Prehospital Therapeutic Hypothermia Research Articles

Survival, neurological and safety outcomes after out of hospital cardiac arrests treated by using prehospital therapeutic hypothermia: A systematic review and meta-analysis

Survival after pre-hospital cardiac arrest (PHCA) remains low. Pre-hospital therapeutic hypothermia (PTH) is believed to improve patient's outcomes, but data on efficacy and safety remains scarce. Herein, we aimed to assess the influence of PTH on survival, neurological outcome, and adverse effects in patients with PHCA. A literature search of PubMed CENTRAL, EMBASE, and The Cochrane Central Register of Controlled Trials databases from inception to August 2019 was conducted and retrieved abstracts were independently assessed by two reviewers. The primary outcome was survival to hospital discharge with a favorable neurological outcome. Secondary outcomes were survival to hospital discharge and temperature upon hospital admission. The safety outcomes included pulmonary edema and recurrent arrest during transport to the hospital. We also considered a favorable neurological function to hospital discharge or longest post arrest follow-up. Eleven studies including 4891 patients were included into final analysis. The survival to hospital discharge did not differ between PTH and control group (RR 1.02; 95%CI 0.93 to 1.12). Among 4891 participants (2466 in PTH group and 2425 in control group), 1087 participants (564 vs. 523, respectively) had a favorable neurological outcome. Pulmonary edema occurred in 320 cases in PTH group and 273 in control group with significant heterogeneity (RR 0.90, 95%CI 0.59–1.38; I2 = 80%). The pooled results showed a significant difference in rearrests between the PTH and control group (RR 1.19; 95%CI 1.00 to 1.42). Our analysis demonstrates that PTH does not improve survival at discharge or neurological outcome.

The efficacy and safety of pre-hospital cooling after out-of-hospital cardiac arrest: a systematic review and meta-analysis

BackgroundMild therapeutic hypothermia (TH), or targeted temperature management, improves survival and neurological outcomes in patients after out-of-hospital cardiac arrest (OHCA). International guidelines strongly support initiating TH for all eligible individuals presenting with OHCA; however, the timing of cooling initiation remains uncertain. This systematic review and meta-analysis was conducted with all available randomised controlled trials (RCTs) included to explore the efficacy and safety of initiating pre-hospital TH in patients with OHCA.MethodsThe MEDLINE and Cochrane databases were searched from inception to October 2017. Inclusion criteria for full-text review included RCTs comparing pre-hospital TH with no pre-hospital TH after cardiac arrest, patients > 14 years of age with documented cardiac arrest from any rhythm, and outcome data that included survival to hospital discharge and temperature at hospital arrival. Results of retrieved studies were compared through meta-analysis using random effects modelling.ResultsA total of 10 trials comprising 4220 patients were included. There were no significant differences between the two arms for the primary outcome of neurological recovery (risk ratio [RR] 1.04, 95% CI 0.93–1.15) or the secondary outcome of survival to hospital discharge (RR 1.01, 95% CI 0.92–1.11). However, there was a significantly lower temperature at hospital arrival in patients receiving pre-hospital TH (mean difference − 0.83, 95% CI − 1.03 to − 0.63). Pre-hospital TH significantly increased the risk of re-arrest (RR 1.19, 95% CI 1.00 to 1.41). No survival differences were observed among subgroups of patients who received intra-arrest TH vs post-arrest TH or who had shockable vs non-shockable rhythms.ConclusionsPre-hospital TH after OHCA effectively decreases body temperature at the time of hospital arrival. However, it does not improve rates of survival with good neurological outcome or overall survival and is associated with increased rates of re-arrest.

Pre-hospital therapeutic hypothermia for survival and neuro-protection after out-of-hospital cardiac arrest: a systematic review and Meta-analysis of randomized controlled trials

To assess the effectiveness of pre-hospital therapeutic hypothermia after out-of-hospital cardiac arrest (OHCA) for survival and neuro-protection. Databases such as Medline, ScienceDirect, Embase, Highwire, Cochrane Library, CNKI and Wanfang digital database were searched from January 2000 to March 2017 to retrieve randomized controlled trials (RCTs) on pre-hospital therapeutic hypothermia after OHCA. Thereafter, the studies retrieved were screened based on predefined inclusion and exclusion criteria. Data were extracted and the quality of the included studies was evaluated. A Meta-analysis was performed using the Cochrane Collaboration RevMan 4.3 software. Analysis of publication bias was depicted by funnel plot. Eight studies involving 3 555 cases were included, among which 1 804 cases were assigned to the treatment group and 1 751 cases to the control group. Meta-analysis showed that compared with in-hospital therapeutic hypothermia, pre-hospital therapeutic hypothermia did not improve the survival rate of patients with OHCA [odds ratio (OR) = 1.00, 95% confidence interval (95%CI) = 0.85-1.18, P = 0.99], and neurological outcome at hospital discharge (OR = 0.97, 95%CI = 0.80-1.16, P = 0.71), but the body temperature was significantly lowered at admission [weighted mean difference (SMD) = -0.88, 95%CI = -1.03 to -0.73, P < 0.000 01]. The funnel plot suggested that there was no publication bias in the 8 studies. But due to the low number of studies, the publication bias could not be completely excluded. Pre-hospital therapeutic hypothermia after OHCA can decrease temperature at hospital admission, but cannot increase the survival rate and neurological outcome at hospital discharge.

Therapeutic hypothermia in cardiac arrest

Therapeutic hypothermia (TH) following cardiac arrest is commonplace in many hospitals. It is thought to improve survival rates and offer neuroprotective benefits. However, its use in the pre-hospital arena is still uncertain. The objective of this literature review is to collect and consider evidence and address these uncertainties with a view to offering recommendations for practice. A systematic search was undertaken, and from the literature reviewed, there was no unanimous evidence that pre-hospital TH improves patient survival or neurological outcomes. It is clear that all of the different modes of initiating TH that were evaluated were effective in reducing patient temperature on arrival at hospital.

Clinical Outcomes in Cardiac Arrest Patients Following Prehospital Treatment with Therapeutic Hypothermia.

Recent studies have brought to question the efficacy of the use of prehospital therapeutic hypothermia for victims of out-of-hospital cardiac arrest (OHCA). Though guidelines recommend therapeutic hypothermia as a critical link in the chain of survival, the safety of this intervention, with the possibility of minimal treatment benefit, becomes important. Hypothesis/Problem This study examined prehospital therapeutic hypothermia for OHCA, its association with survival, and its complication profile in a large, metropolitan, fire-based Emergency Medical Services (EMS) system, where bystander cardiopulmonary resuscitation (CPR) and post-arrest care are in the process of being optimized. This evaluation was a retrospective chart review of all OHCA patients with return of spontaneous circulation (ROSC) treated with therapeutic hypothermia, from January 1, 2013 through November 30, 2013. The primary outcomes were the proportion of patients with initiation of prehospital therapeutic hypothermia with survival to hospital admission, the proportion of patients with initiation of prehospital therapeutic hypothermia with survival to hospital discharge, and the complication profile of therapeutic hypothermia in this population. The complication profile included several clinical, radiographic, and laboratory parameters. Exclusion criteria included: no prehospital therapeutic hypothermia initiation; no ROSC; and age of 17 year old or younger. Fifty-one post-cardiac arrest patients were identified that met inclusion criteria. The mean age was 61 years (SD=14.7 years), and 33 (72%) were male. The initial rhythm was ventricular fibrillation or pulseless ventricular tachycardia in 17 (37%) patients, and bystander CPR was performed in 28 (61%) patients with ROSC. Thirty-nine (85%) patients survived to hospital admission. Twenty-one patients (48%; 95% CI, 33-64) were administered vasopressors, 10 patients (24%; 95% CI, 10-37) were administered diuretics, and 19 patients (44%; 95% CI, 29-60) were administered antibiotics. Initial chest radiograph (CXR) findings were normal in 12 (29%) patients. Overall, 13 (28%; 95% CI, 15-42) study patients survived to hospital discharge. Recent reports have questioned the efficacy and safety of prehospital therapeutic hypothermia. In this evaluation, in the setting of unstandardized post-arrest care, 85% of the patients survived to hospital admission and 28% survived to hospital discharge, with a complication profile which was similar to that noted in other studies. This suggests that further evidence may be needed before EMS systems stop administering therapeutic hypothermia to appropriately selected patients. In less-optimized systems, therapeutic hypothermia may still be an essential link in the chain of survival.

Ein städtischer Rettungsdienstbereich am Beginn eines sektorenübergreifenden Qualitätsmanagementsystems: Eine priorisierte Umsetzung der ERC Empfehlungen von 2010 und das Langzeitüberleben nach Herzkreislaufstillstand

Due to limited resources, the 2010 European Resuscitation Council (ERC) guidelines could not be fully implemented in the Emergency Medical Services (EMS) of Brunswick, Germany. This is why implementation was prioritized according to local conditions. Thus, prehospital therapeutic hypothermia, mechanical chest compression and feedback systems were not established. Clinical data and long-term results were assessed by a QM system and room for improvement was identified. All attempted resuscitations from 2011 until 2014 were recorded and compared against the German Resuscitation Registry. Outcomes of adult patients following non-traumatic cardiac arrest were analyzed by year. 812 resuscitations were attempted (incidence 81.2/100,000 inhabitants/year). In the two years following full implementation since 2013 the discharge rate from hospital was 16.4%, the discharge rate with a favorable neurologic outcome was 14.1%, the 1-year survival rate was 14.4% in 2013. A significant improvement of risk-adjusted ROSC rate during the investigation period was demonstrated. The discharge rates remained unchanged; the increase in the discharge rates paralleled the increase in CPR incidence. EMS response times were remarkably shorter. The implementation of the ERC guidelines chosen appears to be generally safe. Fast EMS response contributed to superior results. All links of the chain of survival showed room for improvement, especially the proportion of lay rescuer CPR and telephone-assisted CPR. The high CPR incidence might indicate room for improvement in prevention. Access to resuscitation care can hardly be evaluated. Age-related access to pre-hospital resuscitation seems to be appropriate.

Trial of pre-hospital therapeutic hypothermia for out-of-hospital cardiac arrest : Takatsuki, Osaka

Trial of pre-hospital therapeutic hypothermia for out-of-hospital cardiac arrest : Takatsuki, Osaka

No benefit to prehospital initiation of therapeutic hypothermia in out-of-hospital cardiac arrest: a systematic review and meta-analysis.

The aim of this review was to define the effect of prehospital therapeutic hypothermia (TH) on survival and neurologic recovery in patients who have suffered out-of-hospital cardiac arrest (OHCA). Included in this review are randomized trials assessing the effect of prehospital TH in adult patients suffering nontraumatic OHCA. Trials assessing the effect of in-hospital TH were excluded. Only studies with a low risk of bias were eligible for meta-analysis. A medical librarian searched PubMed, Ovid, EMBASE, Ovid Global Health, the Cochrane Library, Guidelines.gov, EM Association Websites, CenterWatch, IFPMA Clinical Trial Results Portal, CINAHL, ProQuest, and the Emergency Medical Abstracts Database without language restrictions. Clinicaltrials.gov was searched for unpublished studies. Bibliographies were hand searched and experts in the field were queried about other published or unpublished trials. Using standardized forms, two authors independently extracted data from all included trials. Results from high-quality trials were pooled using a random-effects model. Two authors, using the Cochrane risk of bias tool, assessed risk of bias independently. Of 740 citations, six trials met inclusion criteria. Four trials were at a low risk of bias and were included in the meta-analysis (N=715 patients). Pooled analysis of these trials revealed no difference in overall survival (relative risk [RR]=0.98, 95% CI=0.79 to 1.21) or good neurologic outcome (RR=0.96, 95% CI=0.76 to 1.22) between patients randomized to prehospital TH versus standard therapy. Heterogeneity was low for both survival and neurologic outcome (I2=0). Randomized trial data demonstrate no important patient benefit from prehospital initiation of TH. Pending the results of ongoing larger trials, resources dedicated to this intervention may be better spent elsewhere.

Prehospital Immediate Therapeutic Hypotermia in Galicia: Results and Next Steps

Introduction: Despite mild therapeutic hypothermia (TH) being recommended as a post-resuscitation care by current international resuscitation guidelines, recent evidences have questioned its role. Our objective was to assess the results of immediate TH at the pre hospital level by the Galicia’s Emergencies Medical Service (GEMS) in order to know the potential impact on patient’s outcome. Methods: Observational retrospective study. Patients older than 18 years with a witnessed out-of-hospital cardiac arrest (OHCA), and with recovering of spontaneous circulation (ROSC) after advanced cardiopulmonary resuscitation (CPR) provided by sanitary personnel of the GEMS, between 2005 and 2013 were eligible. The survival and brain function at hospital discharge and one year after OHCA were assessed comparing the patients treated with immediate after ROSC pre hospital mild TH with patients receiving standard care. Results: One hundred ninety one patients were included, 94 (49.2%) with shockable rhythm (VF); 56 (29.3%) received TH; 36 of them (64.3%) with VF. Survival at hospital discharge and 1-year after OHCA was 55.4% and 51.8% in the TH group, versus 28.9% and 22.9% respectively in control group (p<0.001 both). Also, percentage of patients with CPC score 1-2 was higher in the TH group: 80.6% vs. 56.4 at hospital discharge (p<0.05) and 93.10% vs. 70.9% at one year follow-up (p<0.01). TH was an independent predictive factor of long-term survival, both in VF (OR=3.83; 95% CI: 0.40-36.96) as in no-shockable rhythms (OR=3.50; 95% CI: 0.31-39.15). Conclusions: In Galicia, immediate after ROSC pre hospital TH improved survival and functional status at short and long-term, independently of the first recorded ECG rhythm. Although limited, our data have been obtained from the real-life GEMS working conditions and should be considered in before radical modifications of CPR protocols.

Awakening after cardiac arrest and post resuscitation hypothermia: Are we pulling the plug too early?

BackgroundTime to awakening after out-of-hospital cardiac arrest (OHCA) and post-resuscitation therapeutic hypothermia (TH) varies widely. We examined the time interval from when comatose OHCA patients were rewarmed to 37°C to when they showed definitive signs of neurological recovery and tried to identify potential predictors of awakening. MethodsWith IRB approval, a retrospective case study was performed in OHCA patients who were comatose upon presentation to a community hospital during 2006–2010. They were treated with TH (target of 33°C) for 24h, rewarmed, and discharged alive. Comatose patients were generally treated medically after TH for at least 48h before any decision to withdraw supportive care was made. Pre-hospital TH was not used. Data are expressed as medians and interquartile range. ResultsThe 89 patients treated with TH in this analysis were divided into three groups based upon the time between rewarming to 37°C and regaining consciousness. The 69 patients that regained consciousness in ≤48h after rewarming were termed “early-awakeners”. Ten patients regained consciousness 48–72h after rewarming and were termed “intermediate-awakeners”. Ten patients remained comatose and apneic >72h after rewarming but eventually regained consciousness; they were termed “late-awakeners”. The ages for the early, intermediate and late awakeners were 56 [49,65], 62 [48,74], and 58 [55,65] years, respectively. Nearly 67% were male. Following rewarming, the time required to regain consciousness for the early, intermediate and late awakeners was 9 [2,18] (range 0–47), 60.5 [56,64.5] (range 49–71), and 126 [104,151]h (range 73–259), respectively. Within 90 days of hospital admission, favorable neurological function based on a Cerebral Performance Category (CPC) score of 1 or 2 was reported in 67/69 early, 10/10 intermediate, and 8/10 late awakeners. ConclusionFollowing OHCA and TH, arbitrary withdrawal of life support <48h after rewarming may prematurely terminate life in many patients with the potential for full neurological recovery. Additional clinical markers that correlate with late awakening are needed to better determine when withdrawal of support is appropriate in OHCA patients who remain comatose >48h after rewarming.

Prehospital therapeutic hypothermia after cardiac arrest: A systematic review and meta-analysis of randomized controlled trials

BackgroundTherapeutic hypothermia has been recommended for the treatment of cardiac arrest patients who remain comatose after the return of spontaneous circulation. However, the optimal time to initiate therapeutic hypothermia remains unclear. The objective of the present study is to assess the effectiveness and safety of prehospital therapeutic hypothermia after cardiac arrest. MethodsDatabases such as MEDLINE, Embase, and Cochrane Library were searched from their establishment date to May of 2012 to retrieve randomized control trials on prehospital therapeutic hypothermia after cardiac arrest. Thereafter, the studies retrieved were screened based on predefined inclusion and exclusion criteria. Data were extracted and the quality of the included studies was evaluated. A meta-analysis was performed by using the Cochrane Collaboration Review Manager 5.1.6 software. ResultsFive studies involving 633 cases were included, among which 314 cases were assigned to the treatment group and the other 319 cases to the control group. The meta-analysis indicated that prehospital therapeutic hypothermia after cardiac arrest produced significant differences in temperature on hospital admission compared with in-hospital therapeutic hypothermia or normothermia (patient data; mean difference=−0.95; 95% confidence interval −1.15 to −0.75; I2=0%). However, no significant differences were observed in the survival to the hospital discharge, favorable neurological outcome at hospital discharge, and rearrest. The risk of bias was low; however, the quality of the evidence was very low. ConclusionThis review demonstrates that prehospital therapeutic hypothermia after cardiac arrest can decrease temperature on hospital admission. On the other hand, regarding the survival to hospital discharge, favorable neurological outcome at hospital discharge, and rearrest, our meta-analysis and review produces non-significant results. Using the Grading of Recommendations, Assessment, Development and Evaluation methodology, we conclude that the quality of evidence is very low.

Induction of prehospital therapeutic hypothermia after resuscitation from nonventricular fibrillation cardiac arrest*

To evaluate the effects on temperature and outcome at hospital discharge of a pre-hospital rapid infusion of large volume, ice-cold intravenous Hartmann's solution in patients with out-of-hospital cardiac arrest and an initial cardiac rhythm of asystole or pulseless electrical activity. Prospective, randomized, controlled clinical trial. Pre-hospital emergency medical service and 12 critical care units in Melbourne, Australia. One hundred and sixty three patients who had been resuscitated from cardiac arrest with an initial cardiac rhythm of asystole or pulseless electrical activity. : Patients were randomized to either pre-hospital cooling using a rapid infusion of up to two litres ice-cold Hartmann's solution (82 patients) or cooling after hospital admission (81 patients). The planned duration of therapeutic hypothermia (32 °C-34 °C) in both groups was 24 hrs. Patients allocated to pre-hospital cooling received a median of 1500 ml of ice-cold fluid. This resulted in a mean decrease in core temperature of 1.4 °C compared with 0.2 °C in hospital cooled patients (p < .001). The time to therapeutic hypothermia (<34 °C) was 3.2 hrs in the pre-hospital cooled group compared with 4.8 hrs in the hospital cooled group (p = .0328). Both groups received a mean of 15 hrs cooling in the hospital and only 7 patients in each group were cooled for 24 hrs. Overall, there was no difference in outcomes at hospital discharge with favorable outcome (discharge from hospital to home or rehabilitation) in 10 of 82 (12%) in the pre-hospital cooled patients, compared with 7 of 81 (9%) in the hospital cooled patients (p = .50). In the patients with a cardiac cause of the arrest, 8 of 47 patients (17%) who received pre-hospital cooling had a favorable outcome at hospital discharge compared with 3 of 43 (7%) in the hospital cooled group (p = .146). In adults who have been resuscitated from out-of-hospital cardiac arrest with an initial cardiac rhythm of asystole or pulseless electrical activity, pre-hospital cooling using a rapid infusion of large-volume, ice cold intravenous Hartmann's solution decreases core temperature at hospital arrival and decreases the time to therapeutic hypothermia. In patients with a cardiac cause of the arrest, this treatment may increase the rate of favorable outcome at hospital discharge. Further larger studies should evaluate the effects of pre-hospital cooling when the initial cardiac rhythm is asystole or pulseless electrical activity, particularly in patients with a cardiac cause of the arrest.

Prehospital therapeutic hypothermia induced with cold infusions improves haemodynamic stability in nonshockable cardiac arrest patients

Recent studies report an increase of asystole and pulseless electrical activity (PEA) as the first monitored cardiac arrest rhythms after arrival of the Emergency Medical Services [1]. The asystolic patients presumably undergo ischaemia for a longer time and may benefit from treatment reducing hypoxic brain injury. Therapeutic hypothermia (TH) has expanded into prehospital care to be initiated as soon as possible. Rapid cold crystalloid infusion is the most frequent method; however, severe haemodynamic instability is its contraindication. The aim of the study was to assess the adverse effects of prehospital volume expansion in patients with initial nonshockable rhythms when used in a setting with only restricted cardiovascular monitoring.

Prehospital therapeutic hypothermia for comatose survivors of cardiac arrest: a randomized controlled trial

Prehospital therapeutic hypothermia for comatose survivors of cardiac arrest: a randomized controlled trial

Prehospital therapeutic hypothermia for comatose survivors of cardiac arrest: a randomized controlled trial

Intravenous infusion of ice-cold fluid is considered a feasible method to induce mild therapeutic hypothermia in cardiac arrest survivors. However, only one randomized controlled trial evaluating this treatment exists. Furthermore, the implementation rate of prehospital cooling is low. The aim of this study was to evaluate the efficacy and safety of this method in comparison with conventional therapy with spontaneous cooling often observed in prehospital patients. A randomized controlled trial was conducted in a physician-staffed helicopter emergency medical service. After successful initial resuscitation, patients were randomized to receive either +4 degrees C Ringer's solution with a target temperature of 33 degrees C or conventional fluid therapy. As an endpoint, nasopharyngeal temperature was recorded at the time of hospital admission. Out of 44 screened patients, 19 were analysed in the treatment group and 18 in the control group. The two groups were comparable in terms of baseline characteristics. The core temperature was markedly lower in the hypothermia group at the time of hospital admission (34.1+/-0.9 degrees C vs. 35.2+/-0.8 degrees C, P<0.001) after a comparable duration of transportation. Otherwise, there were no significant differences between the groups regarding safety or secondary outcome measures such as neurological outcome and mortality. Spontaneous cooling alone is insufficient to induce therapeutic hypothermia before hospital admission. Infusion of ice-cold fluid after return of spontaneous circulation was found to be well tolerated and effective. This method of cooling should be considered as an important first link in the 'cold chain' of prehospital comatose cardiac arrest survivors.

Immediate prehospital hypothermia protocol in comatose survivors of out-of-hospital cardiac arrest

Therapeutic hypothermia (TH) improves the outcomes of cardiac arrest (CA) survivors. The aim of this study was to evaluate retrospectively the efficacy and safety of an immediate prehospital cooling procedure implemented just after the return of spontaneous circulation with a prehospital setting. During 30 months, the case records of comatose survivors of out-of-hospital CA presumably due to a cardiac disease were studied. A routine protocol of immediate postresuscitation cooling had been tested by an emergency team, which consisted of an infusion of large-volume, ice-cold intravenous saline. We decided to assess the efficacy and tolerance of this procedure. A total of 99 patients were studied; 22 were treated with prehospital TH, and 77 consecutive patients treated with prehospital standard resuscitation served as controls. For all patients, TH was maintained for 12 to 24 hours. The demographic, clinical, and biological characteristics of the patients were similar in the 2 groups. The rate of patients with a body temperature of less than 35°C upon admission was 41% in the cooling group and 18% in the control group. Rapid infusion of fluid was not associated with pulmonary edema. After 1 year of follow-up, 6 (27%) of 22 patients in the cooling group and 30 (39%) of 77 patients in the control group had a good outcome. Our preliminary observation suggests that in comatose survivors of CA, prehospital TH with infusion of large-volume, ice-cold intravenous saline is feasible and can be used safely by mobile emergency and intensive care units.

Prehospital therapeutic hypothermia after cardiac arrest - from current concepts to a future standard

Therapeutic hypothermia has been shown to improve survival and neurological outcome after prehospital cardiac arrest. Existing experimental and clinical evidence supports the notion that delayed cooling results in lesser benefit compared to early induction of mild hypothermia soon after return of spontaneous circulation. Therefore a practical approach would be to initiate cooling already in the prehospital setting.The purpose of this review was to evaluate current clinical studies on prehospital induction of mild hypothermia after cardiac arrest. Most reported studies present data on cooling rates, safety and feasibility of different methods, but are inconclusive as regarding to outcome effects.

Prehospital therapeutic hypothermia in cardiac arrest: will there ever be evidence?

Bruel and colleagues nicely demonstrate that the infusion of 2 l cold saline during resuscitation is a feasible, effective, and safe measure to induce therapeutic hypothermia in out-of-hospital cardiac arrest [1]. Therapeutic hypothermia was induced in 33 eligible advanced life support patients before primary survival was foreseeable, and was continued in 11 patients after intensive care unit admission. The authors conclude that a large randomised trial should be performed. The design of future trials on therapeutic hypothermia, however, seems challenged by the fact that withholding this treatment in a control arm might be considered unjustifiable from an ethical point of view. In the prehospital setting, such a trial would require a large number of study patients to demonstrate an additional benefit. This is due to the fact that both a spontaneous decline in body core temperature occurs, especially in the no-flow and low-flow phase, and that the overall gain of time (typically around 45 min) may be considered marginal against the background of most published data, indicating that target temperatures cannot be reached until about 6 to 8 hours later [2,3]. Given the optimistic view that prehospital cooling increases the number of favourable neurological outcomes from 55% [4] to 60%, about 750 patients would have to be included in a given randomised trial. Nevertheless, although we totally agree with Bruel and colleagues that the intervention is safe and feasible, and that a clear biological rationale for the earliest possible induction of therapeutic hypothermia exists [2-5], we doubt that a prospective randomised trial on additional prehospital cooling is feasible and justifiable. We may have reached another boundary of evidence-based medicine.