Sepsis and therapeutic hypercapnia: sailing too close to the wind?

ALMOST a decade ago, the landmark study of low tidal volume ventilation (6 vs. 12 ml/kg ideal body weight) in the acute respiratory distress syndrome (ARDS) showed that a strategy leading in some cases to carbon dioxide retention (permissive hypercapnia) reduced mortality by a remarkable 25%. Lung protective ventilation is now the standard of care for acute lung injury and ARDS. Lack of obvious harm with permissive hypercapnia, except in those with intracranial hypertension or cardiac instability, impelled some to proceed further and purposefully impose a state of hypercapnic acidosis (therapeutic hypercapnia) in various animal models of lung injury; the working hypothesis being that hypercapnic acidosis modulates the excessive inflammatory milieu of ARDS. One of the leading groups from the start has been that of Laffey and coworkers, who in this issue of ANESTHESIOLOGY comprehensively review the many aspects of protection afforded by hypercapnic acidosis in lung injury. What is important in this review to the intensive care physician is the real concern, heretofore largely ignored, that similar to many antiinflammatory or immune-modulating interventions, therapeutic hypercapnia may impair host defenses against pathogens surely to be encountered by mechanically ventilated patients. The history of therapeutic hypercapnia reaches back to the early days of arterial blood gas analysis and mechanical ventilation. Until the last decade, it was a standard practice to correct hypercapnic acidosis with mechanical ventilation using high tidal volumes and pressures, if necessary, owing to the perceived dangers of respiratory acidosis itself. The evidence for harm, however, had always been weak. Indeed, the advent of clinical blood gas analysis in the 1950s revealed surprisingly profound hypercapnia (PaCO2 150 mmHg, pH 7.0) without negative consequence in thoracic surgical cases involving one-lung ventilation. A PaCO2 of 501 mmHg from massive grain aspiration in a healthy farmer with complete recovery has been reported. The concept of permissive hypercapnia, purposefully limiting tidal volume and pressure and accepting subsequent hypercapnic acidosis, was first studied in status asthmaticus and gained credence in the mid-1980s. Darioli and Perret reported a mortality reduction from 20% to almost 0%, largely by prevention of pneumothorax and hemodynamic compromise, even with the initial PaCO2 exceeding 100 mmHg. Acute hypercapnic acidosis is well tolerated as long as perfusion and arterial oxygenation are assured. In rats maintained at 2 atm (50% O2–50% CO2), cerebral oxidative metabolism is unaffected even at PCO2 more than 750 mmHg and pH as low as 6.1. 7