Abstract
Purpose
We hypothesized that a targeted temperature of 33 °C as compared to that of 36 °C would increase survival and reduce the severity of circulatory shock in patients with shock on admission after out-of-hospital cardiac arrest (OHCA).
Methods
The recently published Target Temperature Management trial (TTM-trial) randomized 939 OHCA patients with no difference in outcome between groups and no difference in mortality at the end of the trial in a predefined subgroup of patients with shock at admission. Shock was defined as a systolic blood pressure of <90 mm Hg for >30 min or the need of supportive measures to maintain a blood pressure ≥90 mmHg and/or clinical signs of end-organ hypoperfusion. In this post hoc analysis reported here, we further analyzed the 139 patients with shock at admission; all had been randomized to receive intervention at 33 °C (TTM33; n = 71) or 36 °C (TTM36; n = 68). Primary outcome was 180-day mortality. Secondary outcomes were intensive care unit (ICU) and 30-day mortality, severity of circulatory shock assessed by mean arterial pressure, serum lactate, fluid balance and the extended Sequential Organ Failure assessment (SOFA) score.
Results
There was no significance difference between targeted temperature management at 33 °C or 36 °C on 180-day mortality [log-rank test, p = 0.17, hazard ratio 1.33, 95 % confidence interval (CI) 0.88–1.98] or ICU mortality (61 vs. 44 %, p = 0.06; relative risk 1.37, 95 % CI 0.99–1.91). Serum lactate and the extended cardiovascular SOFA score were higher in the TTM33 group (p < 0.01).
Conclusions
We found no benefit in survival or severity of circulatory shock with targeted temperature management at 33 °C as compared to 36 °C in patients with shock on admission after OHCA.
References
Dragancea I, Rundgren M, Englund E, Friberg H, Cronberg T (2013) The influence of induced hypothermia and delayed prognostication on the mode of death after cardiac arrest. Resuscitation 84:337–342
Laurent I, Monchi M, Chiche JD, Joly LM, Spaulding C, Bourgeois B, Cariou A, Rozenberg A, Carli P, Weber S, Dhainaut JF (2002) Reversible myocardial dysfunction in survivors of out-of-hospital cardiac arrest. J Am Coll Cardiol 40:2110–2116
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, Investigators TTMT (2013) Targeted temperature management at 33 °C vs 36 °C after cardiac arrest. N Engl J Med 369:2197–2206
Trzeciak S, Jones AE, Kilgannon JH, Milcarek B, Hunter K, Shapiro NI, Hollenberg SM, Dellinger P, Parrillo JE (2009) Significance of arterial hypotension after resuscitation from cardiac arrest. Critical Care Med 37:2895–2903 quiz 2904
Lemiale V, Dumas F, Mongardon N, Giovanetti O, Charpentier J, Chiche JD, Carli P, Mira JP, Nolan J, Cariou A (2013) Intensive care unit mortality after cardiac arrest: the relative contribution of shock and brain injury in a large cohort. Intensive Care Med 39:1972–1980
Nolan JP, Neumar RW, Adrie C, Aibiki M, Berg RA, Bottiger BW, Callaway C, Clark RS, Geocadin RG, Jauch EC, Kern KB, Laurent I, Longstreth WT, Merchant RM, Morley P, Morrison LJ, Nadkarni V, Peberdy MA, Rivers EP, Rodriguez-Nunez A, Sellke FW, Spaulding C, Sunde K, Hoek TV (2008) Post-cardiac arrest syndrome: epidemiology, pathophysiology, treatment, and prognostication. A scientific statement from the International Liaison Committee on Resuscitation; the American Heart Association Emergency Cardiovascular Care Committee; the Council on Cardiovascular Surgery and Anesthesia; the Council on Cardiopulmonary, Perioperative, and Critical Care; the Council on Clinical Cardiology; the Council on Stroke. Resuscitation 79:350–379
Hochman JS, Sleeper LA, Webb JG, Sanborn TA, White HD, Talley JD, Buller CE, Jacobs AK, Slater JN, Col J, McKinlay SM, LeJemtel TH (1999) 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 341:625–634
Bougouin W, Lamhaut L, Marijon E, Jost D, Dumas F, Deye N, Beganton F, Empana JP, Chazelle E, Cariou A, Jouven X (2014) Characteristics and prognosis of sudden cardiac death in Greater Paris : population-based approach from the Paris Sudden Death Expertise Center (Paris-SDEC). Intensive Care Med. doi:10.1007/s00134-014-3252-5
Radsel P, Knafelj R, Kocjancic S, Noc M (2011) Angiographic characteristics of coronary disease and postresuscitation electrocardiograms in patients with aborted cardiac arrest outside a hospital. Am J Cardiol 108:634–638
Deakin CD, Nolan JP, Soar J, Sunde K, Koster RW, Smith GB, Perkins GD (2010) European resuscitation council guidelines for resuscitation 2010 section 4. Adult advanced life support. Resuscitation 81:1305–1352
Bernard SA, Gray TW, Buist MD, Jones BM, Silvester W, Gutteridge G, Smith K (2002) Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. N Engl J Med 346:557–563
Hypothermia after Cardiac Arrest Study G (2002) Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med 346:549–556
Moriyama Y, Iguro Y, Shimokawa S, Saigenji H, Toyohira H, Taira A (1996) Successful application of hypothermia combined with intra-aortic balloon pump support to low-cardiac-output state after open heart surgery. Angiology 47:595–599
Schmidt-Schweda S, Ohler A, Post H, Pieske B (2013) Moderate hypothermia for severe cardiogenic shock (COOL Shock Study I and II). Resuscitation 84:319–325
Skulec R, Kovarnik T, Dostalova G, Kolar J, Linhart A (2008) Induction of mild hypothermia in cardiac arrest survivors presenting with cardiogenic shock syndrome. Acta Anaesthesiol Scand 52:188–194
Yahagi N, Kumon K, Watanabe Y, Tanigami H, Haruna M, Hayashi H, Imanaka H, Takeuchi M, Ohashi Y, Takamoto S (1998) Value of mild hypothermia in patients who have severe circulatory insufficiency even after intra-aortic balloon pump. J Clin Anesth 10:120–125
Zobel C, Adler C, Kranz A, Seck C, Pfister R, Hellmich M, Kochanek M, Reuter H (2012) Mild therapeutic hypothermia in cardiogenic shock syndrome. Crit Care Med 40:1715–1723
Gotberg M, van der Pals J, Olivecrona GK, Gotberg M, Koul S, Erlinge D (2010) Mild hypothermia reduces acute mortality and improves hemodynamic outcome in a cardiogenic shock pig model. Resuscitation 81:1190–1196
Langhelle A, Nolan J, Herlitz J, Castren M, Wenzel V, Soreide E, Engdahl J, Steen PA, Utstein Consensus S (2005) Recommended guidelines for reviewing, reporting, and conducting research on post-resuscitation care: the Utstein style. Resuscitation 66:271–283
Williams JR (2008) The Declaration of Helsinki and public health. Bull World Health Organ 86:650–652
Vincent JL, de Mendonca A, Cantraine F, Moreno R, Takala J, Suter PM, Sprung CL, Colardyn F, Blecher S (1998) Use of the SOFA score to assess the incidence of organ dysfunction/failure in intensive care units: results of a multicenter, prospective study. Working group on “sepsis-related problems” of the European Society of Intensive Care Medicine. Crit Care Med 26:1793–1800
Hovdenes J, Laake JH, Aaberge L, Haugaa H, Bugge JF (2007) Therapeutic hypothermia after out-of-hospital cardiac arrest: experiences with patients treated with percutaneous coronary intervention and cardiogenic shock. Acta Anaesthesiol Scand 51:137–142
Oddo M, Schaller MD, Feihl F, Ribordy V, Liaudet L (2006) From evidence to clinical practice: effective implementation of therapeutic hypothermia to improve patient outcome after cardiac arrest. Crit Care Med 34:1865–1873
Weisser J, Martin J, Bisping E, Maier LS, Beyersdorf F, Hasenfuss G, Pieske B (2001) Influence of mild hypothermia on myocardial contractility and circulatory function. Basic Res Cardiol 96:198–205
Jacobshagen C, Pelster T, Pax A, Horn W, Schmidt-Schweda S, Unsold BW, Seidler T, Wagner S, Hasenfuss G, Maier LS (2010) Effects of mild hypothermia on hemodynamics in cardiac arrest survivors and isolated failing human myocardium. Clin Res Cardiol 99:267–276
Erlinge D, Gotberg M, Grines C, Dixon S, Baran K, Kandzari D, Olivecrona GK (2013) A pooled analysis of the effect of endovascular cooling on infarct size in patients with ST-elevation myocardial infarction. EuroIntervention 8:1435–1440
Huet O, Dupic L, Batteux F, Matar C, Conti M, Chereau C, Lemiale V, Harrois A, Mira JP, Vicaut E, Cariou A, Duranteau J (2011) Postresuscitation syndrome: potential role of hydroxyl radical-induced endothelial cell damage. Crit Care Med 39:1712–1720
Buijs EA, Verboom EM, Top AP, Andrinopoulou ER, Buysse CM, Ince C, Tibboel D (2014) Early microcirculatory impairment during therapeutic hypothermia is associated with poor outcome in post-cardiac arrest children: a prospective observational cohort study. Resuscitation 85:397–404
Nielsen N, Hovdenes J, Nilsson F, Rubertsson S, Stammet P, Sunde K, Valsson F, Wanscher M, Friberg H, Hypothermia N (2009) Outcome, timing and adverse events in therapeutic hypothermia after out-of-hospital cardiac arrest. Acta Anaesthesiol Scand 53:926–934
Schwarzl M, Steendijk P, Huber S, Truschnig-Wilders M, Obermayer-Pietsch B, Maechler H, Pieske B, Post H (2011) The induction of mild hypothermia improves systolic function of the resuscitated porcine heart at no further sympathetic activation. Acta Physiol (Oxf) 203:409–418
Mackowiak PA, Wasserman SS, Levine MM (1992) A critical appraisal of 98.6 °F, the upper limit of the normal body temperature, and other legacies of Carl Reinhold August Wunderlich. JAMA 268:1578–1580
Schortgen F, Clabault K, Katsahian S, Devaquet J, Mercat A, Deye N, Dellamonica J, Bouadma L, Cook F, Beji O, Brun-Buisson C, Lemaire F, Brochard L (2012) Fever control using external cooling in septic shock: a randomized controlled trial. Am J Respir Crit Care Med 185:1088–1095
Lewis ME, Al-Khalidi AH, Townend JN, Coote J, Bonser RS (2002) The effects of hypothermia on human left ventricular contractile function during cardiac surgery. J Am Coll Cardiol 39:102–108
Post H, Schmitto JD, Steendijk P, Christoph J, Holland R, Wachter R, Schondube FW, Pieske B (2010) Cardiac function during mild hypothermia in pigs: increased inotropy at the expense of diastolic dysfunction. Acta Physiol (Oxf) 199:43–52
Bro-Jeppesen J, Kjaergaard J, Soholm H, Wanscher M, Lippert FK, Moller JE, Kober L, Hassager C (2014) Hemodynamics and vasopressor support in therapeutic hypothermia after cardiac arrest: Prognostic implications. Resuscitation 85(5):664–670
Bjelland TW, Klepstad P, Haugen BO, Nilsen T, Dale O (2013) Effects of hypothermia on the disposition of morphine, midazolam, fentanyl, and propofol in intensive care unit patients. Drug Metab Dispos 41:214–223
James JH, Luchette FA, McCarter FD, Fischer JE (1999) Lactate is an unreliable indicator of tissue hypoxia in injury or sepsis. Lancet 354:505–508
Kern KB, Hilwig RW, Berg RA, Rhee KH, Sanders AB, Otto CW, Ewy GA (1997) Postresuscitation left ventricular systolic and diastolic dysfunction. Treatment with dobutamine. Circulation 95:2610–2613
Acknowledgments
Support was provided by independent research grants from the Swedish Heart–Lung Foundation, Arbetsmarknadens Försäkringsaktiebolag Insurance foundation, Swedish Research Council, Region Skåne (Sweden), National Health Service (Sweden), Thelma Zoegas Foundation, Krapperup Foundation, Thure Carlsson Foundation, Hans-Gabriel and Alice Trolle-Wachtmeister Foundation for Medical Research, Skåne University Hospital, TrygFonden (Denmark), European Clinical Research Infrastructures Network and European Union Interreg programme IV A.
Conflicts of interest
Hans Friberg and Tommaso Pellis have received lecture fees from Bard Medical. Matt P. Wise has consulted for Bard and Merck (Advisory Boards), is employed by NISCHR AHSC (research fellowship 0.4 WTE) and has received royalties from Wiley Publishing (book chapters), a fee for lecturing at an educational meeting from Fisher & Paykel, financial support for travel from ISICEM, Eli Lilly, British Thoracic Society and the Intensive Care Society, a loan of EIT equipment for research from Care Fusion and a gift of oral care products for research from Sage Products.
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Annborn, M., Bro-Jeppesen, J., Nielsen, N. et al. The association of targeted temperature management at 33 and 36 °C with outcome in patients with moderate shock on admission after out-of-hospital cardiac arrest: a post hoc analysis of the Target Temperature Management trial. Intensive Care Med 40, 1210–1219 (2014). https://doi.org/10.1007/s00134-014-3375-8
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DOI: https://doi.org/10.1007/s00134-014-3375-8