In a 35-year-old woman with refractory anaphylactic shock who remains hypotensive after adequate fluid resuscitation and two intramuscular epinephrine (epinephrine autoinjector) doses, what is the next appropriate treatment?

Refractory Anaphylactic Shock Management

The correct answer is "None of the above" - the next step is to initiate an intravenous epinephrine infusion (0.05-0.1 mcg/kg/min), not a different vasopressor. 1, 2

Rationale for Continued Epinephrine

After two intramuscular epinephrine doses with persistent hypotension despite adequate fluid resuscitation, this patient has refractory anaphylactic shock requiring escalation of epinephrine therapy, not switching to alternative vasopressors. 1

The British Journal of Anaesthesia guidelines explicitly recommend commencing an epinephrine infusion (0.05-0.1 mcg/kg/min) when there is inadequate sustained response after 10 minutes or when more than three epinephrine boluses have been administered. 1, 2

Why the Listed Options Are Incorrect

Dopamine at 5 mcg/kg/min

• Dopamine is considered third-line therapy for anaphylaxis, only after epinephrine and fluid resuscitation have failed 1
• The stated goal of "increasing urine output" is inappropriate - the priority is restoring mean arterial pressure and tissue perfusion, not diuresis 1
• Dopamine dosing for shock typically requires 2-20 mcg/kg/min titrated to effect, not a fixed 5 mcg/kg/min 1

Norepinephrine at 0.02 mcg/kg/min

• Norepinephrine is an adjunctive vasopressor added only for persistent hypotension after adequate epinephrine therapy 1
• Guidelines recommend adding norepinephrine (0.05-0.5 mcg/kg/min) only when hypotension persists after 10 minutes of appropriate epinephrine treatment 1
• The proposed dose of 0.02 mcg/kg/min is below the recommended range 1

Phenylephrine at 0.5 mcg/kg/min

• Pure alpha-agonists like phenylephrine lack the critical beta-adrenergic effects needed in anaphylaxis (bronchodilation, increased cardiac contractility, and inotropy) 3
• Avoiding phenylephrine because the patient is "tachycardic" reflects a misunderstanding - tachycardia in anaphylactic shock is a compensatory response to maintain cardiac output 3
• Phenylephrine is listed as a potential adjunct only after epinephrine optimization 1

Correct Management Algorithm

Immediate Actions (Now)

• Commence IV epinephrine infusion at 0.05-0.1 mcg/kg/min (approximately 3.5-7 mcg/min for a 70 kg patient) 1, 2
• Continue aggressive crystalloid boluses (escalate up to 20-30 mL/kg total) 1
• Ensure continuous hemodynamic monitoring 2

If Hypotension Persists After 10 Minutes

• Add norepinephrine infusion (0.05-0.5 mcg/kg/min) as a second vasopressor 1
• Consider vasopressin 1-2 IU bolus with or without infusion (2 units/hour) 1
• Escalate epinephrine dose by doubling if inadequate response 1, 2

Additional Considerations

• Administer IV antihistamines (H1 and H2 blockers) after hemodynamic stabilization, but these are not priorities 1
• Consider IV corticosteroids (methylprednisolone 1-2 mg/kg every 6 hours) to prevent biphasic reactions 1
• If patient is on beta-blockers, add glucagon 1-5 mg IV over 5 minutes followed by infusion 1

Critical Pitfalls to Avoid

Do not abandon epinephrine prematurely. The pathophysiology of anaphylactic shock involves profound vasodilation, capillary leak causing effective hypovolemia, and myocardial depression - all of which require epinephrine's combined alpha and beta effects. 3 Switching to alternative vasopressors before optimizing epinephrine therapy contradicts established guidelines. 1

Do not withhold epinephrine due to tachycardia. Compensatory tachycardia maintains cardiac output in distributive shock, and suppressing it with pure alpha-agonists can worsen outcomes. 3

Ensure adequate volume resuscitation. Up to 35% of intravascular volume can shift to the extravascular space within minutes during anaphylaxis. 1 Vasopressors without adequate preload will be ineffective. 1