Online first
Original Article
Published online: 2022-10-04

open access

Page views 1463
Article views/downloads 656
Get Citation

Connect on Social Media

Connect on Social Media

Should targeted temperature management be used in cardiogenic shock patients? Systematic review and meta-analysis

Adam Nieborek1, Jerzy R. Ladny2, Milosz J. Jaguszewski3, Andrea Denegri4, Aleksandra Sikora5, Szymon Pucylo5, Aleksandra Gasecka5, Michal Pruc1, Ivan Savytsky6, Lukasz Szarpak789


Background: Therapeutic hypothermia, or targeted temperature management (TTM), is a strategy of reducing the core body temperature of survivors of sudden cardiac arrest, cardiogenic shock (CS) or stroke. Therefore, a systematic literature review and meta-analysis were performed to tackle the question about whether the implementation of TTM is actually beneficial for patients with CS. Methods: Study was designed as a systematic review and meta-analysis. PubMed, Cochrane Library, Web of Science and Scopus were searched from these databases inception to July 17, 2022. Eligible studies were those comparing TTM and non-TTM treatment in CS patients. Data were pooled with the Mantel-Haenszel method. Results. Thirty-day mortality was reported in 3 studies. Polled analysis of 30-day mortality was 44.2% for TTM group and 48.9% for non-TTM group (risk ratio: 0.90; 95% confidence interval: 0.75 to 1.08; p = 0.27). Other mortality follow-up periods showed also no statistically significant differences (p > 0.05). The occurrence of adverse events in the studied groups also did not show statistically significant differences between TTM and non-TTM groups (p > 0.05 for myocardial infarction, stent thrombosis, sepsis, pneumonia, stroke or bleeding events). Conclusions: The present analysis shows no significant benefit of TTM in patients with CS. Moreover, no statistically significant increase of the incidence of adverse effects was found. However, further randomized studies with higher sample size and greater validity are needed to determine if TTM is worth implementing in CS patients.

Article available in PDF format

View PDF Download PDF file


  1. Vahdatpour C, Collins D, Goldberg S. Cardiogenic shock. J Am Heart Assoc. 2019; 8(8): e011991.
  2. Adrie C, Laurent I, Monchi M, et al. Postresuscitation disease after cardiac arrest: a sepsis-like syndrome? Curr Opin Crit Care. 2004; 10(3): 208–212.
  3. Brener MI, Rosenblum HR, Burkhoff D. Pathophysiology and advanced hemodynamic assessment of cardiogenic shock. Methodist Debakey Cardiovasc J. 2020; 16(1): 7–15.
  4. Thiele H, Ohman EM, de Waha-Thiele S, et al. Management of cardiogenic shock complicating myocardial infarction: an update 2019. Eur Heart J. 2019; 40(32): 2671–2683.
  5. Hochman JS, Sleeper LA, Webb JG, et al. Early revascularization in acute myocardial infarction complicated by cardiogenic shock. SHOCK Investigators. Should We Emergently Revascularize Occluded Coronaries for Cardiogenic Shock. N Engl J Med. 1999; 341(9): 625–634.
  6. Jones Q, Johnston B, Biola H, et al. Implementing standardized substance use disorder screening in primary care. JAAPA. 2018; 31(10): 42–45.
  7. Stegman BM, Newby LK, Hochman JS, et al. Post-myocardial infarction cardiogenic shock is a systemic illness in need of systemic treatment: is therapeutic hypothermia one possibility? J Am Coll Cardiol. 2012; 59: 644–647.
  8. Szarpak L, Filipiak KJ, Mosteller L, et al. Survival, neurological and safety outcomes after out of hospital cardiac arrests treated by using prehospital therapeutic hypothermia: A systematic review and meta-analysis. Am J Emerg Med. 2021; 42: 168–177.
  9. Deye N, Cariou A, Girardie P, et al. Endovascular versus external targeted temperature management for patients with out-of-hospital cardiac arrest: a randomized, controlled study. Circulation. 2015; 132(3): 182–193.
  10. Wieczorek W, Meyer-Szary J, Jaguszewski MJ, et al. Efficacy of targeted temperature management after pediatric cardiac arrest: a meta-analysis of 2002 patients. J Clin Med. 2021; 10(7).
  11. Szarpak L, Smereka J, Ruetzler K. Targeted temperature management: state of the art. Disaster Emerg Med J. 2019; 4(2): 68–73.
  12. Lascarrou JB, Merdji H, Le Gouge A, et al. Targeted temperature management for cardiac arrest with nonshockable rhythm. N Engl J Med. 2019; 381(24): 2327–2337.
  13. Nolan J, Sandroni C, Böttiger B, et al. European Resuscitation Council and European Society of Intensive Care Medicine Guidelines 2021: post-resuscitation care. Resuscitation. 2021; 161: 220–269.
  14. Scholefield BR, Silverstein FS, Telford R, et al. Therapeutic hypothermia after paediatric cardiac arrest: Pooled randomized controlled trials. Resuscitation. 2018; 133: 101–107.
  15. Vargas M, Servillo G, Sutherasan Y, et al. Effects of in-hospital low targeted temperature after out of hospital cardiac arrest: a systematic review with meta-analysis of randomized clinical trials. Resuscitation. 2015; 91: 8–18.
  16. Bro-Jeppesen J, Jeppesen AN, Haugaard S, et al. TTM Investigators. Targeted temperature management at 33°C versus 36°C after cardiac arrest. N Engl J Med. 2013; 369(23): 2197–2206.
  17. Götberg M, van der Pals J, Olivecrona GK, et al. Mild hypothermia reduces acute mortality and improves hemodynamic outcome in a cardiogenic shock pig model. Resuscitation. 2010; 81(9): 1190–1196.
  18. Schwarzl M, Huber S, Maechler H, et al. Left ventricular diastolic dysfunction during acute myocardial infarction: effect of mild hypothermia. Resuscitation. 2012; 83(12): 1503–1510.
  19. Fuernau G, Beck J, Desch S, et al. Mild hypothermia in cardiogenic shock complicating myocardial infarction. Circulation. 2019; 139(4): 448–457.
  20. Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021; 372: n71.
  21. Sterne JAC, Savović J, Page MJ, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ. 2019; 366: l4898.
  22. Sterne JA, Hernán MA, Reeves BC, et al. ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. BMJ. 2016; 355: i4919.
  23. McGuinness LA, Higgins JPT. Risk-of-bias VISualization (robvis): An R package and Shiny web app for visualizing risk-of-bias assessments. Res Synth Methods. 2021; 12(1): 55–61.
  24. Hozo SP, Djulbegovic B, Hozo I. Estimating the mean and variance from the median, range, and the size of a sample. BMC Med Res Methodol. 2005; 5: 13.
  25. Higgins JPT, Thompson SG, Deeks JJ, et al. Measuring inconsistency in meta-analyses. BMJ. 2003; 327(7414): 557–560.
  26. Blatt A, Elbaz-Greener GA, Mizrachi A, et al. Adjunctive mild hypothermia therapy to primary percutaneous coronary intervention in patients with ST segment elevation myocardial infarction complicated with cardiogenic shock: A pilot feasibility study. Cardiol J. 2015; 22(3): 285–289.
  27. Orban M, Mayer K, Morath T, et al. The impact of therapeutic hypothermia on on-treatment platelet reactivity and clinical outcome in cardiogenic shock patients undergoing primary PCI for acute myocardial infarction: Results from the ISAR-SHOCK registry. Thromb Res. 2015; 136(1): 87–93.
  28. Zobel C, Adler C, Kranz A, et al. Mild therapeutic hypothermia in cardiogenic shock syndrome. Crit Care Med. 2012; 40(6): 1715–1723.
  29. Levy B, Girerd N, Amour J, et al. Effect of moderate hypothermia vs normothermia on 30-day mortality in patients with cardiogenic shock receiving venoarterial extracorporeal membrane oxygenation: a randomized clinical trial. JAMA. 2022; 327(5): 442–453.
  30. Oddo M, Schaller MD, Feihl F, et al. From evidence to clinical practice: effective implementation of therapeutic hypothermia to improve patient outcome after cardiac arrest. Crit Care Med. 2006; 34(7): 1865–1873.
  31. Noc M, Laanmets P, Neskovic AN, et al. A multicentre, prospective, randomised controlled trial to assess the safety and effectiveness of cooling as an adjunctive therapy to percutaneous intervention in patients with acute myocardial infarction: the COOL AMI EU Pivotal Trial. EuroIntervention. 2021; 17(6): 466–473.
  32. Erlinge D, Götberg M, Grines C, et al. A pooled analysis of the effect of endovascular cooling on infarct size in patients with ST-elevation myocardial infarction. EuroIntervention. 2013; 8(12): 1435–1440.
  33. Kohlhauer M, Berdeaux A, Ghaleh B, et al. Therapeutic hypothermia to protect the heart against acute myocardial infarction. Arch Cardiovasc Dis. 2016; 109(12): 716–722.
  34. Cho HJ, Kyong YY, Oh YM, et al. Therapeutic hypothermia complicated by spontaneous brain stem hemorrhage. Am J Emerg Med. 2013; 31(1): 266.e1–266.e3.
  35. Wang CH, Chen NC, Tsai MS, et al. Therapeutic hypothermia and the risk of hemorrhage: a systematic review and meta-analysis of randomized controlled trials. Medicine (Baltimore). 2015; 94(47): e2152.
  36. Rosillo SO, Lopez-de-Sa E, Iniesta AM, et al. Is therapeutic hypothermia a risk factor for stent thrombosis? J Am Coll Cardiol. 2014; 63(9): 939–940.
  37. Chisholm GE, Grejs A, Thim T, et al. Safety of therapeutic hypothermia combined with primary percutaneous coronary intervention after out-of-hospital cardiac arrest. Eur Heart J Acute Cardiovasc Care. 2015; 4(1): 60–63.
  38. Shah N, Chaudhary R, Mehta K, et al. Therapeutic hypothermia and stent thrombosis: a nationwide analysis. JACC Cardiovasc Interv. 2016; 9(17): 1801–1811.
  39. Jacob M, Hassager C, Bro-Jeppesen J, et al. The effect of targeted temperature management on coagulation parameters and bleeding events after out-of-hospital cardiac arrest of presumed cardiac cause. Resuscitation. 2015; 96: 260–267.
  40. Batista LM, Lima FO, Januzzi JL, et al. Feasibility and safety of combined percutaneous coronary intervention and therapeutic hypothermia following cardiac arrest. Resuscitation. 2010; 81(4): 398–403.
  41. Geurts M, Macleod MR, Kollmar R, et al. Therapeutic hypothermia and the risk of infection: a systematic review and meta-analysis. Crit Care Med. 2014; 42(2): 231–242.
  42. Mongardon N, Perbet S, Lemiale V, et al. Infectious complications in out-of-hospital cardiac arrest patients in the therapeutic hypothermia era. Crit Care Med. 2011; 39(6): 1359–1364.
  43. Bernard S. Hypothermia after cardiac arrest: expanding the therapeutic scope. Crit Care Med. 2009; 37(7 Suppl): S227–S233.
  44. Schmidt-Schweda S, Ohler A, Post H, et al. Moderate hypothermia for severe cardiogenic shock (COOL Shock Study I & II). Resuscitation. 2013; 84(3): 319–325.