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Should age be a factor for initiating post-cardiac arrest care or for temperature management strategies?
Resuscitation 91 (2015) A1–A2
Contents lists available at ScienceDirect
Resuscitation journal homepage: www.elsevier.com/locate/resuscitation
Editorial
Should age be a factor for initiating post-cardiac arrest care or for temperature management strategies?
In this issue of Resuscitation, Winther-Jensen et al., reports an additional analysis from the TTM trial by Nielsen et al.1,2 The current study is one in a series of recently published secondary and subgroup analyses from the TTM trial3–8 and Winther-Jensen et al. explores two relevant questions within the TTM dataset namely: (1) whether age is associated with outcomes after cardiac arrest and (2) whether the effect of targeted temperature management at 33 ◦ C vs. 36 ◦ C differs by age. The results of the first question follows a long line of research, in out-of-hospital cardiac arrest and elsewhere, showing that increased age is associated with decreased favorable outcome9,10 although some recent studies, focused on patients with initial return of spontaneous circulation, have questioned the robustness of this association.11,12 In the current study of post-cardiac arrest patients undergoing targeted temperature management the authors found that age was associated with the primary outcome of mortality (hazard ratio: 1.04 [95% CI: 1.03–1.06] per year) as well as poor neurological/functional outcome after adjustment for potential confounders. The strength of the current analysis is that a rigorous protocol was used in the TTM trial mandating the use of targeted temperature management and delayed prognostication thereby limiting potential treatment discrepancies between age groups. However, the authors did find a much lower utilization of acute coronary angiography in the elderly patients; this finding remained statistically significant after multivariable analysis. Whether these differences in treatment represents appropriate titration of care or under utilization remains unknown and cannot be answered by the current study. Notably, the cause of death was significantly different between groups. For example, 34% of those with an age >80 years died due to a cardiovascular cause as compared to only 18% of those with an age ≤65 years. The association between age and outcomes after cardiac arrest is complex and likely represents an interaction between physiological factors as well as factors related to post-cardiac arrest treatment and the decision to limit or withdraw care in the elderly population.11,12 Unfortunately, any observational study related to the association between age and outcome will be limited by clinical decision-making implicitly or explicitly influenced by age. Therefore, the most important message from the current, and previous studies, may be that age alone should not be used as a reason to withdraw care since meaningful recovery is possible even in those http://dx.doi.org/10.1016/j.resuscitation.2015.03.013 0300-9572/© 2015 Elsevier Ireland Ltd. All rights reserved.
>80 years old.1 Whether care is futile above a certain age in some subgroups of post-cardiac arrest patients remains to be answered and will require a larger sample size. In their second main analysis the authors found no interaction between age and targeted temperature management with a target of 33 ◦ C or 36 ◦ C.1 These findings are in accordance with the findings reported in the original trial where no interaction between age (dichotomized at 65 years) and temperature group was noticed.2 This is the only study to examine differential effects of temperature based on age in a post-cardiac arrest population. The current study suggests that age-based differences in physiology are not clinically significant when comparing targeted temperature management at 33 ◦ C and 36 ◦ C. While these findings do not favor one temperature over another, the results do illustrate that age should likely not be taken into account when making this decision. Future studies with larger sample sizes and differing temperature ranges may help continue to define whether there are age-based differences in the response to targeted temperature management. The results in the current study follow others recently published by the TTM group who found no difference in outcomes between those treated with 33 ◦ C or 36 ◦ C in patients with shock on admission5 or in those with an initial nonshockable rhythm.8 In conclusion, the current paper illustrates that targeted temperature management (or any post-cardiac arrest treatment) should not be withheld based on age alone. Moreover, differential targeted temperature management does not seem to be influenced by age, at least for the temperatures examined in this paper. Age should not be an excluding factor in future post-cardiac arrest trials or for current clinical care protocols. Conflict of interest statement The authors declare that they have no conflicts of interest. References 1. Winther-Jensen M, Pellis T, Kuiper M, et al. Mortality and neurological outcome in the elderly after target temperature management for out-of-hospital cardiac arrest. Resuscitation 2015;91:92–8. 2. Nielsen N, Wetterslev J, Cronberg T, et al. Targeted temperature management at 33 ◦ C versus 36 ◦ C after cardiac arrest. N Engl J Med 2013;369:2197–206. 3. Bro-Jeppesen J, Hassager C, Wanscher M, et al. Targeted temperature management at 33 ◦ C versus 36 ◦ C and impact on systemic vascular resistance and myocardial function after out-of-hospital cardiac arrest: a sub-study of the Target Temperature Management Trial. Circ Cardiovasc Interv 2014;7:663–72.
A2
Editorial / Resuscitation 91 (2015) A1–A2
4. Bro-Jeppesen J, Kjaergaard J, Wanscher M, et al. The inflammatory response after out-of-hospital cardiac arrest is not modified by targeted temperature management at 33 ◦ C or 36 ◦ C. Resuscitation 2014;85:1480–7. 5. 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 2014;40: 1210–9. 6. Bro-Jeppesen J, Annborn M, Hassager C, et al. Hemodynamics and vasopressor support during targeted temperature management at 33 ◦ C versus 36 ◦ C after out-of-hospital cardiac arrest: a post hoc study of the target temperature management trial*. Crit Care Med 2015;43:318–27. 7. Lilja G, Nielsen N, Friberg H, et al. Cognitive function in survivors of out-ofhospital cardiac arrest after target temperature management at 33 masculineC versus 36 masculineC. Circulation 2015. 8. Frydland M, Kjaergaard J, Erlinge D, et al. Target temperature management of 33 ◦ C and 36 ◦ C in patients with out-of-hospital cardiac arrest with initial nonshockable rhythm – a TTM sub-study. Resuscitation 2015. 9. Deasy C, Bray JE, Smith K, et al. Out-of-hospital cardiac arrests in the older age groups in Melbourne, Australia. Resuscitation 2011;82:398–403. 10. Herlitz J, Svensson L, Engdahl J, et al. Characteristics of cardiac arrest and resuscitation by age group: an analysis from the Swedish Cardiac Arrest Registry. Am J Emerg Med 2007;25:1025–31. 11. Grimaldi D, Dumas F, Perier MC, et al. Short- and long-term outcome in elderly patients after out-of-hospital cardiac arrest: a cohort study. Crit Care Med 2014;42:2350–7. 12. Seder DB, Patel N, McPherson J, et al. Geriatric experience following cardiac arrest at six interventional cardiology centers in the United States 2006–2011:
interplay of age, do-not-resuscitate order, and outcomes. Crit Care Med 2014;42:289–95.
Lars W. Andersen a,b,∗ Department of Emergency Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA b Department of Anesthesiology, Aarhus University Hospital, Aarhus, Denmark a
Michael W. Donnino a,b Department of Emergency Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA b Department of Medicine, Division of Pulmonary and Critical Care, Beth Israel Deaconess Medical Center, MA, USA a
∗ Corresponding
author at: One Deaconess Road, West Clinical Center 2, Boston, MA 02215, USA. E-mail address: [email protected] (L.W. Andersen) 13 March 2015
Contents lists available at ScienceDirect
Resuscitation journal homepage: www.elsevier.com/locate/resuscitation
Editorial
Should age be a factor for initiating post-cardiac arrest care or for temperature management strategies?
In this issue of Resuscitation, Winther-Jensen et al., reports an additional analysis from the TTM trial by Nielsen et al.1,2 The current study is one in a series of recently published secondary and subgroup analyses from the TTM trial3–8 and Winther-Jensen et al. explores two relevant questions within the TTM dataset namely: (1) whether age is associated with outcomes after cardiac arrest and (2) whether the effect of targeted temperature management at 33 ◦ C vs. 36 ◦ C differs by age. The results of the first question follows a long line of research, in out-of-hospital cardiac arrest and elsewhere, showing that increased age is associated with decreased favorable outcome9,10 although some recent studies, focused on patients with initial return of spontaneous circulation, have questioned the robustness of this association.11,12 In the current study of post-cardiac arrest patients undergoing targeted temperature management the authors found that age was associated with the primary outcome of mortality (hazard ratio: 1.04 [95% CI: 1.03–1.06] per year) as well as poor neurological/functional outcome after adjustment for potential confounders. The strength of the current analysis is that a rigorous protocol was used in the TTM trial mandating the use of targeted temperature management and delayed prognostication thereby limiting potential treatment discrepancies between age groups. However, the authors did find a much lower utilization of acute coronary angiography in the elderly patients; this finding remained statistically significant after multivariable analysis. Whether these differences in treatment represents appropriate titration of care or under utilization remains unknown and cannot be answered by the current study. Notably, the cause of death was significantly different between groups. For example, 34% of those with an age >80 years died due to a cardiovascular cause as compared to only 18% of those with an age ≤65 years. The association between age and outcomes after cardiac arrest is complex and likely represents an interaction between physiological factors as well as factors related to post-cardiac arrest treatment and the decision to limit or withdraw care in the elderly population.11,12 Unfortunately, any observational study related to the association between age and outcome will be limited by clinical decision-making implicitly or explicitly influenced by age. Therefore, the most important message from the current, and previous studies, may be that age alone should not be used as a reason to withdraw care since meaningful recovery is possible even in those http://dx.doi.org/10.1016/j.resuscitation.2015.03.013 0300-9572/© 2015 Elsevier Ireland Ltd. All rights reserved.
>80 years old.1 Whether care is futile above a certain age in some subgroups of post-cardiac arrest patients remains to be answered and will require a larger sample size. In their second main analysis the authors found no interaction between age and targeted temperature management with a target of 33 ◦ C or 36 ◦ C.1 These findings are in accordance with the findings reported in the original trial where no interaction between age (dichotomized at 65 years) and temperature group was noticed.2 This is the only study to examine differential effects of temperature based on age in a post-cardiac arrest population. The current study suggests that age-based differences in physiology are not clinically significant when comparing targeted temperature management at 33 ◦ C and 36 ◦ C. While these findings do not favor one temperature over another, the results do illustrate that age should likely not be taken into account when making this decision. Future studies with larger sample sizes and differing temperature ranges may help continue to define whether there are age-based differences in the response to targeted temperature management. The results in the current study follow others recently published by the TTM group who found no difference in outcomes between those treated with 33 ◦ C or 36 ◦ C in patients with shock on admission5 or in those with an initial nonshockable rhythm.8 In conclusion, the current paper illustrates that targeted temperature management (or any post-cardiac arrest treatment) should not be withheld based on age alone. Moreover, differential targeted temperature management does not seem to be influenced by age, at least for the temperatures examined in this paper. Age should not be an excluding factor in future post-cardiac arrest trials or for current clinical care protocols. Conflict of interest statement The authors declare that they have no conflicts of interest. References 1. Winther-Jensen M, Pellis T, Kuiper M, et al. Mortality and neurological outcome in the elderly after target temperature management for out-of-hospital cardiac arrest. Resuscitation 2015;91:92–8. 2. Nielsen N, Wetterslev J, Cronberg T, et al. Targeted temperature management at 33 ◦ C versus 36 ◦ C after cardiac arrest. N Engl J Med 2013;369:2197–206. 3. Bro-Jeppesen J, Hassager C, Wanscher M, et al. Targeted temperature management at 33 ◦ C versus 36 ◦ C and impact on systemic vascular resistance and myocardial function after out-of-hospital cardiac arrest: a sub-study of the Target Temperature Management Trial. Circ Cardiovasc Interv 2014;7:663–72.
A2
Editorial / Resuscitation 91 (2015) A1–A2
4. Bro-Jeppesen J, Kjaergaard J, Wanscher M, et al. The inflammatory response after out-of-hospital cardiac arrest is not modified by targeted temperature management at 33 ◦ C or 36 ◦ C. Resuscitation 2014;85:1480–7. 5. 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 2014;40: 1210–9. 6. Bro-Jeppesen J, Annborn M, Hassager C, et al. Hemodynamics and vasopressor support during targeted temperature management at 33 ◦ C versus 36 ◦ C after out-of-hospital cardiac arrest: a post hoc study of the target temperature management trial*. Crit Care Med 2015;43:318–27. 7. Lilja G, Nielsen N, Friberg H, et al. Cognitive function in survivors of out-ofhospital cardiac arrest after target temperature management at 33 masculineC versus 36 masculineC. Circulation 2015. 8. Frydland M, Kjaergaard J, Erlinge D, et al. Target temperature management of 33 ◦ C and 36 ◦ C in patients with out-of-hospital cardiac arrest with initial nonshockable rhythm – a TTM sub-study. Resuscitation 2015. 9. Deasy C, Bray JE, Smith K, et al. Out-of-hospital cardiac arrests in the older age groups in Melbourne, Australia. Resuscitation 2011;82:398–403. 10. Herlitz J, Svensson L, Engdahl J, et al. Characteristics of cardiac arrest and resuscitation by age group: an analysis from the Swedish Cardiac Arrest Registry. Am J Emerg Med 2007;25:1025–31. 11. Grimaldi D, Dumas F, Perier MC, et al. Short- and long-term outcome in elderly patients after out-of-hospital cardiac arrest: a cohort study. Crit Care Med 2014;42:2350–7. 12. Seder DB, Patel N, McPherson J, et al. Geriatric experience following cardiac arrest at six interventional cardiology centers in the United States 2006–2011:
interplay of age, do-not-resuscitate order, and outcomes. Crit Care Med 2014;42:289–95.
Lars W. Andersen a,b,∗ Department of Emergency Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA b Department of Anesthesiology, Aarhus University Hospital, Aarhus, Denmark a
Michael W. Donnino a,b Department of Emergency Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA b Department of Medicine, Division of Pulmonary and Critical Care, Beth Israel Deaconess Medical Center, MA, USA a
∗ Corresponding
author at: One Deaconess Road, West Clinical Center 2, Boston, MA 02215, USA. E-mail address: [email protected] (L.W. Andersen) 13 March 2015