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Hypothermia for 24 hours after asphyxic cardiac arrest in piglets provides striatal neuroprotection that is sustained 10 days after rewarming.

The neuroprotective effect of hypothermia instituted after resuscitation from asphyxic cardiac arrest has not been studied in immature brain, particularly in a large animal model with recovery periods greater than 4 d. Moreover, protection from severe hypoxia seen with 3 h of hypothermia was reported to be lost when hypothermic duration was extended to 24 h in unsedated piglets, in contrast to the neuroprotection reported by 72 h of intrauterine head cooling in fetal sheep. Piglets (5-7 postnatal days) were subjected to asphyxic cardiac arrest followed by 24 h of either hypothermia (34 degrees C) or normothermia (38.5-39 degrees C). Comparisons were made with normothermic and hypothermic surgical sham animals without asphyxia. All of these groups were sedated, paralyzed, and mechanically ventilated for the first 24 h to prevent shivering and possible depletion of glucose stores. Hypothermia per se did not cause remarkable structural abnormalities. Ischemic damage was evaluated in putamen at 1 d of recovery without rewarming and at 11 d (10 d +/- SD after rewarming). Ischemic cytopathology affected 60 +/- 12% of neurons in putamen of normothermic animals compared with 9 +/- 6% in hypothermic animals at 1 d of recovery without rewarming. At 11 d of recovery from hypoxia-ischemia, the density of viable neurons (neuron profiles/mm2) in putamen was markedly reduced in normothermic animals (81 +/- 40) compared with hypothermic animals (287 +/- 22), which was the same as in sham normothermic (271 +/- 21), sham hypothermic (288 +/- 46) and naïve animals (307 +/- 51). These data demonstrate that 24 h of hypothermia at 34 degrees C with sedation and muscle relaxation after asphyxic cardiac arrest prevents necrotic striatal neuronal cell death in immature brain before rewarming, and that the effect is sustained at 11 d after injury without deleterious side effects.

Acute Disease↗

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.

Animals↗

Comparison of the effects of sevoflurane and propofol on cooling and rewarming during deliberate mild hypothermia for neurosurgery.

BACKGROUND: Because the time available for cooling and rewarming during deliberate mild hypothermia is limited, studies of the rate of the cooling and rewarming are useful. The decrease in core hypothermia caused by heat redistribution depends on the anaesthetic agent used. We therefore investigated possible differences between sevoflurane and propofol on the decrease and recovery of core temperature during deliberate mild hypothermia for neurosurgery. METHODS: After institutional approval and informed consent, 26 patients were assigned randomly to maintenance of anaesthesia with propofol or sevoflurane. Patients in the propofol group (n=13) received propofol induction followed by a continuous infusion of propofol 3-5 mg kg(-1) h(-1). Patients in the sevoflurane group (n=13) received propofol induction followed by sevoflurane 1-2%. Nitrous oxide and fentanyl were also used for anaesthetic maintenance. After induction of anaesthesia, patients were cooled and tympanic membrane temperature was maintained at 34.5 degrees C. After surgery, patients were actively rewarmed. RESULTS: There was no difference in the rate of decrease and recovery of core temperature between the groups. There was also no difference in skin surface temperature gradient (forearm to fingertip), heart rate and mean arterial blood pressure between the groups. CONCLUSIONS: Sevoflurane-based anaesthesia did not affect cooling and rewarming for deliberate mild hypothermia compared with propofol-based anaesthesia.

Adult↗

Heparinless, oxygenatorless perfusion rewarming following surface-induced deep hypothermia for open-heart surgery.

To facilitate perfusion rewarming without the use of total body heparinization or an oxygenator following open-heart correction with surface hypothermia, we divised a pump circuit. The circuit, totally primed with 100 c.c. of saline, consists of polyurethane-polyvinyl-graphite (PPG) coated Tygon tubes (with one end tapered by heat treatment) and a copper-coil heat exchanger. A roller pump was used to achieve partial bypass from the left atrium to the ascending aorta with flow rates up to 70 c.c. per kilogram per minute. Experiments in dogs resulted in rapid rewarming, immediate return of cardiac function, and hematologic alterations similar to those noted during surface rewarming. The safety of the method was also demonstrated. Prothrombin time, partial thromboplastin time, and platelet values returned to control levels upon rewarming, and no thromboemboli or bleeding problems were noted. Six clinical experiences were accumulated. Details of the method, hematologic and blood chemical analyses in dogs, and the first clinical trial in a 3-month-old infant with transposition of the great vessels are reported.

Animals↗

Increased resistance of neutrophils to deformation upon cooling and rate of recovery on rewarming.

Increase in the resistance to deformation of neutrophils upon exposure to the cold may impair their passage through microvessels. However, the potential for such rheological changes to cause prolonged microvascular obstruction in cooled tissue will depend on whether and at what rate the neutrophils recover on rewarming. We tested the ability of neutrophils to pass through micropore filters, and found that neutrophils cooled to 10 degrees C for 10-20 minutes could block either 5 microm or 8 microm pore filters. On return to 37 degrees C, flow resistance remained impaired briefly but recovered over about 5 minutes. The kinetics of changes in flow resistance in the cold and on rewarming were linked to kinetics of actin polymerisation during these periods. However, they were not closely linked to distortion of cell shape in the cold, which recovered only slowly with rewarming. The results suggest that while rigid neutrophils might occlude capillaries in cold tissue, mechanical obstruction should not be long-lived on rewarming. Moreover, rigid neutrophils washed out of cold tissue should experience only temporary mechanical trapping in remote tissues.

Actins↗

Loss of factor VIII and von Willebrand factor activities during cold storage of whole blood is reversed by rewarming.

Documentation of preanalytical conditions that could result in inaccurate results and misdiagnoses of patients is important. It has recently been reported that a significant loss of factor VIII (FVIII) and von Willebrand factor (vWF) activity occurs when citrated whole blood is stored on ice. We tested the hypothesis that the cold-dependent loss of FVIII and vWF activity is due to the formation of cryoprecipitate and is reversed by rewarming the citrated whole blood before centrifugation and removal of plasma. We collected venous blood from 10 healthy subjects into 3.2% sodium citrate glass tubes. One tube was immediately centrifuged and the plasma was stored at -20 degrees C. Following storage in an ice bath (4 degrees C) for 3.5 hours, 1 tube was immediately centrifuged and processed while the second tube was placed in a 37 degrees C water bath for 5 minutes then centrifuged and processed. Subsequently, plasma samples were quickly thawed at 37 degrees C and the following tests were performed: prothrombin time (PT), partial thrombin time (aPTT), FVIII activity, vWF antigen (vWF:Ag), and vWF activity (vWF:Act). Means for each analyte from the 2 tubes stored at 4 degrees C for 3.5 hours with or without rewarming were compared to baseline tube using the Student t test. Compared to the baseline tube results, PT and aPTT showed no significant changes in either of the tubes stored at 4 degrees C for 3.5 hours. However, FVIII, vWF:Ag, and vWF:Act were significantly lower in the tubes stored at 4 degrees C for 3.5 hours, but no differences were detected between baseline and rewarmed tube results. In conclusion, prolonged storage of citrated whole blood at 4 degrees C causes a clinically significant reduction of FVIII and vWF activities. The losses are completely reversed by rewarming the tube prior to processing. This is consistent with a reversible cryoprecipitation of vWF and FVIII rather than a cold-activated enzymatic degradation.

Blood Coagulation Tests↗

Hypothermia and rewarming after cardiac operation.

Those caring for patients who undergo cardiac surgery share a dilemma. Complications associated with hypothermia encourage the care giver to rewarm the patient quickly, but complications associated with rapid temperature changes and hyperthermia can threaten the patient's hemodynamic stability. What are adequate rewarming measures, when to terminate active rewarming measures to avoid hyperthermia, and what is the optimal rate of rewarming are all unanswered questions. Continued nursing research will expand the science of nursing and provide care givers with knowledge for expert care. As the turn of the century approaches and surgical techniques advance, high-risk patients who undergo reoperation and multi-valve cardiac surgery require expert nursing care.

Body Temperature↗

Membrane phospholipid metabolism of rat myocardial cells during hypothermia and rewarming.

The phospholipid bilayer of the plasma membrane plays an important role in forming a functional barrier against leakage of ions and other cell constituents. We have examined the effect of an exogenously added phospholipase C (PLC) on phospholipid degradation in isolated rat myocardial cells subjected to hypothermia (5 degrees C) and hypothermia followed by rewarming to 37 degrees C. The activity of PLC was measured as glycerol output to the incubation medium since the combined action of PLC and endogenous lipases will result in glycerol production. Addition of PLC resulted in a significantly higher output of glycerol in rewarmed myocytes than in myocytes kept constantly at 5 degrees C and 37 degrees C. Rewarmed cells also showed the highest leakage of lactate dehydrogenase (LDH), but there was no additional effect of PLC on LDH leakage. Normal levels of cellular ATP were maintained in all myocyte groups. These results show that rewarming from hypothermia may cause structural derangements in the phospholipid bilayer of the sarcolemma which in turn could favor attack by endogenous phospholipases.

Animals↗

[Rewarming from moderate to deep hypothermia: plasma catecholamine content, metabolism and circulatory function. 2 case reports].

Two patients were rewarmed from hypothermia (esophageal temperature 27.2 degrees C, 27.5 degrees C respectively). The first case suffered from head-injury after alcohol ingestion and was deeply comatose. A metabolic or cardiovascular regulatory response to cold was not observed in this patient. The relationship between esophageal temperature and whole-body-oxygen consumption was quantified with a Q10 of 2.75 during rewarming (27.2-37.2 degrees C). His epinephrine levels were greatly elevated to 1,000 pg/ml whereas norepinephrine levels were only moderately increased to 250 pg/ml. Premature ventricular contractions (PVCs) during intubation or from the pulmonary artery catheter were not observed. The second patient was a 87 year old man with accidental hypothermia. He exhibited shivering at an esophageal temperature of 27.5 degrees C which indicated persistent thermoregulation. In contrast to the first case his norepinephrine levels were elevated to 1,500 pg/ml and his epinephrine levels only to 450 pg/ml. After onset of surface rewarming an additional increase in norepinephrine levels was observed and an increasing rate of PVC's (15/min) recorded, which ceased when temperature returned to normal. Our observations indicate that part of the cardiac complications during rewarming from deep hypothermia may result from thermoregulation and additional catecholamine liberation.

Adult↗

Shivering and rewarming after cardiac surgery: comparison of ventilator circuits with humidifier and heated wires to heat and moisture exchangers.

BACKGROUND: Detrimental physiologic effects of shivering in the cardiac surgery patient have been well documented. Rewarming techniques have been compared, with noted differences in the incidence of shivering. Ventilator circuits have not been examined independently from other rewarming variables. OBJECTIVE: To compare heated wire humidification circuits with heat and moisture exchanger circuits on the incidence of shivering and speed and pattern of rewarming in mechanically ventilated patients. METHODS: A prospective, descriptive, correlational study was done on 140 adult cardiac surgery patients in a university teaching medical center. All subjects underwent cardiac surgical procedures with hypothermic cardiopulmonary bypass. Subjects were randomized to humidified, heated wire circuits (n = 70) or heat and moisture exchanger circuits (n = 70). Heated water blankets were used on all patients. RESULTS: Mean intensive care unit admission temperature was 35.28 degrees C. No statistical differences were found in preoperative, demographic, or operative course data between treatment and control groups. Shivering was more common in the heat and moisture exchanger group than in the heated wire group. In our analysis, the only variable associated with shivering was the type of ventilator circuit. Patients using heated wire systems rewarmed more rapidly and had significantly higher temperatures than did patients using heat and moisture exchangers. CONCLUSION: These data suggest that use of heated wire humidified ventilator circuits with heated water blankets in adult cardiac surgery patients significantly reduces the incidence of shivering and results in a more rapid return to normothermia.

Aged↗

Induced hypothermia and rewarming after hemorrhagic shock.

BACKGROUND: Recent patient and animal studies have shown protective effects of hypothermia (HT) in traumatic brain injury and hemorrhagic shock. We have demonstrated a reduced stress level and a lack of additive hemodynamic effects of HT. The present work was undertaken to evaluate whether these effects persist during and after rewarming. METHODS: Pigs were quickly exsanguinated of 40% of their individually calculated blood volume and randomized to HT (32.5 degrees C) or normothermia (controls). After 30 min of HT, rewarming to baseline temperature was initiated. All animals were followed for 7 h. Thrombolelastography was used to evaluate blood coagulation. RESULTS: HT did not aggravate the hemodynamic signs of hemorrhagic shock. HT decreased the oxygen uptake, however, which reduced the oxygen extraction ratio to the prehemorrhage level (P < 0.05). Serum levels of potassium were transiently stabilized by cooling. Coagulation was slower, but blood clot strength was normal. HT also delayed fibrinolysis (P < 0.05). Rewarming reversed all physiological changes induced by HT including those involving the coagulation system. CONCLUSIONS: HT produced few hemodynamic effects in the presence of hemorrhagic shock, but created a surplus of oxygen in the core circulation. Blood clotting was delayed by HT.

Acidosis↗

[Severe accidental hypothermia with cardiac arrest and extracorporeal rewarming. A case report of a 2-year-old child].

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.

Accidents↗

Effects on dogs of surface-induced hypothermia and rewarming on the right heart function and pulmonary circulation.

Hypothermia is commonly found in accidents on land and at sea, yet its pulmonary circulatory effects have not been studied before. To study the effects of hypothermia on the right heart function and pulmonary circulation, cardiac catheterization was carried out on nine anaesthetized beagle dogs. The dogs were cooled between ice bags until the temperature in the pulmonary artery was 25 degrees C and then rewarmed using a heating box especially constructed for this purpose. Heart rate decreased significantly (P < 0.01) during cooling. Cardiac output also diminished mainly because of decreased heart rate. Total pulmonary resistance increased in the cold (P < 0.05) and returned to the initial level during rewarming. The peak rate of increase in pressure (dP/dtmax) of the right ventricular pressure curve did not show any significant change. Retardation in relaxation in hypothermia was indicated by an increase (P < 0.01) in the peak negative dP/dt of the right ventricular pressure curve. According to our results, the contraction rate did not change, but the relaxation rate decreased significantly during cooling. No signs of heart failure were observed and all parameters returned to normal during rewarming. In conclusion, right ventricular function was not compromised even during deep hypothermia.

Animals↗

Deep hypothermic circulatory arrest: II. Changes in electroencephalogram and evoked potentials during rewarming.

BACKGROUND: Electrophysiologic studies during rewarming after deep hypothermic circulatory arrest probe the state of the brain during this critical period and may provide insight into the neurological effects of circulatory arrest and the neurologic outcome. METHODS: Electroencephalogram (EEG) and evoked potentials were monitored during rewarming in 109 patients undergoing aortic surgery with hypothermic circulatory arrest. RESULTS: The sequence of neurophysiologic events during rewarming did not mirror the events during cooling. The evoked potentials recovered first followed by EEG burst-suppression and then continuous EEG. The time to recovery of the evoked potentials N20-P22 complex was significantly correlated with the time of circulatory arrest even in patients without postoperative neurologic deficits (r = 0.37, (p = 0.002). The nasopharyngeal temperatures at which continuous EEG activity and the N20-P22 complex returned were strongly correlated (r = 0.44, p = 0.0002; r = 0.41, p = 0.00003) with postoperative neurologic impairment. Specifically, the relative risk for postoperative neurologic impairment increased by a factor of 1.56 (95% CI 1.1 to 2.2) for every degree increase in temperature at which the EEG first became continuous. CONCLUSIONS: No trend toward shortened recovery times or improved neurologic outcome was noted with lower temperatures at circulatory arrest, indicating that the process of cooling to electrocerebral silence produced a relatively uniform degree of cerebral protection, independent of the actual nasopharyngeal temperature.

Aged↗

Topical head cooling during rewarming after experimental hypothermic circulatory arrest.

BACKGROUND: The aim of this study was to evaluate the potential neuroprotective effect of topical head cooling during the first 2 postoperative hours after experimental hypothermic circulatory arrest. METHODS: Twenty pigs underwent a 75-minute period of hypothermic circulatory arrest and were randomly assigned to rewarming to 37 degrees C or to undergo topical cooling of the head for 2 hours from the start of rewarming followed by a period of external rewarming to 37 degrees C. RESULTS: The 7-day survival rate was 70% in the control group and 60% in the topical head cooling group. Despite brain tissue oxygenation, intracranial pressures, mixed oxygen venous saturation, oxygen consumption, and extraction tended to be favorable in the topical head cooling group as a clear effect of mild hypothermia. The latter group had significantly higher postoperative brain lactate and pyruvate ratios, and lactate and glucose ratios. Furthermore, the topical head cooling group had worse fluid balance throughout the postoperative period. Brain histopathologic scores were comparable with the study groups, but among 7-days survivors these scores tended to be worse in the topical head cooling group. CONCLUSIONS: Topical cooling of the head during the first 2 postoperative hours after experimental hypothermic circulatory arrest does not appear to provide any neuroprotective effect.

Animals↗

Rewarming from accidental hypothermia by extracorporeal circulation. A retrospective study.

OBJECTIVE: Twenty-six patients with accidental hypothermia combined with circulatory arrest or severe circulatory failure were rewarmed to normothermia by use of extracorporeal circulation (ECC). The aim of the present study was to evaluate our results. PATIENTS AND METHODS: The treatment of six female and 20 male patients (median age: 26.7 years; range 1.9--76.3 years) rewarmed in the period 1987--2000 was evaluated retrospectively. Hypothermia was related to immersion/submersion in cold water (n=17), avalanche (n=1) or prolonged exposure to cold surroundings (n=8). Prior to admission, the trachea was intubated and cardiopulmonary resuscitation (CPR) initiated in all patients with cardiorespiratory arrest (n=22), whereas in those with respiration/circulation (n=4) only oxygen therapy via a face mask was given. RESULTS: Nineteen of the 26 patients were weaned off ECC whereas seven died because of refractory respiratory and/or cardiac failure. Eight of the 19 successfully weaned patients were discharged from hospital after a median of 10 days. One patient died 3 days after circulatory arrest (complete atrioventricular block) resulting in severe cerebral injury. The remaining ten patients died following 1--2 days due to severe hypoxic brain injury (n=5), cerebral bleeding (n=1) or irreversible cardiopulmonary insufficiency (n=4). Based on the reports from the site of accident, two groups of patients were identified: the asphyxia group (n=15) (submersions (n=14); avalanche accident (n=1)) and the non-asphyxia group (n=11) (patients immersed or exposed to cold environment). Seven intact survivors discharged from hospital belonged to the non-asphyxia group whereas one with a severe neurological deficit was identified within the asphyxia group. CONCLUSION: Patients with non-asphyxiated deep accidental hypothermia have a reasonable prognosis and should be rewarmed before further therapeutic decisions are made. In contrast, drowned patients with secondary hypothermia have a very poor prognosis. The treatment protocol under such conditions should be the subject for further discussion.

Adult↗

Deep hypothermia and rewarming alters glutamate levels and glycogen content in cultured astrocytes.

BACKGROUND: Deep hypothermia has been associated with an increased incidence of postoperative neurologic dysfunction after cardiac surgery in children. Recent studies suggest an excitotoxic mechanism involving overstimulation of glutamate receptors. Extracellular glutamate uptake occurs primarily by astrocytes. Astrocytes also store glycogen, which may be used to sustain the energy-consuming glutamate uptake. Extracellular glutamate and glycogen content were studied during temperature changes mimicking cardiopulmonary bypass in vivo. METHODS: Primary cultures of cerebral cortical astrocytes were used in a specially designed incubator allowing continuous changes of temperature and ambient gas concentrations. The sequence of events was as follows: normothermia, rapid cooling (2.8 degrees C/min) followed by 60 min of deep hypothermia (15 degrees C), followed by rewarming (3.0 degrees C/min) and subsequent 5 h of mild hyperthermia (38.5 degrees C). Two different conditions of oxygenation were studied: (1) normoxia (25% O2, 70% N2, 5% CO2); or (2) hyperoxia (95% O2, 5% CO2). The extracellular glutamate concentrations and intracellular glycogen levels were measured at nine time points. RESULTS: One hundred sixty-two cultures were studied in four independent experiments. The extracellular concentration of glutamate in the normoxic group increased significantly from 35+/-10 nM/mg protein at baseline up to 100+/-15 nM/mg protein at the end of 5 h of mild hyperthermia (P < 0.05). In contrast, extracellular glutamate levels did not vary from control in the hyperoxic group. Glycogen levels decreased significantly from 260+/-85 nM/mg protein at baseline to < 25+/-5 nM/mg protein at the end of 5 h in the normoxic group (P < 0.05) but returned to control levels after rewarming in the hyperoxic group. No morphologic changes were observed in either group. CONCLUSION: The extracellular concentration of glutamate increases, whereas the intracellular glycogen content decreases when astrocytes are exposed to a sequence of deep hypothermia and rewarming. This effect of hypothermia is prevented when astrocytes are exposed to hyperoxic conditions.

Algorithms↗

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.

Body Temperature↗