Hypothermia and the Approximate Entropy of the Electroencephalogram

Background: The electroencephalogram is commonly used to monitor the brain during hypothermic cardiopulmonary bypass and circulatory arrest. No quantitative relationship between the electroencephalogram and temperature has been elucidated, even though the qualitative changes are well known. This study was undertaken to define a dose-response relationship for hypothermia and the approximate entropy of the electroencephalogram.

Methods: The electroencephalogram was recorded during cooling and rewarming in 14 patients undergoing hypothermic cardiopulmonary bypass and circulatory arrest. Data were digitized at 128 Hz, and approximate entropy was calculated from 8-s intervals. The dose-response relationship was derived using sigmoidal curve-fitting techniques, and statistical analysis was performed using analysis of variance techniques.

Results: The approximate entropy of the electroencephalogram changed in a sigmoidal fashion during cooling and rewarming. The midpoint of the curve averaged 24.7[degrees]C during cooling and 28[degrees]C (not significant) during rewarming. The temperature corresponding to 5% entropy (T0.05) was 18.7[degrees]C. The temperature corresponding to 95% entropy (T0.95) was 31.3[degrees]C during cooling and 38.2[degrees]C during rewarming (P < 0.02).     

Power spectral analysis of EEG during simple deep hypothermia under ether anesthesia

Power spectral analysis of electroencephalogram was performed during simple deep hypothermia under ether anesthesia, compared with that during hypothermic cardiopulmonary bypass under morphine anesthesia. In ether anesthesia group, EEG isoelectricity developed at average esophageal temperature of 27.2 degrees C which is higher than the temperature previously reported. This remarkable depression of the EEG may be due to deep ether anesthesia, because severe hypotension episodes were not associated with this and no neurological complication was noticed post-operatively. In cardiopulmonary bypass group, EEG activity persisted throughout the procedures even at the lowest esophageal temperature reached of 22.3 degrees C. In ether anesthesia group, the temperature at which EEG activity reappeared correlated with the duration of circulatory arrest. During simple deep hypothermia under ether anesthesia, the EEG is not useful to detect brain ischemia during cooling period, because EEG activity was lost in the early course of cooling, but during rewarming period the EEG demonstrated depression of cerebral function due to total circulatory arrest.     

Auditory brainstem evoked responses and temperature monitoring during pediatric cardiopulmonary bypass

PURPOSE: To examine the effects of temperature on auditory brainstem responses (ABRs) in infants during hypothermic cardiopulmonary bypass for total circulatory arrest (TCA). The relationship between ABRs (as a surrogate measure of core-brain temperature) and body temperature as measured at several temperature monitoring sites was determined. METHODS: In a prospective, observational study, ABRs were recorded non-invasively at normothermia and at every 1 or 2 degrees C change in ear-canal temperature during cooling and rewarming in 15 infants (ages: 2 days to 14 months) that required TCA. The ABR latencies and amplitudes and the lowest temperatures at which an ABR was identified (the threshold) were measured during both cooling and rewarming. Temperatures from four standard temperature monitoring sites were simultaneously recorded. RESULTS: The latencies of ABRs increased and amplitudes decreased with cooling (P < 0.01), but rewarming reversed these effects. The ABR threshold temperature as related to each monitoring site (ear-canal, nasopharynx, esophagus and bladder) was respectively determined as 23 +/- 2.2 degrees C, 20.8 +/- 1.7 degrees C, 14.6 +/- 3.4 degrees C, and 21.5 +/- 3.8 degrees C during cooling and 21.8 +/- 1.6 degrees C, 22.4 +/- 2.0 degrees C, 27.6 +/- 3.6 degrees C, and 23.0 +/- 2.4 degrees C during rewarming. The rewarming latencies were shorter and Q10 latencies smaller than the corresponding cooling values (P < 0.01). Esophageal and bladder sites were more susceptible to temperature variations as compared with the ear-canal and nasopharynx. CONCLUSION: No temperature site reliably predicted an electrophysiological threshold. A faster latency recovery during rewarming suggests that body temperature monitoring underestimates the effects of rewarming in the core-brain. ABRs may be helpful to monitor the effects of cooling and rewarming on the core-brain during pediatric cardiopulmonary bypass.     

The effects of deep hypothermic cardiopulmonary bypass and total circulatory arrest on cerebral blood flow in infants and children

Cardiopulmonary bypass management in infants and children involves extensive alterations in temperature, hemodilution, and perfusion pressure, with occasional periods of circulatory arrest. Despite the use of these biologic extremes of temperature and perfusion, their effects on cerebral blood flow are unknown. This study was designed to examine the relationship of mean arterial pressure and nasopharyngeal temperature to cerebral blood flow during deep hypothermic cardiopulmonary bypass (18 degrees to 22 degrees C) with and without periods of total circulatory arrest. Cerebral blood flow was measured before, during, and after deep hypothermic cardiopulmonary bypass using xenon clearance techniques in 25 children, aged 2 days to 60 months. Fourteen patients underwent repair with circulatory arrest. There was a highly significant correlation of cerebral blood flow with temperature during cardiopulmonary bypass (p = 0.007). During deep hypothermic bypass there was a significant association between cerebral blood flow and mean arterial pressure (p = 0.027). In infants undergoing repair with deep hypothermia alone, cerebral blood flow returned to prebypass levels in the rewarming phase of bypass. However, in patients undergoing repair with circulatory arrest, no significant increase in cerebral blood flow during rewarming or even after bypass was observed (p = 0.01). These data show that deep hypothermic cardiopulmonary bypass significantly decreases cerebral blood flow because of temperature reduction. Under conditions of deep hypothermia, cerebral pressure-flow autoregulation is lost. This study also demonstrates that cerebral reperfusion after deep hypothermia is impaired if the patient is exposed to a period of total circulatory arrest.     

The effect of hypothermic cardiopulmonary bypass and total circulatory arrest on cerebral metabolism in neonates, infants, and children

Cardiopulmonary bypass management in neonates, infants, and children often requires the use of deep hypothermia at 18 degrees C with occasional periods of circulatory arrest and represents marked physiologic extremes of temperature and perfusion. The safety of these techniques is largely dependent on the reduction of metabolism, particularly cerebral metabolism. We studied the effect of hypothermia on cerebral metabolism during cardiac surgery and quantified the changes. Cerebral metabolism was measured before, during, and after hypothermic cardiopulmonary bypass in 46 pediatric patients, aged 1 day to 14 years. Patients were grouped on the basis of the different bypass techniques commonly used in children: group A--moderate hypothermic bypass at 28 degrees C; group B--deep hypothermic bypass at 18 degrees to 20 degrees C with maintenance of continuous flow; and group C--deep hypothermic circulatory arrest at 18 degrees C. Cerebral metabolism significantly decreased under hypothermic conditions in all groups compared with control levels at normothermia, the data demonstrating an exponential relationship between temperature and cerebral metabolism and an average temperature coefficient of 3.65. There was no significant difference in the rate of metabolism reduction (temperature coefficient) in patients cooled to 28 degrees and 18 degrees C. From these data we were able to derive an equation that numerically expresses a hypothermic metabolic index, which quantitates duration of brain protection provided by reduction of cerebral metabolism owing to hypothermic bypass over any temperature range. Based on this index, patients cooled to 28 degrees C have a predicted ischemic tolerance of 11 to 19 minutes. The predicted duration that the brain can tolerate ischemia ("safe" period of deep hypothermic circulatory arrest) in patients cooled to 18 degrees C, based on our metabolic index, is 39 to 65 minutes, similar to the safe period of deep hypothermic circulatory arrest known to be tolerated clinically. In groups A and B (no circulatory arrest), cerebral metabolism returned to control in the rewarming phase of bypass and after bypass. In group C (circulatory arrest), cerebral metabolism and oxygen extraction remained significantly reduced during rewarming and after bypass, suggesting disordered cerebral metabolism and oxygen utilization after deep hypothermic circulatory arrest. The results of this study suggest that cerebral metabolism is exponentially related to temperature during hypothermic bypass with a temperature coefficient of 3.65 in neonates infants and children. Deep hypothermic circulatory arrest changes cerebral metabolism and blood flow after the arrest period despite adequate hypothermic suppression of metabolism.     

The effects of cardiopulmonary bypass and profound hypothermic circulatory arrest on anterior fontanel pressure in infants

The Ladd transducer was used to measure anterior fontanel pressure in 23 infants undergoing cardiopulmonary bypass and profound hypothermic circulatory arrest for surgical correction of congenital heart disease. Mean (+/- SD) minimum oesophageal and rectal temperatures of 11.3 +/- 1.5 degrees C and 18.1 +/- 2.2 degrees C respectively were achieved with a mean duration of arrest of 53.4 +/- 13.9 minutes. During reperfusion cardiopulmonary bypass after circulatory arrest, mean anterior fontanel pressure (18.3 +/- 6.4 mmHg) increased above baseline pre-bypass values (10.6 +/- 2.9 mmHg) (p less than 0.005). Mean arterial blood pressure decreased significantly from pre-bypass values (57.0 +/- 11.8 mmHg) during both cooling (38.8 +/- 8.4 mmHg) and rewarming cardiopulmonary bypass (45.8 +/- 8.9 mmHg) (p less than 0.005). These changes were associated with a significant decrease in cerebral perfusion pressure during cooling (27.3 +/- 11.0 mmHg) and rewarming cardiopulmonary bypass (27.5 +/- 10.6 mmHg), compared with baseline pre-bypass values (46.5 +/- 12.3 mmHg) (p less than 0.005). The data demonstrate significant but transient decreases in cerebral perfusion pressure during cooling and rewarming bypass.     

Hippocampal neuronal death following deep hypothermic circulatory arrest in dogs: involvement of apoptosis.

This study was undertaken to evaluate the histological nature of brain damage caused by deep hypothermic circulatory arrest during cardiopulmonary bypass. Total body cooling to 15 degrees C and rewarming were performed with a conventional cardiopulmonary bypass technique using the femoral artery and vein. Dogs were assigned to one of three groups. In group 1 (n = 4), cardiopulmonary bypass was maintained in a state of deep hypothermia (15 degrees C) for 90 min, group 2 animals (n = 5) underwent 60 min of deep hypothermic circulatory arrest at 15 degrees C, and group 3 (n = 6) underwent 90 min of deep hypothermic circulatory arrest at 15 degrees C. All dogs were killed by perfusion fixation 72 h after cardiopulmonary bypass. The CA1 regions of the hippocampi were examined by light and electron microscopy. Biotinylated dUTP was used for nick-end labeling of apoptotic cells mediated by terminal deoxytransferase. No morphological change was observed in group 1 dogs, and very little in group 2 dogs. More severe neuronal damage was observed in group 3. The nuclei of many cells were shrunken and showed nick-end labeling. Dense chromatin masses were detected electron microscopically in the nuclei of CA1 pyramidal cells. Neuronal cell death observed in CA1 pyramidal cells 72 h after 90 min of deep hypothermic circulatory arrest at 15 degrees C involves apoptosis. Therefore, according to this model, the maximum duration of deep hypothermic circulatory arrest should not be allowed to exceed 60 min.     

Reduced jugular venous oxygen saturation during rewarming from deep hypothermic circulatory arrest: cerebral overextraction?

Deep hypothermic circulatory arrest may impair cerebral cellular functions, and physiological parameters following circulatory arrest may deviate from the normal. The intention of this study was to monitor jugular venous oxygen saturation during cardiopulmonary bypass before and after deep hypothermic circulatory arrest. Jugular venous oxygen saturation were obtained on 18 patients by using a retrograde jugular vein catheter during replacement of the ascending aorta. Indications for operations were ascending aortic dilatation (n=15) and acute aortic dissection (n=3). Hypothermic cardiopulmonary bypass (233+/-60 min), cardioplegic arrest (105+/-37 min) and circulatory arrest (22+/-7 min) were utilized during the operations. Jugular venous oxygen saturation increased during hypothermia and decreased during rewarming. Compared with cooling, jugular venous oxygen saturation during the initial part of rewarming were significantly lower (87+/-5% vs. 97+/-1%, 89+/-4% vs. 95+/-2%, 81+/-4% vs. 87+/-5% at 16, 20 and 24 degrees C respectively, p<0.05). One patient required re-exploration because of bleeding. All patients were found neurologically normal before being discharged from the hospital (mean 14+/-7 days). In conclusion, jugular venous oxygen saturation is inversely related to the body temperature in patients undergoing hypothermic cardiopulmonary bypass. Significantly decreased jugular venous oxygen saturation during the initial part of rewarming may signify an increased cerebral extraction of oxygen.     

Sympathoadrenal function during cardiac operations in infants with the technique of surface cooling, limited cardiopulmonary bypass, and circulatory arrest

The sympathoadrenal response to surface cooling, limited cardiopulmonary bypass, and deep hypothermic circulatory arrest was investigated in 22 infants undergoing correction of congenital heart defects. Surface cooling to 26 degrees C was associated with a significant rise in plasma epinephrine and norepinephrine levels. Both levels fell during the period of core cooling on bypass, presumably because of hemodilution. Following the period of circulatory arrest there was a rise in both catecholamine levels that correlated nonlinearly with the duration of circulatory arrest. The catecholamine levels remained high after rewarming until the chest was closed. The results suggest that this type of surgical procedure produces severe sympathoadrenal stress. The extremely high values found in the postarrest period in some patients, who had had a long period of arrest (greater than 40 minutes), may indicate hypoxic stress. The biological effect of high circulating plasma catecholamines during hypothermia is difficult to assess. The heart rate response to plasma catecholamine levels tended to diminish on cooling in our patients.     

Cold retrograde cerebral perfusion improves cerebral protection during moderate hypothermic circulatory arrest: A long-term study in a porcine model.

BACKGROUND: Deep hypothermic circulatory arrest is an effective method of cerebral protection, but it is associated with long cardiopulmonary bypass times and coagulation disturbances. Previous studies have shown that retrograde cerebral perfusion can improve neurologic outcomes after prolonged hypothermic circulatory arrest. We tested the hypothesis that deep hypothermic retrograde cerebral perfusion could improve cerebral outcome during moderate hypothermic circulatory arrest. METHODS: Twelve pigs (23-29 kg) were randomly assigned to undergo either retrograde cerebral perfusion (15 degrees C) at 25 degrees C or hypothermic circulatory arrest with the head packed in ice at 25 degrees C for 45 minutes. Flow was adjusted to maintain superior vena cava pressure at 20 mm Hg throughout retrograde cerebral perfusion. Hemodynamic, electrophysiologic, metabolic, and temperature monitoring were carried out until 4 hours after the start of rewarming. Daily behavioral assessment was performed until elective death on day 7. A postmortem histologic analysis of the brain was carried out on all animals. RESULTS: In the retrograde cerebral perfusion group, 5 (83%) of 6 animals survived 7 days compared with 2 (33%) of 6 in the hypothermic circulatory arrest group. Complete behavioral recovery was seen in 4 (67%) animals after retrograde cerebral perfusion but only in 1 (17%) animal after hypothermic circulatory arrest. Postoperative levels of serum lactate were higher, and blood pH was lower in the hypothermic circulatory arrest group. There were no significant hemodynamic differences between the study groups. CONCLUSIONS: Cold hypothermic retrograde cerebral perfusion during moderate hypothermic circulatory arrest seems to improve neurologic outcome compared with moderate hypothermic circulatory arrest with the head packed in ice.     

The protective effect of profound hypothermia on the canine central nervous system during one hour of circulatory arrest

Circulatory arrest during profound hypothermia is a safe technique of cardiac surgery when used in selected instances. Despite its proven safety, the degree of cerebral protection offered by this technique is still poorly defined. Ten dogs anesthetized with Pentothal (thiopental sodium) were surface cooled to 32 degrees C. They were placed on cardiopulmonary bypass, cooled to 13 degrees C (cerebral temperature), and then underwent one hour of circulatory arrest. At the end of the arrest period, the dogs were rewarmed, resuscitated, and successfully weaned from bypass. A control group of 6 dogs were subjected to the same protocol but without the one-hour period of circulatory arrest. There were no group differences in animal weight, duration of surface cooling, cardiopulmonary bypass, or rewarming, mean flow, or mean arterial pressure. After a 7-day observation period, the dogs were killed with rapid tissue fixation using formalin. No neurological deficits were noted in any of the dogs during the observation period. The fixed brains were examined by a neuropathologist. No gross or microscopic evidence of cerebral hypoxia was seen in any of the animals. We conclude that one hour of circulatory arrest under profoundly hypothermic temperatures produces no detectable neurological changes or histological evidence of cerebral hypoxia.     

The effect of maternal hypothermic cardiopulmonary bypass on fetal lamb temperature, hemodynamics, oxygenation, and acid-base balance

OBJECTIVE: To evaluate fetal-maternal temperature relationship and fetal cardiovascular and metabolic response during maternal hypothermic cardiopulmonary bypass in pregnant ewes. METHODS: Cardiopulmonary bypass was instituted in 9 pregnant ewes, reaching 2 different levels of maternal hypothermia: 24 degrees C to 20 degrees C (deep hypothermia) in group A (5 cases) and less than 20 degrees C (very deep hypothermia) in group B (4 cases). Hypothermic levels were maintained for 20 minutes, then the rewarming phase was started. Fetal and maternal temperature, blood pressure, heart rate, electrocardiogram, blood gases, and acid-base balance were evaluated at different levels of hypothermia and during recovery. RESULTS: Fetal survival was related to maternal hypothermia: all group A fetuses survived, while 2 of 4 fetuses of group B in which maternal temperature was lowered below 18 degrees C died in a very deep acidotic and hypoxic status. Maternal temperature was always lower than fetal temperature during cooling; during rewarming the gradient was inverted. The start of cardiopulmonary bypass and cooling was associated with transient fetal tachycardia and hypertension; then, both fetal heart rate and blood pressure progressively decreased. The reduction of fetal heart rate was of 7 beats per minute for each degree of fetal cooling. Deep maternal hypothermia was associated with fetal alkalosis and reduction of Po(2). Very deep hypothermia, in particular below 18 degrees C, caused irreversible fetal acidosis and hypoxia. CONCLUSIONS: Deep maternal hypothermic cardiopulmonary bypass was associated with reversible modifications in fetal cardiovascular parameters, blood gases, and acid-base balance and therefore with fetal survival. On the contrary, fetuses did not survive to a very deep hypothermia below 18 degrees C.     

Oxygenator exhaust capnography: a method of estimating arterial carbon dioxide tension during cardiopulmonary bypass.

An in vivo study was undertaken during hypothermic (28 degrees C) cardiopulmonary bypass to compare oxygenator exhaust capnography as a means of estimating arterial carbon dioxide tension (PaCO2) with bench blood gas analysis. A total of 123 pairs of measurements were made in 40 patients. Oxygenator exhaust capnographic measurements systematically underestimated PaCO2 measured by a bench blood gas analyzer. During the cooling and stable hypothermic phases of cardiopulmonary bypass, the relationship was reasonably accurate, but became far more variable during rewarming. Oxygenator exhaust capnography could be used as an inexpensive means of continuously monitoring PaCO2 during the cooling and stable hypothermic phases of cardiopulmonary bypass but should not be used during rewarming.     

The effects of a leukocyte-depleting filter on cerebral and renal recovery after deep hypothermic circulatory arrest

OBJECTIVE: The purpose of this study was to determine the effects of a leukocyte-depleting filter on cerebral and renal recovery after deep hypothermic circulatory arrest. METHODS: Sixteen 1-week-old piglets underwent cardiopulmonary bypass, were cooled to 18 degrees C, and underwent 60 minutes of circulatory arrest, followed by 60 minutes of reperfusion and rewarming. Global and regional cerebral blood flow, cerebral oxygen metabolism, and renal blood flow were determined before cardiopulmonary bypass, after the institution of cardiopulmonary bypass, and at 1 hour of deep hypothermic circulatory arrest. In the study group (n = 8 piglets), a leukocyte-depleting arterial blood filter was placed in the arterial side of the cardiopulmonary bypass circuit. RESULTS: With cardiopulmonary bypass, no detectable change occurred in the cerebral blood flow, cerebral oxygen metabolism, and renal blood flow in either group, compared with before cardiopulmonary bypass. In control animals, after deep hypothermic circulatory arrest, blood flow was reduced to all regions of the brain (P <.004) and the kidneys (P =.02), compared with before deep hypothermic circulatory arrest. Cerebral oxygen metabolism was also significantly reduced to 60.1% +/- 11.3% of the value before deep hypothermic circulatory arrest (P =.001). In the leukocyte-depleting filter group, the regional cerebral blood flow after deep hypothermic circulatory arrest was reduced, compared with the value before deep hypothermic circulatory arrest (P <.01). Percentage recovery of cerebral blood flow was higher in the leukocyte filter group than in the control animals in all regions but not significantly so (P >.1). The cerebral oxygen metabolism fell to 66.0% +/- 22.3% of the level before deep hypothermic circulatory arrest, which was greater than the recovery in the control animals but not significantly so (P =.5). After deep hypothermic circulatory arrest, the renal blood flow fell to 81.0% +/- 29.5% of the value before deep hypothermic circulatory arrest (P =.06). Improvement in renal blood flow in the leukocyte filter group was not significantly greater than the recovery to 70.2% +/- 26.3% in control animals (P =.47). CONCLUSIONS: After a period of deep hypothermic circulatory arrest, there is a significant reduction in cerebral blood flow, cerebral oxygen metabolism, and renal blood flow. Leukocyte depletion with an in-line arterial filter does not appear to significantly improve these findings in the neonatal piglet.     

The methodologies of hypothermic circulatory arrest and of antegrade and retrograde cerebral perfusion for aortic arch surgery

In spite of recent advances in thoracic aortic surgery, postoperative neurological injury still remains the main cause of mortality and morbidity after aortic arch operation. The use of cardiopulmonary bypass (CPB) and hypothermic circulatory arrest, temporary interruption of brain circulation, transient cerebral hypoperfusion, and manipulations on the frequently atheromatic aorta all produce neurological damages. The basic established techniques and perfusion strategies during aortic arch replacement number three: hypothermic circulatory arrest (HCA), antegrade cerebral perfusion (ACP), and retrograde cerebral perfusion (RCP). During the past decade and after several experimental studies, RCP lost its previous place in the armamentarium of brain protection, giving it up to ACP as a major method of brain perfusion during HCA. HCA should be applied at a temperature of asymptotically equal to 20 degrees C with long-lasting cooling and rewarming and should not exceed by itself the time of 20-25 min. RCP does not seem to prolong safe brain-ischemia time beyond 30 min, but it appears to enhance cerebral hypothermia by its massive concentration inside the brain vein sinuses. HCA combined with ACP, however, could prolong safe brain-ischemia time up to 80 min. Cold ACP at 10 degrees -13 degrees C should be initially applied through the right subclavian or axillary artery and continued bihemispherically through the left common carotid artery at first and later the anastomosed graft, with a mean perfusion pressure of 40-70 mm Hg. The safety of temporary perfusion is being confirmed by the meticulous monitoring of brain perfusion through internal jugular bulb O2 saturation, electroencephalogram, and transcranial comparative Doppler velocity of the middle cerebral arteries.     

A comparison of the effects on neuronal Golgi morphology, assessed with electron microscopy, of cardiopulmonary bypass, low-flow bypass, and circulatory arrest during profound hypothermia.

Adult swine (n = 18) were studied to compare the effects on neuronal morphology of hypothermic circulatory arrest with hypothermic very-low-flow cardiopulmonary bypass. Animals were anesthetized with halothane and prepared in a standard manner for nonpulsatile cardiopulmonary bypass. Monitored variables included mean arterial pressure, arterial blood gases, the processed electroencephalogram, and subdural brain temperature. Bypass was initiated with pump flows of 100 ml.kg-1.min-1, and mean arterial pressure was kept above 50 mm Hg at all times. Animals were cooled to 18 degrees C, using a heat exchanger, and were randomly assigned to one of three groups. Group 1 animals were control animals who underwent 1 hour of hypothermic cardiopulmonary bypass. Group 2 animals underwent 1 hour of circulatory arrest. Group 3 animals underwent 1 hour of very-low-flow cardiopulmonary bypass (10% of normal). At the end of the 1 hour of hypothermic bypass, very-low-flow bypass, or arrest period, animals were rewarmed to 37 degrees C with normal bypass flows, and normothermic perfusion continued for 1 additional hour. Animals were then perfusion fixed with formalin and the brains were removed for electron microscopic analysis. Electron microscopic analysis was used to determine the effects of treatment and was limited to 20 neurons of the CA1 sector of the hippocampus in each animal. Golgi bodies were identified and classified as normal, mildly affected, or severely affected. Animals subjected to either very-low-flow bypass or circulatory arrest had significantly more severely affected and significantly fewer normal Golgi bodies than control animals (p < 0.001). Animals maintained with very-low-flow bypass, however, had significantly more severely affected and fewer normal Golgi bodies than animals subjected to circulatory arrest (p < 0.001). We conclude that under the conditions of this experiment very-low-flow hypothermic cardiopulmonary bypass is associated with significantly greater neuronal Golgi abnormalities than total circulatory arrest.     

Do Standard Monitoring Sites Reflect True Brain Temperature When Profound Hypothermia Is Rapidly Induced and Reversed?

Background: Brain temperature is closely approximated by most body temperature measurements under normal anesthetic conditions. However, when thermal autoregulation is overridden, large temperature gradients may prevail. This study sought to determine which of the standard temperature monitoring sites best approximates brain temperature when deep hypothermia is rapidly induced and reversed during cardiopulmonary bypass.

Methods: Twenty-seven patients underwent cardiopulmonary bypass and deep hypothermic circulatory arrest in order for each to have a giant cerebral aneurysm surgically clipped. Brain temperatures were measured directly with a thermocouple embedded in the cerebral cortex. Eight other body temperatures were monitored simultaneously with less invasive sensors at standard sites.

Results: Brain temperature decreased from 32.6 + 1.4 degrees Celsius (mean plus/minus SD) to 16.7 plus/minus 1.7 degrees Celsius in 28 plus/minus 7 min, for an average cerebral cooling rate of 0.59 + 0.15 degree Celsius/min. Circulatory arrest lasted 24 plus/minus 15 min and was followed by 63 + 17 min of rewarming at 0.31 plus/minus 0.09 degree Celsius/min. None of the monitored sites tracked cerebral temperature well throughout the entire hypothermic period. During rapid temperature change, nasopharyngeal, esophageal, and pulmonary artery temperatures corresponded to brain temperature with smaller mean differences than did those of the tympanic membrane, bladder, rectum, axilla, and sole of the foot. At circulatory arrest, nasopharyngeal, esophageal, and pulmonary artery mean temperatures were within 1 degree Celsius of brain temperature, even though individual patients frequently exhibited disparate values at those sites.     

Comparison of neurologic outcome after deep hypothermic circulatory arrest with alpha-stat and pH-stat cardiopulmonary bypass in newborn pigs

OBJECTIVE: Deep hypothermic circulatory arrest for neonatal heart surgery poses the risk of brain damage. Several studies suggest that pH-stat management during cardiopulmonary bypass improves neurologic outcome compared with alpha-stat management. This study compared neurologic outcome in a survival piglet model of deep hypothermic circulatory arrest between alpha-stat and pH-stat cardiopulmonary bypass. METHODS: Piglets were randomly assigned to alpha-stat (n = 7) or pH-stat (n = 7) cardiopulmonary bypass, cooled to 19 degrees C brain temperature, and subjected to 90 minutes of deep hypothermic circulatory arrest. After bypass rewarming/reperfusion, they survived 2 days. Neurologic outcome was assessed by neurologic performance (0-95, 0 = no deficit and 95 = brain death) and functional disability scores, as well as histopathology. Arterial pressure, blood gas, glucose, and brain temperature were recorded before, during, and after bypass. RESULTS: All physiologic data during cardiopulmonary bypass were similar between groups (pH-stat vs alpha-stat) except arterial pH (7.06 +/- 0.03 vs 7.43 +/- 0.09, P <.001) and arterial PCO (2) (98 +/- 8 vs 36 +/- 8 mm Hg, P <.001). No differences existed in duration of cardiopulmonary bypass or time to extubation. Performance was better in pH-stat versus alpha-stat management at 24 hours (2 +/- 3 vs 29 +/- 17, P = 0.004) and 48 hours (1 +/- 2 vs 8 +/- 9, P =.1). Also, functional disability was less severe with pH-stat management at 24 hours (P =.002) and 48 hours (P =.053). Neuronal cell damage was less severe with pH-stat versus alpha-stat in the neocortex (4% +/- 2% vs 15% +/- 7%, P <.001) and hippocampal CA1 region (11% +/- 5% vs 33% +/- 25%, P =.04), but not in the hippocampal CA3 region (3% +/- 5% vs 16% +/- 23%, P =.18) or dentate gyrus (1% +/- 1% vs 3% +/- 6%, P =.63). CONCLUSIONS: pH-stat cardiopulmonary bypass management improves neurologic outcome with deep hypothermic circulatory arrest compared with alpha-stat bypass. The mechanism of protection is not related to hemodynamics, hematocrit, glucose, or brain temperature.     

Barbiturates impair cerebral metabolism during hypothermic circulatory arrest.

Barbiturates have been used as a method of cerebral protection in patients undergoing open heart operations. Phosphorus 31 nuclear magnetic resonance spectroscopy was used to assess barbiturate-induced alterations in the cerebral tissue energy state during cardiopulmonary bypass, hypothermic circulatory arrest, and subsequent reperfusion. Sheep were positioned in a 4.7-T magnet with a radiofrequency coil over the skull. Nuclear magnetic resonance spectra were obtained at 37 degrees C, during cardiopulmonary bypass before and after drug administration at 37 degrees C and 15 degrees C, throughout a 1-hour period of hypothermic circulatory arrest, and during a 2-hour reperfusion period. A group of animals (n = 8) was administered a bolus of sodium thiopental (40 mg/kg) during bypass at 37 degrees C followed by an infusion of 3.3 mg.kg-1 x min-1 until hypothermic arrest. A control group of animals (n = 8) received no barbiturate. The phosphocreatine/adenosine triphosphate ratio, reflecting tissue energy state, was lower during cardiopulmonary bypass at 15 degrees C in the treated animals compared with controls (1.06 +/- 0.08 versus 1.36 +/- 0.17; p < 0.001). Lower phosphocreatine/adenosine triphosphate ratios were observed throughout all periods of arrest and reperfusion in the barbiturate-treated animals compared with controls (p < or = 0.01). Thiopental prevented the increase in cerebral energy state normally observed with hypothermia and resulted in a decrease in the energy state of the brain during hypothermic circulatory arrest and subsequent reperfusion. These results suggest that thiopental administration before a period of hypothermic circulatory arrest may prove detrimental to the preservation of the energy state of the brain.     

Effects of temperature on somatosensory evoked potentials during open heart surgery

Somatosensory evoked potentials (SEPs) have been found to be useful for early detection of brain ischemia during hypothermic cardiopulmonary bypass in cardiac surgery. However, the relationship between temperature and latency period remains unclear. We prospectively analyzed SEPs obtained during hypothermic cardiopulmonary bypass in 20 patients who had valvular replacement.
We concluded that i) a linear correlation was found between temperature and latency period during cooling and rewarming, ii) no hysteresis effect existed in cooling and rewarming, iii) there was a greater hypothermic effect on the synaptic transmission than on the conduction velocity, and, iv) age had also more profound effect on relationship between temperature and latency of SEPs.