• Excited delirium with hyperthermia → a true emergency; deep sedation, aggressive cooling, fluids, and a low threshold to intubate

• Hyperthermia, rhabdomyolysis, and acidosis together → the lethal triad of severe stimulant toxicity

• Severe rhabdomyolysis → AKI, hyperkalemia, and compartment syndrome

• Chest pain or wide-complex arrhythmia → MI and sodium-channel effects; avoid beta-blockers, use bicarbonate

• Focal deficit or severe hypertension → stroke or intracranial hemorrhage → emergent imaging

Senior IM Resident Pearls

• Same anchors as cocaine: benzodiazepines first, no beta-blockers. Sedation controls the heart rate, blood pressure, temperature, and agitation at once.

• Expect a longer, more psychotic course. Methamphetamine's half-life dwarfs cocaine's, so plan for prolonged agitation and psychosis and be ready to escalate sedation.

• The lethal triad is hyperthermia, rhabdomyolysis, and acidosis. In excited delirium, cool aggressively, sedate deeply, flood with fluids, and intubate early — patients die in this spiral.

• Chemical sedation beats physical restraints. Fighting against restraints worsens hyperthermia, rhabdomyolysis, and acidosis; sedate the patient rather than just tying them down.

• Antipsychotics are adjuncts, not the foundation. They help persistent psychosis but lower the seizure threshold and impair heat dissipation — benzodiazepines remain first-line.

• Stimulant psychosis usually clears. Reassess over time before diagnosing a primary psychotic disorder, while still treating safely in the interim.

• Common mistake: under-dosing sedation and relying on restraints in excited delirium — the patient keeps struggling, the temperature and CK climb, and the situation becomes a code.

Toxicology — Iatrogenic / Geriatric

110. Polypharmacy Toxicity

additive toxicity from too many drugs · elderly / multiple CNS depressants / multiple antihypertensives · the cure is deprescribing · the elderly are the high-risk group · Super Compact

Sx: depends on the predominant classes — CNS depressants (opioids + benzos + sleep aids + antihistamines): additive sedation, confusion, falls, respiratory depression · multiple antihypertensives/rate agents: additive hypotension, bradycardia, dizziness, syncope, falls, AKI · anticholinergic burden: delirium, urinary retention, constipation · serotonergic burden → serotonin syndrome · QT additive → arrhythmia · (presentation is often vague and multifactorial — "failure to thrive," recurrent falls, confusion — in a patient on a long med list; each drug may be "in range" but the sum is toxic)

Neg: denies that each drug was judged in isolation rather than the additive total · denies missed renal/hepatic decline making prior-stable doses now toxic · denies missed drug-drug interaction · denies missed non-drug cause (infection, metabolic, structural) · denies missed prescribing cascade (a drug treating another drug's side effect)

SHx: complete med reconciliation incl OTC/herbals/eye drops/topicals + all prescribers · recent additions/dose changes, accidental duplication (brand+generic), adherence/cognitive errors · number of meds + number of prescribers/pharmacies · renal/hepatic function · age/frailty/weight · functional status, falls history

Etiology: cumulative/additive pharmacologic effect of multiple agents (same class or overlapping effects) ± pharmacokinetic interactions (CYP inhibition/induction, protein binding, renal competition) ± declining clearance (age/renal/hepatic) → toxicity even when each drug is individually "appropriate" · driven by fragmented prescribing, prescribing cascades, Beers-criteria drugs, and inadequate deprescribing

RF: elderly/frail (the key group) · ≥5 medications · multiple prescribers/pharmacies · renal/hepatic impairment · cognitive impairment (errors) · recent med changes/transitions of care · Beers-criteria/high-risk drugs

Data: full medication reconciliation + interaction/duplication check (the core "test") · BMP (renal fxn, Na, glucose), LFTs · drug levels where available (digoxin, lithium, AEDs, etc.) · ECG (QT, bradyarrhythmia, conduction) · orthostatic vitals (antihypertensives) · fingerstick glucose · infection workup if AMS · review against Beers/STOPP criteria + renal dosing of every agent · head CT if focal/falls/trauma

DDx: polypharmacy toxicity (multifactorial, improves on deprescribing) · single-agent toxicity/accumulation · drug-drug interaction · serotonin syndrome · infection/sepsis/delirium · metabolic/structural cause · primary cardiac (brady/hypotension) · dementia progression

Home Meds: this IS the problem — systematically deprescribe · stop/reduce overlapping CNS depressants, redundant antihypertensives, anticholinergics, Beers-criteria drugs · renal/hepatic dose-adjust survivors · taper drugs needing it (benzos, beta-blockers, baclofen)

Plan

CONSULT: Pharmacy (comprehensive medication review, interactions, deprescribing — highest yield) · Geriatrics (elderly polypharmacy, Beers/STOPP, frailty) · Cardiology (bradyarrhythmia/hypotension from rate/BP agents) · Toxicology/Poison Control

– Comprehensive medication reconciliation + deprescribing is the central treatment: list every agent (incl OTC/topical/eye drops), identify additive effects, duplications, interactions, and accumulation; stop or reduce the offending/non-essential drugs in a structured way; renally/hepatically dose-adjust what remains
– Treat by predominant toxidrome:
  • CNS depression (opioids/benzos/sedatives): hold the agents, support airway/ventilation, naloxone if opioid respiratory depression (0.04–0.4 mg IV titrated); generally avoid flumazenil (seizure risk); supportive, fall/aspiration precautions
  • Hypotension/bradycardia (multiple antihypertensives/rate agents): hold the offending agents, IV fluids, treat symptomatic bradycardia (atropine; agent-specific antidotes — glucagon for beta-blocker, calcium/high-dose insulin-euglycemia for CCB toxicity if severe); reintroduce only what's truly needed at adjusted doses
  • Anticholinergic burden: remove anticholinergics; supportive; manage urinary retention/delirium non-pharmacologically
  • Serotonergic/QT burden: stop offending agents; manage serotonin syndrome (benzodiazepines, cooling, cyproheptadine) or QT risk (correct electrolytes, telemetry) as needed
– Exclude non-drug causes (infection, metabolic, structural) — don't assume the meds explain everything
– Supportive: IV fluids, electrolyte correction, monitoring, fall precautions, glucose
– The trap is judging each drug in isolation — every level "in range," every dose "appropriate," while the sum quietly poisons a frail elderly patient with falls, confusion, and hypotension. The treatment is mostly subtraction: reconcile the whole list, find the additive overlaps and the prescribing cascades, and deprescribe. And remember a dose that was fine last year may be toxic now if the kidneys have declined.
– PT/OT: falls assessment, gait/balance, home safety, functional evaluation (central in the elderly)
– Trend: mental status, orthostatics/BP/HR, renal function, drug levels, symptom resolution as drugs are withdrawn, fall events
– Escalation triggers: respiratory depression → ICU + naloxone/support; severe bradycardia/hypotension (beta-blocker/CCB) → ICU + antidotes (glucagon, calcium, high-dose insulin); not improving with deprescribing → reinvestigate non-drug causes
– Discharge checklist: medication list streamlined with clear documentation of changes + reconciled across prescribers; one pharmacy/blister-packing if adherence issue; renal dosing applied; PCP + pharmacy follow-up for ongoing deprescribing; falls precautions + home safety; caregiver education; clear list given to patient/family; return precautions (falls, confusion, dizziness/syncope, drowsiness)

110. Polypharmacy Toxicity

complete reference · elderly + multiple CNS depressants + multiple antihypertensives · reconcile and deprescribe · Full Card

Symptoms / Associated Sx

• The presentation depends on the predominant drug classes

• CNS depressants (opioids plus benzodiazepines plus sleep aids plus antihistamines): additive sedation, confusion, falls, and respiratory depression

• Multiple antihypertensives or rate-control agents: additive hypotension, bradycardia, dizziness, syncope, falls, and AKI

• Anticholinergic burden: delirium, urinary retention, and constipation; serotonergic burden progressing to serotonin syndrome; and additive QT prolongation causing arrhythmia

• The presentation is often vague and multifactorial — "failure to thrive," recurrent falls, or confusion — in a patient on a long medication list, where each drug may be individually "in range" but the sum is toxic

Neg

• Pt denies that each drug was judged in isolation rather than as an additive total

• Pt denies a missed renal or hepatic decline that makes previously stable doses now toxic, and denies a missed drug-drug interaction

• Pt denies a missed non-drug cause (infection, metabolic, structural) and denies a missed prescribing cascade (a drug prescribed to treat another drug's side effect)

Social History (SHx)

• A complete medication reconciliation including OTC products, herbals, eye drops, and topicals, with all prescribers identified

• Recent additions or dose changes, accidental duplication (brand plus generic), and adherence or cognitive errors

• The number of medications and the number of prescribers and pharmacies

• Renal and hepatic function, age, frailty, and weight; functional status and falls history

Main Etiology

• The cumulative, additive pharmacologic effect of multiple agents (in the same class or with overlapping effects)

• This may combine with pharmacokinetic interactions (CYP inhibition or induction, protein binding, renal competition) and declining clearance from age or renal/hepatic impairment

• The result is toxicity even when each drug is individually appropriate, driven by fragmented prescribing, prescribing cascades, Beers-criteria drugs, and inadequate deprescribing

RF

• Modifiable: the number of medications (≥5), multiple prescribers and pharmacies, recent medication changes and transitions of care, and high-risk Beers-criteria drugs

• Non-modifiable: advanced age and frailty, renal or hepatic impairment, and cognitive impairment

Data

• A full medication reconciliation with an interaction and duplication check (the core diagnostic step)

• BMP (renal function, sodium, glucose) and LFTs

• Drug levels where available (digoxin, lithium, antiepileptics)

• ECG (QT, bradyarrhythmia, conduction) and orthostatic vitals (for antihypertensives)

• Fingerstick glucose; an infection workup if there is altered mental status; review against the Beers/STOPP criteria with renal dosing of every agent; and a head CT if there are focal findings, falls, or trauma

DDx

Polypharmacy toxicity (multifactorial, improving on deprescribing) · single-agent toxicity or accumulation · a drug-drug interaction · serotonin syndrome · infection/sepsis or delirium · a metabolic or structural cause · a primary cardiac process (bradycardia, hypotension) · progression of dementia

Home Meds

• This is the problem — systematically deprescribe: stop or reduce overlapping CNS depressants, redundant antihypertensives, anticholinergics, and Beers-criteria drugs

• Dose-adjust the remaining medications for renal and hepatic function

• Taper the drugs that require it (benzodiazepines, beta-blockers, baclofen)

Plan

CONSULT: Pharmacy (comprehensive medication review, interactions, deprescribing — the highest yield) · Geriatrics (elderly polypharmacy, Beers/STOPP, frailty) · Cardiology (bradyarrhythmia or hypotension from rate/BP agents) · Toxicology/Poison Control

• Comprehensive medication reconciliation and deprescribing is the central treatment: list every agent (including OTC, topical, and eye drops), identify additive effects, duplications, interactions, and accumulation, stop or reduce the offending and non-essential drugs in a structured way, and dose-adjust what remains for renal and hepatic function

• Treat by the predominant toxidrome:

• • CNS depression (opioids, benzodiazepines, sedatives): hold the agents, support the airway and ventilation, give naloxone for opioid respiratory depression (0.04–0.4 mg IV titrated), generally avoid flumazenil (seizure risk), and provide supportive care with fall and aspiration precautions

• • Hypotension and bradycardia (multiple antihypertensives or rate agents): hold the offending agents, give IV fluids, and treat symptomatic bradycardia (atropine, with agent-specific antidotes — glucagon for beta-blocker toxicity, calcium and high-dose insulin-euglycemia for severe calcium channel blocker toxicity), reintroducing only what is truly needed at adjusted doses

• • Anticholinergic burden: remove the anticholinergics and provide supportive care, managing urinary retention and delirium non-pharmacologically

• • Serotonergic or QT burden: stop the offending agents and manage serotonin syndrome (benzodiazepines, cooling, cyproheptadine) or QT risk (correct electrolytes, telemetry) as needed

• Exclude non-drug causes (infection, metabolic, structural) — don't assume the medications explain everything

• Supportive care: IV fluids, electrolyte correction, monitoring, fall precautions, and glucose

• PT/OT: a falls assessment, gait and balance evaluation, home safety review, and functional assessment — central in the elderly

• Trend: mental status, orthostatics with blood pressure and heart rate, renal function, drug levels, symptom resolution as drugs are withdrawn, and fall events

• Escalation triggers: respiratory depression → ICU with naloxone and support; severe bradycardia or hypotension (beta-blocker or CCB) → ICU with antidotes (glucagon, calcium, high-dose insulin); failure to improve with deprescribing → reinvestigate non-drug causes

• Discharge checklist: a streamlined medication list with clear documentation of changes, reconciled across prescribers; a single pharmacy or blister-packing if adherence is an issue; renal dosing applied; primary care and pharmacy follow-up for ongoing deprescribing; falls precautions and home safety; caregiver education; a clear list given to the patient and family; return precautions for falls, confusion, dizziness or syncope, or drowsiness

Red Flags

• Additive respiratory depression from stacked CNS depressants → airway support, naloxone, and ICU

• Severe bradycardia or hypotension from combined rate/BP agents → fluids, atropine, and agent-specific antidotes (glucagon, calcium, high-dose insulin)

• A previously stable regimen turning toxic as renal or hepatic function declines

• Recurrent falls in a frail elderly patient on sedating or hypotensive drugs → a marker of dangerous cumulative toxicity

• Failure to improve after deprescribing → an unrecognized non-drug cause

Senior IM Resident Pearls

• The trap is judging each drug in isolation. Every level "in range" and every dose "appropriate" while the sum quietly poisons a frail patient with falls, confusion, and hypotension.

• The treatment is mostly subtraction. Reconcile the whole list, find the additive overlaps and the prescribing cascades, and deprescribe — fewer drugs is the intervention.

• Yesterday's safe dose can be today's toxic dose. A regimen that was fine last year becomes dangerous when the kidneys decline — re-dose to current function.

• Hunt for the prescribing cascade. A drug treating the side effect of another drug (e.g. an anticholinergic for a cholinesterase inhibitor's effects) is a chain you can often unwind.

• The elderly are the high-risk group. Reduced reserve, altered pharmacokinetics, and fragmented care converge — and PT/OT falls assessment is as important as the medication changes.

• Use Beers and STOPP as a checklist. They flag the high-risk agents (benzodiazepines, anticholinergics, certain cardiac drugs) worth targeting first.

• Common mistake: sending the patient home on the same long list because no single drug "caused" the problem — document the deprescribing rationale and arrange follow-up to continue it.

Toxicology — Hepatotoxins

111. Acetaminophen Overdose

the most common overdose, and eminently treatable · intentional / unintentional / acute liver injury · Rumack-Matthew nomogram + N-acetylcysteine · NAC by 8h is the goal · Super Compact

Sx: four phases — (I) 0.5–24h: asymptomatic or nausea/vomiting/malaise (deceptively well — don't be reassured) · (II) 24–72h: RUQ pain, ↑transaminases, latent hepatic injury developing · (III) 72–96h: peak hepatotoxicity — fulminant hepatic failure, jaundice, coagulopathy, encephalopathy, AKI, lactic acidosis, hypoglycemia, death · (IV) 4d–2wk: recovery or progression · (the danger is that early presentation looks benign; treat on the level/nomogram, not on how well they look)

Neg: denies that "looks well" was taken as reassurance (phase I is silent) · denies missed co-ingestants/combination products (opioid-APAP, cold remedies) · denies that a single random level was used without timing from ingestion · denies missed staggered/repeated-supratherapeutic or unknown-timing ingestion (nomogram doesn't apply — treat empirically) · denies delayed NAC

SHx: dose + exact timing (single acute vs staggered vs chronic supratherapeutic), intent (suicide vs accidental — often combination cold/pain products), formulation (extended-release alters kinetics), co-ingestants (anticholinergics/opioids delay absorption), alcohol use/malnutrition/chronic liver disease (↑risk), prior overdoses

Etiology: at therapeutic doses APAP is conjugated safely; in overdose those pathways saturate → more is shunted to CYP2E1 → toxic metabolite NAPQI → depletes hepatic glutathione → NAPQI binds hepatocytes → centrilobular necrosis · NAC works by replenishing glutathione (and other mechanisms) → detoxifies NAPQI; risk amplified by glutathione depletion (alcoholism, malnutrition, fasting) and CYP induction

RF: intentional large ingestion · staggered/repeated supratherapeutic dosing · chronic alcohol use / malnutrition / fasting (glutathione depletion) · CYP-inducing drugs · delayed presentation/treatment · combination products (unrecognized APAP)

Data: serum acetaminophen level at 4h post-ingestion (or ASAP if ≥4h) plotted on the Rumack-Matthew nomogram (single acute ingestion, known timing) · AST/ALT, INR/PT, bilirubin, BMP (renal), glucose, lactate, VBG/ABG (acidosis), lipase · repeat APAP + a co-ingestant screen (salicylate, others) + ECG + pregnancy test · serial LFTs/INR to track injury · (nomogram is for a SINGLE acute ingestion with known time; not valid for staggered/chronic/unknown-timing — treat those empirically)

DDx: acetaminophen-induced liver injury (level, phases, NAC-responsive) · other toxic/drug-induced hepatitis · viral/ischemic/alcoholic hepatitis · other anion-gap acidosis · co-ingestant effects · acute fatty liver of pregnancy (if pregnant)

Home Meds: hold all acetaminophen-containing products (check combination meds) · hold hepatotoxins · review for occult APAP sources · psychiatric meds if intentional

Plan

CONSULT: Toxicology / Poison Control 1-800-222-1222 (dosing + nomogram interpretation) · Hepatology + Transplant center (hepatic failure — King's College criteria) · ICU (fulminant failure, encephalopathy) · Psychiatry (intentional/suicidality)

– N-ACETYLCYSTEINE (NAC) is the antidote — give it early, ideally within 8 hours of ingestion (highly effective if started ≤8h; still give later — it benefits even established hepatotoxicity/late presentation):
  • IV (21-hour 3-bag protocol): loading 150 mg/kg over 60 min → 50 mg/kg over 4 h → 100 mg/kg over 16 h (watch for anaphylactoid reactions — slow/pause the infusion, antihistamine); many centers extend NAC if ongoing hepatotoxicity/persistent level
  • PO alternative: 140 mg/kg load → 70 mg/kg q4h × 17 doses
– Decide who gets NAC: treat if the 4h+ level plots above the nomogram treatment line (single acute, known time); OR staggered/repeated supratherapeutic ingestion with elevated level/transaminases; OR unknown timing with detectable level/abnormal LFTs; OR any evidence of hepatotoxicity; OR high-risk massive ingestion — start NAC empirically while awaiting level rather than delay (don't wait if presentation is late or timing unclear)
– Decontamination: activated charcoal 1 g/kg PO if presenting early (~within 1–2 h) and airway intact (especially large ingestion) — doesn't significantly impair subsequent NAC
– Supportive / hepatic failure care: correct hypoglycemia, manage coagulopathy (vitamin K, FFP only for bleeding/procedures — don't mask trending INR), treat acidosis, renal support, manage hepatic encephalopathy, early transfer to a transplant center + apply King's College criteria (e.g. arterial pH <7.3, or the triad of INR >6.5 + creatinine >3.4 mg/dL + grade III–IV encephalopathy) to identify transplant candidates
– Co-ingestant management per screen (salicylate, opioid-APAP combos, etc.)
– Two rules carry this diagnosis: treat on the level and the nomogram, not on how well the patient looks (phase I is silent while the liver is being injured), and give NAC early — it's nearly fully protective within 8 hours and still worthwhile later. When timing is unknown or the ingestion was staggered, the nomogram doesn't apply: treat empirically rather than wait.
– PT/OT: per status; usually minimal unless prolonged illness
– Trend: serial AST/ALT, INR/PT, bilirubin, renal function, glucose, lactate, pH, mental status (encephalopathy), acetaminophen level; response to NAC
– Escalation triggers: rising INR/transaminases, acidosis, encephalopathy, AKI, hypoglycemia → ICU + hepatology + transplant evaluation (King's College); anaphylactoid NAC reaction → pause/treat and resume
– Discharge checklist: NAC course completed with normalizing/normal LFTs + INR + improving clinically; co-ingestants addressed; psychiatric evaluation + suicidality assessment if intentional; counsel on acetaminophen safety + hidden sources in combination products; hepatology follow-up if injury occurred; return precautions (RUQ pain, jaundice, confusion, bleeding, vomiting)

111. Acetaminophen Overdose

complete reference · intentional + unintentional + acute liver injury · Rumack-Matthew nomogram, N-acetylcysteine, King's College criteria · Full Card

Symptoms / Associated Sx

• The course progresses through four phases

• Phase I (0.5–24 hours): asymptomatic or with nausea, vomiting, and malaise — deceptively well, which should not be reassuring

• Phase II (24–72 hours): right upper quadrant pain, rising transaminases, and latent hepatic injury developing

• Phase III (72–96 hours): peak hepatotoxicity — fulminant hepatic failure, jaundice, coagulopathy, encephalopathy, AKI, lactic acidosis, hypoglycemia, and death

• Phase IV (4 days–2 weeks): recovery or progression

• The danger is that the early presentation looks benign — treat on the level and nomogram, not on how well the patient appears

Neg

• Pt denies that "looks well" was taken as reassurance (phase I is silent while injury occurs)

• Pt denies missed co-ingestants or combination products (opioid-acetaminophen, cold remedies)

• Pt denies that a single random level was used without timing from ingestion, denies a missed staggered, repeated-supratherapeutic, or unknown-timing ingestion (where the nomogram does not apply and empiric treatment is warranted), and denies delayed NAC

Social History (SHx)

• Dose and exact timing (single acute versus staggered versus chronic supratherapeutic) and intent (suicidal versus accidental, often from combination cold or pain products)

• Formulation (extended-release alters the kinetics)

• Co-ingestants (anticholinergics and opioids delay absorption)

• Alcohol use, malnutrition, or chronic liver disease (which increase risk); prior overdoses

Main Etiology

• At therapeutic doses acetaminophen is conjugated safely; in overdose those pathways saturate and more is shunted through CYP2E1 to the toxic metabolite NAPQI

• NAPQI depletes hepatic glutathione and then binds hepatocytes, producing centrilobular necrosis

• NAC works by replenishing glutathione (among other mechanisms), detoxifying NAPQI; the risk is amplified by glutathione depletion (alcoholism, malnutrition, fasting) and CYP induction

RF

• Modifiable: the ingested dose, staggered or repeated supratherapeutic dosing, nutritional and alcohol status, and the timeliness of treatment

• Non-modifiable: chronic liver disease and CYP-inducing comedications; unrecognized acetaminophen in combination products is a contributing factor

Data

• Serum acetaminophen level at 4 hours post-ingestion (or as soon as possible if already ≥4 hours) plotted on the Rumack-Matthew nomogram (for a single acute ingestion with known timing)

• AST/ALT, INR/PT, bilirubin, BMP (renal function), glucose, lactate, a venous or arterial blood gas (acidosis), and lipase

• A repeat acetaminophen level with a co-ingestant screen (salicylate and others), an ECG, and a pregnancy test

• Serial LFTs and INR to track the injury

• The nomogram applies only to a single acute ingestion with a known time and is not valid for staggered, chronic, or unknown-timing ingestions, which are treated empirically

DDx

Acetaminophen-induced liver injury (the level, the phases, and a response to NAC) · another toxic or drug-induced hepatitis · viral, ischemic, or alcoholic hepatitis · another anion-gap acidosis · co-ingestant effects · acute fatty liver of pregnancy (if pregnant)

Home Meds

• Hold: all acetaminophen-containing products (check combination medications) and other hepatotoxins

• Review for occult acetaminophen sources

• Review: psychiatric medications if the ingestion was intentional

Plan

CONSULT: Toxicology/Poison Control (1-800-222-1222 — dosing and nomogram interpretation) · Hepatology and a transplant center (hepatic failure — King's College criteria) · ICU (fulminant failure, encephalopathy) · Psychiatry (intentional ingestion, suicidality)

• N-acetylcysteine (NAC) is the antidote — give it early, ideally within 8 hours of ingestion (highly effective if started by 8 hours, and still given later since it benefits even established hepatotoxicity and late presentations):

• • IV (the 21-hour 3-bag protocol): a loading dose of 150 mg/kg over 60 minutes, then 50 mg/kg over 4 hours, then 100 mg/kg over 16 hours (watching for anaphylactoid reactions — slow or pause the infusion and give an antihistamine); many centers extend NAC if hepatotoxicity is ongoing or the level persists

• • PO alternative: a 140 mg/kg loading dose, then 70 mg/kg every 4 hours for 17 doses

• Decide who gets NAC: treat if the level (at ≥4 hours) plots above the nomogram treatment line (single acute, known time); or for a staggered or repeated supratherapeutic ingestion with an elevated level or transaminases; or for unknown timing with a detectable level or abnormal LFTs; or for any evidence of hepatotoxicity; or for a high-risk massive ingestion (start NAC empirically while awaiting the level rather than delay) — don't wait if the presentation is late or the timing is unclear

• Decontamination: activated charcoal 1 g/kg PO if presenting early (roughly within 1–2 hours) with an intact airway (especially after a large ingestion) — it does not significantly impair subsequent NAC

• Supportive and hepatic-failure care: correct hypoglycemia, manage coagulopathy (vitamin K, with FFP only for bleeding or procedures so as not to mask the trending INR), treat acidosis, provide renal support, manage hepatic encephalopathy, and transfer early to a transplant center while applying the King's College criteria (an arterial pH below 7.3, or the triad of INR above 6.5, creatinine above 3.4 mg/dL, and grade III–IV encephalopathy) to identify transplant candidates

• Co-ingestant management per the screen (salicylate, opioid-acetaminophen combinations)

• PT/OT: per status, usually minimal unless the illness is prolonged

• Trend: serial AST/ALT, INR/PT, bilirubin, renal function, glucose, lactate, and pH, mental status (encephalopathy), the acetaminophen level, and the response to NAC

• Escalation triggers: a rising INR or transaminases, acidosis, encephalopathy, AKI, or hypoglycemia → ICU, hepatology, and transplant evaluation (King's College); an anaphylactoid NAC reaction → pause, treat, and resume

• Discharge checklist: the NAC course completed with normalizing or normal LFTs and INR and clinical improvement; co-ingestants addressed; a psychiatric evaluation and suicidality assessment if intentional; counseling on acetaminophen safety and its hidden sources in combination products; hepatology follow-up if injury occurred; return precautions for right upper quadrant pain, jaundice, confusion, bleeding, or vomiting

Red Flags

• A level above the nomogram treatment line → NAC, regardless of how well the patient appears

• Rising INR, transaminases, acidosis, encephalopathy, or AKI → fulminant hepatic failure → ICU, hepatology, and transplant evaluation

• Meeting King's College criteria (pH <7.3, or INR >6.5 + creatinine >3.4 + grade III–IV encephalopathy) → urgent transplant referral

• Staggered, chronic, or unknown-timing ingestion → the nomogram does not apply; treat empirically

• Late presentation → still give NAC; it benefits even established hepatotoxicity

Senior IM Resident Pearls

• Treat on the level, not on appearance. Phase I is silent while the liver is being injured — the well-looking patient with a level above the line still needs NAC.

• NAC within 8 hours is nearly fully protective. Time matters enormously — if the ingestion is approaching that window or timing is unclear, start NAC and sort out the details after.

• The nomogram has strict rules. It's only valid for a single acute ingestion with known timing; staggered, chronic, or unknown-timing ingestions get empiric treatment.

• Always screen for hidden acetaminophen and co-ingestants. Combination cold and pain products and intentional polypharmacy overdoses are common — check a salicylate level too.

• Don't reflexively reverse the INR. In acetaminophen hepatotoxicity the INR is your prognostic marker — give FFP only for active bleeding or procedures, not to "normalize the number."

• Know the King's College criteria. They identify who needs transplant — transfer early, because the window to list a patient can be short.

• Common mistake: discharging an early-presenting overdose because labs are normal — the injury hasn't declared itself yet; risk-stratify with a properly timed level and treat accordingly.

Toxicology — Iatrogenic / CNS

112. Drug-Induced Delirium

acute confusion caused by medications · anticholinergics / sedatives / opioids / muscle relaxants · remove the culprit, non-pharmacologic first · the elderly brain is most vulnerable · Super Compact

Sx: acute, fluctuating disturbance of attention and awareness with cognitive change — hyperactive (agitation, hallucinations, restlessness), hypoactive (lethargy, withdrawn, ↓responsiveness — easily missed, worse prognosis), or mixed · inattention, disorientation, altered sleep-wake cycle, perceptual disturbances · develops over hours–days, waxes/wanes (worse at night — "sundowning") · (the temporal link to a new/changed medication is the clue; hypoactive delirium is frequently overlooked as "just tired/depressed")

Neg: denies that non-drug causes were skipped (infection/UTI/pneumonia, metabolic — Na/glucose/Ca, hypoxia, urinary retention/constipation, pain, dehydration, withdrawal, stroke) · denies missed anticholinergic burden · denies that delirium was mislabeled dementia/psychiatric · denies that more deliriogenic drugs were added to treat it

SHx: med reconciliation with timeline (new starts, dose changes, perioperative meds) · baseline cognition (dementia = major risk) · OTC/sleep aids/antihistamines (anticholinergic), bladder antimuscarinics · alcohol/benzo use (withdrawal) · sensory impairment (vision/hearing), age, functional status

Etiology: medication effect on the vulnerable brain → delirium · high-risk classes: anticholinergics (diphenhydramine, oxybutynin, TCAs, scopolamine — central muscarinic blockade), benzodiazepines/sedative-hypnotics, opioids, muscle relaxants (cyclobenzaprine, baclofen), antipsychotics, corticosteroids, anticonvulsants, dopaminergics, H2 blockers · amplified by polypharmacy, age, dementia, and acute illness (multifactorial — drugs are often the modifiable piece)

RF: elderly · pre-existing dementia/cognitive impairment · polypharmacy/anticholinergic burden · sensory impairment · severe illness/post-op/ICU · prior delirium · functional dependence

Data: CAM (Confusion Assessment Method) to diagnose · medication review + timeline (the key) · rule out other causes: CBC + cultures/UA (infection), BMP (Na/glucose/Ca/renal), fingerstick glucose, LFTs/ammonia, TSH, O2/ABG, bladder scan (retention) · ECG · head CT if focal/trauma/unexplained · consider EEG (nonconvulsive status) · review anticholinergic burden score

DDx: drug-induced delirium (temporal link, culprit, improves on removal) · infection-related delirium · metabolic/hypoxic · withdrawal (alcohol/benzo) · structural (stroke) · nonconvulsive status · dementia (chronic, non-fluctuating attention) · primary psychiatric

Home Meds: stop/reduce deliriogenic drugs (anticholinergics, sedatives, unnecessary opioids/relaxants) · renal/hepatic dose-adjust · do NOT add more deliriogenic drugs to manage it · taper benzos/baclofen rather than abrupt stop

Plan

CONSULT: Geriatrics (elderly delirium, deprescribing) · Pharmacy (anticholinergic burden, med review) · Psychiatry (severe/refractory agitation, dx clarification) · Neurology (focal/atypical/EEG)

– Identify and remove the offending drug(s) — the central intervention: reconcile meds, map timeline to onset, stop or reduce the deliriogenic culprit (anticholinergics, sedatives, opioids, muscle relaxants), substitute safer alternatives, renally dose-adjust
– Treat reversible contributors in parallel: infection, hypoxia, electrolytes/glucose, pain (under-treated pain also causes delirium — balance against opioid burden), urinary retention (bladder scan/catheter), constipation, dehydration, sensory aids (glasses/hearing aids); don't anchor on meds and miss sepsis
– NON-PHARMACOLOGIC MANAGEMENT IS FIRST-LINE: reorientation, familiar faces/objects, day-night lighting + sleep hygiene, early mobilization, minimize lines/restraints/tethers, quiet environment, address sensory deficits, hydration/nutrition, normalize sleep-wake — these reduce duration and severity and are the core treatment
– Pharmacologic only for severe agitation endangering safety (last resort, lowest effective dose, shortest duration): low-dose antipsychotic (e.g. haloperidol 0.25–0.5 mg, or quetiapine) — watch QT/EPS/sedation; avoid benzodiazepines except for alcohol/benzo withdrawal-related delirium (they worsen non-withdrawal delirium); reassess and stop early
– Anticholinergic-specific: remove all anticholinergics; supportive — physostigmine only in select severe pure central anticholinergic toxicity per toxicology (not routine for general delirium)
– The treatment is mostly removal and environment, not addition. Find the culprit drug on a timeline, stop it, fix the reversible contributors (infection, retention, pain, electrolytes), and lean hard on non-pharmacologic measures. Reserve antipsychotics for dangerous agitation, and remember benzodiazepines make non-withdrawal delirium worse — the reflex to "sedate the confused patient" often deepens the problem. Watch especially for quiet hypoactive delirium, which is missed precisely because it isn't disruptive.
– PT/OT: early mobilization (central to treatment), functional/cognitive assessment, falls prevention
– Trend: CAM/attention, mental status, the culprit's withdrawal effect (should improve — confirms dx), reversible contributors, agitation, sleep-wake cycle, safety
– Escalation triggers: not improving off culprit + contributors corrected → reinvestigate (CT/EEG/infection); dangerous agitation → cautious low-dose antipsychotic + reassess; suspected nonconvulsive status → EEG
– Discharge checklist: delirium resolved or improving to baseline trajectory; deliriogenic drugs stopped + documented to prevent re-prescription; med list simplified; reversible causes treated; caregiver education (delirium can take weeks to fully resolve, esp elderly); cognitive follow-up + delirium-prevention plan for future admissions; return precautions (recurrent confusion, agitation, decline)

112. Drug-Induced Delirium

complete reference · anticholinergics + sedatives + opioids + muscle relaxants · remove culprit, non-pharmacologic first · Full Card

Symptoms / Associated Sx

• An acute, fluctuating disturbance of attention and awareness with cognitive change

• Hyperactive (agitation, hallucinations, restlessness), hypoactive (lethargy, withdrawn, reduced responsiveness — easily missed and carrying a worse prognosis), or mixed

• Inattention, disorientation, an altered sleep-wake cycle, and perceptual disturbances

• Develops over hours to days and waxes and wanes, typically worse at night ("sundowning")

• The temporal link to a new or changed medication is the clue, and hypoactive delirium is frequently overlooked as the patient simply being tired or depressed

Neg

• Pt denies that non-drug causes were skipped (infection such as UTI or pneumonia, metabolic derangement of sodium/glucose/calcium, hypoxia, urinary retention or constipation, pain, dehydration, withdrawal, stroke)

• Pt denies a missed anticholinergic burden

• Pt denies that the delirium was mislabeled as dementia or a psychiatric disorder, and denies that more deliriogenic drugs were added to treat it

Social History (SHx)

• A medication reconciliation with a timeline (new starts, dose changes, perioperative medications)

• Baseline cognition (dementia is a major risk factor)

• OTC sleep aids and antihistamines (anticholinergic) and bladder antimuscarinics; alcohol or benzodiazepine use (withdrawal)

• Sensory impairment (vision, hearing), age, and functional status

Main Etiology

• A medication effect on the vulnerable brain producing delirium

• High-risk classes: anticholinergics (diphenhydramine, oxybutynin, TCAs, scopolamine — central muscarinic blockade), benzodiazepines and sedative-hypnotics, opioids, muscle relaxants (cyclobenzaprine, baclofen), antipsychotics, corticosteroids, anticonvulsants, dopaminergics, and H2 blockers

• Amplified by polypharmacy, age, dementia, and acute illness — the picture is usually multifactorial, with drugs often the modifiable piece

RF

• Modifiable: polypharmacy and anticholinergic burden, uncorrected sensory impairment, and the use of tethers and restraints

• Non-modifiable: advanced age, pre-existing dementia, severe illness or a post-operative/ICU state, prior delirium, and functional dependence

Data

• CAM (Confusion Assessment Method) to make the diagnosis

• Medication review with a timeline (the key step)

• Rule out other causes: CBC with cultures and a urinalysis (infection), BMP (sodium, glucose, calcium, renal function), fingerstick glucose, LFTs and ammonia, TSH, oxygenation/ABG, and a bladder scan (retention)

• ECG; a head CT if there are focal findings, trauma, or an unexplained picture; consideration of EEG (nonconvulsive status); and a review of the anticholinergic burden score

DDx

Drug-induced delirium (a temporal link, an identified culprit, improvement on removal) · infection-related delirium · a metabolic or hypoxic cause · withdrawal (alcohol, benzodiazepine) · a structural cause (stroke) · nonconvulsive status epilepticus · dementia (chronic, with non-fluctuating attention) · a primary psychiatric disorder

Home Meds

• Stop/reduce deliriogenic drugs (anticholinergics, sedatives, unnecessary opioids and muscle relaxants)

• Dose-adjust for renal and hepatic function; do not add more deliriogenic drugs to manage it

• Taper benzodiazepines and baclofen rather than stopping abruptly

Plan

CONSULT: Geriatrics (elderly delirium, deprescribing) · Pharmacy (anticholinergic burden, medication review) · Psychiatry (severe or refractory agitation, diagnostic clarification) · Neurology (focal or atypical features, EEG)

• Identify and remove the offending drug(s) — the central intervention: reconcile the medications, map the timeline to the onset, stop or reduce the deliriogenic culprit (anticholinergics, sedatives, opioids, muscle relaxants), substitute safer alternatives, and dose-adjust for renal function

• Treat reversible contributors in parallel: infection, hypoxia, electrolytes and glucose, pain (under-treated pain also causes delirium — balance this against opioid burden), urinary retention (bladder scan and catheter), constipation, dehydration, and sensory aids (glasses, hearing aids) — don't anchor on the medications and miss sepsis

• Non-pharmacologic management is first-line: reorientation, familiar faces and objects, day-night lighting with sleep hygiene, early mobilization, minimizing lines, restraints, and tethers, a quiet environment, addressing sensory deficits, hydration and nutrition, and normalizing the sleep-wake cycle — these reduce the duration and severity and are the core treatment

• Pharmacologic treatment only for severe agitation endangering safety (a last resort, at the lowest effective dose for the shortest duration): a low-dose antipsychotic (haloperidol 0.25–0.5 mg, or quetiapine), watching QT, extrapyramidal symptoms, and sedation; avoid benzodiazepines except in alcohol or benzodiazepine withdrawal-related delirium (they worsen non-withdrawal delirium); and reassess and stop early

• Anticholinergic-specific management: remove all anticholinergics and provide supportive care — physostigmine is reserved for select severe pure central anticholinergic toxicity per toxicology and is not routine for general delirium

• PT/OT: early mobilization (central to treatment), functional and cognitive assessment, and falls prevention

• Trend: CAM and attention, mental status, the effect of withdrawing the culprit (improvement confirms the diagnosis), reversible contributors, agitation, the sleep-wake cycle, and safety

• Escalation triggers: failure to improve after removing the culprit and correcting contributors → reinvestigate (CT, EEG, infection); dangerous agitation → a cautious low-dose antipsychotic with reassessment; suspected nonconvulsive status → EEG

• Discharge checklist: delirium resolved or improving toward baseline; deliriogenic drugs stopped and documented to prevent re-prescription; a simplified medication list; reversible causes treated; caregiver education (delirium can take weeks to fully resolve, especially in the elderly); cognitive follow-up and a delirium-prevention plan for future admissions; return precautions for recurrent confusion, agitation, or decline

Red Flags

• Hypoactive delirium → easily missed as fatigue or depression, yet it carries a worse prognosis — screen with CAM

• Failure to improve after removing the culprit → an unrecognized contributor (sepsis, retention, metabolic, structural)

• Reflexive benzodiazepine use for a confused patient → worsens non-withdrawal delirium

• Focal deficit or new seizure activity → image and consider EEG for nonconvulsive status

• Severe anticholinergic toxicity → discuss physostigmine with toxicology in select cases

Senior IM Resident Pearls

• The treatment is removal and environment, not addition. Stop the culprit drug, fix the reversible contributors, and lean hard on non-pharmacologic measures — they're the core of management.

• Benzodiazepines deepen non-withdrawal delirium. The reflex to "sedate the confused patient" usually makes it worse — reserve them for alcohol or benzodiazepine withdrawal.

• Don't miss the quiet ones. Hypoactive delirium is overlooked precisely because it isn't disruptive, yet it's common and prognostically worse — screen everyone with CAM.

• Hunt the anticholinergic burden. Diphenhydramine, oxybutynin, and similar agents stack silently — totaling the burden often reveals the cause.

• Check the bladder and the bowels. Urinary retention and constipation are classic, easily missed, fully reversible delirium triggers — scan and examine.

• Reserve antipsychotics for dangerous agitation. Lowest dose, shortest duration, with attention to QT — they manage safety, they don't treat the delirium.

• Common mistake: treating delirium as the diagnosis rather than a symptom — and adding a sedative that prolongs it instead of finding and removing the offending drug.