Akzidentelle Hypothermie

Uncertainty exists on how to treat patients suffering from accidental hypothermia and on the optimal transport decisions. The aim of this review is to provide an updated evidence-based reference for the pre-hospital and in-hospital management of patients with accidental hypothermia and for the transport decisions required to facilitate treatment. Advances in the efficiency and availability of rewarming techniques have improved the prognosis for patients presenting with hypothermia. For hypothermic patients with a core body temperature ≥?28?°C without cardiac instability there is increasing evidence to support the use of active external and minimally invasive rewarming techniques (e.g. chemical, electrical or forced air heating packs, blankets and warm parenteral fluids). Hypothermic patients with cardiac instability (i.e. systolic blood pressure <?90 mmHg, ventricular arrhythmia and core body temperature <?28?°C) should be rewarmed with active external and minimally invasive rewarming techniques in a hospital which also has circulation substituting venous-arterial extracorporeal membrane oxygenation (VA-ECMO) and cardiopulmonary bypass (CBP) facilities. In cardiac arrest patients VA-ECMO may be a better treatment option than CBP and survival rates of 100?% can be achieved compared to ~?10?% with traditional methods (e.g. body cavity lavage). Early transport to a hospital appropriately equipped for rewarming has the potential to decrease complication rates and improve survival.     

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.     

Cardiopulmonary bypass for resuscitation of patients with accidental hypothermia and cardiac arrest.

Hypothermic patients have been successfully rewarmed by a number of methods. However, when cardiac arrest occurs, as it frequently does at core temperatures of less than 27 degrees C, prolonged cardiopulmonary resuscitation (CPR) is required, because defibrillation can rarely be achieved until the patient has been rewarmed to 30 degrees to 34 degrees C. Five cases of accidental hypothermia with cardiac arrest treated with cardiopulmonary bypass are discussed. The first patient died as a result of inadequate low-flow cardiopulmonary bypass by the femorofemoral route. The second patient had prolonged CPR by closed-chest cardiac massage and warm peritoneal lavage followed by transthoracic cardiopulmonary bypass. This patient regained consciousness but was found to be paraplegic and died from bowel infarction related to peritoneal rewarming without adequate perfusion. In the last three patients, high-flow cardiopulmonary bypass was rapidly achieved using a no. 28 French chest tube for femoral venous cannulation, and they recovered completely. In cases of accidental hypothermia with cardiac arrest, rapid institution of full cardiopulmonary bypass provides excellent circulatory support and rapid rewarming. This avoids the complications of prolonged inadequate circulation that occur when closed-chest cardiac massage and external rewarming are used.     

Comparison of three methods of rewarming from hypothermia: advantages of extracorporeal blood warming

We developed a new technique, extracorporeal venovenous rewarming (EVR), to rewarm hypothermic patients in the intensive care unit or operating room. We compared this method with the active external (standard) techniques of warming blankets; heated ventilator circuits, intravenous fluids, and gastric and peritoneal lavage; and cardiopulmonary bypass. The EVR technique warmed patients' blood or additional blood products and crystalloids to 40 degrees C at 150-400 mL/min and allowed survival from a core temperature of 31.1 degrees C after massive injury. The EVR technique rewarming patients more rapidly than standard techniques and may be most appropriate in patients with multisystem trauma when rapid correction of hypothermia-related hypovolemia, coagulopathy, and arrhythmia is necessary. Cardiopulmonary bypass is required in severely hypothermic patients with cardiac arrest. Standard techniques can be used when these immediately life-threatening conditions are not present.     

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.     

Hemodialysis as a Treatment of Severe Accidental Hypothermia

We describe a case of severe accidental hypothermia (core body temperature 23.2°C) successfully treated with hemodialysis in a diabetic patient with preexisting renal insufficiency. Consensus exists about cardiopulmonary bypass as the treatment of choice in cases of severe accidental hypothermia with cardiac arrest. Prospective randomized controlled trials comparing the different rewarming modalities for hemodynamically stable patients with hypothermia, however, are lacking. In our opinion, the choice of a rewarming technique should be patient tailored, knowing that hemodialysis is an efficient, minimally invasive, and readily available technique with the advantage of providing electrolyte support.     

Prognostic factors in severe accidental hypothermia: experience from the Mt. Hood tragedy

The May 1986 Mt. Hood climbing disaster presented Portland area hospitals the opportunity to initiate a trial of extracorporeal rewarming using cardiopulmonary bypass in ten severely hypothermic patients (two survivors). The data from this experience as well as others previously reported can yield prognostic indicators of survival in cases of accidental hypothermia. These are demonstrated to include: the presence of underlying medical illness, duration of cold exposure, initial core temperature, mental status, the presence of spontaneous respirations, presenting cardiac rate and rhythm, and arterial oxygen tension. Profound hyperkalemia and markedly elevated serum ammonia levels indicate cell lysis; significant hypofibrinogenemia suggests intravascular thrombosis and each laboratory marker predicts a dire outcome. The treatment of choice for severe accidental hypothermia is felt to be rapid core rewarming on cardiopulmonary bypass.     

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.     

Partial cardiopulmonary bypass for core rewarming in profound accidental hypothermia

Six cases of treatment of severe accidental hypothermia using cardiopulmonary bypass for core rewarming are reported and eleven cases from the literature are analyzed. Thirteen patients survived. Overall survival was more likely in patients who had vital signs initially. Initial mean core temperatures in the new cases was 22.8 C. Surface and conventional core rewarming methods resulted in an average temperature increase of 2.4 C per hr. Electrical defibrillation was generally without success until the core temperature had been raised to above 30 C. Between one and six hours after admission, partial femoral-femoral cardiopulmonary bypass (CPB) for core rewarming was started, causing a mean temperature increase of 9.5 C per hr. Four patients required a thoracotomy. Two patients had a massively dilated heart with contusions, and could not be weaned off bypass. None of the four long-term survivors had a demonstrable central nervous system (CNS) deficit. All patients developed temporary pulmonary problems; two developed wound infections. The average hospital stay was 21 days. CPB for core rewarming allows circulatory support while avoiding myocardial damage from prolonged external cardiac massage; rapidly increases the myocardial temperature and counteracts myocardial temperature gradients so that DC electroversion is successful; avoids "rewarming shock"; and improves microcirculatory flow. A prospective randomized trial to compare rapid surface rewarming and CPB rewarming is suggested. Immediate CPB for rewarming is recommended for patients in ventricular fibrillation with core temperatures below 30 C. Prolonged external cardiac massage (ECM) should not be used. The value of surface rewarming and non-CPB core rewarming methods remains undefined.     

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.     

Schwere akzidentelle Hypothermie mit Kreislaufstillstand und extrakorporaler Erwärmung

In patients with severe hypothermia and cardiac arrest, active rewarming is recommended by extracorporeal circulation with cardiopulmonary bypass. The current guidelines for resuscitation of the European Resuscitation Council now include the recommendation regarding patients with hypothermia remaining comatose after initial resuscitation to accomplish an active rewarming only up to a temperature of 32-34 degrees C and to maintain a mild hypothermia for 12-24 h. We report the case of a 2-year-old boy who suffered from severe hypothermia after falling into ice-cold water. On discovery cardiac arrest with asystole was present and the first measured temperature was 23.8 degrees C. Resuscitation led to restoration of spontaneous circulation. The patient was rewarmed by extracorporeal circulation with cardiopulmonary bypass to 33 degrees C then mild hypothermia was maintained for a further 12 h. On the third day after the accident the patient was extubated and after a further 9 days was discharged without any sequelae.     

Efficacy of two methods for reducing postbypass afterdrop

BACKGROUND: Afterdrop, defined as the precipitous reduction in core temperature after cardiopulmonary bypass, results from redistribution of body heat to inadequately warmed peripheral tissues. The authors tested two methods of ameliorating afterdrop: (1) forced-air warming of peripheral tissues and (2) nitroprusside-induced vasodilation. METHODS: Patients were cooled during cardiopulmonary bypass to approximately 32 degrees C and subsequently rewarmed to a nasopharyngeal temperature near 37 degrees C and a rectal temperature near 36 degrees C. Patients in the forced-air protocol (n = 20) were assigned randomly to forced-air warming or passive insulation on the legs. Active heating started with rewarming while undergoing bypass and was continued for the remainder of surgery. Patients in the nitroprusside protocol (n = 30) were assigned randomly to either a control group or sodium nitroprusside administration. Pump flow during rewarming was maintained at 2.5 l x m(-2) x min(-1) in the control patients and at 3.0 l x m(-2) x min(-1) in those assigned to sodium nitroprusside. Sodium nitroprusside was titrated to maintain a mean arterial pressure near 60 mm Hg. In all cases, a nasopharyngeal probe evaluated core (trunk and head) temperature and heat content. Peripheral compartment (arm and leg) temperature and heat content were estimated using fourth-order regressions and integration over volume from 18 intramuscular needle thermocouples, nine skin temperatures, and "deep" hand and foot temperature. RESULTS: In patients warmed with forced air, peripheral tissue temperature was higher at the end of warming and remained higher until the end of surgery. The core temperature afterdrop was reduced from 1.2+/-0.2 degrees C to 0.5+/-0.2 degrees C by forced-air warming. The duration of afterdrop also was reduced, from 50+/-11 to 27+/-14 min. In the nitroprusside group, a rectal temperature of 36 degrees C was reached after 30+/-7 min of rewarming. This was only slightly faster than the 40+/-13 min necessary in the control group. The afterdrop was 0.8+/-0.3 degrees C with nitroprusside and lasted 34+/-10 min which was similar to the 1.1+/-0.3 degrees C afterdrop that lasted 44+/-13 min in the control group. CONCLUSIONS: Cutaneous warming reduced the core temperature afterdrop by 60%. However, heat-balance data indicate that this reduction resulted primarily because forced-air heating prevented the typical decrease in body heat content after discontinuation of bypass, rather than by reducing redistribution. Nitroprusside administration slightly increased peripheral tissue temperature and heat content at the end of rewarming. However, the core-to-peripheral temperature gradient was low in both groups. Consequently, there was little redistribution in either case.     

End-point temperature of rewarming after hypothermic cardiopulmonary bypass in pediatric patients

In an attempt to find an adequate end-point rewarming temperature after hypothermic cardiopulmonary bypass (CPB), 50 pediatric patients who underwent cardiac surgery were randomly assigned for the end-point rectal rewarming temperature at either 35.5 (Group 1) or 37.0 degrees C (Group 2). The patients' rectal temperature, with heart rate and blood pressure, was measured 0.5, 1.0, 4.0, 8.0, and 16.0 h after the arrival in the intensive care unit. For all patients, nonpulsatile perfusion with a roller pump and a membrane or bubble oxygenator was used for oxygenation. Age, sex, body surface area, total bypass time, and rewarming time were comparable in both groups. No afterdrop and no statistical differences in the rectal temperatures between the two groups were observed. Also, no statistical differences were observed between the two groups with respect to the heart rate and blood pressure. No shivering was noted in all patients. In conclusion, with the restoration of rectal temperature above 35.5 degrees C at the end of CPB in pediatric patients, the present study found no afterdrop.     

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.     

Effectiveness of forced air warming after pediatric cardiac surgery employing hypothermic circulatory arrest without cardiopulmonary bypass

STUDY OBJECTIVE: To evaluate the effectiveness of forced-air warming compared to radiant warming in pediatric cardiac surgical patients recovering from moderate hypothermia after perfusionless deep hypothermic circulatory arrest. DESIGN: Prospective unblinded study. SETIING: Teaching hospitals. PATIENTS: 24 pediatric cardiac surgical patients. INTERVENTION: Noncyanotic patients undergoing repair of atrial or ventricular septal defects were cooled by topical application of ice and rewarmed initially in the operating room by warm saline lavage of the pleural cavities. On arrival at the intensive care unit (ICU), patients were warmed by forced air (n = 13) or radiant heat (n = 11). The time, heart rate, and blood pressure at each 0.5 degrees C increase in rectal temperature were measured until normothermia (36.5 degrees C) to determine the instantaneous rewarming rate. MEASUREMENTS AND MAIN RESULTS: Baseline characteristics were not different in the two groups. The mean (+/- SD) age was 5.6 +/- 3.4 years, weight was 20 +/- 8 kg, esophageal temperature for circulatory arrest was 25.7 +/- 1.3 degrees C, and duration of circulatory arrest was 25 +/- 11 minutes. The mean core temperature on arrival at the ICU was 29.9 +/- 1.3 degrees C and ranged from 26.1 to 31.5 degrees C. The mean rewarming rate for each 0.5 degrees C was greater (p < 0.05) for forced-air (2.43 +/- 1.14 degrees C/hr) than radiant heat (2.16 +/- 1.02 degrees C/hr). At core temperatures <33 degrees C, the rewarming rate for forced-air was 2.04 +/- 0.84 degrees C/hr and radiant heat was 1.68 +/- 0.84 degrees C/hr (p < 0.05). At core temperatures > or = 33 degrees C, the rewarming rate for forced air was 2.76 +/- 1.20 degrees C/hr and radiant heat was 2.46 +/- 1.08 degrees C/min (p = 0.07). Significant determinants of the rewarming rate in a multivariate regression model were age (p < 0.001), temperature (p < 0.05), time after arrival to the intensive care unit (p < 0.05), pulse pressure (p < 0. 05) and warming device (p < 0.001). The duration of ventilatory support and ICU length of stay was not different in the two groups. CONCLUSIONS: Both forced-air and radiant heat were effective for rewarming moderately hypothermic pediatric patients. When core temperature was less than 33 degrees C, the instantaneous rewarming rate by forced air was 21% faster than by radiant heat.     

Cardiopulmonary resuscitation after near drowning and hypothermia: restoration of spontaneous circulation after vasopressin

Recent animal data have challenged the common clinical practice to avoid vasopressor drugs during hypothermic cardiopulmonary resuscitation (CPR) when core temperature is below 30 degrees C. In this report, we describe the case of a 19-year-old-female patient with prolonged, hypothermic, out-of-hospital cardiopulmonary arrest after near drowning (core temperature, 27 degrees C) in whom cardiocirculatory arrest persisted despite 2 mg of intravenous epinephrine; but, immediate return of spontaneous circulation occurred after a single dose (40 IU) of intravenous vasopressin. The patient was subsequently admitted to a hospital with stable haemodynamics, and was successfully rewarmed with convective rewarming, but died of multiorgan failure 15 h later. To the best of our knowledge, this is the first report about the use of vasopressin during hypothermic CPR in humans. This case report adds to the growing evidence that vasopressors may be useful to restore spontaneous circulation in hypothermic cardiac arrest patients prior to rewarming, thus avoiding prolonged mechanical CPR efforts, or usage of extracorporeal circulation. It may also support previous experience that the combination of both epinephrine and vasopressin may be necessary to achieve the vasopressor response needed for restoration of spontaneous circulation, especially after asphyxial cardiac arrest or during prolonged CPR efforts.     

Efficacy of Two Methods for Reducing Postbypass Afterdrop

Background: Afterdrop, defined as the precipitous reduction in core temperature after cardiopulmonary bypass, results from redistribution of body heat to inadequately warmed peripheral tissues. The authors tested two methods of ameliorating afterdrop: (1) forced-air warming of peripheral tissues and (2) nitroprusside-induced vasodilation.

Methods: Patients were cooled during cardiopulmonary bypass to approximately 32[degrees]C and subsequently rewarmed to a nasopharyngeal temperature near 37[degrees]C and a rectal temperature near 36[degrees]C. Patients in the forced-air protocol (n = 20) were assigned randomly to forced-air warming or passive insulation on the legs. Active heating started with rewarming while undergoing bypass and was continued for the remainder of surgery. Patients in the nitroprusside protocol (n = 30) were assigned randomly to either a control group or sodium nitroprusside administration. Pump flow during rewarming was maintained at 2.5 l [middle dot] m-2 [middle dot] min-1 in the control patients and at 3.0 l [middle dot] m-2 [middle dot] min-1 in those assigned to sodium nitroprusside. Sodium nitroprusside was titrated to maintain a mean arterial pressure near 60 mmHg. In all cases, a nasopharyngeal probe evaluated core (trunk and head) temperature and heat content. Peripheral compartment (arm and leg) temperature and heat content were estimated using fourth-order regressions and integration over volume from 18 intramuscular needle thermocouples, nine skin temperatures, and "deep" hand and foot temperature.

Results: In patients warmed with forced air, peripheral tissue temperature was higher at the end of warming and remained higher until the end of surgery. The core temperature afterdrop was reduced from 1.2 +/- 0.2[degrees]C to 0.5 +/- 0.2[degrees]C by forced-air warming. The duration of afterdrop also was reduced, from 50 +/- 11 to 27 +/- 14 min. In the nitroprusside group, a rectal temperature of 36[degrees]C was reached after 30 +/- 7 min of rewarming. This was only slightly faster than the 40 +/- 13 min necessary in the control group. The afterdrop was 0.8 +/- 0.3[degrees]C with nitroprusside and lasted 34 +/- 10 min which was similar to the 1.1 +/- 0.3[degrees]C afterdrop that lasted 44 +/- 13 min in the control group.     

Effect of temperature and cardiopulmonary bypass on the auditory evoked response

We have recorded auditory evoked potentials before and during cardiopulmonary bypass in 10 adult patients undergoing cardiac surgery under moderate hypothermia to 27-28 degrees C. The immediate effect of bypass was a small decrease in latency and increase in amplitude of the early cortical response. We also studied two adults and two children during profound hypothermia with circulatory arrest during cardiopulmonary bypass. Reduction in core temperature to 25 degrees C resulted in an increase in latency and amplitude of the brain stem responses; below this temperature the amplitude decreased but latency continued to increase until the auditory evoked response trace became completely flat between 21 and 19 degrees C. These changes were reversible on rewarming.      

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.     

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.