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Abstract

Submit Manuscript | http://medcraveonline.com from clinical trials illustrates the importance of controlling the partial pressures of carbon dioxide (PCO 2 ) and oxygen (PO 2 ) in order to maximize neurodevelopmental outcomes and ameliorate secondary brain injury resulting from over ventilation and oxygenation.Carbon dioxide regulates cerebrovascular tone by inducing vasodilation and augmenting perfusion at high levels (hypercapnic) and vasoconstriction and diminishing perfusion during low levels (hypocapnic). Knowing that hypocapniamediated vasoconstriction is maintained in hypoxic-ischemic encephalopathy raises concerns that low PCO 2 may accentuate secondary brain injury, not only by reducing cerebral perfusion, but by reducing O 2 delivery, increasing neuronal energy demands and DNA fragmentation, and depleting neuronal energy stores [4][5][6][7]. Indeed newborn animal models demonstrate that hypocapnia reduces cerebral blood flow following asphyxia and is associated with greater brain injury than observed in either eucapnic or hypercapnic animals [8,9]. More severe brain injury, detected on MRI, has also been identified in infants with suboptimal cerebral vasoreactivity determined by near-infrared spectroscopy [10]. Several clinical series reveal that hypocapnia is correlated with adverse neuro developmental outcomes in infants with hypoxicischemic encephalopathy (HIE). In a retrospective cohort study of infants with HIE prior to the use of TH, Klinger et al found that severe hypocapnia (PCO 2 <20 mmHg) was associated with increased risk of death or severe neurologic impairment (relative risk 2.3) [11]. Analysis of data from the NICHD Research Network whole body cooling trial found both minimum and cumulative PCO 2 <35 mmHg were associated with poor neurodevelopment outcome [12]. More recently, post hoc analysis of the CoolCap Study data estimated the probability of poor outcome based upon PCO 2 , finding an inverse correlation between the lowest PCO 2 and the severity of neurologic outcome after controlling for pH, aEEG pattern, birth weight, cooling status, and Sarnat score [13].Although hypocapnia in neonatal encephalopathy may be a surrogate marker for brain injury severity, PCO 2 represents a readily modifiable factor capable of maximizing neurologic recovery. As many infants undergoing TH are intubated for apnea, frequent blood gas monitoring and/or transcutaneous or endtidal CO 2 monitoring are essential. As respiratory drive returns, many infants become tachypneic and hypocapnic. At a minimum, clinicians should minimize ventilator settings and foster rapid extubation in an attempt to not inadvertently lower PCO 2 . For persistent hypocapnia, both sedation and the introduction of dead space into the ventilator circuitry may restore PCO 2 to "normal" levels. To date, however, neither strategy has been studied, rendering the safety and effectiveness for improving neurologic outcomes speculative.In contrast to CO 2 , high partial pressures of oxygen are injurious yet frequently life-sustaining. Even a b...