The Effects of Hypercapnia on Cerebral Autoregulation in Ventilated Very Low Birth Weight Infants

Abstract

Permissive hypercapnia, a strategy allowing high PaCO 2 , is widely used by neonatologists to minimize lung damage in ventilated very low birth weight (VLBW) infants. While hypercapnia increases cerebral blood flow (CBF), its effects on cerebral autoregulation of VLBW infants are unknown. Monitoring of mean CBF velocity (mCBFv), PaCO 2 , and mean arterial blood pressure (MABP) from 43 ventilated VLBW infants during the first week of life was performed during and after 117 tracheal suctioning procedures. Autoregulation status was determined during tracheal suctioning because it perturbs cerebral and systemic hemodynamics. The slope of the relationship between mCBFv and MABP was estimated when PaCO 2 was fixed at 30, 35, 40, 45, 50, 55, and Neonatologists frequently use permissive hypercapnia, a strategy that allows high PaCO 2 (45-55 mm Hg), to avoid ventilator-induced lung injury during mechanical ventilation of premature infants (1). The theoretical benefit of permissive hypercapnia is that lower tidal volumes and mean airway pressures may prevent alveolar overdistension and lung injury (1). Randomized controlled trials of permissive hypercapnia, however, failed to demonstrate significant improvements in survival without chronic lung disease over routine ventilation strategies (1,2). Despite its widespread use, the effects of permissive hypercapnia on cerebral autoregulation of premature infants are not known.Cerebral autoregulation is an essential physiologic mechanism that maintains constant blood flow to the brain despite variations in cerebral perfusion pressure (3). The BP range over which CBF remains constant is known as the autoregulatory plateau. In this portion of the curve, CBF is independent of BP and the slope is 0. Below the autoregulatory plateau, CBF declines; above it, CBF rises in a pressure-passive manner (Fig. 1 A) (4,5). In contrast, in impaired autoregulation, CBF linearly follows changes in BP (over all BPs), where the slope is significantly Ͼ0 (Fig. 1B) (6). Despite the widespread belief that cerebral autoregulation is impaired in sick, ventilated premature infants (6), recent evidence using continuous monitoring systems suggests that many premature infants do have intact autoregulation (7,8

Hypercapnia during the first 3 days of life is associated with severe intraventricular hemorrhage in very low birth weight infants

“…17,18 Further, hypercapnia may abolish or impair cerebral autoregulation, causing the cerebral vasculature to be at risk for ischemia or hyperperfusion during fluctuations of blood pressure. [4][5][6] Consistent with our results, most studies examining the relationship between hypercapnia and IVH identified a positive univariate association. It was first demonstrated in 1978 that umbilical PaCO 2 was significantly greater in premature infants subsequently diagnosed with IVH compared to those without IVH.…”

“…This is concerning given our recent observations that increasing PaCO 2 levels in VLBW infants are associated with progressively impaired cerebral autoregulation. 4 As impaired cerebral autoregulation in premature infants is associated with brain injury, 2,3 hypercapnia may influence the development of severe IVH by vasodilating cerebral resistance arterioles and increasing CBF, and possibly overwhelming the integrity of the germinal matrix vessels causing them to rupture. 17,18 Further, hypercapnia may abolish or impair cerebral autoregulation, causing the cerebral vasculature to be at risk for ischemia or hyperperfusion during fluctuations of blood pressure.…”

“…[1][2][3] We recently observed that increasing PaCO 2 in ventilated very low birth weight (VLBW) infants during the first week of life is associated with progressively impaired cerebral autoregulation. 4 Further, hypercapnia in animals has been shown to abolish intact cerebral autoregulation. 5,6 In addition to low gestational age, low birth weight, male gender, worse acute lung disease, etc., hypercapnia has also been identified as an important risk factor for intraventricular hemorrhage (IVH), [7][8][9][10][11][12][13][14][15][16] the most common acute brain injury of premature infants.…”

“…Although it is unclear whether hypercapnia causes IVH or results from circulatory disturbances that follow severe IVH, hypercapnia may influence the development of IVH by causing vasodilation of cerebral resistance arterioles, increasing CBF, and by impairing intact cerebral autoregulation. [4][5][6]17,18 A majority of the published studies reporting an association between hypercapnia and IVH were performed in the pre-surfactant era, where goals for ventilation 19,20 were different than that currently recommended. 21 Before the surfactant era, hypercapnia was likely a proxy for the sickest infants with the most severe respiratory distress syndrome.…”

“…We therefore initiated a retrospective study of inborn VLBW infants born during the surfactant and permissive hypercapnia eras with the objective of determining if hypercapnia during the early neonatal period was still associated with IVH. Based on our previous studies, 4,18 we hypothesized that hypercapnia (maximum PaCO 2 ) in VLBW infants during the first 3 days of life is still associated with severe IVH.…”