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      Practical considerations for postarrest targeted temperature management

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          Abstract

          Out-of-hospital cardiac arrest remains a major challenge worldwide, with survival to discharge rates of <20% in the great majority of countries. Advancements in prehospital care, including increasing deployment of automated external defibrillators and improvements in bystander cardiopulmonary resuscitation, have led to more victims achieving return of spontaneous circulation (ROSC), yet the majority of patients with ROSC suffer in-hospital mortality or significant neurologic injuries that persist after discharge. This postarrest morbidity and mortality is largely due to a complex syndrome of mitochondrial dysfunction, inflammatory cascades and cellular injuries known as the postcardiac arrest syndrome (PCAS). The management of PCAS represents a formidable task for emergency and critical care providers. A cornerstone of PCAS treatment is the use of aggressive core body temperature control using thermostatically controlled devices, known as targeted temperature management (TTM). This therapy, demonstrated to be effective in improving both survival and neurologic recovery by several randomized controlled trials nearly 20 years ago, remains a major topic of clinical investigation. Important practical questions about TTM remain: How soon must providers initiate the therapy? What TTM goal temperature maximizes benefit while limiting potential adverse effects? How long should TTM therapy be continued in patients following resuscitation? In this review, we will address these issues and summarize clinical research over the past decade that has added to our fund of knowledge surrounding this important treatment of patients following cardiac arrest.

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          Most cited references24

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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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            Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest.

            (2002)
            Cardiac arrest with widespread cerebral ischemia frequently leads to severe neurologic impairment. We studied whether mild systemic hypothermia increases the rate of neurologic recovery after resuscitation from cardiac arrest due to ventricular fibrillation. In this multicenter trial with blinded assessment of the outcome, patients who had been resuscitated after cardiac arrest due to ventricular fibrillation were randomly assigned to undergo therapeutic hypothermia (target temperature, 32 degrees C to 34 degrees C, measured in the bladder) over a period of 24 hours or to receive standard treatment with normothermia. The primary end point was a favorable neurologic outcome within six months after cardiac arrest; secondary end points were mortality within six months and the rate of complications within seven days. Seventy-five of the 136 patients in the hypothermia group for whom data were available (55 percent) had a favorable neurologic outcome (cerebral-performance category, 1 [good recovery] or 2 [moderate disability]), as compared with 54 of 137 (39 percent) in the normothermia group (risk ratio, 1.40; 95 percent confidence interval, 1.08 to 1.81). Mortality at six months was 41 percent in the hypothermia group (56 of 137 patients died), as compared with 55 percent in the normothermia group (76 of 138 patients; risk ratio, 0.74; 95 percent confidence interval, 0.58 to 0.95). The complication rate did not differ significantly between the two groups. In patients who have been successfully resuscitated after cardiac arrest due to ventricular fibrillation, therapeutic mild hypothermia increased the rate of a favorable neurologic outcome and reduced mortality.
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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

                Journal
                Turk J Emerg Med
                Turk J Emerg Med
                TJEM
                Turkish Journal of Emergency Medicine
                Wolters Kluwer - Medknow (India )
                2452-2473
                Oct-Dec 2020
                07 October 2020
                : 20
                : 4
                : 157-162
                Affiliations
                [1] Department of Emergency Medicine, The Center for Resuscitation Science, School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
                Author notes
                Address for correspondence: Dr. Benjamin S. Abella, Department of Emergency Medicine, The Center for Resuscitation Science, School of Medicine, University of Pennsylvania, 3400 Spruce Street, Ground Ravdin, Philadelphia, PA 19104, USA. E-mail: benjamin.abella@ 123456pennmedicine.upenn.edu

                * Corresponding author

                Author contributions

                IM and BA contributed to the conception, drafting and editing of the work.

                Author information
                http://orcid.org/0000-0002-1792-3149
                http://orcid.org/0000-0003-2521-0891
                Article
                TJEM-20-157
                10.4103/2452-2473.297466
                7549514
                e0d3240d-1d4f-4a09-8e13-debc764e45c8
                Copyright: © 2020 Turkish Journal of Emergency Medicine

                This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.

                History
                : 19 June 2020
                : 21 June 2020
                Categories
                Invited Review Article

                hypothermia,induced,postarrest syndrome,resuscitation
                hypothermia, induced, postarrest syndrome, resuscitation

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