Comparison of the Effects of Hypothermia and Normothermia on Cognitive Functions After Coronary Artery Bypass Surgery

Background: Cognitive impairment is among the most prevalent complications in patients undergoing CABG. Selection of the proper temperature is one of the main moderating factors in cognitive impairment following CABG. Today, heart surgery is done using the two methods of hypothermia and normothermia. However, there is no consensus over the method with the least side effects. Objectives: This study aims to compare the effects of hypothermia and normothermia on cognitive functions after undergoing CABG during the hospitalization period. Methods: A total of 130 patients in this cohort observational study were divided into two groups of normothermic (n = 65) and hypothermic (n = 65). In the hypothermic group, the temperature was down to 32°C, and in the normothermic group, the temperature decreased to 35°C. After the surgery and transferring the patients to the ICU, demographic information and MMSE questionnaires were completed from the second to the sixth day at the same time. Results: The results showed no significant differences between the two groups in educational and social demographic characteristics (P > 0.05). Besides, there was no significant differences between the two groups in the history of the disease (P = 1.000). In addition, there was no significant relationship between cognitive performance scores of the two groups before the surgery (P = 1.000). However, there was a significant relationship between the two groups from the second (P = 0.003), third (P = 0.000) and the fourth day (P = 0.023) after the surgery. In the normothermic group, on the second, as well as third and fourth days 14 and 9 patients suffered from cognitive impairment, respectively. Besides, in the hypothermic group, on the second, third, and fourth days after surgery, 28, 30, and 23 patients suffered from cognitive impairment, respectively. However, there was no significant relationship between the two groups on the fifth and sixth days after the surgery (P = 0.079). Conclusions: The present study showed that during hospitalization after undergoing CABG, cognitive impairment in patients with the normothermic method was less severe than that in patients with the hypothermic method. Besides, clinical outcomes were more satisfactory in the former group.

Impact of Temperature and Time Interval Prior to Immature Testicular-Tissue Organotypic Culture on Cellular Niche

Cryopreservation of immature-testicular-tissue (ITT) prior to gonadotoxic treatment, while experimental, is the only recommended option for fertility preservation in prepubertal boys. The handling and manipulation of ITT before cryopreservation could influence the functionality of cells during fertility restoration, which this study explored by evaluating cellular niche and quality of mouse ITT subjected to various temperatures and time durations in vitro. ITT from 6-day-old mice were handled at ultraprofound-hypothermic, profound-hypothermic, and mild-warm-ischemic temperatures for varying time periods prior to 14-day organotypic culture. Viability, functionality, synaptonemal complex and chromatin remodeling markers were assessed. Results have shown that cell viability, testosterone level, and in vitro proliferation ability did not change when ITT were held at ultraprofound-hypothermic-temperature up to 24 h, whereas cell viability was significantly reduced (P < 0.01), when held at profound-hypothermic-temperature for 24 h before culture. Further, cell viability and testosterone levels in cultured cells from profound-hypothermic group were comparable to corresponding ultraprofound-hypothermic group but with moderate reduction in postmeiotic cells (P < 0.01). In conclusion, holding ITT at ultraprofound-hypothermic-temperature is most suitable for organotypic culture, whereas short-term exposure at profound-hypothermic-temperature may compromise postmeiotic germ cell yield post in vitro culture. This data, albeit in mouse model, will have immense value in human prepubertal fertility restoration research.

Open Heart Surgery at Patient’s Own Temperature Without Active Cooling

Background: Hypothermia is a method of myocardial protection in cardiac surgery. This protection occurs by decreasing the metabolic demands, however, it creates susceptibility to various problems. In this study, we investigated patients operated on under normothermia (at the patient’s own temperature) and hypothermia for postoperative differences.Methods: The study was conducted between June 2015 and September 2016 with 167 patients. The patients were divided into two groups in accordance with our routine clinical practice: the normothermic group (native temperature goup; intraoperative body temperature ≥ 34°C), and the hypothermic group intraoperative body temperature < 34°C - ≥ 28°C). Preoperative and postoperative data of patients were recorded and the two groups were compared.Results: There was no significant difference between the two groups in terms of cross clamp time, cardiopulmonary bypass time, awakening and extubation times, intensive care unit and hospital stay, drainage, mean serum lactate levels, arrhytmia, all causes infection, renal insufficiency, neurologic complications, myocardial infarction, or mortality (P > .05). Inotrope and transfusion requirements were found to be statistically significantly lower in the normothermic group than the hypothermic group (P < .05).Conclusion: Although hypothermia is commonly used in cardiac surgery, it has harmful effects. We believe that cardiac surgery can safely be performed at a patient’s own temperature without active cooling to avoid these dangers.

Twenty minutes of normothermic cardiac arrest in a pig model: the role of short-term hypothermia for neurological outcome

Introduction: Cardiopulmonary resuscitation restores circulation, but with inconsistent blood-flow and pressures. Our recent approach using an extracorporeal life support system, named “controlled integrated resuscitation device” (CIRD), may lead to improved survival and neurological recovery after cardiac arrest (CA). The basic idea is to provide a reperfusion tailored to the individual patient by control of the conditions of reperfusion and the composition of the reperfusate. Hypothermia is one aspect of this concept. Here, we investigated the role of immediate short-term blood cooling after experimental CA and its influence on survival and neurological recovery. Methods: Twenty-one pigs were exposed to 20 minutes of normothermic CA. Afterwards, CIRD was immediately started for 60 minutes in all animals and the heart was converted to a sinus rhythm. The pigs either received normothermic reperfusion (37°C, n=11) or the temperature was maintained at 32°C for the first 30 minutes (n=10). Thermometric, hemodynamic and serologic data were collected during the experiment. After weaning from CIRD, neurological recovery was assessed daily by a species-specific neurological deficit score (NDS; 0: normal; 500: brain death). Results: One pig in each group could not be successfully resuscitated. Due to severe neurological deficits, only 6/11 animals in the normothermic group finished the observation time of seven days with an NDS of 37±34. In the hypothermic group, all nine surviving animals reached day seven with an NDS of 16±13. Analogous to the lower NDS, animals in the hypothermic group also showed lower neuron-specific enolase end values as a marker of brain injury. Conclusions: Within this experimental setting, immediate moderate and short-term hypothermia after CA improves survival and seems to result in statistically non-significant better neurological recovery.

PRELIMINARY RESULTS OF TOPICAL HEPATIC HYPOTHERMIA IN A MODEL OF LIVER ISCHEMIA/REPERFUSION INJURY IN RATS

ABSTRACT BACKGROUND Ischemia/reperfusion causes organ damage but it is mandatory in hepatic transplantation, trauma and other complex liver surgeries, when Pringle maneuver is applied to minimize bleeding during these procedures. It is well known that liver ischemia/reperfusion leads to microcirculatory disturbance and cellular injury. In this setting hypothermia is known to reduce oxygen demand, lowering intracellular metabolism. OBJECTIVE: To evaluate the effects of hypothermia in liver ischemia/reperfusion injury, using a new model of topic isolated liver hypothermia. METHODS We used male Wistar rats weighting about 250 grams, kept in ad libitum feeding regime and randomly divided into two groups of nine animals: 1) Normothermic group, rats were submitted to normothermic ischemia of the median and left hepatic lobes, with subsequent resection of right and caudate lobes during liver reperfusion; and 2) Hypothermic group, rats were submitted to liver ischemia under hypothermia at 10°C. Liver ischemia was performed for 45 minutes. The animals were euthanized 48 hours after liver reperfusion for blood and liver tissue sampling. RESULTS The transaminases analyses showed a significant decrease of AST and ALT in Hypothermic group (P<0.01) compared to Normothermic group (1403±1234 x 454±213 and 730±680 x 271±211 U/L, respectively). Histology showed severe necrosis in 50% and mild necrosis in 50% of cases in Normothermic group, but severe necrosis in 10% and mild or absent necrosis 90% of the cases in hypothermic group. CONCLUSION: A simplified model of liver ischemia/reperfusion that simulates orthotopic liver autotransplantion was demonstrated. Topical hypothermia of isolated hepatic lobules showed liver protection, being a viable and practical method for any kind of in vivo liver preservation study.

Improved Early Postresuscitation EEG Activity for Animals Treated with Hypothermia Predicted 96 hr Neurological Outcome and Survival in a Rat Model of Cardiac Arrest

Purpose.To investigate the effect of hypothermia on 96 hr neurological outcome and survival by quantitatively characterizing early postresuscitation EEG in a rat model of cardiac arrest.Materials and Methods.In twenty male Sprague-Dawley rats, cardiac arrest was induced through high frequency transesophageal cardiac pacing. Cardiopulmonary resuscitation was initiated after 5 mins untreated arrest. Immediately after resuscitation, animals were randomized to either 2 hrs of hypothermia (N=10) or normothermia (N=10). EEG, ECG, aortic pressure, and core temperature were continuously recorded for 6 hrs. Neurological outcome was evaluated daily during the 96 hrs postresuscitation period.Results.No differences in the baseline measurements and resuscitation outcome were observed between groups. However, 96 hr neurological deficit score (204 ± 255 versus 500 ± 0,P=0.005) and survival (6/10 versus 0/10,P=0.011) were significantly better in the hypothermic group. Quantitative analysis of early postresuscitation EEG revealed that burst frequency and spectrum entropy were greatly improved in the hypothermic group and correlated with 96 hr neurological outcome and survival.Conclusion.The improved burst frequency during burst suppression period and preserved spectrum entropy after restoration of continuous background EEG activity for animals treated with hypothermia predicted favorable neurological outcome and survival in this rat model of cardiac arrest.

Naturally occurring hypothermia is more advantageous than fever in severe forms of lipopolysaccharide- and Escherichia coli-induced systemic inflammation

The natural switch from fever to hypothermia observed in the most severe cases of systemic inflammation is a phenomenon that continues to puzzle clinicians and scientists. The present study was the first to evaluate in direct experiments how the development of hypothermia vs. fever during severe forms of systemic inflammation impacts the pathophysiology of this malady and mortality rates in rats. Following administration of bacterial lipopolysaccharide (LPS; 5 or 18 mg/kg) or of a clinical Escherichia coli isolate (5 × 109or 1 × 1010CFU/kg), hypothermia developed in rats exposed to a mildly cool environment, but not in rats exposed to a warm environment; only fever was revealed in the warm environment. Development of hypothermia instead of fever suppressed endotoxemia in E. coli -infected rats, but not in LPS-injected rats. The infiltration of the lungs by neutrophils was similarly suppressed in E. coli -infected rats of the hypothermic group. These potentially beneficial effects came with costs, as hypothermia increased bacterial burden in the liver. Furthermore, the hypotensive responses to LPS or E. coli were exaggerated in rats of the hypothermic group. This exaggeration, however, occurred independently of changes in inflammatory cytokines and prostaglandins. Despite possible costs, development of hypothermia lessened abdominal organ dysfunction and reduced overall mortality rates in both the E. coli and LPS models. By demonstrating that naturally occurring hypothermia is more advantageous than fever in severe forms of aseptic (LPS-induced) or septic ( E. coli -induced) systemic inflammation, this study provides new grounds for the management of this deadly condition.

Propofol requirement titrated to bispectral index: a comparison between hypothermic and normothermic cardiopulmonary bypass

Though propofol requirement is expected to decrease during cardiopulmonary bypass (CPB), a few studies have failed to demonstrate this. The factors affecting pharmacokinetics of propofol and, therefore, the requirement, are different during hypothermic and normothermic CPB. We evaluated and compared the requirement of propofol during hypothermic and normothermic CPB. Fifty adult patients scheduled for elective cardiac surgery on CPB were recruited and randomly allocated into hypothermic CPB (28–300 C) (Group H) and normothermic CPB (35–370 C) (Group N) groups. Patients were induced and maintained with propofol titrated to maintain a target bispectral index (BIS) of 50 ± 10. Propofol requirement (mean ± SD) was similar in normothermic and hypothermic groups, both before CPB (4.9 ± 1.5 mg.kg−1hr−1 in Group N, 4.6 ± 1.5 mg.kg−1hr−1 in Group H) and after cessation of bypass (p > 0.05) (4.6 ± 1.8 mg.kg−1hr−1 in Group N and 4.3 ± 1.7 mg.kg−1hr−1 in Group H). CPB significantly reduced (p < 0.001) propofol requirements in both arms of the study (Group N: 2.9 ± 1.4 mg.kg−1hr−1and Group H: 1.3 ± 0.7 mg.kg−1hr−1). This reduction was more pronounced in the hypothermic group (p < 0.001). The BIS (median ± inter quartile range) remained constant during normothermic CPB (50 ± 8.8), but declined significantly during hypothermic CPB (41 ± 5.6) despite decreased usage of propofol during hypothermia. No patient had recall of intra-operative events. CPB decreases the magnitude of propofol requirements and the effect of hypothermic CPB is significantly more than that of normothermic CPB.

Effects of Increasing Concentrations of Propofol on Jugular Venous Bulb Oxygen Saturation in Neurosurgical Patients under Normothermic and Mildly Hypothermic Conditions

Background Recent evidence suggested that propofol can deteriorate the cerebral oxygen balance compared with inhalational anesthetics. However, dose-related influences of propofol on cerebral oxygen balances were not clearly investigated. In the current study, the authors investigated the effects of increasing concentrations of propofol on jugular venous bulb oxygen saturation (Sj(O2)) in neurosurgical patients under normothermic and mildly hypothermic conditions. Methods After institutional approval and informed consent were obtained, 30 adult patients undergoing elective craniotomy were studied. Patients were randomly allocated to either normothermic or hypothermic group (n = 15 in each group). In the normothermic and hypothermic groups, tympanic membrane temperature was maintained at 36.5 degrees and 34.5 degrees C, respectively. Sj(O2) was measured at predicted propofol concentrations of 3, 5, and 7 microg/ml using a target-controlled infusion system in both groups. Results At a predicted propofol concentration of 3 microg/ml, there were no significant differences in Sj(O2) values between the normothermic and hypothermic groups, although the incidence of desaturation (Sj(O2) &lt; 50%) was significantly higher in the normothermic group than in the hypothermic group (30% vs. 13%; P &lt; 0.05). Sj(O2) values and the incidence of desaturation remained unchanged during the changes in predicted propofol concentration from 3 to 7 microg/ml both in the normothermic and hypothermic groups. Conclusion The results indicated that the increasing concentrations of propofol did not affect Sj(O2) values in neurosurgical patients under normothermic and mildly hypothermic conditions.

Factors influencing the change in cerebral hemodynamics in pediatric patients during and after corrective cardiac surgery of congenital heart diseases by means of full-flow cardiopulmonary bypass

Background: The pathophysiology of hypoxic -ischemic brain injury in relation to extracorporeal circulation is multifactorial and can be interpreted, in part, as possible alteration in cerebral perfusion and inadequate oxygen delivery to the brain cells. The aim of this study was to evaluate influencing factors on the change in cerebral blood flow velocity (CBFV) patterns determined by transcranial Doppler sonography (TCD) in infants who undergo corrective cardiac surgery by means of full-flow cardio-pulmonary bypass (CPB). Methods: Included in the study were 67 neonates, infants, and children with a median age of 4 months (0.1-70 months), median weight of 4.8 kg (2.5-18.8 kg), and with cyanotic and noncyanotic congenital heart disease (CHD), who underwent surgical correction of CHD by means of CPB [flow rate 144± 47 ml/kg body weight (BW)] and the alpha-stat strategy. The patients were divided into three groups with respect to the minimum rectal temperature during perfusion: deep hypothermic CPB (< 18°C) n= 18, moderate hypothermic CPB (22-35°C) n= 29, normothermic CPB (36°C) n=20. Continuous determination of mean flow velocity (Vmean) in the middle cerebral artery (MCA) by TCD provided qualitative on-line information on cerebral perfusion. The pulsatility index (PI) was calculated in accordance with the formula: PI = Maximum flow velocity -end -diastolic flow velocity/Mean flow velocity and was used as a parameter for the qualitative assessment of cerebrovascular resistance after the end of CPB. Results: The Vmean was significantly increased 15 min after cross-clamping in the normothermic group ( p= 0.03) and decreased in the moderate hypothermic group ( p=0.02) and deep hypothermic group ( p= 0.009). The postoperative Vmean values correlated significantly with age ( r= 0.79, p< 0.0001), weight ( r= 0.75, p< 0.0001), bypass time ( r=-0.51, p=0.0006), and minimum rectal temperature ( r= 0.60, p= 0.0001). Mean arterial pressure and hemoglobin concentration, but not pCO2, seem to significantly influence the change in Vmean after the termination of CPB ( r= 0.5, p= 0.001; r= -0.55, p= 0.002, respectively). In comparison with the values at the start of CPB, the Vmeanwas significantly decreased after the end of CPB in the hypothermic and moderate hypothermic groups and still significantly elevated in the normothermic group. The age-independent PI was increased after termination of bypass in all groups ( p<0.05) and still slightly elevated after the end of operation in the hypothermic group ( p= 0.05). Conclusions: The changes in CBFV patterns before, during, and after the termination of CPB were dependent on age, weight, perfusion pressure, and degree of hypothermia during CPB.