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Subsequent shockable rhythm and survival from out-of-hospital cardiac arrest: Another piece of the puzzle?
Accepted Manuscript Title: Subsequent Shockable Rhythm and Survival from Out-of-Hospital Cardiac Arrest: Another Piece of the Puzzle? Author: Mohamud R. Daya PII: DOI: Reference:
S0300-9572(17)30110-7 http://dx.doi.org/doi:10.1016/j.resuscitation.2017.03.010 RESUS 7102
To appear in:
Resuscitation
Author: Dana M. Zive PII: DOI: Reference:
S0300-9572(17)30110-7 http://dx.doi.org/doi:10.1016/j.resuscitation.2017.03.010 RESUS 7102
To appear in:
Resuscitation
Received date:
3-3-2017
Please cite this article as: Zive Dana M.Subsequent Shockable Rhythm and Survival from Out-of-Hospital Cardiac Arrest: Another Piece of the Puzzle?.Resuscitation http://dx.doi.org/10.1016/j.resuscitation.2017.03.010 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Subsequent Shockable Rhythm and Survival from Out-of-Hospital Cardiac Arrest: Another Piece of the Puzzle?
Mohamud R. Daya, MD, MS* Department of Emergency Medicine Oregon Health & Science University Portland, Oregon, United States Dana M. Zive, MPH Center for Policy and Research in Emergency Medicine Oregon Health & Science University Portland, Oregon, United States
Word Count: 1231
*Corresponding Author Mohamud R. Daya, MD, MS* Department of Emergency Medicine Oregon Health & Science University 3181 SW Sam Jackson Drive, Mail Code CDW-EM Portland, Oregon, 97239 United States [email protected] 503-494-7248
Keywords: This was a solicited editorial re: subsequent shockable rhythms in OHCA
Of the factors associated with survival following out-of-hospital cardiac arrest (OHCA), one of the most important is initial rhythm. The majority of OHCA survivors have a presenting rhythm that is shockable (ventricular fibrillation or pulseless ventricular tachycardia).1 Patients who present with nonshockable rhythms such as pulseless electrical activity (PEA) or asystole have extremely poor outcomes. The treatment of patients who present with initially non-shockable rhythms who subsequently develop a shockable rhythm has been a source of debate in the literature for the last decade. Traditionally, these patients have been managed in a fashion similar to patients presenting with initially shockable rhythms with periodic interruptions in CPR to assess underlying rhythm followed by defibrillation when indicated as well as standard arrest medications such as epinephrine and antiarrhythmic agents in shock refractory cases. A publication in 2007 by Hallstrom et al. based on ancillary observations from the ASPIRE trial noted that survival to hospital discharge in patients with initial non-shockable rhythms was greater in the group that never received a subsequent shock compared to the group that developed a subsequent shockable rhythm. (4.9% vs. 0.6 %, p 0.01).2 These authors therefore questioned the traditional approach of periodic interruptions to assess underling rhythm and suggested that alternative treatment approaches were needed for patients presenting with an initial non-shockable rhythm.. In response to this article, several investigators subsequently reported contradictory findings. Herlitz et al. studied the Swedish OHCA Registry and noted that in patients with an initial non-shockable rhythm, the need for a defibrillatory shock was one of six key factors associated with improved outcome.3 Other factors included younger age, witnessed event, bystander CPR, public location and a short ambulance response time. Kajino et al. examined the Osaka Utstein Registry and noted that in presumed cardiac OHCA patients with an initial non-shockable rhythm, conversion to a shockable rhythm was associated with improved one-month neurological favorable survival with an adjusted odds ratio of 4.3 (95% CI: 2.8 – 6.7).4 Finally, Olasveengen et al. from Oslo, Norway reported a higher survival to hospital discharge rate
in patients who developed a subsequent shockable rhythm compared to those that remained in a nonshockable rhythm. (7% vs. 2%, p = 0.014).5 The lead authors of these four publications subsequently contributed a commentary and suggested that different rates of conversion to a shockable rhythm as well as treatment protocol differences between EMS systems and publication bias may account for the observed findings.6 Since then, other investigators have continued to report inconsistent findings with regards to outcomes following conversion to a shockable rhythm during OHCA. Thomas et al. studied the Resuscitation Outcomes Consortium Epistry – Cardiac Arrest dataset and reported no difference in outcomes for initially non-shockable rhythm patients who converted to a shockable rhythm compared to those that did not (2.77% vs. 2.72%, p = 0.92).7 More recently, investigators from the Pan Asian Resuscitation Outcomes Study (PAROS) examined their dataset and reported that conversion to a shockable rhythm was associated with improved survival to hospital discharge with an adjusted odds ratio of 2.0 (95% CI: 1.10 -3.65) in adults with OHCA of presumed cardiac etiology presenting with an initial non-shockable rhythm.8 In this issue of the journal, Rajan and colleagues9 report on their findings from an examination of survival outcome according to initial rhythm in adults (≥ 18 years) with OHCA of presumed cardiac etiology from the Danish Cardiac Arrest Register between 2005 and 2012. As part of the study, the investigators linked data on known co-morbidities up to 10 years prior to the cardiac arrest from the National Public Register which contained detailed information related to prior hospitalizations. Comorbidities were categorized as cardiac (ischemic heart disease, myocardial infarction, heart failure) and non-cardiac (chronic obstructive pulmonary disease [COPD], diabetes, malignancy, psychiatric and renal disease). The authors then examined survival from all initial rhythms including those cases that developed a subsequent shockable rhythm after initially presenting in a non-shockable rhythm as well as those who had a sustained non-shockable rhythm. Primary outcomes were 30-day survival and return of spontaneous circulation (ROSC) at hospital arrival. As expected, the highest survival (27.1%) occurred
in patients with an initially shockable rhythm while the survival rate was 4.2% for subsequent shockable rhythm and 1.2 % for that for sustained non-shockable rhythm. After adjusting for co-variates, the adjusted OR for survival for conversion to a shockable rhythm was 2.6 (95% CI: 1.8-3.8) compared to sustained non-shockable rhythm. In a logistic regression model, factors positively associated with conversion to a shockable rhythm included age < 65, male sex, witnessed event, time from recognition of arrest to first EMS rhythm analysis under 15 minutes, history of ischemic heart disease and prior myocardial infarction. Factors negatively associated with conversion including a history of COPD and psychiatric disease. An important limitation of this study is selection bias as 11,310 (44.9%) of the 25,170 cases in their adult (age ≥ 18) OHCA registry were excluded from the final analysis. Exclusions were primarily due to a presumed non-cardiac (n = 6,950 [27.6%]) cause of cardiac arrest, EMS witnessed arrest (n = 2039 [8.1%]) and missing information on first recorded rhythm (n= 1891 [7.5%]). The exclusion of over a quarter of the cases due to non-cardiac etiology seems high in relation to other reported studies.1 Another key imitation is the absence of details regarding long-term functional status of survivors. Functional status is critically important since the long term survival from initially non-shockable rhythm is unfortunately very poor.10 What therefor should we take away from this study? First, it is important when comparing studies examining outcomes from patients with initially non-shockable rhythms that convert to a subsequent shockable rhythm that we understand in detail the populations being studied. The published papers to date examining this question have unfortunately used different cohorts from their existing registries. Some have used all adult cases while others have restricted analysis to those with presumed cardiac etiology. Some have also excluded OHCA that received bystander defibrillation and those that were EMS witnessed. These differences make direct comparisons challenging and may well explain some of the inconsistent results reported to date. Second, the ability of this registry to link cases to a
hospitalization registry permitted the investigators to examine the impact of pre-existing co-morbidities to outcomes following conversion to a shockable rhythm. The findings that cardiac co-morbidities in particular ischemic heart disease and prior MI were predictors of conversion to a shockable rhythm is important since it highlights the importance of considering the underlying substrate when examining resuscitation outcomes. These findings are consistent with the 3-phase model of cardiac arrest and may also explain some of the conflicting results by highlighting another piece of the puzzle.12 Linking data registries is no small feat and the authors deserve credit for this approach. Should this study change our clinical practice at the scene? The simple answer is no. Information regarding comorbidities is either unavailable or impractical to obtain during a resuscitation effort. Our focus must remain on high quality CPR, timely defibrillation and when necessary, the use of vasopressors and antiarrhythmic agents. Periodic pauses to assess the underlying rhythm remain appropriate but these should be brief given the known harmful effect of prolonged interruptions. Finally these authors report extremely encouraging trends in survival over time in their registry for all patient groups (initially shockable, subsequently shockable and persistent non-shockable). This suggests that evidence-driven resuscitation guidelines have had meaningful impact in improving OHCA outcomes in Denmark.
Conflict of Interest Statement: Neither author reports any conflicts
1. Daya MR, Schmicker RH, Zive DM, et al. Out-of-hospital cardiac arrest survival improving over time: Results from the Resuscitation Outcomes Consortium (ROC). Resuscitation. 2015;91:108-15. 2. Hallstrom A, Rea TD, Mosesso VN Jr, et al. The relationship between shocks and survival in out-ofhospital cardiac arrest patients initially found in PEA or asystole. Resuscitation. 2007;74:418-26. 3. Herlitz J, Svensson L, Engdahl J, et al. Characteristics and outcome in out-of-hospital cardiac arrest when patients are found in a non-shockable rhythm. Resuscitation. 2008;76:31-6. 4. Kajino K, Iwami T, Daya M, et al. Subsequent ventricular fibrillation and survival in out-of-hospital cardiac arrests presenting with PEA or asystole. Resuscitation. 2008;79:34-40. 5. Olasveengen TM, Samdal M, Steen PA, et al. Progressing from initial non-shockable rhythms to a shockable rhythm is associated with improved outcome after out-of-hospital cardiac arrest. Resuscitation. 2009;80:24-9. 6. Hallstrom A, Herlitz J, Kajino K, et al. Treatment of asystole and PEA. Resuscitation. 2009;80:975-6. 7. Thomas AJ, Newgard CD, Fu R, et al. Survival in out-of-hospital cardiac arrests with initial asystole or pulseless electrical activity and subsequent shockable rhythms. Resuscitation. 2013;84:1261-6. 8. Wah W, Wai KL, Pek PP, et al. Conversion to shockable rhythms during resuscitation and survival for out-of hospital cardiac arrest. Am J Emerg Med. 2017;35:206-213. 9. Rajan S, Folke F, Hansen SM, et al. Incidence and survival outcome according to heart rhythm during resuscitation attempt in out-of-hospital cardiac arrest patients with presumed cardiac etiology. Resuscitation. 2017 Jan 11. [Epub ahead of print] 10. Andrew E, Nehme Z, Lijovic M, et al. Outcomes following out-of-hospital cardiac arrest with an initial cardiac rhythm of asystole or pulseless electrical activity in Victoria, Australia. Resuscitation. 2014;85:1633-9. 11. Weisfeldt ML, Becker LB. Resuscitation after cardiac arrest: a 3-phase time-sensitive model. JAMA. 2002;288:3035-8.
S0300-9572(17)30110-7 http://dx.doi.org/doi:10.1016/j.resuscitation.2017.03.010 RESUS 7102
To appear in:
Resuscitation
Author: Dana M. Zive PII: DOI: Reference:
S0300-9572(17)30110-7 http://dx.doi.org/doi:10.1016/j.resuscitation.2017.03.010 RESUS 7102
To appear in:
Resuscitation
Received date:
3-3-2017
Please cite this article as: Zive Dana M.Subsequent Shockable Rhythm and Survival from Out-of-Hospital Cardiac Arrest: Another Piece of the Puzzle?.Resuscitation http://dx.doi.org/10.1016/j.resuscitation.2017.03.010 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Subsequent Shockable Rhythm and Survival from Out-of-Hospital Cardiac Arrest: Another Piece of the Puzzle?
Mohamud R. Daya, MD, MS* Department of Emergency Medicine Oregon Health & Science University Portland, Oregon, United States Dana M. Zive, MPH Center for Policy and Research in Emergency Medicine Oregon Health & Science University Portland, Oregon, United States
Word Count: 1231
*Corresponding Author Mohamud R. Daya, MD, MS* Department of Emergency Medicine Oregon Health & Science University 3181 SW Sam Jackson Drive, Mail Code CDW-EM Portland, Oregon, 97239 United States [email protected] 503-494-7248
Keywords: This was a solicited editorial re: subsequent shockable rhythms in OHCA
Of the factors associated with survival following out-of-hospital cardiac arrest (OHCA), one of the most important is initial rhythm. The majority of OHCA survivors have a presenting rhythm that is shockable (ventricular fibrillation or pulseless ventricular tachycardia).1 Patients who present with nonshockable rhythms such as pulseless electrical activity (PEA) or asystole have extremely poor outcomes. The treatment of patients who present with initially non-shockable rhythms who subsequently develop a shockable rhythm has been a source of debate in the literature for the last decade. Traditionally, these patients have been managed in a fashion similar to patients presenting with initially shockable rhythms with periodic interruptions in CPR to assess underlying rhythm followed by defibrillation when indicated as well as standard arrest medications such as epinephrine and antiarrhythmic agents in shock refractory cases. A publication in 2007 by Hallstrom et al. based on ancillary observations from the ASPIRE trial noted that survival to hospital discharge in patients with initial non-shockable rhythms was greater in the group that never received a subsequent shock compared to the group that developed a subsequent shockable rhythm. (4.9% vs. 0.6 %, p 0.01).2 These authors therefore questioned the traditional approach of periodic interruptions to assess underling rhythm and suggested that alternative treatment approaches were needed for patients presenting with an initial non-shockable rhythm.. In response to this article, several investigators subsequently reported contradictory findings. Herlitz et al. studied the Swedish OHCA Registry and noted that in patients with an initial non-shockable rhythm, the need for a defibrillatory shock was one of six key factors associated with improved outcome.3 Other factors included younger age, witnessed event, bystander CPR, public location and a short ambulance response time. Kajino et al. examined the Osaka Utstein Registry and noted that in presumed cardiac OHCA patients with an initial non-shockable rhythm, conversion to a shockable rhythm was associated with improved one-month neurological favorable survival with an adjusted odds ratio of 4.3 (95% CI: 2.8 – 6.7).4 Finally, Olasveengen et al. from Oslo, Norway reported a higher survival to hospital discharge rate
in patients who developed a subsequent shockable rhythm compared to those that remained in a nonshockable rhythm. (7% vs. 2%, p = 0.014).5 The lead authors of these four publications subsequently contributed a commentary and suggested that different rates of conversion to a shockable rhythm as well as treatment protocol differences between EMS systems and publication bias may account for the observed findings.6 Since then, other investigators have continued to report inconsistent findings with regards to outcomes following conversion to a shockable rhythm during OHCA. Thomas et al. studied the Resuscitation Outcomes Consortium Epistry – Cardiac Arrest dataset and reported no difference in outcomes for initially non-shockable rhythm patients who converted to a shockable rhythm compared to those that did not (2.77% vs. 2.72%, p = 0.92).7 More recently, investigators from the Pan Asian Resuscitation Outcomes Study (PAROS) examined their dataset and reported that conversion to a shockable rhythm was associated with improved survival to hospital discharge with an adjusted odds ratio of 2.0 (95% CI: 1.10 -3.65) in adults with OHCA of presumed cardiac etiology presenting with an initial non-shockable rhythm.8 In this issue of the journal, Rajan and colleagues9 report on their findings from an examination of survival outcome according to initial rhythm in adults (≥ 18 years) with OHCA of presumed cardiac etiology from the Danish Cardiac Arrest Register between 2005 and 2012. As part of the study, the investigators linked data on known co-morbidities up to 10 years prior to the cardiac arrest from the National Public Register which contained detailed information related to prior hospitalizations. Comorbidities were categorized as cardiac (ischemic heart disease, myocardial infarction, heart failure) and non-cardiac (chronic obstructive pulmonary disease [COPD], diabetes, malignancy, psychiatric and renal disease). The authors then examined survival from all initial rhythms including those cases that developed a subsequent shockable rhythm after initially presenting in a non-shockable rhythm as well as those who had a sustained non-shockable rhythm. Primary outcomes were 30-day survival and return of spontaneous circulation (ROSC) at hospital arrival. As expected, the highest survival (27.1%) occurred
in patients with an initially shockable rhythm while the survival rate was 4.2% for subsequent shockable rhythm and 1.2 % for that for sustained non-shockable rhythm. After adjusting for co-variates, the adjusted OR for survival for conversion to a shockable rhythm was 2.6 (95% CI: 1.8-3.8) compared to sustained non-shockable rhythm. In a logistic regression model, factors positively associated with conversion to a shockable rhythm included age < 65, male sex, witnessed event, time from recognition of arrest to first EMS rhythm analysis under 15 minutes, history of ischemic heart disease and prior myocardial infarction. Factors negatively associated with conversion including a history of COPD and psychiatric disease. An important limitation of this study is selection bias as 11,310 (44.9%) of the 25,170 cases in their adult (age ≥ 18) OHCA registry were excluded from the final analysis. Exclusions were primarily due to a presumed non-cardiac (n = 6,950 [27.6%]) cause of cardiac arrest, EMS witnessed arrest (n = 2039 [8.1%]) and missing information on first recorded rhythm (n= 1891 [7.5%]). The exclusion of over a quarter of the cases due to non-cardiac etiology seems high in relation to other reported studies.1 Another key imitation is the absence of details regarding long-term functional status of survivors. Functional status is critically important since the long term survival from initially non-shockable rhythm is unfortunately very poor.10 What therefor should we take away from this study? First, it is important when comparing studies examining outcomes from patients with initially non-shockable rhythms that convert to a subsequent shockable rhythm that we understand in detail the populations being studied. The published papers to date examining this question have unfortunately used different cohorts from their existing registries. Some have used all adult cases while others have restricted analysis to those with presumed cardiac etiology. Some have also excluded OHCA that received bystander defibrillation and those that were EMS witnessed. These differences make direct comparisons challenging and may well explain some of the inconsistent results reported to date. Second, the ability of this registry to link cases to a
hospitalization registry permitted the investigators to examine the impact of pre-existing co-morbidities to outcomes following conversion to a shockable rhythm. The findings that cardiac co-morbidities in particular ischemic heart disease and prior MI were predictors of conversion to a shockable rhythm is important since it highlights the importance of considering the underlying substrate when examining resuscitation outcomes. These findings are consistent with the 3-phase model of cardiac arrest and may also explain some of the conflicting results by highlighting another piece of the puzzle.12 Linking data registries is no small feat and the authors deserve credit for this approach. Should this study change our clinical practice at the scene? The simple answer is no. Information regarding comorbidities is either unavailable or impractical to obtain during a resuscitation effort. Our focus must remain on high quality CPR, timely defibrillation and when necessary, the use of vasopressors and antiarrhythmic agents. Periodic pauses to assess the underlying rhythm remain appropriate but these should be brief given the known harmful effect of prolonged interruptions. Finally these authors report extremely encouraging trends in survival over time in their registry for all patient groups (initially shockable, subsequently shockable and persistent non-shockable). This suggests that evidence-driven resuscitation guidelines have had meaningful impact in improving OHCA outcomes in Denmark.
Conflict of Interest Statement: Neither author reports any conflicts
1. Daya MR, Schmicker RH, Zive DM, et al. Out-of-hospital cardiac arrest survival improving over time: Results from the Resuscitation Outcomes Consortium (ROC). Resuscitation. 2015;91:108-15. 2. Hallstrom A, Rea TD, Mosesso VN Jr, et al. The relationship between shocks and survival in out-ofhospital cardiac arrest patients initially found in PEA or asystole. Resuscitation. 2007;74:418-26. 3. Herlitz J, Svensson L, Engdahl J, et al. Characteristics and outcome in out-of-hospital cardiac arrest when patients are found in a non-shockable rhythm. Resuscitation. 2008;76:31-6. 4. Kajino K, Iwami T, Daya M, et al. Subsequent ventricular fibrillation and survival in out-of-hospital cardiac arrests presenting with PEA or asystole. Resuscitation. 2008;79:34-40. 5. Olasveengen TM, Samdal M, Steen PA, et al. Progressing from initial non-shockable rhythms to a shockable rhythm is associated with improved outcome after out-of-hospital cardiac arrest. Resuscitation. 2009;80:24-9. 6. Hallstrom A, Herlitz J, Kajino K, et al. Treatment of asystole and PEA. Resuscitation. 2009;80:975-6. 7. Thomas AJ, Newgard CD, Fu R, et al. Survival in out-of-hospital cardiac arrests with initial asystole or pulseless electrical activity and subsequent shockable rhythms. Resuscitation. 2013;84:1261-6. 8. Wah W, Wai KL, Pek PP, et al. Conversion to shockable rhythms during resuscitation and survival for out-of hospital cardiac arrest. Am J Emerg Med. 2017;35:206-213. 9. Rajan S, Folke F, Hansen SM, et al. Incidence and survival outcome according to heart rhythm during resuscitation attempt in out-of-hospital cardiac arrest patients with presumed cardiac etiology. Resuscitation. 2017 Jan 11. [Epub ahead of print] 10. Andrew E, Nehme Z, Lijovic M, et al. Outcomes following out-of-hospital cardiac arrest with an initial cardiac rhythm of asystole or pulseless electrical activity in Victoria, Australia. Resuscitation. 2014;85:1633-9. 11. Weisfeldt ML, Becker LB. Resuscitation after cardiac arrest: a 3-phase time-sensitive model. JAMA. 2002;288:3035-8.