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      Intravascular versus surface cooling for targeted temperature management after out-of-hospital cardiac arrest – an analysis of the TTM trial data

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          Abstract

          Background

          Targeted temperature management is recommended after out-of-hospital cardiac arrest and may be achieved using a variety of cooling devices. This study was conducted to explore the performance and outcomes for intravascular versus surface devices for targeted temperature management after out-of-hospital cardiac arrest.

          Method

          A retrospective analysis of data from the Targeted Temperature Management trial. N = 934. A total of 240 patients (26%) managed with intravascular versus 694 (74%) with surface devices. Devices were assessed for speed and precision during the induction, maintenance and rewarming phases in addition to adverse events. All-cause mortality, as well as a composite of poor neurological function or death, as evaluated by the Cerebral Performance Category and modified Rankin scale were analysed.

          Results

          For patients managed at 33 °C there was no difference between intravascular and surface groups in the median time taken to achieve target temperature (210 [interquartile range (IQR) 180] minutes vs. 240 [IQR 180] minutes, p = 0.58), maximum rate of cooling (1.0 [0.7] vs. 1.0 [0.9] °C/hr, p = 0.44), the number of patients who reached target temperature (within 4 hours (65% vs. 60%, p = 0.30); or ever (100% vs. 97%, p = 0.47), or episodes of overcooling (8% vs. 34%, p = 0.15). In the maintenance phase, cumulative temperature deviation (median 3.2 [IQR 5.0] °C hr vs. 9.3 [IQR 8.0] °C hr, p = <0.001), number of patients ever out of range (57.0% vs. 91.5%, p = 0.006) and median time out of range (1 [IQR 4.0] hours vs. 8.0 [IQR 9.0] hours, p = <0.001) were all significantly greater in the surface group although there was no difference in the occurrence of pyrexia. Adverse events were not different between intravascular and surface groups. There was no statistically significant difference in mortality (intravascular 46.3% vs. surface 50.0%; p = 0.32), Cerebral Performance Category scale 3–5 (49.0% vs. 54.3%; p = 0.18) or modified Rankin scale 4–6 (49.0% vs. 53.0%; p = 0.48).

          Conclusions

          Intravascular and surface cooling was equally effective during induction of mild hypothermia. However, surface cooling was associated with less precision during the maintenance phase. There was no difference in adverse events, mortality or poor neurological outcomes between patients treated with intravascular and surface cooling devices.

          Trial registration

          TTM trial ClinicalTrials.gov number https://clinicaltrials.gov/ct2/show/NCT01020916NCT01020916; 25 November 2009

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          Most cited references41

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          Therapeutic hypothermia and controlled normothermia in the intensive care unit: practical considerations, side effects, and cooling methods.

          Hypothermia is being used with increasing frequency to prevent or mitigate various types of neurologic injury. In addition, symptomatic fever control is becoming an increasingly accepted goal of therapy in patients with neurocritical illness. However, effectively controlling fever and inducing hypothermia poses special challenges to the intensive care unit team and others involved in the care of critically ill patients. To discuss practical aspects and pitfalls of therapeutic temperature management in critically ill patients, and to review the currently available cooling methods. Review article. None. Cooling can be divided into three distinct phases: induction, maintenance, and rewarming. Each has its own risks and management problems. A number of cooling devices that have reached the market in recent years enable reliable maintenance and slow and controlled rewarming. In the induction phase, rapid cooling rates can be achieved by combining cold fluid infusion (1500-3000 mL 4 degrees C saline or Ringer's lactate) with an invasive or surface cooling device. Rapid induction decreases the risks and consequences of short-term side effects, such as shivering and metabolic disorders. Cardiovascular effects include bradycardia and a rise in blood pressure. Hypothermia's effect on myocardial contractility is variable (depending on heart rate and filling pressure); in most patients myocardial contractility will increase, although mild diastolic dysfunction can develop in some patients. A risk of clinically significant arrhythmias occurs only if core temperature decreases below 30 degrees C. The most important long-term side effects of hypothermia are infections (usually of the respiratory tract or wounds) and bedsores. Temperature management and hypothermia induction are gaining importance in critical care medicine. Intensive care unit physicians, critical care nurses, and others (emergency physicians, neurologists, and cardiologists) should be familiar with the physiologic effects, current indications, techniques, complications and practical issues of temperature management, and induced hypothermia. In experienced hands the technique is safe and highly effective.
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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
                guy.glover@gstt.nhs.uk
                r.thomas@doctors.org.uk
                george.vamvakas@kcl.ac.uk
                nalsubaie@gmail.com
                julescranshaw@hotmail.com
                apwalden@hotmail.com
                mattwise@doctors.org.uk
                marlies.ostermann@gstt.nhs.uk
                Thomas-JonesE@cardiff.ac.uk
                Tobias.Cronberg@skane.se
                david.erlinge@gmail.com
                Yvan.Gasche@hcuge.ch
                hassager@dadlnet.dk
                j.horn@amc.uva.nl
                jesper.kjaergaard@dadlnet.dk
                mi.kuiper@wxs.nl
                thomas.pellis@gmail.com
                Stammet.Pascal@chl.lu
                wanscher@dadlnet.dk
                wetterslev@ctu.dk
                hans.a.friberg@gmail.com
                niklas.nielsen@telia.com
                Journal
                Crit Care
                Critical Care
                BioMed Central (London )
                1364-8535
                1466-609X
                26 November 2016
                26 November 2016
                2016
                : 20
                : 381
                Affiliations
                [1 ]Department Intensive Care, Guy’s and St Thomas’ Hospital, King’s College London, London, UK
                [2 ]Department of Intensive Care, University College Hospital, London, UK
                [3 ]Department of Biostatistics, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK
                [4 ]Department of Intensive Care, St George’s Hospital, London, UK
                [5 ]Department of Intensive Care, Royal Bournemouth Hospital, Bournemouth, UK
                [6 ]Department of Intensive Care, Royal Berkshire Hospital, Reading, UK
                [7 ]Adult Critical Care, University Hospital of Wales, Cardiff, UK
                [8 ]Centre for Trials Research, College of Biomedical and Life Sciences, Cardiff University, Cardiff, UK
                [9 ]Department of Neurology, Skåne University Hospital, Lund University, Lund, Sweden
                [10 ]Department of Cardiology, Skåne University Hospital, Lund University, Lund, Sweden
                [11 ]Department of Intensive Care, Geneva University Hospital, Geneva, Switzerland
                [12 ]The Heart Center, Copenhagen University Hospital, Righospitalet, Copenhagen, Denmark
                [13 ]Department of Intensive Care, Academic Medical Centre, Amsterdam, The Netherlands
                [14 ]Department of Intensive Care, Medical Center Leeuwarden, Leeuwarden, The Netherlands
                [15 ]Department of Intensive Care, Santa Maria degli Ángeli, Pordenone, Italy
                [16 ]Department of Anesthesiology and Intensive Care, Centre Hospitalier de Luxembourg, Luxembourg City, Luxembourg
                [17 ]Copenhagen Trial Unit, Center for Clinical Intervention Research, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
                [18 ]Department of Anesthesiology and Intensive Care, Skåne University Hospital, Lund University, Lund, Sweden
                [19 ]Department of Anesthesiology and Intensive Care, Helsingborg Hospital, Helsingborg, Sweden
                [20 ]Department of Critical Care, Guy’s and St Thomas’ NHS Foundation Trust, Kings Health Partners, Westminster Bridge Road, London, SE1 7EH UK
                Article
                1552
                10.1186/s13054-016-1552-6
                5124238
                27887653
                1ca3a838-dc29-43cf-b97d-081dbcf492dd
                © The Author(s). 2016

                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
                : 13 July 2016
                : 31 October 2016
                Funding
                Funded by: Hjärt-Lungfonden (SE)
                Funded by: Arbetsmarknadens försäkringsaktiebolag (AFA)-insurance Foundation
                Funded by: The Swedish Research Council
                Funded by: Regional research support, Region Skåne
                Funded by: Governmental funding of clinical research within the Swedish NHS (National Health Services)
                Funded by: Thelma Zoega Foundation
                Funded by: Krapperup Foundation
                Funded by: Thure Carlsson Foundation
                Funded by: Hans-Gabriel and Alice Trolle-Wachtmeister Foundation for Medical Research
                Funded by: Skåne University Hospital
                Funded by: Sweden, TrygFonden, Denmark, and the European Clinical Research Infrastructures Network
                Categories
                Research
                Custom metadata
                © The Author(s) 2016

                Emergency medicine & Trauma
                temperature,hypothermia,induced,out-of-hospital cardiac arrest,fever,critical care,shivering,brain injuries

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