Benefits Of Therapeutic Hypothermia Research Articles

Current Advances in the Use of Therapeutic Hypothermia.

Temperature management and therapeutic hypothermia is being investigated in stroke, subarachnoid hemorrhage, myocardial infarction, and neonatal encephalopathy. Previous clinical studies have provided support for the use of hypothermia in these clinical conditions, and new studies are currently underway to establish safety and efficacy of this therapeutic intervention. Thus, this particular session brought together experts in the field of therapeutic hypothermia to discuss its use in several important patient populations. Dr. Neeraj Badjatia from the University of Maryland School of Medicine discussed antishivering strategies targeting stroke and subarachnoid hemorrhage. This lecture emphasized thermoregulatory systems and systematic approaches toward shiver control during cooling in patients with acute stroke. Various pharmacological strategies are currently used for shiver control, including drug combinations and counterwarming approaches. Dr. Christopher J. White of the Ochsner Medical Center emphasized the use of hypothermia in myocardial infarction. Myocardial infarction is an extremely important clinical problem, and the use of hypothermia to reduce ischemic injury and reperfusion-injury is currently being assessed in both preclinical and clinical studies. Previous clinical studies including a prospective randomized trial reported that postreperfusion cooling provided no significant improvement. However, recent investigations are concentrating on hypothermia treatment initiated before reperfusion, and these have been very promising. Dr. Abbot Laptook, Brown University, updated the attendees on therapeutic cooling and neonatal hypoxic ischemic encephalopathy. Results from published multicenter trials have emphasized the benefits of therapeutic hypothermia in newborn hypoxic ischemic encephalopathy patients, and issues regarding implementation of hypothermia on transport to hospitals are being evaluated along with combination approaches. Dr. Markus Foedisch from Bonn, Germany, discussed the use of brain damage markers to determine how best to utilize hypothermia after cardiac arrest. Dr. Foedisch updated the attendees regarding the cool brain register as well as the effects of cooling on available biomarkers, including neuron-specific enolase and S100B. This session had an extensive question-and-answer exchange and provided new information regarding the advances being made in the use of hypothermia in these clinical conditions.

Does Erythropoietin monotherapy reduce mortality or moderate/severe disability in neonates with hypoxic ischaemic encephalopathy?

Commentary on: Malla RR, Asimi R, Teli MA, Shaheen F, Bhat MA. Erythropoietin monotherapy in perinatal asphyxia with moderate to severe encephalopathy: a randomized placebo-controlled trial. Journal of Perinatology 2017; 37: 596-601. PMID 28277490. Erythropoietin (EPO) works by a number of mechanisms that gives it neuroprotective properties including decreasing neuronal apoptosis in the acute phase and enhancing angiogenesis and neurogenesis for long-term brain healing 1. Malla et al. 2 demonstrate improved neurologic outcomes in patients treated with EPO monotherapy vs placebo when treating moderate or severe hypoxic ischaemic encephalopathy (HIE). A study carried out in China by Zhu et al. 3 comparing EPO vs placebo, also without adjunctive therapeutic hypothermia (TH), showed similar results. Importantly, these studies showed a significant improvement in neurologic outcome in patients with moderate but not severe encephalopathy. There was also no difference in mortality between the placebo and EPO groups. This differs from trials with TH, the current standard of care in most resource-rich areas, which show a similar reduction in combined mortality and morbidity, but also demonstrate a reduction in mortality [RR–0.75 (95% CI: 0.64, 0.88) [Table 1.2, reference (4)] and disability [RR–0.77 (95% CI: 0.63, 0.94) [Table 1.3, reference (4)], when stratified by moderate or severe encephalopathy (data not shown) (4). These differences could be attributed to the larger sample size of patients in the Cochrane review 4 compared to the single-center study 2 and are certainly reflected in the forest plots when looking at individual trials 4. In settings where TH is widely available, there is significant interest in the potential benefits of EPO as an adjunct therapy to TH. A phase I trial by Wu et al. 5 showed that a presumably effective dosing regimen of EPO could be safely given to neonates undergoing TH for HIE. In a phase II trial, Wu et al. 6 showed that infants treated with EPO as an adjunct to TH had less MRI brain injury and improved motor outcomes at 1 year of age. Currently, there are three phase III clinical trials underway (HEAL, PAEAN and Neurepo) comparing mortality and neurodevelopmental disability in term infants with HIE treated with EPO+ TH vs TH alone 7. These may reaffirm the safety of EPO as adjunct therapy to TH and substantiate evidence that it improves neurologic outcome. The number needed to treat (NNT) to prevent the composite measure of death or moderate or severe disability in this EPO monotherapy study was four 2, which is lower than most trials using TH alone, with an NNT of 7–9 1; however, the number of patients studied to date is far fewer. There has never been a head to head trial comparing EPO monotherapy vs TH. Given the findings of Malla et al. 2, is it an investigation worth considering given the resource intensity associated with TH compared to EPO monotherapy? Perhaps more importantly, would this ever be ethically feasible given the lack of clinical equipoise for the proven effectiveness of TH – although TH as compared to placebo has not been studied in the developing world either. Therefore, if the addition of EPO as an adjunct to TH in the current phase three trials fails to show a benefit, there may be an opportunity to ask this question again. The more challenging issue will be if adjunct EPO therapy does show incremental benefit compared to placebo, does that close the door on a head to head EPO vs TH? The use of simulation models may help to tease out some of the incremental cost-benefit challenges and potentially lay groundwork for a head to head trial. Careful consideration, however, must be given to the benefits of TH beyond neuroprotection that EPO may not offer (i.e. cardiovascular, gastrointestinal system, etc.). https://ebneo.org/2017/12/does-erythropoietin-monotherapy-reduce-mortality-or-moderatesevere-disability-in-neonates-with-hypoxic-ischemic-encephalopathy/ None. No relevant conflict of interests to declare.

Implementation of mild therapeutic hypothermia for post-resuscitation care of sudden cardiac arrest survivors in cardiology units in Poland.

The post-cardiac arrest (CA) period is often associated with secondary damage of the brain that leads to severe neurological deficits. The current practice guidelines recommend the use of therapeutic hypothermia (TH) to prevent neurological deficit and improve survival. The aim of the study was to investigate the implementation of medical guidelines in clinical practice and to evaluate the barriers for implementation of TH in cardiology units in Poland. A telephone survey, fax and online inquiry form were used to assess the implementation of TH in cardiology units in the management of unconscious patients after cardiac arrest (CA). The questions addressed the local practice, TH protocol, reasons for not using TH and outcomes of CA patients. We obtained information from 79 units out of 150 asked (53%). At the time of the survey, 24 units (30.8%) were using TH as part of their post-CA management. Of all CA patients, 45% underwent TH in cardiac intensive care units (CICU), 37.5% in the coronary care unit (CCU) and 12.5% in the intensive care unit (ICU). The major barrier for the implementation of TH declared by the non-cooling centers was lack of sufficient knowledge regarding the technique and protocol, as well as experience (37%); access to dedicated equipment was not perceived as an obstacle. The number of cardiology units that provide TH for comatose CA patients is low. The main limiting factor for wider use of TH is lack of knowledge and experience. There is a clear need for urgent educational activities for cardiology units. The benefits of TH still have not reached their potential in cardiology units.

Effects of therapeutic hypothermia on white matter injury from murine neonatal hypoxia-ischemia.

BackgroundTherapeutic hypothermia (TH) is the standard of care for neonates with hypoxic-ischemic encephalopathy but is not fully protective in the clinical setting. Hypoxia-ischemia (HI) may cause white matter injury (WMI), leading to neurological and cognitive dysfunction.MethodsP9 mice were subjected to HI as previously described. Pups underwent 3.5 hours of systemic hypothermia or normothermia. Cresyl violet and Perl’s iron stain for histopathological scoring of brain sections was completed blindly on all brains. Immunocytochemical (ICC) staining for myelin basic protein (MBP), microglia (Iba1), and astrocytes (GFAP) was performed on adjacent sections. Volumetric measurements of MBP coverage were used for quantitative analysis of white matter.ResultsTH provided neuroprotection by injury scoring for the entire group (n=44) (p<0.0002). ICC analysis of a subset of brains showed that the lateral caudate was protected from WMI (p<0.05). Analysis revealed decreased GFAP and Iba1 staining in hippocampal regions, mostly CA2/CA3. GFAP and Iba1directly correlated with injury scores of normothermic brains.ConclusionsTH reduced injury and qualitative data suggest that hippocampus and lateral caudate are protected from HI. Mildly injured brains may better show the benefits of TH. Overall these data indicate regional differences in WMI susceptibility and inflammation in a P9 murine HI model.

Survey of Neonatal Intensive Care Unit Nurse Attitudes Toward Therapeutic Hypothermia Treatment

The traumatic experiences of parents of babies treated with therapeutic hypothermia (TH) have been described. No research has assessed neonatal intensive care unit (NICU) nurse experience in providing care to hypothermic babies and emotional support to their parents. To assess NICU nurse attitudes to the provision of TH with respect to perceptions about baby pain/sedation, need for nurse and parent education, decision making about initiation of TH, and barriers to best care. A survey was electronically sent to 219 nurses at 2 affiliated academic level III NICUs: 1 rural and 1 urban location. There were 17 questions where responses were selected from a preset list and 7 opportunities for nurses to provide free text responses. The response rate was 38% (N = 83). Overwhelming similarities between the urban and rural institutions were found with NICU nurses expressing understanding of the indications for initiating TH, agreement that TH improves long-term outcomes and that the benefits of TH outweigh the risks. Nurses at the urban institution more frequently expressed concerns surrounding inadequate treatment of baby pain/sedation, and nurses at both institutions strongly emphasized the need for more nurse and parent education about TH and improved timeliness of decision making for initiation of TH. NICU nurses specifically want to learn more about outcomes of babies after treatment with TH and feel that parents need more education about TH. Research is urgently needed to better understand the implications of TH treatment for parent-baby bonding.

THERAPEUTIC HYPOTHERMIA FOR IN-HOSPITAL CARDIAC ARREST: A META ANALYSIS

Background: Multiple randomized controlled trials have demonstrated the favorable impact of Therapeutic Hypothermia (TH) in out of hospital cardiac arrest. The benefit of TH for patients with In-Hospital Cardiac Arrest (IHCA) remains unclear. There have been no RCTs and results of observational

Therapeutic Hypothermia Provides Variable Protection against Behavioral Deficits after Neonatal Hypoxia-Ischemia: A Potential Role for Brain-Derived Neurotrophic Factor

Background: Despite treatment with therapeutic hypothermia (TH), infants who survive hypoxic ischemic (HI) encephalopathy (HIE) have persistent neurological abnormalities at school age. Protection by TH against HI brain injury is variable in both humans and animal models. Our current preclinical model of hypoxia-ischemia (HI) and TH displays this variability of outcomes in neuropathological and neuroimaging end points with some sexual dimorphism. The detailed behavioral phenotype of this model is unknown. Whether there is sexual dimorphism in certain behavioral domains is also not known. Brain-derived neurotrophic factor (BDNF) supports neuronal cell survival and repair but may also be a marker of injury. Here, we characterize the behavioral deficits after HI and TH stratified by sex, as well as late changes in BDNF and its correlation with memory impairment. Methods: HI was induced in C57BL6 mice on postnatal day 10 (p10) (modified Vannucci model). Mice were randomized to TH (31°C) or normothermia (NT, 36°C) for 4 h after HI. Controls were anesthesia-exposed, age- and sex-matched littermates. Between p16 and p39, growth was followed, and behavioral testing was performed including reflexes (air righting, forelimb grasp and negative geotaxis) and sensorimotor, learning, and memory skills (open field, balance beam, adhesive removal, Y-maze tests, and object location task [OLT]). Correlations between mature BDNF levels in the forebrain and p42 memory outcomes were studied. Results: Both male and female HI mice had an approximately 8-12% lower growth rate (g/day) than shams (p ≤ 0.01) by p39. TH ameliorated this growth failure in females but not in males. In female mice, HI injury prolonged the time spent at the periphery (open field) at p36 (p = 0.004), regardless of treatment. TH prevented motor impairments in the balance beam and adhesive removal tests in male and female mice, respectively (p ≤ 0.05). Male and female HI mice visited the new arm of the Y-maze 12.5% (p = 0.05) and 10% (p = 0.03) less often than shams, respectively. Male HI mice also had 35% lower exploratory preference score than sham (p ≤ 0.001) in the OLT. TH did not prevent memory impairments found with Y-maze testing or OLT in either sex (p ≤ 0.01) at p26. At p42, BDNF levels in the forebrain ipsilateral to the HI insult were 1.7- to 2-fold higher than BDNF levels in the sham forebrain, and TH did not prevent this increase. Higher BDNF levels in the forebrain ipsilateral to the insult correlated with worse performance in the Y-maze in both sexes and in OLT in male mice (p = 0.01). Conclusions: TH provides benefit in specific domains of behavior following neonatal HI. In general, these benefits accrued to both males and females, but not in all areas. In some domains, such as memory, no benefit of TH was found. Late differences in individual BDNF levels may explain some of these findings.

Understanding therapeutic hypothermia.

Therapeutic hypothermia is a relatively new protocol that can improve patients' chances of favorable neurologic outcomes after cardiac arrest. However, implementation rates remain low nationwide. This article describes recommendations for and benefits of therapeutic hypothermia in postresuscitation care.

Therapeutic hypothermia and targeted temperature management for traumatic brain injury: Experimental and clinical experience

Traumatic brain injury (TBI) is a worldwide medical problem, and currently, there are few therapeutic interventions that can protect the brain and improve functional outcomes in patients. Over the last several decades, experimental studies have investigated the pathophysiology of TBI and tested various pharmacological treatment interventions targeting specific mechanisms of secondary damage. Although many preclinical treatment studies have been encouraging, there remains a lack of successful translation to the clinic and no therapeutic treatments have shown benefit in phase 3 multicenter trials. Therapeutic hypothermia and targeted temperature management protocols over the last several decades have demonstrated successful reduction of secondary injury mechanisms and, in some selective cases, improved outcomes in specific TBI patient populations. However, the benefits of therapeutic hypothermia have not been demonstrated in multicenter randomized trials to significantly improve neurological outcomes. Although the exact reasons underlying the inability to translate therapeutic hypothermia into a larger clinical population are unknown, this failure may reflect the suboptimal use of this potentially powerful therapeutic in potentially treatable severe trauma patients. It is known that multiple factors including patient recruitment, clinical treatment variables, and cooling methodologies are all important in yielding beneficial effects. High-quality multicenter randomized controlled trials that incorporate these factors are required to maximize the benefits of this experimental therapy. This article therefore summarizes several factors that are important in enhancing the beneficial effects of therapeutic hypothermia in TBI. The current failures of hypothermic TBI clinical trials in terms of clinical protocol design, patient section, and other considerations are discussed and future directions are emphasized.

The significance of cord gases in neonatal encephalopathy – overview

Experimental studies and animal models have shown that hypoxic ischaemic encephalopathy (HIE) is not a single event, but rather an evolving process, resulting in cell death. Therapeutic hypothermia is used to break the process and protect the neurons from secondary injury. Cord gases analysis plays an important role in defining the population of babies who will benefit of therapeutic hypothermia. However, the physiology of cord gases is complicated and one should be aware of the pitfalls associated with interpreting their values.

ERP evidence of preserved early memory function in term infants with neonatal encephalopathy following therapeutic hypothermia.

Neonatal encephalopathy (NE) carries high risk for neurodevelopmental impairments. Therapeutic hypothermia (TH) reduces this risk, particularly for moderate encephalopathy (ME). Nevertheless, these infants often have subtle functional deficits, including abnormal memory function. Detection of deficits at the earliest possible time-point would allow for intervention during a period of maximal brain plasticity. Recognition memory function in 22 infants with NE treated with TH was compared to 23 healthy controls using event-related potentials (ERPs) at 2 wk of age. ERPs were recorded to mother's voice alternating with a stranger's voice to assess attentional responses (P2), novelty detection (slow wave), and discrimination between familiar and novel (difference wave). Development was tested at 12 mo using the Bayley Scales of Infant Development, Third Edition (BSID-III). The NE group showed similar ERP components and BSID-III scores to controls. However, infants with NE showed discrimination at midline leads (P = 0.01), whereas controls showed discrimination in the left hemisphere (P = 0.05). Normal MRI (P = 0.05) and seizure-free electroencephalogram (EEG) (P = 0.04) correlated positively with outcomes. Infants with NE have preserved recognition memory function after TH. The spatially different recognition memory processing after early brain injury may represent compensatory changes in the brain circuitry and reflect a benefit of TH.

Abstract 20023: Impact of Targeted Temperature During Therapeutic Hypothermia: A Pooling Analysis of Published Literature

Introduction: Two small RCTs demonstrated benefit of therapeutic hypothermia (TH) after out-hospital cardiac arrest (OHCA). We explored the benefit of targeted temperature during TH and also performed an updated meta-analysis to determine the intervention effect in the community. Methods: We identified studies by searching electronic databases (MEDLINE, EMBASE and Cochrane Library). We selected RCTs and cohort studies restricted to those reporting achieved temperature during TH after OHCA, and describing mortality and neurological outcomes at discharge. Studies were assessed for risk of bias. Data from all individual hypothermia arms were pooled by achieved temperature. Pooled outcomes were compared across achieved temperatures. Meanwhile, we meta-analyzed controlled studies comparing hypothermia against normothermia. Results: The search identified 32,275 studies of which 24 studies (34 hypothermia arms) were used in the pooling analysis and 14 controlled studies were meta-analyzed. Pooling analysis reported an overall in-hospital mortality of 47.2% with a rate of good neurological outcome at discharge of 38%. There was no difference in hospital mortality (p=0.86) or neurological outcomes at discharge (p=0.32) across temperatures (Figure 1). Sub-group analysis by rhythm showed a non-significant trend towards benefit when the lower temperature were applied to non-shockable rhythms. Meta-analysis demonstrated a MTH mortality (OR 0.51, 95%CI:0.41-0.64, I2=4.1%) and neuro-protective benefit (OR 2.48, 95%CI:1.91-3.22, I2=0%). Conclusions: No discernible clinical benefit was noted based on target temperature achieved. The signal toward potential benefit when applying lower temperature to non-shockable rhythms warrants exploration. Consistent with prior meta-analysis, TH provides mortality and neuro-protective benefit after OHCA even when including cohort studies thought to be more representative of performance in the community.

Effectiveness of therapeutic hypothermia on neurological status and survival in patients after cardiac arrest: a Meta-analysis

Objective To evaluate the effects of therapeutic hypothermia on both neurological status and survival rate in patients after cardiac arrest. Methods The data were searched from MEDLINE, PubMed, EMBASE, Cochrane Library, Wanfang database, CNKI and CBM. The randomized and controlled trials were selected for evaluating the main outcomes of neurological status and survival rate in patients after cardiac arrest. Meta-analysis was carried out by using Review Manger 5.0 software. The results were expressed in risk ratio (RR) for dichotomous outcomes data with 95% confidence intervals (CI) , and P < 0.05 was considered to be significant. Results Eight randomized controlled clinical trials with a total of 1 512 patients met our inclusion criteria. The overall risk ratio of favorable neurological status was 1.34 (95% CI: 1.01 -1.78, P 0.05) with therapeutic hypothermia compared with controls, however, when the applications of conventional cooling trials were analyzed, the risk ratio was 1.51 (95% CI: 1.22-1.87, P <0.01) and 1.36 (95% CI: 1.13-1.63, P <0.01) , respectively. Conclusions Patients treated with therapeutic hypothermia after cardiac arrest had more favorable neurological status compared with the controls. There was no benefit of therapeutic hypothermia to survival rate identified. Compare with conventional cooling methods, the therapeutic hypothermia could improve neurological status and survival rate in patients after cardiac arrest. Key words: Therapeutic hypothermia; Cardiac arrest; Neurological status; Survival; Meta-analysis

Treating Hypoxic Ischemic Encephalopathy With Hypothermia

Hypoxic-ischemic encephalopathy (HIE) is associated with high rates of morbidity and mortality, and only recently has an effective treatment been developed to mitigate its sequelae. Moderate therapeutic hypothermia (TH) (core temperatures of 33oC–35oC) has been found in a number of randomized clinical trials to reduce mortality and improve neurodevelopmental outcomes in full-term neonates with moderate or severe HIE. TH can be administered using various techniques, but optimal use dictates meticulous control of targeted core temperature (usually assessed as rectal temperature), and thus servo-controlled devices have an advantage. Treatment is applied for 72 hours, and then gradual rewarming is performed at a slow rate. Rapid rewarming and hyperthermia should be avoided because they may be associated with neuronal damage and reversal of the benefits of TH. Long-term outcomes, at ages 6 to 8 years, correlate well with the benefits observed at 18- to 24-month follow-up. Although better than any alternative therapy currently available, the rates of mortality and morbidity still remain high even when using TH.

Does the Benefit of Therapeutic Hypothermia in Refractory Status Epilepticus Depend on Seizure Etiology?

Does the Benefit of Therapeutic Hypothermia in Refractory Status Epilepticus Depend on Seizure Etiology?

Cardiac resuscitation: No benefit of therapeutic hypothermia after cardiac arrest in children.

Cardiac resuscitation: No benefit of therapeutic hypothermia after cardiac arrest in children

P123 – 2671: Follow up of neurodevelopmental outcome after therapeutic hypothermia for perinatal asphyxia

Objective Neuroprotective benefit of therapeutic hypothermia in term newborns with hypoxic-ischemic encephalopathy was assessed by analyzing survival and neurodevelopmental outcome of neonates subjected to this procedure. Methods Newborns with gestational age of more than 36 weeks and less than 6 hours of age with moderate to severe asphyxial encephalopathy underwent cooling protocol at a temperature of 33.5 °C for 72 hours and rewarming period of 6 hours. The outcome measures assessed were death and neurodevelopmental characteristics, which we compared at the different age using ASQ-3, at least 3 times during follow-up. Results Twenty-five children were assessed during the period from October 2010 to October 2013. Median gestational age was 40 weeks, birth weight 3470 g, Apgar score 2/4 and pH on admission to the hospital 7.02. Four (16%) children died and two were lost for follow up. At the first assessment developmental categories of communication were normal in 68.4%, problem solving in 73.7%, personal-social in 68.4%, gross motor in 57.9%, and fine motor in 36.8% but with a high need of retesting in this area. Seven of 19 patients (36.8%) had completely normal results for all five categories, while three (15.8%) had abnormal results for all categories. Second assesment was done in 17 patients with developmental categories of communication normal in 70.5%, problem solving in 76.5%, personal-social in 70.5%, gross motor in 58.8%, and fine motor in 41.1%. Third evaluation was done in 13 patients: developmental categories of communication were normal in 69.2%, problem solving in 76.9%, personal-social in 69.2%, gross motor in 61.5%, and fine motor in 46.2%. Conclusion Relatively small number of patients and limitations of this study design precluded any far-reaching conclusions, but we think that therapeutic hypothermia in term newborns can provide better survival and less neurologic sequels in hypoxic-ischemic encephalopathy patients.

Therapeutic hypothermia in acute liver failure: a multicenter retrospective cohort analysis.

The benefit of therapeutic hypothermia (TH) in acute liver failure (ALF) has not been previously demonstrated in a controlled fashion. This study sought to determine the impact of TH on 21-day survival and complications in ALF patients at high risk for cerebral edema. This was a retrospective cohort study of ALF patients in the US Acute Liver Failure Study Group with grade III or IV hepatic encephalopathy. TH (32°C-35°C) was used in 97 patients (8%); 1135 (92%) who were not cooled were controls. Intracranial pressure was monitored in 38 TH ALF patients (39.2% versus 22% of controls, P < 0.001). Rates of bleeding (12% for both) and bloodstream (17% versus 18%) and tracheal infections (21% versus 23%, P > 0.5 for all) were similar. Unadjusted 21-day overall (62% versus 60%) and transplant-free survival rates (45% versus 39%, P > 0.4 for both) were similar. Multivariate models were created for acetaminophen (APAP) patients (n = 582) and non-APAP patients (n = 613). For APAP patients, the Model for End-Stage Liver Disease [MELD; odds ratio (OR) = 0.91 per increment, 95% confidence interval (CI) = 0.89-0.94, P < 0.001] and vasopressors (OR = 0.16, 95% CI = 0.11-0.24, P < 0.001) were associated with decreased 21-day spontaneous survival. Survival was improved with TH in APAP patients who were <25 years old (age of 25 years: OR = 2.735, 95% CI = 1.001-7.467) but worsened for APAP patients who were 64 years old or older (age of 64 years: OR = 0.167, 95% CI = 0.028-0.999). For non-APAP patients, MELD (OR = 0.93 per increment, 95% CI = 0.91-0.95, P < 0.001) and vasopressors (OR = 0.60, 95% CI = 0.40-0.90, P = 0.01) were associated with worse outcomes, whereas TH had no impact (P = 0.93). In conclusion, TH in ALF was not associated with increased bleeding or infections. Although young APAP ALF patients may benefit, TH did not consistently affect 21-day survival. A prospective trial is required to clarify the utility of TH in ALF patients.

Treatment following OHCA: How, When, and Where?

For people who experience an out-of-hospital cardiac arrest (OHCA), prehospital body cooling has been linked to improved survival rates. The benefits of therapeutic hypothermia after an OHCA were discussed by a panel of experts, including background information on the epidemiology and prognostic importance of pre-hospital factors on survival outcomes, whether all patients should be cooled after experiencing an OHCA, and issues involved in percutaneous coronary intervention during cardiopulmonary resuscitation.

Impact of intra-arrest therapeutic hypothermia in outcomes of prehospital cardiac arrest: a randomized controlled trial.

Mild therapeutic hypothermia (TH) is recommended as soon as possible after the return of spontaneous circulation to improve outcomes after out-of-hospital cardiac arrest (OHCA). Preclinical data suggest that the benefit of TH could be increased if treatment is started during cardiac arrest. We aimed to study the impact of intra-arrest therapeutic hypothermia (IATH) on neurological injury and inflammation following OHCA. We conducted a 1:1 randomized, multicenter study in three prehospital emergency medical services and four critical care units in France. OHCA patients, irrespective of the initial rhythm, received either an infusion of cold saline and external cooling during cardiac arrest (IATH group) or TH started after hospital admission (hospital-cooling group). The primary endpoint was neuron-specific enolase (NSE) serum concentrations at 24 h. Secondary endpoints included IL-6, IL-8, and IL-10 concentrations, and clinical outcome. Of the 245 patients included, 123 were analyzed in the IATH group and 122 in the hospital-cooling group. IATH decreased time to reach temperature ≤ 34 °C by 75 min (95% CI: 4; 269). The rate of patients admitted alive to hospital was not different between groups [IATH n = 41 (33%) vs. hospital cooling n = 36 (30%); p = 0.51]. Levels of NSE and inflammatory biomarkers were not different between groups [median NSE at 24 h: IATH 96.7 μg/l (IQR: 49.9-142.8) vs. hospital cooling 97.6 μg/l (IQR: 74.3-142.4), p = 0.64]. No difference in survival and cerebral performance were found at 1 month. IATH did not affect biological markers of inflammation or brain damage or clinical outcome.