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.

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.

Acute mountain sickness, antacids, and ventilation during rapid, active ascent of Mount Rainier.

A double-blind randomized study of 45 climbers on Mt. Rainier was conducted to test the effectiveness of antacids in preventing acute mountain sickness. All 45 climbed to 3353 m, and 31 continued to the summit. Ten climbers listed acute mountain sickness as the reason for not attaining the summit. Of symptoms monitored throughout the climb, neither headache, nausea, dizziness, pounding heart, nor shortness of breath differed in severity between antacid-treated and placebo-treated groups. In both groups vital capacity decreased significantly with ascent (p less than 0.05), while peak flow (p less than 0.005) and minute ventilation (p less than 0.001) increased significantly. The 7 climbers with the most severe AMS symptom scores above 4000 m had significantly lower peak flow at sea level prior to ascent compared with the other 25 climbers who completed sea level tests (p less than 0.005). The results of this study fail to document efficacy for antacid use for the prevention of acute mountain sickness.

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.

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.

Distribution of H+ and HCO3 minus between CSF and blood during metabolic acidosis in dogs.

To determine whether the regulation of brain extracellular fluid acid-base balance is by active ion transport or passive distribution, changes in cisternal and lumbar cerebrospinal fluid (CSF) (H+) and (HCO3 minus) were assessed in five dogs with normal acid-base status and in six dogs during metabolic acidosis. Both groups were mechanically ventilated to maintain a constant PaCO2. The pH, PCO2, (HCO3 minus), and (lactate) in CSF and arterial plasma and the CSF/plasma DC potential difference were determined at intervals, and the electrochemical potential differnces (mu) for H+ and HCO3 minus were calculated. Following control measurements at pHa equal to 7.40, metabolic acidosis was induced by infusion of 0.6 N HCl. Measurements were made 0, 3, 4.5, and 6 h thereafter and at 0, 3, and 6 h in the control series. A steady state for ion distribution was reached by 4.5 h. In the control series at 6 h the values of mu for H+ and HCO3 minus were within minus 0.2 and +0.5 mV of initial values at the cistern and +0.1 and +0.9 mV at the lumbar site. During metabolic acidosis, the 6-h values at the cistern returned to 0.0 and +0.7 mV of control for muH+ and muHCO3 minus while lumbar values returned to +0.5 and minus 0.4 mV. The closeness of these 6-h values of mu to control is compatible with passive distribution of H+ and HCO3 minus between CSF and blood.

Distribution of H+ and HCO3 minus between CSF and blood during respiratory acidosis in dogs.

To evaluate the regulation of (H+) and (HCO3 minus) in brain extracellular fluid during respiratory acidosis, the changes in cisternal and lumbar CSF acid-base state were assessed in six anteshetized, paralyzed, mechanically ventilated dogs rendered hypercapnic by increase in FIco2. Arterial (HCO3 minus) was held constant. The electrochemical potential difference (mu) between CSF and blood for H+ and HCO3 minus was calculated from values for (H+) and (HCO3 minus) in CSF and arterial plasma and the simultaneously measured CSF/plasma DC potential difference. Measurements were made at pHa equal to 7.40, after stable arterial values of pHa of about 7.2 were attained and 3, 4.5, and 6 h thereafter. A steady state for ion distribution was attained by 4.5 h. Values of mu for H+ and HCO3 minus at 6 h had returned to +0.7 and minus 0.7 mV of control for cisternal CSF and +1.3 and minus 0.6 mV of control for lumbar CSF. The attainment of steady-state values for mu close to control is comparable with passive distribution of these ions between CSF and blood.

Distribution of H+ and HCO3 minus between CSF and blood during respiratory alkalosis in dogs.

Anesthetized, paralyzed dogs after a control period at normal pHa were hyperventilated to produce a hypocapnic alkalosis. The pH, PCO2, (HCO3 minus), and (lactate) in cisternal and lumbar CSF and arterial blood were determined at normal conditions (control) shortly after induction of respiratory alkalosis (time 0) and 3, 4.5, and 6 h thereafter. These values along with measurements of the CSF/plasma DC potential (E) allowed calculations of the electrochemical potential difference (mu) between CSF and blood for H+ and HCO3 minus. After 6 h of hypocapnic alkalosis, muH+ and muHCO3 minus had returned to minus 0.7 and minus 1.0 mV of control at the cistern and to minus 1.0 and +0.4 mV of control for lumbar CSF. This return of mu is compatible with a passive distribution of these ions though active ion regulation is not ruled out. Assuming passive distribution, differences in deltaE/DELTApHa between metabolic and respiratory acid-base changes determined the extent of CSF pH homeostasis during compensated acid-base derangements.

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)

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.

Acute mountain sickness and acetazolamide. Clinical efficacy and effect on ventilation.

Sixty-four climbers participated in a randomized clinical trial of acetazolamide prophylaxis for acute mountain sickness (AMS) during rapid, active ascent of MT Rainier. Twenty-nine (93.6%) of 31 climbers receiving acetazolamide and 25 (75.8%) of 33 receiving placebo attained the summit. Time spent ascending from sea level to the summit (4,394 m) averaged 33.5 hours (range, 23 to 48 hours). On the summit AMS was less common in climbers receiving acetazolamide, and they experienced less headache, nausea, drowsiness, shortness of breath, and dizziness and a greater sense of satisfaction and psychological well-being. Minute ventilation on the summit was significantly greater in subjects taking acetazolamide (24.9 +/- 2.0 L/min compared with 16.9 +/- 3.8 L/min). Expired vital capacity was also greater on the summit in the acetazolamide group (6.9 +/- 0.4 L compared with 5.8 +/- 0.4 L). We conclude that acetazolamide is effective in the prophylaxis of AMS for climbers attempting rapid, active ascent. Increased ventilation at altitude, producing an increased alveolar oxygen tension, may be related to the observed amelioration of symptoms.

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)