What is the best course of treatment for a patient with hypotension due to a drug overdose?

Management of Drug Overdose with Hypotension

For hypotension due to drug overdose, immediately initiate fluid resuscitation with crystalloid boluses (minimum 30 mL/kg) while simultaneously identifying the specific toxin, then administer targeted antidotes and vasopressors based on the causative agent. 1

Initial Resuscitation and Assessment

Determine the underlying cause of hypotension through rapid assessment: evaluate for hypovolemia, vasodilation, bradycardia, or low cardiac output to guide treatment selection. 1 Approximately 50% of hypotensive patients are not fluid-responsive, making cause-directed therapy essential rather than reflexive fluid administration alone. 1

Immediate Fluid Resuscitation

• Administer crystalloid boluses of 10-20 mL/kg in children or 250-500 mL in adults as initial therapy. 1
• For suspected hypovolemia, perform a passive leg raise test (positive likelihood ratio of 11, specificity 92%) to determine fluid responsiveness before additional boluses. 1
• Use crystalloids (normal saline or balanced crystalloids like lactated Ringer's) as first-line fluid therapy. 2

Toxin-Specific Antidote Administration

Beta-Blocker Overdose

High-dose insulin is the first-line antidote for β-blocker-induced hypotension refractory to vasopressors. 3

• Administer regular human insulin 1 U/kg IV bolus, followed by continuous infusion of 1-10 U/kg/h. 3
• Monitor closely for hypoglycemia and hypokalemia; provide supplemental dextrose as needed. 3
• Add vasopressors (norepinephrine preferred) for persistent hypotension. 3, 2
• Glucagon 2-10 mg IV bolus followed by 1-15 mg/h infusion is reasonable for bradycardia or hypotension. 3
• Atropine 0.5-1.0 mg IV every 3-5 minutes (up to 3 mg) may be used for bradycardia, though evidence is limited. 3
• Consider VA-ECMO for refractory cardiogenic shock unresponsive to pharmacological interventions. 3

Calcium Channel Blocker Overdose

• High-dose insulin therapy (same dosing as β-blocker overdose) is effective for severe cardiovascular toxicity. 3
• Calcium chloride 2000 mg IV (20 mg/kg pediatric) or calcium gluconate 6000 mg IV (60 mg/kg pediatric), followed by continuous infusion titrated to blood pressure. 3
• Target ionized calcium concentration 1.5-2 times upper limits of normal; administer through central line especially in children. 3
• Add vasopressors if hypotension persists despite antidote therapy. 3

Sodium Channel Blocker Overdose (TCAs, Cocaine, Others)

Administer sodium bicarbonate for life-threatening cardiotoxicity from tricyclic antidepressants and other sodium channel blockers. 3

• Give hypertonic sodium bicarbonate 50-150 mEq IV bolus (1-3 mEq/kg pediatric). 3
• Prepare maintenance infusion of 150 mEq/L solution, infuse at 1-3 mL/kg/h. 3
• Monitor for hypernatremia, alkalemia, hypokalemia, and hypochloremia. 3
• For cocaine-induced hypotension with suspected coronary ischemia: administer benzodiazepines first, then consider phentolamine, nicardipine, or nitroprusside. 3
• Avoid β-blockers (including labetalol) in cocaine toxicity as they do not reduce coronary vasoconstriction. 3
• Consider VA-ECMO for refractory cardiogenic shock. 3

Opioid Overdose with Hypotension

If combined opioid and benzodiazepine poisoning is suspected, administer naloxone first before other antidotes. 3

• Naloxone 0.2-2 mg IV/IO/IM (0.1 mg/kg pediatric), repeated every 2-3 minutes as needed. 3, 4
• Titrate to reversal of respiratory depression and restoration of protective airway reflexes, not full consciousness. 3
• Intranasal naloxone 2-4 mg may be used if IV access unavailable. 3
• Maintain continuous infusion at two-thirds of the waking dose per hour for sustained effect. 3
• Address hypotension with fluid resuscitation and vasopressors as opioids rarely cause isolated hypotension without other coingestants. 3

Benzodiazepine Overdose

• Flumazenil 0.2 mg IV, titrated up to 1 mg (0.01 mg/kg pediatric), can be effective in select patients with pure benzodiazepine poisoning and respiratory depression. 3
• Flumazenil is contraindicated in patients at risk for seizures or dysrhythmias (chronic benzodiazepine use, coingestion of proconvulsant drugs like TCAs, preexisting seizure disorder). 3
• Flumazenil has no role in cardiac arrest related to benzodiazepine poisoning. 3

Organophosphate/Carbamate Poisoning

• Atropine 1-2 mg IV, doubled every 5 minutes until full atropinization (clear chest, heart rate >80/min, systolic BP >80 mmHg). 3
• Maintenance infusion: 10-20% of total loading dose per hour up to 2 mg/h. 3
• Pralidoxime 1-2 g IV (20-50 mg/kg pediatric), followed by 400-600 mg/h infusion. 3

Digoxin Overdose

• Digoxin immune Fab: 1 vial for every 0.5 mg digoxin ingested in acute overdose. 3
• For critically ill patients with unknown ingested dose: 10-20 vials. 3
• For chronic toxicity: calculate dose = serum digoxin concentration (ng/mL) × weight (kg) / 100. 3

Vasopressor Therapy

First-Line Vasopressor Selection

Norepinephrine is the first-choice vasopressor for drug overdose-induced hypotension. 1, 2

• Start norepinephrine at 0.1-0.5 mcg/kg/min (7-35 mcg/min in 70 kg adult) via continuous IV infusion. 2
• Standard concentration: 4 mg norepinephrine in 250 mL D5W (16 mcg/mL). 2
• Target mean arterial pressure (MAP) ≥65 mmHg. 1, 2
• Central venous access is strongly preferred to minimize extravasation risk. 2
• If central access unavailable, peripheral IV or intraosseous administration can be used temporarily. 2
• Monitor blood pressure every 5-15 minutes during initial titration. 2

Escalation for Refractory Hypotension

• Add vasopressin 0.03-0.04 units/min when norepinephrine reaches 0.25 mcg/kg/min and hypotension persists. 2
• Consider epinephrine 0.1-0.5 mcg/kg/min as second-line agent. 2
• For low cardiac output states, add dobutamine 2.5-20 mcg/kg/min rather than escalating vasopressors. 2
• Avoid phenylephrine as first-line therapy as it may raise blood pressure while worsening tissue perfusion through reflex bradycardia. 1, 2

Alternative Vasopressors for Specific Overdoses

• Vasopressin is particularly effective for catecholamine-resistant shock from drug overdose, including prazosin and methyldopa overdose. 5, 6, 7
• Angiotensin II 10 ng/kg/min may be effective for refractory shock from antihypertensive overdose, particularly ACE inhibitor overdose. 8
• Methylene blue 1-2 mg/kg IV (repeated every hour if needed, maximum 5-7 mg/kg) for vasodilatory shock. 3

Extracorporeal Support

• VA-ECMO is reasonable for life-threatening β-blocker, calcium channel blocker, or sodium channel blocker poisoning with cardiogenic shock refractory to pharmacological interventions. 3
• Hemodialysis may be reasonable for life-threatening atenolol or sotalol poisoning (water-soluble β-blockers). 3

Critical Monitoring Parameters

• Continuous arterial blood pressure monitoring via arterial catheter as soon as practical. 2
• Assess tissue perfusion markers: lactate clearance, urine output >50 mL/h, mental status, capillary refill. 2
• Monitor for complications: arrhythmias, excessive vasoconstriction (cold extremities, decreased urine output), pulmonary edema. 2, 9
• Serial electrolytes and renal function monitoring, especially with calcium or insulin therapy. 3

Critical Pitfalls to Avoid

• Do not administer reflexive fluid boluses without assessing fluid responsiveness, as approximately 50% of hypotensive patients are not hypovolemic. 1
• Avoid using dopamine as first-line vasopressor as it is associated with higher mortality and arrhythmias compared to norepinephrine. 2
• Do not use flumazenil in undifferentiated coma or patients with chronic benzodiazepine use due to risk of seizures and dysrhythmias. 3
• Avoid β-blockers (including labetalol) in cocaine toxicity as they do not reduce coronary vasoconstriction and may worsen outcomes. 3
• Do not use low-dose dopamine for renal protection as it has no benefit. 2
• Ensure adequate volume resuscitation before starting vasopressors to prevent severe organ hypoperfusion from vasoconstriction in hypovolemic patients. 1, 2
• If extravasation of vasopressors occurs, immediately infiltrate phentolamine 5-10 mg diluted in 10-15 mL saline at the site to prevent tissue necrosis. 2, 9