01Approach to the Critical Patient/attcp68

Immediate priorities

›Airway and breathing threats

›High aspiration risk from depressed mental status or vomiting

›GCS < 8 is a strong indication for definitive airway management

›60% of ICU-admitted SC patients had acute respiratory failure; 70% required intubation

›Lateral decubitus positioning and suction if active vomiting

›Respiratory failure triggers

›SpO2 < 92% on room air

›PaO2 < 60 mmHg or rising PaCO2

›Respiratory fatigue with accessory muscle use

›If unable to protect airway, proceed to rapid sequence intubation

›Ketamine 1-2 mg/kg IV preferred induction agent in agitated SC toxicity

›Rocuronium 1.2 mg/kg IV for paralysis

›Circulation and hemodynamic threats

›Bradycardia with hypotension pattern

›Atropine 0.5-1 mg IV immediately for heart rate < 50 with hemodynamic compromise

›SC toxicity demonstrates unique bradycardic-hypotensive pattern distinct from classic sympathomimetics

›GCS < 8 is strongly associated with bradycardia and risk of cardiac arrest

›Cardiac arrest preparation

›Initiate standard ACLS

›Consider VA-ECMO for refractory arrest or stress cardiomyopathy

›AHA 2023 guidelines support consideration of ECMO for toxin-mediated cardiac arrest

›Hyperthermia crisis

›Core temperature > 39.5 degrees Celsius requires immediate aggressive cooling

›Evaporative/convective cooling preferred; cooling blankets alone are insufficient

›Benzodiazepines to suppress heat-generating muscle activity

›Key early branching decisions

›Agitation and psychomotor excitation pathway

›Benzodiazepines as first-line: lorazepam 2-4 mg IV or midazolam 5 mg IM/IV

›Avoid prolonged physical restraints without adequate sedation — markedly increases rhabdomyolysis and hyperthermia risk

›Escalate to ketamine or propofol for refractory agitation

›CNS depression pathway

›Trial of naloxone 0.4 mg IV if respiratory depression — may unmask coingestant opioid use

›Dextrose 1 amp IV if capillary glucose < 3.5 mmol/l

›CT head if focal deficits or seizure without recovery

Monitoring and targets

›Continuous monitoring bundle

›Cardiac monitor: SC toxicity causes both tachyarrhythmias and bradyarrhythmias

›12-lead ECG for QTc prolongation, ST changes

›Repeat ECG if QTc > 500 ms or new ST changes

›Pulse oximetry target SpO2 94-98%

›ETCO2 monitoring if intubated

›Serial blood gases for respiratory failure

›Temperature monitoring every 30 minutes in agitated or restrained patients

›Rectal or esophageal probe for accuracy

›Hyperthermia > 40 degrees Celsius is life-threatening

›Laboratory surveillance cadence

›CPK every 4-6 hours in rhabdomyolysis

›Urine output target 1-3 mL/kg/hr during rhabdomyolysis management

›CPK > 10,000 U/L with rising creatinine mandates nephrology involvement

›Electrolytes every 4-6 hours: potassium and phosphorus critical in rhabdomyolysis

›Treat hyperkalaemia urgently if > 6.5 mmol/l with ECG changes

›Escalation triggers requiring ICU

›GCS < 8 or requirement for intubation

›Refractory seizures meeting status epilepticus criteria

›Severe rhabdomyolysis with AKI (CPK > 10,000 U/L)

›Hemodynamic instability requiring vasopressors

›Respiratory failure requiring mechanical ventilation

›Cardiac arrest or significant arrhythmia

Immediate consults

›Consultation triggers

›Poison Control Center (1-800-222-1222) for all moderate-to-severe SC toxicity cases

›Assistance with identification of specific SC compound if packaging available

›Guidance on novel compound toxicity management

›Critical care/ICU for hemodynamic instability, respiratory failure, or GCS < 8

›Anesthesia for difficult airway management

›Nephrology for AKI requiring renal replacement therapy

›Cardiology for refractory arrhythmia or ST-elevation pattern

›SC-mediated coronary vasospasm can produce STEMI in patients with normal coronary arteries

›Psychiatry for persistent psychosis, catatonia, or suicidality

›Surgery for suspected compartment syndrome from rhabdomyolysis

02History/hx53

Presenting complaint

›Substance identification

›Street names: "K2," "Spice," "Cloud 9," "Mojo," "herbal incense," "fake weed," "paper strips," "gummies"

›Products vary widely in composition — compound identity rarely known to patient

›SC-laced paper strips are an emerging route in correctional facilities

›Route of administration

›Smoked/inhaled: onset within minutes, shorter but variable duration

›Ingested (gummies, edibles): onset 30-90 minutes, prolonged and less predictable

›Time since last use and quantity

›Duration of symptoms and trajectory (improving vs. worsening)

›Chronic daily use raises withdrawal risk

›Symptom timeline

›Neurologic symptoms

›Altered consciousness, confusion, agitation, hallucinations

›Seizures: generalized tonic-clonic, may be refractory to initial benzodiazepines

›Tremor, myoclonus, headache

›Cardiovascular symptoms

›Chest pain, palpitations, syncope

›Palpitations and chest pain raise concern for vasospasm-mediated MI

›Psychiatric symptoms

›Agitation, paranoia, psychosis, suicidal ideation

›Catatonia: reported with SC use, particularly in patients with no prior psychosis

Risk factors and exposures

›Demographic and social risk profile

›Young adult male (median age approximately 35 years) — predominant demographic

›Populations subject to drug testing use SCs to evade standard urine screens

›Homelessness: 43% of ICU-admitted patients in one case series were undomiciled

›Incarceration: SC-laced paper strips ingested or smoked in correctional facilities

03Physical Exam/exam49

Vital signs

›Hemodynamic and temperature profile

›Blood pressure

›Hypertension common (sympathomimetic-like activation)

›Hypotension in severe CNS depression or bradycardic presentations

›Heart rate

›Tachycardia in agitated/hyperadrenergic presentations

›Bradycardia: unique SC finding, particularly with deep CNS depression; associated with GCS < 8

›Temperature: hyperthermia is a critical finding

›Temperature > 40 degrees Celsius requires immediate aggressive cooling

›Hyperthermia exacerbated by physical restraints and prolonged agitation

›Respiratory rate and SpO2

›Tachypnea in agitated or hypoxic presentations

›Bradypnea or apnea in severe CNS depression

Neurologic exam

›Level of consciousness

›GCS: document eye, verbal, and motor components

›GCS < 8 strongly associated with bradycardia and cardiac arrest risk

›Fluctuating mental status is characteristic of SC toxicity

›Pupils

›Mydriasis: common but not universal in SC toxicity

›Miosis: raises suspicion for opioid coingestant

›Focal neurologic deficits

›New focal deficits or asymmetry require CT head to exclude structural lesion

›Posterior reversible encephalopathy syndrome (PRES) reported with ADB-CHMINACA

›Movement and muscle tone

›Tremor, myoclonus, rigidity

›Rigidity or clonus raises consideration for serotonin syndrome

04Differential Diagnosis/ddx50

CNS depression mimics

›Opioid overdose

›ICD-10: T40.0-T40.4

›Miosis, respiratory depression, response to naloxone

›Coingestant possibility must always be considered in SC presentations

›Sedative-hypnotic overdose (benzodiazepines, GHB, alcohol)

›ICD-10: T42.4 (benzodiazepines), T51.0 (alcohol)

›CNS and respiratory depression; check serum ethanol, urine drug screen

›Hypoglycaemia

›ICD-10: E11.641

›Capillary glucose must be checked immediately in any altered mental status

›Rapid reversal with dextrose excludes diagnosis

Sympathomimetic and excitatory toxidromes

›Sympathomimetic toxicity (amphetamines, cocaine, cathinones)

›ICD-10: T43.6 (amphetamines), T40.5 (cocaine)

›Tachycardia, hypertension, mydriasis, hyperthermia, agitation

›SC may present with CNS depression and bradycardia, distinguishing it from classic sympathomimetics

›Anticholinergic toxicity

›ICD-10: T44.3

›Agitation, hallucinations, tachycardia, dry skin, urinary retention, mydriasis

›Dry skin and urinary retention are ABSENT in SC toxicity

›Serotonin syndrome

›ICD-10: T43.9

›Agitation, hyperthermia, clonus, hyperreflexia

›Medication history for serotonergic drugs is key distinguishing factor

Psychiatric emergencies

›First-episode psychosis or acute mania

›ICD-10: F29, F30.1

05Laboratory Tests/lt60

Essential metabolic panel

›Point-of-care glucose

›Immediate capillary glucose in all patients with altered mental status

›Threshold for treatment: glucose < 3.5 mmol/l

›Dextrose 50% 50 mL IV if hypoglycaemic

›Comprehensive metabolic panel

›Creatinine and BUN: AKI is a major complication

›SC-associated AKI: from rhabdomyolysis, direct nephrotoxicity, or dehydration

›Baseline creatinine informs severity staging

›Electrolytes: sodium, potassium, bicarbonate, chloride

›Hyperkalaemia from rhabdomyolysis can cause fatal arrhythmia

›Anion gap metabolic acidosis in severe multi-organ failure

›Liver function tests (AST, ALT, bilirubin, INR)

›Fulminant hepatic failure reported; may require liver transplant evaluation

›Elevated transaminases common in rhabdomyolysis

Muscle and renal injury markers

›Creatine phosphokinase (CPK)

›Mandatory in any patient with agitation, restlessness, or altered mental status

›CPK > 320,000 U/L reported in severe SC-induced rhabdomyolysis

›Repeat every 4-6 hours; peak CPK level guides management intensity

›Urine myoglobin

›Dark (tea-coloured) urine suggests myoglobinuria

›Urine dipstick positive for blood with no red cells on microscopy = myoglobinuria

›Urinalysis and urine microscopy

›Microscopy for casts (granular casts indicate established AKI)

›Urine output monitoring: target > 1 mL/kg/hr during rhabdomyolysis

›Foley catheter insertion for accurate output monitoring in severe cases

Hematologic and coagulation studies

›Complete blood count

›Leukocytosis: may reflect agitation and catecholamine surge rather than infection

›Thrombocytopenia: rare, associated with brodifacoum-contaminated SC

›Anaemia: haemolysis or haemorrhage in severe cases

›Coagulation profile (INR, PTT, fibrinogen)

›Brodifacoum is a long-acting anticoagulant rodenticide added as adulterant to some SC products

›Supertherapeutic INR with bleeding is the presentation of brodifacoum-contaminated SC

›Vitamin K1 therapy for brodifacoum coagulopathy (large doses required)

Toxicology screening

›Standard urine drug screen

›Does NOT detect synthetic cannabinoids — a negative THC result does NOT rule out SC use

›Standard immunoassay screens only detect natural THC metabolites

›Confirmatory testing requires specialized gas or liquid chromatography-mass spectrometry

›Serum ethanol

›Alcohol is a common coingestant; quantitative level guides management

›Serum acetaminophen and salicylate levels

›Mandatory in any undifferentiated toxicology presentation given potential polysubstance use

›Specialized toxicology testing

›Mass spectrometry (GC-MS or LC-MS/MS) for SC compound identification

›Requires reference laboratory; results not available acutely

›Useful for epidemiological surveillance and outbreak investigation

›Serum and urine samples should be frozen and preserved for analysis

Cardiac markers

›Troponin I or T

›Mandatory in patients with chest pain, palpitations, or syncope

›SC-mediated coronary vasospasm can produce troponin elevation with STEMI pattern

›Serial troponins at 0, 3, and 6 hours if initial presentation within first 2 hours of symptoms

›BNP or NT-proBNP

›Stress cardiomyopathy (Takotsubo) reported in SC toxicity

›Elevated BNP with ventricular dysfunction on echo indicates stress cardiomyopathy

Arterial blood gas

›Arterial blood gas in respiratory failure or altered mental status

›PaO2: hypoxia threshold < 60 mmHg requires supplemental oxygen or ventilatory support

›PaCO2: hypercapnia > 50 mmHg indicates respiratory failure or CNS depression

›pH: acidaemia < 7.30 from lactic acidosis or rhabdomyolysis

›Lactate

›Lactate > 2 mmol/l indicates tissue hypoperfusion

›Serial lactate to monitor treatment response

06Diagnostic Tests/dt68

Scoring Systems

›Modified GCS for toxicological assessment

›GCS < 8 is a critical threshold in SC toxicity

›Associated with bradycardia risk and requirement for definitive airway

›GCS < 13 requires immediate CT head to exclude structural lesion

›GCS trend more important than single value in SC toxicity

›Fluctuating consciousness is characteristic; reassess every 15-30 minutes

›Toxicology severity scoring

›Poison Severity Score (PSS)

›Grades 0 (none) to 4 (fatal): guides admission level

›PSS 2-3 (moderate-severe) meets ICU admission threshold in SC toxicity

›CIWA-B (Clinical Institute Withdrawal Assessment for Benzodiazepines) for chronic SC users

›SC withdrawal syndrome: anxiety, insomnia, diaphoresis, irritability

›Onset typically 24-72 hours after cessation of chronic SC use

›Rhabdomyolysis severity staging

›CPK < 1000 U/L: mild, outpatient monitoring may be appropriate

›CPK 1000-10,000 U/L: moderate, IV hydration and admission

›CPK > 10,000 U/L: severe, high risk of AKI, ICU-level care consideration

Scoring Systems Additional

›NIHSS for patients with focal neurologic deficits

›Quantifies neurologic deficit severity to monitor for PRES or ischemic stroke

›Score > 4 should prompt urgent MRI

›APACHE II or SOFA for ICU-admitted patients

›SOFA score > 2 indicates organ dysfunction consistent with sepsis-level illness

›APACHE II used for ICU prognosis and resource allocation

MRI

›MRI brain indications in SC toxicity

›Focal neurologic deficits, new seizures without rapid recovery, or prolonged altered mental status

›PRES: diagnosed by MRI FLAIR sequences showing bilateral posterior white matter changes

›ADB-CHMINACA specifically associated with PRES in published case series

›DWI (diffusion-weighted imaging) sequences

›Restricted diffusion in cortex or white matter suggests ischemic injury or PRES

›Transient cytotoxic edema reported in severe SC toxicity on DWI

›MRI superior to CT for posterior fossa and white matter pathology

›Gadolinium contrast enhancement for meningitis or encephalitis evaluation

›FLAIR sequences for posterior reversible encephalopathy syndrome

›MRI limitations in acute SC toxicity

›Agitation and lack of cooperation make MRI impractical acutely in most patients

›CT head is the preferred initial imaging in agitated or unstable patients

›MRI is reserved for post-stabilization evaluation of unexplained neurological findings

CT

›Non-contrast CT head

›Indications: new focal deficits, seizure without recovery, GCS < 13 without clear explanation

›Loss of grey-white differentiation on CT reported in severe SC toxicity (transient cerebral edema)

›Excludes haemorrhage, mass lesion, hydrocephalus

›CT interpretation in SC toxicity

›Diffuse cerebral edema may appear as sulcal effacement with loss of grey-white differentiation

›Normal CT does not exclude PRES; follow with MRI if clinical suspicion persists

›CT chest

›Indications: respiratory failure, hypoxia, suspected aspiration, or diffuse alveolar hemorrhage

›Diffuse alveolar hemorrhage pattern: bilateral ground glass opacities

›Aspiration pneumonitis: dependent consolidation (right lower and middle lobes predominant)

›CT angiography (pulmonary)

›Pulmonary embolism in the differential for unexplained hypoxia without bronchospasm

›SC use may increase clotting risk in severely immobilized patients

Ultrasound

›Point-of-care cardiac ultrasound (POCUS)

›Left ventricular function assessment for stress cardiomyopathy (Takotsubo)

›Apical ballooning with preserved basal function is characteristic of Takotsubo

›Pericardial effusion exclusion

›Global LV systolic function

›LVEF < 40% in context of SC toxicity suggests stress cardiomyopathy or myocarditis

›Serial POCUS to monitor recovery of ventricular function

›FAST and abdominal ultrasound

›Free fluid in context of trauma (SC-intoxicated patients have high fall and trauma risk)

›Hepatomegaly or heterogeneous liver echotexture in suspected fulminant hepatic failure

›Renal ultrasound

›Cortical echogenicity in established AKI

›Bladder scan to exclude urinary retention if output is low

›Vascular POCUS

›DVT assessment in immobilized patients with prolonged ICU course

›Compressibility of femoral, popliteal, and tibial veins

›SC-related immobility and prolonged agitation increase VTE risk

07Disposition/dispo36

Discharge criteria

›Safe for discharge from ED

›Symptoms fully resolved within 4-6 hours of observation

›Most uncomplicated SC presentations have ED length of stay < 8 hours

›Normal vital signs sustained for at least 2 hours

›Normal mental status: alert, oriented, able to ambulate

›Tolerating oral fluids without nausea or vomiting

›No laboratory abnormalities (CPK trending down, creatinine normal)

›Safe social situation

›Not actively suicidal with confirmed follow-up plan

›Responsible adult supervision if recent SC use

›Discharge instructions provided

›Return precautions reviewed and understood

›Substance use disorder resources provided

›PCP or urgent care follow-up within 48-72 hours arranged

Admission criteria

›Floor or telemetry admission

›Persistent vital sign abnormalities (bradycardia, tachycardia, or hypertension beyond 4-6 hours)

›Mild-to-moderate rhabdomyolysis requiring ongoing IV hydration (CPK 1000-10,000)

›Prolonged altered mental status beyond initial observation period

›Mild AKI with improving creatinine on IV hydration

›Psychiatric admission for persistent psychosis, catatonia, or active suicidality

›Coagulopathy from brodifacoum-contaminated SC requiring vitamin K therapy

ICU admission criteria

›Critical care level required

›GCS < 8 or requirement for intubation and mechanical ventilation

›60% of ICU-admitted SC patients had acute respiratory failure; 70% required intubation

›Refractory seizures meeting status epilepticus criteria

08Treatment/t102

Airway and ventilatory support

›Supplemental oxygen and airway positioning

›Supplemental oxygen to maintain SpO2 > 94%

›Jaw thrust and nasopharyngeal airway for obtunded patient

›Lateral decubitus positioning to reduce aspiration risk

›Endotracheal intubation indications

›GCS < 8, failure to protect airway, apnea, or refractory hypoxia

›Rapid sequence intubation: ketamine 1-2 mg/kg IV + rocuronium 1.2 mg/kg IV

›Post-intubation ventilator settings

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

›PEEP 5-8 cmH2O titrated to oxygenation

›Target plateau pressure < 30 cmH2O

Agitation management

›Benzodiazepines (first-line for agitation, seizures, rhabdomyolysis prevention)

›Lorazepam 2-4 mg IV every 5-10 minutes titrated to sedation

›Alternative: midazolam 5 mg IM or IV if no IV access

›Diazepam 5-10 mg IV as alternative; longer duration of action

›Repeat dosing every 5-10 minutes until adequate sedation achieved

›No ceiling dose: titrate to clinical effect

›Respiratory depression risk with high cumulative doses; have airway equipment ready

›Ketamine for refractory agitation

›Ketamine 1-2 mg/kg IV or 4-5 mg/kg IM for severe refractory agitation

›Dissociative dose provides rapid sedation without respiratory depression at standard doses

›AHA 2023 guideline supports ketamine for refractory agitation in toxicological emergencies

›Ketamine infusion for ICU sedation

›0.1-0.5 mg/kg/hr IV infusion for intubated patients

›Titrate every 15-30 minutes to RASS target -2 to -3

›Antipsychotics for SC-induced psychosis (adjunct to benzodiazepines)

›Olanzapine 5-10 mg IM for acute psychosis not controlled by benzodiazepines alone

›Avoid combining with benzodiazepines parenterally due to respiratory depression risk

›Do not use if QTc > 500 ms

›Quetiapine 25-50 mg PO for milder or resolving psychosis

›Second-generation antipsychotics preferred over haloperidol in SC toxicity

›Avoid haloperidol if hyperthermia present (reduces seizure threshold)

Bradycardia management

›Atropine for symptomatic bradycardia

›Atropine 0.5-1 mg IV for heart rate < 50 with hypotension or symptoms

›Repeat every 3-5 minutes to maximum cumulative dose of 3 mg

›Demonstrated efficacy in SC-specific bradycardic presentations (JAMA Network Open 2024)

›Transcutaneous pacing for atropine-refractory symptomatic bradycardia

›Temporary transvenous pacing if transcutaneous pacing fails

›Escalation

›Dopamine 5-20 mcg/kg/min IV infusion if persistent bradycardia with hypotension

›Isoproterenol 2-10 mcg/min IV for refractory bradycardia

Hyperthermia management

›Active cooling measures

›Evaporative cooling: tepid water misting with fans — most effective and rapid cooling method

›Remove all clothing and restraints as soon as safely possible

›Ice packs to axilla, groin, and neck (high-flow areas)

›Cooling blankets alone insufficient — use in combination with evaporative methods

›Target core temperature < 38.5 degrees Celsius

›Rectal or esophageal temperature probe for accurate monitoring

›Pharmacological cooling adjuncts

›Benzodiazepines reduce heat-generating muscle activity

›Lorazepam 2-4 mg IV to suppress agitation and reduce thermogenesis

›Dantrolene is NOT indicated for SC-induced hyperthermia (mechanism is not malignant hyperthermia)

›Paralysis (rocuronium) and intubation for refractory hyperthermia > 41 degrees Celsius

›Target temperature achieved before paralysis wears off or continuous infusion

Rhabdomyolysis management

›IV fluid resuscitation

›Normal saline or lactated Ringer's: initial bolus 1-2 L IV over 30-60 minutes

›Target urine output 1-3 mL/kg/hr

›Ongoing rate typically 200-500 mL/hr; titrate to urine output

›Serial CPK monitoring every 4-6 hours

›Continue aggressive hydration until CPK trending down to < 1000 U/L

›Electrolyte replacement: potassium, phosphorus, calcium as needed

›Urine alkalinisation (controversial, consider in severe cases)

›Sodium bicarbonate 1 mEq/kg in 1L D5W at 100-150 mL/hr

›Target urine pH > 6.5 to reduce myoglobin precipitation in renal tubules

›Avoid if serum bicarbonate > 30 mmol/l or pH > 7.50

›Nephrology consultation for CPK > 10,000 U/L or rising creatinine

›CRRT indications: oliguria, metabolic acidosis, refractory hyperkalaemia, volume overload

›Compartment syndrome management

›Surgical consultation if compartment pressure > 30 mmHg or within 30 mmHg of diastolic pressure

›Emergent fasciotomy for confirmed compartment syndrome

›Limb firmness and pain with passive stretch are indications for pressure measurement

Seizure management

›First-line benzodiazepines

›Lorazepam 0.1 mg/kg IV (4-8 mg in adults); repeat in 5 minutes if seizure continues

›Midazolam 10 mg IM as alternative if IV access not established

›Diazepam 10-20 mg IV rectally if unable to obtain IV access

›SC-induced seizures may be refractory to initial benzodiazepine dosing

›Do not hesitate to escalate rapidly if no response within 5-10 minutes

›Second-line agents (refractory seizures)

›Phenobarbital 20 mg/kg IV at 50 mg/min for SC-induced seizures

›ACEP supports phenobarbital as second-line for toxin-induced seizures (Level C)

›Levetiracetam 60 mg/kg IV (max 4500 mg) as alternative

›Third-line: propofol infusion 1-2 mg/kg IV bolus then 1-4 mg/kg/hr

›Intubation mandatory before propofol infusion for airway protection

›Continuous EEG monitoring for non-convulsive status epilepticus if persistent encephalopathy

IV fluid and antiemetic management

›Intravenous fluid resuscitation

›Normal saline 1-2 L IV bolus for volume depletion or vomiting

›Reassess volume status and response after initial bolus

›Maintenance fluids at 125-150 mL/hr while NPO

›Antiemetics

›Ondansetron 4-8 mg IV for nausea and vomiting (most common and safe)

›Avoid with prolonged QTc > 500 ms (additive QTc effect)

›Metoclopramide 10 mg IV as alternative

›SC hyperemesis pattern: cannabinoid hyperemesis syndrome variant

›Topical capsaicin cream may reduce symptoms in hyperemesis pattern (emerging evidence)

Cardiac arrest management

›Standard ACLS algorithm

›Defibrillation for VF or pulseless VT: 200 J biphasic, escalate to maximum energy

›Epinephrine 1 mg IV every 3-5 minutes for pulseless arrest

›Amiodarone 300 mg IV bolus for refractory VF/pVT

›Extracorporeal membrane oxygenation (VA-ECMO)

›Consider for refractory SC-mediated cardiac arrest

›AHA 2023 focused update supports ECMO consideration in poisoning-related cardiac arrest

›Stress cardiomyopathy may recover fully with circulatory support

09Special Populations/sp53

Pregnancy

›Physiologic considerations in pregnant patients with SC toxicity

›SC use during pregnancy associated with fetal growth restriction, preterm birth, and stillbirth

›Maternal hypoxia and hypotension may have greater impact on fetal outcomes than SC directly

›Standard resuscitation of mother is the priority; fetal outcomes improve with maternal stabilization

›Fetal monitoring

›Continuous external fetal monitoring for > 20 weeks gestation with any hemodynamic instability

›Obstetrics consultation for any pregnant patient with SC toxicity beyond 20 weeks

›Medication safety in pregnancy

›Benzodiazepines: Category D; use with caution but do not withhold for seizures or severe agitation

›Lorazepam preferred for seizures; avoid prolonged high-dose use near term

›Neonatal withdrawal possible if large doses used near delivery

›Ketamine: generally avoided in pregnancy; may increase uterine tone

›Olanzapine: limited data; use if benefit outweighs risk for refractory psychosis

›SC-exposed neonates at delivery

›Neonatal toxicology and pediatric notification if recent maternal SC use

›Monitor neonate for CNS depression, respiratory distress, and withdrawal

Geriatric

›Physiologic considerations in elderly patients

›Reduced hepatic and renal clearance prolongs duration of SC toxicity

›Reduced volume of distribution increases effective drug concentration

›Baseline cognitive impairment may mask SC-induced encephalopathy

›Increased fall risk with any degree of CNS alteration

›SC use less common in elderly but misidentification of substances occurs

›Medication adjustments in elderly patients

›Benzodiazepines: reduce initial dose by 50% (lorazepam 1-2 mg IV)

›Increased risk of respiratory depression and paradoxical agitation

›Prefer short-acting agents (lorazepam, midazolam) over long-acting (diazepam)

›Antipsychotics: avoid in elderly with dementia history (increased stroke and mortality risk)

›Careful QTc monitoring before antipsychotic administration

›Fluid resuscitation in rhabdomyolysis requires careful balance to avoid fluid overload

›Consider early nephrology consultation given reduced renal reserve

›Differential diagnosis in elderly

›SC toxicity presenting as delirium may mimic Wernicke encephalopathy, CVA, or dementia exacerbation

›Thiamine 100 mg IV before any dextrose in elderly patients with altered mental status

›CT head has lower threshold in elderly (higher risk of subdural haematoma from falls)

Pediatrics

›Epidemiology and risk profile in pediatric patients

›Adolescents (13-18 years) are the pediatric population most commonly affected

›Accidental exposure in young children via ingestion of gummies or edibles marketed as cannabis

›SC toxicity in children tends to be more severe per body weight due to full CB1 agonism

›Child protective services involvement for unintentional pediatric exposure

›Pediatric toxicology consultation for all pediatric SC cases

›Weight-based dosing in pediatric SC toxicity

›Lorazepam 0.05-0.1 mg/kg IV (maximum 4 mg per dose) for seizures or agitation

›Midazolam 0.1-0.2 mg/kg IM or IN (maximum 10 mg) if no IV access

›Diazepam 0.2-0.5 mg/kg IV for refractory seizures

›IV fluid resuscitation for rhabdomyolysis

›Normal saline 10-20 mL/kg IV bolus, then titrate to urine output > 1 mL/kg/hr

›More aggressive monitoring of electrolytes and volume status required

›Pediatric specific clinical features

›Younger children may present primarily with CNS depression rather than agitation

›Hypoglycaemia more common in children: check capillary glucose immediately

›Pediatric cardiology consultation for arrhythmia given smaller margin for hemodynamic compromise

›All pediatric SC cases require consideration of child abuse or neglect reporting

›Mandatory reporting to child protective services when intentional or negligent exposure is suspected

10Background/b58

Epidemiology

›Prevalence and trends

›Synthetic cannabinoids are the most commonly used new psychoactive substances worldwide

›Over 150 distinct SC compounds identified; new analogs emerge continuously to evade scheduling

›SC-related ED visits have fluctuated: peak in 2015 in United States with > 7,000 cases in one week

›Demographic profile

›Predominant demographic: young adult males, median age approximately 35 years

›Prevalence higher in homeless, incarcerated, and military/drug-tested populations

›Homelessness present in 43% of ICU-admitted patients in a 2020 JAMA Network Open case series

›Exposure patterns and setting

›Most commonly smoked or inhaled; increasing ingestion via gummies and edibles

›Correctional facility exposure via SC-laced paper strips is an emerging pattern (JAMA Network Open 2024)

›Internet, head shops, and street sales are primary distribution channels

›United States Poison Control data: SC exposures peaked in 2015 at approximately 7,794 calls per week

›Mortality: estimated 0.15% of reported cases; severe morbidity substantially higher

›Outbreak potential: multiple documented mass-casualty SC events in public spaces

Pathophysiology

›Mechanism of action

›Full CB1 and CB2 receptor agonists: SC bind with approximately 100-fold greater affinity than natural THC

›Natural THC is a partial agonist; SC compounds produce full receptor activation without ceiling effect

›Full agonism explains disproportionate severity compared to natural cannabis

›CNS effects

›CB1 receptors concentrated in cortex, hippocampus, basal ganglia, cerebellum

›Inhibition of adenylyl cyclase reduces neuronal excitability (paradoxically, some SC cause seizures)

›Glutamate and GABA modulation produces variable excitatory and inhibitory effects

›Multi-organ toxicity mechanisms

›Cardiovascular: catecholamine surge (tachycardia, hypertension) and direct CB1-mediated vasospasm

›Coronary vasospasm: mechanism for MI in patients with structurally normal coronary arteries

›Stress cardiomyopathy (Takotsubo): catecholamine excess and direct cardiotoxicity

›Rhabdomyolysis pathway

›SC-induced seizures and prolonged agitation → muscle ischemia and necrosis

›Hyperthermia potentiates muscle protein denaturation

›Direct nephrotoxicity from myoglobin precipitation in renal tubules

›Hepatotoxicity

›Rare fulminant hepatic failure: direct hepatocellular toxicity from SC metabolites

›Mechanism not fully elucidated; may involve CYP450-mediated reactive metabolite production

›Chemical classification of synthetic cannabinoids

›Classical cannabinoids: dibenzopyran derivatives (HHC)

›Non-classical cannabinoids: cyclohexylphenol and adamantyl derivatives (CP-47,497)

›Indole alkaloids: JWH series, AB-PINACA, ADB-FUBINACA, ADB-CHMINACA (most common current generation)

›Each generation of compounds replaced by more potent analogs after regulatory scheduling

›Third-generation compounds (5F-ADB, 5F-MDMB-PICA) are more potent and associated with higher lethality

Therapeutic Considerations

›No specific antidote exists for SC toxicity

›Naloxone does not reverse SC effects but should be given if opioid coingestant cannot be excluded

›Flumazenil is not indicated and may precipitate seizures if benzodiazepines have been coinsumed

›Treatment is entirely supportive and symptom-directed

›Benzodiazepines are the therapeutic cornerstone: address agitation, seizures, hyperthermia, and rhabdomyolysis simultaneously

›Evidence base for specific interventions

›AHA 2023 Focused Update on Toxicological Cardiac Arrest: supports ECMO for refractory poisoning arrest

›AHA 2025 Guidelines support standard ACLS with toxicological modifications

›No randomized controlled trials for specific SC treatment: evidence from case series and expert consensus

›ACEP Level C recommendation: supportive care with benzodiazepines for SC toxicity

›Clinical Toxicology 2015 systematic review: benzodiazepines most commonly used and effective agent

›Duration of toxicity and prognosis

›Mild SC toxicity resolves within 4-8 hours; severe cases may persist 24-72 hours

›ICU length of stay median 3-5 days in published case series (JAMA Network Open 2020)

›SC-associated rhabdomyolysis and AKI may require weeks of recovery

›Mortality in ICU-admitted patients estimated 5-10% in published series

›Severe cardiac arrest or MODS carries highest mortality

›Survivors of severe SC toxicity may have persistent cognitive or psychiatric sequelae

11Patient Discharge Instructions/pdi32

copy discharge instructions

›Discharge instructions for Synthetic Cannabinoid Toxicity

›What happened: You were treated in the emergency department for toxic effects from synthetic cannabinoids (also known as K2, Spice, or fake weed). These are man-made chemicals that are much stronger and more dangerous than natural marijuana.

›Your symptoms are expected to improve over the next 24-48 hours.

›You may feel tired, slightly confused, or have muscle aches for the next 1-2 days.

›Medications prescribed

›Take all medications as directed by your doctor.

›Do not take any additional sedatives, alcohol, or drugs — these can interact dangerously with residual effects.

›Activity and diet

›Rest for 24-48 hours after discharge.

›Drink plenty of water (at least 2-3 litres per day) to help flush your kidneys.

›Avoid strenuous activity until follow-up.

›Follow-up appointments

›See your family doctor or urgent care within 48-72 hours.

›Blood tests to recheck your kidneys and muscle enzyme levels in 24-48 hours if prescribed.

›Psychiatry or addictions counselling referral if arranged.

›Return to the emergency department immediately if you experience

›Seizures or convulsions

›Chest pain, fast or irregular heartbeat, or fainting

›Dark, brown, or cola-coloured urine

›Decreased urination or no urine output

›Severe muscle pain, swelling, or firmness of any limb

›Worsening confusion, hallucinations, or inability to think clearly

›High fever (temperature above 38.5 degrees Celsius)

›Thoughts of harming yourself or others

›Yellowing of skin or eyes (jaundice)

›Important safety information

›Synthetic cannabinoids are NOT safe alternatives to marijuana — they are far more dangerous and unpredictable

12References/r21

Guidelines and key sources

›AHA 2023 Focused Update on Cardiac Arrest and Life-Threatening Toxicity

›Lavonas EJ, Akpunonu PD, Arens AM, et al. 2023 American Heart Association Focused Update. Circulation. 2023

›Supports ECMO for refractory toxicological cardiac arrest

›Standard ACLS modifications for toxin-mediated arrest

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

›Systematic reviews and cohort studies

›Prete MM, Feitosa GTB, et al. Adverse Clinical Effects Associated With the Use of Synthetic Cannabinoids: A Systematic Review. Drug and Alcohol Dependence. 2025

›Tait RJ, Caldicott D, Mountain D, et al. A Systematic Review of Adverse Events Arising From the Use of Synthetic Cannabinoids. Clinical Toxicology. 2015

›Kourouni I, Mourad B, Khouli H, et al. Critical Illness Secondary to Synthetic Cannabinoid Ingestion. JAMA Network Open. 2020

›Kuai D, Rivera Blanco LE, Krotulski A, et al. Health Risks of Emerging Drug Use in Correctional Facilities. JAMA Network Open. 2024

›Shopan N, Scolnik D, Hassoun E, et al. Acute Intoxication Caused by Three Common Synthetic Cannabinoids. Am J Emergency Medicine. 2023

Additional references

›Key case series and clinical studies

›Armstrong F, McCurdy MT, Heavner MS. Synthetic Cannabinoid-Associated Multiple Organ Failure. Pharmacotherapy. 2019

›Cooper ZD. Adverse Effects of Synthetic Cannabinoids: Management of Acute Toxicity and Withdrawal. Current Psychiatry Reports. 2016

›Gorelick DA. Cannabis-Related Disorders and Toxic Effects. New England Journal of Medicine. 2023

›Armenian P, Darracq M, Gevorkyan J, et al. Intoxication From Novel Synthetic Cannabinoids AB-PINACA and ADB-PINACA. Neuropharmacology. 2018

›Hermanns-Clausen M, Sommer M, Zschiesche A, et al. Acute Toxicity of ADB-CHMINACA Including PRES. British Journal of Clinical Pharmacology. 2026

›Waters ML, Dargan PI, Yates C, et al. Clinical Effects of Cannabis vs Synthetic Cannabinoid Receptor Agonists: European Hospital Cohort. Clinical Toxicology. 2024

›Cordeiro SK, Daro RC, Klein-Schwartz W, Kim HK. Evolution of SC Receptor Agonist Exposure in the United States 2010-2015. Addiction. 2018

›ICD-10-CM: T40.7XXA — Poisoning by other synthetic narcotics/cannabinoids, initial encounter

›SNOMED CT: 767023003 — Toxic effect of synthetic cannabinoid

Evidence & Review

Evidence & Review