01Approach to the Critical Patient/attcp67

Immediate stabilization

›Airway and breathing threats

›Severely altered mental status requiring airway protection

›GCS <8 or rapidly declining

›Unable to manage secretions

›Respiratory failure from prolonged seizure or rhabdomyolysis

›Respiratory acidosis on VBG

›Accessory muscle use with fatigue

›If intubation required, avoid succinylcholine when rhabdomyolysis suspected

›Risk of fatal hyperkalemia

›Use rocuronium as preferred paralytic

›Hemodynamic stabilization

›Severe hypertension targets

›SBP >180 mmHg with end-organ damage requires urgent intervention

›Adequate sedation with benzodiazepines as first step

›Tachycardia management

›Heart rate often resolves with adequate sedation

›Persistent tachycardia after sedation triggers further workup

›Hypotension late sign

›May indicate cardiovascular collapse or Takotsubo cardiomyopathy

›Vasopressors if refractory to fluids

Critical alarm features

›Hyperthermia alarm

›Core temperature >40 degrees C is rapidly life-threatening

›Associated with mortality if not reversed rapidly

›Cooling rate >0.15 degrees C/min associated with improved survival

›Immediate external cooling initiation

›Ice water immersion preferred as fastest method

02History/hx83

Substance and exposure history

›Substance identification

›Cocaine (powder or crack)

›Intranasal, smoked, or IV route

›Fastest onset by smoked or IV routes

›Methamphetamine

›Longer duration than cocaine (up to 24 hours)

›Crystal, pill, or smoked forms

›MDMA

›Serotonergic component overlaps

›Hyponatremia risk from water intake

›Cathinones (bath salts)

›Mephedrone, N-ethylpentylone

›Particularly associated with severe agitation and fatal polydrug toxicity

›Prescription stimulants

›Amphetamine salts, methylphenidate, lisdexamfetamine

›Intentional overdose or diversion

›OTC decongestants and supplements

›Pseudoephedrine, phenylephrine

›Ephedra, large-dose caffeine

›Route and timing

›IV and smoked routes fastest onset (minutes)

›Oral route 30 to 60 minutes to onset

›Time since last use and expected duration of action

Symptom timeline

›Initial symptom progression

›Agitation onset and severity

›Escalating vs plateau

›Response to initial management

›Chest pain

›Character, radiation, and pleuritic vs pressure quality

›Associated diaphoresis or nausea

›Palpitations

›Rapid vs irregular

›Associated syncope or presyncope

›Alarm symptom history

›Seizure activity

›Witnessed or self-reported

›Duration and post-ictal state

›Dark urine suggesting rhabdomyolysis

›Headache or visual changes suggesting hypertensive emergency

›Confusion or psychosis

Co-ingestants and context

›Polydrug use

›Opioids co-ingested

›Mitigates some sympathomimetic features

›Dramatically increases mortality

›Alcohol or benzodiazepines co-ingested

›May delay toxidrome recognition

›Withdrawal syndromes complicate course

›GHB co-ingestion

›Rapid loss of consciousness risk

›Other stimulants combined

›Dramatically increases mortality risk

›Environmental and contextual clues

›Rave or music festival attendance

›Combined heat exposure and exertion

›MDMA most common in this context

›EMS and bystander collateral

›Witnessed substance use or paraphernalia

›Duration of agitation prior to EMS

›Physical restraint duration

›Body packing or stuffing suspicion

›Travel history and law enforcement involvement

›Risk of packet rupture and massive toxicity

Past medical and social history

›Relevant past medical history

›Prior stimulant overdose episodes

›Cardiovascular disease

›CAD, prior MI, cardiomyopathy, arrhythmias

›Lowers threshold for drug-induced cardiac events

›Psychiatric history

›Bipolar disorder or schizophrenia may confound presentation

›Seizure disorder

›Renal disease

›Lower threshold for AKI from rhabdomyolysis

›Pregnancy status

›Placental abruption and preeclampsia mimic risk

›Risk factors

›IV drug use route

›Faster onset and higher peak levels

›Infection risk including endocarditis

›Hot or humid environment exposure

›Impaired heat dissipation

›Chronic stimulant use

›Structural cardiac changes and accelerated atherosclerosis

›Family history of cardiac arrhythmias or sudden cardiac death

03Physical Exam/exam66

Vital signs and toxidrome recognition

›Vital sign pattern of toxidrome

›Tachycardia

›Often >120 bpm

›Persistent after sedation requires further workup

›Hypertension

›SBP >200 mmHg possible

›Refractory despite adequate sedation

›Hyperthermia

›Core temp >40 degrees C is critical threshold

›Rectal or esophageal measurement preferred for accuracy

›Tachypnea

›From agitation, acidosis, or respiratory compromise

Neurological examination

›Level of consciousness and mental status

›Agitation severity

›Mild restlessness to uncontrollable violent behavior

›Excited delirium endpoint

›Psychomotor hyperactivity

›Tremor

›Repetitive stereotyped movements

›Orientation and cognition

›Paranoia and hallucinations

›Tactile formication (cocaine)

›Neurological findings

›Hyperreflexia

›Serotonergic component if clonus present (especially lower extremity)

›Distinguishes from anticholinergic toxidrome

04Differential Diagnosis/ddx66

Life-threatening toxidromes to distinguish

›Anticholinergic toxidrome

›ICD-10 T44.3

›Key differentiating features

›Dry skin vs diaphoresis in sympathomimetic

›Urinary retention and absent bowel sounds

›Mydriasis shared feature

›Red as a beet, dry as a bone, hot as hades, mad as a hatter

›Serotonin syndrome

›ICD-10 T43.9

›Key differentiating features

›Clonus especially lower extremity

›Hyperreflexia more pronounced

›Diarrhea

›History of serotonergic medications (SSRIs, tramadol, linezolid)

›Overlaps significantly with sympathomimetic toxicity

›Neuroleptic malignant syndrome

›ICD-10 G21.0

›Key differentiating features

›Lead-pipe rigidity

›Bradykinesia

›Slow onset over days

›Recent antipsychotic use or dose change

›Malignant hyperthermia

›ICD-10 T88.3

›Key differentiating features

›Perioperative setting

›Exposure to volatile anesthetics or succinylcholine

05Laboratory Tests/lt64

Core metabolic panel

›Basic metabolic panel

›Electrolytes

›Hyperkalemia from rhabdomyolysis

›Hyponatremia in MDMA users from excess water intake

›Bicarbonate low indicating metabolic acidosis

›Renal function

›Creatinine elevation from AKI

›BUN rise

›Glucose

›Hypoglycemia may mimic agitation

›Hyperglycemia from catecholamine surge

›Liver function tests

›Hepatotoxicity from hyperthermia

›Transaminase elevation

›Coagulation factor production impairment

›Elevated bilirubin in severe cases

Rhabdomyolysis and renal markers

›Creatine kinase

›Serial CK measurements

›>5000 U/L indicates significant rhabdomyolysis

›Rising trend more important than single value

›Repeat every 6 to 8 hours

›CK >10000 U/L high risk for AKI

›Urinalysis

›Myoglobinuria detection

›Dark or tea-colored urine

›Dipstick positive for blood with no RBCs on microscopy

06Diagnostic Tests/dt75

Scoring Systems

›AGITATED BEHAVIOR severity assessment

›Richmond Agitation-Sedation Scale (RASS)

›+4 combative to -5 unarousable

›Target RASS -1 to 0 with sedation

›Reassess every 15 to 30 minutes

›Excited delirium clinical criteria

›6 or more of: hyperthermia, diaphoresis, tachycardia, agitation, hyperstrength, tolerance to pain, tachypnea, dilated pupils

›Presence of excited delirium mandates immediate chemical sedation

›Toxidrome identification framework

›Sympathomimetic vs anticholinergic vs serotonin syndrome vs NMS

›Skin moisture: wet (sympathomimetic) vs dry (anticholinergic)

›Bowel sounds: present (sympathomimetic) vs absent (anticholinergic)

›Clonus: present in serotonin syndrome

›Onset speed: rapid (sympathomimetic) vs days (NMS)

›Poison Control scoring not standardized but clinical severity classification used

›Mild: agitation only, vital signs mildly elevated

›Moderate: significant vital sign elevation, single-system involvement

›Severe: multi-system failure, hyperthermia >40 degrees C, seizures

›GRACE or TIMI score if ACS suspected

›TIMI score for chest pain risk stratification

›Stimulant use increases risk even in young low-score patients

›AHA Class IIa: consider coronary evaluation in cocaine chest pain

MRI

›Brain MRI indications

›Focal neurological deficits after initial stabilization

›Ischemic stroke from cocaine vasospasm

›Intracerebral hemorrhage from hypertensive emergency

07Disposition/dispo49

ICU admission criteria

›ICU-level indications

›Hyperthermia >40 degrees C

›Continuous cooling therapy required

›Organ failure monitoring

›Cardiac arrest or life-threatening arrhythmias

›Post-resuscitation care

›Targeted temperature management consideration

›Seizures or status epilepticus

›Continuous EEG monitoring consideration

›Refractory status protocol

›Severe metabolic acidosis

›pH <7.0 or lactate >4 mmol/l

›Hemodynamic instability requiring vasopressors

›Significant rhabdomyolysis

›CK >5000 U/L or rising

›AKI requiring aggressive IVF

›ACS or Takotsubo cardiomyopathy

›Intracranial hemorrhage or ischemic stroke

Telemetry or monitored bed criteria

›Stepdown or telemetry indications

›Persistent tachycardia or hypertension requiring ongoing sedation

›Troponin elevation without hemodynamic compromise

›Moderate rhabdomyolysis requiring IV fluids

›CK 1000 to 5000 U/L

›Normal renal function

›Ongoing benzodiazepine dosing required

›QTc prolongation on ECG

08Treatment/t148

Immediate sedation protocol

›Benzodiazepines (first-line)

›Diazepam IV

›5 to 10 mg IV every 5 minutes

›No ceiling dose in severe agitation

›Titrate to cessation of agitation and normalization of vitals

›Midazolam IV or IM

›5 mg IV or IM every 5 minutes

›IM preferred when IV access unavailable

›Rapid onset by IM route

›Lorazepam IV

›2 to 4 mg IV every 5 to 10 minutes

›Alternative when diazepam or midazolam unavailable

›AHA 2023 Guideline: benzodiazepines are first-line GABAergic therapy for sympathomimetic toxicity

Second-line sedation and adjuncts

›Phenobarbital

›15 to 20 mg/kg IV loading dose

›Rate 50 to 100 mg/min

›For refractory agitation after benzodiazepines

›Synergistic with benzodiazepines via GABA-A receptor

›Propofol

›1 to 2 mg/kg IV bolus then infusion

›Infusion rate 5 to 50 mcg/kg/min

›Requires intubation and airway protection

›ASAM/AAAP 2024 Guideline: second-line GABAergic agent

›Dexmedetomidine

›0.2 to 1.5 mcg/kg/h IV infusion

›No bolus loading in hemodynamically unstable patients

›Alpha-2 agonist reduces central sympathetic outflow

›For severe symptoms with preserved airway

›Ketamine

›1 to 2 mg/kg IV or 4 to 5 mg/kg IM

›Dissociative sedation for extreme agitation

›May transiently worsen tachycardia and hypertension

›Short duration allows reassessment

Hyperthermia management

›External cooling

›Ice water immersion

›Most effective cooling method

›Cooling rate >0.15 degrees C/min target

›Cold water with agitation of extremities

›Evaporative cooling

›Cold water misting with fan

›Alternative when immersion not feasible

›Ice packs to groin, axillae, and neck

›Adjunct to primary cooling method

›Less effective as sole method

›Cooling adjuncts

›Antipyretics ineffective

›Acetaminophen does not reduce metabolic hyperthermia

›Hyperthermia from muscular and metabolic heat not hypothalamic reset

›Dantrolene sodium

›Conflicting data for MDMA-induced hyperthermia

›Not standard of care for sympathomimetic toxicity

›Consider only in refractory malignant hyperthermia

Antihypertensive therapy

›Adequate sedation first

›Most hypertension resolves with benzodiazepine sedation

›AHA 2023 Guideline: sedation should precede antihypertensive therapy

›Reassess BP after adequate sedation achieved

›Persistent hypertensive emergency management

›Phentolamine

›5 mg IV bolus then infusion

›Alpha-1 antagonist: ideal for cocaine-induced hypertension

›Short duration of action

›Nicardipine

›5 mg/h IV infusion titrating by 2.5 mg/h every 15 minutes

›Maximum 15 mg/h

›Dihydropyridine CCB: safe in cocaine toxicity

›Sodium nitroprusside

›0.3 mcg/kg/min IV starting dose

›Titrate to 10 mcg/kg/min

›For refractory hypertensive emergency

›Nitroglycerin

›5 to 200 mcg/min IV infusion

›Preferred when cardiac ischemia present

›Coronary vasodilation benefit in cocaine-induced vasospasm

›Contraindicated antihypertensives

›Pure beta-blockers (propranolol, metoprolol)

›Risk of unopposed alpha stimulation

›Worsening hypertension and vasospasm especially with cocaine

›ASAM/AAAP 2024 Guideline: avoid pure beta-blockers

›Long-acting antihypertensives

›Risk of abrupt hemodynamic collapse as stimulant wears off

Mixed alpha-beta blocker use

›Labetalol or carvedilol

›Alpha-1 and non-selective beta blockade

›Reduces unopposed alpha risk vs pure beta-blockers

›Labetalol 20 mg IV bolus, repeat 40 to 80 mg every 10 min

›Maximum cumulative dose 300 mg

›Caution in cocaine toxicity

›ASAM/AAAP 2024: consult cardiology or toxicology before use

›Safer than pure beta-blockers but not first-line

Seizure management

›Benzodiazepines first-line for toxin-induced seizures

›Diazepam 5 to 10 mg IV or lorazepam 2 to 4 mg IV

›Repeat every 5 to 10 minutes until seizure controlled

›Midazolam 5 to 10 mg IM if no IV access

›Refractory seizure management

›Phenobarbital 15 to 20 mg/kg IV

›For benzodiazepine-refractory seizures

›Propofol infusion with intubation

›For status epilepticus refractory to phenobarbital

›Avoid phenytoin

›Ineffective for toxin-induced seizures

›May worsen cardiac conduction abnormalities

Rhabdomyolysis management

›IV fluid resuscitation

›Normal saline 0.9% aggressive resuscitation

›Initial 1 to 2 L bolus

›Target urine output >2 mL/kg/h

›Adjust rate to maintain target output

›Lactated Ringer acceptable alternative

›Monitoring during fluid resuscitation

›Serial CK every 6 to 8 hours

›Electrolytes with potassium monitoring

›Hyperkalemia from muscle breakdown

›Renal function trend

›Urinary alkalinization

›Avoid in amphetamine-related rhabdomyolysis

›Inhibits amphetamine elimination by raising urine pH

›AAAP 2023 Guideline: alkalinization not recommended with amphetamines

›Theoretical benefit in myoglobin precipitation prevention outweighed by concerns

›Electrolyte management

›Hyperkalemia treatment

›Calcium gluconate for cardiac stabilization if ECG changes

›Insulin-dextrose for intracellular shift

›Hyponatremia correction

›Careful correction rate in MDMA-induced cases

›Maximum 10 to 12 mmol/l per 24 hours

Cardiac complication management

›Cocaine or amphetamine-induced ACS

›Nitroglycerin for vasospasm

›Sublingual or IV based on severity

›First-line for vasospasm-mediated ischemia

›Aspirin 325 mg oral

›Antiplatelet therapy for thrombotic component

›CCBs for refractory vasospasm

›Verapamil or diltiazem

›Avoid in decompensated HF

›Avoid pure beta-blockers in cocaine ACS

›JACC 2021 Guideline: increased mortality risk

›Takotsubo cardiomyopathy

›Often resolves spontaneously in days to weeks

›Supportive care with hemodynamic monitoring

›Cardiogenic shock management

›Consider VA-ECMO or IABP in refractory cases

›AHA 2025 Guidelines: mechanical circulatory support as bridge

Body packing management

›Conservative vs surgical approach

›Stable patient without packet rupture

›Whole bowel irrigation with polyethylene glycol

›1 to 2 L/h via nasogastric tube until rectal effluent clear

›Surgical emergency indications

›Packet rupture with toxidrome

›Bowel obstruction

›Failure of conservative management

09Special Populations/sp73

Pregnancy

›Physiological considerations in pregnancy

›Cocaine use in pregnancy

›Placental abruption risk dramatically increased

›Placental vasoconstriction mechanism

›Preeclampsia mimic from hypertension and proteinuria

›Fetal effects

›Fetal tachycardia and distress

›Preterm labor risk

›Uteroplacental insufficiency

›Modified management in pregnancy

›Benzodiazepines relatively safe in acute overdose

›Risk of neonatal withdrawal with prolonged use

›First-line remains benzodiazepines for maternal safety

›Antihypertensive selection

›Hydralazine 5 to 10 mg IV every 20 minutes acceptable

›Labetalol IV acceptable in pregnancy

›Avoid ACE inhibitors and sodium nitroprusside (fetal cyanide toxicity)

›Continuous fetal monitoring

›External fetal monitoring for viable fetus (>24 weeks)

›Obstetrics consult mandatory for all cases

›MDMA and hyponatremia

›Severe hyponatremia particularly dangerous in pregnancy

›Seizure threshold lower

Geriatric

›Physiological changes affecting presentation

›Blunted sympathomimetic response

›Tachycardia may be less pronounced despite significant toxicity

10Background/b96

Epidemiology

›Prevalence and incidence

›Stimulant use rates

›Cocaine use affects approximately 1.9% of adults in North America annually

›Methamphetamine use increased dramatically in last decade

›MDMA use most prevalent in rave and festival settings

›ED visits

›Stimulant-related ED visits increasing year over year

›Methamphetamine overtaking cocaine in many regions

›Cathinone (bath salt) emergence since 2010

›Demographics

›Young adults most affected (18 to 35 years)

›However, stimulant-induced MI can occur in young patients with normal coronaries

›JACC 2021: chronic stimulant use causes accelerated atherosclerosis

›Sex distribution

›Males predominant in most stimulant toxicity presentations

›MDMA more equal sex distribution

›Mortality and morbidity

›Hyperthermia-associated mortality highest risk

›Core temp >41 degrees C associated with multi-organ failure

›Polydrug toxicity dramatically increases mortality

›Synthetic cathinone combinations particularly fatal

›JEM 2026: fatal polydrug cathinone toxicity case series

Pathophysiology

›Mechanism of adrenergic excess

›Catecholamine release and reuptake inhibition

›Cocaine: blocks reuptake of dopamine, norepinephrine, serotonin

›Amphetamines: reverse transport releasing catecholamines from vesicles

›Cathinones: similar to amphetamines but variable potency

›Downstream receptor activation

›Alpha-1 activation: vasoconstriction, hypertension

›Beta-1 activation: tachycardia, increased contractility

›Beta-2 activation: bronchodilation, metabolic effects

›Dopamine activation: psychomotor effects, paranoia

›Hyperthermia pathophysiology

›Muscular hyperactivity as primary heat source

›Agitation, seizures, and rigidity all generate heat

›Not hypothalamic-mediated (explains antipyretic ineffectiveness)

›Impaired heat dissipation

›Peripheral vasoconstriction reduces radiation

›Hot environment limits conduction and convection

›Mitochondrial uncoupling in severe cases

›Direct cellular thermogenic effect

›Rhabdomyolysis mechanism

›Prolonged muscle hyperactivity and seizures

›ATP depletion in muscle cells

›Calcium influx and cell death

›Direct toxic effects on muscle

›Cocaine-induced vasospasm causing ischemia

›Myoglobin release and renal tubular injury

›Direct tubular toxicity at low pH

›Cast formation causing obstruction

›Cardiac pathophysiology

›Coronary vasospasm

›Alpha-1 mediated in cocaine toxicity

›Can occur with angiographically normal coronaries

›Accelerated atherosclerosis from chronic use

›Endothelial dysfunction

›Premature CAD in young chronic users

›Catecholamine-mediated cardiomyopathy

›Takotsubo pattern from massive catecholamine surge

›Apical ballooning pattern

›Usually reversible over days to weeks

Therapeutic Considerations

›GABAergic sedation rationale

›Benzodiazepines address root cause of most complications

›Reduce agitation and muscle hyperactivity

›Blunt sympathetic overdrive

›Reduce seizure activity

›Treat hyperthermia indirectly via muscle relaxation

›No ceiling dose principle

›Large doses may be required in severe toxicity

›Resistance common in chronic stimulant users

›Escalate to second-line agents promptly if inadequate response

›Beta-blocker controversy

›Pure beta-blockers avoid due to unopposed alpha

›Reflex increase in peripheral vasoconstriction

›Hypertension worsening and coronary vasospasm

›Mixed alpha-beta blockers debated

›Labetalol may be safer than pure beta-blockers

›Still not first-line due to theoretical concerns

›AHA 2023 Guideline: adequate sedation is primary intervention for BP control

›Duration of observation

›Cocaine: relatively short half-life (30 to 90 minutes)

›Metabolites may have longer cardiovascular effects

›Clinical observation typically 4 to 6 hours

›Methamphetamine: much longer duration (12 to 24 hours)

›Extended observation required

›Discharge timing adjusted accordingly

›Synthetic cathinones: variable and often prolonged

›Some cases require 24 to 48 hours observation

›Evidence levels summary

›Class I recommendation: benzodiazepines for agitation and seizures

›AHA 2023 Guideline

›Class I recommendation: external cooling for hyperthermia >40 degrees C

›AHA 2025 Guidelines for Special Circumstances

›Class IIa recommendation: avoid pure beta-blockers in cocaine toxicity

›AHA 2023 Guideline

›ACEP Level B: poison control consultation for all significant stimulant toxicity

11Patient Discharge Instructions/pdi29

copy discharge instructions

›Discharge instructions for sympathomimetic toxicity

›What happened

›You were treated for an overdose or toxic reaction to a stimulant drug

›Your symptoms were caused by the drug overstimulating your nervous system

›There is no antidote for stimulant drugs; treatment is supportive care

›What to expect at home

›Fatigue and low mood are common after stimulant intoxication (crash phase)

›Duration depends on the substance: cocaine effects last 4 to 8 hours; methamphetamine effects can last up to 24 hours

›Muscle soreness may persist for several days if muscle breakdown occurred

›Medications prescribed

›Take as directed; do not miss follow-up blood work if ordered

›Follow-up instructions

›Primary care or addiction medicine within 1 to 2 weeks

›Cardiology follow-up if heart involvement occurred

›Blood work for kidney function and muscle enzymes if rhabdomyolysis present

›Return to emergency department immediately for

›Chest pain, pressure, or palpitations

›Seizures

›Muscle pain with dark or tea-colored urine

›Decreased urine output

›High fever or confusion

›Severe headache

›Weakness in any limb

›Safety and harm reduction

›Stimulant drugs can cause heart attacks and strokes even in young healthy people

›Mixing stimulants with other drugs dramatically increases the risk of death

›Avoid using stimulants alone; have someone present

12References/r45

Guidelines and key sources

›AHA 2025 Resuscitation Guidelines

›Cao D, Arens AM, Chow SL, et al.

›Part 10: Adult and Pediatric Special Circumstances of Resuscitation

›2025 American Heart Association Guidelines for CPR and ECC

›Circulation 2025

›AHA 2023 Focused Update on Toxicology

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

›2023 AHA Focused Update: Management of Patients With Cardiac Arrest or Life-Threatening Toxicity Due to Poisoning

›Circulation 2023

›ASAM/AAAP Clinical Practice Guideline 2024

›The ASAM/AAAP Clinical Practice Guideline on the Management of Stimulant Use Disorder

›Journal of Addiction Medicine 2024

›PMCID PMC11105801

›AAAP Stimulant Use Disorder Guideline 2023

›Batki S, Ciccarone D, Hadland SE, et al.

›Management of Stimulant Use Disorder

›American Academy of Addiction Psychiatry 2023

›AHA/ACC Chest Pain Guideline 2021

›Gulati M, Levy PD, Mukherjee D, et al.

›2021 AHA/ACC Guideline for the Evaluation and Diagnosis of Chest Pain

›Journal of the American College of Cardiology 2021

Additional references

›Cardiac arrhythmias from stimulants

›Dominic P, Ahmad J, Awwab H, et al.

›Stimulant Drugs of Abuse and Cardiac Arrhythmias

›Circ Arrhythm Electrophysiol 2022

›PMID 34061335

Evidence & Review