Effect of Moderate Hypothermia vs Normothermia on 30-Day Mortality in Patients With Cardiogenic Shock Receiving Venoarterial Extracorporeal Membrane Oxygenation: A Randomized Clinical Trial.

IMPORTANCE: The optimal approach to the use of venoarterial extracorporeal membrane oxygenation (ECMO) during cardiogenic shock is uncertain. OBJECTIVE: To determine whether early use of moderate hypothermia (33-34 °C) compared with strict normothermia (36-37 °C) improves mortality in patients with cardiogenic shock receiving venoarterial ECMO. DESIGN, SETTING, AND PARTICIPANTS: Randomized clinical trial of patients (who were eligible if they had been endotracheally intubated and were receiving venoarterial ECMO for cardiogenic shock for <6 hours) conducted in the intensive care units at 20 French cardiac shock care centers between October 2016 and July 2019. Of 786 eligible patients, 374 were randomized. Final follow-up occurred in November 2019. INTERVENTIONS: Early moderate hypothermia (33-34 °C; n = 168) for 24 hours or strict normothermia (36-37 °C; n = 166). MAIN OUTCOMES AND MEASURES: The primary outcome was mortality at 30 days. There were 31 secondary outcomes including mortality at days 7, 60, and 180; a composite outcome of death, heart transplant, escalation to left ventricular assist device implantation, or stroke at days 30, 60, and 180; and days without requiring a ventilator or kidney replacement therapy at days 30, 60, and 180. Adverse events included rates of severe bleeding, sepsis, and number of units of packed red blood cells transfused during venoarterial ECMO. RESULTS: Among the 374 patients who were randomized, 334 completed the trial (mean age, 58 [SD, 12] years; 24% women) and were included in the primary analysis. At 30 days, 71 patients (42%) in the moderate hypothermia group had died vs 84 patients (51%) in the normothermia group (adjusted odds ratio, 0.71 [95% CI, 0.45 to 1.13], P = .15; risk difference, -8.3% [95% CI, -16.3% to -0.3%]). For the composite outcome of death, heart transplant, escalation to left ventricular assist device implantation, or stroke at day 30, the adjusted odds ratio was 0.61 (95% CI, 0.39 to 0.96; P = .03) for the moderate hypothermia group compared with the normothermia group and the risk difference was -11.5% (95% CI, -23.2% to 0.2%). Of the 31 secondary outcomes, 30 were inconclusive. The incidence of moderate or severe bleeding was 41% in the moderate hypothermia group vs 42% in the normothermia group. The incidence of infections was 52% in both groups. The incidence of bacteremia was 20% in the moderate hypothermia group vs 30% in the normothermia group. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial involving patients with refractory cardiogenic shock treated with venoarterial ECMO, early application of moderate hypothermia for 24 hours did not significantly increase survival compared with normothermia. However, because the 95% CI was wide and included a potentially important effect size, these findings should be considered inconclusive. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02754193.

A Simple Risk Score for Predicting Neurologic Outcome in Out-of-Hospital Cardiac Arrest Patients After Targeted Temperature Management.

OBJECTIVES: Although several risk factors for outcomes of out-of-hospital cardiac arrest patients have been identified, the cumulative risk of their combinations is not thoroughly clear, especially after targeted temperature management. Therefore, we aimed to develop a risk score to evaluate individual out-of-hospital cardiac arrest patient risk at early admission after targeted temperature management regarding poor neurologic status at discharge. DESIGN: Retrospective observational cohort study. SETTING: Two large academic medical networks in the United States. PATIENTS: Out-of-hospital cardiac arrest survivors treated with targeted temperature management with age of 18 years old or older. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Based on the odds ratios, five identified variables (initial nonShockable rhythm, Leucocyte count < 4 or > 12 K/µL after targeted temperature management, total Adrenalin [epinephrine] ≥ 5 mg, lack of oNlooker cardiopulmonary resuscitation, and Time duration of resuscitation ≥ 20 min) were assigned weighted points. The sum of the points was the total risk score known as the SLANT score (range 0-21 points) for each patient. Based on our risk prediction scores, patients were divided into three risk categories as moderate-risk group (0-7), high-risk group (8-14), and very high-risk group (15-21). Both the ability of our risk score to predict the rates of poor neurologic outcomes at discharge and in-hospital mortality were significant under the Cochran-Armitage trend test (p < 0.001 and p < 0.001, respectively). CONCLUSIONS: The risk of poor neurologic outcomes and in-hospital mortality of out-of-hospital cardiac arrest survivors after targeted temperature management is easily assessed using a risk score model derived using the readily available information. Its clinical utility needed further investigation.

Effect of Moderate vs Mild Therapeutic Hypothermia on Mortality and Neurologic Outcomes in Comatose Survivors of Out-of-Hospital Cardiac Arrest: The CAPITAL CHILL Randomized Clinical Trial.

Importance: Comatose survivors of out-of-hospital cardiac arrest experience high rates of death and severe neurologic injury. Current guidelines recommend targeted temperature management at 32 °C to 36 °C for 24 hours. However, small studies suggest a potential benefit of targeting lower body temperatures. Objective: To determine whether moderate hypothermia (31 °C), compared with mild hypothermia (34 °C), improves clinical outcomes in comatose survivors of out-of-hospital cardiac arrest. Design, Setting, and Participants: Single-center, double-blind, randomized, clinical superiority trial carried out in a tertiary cardiac care center in eastern Ontario, Canada. A total of 389 patients with out-of-hospital cardiac arrest were enrolled between August 4, 2013, and March 20, 2020, with final follow-up on October 15, 2020. Interventions: Patients were randomly assigned to temperature management with a target body temperature of 31 °C (n = 193) or 34 °C (n = 196) for a period of 24 hours. Main Outcomes and Measures: The primary outcome was all-cause mortality or poor neurologic outcome at 180 days. Neurologic outcome was assessed using the Disability Rating Scale, with poor neurologic outcome defined as a score greater than 5 (range, 0-29, with 29 being the worst outcome [vegetative state]). There were 19 secondary outcomes, including mortality at 180 days and length of stay in the intensive care unit. Results: Among 367 patients included in the primary analysis (mean age, 61 years; 69 women [19%]), 366 (99.7%) completed the trial. The primary outcome occurred in 89 of 184 patients (48.4%) in the 31 °C group and in 83 of 183 patients (45.4%) in the 34 °C group (risk difference, 3.0% [95% CI, 7.2%-13.2%]; relative risk, 1.07 [95% CI, 0.86-1.33]; P = .56). Of the 19 secondary outcomes, 18 were not statistically significant. Mortality at 180 days was 43.5% and 41.0% in patients treated with a target temperature of 31 °C and 34 °C, respectively (P = .63). The median length of stay in the intensive care unit was longer in the 31 °C group (10 vs 7 days; P = .004). Among adverse events in the 31 °C group vs the 34 °C group, deep vein thrombosis occurred in 11.4% vs 10.9% and thrombus in the inferior vena cava occurred in 3.8% and 7.7%, respectively. Conclusions and Relevance: In comatose survivors of out-of-hospital cardiac arrest, a target temperature of 31 °C did not significantly reduce the rate of death or poor neurologic outcome at 180 days compared with a target temperature of 34 °C. However, the study may have been underpowered to detect a clinically important difference. Trial Registration: ClinicalTrials.gov Identifier: NCT02011568.

Sex-Specific Outcome after Ascending Aortic Surgery in Moderate Hypothermic Circulatory Arrest.

BACKGROUND: Historically, female patients had worse outcome undergoing heart surgery. No recent data exist on gender-specific outcome after moderate hypothermic circulatory arrest (MHCA). The aim of this large retrospective analysis was to investigate gender disparity in patients undergoing elective surgery of ascending aorta in MHCA at 24°C. METHODS: We conducted a retrospective review of 905 (33.3% female) cases of elective heart surgery in MHCA for ascending aortic aneurysm (90.9%) or severely calcified aorta (12.5%) between 2001 and 2015. Furthermore, 299 female and 299 male patients matched by propensity score were compared. Patients with dissection of the aorta were excluded. RESULTS: Women were older (68.4 ± 9.9 vs. 65.8 ± 11.6 years; p = 0.002), had higher logistic EuroSCORE I (18.4 [11.7; 29.2] vs. 12.3% [7.4; 22.6]; p < 0.001), and significantly shorter cardiopulmonary bypass (CPB) time (132 [105; 175] vs. 150 [118; 192] minutes; p < 0.001), while mean MHCA time was longer (15 [13; 19] vs. 14 [12; 17] minutes; p = 0.003). Surgical procedures were less complex in women and they were treated more frequently by isolated supracoronary ascending aorta replacement (61 vs. 54%; p = 0.046). Postoperatively, men showed a higher incidence of neurologic complications (7.0 vs. 3.3%; p = 0.03). The 30-day mortality (women 4.9% vs. men 3.9%; p = 0.48) did not differ significantly, likewise after statistical matching (4.7 vs. 2.3%; p = 0.120). Age, CPB time, and blood transfusion, but not female gender, were risk factors for mortality in multivariable regression analysis. CONCLUSION: This study supports the hypothesis that female gender is not associated with increased short-term mortality or perioperative adverse events in elective aortic surgery in MHCA.

Risk Factors for Mortality in Acute Aortic Dissection Type A: A Centre Experience Over 15 Years.

INTRODUCTION: Acute aortic dissection Type A (AADA) is still associated with a high mortality rate and frequent postoperative complications. This study was designed to evaluate the risk factors for mortality in AADA patients. PATIENTS AND METHODS: This retrospective analysis included 344 consecutive patients who underwent surgery for AADA in moderate hypothermic circulatory arrest (20-24°C nasopharyngeal) between 2001 and 2016. RESULTS: The 30-day mortality rate was 18%. Nonsurvivors were significantly older (65.7 ± 12.0 years vs. 62.0 ± 12.5 years; p = 0.034) with significantly higher Euro-score II [15.4% (6.6; 23.0) vs. 4.63% (2.78; 9.88); p < 0.001)]. Intraoperatively, survivors had statistically shorter cardiopulmonary bypass times [163 (134; 206) vs. 198 min (150; 245); p = 0.001]. However, the hypothermic circulatory arrest time was similar between both groups. Postoperatively, the incidence of acute kidney injury (AKI) (55.9 vs. 15.2%; p < 0.001), stroke (27.9 vs. 12.1%; p = 0.002) and sepsis (18.0 vs. 2.1%; p < 0.001) were significantly higher among nonsurvivors. The multi-variable logistic regression confirmed that older age, previous cardiac surgery, preoperative cardiopulmonary resuscitation (CPR), blood transfusion and postoperative acute kidney injury (AKI) were independent risk factors for mortality. CONCLUSION: Our analysis suggested that the reason for mortality was multifactorial, especially age, previous cardiac surgery, CPR, transfusion, as well as postoperative AKI were considered risk factors for mortality.

Interventions to reduce body temperature to 35 °C to 37 °C in adults and children with traumatic brain injury.

BACKGROUND: Traumatic brain injury (TBI) is a major cause of death and disability, with an estimated 5.5 million people experiencing severe TBI worldwide every year. Observational clinical studies of people with TBI suggest an association between raised body temperature and unfavourable outcome, although this relationship is inconsistent. Additionally, preclinical models suggest that reducing temperature to 35 °C to 37.5 °C improves biochemical and histopathological outcomes compared to reducing temperature to a lower threshold of 33 °C to 35 °C. It is unknown whether reducing body temperature to 35 °C to 37.5 °C in people admitted to hospital with TBI is beneficial, has no effect, or causes harm. This is an update of a review last published in 2014. OBJECTIVES: To assess the effects of pharmacological interventions or physical interventions given with the intention of reducing body temperature to 35 °C to 37.5 °C in adults and children admitted to hospital after TBI. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Web of Science, and PubMed on 28 November 2019. We searched clinical trials registers, grey literature and references lists of reviews, and we carried out forward citation searches of included studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) with participants of any age admitted to hospital following TBI. We included interventions that aimed to reduce body temperature to 35 °C to 37.5 °C: these included pharmacological interventions (such as paracetamol, or non-steroidal anti-inflammatory drugs), or physical interventions (such as surface cooling devices, bedside fans, or cooled intravenous fluids). Eligible comparators were placebo or usual care. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion, extracted data, and assessed risks of bias. We assessed the certainty of the evidence with GRADE. MAIN RESULTS: We included one RCT with 41 participants. This study recruited adult participants admitted to two intensive care units in Australia, and evaluated a pharmacological intervention. Researchers gave participants 1 g paracetamol or a placebo intravenously at four-hourly intervals for 72 hours. We could not be certain whether intravenous paracetamol influenced mortality at 28 days (risk ratio 2.86, 95% confidence interval 0.32 to 25.24). We judged the evidence for this outcome to be very low certainty, meaning we have very little confidence in this effect estimate, and the true result may be substantially different to this effect. We downgraded the certainty for imprecision (because the evidence was from a single study with very few participants), and study limitations (because we noted a high risk of selective reporting bias). This study was otherwise at low risk of bias. The included study did not report the primary outcome for this review, which was the number of people with a poor outcome at the end of follow-up (defined as death or dependency, as measured on a scale such as the Glasgow Outcome Score), or any of our secondary outcomes, which included the number of people with further intracranial haemorrhage, extracranial haemorrhage, abnormal intracranial pressure, or pneumonia or other serious infections. The only other completed trial that we found was of a physical intervention that compared advanced fever control (using a surface cooling device) versus conventional fever control in 12 participants. The trial was published as an abstract only, with insufficient details to allow inclusion, so we have added this to the 'studies awaiting classification' section, pending further information from the study authors or publication of the full study report. We identified four ongoing studies that will contribute evidence to future updates of the review if they measure relevant outcomes and, in studies with a mixed population, report data separately for participants with TBI. AUTHORS' CONCLUSIONS: One small study contributed very low-certainty evidence for mortality to this review. The uncertainty is largely driven by limited research into reduction of body temperature to 35 °C to 37.5 °C in people with TBI. Further research that evaluates pharmacological or physical interventions, or both, may increase certainty in this field. We propose that future updates of the review, and ongoing and future research in this field, incorporate outcomes that are important to the people receiving the interventions, including side effects of any pharmacological agent (e.g. nausea or vomiting), and discomfort caused by physical therapies.

Outcome after ex situ or ante situm liver resection with hypothermic perfusion and auto-transplantation: A single-centre experience in adult and paediatric patients.

BACKGROUND: Evolving surgical technology and medical treatment have led to an expansion of indications to enable resection of large hepatic tumours with involvement of other abdominal structures. METHODS: Twelve extended liver and abdominal resections, either ex situ with auto-transplantation of the liver remnant or ante situm with veno-venous bypass (VVBP) were performed between 2016 and 2018. We describe our preoperative assessment, compare surgical strategies and assess outcomes. RESULTS: The median age of the 10 adult patients was 50.5 years with a majority suffering from sarcoma-like tumours. The two paediatric patients were 3 and 8 years of age, both with hepatoblastoma. Two patients underwent ex situ resections with auto-transplantation of the liver remnant, and nine patients had ante situm tumour removal with the use of VVBP in four. All patients achieved a good immediate liver function. Local infection and acute kidney injury were found in two patients. One patient underwent biliary reconstruction for bile leak. Tumour recurrence was seen in seven patients (58.3%), with four lung metastases. Five patients died from tumour recurrence (41.7%) during the follow-up. CONCLUSION: Extreme liver resections should be performed in experienced centres, where surgical subspecialties are available with access to cardiovascular support. Additionally, experience in split and living-donor liver transplantation is beneficial.

Relationship Between Duration of Targeted Temperature Management, Ischemic Interval, and Good Functional Outcome From Out-of-Hospital Cardiac Arrest.

OBJECTIVES: Tailoring hypothermia duration to ischemia duration may improve outcome from out-of-hospital cardiac arrest. We investigated the association between the hypothermia/ischemia ratio and functional outcome in a secondary analysis of data from the Resuscitation Outcomes Consortium Amiodarone, Lidocaine, or Placebo Study trial. DESIGN: Cohort study of out-of-hospital cardiac arrest patients screened for Resuscitation Outcomes Consortium-Amiodarone, Lidocaine, or Placebo Study. SETTING: Multicenter study across North America. PATIENTS: Adult, nontraumatic, out-of-hospital cardiac arrest patients screened for Resuscitation Outcomes Consortium-Amiodarone, Lidocaine, or Placebo Study who survived to hospital admission and received targeted temperature management between May 2012 and October 2015. INTERVENTIONS: Targeted temperature management in comatose survivors of out-of-hospital cardiac arrest. We defined hypothermia/ischemia ratio as total targeted temperature management time (initiation through rewarming) divided by calculated total ischemia time (approximate time of arrest [9-1-1 call or emergency medical services-witnessed] to return of spontaneous circulation). MEASUREMENTS AND MAIN RESULTS: The primary outcome was hospital survival with good functional status (modified Rankin Score, 0-3) at hospital discharge. We fitted logistic regression models to estimate the association between hypothermia/ischemia ratio and the primary outcome, adjusting for demographics, arrest characteristics, and Resuscitation Outcomes Consortium enrolling site. A total of 3,429 patients were eligible for inclusion, of whom 36.2% were discharged with good functional outcome. Patients had a mean age of 62.0 years (SD, 15.8), with 69.7% male, and 58.0% receiving lay-rescuer cardiopulmonary resuscitation. Median time to return of spontaneous circulation was 21.1 minutes (interquartile range, 16.1-26.9), and median duration of targeted temperature management was 32.9 hours (interquartile range, 23.7-37.8). A total of 2,579 had complete data and were included in adjusted regression analyses. After adjustment for patient characteristics and Resuscitation Outcomes Consortium site, a greater hypothermia/ischemia ratio was associated with increased survival with good functional outcome (odds ratio, 2.01; 95% CI, 1.82-2.23). This relationship, however, appears to be primarily driven by time to return of spontaneous circulation in this patient cohort. CONCLUSIONS: Although a larger hypothermia/ischemia ratio was associated with good functional outcome after out-of-hospital cardiac arrest in this cohort, this association is primarily driven by duration of time to return of spontaneous circulation. Tailoring duration of targeted temperature management based on duration of time to return of spontaneous circulation or patient characteristics requires prospective study.

Hypothermic to ischemic ratio and mortality in post-cardiac arrest patients.

BACKGROUND: We studied the associations between ischemia and hypothermia duration, that is, the hypothermic to ischemic ratio (H/I ratio), with mortality in patients included in a trial on two durations of targeted temperature management (TTM) at 33°C. METHODS: The TTH48 (NCT01689077) trial compared 24 and 48 hours of TTM in patients after cardiac arrest. We calculated the hypothermia time from return of spontaneous circulation (ROSC) until the patient reached 37°C after TTM and the ischemic time from CA to ROSC. We compared continuous variables with the Mann-Whitney U test. Using COX regression, we studied the independent association of the logarithmically transformed H/I ratio and time to death as well as interaction between time to ROSC, hypothermia duration, and intervention group. We visualized the predictive ability of variables with receiver operating characteristic curve analysis. RESULTS: Of the 338 patients, 237 (70%) survived for 6 months. The H/I ratio was 155 (IQR 111-238) in survivors and 114 (IQR 80-169) in non-survivors (P < .001). In a Cox regression model including factors associated with outcome in univariate analysis, the logarithmically transformed H/I ratio was a significant predictor of outcome (hazard ratio 0.52 (0.37-0.72, P = .001)). After removing an outlier, we found no interaction between time to ROSC and intervention group (P = .55) or hypothermia duration in quartiles (P = .07) with mortality. There was no significant difference in the area under the curve (AUC) between time to ROSC and H/I ratio (ΔAUC 0.03 95% CI -0.006-0.07, P = .10). CONCLUSIONS: We did not find any consistent evidence of a modification of the effect of TTM based on ischemia duration.

Targeted Temperature Management at 33 Versus 36 Degrees: A Retrospective Cohort Study.

OBJECTIVES: To determine the association between targeted temperature management goal temperature of 33°C versus 36°C and neurologic outcome after out-of-hospital cardiac arrest. DESIGN: This was a retrospective, before-and-after, cohort study. SETTING: Urban, academic, level 1 trauma center from 2010 to 2017. PATIENTS: Adults with nontraumatic out-of-hospital cardiac arrest who received targeted temperature management. INTERVENTIONS: Our primary exposure was targeted temperature management goal temperature, which was changed from 33°C to 36°C in April of 2014 at the study hospital. Primary outcome was neurologically intact survival to discharge. Secondary outcomes included hospital mortality and care processes. MEASUREMENTS AND MAIN RESULTS: Of 782 out-of-hospital cardiac arrest patients transported to the study hospital, 453 (58%) received targeted temperature management. Of these, 258 (57%) were treated during the 33°C period (targeted temperature management 33°C) and 195 (43%) were treated during the 36°C period (targeted temperature management 36°C). Patients treated during targeted temperature management 33°C were older (57 vs 52 yr; p < 0.05) and had more arrests of cardiac etiology (45% vs 35%; p < 0.05), but otherwise had similar baseline characteristics, including initial cardiac rhythm. A total of 40% of patients treated during targeted temperature management 33°C survived with favorable neurologic outcome, compared with 30% in the targeted temperature management 36°C group (p < 0.05). After adjustment for demographic and cardiac arrest characteristics, targeted temperature management 33°C was associated with increased odds of neurologically intact survival to discharge (odds ratio, 1.79; 95% CI, 1.09-2.94). Targeted temperature management 33°C was not associated with significantly improved hospital mortality. Targeted temperature management was implemented faster (1.9 vs 3.5 hr from 911 call; p < 0.001) and more frequently in the emergency department during the targeted temperature management 33°C period (87% vs 55%; p < 0.001). CONCLUSIONS: Comatose, adult out-of-hospital cardiac arrest patients treated during the targeted temperature management 33°C period had higher odds of neurologically intact survival to hospital discharge compared with those treated during the targeted temperature management 36°C period. There was no significant difference in hospital mortality.

Outcome and Feasibility after 7 Years of Therapeutic Hypothermia in Southern Brazil.

OBJECTIVE: This study aimed to describe the experience with a protocol of therapeutic hypothermia (TH) in southern Brazil. STUDY DESIGN: Newborns with gestational age > 35 weeks with evidence of perinatal asphyxia plus moderate or severe encephalopathy were recruited between March 2011 and November 2017. Whole-body hypothermia for 72 hours, starting within the first 6 hours of life was used. Survivors underwent magnetic resonance imaging (MRI) and electroencephalogram (EEG). The primary outcome was death during hospitalization and neurodevelopment assessed using the Bayley Scales of Infant Development III (BSID III) at 12 months of age. RESULTS: A total of 72 newborns were treated (41 with moderate encephalopathy and 31 with severe encephalopathy), of whom 16 died. MRI was performed in 56 patients, and 24 presented some alterations. Fifty-three patients had an EEG: 11 normal, 20 mildly altered, 12 moderately altered, and 10 severely altered. Forty patients were evaluated through BSID III: 45% presented with some delay in neurodevelopment, 8 (20%) had motor retardation, 15 (37.5%) had language delay, and 13 (32.5%) had a delay in cognitive development. CONCLUSION: Mortality and adverse events were similar to those described in large randomized controlled trials. TH is a safe and an effective method of neurologic protection in asphyxiated newborns in a developing country when performed adequately.

Therapeutic hypothermia and mortality in the intensive care unit: systematic review and meta-analysis.

OBJECTIVE: Therapeutic hypothermia (TH) is defined as the designed reduction of the human body's core temperature to 32°C-35°C for a period of 24-48 hours. TH has been studied extensively in many diseases related to critical care illness. This meta-analysis assesses the effect of TH on mortality across different indications in medical, neurological and cardiothoracic care. DATA SOURCES: The online databases Embase, Ovid MEDLINE, TRIP and CINAHL were searched for eligible studies published between 1940 and October 2018. STUDY SELECTION: Randomised clinical trials of induced TH in adults for any indication. DATA EXTRACTION: Information about baseline characteristics of patients, mortality outcomes, cooling strategy and target temperature achieved in hypothermia and normothermia groups was collected. DATA SYNTHESIS: Eighty studies, with a total of 13 418 patients, were included in this meta-analysis: 22 studies for traumatic brain injury, six studies for stroke, five studies for out-of-hospital cardiac arrest (OHCA), 34 studies for intraoperative cardiopulmonary bypass, and 13 studies for other diseases. A total of 6901 patients (51.4%) were randomly allocated to the TH group and 6517 patients (48.6%) were randomised to the normothermia control group. The unadjusted analysis showed no significant difference in mortality across different critical care illnesses. However, after adjusting for population, gender, age and temperature, only the OHCA group showed a small statistically significant difference favouring TH, but this had a questionable clinical significance. CONCLUSIONS: This meta-analysis suggests that after decades of extensive research, TH has yet to show a beneficial effect on mortality across different critical care diseases.

Early and late outcomes of aortic surgery under hypothermic circulatory arrest in the elderly: a single center study.

BACKGROUND: With the progressive aging of the population, aortic surgeons are caring for an increasing number of elderly patients. The objective of this study was to analyze early and late outcomes of aortic surgery with hypothermic circulatory arrest in patients aged 70 and above at our institution. METHODS: We performed a retrospective cohort study including every patient aged 70 years or older who underwent aortic surgery with hypothermic circulatory arrest between January 1995 and June 2016 at our institution. Operative results were compared with the contemporary younger counterparts aged <70 years. In-hospital mortality and postoperative stroke were primary outcomes of interest. The main secondary outcomes included acute renal failure, reoperation for bleeding, and spinal cord injury. RESULTS: In the study population, the in-hospital mortality was 16.8% (21/125). Ten (8.0%) patients presented postoperative stroke, and 6 had temporary neurologic disturbance (4.8%). Spinal cord injury occurred in 1 (0.8%) patient. For elective interventions and type A aortic dissections, the in-hospital mortality and stroke rates were 4.6% (3/65) and 7.7% (5/65), 26.8% (11/41) and 12.2% (5/41), respectively. The proportion of non-elective interventions, including type A aortic dissection, and the type of neuroprotective strategy were similar in septuagenarians and younger patients. Patients aged ≥70 had significant shorter cardiopulmonary bypass, myocardial ischemia, and circulatory arrest durations, compared to their younger counterparts. The in-hospital mortality of septuagenarians and younger patients were similar for elective surgery (4.6% vs. 4.7%, P=0.900) and aortic dissections (26.8% vs. 15.1%, P=0.107). There was no statistically significant difference between the two age groups regarding postoperative stroke, spinal cord injury, renal failure requiring dialysis or reintervention for bleeding. Estimated 1-, 3-, and 5-year survival was 78.0%, 70.6%, and 65.7%, respectively. The 5-year survival for elective surgery was 74.9% and 56.0% for non-elective procedures. CONCLUSIONS: Aortic surgery with circulatory arrest in the elderly demonstrated favorable early and late results when compared with younger individuals, with an acceptable operative risk even under emergency conditions, and should not be denied only because of the chronological age of the patients.

Prognostication via early computed tomography head in patients treated with targeted temperature management after cardiac arrest.

BACKGROUND: We evaluated computed tomography head (CTH) imaging obtained prior to targeted temperature management (TTM) in patients after cardiac arrest, and its role in prognostication. METHODS: In this retrospective cohort study in a tertiary-care hospital, 341 adults presenting with out-of-hospital cardiac arrest received a CTH prior to TTM. Associations between outcomes and neuroimaging variables were evaluated with Chi-square analysis for significant associations that yielded a composite neuroimaging score-Tennessee Early Neuroimaging Score (TENS). Univariable and multivariable logistic regression analysis including TENS as an independent variable and the four outcome dependent variables were analyzed. RESULTS: Four of the neuroimaging variables-sulcal effacement, partial gray-white matter effacement, total gray-white matter effacement, deep nuclei effacement-had significant associations with each of the four outcome variables and yielded TENS. In multivariable logistic regression models adjusted for potential confounders, TENS was associated with poor discharge CPC (OR 2.15, 95%CI 1.16-3.98, p = .015), poor disposition (OR 2.62, 95%CI 1.37-5.02, p = .004), in-hospital mortality (OR 1.99, 95%CI 1.09-3.62, p = .024), and ICU mortality (OR 1.89, 95%CI 1.12-3.20, p = .018). CONCLUSION: Imaging prior to TTM may help identify post-cardiac arrest patients with severe anoxic brain injury and poor outcomes.

Risk of Mortality Associated With Therapeutic Hypothermia Among Sudden Cardiac Arrest Survivors With Known Heart Failure.

Current guidelines do not inform about use of therapeutic hypothermia among heart failure (HF) patients who suffer from cardiac arrest. We assessed the risk of mortality associated with hypothermia among cardiac arrest survivors with HF. This analysis includes 1,416 comatose patients with cardiac arrest who achieved return of spontaneous circulation on admission and had a left ventricular ejection fraction (LVEF) assessment or HF admission within the previous year. HF was defined as either previous episode of HF or presence of left ventricular ejection fraction <50%. Hazard ratios (HR) and 95% confidence intervals (CI) for association of hypothermia and mortality among patients with and without HF were computed using Cox proportional hazard models adjusted for several risk factors. A propensity score matched analysis was also performed. There were 624 patients (44%) with pre-existing HF and 467 patients (33.0%) received hypothermia. The mortality rate was higher in HF patients treated with hypothermia compared with patients without hypothermia (75.4% vs 53.2%, p <0.0001). Hypothermia was associated with increased mortality among HF patients (HR 1.69; 95% CI 1.27, 2.24, p <0.001) and was not associated with mortality among non-HF patients (HR 1.21; 95% CI 0.93, 1.56, p = 0.15). The association of hypothermia with mortality was higher among HF patients who presented with shockable rhythm compared with nonshockable rhythm (interaction p value = 0.0495). Hypothermia is associated with increased mortality among cardiac arrest survivors with known HF.

Door-to-Targeted Temperature Management Initiation Time and Outcomes in Out-of-Hospital Cardiac Arrest: Insights From the Continuous Chest Compressions Trial.

Background Targeted temperature management ( TTM ) is a recommended treatment modality to improve neurological outcomes in patients with out-of-hospital cardiac arrest. The impact of the duration from hospital admission to TTM initiation (door-to- TTM ; DTT ) on clinical outcomes has not been well elucidated. We hypothesized that shorter DTT initiation intervals would be associated with improved survival with favorable neurological outcome. Methods and Results We performed a post hoc analysis of nontraumatic paramedic-treated out-of-hospital cardiac arrests. The primary outcome was favorable neurological status at hospital discharge, with a secondary outcome of survival to discharge. We fit a logistic regression analysis to determine the association of early compared with delayed DTT , dichotomized by the median DTT duration, and outcomes. Of 3805 patients enrolled in the CCC (Continuous Chest Compressions) Trial in British Columbia, 570 were included in this analysis. There was substantial variation in DTT among patients receiving TTM . The median DTT duration was 122 minutes (interquartile range 35-218). Favorable neurological outcomes in the early and delayed DTT groups were 48% and 38%, respectively. Compared with delayed DTT (interquartile range 167-319 minutes), early DTT (interquartile range 20-81 minutes) was associated with survival (adjusted odds ratio 1.56, 95% CI 1.02-2.38) but not with favorable neurological outcomes (adjusted odds ratio 1.45, 95% CI , 0.94-2.22) at hospital discharge. Conclusions There was wide variability in the initiation of TTM among comatose out-of-hospital cardiac arrest survivors. Initiation of TTM within 122 minutes of hospital admission was associated with improved survival. These results support in-hospital efforts to achieve early DTT among out-of-hospital cardiac arrest patients admitted to the hospital.

Association of cerebral activity with MRI scans in infants with neonatal encephalopathy undergoing therapeutic hypothermia.

We aimed to correlate amplitude-integrated EEG (aEEG) in neonatal hypoxic ischemic encephalopathy (HIE) with early magnetic resonance imaging (MRI). In this retrospective study, 32 neonates over 35 weeks' gestation with moderate/severe HIE who were treated with hypothermia were included. Early MRI scans and daily aEEG background were categorized to mild/normal, moderate, and severely abnormal. Time to sleep cycling was noted on aEEG. Mantel-Haenszel test for trends was used to explore associations between aEEG and MRI and outcome. LOESS regression was used for exploring the association of cycling with MRI scores. MRI was normal/mildly abnormal in 20 (63%) infants; in 9 (28%), moderately abnormal; and in 3 (9%), severely abnormal. Twenty-seven (84%) infants s urvived. MRI severity score was significantly associated with aEEG background score on the third and fourth days of life (p < 0.01). An increase in the MRI severity score was noted if sleep cycling appeared after the fifth day of life.Conclusions: Depressed aEEG at the third and fourth days of life and appearance of cycling beyond the fifth day of life are associated with cerebral MRI abnormalities and may be associated with increased risk of abnormal outcome. What is known: • Since therapeutic hypothermia has been shown to change long-term outcome, amplitude-integrated EEG in infants with hypoxic ischemic neonatal encephalopathy soon after birth have a limited predictive power for long-term outcome in treated infants. • Brain MRI after therapeutic hypothermia in the above infants has a significant predictive value for long-term outcome What is new: • Background amplitude-integrated EEG activity depression at the age of 3 and 4 days and delay of appearance of cycling activity are associated with worse MRI scores and may be predictive of worse long-term outcome.

Mild Hypothermia in Cardiogenic Shock Complicating Myocardial Infarction.

BACKGROUND: Experimental trials suggest improved outcome by mild therapeutic hypothermia for cardiogenic shock after acute myocardial infarction. The objective of this study was to investigate the hemodynamic effects of mild therapeutic hypothermia in patients with cardiogenic shock complicating acute myocardial infarction. METHODS: Patients (n=40) with cardiogenic shock undergoing primary percutaneous coronary intervention without classic indications for mild therapeutic hypothermia underwent randomization in a 1:1 fashion to mild therapeutic hypothermia for 24 hours or control. The primary end point was cardiac power index at 24 hours; secondary end points included other hemodynamic parameters and serial measurements of arterial lactate. RESULTS: No relevant differences were observed for the primary end point of cardiac power index at 24 hours (mild therapeutic hypothermia versus control: 0.41 [interquartile range, 0.31-0.52] versus 0.36 [interquartile range, 0.31-0.48] W/m2; P=0.50; median difference, -0.025 W/m2; 95% CI, -0.12 to 0.06). Similarly, all other hemodynamic measurements were not statistically different. Arterial lactate levels at 6, 8, and 10 hours were significantly higher in patients in the mild therapeutic hypothermia group with a slower decline ( P for interaction=0.03). There were no differences in 30-day mortality (60% versus 50%; hazard ratio, 1.27; 95% CI, 0.55-2.94; P=0.55). CONCLUSIONS: In this randomized trial, mild therapeutic hypothermia failed to show a substantial beneficial effect on cardiac power index at 24 hours in patients with cardiogenic shock after acute myocardial infarction. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01890317.

Target Temperature Management May Not Improve Clinical Outcomes of Extracorporeal Cardiopulmonary Resuscitation.

PURPOSE: Target temperature management (TTM) and extracorporeal cardiopulmonary resuscitation (ECPR) have been established as important interventions during cardiopulmonary arrest. However, the impact of combined TTM and ECPR on clinical outcomes has not been studied in detail. METHODS: We reviewed the records of 245 patients who received extracorporeal life support (ECLS) between January 2012 and June 2015. Exclusion criteria were as follows: Extracorporeal life support performed for reasons other than cardiac arrest, age less than 18 years, and death within 24 hours. A total of 101 patients were finally included in the study. Twenty-five patients underwent TTM, and 76 patients did not. RESULTS: The patients' mean age was 55 ± 16.7 years. The mean cardiac arrest time was 44.6 ± 33.5 minutes. There were 84 patients whose cardiac arrest was due to a cardiac cause (83.2%) and 79 patients with in-hospital cardiac arrest (78.2%). There was a significant difference in average body temperature during the first 24 hours following ECPR (33.4°C vs 35.6°C; P = .001). The overall favorable neurological outcome rate was 34% and hospital survival rate was 47%. There was no difference in favorable neurological outcomes and hospital survival between the TTM and non-TTM groups (P = .91 and .84, respectively). On multivariate analysis of neurological outcomes and hospital survival, TTM was not a significant prognostic factor. CONCLUSION: We did not observe any benefits of TTM in patients undergoing ECPR. Natural hypothermia or normothermia related to ECLS may explain this result. Further research is needed to understand the role of TTM in ECPR.