Strategies for Cooling Surface cooling can begin with induction of anesthesia, which promotes loss of heat and impairs thermoregulatory responses A reduction in temperature to 35°C is generally well tolerated, and may confer protection against ischemia in the period prior to bypass by metabolic suppression and alteration of responses to cellular injury Further cooling on bypass is targeted based on the anticipated level of flow required to complete the surgical repair If DHCA is anticipated, a nasopharyngeal temperature of 18°C is generally the target, with evidence for increased complications at significantly higher and lower temperatures Active cooling should be accompanied by measures of the adequacy of uniform cerebral cooling, for which measurements of surface temperature are inadequate.227 Other indicators include jugular venous saturation, the electroencephalogram, and NIRS, from which evidence of metabolic suppression can be more directly ascertained.228–232 At least 20 minutes of cooling is associated with improved outcome if hypothermic circulatory arrest is utilized.233,234 A high-flow hardcooling pump strategy is necessary to raise the jugular venous saturation above 95%.182 Measures that increase cerebral blood flow, such as a pH-stat strategy, can improve brain cooling as previously discussed.183 Recent evidence-based reviews cite no advantage to hypothermia in either neurosurgery or open heart operations.235,236 Since many operations can be completed without significant interruption in flow of blood, this finding may be unsurprising.237 These meta-analytic reviews, nonetheless, fly in the face of overwhelming laboratory and clinical evidence of protection from ischemic injury with hypothermia in global ischemia.238–242 Because the metabolic benefit of cooling and hypothermia is lost during rewarming, which may be superimposed on a period of reduced delivery of oxygen, a greater risk of ischemia to both heart and central nervous system occurs with rewarming.243 Given the multiple factors that may cause unexpected disruption in perfusion at full flow, some emergent in nature, most centers continue to use mild or moderate hypothermia as a protective adjunct to CPB without planned reduction of flow or circulatory arrest.237,244 While the overall perioperative inflammatory response, although reduced during hypothermia, does not seem to be altered by strategies depending on temperature,245 moderate hypothermia probably induces cellular adaptations at the transcriptional and translational level that result in survival programming.246,247 In practical terms, schemes for cooling are relatively standardized in most institutions The complexity of the defect to be corrected or palliated dictates the strategy for the temperature used during bypass, albeit compounding anatomic features such as the presence of aortopulmonary collateral arteries may influence the strategy Typically, mild hypothermia, at 37°C to 32°C, will be employed for simple defects such as atrial and ventricular septal defects Moderate hypothermia, between 32°C and 28°C, is used for more complex lesions such as atrioventricular septal defect or tetralogy of Fallot Deep hypothermia, from 28°C down to 18°C, is reserved for the most complex lesions requiring a period of circulatory arrest, such as palliation of hypoplasia of the left heart, repair of interrupted aortic arch or correction of discordant ventriculoarterial connections While the described cooling practice is common, some have begun using warm CPB for even the most complex procedures, cooling only to a mild hypothermic temperature of 34°C.248,249 Apparent acute benefits of this approach include decreased CPB times and a reduction in perioperative bleeding, but longer-term measures of end-organ preservation including neurologic function are necessary Acid-Base Management The management of blood gases during CPB is intertwined with that of temperature and has been widely investigated and debated The complexity ensues because metabolic rate, the solubility of gases in blood, the ionization of water and therefore the pH of electroneutrality, the ionization of intracellular buffer, and the affinity of both oxygen and carbon dioxide for hemoglobin are all dependent on temperature.250 There are two strategies for pH management A pH-stat strategy maintains normal levels of carbon dioxide and hydrogen ions when measured at hypothermia or temperature corrected An alpha-stat strategy maintains normal gas tensions and acid-base balance when measured at normothermia or temperature uncorrected The alpha-stat approach is associated with minimal metabolic suppression and represents the physiologic situation in homeotherms with temperature gradients across parts of the body but with thermoregulation maintained The pH-stat approach is associated with metabolic suppression and more closely mimics the metabolic milieu of hibernation with induction of metabolic suppression.251 The pH affects the ratio of flow of blood to metabolism.215 While levels of adenosine triphosphate in the brain are maintained during alpha-stat cooling,213,252 with pH-stat cooling there is evidence of luxury perfusion At temperatures below 30°C blood flow is pressure-passive over a wider range of metabolism with over-perfusion evidenced by the appearance of edema.253 The increased flow with pH-stat strategy is widely utilized to increase uniformity of cerebral cooling, oxygenation,204,213,254–258 and metabolic suppression.212,250,258 There is evidence of improved outcome in children subjected to DHCA259–261 or low-flow bypass when using the pH-stat strategy.262–264 Evidence also exists for improved myocardial function with pH-stat techniques.265 The effects of pH on noncerebral tissue are also important in determining the distribution of flow on CPB A pH-stat strategy directs more blood to the brain in the presence of aortopulmonary collateral connections.204 Approaches that combine pH-stat strategy for cooling with alpha-stat strategy for maintenance of high-flow hypothermic perfusion may represent a compromise between inadequate delivery of oxygen and metabolic suppression and over-perfusion–related formation of edema and postacidotic increased cerebrovascular resistance.266,267 Cerebral Protection and Anesthesia Suppression of cerebral consumption of oxygen occurs with both vapor- and barbiturate-based anesthesia and hypoxia tolerance, based on lactate production, is enhanced.268 The suppression of metabolism by anesthetic vapors is accompanied by maintenance of high energy phosphates indicating desirable energetic balance.269 Because vapor agents are also cerebral vasodilators, the ratio of cerebral flow to metabolism is higher with these agents and the increase in cerebral flow may be maintained for hours.270–272 Suppression of thermoregulatory273 responses to hypothermia may be an important role for the salutary effect of lower-stress anesthetic strategies on survival in complex repairs.274 Inhibition of potassium–adenosine triphosphate (K-ATP) channels by vapors may induce preconditioning, reduce reperfusion injury, and reduce apoptosis in ischemic models.275–277 The vasodilatory effects of vapor anesthetics can be expected to improve the uniformity of cerebral cooling and warming Withdrawal of anesthetic vapor is likely to induce cerebral vasoconstriction in a fashion parallel to the vasodilation seen on acute introduction Because the neonatal brain is particularly vulnerable to apoptosis via excitotoxic injury, vapor anesthetics might be particularly indicated.276,278–281 However, all anesthetic agents with the exception of dexmedetomidine and opioids have been implicated in enhanced apoptotic