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.

Hypothermia reduction during neonatal transport in a tertiary care center in South India: a quality improvement initiative

Background: Each degree drop in target temperature at admission increases mortality by 28% in neonates. Maintenance of target temperature during neonatal transport and at admission will pose an enormous challenge in developing countries due to various factors. The objective of the study was to decrease the incidence of hypothermia in transported babies at admission by 50% from a baseline of 64% over 12 months period. Prospective cohort study by QI methodology.Methods: Neonates transported to NICU from March 2019 – February 2020 were included. A baseline data was collected retrospectively to determine the incidence of existing hypothermic babies at admission. Problems were identified using Fishbone analysis. Evidence-based changes were implemented as per local needs in the Plan-Do Study cycle (PDSA) cycles.Results: A total of 96 babies were transported (62 babies during implementation, 34 during the sustenance Phase) during the study period. The mean (SD) gestation and birthweight was similar in the two groups. The distance travelled in kilometres in the hypothermic group was significantly more 7.3 (5.5) compared to the normothermic group 4.1(3.8) (p,0.01). We reduced the incidence of hypothermia from 64% to 16% over 12 months from the time of implementation. There was no correlation seen noted between hypothermia at admission and gestational age (r, - 0.18), birthweight (r, 0.04), or distance travelled in kilometres (r, 0.02). However, there was a positive correlation seen between adherence to the ‘5 Point -protocol’ and admission temperature (r, 0.86).Conclusions: Thermoregulation during neonatal transport is a huge challenge especially in the Indian scenario due to multiple incorrigible factors contributing to its high incidence even in the best of the centres. QI initiatives is a way forward to deal with some of these aspects. Involving the nursing team who forms the core team of neonatal transport is imperative.

Abstract 120: Effects of Therapeutic Hypothermia on Blood Parameters in Rats With Acute Hemorrhagic Shock

Background: Our research group recently observed that therapeutic hypothermia (TH) compared with normothermia improved long-term survival in an experimental model of hemorrhagic shock. The effect of TH on blood counts, blood gases and chemistries during the early phase of recovery from hemorrhagic shock are unknown. Therefore, the purpose of the present study was to examine the effects of TH on blood parameters in the early phase of resuscitation from hemorrhagic shock. Methods and results: Sprague Dawley rats (both genders) were randomly assigned to TH (n= 16) or normothermia group (n= 15). Rats were anesthetized with intraperitoneal ketamine and xylazine. After heparinizing, hemorrhagic shock was induced by withdrawing blood to a fixed mean blood pressure (MBP) of 30 mmHg for 30 minutes and then shed blood was reinfused. TH was started 5 minutes after MBP reached 30 mmHg. Core temperature was maintained at ~ 32 °C until blood volume was fully restored, after which the rats were allowed to warm back to normal temperature. In the normothermia group, body temperature was maintained at ~ 37°C. Arterial blood samples were collected 1 hour after resuscitation with shed blood. We found that pO2 (partial pressure of oxygen) was significantly higher in TH group versus the normothermic group. The rats in normothermic group had significantly elevated potassium, chloride and lactate levels and more negative base excess compared to rats that in TH group (Table). The neutrophil was lower in the TH group; the lymphocyte (%) was higher in the TH group. There were no significantly differences in pH, pCO2, sodium, calcium or glucose between the normothermia and TH groups. Conclusions: pO2 remained normal and levels of potassium, chloride, lactate and neutrophil were lower in TH group. These results may contribute to the protective effect of TH during hemorrhagic shock.

Abstract 100: Neuroprotection Provided by Transnasal Airflow-Induced Brain Cooling in a Model of Pediatric Cardiac Arrest

Introduction: High transnasal airflow at ambient temperature increases evaporative cooling of the nasal passages and drives a countercurrent heat exchange between cooled venous blood draining the nasal turbinates with cephalic arterial blood. Hypothesis: High transnasal airflow is not inferior to standard surface cooling in protecting the brain in an infant swine model of asphyxic cardiac arrest. Methods: Arterial O2 saturation was decreased to ~35% for 45 min followed by 7 min airway occlusion to produce asphyxic cardiac arrest in 2-week-old anesthetized piglets (4 kg). Viable neuronal counts were assessed at 6 days of recovery in 6 groups (n=5-9): 1) sham surgery, 2) normothermic recovery, 3) surface cooling to decrease rectal temperature from 38.5 to 34C between 10-120 min 4) transnasal cooling with airflow of 32 L/min from 10-120 min, 5) surface cooling onset delayed until 120 min ROSC, and 6) transnasal cooling delayed by 120 min ROSC. In all 4 cooling groups, hypothermia was sustained at 34C with surface cooling until 20 h ROSC followed by 6-8 h of rewarming. Results: Nasal airflow of 32 L/min decreased brain temperature from 38.3±0.3°C to 33.8±0.6 within 60 min without spatial temperature gradients in these 45-g brains. Surface cooling and transnasal airflow rescued the number of viable neurons in putamen from 38±23% (% of sham viable neurons; ±SD) in the normothermic group to 67±33% and 76±36%, respectively, when initiated at 10 min ROSC, and to 72±30% and 61±25%, respectively, when initiated at 120 min. In sensorimotor cortex, surface cooling and transnasal airflow rescued neurons from 56±36% in the normothermic group to 89±37% and 89±29%, respectively, when initiated at 10 min ROSC, and to 84±19% and 81±28%, respectively, when initiated at 120 min. Conclusions: The use of a high transnasal airflow is as effective as standard surface cooling when initiated at 10 or 120 min after ROSC in protecting vulnerable putamen and sensorimotor cortex from asphyxic cardiac arrest in infant piglets. Because of its simplicity, portability, and low cost, we postulate that transnasal cooling potentially could be deployed in the field by first responders for early initiation of brain cooling prior to maintenance with standard surface cooling after pediatric cardiac arrest.

Intraperitoneal mitomycin C improves survival compared to cytoreductive surgery alone in an experimental model of high-grade pseudomyxoma peritonei

Pseudomyxoma peritonei (PMP) is a rare cancer commonly originating from appendiceal neoplasms that presents with mucinous tumor spread in the peritoneal cavity. Patients with PMP are treated with curative intent by cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). The value of adding HIPEC to CRS has not been proven in randomized trials, and the objective of this study was to investigate the efficacy of intraperitoneal mitomycin C (MMC) and regional hyperthermia as components of this complex treatment. Xenograft tissue established from a patient with histologically high-grade PMP with signet ring cell differentiation was implanted intraperitoneally in 65 athymic nude male rats and the animals were stratified into three treatment groups; the cytoreductive surgery group (CRSG, CRS only), the normothermic group (NG, CRS and intraperitoneal chemotherapy perfusion (IPEC) with MMC at 35 ºC), and the hyperthermic group (HG, CRS and IPEC at 41 ºC). The main endpoints were survival and tumor weight at autopsy. Adequate imitation of the clinical setting and treatment approach was achieved. The median survival was 31 days in the CRSG, 60 days in NG and 67 days in HG. The median tumor weights at autopsy were 34 g in CRSG, 23 g NG and 20 g in HG. In conclusion, the addition of IPEC with MMC after CRS doubled the survival time and reduced tumor growth compared to CRS alone. Adding regional hyperthermia resulted in a modest improvement of treatment outcome.

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.

Selective head cooling during neonatal seizures prevents postictal cerebral vascular dysfunction without reducing epileptiform activity

Epileptic seizures in neonates cause cerebrovascular injury and impairment of cerebral blood flow (CBF) regulation. In the bicuculline model of seizures in newborn pigs, we tested the hypothesis that selective head cooling prevents deleterious effects of seizures on cerebral vascular functions. Preventive or therapeutic ictal head cooling was achieved by placing two head ice packs during the preictal and/or ictal states, respectively, for the ∼2-h period of seizures. Head cooling lowered the brain and core temperatures to 25.6 ± 0.3 and 33.5 ± 0.1°C, respectively. Head cooling had no anticonvulsant effects, as it did not affect the bicuculline-evoked electroencephalogram parameters, including amplitude, duration, spectral power, and spike frequency distribution. Acute and long-term cerebral vascular effects of seizures in the normothermic and head-cooled groups were tested during the immediate (2–4 h) and delayed (48 h) postictal periods. Seizure-induced cerebral vascular injury during the immediate postictal period was detected as terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive staining of cerebral arterioles and a surge of brain-derived circulating endothelial cells in peripheral blood in the normothermic group, but not in the head-cooled groups. During the delayed postictal period, endothelium-dependent cerebral vasodilator responses were greatly reduced in the normothermic group, indicating impaired CBF regulation. Preventive or therapeutic ictal head cooling mitigated the endothelial injury and greatly reduced loss of postictal cerebral vasodilator functions. Overall, head cooling during seizures is a clinically relevant approach to protecting the neonatal brain by preventing cerebrovascular injury and the loss of the endothelium-dependent control of CBF without reducing epileptiform activity.

Prolonged Therapeutic Hypothermia does not Adversely Impact Neuroplasticity after Global Ischemia in Rats

Hypothermia improves clinical outcome after cardiac arrest in adults. Animal data show that a day or more of cooling optimally reduces edema and tissue injury after cerebral ischemia, especially after longer intervention delays. Lengthy treatments, however, may inhibit repair processes (e.g., synaptogenesis). Thus, we evaluated whether unilateral brain hypothermia (∼33°C) affects neuroplasticity in the rat 2-vessel occlusion model. In the first experiment, we cooled starting 1 hour after ischemia for 2, 4, or 7 days. Another group was cooled for 2 days starting 48 hours after ischemia. One group remained normothermic throughout. All hypothermia treatments started 1 hour after ischemia equally reduced hippocampal CA1 injury in the cooled hemisphere compared with the normothermic side and the normothermic group. Cooling only on days 3 and 4 was not beneficial. Importantly, no treatment influenced neurogenesis (Ki67/Doublecortin (DCX) staining), synapse formation (synaptophysin), or brain-derived neurotropic factor (BDNF) immunohistochemistry. A second experiment confirmed that BDNF levels (ELISA) were equivalent in normothermic and 7-day cooled rats. Last, we measured zinc (Zn), which is important in plasticity, with X-ray fluorescence imaging in normothermic and 7-day cooled rats. Hypothermia did not alter the postischemic distribution of Zn within the hippocampus. In summary, cooling significantly mitigates injury without compromising neuroplasticity.