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.     

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.     

Hemodilution elevates cerebral blood flow and oxygen metabolism during cardiopulmonary bypass in piglets

BACKGROUND: Hemodilution continues to be widely used during cardiopulmonary bypass (CPB) for both adults and children. Previous studies with nonbypass models have suggested that an increase in cerebral blood flow (CBF) compensates for the reduced oxygen-carrying capacity; however, this increased CBF is achieved by an increase in cardiac output. We hypothesized that even with the fixed-flow perfusion of CPB, CBF would be increased during hemodilution. METHODS: Two experiments were conducted and analyzed separately. In each experiment, 10 piglets were randomized to two different groups, one with a total blood prime yielding a high hematocrit (25% or 30%), and the other with a crystalloid prime resulting in a low hematocrit (10% or 15%). Animals were cooled with pH-stat strategy at full flow (100 or 150 mL.kg(-1).min(-1)) to a nasopharyngeal temperature of 15 degrees C, a period of low flow (50 mL.kg(-1).min(-1)) preceding deep hypothermic circulatory arrest (45 or 60 minutes), and a period of rewarming at full flow. Cerebral blood flow was measured at the beginning of CPB, at the end of cooling, at the end of low flow, 5 minutes after the start of rewarming, and at the end of rewarming by injection of radioactive microspheres. RESULTS: Mean arterial pressure was significantly greater with higher hematocrit at each time point (p< 0.05). Cerebral blood flow and the cerebral metabolic rate of oxygen decreased during cooling and further during low flow bypass but were significantly greater with lower hematocrit during mild hypothermia and at the end of rewarming (p< 0.05). CONCLUSIONS: Hemodilution is associated with decreased perfusion pressure, increased CBF and increased the cerebral metabolic rate of oxygen during hypothermic CPB.     

Effect of deep hypothermia on cerebral hemodynamics during selective cerebral perfusion with systemic circulatory arrest

OBJECTIVE: We studied the effect of deep hypothermia on cerebral hemodynamics during selective cerebral perfusion with systemic circulatory arrest. METHODS: Ten anesthesized pigs were placed on cardiopulmonary bypass and cooled to a rectal temperature of 22 degrees C (n = 5) or 15 degrees C (n = 5). During selective cerebral perfusion, the descending aorta was clamped and perfusion of the lower body was discontinued. As the pump flow was changed, we monitored the perfusion pressure, local cerebral blood flow, and local cerebral oxygenation using laser Doppler flowmetry and near-infrared spectroscopy. We also measured the free flow of the left internal thoracic artery during selective cerebral perfusion. RESULTS: Perfusion pressure and local cerebral blood flow decreased as the pump flow decreased. Oxygenated and deoxygenated hemoglobin in cerebral tissue remained unchanged at a perfusion flow of 10 ml/kg/min, whereas oxygenated hemoglobin decreased and deoxygenated hemoglobin increased progressively and reciprocally as the pump flow decreased. The pump flow for maintaining perfusion pressure above 35 mmHg with stabilized local cerebral oxygenation was significantly higher at 15 degrees C than at 22 degrees C. The internal thoracic artery free flow was higher at 15 degrees C than at 22 degrees C. CONCLUSIONS: Selective hypothermic cerebral perfusion with systemic circulatory arrest produces an extracranial shunt through the internal thoracic artery, especially under deep hypothermia. Our data suggests that selective cerebral perfusion during deep hypothermia is best managed by perfusion pressure control rather than by flow control.     

Cerebral blood flow response to changes in arterial carbon dioxide tension during hypothermic cardiopulmonary bypass in children

We examined the relationship of changes in partial pressure of carbon dioxide on cerebral blood flow responsiveness in 20 pediatric patients undergoing hypothermic cardiopulmonary bypass. Cerebral blood flow was measured during steady-state hypothermic cardiopulmonary bypass with the use of xenon 133 clearance methodology at two different arterial carbon dioxide tensions. During these measurements there was no significant change in mean arterial pressure, nasopharyngeal temperature, pump flow rate, or hematocrit value. Cerebral blood flow was found to be significantly greater at higher arterial carbon dioxide tensions (p less than 0.01), so that for every millimeter of mercury rise in arterial carbon dioxide tension there was a 1.2 ml.100 gm-1.min-1 increase in cerebral blood flow. Two factors, deep hypothermia (18 degrees to 22 degrees C) and reduced age (less than 1 year), diminished the effect carbon dioxide had on cerebral blood flow responsiveness but did not eliminate it. We conclude that cerebral blood flow remains responsive to changes in arterial carbon dioxide tension during hypothermic cardiopulmonary bypass in infants and children; that is, increasing arterial carbon dioxide tension will independently increase cerebral blood flow.     

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.     

Is Maintenance of Cerebral Hypothermia the Principal Mechanism by which Retrograde Cerebral Perfusion Provides Better Brain Protection than Hypothermic Circulatory Arrest?

OBJECTIVE: Retrograde cerebral perfusion (RCP) provides better brain protection than hypothermic circulatory arrest (HCA) alone. The mechanism by which RCP improves brain protection during circulatory arrest remains unknown. The purpose of the study in pigs was to determine if RCP improves brain protection mainly as a result of its ability to maintain cerebral hypothermia. METHODS: Fifteen pigs were subjected to 120 minutes of HCA alone (HCA group, n = 5), HCA + RCP at perfusion pressures of 23 to 29 mmHg (RCP-low group, n = 5), or at perfusion pressures of 34-40 mmHg (RCP-high group, n = 5) at 15 degrees C, followed by 60 minutes of normothermic cardiopulmonary bypass (CPB). After brain temperature reached 15 degrees C, HCA was initiated with or without RCP. Temperatures in the brain, esophagus, and perfusate/blood were monitored continuously. Brain tissue blood flow was measured continuously using a laser flowmeter. Brain oxygen extraction was calculated from the oxygen contents in arterial and venous blood samples. RESULTS: During cooling and rewarming, the change in temperature was slower in the brain than in the esophagus. A similar degree of spontaneous rewarming (from 15 degrees C to 17/18 degrees C) occurred in the brain during HCA and RCP. This indicates that RCP does not provide better maintenance of cerebral hypothermia during circulatory arrest than HCA alone. The esophageal temperature rose more slowly during RCP than during HCA alone, indicating that RCP maintains better hypothermia in the body. During RCP, the brain extracted oxygen continuously from the blood, indicating that RCP may provide nutrient flow to the brain. CONCLUSION: In an acute pig model, maintenance of cerebral hypothermia does not appear to be the principal mechanism by which RCP provides better brain protection than HCA alone. Retrograde cerebral perfusion provides nutrient flow/oxygen to brain tissue, leading to better brain protection than HCA alone.     

Cerebral hemodynamics in neonates and infants undergoing cardiopulmonary bypass and profound hypothermic circulatory arrest: assessment by transcranial Doppler sonography

Profound hypothermic circulatory arrest (PHCA) is followed by a transient period of increased intracranial pressure and a longer period of neurophysiologic dysfunction. To investigate the effect of cardiopulmonary bypass (CPB) with PHCA on cerebral hemodynamics, we used transcranial Doppler sonography to measure cerebral blood flow velocity in 10 neonates and infants before and after PHCA. Cerebral blood flow velocity was compared before and after PHCA during normothermic cardiopulmonary bypass at the same mean arterial pressure, central venous pressure, hematocrit, and arterial carbon dioxide tension. Cerebral blood flow velocity decreased exponentially with decreasing nasopharyngeal temperature before PHCA (P less than 0.05) and remained decreased after PHCA during normothermic CPB, compared with values for normothermic CPB before PHCA (P less than 0.005). During normothermic CPB after PHCA, the modified cerebral vascular resistance (mm Hg.cm.s-1) was increased above values for normothermic CPB before PHCA (P less than 0.05). The results of this study suggest that the observed increase in intracranial pressure during PHCA is not caused by increased cerebral perfusion, but rather that cerebral perfusion is reduced in response to a decreased demand for cerebral metabolic oxygen.     

Physiologic effects of deep hypothermia and microwave rewarming: possible application for neonatal cardiac surgery

Deep hypothermia (20 C) without cardiopulmonary bypass is a valuable technique during cardiac surgery in infants but rewarming of the heart following circulatory arrest and cardiac repair has traditionally been a lengthy and difficult process. In experimental animals rewarming the heart with microwave energy, as reported in this work, warms the heart before warming the periphery. In 18 mongrel dogs that were surface cooled to 20 C, we found that during microwave rewarming the core temperature rose 4.7 C per hour. Whole body oxygen consumption, heart rate, and cardiac output returned to normal at rates equal to the rates at which they decreased during surface cooling. Blood pressure and arterial gases remained adequate. Microwave rewarming appears to be a useful method for reestablishment of cardiac function and normothermia following deep hypothermia.     

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.     

Profound hypothermia (less than 10 degrees C) compared with deep hypothermia (15 degrees C) improves neurologic outcome in dogs after two hours' circulatory arrest induced to enable resuscitative surgery

Deaths from uncontrollable hemorrhage might be prevented by arresting the circulation under protective hypothermia to allow resuscitative surgery to repair these injuries in a bloodless field. We have shown previously that in hemorrhagic shock, circulatory arrest of 60 minutes under deep hypothermia (tympanic membrane temperature, Ttm = 15 degrees C) was the maximum duration of arrest that allowed normal brain recovery. We hypothesize that profound cerebral hypothermia (Ttm less than 10 degrees C) could extend the duration of safe circulatory arrest. In pilot experiments, we found that the cardiopulmonary system did not tolerate arrest at a core (esophageal) temperature (Tes) of less than 10 degrees C. Twenty-two dogs underwent 30-minute hemorrhagic shock (mean arterial pressure 40 mm Hg), rapid cooling by cardiopulmonary bypass (CPB), blood washout to a hematocrit of less than 10%, and circulatory arrest of 2 hours. In deep hypothermia group 1 (n = 10), Ttm was maintained at 15 degrees C during arrest. In profound hypothermia group 2 (n = 12), during cooling with CPB, the head was immersed in ice water, which decreased Ttm to 4 degrees-7 degrees C. The Tes was 10 degrees C in all dogs during arrest. Reperfusion and rewarming were by CPB for 2 hours. Controlled ventilation was to 24 hours, intensive care to 72 hours. In the 20 dogs that followed protocol, best neurologic deficit scores (0% = normal, 100% = brain death) at 24-72 hours were 23% +/- 19% in group 1 and 12% +/- 8% in group 2 (p = 0.15). Overall performance categories and histologic damage scores were significantly better in group 2 (p = 0.04 and p less than 0.001, respectively). We conclude that profound cerebral hypothermia with CPB plus ice water immersion of the head can extend the brain's tolerance of therapeutic circulatory arrest beyond that achieved with deep hypothermia.     

Neurologic monitoring for special cardiopulmonary bypass techniques

Low flow hypothermic cardiopulmonary bypass, deep hypothermic circulatory arrest, and regional low-flow cerebral perfusion are special techniques used to facilitate complex intracardiac and aortic surgery in neonates and infants. Each carries a risk of cerebral hypoxia and neurologic morbidity. Neurologic monitoring in the form of near-infrared spectroscopy for cerebral oxygenation, transcranial Doppler ultrasound, and the bispectral index electroencephalogram can monitor the brain during these techniques to determine the minimum acceptable bypass flow rates or maximum acceptable duration of deep hypothermic circulatory arrest. The use of this monitoring has the potential to improve long-term neurologic and developmental outcome.     

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.     

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.     

Comparative analysis of alpha-stat and pH-stat strategies with a membrane oxygenator during deep hypothermic circulatory arrest in young pigs

Using young pigs, this study compared the strategies of alpha-stat and pH-stat during deep hypothermic circulatory arrest (DHCA) for the cooling time of brains during the induction of hypothermia and rewarming time with cardiopulmonary bypass (CPB); the cerebral perfusion rate and metabolism rate, and the ratio of these 2 rates; and the extent of the cerebral edema development after circulatory arrest. Fourteen young pigs were assigned to 1 of 2 strategies of gas management. Cerebral blood flow was measured with a cerebral venous outflow technique. With CPB, core cooling was initiated and continued until the nasopharyngeal temperature fell below 20 degrees C. The flow rate was set at 2,500 ml/min. Once the temperature reached below 20 degrees C, the animals were subjected to DHCA for 40 min. During the cooling period, the acid-base balance was maintained using either alpha-stat or pH-stat strategy. After DHCA, the body was rewarmed to the normal body temperature. The animals then were sacrificed, and we measured the brain water content. The cerebral perfusion and metabolism rates were measured before the onset of CPB, before cooling, before DHCA, 15 min after rewarming, and upon the completion of rewarming. The cooling time was significantly shorter with alpha-stat than with pH-stat strategy while no significant differences were observed in the rewarming time between groups. Also, no significant differences were found in cerebral blood flow volume, metabolic rate, or flow/metabolic rate ratio between groups. In each group, the cerebral blood flow volume, metabolic rate, and flow/metabolic rate ratio showed significant differences in body temperature. Brain water content showed no significant differences between the 2 groups. In summary, this study found no significant differences between alpha-stat and pH-stat strategies, except in the cooling time. The cooling time was rather shorter with the alpha-stat than with the pH-stat strategy.     

Brain protection during surgery of the aortic arch

Deep hypothermia with circulatory arrest is the usual method of cerebral protection during replacement of the aortic arch. It has the enormous advantage of allowing the surgical repair to be carried out in a complete bloodless field with no aortic cross-clamping. However, this method only gives the surgeon a limited period of time to carry out the aortic repair. It also requires that cardiopulmonary bypass be prolonged to cool and rewarm the patient which may be the cause of various complications. It has been proposed to improve the efficiency and the results of deep hypothermia, by associating it with retrograde cerebral perfusion of the brain with oxygenated blood through the superior vena cava. This technique improves the tolerance of the brain to cold ischemia and increases the time of repair allowed to the surgeon. Antegrade selective cerebral perfusion has also been in use for more than three decades. When the perfusion is derived from the main arterial line and performed at moderate hypothermia, the aorta must be cross-clamped to perform the repair. In addition, there is some uncertainty as to what constitutes adequate perfusion flow at normal or moderate hypothermic conditions. To reconcile the advantages of both approaches while avoiding their major drawbacks, in 1986 we proposed an original method of selective antegrade brain perfusion. The principle is to perfuse selectively the brain with cold blood (10 to 12 degrees C) while maintaining the central temperature in moderate hypothermia (25-28 degrees C). During the time of the distal anastomosis the cardiopulmonary bypass is stopped, maintaining only the cerebral perfusion at a flow rate of about 400 to 500 mL/mn and a pressure of about 70 mmHg. As soon as the distal anastomosis is completed the main perfusion is resumed. Two hundred and six patients with a mean age of 57 years (22 to 83) were operated on with this technique between October 1984 and March 2001. One hundred forty three patients underwent an elective procedure and 63 patients were operated on in emergency, mainly for acute type A dissection (54 of 63). The hospital mortality was 17% (34 patients). Death was directly related to neurological injury in 9 patients (4.4%). All others patients awoke within 6 to 8 hours and were conscious at 24 hours postoperatively. Thirteen nonfatal neurological complications were observed. The type of lesion, gender, age, duration of CPB, cerebral perfusion, and circulatory arrest had no influence on the neurological outcome of the patients. In our experience, antegrade selective perfusion of the brain with cold blood and moderate hypothermic central temperature constitutes the method of choice for cerebral protection during surgery of the aortic arch as it requires no prolonged CPB and does not limit the time available to perform the aortic repair.     

Blood flow distribution in infant pigs subjected to surface cooling, deep hypothermia, and circulatory arrest. Deleterious effects in pigs with left-to-right shunts

Surface cooling, deep hypothermia and circulatory arrest have been used effectively for correction of congenital heart defects in infancy. Which patients are best suited for this technique has not been addressed. The addition of surface cooling to deep hypothermia and circulatory arrest provides homogeneous cooling and avoids swelling due to reperfusion injury after circulatory arrest. However, surface cooling in patients with large left-to-right shunts causes increased peripheral resistance and increased shunting which can result in decreased perfusion of vital organs. The purpose of this study is to measure the effect of a large left-to-right shunt on total organ blood flow distribution in infant piglets during surface cooling, deep hypothermia, and circulatory arrest. Eleven 2-week-old piglets had surface cooling, deep hypothermia, and circulatory arrest for 45 minutes, followed by rewarming and weaning from cardiopulmonary bypass. Microspheres (15 mu) were injected before surface cooling, at 28 degrees C, at 15 degrees C, and after weaning from cardiopulmonary bypass. Group I (five piglets) was the control. Group II (six piglets) had a large (6 mm) left-to-right aortopulmonary shunt established before microsphere injection. Cardiac outputs in both Groups I and II decreased with surface cooling. The distribution of cardiac output in Group I did not change with surface cooling; however, Group II pigs showed marked change in distribution of cardiac output, resulting in decreased renal, visceral, and pulmonary flow (p less than 0.05). Amylase determinations before and after surface cooling, deep hypothermia, and circulatory arrest were unchanged in Group I but elevated in Group II (p less than 0.05). These observations suggest altered cellular metabolism in visceral organs during the period of surface cooling which may be compounded by circulatory arrest and rewarming.     

Bispectral index in a 3-year old undergoing deep hypothermia and circulatory arrest

We report a 3-year-old girl who presented with Scimitar syndrome and underwent hypothermic circulatory arrest for correction of anomalous pulmonary veins and an atrial septal defect. In this case the Bispectral Index (BIS) correlated significantly with the gradual onset of hypothermia and circulatory arrest. However, BIS remained low during the rewarming phase of cardiopulmonary bypass, in spite of adequate pump flows and stable haemodynamics. We postulate that this significant lag in BIS during the rewarming phase of deep hypothermic circulatory arrest may represent neuronal bewilderment or perhaps stunning, and differs from previous studies that show significant increase in BIS during rewarming from mild hypothermia.     

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.