Optimal Target Temperature Research Articles

Impact of temperature on the magnitude and duration of relief after lumbar facets medial branch nerves radiofrequency ablation: a randomized double-blinded study

IntroductionThere are numerous studies appraising the variables that may influence the clinical outcomes after lumbar thermal radiofrequency ablation (RFA). Expanding the lesion size may increase the likelihood of capturing the...

Procedure after successful cardiopulmonary resuscitation-Cooling or no more cooling?

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

Multi-camera imaging to characterize jet and liner uniformity on the Plasma Liner Experiment (PLX).

At Plasma Liner Experiment, a set of 36 coaxial plasma guns are deployed quasi-uniformly over a 9 ft diameter spherical chamber and are used to form a high-Z spherically compressive plasma liner. Simulations indicate that for the concept to ultimately achieve optimal target density and temperature, a high degree of timing uniformity is required between all guns. To aid in quantifying and correcting gun-to-gun nonuniformities, a key diagnostic will consist of up to six fisheye-view CCD cameras positioned inside the main chamber such that each has all plasma guns within its view. The individual cameras can be triggered at different times to determine each plasma jet's muzzle velocity and structure for different operating conditions. This camera array is currently under development, and the implementation needs and challenges for this camera array are discussed here. Additionally, we detail the analysis methodology for determining jet-to-jet uniformity deviations and how we can correct them, thereby improving overall liner uniformity.

The association of different target temperatures in targeted temperature management with neurological outcome after out-of-hospital cardiac arrest based on a prospective multicenter observational study in Korea (the KORHN-PRO registry): IPTW analysis.

BackgroundAmong comatose survivors of out-of-hospital cardiac arrest (OHCA), targeted temperature management (TTM) has improved neurological outcomes. However, although the target temperature shifted from 33°C to 33°C~36°C, the optimal target temperature is still unclear. The goal of this study was to evaluate neurological outcomes at 6 months at target temperatures of 33°C and 36°C.Materials and methodsWe analyzed OHCA survivors who underwent TTM and were recorded in the Korean Hypothermia Network, a prospective multicenter registry, from October 2015 to December 2018. The primary outcome was good neurological outcome at six months, defined as a cerebral performance category of 1–2, and the secondary outcome was survival at 6 months.ResultsA total of 1339 patients were treated with TTM in twenty-two emergency departments. Of those, 1054 were treated at 33°C, and 285 were treated at 36°C. There was no significant difference in good neurological outcomes at 6 months (30.6% vs. 31.2%, p = 0.850, adjusted OR 0.97, 95% CI = 0.73–1.29]) and survival at six months (41.4% vs. 38.7%, p = 0.401, adjusted HR 1.08, 95% CI = 0.91–1.28]) between TTM 33°C and TTM 36°C. After propensity score matching, good neurological outcomes at 6 months (OR 0.93, 95% CI = 0.74–1.18) and survival at 6 months (HR 1.05, 95% CI = 0.92–1.21) were still not associated with TTM 33°C and TTM 36°C.ConclusionIn this study, patients treated with a target temperature of 33°C had similar good neurological outcomes and survival at six months compared with those treated with a target temperature of 36°C.

Protocolized Post-Cardiac Arrest Care with Targeted Temperature Management.

Improvements in teamwork and resuscitation science have considerably increased the success rate of cardiopulmonary resuscitation. Cerebral injury, myocardial dysfunction, systemic ischemia and reperfusion response, and precipitating pathology after the return of spontaneous circulation (ROSC) constitute post-cardiac arrest syndrome. Because the entire body is involved in cardiac arrest and the early post-arrest period, protocolized post-arrest care consisting of cardiovascular optimization, ventilation and oxygenation adjustment, coronary revascularization, targeted temperature management (TTM), and control of seizures and blood sugar would benefit survival and neurological outcomes. Emergent coronary angiography is suggested for cardiac arrest survivors suspected of having ST-elevation myocardial infarction, however the superiority of culprit or complete revascularization in patients with multivessel coronary lesions remains undetermined. High-quality TTM should be considered for comatose patients who are successfully resuscitated from cardiac arrest, however the optimal target temperature may depend on the severity of their condition. The optimal timing for making prognostication should be no earlier than 72 h after rewarming in TTM patients, and 72 h following ROSC in non-TTM patients. To predict neurological recovery correctly may need the use of several prognostic tools together, including clinical neurological examinations, brain images, neurological studies and biomarkers.

Targeted temperature management following out-of-hospital cardiac arrest: a systematic review and network meta-analysis of temperature targets.

Targeted temperature management (TTM) may improve survival and functional outcome in comatose survivors of out-of-hospital cardiac arrest (OHCA), though the optimal target temperature remains unknown. We conducted a systematic review and network meta-analysis to investigate the efficacy and safety of deep hypothermia (31-32°C), moderate hypothermia (33-34°C), mild hypothermia (35-36°C), and normothermia (37-37.8°C) during TTM. We searched six databases from inception to June 2021 for randomized controlled trials (RCTs) evaluating TTM in comatose OHCA survivors. Two reviewers performed screening, full text review, and extraction independently. The primary outcome of interest was survival with good functional outcome. We used GRADE to rate our certainty in estimates. We included 10 RCTs (4218 patients). Compared with normothermia, deep hypothermia (odds ratio [OR] 1.30, 95% confidence interval [CI] 0.73-2.30), moderate hypothermia (OR 1.34, 95% CI 0.92-1.94) and mild hypothermia (OR 1.44, 95% CI 0.74-2.80) may have no effect on survival with good functional outcome (all low certainty). Deep hypothermia may not improve survival with good functional outcome, as compared to moderate hypothermia (OR 0.97, 95% CI 0.61-1.54, low certainty). Moderate hypothermia (OR 1.23, 95% CI 0.86-1.77) and deep hypothermia (OR 1.27, 95% CI 0.70-2.32) may have no effect on survival, as compared to normothermia. Finally, incidence of arrhythmia was higher with moderate hypothermia (OR 1.45, 95% CI 1.08-1.94) and deep hypothermia (OR 3.58, 95% CI 1.77-7.26), compared to normothermia (both high certainty). Mild, moderate, or deep hypothermia may not improve survival or functional outcome after OHCA, as compared to normothermia. Moderate and deep hypothermia were associated with higher incidence of arrhythmia. Routine use of moderate or deep hypothermia in comatose survivors of OHCA may potentially be associated with more harm than benefit.

Outcome Related to Level of Targeted Temperature Management in Postcardiac Arrest Syndrome of Low, Moderate, and High Severities: A Nationwide Multicenter Prospective Registry.

The optimal target temperature during targeted temperature management for patients after cardiac arrest remains under debate. The aim of this study was to evaluate the association between targeted temperature management at lower target temperatures and the neurologic outcomes among patients classified by the severity of postcardiac arrest syndrome. A multicenter observational study from the out-of-hospital cardiac arrest registry of the Japanese Association for Acute Medicine, which is a nationwide prospective registry of out-of-hospital cardiac arrest patients. A total of 125 critical care medical centers or hospitals with an emergency care department across Japan. A total of 1,111 out-of-hospital cardiac arrest patients who had received targeted temperature management. We divided all 1,111 postcardiac arrest syndrome patients treated with targeted temperature management into two groups: those who received targeted temperature management at a lower target temperature (33-34°C) and those who received targeted temperature management at a higher target temperature (35-36°C). In regard to classification of the patients, we divided the patients into three categories of severity (low, moderate, and high severities) using the risk classification tool, post-Cardiac Arrest Syndrome for Therapeutic hypothermia, which was previously validated. The primary outcome was the percentage of patients with a good neurologic outcome at 30 days, and the secondary outcome was the survival rate at 30 days. Multivariate analysis showed that targeted temperature management at 33-34°C was significantly associated with a good neurologic outcome and survival at 30 days in the moderate severity (odds ratio, 1.70 [95% CI, 1.03-2.83] and 1.90 [95% CI, 1.15-3.16], respectively), but not in the patients of low or high severity (pinteraction = 0.033). Propensity score analysis also showed that targeted temperature management at 33-34°C was associated with a good neurologic outcome in the moderate-severity group (p = 0.022). Targeted temperature management at 33-34°C was associated with a significantly higher rate of a good neurologic outcome in the moderate-severity postcardiac arrest syndrome group, but not in the low- or high-severity group.

Which Target Temperature for Post-Anoxic Brain Injury? A Systematic Review from "Real Life" Studies.

There is a persistent debate on the optimal target temperature to use during cooling procedures in cardiac arrest survivors. A large randomized clinical trial (RCT) including more than 900 patients showed that targeted temperature management (TTM) at 33 °C had similar mortality and unfavorable neurological outcome (UO) rates as TTM at 36 °C in out-of-hospital cardiac arrest patients with any initial rhythm. Since then, several observational studies have been published on the effects of changes in target temperature (i.e., from 33 to 36 °C) on patients’ outcome. We performed a systematic literature search from 1 January 2014 to 4 December 2020 and identified ten retrospective studies (very low levels of certainty; high risk of bias), including 5509 patients, that evaluated TTM at 33 °C vs. TTM at 36 °C on the occurrence of UO (n = eight studies) and mortality (n = ten studies). TTM at 33 °C was associated with a lower risk of UO when studies assessing neurological outcome with the Cerebral Performance Categories were analyzed (OR 0.80 [95% CIs 0.72–0.98]; p = 0.03). No differences in mortality were observed within the two TTM strategies. These results suggest that an inappropriate translation of TTM protocols from large well-conducted randomized trials into clinical management may result in unexpected effects on patients’ outcome. As for all newly commercialized drugs, epidemiological studies and surveillance programs with an adequate follow-up on large databases are necessary to understand how RCTs are implemented into medical practice.

Outcome and status of postcardiac arrest care in Korea: results from the Korean Hypothermia Network prospective registry.

ObjectiveHigh-quality intensive care, including targeted temperature management (TTM) for patients with postcardiac arrest syndrome, is a key element for improving outcomes after out-of-hospital cardiac arrest (OHCA). We aimed to assess the status of postcardiac arrest syndrome care, including TTM and 6-month survival with neurologically favorable outcomes, after adult OHCA patients were treated with TTM, using data from the Korean Hypothermia Network prospective registry.MethodsWe used the Korean Hypothermia Network prospective registry, a web-based multicenter registry that includes data from 22 participating hospitals throughout the Republic of Korea. Adult comatose OHCA survivors treated with TTM between October 2015 and December 2018 were included. The primary outcome was neurological outcome at 6 months.ResultsOf the 1,354 registered OHCA survivors treated with TTM, 550 (40.6%) survived 6 months, and 413 (30.5%) had good neurological outcomes. We identified 839 (62.0%) patients with preClinsumed cardiac etiology. A total of 937 (69.2%) collapses were witnessed, shockable rhythms were demonstrated in 482 (35.6%) patients, and 421 (31.1%) patients arrived at the emergency department with prehospital return of spontaneous circulation. The most common target temperature was 33°C, and the most common target duration was 24 hours.ConclusionThe survival and good neurologic outcome rates of this prospective registry show great improvements compared with those of an earlier registry. While the optimal target temperature and duration are still unknown, the most common target temperature was 33°C, and the most common target duration was 24 hours.

Association of Initial Illness Severity and Outcomes After Cardiac Arrest With Targeted Temperature Management at 36 °C or 33 °C

It is uncertain what the optimal target temperature is for targeted temperature management (TTM) in patients who are comatose following cardiac arrest. To examine whether illness severity is associated with changes in the association between target temperature and patient outcome. This cohort study compared outcomes for 1319 patients who were comatose after cardiac arrest at a single center in Pittsburgh, Pennsylvania, from January 2010 to December 2018. Initial illness severity was based on coma and organ failure scores, presence of severe cerebral edema, and presence of highly malignant electroencephalogram (EEG) after resuscitation. TTM at 36 °C or 33 °C. Primary outcome was survival to hospital discharge, and secondary outcomes were modified Rankin Scale and cerebral performance category. Among 1319 patients, 728 (55.2%) had TTM at 33 °C (451 [62.0%] men; median [interquartile range] age, 61 [50-72] years) and 591 (44.8%) had TTM at 36 °C (353 [59.7%] men; median [interquartile range] age, 59 [48-69] years). Overall, 184 of 187 patients (98.4%) with severe cerebral edema died and 234 of 243 patients (96.3%) with highly malignant EEG died regardless of TTM strategy. Comparing TTM at 33 °C with TTM at 36 °C in 911 patients (69.1%) with neither severe cerebral edema nor highly malignant EEG, survival was lower in patients with mild to moderate coma and no shock (risk difference, -13.8%; 95% CI, -24.4% to -3.2%) but higher in patients with mild to moderate coma and cardiopulmonary failure (risk difference, 21.8%; 95% CI, 5.4% to 38.2%) or with severe coma (risk difference, 9.7%; 95% CI, 4.0% to 15.3%). Interactions were similar for functional outcomes. Most deaths (633 of 968 [65.4%]) resulted after withdrawal of life-sustaining therapies. In this study, TTM at 33 °C was associated with better survival than TTM at 36 °C among patients with the most severe post-cardiac arrest illness but without severe cerebral edema or malignant EEG. However, TTM at 36 °C was associated with better survival among patients with mild- to moderate-severity illness.

Cardioprotection by very mild hypothermia in mice.

Target temperature management is recommended in post-resuscitation care. Additionally, hypothermia is a promising option in adjunctive therapy of acute myocardial infarction (MI). However, first in men data are contradicting. There are still many open questions to identify the optimal regimen and target temperature. In this study, we aimed to investigate the effect of very mild hypothermia on infarct size (IS) in mice. Mice underwent cardiac ischemia by temporary occlusion of the left anterior descending (LAD) artery under conditions of very mild hypothermia (34-36 °C). Hypothermia was reached within the first 5 minutes of ischemia (temperature: 34.6±0.5 vs. 36.8±1.1 °C, P=0.035). Very mild hypothermia reduced IS in mice undergoing 30 minutes ischemia [IS/area at risk (AAR): 45±12% vs. 22±4%, P=0.018] as well as mice undergoing 60 minutes ischemia [IS/AAR: 67±7% vs. 28±2%, P=0.0003]. Very mild hypothermia reduces IS. This new approach in adjunctive therapy of patients with acute MI should be investigated in clinical trials.

Targeted Temperature Management for Improved Outcomes: Are We There Yet?

Therapeutic hypothermia, also referred to as targeted temperature management, has been a component of the postcardiac arrest treatment guidelines since 2010. Although almost a decade has passed since its inclusion in the postarrest guidelines, many unanswered questions remain regarding selection of the appropriate patient population, optimal target temperature, ideal window of time in which to initiate therapy after arrest, most efficient, safe, and accurate equipment choice for inducing and maintaining hypothermia, most effective duration of treatment, and rate of cooling or rewarming. On a national and international level, critical care nurses are in a unique position to participate in research that will define targeted temperature management protocols and practices. Nurses are also ideal for standardizing the targeted temperature management policy and protocol locally and nationally based on current available evidence. This review aims to serve 2 purposes: first, to provide a broad update on the current clarifications and limitations per research findings on target temperature management therapy; second, to explain how critical care nurses can use this updated information to improve outcomes for their patients with cardiac arrest.

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.

Targeted temperature management for adult out-of-hospital cardiac arrest: current concepts and clinical applications.

Targeted temperature management (TTM) (primarily therapeutic hypothermia (TH)) after out-of-hospital cardiac arrest (OHCA) has been considered effective, especially for adult-witnessed OHCA with a shockable initial rhythm, based on pathophysiology and on several clinical studies (especially two randomized controlled trials (RCTs) published in 2002). However, a recently published large RCT comparing TTM at 33 °C (TH) and TTM at 36 °C (normothermia) showed no advantage of 33 °C over 36 °C. Thus, this RCT has complicated the decision to perform TH after cardiac arrest. The results of this RCT are sometimes interpreted fever control alone is sufficient to improve outcomes after cardiac arrest because fever control was not strictly performed in the control groups of the previous two RCTs that showed an advantage for TH. Although this may be possible, another interpretation that the optimal target temperature for TH is much lower than 33 °C may be also possible. Additionally, there are many points other than target temperature that are unknown, such as the optimal timing to initiate TTM, the period between OHCA and initiating TTM, the period between OHCA and achieving the target temperature, the duration of maintaining the target temperature, the TTM technique, the rewarming method, and the management protocol after rewarming. RCTs are currently underway to shed light on several of these underexplored issues. In the present review, we examine how best to perform TTM after cardiac arrest based on the available evidence.

What is the right temperature to cool post-cardiac arrest patients?

Expanded abstractCitationNiklas Nielsen, Wetterslev J, Cronberg T, Erlinge D, Gasche Y, Hassager C, Horn J, Hovdenes J, Kjaergaard J, Kuiper M, Pellis T, Stammet P, Wanscher M, Wise MP, Åneman A, Al-Subaie N, Boesgaard S, Bro-Jeppesen J, Brunetti I, Bugge JF, Hingston CD, Juffermans NP, Koopmans M, Køber L, Langørgen J, Lilja G, Møller JE, Rundgren M, Rylander C, Smid O, Werer C, Winkel P, Friberg H. Targeted temperature management at 33 °C versus 36 °C after cardiac arrest. N Engl J Med. 2013;369:2197–206. doi:10.1056/NEJMoa1310519. Epub 2013 Nov 17. Pub Med PMID: 20089970.BackgroundBrain ischemia and reperfusion injury leading to tissue degeneration and loss of neurological function following return of spontaneous circulation after cardiac arrest (CA) is a well-known entity. Two landmark trials in 2002 showed improved survival and neurological outcome of comatose survivors of out-of-hospital cardiac arrest (OHCA) of presumed cardiac origin when the patients were subjected to therapeutic hypothermia of 32 to 34 °C for 12 to 24 hours. However, the optimal target temperature for these cohorts is yet to be established and also it is not clear whether strict fever management and maintaining near normal body temperature are alone sufficient to improve the outcome.MethodsObjective: The objective is to determine whether a hypothermic goal of a near-normal body temperature of 36 °C reduces all-cause mortality compared with a moderate hypothermia of 33 °C for the unconscious survivors of OHCA of presumed cardiac origin when subjected randomly to these different targeted temperatures.Design: A multicenter, international, open label, randomized controlled trial.Setting: Thirty-six ICUs in Europe and Australia participated in this study.Participants: Unconscious adults (older than 18 years of age) who survived (Glasgow coma scale less than 8) OHCA due to presumed cardiac origin with subsequent persistent return of spontaneous circulation (more than 20 minutes without chest compressions).Intervention: The above participant cohorts were randomized to targeted body temperature of either 33 °C or 36 °C for 36 hours after the CA with gradual rewarming of both groups to 37 °C (hourly increments of 0.5 °C) after the initial 28 hours. Body temperatures in both the groups were then maintained below 37.5 °C for 72 hours after the initial 36 hours.Outcomes: Primary outcome measure of all-cause mortality in both the groups at the end of the trial with the secondary outcome measure of all-cause mortality, composite neurological function as evaluated by cerebral performance category scale and modified ranking scale at the end of 180 days were studied.ResultsOut of the 939 participants, all-cause mortality at the end of the trial was 50 % in the 33 °C group (225 of 466 patients) compared with 48 % in the 36 °C group (235 of 473 patients); the hazard ratio with a temperature of 33 °C was 1.06 (95 % confidence interval (CI) 0.89 to 1.28, P = 0.51). At the end of 180 days, 54 % of patients in the 33 °C group versus 52 % in the 36 °C group had died or had poor neurological outcome according to cerebral performance category (risk ratio 1.02, 95 % CI 0.88 to 1.16, P = 0.78) but the modified ranking scale at the end of 180 days was unchanged (52 %) in both groups (risk ratio 1.01, 95 % CI 0.89 to 1.14, P = 0.87).ConclusionsMaintaining targeted lower normothermia of 36 °C had similar outcomes compared with induced moderate hypothermia of 33 °C for unconscious survivors of OHCA of presumed cardiac cause.

Time to start of cardiopulmonary resuscitation and the effect of target temperature management at 33°C and 36°C

The optimal target temperature for comatose patients resuscitated from out of hospital cardiac arrest is unknown. It has been hypothesized that patients with long no-flow times, for example those without bystander CPR would have the most to gain from temperature management at lower temperatures [1]. The generalizability of the TTM-trial [2] has been questioned because of a high fraction of patients receiving bystander cardiopulmonary resuscitation (CPR) (73%) and a median start of basic life support (for patients with bystander CPR) of 1 minute (Interquartile range 1-2 minutes).

What is the proper target temperature for out-of-hospital cardiac arrest?

The implementation of target temperature management (TTM) or therapeutic hypothermia has been demonstrated in several major studies to be an effective neuroprotective strategy in postresuscitation care after cardiac arrest. Although several landmark studies found the promising results of lower targeted temperature (32-34°C) in terms of survival and neurological outcomes, recent evidence showed no difference in either survival or long-term neurological outcome when compared with higher targeted temperature (36°C). Thus, recent data suggest that avoiding hyperpyrexia, rather than cooling "per se," may be considered the main therapeutic target to avoid secondary brain damage after out-of-hospital cardiac arrest. Many questions are still debated about the exact protocol of TTM to be used, including whether temperature control is more beneficial than standard of care without active temperature control, the optimal cooling temperature, patient selection, and duration of cooling. The aim of this review article was to discuss the physiology of hypothermia, available cooling methods, and current evidence about the optimal target temperature and timing of hypothermia.

TTM 2.0

The professional treatment of the reperfusion syndrome following cardiac arrest and successful resuscitation has improved over the past decade. In 2002 and 2003 mild hypothermia treatment was first recommended by international guidelines following remarkable milestone trials. With growing experience and an increasing number of hospitals implementing hypothermia as standard treatment, technical devices also improved to enhance patient safety. The term target temperature management (TTM) has been introduced by several societies indicating that cooling down is not enough [1]. We are supposed to manage temperature therapy as part of a package of interventions after cardiac arrest [2,3]. As intracranial pressure can correlate with brain and body temperature, modern TTM is about precision although the optimal target temperature is still unknown. This has been shown by the current TTM Trial by Nielsen and colleagues comparing 33°C and 36°C as different target levels without a significant difference in outcome variables [4]. As these results have been criticized in several points, the conclusion can only be that obviously different patient characteristics need a more individual TTM following cardiac arrest. As stated, TTM 2.0 indicates we have reached the next step that includes professional TTM in a large bundle of therapy steps such as early coronary intervention, close monitoring of supportive care and precise neurological prognostication. The way to go is still long as TTM is still underused worldwide [5,6]. If TTM would be seen as a medication or drug, it should be adjusted or dosed depending on the severity of the disease or hypoxic brain damage. Especially, a moderate reperfusion injury will respond and benefit from a medication like TTM compared with a severe and long-lasting hypoxia leading to death despite any therapy. Therefore, a key in the near future will be the early grading of the hypoxic brain damage by a combination of clinical data, biomarkers, advanced neurological monitoring and radiological findings. This might lead to a more personalized and adjusted post-cardiac arrest treatment.

Therapeutic hypothermia in 2015 : Influence of the TTM study on the intensive care procedure after cardiac arrest

In the 1960s, Peter Safar et al. postulated the benefit of postcardiac arrest hypothermia after successful cardiopulmonary resuscitation (CPR). However, therapeutic hypothermia postCPR did not become a standard procedure until the first few years of the new millennium. Various noninvasive and invasive cooling methods are available. Generally, more invasive cooling methods are more effective-but also tend to involve more complications. Furthermore, invasive measures need more time and thus may be instituted late in the postCPR process, delaying the cooling efforts in the initial phase. There is ongoing controversy about when best to commence cooling. Recent studies of initial out-of-hospital cooling did not show any benefit for the patients compared to starting cooling in the hospital. The exact target temperature is the subject of multiple ongoing discussions. A recent study showed no disadvantage of cooling to 36 ℃ compared to 33 ℃, which is in the widely accepted standard target temperature range of 32-34 ℃. Nevertheless, cooling to 32-34 ℃ according to the 2010 guidelines is still the accepted standard procedure unless and until new studies generate more evidence. The European Resuscitation Council has given advance notice of a statement on the optimal target temperature in the near future. Finally, large registry studies have demonstrated the benefit of combining postCPR hypothermia with early percutaneous cardiac interventions (PCI) in acute coronary syndromes, which are often a cause of cardiac arrest. Transport of patients after CPR to specialized postcardiac arrest centres with the possibility of acute PCI and cooling, comparable to the transfer of multiple trauma patients to trauma centres, may be beneficial.

2013 Late-Breaking Clinical Trial Abstracts

### Nitrites in Acute Myocardial Infarction Nishat Siddiqi1, Margaret Bruce1, Christopher J. Neil1, Graeme MacLennan2, Seonaidh Cotton2, Sofia A. Papadopoulou3, Baljit Jagpal1, Sue Brown3, Fatima Perez Gonzalez3, Satnam Singh1, Konstantin Schwarz1, Martin Feelisch4, Nicholas Bunce5, Pitt O Lim5, David Hildick-Smith6, John Horowitz7, Melanie Madhani8, Nicholas Boon9, Dana Dawson10, Juan-Carlos Kaski3, Michael P Frenneaux10. 1Dept of Cardiovascular Rsch, Univ of Aberdeen, Aberdeen, United Kingdom, 2Health Sciences Building (third floor), Centre for Healthcare Randomised Trials (CHaRT), Aberdeen, United Kingdom, 3Cardiovascular Sciences Rsch Centre, St George’s Univ of London, London, United Kingdom, 4Faculty of Medicine, Univ of Southampton, Southampton, 5Cardiology Dept, St George’s Healthcare NHS Trust, 6Cardiology Research Unit, Brighton and Sussex Univ Hospitals, Brighton, United Kingdom, 7Basil Hetzel Unit for Translational Health Research, The Queen Elizabeth Hospital, Adelaide, 8Centre for Cardiovascular Sciences, Univ of Birmingham, Birmingham, United Kingdom, 9Centre for Cardiovascular Sciences, Univ of Edinburgh, Edinburgh, United Kingdom, 10School of Medicine and Dentistry, Univ of Aberdeen, Aberdeen Introduction :Despite reperfusion therapy for acute myocardial infarction (AMI), heart failure remains a major sequel. Reperfusion leads to further damage, described as ischemia-reperfusion-injury (IRI). This contributes up to 50% of the final infarct size. In pre-clinical models nitrite potently protects against IRI in the heart and other organs. Hypothesis :Intravenous (iv) sodium nitrite, administered immediately before opening of the infarct-related artery, results in significant reduction of IRI in patients with acute ST elevation MI (STEMI). Methods :In this phase II, randomised, placebo-controlled, double-blind, multicentre trial, 220 patients with first acute STEMI and TIMI 0 or 1 flow were randomised …