›Benzodiazepine rationale
›Reduce muscle activity and thermogenesis
›Control agitation
›First-line seizure treatment
›Class I recommendation for sympathomimetic toxicity agitation
›Symptomatic hyponatremia (seizures or coma)
›Hypertonic saline 3% IV
›150 ml IV bolus over 10-20 minutes
›Repeat bolus if seizures persist (up to 3 boluses)
›Target Na increase of 4-6 mmol/l acutely for symptom control
›Maintenance phase after acute treatment
›Fluid restriction as primary ongoing management
›Target Na correction rate < 8-10 mmol/l per 24 hours to prevent osmotic demyelination
›Serial sodium monitoring every 2-4 hours
›Mild to moderate asymptomatic hyponatremia
›Fluid restriction
›First-line approach to prevent and treat MDMA-induced hyponatremia
›Restrict to < 500 ml/hour in rave or event setting
›Normal saline IV only if volume depleted
›Avoid in euvolemic or hypervolemic SIAD
›Reassess electrolytes after any IV fluid
Rhabdomyolysis management
›IV fluid resuscitation
›NS or LR 1-2 L/hour initially for severe rhabdomyolysis
›Target urine output >= 1 ml/kg/hour
›Monitor for fluid overload in AKI
›Urine myoglobin clearance endpoint
›Clear urine as target
›CK trending down
›Avoid urine acidification
›Contraindicated if CK elevated
›Promotes renal myoglobin precipitation
›Alkalization of urine
›Sodium bicarbonate in IV fluids
›50-100 mEq/L in D5W
›Controversial — may protect renal tubules
›Monitor pH and electrolytes carefully
›Benzodiazepines first-line
›Lorazepam IV 2-4 mg
›Repeat every 5-10 minutes if seizures persist
›Address hyponatremia simultaneously
›Diazepam IV 5-10 mg
›Alternative if lorazepam unavailable
›Midazolam IM 10 mg
›Pre-hospital or no IV access
›Second-line if refractory
›Phenobarbital IV
›15-20 mg/kg IV at 60 mg/minute
›Preferred over phenytoin in toxidrome-related seizures
›Levetiracetam IV
›1,000-3,000 mg IV over 15 minutes
›Reasonable alternative
›Avoid phenytoin
›Less effective for drug-induced seizures
›Sodium channel mechanism less relevant in sympathomimetic toxicity
›Propofol infusion for status epilepticus
›ICU setting with intubation
›1-4 mg/kg/hour infusion
›Titrate to seizure suppression
›Role in severe hyperthermia
›Mechanism: blocks calcium release from sarcoplasmic reticulum
›Reduces muscle-generated heat
›Not primarily a serotonin antagonist
›Indication
›Consider if core temp > 39 C not responding to external cooling and benzodiazepines
›Evidence controversial — meta-analysis suggested improved survival
›Some series showed no benefit
›Dosing
›Dantrolene IV 1-2.5 mg/kg
›Repeat every 5-10 minutes to maximum 10 mg/kg
›Hepatotoxicity with prolonged use
›Contraindications and cautions
›Not for NMS primary treatment (adjunct only)
›Liver function monitoring
›Do not confuse with cyproheptadine indication
›Serotonin syndrome adjunct
›Mechanism: serotonin receptor antagonist (5-HT2A)
›Theoretical benefit in serotonin syndrome features
›No controlled trial evidence in MDMA toxicity
›Dosing
›Cyproheptadine 12 mg PO loading dose
›Maintenance 2 mg every 2 hours while awake
›Maximum 32 mg per day
›Limitations
›Oral only — challenging in obtunded patient
›Sedating antihistamine properties
›Evidence limited to case reports
Contraindicated and cautioned treatments
›Treatments to avoid
›Antipsychotics (haloperidol, droperidol)
›Lower seizure threshold
›Impair thermoregulation (reduce sweating)
›Risk of NMS overlap syndrome
›Hypotension risk
›SSRIs or SNRIs
›Worsen serotonin syndrome
›Never add to active MDMA toxicity
›Physical restraints without adequate sedation
›Associated with death in agitated sympathomimetic-poisoned patients
›Amplify thermogenesis and metabolic acidosis
›Beta-blockers alone without alpha coverage
›Unopposed alpha-adrenergic effect
›Severe hypertension paradox
›Urine acidification
›Contraindicated if CK elevated
›Promotes myoglobin tubular precipitation