Neurobehavioral outcomes in cardiac operations. A prospective controlled study.

To assess the severity and duration of new organic brain dysfunction after cardiac operations, we used an extensive battery of neuropsychologic tests to evaluate 65 patients undergoing coronary artery bypass grafting and 25 patients undergoing intracardiac operations with cardiopulmonary bypass. Patients were tested the day before the operation, before discharge from the hospital, and approximately 7 months later. Compared to 47 nonsurgical control subjects tested at comparable time intervals, surgical subjects showed generalized impairment of neuropsychologic abilities near the time of discharge from the hospital. At follow-up testing, there was no evidence of residual impairment among the surgically treated patients as a whole. In fact, they showed greater improvement compared to initial test scores than did control subjects. However, performance of 10 patients (11%) declined on half of the neuropsychologic variables between preoperative and follow-up testing. Neurobehavioral outcome was not related to the type of operation (coronary bypass versus intracardiac), to factors of cardiopulmonary bypass (duration, aortic occlusion time, hypotension, arterial carbon dioxide tension, minimum hematocrit value, minimum temperature). The only predictor of negative outcome was advanced age. We conclude that, although neurobehavioral impairment is common during hospitalization after cardiac operations, the prognosis for eventual full recovery is favorable, although less so among the elderly.

Failure of an epinephrine test dose to elicit tachycardia after intravascular epidural catheter placement.

A 58-year-old woman who was not taking beta-adrenergic block medication had a lumbar epidural catheter placed intravascular unintentionally. Epinephrine 15 micrograms in 3 ml saline or 2% lidocaine caused an increase in blood pressure and a decrease in heart rate. Observation of the patient for other signs of intravascular injection besides an increase in heart rate is discussed.

Effect of plasma [K+] on the DC potential and on ion distributions between CSF and blood.

Keeping the arterial pH at 7.4 and PaCO2 at 40 mmHg in eight anesthetized dogs, we acutely raised plasma potassium concentration from 3.4 to 8.2 meq/1, then allowed it to decay back to control levels. The cerebrospinal fluid (CSF)-blood electrical potential difference (pd) increased 13.2 mV per 10-fold increase in plasma [K+]. Again keeping arterial pH at 7.4 and PaCO2 at 40 mmHg, we elevated plasma [K+] in four dogs from 3.3 to 8.0 meq/1 and maintained this level for 6 h. We found 1) that the PD increased from a control value of +1.3 to +8.9mV, showing no tendency to decay over the 6 h; and 2) that the change in PD did not affect the distribution of Na+, K+, H+, Cl-, or HCO3- between blood and CSF over the 6 h. These results suggest that under these conditions the PD between CSF and blood may play no effective role in determining the distributions of these charged species by 6 h. These results are contrasted with recent findings which suggest that H+ and HCO3- are distributed according to passive forces between CSF and blood.

Salivary gland K+ transport: in vivo studies with K+-specific microelectrodes.

Stimulation-induced transport of K+ in the submandibular salivary gland of cats and dogs anesthetized with pentobarbital was studied with an extracellular K+-specific microelectrode. Electrical stimulation of the para-sympathetic chorda-lingual nerve caused a rapid transient increase in extracellular K+ concentration from 2.2 to 18.7 meq/liter in the cat and from 2.3 to 15.2 meq/liter in the dog. Eventually the K+ concentration fell below the prestimulatory level, indicating uptake of K+ by the gland cells. In case of prolonged stimulation (2-10 min), the uptake began during stimulation. However, a further reduction in extracellular K+ concentration occurred upon cessation of stimulation, a result that demonstrated that the cells did not fully recover their K+ ,content during stimulation. The latency of the release of K+, defined as the time from the beginning of stimulation to the point at which, the K+-specific microelectrode signal had increased by 2 mV, was 0.6 s in the cat and 0.8 s in the dog. Because these are overestimates of the "true" latencies, we conclude that the K+ release begins simultaneously with the hyperpolarization of the acinar cell membrane.

Evidence of active regulation of cerebrospinal fluid acid-base balance.

To test the passive transport hypothesis of cerebrospinal fluid (CSF) [H+] regulation, we altered the relationship between plasma [H+] and the electrical potential difference between CSF and blood (PD) by elevating plasma [K+] during 6-h systemic acid-base disturbances. In five groups of pentobarbital-anesthetized dogs, we increased plasma [K+] from 3.5 to an average of 7.8 meq/l. Hyperkalemia produced an increase in the PD of 6.3 mV by 6 h with normal plasma acid-base status (pHa 7.4), of 8.3 mV with isocapnic metabolic acidosis (pHa 7.2), of 5.3 mV with isocapnic metabolic alkalosis (pHa 7.6), of 9.2 mV with isobicarbonate respiratory acidosis (PaCO2 61 Torr) and of 5.7 mV with isobicarbonate respiratory alkalosis (PaCO2 25 Torr). The change in CSF [H+] at 6 h in each group was the same as that observed in normokalemic animals (Am. J. Physiol. 228: 1134-1154, 1975). This result is not consistent with the passive transport hypothesis. The CSF-blood PD is therefore not an important determinant of CSF [H+] CSF [H+] homeostasis must result from some form of active transport control.

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.

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.

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 Ringer's 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.(ABSTRACT TRUNCATED AT 250 WORDS)

Electroencephalography during surgery with cardiopulmonary bypass and hypothermia.

After more than 30 yr of use, electroencephalographic (EEG) monitoring during cardiopulmonary bypass has not gained wide clinical acceptance. To assess its utility to predict central nervous system injury, two-channel recordings were made from 78 patients undergoing cardiopulmonary bypass and anesthetized with fentanyl/diazepam/enflurane. The perfusion regimen included the use of high pump flow, a bubble oxygenator, and no arterial tubing filter. Target values were 28-32 degrees C for the minimum rectal temperature, 60-80 mmHg for mean arterial pressure, and 20-25% for hematocrit. Eight descriptors of the Fourier power spectra of the EEG were calculated off-line, and outcome comparisons were made with the results from neuropsychological tests. Among 58 patients yielding complete data of acceptable quality, a statistically significant reduction in total power was observed from prebypass to postbypass, accompanied by an increase in the fractional power in the theta and beta frequency bands and in the spectral edge frequency. The shifts in total and theta power were weakly associated with short-term but not with long-term changes in neuropsychological scores. Nearly 40% of the patients' EEGs were corrupted with electrical noise at some time during bypass. In 15 patients selected for having high-quality recordings and no neuropsychological deficit, an extensive statistical analysis failed to reveal any consistent variation in the EEG descriptors with hypothermia. Under the conditions studied, it appears that for other than gross signal dropout, the strong background variability in the EEG makes it have little value for detecting harbingers of brain injury.

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 patient's 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.

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 (EEG) 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, EEG 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 with minimal 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 transaminase (SGOT), and alkaline phosphatase. Animals with the greatest increases in these enzymes showed centrilobular hepatocyte degeneration.