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• W4387364103 abstract "In this issue of Resuscitation, Vlachos and colleagues demonstrate that withdrawal of life-sustaining treatment (WLST) is common (22%) and often performed early among patients receiving intensive care after resuscitation from out of hospital cardiac arrest in hospitals throughout the United Kingdom.[1]Vlachos G, Rubenfeld G, Menon D, Harrison D, Rowan K, Maharaj R. Early and late withdrawal of life-sustaining treatment after out-of-hospital cardiac arrest in the United Kingdom: institutional variation and association with hospital mortality. Resuscitation. 2023;In PressGoogle Scholar Early WLST was defined as within 72 h of admission to intensive care. This analysis also demonstrated a significant and important variation in inter-hospital use of WLST which was correlated with inter-hospital differences in mortality. Such an observation is important, as the regional variation in outcomes after OHCA[2]Nichol G. Thomas E. Callaway C.W. et al.Regional variation in out-of-hospital cardiac arrest incidence and outcome.JAMA. 2008; 300: 1423-1431https://doi.org/10.1001/jama.300.12.1423Google Scholar are substantially greater than that of other acute cardiovascular conditions such as ST-elevation myocardial infarction.[3]Bradley E.H. Herrin J. Curry L. et al.Variation in hospital mortality rates for patients with acute myocardial infarction.Am J Cardiol. 2010; 106: 1108-1112https://doi.org/10.1016/j.amjcard.2010.06.014Google Scholar Understanding and reducing variation in care after OHCA is an important strategy to achieve improvements in public health. Contemporary evidence-based practice guidelines recommend active prevention of fever for 72 hours after restoration of spontaneous circulation.[4]Nolan J.P. Sandroni C. Andersen L.W. et al.ERC-ESICM guidelines on temperature control after cardiac arrest in adults.Resuscitation. 2022; 172: 229-236https://doi.org/10.1016/j.resuscitation.2022.01.009Google Scholar Application of induced hypothermia (also known as targeted temperature management) to reduce heart and brain injury as well as fever after resuscitation prolongs the metabolism of drugs used for sedation,5Riker R.R. Gagnon D.J. May T. Seder D.B. Fraser G.L. Analgesia, sedation, and neuromuscular blockade during targeted temperature management after cardiac arrest.Best Pract Res Clin Anaesthesiol. 2015; 29: 435-450https://doi.org/10.1016/j.bpa.2015.09.006Google Scholar, 6Sunjic K.M. Webb A.C. Sunjic I. Pala Creus M. Folse S.L. Pharmacokinetic and Other Considerations for Drug Therapy During Targeted Temperature Management.Crit Care Med. 2015; 43: 2228-2238https://doi.org/10.1097/CCM.0000000000001223Google Scholar delays awakening, and can modify the accuracy of the prognosis assessment that is usually performed prior to WLST. Presumably patients who had early WLST in Vlachos study did so before they had completed the recommended interval of fever management as well as before medications which confound prognosis assessment had fully metabolized. Thus, it is not surprising that early WLST was associated with significantly increased mortality. Other studies with smaller catchment populations in a variety of geographically separate locations have reported frequent use of WLST in patients resuscitated from OHCA.7Devanand N.A. Ruknuddeen M.I. Soar N. Edwards S. Withdrawal of life-sustaining therapy in intensive care unit patients following out-of-hospital cardiac arrest: An Australian metropolitan ICU experience.Heart Lung. Nov-Dec. 2022; 56: 96-104https://doi.org/10.1016/j.hrtlng.2022.06.019Google Scholar, 8Nakstad E.R. Staer-Jensen H. Wimmer H. et al.Late awakening, prognostic factors and long-term outcome in out-of-hospital cardiac arrest - results of the prospective Norwegian Cardio-Respiratory Arrest Study (NORCAST).Resuscitation. 2020; 149: 170-179https://doi.org/10.1016/j.resuscitation.2019.12.031Google Scholar, 9Grossestreuer A.V. Gaieski D.F. Abella B.S. et al.Factors associated with post-arrest withdrawal of life-sustaining therapy.Resuscitation. 2017; 110: 114-119https://doi.org/10.1016/j.resuscitation.2016.10.021Google Scholar, 10Mulder M. Gibbs H.G. Smith S.W. Dhaliwal R. Scott N.L. Sprenkle M.D. Geocadin R.G. Awakening and withdrawal of life-sustaining treatment in cardiac arrest survivors treated with therapeutic hypothermia*.Crit Care Med. 2014; 42: 2493-2499https://doi.org/10.1097/CCM.0000000000000540Google Scholar, 11Elmer J. Torres C. Aufderheide T.P. et al.Association of early withdrawal of life-sustaining therapy for perceived neurological prognosis with mortality after cardiac arrest.Resuscitation. 2016; 102: 127-135https://doi.org/10.1016/j.resuscitation.2016.01.016Google Scholar This suggests that the current observations are likely generalizable to patients resuscitated from OHCA around the world. In a prior multicenter, prospective, cohort study in Norway, the mean time to awakening among those who were discharged alive with good neurologic outcome was six days.[8]Nakstad E.R. Staer-Jensen H. Wimmer H. et al.Late awakening, prognostic factors and long-term outcome in out-of-hospital cardiac arrest - results of the prospective Norwegian Cardio-Respiratory Arrest Study (NORCAST).Resuscitation. 2020; 149: 170-179https://doi.org/10.1016/j.resuscitation.2019.12.031Google Scholar Patients who have WLST before six days have reduced opportunity to awaken or to survive to discharge. Collectively, these studies suggest that unstructured application of WLST is an important barrier to reducing the public health impact of OHCA globally. After adjustment for available patient-level information about demographics and pre-existing conditions, there was significant variation between intensive care units in use of early as well as late WLST. A prior observational analysis demonstrated that hospital-based post-resuscitation care was indeed an important contributor to survival after OHCA.[12]Stub D. Nichol G. Hospital care after resuscitation from out-of-hospital cardiac arrest: the emperor's new clothes?.Resuscitation. 2012; 83: 793-794https://doi.org/10.1016/j.resuscitation.2012.03.034Google Scholar However a limitation of the present analysis is that it did not adjust for the characteristics of the initial cardiac arrest event or treatment by emergency medical services providers, which are both strongly correlated with outcome after OHCA.[13]Rea T.D. Cook A.J. Stiell I.G. et al.Predicting survival after out-of-hospital cardiac arrest: role of the Utstein data elements.Ann Emerg Med. 2010; 55: 249-257https://doi.org/10.1016/j.annemergmed.2009.09.018Google Scholar Nonetheless, the results of the current analysis were robust to alternative approaches to analysis. A prior case-control study reported that a minority of patients with refractory cardiac arrest who received mechanical circulatory support consisting of extracorporeal membrane oxygenation (ECMO) had poor neurologic function at discharge, as compared to those who did not receive mechanical circulatory support.[14]Bartos J.A. Grunau B. Carlson C. et al.Improved Survival With Extracorporeal Cardiopulmonary Resuscitation Despite Progressive Metabolic Derangement Associated With Prolonged Resuscitation.Circulation. 2020; 141: 877-886https://doi.org/10.1161/CIRCULATIONAHA.119.042173Google Scholar It seems plausible that the high rate of use of WLST throughout the United Kingdom could reflect in part lack of application of ECMO or other effective field or hospital-based resuscitation interventions to preserve neurologic function. Different centers have reported discordant estimates of the benefit of ECMO in patients with refractory cardiac arrest.15Yannopoulos D. Bartos J. Raveendran G. et al.Advanced reperfusion strategies for patients with out-of-hospital cardiac arrest and refractory ventricular fibrillation (ARREST): a phase 2, single centre, open-label, randomised controlled trial.Lancet. 2020; 396: 1807-1816https://doi.org/10.1016/S0140-6736(20)32338-2Google Scholar, 16Belohlavek J. Smalcova J. Rob D. et al.Effect of Intra-arrest Transport, Extracorporeal Cardiopulmonary Resuscitation, and Immediate Invasive Assessment and Treatment on Functional Neurologic Outcome in Refractory Out-of-Hospital Cardiac Arrest: A Randomized Clinical Trial.JAMA. 2022; 327: 737-747https://doi.org/10.1001/jama.2022.1025Google Scholar, 17Suverein M.M. Delnoij T.S.R. Lorusso R. et al.Early Extracorporeal CPR for Refractory Out-of-Hospital Cardiac Arrest.N Engl J Med. 2023; 388: 299-309https://doi.org/10.1056/NEJMoa2204511Google Scholar Additional research is required to understand whether use of ECMO or other advanced resuscitation therapies obviates the need to consider WLST. Most randomized trials evaluating field interventions in patients with OHCA have sought to detect about a 25% relative difference in survival.18Perkins G.D. Ji C. Deakin C.D. et al.A Randomized Trial of Epinephrine in Out-of-Hospital Cardiac Arrest.N Engl J Med. 2018; 379: 711-721https://doi.org/10.1056/NEJMoa1806842Google Scholar, 19Kudenchuk P.J. Brown S.P. Daya M. et al.Amiodarone, Lidocaine, or Placebo in Out-of-Hospital Cardiac Arrest.N Engl J Med. 2016; 374: 1711-1722https://doi.org/10.1056/NEJMoa1514204Google Scholar Multiple recent evaluations of promising field interventions in patients with OHCA reported small but non-significant differences in favor of the intervention. The current analysis suggests that about 22% of patients resuscitated from OHCA undergo WLST. This proportion is large enough to attenuate the relative difference between intervention and control in a field trial. In particular, for patients undergoing early WLST, their response to treatment becomes a counterfactual of whether they would have benefited from therapy, had early WLST not occurred. Table 1 shows planned versus effective power under 22% WLST in a field trial randomized 1:1 to control:intervention assuming a 25% relative improvement in survival conferred by the intervention. Across control survival rates ranging from 10 to 25%, the effective power under 22% WLST is 8-9% lower than the planned power per the trial design. Furthermore, WLST in unblinded field trials may be utilized less frequently in the intervention arm due to optimism for the new therapy, resulting in considerable study bias. Thus, unstructured application of WLST is an important barrier to evidence-based improvements in the public health impact of OHCA.Table 1Planned versus effective power under 22% WLST in a field trial randomized 1:1 to control:intervention under varying control arm survival rates, assuming a 25% relative improvement in survival.Control Survival RateIntervention Survival Rate(25% Relative Improvement)Sample SizePlanned PoweraEstimated power assuming binomial outcomes, 1:1 randomization to control:intervention, and two-sided alpha=0.05.Effective PowerbEstimated power excluding 22% of patients due to WLST, assuming equal frequency of WLST across trial arms.10.00%12.50%671090%82%15.00%18.75%420090%82%20.00%25.00%293090%82%25.00%31.25%218090%81%a Estimated power assuming binomial outcomes, 1:1 randomization to control:intervention, and two-sided alpha=0.05.b Estimated power excluding 22% of patients due to WLST, assuming equal frequency of WLST across trial arms. Open table in a new tab In summary, the work by Vlachos and colleagues has important implications for provision of intensive care in the United Kingdom and the rest of the world, as well as for evaluation and implementation of field or hospital-based interventions to improve care for patients with OHCA. Emily Goren PhD- Conceptualization; Data curation; Formal analysis; Investigation; Methodology; Writing – original draft; and Writing – review & editing Antje Hoering- Conceptualization; Data curation; Formal analysis; Investigation; Methodology; Writing – original draft; Writing, review and editing Graham Nichol MD MPH- Conceptualization; Data curation; Formal analysis; Funding acquisition; Investigation; Methodology; Project administration; Resources; Supervision; Roles/Writing – original draft; and Writing – review & editing" @default.
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• W4387364103 title "Withdrawal of Life Sustaining Treatment After Resuscitation from Cardiac Arrest: Quo Vadis?" @default.
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