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      Effect of different methods of cooling for targeted temperature management on outcome after cardiac arrest: a systematic review and meta-analysis

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          Abstract

          Background

          Although 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.

          Methods

          We 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.

          Results

          Our 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.

          Conclusions

          Although 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).

          Electronic supplementary material

          The online version of this article (10.1186/s13054-019-2567-6) contains supplementary material, which is available to authorized users.

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          Most cited references43

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          GRADE: an emerging consensus on rating quality of evidence and strength of recommendations.

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            Targeted Temperature Management at 33°C versus 36°C after Cardiac Arrest

            Unconscious survivors of out-of-hospital cardiac arrest have a high risk of death or poor neurologic function. Therapeutic hypothermia is recommended by international guidelines, but the supporting evidence is limited, and the target temperature associated with the best outcome is unknown. Our objective was to compare two target temperatures, both intended to prevent fever. In an international trial, we randomly assigned 950 unconscious adults after out-of-hospital cardiac arrest of presumed cardiac cause to targeted temperature management at either 33°C or 36°C. The primary outcome was all-cause mortality through the end of the trial. Secondary outcomes included a composite of poor neurologic function or death at 180 days, as evaluated with the Cerebral Performance Category (CPC) scale and the modified Rankin scale. In total, 939 patients were included in the primary analysis. At the end of the trial, 50% of the patients in the 33°C group (235 of 473 patients) had died, as compared with 48% of the patients in the 36°C group (225 of 466 patients) (hazard ratio with a temperature of 33°C, 1.06; 95% confidence interval [CI], 0.89 to 1.28; P=0.51). At the 180-day follow-up, 54% of the patients in the 33°C group had died or had poor neurologic function according to the CPC, as compared with 52% of patients in the 36°C group (risk ratio, 1.02; 95% CI, 0.88 to 1.16; P=0.78). In the analysis using the modified Rankin scale, the comparable rate was 52% in both groups (risk ratio, 1.01; 95% CI, 0.89 to 1.14; P=0.87). The results of analyses adjusted for known prognostic factors were similar. In unconscious survivors of out-of-hospital cardiac arrest of presumed cardiac cause, hypothermia at a targeted temperature of 33°C did not confer a benefit as compared with a targeted temperature of 36°C. (Funded by the Swedish Heart-Lung Foundation and others; TTM ClinicalTrials.gov number, NCT01020916.).
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              Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia.

              Cardiac arrest outside the hospital is common and has a poor outcome. Studies in laboratory animals suggest that hypothermia induced shortly after the restoration of spontaneous circulation may improve neurologic outcome, but there have been no conclusive studies in humans. In a randomized, controlled trial, we compared the effects of moderate hypothermia and normothermia in patients who remained unconscious after resuscitation from out-of-hospital cardiac arrest. The study subjects were 77 patients who were randomly assigned to treatment with hypothermia (with the core body temperature reduced to 33 degrees C within 2 hours after the return of spontaneous circulation and maintained at that temperature for 12 hours) or normothermia. The primary outcome measure was survival to hospital discharge with sufficiently good neurologic function to be discharged to home or to a rehabilitation facility. The demographic characteristics of the patients were similar in the hypothermia and normothermia groups. Twenty-one of the 43 patients treated with hypothermia (49 percent) survived and had a good outcome--that is, they were discharged home or to a rehabilitation facility--as compared with 9 of the 34 treated with normothermia (26 percent, P=0.046). After adjustment for base-line differences in age and time from collapse to the return of spontaneous circulation, the odds ratio for a good outcome with hypothermia as compared with normothermia was 5.25 (95 percent confidence interval, 1.47 to 18.76; P=0.011). Hypothermia was associated with a lower cardiac index, higher systemic vascular resistance, and hyperglycemia. There was no difference in the frequency of adverse events. Our preliminary observations suggest that treatment with moderate hypothermia appears to improve outcomes in patients with coma after resuscitation from out-of-hospital cardiac arrest.
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                Author and article information

                Contributors
                lorenzo.calabro94@gmail.com
                wulfran.bougouin@gmail.com
                alain.cariou@aphp.fr
                chiara.defazio@student.unife.it
                Markus.Skrifvars@hus.fi
                eldar.soreide@sus.no
                jcreteur@ulb.ac.be
                hanskirkegaard@dadlnet.dk
                slegriel@ch-versailles.fr
                Jeanbaptiste.lascarrou@chu-nantes.fr
                bruno.megarbane@aphp.fr
                nicolas.deye@aphp.fr
                +322 555 3380 , ftaccone@ulb.ac.be
                Journal
                Crit Care
                Critical Care
                BioMed Central (London )
                1364-8535
                1466-609X
                23 August 2019
                23 August 2019
                2019
                : 23
                : 285
                Affiliations
                [1 ]ISNI 0000 0001 2348 0746, GRID grid.4989.c, Department of Intensive Care, Cliniques Universitaires de Bruxelles Hopital Erasme, Erasmus Hospital, , Université Libre de Bruxelles (ULB), ; Route de Lennik, 808, 1070 Brussels, Belgium
                [2 ]ISNI 0000 0001 2188 0914, GRID grid.10992.33, UFR de Médecine, , Université Paris-Descartes-Sorbonne-Paris-Cité, ; Paris, France
                [3 ]Paris Sudden Death Expertise Center, Paris, France
                [4 ]ISNI 0000 0004 0495 1460, GRID grid.462416.3, Paris Cardiovascular Research Center, , INSERM U970, ; Paris, France
                [5 ]ISNI 0000 0001 2175 4109, GRID grid.50550.35, Medical ICU, Cochin Hospital, , Assistance Publique-Hôpitaux de Paris, ; Paris, France
                [6 ]ISNI 0000 0000 9950 5666, GRID grid.15485.3d, Division of Intensive Care, Department of Anesthesiology, Intensive Care and Pain Medicine, , Helsinki University Hospital and Helsinki University, ; Helsinki, Finland
                [7 ]ISNI 0000 0004 0627 2891, GRID grid.412835.9, Department of Anaesthesiology and Intensive Care, , Stavanger University Hospital, ; Stavanger, Norway
                [8 ]ISNI 0000 0004 0512 597X, GRID grid.154185.c, Research Center for Emergency Medicine, Department of Anesthesiology and Intensive Care Medicine, , Aarhus University Hospital and Aarhus University, ; Aarhus, Denmark
                [9 ]Intensive Care Unit, Centre Hospitalier de Versailles, PARCC Inserm UMR 970, Le Chesnay, France
                [10 ]ISNI 0000 0004 0472 0371, GRID grid.277151.7, Medical Intensive Care Unit, , University Hospital Center, PARCC Inserm UMR 970, ; Nantes, France
                [11 ]Medical and Toxicology Intensive Care Unit, Hôpitaux Universitaires Saint Louis-Lariboisière, Assistance Publique-Hôpitaux de Paris, Université Paris Diderot-Paris 7, Inserm U942, Paris, France
                Article
                2567
                10.1186/s13054-019-2567-6
                6708171
                31443696
                b407389a-17dc-4355-b94f-78f786360e27
                © The Author(s). 2019

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 2 April 2019
                : 13 August 2019
                Categories
                Research
                Custom metadata
                © The Author(s) 2019

                Emergency medicine & Trauma
                targeted temperature management,methods,endovascular,surface cooling,survival,neurological outcome,meta-analysis

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