Thomas F. Hornbein

Hemodynamic Effects of Intermittent Positive Pressure Respiration

The hemodynamic effects of intermittent positive pressure ventilation were studied in lightly anesthetized dogs following recovery from implantation of pulsed ultrasonic flow transducers on the aorta and vena cava. A partial rebreathing system was utilized to maintain constant PaCO. Data were obtained during spontaneous respiration and using a respirator, with peak airway pressures of 10, 20 and 30 cm. of water, inspiratory to expiratory ratios of 1:2, 1:1 and 2:1. Maximum values for stroke volume and cardiac output occurred during spontaneous breathing. Cardiac output and aortic stroke volume decreased with increasing airway pressure and increasing inspiratory to expiratory ratios. Venous return was inhibited by increasing pressure, and changes in vena caval flow were reflected in changes in aortic flow within the time of two heart beats. The circulatory effects of positive pressure breathing are related to the mean intrathoracic pressure and the effect on venous return.

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.

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.

Human Cerebral Function at Extreme Altitude

in the fall of 1981 the American Medical Research Expedition to Everest completed a series of physiological and psychological studies on mountaineers ascending to the summit of Mount Everest. This expedition afforded the unique opportunity to observe the consequences of extreme, sustained hypoxia on human cerebral function. The goal was to ascertain whether exposing healthy acclimatized individuals to extreme high altitude causes long-term alterations in cognition or behavior indicative of hypoxic brain dysfunction.

The Cardiovascular Effects of Morphine Sulfate with Oxygen and with Nitrous Oxide in Man

The cardiovascular effects of morphine, 2 mg/kg, administered intravenously at the rate of 10 mg/min with oxygen and with nitrous oxide—oxygen, were studied in ten healthy unmedicated male volunteers. Respiration was mechanically controlled to maintain a constant, normal Paco2. Morphine— oxygen increased cardiac index, heart rate, forearm blood flow, peak inspiratory pressure, blood glucose, and central venous pressure; decreased total peripheral resistance; and caused insignificant changes in stroke volume index, mean arterial pressure, forearm venous compliance, blood lactate and pyruvate, base excess, and oxygen consumption. The pre–ejection period, which provides an estimation of the period of isovolemic cardiac contraction, was prolonged. Addition of 70 per cent nitrous oxide to morphine—oxygen 60 minutes after administration of morphine increased total peripheral resistance, central venous pressure, and peak inspiratory pressure; decreased base excess, cardiac index, and heart rate; and did not significantly change the other variables. Morphine did not produce amnesia or unconsciousness in these subjects until nitrous oxide was added. The concentration of morphine in plasma was 8.6 ± 0.8 µg/100 ml 5 minutes after administration.

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.

Hemodynamic Effects of Changes in Arterial Carbon Dioxide Tension During Intermittent Positive Pressure Ventilation

Hemodynamic effects of changes in arterial carbon dioxide tension during intermittent positive pressure ventilation (IPPV) were studied in lightly anesthetized dogs following recovery from implantation of pulsed ultrasonic flow transducers on aorta and vena cava. Alveolar ventilation was maintained in excess of normal, and arterial PCO2 was varied by alteration of inspired CO2 concentration. Data were obtained at PaCO2 20, 40 and 60 torr, and at each PaCO2 high (peak airway pressure 30 cm. of water, inspiratory to expiratory ratio of 2:1) and low (peak airway pressure 10 cm. of water, inspiratory to expiratory ratio of 1:2) levels of ventilation were employed. Two separate hemodynamic effects were observed, the effects of changes in intrathoracic pressure and those produced by alterations in PaCO2 At each PaCO2 high level of ventilation decreased stroke volume and cardiac output compared to low level of ventilation. At each level of ventilation, stroke volume and cardiac output were decreased during respiratory alkalosis and increased during respiratory acidosis.

Abdominal-muscle rigidity induced by morphine and nitrous oxide.

Standard and integrated abdominal-muscle electromyograms and H reflex amplitudes of nine volunteers mechanically ventilated to maintain normal Paco2 were studied. Morphine, 2 mg/kg, was given iv during ventilation with oxygen. One hour later 70 per cent nitrous oxide-30 per cent oxygen was substitut

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.