Emergency Medicine Hub / Neurology & Psychiatry • 3 min read • 4 sections

Substance-Induced Psychosis & Excited Delirium Syndrome

Comprehensive emergency evaluation and protocolized resuscitation for acute substance-induced psychosis, novel psychoactive substances (NPS), and hyperadrenergic excited delirium syndrome: pharmacology and clinical toxidromes of Synthetic Cathinones ('bath salts', MDPV, Flakka); Phencyclidine (PCP) NMDA antagonism, analgesia, and pathognomonic multidirectional nystagmus; Synthetic Cannabinoids ('K2/Spice'); the lethal physiological triad of Excited Delirium Syndrome (ExDS: severe agitated delirium, physical restraint struggle, and malignant hyperthermia); the extreme hazard of physical-only restraints; protocolized rapid chemical sedation (intramuscular Ketamine vs. Droperidol vs. Midazolam); and aggressive cooling.

Resuscitation Quick Actions • First 2 Minutes

High-Acuity

Physical Restraint Hazard

NEVER physically restrain an agitated hyperadrenergic patient without IMMEDIATELY administering chemical sedation (prolonged struggle triggers fatal hyperkalemic arrest)

First-Line Rapid Sedation

Ketamine 4 to 5 mg/kg IM (or 1-2 mg/kg IV); achieves complete dissociation and behavioral control within 2 to 4 minutes without depressing airway tone

Alternative Neuroleptic

Droperidol 5 to 10 mg IM or IV (or Haloperidol 5-10 mg IM PLUS Midazolam 5 mg IM); achieves rapid tranquility with low adverse effect profile

PCP Pathognomonic Sign

Multidirectional (rotatory, vertical, and horizontal) nystagmus + profound analgesia + bizarre violent behavior = Phencyclidine (PCP) toxicity

Malignant Hyperthermia Target

Rectal core temperature > 40.0°C (104°F) is a medical emergency: initiate evaporative cooling/ice-water immersion immediately (target core temp < 38.5°C within 30 min)

Metabolic Acidosis & Rhabdo

Draw stat blood gas, potassium, and CK: severe lactic acidosis (pH < 7.0) requires IV Sodium Bicarbonate and 20-30 mL/kg cold IV crystalloids

Bottom-Line Clinical Pearl

In patients presenting with severe agitated delirium, extreme paranoia, imperviousness to pain, and hyperthermia, **PHYSICAL RESTRAINT WITHOUT IMMEDIATE CHEMICAL SEDATION IS A FATAL ERROR**: when an agitated, sympathomimetic-poisoned patient fights against physical straps, isometric muscular contractions generate massive lactic acidosis, profound hyperkalemia, and rhabdomyolysis, precipitating sudden cardiovascular collapse and cardiac arrest within minutes. Emergency management requires immediate rapid chemical sedation: **Ketamine 4 to 5 mg/kg IM** (or Droperidol 5-10 mg IM/IV) to achieve complete calming within 3 to 5 minutes, followed by immediate rectal core temperature measurement, aggressive evaporative or ice-water cooling, and large-volume IV crystalloid hydration.

1. Pharmacology of Novel Psychoactive Substances (NPS)

Novel psychoactive substances are synthetic compounds engineered to evade controlled-substance legislation while producing intense psychoactive, hallucinogenic, or stimulant effects. They present with hyperadrenergic, anticholinergic, or dissociative toxidromes:

Drug Class & Common Names	Receptor Mechanism of Action	Clinical Hallmark & Toxidrome
Synthetic Cathinones ('Bath Salts', Flakka, Gravel, Bloom, MDPV, alpha-PVP)	Potent, prolonged inhibition of presynaptic reuptake of dopamine, norepinephrine, and serotonin, coupled with stimulated vesicular release. Potency exceeds methamphetamine by 10- to 50-fold.	Severe, prolonged sympathomimetic delirium: extreme paranoia, hyperthermia, suicidal/homicidal violent outbursts, tachydysrhythmias, jaw clenching (trismus), severe rhabdomyolysis, and prolonged psychosis lasting days.
Phencyclidine (PCP) & Ketamine Analogs ('Angel Dust', Wet, Special K)	Non-competitive antagonism of the NMDA (N-methyl-D-aspartate) glutamate receptor, inhibition of dopamine/norepinephrine reuptake, and sigma receptor stimulation.	PATHOGNOMONIC HALLMARK: Multidirectional Nystagmus (rotatory, vertical, and horizontal). Profound sensory anesthesia (patients feel zero pain despite severe fractures/lacerations), bizarre violent behavior, and extraordinary physical strength.
Synthetic Cannabinoids ('K2', 'Spice', AK-47, Black Mamba)	Full agonists at cannabinoid CB1 and CB2 receptors with binding affinity up to 100 times greater than delta-9-THC.	Unlike natural cannabis, synthetic cannabinoids trigger unprovoked seizures, myocardial infarction, acute tubular necrosis, profound catatonia, and severe psychotic agitation.

2. Excited Delirium Syndrome (ExDS): The Lethal Restraint Triad

Excited Delirium Syndrome (also classified by ACEP as Hyperactive Delirium with Severe Agitation and Autonomic Dysfunction) represents an acute medical emergency characterized by extreme adrenergic surge, altered dopaminergic neurotransmission, and failure of thermoregulatory homeostasis. It carries a pre-hospital and emergency department mortality rate approaching 10%:

Component of the Lethal Triad	Biochemical & Physiological Cascade	Clinical Manifestation
1. Hyperactive Delirium & Analgesia	Extreme central dopamine and norepinephrine excess. Loss of normal cortical inhibitory feedback produces delirium, disorientation, paranoia, and complete insensitivity to pain.	Patient screams incoherently, smashes glass, strips naked (due to hyperthermia), and exhibits 'superhuman' strength that requires multiple responders to contain.
2. The Physical Restraint Struggle	When placed in physical handcuffs, hobbles, or stretcher straps, the patient continues to struggle with maximal isometric force.	Sustained isometric muscle contraction halts capillary microcirculation, driving massive anaerobic glycolysis, severe lactic acidosis (pH frequently < 6.8 to 7.0), and massive rhabdomyolysis.
3. Malignant Hyperthermia & Acidotic Arrest	Continuous uncoupled mitochondrial thermogenesis drives core body temperature above 40.5°C to 42°C (105°F to 108°F). Massive cellular ATP depletion triggers potassium leakage into the extracellular space.	The combination of extreme hyperkalemia + profound acidemia + catecholamine toxicity triggers sudden Ventricular Fibrillation, asystole, and sudden in-custody death!

3. Rapid Chemical Sedation Protocols

The primary emergency intervention for severe agitated delirium is immediate chemical sedation to halt the physical struggle. Physical restraints alone are dangerous and must be accompanied by immediate medication:

Agent	Emergency Dose & Route	Onset of Action & Clinical Pearls
Ketamine (First-Line for Extreme Violence)	4.0 to 5.0 mg/kg Intramuscularly (IM) OR 1.0 to 2.0 mg/kg Intravenously (IV). (In adults: typical IM dose is 300 to 500 mg IM into lateral thigh/deltoid).	Onset: 2 to 4 minutes. Non-competitive NMDA antagonist providing instant dissociative anesthesia while preserving spontaneous airway reflexes and respiratory drive. Immediately halts the muscle struggle and terminates hyperthermia generation.
Droperidol (First-Line Butyrophenone)	5.0 to 10.0 mg IM or IV (start with 5 mg; can repeat 5 mg in 15 min if needed).	Onset: 5 to 10 minutes. Potent central D2 dopamine antagonist providing rapid tranquility without excessive respiratory depression. Excellent safety profile; QTc prolongation risk is negligible in acute agitation.
Midazolam + Haloperidol ('5 and 5' Combination)	Midazolam 5 mg IM PLUS Haloperidol 5 mg IM (can combine in single syringe).	Onset: 10 to 15 minutes. Synergistic combination: midazolam provides rapid GABA-mediated sedation while haloperidol provides sustained dopaminergic suppression.

4. Post-Sedation Resuscitation & Cooling Protocols

Intervention	Clinical Goal & Target	Procedure Details
Immediate Core Temperature Measurement	Identify malignant hyperthermia immediately.	Rectal core temperature probe (tympanic, axillary, and forehead thermometers are completely inaccurate in excited delirium!).
Aggressive External Core Cooling	Target Core Temperature < 38.5°C (101.3°F) within 30 minutes.	If core temp > 40.0°C (104°F): 1. Ice-Water Immersion (gold standard): Submerge torso in ice-water slurry. 2. Evaporative Cooling: Strip patient, spray continuously with tepid water, and direct high-velocity fans over body. 3. Ice packs to axillae, groin, and neck.
Intravenous Crystalloid Resuscitation	Restore intravascular volume, clear lactic acidosis, and prevent myoglobinuric acute tubular necrosis.	Infuse 20 to 30 mL/kg of cold (4°C) IV balanced crystalloids (Lactated Ringer's or Plasmalyte). Administer Sodium Bicarbonate 1 to 2 mEq/kg IV if severe high anion gap metabolic acidosis (pH < 7.1) or hyperkalemia is present.

The Prone Position Death Trap & The Physical Restraint Tragedy

Two fatal mistakes occur repeatedly in the management of hyperadrenergic excited delirium. First, NEVER place an agitated, combative patient in the PRONE position (face down), and NEVER allow law enforcement or staff to kneel or compress the patient's thorax or back! Prone positioning combined with mechanical chest compression causes positional asphyxiation: the severely acidotic, hyperventilating patient cannot expand their ribcage or diaphragm, triggering sudden, irreversible hypoxic cardiac arrest within 60 to 90 seconds. Always maintain patients in the supine or lateral recovery position with continuous pulse oximetry. Second, NEVER rely on physical restraints alone: holding down a violently agitated patient while waiting for security personnel without administering immediate chemical sedation (Ketamine 4-5 mg/kg IM) causes continuous maximal isometric muscle contraction. This drives serum potassium above 7.0 to 8.0 mEq/L and blood pH below 6.8, precipitating sudden, refractory hyperkalemic asystole. Chemical sedation must be given within seconds of physical contact.

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