Is Deep Hypothermic Cardiac Arrest Mandatory in Aortic Arch Surgeries?

Cannulation strategies in aortic arch surgeries are a matter of immense discussion. Majority of time deep hypothermic circulatory arrest (DHCA) is the way out, but it does come with its set of demerits. Here we demonstrate a case with aortic arch dissection dealt with dual cannulation strategy in axillary and femoral artery without need for DHCA and ensuring complete neuroprotection of brain and spinal cord without hinderance of time factor. Inception of new ideas like this may decrease the need for DHCA and hence its drawbacks, thus decreasing the morbidity and mortality associated.

Cannula Placement for Cerebral Protection Without Circulatory Arrest in Patients Undergoing Hemiarch Aortic Aneurysm Repair.

BACKGROUND: Aortic aneurysms involving the proximal aortic arch, which require hemiarch-type repair, typically require circulatory arrest with antegrade cerebral perfusion. Left carotid antegrade cerebral perfusion (LCP) via distal arch cannulation without circulatory arrest was used in this study's patient population. The goal was to assess the operative efficiency and clinical outcomes of using a distal arch cannulation technique that would not require any hypothermic circulatory arrest (HCA) time compared with more traditional brachiocephalic artery cannulation with right-sided unilateral antegrade cerebral perfusion (RCP) and HCA. METHODS: A single-center retrospective review of patients with replacement of the distal ascending aorta involving the proximal arch was performed. Patients with an intramural hematoma or dissection were excluded. Between January 2015 and December 2019, 68 adult patients had undergone a hemiarch repair because of aneurysmal disease. Analysis of baseline demographics, operative data, and clinical outcomes was performed. RESULTS: Comparing the 68 patients: 21 patients were treated with RCP (via brachiocephalic artery graft with HCA), and 47 patients were treated with LCP (via distal aortic arch cannulation with cross-clamp between the brachiocephalic and left common carotid arteries without HCA). Baseline characteristics and outcomes were evaluated for both groups. The LCP group was younger (LCP median [IQR] age, 60 [53-65] years vs RCP median [IQR] age, 67 [59-71] years]. Sex, race, body mass index, comorbidities, and ejection fraction were similar between the groups. Cardiopulmonary bypass time (LCP, 123 minutes vs RCP, 149 minutes) and unilateral cerebral perfusion time (LCP, 17 minutes vs RCP, 22 minutes) were longer in the RCP group. Bleeding, prolonged ventilatory support, kidney failure, and length of stay were similar. In-hospital mortality was 2% in the LCP group vs 0% in the RCP group. Stroke occurred in 2 patients (4.2%) in the LCP group and in 0% of the RCP group. Mortality at 6 months in the LCP and RCP groups was 3% and 10%, respectively. CONCLUSION: Distal arch cannulation with LCP without HCA is a reasonable and safe alternative strategy for patients requiring hemiarch replacement for aneurysmal disease. This technique may provide additional benefits by avoiding circulatory arrest in these complex cases.

The Precision Between Transcutaneous Carbon Dioxide Versus PaCO2 in Infants Undergoing Therapeutic Hypothermia.

BACKGROUND: Infants with hypoxic-ischemic encephalopathy are often treated with therapeutic hypothermia and high-frequency ventilation. Fluctuations in PaCO2 during therapeutic hypothermia are associated with poor neurodevelopmental outcomes. Transcutaneous CO2 monitors offer a noninvasive estimate of PaCO2 represented by transcutaneously measured partial pressure of carbon dioxide (PtcCO2 ). We aimed to assess the precision between PtcCO2 and PaCO2 values in neonates undergoing therapeutic hypothermia. METHODS: This was a retrospective chart review of 10 neonates who underwent therapeutic hypothermia requiring respiratory support over 2 y. A range of 2-27 simultaneous PtcCO2 and PaCO2 pairs of measurements per neonate were analyzed via linear mixed models and a Bland-Altman plot for multiple observations per neonate. RESULTS: A linear mixed-effect model demonstrated that PtcCO2 and PaCO2 (controlling for sex) were similar. The 95% CI of the mean difference ranged from -2.3 to 5.7 mm Hg (P = .41). However, precision was poor as the PtcCO2 ranged from > 18 mm Hg to < 13 mm Hg than PaCO2 values for 95% of observations. CONCLUSIONS: The neonates' PtcCO2 was as much as 18 mm Hg higher to 13 mm Hg lower than the PaCO2 95% of the time. Transcutaneous CO2 monitoring may not be a good trending tool, nor is it appropriate for estimating PaCO2 in patients undergoing therapeutic hypothermia.

Is Deep Hypothermic Cardiac Arrest Mandatory in Aortic Arch Surgeries?

ABSTRACT Cannulation strategies in aortic arch surgeries are a matter of immense discussion. Majority of time deep hypothermic circulatory arrest (DHCA) is the way out, but it does come with its set of demerits. Here we demonstrate a case with aortic arch dissection dealt with dual cannulation strategy in axillary and femoral artery without need for DHCA and ensuring complete neuroprotection of brain and spinal cord without hinderance of time factor. Inception of new ideas like this may decrease the need for DHCA and hence its drawbacks, thus decreasing the morbidity and mortality associated.

The Learning Curve of Total Arch Replacement via Single Upper Hemisternotomy Approach in Aortic Dissection.

Purpose: Upper hemisternotomy (UHS) has benefits over conventional full sternotomy because it ameliorates trauma during cardiac surgery. Owing to its challenging and technically demanding nature, this incision in acute type A aortic dissection (ATAAD) has rarely been reported. This study aimed to analyze the learning curve of total arch replacement (TAR) with moderate hypothermic circulatory arrest via a single UHS approach, which is necessary to guide the training of surgeons in adopting minimally invasive procedures. Patients and Methods: A total of 202 consecutive patients who were definitively diagnosed with ATAAD between July 2016 and June 2021 were enrolled in this retrospective analysis. Patients were divided into three groups based on cumulative sum plots for circulatory arrest time in chronological order. Perioperative characteristics were compared between the groups. Results: There was significant difference in the circulatory arrest time and cross-clamp time respectively among three groups (39.0 min vs 28.0 min vs 15.0 min, P < 0.001; 104.5 min vs 106.2 min vs 84.1 min, P < 0.001). The ventilation time and first 24-h chest tube drainage were statistically different among groups (35.5 h vs 24.0 h vs 19.0 h, P = 0.031; 220.0 mL vs 192.5 mL vs 125.5 mL, P = 0.043). No other clinical outcome was observed as significant difference. Conclusion: A cardiac surgeon can convert a conventional full sternotomy to a single UHS for TAR after experiencing a learning curve, to ensure patient safety. The mastery of this minimally invasive surgical technique may be beneficial for the prognosis of patients with ATAAD.

Long-term survival after cardiac arrest in patients undergoing emergent coronary angiography.

AIM: To determine long-term survival of patients after cardiac arrest undergoing emergent coronary angiography and therapeutic hypothermia. METHODS: We analysed data from patients treated within the regional STEMI Network from January 2015 to December 2020. The primary endpoint was all-cause mortality at median follow-up. Secondary endpoints were periprocedural complications (arrhythmias, pulmonary edema, cardiogenic shock, mechanical complication, stent thrombosis, reinfarction, bleeding) and 6-month all-cause death. A landmark analysis was performed, studying two time periods; 0-6 months and beyond 6 months. RESULTS: From a total of 24,125 patients in the regional STEMI network, 494 patients who suffered from cardiac arrest were included and divided into two groups: treated with (n = 119) and without therapeutic hypothermia (n = 375). At median follow-up (16.0 [0.2-33.3] months), there was no difference in the adjusted mortality rate between groups (51.3 % with hypothermia vs 48.0 % without hypothermia; HRadj1.08 95%CI [0.77-1.53]; p = 0.659). There was a higher frequency of bleeding in the hypothermia group (6.7 % vs 1.1 %; ORadj 7.99 95%CI [2.05-31.2]; p = 0.002), without difference for the rest of periprocedural complications. At 6-month follow-up, adjusted all-cause mortality rate was similar between groups (46.2 % with hypothermia vs 44.5 % without hypothermia; HRadj1.02 95%CI [0.71-1.47]; p = 0.900). Also, no differences were observed in the adjusted mortality rate between 6 months and median follow-up (9.4 % with hypothermia vs 6.3 % without hypothermia; HRadj2.02 95%CI [0.69-5.92]; p = 0.200). CONCLUSIONS: In a large cohort of patients with cardiac arrest within a regional STEMI network, those treated with therapeutic hypothermia did not improve long-term survival compared to those without hypothermia.

[Procedure after successful cardiopulmonary resuscitation-Cooling or no more cooling?] / Vorgehen nach erfolgreicher Reanimation ­ kühlen oder nicht mehr kühlen?

Approximately 84 out of 100,000 inhabitants in Europe suffer from an out of hospital cardiac arrest (OHCA) each year. The mortality after cardiac arrest (CA) is high and is particularly determined by the predominant cardiogenic shock condition and hypoxic ischemic encephalopathy. For almost two decades hypothermic temperature control was the only neuroprotective intervention recommended in guidelines for postresuscitation care; however, recently published studies failed to demonstrate any improvement in the neurological outcome with hypothermia in comparison to strict normothermia in postresuscitation treatment. According to the European Resuscitation Council (ERC) and European Society of Intensive Care Medicine (ESICM) guidelines published in 2022, unconscious adults after CA should be treated with temperature management and avoidance of fever; however, many questions remain open regarding the optimal target temperature, the cooling methods and the optimal duration. Despite these currently unanswered questions, a structured and high-quality postresuscitation care that includes a targeted temperature management should continue to be provided for all patients in the postresuscitation phase, independent of the selected target temperature. Furthermore, fever avoidance remains an important component of postresuscitation care.

Comparison between selective head cooling and whole-body cooling in neonatal therapeutic hypothermia / Comparação entre resfriamento seletivo da cabeça e resfriamento de corpo inteiro na hipotermia terapêutica neonatal

INTRODUCTION: Experimental evidence, as well as improved clinical studies of the reduction of brain injury and, improves the neurological outcome, in newborns with hypoxic-ischemic encephalopathy (HIE) occurring in therapeutic hypothermia (TH). OBJECTIVE: To verify the potential of hypothermic hypoxic-ischemic encephalopathy (HIE) therapy in neonatal asphyxia, based on literature data, comparing the benefits between selective head cooling (SHC) and whole-body cooling (WBC), see that the use of TH as a standard treatment in newborns with moderate or severe HIE has been adopted. METHODS: A search was performed in the PubMed and SciELO databases of human studies, using the keywords "Therapeutic Hypothermia", "Induced Hypothermia", and "Hypoxic-Ischemic Encephalopathy", "Selective cooling of the head", "Total body cooling" and its variables. RESULTS: Eleven articles were selected to compose the review, after detailed reading. There is a consensus, that the reduction of the risk of death or disability at 18 months of life in neonates with moderate to severe HIE, occurs to TH through the techniques of WBC or SHC. It was found in the studies that there is no difference in terms of adverse effects between the two methods. As for radiological changes, such as hypoxic-ischemic injuries and the incidence of seizures after cooling, they are more frequent with SHC. CONCLUSION: Both WBC and SHC demonstrated neuroprotective properties, although WBC provides a broader area of brain protection. However, no significant differences were found between the methods in terms of adverse effects and beneficial short or long-term results.

INTRODUÇÃO: Evidências experimentais, assim como estudos clínicos, sugerem a redução da lesão cerebral e melhora do desfecho neurológico, em recém-nascidos com encefalopatia isquêmica hipóxica (EHI) submetidos à hipotermia terapêutica (HT). OBJETIVO: Verificar a potencialidade da terapia hipotérmica de encefalopatia hipóxico-isquêmica (EHI) na asfixia neonatal, com base em dados da literatura, comparando os benefícios entre o resfriamento seletivo da cabeça (RSC) e o resfriamento de corpo inteiro (RCI), visto que o uso de hipotermia terapêutica (HT) como tratamento padrão em recém-nascidos com EHI moderada ou grave tem sido amplamente adotada. MÉTODOS: Foi realizada uma busca nas bases de dados PubMed e SciELO de estudos em humanos, utilizando-se as palavras-chave "Therapeutic Hypothermia", "Induced Hypothermia", "Hypoxic-Ischemic Encephalopathy", "selective head cooling", "whole body cooling" e suas respectivas variáveis. RESULTADOS: Foram selecionados 11 artigos para compor a revisão, após leitura detalhada. É consenso, a redução do risco de morte ou incapacidade aos 18 meses de vida nos neonatos com EHI moderado a grave, submetidos à HT através das técnicas de RCI ou RSC. Constatou-se diante dos estudos que não há diferença em termos de efeitos adversos entre os dois métodos. Quanto às alterações radiológicas, as lesões hipóxico-isquêmicas e incidência de convulsões após o resfriamento são mais frequentes com o RSC. CONCLUSÃO: Tanto RCI quanto o RSC demonstraram propriedades neuroprotetoras, embora o RCI proporcione uma área de proteção cerebral mais ampla. No entanto, não foram constatadas diferenças significativas entre os métodos quanto a efeitos adversos e a resultados benéficos em curto e longo prazo.

Robotic Level IV Inferior Vena Cava Thrombectomy Using an Intrapericardial Control Technique: Is It Safe Without Cardiopulmonary Bypass?

PURPOSE: We introduce an intrapericardial control technique using a robotic approach in the surgical treatment of renal tumor with level IV inferior vena cava thrombus to decrease the severe complications associated with cardiopulmonary bypass and deep hypothermic circulatory arrest. MATERIALS AND METHODS: Eight patients with level IV inferior vena cava thrombi not extending into the atrium underwent transabdominal-transdiaphragmatic robot-assisted inferior vena cava thrombectomy obviating cardiopulmonary bypass/deep hypothermic circulatory arrest (cardiopulmonary bypass-free group) by an expert team comprising urological, hepatobiliary, and cardiovascular surgeons. The central diaphragm tendon and pericardium were transabdominally dissected until the intrapericardial inferior vena cava were exposed and looped proximal to the cranial end of the thrombi under intraoperative ultrasound guidance. As controls, 14 patients who underwent robot-assisted inferior vena cava thrombectomy with cardiopulmonary bypass (cardiopulmonary bypass group) and 25 patients who underwent open thrombectomy with cardiopulmonary bypass/deep hypothermic circulatory arrest (cardiopulmonary bypass/deep hypothermic circulatory arrest group) were included. Clinicopathological, operative, and survival outcomes were retrospectively analyzed. RESULTS: Eight robot-assisted inferior vena cava thrombectomies were successfully performed without cardiopulmonary bypass, with 1 open conversion. The median operation time and first porta hepatis occlusion time were shorter, and estimated blood loss was lower in the cardiopulmonary bypass-free group as compared to the cardiopulmonary bypass group (540 vs 586.5 minutes, 16.5 vs 38.5. minutes, and 2,050 vs 3,500 mL, respectively). Severe complications (level IV-V) were also lower in the cardiopulmonary bypass-free group than in cardiopulmonary bypass and cardiopulmonary bypass/deep hypothermic circulatory arrest groups (25% vs 50% vs 40%). Oncologic outcomes were comparable among the 3 groups in short-term follow-up. CONCLUSIONS: Pure transabdominal-transdiaphragmatic robot-assisted inferior vena cava thrombectomy without cardiopulmonary bypass/deep hypothermic circulatory arrest represents as an alternative minimally invasive approach for selected level IV inferior vena cava thrombi.

Effect of selective cerebral mild hypothermia on SUMO2/3 modification of Drp1 in a rat model of cerebral ischemia-reperfusion / 中华麻醉学杂志

Objective:To evaluate the effect of selective cerebral mild hypothermia on small ubiquitin-like modifier 2/3 (SUMO2/3) modification of dynamin-related protein 1 (Drp1) in a rat model of cerebral ischemia-reperfusion (I/R).Methods:Sixty clean-grade healthy male Sprague-Dawley rats, aged 6-8 weeks, weighing 240-260 g, were divided into 4 groups ( n=15 each) using a random number table method: sham operation group (S group), cerebral I/R group (I/R group), selective cerebral mild hypothermia group (HT group) and normal temperature group (NT group). The operation was performed under the monitoring of cerebral temperature and rectal temperature.Only the cervical blood vessels were exposed in S group, while focal cerebral I/R was induced by 2 h middle cerebral artery occlusion (MCAO) followed by 24 h reperfusion in anesthetized animals in the other three groups.In HT group and NT group, 4 and 37 ℃ normal saline was perfused through the left internal carotid artery at a rate of 80 ml·kg -1·h -1 for 15 min, respectively. Modified neurological severity score (mNSS) was assessed at 24 h of reperfusion. Then the rats were sacrificed under deep anesthesia, brains were removed, brain tissues were obtained for determination of the percentage of cerebral infarct size (by TTC staining), and the ischemic penumbra tissues in the cerebral cortex were removed for examination of the ultra-structural changes of mitochondria (with a transmission electron microscope) and for determination of the SUMO2/3 modification of Drp1 (by CO-IP), expression of total Drp1 (T-Drp1) and total cytochrome c (T-Cytc) (by Western blot), and expression of mitochondrial outer membrane Drp1 (M-Drp1) and cytoplasmic Cytc (C-Cytc) (by Western blot) after isolation of mitochondria and cytoplasm. Results:Compared with S group, the mNSS and percentage of cerebral infarct size were significantly increased, the expression of M-Drp1, T-Drp1, C-Cytc and T-Cytc was up-regulated, and SUMO2/3 modification of Drp1 in ischemic penumbra area was increased ( P<0.05), the fragmentation of mitochondria was aggravated, and cristae rupture and vacuolation were obvious in the other three groups. Compared with I/R group, the mNSS and percentage of cerebral infarct size were significantly decreased, the expression of M-Drp1, T-Drp1, C-Cytc and T-Cytc was down-regulated, SUMO2/3 modification of Drp1 was increased ( P<0.05), the fragmentation of mitochondria was significantly attenuated, and cristae rupture and vacuolation were weakened in HT group. There were no significant differences in these detection parameters between NT group and I/R group ( P>0.05). Conclusions:The mechanism by which selective cerebral mild hypothermia alleviates the cerebral I/R injury is related to increased SUMO2/3 modification of Drp1, decreased binding of Drp1 to mitochondrial outer membrane, and reduced mitochondrial excessive fission in rats.

Effects of mild hypothermia on microglia polarization and JAK2/STAT3 signaling pathway during cerebral ischemia-reperfusion in rats / 中华麻醉学杂志

Objective:To investigate the effects of mild hypothermia on microglia polarization and janus kinase 2/signal transduction and transcriptional activation factor 3 (JAK2/STAT3) signaling pathway during cerebral ischemia-reperfusion (I/R) in rats.Methods:Forty-five clean-grade healthy male Sprague-Dawley rats, aged 8 weeks, weighing 260-280 g, were divided into 3 groups ( n=15 each) by the random number table method: sham operation group (S group), cerebral I/R group (I/R) and mild hypothermia group (H group). In I/R group and H group, cerebral I/R was induced by middle cerebral artery occlusion using a nylon thread in anesthetized animals, the nylon thread was removed to restore the perfusion after 2 h of occlusion, and the rectal temperature was maintained at 36-37 ℃ during the period. Group H was wiped with 75% alcohol for 3 h starting from the time point immediately after reperfusion, and the rectal temperature was maintained at 32-33℃. Modified neurological severity score (mNSS) was evaluated at 24 h of reperfusion. Animals were then sacrificed for determination of the cerebral infarct size (using TTC staining), expression of M1 marker inducible nitric oxide synthase (iNOS), M2 marker arginase 1(Arg-1), phosphorylated JAK2(p-JAK2)and phosphorylated STAT3(p-STAT3)(by Western blot), expression of iNOS mRNA and Arg-1 mRNA (by quantitative polymerase chain reaction), and contents of interleukin-6 (IL-6) and IL-10 (by enzyme-linked immunosorbent assay). Results:Compared with group S, mNSS and cerebral infarct size were significantly increased, the expression of iNOS, Arg-1 protein and mRNA in cerebral ischemic penumbral zone was up-regulated, and the p-JAK2/JAK2 ratio, p-STAT3/STAT3 ratio, and contents of IL-6 and IL-10 were increased in the other two groups ( P<0.05). Compared with I/R group, mNSS and cerebral infarct size were significantly decreased, the expression of iNOS protein and mRNA in cerebral ischemic penumbral zone was down-regulated, the expression of Arg-1 and mRNA was up-regulated, and the p-JAK2/JAK2 ratio, p-STAT3/STAT3 ratio and IL-6 content were decreased, and the IL-10 content was increased in group H ( P<0.05). Conclusions:Mild hypothermia can promote the polarization shift of microglia from M1 to M2 phenotype during cerebral I/R and inhibit the central inflammatory responses, and the mechanism may be related to inhibition of JAK2/STAT3 signaling pathway in rats.

Role of SIRT1/NF-κB signaling pathway in mild hypothermia-induced promotion of microglial polarization during oxygen-glucose deprivation and restoration / 中华麻醉学杂志

Objective:To evaluate the role of Sirtuin 1/nuclear factor κB (SIRT1/NF-κB) signaling pathway in mild hypothermia-induced promotion of microglial polarization during oxygen-glucose deprivation and restoration (OGD/R).Methods:The well-grown BV2 microglia were divided into 4 groups ( n=36 each) using the random number table method: control group (group C), OGD/R group (group O), mild hypothermia group (group M), and mild hypothermia+ SIRT1 specific inhibitor EX527 group (group ME). Cells in group C were commonly cultured without any treatment. Cells in group O were subjected to 3 h of OGD followed by 21 h of restoration of O 2-glucose supply at 37 ℃. Cells in group M were subjected to 3 h of OGD followed by 21 h of restoration of O 2-glucose supply at 33 ℃. Cells in group ME were co-cultured with inhibitor EX527 (final concentration 5 nmol/L) for 12 h in the medium before OGD/R, and the other procedures were conducted as previously described in group M. The cell survival rate was detected by CCK-8 assay. The levels of tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β) and interleukin-10 (IL-10) in supernatant were detected by enzyme-linked immunosorbent assay. The expression of CD206, CD32, inducible nitric oxide synthase (iNOS) and arginine synthase 1 (Arg-1) mRNA was detected by quantitative real-time polymerase chain reaction. The expression of CD206 and CD32 was detected by immunofluorescent staining. The expression of iNOS, Arg-1, SIRT1, NF-κB p65 (p65) and acetylated NF-κB (Ac-p65) was detected by Western blot. Results:Compared with group C, the cell survival rate was significantly decreased, the concentrations of TNF-α, IL-6 and IL-10 in the supernatant were increased, the expression of CD206, Arg-1, CD32 and iNOS was up-regulated, the expression of SIRT1 was down-regulated, and the Ac-p65/p65 ratio was increased in group O ( P<0.05). Compared with group O, the cell survival rate was significantly increased, the concentrations of TNF-α and IL-6 in the supernatant were decreased, the concentration of IL-10 was increased, the expression of CD206, Arg-1 and SIRT1 was up-regulated, the expression of CD32 and iNOS was down-regulated, and the Ac-p65/p65 ratio was decreased in group M ( P<0.05). Compared with group M, the cell survival rate was significantly decreased, the concentrations of TNF-α and IL-6 in the supernatant were increased, the concentration of IL-10 was decreased, the expression of CD206, Arg-1 and SIRT1 was down-regulated, the expression of CD32 and iNOS was up-regulated, and the Ac-p65/p65 ratio was increased in group ME ( P<0.05). Conclusions:SIRT1/NF-κB signaling pathway is involved in mild hypothermia-induced promotion of microglial polarization during OGD/R.

Temperature Control After In-Hospital Cardiac Arrest: A Randomized Clinical Trial.

BACKGROUND: This study was conducted to determine the effect of hypothermic temperature control after in-hospital cardiac arrest (IHCA) on mortality and functional outcome as compared with normothermia. METHODS: An investigator initiated, open-label, blinded-outcome-assessor, multicenter, randomized controlled trial comparing hypothermic temperature control (32-34°C) for 24 h with normothermia after IHCA in 11 hospitals in Germany. The primary endpoint was all-cause mortality after 180 days. Secondary end points included in-hospital mortality and favorable functional outcome using the Cerebral Performance Category scale after 180 days. A Cerebral Performance Category score of 1 or 2 was defined as a favorable functional outcome. RESULTS: A total of 1055 patients were screened for eligibility and 249 patients were randomized: 126 were assigned to hypothermic temperature control and 123 to normothermia. The mean age of the cohort was 72.6±10.4 years, 64% (152 of 236) were male, 73% (166 of 227) of cardiac arrests were witnessed, 25% (57 of 231) had an initial shockable rhythm, and time to return of spontaneous circulation was 16.4±10.5 minutes. Target temperature was reached within 4.2±2.8 hours after randomization in the hypothermic group and temperature was controlled for 48 hours at 37.0°±0.9°C in the normothermia group. Mortality by day 180 was 72.5% (87 of 120) in hypothermic temperature control arm, compared with 71.2% (84 of 118) in the normothermia group (relative risk, 1.03 [95% CI, 0.79-1.40]; P=0.822). In-hospital mortality was 62.5% (75 of 120) in the hypothermic temperature control as compared with 57.6% (68 of 118) in the normothermia group (relative risk, 1.11 [95% CI, 0.86-1.46, P=0.443). Favorable functional outcome (Cerebral Performance Category 1 or 2) by day 180 was 22.5% (27 of 120) in the hypothermic temperature control, compared with 23.7% (28 of 118) in the normothermia group (relative risk, 1.04 [95% CI, 0.78-1.44]; P=0.822). The study was prematurely terminated because of futility. CONCLUSIONS: Hypothermic temperature control as compared with normothermia did not improve survival nor functional outcome at day 180 in patients presenting with coma after IHCA. The HACA in-hospital trial (Hypothermia After Cardiac Arrest in-hospital) was underpowered and may have failed to detect clinically important differences between hypothermic temperature control and normothermia. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique Identifier: NCT00457431.

Functional recovery after accidental deep hypothermic cardiac arrest: Comparison of different cardiopulmonary bypass rewarming strategies.

Introduction: Using a porcine model of accidental immersion hypothermia and hypothermic cardiac arrest (HCA), the aim of the present study was to compare effects of different rewarming strategies on CPB on need for vascular fluid supply, level of cardiac restitution, and cerebral metabolism and pressures. Materials and Methods: Totally sixteen healthy, anesthetized castrated male pigs were immersion cooled to 20°C to induce HCA, maintained for 75 min and then randomized into two groups: 1) animals receiving CPB rewarming to 30°C followed by immersion rewarming to 36°C (CPB30, n = 8), or 2) animals receiving CPB rewarming to 36°C (CPB36, n = 8). Measurements of cerebral metabolism were collected using a microdialysis catheter. After rewarming to 36°C, surviving animals in both groups were further warmed by immersion to 38°C and observed for 2 h. Results: Survival rate at 2 h after rewarming was 5 out of 8 animals in the CPB30 group, and 8 out of 8 in the CPB36 group. All surviving animals displayed significant acute cardiac dysfunction irrespective of rewarming method. Differences between groups in CPB exposure time or rewarming rate created no differences in need for vascular volume supply, in variables of cerebral metabolism, or in cerebral pressures and blood flow. Conclusion: As 3 out of 8 animals did not survive weaning from CPB at 30°C, early weaning gave no advantages over weaning at 36°C. Further, in surviving animals, the results showed no differences between groups in the need for vascular volume replacement, nor any differences in cerebral blood flow or pressures. Most prominent, after weaning from CPB, was the existence of acute cardiac failure which was responsible for the inability to create an adequate perfusion irrespective of rewarming strategy.

Influence of temperature management at 33 °C versus normothermia on survival in patients with vasopressor support after out-of-hospital cardiac arrest: a post hoc analysis of the TTM-2 trial.

BACKGROUND: Targeted temperature management at 33 °C (TTM33) has been employed in effort to mitigate brain injury in unconscious survivors of out-of-hospital cardiac arrest (OHCA). Current guidelines recommend prevention of fever, not excluding TTM33. The main objective of this study was to investigate if TTM33 is associated with mortality in patients with vasopressor support on admission after OHCA. METHODS: We performed a post hoc analysis of patients included in the TTM-2 trial, an international, multicenter trial, investigating outcomes in unconscious adult OHCA patients randomized to TTM33 versus normothermia. Patients were grouped according to level of circulatory support on admission: (1) no-vasopressor support, mean arterial blood pressure (MAP) ≥ 70 mmHg; (2) moderate-vasopressor support MAP < 70 mmHg or any dose of dopamine/dobutamine or noradrenaline/adrenaline dose ≤ 0.25 µg/kg/min; and (3) high-vasopressor support, noradrenaline/adrenaline dose > 0.25 µg/kg/min. Hazard ratios with TTM33 were calculated for all-cause 180-day mortality in these groups. RESULTS: The TTM-2 trial enrolled 1900 patients. Data on primary outcome were available for 1850 patients, with 662, 896, and 292 patients in the, no-, moderate-, or high-vasopressor support groups, respectively. Hazard ratio for 180-day mortality was 1.04 [98.3% CI 0.78-1.39] in the no-, 1.22 [98.3% CI 0.97-1.53] in the moderate-, and 0.97 [98.3% CI 0.68-1.38] in the high-vasopressor support groups with regard to TTM33. Results were consistent in an imputed, adjusted sensitivity analysis. CONCLUSIONS: In this exploratory analysis, temperature control at 33 °C after OHCA, compared to normothermia, was not associated with higher incidence of death in patients stratified according to vasopressor support on admission. Trial registration Clinical trials identifier NCT02908308 , registered September 20, 2016.

Cooling to Hypothermic Circulatory Arrest by Immersion vs. Cardiopulmonary Bypass (CPB): Worse Outcome After Rewarming in Immersion Cooled Pigs.

Introduction: Cooling by cardiopulmonary bypass (CPB) to deep hypothermic cardiac arrest (HCA) for cardiac surgical interventions, followed by CPB-rewarming is performed on a routine basis with relatively low mortality. In contrast, victims of deep accidental hypothermia rewarmed with CPB generally have a much worse prognosis. Thus, we have developed an intact pig model to compare effects on perfusion pressures and global oxygen delivery (DO2) during immersion cooling versus cooling by CPB. Further, we compared the effects of CPB-rewarming between groups, to restitute cardiovascular function, brain blood flow, and brain metabolism. Materials and Methods: Total sixteen healthy, anesthetized juvenile (2-3 months) castrated male pigs were randomized in a prospective, open placebo-controlled experimental study to immersion cooling (IMM c , n = 8), or cooling by CPB (CPB c , n = 8). After 75 minutes of deep HCA in both groups, pigs were rewarmed by CPB. After weaning from CPB surviving animals were observed for 2 h before euthanasia. Results: Survival rates at 2 h after completed rewarming were 4 out of 8 in the IMM c group, and 8 out of 8 in the CPB c group. Compared with the CPB c -group, IMM c animals showed significant reduction in DO2, mean arterial pressure (MAP), cerebral perfusion pressure, and blood flow during cooling below 25°C as well as after weaning from CPB after rewarming. After rewarming, brain blood flow returned to control in CPB c animals only, and brain micro dialysate-data showed a significantly increase in the lactate/pyruvate ratio in IMM c vs. CPB c animals. Conclusion: Our data indicate that, although global O2 consumption was independent of DO2, regional ischemic damage may have taken place during cooling in the brain of IMM c animals below 25°C. The need for prolonged extracorporeal membrane oxygenation (ECMO) should be considered in all victims of accidental hypothermic arrest that cannot be weaned from CPB immediately after rewarming.

Hypothermia for Patients Requiring Evacuation of Subdural Hematoma: A Multicenter Randomized Clinical Trial.

BACKGROUND: Hypothermia is neuroprotective in some ischemia-reperfusion injuries. Ischemia-reperfusion injury may occur with traumatic subdural hematoma (SDH). This study aimed to determine whether early induction and maintenance of hypothermia in patients with acute SDH would lead to decreased ischemia-reperfusion injury and improve global neurologic outcome. METHODS: This international, multicenter randomized controlled trial enrolled adult patients with SDH requiring evacuation of hematoma within 6 h of injury. The intervention was controlled temperature management of hypothermia to 35 °C prior to dura opening followed by 33 °C for 48 h compared with normothermia (37 °C). Investigators randomly assigned patients at a 1:1 ratio between hypothermia and normothermia. Blinded evaluators assessed outcome using a 6-month Glasgow Outcome Scale Extended score. Investigators measured circulating glial fibrillary acidic protein and ubiquitin C-terminal hydrolase L1 levels. RESULTS: Independent statisticians performed an interim analysis of 31 patients to assess the predictive probability of success and the Data and Safety Monitoring Board recommended the early termination of the study because of futility. Thirty-two patients, 16 per arm, were analyzed. Favorable 6-month Glasgow Outcome Scale Extended outcomes were not statistically significantly different between hypothermia vs. normothermia groups (6 of 16, 38% vs. 4 of 16, 25%; odds ratio 1.8 [95% confidence interval 0.39 to ∞], p = .35). Plasma levels of glial fibrillary acidic protein (p = .036), but not ubiquitin C-terminal hydrolase L1 (p = .26), were lower in the patients with favorable outcome compared with those with unfavorable outcome, but differences were not identified by temperature group. Adverse events were similar between groups. CONCLUSIONS: This trial of hypothermia after acute SDH evacuation was terminated because of a low predictive probability of meeting the study objectives. There was no statistically significant difference in functional outcome identified between temperature groups.

Impacto de uma intervenção educativa no manejo da hipotermia terapêutica neonatal: estudo quase experimental / Impact of an educational intervention in the management of neonatal therapeutic hypothermia: a quasi-experimental study

Introdução: A hipotermia terapêutica é o tratamento indicado para encefalopatia moderada a grave em recém-nascidos. A terapia requer uma equipe de enfermagem capacitada e integrada, visando um cuidado qualificado, efetivo e seguro. Modelos teóricos têm sido desenvolvidos para auxiliar a incorporação de evidências científicas à prática dos enfermeiros, representando um desafio na área da saúde. A implementação de uma intervenção educativa, guiada pela estrutura i-PARIHS (Estrutura Integrada de Promoção da Ação na Implementação de Pesquisa em Serviços de Saúde), poderá preencher a lacuna entre a teoria e a prática, beneficiando a assistência e tornando os sujeitos ativos no manejo do recém-nascido em hipotermia terapêutica. Objetivo geral: avaliar o impacto de uma intervenção educativa, guiada pelo referencial teórico i-PARIHS, sobre o manejo do recém-nascido com asfixia perinatal em hipotermia terapêutica na unidade intensiva neonatal no conhecimento, atitudes e práticas de enfermeiros. Objetivos específicos: analisar o conhecimento, atitude e prática dos enfermeiros sobre o manejo do recém-nascido com asfixia perinatal em hipotermia terapêutica pré e pós-intervenção educativa; identificar as barreiras e facilitadores percebidos pelos enfermeiros sobre o manejo do recém-nascido com asfixia perinatal em hipotermia terapêutica na unidade intensiva neonatal; implementar uma intervenção educativa, guiada pelo referencial i-PARIHS, para melhorar o conhecimento, a atitude e a prática dos enfermeiros sobre o manejo do recém-nascido com asfixia perinatal em hipotermia terapêutica na unidade intensiva neonatal; comparar o conhecimento, atitude e prática dos enfermeiros após a intervenção educativa e os indicadores quanto ao manejo do recém-nascido com asfixia perinatal em hipotermia terapêutica. Método: trata-se de um estudo de intervenção, do tipo quase-experimental, realizado com 29 enfermeiros de uma unidade intensiva neonatal, referência no Rio de Janeiro. O desfecho principal: conhecimento, atitudes e práticas dos enfermeiros no manejo do recém-nascido com asfixia perinatal em hipotermia terapêutica na unidade intensiva neonatal A intervenção compreendeu três fases: pré-intervenção - intervenção educativa- pós-intervenção. A intervenção educativa contou com cinco encontros: "Asfixia Perinatal x Hipotermia Terapêutica", "Controle da temperatura", "Cuidados de enfermagem na HT: avaliação de dor", "Monitoramento neurológico" e "Cuidado Centrado na Família". Para a análise estatística utilizou-se de análise descritiva e aplicação dos testes Wilcoxon-Mann-Whitney e Mc Nemar, sendo o nível de significância adotado de 0,05. Resultados: a análise dos resultados do pré e pós-teste demonstrou um incremento no escore de acertos das questões sobre conhecimento, atitude e prática dos enfermeiros no manejo do recém-nascido submetido à hipotermia terapêutica na unidade intensiva neonatal, apresentando significância estatística para a maioria dos itens. Para a inovação foram construídos lembretes, fluxo de admissão para recém-nascido da instituição e uma cartilha para os pais como produto da intervenção com os enfermeiros. Conclusão: O resultado das auditorias realizadas, após a implementação das evidências, constatou uma transformação positiva da prática dos enfermeiros. A utilização da estrutura i-PARIHS evidenciou a necessidade e o valor de investir no engajamento das partes interessadas, na avaliação colaborativa do contexto e na cocriação de inovação usando facilitação qualificada. A intervenção educativa, guiada pela estrutura i-PARIHS, mostrou ter impacto no manejo do recém-nascido submetido à hipotermia terapêutica por enfermeiros.

Introduction: Therapeutic hypothermia is the currently indicated treatment for moderate to severe encephalopathy in newborns. Therapy requires a trained and integrated nursing team, aiming at qualified, effective and safe care. Theoretical models have been developed to help the incorporation of scientific evidence into nurses' practice, representing a challenge in the health area. The implementation of an educational intervention, guided by the i-PARIHS (Integrated Promoting Action on Research Implementation in Health Services Framework) framework, can fill the gap between theory and professional practice, benefiting care and making subjects active in the management of newborns with therapeutic hypothermia. General objective: to evaluate the impact of an educational intervention guided by the theoretical framework i-PARIHS, on the management of newborns with perinatal asphyxia in therapeutic hypothermia in the neonatal intensive care unit on the knowledge, attitudes and practices of nurses. Specific objectives: to analyze the knowledge, attitude and practice of nurses on the management of newborns with perinatal asphyxia in pre- and post-educational therapeutic hypothermia; to identify barriers and facilitators perceived by nurses on the management of newborns with perinatal asphyxia in therapeutic hypothermia in the neonatal intensive care unit; implement an educational intervention, guided by the i-PARIHS framework, to improve nurses' knowledge, attitude and practice on the management of newborns with perinatal asphyxia in therapeutic hypothermia in the neonatal intensive care unit and compare the knowledge, attitude and practice of nurses after the participatory educational intervention program and indicators regarding the management of newborns with perinatal asphyxia in therapeutic hypothermia. Method: this is a quasi-experimental intervention study carried out with 29 nurses from a neonatal intensive care unit, a reference in Rio de Janeiro. The main outcome: knowledge, attitudes and practices of nurses in the management of newborns with perinatal asphyxia in therapeutic hypothermia in the neonatal intensive unit The intervention comprised three phases: pre-intervention - educational intervention - post-intervention. The educational intervention had five meetings: "Perinatal Asphyxia x Therapeutic Hypothermia", "Temperature control", "Nursing care in HT: pain assessment", "Neurological monitoring" and "Family-Centered Care". For the statistical analysis, descriptive analysis and application of the Wilcoxon-Mann-Whitney and Mc Nemar tests were used, with the adopted significance level of 0.05. Results: the analysis of pre- and post-test results showed an increase in the correct score of questions about nurses' knowledge and practices in the management of newborns submitted to therapeutic hypothermia in the neonatal intensive care unit, showing statistical significance for most items. For innovation, reminders, admission flow for newborns at the institution and a booklet for parents were created as a product of the intervention with nurses. Conclusion: The result of the audits carried out, after the implementation of the evidence, found a positive transformation of the nurses' practice. Using the i-PARIHS framework highlighted the need and value of investing in stakeholder engagement, collaborative context assessment, and co-creation of innovation using qualified facilitation. The educational intervention guided by the i-PARIHS framework was shown to have an impact on the management of newborns with perinatal asphyxia in therapeutic hypothermia by nurses.

Effects of different densities of rat cardiac fibroblasts subjected to hypothermic hypoxia-reoxygenation on cardiomyocyte injury / 中华麻醉学杂志

Objective:To evaluate the effects of different densities of rat cardiac fibroblasts (RCF) subjected to hypothermic hypoxia-reoxygenation on cardiomyocyte injury and intercellular coupling.Methods:RCF was cultured in vitro and divided into 3 groups ( n=12 each) using a random number table method: RCF density 0.5×10 5 cells/ml group (T 0.5 group), RCF density 1.0×10 5 cells/ml group (T 1.0 group), and RCF density 2.0×10 5 cells/ml group (T 2.0 group). The three groups were placed in an anoxic device, into which 95% N 2 + 5% CO 2 was continuously blown at the speed of 5 L/min for 15 min, and then placed in a 4 ℃ refrigerator for 1 h for low temperature treatment.After completion of culture, cells were placed in a incubator containing 95% air + 5% CO 2 at 37 ℃ for 4 h of reoxygenation.After the end of culture, RCF in three groups were indirectly co-cultured with cardiomyocytes of the same density (1.0×10 5 cells/ml) in a Transwell chamber for 16 h, cardiomyocytes were seeded in the lower chamber of Transwell, and RCF were seeded in the upper chamber of Transwell.After the end of co-culture, cardiomyocytes were collected for determination of the cell viability (by CCK8 method), apoptosis rate (by flow cytometry), expression of connexin 43 (Cx43) mRNA (by real-time fluorescence quantitative polymerase chain reaction), and expression of Cx43 and phosphorylated Cx43 (p-Cx43) (by Western blot). Results:Compared with T 0.5 group, the cell viability, apoptosis rate and expression of Cx43, p-Cx43 and Cx43 mRNA were significantly decreased in T 1.0 and T 2.0 groups ( P<0.01). Compared with T 1.0 group, the cell viability, apoptosis rate and expression of Cx43 and p-Cx43 were significantly decreased ( P<0.01), and no significant change was found in expression of Cx43 mRNA in cardiomyocytes in T 2.0 group ( P>0.05). Conclusions:RCF subjected to hypothermic hypoxia-reoxygenation induces cardiomyocyte injury in a density-dependent manner in a certain range, and the mechanism may be related to down-regulation of the expression of Cx43 and reduction of the activity of Cx43.

Brain temperature changes and mild hypothermia treatment after subarachnoid hemorrhage / 国际脑血管病杂志

Subarachnoid hemorrhage (SAH) is a common and serious type of stroke. Studies have shown that multimodal monitoring of brain temperature, intracranial pressure and cerebral blood flow is helpful for the perioperative management of patients with SAH, and further improves the outcomes of patients. This article reviews the brain temperature changes and mechanism after SAH as well as the role of mild hypothermia treatment.