Profound Hypothermic Cardiopulmonary Bypass Research Articles

Putting Life On Hold—For How Long? Profound Hypothermic Cardiopulmonary Bypass in a Swine Model of Complex Vascular Injuries

Rapid induction of profound hypothermia for emergency preservation and resuscitation can improve survival from uncontrolled lethal hemorrhage in large animal models. We have previously demonstrated that profound hypothermia (10 degrees C) must be induced rapidly (2 degrees C/min) and reversed gradually (0.5 degrees C/min) for best results. However, the maximum duration of hypothermic arrest in a clinically relevant trauma model remains unknown. Uncontrolled lethal hemorrhage was induced in 22 swine by creating an iliac artery and vein injury, followed 30 minutes later (simulating transport time) by laceration of the descending thoracic aorta. Through a thoracotomy approach, a catheter was placed in the aorta, and cold organ preservation solution was infused using a roller pump to rapidly induce profound hypothermia (10 degrees C) which was maintained with low-flow cardiopulmonary bypass. Vascular injuries were repaired during the asanguinous hypothermic low flow period. Profound hypothermia was maintained (n = 10-12 per group) for either 60 minutes or 120 minutes. After repair of injuries, animals were rewarmed (0.5 degrees C/min) and resuscitated on cardiopulmonary bypass, and whole blood was infused during this period. Animals were monitored for 4 weeks for neurologic deficits, organ dysfunction, and postoperative complications. The 4-week survival rates in 60- and 120-minute groups were 92% and 50%, respectively (p < 0.05). The surviving animals were neurologically intact and had no long-term organ dysfunction, except for one animal in the 120-minute group. The animals subjected to 120 minutes of hypothermia had significantly worse lactic acidosis, displayed markedly slower recovery, and had significantly higher rates of postoperative complications, including late deaths because of infections. In a model of lethal injuries, rapid induction of profound hypothermia can prevent death. Profound hypothermia decreases but does not abolish metabolism. With current methods, the upper limit of hypothermic arrest in the setting of uncontrolled hemorrhage is 60 minutes.

Moderate Hypothermia With Low Flow Rate Cardiopulmonary Bypass Used in Surgeries for Congenital Heart Defects

Low flow rate perfusion has been recommended in profound hypothermic cardiopulmonary bypass (CPB) in recent years. However, most patients with congenital heart defects are still operated on under moderate hypothermic CPB, where high flow rate perfusion has been adopted by most perfusionists. Fifty patients with congenital heart defects, ranging from 1 to 11 yr of age and 6.5 to 25 kg of weight, were included in the trial. Once on CPB, a high flow rate of 2.37 +/- 0.39 L/min/m was used to cool the patient to 27.3 degrees C +/- 0.84 degrees C rectal temperature, followed by a low flow rate of 1.31 +/- 0.09 L/min/m until the main intracardiac repair was completed and rewarming started. High flow rate was still used in rewarming the patients to a rectal temperature of 35 degrees C-36 degrees C. The total CPB, cross-clamp, and low flow rate perfusion time were 86.4 +/- 26.6, 46.4 +/- 22.3, and 40.7 +/- 22.4 min, respectively. After 24-99 min low flow rate perfusion, venous oxygen saturation remained above 80% for all the patients, and lactate concentration did not increase. Only three patients showed slight metabolic acidosis during CPB and required an extra 6-12 mEq sodium bicarbonate. Average urine output was 199 +/- 155 (50-600) ml during CPB. All patients recovered well after operation. No surgical death or neurologic complications occurred. Low flow rate perfusion might be safely used in moderate hypothermic CPB as long as the oxygen saturation of returned venous blood was kept above 80%.

Profound Hypothermic Cardiopulmonary Bypass Facilitates Survival Without a High Complication Rate in a Swine Model of Complex Vascular, Splenic, and Colon Injuries

Induction of a profound hypothermia for emergency preservation and resuscitation in severe hemorrhagic shock can improve survival from lethal injuries, but the impact of hypothermia on bleeding and infectious complications has not been completely determined. Uncontrolled hemorrhage was induced in 26 swine (95 to 135 lbs) by creating an iliac artery and vein injury, and 30 minutes later, by lacerating the descending thoracic aorta. Through a left thoracotomy approach, profound total body hypothermia (10 degrees C) was induced (2 degrees C/min) by infusing cold organ preservation solution into the aorta. The experimental groups were: vascular injuries alone (group 1, n=10), vascular and colon injuries (group 2, n=8), and vascular, colon, and splenic injuries (group 3, n=8). All injuries were repaired during 60 minutes of low-flow cardiopulmonary bypass (CPB) with hemodilution and profound hypothermia; then the animals were slowly rewarmed (0.5 degrees C/min) back to normothermia. Survivors were monitored for 6 weeks for postoperative bleeding, neurologic deficits, cognitive function (learning new skills), organ dysfunction, and septic complications. Six-week survival rates were 90% in group 1, 87.5% in group 2, and 75% in group 3 (p > 0.05). One animal in each group died from acute cardiac failure during the early postoperative phase. Splenic salvage was possible in all animals, and none required complete splenectomy for hemorrhage control. All surviving animals were neurologically intact, displayed normal learning capacity, and had no longterm organ dysfunction. None of the animals had postoperative hemorrhage or experienced septic complications. One animal in group 3 died on the ninth postoperative day because of bowel obstruction (volvulus). Induction of profound hypothermia can preserve the viability of key organs during repair of lethal injuries. This strategy can be used even in the presence of solid organ and bowel injuries to improve survival, without any considerable increase in postoperative complication rates.

Cardiopulmonary Bypass in Surgery for Interrupted Aortic Arch

Interrupted aortic arch is a complicated congenital heart defect. Because of its anatomic features, the conventional cardiopulmonary bypass (CPB) procedure is not suitable for the surgery of this type of lesion. Thus, we conducted a retrospective study of CPB in surgery for the disease. Ten patients with interrupted aortic arch underwent surgery by one of three different CPB methods, including profound hypothermia with circulatory arrest in four cases, profound hypothermia with low flow rate in five cases, and normothermia in one case. In profound hypothermic CPB, both ascending aorta and main pulmonary artery were cannulated. Through these two cannulas, the flow was pumped to the upper and lower body separately to cool down the body temperature. After cooling, the main pulmonary artery cannula was removed and interrupted aortic arch was corrected either under low flow rate perfusion or under circulatory arrest. After this, the other intracardiac lesions were repaired under conventional CPB. At the end of CPB, one patient demonstrated third-degree atria-ventricular block and required reinstituting CPB and a second procedure to repair the ventricular septal defect (VSD). In the intensive care unit, one patient developed lung infection and dyspnea after extubation that required intubation and mechanical ventilation for another several days. Another patient required 3 days of peritoneal dialysis caused by low cardiac output, hyperkalemia, and oliguria. All patients survived. The mechanical ventilation times were from 8 hours to 8 days and stays in the intensive care unit were from 4 to 12 days. Profound hypothermic cardiopulmonary bypass either with low flow rate or with circulatory arrest is equally the preferable choice for the surgery of interrupted aortic arch.

Changes in body temperature during profound hypothermic cardiopulmonary bypass in adult patients undergoing aortic arch reconstruction.

Our aim was to characterize changes in body temperatures during profound hypothermic cardiopulmonary bypass (CPB) conducted with the sternum opened. In ten adult patients who underwent profound hypothermic (< 20 degrees C) CPB for aortic arch reconstruction, pulmonary arterial temperature (PAT), nasopharyngeal temperature (NPT), forehead deep-tissue temperature (FHT), and urinary bladder temperature (UBT) were recorded every 1 min throughout the surgery. In addition, the CPB venous line temperature (CPBT), a reasonable indicator of mixed venous blood temperature during CPB and believed to best reflect core temperature during stabilized hypothermia on CPB, was recorded during the period of total CPB. PAT began to change immediately after the start of cooling or rewarming, closely matching the CPBT ( r = 0.98). During either situation, the other four temperatures lagged behind PAT ( P < 0.05); however, NPT followed PAT more closely than the other three temperatures ( P < 0.05). During stabilized hypothermia, PAT, NPT, and FHT, but not UBT, closely matched the CPBT, with gradients of less than 0.5 degrees C. During induction of profound hypothermia and its reversal on total CPB with the heart in situ, a PA catheter thermistor, presumably because of its placement immediately behind the superior vena cava, would provide a reliable measure of the mixed venous blood temperature. During stabilized profound hypothermia, PAT, NPT, and FHT, but not UBT, serve as a reliable index of core temperature.

Serum S-100 Protein in Stroke and Cardiac Surgery

To the Editor: We have read with interest the articles1 2 3 and correspondence4 of Butterworth and Missler, which dicusses the correlation of S-100 protein release with cerebral infarction and hemorrhagic strokes. The authors suggest that S-100 protein levels may be a reliable index of the mass of injured brain and the patient’s prognosis and may facilitate differentiation of hemorrhagic and nonhemorrhagic strokes. However, we would like to report that this use of S-100 protein to estimate the extent of cerebral damage cannot be extrapolated to other clinical scenarios in which cerebral injury may occur. Open-heart surgery is associated with a small but significant incidence of stroke. Surgery requiring hypothermic circulatory arrest for reconstruction of the aortic arch is associated with an incidence of stroke of 5% to 12%5–7; that for coronary artery bypass grafting (CABG) is 3% to 6%.8 Several biochemical markers of cerebral injury have been investigated as potential substitutes for serial neuropsychological assessment in studies assessing different methods of cerebral protection during surgery.9 We measured serum S-100 protein in 10 patients undergoing CABG using simple mild hypothermic cardiopulmonary bypass and in 30 patient with thoracic aortic aneurysms using profound hypothermic cardiopulmonary bypass and circulatory arrest (HCA) for up to 60 …

Aneurysm of Right Cervical Aortic Arch with Abnormal Branching Pattern

We report a rare case of congenital saccular aneurysm of the right cervical aortic arch in a 16-year-old girl. There were no branches arising from the aortic arch but 3 branches arose from the ascending aorta: the left innominate artery, the right common carotid artery, and the right subclavian artery. The aneurysm was successfully repaired with a plasma-preclotted woven Dacron interposition graft during profound hypothermic cardiopulmonary bypass without total circulatory arrest.

The Brain Uses Mostly Dissolved Oxygen During Profoundly Hypothermic Cardiopulmonary Bypass

Background. During profoundly hypothermic cardiopulmonary bypass, cerebral venous oxygen saturation increases (eg, to 98% at 15°C). We reanalyzed results of clinical studies to learn why.Methods. One hundred sixty-eight cerebral oxygen transport measurements were available from 96 infants and children undergoing profoundly hypothermic cardiopulmonary bypass during repair of congenital heart defects.Results. Dissolved oxygen accounted for 2% to 17% of arterial oxygen content, depending on the arterial oxygen partial pressure and hemoglobin concentration. The fraction of the cerebral metabolic rate for oxygen obtained from dissolved oxygen depended on pump flow, temperature, hemoglobin concentration, and arterial oxygen partial pressure (all p < 10−3). For “full-flow” cardiopulmonary bypass, temperatures less than 18°C, and arterial oxygen partial pressure measurements more than 180 mm Hg, the mean ± standard deviation of the fraction of cerebral metabolic rate for oxygen obtained from dissolved oxygen equaled 77% ± 19%.Conclusions. Dissolved oxygen satisfies most of the brain’s oxygen requirements during profound hypothermic cardiopulmonary bypass. This result reflects four properties of profound hypothermic cardiopulmonary bypass: (1) increases in hemoglobin’s oxygen affinity due to profound hypothermia (which impairs oxygen transfer from hemoglobin to cerebral tissue), (2) use of hemodilution, (3) use of high arterial oxygen partial pressure, and (4) low cerebral metabolic rate of oxygen.(Ann Thorac Surg 1997;63:1725–9)

Interactive effects of pH and temperature on N-methyl-D-aspartate receptor activity in rat cortical brain slices.

Low extracellular pH decreases the activity of the N-methyl-D-aspartate (NMDA) glutamate receptor, and may thus limit neuronal calcium overload during cerebral ischemia. During induced hypothermia, alkaline pH ("alphastat regulation") is often used to preserve cardiac and enzymatic function. The purpose of this study is to measure the functional activity of cerebral cortex NMDA receptors over the range of temperatures used in profound hypothermic cardiopulmonary bypass (20-37 degrees C). Extracellular pH was varied over a broad range relevant to both alphastat and pH stat acid-base management (7.0-7.8). Change in cytosolic free calcium evoked by 50 microM NMDA in brain slices was used as an index of NMDA receptor activity. Cortical slices (300 microns thick) were loaded with fura-2 Aspartate Methyl for study in a fluorometer. At 37 degrees C, a change in extracellular pH from 7.1 to 7.8 increased the NMDA-evoked change in cytosolic calcium in brain slices by a factor of 4 (p < 0.05). In contrast, at 20 degrees C there was minimal effect of changing extracellular pH from 7.1 to 7.8 (27% increase). We conclude that hypothermia results in decreased pH sensitivity of the NMDA receptor. The results predict that different strategies of pH management during induced hypothermia may have limited impact on NMDA receptor-mediated processes, such as neuronal calcium overload.

Persistent low cerebral blood flow velocity following profound hypothermic circulatory arrest in infants

Acute neurological morbidity following repair of congenital heart disease (CHD) in infancy is well recognized, particularly with the modalities of hypothermic cardiopulmonary bypass (CPB) and profound hypothermic circulatory arrest (PHCA). Reduced O2 delivery (perfusion defect) during rewarming following PHCA has been shown in the operating room. This reduction in cerebral blood flow coincides with disordered cerebral metabolism and oxygen utilisation after PHCA. The objective of this study was to extend the period of investigation of cerebral blood flow velocity (CBFV) behaviour in infants following PHCA to determine if hypoperfusion persisted in the paediatric intensive care unit (PICU). Ten patients undergoing CHD surgery were divided, based on the pump modality employed, into either mild hypothermic CPB or profound hypothermic CPB with circulatory arrest. Following admission to the PICU, sequential recordings of the mean CBFV in the middle cerebral artery, anterior fontanelle pressure, haemodynamic variables, tympanic membrane temperature, haematocrit and PaCO2 were performed. The PHCA group had a consistently reduced CBFV compared with the control group (P < 0.05). The CBFV values at one, two and four hours were 60 +/- 11, 51.8 +/- 11.4 and 52.6 +/- 11.9 respectively in the mild hypothermic CPB group. The CBFV values at one, two and four hours were 26.6 +/- 6.8, 32.6 +/- 10 and 34 +/- 8 respectively in the PHCA group. There was no difference in cerebral perfusion pressure between both groups. Tympanic temperature, haematocrit and PaCO2 did not vary between groups at any interval. This study demonstrates a sustained reduction in the CBFV pattern following PHCA into the postoperative period despite adequate cerebral perfusion pressures. This abnormality correlates with electroencephalographic aberrations documented after PHCA. It supports the concept of a prolonged unreactive cerebrovascular bed which could potentially contribute to the acute neurological morbidity following PHCA in neonates.

Replacement of the thoracic aorta with collagen-impregnated woven Dacron grafts: Early results

We used the collagen-impregnated woven double-velour Dacron graft in 120 patients undergoing 122 aortic reconstructions. Seventy-nine aortic root, ascending, or arch replacements were performed during cardiopulmonary bypass with or without circulatory arrest; 53 of the 79 were for acute aortic dissection. In addition, three infants and one child underwent repair of truncus arteriosus. There were no deaths caused by hemorrhage or bleeding-related complications. For aortic root replacement, the impervious nature of the collagen-impregnated woven double velour Dacron graft allowed elimination of wrap-around techniques. Eight deaths occurred as a result of multisystem organ failure, which followed late diagnosis of type A dissection. Two patients underwent reoperation for late complications of type A dissection. Thirty-nine patients underwent treatment for disease of the descending aorta; eight of these patients underwent a central cannulation technique with profound hypothermic cardiopulmonary bypass. The other 31 underwent repair with aortic crossclamping without bypass. Four of these patients died: two as a result of multisystem organ failure, one as a result of uncontrolled bleeding from the native dissected aorta, and one as a result of intestinal necrosis. Follow-up studies for 2 months to 5 years revealed three late deaths caused by the rupture of a persistent aneurysmal false lumen after type A dissection. The intraoperative advantages of the collagen-impregnated woven double velour Dacron graft represent an important advance in vascular graft technology. Its handling and suturing characteristics are excellent, and the graft is completely impervious in its originally manufactured state. Needle holes self-seal rapidly. Medium-term follow-up by clinical, angiographic, computed tomographic, and magnetic resonance imaging techniques showed no late graft complications--specifically, no dilatation or thrombus formation.

Cardiopulmonary bypass—organ blood flow and metabolism in the pediatric patient

Congenital heart disease occurs in roughly 0.7% of live-births. Approximately one-half of these defects are severe, requiring surgical correction or palliation. In a large percentage of such procedures in children, moderate or profound hypothermic cardiopulmonary bypass is employed. Because, nowadays, early correction of the defect rather than a palliative procedure is more frequently pursued, the surgeon, anesthesiologist, and perfusionist are called upon to manage younger and smaller children undergoing longer and more complex operations which necessitate longer times on bypass. Due to the particular underlying heart defect, the pathway of flow and viscosity of the blood are frequently different from those encountered in the adult with atherosclerotic coronary arterial or valvar heart disease. Thus, it is important for those caring for children undergoing cardiac surgery utilizing bypass to be well informed about its possible detrimental effects on the various organs. The purpose of this review will be to focus on the effects of bypass on flow to, and metabolism of, the organs and to highlight what is known with regard to these features in children rather than adults.

Cerebral Pressure-Flow Velocity Relationship During Hypothermic Cardiopulmonary Bypass in Neonates and Infants

To examine the effect of temperature on the relationship between cerebral perfusion pressure (CPP) and cerebral blood flow velocity (CBFV) and the effect of low-flow cardiopulmonary bypass (CPB) on cerebral perfusion, we studied 25 neonates and infants ranging from 3 to 210 days of age at three nasopharyngeal temperature (NPT) ranges during cardiopulmonary bypass. Pressure-flow velocity relationships were studied during normothermic (NPT = 36-37 degrees C), moderate hypothermic (NPT = 23-25 degrees C), and profound hypothermic (NPT = 14-20 degrees C) CPB. A transcranial Doppler monitor was used to obtain CBFV, which was measured in the M1 segment of the middle cerebral artery. The CBFV was used as an index of cerebral perfusion. Anterior fontanel pressure (AFP) was subtracted from mean arterial pressure (MAP) to calculate CPP in mm Hg. Nasopharyngeal temperature, PaCO2, and hematocrit were controlled during the study period. Arterial blood gases were analyzed at 37 degrees C, uncorrected for body temperature (alpha-stat acid-base management). The CBFV measurements were made over a range of CPP from 6 to 90 mm Hg. Using nonlinear regression analysis, we showed that cerebral pressure-flow velocity autoregulation was present during normothermic CPB (r2 = 0.68). Autoregulation became pressure-passive, using linear regression analysis, during moderate hypothermic CPB (r2 = 0.33) and profound hypothermic CPB (r2 = 0.69). Cerebral blood-flow velocity was not detectable at a mean (+/- SD) CPP of 9 (+/- 2) mm Hg induced by the low-flow CBP state but became apparent when CPP was increased to 13 (+/- 1) mm Hg (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)