Carbon dioxide attenuates pulmonary impairment resulting from hyperventilation

Crit Care Med. 2003 Nov;31(11):2634-40. doi: 10.1097/01.CCM.0000089646.52395.BA.


Objective: Deliberate elevation of PaCO2 (therapeutic hypercapnia) protects against lung injury induced by lung reperfusion and severe lung stretch. Conversely, hypocapnic alkalosis causes lung injury and worsens lung reperfusion injury. Alterations in lung surfactant may contribute to ventilator-associated lung injury. The potential for CO2 to contribute to the pathogenesis of ventilator-associated lung injury at clinically relevant tidal volumes is unknown. We hypothesized that: 1) hypocapnia would worsen ventilator-associated lung injury, 2) therapeutic hypercapnia would attenuate ventilator-associated lung injury; and 3) the mechanisms of impaired compliance would be via alteration of surfactant biochemistry.

Design: Randomized, prospective animal study.

Setting: Research laboratory of university-affiliated hospital.

Subjects: Anesthetized, male New Zealand Rabbits.

Interventions: All animals received the same ventilation strategy (tidal volume, 12 mL/kg; positive end-expiratory pressure, 0 cm H2O; rate, 42 breaths/min) and were randomized to receive FiCO2 of 0.00, 0.05, or 0.12 to produce hypocapnia, normocapnia, and hypercapnia, respectively.

Measurements and main results: Alveolar-arterial oxygen gradient was significantly lower with therapeutic hypercapnia, and peak airway pressure was significantly higher with hypocapnic alkalosis. However, neither static lung compliance nor surfactant chemistry (total surfactant, aggregates, or composition) differed among the groups.

Conclusions: At clinically relevant tidal volume, CO2 modulates key physiologic indices of lung injury, including alveolar-arterial oxygen gradient and airway pressure, indicating a potential role in the pathogenesis of ventilator-associated lung injury. These effects are surfactant independent.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carbon Dioxide / adverse effects
  • Carbon Dioxide / therapeutic use*
  • Hyperventilation*
  • Hypocapnia / complications*
  • Hypocapnia / physiopathology
  • Male
  • Rabbits
  • Respiratory Distress Syndrome / etiology*
  • Respiratory Distress Syndrome / therapy
  • Tidal Volume


  • Carbon Dioxide