16/01/2006
The effect of hypercapnia on cerebral autoregulation in VLBW infants
An observational study raises concerns regarding the use of permissive hypercapnia in ventilated very low birth weight infants

Permissive hypercapnia is a widespread-used method to avoid ventilator-induced lung injury during mechanical ventilation of premature infants. This method allows high PaCO₂ levels (45- 55 mm Hg) in order to prevent alveolar overdistension . Permissive hypercapnia increases cerebral blood flow (CBF) and is often suggested in order to avoid accidental hypocapnia, which in premature infants is associated with poor neurodevelopment.

Anyway, the effects of permissive hypercapnia on cerebral autoregulation in premature infants are unknown. Cerebral autoregulation is a physiological mechanism that maintains CBF constant, despite changes in cerebral perfusion pressure. CBF remains constant in a precise range of blood pressure (BP), known as autoregulation plateau, in which the slope of the BP-CBF curve is 0. Above the plateau, CBF increases in a pressure-passive manner. In the case of an impaired regulation, CBF is linearly dependent from BP (i.e., the slope is always > 0). As yet the ideal PaCO₂ range for premature infants is unknown. In fact, hypercapnia contributes to the development of intraventricular hemorrhage (IVH) and is associated with impaired cerebral regulation in animal models. Conversely, impaired autoregulation associated with a number of pathologic conditions can be restored by hyperventilation (PaCO₂ 25- 30 mm Hg).

On the hypothesis that cerebral autoregulation would become progressively impaired by increasing PaCO₂, an observational study was conducted at the University of Arkansas, in order to examine for the first time the effects of PaCO₂ on cerebral autoregulatory capacity of ventilated premature infants in the first week of life.

In total, 43 infants with a very low birth weight (VLBW) [501-1500 g], all requiring mechanical ventilation for respiratory distress syndrome, were enrolled in the study. Autoregulatory capacity was tested by comparing simultaneous changes in CBF velocity with those in mean arterial BP, before, during and after 117 tracheal suctioning procedures, which perturb cerebral and systemic hemodynamics. The slope of the CBF velocity versus BP was estimated with fixed PaCO₂ values in 30- 60 mm Hg range.

Results showed that autoregulatory slope raised according to increasing in PaCO₂. In particular, statistical differences were observed starting from a PaCO₂ equal to 45 mm Hg, therefore indicating a progressive loss of cerebral autoregulation. These observations are consistent with previous data, obtained in animal models and in adults, which demonstrated that hypercapnia is associated with impaired cerebral autoregulation. Moreover, premature infants who lack autoregulation capacity and have BP perturbations leading to CBF fluctuations are more likely to develop brain injury if compared with those with normal CBF regulations. Therefore, hypercapnia is associated to an impaired autoregulation, which eventually can lead to an increased violability to brain injury.

These findings raise concerns regarding the widespread use of permissive hypercapnia in VLBW infants. Careful control of PaCO₂ during the first week of life, by preventing hypercapnia as well as hypocapnia may be identified as a potential clinical goal to restore intact cerebral autoregulation and to prevent IVH in ventilated VLBW infants.

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