Use Of Mild Therapeutic Hypothermia Research Articles

What has changed over 10 years in neonatal therapeutic hypothermia? Part 1: Hypothermia in paediatric brain injury – a literature review

It is estimated that brain injury, broadly understood, is the most common cause of death and severe neurological complications in the paediatric population under 18 years of age. A number of preclinical studies have demonstrated the effectiveness of moderate cooling in terms of neuroprotection. In paediatrics, mild therapeutic hypothermia is a well-established procedure in the treatment of term or near-term newborns with deep asphyxia. Since 2015, in accordance with the guidelines of the American Academy of Pediatrics, mild therapeutic hypothermia is no longer an experimental method and it is widely recognised as a factor that improves survival and long-term neurological prognosis compared to traditional treatments. Thus, it is not surprising that, based on strong preclinical data from animal studies and the acceptance of mild therapeutic hypothermia in neonatology, opportunities to extend the range of patients benefiting from it beyond neonates in the first 6 hours of life as well as its new applications beyond the neonatal period are still being sought. In adults who underwent successful resuscitation due to sudden cardiac arrest in shockable rhythms, therapeutic cooling was recommended as a treatment method in post-resuscitation management almost a decade earlier than in newborns; however, a simple extrapolation of data from the adult population to the neonate population or from adults to neonates did not prove effective. The variation in terms of mechanisms leading to cardiac arrest (i.e. respiratory cause in children vs. cardiac cause in adults) entails differences in neurohormonal modulation between these two groups, which affects the results. This paper presents aspects of the use of mild therapeutic hypothermia over the last decade and discusses the mechanisms of encephalopathy development in the paediatric population, the conditions for its effective application as well as its place in the treatment of brain injury unrelated to perinatal asphyxia.

Adaptation of global hemostasis to therapeutic hypothermia in patients with out-of-hospital cardiac arrest: Thromboelastography study.

The use of mild therapeutic hypothermia (MTH) in patients after out-of-hospital cardiac arrest (OHCA) who are undergoing primary percutaneous coronary intervention (pPCI) can protect patients from thromboembolic complications. The aim of the study was to evaluate the adaptive mecha- nisms of the coagulation system in MTH-treated comatose OHCA survivors. Twenty one comatose OHCA survivors with acute coronary syndrome undergoing imme- diate pPCI were treated with MTH. Quantitative and qualitative analyses of physical clot properties were performed using thromboelastography (TEG). Two analysis time points were proposed: 1) during MTH with in vitro rewarming conditions (37°C) and 2) after restoration of normothermia (NT) under normal (37°C) and in vitro cooling conditions (32°C). During MTH compared to NT, reaction time (R) was lengthened, clot kinetic parameter (a) was significantly reduced, but no effect on clot strength (MA) was observed. Finally, the coagulation index (CI) was significantly reduced with clot fibrinolysis attenuated during MTH. The clot lysis time (CLT) was shortened, and clot stability (LY60) was lower compared with those values during NT. In vitro cooling generally influenced clot kinetics and reduced clot stability after treatment. Thromboelastography is a useful method for evaluation of coagulation system dysfunc- tion in OHCA survivors undergoing MTH. Coagulation impairment in hypothermia was associated with a reduced rate of clot formation, increased weakness of clot strength, and disturbances of fibrinoly- sis. Blood sample analyses performed at 32°C during MTH, instead of the standard 37°C, seems to enhance the accuracy of the evaluation of coagulation impairment in hypothermia.

Is 48-hour targeted temperature management not superior to 24-hour targeted temperature management after out-of-hospital cardiac arrest in adults? Feasible but still inconclusive

Since positive results of a quasi-randomized controlled trial and a randomized controlled trial were reported in 2002, mild therapeutic hypothermia (TH) has been accepted as an intervention to improve both survival and neurological outcomes following out-of-hospital cardiac arrest (OHCA) with shockable rhythm and has been actively implemented for all cardiac arrest patients around the world over the past decade (1,2). However, many questions for the optimal use of mild TH remain unresolved. Some researchers asserted that the scientific evidence is not sufficient to use mild TH for comatose survivors after cardiac arrest and have undertaken well-designed randomized controlled trials (RCTs) to demonstrate the efficacy and to determine an optimal dose for this intervention (3,4). In 2013, the largest trial including 939 patients after OHCA that compared a target temperature of 33 vs. 36 ℃ found no difference in 6-month mortality between the two temperatures (4). The results of the trial cast doubt on the efficacy of mild TH, and a following trial comparing targeted temperature management (TTM) at 33 ℃ with standard normothermia care (<37.5 ℃) will be just started by the same investigators (5). One of the important knowledge gaps for dose of TTM is the optimal duration of treatment.

Preclinical use of mild therapeutic hypothermia after cardiac arrest by the emergency services in Baden-Württemberg, Germany

During the last decade target temperature management has become an integral part of postresuscitation care. Within recent years there was astrong debate about the optimal target temperature, which might have effects on the preclinical induction of hypothermia. The present investigation focuses on the use of mild therapeutic hypothermia by emergency services in the state of Baden-Württemberg (Germany) and compares it to results of aprior study in 2008. Between April and August 2014 aquestionnaire was sent to all senior emergency physicians of emergency services in Baden Württemberg. The survey period was April to August of 2014. Parts of the questionnaire were similar to aprevious one in 2008, to ensure comparability to the former data; other parts were added to set new focuses. The data were analyzed in anonymized form. The response rate was 72.4% (97/134). Of the 97sites which responded to the questionnaire significantly more use preclinical hypothermia, compared to 2008 (72.2% [70/97] vs. 41.7%); 62.9% (44/70) declare cooling resuscitated patients routinely (vs. 17.7% in 2008). Cold infusions (85.7%), icepacks (64.3%), passive cooling (37.1%), nasal cooling (2.9%) and cooling caps (1.4%) are used (multiple naming was possible). Sites that did not use mild therapeutic hypothermia stated the following reasons: lack of equipment, short transport time and missing data for the intervention. Four sites reported on complications with therapeutic hypothermia. The present investigation shows an increased use of preclinical cooling after cardiopulmonary resuscitation as compared to 2008. Therefore, recent discussions concerning the optimal target temperature in postresuscitation care did not result in awaiving of preclinical therapeutic strategies in Baden-Württemberg. The emergency services sites/locations estimated the complication rates of mild therapeutic hypothermia as very low. Lack of equipment seems to be the main reason to refuse the preclinical use of therapeutic hypothermia. In conclusion, preclinical mild therapeutic hypothermia has become an integral part in the standard care of resuscitated patients in Baden-Württemberg.

Platelet reactivity during mild therapeutic hypothermia in patients with acute myocardial infarction treated with ticagrelor: study protocol of a single-centre study

In summary, the available data on the antiplatelet efficacy of P2Y12 receptor inhibitors suggest their less potent and/or delayed effect in patients undergoing mild therapeutic hypothermia (MTH). However, previous studies do not explain the mechanisms of the impact of MTH on platelet function. Moreover, there is a lack of evidence of any relationship between the increased prevalence of thrombotic complications in MTH patients and the anti-platelet effect of P2Y12 receptor inhibitors. We hypothesise that MTH may interfere with the absorption of ticagrelor and consequently results in significant changes in the pharmacokinetic and pharmacodynamic profile of this P2Y12 receptor inhibitor. It cannot be ruled out that the high initial level of platelet activation in MTH patients may additionally modify the pharmacodynamics of ticagrelor. Malabsorption may slow down the desired antiplatelet effect, while high levels of platelet activation may reduce the antiplatelet effect of ticagrelor. The aim of this study is to verify whether the use of MTH after resuscitation in out-of-hospital cardiac arrest (OHCA) patients with STEMI (ST-segment elevation myocardial infarction) treated with primary percutaneous coronary intervention (pPCI), affects the anti-platelet effect of ticagrelor. Moreover, we attempt to elucidate the mechanisms of impaired effect of ticagrelor in MTH patients based on pharmacodynamic and pharmacokinetic measurements. To achieve the aim of the study, we planned the following: 1) comparison of the pharmacokinetic and pharmacodynamic results obtained from the study population (MTH + pPCI + ticagrelor) with results obtained from a demographically and clinically comparable population of patients with STEMI treated with primary PCI and receiving ticagrelor (pPCI + ticagrelor); and 2) analysis of the pharmacodynamic results in relation to the pharmacokinetic measurements in the target population. Understanding the mechanisms standing behind the impact of MTH on the efficacy of platelet inhibition with P2Y12 inhibitors is pivotal in reducing the risk of thrombotic complications. The study is expected to provide information leading to improvement of the safety of MTH in STEMI patients with OHCA treated with pPCI and receiving ticagrelor.

Decompressive Craniectomy in a Patient with Severe Traumatic Brain Injury during Mild Therapeutic Hypothermia

Mild Therapeutic Hypothermia (MTH) and decompressive craniectomy are therapeutic measures used for the treatment of intracranial hypertension (ICHT) refractory to medical treatment and cerebrospinal fluid drainage. One of the side effects of MTH is the increased risk of coagulopathy, thus the performance of neurosurgical procedures in these cases is very controversial.We present the case of a patient with traumatic brain injury and ICHT refractory to medical treatment, in which moderate therapeutic hypothermia was initiated. After a transient improvement, the patient presented ICHT again, requiring a decompressive craniotomy while keeping the patient in moderate hypothermia. Due to the history of traumatic brain injury and the use of MTH, we decided on the use of viscoelastic tests as goal-directed therapy to assess haemostasis prior to surgery.

EEG in postanoxic coma: Prognostic and diagnostic value.

Evolution of the EEG background pattern is a robust contributor to prediction of poor or good outcome of comatose patients after cardiac arrest. At 24h, persistent isoelectricity, low voltage activity, or burst-suppression with identical bursts predicts a poor outcome without false positives. Rapid recovery toward continuous patterns within 12h is strongly associated with a good neurological outcome. Predictive values are highest in the first 24h, despite the use of mild therapeutic hypothermia and sedative medication. Studies on reactivity or mismatch negativity have not included the EEG background pattern. Therefore, the additional predictive value of reactivity parameters remains unclear. Whether or not treatment of electrographic status epilepticus improves outcome is studied in the randomized multicenter Treatment of Electroencephalographic STatus epilepticus After cardiopulmonary Resuscitation (TELSTAR) trial (NCT02056236).

Effect of therapeutic hypothermia on the outcomes after out-of-hospital cardiac arrest according to initial ECG rhythm and witnessed status: A nationwide observational interaction analysis

BackgroundThe use of mild therapeutic hypothermia (TH) in out-of-hospital cardiac arrest (OHCA) with shockable rhythms is recommended and widely used. However, it is unclear whether TH is associated with better outcomes in non-shockable rhythms. MethodsThis is a retrospective observational study using a national OHCA cohort database composed of emergency medical services (EMS) and hospital data. We included adult EMS-treated OHCA patients of presumed cardiac etiology who were admitted to the hospital during Jan. 2008 to Dec. 2013. Patients without hospital outcome data were excluded. The primary outcome was good neurological outcome at discharge; secondary outcome was survival to discharge. The primary exposure was TH. We compared outcomes between TH and non-TH groups using multivariable logistic regression, adjusting for individual and Utstein factors. Interactions of initial ECG rhythm and witnessed status on the effect of TH on outcomes were tested. ResultsThere were 11,256 patients in the final analysis. TH was performed in 1703 patients (15.1%). Neurological outcome was better in TH (23.5%) than non-TH (15.0%) (Adjusted OR=1.25, 95% CI 1.05–1.48). The effect of TH on the odds for good neurological outcome was highest in the witnessed PEA group (Adjusted OR=3.91, 95% CI 1.87–8.14). Survival to discharge was significantly higher in the TH group (55.1%) than non-TH (35.9%) (Adjusted OR=1.76, 95% CI 1.56–2.00). ConclusionsIn a nationwide observational study, TH is associated with better neurological outcome and higher survival to discharge. The effect of TH is greatest in witnessed OHCA patients with PEA as the initial ECG rhythm.

History and current use of mild therapeutic hypothermia after cardiac arrest.

In spite of many years of development and implementation of pre-hospital advanced life support programmes, the survival rate of out-of-hospital cardiac arrest (OHCA) used to be very poor. Neurologic injury from cerebral hypoxia is the most common cause of death in patients with OHCA. In the past two decades, post-resuscitation care has developed many new concepts aimed at improving the neurological outcome and survival rate of patients after cardiac arrest. Systematic post-cardiac arrest care after the return of spontaneous circulation, including induced mild therapeutic hypothermia (TH) in selected patients, is aimed at significantly improving rates of long-term neurologically intact survival. This review summarises the history and current knowledge in the field of mild TH after OHCA.

Targeted Temperature Management (TTM 2014).

Cardiac arrest (CA) remains a major cause of death and severe disability worldwide. The ischemic process that follows the cessation of cerebral perfusion and oxygenation, which is further worsened by the reperfusion injury occurring after the return of spontaneous circulation, can lead to severe hypoxic brain damage, resulting in a high rate of poor neurological recovery among CA survivors. The use of mild therapeutic hypothermia, or targeted temperature management (TTM) as recently suggested [1], has been recommended in CA patients since the publication of two randomized clinical trials in 2002, the results of which demonstrated a significant improvement in neurologically intact survival for comatose CA patients presenting with ventricular fibrillation or ventricular tachycardia [1,2]. Current guidelines suggest that mild therapeutic hypothermia should also be considered in patients presenting with other rhythms, although this has been less well studied [3]. In experimental studies, TTM provided significant cardiac and neurological protective effects through different pathways. Hypothermic mechanisms providing myocardial protection include, amongst all, improved energy production during ischemia, increased calcium sensitivity of myocytes, regulation of mitochondrial oxidative phosphorylation and preserved myocardial vascular autoregulation [4,5]. All of these protective mechanisms would result in increased myocardial contractility. After a post-anoxic injury, TTM may also protect cerebral function through reduced release of excitatory (that is, glutamate and dopamine) neurotransmitters, attenuation of reactive oxygen species production, preservation of the blood–brain barrier, protection of cerebral microcirculation and decrease in intracranial pressure [6,7]. As several pathways are involved in the pathogenesis of extended post-anoxic brain damage, TTM can be considered as a general and nonspecific neuroprotective strategy, which may efficiently attenuate and mitigate most of these mechanisms and potentially improve patients’ neurological outcome. Interestingly, recent studies have underlined not only that the hypothermic phase is important in this process, but that strict control of the patient’s temperature during the first 3 days since hospital admission (that is, rapid achievement of target temperature, a precise control of temperature during the maintenance phase, a slow and controlled rewarming and avoidance of fever for 48 to 72 hours) are key components to enhance TTM effectiveness after post-anoxic brain injury [8].

Favorable Outcome and Survival Using a Hypothermia Protocol After Successful Cardiopulmonary Resuscitation.

Use of mild therapeutic hypothermia to goal 32 34 °C, after return of spontaneous circulation (ROSC) in cardiac arrest patients, has been shown to increase the rates of survival and favorable neurological outcomes [1, 2]. The American Heart Association (AHA) recommends mild therapeutic hypothermia after ROSC for out-of-hospital cardiac arrest with an initial documented rhythm of ventricular fibrillation (class I, level of evidence B) [3]. International resuscitation guidelines also support mild therapeutic hypothermia as the best medical practice for shockable rhythms in patients resuscitated from cardiac arrest due to ventricular fibrillation and pulseless ventricular tachycardia after ROSC [4]. Herein, we wish to notify the readers on a case of therapeutic hypothermia after ROSC in a young man associated with favorable neurologic outcome and survival. A 34-yearold electrical worker is brought to the emergency department (ED) by co-workers having been injured by electrical strike at work. On arrival in the ED, he had a Glasgow coma score (GCS) of 3/15 and dilated sluggish pupils. Additionally, there were no heartbeats or respiration. Cardiac monitoring revealed ventricular fibrillation and the patient received treatment with 150-J biphasic waveform shock. Cardiopulmonary resuscitation (CPR) was immediately instituted after the shock. After 2 min of CPR, ROSC was achieved and his rhythm has restored to sinus rhythm. Neither epinephrine nor antidysrhythmic agents were administered. He was resuscitated succesufully but yet remained comatose after CPR at the ED, following vital signs: GCS 8, heart rate 110/min, and blood pressure 80/50 mm Hg. Advanced cardiac life support measures were initiated (i.e., controlled intravenous fluid support, administration of dopamine, adequate oxygenation, and support of respiration with bag ventilation) following ROSC in the ED. Furthermore, therapeutic hypothermia protocol was started immediately with ice packs in the ED to decrease the patient’s temperature below 34 °C. Two hours after admission to the ED, he was transferred to the intensive care unit (ICU) for optimal care. Therapeutic cooling was maintained for 24 h by gel-circulation cooling pads (temperature management system; Artric Sun® 5000) in the ICU, and the patient was discharged home with mild neurologic deficit on ICU day 20. Therapeutic hypothermia is associated with favorable neurologic outcome and survival in patients who have experienced cardiac arrest and resuscitated succesufully, as it was in the present case. This therapy should be started as quickly as possible in post-cardiac arrest care patients, particularly with shockable cardiac arrest rhythms.

Neurological consequences of cardiac arrest: Where do we stand?

With increasing public education in basic life support and with the widespread use of automated defibrillators, post-cardiac arrest comatose patients represent a growing part of ICU admissions. However the prognosis remains very poor and only a very low proportion of these resuscitated patients will recover and will leave the hospital without major neurological impairments. Neurological dysfunction predominantly includes disorders of consciousness, and may also include other manifestations such as seizures, myoclonus status epilepticus and other forms of movement disorders including post-anoxic myoclonus. In the most severe cases, coma may be irreversible or evolve towards a minimally conscious state, a vegetative state or even brain death. These severe conditions represent by far the leading cause of mortality and disability in such patients. Currently, early use of mild therapeutic hypothermia is the only treatment that demonstrated its ability to decrease neurological consequences and to improve the prognosis. Prognostication outcome is still mainly based on a rigorous clinical evaluation coupled with neuro-physiological investigations, but brain functional imaging could become a valuable tool in the near future. Clinical research focusing on survivors should be strongly encouraged in order to assess the mid- and long-terms outcome of survivors and to evaluate the impact of new treatments or strategies.

Therapeutic hypothermia.

There is growing evidence to support the use of mild therapeutic hypothermia (MTH), also known as targeted temperature management, in out-of-hospital patients who have experienced cardiac arrest. Reducing core body temperatures to 32-34°C can reduce mortality and neurological disability significantly among such patients, but recent surveys have shown that use of MTH is variable and there can be a considerable delay in initiating it.

Importance of invasive interventional strategies in resuscitated patients following sudden cardiac arrest

Post-resuscitation care has become a major part of the chain of survival for victims of cardiac arrest. Once spontaneous circulation is restored, it is important to consider early coronary angiography and concurrent use of mild therapeutic hypothermia. In those resuscitated from an arrest considered to be cardiac in origin, coronary angiography should be performed inmmediately to identify any culprit coronary occlusion or unstable lesions. If a culprit lesion is found, immediate percutaneous coronary intervention should be performed. Any out-of-hospital cardiac arrest victim successfully resuscitated, but who remain comatose after return of spontaneous circulation, should be cooled to 32–24°C for 24 h. Induction of mild hypothermia can be accomplished without delaying coronary intervention. When these two post-resuscitation therapies are provided concurrently long-term survival is 50–60%, with favorable neurological function achieved in 80–90% of such survivors.

Hipotermia terapéutica en la parada cardiorrespiratoria pediátrica

IntroductionTherapeutic hypothermia (TH) improves neurological outcome in adults after ventricular fibrillation cardiac arrest and in neonates with hypoxic ischemic encephalopathy. The effect of TH in children is under investigation. ObjectivesTo assess the feasibility, efficacy and safety of a pilot program of TH in pediatric cardiac arrest. Material and methodsProspective study in a pediatric intensive care unit. An external cooling method with a servo system was used on all patients according to an established protocol. Values expressed as median (IQ range). ResultsSix patients were included, of whom 5 had an out of hospital cardiac arrest. The mean age was 33 months (16-120) and Glasgow coma scale 6 (4-7). The T° prior to the induction of TH was 39.2° C (39.1-39.4). The median T° used was 34.0° C (33.5-34.8° C), which was reached in 4h. (3-7) after the start and maintained for 48h. (45-54). The rewarming was carried out over a period of 14h. (12-16). Hypokalemia was the most common adverse event found. Five patients survived to hospital discharge with a Glasgow Coma Scale of 13 (11-14). At 6 months follow up the Pediatric Cerebral Performance Category score was ≤ 2 in three patients. ConclusionIn this pilot study, the use of mild therapeutic hypothermia with a protocol that included rapid sequence induction with an external surface cooling technique was feasible, effective and safe in children with cardiac arrest.

Early in-hospital management of out-of-hospital cardiac arrest in Scotland

Guidelines recommend the use of mild therapeutic hypothermia (MTH) and percutaneous coronary intervention (PCI) in the early post-resuscitation management of select out-of-hospital cardiac arrest (OHCA) cases. This study aims to assess the current use of MTH and PCI in Scottish Emergency Departments (ED) and Intensive Care Units (ICU). We conducted a questionnaire survey of all the Scottish Emergency Medicine Consultants, EDs and ICUs. MTH was more commonly initiated in ICU than in the ED (19; 91 vs. 7; 37%, P<0.05). Only a minority two (11%) EDs routinely referred OHCA patients for early PCI and only three (16%) EDs receiving patients after OHCA had on-site access to PCI facilities. The use of MTH after OHCA appears to be widespread, although it is infrequently initiated in the ED. The utilization of PCI in OHCA management has yet to be widely established. Increased awareness may increase the use of promising therapies such as MTH and PCI following OHCA to save lives.

'Cooling and cathing' the post-resuscitated

Cronier and co-workers provide additional evidence that routine use of mild therapeutic hypothermia combined with emergent coronary angiography and percutaneous intervention results in excellent survival with intact neurological function for post-resuscitation patients with ventricular fibrillation.

Field-induced Therapeutic Hypothermia for Neuroprotection after Out-of Hospital Cardiac Arrest: A Systematic Review of the Literature

Emergency Medical Services (EMS) has started to embrace the early use of therapeutic hypothermia as standard treatment to improve neurological recovery in out-of hospital cardiac arrest (OHCA) survivors. We conducted a systematic review to provide an overall description of the current literature on the use of therapeutic hypothermia in OHCA and to identify possible gaps in the literature. Comprehensive searches of MEDLINE, PubMed, CINAHL, and ISI Web of Science from 1950 to March 2009, and EMBASE from 1988 to March 2009 were performed. Bibliographies of selected articles were hand searched. Two reviewers independently selected studies on the basis of three inclusion criteria. Two additional independent reviewers assessed selected studies for quality. Of more than 800 screened citations, a total of 11 published studies were included in the systematic review. Three studies were conducted in the United States, three in Finland, and one eachin Australia, France, Germany, Austria, and Norway. Four of the studies were pilot clinical trials that provided prehospital mild therapeutic hypothermia during active cardiopulmonary resuscitation. The remaining seven studies performed cooling after return of spontaneous circulation. Significant differences in research methodology and outcome measures were noted. Eight studies scored poor for quality. The use of mild therapeutic hypothermia is gaining acceptance within the EMS community. It seems that hypothermia can be efficiently induced in the prehospital environment. There is a need for more research in this area to understand the effectiveness and timing ofearly therapeutic hypothermia in the prehospital environment.

Review: Contemporary practices in postcardiac arrest syndrome: the role of mild therapeutic hypothermia

Out-of-hospital cardiac arrest remains a major cause of mortality and morbidity despite progress in resuscitative practices. The number of survivors with severe neurological impairment at hospital discharge is similarly dismal. Recently, much attention has been directed toward the use of mild therapeutic hypothermia in the care of comatose survivors with postcardiac arrest syndrome. Recent research suggests mild hypothermia lowers mortality and improves neurological outcome after successful treatment of cardiac arrest. The current 2005 updated guidelines of International Liaison Committee on Resuscitation and European Resuscitation Council recommend the utilization of mild induced hypothermia in postresuscitation treatment. Hypothermia induction in order to avoid the pathophysiological mechanisms of euthermia and hyperthermia and subsequent complications are briefly discussed. Cooling methods, potential side effects and questions regarding implementation of therapeutic hypothermia recommendations in every day clinical practice and future investigation are also addressed.

Use of mild therapeutic hypothermia improves outcomes in cardiac arrest

Use of mild therapeutic hypothermia improves outcomes in cardiac arrest