What is the management of severe leptospirosis with signs of Acute Respiratory Distress Syndrome (ARDS)?

Management of Severe Leptospirosis with ARDS

Implement lung-protective mechanical ventilation with tidal volumes of 4-8 mL/kg predicted body weight, plateau pressures ≤30 cmH₂O, prone positioning for severe hypoxemia, early antibiotics within 6 hours, conservative fluid resuscitation, and consider corticosteroids—this approach achieves mortality rates as low as 4% in severe leptospirosis with ARDS. 1

Immediate Antibiotic Therapy

• Administer intravenous antibiotics within the first 6 hours of presentation—this is critical and was achieved in 82% of survivors in the highest-quality leptospirosis-ARDS cohort 1
• Do not delay antibiotics while awaiting confirmatory testing, as early treatment significantly impacts outcomes 1

Lung-Protective Mechanical Ventilation Strategy

Core ventilation parameters:

• Set tidal volume at 6 mL/kg predicted body weight (acceptable range 4-8 mL/kg PBW) 2
• Calculate predicted body weight: Males = 50 + 0.91 × [height (cm) - 152.4] kg; Females = 45.5 + 0.91 × [height (cm) - 152.4] kg 2
• Never exceed 8 mL/kg PBW even if plateau pressures appear acceptable 2
• Maintain plateau pressure ≤30 cmH₂O as an absolute ceiling 2
• Target driving pressure (plateau pressure minus PEEP) ≤15 cmH₂O, as this predicts mortality better than tidal volume or plateau pressure alone 2

PEEP management:

• For moderate-to-severe ARDS (PaO₂/FiO₂ <200 mmHg), use higher PEEP levels typically >10 cmH₂O 2
• Higher PEEP reduces mortality in this population with an adjusted relative risk of 0.90 2

Prone Positioning

• Implement prone positioning immediately for severe ARDS with PaO₂/FiO₂ <150 mmHg—this is a strong recommendation that reduces mortality (RR 0.74) 2
• Position the patient prone for at least 12-16 hours daily 2
• In leptospirosis-specific cohorts, 67% developed moderate-to-severe ARDS and 58% had pulmonary hemorrhage, making protective ventilation strategies essential 1

Fluid Management

• Use conservative fluid resuscitation strategies—the median fluid balance in the first three days should be approximately +1500 ml 1
• Conservative fluid management improves ventilator-free days without increasing non-pulmonary organ failures 2
• Avoid aggressive fluid loading despite hypotension; prioritize vasopressor support instead 1

Vasopressor Support

• Initiate vasopressor support early when needed—62% of severe leptospirosis patients with ARDS required vasopressors 1
• Do not delay vasopressors in favor of excessive fluid resuscitation 1

Corticosteroid Therapy

• Administer systemic corticosteroids to mechanically ventilated patients with ARDS 2
• In severe leptospirosis specifically, corticosteroids were used in 36% of patients in the highest-quality cohort with excellent outcomes 1
• Consider intravenous corticosteroids as part of supportive care, particularly in severe cases 3
• Use for a short duration (3-5 days) at doses not exceeding the equivalent of 1-2 mg/kg methylprednisolone per day 4

Renal Replacement Therapy

• Acute kidney injury occurs in 87% of severe leptospirosis cases 1
• Initiate renal replacement therapy using traditional criteria for initiation—do not delay unnecessarily, but early prophylactic RRT is not required 1
• Early initiation of sustained low-efficiency dialysis (SLED) followed by daily SLED significantly decreases mortality in severe leptospirosis 5
• Consider hemodiafiltration (SLEDf) over traditional hemodialysis, as it produces greater decreases in inflammatory mediators (IL-17, IL-7, MCP-1), though mortality differences have not been definitively established 5

Neuromuscular Blockade

• For early severe ARDS with PaO₂/FiO₂ <150 mmHg, use neuromuscular blocking agents for up to 48 hours 2
• Neuromuscular blockade improves oxygen supply, especially with ventilator-patient dyssynchrony 4

Oxygenation Targets

• Target SpO₂ of 88-95% to avoid hyperoxia while maintaining adequate oxygenation 2
• Target PaO₂ of 70-90 mmHg 4

Sedation Management

• Adopt deep sedation and analgesia with muscle relaxation strategy within the first 48 hours of mechanical ventilation 4
• Minimize continuous or intermittent sedation thereafter, targeting specific titration endpoints 2

ECMO Consideration

• Consider venovenous ECMO for refractory hypoxemia when PaO₂/FiO₂ remains <80 mmHg for at least 3 hours despite optimal ventilation, or <100 mmHg for at least 6 hours 6
• ECMO should only be performed at centers with sufficient experience (>20-25 cases per year) 6
• Initiate ECMO within 7 days of respiratory failure onset for optimal outcomes 6
• Do not delay ECMO until after prolonged mechanical ventilation (>9.6 days), as this is associated with worse outcomes 6

Interventions to AVOID

• Do not use high-frequency oscillatory ventilation—this is strongly contraindicated and associated with harm 2
• Do not routinely use pulmonary artery catheters 2
• Do not use β-2 agonists without bronchospasm 2
• Do not perform prolonged recruitment maneuvers—these are associated with harm 2

Prognostic Indicators

Poor prognostic factors requiring intensified monitoring:

• PaO₂/FiO₂ ratio <100 on day 3 is associated with 90% mortality 7
• Requirement for invasive mechanical ventilation carries 70.4% mortality risk 7
• Age ≥55 years (67% sensitivity, 91% specificity for mortality) 5
• APACHE II score ≥39.5 (67% sensitivity, 88% specificity) 5
• SOFA score ≥20.5 (67% sensitivity, 85% specificity) 5
• Inspiratory pressure ≥31 mmHg (84% sensitivity, 85% specificity) 5

Expected Outcomes

• With optimal ICU management including early antibiotics, protective ventilation, conservative fluids, and appropriate use of corticosteroids, mortality can be reduced to 4% even in severe leptospirosis with ARDS 1
• Without optimal management, mortality ranges from 39.6% to 52% 7, 8
• The requirement for mechanical ventilation and presence of ARDS are major determinants of mortality 8