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PubMed1991

Peripheral tissue energy metabolism during recovery from hypothermia after cardiopulmonary bypass: effect of amino-acid infusions.

We studied the effects of amino-acid administration on the leg exchange of energy substrates and amino-acids during recovery from hypothermia after open heart surgery. Glucose (G, n = 5), glucose and conventional amino-acids (CA, n = 5) or glucose and branched chain amino-acids (BC, n = 5) were infused during recovery from hypothermia after open heart surgery. The leg exchange of energy substrates and amino-acids were measured after arrival at the intensive care unit, after rewarming, and 2h and 4h after rewarming during increasing amino-acid intake. Despite a normal stress response to surgery, reflected by increased energy expenditure and increased concentrations of insulin and catabolic hormones, amino-acids had no effect on the leg exchange of branched chain amino-acids, glutamine, alanine and energy substrates. This suggests that the transport of amino-acids and energy substrates into the cell are impaired after hypothermic cardiopulmonary bypass and intracellular substrates are utilised for the increased demand for energy during rewarming.

Journal Article↗
PubMed1985

Glucagon secretion in the hibernating edible dormouse (Glis glis).

Plasma glucose and glucagon concentrations were measured in edible dormice during the bout of hibernation, arousal and active periods. During lethargy, plasma glucose and glucagon were low, compared to active values and did not fluctuate throughout the phase. During rewarming, plasma glucose regularly increased from 17 degrees to 37 degrees C while plasma glucagon rose after the 17 degrees C stage and reached the higher values at 26 degrees C, then slightly decreased at 37 degrees C. During arousal, plasma levels of free amino acids progressively increased. The effect of temperature and secretagogue (glucose and arginine) on glucagon secretion was studied using perfused pancreas from hibernating edible dormouse. In vitro rewarming of pancreas induced an increase in glucagon secretion. Glucagon secretion was regulated by glucose (inhibitory effect) and by arginine (stimulating effect) up to 25 degrees C. The effect of temperature and glucagon on oxygen uptake of hibernating edible dormouse brown fat was studied using an in vitro technique. Rewarming strongly increased oxygen consumption from 10 to 37 degrees C. Glucagon enhanced oxygen consumption up to 20 degrees C.

Adipose Tissue, Brown↗
PubMed1982

Brain norepinephrine and serotonin in the golden hamster during heat and cold acclimation and hypothermia.

1. Norepinephrine (NE) and serotonin (5-HT) were simultaneously assessed in 4 discrete regions of the brain of the golden hamster. 2. Hypothalamic concentrations of both these amines are reported for the following groups: (1) normothermic controls; (2) heat acclimated; (3) cold acclimated; (4) helium-cold hypothermic; (5) rewarming; and (6) rewarmed. 3. Heat acclimated animals demonstrated approximately 35 and 25% decreases from control values for NE and 5-HT, respectively. Cold acclimated hamsters were not significantly different from controls. Helium-cold hypothermia resulted in approximately a 30 and 20% decrease in NE and 5-HT, respectively, with the latter returning to control values during rewarming. 4. The data provide indirect evidence for the involvement of NE in central pathways involving heat gain and 5-HT in pathways involving heat loss, and are discussed in terms of FELBERG & MYER'S (1964 J. Physiol., Lond. 173. 226-236) bioamine theory of thermoregulation.

Acclimatization↗
PubMed1991

Postbypass hypothermia and its relationship to the energy balance of cardiopulmonary bypass.

Using a newly developed computerized intraoperative data acquisition system, the apparent adequacy of rewarming and its relation to the energy exchange between the patient and the bypass system was investigated. Retrospective analysis of comparable patients identified two groups that had, at the end of surgery, either a nasopharyngeal temperature (NPT) of 36 degrees C or more ("warm" group, n = 19), or a NPT of 35 degrees C or less ("cold" group, n = 19). Temperatures from the nasopharynx, thenar eminence skin, and bypass pump arterial and venous lines were continually recorded and sent to the computer data base together with the pump flow rate. There were no significant differences between the groups regarding time on perfusion, time taken to cool, time of hypothermia, or the time interval from end of perfusion to the end of surgery. However, rewarming time was greater in the warm group (P less than 0.01). The cold group were subjected to more profound hypothermia (P less than 0.001), and had lower NPTs and skin temperatures at the end of bypass (P less than 0.0001 and P less than 0.01, respectively). However, the difference between NPT and thenar skin temperature in each group at either the end of bypass or the end of surgery was the same. The net energy exchange between patient and pump was significantly different (mean in warm, 130 kJ [SD = 530]; in cold, -389 kJ [SD = 427]; P less than 0.003). In conclusion, the adequacy of rewarming can be expressed in terms of the energy exchanged in the bypass system, and cannot be assessed by the nasopharynx:skin temperature gradient.

Anesthesia, Intravenous↗
PubMed2005

Specific bypass conditions determine safe minimum flow rate.

BACKGROUND: The purpose of this study is to define a safe minimum flow rate for specific bypass conditions using continuous monitoring with near-infrared spectroscopy and direct observation of the cerebral microcirculation. METHODS: Two series of experiments (n = 72 in each) were conducted in which piglets were cooled to a temperature of 15 degrees, 25 degrees, or 34 degrees C on cardiopulmonary bypass with hematocrit 20% or 30%, pH-stat management in all, followed by 1 or 2 hours of reduced flow (10, 25, or 50 mL.kg(-1).min(-1)). Animals in series one had a cranial window placed over the parietal cortex to evaluate the microcirculation with intravital microscopy. Plasma was labeled with fluorescein-isothiocyanate-dextran for assessment of functional capillary density (FCD) and microvascular diameter. In series two, near-infrared spectroscopy was utilized to detect tissue oxygenation index (TOI). Outcome measures included histologic and neurologic injury scores. RESULTS: The TOI during low flow and FCD during rewarming and after weaning from cardiopulmonary bypass were associated with neurologic injury. Failure of FCD to return to baseline during rewarming predicted worse functional and histologic outcome (p < 0.001). Regression analysis indicated that temperature and low-flow rate were multivariable predictors of TOI and FCD during rewarming (p < 0.001). CONCLUSIONS: Tissue oxygen index derived from near-infrared spectroscopy is a useful real-time monitor for detecting inadequate cerebral perfusion during cardiopulmonary bypass. Minimal safe pump flow rate varies according to the conditions of bypass: using pH stat management and with an hematocrit of either 20% or 30%, a flow rate as low as 10 mL.kg(-1).min(-1) is safe for as long as 2 hours at a temperature of 15 degrees C. However, under the same conditions at 34 degrees C, a flow rate of 10 mL.kg(-1).min(-1) is very likely to be associated with neurologic injury.

Animals↗
PubMed2006

Gene expression and activity of urea cycle enzymes of rat hepatocytes cold stored up to 120h in University of Wisconsin solution.

Urea cycle (UC) is the main pathway of ammonium removal. A deficiency in any of the five classical enzymes of the pathway causes a urea cycle disorder. Hepatocellular transplantation is one of the techniques applicable to treat this disorder. In the present work, we investigated the activities and the relative expression levels of two of the UC enzymes: Carbamyl phosphate synthetase I (CPSI) and ornithine transcarbamylase (OTC), in isolated hepatocytes preserved up to 120 h in University of Wisconsin (UW) solution at 0 degrees C, and during the rewarming of these suspensions. During preservation, CPSI showed differences in mRNA levels respect to time 0, while ornithine transcarbamylase remained unchanged. At the end of the rewarming, CPSI showed values of enzymatic activity and relative mRNA level comparable with the control, meanwhile, there was an increment in OTC activity. In line with these results, we found that hepatocytes cold preserved up to 120h in UW solution maintained their ability to remove an ammonium load comparable to freshly isolated hepatocytes. These data indicated that our preservation conditions up to 120h in UW solution followed by rewarming, preserves UC enzymes at levels similar to freshly isolated hepatocytes, allowing the use of these cells in bioartificial liver devices or hepatocellular transplantation.

Adenosine↗
PubMed2005

In vivo effects of hypothermia on the microcirculation during extracorporeal circulation.

OBJECTIVE: Induced hypothermia has been shown to be protective during cardiac surgery, but also in traumatic, ischemic, burn, and neurological injury. In previous in vivo animal experiments, we documented increased leukocyte/endothelial (L/E) cell interaction following normothermic extracorporeal blood circulation (ECC). This study was carried out to investigate whether reduced core temperature during ECC affects the damage to the microcirculation as evidenced by leukocyte adherence and edema formation. METHODS: Intravital fluorescence microscopy was used on the dorsal skinfold chamber preparation in Syrian golden hamsters. ECC was introduced via a micro-rollerpump (1 ml/min) and a 60 cm silicon tube (1mm inner diameter) shunted between the carotid artery and the jugular vein after application of 300IE Heparin/kg per body weight. Experiments were performed in chronically instrumented, awake animals (age 10-14 weeks, weight 65-75 g). Animals of the experimental group were cooled to 18 degrees C body temperature while ECC, followed by a rewarming period (n=7), controls experienced ECC under normothermia (37 degrees C, n=7). RESULTS: 30 min ECC at 18 degrees C resulted in a decrease of rolling and adherent leucocytes (stickers) in postcapillary venules after 1, 4 and 8h compared with the control group (119+/-46 vs. 274+/-113 n/mm2, P<0.05, mean+/-SD; n=7 in each group). Functional capillary density was significantly reduced during hypothermia (80+/-16 vs. 148+/-16 cm/cm2, P<0.05), but restored after rewarming. In contrast, edema formation was markedly increased during hypothermia. CONCLUSIONS: Hypothermia during ECC significantly reduced L/E cell interaction in the early post-ECC period. Hypothermia markedly reduced microvascular perfusion, but was completely restored upon rewarming. Despite a reduced number of adherent leukocytes, no protection of endothelial barrier function was seen as a consequence of induced hypothermia.

Animals↗
PubMed1999

Cardiopulmonary bypass and oxygen consumption: oxygen delivery and hemodynamics.

BACKGROUND: This study was undertaken to investigate the relations between whole body oxygen consumption (VO2), oxygen delivery (DO2), and hemodynamic variables during cardiopulmonary bypass. METHODS: One hundred one patients were studied during cooling, hypothermia, and rewarming. Oxygen consumption, DO2, hemodynamics, and DO2crit were measured at these times. RESULTS: There was a direct linear relation between DO2 and VO2 during all three times. No relation between VO2 and hemodynamics was detected during cooling; during hypothermia, an inverse linear relation with peripheral arterial resistance was found. Finally, during rewarming, there was a direct relation with pump flow rate, and an inverse relation with arterial pressure and arterial resistance. The same relations among the variables were found at delivery levels above or below DO2crit. CONCLUSIONS: During cardiopulmonary bypass there is a direct linear relation between DO2 and VO2; the relations with hemodynamic variables depend on the phases of cardiopulmonary bypass. This suggests that increasing delivery levels may recruit and perfuse more vascular beds, and higher delivery levels are advisable during perfusion. During rewarming and hypothermia, lower arterial resistances are also desirable to optimize VO2.

Aged↗
PubMed2003

Vitrification of ECV304 cell suspensions using solutions containing propane-1,2-diol and trehalose.

In this paper, we report on the suitability of solutions containing propane-1,2-diol (propylene glycol, PD), sugars, and salts for the vitrification of the human cell line, ECV304. Cooling (at 10 degrees C/min) and rewarming (at 80 degrees C/min) were at rates that are practicable for the tissues to be studied later. Under these conditions, 45% PD in phosphate-buffered saline (PBS) sometimes froze during cooling and always devitrified during rewarming but both events were avoided if the PBS salts were replaced by an osmotically equivalent concentration of sucrose or trehalose. The effect of such solutions on cells was evaluated using a cell culture assay in which the number of cells recovered after 3 days of culture was divided by the number cells plated, giving a cell multiplication factor or CMF. In the absence of PD the cells tolerated a low-salt concentration in solutions that were made isotonic with sugars, but they recovered poorly when 45% PD was also present. Trehalose gave significantly better recovery than sucrose. When 39% PD and 15% trehalose were included in a low-salt vehicle solution (LSV) that contained approximately 5% of the total salt concentration of PBS (this solution was designated LSV/39/15), the cells exhibited approximately 40% of untreated control CMF following exposure for 9min. LSV/39/15 vitrifies with a glass transition temperature of -102 degrees C, does not devitrify when warmed at 80 degrees C/min, and has suitable dielectric properties for uniform and rapid dielectric heating. An improved method for adding and removing LSV/39/15 gave a CMF of approximately 55% of untreated controls. Using this method, 1.0ml suspensions of ECV304 cells was cooled to, and stored briefly at, -120 degrees C and then rewarmed by immersion in a 37 degrees C water bath ( approximately 75 degrees C/min). The CMF of the cooled samples was similar to that of the exposure-only controls, approximately 50% of the untreated control CMF in both cases.

Calorimetry, Differential Scanning↗
PubMed1999

Regional blood flow response to hypothermia in premature, newborn, and neonatal piglets.

BACKGROUND/PURPOSE: Hypothermia (HT) remains a significant stress to the newborn and has been implicated in the pathogenesis of necrotizing enterocolitis (NEC). The authors assessed the effect of transient HT (32 degrees C) on regional organ blood flow in anesthetized piglets at age 7 to 10 days preterm (PREM), 1 to 2 days (NB), and 1 to 2 weeks (NEO). METHODS: Radiolabeled microspheres were used to determine organ blood flows (mL/min/g) at baseline, 15, and 60 minutes after HT and 60 minutes after rewarming to baseline core temperature. RESULTS: Heart rate and cardiac output decreased significantly in all groups. Cardiac flow decreased significantly in the NEO group, and central nervous system (CNS) flow decreased significantly in the NB and NEO groups. Both returned to baseline levels after rewarming. The PREM group experienced decreased cardiac, CNS, and intestinal blood flows but not to significant levels. NB and NEO intestinal blood flow showed significant decreases, which remained so after rewarming (a response not seen in hypoxia or hypovolemia). Cardiac output did not return to baseline levels in any group. CONCLUSIONS: HT causes derangements in organ blood flows that differ from other deleterious stimuli such as hypoxia and hypovolemia. The prolonged intestinal ischemia supports HT as a factor in the development of NEC. This delay may offer opportunity to intervene in an attempt to lessen ischemia-reperfusion injury.

Age Factors↗
PubMed1995

Metabolic correlates of neurologic and behavioral injury after prolonged hypothermic circulatory arrest.

Thirty-two inbred weanling puppies were divided into four groups to study the effect on cerebral blood flow and metabolism of different hypothermic strategies for cerebral protection similar to those used during cardiac operations in infancy. All animals were cooled to 18 degrees C. The animals in the hypothermic control group were immediately rewarmed. One group underwent 30 minutes of hypothermic circulatory arrest at 18 degrees C; another group had 90 minutes of hypothermic circulatory arrest at 18 degrees C, and the final group had low-flow cardiopulmonary bypass (25 ml/kg per minute) at 18 degrees C for 90 minutes. All animals had preoperative and postoperative neurologic and behavioral evaluation and extensive intraoperative monitoring of cerebral blood flow, cerebral vascular resistance, and oxygen and glucose uptake and metabolism: quantitative electroencephalography was also monitored before, during and after operation, but those results are reported separately. Two animals in the 90-minute arrest group died, and all the survivors showed evidence of clinical, neurologic, and behavioral impairment on postoperative day 1, with residual abnormalities in all but one animal on day 6. In contrast, the survivors in all the other groups showed no significant clinical or behavioral sequelae. Cerebral metabolism was reduced only to 32% to 40% of baseline values at 18 degrees C in all groups, although systemic metabolism was only 16% of normal. Cerebral metabolism returned promptly to baseline in all groups during rewarming and remained at baseline levels throughout the 8 hours of follow-up. Cerebral blood flow showed marked hyperemia in the hypothermic arrest groups during rewarming but then significant reductions below baseline values in all groups except the controls at 2 and 4 hours after the operation, lasting as late as 8 hours after the operation in the 90-minute arrest group. Cerebral vascular resistance showed increases in all groups at 2 and 4 hours after the operation, which persisted in the 90-minute arrest group at 8 hours. Cerebral metabolism was maintained at baseline levels despite postoperative decreases in cerebral blood flow and increases in cerebral vascular resistance by increases in oxygen and glucose extraction. The result was very low sagittal sinus oxygen saturations in all groups, most marked in the 90-minute arrest groups, which had a saturation of only 24% 8 hours after the operation. Our data show a severe, prolonged disturbance in cerebral blood flow and cerebral vascular resistance after 90 minutes of hypothermic circulatory arrest at 18 degrees C, which correlates with clinical evidence of cerebral injury.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1997

Neurophysiologic monitoring to assure delivery of retrograde cerebral perfusion.

BACKGROUND: Patients undergoing complex aortic procedures performed with deep hypothermia and circulatory arrest have a significant risk of an adverse neurologic event when the arrest period is prolonged. Retrograde cerebral perfusion appears to improve cerebral protection, although collapsed cortical veins or functional jugular venous valves may restrict flow at the frequently recommended maximum pressure of 25 mm Hg. Therefore, the purpose of this study was to demonstrate the benefit of multimodality neurophysiologic monitoring in assuring delivery of retrograde cerebral perfusion. METHODS: Electroencephalography, cerebral blood flow velocity, and regional cerebral venous oxygen saturation were used to quantify the intraoperative neurophysiologic changes accompanying retrograde cerebral perfusion. The magnitude of changes was compared with those previously observed during arrest without retrograde cerebral perfusion. RESULTS: Thirty patients underwent complex aortic procedures necessitating circulatory arrest, 22 with retrograde cerebral perfusion. The mean retrograde perfusion pressure of 40 mm Hg (30 to 49 mm Hg, 95% confidence interval) and flow rate of 1.2 L/min (0.9 to 1.6 L/min) necessary to achieve documented retrograde cerebral perfusion was much higher than previously recommended. During both retrograde cerebral perfusion and rewarming, cerebral oximetric monitoring guided adjustments in perfusion parameters to limit the rate of desaturation to 0.4% per minute (0.3% to 0.6%). With retrograde cerebral perfusion there was a rapid (1) recovery of electroencephalographic activity during rewarming (21 minutes [range 16 to 26 minutes]) and (2) return of consciousness after the operation (81% [58% to 95%, 95% confidence interval] awake by 12 hours). There was no transcranial Doppler evidence of cerebral edema with retrograde cerebral perfusion. Two neurologic complications occurred in the 22 patients managed with retrograde cerebral perfusion and one in the eight patients managed with arrest only. CONCLUSIONS: Multimodality neurologic monitoring assured optimal brain cooling and bihemispheric delivery of retrograde cerebral perfusion. Necessary retrograde pressure and flow were often higher than values previously reported. Avoidance of profound cerebral venous oxygen desaturation during retrograde cerebral perfusion and rewarming was associated with rapid recovery of neurologic function.

Adult↗
PubMed1990

Treatment of moderate-to-severe hypothermia in an urban setting.

STUDY OBJECTIVES: To study the treatment of moderate-to-severe hypothermia using a combination of core rewarming techniques. DESIGN: A prospective study. SETTING: The emergency department of an urban, community hospital. TYPE OF PATIENTS: Sixteen patients who presented with accidental hypothermia with a core temperature of less than 32 C. INTERVENTIONS: All patients were treated with warmed IV fluids either through central or peripheral IV lines and heated aerosol masks. MEASUREMENTS AND MAIN RESULTS: The patients had a mean rewarming rate of 1.16 C/hr; all survived. The majority were chronic alcoholic patients who presented with multiple medical conditions that required hospitalization. CONCLUSION: All patients recovered with this method of core rewarming.

Adult↗
PubMed1999

Cold acclimation-induced increase of systolic blood pressure in rats is associated with volume expansion.

To investigate the mechanisms of cold-induced hypertension, the systolic blood pressure (SBP) and average daily water consumption were measured weekly in 6-month-old male Wistar rats; they were subsequently acclimated to thermoneutrality (26 degrees C for 7 weeks), to cold temperature (6 degrees C for 9 weeks), and then again reacclimated to 26 degrees C for 5 weeks. Circulating plasma volume and whole blood viscosity were measured in subgroups of rats at the end of acclimation to 26 degrees C after 2 days, after 1, 6, and 8 weeks of cold, and after 2 and 5 weeks of rewarming. The control values obtained at the end of thermoneutral period were: SBP = 130.8 +/- 18.6 mm Hg, plasma volume = 41.9 +/- 4.64 mL/kg, whole body viscosity at shear rate of 22.5 per sec = 6.7 +/- 0.48 cps, and daily water consumption = 42.25 +/- 16.81 mL. After 48 h of cold exposure there was almost a 50% increase in plasma volume that persisted to a lesser degree throughout the whole period of cold exposure (P < .05). After 2 weeks of cold exposure the daily water consumption increased and SBP began to increase. After 6 weeks of cold exposure the SBP was 30 mm Hg above that of the control level (P < .001) and was accompanied by a 25% increase in whole blood viscosity (P < .05). At the end of 8 weeks of cold exposure the plasma volume was 56.8 +/- 9.51 mL/ kg and the whole blood viscosity was 8.0 +/- 1.79 cps at the 22.5 per sec shear rate. During the 5 weeks of rewarming the elevation of SBP and increased whole blood viscosity persisted, whereas the increased daily water consumption and expanded plasma volume returned to normal. Therefore, the acclimation to cold is accompanied by the development of a volume-associated hypertension, which is sustained after rewarming without volume expansion.

Acclimatization↗
PubMed1999

Renal hypoxanthine balance in cardiac surgery: effects of felodipine.

OBJECTIVE: To test the hypothesis that felodipine, a renal vasodilator, can prevent a release of hypoxanthine during rewarming after moderate hypothermic cardiopulmonary bypass and that this is related to improved renal oxygen supply. DESIGN: A prospective, randomized, and controlled study. SETTING: Operating room in the cardiothoracic surgery department of a university hospital. PARTICIPANTS: Twenty-two patients submitted to elective first-time coronary bypass surgery. INTERVENTIONS: A catheter was placed in the left renal vein for thermodilution renal blood flow (RBF) measurement and blood sampling. In 11 patients, felodipine was infused during the hypothermic period of cardiopulmonary bypass. MEASUREMENTS AND MAIN RESULTS: Renal uptake (renal arteriovenous concentration difference x RBF) of hypoxanthine was maintained during rewarming in felodipine-treated patients but not in control patients (55+/-28 v. -39+/-1 nmol/min, p<0.05). Oxygen consumption was higher after felodipine infusion despite unchanged total RBF. A positive correlation between renal oxygen consumption and hypoxanthine uptake and release (r = 0.74, p<0.01) was observed. CONCLUSIONS: Felodipine maintained renal uptake of hypoxanthine during rewarming after hypothermic cardiopulmonary bypass. This maintenance is the effect of improved renal oxygen supply secondary to improved nutritive blood flow at the expense of nonnutritive renal blood flow.

Aged↗
PubMed1999

Markers of splanchnic perfusion and intestinal translocation of endotoxins during cardiopulmonary bypass: effects of dopamine and milrinone.

OBJECTIVES: To investigate markers of splanchnic perfusion and the extent of endotoxemia during cardiopulmonary bypass (CPB) and to compare the effects of dopamine and milrinone on both splanchnic perfusion and endotoxemia. DESIGN: Prospective, randomized, blinded study. SETTING: University teaching hospital. PARTICIPANTS: Twenty-four patients scheduled for elective coronary artery bypass graft surgery (CABG). INTERVENTIONS: Patients were allocated to receive placebo (eight patients), dopamine (eight patients), or milrinone (eight patients) during CPB, and at seven times intraoperatively assays were performed of arterial and hepatic venous endotoxin levels, as well as measurements and/or calculations of intramucosal gastric pH (pHi), arterial and hepatic venous lactate-pyruvate ratio (lac/pyr), and hepatic venous oxygen saturation (S(HV)O2). MEASUREMENTS AND MAIN RESULTS: Both splanchnic and systemic endotoxin levels increased significantly, and this was unaffected by either dopamine or milrinone. Gastric pHi did not change, and there were only modest increases in lac/pyr, which remained within the normal range of less than 10 in both splanchnic and systemic blood. In the placebo group, S(HV)O2 decreased at the onset of CPB and also significantly decreased during rewarming and at the end of CPB and surgery. In the dopamine-treated patients, S(HV)O2 was greater compared with placebo and milrinone during both hypothermic and rewarming phases. CONCLUSION: Endotoxemia occurs during routine CPB. Neither pHi nor lac/pyr values showed adverse change, but hepatic venous oximetry may be a more sensitive indicator of splanchnic dysoxia in that S(HV)O2 was reduced during rewarming. Whether dopamine or milrinone confer protection against splanchnic ischemia remains uncertain.

Adult↗
PubMed2001

[The use of moderate hypothermia in the treatment of patients with severe craniocerebral trauma].

Traumatic brain injury initiates several metabolic processes that can increase the primary injury. It is well established that in severe head injuries, posttraumatic secondary insults, such as brain hypoxia, hypotension or anemia, exacerbate neuronal injury and lead to a poorer outcome. Experimental and clinical evidence suggests that moderate hypothermia (32-34 degrees C), may limit some of these deleterious secondary metabolic responses. Recent laboratory studies and prospective controlled clinical trials of induced moderate hypothermia for relatively short periods (24-48 h) in patients with severe head injury, have demonstrated good intracranial pressure control and better outcome when compared with patients maintained in normothermia and given conventional treatment. Despite its proven clinical role in neuroprotection, hypothermia research has been inconstantly followed for various reasons. In this paper we review the mechanisms of neuroprotection in hypothermia, the different preclinical and clinical studies that favor its use as a neuroprotector in severe head injury or in patients in whom high intracranial pressure is refractory to first tier measures. The evidence that favors hypothermia is discussed. We also discuss the negative results of the still unpublished multicentre trial on prophylactic moderate hypothermia developed in the USA. The main problem with moderate hypothermia is the lack of a systematic methodology to induce and maintain it. Also, optimal duration of its use and the methodology and timing for rewarming have not been determined. Consequently, the results of different trials are difficult to analyze and compare. However, most evidence suggests that hypothermia provides remarkable protection against the adverse effects of neuronal damage that is exacerbated by secondary injury. Further prospective controlled trials with clearly defined methodology are needed before this method is implemented in daily clinical practice. The most important task for the years to come may be to focus on refining this procedure, defining the optimal time of cooling and rewarming and to optimize the methods of rapidly inducing and maintaining low temperature. It is also essential to define the most appropriate method and velocity of the rewarming phase, in which many successfully controlled patients deteriorate and die.

Brain Injuries↗
PubMed1985

Effect of hypothermic cardiopulmonary bypass on nitroprusside metabolism.

At a rectal temperature of 25 degrees C, six patients undergoing hypothermic cardiopulmonary bypass received intravenous infusions of sodium nitroprusside (SNP) at a rate of 7.3 +/- 1.7 micrograms/kg/min for 20 minutes. Total SNP dose per patient was 11.0 +/- 1.1 mg. Blood samples for serum cyanide (CN-), red blood cell cyanide (RBC CN-), and thiocyanate (SCN-) determinations were drawn immediately before SNP infusion. These determinations were repeated at the end of the infusion, at the start of rewarming, and at a rectal temperature greater than 34 degrees C and 1, 4 (five subjects), and 24 hours (three subjects) thereafter. Extracorporeal blood flow was held constant at 2.4 L/min/m2 and mean arterial pressure was maintained between 50 to 100 mm Hg with phenylephrine (3.62 +/- 0.75 mg) during SNP infusion and trimethaphan (37.8 +/- 15.6 mg) after the end of the infusion. There was a significant increase in RBC CN- after the SNP infusion that lasted until the subjects were rewarmed. One subject developed a peak RBC CN- level of 0.8 microgram/ml. Plasma CN- levels changed little throughout and SCN- levels were elevated only after rewarming. The nonenzymatic release of free CN- from SNP was not inhibited by hypothermia, while the enzymatic detoxification of CN- to SCN- may have been delayed.

Aged↗