What to give to a patient with leptospirosis (Weil's disease) who remains hypotensive despite dopamine infusion?

Vasopressor Management for Dopamine-Refractory Hypotension in Leptospirosis

Switch from dopamine to norepinephrine immediately, as norepinephrine is the first-line vasopressor with superior mortality outcomes, and add vasopressin at 0.03 units/minute if hypotension persists despite norepinephrine. 1

Why Dopamine Should Be Discontinued

• Dopamine is associated with an 11% absolute increase in mortality compared to norepinephrine (number needed to harm = 9 patients), making it an inferior choice for septic shock management. 1

• Dopamine carries a 53% increased risk of supraventricular arrhythmias (RR 0.47 for norepinephrine vs dopamine) and a 65% increased risk of ventricular arrhythmias (RR 0.35), which is particularly dangerous in critically ill patients with leptospirosis who may already have cardiac involvement. 1

• The Society of Critical Care Medicine gives norepinephrine a Grade 1B (strong) recommendation as first-line vasopressor, while dopamine should only be used in highly selected patients with low risk of tachyarrhythmias or absolute bradycardia—conditions rarely present in severe leptospirosis. 1

Immediate Management Algorithm

Step 1: Ensure Adequate Fluid Resuscitation

• Administer at least 30 mL/kg of crystalloid fluids in the first 3 hours if not already completed, as vasopressors work optimally only after adequate volume replacement. 1

• In severe leptospirosis specifically, conservative fluid resuscitation (median +1493 mL over first 3 days) is associated with very low mortality (4%) in ICU settings, so avoid excessive fluid administration. 2

Step 2: Transition to Norepinephrine

• Discontinue dopamine and initiate norepinephrine as the first-line vasopressor, targeting a mean arterial pressure (MAP) ≥65 mmHg. 1

• Start norepinephrine at 0.1-0.5 mcg/kg/min and titrate based on hemodynamic response, using continuous arterial blood pressure monitoring via arterial catheter. 1

• Administer through central venous access whenever possible to minimize risk of tissue necrosis from extravasation; if unavailable, use a large-bore peripheral vein with frequent monitoring for infiltration. 3

Step 3: Add Vasopressin for Refractory Hypotension

• If MAP remains <65 mmHg despite norepinephrine, add vasopressin at 0.03 units/minute (not as monotherapy, but in addition to norepinephrine). 1

• Vasopressin at this dose allows reduction of norepinephrine requirements and does not increase heart rate, unlike catecholamine vasopressors. 4

• Never exceed 0.03-0.04 units/minute of vasopressin for routine use, as higher doses are associated with cardiac, digital, and splanchnic ischemia. 1

Step 4: Consider Third-Line Agents if Needed

• If hypotension persists despite norepinephrine plus vasopressin, add epinephrine at 0.05-2 mcg/kg/min as a third vasopressor agent. 1

• Alternatively, if there is evidence of myocardial dysfunction with persistent hypoperfusion despite adequate MAP, add dobutamine at 2.5-20 mcg/kg/min to improve cardiac output rather than further escalating vasopressors. 1

Leptospirosis-Specific Considerations

• Early antibiotic therapy is critical—all patients should receive appropriate antibiotics (penicillin, ceftriaxone, or cefepime) within the first 6 hours, as 82% of survivors in one series received antibiotics this early. 2, 5

• Be prepared for Jarisch-Herxheimer reaction after antibiotic initiation, which can cause transient worsening of hypotension, fever, and chills requiring temporary escalation of vasopressor support. 5

• Pulmonary hemorrhage occurs in 58% of severe leptospirosis cases requiring ICU admission, so protective ventilation strategies and early recognition of respiratory deterioration are essential. 2

• Acute kidney injury develops in 87% of severe cases, but traditional thresholds for renal replacement therapy initiation (rather than early prophylactic RRT) are associated with excellent outcomes. 2

• Consider corticosteroid therapy (hydrocortisone 200 mg/day) for refractory shock, as 36% of ICU survivors received corticosteroids and this may improve shock reversal. 1, 2

Critical Monitoring Parameters

• Continuously monitor MAP, heart rate, urine output (target ≥0.5 mL/kg/hr), lactate clearance, mental status, and peripheral perfusion to assess adequacy of resuscitation. 1

• Watch for signs of excessive vasoconstriction: digital ischemia, decreased urine output, rising lactate, or worsening organ dysfunction despite adequate MAP. 1

• Monitor for cardiac manifestations of leptospirosis including atrial fibrillation, which may develop during the illness course and can spontaneously resolve. 6

Common Pitfalls to Avoid

• Do not use low-dose dopamine for renal protection—this is strongly discouraged and has no benefit while increasing arrhythmia risk. 1

• Do not combine dopamine with epinephrine—combined use is discouraged due to additive adverse effects. 3

• Do not delay switching from dopamine to norepinephrine—every hour of continued dopamine use exposes the patient to increased mortality risk. 1

• Do not use phenylephrine as first-line therapy—it may raise blood pressure numbers while actually worsening tissue perfusion through excessive vasoconstriction without cardiac output support. 1