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      Intravascular versus surface cooling for targeted temperature management after out-of-hospital cardiac arrest: an analysis of the TTH48 trial

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          Abstract

          Background

          The aim of this study was to explore the performance and outcomes for intravascular (IC) versus surface cooling devices (SFC) for targeted temperature management (TTM) after out-of-hospital cardiac arrest.

          Methods

          A retrospective analysis of data from the Time-differentiated Therapeutic Hypothermia (TTH48) trial (NCT01689077), which compared whether TTM at 33 °C for 48 h results in better neurologic outcomes compared with standard 24-h duration. Devices were assessed for the speed of cooling and rewarming rates. Precision was assessed by measuring temperature variability (TV), i.e., the standard deviation (SD) of all temperature measurements in the cooling phase. Main outcomes were overall mortality and poor neurological outcome, including death, severe disability, or vegetative status.

          Results

          A total of 352 patients had available data and were included in the analysis; of those, 218 (62%) were managed with IC. A total of 114/218 (53%) patients with IC and 61/134 (43%) with SFC were cooled for 48 h ( p = 0.22). Time to target temperature (≤ 34 °C) was significantly shorter for patients treated with endovascular devices (2.2 [1.1–4.0] vs. 4.2 [2.7–6.0] h, p < 0.001), but temperature was also lower on admission (35.0 [34.2–35.6] vs. 35.3 [34.5–35.8]°C; p = 0.02) and cooling rate was similar (0.4 [0.2–0.8] vs. 0.4 [0.2–0.6]°C/h; p = 0.14) when compared to SFC. Temperature variability was significantly lower in the endovascular device group when compared with SFC methods (0.6 [0.4–0.9] vs. 0.7 [0.5–1.0]°C; p = 0.007), as was rewarming rate (0.31 [0.22–0.44] vs. 0.37 [0.29–0.49]°C/hour; p = 0.02). There was no statistically significant difference in mortality (endovascular 65/218, 29% vs. others 43/134, 32%; p = 0.72) or poor neurological outcome (endovascular 69/218, 32% vs. others 51/134, 38%; p = 0.24) between type of devices.

          Conclusions

          Endovascular cooling devices were more precise than SFC methods in patients cooled at 33 °C after out-of-hospital cardiac arrest. Main outcomes were similar with regard to the cooling methods.

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          Most cited references24

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          Application of therapeutic hypothermia in the intensive care unit. Opportunities and pitfalls of a promising treatment modality--Part 2: Practical aspects and side effects.

          Induced hypothermia can be used to protect the brain from post-ischemic and traumatic neurological injury. Potential clinical applications and the available evidence are discussed in a separate paper. This review focuses on the practical aspects of cooling and physiological changes induced by hypothermia, as well as the potential side effects that may develop. These side effects can be serious and, if not properly dealt with, may negate some or all of hypothermia's potential benefits. However, many of these side effects can be prevented or modified by high-quality intensive care treatment, which should include careful monitoring of fluid balance, tight control of metabolic aspects such as glucose and electrolyte levels, prevention of infectious complications and various other interventions. The speed and duration of cooling and rate of re-warming are key factors in determining whether hypothermia will be effective; however, the risk of side effects also increases with longer duration. Realizing hypothermia's full therapeutic potential will therefore require meticulous attention to the prevention and/or early treatment of side effects, as well as a basic knowledge and understanding of the underlying physiological and pathophysiological mechanisms. These and other, related issues are dealt with in this review.
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            From evidence to clinical practice: effective implementation of therapeutic hypothermia to improve patient outcome after cardiac arrest.

            Therapeutic hypothermia has been recommended for postcardiac arrest coma due to ventricular fibrillation. However, no studies have evaluated whether therapeutic hypothermia could be effectively implemented in intensive care practice and whether it would improve the outcome of all comatose patients with cardiac arrest, including those with shock or with cardiac arrest due to nonventricular fibrillation rhythms. Retrospective study. Fourteen-bed medical intensive care unit in a university hospital. Patients were 109 comatose patients with out-of-hospital cardiac arrest due to ventricular fibrillation and nonventricular fibrillation rhythms (asystole/pulseless electrical activity). We analyzed 55 consecutive patients (June 2002 to December 2004) treated with therapeutic hypothermia (to a central target temperature of 33 degrees C, using external cooling). Fifty-four consecutive patients (June 1999 to May 2002) treated with standard resuscitation served as controls. Efficacy, safety, and outcome at hospital discharge were assessed. Good outcome was defined as Glasgow-Pittsburgh Cerebral Performance category 1 or 2. In patients treated with therapeutic hypothermia, the median time to reach the target temperature was 5 hrs, with a progressive reduction over the 18 months of data collection. Therapeutic hypothermia had a major positive impact on the outcome of patients with cardiac arrest due to ventricular fibrillation (good outcome in 24 of 43 patients [55.8%] of the therapeutic hypothermia group vs. 11 of 43 patients [25.6%] of the standard resuscitation group, p = .004). The benefit of therapeutic hypothermia was also maintained in patients with shock (good outcome in five of 17 patients of the therapeutic hypothermia group vs. zero of 14 of the standard resuscitation group, p = .027). The outcome after cardiac arrest due to nonventricular fibrillation rhythms was poor and did not differ significantly between the two groups. Therapeutic hypothermia was of particular benefit in patients with short duration of cardiac arrest (<30 mins). Therapeutic hypothermia for the treatment of postcardiac arrest coma can be successfully implemented in intensive care practice with a major benefit on patient outcome, which appeared to be related to the type and the duration of initial cardiac arrest and seemed maintained in patients with shock.
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              Comparison of cooling methods to induce and maintain normo- and hypothermia in intensive care unit patients: a prospective intervention study

              Background Temperature management is used with increased frequency as a tool to mitigate neurological injury. Although frequently used, little is known about the optimal cooling methods for inducing and maintaining controlled normo- and hypothermia in the intensive care unit (ICU). In this study we compared the efficacy of several commercially available cooling devices for temperature management in ICU patients with various types of neurological injury. Methods Fifty adult ICU patients with an indication for controlled mild hypothermia or strict normothermia were prospectively enrolled. Ten patients in each group were assigned in consecutive order to conventional cooling (that is, rapid infusion of 30 ml/kg cold fluids, ice and/or coldpacks), cooling with water circulating blankets, air circulating blankets, water circulating gel-coated pads and an intravascular heat exchange system. In all patients the speed of cooling (expressed as°C/h) was measured. After the target temperature was reached, we measured the percentage of time the patient's temperature was 0.2°C below or above the target range. Rates of temperature decline over time were analyzed with one-way analysis of variance. Differences between groups were analyzed with one-way analysis of variance, with Bonferroni correction for multiple comparisons. A p < 0.05 was considered statistically significant. Results Temperature decline was significantly higher with the water-circulating blankets (1.33 ± 0.63°C/h), gel-pads (1.04 ± 0.14°C/h) and intravascular cooling (1.46 ± 0.42°C/h) compared to conventional cooling (0.31 ± 0.23°C/h) and the air-circulating blankets (0.18 ± 0.2°C/h) (p < 0.01). After the target temperature was reached, the intravascular cooling device was 11.2 ± 18.7% of the time out of range, which was significantly less compared to all other methods. Conclusion Cooling with water-circulating blankets, gel-pads and intravascular cooling is more efficient compared to conventional cooling and air-circulating blankets. The intravascular cooling system is most reliable to maintain a stable temperature.
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                Author and article information

                Contributors
                chiara.defazio@student.unife.it
                Markus.Skrifvars@hus.fi
                eldar.soreide@sus.no
                jcreteur@ulb.ac.be
                andersgrejs@dadlnet.dk
                jesper.kjaergaard@dadlnet.dk
                timo.laitio@elisanet.fi
                jens.nee@charite.de
                hanskirkegaard@dadlnet.dk
                +322 555 3380 , ftaccone@ulb.ac.be
                Journal
                Crit Care
                Critical Care
                BioMed Central (London )
                1364-8535
                1466-609X
                22 February 2019
                22 February 2019
                2019
                : 23
                : 61
                Affiliations
                [1 ]ISNI 0000 0001 2348 0746, GRID grid.4989.c, Department of Intensive Care, , Cliniques Universitaires de Bruxelles Hopital Erasme, Université Libre de Bruxelles (ULB), ; Route de Lennik, 808, 1070 Brussels, Belgium
                [2 ]ISNI 0000 0004 0410 2071, GRID grid.7737.4, Division of Intensive Care, Department of Anesthesiology, Intensive Care and Pain Medicine, , University of Helsinki and Helsinki University Hospital, ; Helsinki, Finland
                [3 ]ISNI 0000 0004 0627 2891, GRID grid.412835.9, Critical Care and Anaesthesiology Research Group, , Stavanger University Hospital, ; Stavanger, Norway
                [4 ]ISNI 0000 0004 1936 7443, GRID grid.7914.b, Department of Clinical Medicine, , University of Bergen, ; Bergen, Norway
                [5 ]ISNI 0000 0004 0512 597X, GRID grid.154185.c, Department of Intensive Care Medicine, , Aarhus University Hospital, ; Aarhus, Denmark
                [6 ]GRID grid.475435.4, Department of Cardiology B, , Copenhagen University Hospital Rigshospitalet, ; Copenhagen, Denmark
                [7 ]ISNI 0000 0004 0628 215X, GRID grid.410552.7, Division of Perioperative Services, Intensive Care Medicine and Pain Management, , Turku University Hospital, ; Turku, Finland
                [8 ]ISNI 0000 0001 2218 4662, GRID grid.6363.0, Medizinische Klinik mit Schwerpunkt, Nephrologie und Internistische Intensivmedizin, , Charité-Universitätsmedizin Berlin, ; Berlin, Germany
                [9 ]ISNI 0000 0004 0512 597X, GRID grid.154185.c, Research Center for Emergency Medicine, Department of Emergency Medicine and Department of Clinical Medicine, , Aarhus University Hospital and Aarhus University, ; Aarhus, Denmark
                [10 ]ISNI 0000 0004 0410 2071, GRID grid.7737.4, Department of Emergency Care and Services, , University of Helsinki and Helsinki University Hospital, ; Helsinki, Finland
                Article
                2335
                10.1186/s13054-019-2335-7
                6385423
                30795782
                97a10dbc-c6e2-425f-9ca5-7f051e9bb55d
                © 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
                : 19 November 2018
                : 25 January 2019
                Categories
                Research
                Custom metadata
                © The Author(s) 2019

                Emergency medicine & Trauma
                methods,cooling,hypothermia,ttm,cardiac arrest,outcome
                Emergency medicine & Trauma
                methods, cooling, hypothermia, ttm, cardiac arrest, outcome

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