End Of Rewarming Research Articles

Late Awakening Is Common in Settings Without Withdrawal of Life-Sustaining Therapy in Out-of-Hospital Cardiac Arrest Survivors Who Undergo Targeted Temperature Management.

We investigated awakening time and characteristics of awakening compared nonawakening and factors contributing to poor neurologic outcomes in out-of-hospital cardiac arrest survivors in no withdrawal of life-sustaining therapy settings. Retrospective analysis of the Korean Hypothermia Network Pro registry. Multicenter ICU. Adult (≥ 18 yr) comatose out-of-hospital cardiac arrest survivors who underwent targeted temperature management at 33-36°C between October 2015 and December 2018. None. We measured the time from the end of rewarming to awakening, defined as a total Glasgow Coma Scale score greater than or equal to 9 or Glasgow Coma Scale motor score equals to 6. The primary outcome was awakening time. The secondary outcome was 6-month neurologic outcomes (poor outcome: Cerebral Performance Category 3-5). Among 1,145 out-of-hospital cardiac arrest survivors, 477 patients (41.7%) regained consciousness 30 hours (6-71 hr) later, and 116 patients (24.3%) awakened late (72 hr after the end of rewarming). Young age, witnessed arrest, shockable rhythm, cardiac etiology, shorter time to return of spontaneous circulation, lower serum lactate level, absence of seizures, and multisedative requirement were associated with awakening. Of the 477 who woke up, 74 (15.5%) had poor neurologic outcomes. Older age, liver cirrhosis, nonshockable rhythm, noncardiac etiology, a higher Sequential Organ Failure Assessment score, and higher serum lactate levels were associated with poor neurologic outcomes. Late awakeners were more common in the poor than in the good neurologic outcome group (38/74 [51.4%] vs 78/403 [19.4%]; p < 0.001). The awakening time (odds ratio, 1.005; 95% CIs, 1.003-1.008) and late awakening (odds ratio, 3.194; 95% CIs, 1.776-5.746) were independently associated with poor neurologic outcomes. Late awakening after out-of-hospital cardiac arrest was common in no withdrawal of life-sustaining therapy settings and the probability of awakening decreased over time.

Impact of controlled normothermia following hypothermic targeted temperature management for post-rewarming fever and outcomes in post-cardiac arrest patients: A propensity score-matched analysis from a multicentre registry

Aim of the studyWe investigated whether controlled normothermia (CN) after the rewarming phase of targeted temperature management (TTM) is associated with preventing post-rewarming fever and outcomes 6 months after out-of-hospital cardiac arrest (OHCA). MethodsThis was an analysis of a prospective registry comprising OHCA patients treated with TTM at 22 academic hospitals between October 2015 and December 2018. We calculated the incremental area under the curve (iAUC) for body temperature greater than or equal to 37.5 °C for each patient during the first 24 h after the end of rewarming. The relationships among CN and iAUC, 6-month survival and good neurological outcome were analysed. To minimize differences in the baseline characteristics of the patients, we used propensity score-matched analysis. ResultsIn total, 1144 patients were enrolled. After propensity score matching, 646 patients (comprising 323 pairs) were obtained. In the unmatched cohort, post-rewarming CN was significantly associated with a lower iAUC (0.34 [1.38] vs. 1.19 [2.27]; p < 0.001) but not 6-month survival (adjusted odds ratio (OR): 1.121; 95% confidence interval (CI): 0.836−1.504; p = 0.446) and good neurological outcome (adjusted OR: 1.030; 95% CI: 0.734−1.446; p = 0.863). The results were similar in the propensity score-matched cohort (0.38 [1.56] vs. 1.03 [2.21], p < 0.001, OR: 1.347, 95% CI: 0.989−1.835, p = 0.059 and OR: 1.280, 95% CI 0.925−1.772, p = 0.137, respectively). ConclusionPost-rewarming CN prevents high fever in the normothermia phase of TTM. However, our data suggest the lack of association between CN and the patient’s 6-month survival and good neurological outcome.

Pediatrik Hastalarda Kardiyopulmoner Baypas Sırasında Farklı Hipotermik Seviyelerinde Serebral Oksimetri Değişimi ve Klinik Sonuçları

Introduction: Cardiopulmonary bypass (CPB) may not provide sufficient tissue perfusion. Hypothermia is used to protect the organs, especially the brain and heart, from this perfusion insufficiency. We investigated the effect of different hypothermic levels on cerebral oxygenation during CPB by using a cerebral oxymeter. Patients and Methods: The study included 30 consecutive pediatric patients with congenital heart disease who were planned to be operated on in the year 2012. The mean age was 41.83 ± 39.96 months (2-156 months), with 19 males. Children were divided into three groups by different hypothermic levels at CPB (32°C, 30°C, and 28°C). The measurements were made five times: before anesthesia induction (baseline values), during cooling (34°C), at the coldest value (first group 32°C, second group 30°C, third group 28°C), during rewarming (34°C), and at the end of rewarming (37°C-38°C). Cerebral-oxygen saturation, arterial-oxygen saturation, arterial carbon dioxide pressure, mean arterial pressure, pH, lactate, base excess, and hematocrit measurements were made for all patients, and mean values were calculated for each group. Results: There were no significant differences between the 32°C, 30°C, and 28°C groups (p> 0.05). When comparing change in cerebral-oxygen saturation values with the other parameters' changes between the periods, mean arterial pressure, and hematocrit changes showed noteworthy similarities. However, no relationship had been found between the other parameters and cerebral-oxygen saturation. Conclusion: In our study, it was observed that cerebral oxygenation had not changed significantly at different hypothermic degrees of moderate levels during CPB. The highest temperature level of moderate hypothermic degrees (32°C instead of 28°C) was secure enough. This might be more advantageous to avoid the possible negative effects of hypothermia. Close monitoring of the cerebral oxygenation with cerebral oximetry may play an important role in ensuring patients' safety.

Cardiopulmonary-Bypass Glial Fibrillary Acidic Protein Correlates With Neurocognitive Skills

Neurocognitive deficits at school starting age may affect as many as 50% of children who underwent cardiac surgery for complex congenital heart disease (CHD). The aim of this study was to identify which phases of cardiopulmonary bypass (CPB) are associated with an increased risk of impaired neurodevelopmental skills in children with complex CHD. This was assessed by means of glial fibrillary acidic protein (GFAP) plasma levels during CPB for CHD surgery, as a marker of neurologic insult. We correlated GFAP levels with clinical parameters and neurodevelopmental outcome. We studied 45 children undergoing surgery for complex CHD. We measured plasma GFAP levels by enzyme-linked immunosorbent assay at the following steps: anesthesia induction, CPB start, end of hypothermia, end of rewarming, and end of CPB. Neurologic assessment and Vineland Adaptive Behavior Scales (VABS-I) were administered to patients at least 18 months after surgery. GFAP was undetectable before surgery and it peaked at the end of hypothermia or rewarming. Multiple regression analyses showed that GFAP peak level and preoperative neurologic comorbidity were significant independent predictors of neurologic impairment, as showed by VABS-I communication domain intelligence quotient (IQ). Receiver operating characteristic curve showed that the model was highly significant. Impaired neurodevelopment was associated with increase of GFAP plasma levels during cardiac surgery in infants. The identification of the neurologic high-risk phases of CPB run could support the application of new neuroprotective strategies for CHD repair.

Comparison of two sedation regimens during targeted temperature management after cardiac arrest

PurposeAlthough guidelines on post-resuscitation care recommend the use of short-acting agents for sedation during targeted temperature management (TTM) after cardiac arrest (CA), the potential advantages of this strategy have not been clinically demonstrated. MethodsWe compared two sedation regimens (propofol-remifentanil, period P2, vs midazolam-fentanyl, period P1) among comatose TTM-treated CA survivors. Management protocol, apart from sedation and neuromuscular blockers use, did not change between the two periods. Baseline severity was assessed with Cardiac-Arrest-Hospital-Prognosis (CAHP) score. Time to awakening was measured starting from discontinuation of sedation at the end of rewarming. Awakening was defined as delayed when it occurred after more than 48 h. Results460 patients (134 in P2, 326 in P1) were included. CAHP score did not significantly differ between P2 and P1 (P = 0.93). Sixty percent of patients awoke in both periods (81/134 vs. 194/326, P = 0.85). Median time to awakening was 2.5 (IQR 1–9) hours in P2 vs. 17 (IQR 7–60) hours in P1. Awakening was delayed in 6% of patients in P2 vs. 29% in P1 (p < 0.001). After adjustment, P2 was associated with significantly lower odds of delayed awakening (OR 0.08, 95% CI 0.03–0.2; P < 0.001). Patients in P2 had significantly more ventilator-free days (25 vs. 24 days; P = 0.007), and lower catecholamine-free days within day 28. Survival and favorable neurologic outcome at discharge did not differ across periods. ConclusionsDuring TTM following resuscitation from CA, sedation with propofol-remifentanil was associated with significantly earlier awakening and more ventilator-free days as compared with midazolam-fentanyl.

Oxidative stress and abnormal cholesterol metabolism in patients with post-cardiac arrest syndrome.

Patients with post-cardiac arrest syndrome (PCAS) suffer from whole body ischemia/reperfusion injury similar to that experienced by newborn babies. Increased oxidative stress was confirmed in PCAS patients (n = 40) at the time of hospitalization by a significant increase in the percentage of the oxidized form of coenzyme Q10 in total coenzyme Q10 compared to age-matched healthy controls (n = 55). Tissue oxidative damage in patients was suggested by the significant increase in plasma levels of free fatty acids (FFA) and the significant decrease in polyunsaturated fatty acid contents in total FFA. A greater decrease in free cholesterol (FC) compared to cholesterol esters (CE) was observed. Therefore, the FC/CE ratio significantly increased, suggesting deficiency of lecithin-cholesterol acyltransferase secreted from the liver. Time course changes of the above parameters were compared among 6 groups of patients divided according to outcome severity. Rapid declines of FC and CE were observed in patients who died within a day, while levels remained unchanged in patients discharged in a week. These data suggest that liver function is one of the key factors determining the survival of patients. Interestingly, therapeutic hypothermia treatment enhanced the increment of plasma ratio of coenzyme Q10 to total cholesterol at the end of rewarming.

Glial fibrillary acidic protein plasma levels are correlated with degree of hypothermia during cardiopulmonary bypass in congenital heart disease surgery.

Improved congenital heart defect (CHD) operations have reduced operative mortality to 3%. The major concern is now long-term neurological outcomes. We measured plasma glial fibrillary acidic protein (GFAP), an early marker of brain injury, during different phases of cardiopulmonary bypass (CPB), to correlate the increase of GFAP to clinical parameters or specific operative phases. We performed a prospective, single-centre, observational study in children undergoing cardiac operations. We studied 69 children with CHD and biventricular heart physiology: 26 had tetralogy of Fallot; 17 transposition of the great arteries; and 26 ventricular/atrial septal defects with or without associated arch defects. GFAP levels were measured by ELISA at different stages of CPB. We recorded clinical and surgical parameters and applied multivariable and logistic regressions to assess which parameters were independent predictors of variations in plasma GFAP. GFAP increased during CPB and peaked at the end of rewarming. Multivariable regression showed degree of hypothermia as the only significant independent predictor of GFAP increase, adjusted for age, prematurity, type of CHD, cyanosis, aortic cross-clamp time, haemodilution, neurological risk time interval and rewarming rate. Temperature nadir and neurological risk time interval were significant independent predictors of a GFAP value > 0.46 ng/ml. Hypothermia degree during CPB is correlated with GFAP plasma increase in children with biventricular heart defects undergoing surgical repair. Rewarming is the most critical CPB phase for GFAP increase. The implication of high plasma GFAP is still under evaluation. Follow-up studies are ongoing to assess the reliability of GFAP as a marker of brain injury and/or as a predictor of neurodevelopmental abnormalities.

The functional requirements of mammalian hair: a compromise between crypsis and thermoregulation?

Mammalian fur often shows agouti banding with a proximal dark band near the skin and a lighter distal band. We examined the function of both bands in relation to camouflage, thermal properties of pelts, and thermal energetics of dunnarts (Sminthopsis crassicaudata), which are known to use torpor and basking. Although the distal band of dunnart fur darkened with increasing latitude, which is important for camouflage, it did not affect the thermal properties and the length of the dark band and total hair length were not correlated. In contrast, the length of the proximal dark band of preserved pelts exposed to sunlight was positively correlated (r (2) = 0.59) with the temperature underneath the pelt (T pelt). All dunnarts offered radiant heat basked by exposing the dark band of the hair during both rest and torpor. Basking dunnarts with longer dark bands had lower resting metabolism (r (2) = 0.69), warmed faster from torpor (r (2) = 0.77), required less energy to do so (r (2) = 0.32), and reached a higher subcutaneous temperature (T sub) at the end of rewarming (r (2) = 0.75). We provide the first experimental evidence on the possible dual function of the color banding of mammalian fur. The distal colored band appears to be important for camouflage, whereas the length of the dark proximal hair band facilitates heat gain for energy conservation and allows animals to rewarm quickly and economically from torpor.

Delayed awakening after cardiac arrest: prevalence and risk factors in the Parisian registry.

Although prolonged unconsciousness after cardiac arrest (CA) is a sign of poor neurological outcome, limited evidence shows that a late recovery may occur in a minority of patients. We investigated the prevalence and the predictive factors of delayed awakening in comatose CA survivors treated with targeted temperature management (TTM). Retrospective analysis of the Parisian Region Out-of-Hospital CA Registry (2008-2013). In adult comatose CA survivors treated with TTM, sedated with midazolam and fentanyl, time to awakening was measured starting from discontinuation of sedation at the end of rewarming. Awakening was defined as delayed when it occurred after more than 48h. A total of 326 patients (71% male, mean age 59±16years) were included, among whom 194 awoke. Delayed awakening occurred in 56/194 (29%) patients, at a median time of 93h (IQR 70-117) from discontinuation of sedation. In 5/56 (9%) late awakeners, pupillary reflex and motor response were both absent 48h after sedation discontinuation. In multivariate analysis, age over 59years (OR 2.1, 95% CI 1.0-4.3), post-resuscitation shock (OR 2.6 [1.3-5.2]), and renal insufficiency at admission (OR 3.1 [1.4-6.8]) were associated with significantly higher rates of delayed awakening. Delayed awakening is common among patients recovering from coma after CA. Renal insufficiency, older age, and post-resuscitation shock were independent predictors of delayed awakening. Presence of unfavorable neurological signs at 48h after rewarming from TTM and discontinuation of sedation did not rule out recovery of consciousness in late awakeners.

Abstract 12120: Intracranial Pressure Increases Both During Mild Therapeutic Hypothermia and During Rewarming Period in Post Cardiac Arrest Patients

Introduction: Elevation of intracranial pressure (ICP) may induce secondary brain injury and worsen the neurological outcome. Some studies on traumatic brain injury show that rapid rewarming can result in poorer outcomes contributory due to elevation of ICP. However, little is known about ICP during therapeutic hypothermia (TH) and rewarming period in post cardiac arrest patients. Hypothesis: We tested if there is occurrence of increased ICP during mild TH and rewarming period and whether it is related to outcome in patients resuscitated after cardiac arrest. Methods: Comatose patients resuscitated from cardiac arrest, treated with TH and ICP monitored were enrolled in the study. Surface cooling device was used for TH. Patients were maintained in target core temperature of 34 °C for 24 hrs. Thereafter, the temperature was regulated to increase to normothermia (37.0 °C) at the rate of 0.25 °C/hr. ICP and cerebral perfusion pressure (CPP) were monitored during the period. Cerebral Performance Category (CPC) scale was obtained 28 days later. Results: Data of 9 patients were analyzed (8 [89 %] men, age: 62 ± 17 years, cardiac origin 3 [33 %]/non-cardiac origin: 6 [67 %], CPC 1: 2 patients; CPC 2: 1 patient; CPC 3: 1 patient; CPC 4: 2 patients; CPC 5: 3 patients). ICP was 7.7 ± 4.4 mmHg at the beginning of TH and significantly elevated to 17.4 ± 13.3 mmHg at the end of TH (p = 0.03). ICP was 23.6 ± 19.1 mmHg at the end of rewarming which was higher than the end of TH (p = 0.04). At the end of rewarming, ICP value ranged in variety from 10 mmHg (CPC 1) to 68 mmHg (CPC 5). CPP was 81.3 ± 15.6 mmHg at the beginning of TH and was 72.1 ± 22.7 mmHg (p = 0.22) at the end of rewarming. All the cases with CPP less than 40 mmHg within 48 hrs died. Conclusions: ICP is increasing both during TH of target temperature 34°C and during rewarming at speed of 0.25 °C/hr in patients after cardiac arrest. Increment of ICP seems to be greater in cases with poorer outcome. CPP decrease was not usually observed and was limited to fatal cases.

Cardiopulmonary Bypass Increases Plasma Glial Fibrillary Acidic Protein Only in First Stage Palliation of Hypoplastic Left Heart Syndrome

BackgroundUniventricular congenital heart defects require open-heart surgery soon after birth, and are associated with risk of brain injury and poor neurologic outcome. MethodsThis is a prospective, observational study on children undergoing cardiac surgery. Plasma glial fibrillary acidic protein (GFAP), as an early marker of brain injury, was measured by ELISA at the end of anaesthesia induction, initiation of cardiopulmonary bypass (CPB), the end of cooling, the end of rewarming, the end of CPB, and after protamine administration. We recorded clinical and surgical parameters to assess which CPB phase and clinical parameters were associated with a GFAP increase. ResultsWe studied 13 children less than 50 months of age: 8 underwent Norwood or Damus-Kaye-Stansel palliation (group 1) and 5 underwent Fontan procedure (group 2). A GFAP increase was only observed in group 1, with the highest median value at the end of rewarming. No quantifiable levels of GFAP were measured at pre-bypass and the start of CPB stages in all patients. End of cooling and CPB-end GFAP, GFAP maximum value, and GFAP area under the curve all correlated with the CPB time spent at a cerebral regional saturation < 45% (P = 0.021, 0.028, 0.007, 0.021, respectively). ConclusionsChildren with univentricular heart defects exhibit a CPB plasma-GFAP increase only after stage 1 palliation. The maximum GFAP increase occurred at the end of rewarming. Further studies are needed to identify which clinical or surgical parameter(s) could reflect a GFAP increase during surgery for congenital heart defects, and whether GFAP levels correlate with the neurologic outcome.

Is the venoarterial carbondioxide gradient and lactate predictor of inadequate tissue perfusion during cardiopulmonary bypass?

Background: In this study, we aimed to investigate the possible relationship between the venoarterial gradient of carbon dioxide (Dv-a PCO2) and lactate during cardiopulmonary bypass (CPB). Methods: Sixty consecutive patients (35 males, 53 females; mean age 64 years; range 38 to 78 years) who were scheduled for elective isolated coronary artery bypass graft (CABG) surgery were included in the study after obtaining their informed consent and the approval of the ethics committee of the hospital. All patients were followed up by the same surgical and anesthesia team. The adequacy of tissue perfusion during CPB was evaluated by the venoarterial partial carbon dioxide gradient, lactate level, measurement of arterial and venous blood gas, urinary flow rate, and hemodynamic parameters. The measurements were performed in four periods: before CPB (T1), at the beginning of CPB (T2) at 36 ºC and 32 ºC of hypothermia (T3) and at the end of rewarming (T4) at 37 ºC. The relationship between tissue perfusion parameters was assessed by Pearson&#8217;s correlation analysis. Results: There was a significant correlation between Dv-aPCO2 and the venous lactate level (r=0.54, p=0.046) as well as between Dv-aPCO2 and the arterial lactate level (r=0.55, p=0.042) during the T2 a nd T 4 periods of CPB. There was also a significant correlation between Dv-aPCO2 and arterial base excess (BE) (r=0.64, p=0.013) and between Dv-aPCO2 a nd a rterial H CO3 (r=0.54, p=0.048) during the T3 and T4 periods. Conclusion: Our study results suggest that in the hypothermia period, the increase in the venoarterial carbon dioxide gradient (Dv-aPCO2) is not inversely associated with insufficient blood flow during CPB and there was a significant correlation between Dv-aPCO2 and the tissue perfusion parameters during the periods other than hypothermia.

A42 Post-cooling Fever in Cardiac Arrest Patients Treated with Therapeutic Hypothermia

Background: Incidence and characteristics of post-cooling fever were rarely described. In this study, we analysed the possible link between cardiac arrest (CA), therapeutic hypothermia and fever. Patients and Methods: Data of 11 post-CA pts were analysed. All hemodynamic, respiratory and laboratory data were collected. Hyperthermia was defined as a core (rectal) temperature exceeding 37.7°C, Results: Of the 11 pts, there were 5 (45%) survivors and 6 (55%) non-survivors, 2 died of hemodynamic shock (first 24hrs), 4 died due to post-ischemic brain damage. Results: All pts were successfully cooled (33° for 24hrs). Rewarming procedure was uneventfull. Results: Eight (89%) pts developed hyperthermia at the end of rewarming. Six (75%) of them did so immediately, while the other 2 pts developed fever 2 to 5 hours after rewarming. Three (37.5%) pts showed short periods of fever (2 -10hrs), while the remaining 5 (62.5%) had fever for a few days. In all patients, WBC at admission were significantly increased whereas CRP only increased after 2–3 days ICU-admission, in 8 patients this occurred simultaneously with the post-cooling fever. In 7 of these 8 pts, antibiotic treatment was initiated. In 5 of 8 pts, pneumonia, prolonged weaning and awakening, but did not influence final mortality. Conclusion: We found a 89% incidence of post-cooling fever, associated with ending of rewarming and increase in inflammatory parameters (CRP).

Hand and Finger Dexterity as a Function of Skin Temperature, EMG, and Ambient Condition

This article examines the changes in skin temperature (finger, hand, forearm), manual performance (hand dexterity and strength), and forearm surface electromyograph (EMG) through 40-min, 11 degrees C water cooling followed by 15-min, 34 degrees C water rewarming; additionally, it explores the relationship between dexterity and the factors of skin temperature, EMG, and ambient condition. Hand exposure in cold conditions is unavoidable and significantly affects manual performance. Two tasks requiring gross and fine dexterity were designed, namely, nut loosening and pin insertion, respectively. The nested-factorial design includes factors of gender, participant (nested within gender), immersion duration, muscle type (for EMG), and location (for skin temperature). The responses are changes in dexterity, skin temperature, normalized amplitude of EMG, and grip strength. Finally, factor analysis and stepwise regression are used to explore factors affecting hand and finger dexterity. Dexterity, EMG, and skin temperature fell with prolonged cooling, but the EMG of the flexor digitorum superficialis remained almost unchanged during the nut loosening task. All responses but the forearm skin temperature recovered to the baseline level at the end of rewarming. The three factors extracted by factor analysis are termed skin temperature, ambient condition, and EMG. They explain approximately two thirds of the variation of the linear models for both dexterities, and the factor of skin temperature is the most influential. Sustained cooling and warming significantly decreases and increases finger, hand, and forearm skin temperature. Dexterity, strength, and EMG are positively correlated to skin temperature. Therefore, keeping the finger, hand, and forearm warm is important to maintaining hand performance. The findings could be helpful to building safety guidelines for working in cold environments.

Neurocognitive Function in Patients Undergoing Coronary Artery Bypass Graft Surgery With Cardiopulmonary Bypass: The Effect of Two Different Rewarming Strategies

Hypothermia followed by rewarming during cardiopulmonary bypass can lead to cerebral hyperthermia, which has been implicated as 1 of the causes for postoperative deterioration in neurocognitive function in patients undergoing coronary revascularization. Hence, the authors studied the effects of 2 different rewarming strategies on postoperative neurocognitive function in adult patients undergoing coronary artery bypass graft surgery with the aid of cardiopulmonary bypass. This was a randomized clinical trial. A cardiothoracic center of a tertiary level referral, teaching hospital. A total of 80 adult patients aged 45 to 70 years undergoing elective primary isolated coronary artery bypass graft surgery with cardiopulmonary bypass under moderate hypothermia at 30 degrees C were included in this study. The patients were randomly allocated into 2 groups of 40 each. In group A, patients were rewarmed to a nasopharyngeal temperature of 37 degrees C; whereas, in group B, patients were rewarmed to a nasopharyngeal temperature of 33 degrees C before weaning off bypass. The anesthetic and bypass management were standardized for both groups. All patients were assessed for neurocognitive function preoperatively and on the fifth postoperative day using the Post Graduate Institute Memory Scale. The amount of blood loss and need for blood and blood product transfusion postoperatively, the need for pacing, increased inotrope or vasodilator use, and time to extubation were also noted. Serum S100beta levels were measured after anesthetic induction and at 24 hours postoperatively. The jugular venous oxygen saturation and oxygen tension were noted at 30 degrees C and at the end of full rewarming (ie, at 37 degrees C or 33 degrees C, respectively, in the 2 groups). There was a significant deterioration in neurocognitive function postoperatively as compared with preoperative function in patients of group A (37 degrees C). This was associated with higher S100beta levels 24 hours postoperatively in group A (37 degrees C) compared with group B (33 degrees C) patients. Also, there was a significant decrease in jugular venous oxygen saturation in group A (37 degrees C) as compared with group B (33 degrees C) at the end of rewarming. The time to extubation was longer in group B (33 degrees C). No significant differences were noted in the amount of postoperative blood loss, blood and blood product use, inotrope or vasodilator use, and the need for pacing. Weaning from CPB at 33 degrees C may be a simple and useful strategy to lower the postoperative impairment of neurocognitive function and may be used as a tool to decrease morbidity after coronary revascularization.

Failure of surface-modified bypass circuits to improve platelet function during pediatric cardiac surgery

Surface-modified cardiopulmonary bypass circuits have been shown to improve platelet function and decrease postoperative bleeding after heart surgery in adults. Two surface-modified cardiopulmonary bypass circuits are approved and commercially available for pediatric cardiac surgery. There have been few studies demonstrating the efficacy of these modifications for children. We performed a prospective, randomized trial comparing surface-modified cardiopulmonary bypass circuits to a standard unmodified circuit in pediatric cardiac surgery. Sixty-nine children (median 6 months old) undergoing first-time cardiac surgery were enrolled and randomized to an uncoated circuit or one of the two commercially available surface modified circuits for their operation. Blood samples were collected at baseline, on cardiopulmonary bypass, at the end of rewarming, after protamine, and at 18 to 24 postoperative hours. Platelet count, beta-thromboglobulin, and thromboelastography with and without abciximab were measured. Postoperative chest tube outputs and blood product utilization were also analyzed. The platelet counts, beta-thromboglobulin levels, thromboelastographic measures of platelet function, and postoperative bleeding were not significantly different between the surface-modified cardiopulmonary bypass circuit groups and the control group. Currently available surface-modified cardiopulmonary bypass circuits do not significantly improve platelet function or clinical outcomes after routine pediatric cardiac surgery.

Hemodynamics Among Neonates With Hypoxic-Ischemic Encephalopathy During Whole-Body Hypothermia and Passive Rewarming

To assess changes in cardiac performance, with Doppler echocardiography, among newborns with hypoxic-ischemic encephalopathy during mild therapeutic hypothermia and during rewarming. For 7 asphyxiated neonates (birth weight: 1840-3850 g; umbilical artery pH: 6.70-6.95) who received mild whole-body hypothermia, the following hemodynamic parameters were determined immediately before rewarming (33 degrees C) and during passive rewarming (35 degrees C and 37 degrees C): heart rate, systolic and diastolic blood pressure, core and peripheral temperatures, left ventricular ejection time, mean velocity of aortic flow, stroke volume, and cardiac output. Heart rate decreased during hypothermia. Bradycardia, with heart rates below 80 beats per minute, did not occur. The median difference between core and peripheral temperatures decreased from 2.0 degrees C (range: 0-6.2 degrees C) during hypothermia to 0.7 degrees C (range: 0.4-1.9 degrees C) at normothermia. Cardiac output was reduced to 67% and stroke volume to 77% of the posthypothermic level. The median heart rate was 129 beats per minute before rewarming and increased to 148 beats per minute during complete rewarming. Before and during passive rewarming, hypotension was not observed. Before, during, and at the end of rewarming, the following parameters increased: mean velocity of aortic flow (median: 44, 55, and 58 cm/second, respectively), stroke volume (median: 1.42, 1.55, and 1.94 mL/kg, respectively), and cardiac output (median: 169, 216, and 254 mL/kg per minute, respectively). Left ventricular ejection time remained unchanged. Whole-body hypothermia resulted in reduced cardiac output, which reached normal levels at the end of passive rewarming, at normothermia. Physiologic cardiovascular mechanisms seemed to be intact to provide sufficient tissue perfusion, with normal blood lactate levels.

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

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

Moderate hypothermia may be detrimental after traumatic brain injury in fentanyl-anesthetized rats.

To determine whether transient, moderate hypothermia is beneficial after traumatic brain injury in fentanyl-anesthetized rats. Prospective, randomized study. University-based animal research facility. Adult male Sprague-Dawley rats. All rats were intubated, mechanically ventilated, and anesthetized with fentanyl (10 microg/kg intravenous bolus and then 50 microg.kg(-1).hr(-1) infusion). Controlled cortical impact was performed to the left parietal cortex, followed immediately by 1 hr of either normothermia (brain temperature 37 +/- 0.5 degrees C) or hypothermia (brain temperature 32 +/- 0.5 degrees C). Hypothermic rats were rewarmed gradually over 1 hr. Fentanyl anesthesia and mechanical ventilation were continued in both groups until the end of rewarming (2 hrs after traumatic brain injury). Histologic assessment performed 72 hrs after traumatic brain injury was the primary outcome variable. Secondary outcome variables were physiologic variables monitored during the first 2 hrs after traumatic brain injury and plasma catecholamine and serum fentanyl concentrations measured at the end of both hypothermia and rewarming (1 and 2 hrs after traumatic brain injury). Contusion volume was larger in hypothermic vs. normothermic rats (44.3 +/- 4.2 vs. 28.6 +/- 4.0 mm, p <.05), but hippocampal neuronal survival did not differ between groups. Physiologic variables did not differ between groups. Plasma dopamine and norepinephrine concentrations were increased at the end of hypothermia in hypothermic (vs. normothermic) rats (p <.05), indicating that hypothermia augmented the systemic stress response. Similarly, serum fentanyl concentrations were higher in hypothermic (vs. normothermic) rats at the end of both hypothermia and rewarming (p <.05), demonstrating that hypothermia reduced the clearance and/or metabolism of fentanyl. Moderate hypothermia was detrimental after experimental traumatic brain injury in fentanyl-anesthetized rats. Since treatment with hypothermia has provided reliable benefit in experimental traumatic brain injury with inhalational anesthetics, these results indicate that the choice of anesthesia/analgesia after traumatic brain injury may dramatically influence response to other therapeutic interventions, such as hypothermia. Given that narcotics commonly are administered to patients after severe traumatic brain injury, this study may have clinical implications.

Do rapid systemic changes of brain temperature have an influence on the brain?

The purpose of the present study was to examine the influence of cooling and rewarming conditions using an accurate brain temperature control system. The brain temperature of animals was measured with a thermometer while feedback regulation was achieved with a cold (4( degrees )C) and hot (50( degrees )C) water on-off flow system. Brain temperature was well controlled throughout the experiment by using both cold water and hot water simultaneously. Three groups were studied, as follows: 1) the standard group (cooled to 24( degrees )C for 1 hour, kept at 24( degrees )C for 2 hours and rewarmed to 37( degrees )C for 1 hour), 2) the rapid-cooling group (cooled to 24( degrees )C for 30 min, kept at 24( degrees )C for 2 h, and rewarmed to 37( degrees )C for 1 h), 3) the rapid-rewarming group (cooled to 24( degrees )C for 1 h, kept at 24( degrees )C for 2 h, and rewarmed to 37( degrees )C for 30 min) and the normal-control group. An increase of MAP-2 immunoreactivity of the CA1 neurons in the dorsal hippocampus was observed one week but not one month after hypothermia in the rapid-rewarming group. There was also a significant increase in the glutamate and lactate value at the end of rewarming compared with the baseline in the rapid-rewarming group (p<0.01). Our results suggest that rapid rewarming after hypothermia triggered an uncoupling of cerebral circulation and metabolism, inducing an increase of extracellular glutamate and lactate, consequently reversible neuronal cell damage.