Stephen W. Bledsoe

A Randomized Study of Carbon Dioxide Management during Hypothermic Cardiopulmonary Bypass

Eighty-six patients undergoing coronary artery bypass graft (n = 63) or intracardiac (n = 23) surgery were randomly assigned with respect to the target value for PaCO2 during cardiopulmonary bypass. In 44 patients the target PaCO2 was 40 mmHg, measured at the standard electrode temperature of 37 degrees C, while in 42 patients the target PaCO2 was 40 mmHg, corrected to the patients rectal temperature (lowest value reached: mean 30.1, SD 1.9 degrees C). Other salient features of bypass management include use of bubble oxygenators without arterial filtration, flows of 1.8-2.4 l.min-1.m-2, mean hematocrit of 23%, and mean arterial blood pressure of approximately 70 mmHg, achieved by infusion of phenylephrine or sodium nitroprusside. Neuropsychologic function was assessed with series of tests administered on the day prior to surgery, just before discharge from the hospital (mean 8.0, SD 5.8 days postoperatively, n = 82), and again 7 months later (mean 220.7, SD 54.4 days postoperatively, n = 75). The scores at 8 days showed wide variability and generalized impairment unrelated to the PaCO2 group or to hypotension during cardiopulmonary bypass. At 7 months no significant difference was observed in neuropsychologic performance between the PaCO2 groups. Regarding cardiac outcome, there were no significant differences between groups in the appearance of new Q-waves on the electrocardiogram, the postoperative creatine kinase-MB fraction, the need for inotropic or intraaortic balloon pump support, or the length of postoperative ventilation or intensive care unit stay. These findings support the hypothesis that CO2 management during cardiopulmonary bypass at moderate hypothermia has no clinically significant effect on either neurobehavioral or cardiac outcome.

Neuropsychological changes in a young, healthy population after controlled hypotensive anesthesia.

We investigated the effect of controlled hypotension during halothane anesthesia on brain functions as measured by neuropsychological tests. Anesthesia in 17 patients included controlled hypotension, whereas in another 27 patients hypotension was not induced during surgery for correction of facial abnormalities. Intraoperative EEG recording showed no significant changes in EEG power during the induction of hypotension. Hypotensive anesthesia was not associated with greater postoperative impairment than normotensive anesthesia. Both groups did show short-term postoperative impairment of memory and learning. For at least the first 24 hrs after administration of a general anesthetic agent such as halothane, there is interference with consolidation of memory. This impairment was not apparent in follow-up examinations 6 months later.

Profound Arterial Hypotension in Dogs: Brain Electrical Activity and Organ Integrity

To determine whether non-invasive measurement of brain electrical activity can predict ischemic brain damage, we recorded the electroencephalogram (EEC) and somatosensory- (SEP) and auditory- (AEP) evoked potentials before, during, and after trimethaphan-induced profound arterial hypotension in dogs. The authors set out to compare the change in electrical activity with the degree of brain damage, as determined by microscopic examination. Dogs were anesthetized with halothane (1.4 vol % inspired), maintained horizontal (head at the level of the heart), and ventilated mechanically (FIo2 0.50); deviations from normal acid-base status were corrected. Twenty animals received a 1.5-mg/kg intravenous bolus of trimethaphan. Three animals were resistant to the drug. The remaining animals had profound hypotension [mean arterial blood pressure (MABP) at some steady level between 12 and 25 mmHg] for 1 h. Eight of these animals died during or soon after the hypotensive period as a consequence of cardiac arrest (three), intestinal bleeding (three) or unknown causes (two). In all survivors, EEC intensity and the amplitude of the SEP decreased during hypotension; both variables recovered with restoration of MABP. All nine animals surviving hypotension had no apparent neurologic or behavioral deficit nor any histologic evidence of ischemic brain cell injury. We were thus unable to find a MABP threshold for brain injury or to determine what degree of electrical change correlated with mimimal brain injury. Our findings suggest, under the conditions of our experiments, a great margin of tolerance for profound hypotension by the brain in this species. Other organ systems–-the heart, gastrointestinal tract, and liver–-proved to be more susceptible to ischemic damage. Eight of the nine surviving animals had elevations in serum alanine transaminase (SGPT), aspartate trans-aminase (SCOT), and alkaline phosphatase. Animals with the greatest increases in these enzymes showed centrilobular hepatocyte degeneration.

Electrical Correlates of Brain Injury Resulting from Severe Hypotension and Hemodilution in Monkeys

The effects of hypotension, hemodilution, and their combination on the relationship between concurrent brain electrical activity and resulting brain injury were studied in anesthetized monkeys. The authors compared changes in the electroencephalogram and somatosensory and auditory evoked potentials with eventual neuropathologic outcome. Our goals were: 1) to define the margin of safety for the monkey brain during hemodilution and hypotension under several simulated clinical conditions; and 2) to determine whether noninvasive measurements of brain electrical activity can predict ischemic brain cell damage. Forty-one monkeys were anesthetized with halothane (0.8 vol % inspired) and ventilated mechanically. Arterial hypotension was induced with trimethaphan (25 ± 8 mmHg mean arterial blood pressure [MABP] for 30 min). Hemodilution was induced by replacing blood with lactated Ringers solution (14 ± 2% hematocrit for 1 h). Combined hemodilution and hypotension consisted of 30 min of hemodilution alone followed by superimposing hypotension for 30 min (16 ± 3% hematocrit and 29 ± 5 mmHg MABP). Ten monkeys died following severe hypotension alone or combined hemodilution and hypertension as a consequence of cardiac arrest or undetermined (possibly neurologic) causes. No histologic evidence of ischemic brain cell injury was found in surviving monkeys subjected to hemodilution or hypotension alone. Neuropathologic alterations in the cerebral cortex, cerebellum, hippocampus and globus pallidus as well as neurologic and behavioral deficits were found in seven of 16 surviving monkeys subjected to both hemodilution and hypotension. These findings resulted from combinations of hematocrit less than 20% and MABP below 40 mmHg. Only the degree of amplitude reduction in cortical components of the somatosensory evoked potentials during the stress period indicated a high probability of neuropathologic outcome.

Tools for Assessing Central Nervous System Injury in the Cardiac Surgery Patient

Despite improvements in surgical, anesthetic, and perfusion techniques in recent years, central nervous system (CNS) complications remain “a principal cause of the morbidity after open-heart surgery” [1]. Just as the improvement in cardiac outcome owes much to the growth in the number and sophistication of the tools to measure cardiac function, having better tools to assess brain function will contribute to development of new ways of avoiding CNS damage due to cardiopulmonary bypass (CPB). The importance to the CNS of oxygenator design, perfusion flow, pressure, arterial filtering, carbon dioxide tension, pharmacologic protection, and other factors can only be evaluated if proper measuring tools are available to the investigators.

A data acquisition system for clinical research

We developed a system for automatic collection and synchronization of multiple physiological variables during clinical investigations. Centered around an eight-track instrumentation tape recorder, the system solves several problems encountered in gathering this type of research data: (1) slowly changing variables are digitized and compressed onto a single track by recording them in one serial message, allowing for recording many more variables than there are tape tracks available; (2) simultaneous analog recording allows retention of original data for variables that may be processed subsequently by multiple schemes; (3) data acquisition is verified with both analog chart recording and numerical video display monitors; (4) off-line computer processing time is decreased at least twofold by using tape playback speeds faster than the recording speed; (5) cost is kept low by using an inexpensive 1/4-inch (0.64-cm) tape medium and dedicated microcomputers; and (6) the system is unobtrusive, portable, and easily reconfigured for different clinical studies. It proved to be reliable in a study of more than 80 patients undergoing cardiac surgery.

ELECTRICAL CORRELATES OF BRAIN INJURY RESULTING FROM SEVERE HYPOTENSION AND HEMODILUTION

The effects of hypotension, hemodilution, and their combination on the relationship between concurrent brain electrical activity and resulting brain injury were studied in anesthetized monkeys. The authors compared changes in the electroencephalogram and somatosensory and auditory evoked potentials with eventual neuropathologic outcome. Our goals were: 1) to define the margin of safety for the monkey brain during hemodilution and hypotension under several simulated clinical conditions; and 2) to determine whether noninvasive measurements of brain electrical activity can predict ischemic brain cell damage. Forty-one monkeys were anesthetized with halothane (0.8 vol % inspired) and ventilated mechanically. Arterial hypotension was induced with trimethaphan (25 ± 8 mmHg mean arterial blood pressure [MABP] for 30 min). Hemodilution was induced by replacing blood with lactated Ringers solution (14 ± 2% hematocrit for 1 h). Combined hemodilution and hypotension consisted of 30 min of hemodilution alone followed by superimposing hypotension for 30 min (16 ± 3% hematocrit and 29 ± 5 mmHg MABP). Ten monkeys died following severe hypotension alone or combined hemodilution and hypertension as a consequence of cardiac arrest or undetermined (possibly neurologic) causes. No histologic evidence of ischemic brain cell injury was found in surviving monkeys subjected to hemodilution or hypotension alone. Neuropathologic alterations in the cerebral cortex, cerebellum, hippocampus and globus pallidus as well as neurologic and behavioral deficits were found in seven of 16 surviving monkeys subjected to both hemodilution and hypotension. These findings resulted from combinations of hematocrit less than 20% and MABP below 40 mmHg. Only the degree of amplitude reduction in cortical components of the somatosensory evoked potentials during the stress period indicated a high probability of neuropathologic outcome.