Targeted Temperature Management after Cardiac Arrest: A Systematic Review and Meta-Analysis with Trial Sequential Analysis.
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ABSTRACT:
SUBMITTER: Sanfilippo F
PROVIDER: S-EPMC8432025 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BACKGROUND:Targeted temperature management (TTM) with therapeutic hypothermia is an integral component of postarrest care for survivors. However, recent randomized controlled trials (RCTs) have failed to demonstrate the benefit of TTM on clinical outcomes. We sought to determine if the pooled data from available RCTs support the use of prehospital and/or in-hospital TTM after cardiac arrest. METHODS:A comprehensive search of SCOPUS, Elsevier's abstract and citation database of peer-reviewed literature, from 1966 to November 2016 was performed using predefined criteria. Therapeutic hypothermia was defined as any strategy that aimed to cool post-cardiac arrest survivors to a temperature ≤34°C. Normothermia was temperature of ≥36°C. We compared mortality and neurologic outcomes in patients by categorizing the studies into 2 groups: (1) hypothermia versus normothermia and (2) prehospital hypothermia versus in-hospital hypothermia using standard meta-analytic methods. A random effects modeling was utilized to estimate comparative risk ratios (RR) and 95% confidence intervals (CIs). RESULTS:The hypothermia and normothermia strategies were compared in 5 RCTs with 1389 patients, whereas prehospital hypothermia and in-hospital hypothermia were compared in 6 RCTs with 3393 patients. We observed no difference in mortality (RR, 0.88; 95% CI, 0.73-1.05) or neurologic outcomes (RR, 1.26; 95% CI, 0.92-1.72) between the hypothermia and normothermia strategies. Similarly, no difference was observed in mortality (RR, 1.00; 95% CI, 0.97-1.03) or neurologic outcome (RR, 0.96; 95% CI, 0.85-1.08) between the prehospital hypothermia versus in-hospital hypothermia strategies. CONCLUSIONS:Our results suggest that TTM with therapeutic hypothermia may not improve mortality or neurologic outcomes in postarrest survivors. Using therapeutic hypothermia as a standard of care strategy of postarrest care in survivors may need to be reevaluated.
| S-EPMC5820193 | biostudies-other
Project description:BACKGROUND:Targeted temperature management (TTM) of 32 to 34 °C has been the standard treatment for out-of-hospital cardiac arrest since clinical trials in 2002 indicated benefit on survival and neurological outcome. In 2013, a clinical trial showed no difference in outcome between TTM of 33 °C and TTM of 36 °C. In this meta-analysis, we investigate the evidence for TTM in animal models of cardiac arrest. METHODS:We searched PubMed and EMBASE for adult animal studies using TTM as a treatment in different models of cardiac arrest or global brain ischemia which reported neurobehavioural outcome, brain histology or mortality. We used a random effects model to calculate estimates of efficacy and assessed risk of bias using an adapted eight-item version of the Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Studies (CAMARADES) quality checklist. We also used a scoring system based on the recommendations of the Stroke Treatment Academic Industry Roundtable (STAIR), to assess the scope of testing in the field. Included studies which investigated a post-ischemic induction of TTM had their treatment regimens characterized with regard to depth, duration and time to treatment and scored against the modified STAIR criteria. RESULTS:The initial and updated search generated 17809 studies after duplicate removal. One hundred eighty-one studies met the inclusion criteria, including data from 1,787, 6,495 and 2,945 animals for neurobehavioural, histological and mortality outcomes, respectively. TTM was favoured compared to control for all outcomes. TTM was beneficial using short and prolonged cooling, deep and moderate temperature reduction, and early and delayed time to treatment. Median [IQR] study quality was 4 [3 to 6]. Eighteen studies checked seven or more of the eight CAMARADES quality items. There was no clear correlation between study quality and efficacy for any outcome. STAIR analysis identified 102 studies investigating post-ischemic induction of TTM, comprising 147 different treatment regimens of TTM. Only 2 and 8 out of 147 regimens investigated comorbid and gyrencephalic animals, respectively. CONCLUSIONS:TTM is beneficial under most experimental conditions in animal models of cardiac arrest or global brain ischemia. However, research on gyrencephalic species and especially comorbid animals is uncommon and a possible translational gap. Also, low study quality suggests risk of bias within studies. Future animal research should focus on mimicking the clinical scenario and employ similar rigour in trial design to that of modern clinical trials.
| S-EPMC6969098 | biostudies-literature
Project description:Background: Neuromuscular-blocking agents (NMBA) are often administered to control shivering in comatose cardiac arrest (CA) survivors during targeted temperature management (TTM) management. Thus, we performed a systematic review and meta-analysis to investigate the effectiveness and safety of NMBA in such a patient population. Methods: We searched for relevant studies in PubMed, Embase, and the Cochrane Library until 15 Jul 2021. Studies were included if they reported data on any of the predefined outcomes in adult comatose CA survivors managed with any NMBA regimens. The primary outcomes were mortality and neurological outcome. Results were expressed as odds ratio (OR) or mean difference (MD) with an accompanying 95% confidence interval (CI). Heterogeneity, sensitivity analysis, and publication bias were also investigated to test the robustness of the primary outcome. Data Synthesis: We included 12 studies (3 randomized controlled trials and nine observational studies) enrolling 11,317 patients. These studies used NMBA in three strategies: prophylactic NMBA, bolus NMBA if demanded, or managed without NMBA. Pooled analysis showed that CA survivors with prophylactic NMBA significantly improved both outcomes of mortality (OR 0.74; 95% CI 0.64-0.86; I 2 = 41%; p < 0.0001) and neurological outcome (OR 0.53; 95% CI 0.37-0.78; I 2 = 59%; p = 0.001) than those managed without NMBA. These results were confirmed by the sensitivity analyses and subgroup analyses. Only a few studies compared CA survivors receiving continuous versus bolus NMBA if demanded strategies and the pooled results showed no benefit in the primary outcomes between the two groups. Conclusion: Our results showed that using prophylactic NMBA strategy compared to the absence of NMBA was associated with improved mortality and neurologic outcome in CA patients undergoing TTM. However, more high-quality randomized controlled trials are needed to confirm our results.
| S-EPMC9171045 | biostudies-literature
Project description:Cardiac arrest (CA) is associated with high mortality and poor life quality. Targeted temperature management (TTM) or therapeutic hypothermia is a therapy increasing the survival of adult patients after CA. The study aim was to assess the feasibility of therapeutic hypothermia after pediatric CA. We performed a systematic review and meta-analysis of randomized controlled trials and observational studies evaluating the use of TTM after pediatric CA. The primary outcome was survival to hospital discharge or 30-day survival. Secondary outcomes included a one-year survival rate, survival with a Vineland adaptive behavior scale (VABS-II) score ≥ 70, and occurrence of adverse events. Ten articles (n = 2002 patients) were included, comparing TTM patients (n = 638) with controls (n = 1364). In a fixed-effects meta-analysis, survival to hospital discharge in the TTM group was 49.7%, which was higher than in the non-TTM group (43.5%; odds ratio, OR = 1.22; 95% confidence interval, CI: 1.00, 1.50; p = 0.06). There were no differences in the one-year survival rate or the occurrence of adverse events between the TTM and non-TTM groups. Altogether, the use of TTM was associated with a higher survival to hospital discharge; however, it did not significantly increase the annual survival. Additional high-quality prospective studies are necessary to confer additional TTM benefits.
| S-EPMC8037776 | biostudies-literature
Project description:BACKGROUND:We sought to determine the outcome of suicidal hanging and the impact of targeted temperature management (TTM) on hanging-induced cardiac arrest (CA) through an Eastern Association for the Surgery of Trauma (EAST) multicenter retrospective study. METHODS:We analyzed hanging patient data and TTM variables from January 1992 to December 2015. Cerebral performance category score of 1 or 2 was considered good neurologic outcome, while cerebral performance category score of 3 or 4 was considered poor outcome. Classification and Regression Trees recursive partitioning was used to develop multivariate predictive models for survival and neurologic outcome. RESULTS:A total of 692 hanging patients from 17 centers were analyzed for this study. Their overall survival rate was 77%, and the CA survival rate was 28.6%. The CA patients had significantly higher severity of illness and worse outcome than the non-CA patients. Of the 175 CA patients who survived to hospital admission, 81 patients (46.3%) received post-CA TTM. The unadjusted survival of TTM CA patients (24.7% vs 39.4%, p < 0.05) and good neurologic outcome (19.8% vs 37.2%, p < 0.05) were worse than non-TTM CA patients. However, when subgroup analyses were performed between those with an admission Glasgow Coma Scale score of 3 to 8, the differences between TTM and non-TTM CA survival (23.8% vs 30.0%, p = 0.37) and good neurologic outcome (18.8% vs 28.7%, p = 0.14) were not significant. Targeted temperature management implementation and post-CA management varied between the participating centers. Classification and Regression Trees models identified variables predictive of favorable and poor outcome for hanging and TTM patients with excellent accuracy. CONCLUSION:Cardiac arrest hanging patients had worse outcome than non-CA patients. Targeted temperature management CA patients had worse unadjusted survival and neurologic outcome than non-TTM patients. These findings may be explained by their higher severity of illness, variable TTM implementation, and differences in post-CA management. Future prospective studies are necessary to ascertain the effect of TTM on hanging outcome and to validate our Classification and Regression Trees models. LEVEL OF EVIDENCE:Therapeutic study, level IV; prognostic study, level III.
| S-EPMC6026030 | biostudies-literature
Project description:BackgroundAlthough targeted temperature management (TTM) is recommended in comatose survivors after cardiac arrest (CA), the optimal method to deliver TTM remains unknown. We performed a meta-analysis to evaluate the effects of different TTM methods on survival and neurological outcome after adult CA.MethodsWe searched on the MEDLINE/PubMed database until 22 February 2019 for comparative studies that evaluated at least two different TTM methods in CA patients. Data were extracted independently by two authors. We used the Newcastle-Ottawa Scale and a modified Cochrane ROB tools for assessing the risk of bias of each study. The primary outcome was the occurrence of unfavorable neurological outcome (UO); secondary outcomes included overall mortality.ResultsOur search identified 6886 studies; 22 studies (n?=?8027 patients) were included in the final analysis. When compared to surface cooling, core methods showed a lower probability of UO (OR 0.85 [95% CIs 0.75-0.96]; p?=?0.008) but not mortality (OR 0.88 [95% CIs 0.62-1.25]; p?=?0.21). No significant heterogeneity was observed among studies. However, these effects were observed in the analyses of non-RCTs. A significant lower probability of both UO and mortality were observed when invasive TTM methods were compared to non-invasive TTM methods and when temperature feedback devices (TFD) were compared to non-TFD methods. These results were significant particularly in non-RCTs.ConclusionsAlthough existing literature is mostly based on retrospective or prospective studies, specific TTM methods (i.e., core, invasive, and with TFD) were associated with a lower probability of poor neurological outcome when compared to other methods in adult CA survivors (CRD42019111021).
| S-EPMC6708171 | biostudies-literature
Project description:BackgroundTargeted temperature management (TTM) is recommended in adult patients following cardiac arrest (CA) with any rhythm. However, as to non-shockable (NSR) CA, high-quality evidence of TTM supporting its practices remains uncertain. Thus, we aimed to conduct a systematic review and meta-analysis with randomized controlled trials (RCTs) to explore the efficacy and safety of TTM in this population.MethodsWe searched PubMed, Embase, and Cochrane library databases for potential trials from inception through Aug 25, 2021. RCTs evaluating TTM for CA adults due to NSR were included, regardless of the timing of cooling initiation. Outcome measurements were mortality and good neurological function. We used the Cochrane bias tools to evaluate the quality of the included studies. Heterogeneity, subgroup analyses, and sensitivity analysis were investigated to test the robustness of the primary outcomes.ResultsA total of 14 RCTs with 4,009 adults were eligible for the final analysis. All trials had a low to moderate risk of bias. Of the included trials, six compared NSR patients with or without TTM, while eight compared pre-hospital to in-hospital TTM. Pooled data showed that TTM was not associated with improved mortality (Risk ratio [RR] 1.00; 95% CI, 0.944-1.05; P = 0.89, I 2 = 0%) and good neurological outcome (RR 1.18; 95% CI 0.90-1.55; P = 0.22, I 2 = 8%). Similarly, use of pre-hospital TTM resulted in neither an improved mortality (RR 0.99, 95% CI 0.97-1.03; I 2 = 0%, P = 0.32) nor favorable neurological outcome (RR 1.13, 95% CI 0.93-1.38; I 2 = 0%, P = 0.22). These results were further confirmed in the sensitivity analyses and subgroup analyses.ConclusionsOur results showed that using the TTM strategy did not significantly affect the mortality and neurologic outcomes in CA survival presenting initial NSR.
| S-EPMC9203727 | biostudies-literature
Project description:BackgroundTargeted temperature management (TTM) has been shown to improve neurological outcomes and survival in patients resuscitated from cardiac arrest; however, the cost effectiveness of multiple TTM methods is not well studied.ObjectiveThis study aimed to evaluate the cost effectiveness of intravascular temperature management (IVTM) using Thermogard XP compared with surface cooling methods after cardiac arrest in the England from the perspectives of the UK national health service and Personal Social Services.MethodsWe developed a multi-state Markov model that evaluated IVTM (Thermogard XP) compared with surface cooling using two different devices (Blanketrol III and Arctic Sun 5000) over a short-term and lifetime time horizon. Model input parameters were obtained from the literature and local databases. We assumed a hypothetical cohort of 1000 patients who required TTM after cardiac arrest per year in the England. The outcomes were costs (in £, year 2019 values) and quality-adjusted life-years (QALYs), discounted at 3.5% annually. Deterministic and probabilistic sensitivity analyses were undertaken to examine the effect of alternative assumptions and uncertainty in model parameters on the results.ResultsThe cost-effectiveness analysis determined that Thermogard XP resulted in direct cost savings of £2339 and £2925 (per patient) compared with Blanketrol III and Arctic Sun 5000, respectively, and a gain of 0.98 QALYs over the patient lifetime. The probabilistic sensitivity analysis demonstrated that the probability of Thermogard XP being cost saving would be 69.2% and 65.3% versus the Arctic Sun 5000 and Blanketrol III, respectively.ConclusionImplementation of IVTM using Thermogard XP can lead to cost savings and improved patient quality of life versus surface cooling methods.
| S-EPMC9283555 | biostudies-literature
Project description:Targeted temperature management (TTM) is a recommended neuroprotective intervention for coma after out-of-hospital cardiac arrest (OHCA). However, controversies exist concerning the proper implementation and overall efficacy of post-CA TTM, particularly related to optimal timing and depth of TTM and cooling methods. A review of the literature finds that optimizing and individualizing TTM remains an open question requiring further clinical investigation. This paper will summarize the preclinical and clinical trial data to-date, current recommendations, and future directions of this therapy, including new cooling methods under investigation. For now, early induction, maintenance for at least 24 hours, and slow rewarming utilizing endovascular methods may be preferred. Moreover, timely and accurate neuro-prognostication is valuable for guiding ethical and cost-effective management of post-CA coma. Current evidence for early neuro-prognostication after TTM suggests that a combination of initial prediction models, biomarkers, neuroimaging, and electrophysiological methods is the optimal strategy in predicting neurological functional outcomes.
| S-EPMC8142127 | biostudies-literature
Project description:The established benefits of cooling along with development of sophisticated methods to safely and precisely induce, maintain, monitor, and reverse hypothermia have led to the development of targeted temperature management (TTM). Early trials in human subjects showed that hypothermia conferred better neurological outcomes when compared to normothermia among survivors of cardiac arrest, leading to guidelines recommending targeted hypothermia in this patient population. Multiple studies have sought to explore and compare the benefit of hypothermia in various subgroups of patients, such as survivors of out-of-hospital cardiac arrest versus in-hospital cardiac arrest, and survivors of an initial shockable versus non-shockable rhythm. Larger and more recent trials have shown no statistically significant difference in neurological outcomes between patients with targeted hypothermia and targeted normothermia; further, aggressive cooling is associated with a higher incidence of multiple systemic complications. Based on this data, temporal trends have leaned towards using a lenient temperature target in more recent times. Current guidelines recommend selecting and maintaining a constant target temperature between 32 and 36 °C for those patients in whom TTM is used (strong recommendation, moderate-quality evidence), as soon as possible after return of spontaneous circulation is achieved and airway, breathing (including mechanical ventilation), and circulation are stabilized. The comparative benefit of lower (32-34 °C) versus higher (36 °C) temperatures remains unknown, and further research may help elucidate this. Any survivor of cardiac arrest who is comatose (defined as unarousable unresponsiveness to external stimuli) should be considered as a candidate for TTM regardless of the initial presenting rhythm, and the decision to opt for targeted hypothermia versus targeted normothermia should be made on a case-by-case basis.
| S-EPMC9986171 | biostudies-literature