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Factoring in Postresuscitative Measures
CORRESPONDENCE
Guidelines for Letters to the Editor Annals welcomes letters to the editor, including observations, opinions, corrections, very brief reports, and comments on published articles. Letters to the editor should not exceed 500 words and 5 references. They should be submitted using Annals’ Web-based peer review system, Editorial ManagerTM (http://www.editorialmanager.com/annemergmed). Annals no longer accepts submissions by mail. Letters should not contain abbreviations. Financial association or other possible conflicts of interest should always be disclosed, and their presence or absence will be published with the correspondence. Letters discussing an Annals article must be received within 8 weeks of the article’s publication. Published letters may be edited and shortened. Authors of articles for which comments are received will be given the opportunity to reply. If those authors wish to respond, their reply will not be shared with the author of the letter before publication. Neither Annals of Emergency Medicine nor the Publisher accepts responsibility for statements made by contributors.
0196-0644/$-see front matter Copyright © 2014 by the American College of Emergency Physicians.
Factoring in Postresuscitative Measures To the Editor: Bobrow et al1 report in an observational before-and-after study that the implementation of resuscitation training combined with real-time audiovisual feedback is associated with improved patient survival. Although the investigators should be commended for the development of scenario-based training and techniques for improved CPR delivery, we wish to offer a potential alternative explanation to the study while asking the authors to expand on the potential influence of postresuscitation care. As with many cardiac arrest registries, provision of detailed postresuscitative care is variable but raises a significant confounding explanation to the studies reporting improved clinical outcomes. The authors report the use of therapeutic hypothermia, albeit it remains unclear whether this was emergency medical services initiated or hospital based. Details are limited on other important postresuscitation measures, such as coronary angiography,2 optimizing hemodynamics, and other metabolic parameters3 and prognostication.4 This is particularly relevant, given the authors’ interesting finding of a nonsignificant reduction in rates of return of spontaneous circulation after intervention (25% versus 21%) and yet a dramatic increase in survival to hospital discharge, primarily driven by patients with a shockable rhythm (55.6% versus 26.3%). Given that the strongest independent predictor of survival in their multivariate model was use of hypothermia (odds ratio 14.6; 95% confidence interval 6.98 to 30.51) and that the use of therapeutic hypothermia was numerically but not significantly greater in the intervention period (9.9% versus 11.5%), we thought that consideration of the potential effects of therapeutic hypothermia
Volume 63, no. 2 : February 2014
and other postresuscitative measures on the study’s observed clinical improvement is warranted. Dion Stub, MD, PhD, FRACP Graham Nichol, MD, MPH, FRCP(C) University of Washington–Harborview Center for Prehospital Emergency Care Seattle, WA Baker IDI Heart and Diabetes Institute Melbourne, Australia http://dx.doi.org/10.1016/j.annemergmed.2013.08.029
Funding and support: By Annals policy, all authors are required to disclose any and all commercial, financial, and other relationships in any way related to the subject of this article as per ICMJE conflict of interest guidelines (see www.icmje.org). The authors have stated that no such relationships exist. Dr. Stub is supported by a Victoria Fellowship, Royal Australian College Physicians Fellowship, and Australian & New Zealand Cardiac Society award. Dr. Nichol is supported by NIH NHLBI R21 HL09364101A1, 2009 to 2013; NIH NHLBI R01 HL089554-03, 2007 to 2013; NIH U01 HL077863-06, 2010 to 2015; Velomedix Inc., 2012 to 2014 (waived personal compensation); Hypothermia Duration After Resuscitation Trial (HART) pilot study (submitted to NHLBI); CR Bard Medical Division Inc.; Cincinnati Sub-Zero Inc.; EMCOOLS AG; Gaymar/Stryker Inc.; ZOLL Circulation Inc., 2013 to 2015; Washington Study of Ultrasound in Resuscitation (Philips Healthcare Inc.), 2013 to 2014; and IU0lFD004933-01, Dynamic AED Registry (Food and Drug
Annals of Emergency Medicine 269
Correspondence Administration, Philips Healthcare Inc., Physio-Control Inc., ZOLL Inc.), 2012 to 2015. 1. Bobrow BJ, Vadeboncoeur TF, Stolz U, et al. The influence of scenario-based training and real-time audiovisual feedback on out-of-hospital cardiopulmonary resuscitation quality and survival from out-of-hospital cardiac arrest. Ann Emerg Med. 2013;62: 47-56.e1. 2. Dumas F, Cariou A, Manzo-Silberman S, et al. Immediate percutaneous coronary intervention is associated with better survival after out-ofhospital cardiac arrest: insights from the PROCAT (Parisian Region Out of hospital Cardiac Arrest) registry. Circ Cardiovasc Interv. 2010;3:200-207. 3. Tømte Ø, Andersen GØ, Jacobsen D, et al. Strong and weak aspects of an established post-resuscitation treatment protocol—a five-year observational study. Resuscitation. 2011;82:1186-1193. 4. Stub D, Bernard S, Duffy SJ, et al. Post cardiac arrest syndrome: a review of therapeutic strategies. Circulation. 2011;123:1428-1435.
In reply: We agree with Drs. Stub and Nichol in their assertion that cardiac resuscitation is a complex event with multiple factors known to affect survival.1 They have the appropriate concern that the influence of therapeutic hypothermia on our results could be substantial. Therapeutic hypothermia has been established as one of the factors that significantly affect both survival and functional outcome after out-of-hospital cardiac arrest.2,3 This is why we included it in the regression model even though there was not a significant difference in its use in the before/after cohorts. If we had not included therapeutic hypothermia as an independent risk factor/confounder, speculation about its role as a causative agent for our outcomes would be valid. However, the influence of therapeutic hypothermia was fully accounted for in our model. Thus, any concern that this identified confounder was responsible for the improved outcomes can be allayed because even after controlling for the profound influence of therapeutic hypothermia (as well as all other identifiable known confounders), the postintervention group fared significantly better than the preintervention cohort (adjusted odds ratio for survival¼2.72; adjusted odds ratio for good functional outcome¼2.69). Their second concern, that another unmeasured postarrest confounder could be responsible for our findings, is valid. No one would argue with the fact that there are at least several other postarrest interventions that could, and probably do, affect outcome4,5; however, this limitation exists in essentially the entire extant out-of-hospital cardiac arrest literature. Indeed, the fact that we have the therapeutic hypothermia data on all of the patients means that this analysis is one of only a few studies that properly controls for this factor. Furthermore, essentially no previous studies have data related to other postresuscitation interventions (such as optimization of hemodynamics and other metabolic parameters) that Stub and Nichol1 imply must be known to confidently make conclusions. However, if the absence of data on these other postresuscitation factors invalidates this study, then it also invalidates essentially the entire out-of-hospital
270 Annals of Emergency Medicine
cardiac arrest literature. If this is a new standard to which the outof-hospital cardiac resuscitation literature will be held, only a tiny number of studies will be published in the foreseeable future. We believe that our testable, a priori hypothesis that improving out-of-hospital cardiopulmonary resuscitation (CPR) quality (which was clearly demonstrated) would be independently associated with a significant improvement in survival and neurologic outcome was confirmed. Furthermore, our findings are both biologically plausible and well supported in the animal and human resuscitation literature.6 Thus, the significant improvements in out-of-hospital CPR quality metrics that were achieved were most likely responsible for the improvements in survival and functional outcome. As we acknowledged in the limitations section of the article, a wellcontrolled (but nonrandomized) before/after design does not allow the definite determination of causation between the intervention and outcomes. However, the a priori research question prospectively evaluated in this way does allow identification of meaningful independent associations when confounders are appropriately identified and addressed. We believe that our study successfully and satisfactorily met this goal. Bentley J. Bobrow, MD Arizona Department of Health Services Bureau of Emergency Medical Services and Trauma System Maricopa Medical Center University of Arizona College of Medicine Phoenix, AZ Uwe Stolz, PhD, MPH Daniel W. Spaite, MD Arizona Emergency Medicine Research Center University of Arizona College of Medicine Tucson, AZ http://dx.doi.org/10.1016/j.annemergmed.2013.09.010
Funding and support: By Annals policy, all authors are required to disclose any and all commercial, financial, and other relationships in any way related to the subject of this article as per ICMJE conflict of interest guidelines (see www.icmje.org). Drs. Bobrow and Spaite disclose that the University of Arizona receives support from the Medtronic Foundation involving communitybased translation of resuscitation science. 1. Stub D, Nichol G. Factoring in postresuscitative measures. Ann Emerg Med. 2014;63:269. 2. Bernard SA, Gray TW, Buist MD, et al. Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. N Engl J Med. 2002;346:557-563. 3. The Hypothermia after Cardiac Arrest Study Group. Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med. 2002;346:549-556. 4. Neumar RW, Nolan JP, Adrie C, et al. Post-cardiac arrest syndrome: epidemiology, pathophysiology, treatment, and prognostication. A
Volume 63, no. 2 : February 2014
Guidelines for Letters to the Editor Annals welcomes letters to the editor, including observations, opinions, corrections, very brief reports, and comments on published articles. Letters to the editor should not exceed 500 words and 5 references. They should be submitted using Annals’ Web-based peer review system, Editorial ManagerTM (http://www.editorialmanager.com/annemergmed). Annals no longer accepts submissions by mail. Letters should not contain abbreviations. Financial association or other possible conflicts of interest should always be disclosed, and their presence or absence will be published with the correspondence. Letters discussing an Annals article must be received within 8 weeks of the article’s publication. Published letters may be edited and shortened. Authors of articles for which comments are received will be given the opportunity to reply. If those authors wish to respond, their reply will not be shared with the author of the letter before publication. Neither Annals of Emergency Medicine nor the Publisher accepts responsibility for statements made by contributors.
0196-0644/$-see front matter Copyright © 2014 by the American College of Emergency Physicians.
Factoring in Postresuscitative Measures To the Editor: Bobrow et al1 report in an observational before-and-after study that the implementation of resuscitation training combined with real-time audiovisual feedback is associated with improved patient survival. Although the investigators should be commended for the development of scenario-based training and techniques for improved CPR delivery, we wish to offer a potential alternative explanation to the study while asking the authors to expand on the potential influence of postresuscitation care. As with many cardiac arrest registries, provision of detailed postresuscitative care is variable but raises a significant confounding explanation to the studies reporting improved clinical outcomes. The authors report the use of therapeutic hypothermia, albeit it remains unclear whether this was emergency medical services initiated or hospital based. Details are limited on other important postresuscitation measures, such as coronary angiography,2 optimizing hemodynamics, and other metabolic parameters3 and prognostication.4 This is particularly relevant, given the authors’ interesting finding of a nonsignificant reduction in rates of return of spontaneous circulation after intervention (25% versus 21%) and yet a dramatic increase in survival to hospital discharge, primarily driven by patients with a shockable rhythm (55.6% versus 26.3%). Given that the strongest independent predictor of survival in their multivariate model was use of hypothermia (odds ratio 14.6; 95% confidence interval 6.98 to 30.51) and that the use of therapeutic hypothermia was numerically but not significantly greater in the intervention period (9.9% versus 11.5%), we thought that consideration of the potential effects of therapeutic hypothermia
Volume 63, no. 2 : February 2014
and other postresuscitative measures on the study’s observed clinical improvement is warranted. Dion Stub, MD, PhD, FRACP Graham Nichol, MD, MPH, FRCP(C) University of Washington–Harborview Center for Prehospital Emergency Care Seattle, WA Baker IDI Heart and Diabetes Institute Melbourne, Australia http://dx.doi.org/10.1016/j.annemergmed.2013.08.029
Funding and support: By Annals policy, all authors are required to disclose any and all commercial, financial, and other relationships in any way related to the subject of this article as per ICMJE conflict of interest guidelines (see www.icmje.org). The authors have stated that no such relationships exist. Dr. Stub is supported by a Victoria Fellowship, Royal Australian College Physicians Fellowship, and Australian & New Zealand Cardiac Society award. Dr. Nichol is supported by NIH NHLBI R21 HL09364101A1, 2009 to 2013; NIH NHLBI R01 HL089554-03, 2007 to 2013; NIH U01 HL077863-06, 2010 to 2015; Velomedix Inc., 2012 to 2014 (waived personal compensation); Hypothermia Duration After Resuscitation Trial (HART) pilot study (submitted to NHLBI); CR Bard Medical Division Inc.; Cincinnati Sub-Zero Inc.; EMCOOLS AG; Gaymar/Stryker Inc.; ZOLL Circulation Inc., 2013 to 2015; Washington Study of Ultrasound in Resuscitation (Philips Healthcare Inc.), 2013 to 2014; and IU0lFD004933-01, Dynamic AED Registry (Food and Drug
Annals of Emergency Medicine 269
Correspondence Administration, Philips Healthcare Inc., Physio-Control Inc., ZOLL Inc.), 2012 to 2015. 1. Bobrow BJ, Vadeboncoeur TF, Stolz U, et al. The influence of scenario-based training and real-time audiovisual feedback on out-of-hospital cardiopulmonary resuscitation quality and survival from out-of-hospital cardiac arrest. Ann Emerg Med. 2013;62: 47-56.e1. 2. Dumas F, Cariou A, Manzo-Silberman S, et al. Immediate percutaneous coronary intervention is associated with better survival after out-ofhospital cardiac arrest: insights from the PROCAT (Parisian Region Out of hospital Cardiac Arrest) registry. Circ Cardiovasc Interv. 2010;3:200-207. 3. Tømte Ø, Andersen GØ, Jacobsen D, et al. Strong and weak aspects of an established post-resuscitation treatment protocol—a five-year observational study. Resuscitation. 2011;82:1186-1193. 4. Stub D, Bernard S, Duffy SJ, et al. Post cardiac arrest syndrome: a review of therapeutic strategies. Circulation. 2011;123:1428-1435.
In reply: We agree with Drs. Stub and Nichol in their assertion that cardiac resuscitation is a complex event with multiple factors known to affect survival.1 They have the appropriate concern that the influence of therapeutic hypothermia on our results could be substantial. Therapeutic hypothermia has been established as one of the factors that significantly affect both survival and functional outcome after out-of-hospital cardiac arrest.2,3 This is why we included it in the regression model even though there was not a significant difference in its use in the before/after cohorts. If we had not included therapeutic hypothermia as an independent risk factor/confounder, speculation about its role as a causative agent for our outcomes would be valid. However, the influence of therapeutic hypothermia was fully accounted for in our model. Thus, any concern that this identified confounder was responsible for the improved outcomes can be allayed because even after controlling for the profound influence of therapeutic hypothermia (as well as all other identifiable known confounders), the postintervention group fared significantly better than the preintervention cohort (adjusted odds ratio for survival¼2.72; adjusted odds ratio for good functional outcome¼2.69). Their second concern, that another unmeasured postarrest confounder could be responsible for our findings, is valid. No one would argue with the fact that there are at least several other postarrest interventions that could, and probably do, affect outcome4,5; however, this limitation exists in essentially the entire extant out-of-hospital cardiac arrest literature. Indeed, the fact that we have the therapeutic hypothermia data on all of the patients means that this analysis is one of only a few studies that properly controls for this factor. Furthermore, essentially no previous studies have data related to other postresuscitation interventions (such as optimization of hemodynamics and other metabolic parameters) that Stub and Nichol1 imply must be known to confidently make conclusions. However, if the absence of data on these other postresuscitation factors invalidates this study, then it also invalidates essentially the entire out-of-hospital
270 Annals of Emergency Medicine
cardiac arrest literature. If this is a new standard to which the outof-hospital cardiac resuscitation literature will be held, only a tiny number of studies will be published in the foreseeable future. We believe that our testable, a priori hypothesis that improving out-of-hospital cardiopulmonary resuscitation (CPR) quality (which was clearly demonstrated) would be independently associated with a significant improvement in survival and neurologic outcome was confirmed. Furthermore, our findings are both biologically plausible and well supported in the animal and human resuscitation literature.6 Thus, the significant improvements in out-of-hospital CPR quality metrics that were achieved were most likely responsible for the improvements in survival and functional outcome. As we acknowledged in the limitations section of the article, a wellcontrolled (but nonrandomized) before/after design does not allow the definite determination of causation between the intervention and outcomes. However, the a priori research question prospectively evaluated in this way does allow identification of meaningful independent associations when confounders are appropriately identified and addressed. We believe that our study successfully and satisfactorily met this goal. Bentley J. Bobrow, MD Arizona Department of Health Services Bureau of Emergency Medical Services and Trauma System Maricopa Medical Center University of Arizona College of Medicine Phoenix, AZ Uwe Stolz, PhD, MPH Daniel W. Spaite, MD Arizona Emergency Medicine Research Center University of Arizona College of Medicine Tucson, AZ http://dx.doi.org/10.1016/j.annemergmed.2013.09.010
Funding and support: By Annals policy, all authors are required to disclose any and all commercial, financial, and other relationships in any way related to the subject of this article as per ICMJE conflict of interest guidelines (see www.icmje.org). Drs. Bobrow and Spaite disclose that the University of Arizona receives support from the Medtronic Foundation involving communitybased translation of resuscitation science. 1. Stub D, Nichol G. Factoring in postresuscitative measures. Ann Emerg Med. 2014;63:269. 2. Bernard SA, Gray TW, Buist MD, et al. Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. N Engl J Med. 2002;346:557-563. 3. The Hypothermia after Cardiac Arrest Study Group. Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med. 2002;346:549-556. 4. Neumar RW, Nolan JP, Adrie C, et al. Post-cardiac arrest syndrome: epidemiology, pathophysiology, treatment, and prognostication. A
Volume 63, no. 2 : February 2014