Transcript ALS428 Antiarrhythmics During Cardiac Arrest

Dallas 2015
ALS 428 : Antiarrhythmic drugs
for cardiac arrest
TFQO: Jonathan Witt (COI #418)
EVREVs: Steve Lin (COI #137), Thomas Pellis
(COI #186) and Katie Dainty (COI #)
Taskforce: ALS
COI Disclosure
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(specific to this systematic review)
Commercial/industry
None
Potential intellectual conflicts
None
2010 CoSTR
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Consensus on Science
There was little evidence to suggest a survival-to-discharge advantage with
any antiarrhythmic drug used during resuscitation from out-of-hospital or inhospital cardiac arrest. Two randomized trials demonstrated the benefit of
amiodarone over standard of care, which included lidocaine in 80% of cases,
or routine use of lidocaine for shock refractory or recurrent VT/VF for the end
point of survival to hospital admission, but not to survival to hospital
discharge. A retrospective review demonstrated improved survival to
admission with lidocaine (compared with standard treatment) for patients in
VF out of hospital (LOE 4).
A retrospective review found procainamide was associated with increased
survival to 1 hour postarrest in patients with VF in hospital (LOE 4). Four
randomized, controlled trials did not show any increase in ROSC or survival
when magnesium was compared with placebo for patients in VF in out-ofhospital, ICU, and emergency department (ED) settings (LOE 1).
Treatment Recommendation
Amiodarone may be considered for those who have refractory VT/VF, defined
as VT/VF not terminated by defibrillation, or VT/VF recurrence in out-ofhospital cardiac arrest or in-hospital cardiac arrest. There is inadequate
evidence to support or refute the use of lidocaine in the same settings.
C2015 PICO
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P: Adults who are in cardiac arrest in any setting
I: Does antiarrhythmic drugs (e.g. lidocaine,
amiodarone, other) administration
C: Compared with not using antiarrhythmic drugs
(no drug or placebo)
O: Change Survival with Favorable
neurological/functional outcome at discharge, 30
days, 60 days, 180 days AND/OR 1 year, Survival
only at discharge, 30 days, 60 days, 180 days
AND/OR 1 year, ROSC
Inclusion/Exclusion
& Articles Found
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Inclusions/Exclusions
Included RCTs and non-RCTs evaluating
antiarrhythmics given during cardiac arrest
resuscitation compared to no antiarrhythmics
Excluded studies comparing antiarrhythmic
vs. antiarrhythmic (e.g. amiodarone vs.
lidocaine)
2052 articles initially identified, and 8 studies
included (5 RCTs and 3 non-RCTs)
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2015 Proposed
Treatment Recommendations
There are no studies that show improved survival to hospital
discharge or functional survival with the use of antiarrhythmics
in cardiac arrest patients refractory to VF/pVT.
We suggest the use of amiodarone in adult patients who suffer
OHCA with refractory VF/pVT to improve rates of ROSC (Weak
recommendation; high confidence in effect estimate).
Clinicians might consider lidocaine or nifekalant in adult
patients who suffer OHCA and IHCA, respectively (Weak
recommendation, very low confidence in effect estimates).
We suggest against the use of magnesium in adult patients
who are in OHCA in any rhythm (Strong recommendation,
moderate confidence in effect estimate).
Risk of Bias in studies
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SEERS not updated to insert risk of bias tables
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Key data from key studies
Reference: Kudenchuk et al., 1999
P: OHCA with VF/VT refractory to 3 defibrillations
I: Amiodarone 300mg
C: Placebo (polysorbate 80)
O: ROSC 64% vs 41%; p=0.03
Survival to admission 44% vs 34%; p=0.03
Suvival to discharge 13.4% vs 13.2%; p=ns
Neuro 53% vs 50% of survivors; p=ns
Evidence profile tables
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Evidence profile tables
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Evidence profile tables
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Evidence profile tables
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Proposed Consensus on Science
statements
Amiodarone (I) versus no amiodarone (C)
For the important outcome of ROSC, we have identified one RCT (GRADE: high)
of 504 patients who suffered from OHCA with an initial rhythm of (or developing)
VF or pulseless VT refractory to 3 shocks showing an improved rate of ROSC with
administration of amiodarone (300 mg after 1 mg of adrenaline) compared with
no drug (64% vs 41%; p=0.03) [Kundenchuk 1999].
For the critical outcome of survival at discharge, we have identified one RCT
(GRADE: high) of 504 patients who suffered from OHCA with an initial rhythm of
(or developing) VF or pulseless VT refractory to 3 shocks showing a similar rate of
survival with administration of amiodarone (300 mg after 1 mg of adrenaline)
compared with no drug (13.4% vs 13.2%; p=ns) [Kundenchuk 1999].
For the critical outcome of survival with favorable neurological/functional outcome
at discharge, we have identified one RCT (GRADE: high) of 504 patients who
suffered from OHCA with an initial rhythm of (or developing) VF or pulseless VT
refractory to 3 shocks showing a similar rate of survival with favorable
neurological outcome with administration of amiodarone (300 mg after 1 mg of
adrenaline) compared with no drug (53% vs 50% of survivors; p=ns)
[Kundenchuk 1999].
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Proposed Consensus on Science
statements
Lidocaine (I) versus no lidocaine (C)
For the important outcome of ROSC, we identified 2 retrospective observational single
center studies (GRADE: very low; very serious risk of bias) with conflicting results:
Herlitz [1997] et al. showed in 290 patients who suffered from OHCA with VF
refractory to 3 shocks an improved rate of ROSC with administration of lidocaine (50
mg, repeatable up to 200 mg) compared with no drug (45% vs 23%; p<0.001).
Harrison [1981] showed in 116 patients who suffered from OHCA with VF refractory
to 3 shocks a similar rate of ROSC with administration of lidocaine (100 mg)
compared with no drug (55% vs 54%; p=ns).
For the critical outcome of survival at discharge, we have identified 2 retrospective
observational studies (GRADE: very low; very serious risk of bias) with consistent
results:
Herlitz [1997] et al. showed in a single center study of 290 patients who suffered
from OHCA with VF refractory to 3 shocks a similar rate of survival rate of survival
with administration of lidocaine (50 mg, repeatable up to 200 mg) compared with
no drug (14% vs 8%; p=ns).
Harrison [1981] showed in a single center study of 116 patients who suffered from
OHCA with VF refractory to 3 shocks a similar rate of survival with administration of
lidocaine (100 mg) compared with no drug (11% vs 2%; p=ns).
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Proposed Consensus on Science
statements
Nifekalant (I) versus no nifekalant (C)
For the critical outcome of survival at discharge, we have identified one
retrospective single center study (GRADE: very low; downgraded due to very
serious risk bias, very serious indirectness and confounding) of 63 patients who
suffered from cardiac arrest upon or during hospitalization with VF/VT due to
coronary artery disease showing improved survival with administration of
nifekalant (loading dose 0.27 mg/kg followed by infusion of 0.26 mg/kg/h)
comparing with no drug in historical controls with an adjusted OR for cardiac
death of 0.26 (95% CI 0.07-0.95; P = 0.041) [Ando 2005].
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Proposed Consensus on Science
statements
Magnesium (I) versus no magnesium (C)
For the important outcome of ROSC, we have identified 3 double-blind RCT
(GRADE: moderate; downgraded due to imprecision in small study sample sizes)
with consistent results:
Fatovich [1997] et al. showed in a single center study of 67 patients who
suffered OHCA (but with ongoing CPR at ED arrival) with all rhythms a similar
rate of ROSC with administration of magnesium (5 g (20 mmol) bolus)
comparing with no drugs (23% vs 22%, p=0.97).
Allegra [2001] et al. showed in a multi-center study of 109 patients who
suffered OHCA with VF refractory to 3 shocks a similar rate of ROSC with
administration of magnesium (2 g (8 mmol) bolus) comparing with no drugs
(25% vs 19%, p=0.39).
Hassan [2002] et al. showed in a single center study of 105 patients who
suffered OHCA with VF refractory to 3 shocks or recurrent a similar rate of
ROSC with administration of magnesium (2 g (8 mmol) bolus, repeatable
once) comparing with no drugs (17% vs 13%, p=0.56).
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Proposed Consensus on Science
statements
For the critical outcome of survival at discharge, we have identified 4 double-blind RCT
(GRADE: moderate; downgraded due to imprecision in small study sample sizes) with
consistent results:
Thel [1997] et al. showed in a single centre study of 156 patients who suffered IHCA
(only ICU and general wards) with all initial rhythms (50% in VF/VT) and of all causes a
similar survival with administration of magnesium (2 g (8 mmol) bolus followed infusion
of 8 g (32 mmol) in 24 h) comparing with no drugs (21% vs 21%, p=ns). After
multivariate adjustment, the OR for survival was similar (1.22, 95% CI 0.53-2.81).
Fatovich [1997] et al. showed in a single center study of 67 patients who suffered OHCA
(but with ongoing CPR at ED arrival) with all rhythms a similar survival with
administration of magnesium (5 g (20 mmol) bolus) comparing with no drugs (1 vs 0
patients, p=0.46).
Allegra [2001] et al. showed in a multi-center study of 109 patients who suffered OHCA
with VF refractory to 3 shocks a similar survival with administration of magnesium (2 g
(8 mmol) bolus) comparing with no drugs (3.6% vs 3.7%, p=1.0; unadjusted RR of
increased survival 0.98, 95% CI 0.53-2.81).
Hassan [2002] et al. showed in a single center study of 105 patients who suffered OHCA
with VF refractory to 3 shocks or recurrent a similar survival with administration of
magnesium (2 g (8 mmol) bolus, repeatable once) comparing with no drugs (4% vs 2%,
p=0.99). Multivariate logistic regression was not possible due to the low number of
survivors (respectively 2 and 1 patient).
Dallas 2015
Proposed Consensus on Science
statements
For the critical outcome of survival with favorable neurological/functional outcome
at discharge, we have identified one single centre double-blind RCT (GRADE:
moderate) of 156 patients who suffered IHCA (only ICU and general wards, no
ED etc.) with all initial rhythms (50% in VF/VT) and of all causes showing a
similar survival with favorable neurological outcome with administration of
magnesium (2 g (8 mmol) bolus followed infusion of 8 g (32 mmol) in 24 h)
comparing with no drugs (favorable return to independent living 14.5% vs 7.5%,
p=ns; median GCS at hospital discharge 15 (IQR 15-15) vs 15 (IQR 15-15),
p=ns) [Thel 1997].
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Draft
Treatment Recommendations
There are no studies that show improved survival to hospital
discharge or functional survival with the use of antiarrhythmics
in cardiac arrest patients refractory to VF/pVT.
We suggest the use of amiodarone in adult patients who suffer
OHCA with refractory VF/pVT to improve rates of ROSC (Weak
recommendation; high confidence in effect estimate).
Clinicians might consider lidocaine or nifekalant for in adult
patients who suffer OHCA and IHCA , respectively (Weak
recommendation, very low confidence in effect estimates).
We suggest against the use of magnesium in adult patients who
are in OHCA in any rhythm (Strong recommendation, moderate
confidence in effect estimate).
Knowledge Gaps
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There is a need for sufficiently powered RCTs to detect a
difference in survival to hospital discharge or favorable
neurological outcomes
Next Steps
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