Permissive hypercapnia in neonates: the case of the good, the bad, and the ugly.

Advances in neonatology have resulted in an increase in the absolute number of survivors with chronic lung disease (CLD), though its overall incidence has not changed. Though the single most important high-risk factor for CLD is prematurity, the focus of attention has recently changed over to minimizing the impact of other two risk factors: baro/volutrauma related to mechanical ventilation, and oxygen toxicity. Permissive hypercapnia (PHC) or controlled ventilation is a strategy that minimizes baro/volutrauma by allowing relatively high levels of arterial CO(2), provided the arterial pH does not fall below a preset minimal value. The benefits of PHC are primarily mediated by the reduction of lung stretch that occurs when tidal volumes are minimized. PHC can be a deliberate choice to restrict ventilation in order to avoid overdistention, while application of high airway pressures and large tidal volumes would permit normocapnia, or relative hypocapnia (PaCO(2), < or = 25-30 mmHg), but may result in CLD and be harmful to the developing lung. The current concept that PaCO(2) levels of 45-55 mmHg in high-risk neonates are "safe" and "well tolerated" is based on limited data. Further prospective trials are needed to study the definition, safety and efficacy of PHC in ventilated preterm and term neonates. However, designing disease/gestational-postnatal age-specific clinical trials of PHC will be difficult in neonates, given the diverse pathophysiology of their diseases and the various ventilatory modes/variables currently available. The potential benefits and adverse effects of PHC are reviewed, and its relationship to current ventilatory strategies like synchronized mechanical ventilation and high-frequency ventilation in high-risk neonates is briefly discussed. Copyright 2002 Wiley-Liss, Inc.