Antiarrhythmic Drugs for Nonshockable-Turned-Shockable Out-of-Hospital Cardiac Arrest

The ALPS Study (Amiodarone, Lidocaine, or Placebo)

Peter J. Kudenchuk, Brian G. Leroux, Mohamud Ramzan Daya, Thomas Rea, Christian Vaillancourt, Laurie J. Morrison, Clifton W. Callaway, James Christenson, Joseph P. Ornato, James V. Dunford, Lynn Wittwer, Myron L. Weisfeldt, Tom P. Aufderheide, Gary M. Vilke, Ahamed H. Idris, Ian G. Stiell, M. Riccardo Colella, Tami Kayea, Debra Egan, Patrice Desvigne-Nickens & 4 others Pamela Gray, Randal Gray, Ron Straight, Paul Dorian

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Background: Out-of-hospital cardiac arrest (OHCA) commonly presents with nonshockable rhythms (asystole and pulseless electric activity). It is unknown whether antiarrhythmic drugs are safe and effective when nonshockable rhythms evolve to shockable rhythms (ventricular fibrillation/pulseless ventricular tachycardia [VF/VT]) during resuscitation. Methods: Adults with nontraumatic OHCA, vascular access, and VF/VT anytime after ≥1 shock(s) were prospectively randomized, double-blind, to receive amiodarone, lidocaine, or placebo by paramedics. Patients presenting with initial shock-refractory VF/VT were previously reported. The current study was a prespecified analysis in a separate cohort that initially presented with nonshockable OHCA and was randomized on subsequently developing shock-refractory VF/VT. The primary outcome was survival to hospital discharge. Secondary outcomes included discharge functional status and adverse drug-related effects. Results: Of 37 889 patients with OHCA, 3026 with initial VF/VT and 1063 with initial nonshockable-turned-shockable rhythms were treatment-eligible, were randomized, and received their assigned drug. Baseline characteristics among patients with nonshockable-turned-shockable rhythms were balanced across treatment arms, except that recipients of a placebo included fewer men and were less likely to receive bystander cardiopulmonary resuscitation. Active-drug recipients in this cohort required fewer shocks, supplemental doses of their assigned drug, and ancillary antiarrhythmic drugs than recipients of a placebo (P<0.05). In all, 16 (4.1%) amiodarone, 11 (3.1%) lidocaine, and 6 (1.9%) placebo-treated patients survived to hospital discharge (P=0.24). No significant interaction between treatment assignment and discharge survival occurred with the initiating OHCA rhythm (asystole, pulseless electric activity, or VF/VT). Survival in each of these categories was consistently higher with active drugs, although the trends were not statistically significant. Adjusted absolute differences (95% confidence interval) in survival from nonshockable-turned-shockable arrhythmias with amiodarone versus placebo were 2.3% (-0.3, 4.8), P=0.08, and for lidocaine versus placebo 1.2% (-1.1, 3.6), P=0.30. More than 50% of these survivors were functionally independent or required minimal assistance. Drug-related adverse effects were infrequent. Conclusions: Outcome from nonshockable-turned-shockable OHCA is poor but not invariably fatal. Although not statistically significant, point estimates for survival were greater after amiodarone or lidocaine than placebo, without increased risk of adverse effects or disability and consistent with previously observed favorable trends from treatment of initial shock-refractory VF/VT with these drugs. Together the findings may signal a clinical benefit that invites further investigation. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01401647.

Original languageEnglish (US)
Pages (from-to)2119-2131
Number of pages13
JournalCirculation
Volume136
Issue number22
DOIs
StatePublished - Nov 28 2017

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Out-of-Hospital Cardiac Arrest
Amiodarone
Anti-Arrhythmia Agents
Ventricular Fibrillation
Ventricular Tachycardia
Lidocaine
Placebos
Shock
Pharmaceutical Preparations
Survival
Heart Arrest
Allied Health Personnel
Cardiopulmonary Resuscitation
Therapeutics
Resuscitation
Blood Vessels
Survivors
Cardiac Arrhythmias
Clinical Trials
Confidence Intervals

Keywords

  • amiodarone
  • cardiac arrest
  • lidocaine
  • placebo
  • resuscitation

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Antiarrhythmic Drugs for Nonshockable-Turned-Shockable Out-of-Hospital Cardiac Arrest : The ALPS Study (Amiodarone, Lidocaine, or Placebo). / Kudenchuk, Peter J.; Leroux, Brian G.; Daya, Mohamud Ramzan; Rea, Thomas; Vaillancourt, Christian; Morrison, Laurie J.; Callaway, Clifton W.; Christenson, James; Ornato, Joseph P.; Dunford, James V.; Wittwer, Lynn; Weisfeldt, Myron L.; Aufderheide, Tom P.; Vilke, Gary M.; Idris, Ahamed H.; Stiell, Ian G.; Colella, M. Riccardo; Kayea, Tami; Egan, Debra; Desvigne-Nickens, Patrice; Gray, Pamela; Gray, Randal; Straight, Ron; Dorian, Paul.

In: Circulation, Vol. 136, No. 22, 28.11.2017, p. 2119-2131.

Research output: Contribution to journalArticle

Kudenchuk, PJ, Leroux, BG, Daya, MR, Rea, T, Vaillancourt, C, Morrison, LJ, Callaway, CW, Christenson, J, Ornato, JP, Dunford, JV, Wittwer, L, Weisfeldt, ML, Aufderheide, TP, Vilke, GM, Idris, AH, Stiell, IG, Colella, MR, Kayea, T, Egan, D, Desvigne-Nickens, P, Gray, P, Gray, R, Straight, R & Dorian, P 2017, 'Antiarrhythmic Drugs for Nonshockable-Turned-Shockable Out-of-Hospital Cardiac Arrest: The ALPS Study (Amiodarone, Lidocaine, or Placebo)', Circulation, vol. 136, no. 22, pp. 2119-2131. https://doi.org/10.1161/CIRCULATIONAHA.117.028624
Kudenchuk, Peter J. ; Leroux, Brian G. ; Daya, Mohamud Ramzan ; Rea, Thomas ; Vaillancourt, Christian ; Morrison, Laurie J. ; Callaway, Clifton W. ; Christenson, James ; Ornato, Joseph P. ; Dunford, James V. ; Wittwer, Lynn ; Weisfeldt, Myron L. ; Aufderheide, Tom P. ; Vilke, Gary M. ; Idris, Ahamed H. ; Stiell, Ian G. ; Colella, M. Riccardo ; Kayea, Tami ; Egan, Debra ; Desvigne-Nickens, Patrice ; Gray, Pamela ; Gray, Randal ; Straight, Ron ; Dorian, Paul. / Antiarrhythmic Drugs for Nonshockable-Turned-Shockable Out-of-Hospital Cardiac Arrest : The ALPS Study (Amiodarone, Lidocaine, or Placebo). In: Circulation. 2017 ; Vol. 136, No. 22. pp. 2119-2131.
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abstract = "Background: Out-of-hospital cardiac arrest (OHCA) commonly presents with nonshockable rhythms (asystole and pulseless electric activity). It is unknown whether antiarrhythmic drugs are safe and effective when nonshockable rhythms evolve to shockable rhythms (ventricular fibrillation/pulseless ventricular tachycardia [VF/VT]) during resuscitation. Methods: Adults with nontraumatic OHCA, vascular access, and VF/VT anytime after ≥1 shock(s) were prospectively randomized, double-blind, to receive amiodarone, lidocaine, or placebo by paramedics. Patients presenting with initial shock-refractory VF/VT were previously reported. The current study was a prespecified analysis in a separate cohort that initially presented with nonshockable OHCA and was randomized on subsequently developing shock-refractory VF/VT. The primary outcome was survival to hospital discharge. Secondary outcomes included discharge functional status and adverse drug-related effects. Results: Of 37 889 patients with OHCA, 3026 with initial VF/VT and 1063 with initial nonshockable-turned-shockable rhythms were treatment-eligible, were randomized, and received their assigned drug. Baseline characteristics among patients with nonshockable-turned-shockable rhythms were balanced across treatment arms, except that recipients of a placebo included fewer men and were less likely to receive bystander cardiopulmonary resuscitation. Active-drug recipients in this cohort required fewer shocks, supplemental doses of their assigned drug, and ancillary antiarrhythmic drugs than recipients of a placebo (P<0.05). In all, 16 (4.1{\%}) amiodarone, 11 (3.1{\%}) lidocaine, and 6 (1.9{\%}) placebo-treated patients survived to hospital discharge (P=0.24). No significant interaction between treatment assignment and discharge survival occurred with the initiating OHCA rhythm (asystole, pulseless electric activity, or VF/VT). Survival in each of these categories was consistently higher with active drugs, although the trends were not statistically significant. Adjusted absolute differences (95{\%} confidence interval) in survival from nonshockable-turned-shockable arrhythmias with amiodarone versus placebo were 2.3{\%} (-0.3, 4.8), P=0.08, and for lidocaine versus placebo 1.2{\%} (-1.1, 3.6), P=0.30. More than 50{\%} of these survivors were functionally independent or required minimal assistance. Drug-related adverse effects were infrequent. Conclusions: Outcome from nonshockable-turned-shockable OHCA is poor but not invariably fatal. Although not statistically significant, point estimates for survival were greater after amiodarone or lidocaine than placebo, without increased risk of adverse effects or disability and consistent with previously observed favorable trends from treatment of initial shock-refractory VF/VT with these drugs. Together the findings may signal a clinical benefit that invites further investigation. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01401647.",
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TY - JOUR

T1 - Antiarrhythmic Drugs for Nonshockable-Turned-Shockable Out-of-Hospital Cardiac Arrest

T2 - The ALPS Study (Amiodarone, Lidocaine, or Placebo)

AU - Kudenchuk, Peter J.

AU - Leroux, Brian G.

AU - Daya, Mohamud Ramzan

AU - Rea, Thomas

AU - Vaillancourt, Christian

AU - Morrison, Laurie J.

AU - Callaway, Clifton W.

AU - Christenson, James

AU - Ornato, Joseph P.

AU - Dunford, James V.

AU - Wittwer, Lynn

AU - Weisfeldt, Myron L.

AU - Aufderheide, Tom P.

AU - Vilke, Gary M.

AU - Idris, Ahamed H.

AU - Stiell, Ian G.

AU - Colella, M. Riccardo

AU - Kayea, Tami

AU - Egan, Debra

AU - Desvigne-Nickens, Patrice

AU - Gray, Pamela

AU - Gray, Randal

AU - Straight, Ron

AU - Dorian, Paul

PY - 2017/11/28

Y1 - 2017/11/28

N2 - Background: Out-of-hospital cardiac arrest (OHCA) commonly presents with nonshockable rhythms (asystole and pulseless electric activity). It is unknown whether antiarrhythmic drugs are safe and effective when nonshockable rhythms evolve to shockable rhythms (ventricular fibrillation/pulseless ventricular tachycardia [VF/VT]) during resuscitation. Methods: Adults with nontraumatic OHCA, vascular access, and VF/VT anytime after ≥1 shock(s) were prospectively randomized, double-blind, to receive amiodarone, lidocaine, or placebo by paramedics. Patients presenting with initial shock-refractory VF/VT were previously reported. The current study was a prespecified analysis in a separate cohort that initially presented with nonshockable OHCA and was randomized on subsequently developing shock-refractory VF/VT. The primary outcome was survival to hospital discharge. Secondary outcomes included discharge functional status and adverse drug-related effects. Results: Of 37 889 patients with OHCA, 3026 with initial VF/VT and 1063 with initial nonshockable-turned-shockable rhythms were treatment-eligible, were randomized, and received their assigned drug. Baseline characteristics among patients with nonshockable-turned-shockable rhythms were balanced across treatment arms, except that recipients of a placebo included fewer men and were less likely to receive bystander cardiopulmonary resuscitation. Active-drug recipients in this cohort required fewer shocks, supplemental doses of their assigned drug, and ancillary antiarrhythmic drugs than recipients of a placebo (P<0.05). In all, 16 (4.1%) amiodarone, 11 (3.1%) lidocaine, and 6 (1.9%) placebo-treated patients survived to hospital discharge (P=0.24). No significant interaction between treatment assignment and discharge survival occurred with the initiating OHCA rhythm (asystole, pulseless electric activity, or VF/VT). Survival in each of these categories was consistently higher with active drugs, although the trends were not statistically significant. Adjusted absolute differences (95% confidence interval) in survival from nonshockable-turned-shockable arrhythmias with amiodarone versus placebo were 2.3% (-0.3, 4.8), P=0.08, and for lidocaine versus placebo 1.2% (-1.1, 3.6), P=0.30. More than 50% of these survivors were functionally independent or required minimal assistance. Drug-related adverse effects were infrequent. Conclusions: Outcome from nonshockable-turned-shockable OHCA is poor but not invariably fatal. Although not statistically significant, point estimates for survival were greater after amiodarone or lidocaine than placebo, without increased risk of adverse effects or disability and consistent with previously observed favorable trends from treatment of initial shock-refractory VF/VT with these drugs. Together the findings may signal a clinical benefit that invites further investigation. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01401647.

AB - Background: Out-of-hospital cardiac arrest (OHCA) commonly presents with nonshockable rhythms (asystole and pulseless electric activity). It is unknown whether antiarrhythmic drugs are safe and effective when nonshockable rhythms evolve to shockable rhythms (ventricular fibrillation/pulseless ventricular tachycardia [VF/VT]) during resuscitation. Methods: Adults with nontraumatic OHCA, vascular access, and VF/VT anytime after ≥1 shock(s) were prospectively randomized, double-blind, to receive amiodarone, lidocaine, or placebo by paramedics. Patients presenting with initial shock-refractory VF/VT were previously reported. The current study was a prespecified analysis in a separate cohort that initially presented with nonshockable OHCA and was randomized on subsequently developing shock-refractory VF/VT. The primary outcome was survival to hospital discharge. Secondary outcomes included discharge functional status and adverse drug-related effects. Results: Of 37 889 patients with OHCA, 3026 with initial VF/VT and 1063 with initial nonshockable-turned-shockable rhythms were treatment-eligible, were randomized, and received their assigned drug. Baseline characteristics among patients with nonshockable-turned-shockable rhythms were balanced across treatment arms, except that recipients of a placebo included fewer men and were less likely to receive bystander cardiopulmonary resuscitation. Active-drug recipients in this cohort required fewer shocks, supplemental doses of their assigned drug, and ancillary antiarrhythmic drugs than recipients of a placebo (P<0.05). In all, 16 (4.1%) amiodarone, 11 (3.1%) lidocaine, and 6 (1.9%) placebo-treated patients survived to hospital discharge (P=0.24). No significant interaction between treatment assignment and discharge survival occurred with the initiating OHCA rhythm (asystole, pulseless electric activity, or VF/VT). Survival in each of these categories was consistently higher with active drugs, although the trends were not statistically significant. Adjusted absolute differences (95% confidence interval) in survival from nonshockable-turned-shockable arrhythmias with amiodarone versus placebo were 2.3% (-0.3, 4.8), P=0.08, and for lidocaine versus placebo 1.2% (-1.1, 3.6), P=0.30. More than 50% of these survivors were functionally independent or required minimal assistance. Drug-related adverse effects were infrequent. Conclusions: Outcome from nonshockable-turned-shockable OHCA is poor but not invariably fatal. Although not statistically significant, point estimates for survival were greater after amiodarone or lidocaine than placebo, without increased risk of adverse effects or disability and consistent with previously observed favorable trends from treatment of initial shock-refractory VF/VT with these drugs. Together the findings may signal a clinical benefit that invites further investigation. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01401647.

KW - amiodarone

KW - cardiac arrest

KW - lidocaine

KW - placebo

KW - resuscitation

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