Optimal pH strategy for hypothermic circulatory arrest

Abstract

I t was several years after the beginning of open heart surgery before hypothermia was introduced as a component of cardiopulmonary bypass (CPB). At about this time in the late 1950s, blood gas analysis became more readily available and revealed a surprising fact: when blood is cooled by the heat exchanger in the circuit, pH changes in an alkaline direction. The usual response in the 1960s and 1970s was to compensate for this alkaline shift by adding carbon dioxide, a technique that has come to be known as the pH-stat strategy. This also had what was perceived to be an important advantage in that carbon dioxide is a potent cerebral vasodilator. It was believed that adding carbon dioxide would increase the safety margin for cerebral oxygen supply and reduce the risk of major neurologic injury, which was all too common in the early years of CPB. In the late 1970s and early 1980s, a number of reports appeared that questioned whether the pH-stat strategy was indeed the correct response to the alkaline shift with hypothermia. It was found that cold-blooded vertebrates simply allow their blood pH to drift in an alkaline direction. It appeared that this alpha-stat strategy optimized intracellular enzyme function. Studies in dogs showed that the threshold for ventricular fibrillation was lower with the more acidotic pH-stat strategy. It also became increasingly apparent that the most common cause of neurologic injury in adults was embolic stroke rather than the global hypoxic insults that had been more common in the early years of bypass. Even if there was not a definite stroke, psychologists could measure important deficits in cognitive function in a remarkably high percentage of adult patients after heart surgery. Microembolization of atherosclerotic debris, fat, and air was probably the cause. It followed that if cerebral blood flow was increased to excessive, “luxuriant” levels by adding carbon dioxide, then injury would be increased. Randomized trials of neuropsychometric outcome have confirmed just this. Three of four trials demonstrated an improved cognitive outcome in adults undergoing continuous mildly or moderately hypothermic CPB with the alpha-stat strategy relative to the pH-stat strategy. The shift in pH strategy from pH-stat to alpha-stat was applied just as enthusiastically to children as adults in the early 1980s, although there was little evidence to support macroembolization or microembolization as important mechanisms of injury in this population. Apart from their lack of atherosclerotic vessels and calcified valves, in contrast to adults, children have intracardiac problems that require exposure through small incisions. Blood returning to the heart impairs exposure and can result in less accurate repair. This collateral return is almost always increased in patients who have cyanotic conditions and steals an important proportion of blood from the systemic circulation. A common response of surgical teams is to reduce flow and temperature or to apply deep hypothermic circulatory arrest (DHCA). Is a pH strategy that reduces cerebral blood flow the appropriate one under such circumstances? The article by Priestley and associates1 in this issue of the Journal is further evidence that the alpha-stat strategy results in a greater degree of cerebral injury when DHCA is used. Priestley and colleagues1 subjected 5to 10-day-old piglets to 90 minutes of DHCA at a brain temperature of 20°C. Animals were hemodiluted to a hematocrit value of 20% to 25% and were cooled at a flow rate of 100 mL kg 1 min . After being rewarmed, the animals were taken off CPB and were allowed to survive for the next 48 hours. They were assessed for neurologic injury by means of a graded scoring system by a blinded observer. Brain histologic features were also From Children’s Hospital (Cardiovascular Surgeon-in-Chief) and Harvard Medical School (William E. Ladd Professor of Surgery), Boston, Mass.