The high-altitude brain.

The highest place on our planet, Mount Everest (8850 m), appears to be close to the limit of how high an acclimatized human can go, albeit slowly. In this paper, I will explore the possibility that what limits human performance at such extreme degrees of hypoxia is the availability of oxygen to the brain. Also, one of the known costs of such extreme exposure is residual mild impairment of performance on neuropsychometric tests after return to sea level, implying injury to brain cells. That such injury could occur in the absence of any overt impairment of function, much less without loss of consciousness, is unexpected. I will speculate about physiological mechanisms that might cause or contribute to both decrements in real-time performance while at altitude and residual deficits for a time after return to low elevations; the effects of hypoxia on brain cells are an even greater puzzle at the present time.

Long term effects of high altitude on brain function.

Absence of oxygen to the brain for even a very few minutes results in loss of consciousness and can cause permanent injury. Can the wanderer to the limits of earth-bound hypoxia suffer similar harm from more prolonged exposure to milder hypoxia that does not cause loss of consciousness? I shall review the results from studies where neurobehavioral function has been compared in mountaineers before and after return from great heights and in individuals with chronic pulmonary disease before and after prolonged, continuous oxygen therapy. Many (although not all) of these studies report mild impairment of neurobehavioral function after fairly prolonged hypoxic exposure. Impairment was manifest by deficits in memory storage and recall, aphasia, concentration, and finger tapping speed; the last deficit was still detectable a year later in one group of mountaineers. Limited evidence suggests that climbers with a high ventilatory response to hypoxia (HVR) may be more susceptible to impairment than those with a lower HVR.

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.

The cost to the central nervous system of climbing to extremely high altitude.

To assess the possibility that climbing to extremely high altitude may result in hypoxic injury to the brain, we performed neuropsychological and physiologic testing on 35 mountaineers before and 1 to 30 days after ascent to altitudes between 5488 and 8848 m, and on 6 subjects before and after simulation in an altitude chamber of a 40-day ascent to 8848 m. Neuropsychological testing revealed a decline in visual long-term memory after ascent as compared with before; of 14 visual items of information on the Wechsler Memory Scale, fewer were recalled after ascent by both the simulated-ascent group (a mean [+/- SD] of 10.14 +/- 1.68 items before, as compared with 7.00 +/- 3.35 items after; P less than 0.05) and the mountaineers (12.33 +/- 1.96 as compared with 11.36 +/- 1.88; P less than 0.05). Verbal long-term memory was also affected, but only in the simulated-ascent group; of a total of 10 words, an average of 8.14 +/- 1.86 were recalled before simulated ascent, but only 6.83 +/- 1.47 afterward (P less than 0.05). On the aphasia screening test, on which normal persons make an average of less than one error in verbal expression, the mountaineers made twice as many aphasic errors after ascent (1.03 +/- 1.10) as before (0.52 +/- 0.80; P less than 0.05). A higher ventilatory response to hypoxia correlated with a reduction in verbal learning (r = -0.88, P less than 0.05) and with poor long-term verbal memory (r = -0.99, P less than 0.01) after ascent. An increase in the number of aphasic errors on the aphasia screening test also correlated with a higher ventilatory response to hypoxia in both the simulated-ascent group (r = 0.94, P less than 0.01) and a subgroup of 11 mountaineers (r = 0.59, P less than 0.05). We conclude that persons with a more vigorous ventilatory response to hypoxia have more residual neurobehavioral impairment after returning to lower elevations. This finding may be explained by poorer oxygenation of the brain despite greater ventilation, perhaps because of a decrease in cerebral blood flow caused by hypocapnia that more than offsets the increase in arterial oxygen saturation.

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.

Clinical assessment of a flow-through fluorometric blood gas monitor.

We performed an observational study to evaluate a flow-through fluorometric instrument (Gas-STAT) that continuously measures the carbon dioxide tension (PCO2), oxygen tension (PO2), and pH of blood in the cardiopulmonary bypass circuit. Setup and calibration of the instrument typically required 20 minutes. During bypass, 129 blood samples were drawn from 16 patients for comparison with conventional measurements obtained with a blood gas machine. Data for each variable, within each sensor, were analyzed by linear regression. The ranges of the standard errors of the estimate were 0.7 to 4.2 mm Hg for PCO2, 18.3 to 78.7 mm Hg for the high PO2 range, 1.4 to 7.1 mm Hg for the low PO2 range, and 0.008 to 0.049 for pH. The regression lines differed from the identity line (P less than 0.05) in at least one variable in most patients, and large deviations from the line of identity in both slope and intercept were common. Among 58 sensors evaluated, failures occurred in 5 (2.9%) of the 174 optodes, and minor leakage occurred in 2 (3.4%) of the flow-through cells. We conclude that although this flow-through fluorometric instrument is an adequate monitor of trends in blood gases during cardiopulmonary bypass, it is not accurate enough to supplant conventional laboratory measurements.

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.

Prolonged hypocapnia does not alter the rate of CSF production in dogs during halothane anesthesia or sedation with nitrous oxide.

This study examined the effect of prolonged hypocapnia on the rate of cerebrospinal fluid (CSF) production (Vf) and on other CSF dynamics in dogs. Determination of CSF values began 2 h after the onset of hypocapnia and continued for an additional 3 h. Two separate methods were used to determine Vf: modified open ventriculocisternal perfusion and closed ventriculocisternal perfusion. Dogs were examined both during hypocapnia plus anesthesia with halothane (0.8%) and nitrous oxide (66%), and during hypocapnia plus sedation with nitrous oxide (66%) and halothane (0.15%) combined with bupivacaine (0.75%) infiltration of wound edges. There were no differences in Vf measured by the two methods. At the first measurable time period, mean Vf values during hypocapnia and halothane anesthesia, 32 +/- 9 and 35 +/- 10 microliters/min (mean +/- SD), were lower than mean Vf values during hypocapnia and nitrous oxide sedation, 48 +/- 11 and 49 +/- 8 microliters/min. Vf did not change significantly during 3 h of hypocapnia. For both halothane anesthesia and nitrous oxide sedation, mean Vf values during hypocapnia were not significantly different from Vf values previously reported during normocapnia, 31 +/- 12 and 33 +/- 12 microliters/min and 44 +/- 13 and 47 +/- 14 microliters/min, respectively. The results indicate that prolonged hypocapnia does not decrease Vf, and, therefore, reduction of Vf is probably not one of the causes for reduction of elevated CSF pressure by prolonged hypocapnia. Regarding the other data on CSF dynamics, CSF pressure at hypocapnia was similar to that at normocapnia, suggesting that hypocapnia did not affect resistance to reabsorption of CSF.(ABSTRACT TRUNCATED AT 250 WORDS)

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)

Closed ventriculocisternal perfusion to determine CSF production rate and pressure.

When the rate of cerebrospinal fluid (CSF) production (Vf) is determined using the classical open ventriculocisternal perfusion technique, it is not possible to observe natural fluctuations in CSF pressure, or the effects of experimental treatments on CSF pressure, or to make inferences about CSF volume or resistance to reabsorption of CSF, because CSF pressure is fixed according to the level of the distal end of the cisternal outflow cannula. In addition, the convention of placing the distal end of the cisternal outflow cannula at the interaural line fixes CSF pressure at a value that may not be usual for the animal, thereby introducing potential causes for error in the determination of Vf. The present study describes and evaluates a method of closed ventriculocisternal perfusion that allows the simultaneous determination of Vf and CSF pressure. With this method the time to tracer equilibration was less, and the volume of distribution of the tracer was smaller than with the classical open perfusion system. CSF pressure tracings were of high fidelity showing both respiratory and cardiovascular variation. During both sedation with nitrous oxide or halothane anesthesia, Vf values using closed perfusion were similar to values previously reported using open perfusion. Vf decreased during halothane anesthesia compared with nitrous oxide sedation. No time-related change in Vf from the first measurable time period (approximately 2 h) to the end of the study (approximately 5 h) was observed.

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.

A new system of infiltration anesthesia and sedation for plastic surgery.

This technique produces patient cooperation during the phase of local anesthetic injection by judicious use of intravenous ketamine. The addition of diazepam and a narcotic drug to low-dose ketamine may account for a low incidence of hallucinations and psychic sensations. The use of a dilute solution of lidocaine and a very low concentration of epinephrine allows large areas to be anesthetized. The ultralow concentration of epinephrine provides effective vasoconstriction. The result is good patient acceptance, a stable blood pressure and heart rate, and a low incidence of complications classically associated with local anesthetic toxicity.