01Approach to the Critical Patient/attcp58

Immediate life threats

›Airway threats

›Altered mental status with inability to protect airway

›GCS < 8 or rapidly declining

›Active vomiting with obtundation

›If airway compromise, proceed to rapid sequence intubation

›Ketamine 1 to 2 mg/kg IV preferred induction agent

›Avoid succinylcholine if rhabdomyolysis suspected due to hyperkalemia risk

›Hyperthermia emergency

›Core temperature > 40 degrees C

›Rapidly life-threatening, especially with MDMA

›Immediate aggressive cooling required

›Initiate evaporative cooling or ice water immersion

›Target temperature < 39 degrees C within 30 minutes

›Continuous core temperature monitoring

›Benzodiazepines to reduce thermogenesis from agitation

›Lorazepam 2 to 4 mg IV or IM

›Repeat dosing as needed every 5 to 10 minutes

›Seizure management

›Benzodiazepines first-line for all toxin-associated seizures

›Lorazepam 2 to 4 mg IV or midazolam 5 mg IM

›Repeat in 5 minutes if seizure persists

›If refractory, phenobarbital 15 to 20 mg/kg IV

›Avoid phenytoin for toxin-associated seizures

›Consider propofol infusion for status epilepticus

Hemodynamic priorities

›Hemodynamic targets

›Heart rate target < 100 beats per minute

02History/hx76

Substance identification

›Specific substance ingested

›Classic serotonergic psychedelics

›LSD (lysergic acid diethylamide)

›Psilocybin (mushrooms)

›DMT (dimethyltryptamine)

›Mescaline or peyote

›Phenethylamine derivatives

›MDMA (ecstasy, molly)

›2C series compounds

›NBOMe compounds (sold as LSD but far more toxic)

›Dissociative hallucinogens

›PCP (phencyclidine)

›Ketamine

›Route, dose, and timing

›Route of exposure

›Oral, sublingual, insufflation, IV

›Sublingual blotter paper may be NBOMe not LSD

›Time of ingestion

›LSD duration 8 to 12 hours

›Psilocybin duration 4 to 6 hours

›Dose if known

›LSD typically 75 to 150 micrograms

›NBOMe active at much lower doses with higher toxicity

Co-ingestions and risk context

›Co-ingestions

›Polysubstance use present in 41% of psychedelic exposures

›Alcohol co-ingestion common

03Physical Exam/exam58

Vital signs

›Vital sign abnormalities

›Temperature

›Core temperature via rectal probe preferred

›Oral and axillary measurements unreliable in agitated patients

›Hyperthermia > 40 degrees C requires immediate intervention

›Heart rate

›Tachycardia in 18 to 39% of cases

›Extreme tachycardia risk for dysrhythmia

›Blood pressure

›Hypertension from sympathomimetic effects

›SBP > 180 mmHg with symptoms requires urgent management

›Respiratory rate

›Tachypnea with agitation or hyperthermia

›Respiratory depression with polysubstance use including opioids

Toxidrome characterization

›Classic hallucinogen findings

›Mydriasis

›Hallmark finding across most hallucinogens

›Bilateral and symmetric

›Diaphoresis

›Distinguishes from anticholinergic toxidrome where skin is dry

›Prominent with serotonergic agents and MDMA

›Tachycardia and hypertension

›Sympathomimetic component

›Most prominent with phenethylamine class

›Serotonin toxicity exam

›Hyperreflexia

04Differential Diagnosis/ddx53

Life-threatening mimics

›Serotonin syndrome

›ICD-10 T65.891

›Clonus, hyperreflexia, and diaphoresis distinguishing triad

›Can co-occur with hallucinogen use

›Most common with MDMA plus serotonergic medications

›SSRIs, MAOIs, tramadol, linezolid

›Rapid onset within hours of drug use

›Neuroleptic malignant syndrome

›ICD-10 G21.0

›Slow onset over days distinguishes from serotonin syndrome

›Lead-pipe rigidity and bradykinesia

›Associated with antipsychotic use

›Hyporeflexia rather than hyperreflexia

›Significant temperature elevation and autonomic instability

›Malignant hyperthermia

›Triggered by volatile anesthetics or succinylcholine

›Severe muscle rigidity

›Rapid rise in core temperature

Sympathomimetic toxidromes

›Amphetamine or cocaine toxicity

›Similar tachycardia, hypertension, agitation, and mydriasis

›Prominent hallucinations and perceptual distortions favor hallucinogen

›Cocaine chest pain from coronary vasospasm

›Urine drug screen may cross-react

›MDMA cross-reacts with amphetamine immunoassay

›Clinical toxidrome guides management regardless

›Anticholinergic toxidrome

05Laboratory Tests/lt61

Point-of-care and urgent labs

›Glucose

›Bedside POC glucose in all altered mental status

›Hypoglycemia mimics and co-exists with intoxication

›Target normoglycemia

›Creatine kinase

›CK elevation for rhabdomyolysis screening

›Elevated CK in 100% of confirmed 25I-NBOMe cases in one series

›Serial CK monitoring every 6 to 12 hours if elevated

›CK > 5000 units/L indicates severe rhabdomyolysis

›Aggressive IV fluid resuscitation indicated

›Monitor for AKI

›Comprehensive metabolic panel

›Electrolytes

›Hyponatremia from MDMA-induced SIADH

›Avoid free water overload; use isotonic fluids

›Renal function

›AKI from rhabdomyolysis or direct toxicity

›Creatinine and BUN trending

›Hepatic function

›MDMA hepatotoxicity possible

›Drug metabolism assessment

Toxicology screening

›Urine drug screen

›Limited utility for classic hallucinogens

›LSD, psilocybin, and NBOMes not detected on standard immunoassay

›MDMA cross-reacts with amphetamine immunoassay panel

›PCP detected on most standard urine screens

06Diagnostic Tests/dt63

Scoring Systems

›Hunter Serotonin Toxicity Criteria

›Diagnostic tool for serotonin syndrome

›Requires serotonergic agent exposure

›Plus one of: spontaneous clonus, inducible clonus with agitation or diaphoresis, ocular clonus with agitation or diaphoresis, tremor with hyperreflexia, or hypertonia with temperature > 38 degrees C and ocular or inducible clonus

›Sensitivity 84% and specificity 97% versus Sternbach criteria

›More specific than the original Sternbach criteria

›Clonus is the most important clinical feature

›Stimulant Observation Scale and Agitation Scoring

›Clinical assessment of agitation severity

›Guides chemical sedation dosing

›Aids monitoring of treatment response

›Richmond Agitation Sedation Scale (RASS) for ICU

›Target RASS 0 to -1 for sedated patients

›Avoid over-sedation with respiratory compromise

›MDMA-specific risk stratification

›No validated ED risk score

›Temperature, CK, sodium, and hemodynamic status guide severity

›Clinical trajectory more important than single values

MRI

›MRI brain indications in hallucinogen toxicity

›Limited acute utility as first-line imaging

›CT head preferred for acute hemorrhage exclusion

›Availability and patient cooperation constraints

›Problem-solving indications

›Persistent altered mental status beyond expected drug duration

›Suspected encephalitis or posterior reversible encephalopathy syndrome

›PRES risk with severe hypertension

07Disposition/dispo57

Admission criteria

›Inpatient admission indications

›Persistent hyperthermia

›Temperature > 39 degrees C on repeat measurement

›Ongoing cooling requirement

›Seizures

›Any seizure activity warrants observation period

›Risk of recurrence especially with NBOMe compounds

›Rhabdomyolysis

›Elevated CK requiring IV fluid management

›Serial renal function monitoring required

›Hemodynamic instability

›Dysrhythmias requiring monitoring or treatment

›Hypertensive emergency

›Persistent altered mental status or psychosis

›Beyond expected drug duration

›LSD patients more likely to require admission than psilocybin

›ICU admission indications

›Core temperature > 40 degrees C with rigidity or clonus

›Multi-organ failure risk

›May require intubation for cooling

›DIC or multi-organ failure

›Coagulopathy, AKI, hepatic injury

›High mortality without aggressive support

›Cardiac arrest or life-threatening dysrhythmia

›Post-resuscitation care

›Continuous hemodynamic monitoring

08Treatment/t98

Chemical sedation for agitation

›Benzodiazepines as cornerstone therapy

›Lorazepam IV or IM

›2 to 4 mg IV or IM initially

›Repeat every 5 to 10 minutes as needed

›Preferred when IV access available

›Midazolam IM

›5 mg IM as initial dose

›Fastest onset for agitated patient without IV access

›May repeat 5 mg in 10 minutes if inadequate effect

›Diazepam IV

›5 to 10 mg IV for seizures or severe agitation

›Longer duration of action reduces repeat dosing need

›Avoid antipsychotics in hallucinogen toxicity

›Risk of lowering seizure threshold

›Particularly with NBOMe and MDMA

›Increased seizure frequency reported

›Risk of worsening hyperthermia

›Impair heat dissipation

›NMS risk in susceptible patients

›Risk of hypotension and QTc prolongation

›Haloperidol increases QTc

›Droperidol and ziprasidone additional QTc risk

Hyperthermia management

›Aggressive cooling protocol

›First-line evaporative cooling

›Mist sprayed on skin with fan

›Effective and widely available

›Ice water immersion

›Preferred for fastest cooling rate

›Target temperature < 39 degrees C

›Avoid cooling blankets alone

›Inferior cooling rate

›Acceptable as adjunct only

›Pharmacologic adjuncts

›Dantrolene

›1 to 2.5 mg/kg IV for MDMA-induced hyperthermia

›Conflicting evidence; consider if temperature > 39 degrees C refractory to cooling

›Maximum 10 mg/kg per day

›Benzodiazepines reduce thermogenesis

›Decrease agitation-driven muscle heat generation

›First-line before dantrolene

›Paralysis and ventilation if refractory

›Non-depolarizing neuromuscular blockade

›Rocuronium 1.2 mg/kg IV

›Eliminates muscle rigidity as heat source

›Requires intubation and mechanical ventilation

›Continuous EEG monitoring to detect occult seizures

›Temperature monitoring every 15 minutes

Serotonin syndrome management

›Discontinue all serotonergic agents

›SSRIs, MAOIs, triptans, tramadol, linezolid

›Half-life determines duration of effect

›MAOIs may have prolonged effect requiring extended monitoring

›Cyproheptadine for moderate to severe serotonin syndrome

›12 mg PO loading dose

›Then 2 mg every 2 hours until improvement

›Only available as oral formulation

›Mechanism: serotonin 5-HT2A receptor antagonist

›Adjunct to benzodiazepines not replacement

›Maximum 32 mg in 24 hours

›Benzodiazepines for agitation and rigidity

›Lorazepam 2 to 4 mg IV repeated as needed

›Reduce muscle heat generation

›Titrate to clinical improvement

Rhabdomyolysis management

›Aggressive IV fluid resuscitation

›Normal saline 1 to 1.5 L per hour initially

›Target urine output 1 to 2 mL/kg/hr

›Adjust rate based on urine output and cardiac status

›Serial CK monitoring

›Every 6 to 12 hours until trending down

›Creatinine and electrolytes concurrent

›Urine alkalinization

›Sodium bicarbonate if CK very elevated

›Target urine pH > 6.5

›Reduces myoglobin precipitation in tubules

›Contraindication: avoid urine acidification

›Acidification promotes myoglobin precipitation

›Contraindicated when CK elevated

Hypertension management

›Benzodiazepines as first-line

›Reduce sympathomimetic drive

›Effective for most cases of drug-induced hypertension

›Lorazepam 2 to 4 mg IV titrated to effect

›Nitrates for refractory hypertension with chest pain

›Nitroglycerin IV infusion

›5 to 200 mcg/min titrated to SBP < 160 mmHg

›Monitor for reflex tachycardia

›Phentolamine IV for alpha-adrenergic excess

›5 to 10 mg IV bolus

›Alpha blocker preferred when catecholamine excess dominant

›Avoid beta-blockers

›Risk of unopposed alpha-adrenergic stimulation

›Paradoxical severe hypertension possible

›Particularly dangerous with phenethylamine class hallucinogens

MDMA-induced hyponatremia

›Mechanism: SIADH plus excessive water intake

›Free water restriction

›Isotonic saline preferred over hypotonic fluids

›Avoid free water overload

›Sodium monitoring every 2 to 4 hours

›Severe hyponatremia < 120 mmol/l requires hypertonic saline

›Correction rate < 10 to 12 mmol/l per 24 hours to avoid osmotic demyelination

09Special Populations/sp75

Pregnancy

›Pregnancy-specific considerations

›Hallucinogen use in pregnancy

›Limited safety data for most agents

›Reported spontaneous abortion and preterm labor association with MDMA

›Teratogenicity risk

›Psilocybin and LSD animal data show embryotoxicity at high doses

›Human data insufficient to quantify risk

›Management modifications in pregnancy

›Imaging

›CT head with lead shielding when clinically indicated

›MRI preferred over CT if both are acceptable options

›Fetal radiation dose from single CT head is < 1 mGy

›Medication safety

›Benzodiazepines category D but acceptable for life-threatening agitation or seizures

›Lorazepam preferred over diazepam for shorter fetal exposure

›Maternal hyperthermia treatment

›Temperature > 38.5 degrees C associated with neural tube defect risk in first trimester

›Aggressive cooling priority same as non-pregnant patients

›Fetal monitoring

›Continuous fetal heart rate monitoring when viable gestation

›Maternal tachycardia and hyperthermia can cause fetal distress

›Obstetrics consultation for viable gestations

›MDMA-induced vasoconstriction

›Reduced uteroplacental blood flow

›Fetal acidosis risk

Geriatric

›Older adult presentation differences

›Atypical presentations more common

›Delirium may be the primary symptom

›Baseline dementia complicates assessment

›Physiologic reserve reduced

›Higher risk of severe hyperthermia complications

›Rhabdomyolysis with lower CK elevations causing AKI

›Pharmacokinetic differences

›Reduced hepatic and renal clearance

›Prolonged drug effect duration

›Accumulation risk with repeated benzodiazepine dosing

›Benzodiazepine sensitivity increased

›Lower initial doses recommended

›Lorazepam 1 to 2 mg IV initial dose

›Risk of paradoxical agitation

›Co-medication risks

›Polypharmacy with serotonergic agents common

›SSRIs for depression and anxiety prevalent in older adults

›MAOIs used for atypical depression

›QTc prolongation risk higher

›Baseline QTc review before any QTc-prolonging treatment

›Cardiac monitoring mandatory

›Disposition tendency toward admission

›Limited physiologic reserve

›Frailty increases complication risk

›Social supports may be limited

Pediatrics

›Pediatric epidemiology

›Adolescents 13 to 17 years at highest risk

›Emerging use of psilocybin and MDMA

›NBOMe sold as LSD particular danger

›HPPD in adolescents

›Case reports in 16-year-olds after single use

›Developing brain may have prolonged vulnerability

›Pediatric management differences

›Weight-based benzodiazepine dosing

›Lorazepam 0.05 to 0.1 mg/kg IV or IM, maximum 4 mg per dose

›Midazolam 0.1 to 0.15 mg/kg IM, maximum 10 mg per dose

›Temperature thresholds

›Hyperthermia > 38.5 degrees C warrants treatment in children

›Lower threshold than adults due to metabolic rate differences

›Rhabdomyolysis fluid targets

›Normal saline 20 mL/kg IV bolus for rhabdomyolysis

›Target urine output 2 to 3 mL/kg/hr in young children

›Mandatory reporting considerations

›Child protection assessment if chronic substance use in minors

›Neglect or abuse assessment when appropriate

›Social work consultation for substance use in young adolescents

›Adolescent confidentiality laws vary by jurisdiction

›Consult institutional policy

›Safety considerations override confidentiality when life-threatening

10Background/b97

Epidemiology

›Incidence and population data

›Age and sex distribution

›Age 13 to 29 years predominate in case series

›74 to 78% male in poison center data

›Poison center exposure trends

›Psychedelic exposures to US poison centers increasing 2012 to 2022

›LSD and psilocybin most common classic agents reported

›Polysubstance co-exposure

›41% of psychedelic exposures involve concomitant substances

›Alcohol most common co-ingestant

›Agent-specific mortality and morbidity

›Classic psychedelics low mortality

›LSD and psilocybin rarely fatal in isolation

›Most treated and released from ED

›NBOMe compounds significantly higher morbidity and mortality

›Death rate approximately 2.3% in poison center data

›Seizures in 8.8% of NBOMe exposures

›MDMA mortality associated with hyperthermia

›Dance festival deaths predominantly from hyperthermia

›Hyponatremia secondary cause of MDMA-associated death

›Novel psychoactive substance concern

›NBOMes sold as LSD on blotter paper

›Users often unaware of actual agent ingested

›Dramatically higher toxicity profile than classic LSD

›2C series phenethylamines

›Potent sympathomimetic and serotonergic activity

›Emerging case reports of severe toxicity

Pathophysiology

›Classic serotonergic psychedelics mechanism

›Primary 5-HT2A receptor agonism

›Cortical serotonin receptor activation

›Glutamate release in prefrontal cortex mediates perceptual effects

›LSD pharmacokinetics

›Oral bioavailability high

›Half-life approximately 3 to 5 hours with prolonged receptor binding

›Duration of effect 8 to 12 hours despite short plasma half-life

›Psilocybin pharmacokinetics

›Metabolized to psilocin as active compound

›Duration 4 to 6 hours

›Excreted renally

›MDMA mechanism and toxicity

›Monoamine release and reuptake inhibition

›Serotonin, dopamine, norepinephrine simultaneous release

›Reversal of transporter function increases synaptic monoamines

›Thermogenesis mechanisms

›Serotonin-mediated hypothalamic dysregulation

›Increased skeletal muscle activity and reduced heat dissipation

›Exertion and hot environment dramatically amplify risk

›SIADH mechanism

›MDMA stimulates ADH release

›Combined with excessive hypotonic fluid intake at dance events

›Results in severe and rapidly developing hyponatremia

›NBOMe compound toxicology

›High potency 5-HT2A partial agonists with additional activity

›Sublingual absorption from blotter paper

›Active at microgram doses similar to LSD

›Cardiovascular toxicity

›Direct cardiotoxicity demonstrated in iPSC cardiomyocyte models

›Coronary vasospasm and dysrhythmia mechanisms

›PCP and dissociative mechanism

›NMDA receptor antagonism

›Blocks glutamate at NMDA receptor

›Dissociative anesthesia, analgesia, and psychotomimetic effects

›Dopaminergic and sigma receptor activity

›Psychosis component mediated by dopamine

›Sigma receptor binding contributes to unusual behavioral effects

Therapeutic Considerations

›Benzodiazepine primacy in management

›Address multiple mechanisms simultaneously

›Reduce agitation and thermogenesis

›Anticonvulsant effect for seizures

›Anxiolytic for panic and bad trip

›No ceiling effect concerns in acute toxicity

›Titrate to clinical effect

›Monitor respiration with high doses

›Antipsychotic avoidance rationale

›Proconvulsant effects documented

›Lower seizure threshold particularly dangerous with NBOMe

›Risk outweighs benefits versus benzodiazepines

›Hyperthermia worsening

›Block dopamine-mediated thermoregulation

›May precipitate NMS in vulnerable patients

›QTc prolongation additive with hallucinogen-induced cardiac effects

›Risk of torsade de pointes

›Cooling modality evidence

›Evaporative cooling vs ice water immersion

›Both superior to cooling blankets

›Ice water immersion fastest reduction in core temperature

›Practical in most ED settings with ice bags in axillae, groin, and neck

›Target temperature < 39 degrees C

›Avoid overshoot into hypothermia with aggressive cooling

›Stop active cooling at 39 degrees C and monitor

›Novel psychoactive substance management uncertainty

›Unknown agent creates management challenges

›Treat toxidrome not substance

›Supportive care with benzodiazepines appropriate for all classes

›Poison Control consultation essential

›Emerging toxicology data for novel agents

›Expert guidance for unusual presentations

11Patient Discharge Instructions/pdi46

copy discharge instructions

›Hallucinogen toxicity home care

›Rest at home with a responsible adult present for 24 hours

›Classic psychedelic effects resolve within 6 to 12 hours for LSD

›Psilocybin effects resolve within 4 to 6 hours

›Mood changes, anxiety, or sleep disturbance may persist days to weeks

›This is called the subacute afterglow period

›Does not mean lasting brain damage in most cases

›Avoid alcohol and other substances

›Do not take any new medications without consulting a doctor

›Avoid serotonergic medications unless your doctor approves

›Stay well hydrated with water or sports drinks

›Do not drink excessive amounts of plain water

›Isotonic fluids preferred

›Warning signs to return to the emergency department immediately

›Hallucinations returning hours or days after the drug wore off

›This may indicate HPPD (hallucinogen persisting perception disorder)

›Can develop after even a single use

›Fever, shaking chills, or feeling very hot

›Temperature above 38.5 degrees C at home

›Do not wait to seek help

›Dark or cola-colored urine

›Decreased urine output

›Signs of muscle breakdown in kidneys

›Chest pain, racing heart, or fainting

›Cardiac complications from stimulant-type hallucinogens

›Call 911 or go to ER immediately

›Persistent anxiety, paranoia, or inability to distinguish reality

12References/r38

Guidelines and key sources

›Primary clinical guidelines

›2023 American Heart Association Focused Update on Management of Patients with Cardiac Arrest or Life-Threatening Toxicity Due to Poisoning (Lavonas et al., Circulation 2023)

›Management of toxin-associated cardiac arrest

›Class recommendations for antidotal and resuscitative therapies

›2025 AHA CPR and Emergency Cardiovascular Care Guidelines Part 10 (Cao et al., Circulation 2025)

›Adult and pediatric special circumstances of resuscitation

›Toxicology resuscitation updates

›ACEP Clinical Policy: Critical Issues in Diagnosis and Management of Adult Psychiatric Patient in ED (Nazarian et al., Annals of Emergency Medicine 2017)

›ACEP Level recommendations for psychiatric emergencies

›Key epidemiologic and pharmacology studies

›Leonard JB, Anderson B, Klein-Schwartz W. Journal of Psychopharmacology 2018

›LSD and psilocybin-containing mushroom exposures to national poison centers 2000 to 2016

›41% polysubstance co-exposure rate; demographic and outcome data

›Simon MW, Olsen HA, Hoyte CO et al. Annals of Emergency Medicine 2024

›Clinical effects of psychedelic substances reported to US poison centers 2012 to 2022

›Srisuma S, Bronstein AC, Hoyte CO. Clinical Toxicology 2015

›NBOMe and 2C substitute phenylethylamine exposures to national poison data system

›NBOMe death rate approximately 2.3% and seizure rate 8.8%

›Serotonin syndrome references

›Boyer EW, Shannon M. New England Journal of Medicine 2005

›Serotonin syndrome: mechanism, clinical features, Hunter criteria

›Malcolm B, Thomas K. Psychopharmacology 2022

›Serotonin toxicity of serotonergic psychedelics

›Cyproheptadine dosing and evidence

›Spadaro A, Scott KR, Koyfman A, Long B. American Journal of Emergency Medicine 2022

›High risk and low prevalence diseases: serotonin syndrome review

›HPPD and adverse event literature

Evidence & Review