Development and internal validation of an algorithm to predict intraoperative risk of inadvertent hypothermia based on preoperative data

Intraoperative hypothermia increases perioperative morbidity and identifying patients at risk preoperatively is challenging. The aim of this study was to develop and internally validate prediction models for intraoperative hypothermia occurring despite active warming and to implement the algorithm in an online risk estimation tool. The final dataset included 36,371 surgery cases between September 2013 and May 2019 at the Vienna General Hospital. The primary outcome was minimum temperature measured during surgery. Preoperative data, initial vital signs measured before induction of anesthesia, and known comorbidities recorded in the preanesthetic clinic (PAC) were available, and the final predictors were selected by forward selection and backward elimination. Three models with different levels of information were developed and their predictive performance for minimum temperature below 36 °C and 35.5 °C was assessed using discrimination and calibration. Moderate hypothermia (below 35.5 °C) was observed in 18.2% of cases. The algorithm to predict inadvertent intraoperative hypothermia performed well with concordance statistics of 0.71 (36 °C) and 0.70 (35.5 °C) for the model including data from the preanesthetic clinic. All models were well-calibrated for 36 °C and 35.5 °C. Finally, a web-based implementation of the algorithm was programmed to facilitate the calculation of the probabilistic prediction of a patient’s core temperature to fall below 35.5 °C during surgery. The results indicate that inadvertent intraoperative hypothermia still occurs frequently despite active warming. Additional thermoregulatory measures may be needed to increase the rate of perioperative normothermia. The developed prediction models can support clinical decision-makers in identifying the patients at risk for intraoperative hypothermia and help optimize allocation of additional thermoregulatory interventions.

Neonatal Mortality is Modulated by Gestational Age, Birthweight and Fetal Heart Rate Abnormalities in the Low Resource Setting in Tanzania – a Five Year Review 2015-2019

Background Neonatal mortality (NM) remains a significant problem in low resource settings. Birth asphyxia (BA) and prematurity contribute significantly to NM. The study objectives were to determine first, the overall NM as well as yearly neonatal mortality rate from 2015 to 2019. Second, the impact of decreasing GA (<37 weeks) and BW (<2500 grams) on NM. Third, the contribution of intrapartum and delivery room (DR) factors and in particular fetal heart rate abnormalities (FHRT) on NM <7 days. Methods Retrospective cohort study. Labor and delivery room data were obtained from 2015 to 2019 and included BW, GA, fetal heart rate (FHRT) abnormalities, bag mask ventilation (BMV) during resuscitation, initial temperature, antenatal steroids use. Outcome was binary i.e. either death < 7 days or survival. Analysis included t tests, odds ratios (OR) and multiple logistic regression Results The overall neonatal mortality rate was 18/1000 livebirths over the five years. NM was significantly higher for newborns <37 versus ≥37 weeks, OR 10.5 (p<0.0001) and BW <2500 versus ≥2500g OR 9.9 (p<0.0001). For infants <1000g / <28 weeks, the neonatal mortality rate was ~ 588/1000 livebirths. Variables associated with NM included BW - odds of death decreased by 0.55 for every 500g increase in weight, by 0.89 for every week increase in GA, NM increased 6.8-fold with BMV, 2.6-fold with abnormal FHRT, 2.2 fold with no antenatal corticosteroid (ACS), 2.6-fold with moderate hypothermia (all <0.0001). Conclusion NM rates was predominantly modulated by decreasing BW and GA, with smaller/ less mature newborns 10-fold more likely to die. NM in term newborns is strongly associated with FHRT abnormalities and when coupled with respiratory depression suggests BA. In smaller newborns, lack of ACS and moderate hypothermia were additional contributing factors. A composite perinatal approach is essential to achieve a sustained reduction in NM.

Moderate Hypothermia Attenuates Pro-Arrhythmic Electromechanical Relations in the Left Ventricle – A Clinical Study

BackgroundTargeted temperature management is recommended after cardiac arrest, but the beneficial effects are controversial. The recently published TTM2 study reports that arrhythmias causing hemodynamic compromise are more common during moderate hypothermia. The causation is not explored. Experimentally, moderate hypothermia attenuates electromechanical relations with pro-arrhythmic impact. Mechanical systole outlasts the electrical systole to a greater extent giving increased electromechanical window positivity, and dispersion of electrical and mechanical activity are unaltered. In this prospective clinical study, we explored the effect of moderate hypothermia on electromechanical relations in un-insulted left ventricles. We hypothesized that during moderate hypothermia, prolongation of systolic duration would exceed electrical duration without dispersed electrical- or mechanical activity. Methods20 patients with normal left ventricular function, undergoing surgery on the ascending aorta and connected to cardiopulmonary bypass, were included. Measurements were obtained at 36 °C and 32 °C prior to aortic-repair, and at 36 °C after repair at spontaneous and paced heart rate 90 bpm. Comparable loading conditions were ensured and cardiopulmonary bypass was reduced to 20% of estimated maximum during the measurements. Global cardiac function was measured invasively and with echocardiography. Electromechanical window, dispersion of repolarization by ECG and mechanical dispersion by echocardiography, were calculated. ResultsAt moderate hypothermia (32°C), mechanical systolic prolongation exceeded electrical prolongation so that electromechanical window increased (29 ± 30 to 86 ± 50 ms, p <0.001). Dispersion of repolarization and mechanical dispersion remained unchanged. Myocardial function was preserved with maintained strain, fractional shortening and stroke volume. Similar electromechanical relations were present also at comparable increased heart rate during moderate hypothermia. After rewarming to 36°C, electromechanical alterations were reversed. ConclusionModerate hypothermia increased electromechanical window positivity. Dispersion of repolarisation, mechanical dispersion, and myocardial function were unchanged. Moderate hypothermia did not induce adverse electromechanical changes in the left ventricle during standardized conditions, but rather an attenuation of pro-arrhythmic electromechanical relations.

Acute Kidney Injury After Neonatal Aortic Arch Surgery: Deep Hypothermic Circulatory Arrest Versus Moderate Hypothermia With Distal Aortic Perfusion

Background: Acute kidney injury (AKI) is a common complication observed after neonatal aortic arch repair. We studied its incidence after procedures carried out using deep hypothermic circulatory arrest (DHCA) versus moderate hypothermia with distal aortic perfusion (MHDP), usually through the common femoral artery. In both groups, continuous regional cerebral perfusion (RCP) was used during the time required for aortic arch repair. Methods: A total of 125 neonates underwent aortic arch repair. Between 2007 and 2012, DHCA with RCP was used in 51 neonates. From 2013 to 2019, MHDP with RCP was performed on 74 newborns. Operative complexity was similar in both periods. Acute kidney injury was defined as a significant elevation of serum creatinine and was classified according to the neonatal modified n-KDIGO (neonatal Kidney Disease: Improving Global Outcomes) stages 1 to 3 (Kidney Disease Improving: Global Outcomes). Results: Acute kidney injury was observed in a total of 68 patients (68/125: 54.4%). In the majority (44/68: 64.7%), n-KDIGO stage 1 occurred. Stage 2 (n = 14) and stage 3 (n = 10) were observed more frequently after DHCA versus MHDP: 29.4% (15/51) versus 12.2% (9/74), P = .02. At cardiopulmonary bypass end, lactate levels were significantly higher ( P = .001) after DHCA: 3.4 (2.9-4.3) mmol/L compared to 2.7 (2.3-3.7) mmol/L after MHDP. Early mortality was 12% (15/125) in the entire cohort. It was 17.6% (9/51) after DHCA versus 8.1% (6/74) after MHDP, however not statistically significant ( P = .16). Conclusion: Mild (stage 1) AKI occurred frequently after neonatal aortic arch repair. The use of MHDP was associated with a significantly lower incidence of moderate (stage 2) and severe (stage 3) AKI forms.

Moderate Hypothermia Has the Potential to Reveal the Dominant/Submissive Relationship in a Co-Culture System Consisting of Osteoblasts and Endothelial Cells

Microvessels in bone are indispensable for maintaining bone homeostasis based on a dynamic remodeling system. In cell-based tissue engineering, vascularization into the regenerative bone is a key strategy to avoid hypoxia and necrosis around re-implanted tissues. Previous studies have shown that direct contact between osteoblasts and endothelial cells stimulates differentiation of both cell types. However, no studies have revealed the dominant/submissive relationship. In the present study, we examined the effect of hypothermia on monoculture and co-culture to assess which cells tightly coordinated osteogenesis and angiogenesis in the co-culture system. As for osteoblasts, exposure to hypothermia suppressed cellular proliferation, migration, and differentiation. Evaluation of the behavior of endothelial cells showed that hypothermia should not affect basic functions such as proliferation and migration. Under co-culture conditions, both osteogenic differentiation and the formation of vessel-like angiogenic structures were suppressed by hypothermia, but the spatial organization of alkaline phosphatase-positive cell clusters, which tend to localize around microvascular lumens, was not altered. These data suggest that hypothermia attenuates heterotypic intercellular crosstalk which robustly depends on osteoblasts to inhibit both osteogenesis and angiogenesis in the co-culture system. Taken together, this approach will provide new insights into the relationship between osteoblasts and endothelial cells in tissue engineering.

In vivo demonstration of a novel non-invasive model for inducing localized hypothermia to ameliorate hepatotoxicity

Moderate hypothermia (32 °C) has been previously shown to ameliorate drug-induced liver injuries in vitro. However, there are concerns regarding its clinical relevance as it remains a challenge to perform selective liver cooling in a non-invasive manner. To reconcile this dilemma, we propose the use of pulsed cooling for regional hypothermic conditioning in liver. This involves intermittent cooling applied in pulses of 15 min each, with a one-hour recovery interval between pulses. Cooling is achieved by applying ice packs to the cutaneous region overlying the liver. Through an in vivo C57BL/6NTac mouse study, we demonstrated the feasibility of attaining localized hypothermia close to the liver while maintaining core body temperature. This has successfully ameliorated acetaminophen-induced liver injury based on the liver function tests, liver histology and total weight change. Collectively, we provide a proof of concept for pulsed external localized cooling as being clinically actionable to perform induced selective hypothermia.

Therapeutic Hypothermia Reduces Peritoneal Dialysis Induced Myocardial Blood Flow Heterogeneity and Arrhythmia

Background: Moderate therapeutic hypothermia (TH) is a well-recognized cardio-protective strategy. The instillation of fluid into the peritoneum provides an opportunity to deliver moderate hypothermia as primary prevention against cardiovascular events. We aimed to to investigate both cardiac perfusion consequences (overall blood flow and detailed assessment of perfusion heterogeneity) and subsequently simulate the associated arrhythmic risk for patients undergoing peritoneal dialysis (PD) induced TH.Methods: Patients underwent high resolution myocardial perfusion scanning using high resolution 256 slice CT scanning, at rest and with adenosine stress. The first visit using the patient's usual PD regimen, on the second visit the same regime was utilized but with cooled peritoneal dialysate at 32°C. Myocardial blood flow (MBF) was quantified from generated perfusion maps, reconstructed in 3D. MBF heterogeneity was assessed by fractal dimension (FD) measurement on the 3D left ventricular reconstruction. Arrhythmogenicity was quantified from a sophisticated computational simulation using a multi-scale human 3D ventricle wedge electrophysiological computational model.Results: We studied 7 PD patients, mean age of 60 ± 7 and mean vintage dialysis of 23.6 ± 17.6 months. There were no significant different in overall segmental MBF between normothermic condition (NT) and TH. MBF heterogeneity was significantly decreased (−14%, p = 0.03) at rest and after stress (−14%, p = 0.03) when cooling was applied. Computational simulation showed that TH allowed a normalization of action potential, QT duration and T wave.Conclusion: TH-PD results in moderate hypothermia leading to a reduction in perfusion heterogeneity and simulated risk of non-terminating malignant ventricular arrhythmias.