PURPOSE: To compare the performance of targeted temperature management (TTM) at 33 °C using intravascular (IC) vs. surface-cooling (SFC) devices after out-of-hospital cardiac arrest (OHCA). METHODS: A post hoc analysis including OHCA patients randomized to hypothermia in the TTM2-trial (NCT02908308) comparing hypothermia with normothermia. The main outcome was cooling performance, defined as the proportion of patients reaching target temperature < 33.5 °C within 4 h, time outside temperature ranges during maintenance, rewarming rate and post-TTM fever. Exploratory outcomes included survival and good functional outcome, defined as modified Rankin Scale (mRS) scores of 0-3 at 6 months, analyzed using Inverse Probability Treatment Weighting (IPTW). RESULTS: Among 930 patients randomized to hypothermia, 876 were treated with a cooling device and included in this study. Of those, 27.3% received IC devices, while 72.7% received SFC devices. The proportion reaching target temperature within 4 h was higher with IC (IC: 69.6% vs. SFC: 49.2%; p < 0.001). Temperature outside ranges during the cooling period and post-TTM fever were lower with IC compared to SFC (17.2% vs. 39.6%; p < 0.001 and 0% vs. 6.3%; p < 0.001, respectively). In the exploratory IPTW analysis, 6-month survival rates were 55.2% in the IC group and 50.2% in the SFC group (OR 1.22, 95% CI 0.89-1.68) and survival with good functional outcome at 6 months was 51.1% patients in the IC group and 44.9% in the SFC (OR 1.28, 95% CI 0.93-1.77). CONCLUSIONS: Among OHCA patients randomized to hypothermia in the TTM2 study, intravascular cooling, compared with surface cooling, was associated with better cooling performance.

2nd Department of Medicine Department of Cardiovascular Medicine 1st Faculty of Medicine Charles University Prague and General University Hospital Prague Czech Republic

Anesthesiology and Intensive Care Department of Clinical Sciences Lund Lund University Lund Sweden

Anesthesiology and Intensive Care Department of Surgical Sciences Uppsala University Uppsala Sweden

Center for Resuscitation Sciences Department of Clinical Science and Education Södersjukhuset Karolinska Institutet Stockholm Sweden

Cochin University Hospital Paris France

Copenhagen Trial Unit Centre for Clinical Intervention Research Rigshospitalet Copenhagen University Hospital Copenhagen Denmark

Department of Clinical Medicine Aarhus University Aarhus Denmark

Department of Clinical Sciences Cardiology Lund University Skåne University Hospital Lund Sweden

Department of Clinical Sciences Lund Anesthesia and Intensive Care Lund University Helsingborg Hospital Lund Sweden

Department of Intensive Care Erasme Hospital Université Libre de Bruxelles Brussels Belgium

Department of Intensive Care Medicine Aarhus University Hospital Aarhus Denmark

Department of Neurology Skane University Hospital Lund Sweden

Department of Physiology and Pharcmacology Karolinska Institute Stockholm Sweden

Department of Regional Health Research Faculty of Health Sciences University of Southern Denmark Copenhagen Denmark

Essex Cardio Thoracic Centre Basildon Essex UK Thurrock University Hospitals Basildon UK

Faculty of Health Education Medicine and Social Care MTRC Anglia Ruskin University Chelmsford Essex UK

Function Perioperative Medicine and Intensive Care Karolinska University Hospital 17176 Stockholm Sweden

Institute of Heart Diseases Wroclaw Medical University Wroclaw Poland

Institute of Intensive Care Medicine University Hospital of Zurich Rämistrasse 100 8091 Zurich Switzerland

Neurology Department of Clinical Sciences Lund Lund University Lund Sweden

University Hospitals Bristol NHS Foundation Trust Bristol UK

See more in PubMed

Sandroni C, Nolan JP, Andersen LW, Böttiger BW, Cariou A, Cronberg T, Friberg H, Genbrugge C, Lilja G, Morley PT, Nikolaou N, Olasveengen TM, Skrifvars MB, Taccone FS, Soar J (2022) ERC-ESICM guidelines on temperature control after cardiac arrest in adults. Intensive Care Med 48:261–269 PubMed

Fernando SM, Di Santo P, Sadeghirad B, Lascarrou JB, Rochwerg B, Mathew R, Sekhon MS, Munshi L, Fan E, Brodie D, Rowan KM, Hough CL, McLeod SL, Vaillancourt C, Cheskes S, Ferguson ND, Scales DC, Sandroni C, Nolan JP, Hibbert B (2021) Targeted temperature management following out-of-hospital cardiac arrest: a systematic review and network meta-analysis of temperature targets. Intensive Care Med 47:1078–1088 PubMed

Nielsen N, Wetterslev J, Cronberg T, Erlinge D, Gasche Y, Hassager C, Horn J, Hovdenes J, Kjaergaard J, Kuiper M, Pellis T, Stammet P, Wanscher M, Wise MP, Aneman A, Al-Subaie N, Boesgaard S, Bro-Jeppesen J, Brunetti I, Bugge JF, Hingston CD, Juffermans NP, Koopmans M, Kober L, Langorgen J, Lilja G, Moller JE, Rundgren M, Rylander C, Smid O, Werer C, Winkel P, Friberg H (2013) Targeted temperature management at 33 degrees C versus 36 degrees C after cardiac arrest. N Engl J Med 369:2197–2206 PubMed

Dankiewicz J, Cronberg T, Lilja G, Jakobsen JC, Levin H, Ullén S, Rylander C, Wise MP, Oddo M, Cariou A, Bělohlávek J, Hovdenes J, Saxena M, Kirkegaard H, Young PJ, Pelosi P, Storm C, Taccone FS, Joannidis M, Callaway C, Eastwood GM, Morgan MPG, Nordberg P, Erlinge D, Nichol AD, Chew MS, Hollenberg J, Thomas M, Bewley J, Sweet K, Grejs AM, Christensen S, Haenggi M, Levis A, Lundin A, Düring J, Schmidbauer S, Keeble TR, Karamasis GV, Schrag C, Faessler E, Smid O, Otáhal M, Maggiorini M, Wendel Garcia PD, Jaubert P, Cole JM, Solar M, Borgquist O, Leithner C, Abed-Maillard S, Navarra L, Annborn M, Undén J, Brunetti I, Awad A, McGuigan P, Bjørkholt Olsen R, Cassina T, Vignon P, Langeland H, Lange T, Friberg H, Nielsen N (2021) Hypothermia versus normothermia after out-of-hospital cardiac arrest. N Engl J Med 384:2283–2294 PubMed

Lascarrou JB, Merdji H, Le Gouge A, Colin G, Grillet G, Girardie P, Coupez E, Dequin PF, Cariou A, Boulain T, Brule N, Frat JP, Asfar P, Pichon N, Landais M, Plantefeve G, Quenot JP, Chakarian JC, Sirodot M, Legriel S, Letheulle J, Thevenin D, Desachy A, Delahaye A, Botoc V, Vimeux S, Martino F, Giraudeau B, Reignier J (2019) Targeted temperature management for cardiac arrest with nonshockable rhythm. N Engl J Med 381(24):2327–2337 PubMed

Polderman KH, Herold I (2009) Therapeutic hypothermia and controlled normothermia in the intensive care unit: practical considerations, side effects, and cooling methods. Crit Care Med 37:1101–1120 PubMed

Seder DB, Van der Kloot TE (2009) Methods of cooling: practical aspects of therapeutic temperature management. Crit Care Med 37:S211-222 PubMed

Holzer M (2008) Devices for rapid induction of hypothermia. Eur J Anaesthesiol Suppl 42:31–38 PubMed

Taccone FS, Donadello K, Mayer SA (2022) Manipulating temperature: devices for targeted temperature management (TTM) in brain injury. Intensive Care Med 48:1409–1412 PubMed

Keller E, Imhof HG, Gasser S, Terzic A, Yonekawa Y (2003) Endovascular cooling with heat exchange catheters: a new method to induce and maintain hypothermia. Intensive Care Med 29:939–943 PubMed

Gillies MA, Pratt R, Whiteley C, Borg J, Beale RJ, Tibby SM (2010) Therapeutic hypothermia after cardiac arrest: a retrospective comparison of surface and endovascular cooling techniques. Resuscitation 81:1117–1122 PubMed

Hoedemaekers CW, Ezzahti M, Gerritsen A, van der Hoeven JG (2007) Comparison of cooling methods to induce and maintain normo- and hypothermia in intensive care unit patients: a prospective intervention study. Crit Care 11:R91 PubMed PMC

Calabró L, Bougouin W, Cariou A, De Fazio C, Skrifvars M, Soreide E, Creteur J, Kirkegaard H, Legriel S, Lascarrou JB, Megarbane B, Deye N, Taccone FS (2019) Effect of different methods of cooling for targeted temperature management on outcome after cardiac arrest: a systematic review and meta-analysis. Crit Care 23:285 PubMed PMC

Heard KJ, Peberdy MA, Sayre MR, Sanders A, Geocadin RG, Dixon SR, Larabee TM, Hiller K, Fiorello A, Paradis NA, O’Neil BJ (2010) A randomized controlled trial comparing the Arctic Sun to standard cooling for induction of hypothermia after cardiac arrest. Resuscitation 81:9–14 PubMed PMC

Mayer SA, Kowalski RG, Presciutti M, Ostapkovich ND, McGann E, Fitzsimmons BF, Yavagal DR, Du YE, Naidech AM, Janjua NA, Claassen J, Kreiter KT, Parra A, Commichau C (2004) Clinical trial of a novel surface cooling system for fever control in neurocritical care patients. Crit Care Med 32:2508–2515 PubMed

Tømte Ø, Drægni T, Mangschau A, Jacobsen D, Auestad B, Sunde K (2011) A comparison of intravascular and surface cooling techniques in comatose cardiac arrest survivors. Crit Care Med 39:443–449 PubMed

Deye N, Cariou A, Girardie P, Pichon N, Megarbane B, Midez P, Tonnelier JM, Boulain T, Outin H, Delahaye A, Cravoisy A, Mercat A, Blanc P, Santré C, Quintard H, Brivet F, Charpentier J, Garrigue D, Francois B, Quenot JP, Vincent F, Gueugniaud PY, Mira JP, Carli P, Vicaut E, Baud FJ (2015) Endovascular versus external targeted temperature management for patients with out-of-hospital cardiac arrest: a randomized, controlled study. Circulation 132:182–193 PubMed

Oh SH, Oh JS, Kim YM, Park KN, Choi SP, Kim GW, Jeung KW, Jang TC, Park YS, Kyong YY (2015) An observational study of surface versus endovascular cooling techniques in cardiac arrest patients: a propensity-matched analysis. Crit Care 19:85 PubMed PMC

Tommasi E, Lazzeri C, Bernardo P, Sori A, Chiostri M, Gensini GF, Valente S (2017) Cooling techniques in mild hypothermia after cardiac arrest. J Cardiovasc Med (Hagerstown) 18:459–466 PubMed

Ramadanov N, Arrich J, Klein R, Herkner H, Behringer W (2022) Intravascular versus surface cooling in patients resuscitated from cardiac arrest: a systematic review and network meta-analysis with focus on temperature feedback. Crit Care Med 50:999–1009 PubMed PMC

Jarrah S, Dziodzio J, Lord C, Fraser GL, Lucas L, Riker RR, Seder DB (2011) Surface cooling after cardiac arrest: effectiveness, skin safety, and adverse events in routine clinical practice. Neurocrit Care 14:382–388 PubMed

Glover GW, Thomas RM, Vamvakas G, Al-Subaie N, Cranshaw J, Walden A, Wise MP, Ostermann M, Thomas-Jones E, Cronberg T, Erlinge D, Gasche Y, Hassager C, Horn J, Kjaergaard J, Kuiper M, Pellis T, Stammet P, Wanscher M, Wetterslev J, Friberg H, Nielsen N (2016) Intravascular versus surface cooling for targeted temperature management after out-of-hospital cardiac arrest - an analysis of the TTM trial data. Crit Care 20:381 PubMed PMC

De Fazio C, Skrifvars MB, Søreide E, Creteur J, Grejs AM, Kjærgaard J, Laitio T, Nee J, Kirkegaard H, Taccone FS (2019) Intravascular versus surface cooling for targeted temperature management after out-of-hospital cardiac arrest: an analysis of the TTH48 trial. Crit Care 23:61 PubMed PMC

Pittl U, Schratter A, Desch S, Diosteanu R, Lehmann D, Demmin K, Hörig J, Schuler G, Klemm T, Mende M, Thiele H (2013) Invasive versus non-invasive cooling after in- and out-of-hospital cardiac arrest: a randomized trial. Clin Res Cardiol 102:607–614 PubMed

Look X, Li H, Ng M, Lim ETS, Pothiawala S, Tan KBK, Sewa DW, Shahidah N, Pek PP, Ong MEH (2018) Randomized controlled trial of internal and external targeted temperature management methods in post- cardiac arrest patients. Am J Emerg Med 36:66–72 PubMed

Matsumoto S, Kuno T, Mikami T, Takagi H, Ikeda T, Briasoulis A, Bortnick AE, Sims D, Katz JN, Jentzer J, Bangalore S, Alviar CL (2022) Effect of cooling methods and target temperature on outcomes in comatose patients resuscitated from cardiac arrest: Systematic review and network meta-analysis of randomized trials. Am Heart J 256:73–84 PubMed

Bartlett ES, Valenzuela T, Idris A, Deye N, Glover G, Gillies MA, Taccone FS, Sunde K, Flint AC, Thiele H, Arrich J, Hemphill C, Holzer M, Skrifvars MB, Pittl U, Polderman KH, Ong MEH, Kim KH, Oh SH, Do Shin S, Kirkegaard H, Nichol G (2020) Systematic review and meta-analysis of intravascular temperature management vs. surface cooling in comatose patients resuscitated from cardiac arrest. Resuscitation 146:82–95 PubMed

Dankiewicz J, Cronberg T, Lilja G, Jakobsen JC, Bělohlávek J, Callaway C, Cariou A, Eastwood G, Erlinge D, Hovdenes J, Joannidis M, Kirkegaard H, Kuiper M, Levin H, Morgan MPG, Nichol AD, Nordberg P, Oddo M, Pelosi P, Rylander C, Saxena M, Storm C, Taccone F, Ullén S, Wise MP, Young P, Friberg H, Nielsen N (2019) Targeted hypothermia versus targeted Normothermia after out-of-hospital cardiac arrest (TTM2): a randomized clinical trial-Rationale and design. Am Heart J 217:23–31 PubMed

Busch M, Soreide E, Lossius HM, Lexow K, Dickstein K (2006) Rapid implementation of therapeutic hypothermia in comatose out-of-hospital cardiac arrest survivors. Acta Anaesthesiol Scand 50:1277–1283 PubMed

Merchant RM, Abella BS, Peberdy MA, Soar J, Ong ME, Schmidt GA, Becker LB, Vanden Hoek TL (2006) Therapeutic hypothermia after cardiac arrest: unintentional overcooling is common using ice packs and conventional cooling blankets. Crit Care Med 34:S490-494 PubMed

Granfeldt A, Holmberg MJ, Nolan JP, Soar J, Andersen LW (2021) Targeted temperature management in adult cardiac arrest: systematic review and meta-analysis. Resuscitation 167:160–172 PubMed

Nolan JP, Sandroni C, Böttiger BW, Cariou A, Cronberg T, Friberg H, Genbrugge C, Haywood K, Lilja G, Moulaert VRM, Nikolaou N, Olasveengen TM, Skrifvars MB, Taccone F, Soar J (2021) European Resuscitation Council and European Society of Intensive Care Medicine guidelines 2021: post-resuscitation care. Intensive Care Med 47:369–421 PubMed PMC

Simpson RFG, Dankiewicz J, Karamasis GV, Pelosi P, Haenggi M, Young PJ, Jakobsen JC, Bannard-Smith J, Wendel-Garcia PD, Taccone FS, Nordberg P, Wise MP, Grejs AM, Lilja G, Olsen RB, Cariou A, Lascarrou JB, Saxena M, Hovdenes J, Thomas M, Friberg H, Davies JR, Nielsen N, Keeble TR (2022) Speed of cooling after cardiac arrest in relation to the intervention effect: a sub-study from the TTM2-trial. Crit Care 26:356 PubMed PMC

Nayeri A, Bhatia N, Holmes B, Borges N, Armstrong W, Xu M, Farber-Eger E, Wells QS, McPherson JA (2017) Temperature variability during targeted temperature management is not associated with neurological outcomes following cardiac arrest. Am J Emerg Med 35:889–892 PubMed

Nobile L, Lamanna I, Fontana V, Donadello K, Dell’anna AM, Creteur J, Vincent JL, Pappalardo F, Taccone FS (2015) Greater temperature variability is not associated with a worse neurological outcome after cardiac arrest. Resuscitation 96:268–274 PubMed

Sendelbach S, Hearst MO, Johnson PJ, Unger BT, Mooney MR (2012) Effects of variation in temperature management on cerebral performance category scores in patients who received therapeutic hypothermia post cardiac arrest. Resuscitation 83:829–834 PubMed