Neuropharmacology, Sedation, Analgesia, and Toxic-Metabolic Encephalopathy
Sedation and analgesia
Target a defined sedation scale rather than a subjective impression. Propofol is short acting but causes propofol infusion syndrome with high doses (above roughly 4-5 mg/kg/hour), prolonged infusions, acidosis, rhabdomyolysis, and bradycardia. Dexmedetomidine causes bradycardia and hypotension but preserves respiratory drive, useful for extubation and awake procedures. Midazolam accumulates in renal failure, prolonging coma. Never use neuromuscular blockade without adequate sedation. Antiseizure drug pitfalls: phenytoin shows zero-order kinetics, induces hepatic enzymes, and causes hypotension with rapid infusion; levetiracetam requires renal dosing; valproate can cause hyperammonemia and hepatotoxicity; lacosamide prolongs the PR interval.
Toxic-metabolic encephalopathy
Consider hepatic encephalopathy (ammonia, lactulose, rifaximin), uremia, hypoglycemia, hyponatremia, hypercalcemia, Wernicke encephalopathy (give thiamine before glucose), and osmotic demyelination. Review every medication for anticholinergic and sedative burden. Recognize toxidromes: opioid (miosis, hypoventilation), serotonin syndrome (clonus, hyperreflexia), neuroleptic malignant syndrome (rigidity, hyperthermia), and baclofen withdrawal.
Trap: attributing persistent unresponsiveness to a metabolic cause while missing nonconvulsive status epilepticus, or giving flumazenil to a patient with a mixed overdose and seizure risk.
Rule of thumb: in unexplained encephalopathy, check glucose, sodium, ammonia, lactate, and an EEG before accepting a metabolic explanation.