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Antiarrhythmic Drugs for Cardiac Arrest

Question Type:
Intervention
Full Question:
Among adults who are in cardiac arrest in any setting (P), does does administration of antiarrhythmic drugs (eg, amiodarone, lidocaine, other)  (I), compared with compared with not using antiarrhythmic drugs (no drug or placebo)  (C), 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 (O)?
Consensus on Science:
Comparative data on the use of antiarrhythmic drugs were identified for amiodarone, lidocaine, magnesium, and nifekalant. The data reviewed for magnesium only addressed the use of this drug for undifferentiated VF/VT and not the treatment of torsades de pointes or known hypomagnesemic patients. Nifekalant is only available in certain regions.

Amiodarone (I) Versus No Amiodarone (C)

For the critical outcome of survival with favorable neurologic/functional outcome at discharge, there was moderate-quality evidence (downgraded due to serious risk of indirectness) from 1 RCT involving 504 OHCA patients, which detected no difference with administration of amiodarone (300 mg after 1 mg of adrenaline) compared with no drug (7.3% versus 6.6%; P=not significant [NS]; RR, 1.11; 95% CI, 0.59–2.10).(Kudenchuk 1999, 871)

For the critical outcome of survival at discharge, there was moderate-quality evidence (downgraded due to serious risk of indirectness) from 1 RCT involving 504 OHCA patients that detected no difference with the administration of amiodarone (300 mg after 1 mg of adrenaline) compared with no drug (13.4% versus 13.2%; P=NS; RR, 1.02; 95% CI, 0.65–1.59).(Kudenchuk 1999, 871)

For the important outcome of ROSC, there was moderate-quality evidence (downgraded due to serious risk of indirectness) from 1 RCT involving 504 OHCA patients that showed higher ROSC with administration of amiodarone (300 mg after 1 mg of adrenaline) compared with no drug (64% versus 41%; P=0.03; RR, 1.55; 95% CI, 1.31–1.85).(Kudenchuk 1999, 871)

Lidocaine (I) Versus No Lidocaine (C)

For the critical outcome of survival at discharge, there was very-low-quality evidence (downgraded for very serious risk of bias and serious indirectness) from 2 retrospective observational studies that did not detect a difference with treatment. In 290 OHCA patients, rates of survival with administration of lidocaine (50 mg, repeatable up to 200 mg) or with no drug did not differ (14% versus 8%; P=NS).(Herlitz 1997, 199) In 116 OHCA patients, survival with administration of lidocaine (100 mg) compared with no drug did not differ (11% versus 2%; P=NS).(Harrison 1981, 420)

For the important outcome of ROSC, there was very-low-quality evidence (downgraded for very serious risk of bias and serious indirectness) from 2 retrospective observational single-center studies, which showed conflicting results. In 290 OHCA patients, rates of ROSC were not different after administration of lidocaine (50 mg, repeatable up to 200 mg) compared with no drug (45% versus 23%; P

Magnesium (I) Versus No Magnesium (C)

For the critical outcome of survival with favorable neurologic/functional outcome at discharge, there was low-quality evidence (downgraded for serious risk of imprecision and indirectness) from 1 single-center RCT of 156 IHCA patients with all initial rhythms (50% in VF/VT), which showed similar survival with favorable neurologic outcome with administration of magnesium (2 g [8 mmol] bolus followed by infusion of 8 g [32 mmol] in 24 hours) compared with no drugs (favorable return to independent living 14.5% versus 7.5%; P=NS; RR, 1.93; 95% CI, 0.75–4.96; median Glasgow Coma Scale [GCS] score at hospital discharge 15 [interquartile range, 15–15] versus 15 [interquartile range, 15–15]; P=NS).(Thel 1997, 1272)

For the critical outcome of survival at discharge, there was low-quality evidence (downgraded for serious risk of imprecision and indirectness) from 4 RCTs, which showed no differences in outcome with treatment. One single-center RCT of 156 IHCA patients with all initial rhythms (50% in VF/VT) showed similar survival with administration of magnesium (2 g [8 mmol] bolus followed by infusion of 8 g [32 mmol] in 24 hours) compared with no drugs (21% versus 21%; P=NS; adjusted OR, 1.22; 95% CI, 0.53–2.81).(Thel 1997, 1272) One single-center trial of 67 OHCA patients with all rhythms and ongoing CPR at ED arrival detected no difference with administration of magnesium (5 g [20 mmol] bolus) compared with no drugs (1 versus 0 patients; P=0.46).(Fatovich 1997, 237)

A multicenter study of 109 OHCA patients with VF did not detect a difference in survival with administration of magnesium (2 g [8 mmol] bolus) compared with no drugs (3.6% versus 3.7%; P=1.0; unadjusted RR of increased survival, 0.98; 95% CI, 0.53–2.81).(Allegra 2001, 245-249) A single-center trial of 105 OHCA patients with VF did not detect a difference in survival with administration of magnesium (2 g [8 mmol] bolus, repeatable once) compared with no drugs (4% versus 2%; P=0.99).(Hassan 2002, 57)

For the important outcome of ROSC, there was low-quality evidence (downgraded for serious risk of imprecision and indirectness) from 3 RCTs that did not detect a difference with treatment. One single-center trial of 67 OHCA patients with all rhythms and ongoing CPR at ED arrival detected no difference with administration of magnesium (5 g [20 mmol] bolus) compared with no drugs (23% versus 22%; P=0.97).(Fatovich 1997, 237) A multicenter study of 109 OHCA patients with VF did not detect difference in ROSC rates with administration of magnesium (2 g [8 mmol] bolus) compared with no drugs (25% versus 19%; P=0.39).(Allegra 2001, 245) A single-center trial of 105 OHCA patients with VF did not detect a difference in ROSC rates with administration of magnesium (2 g [8 mmol] bolus, repeatable once) compared with no drugs (17% versus 13%; P=0.56).(Hassan 2002, 57)

Nifekalant (I) Versus No Nifekalant (C)

For the critical outcome of survival at discharge, there was very-low-quality evidence (downgraded for very serious risk of bias, very serious indirectness, and imprecision) from 1 retrospective single-center observational study of 63 patients with cardiac arrest upon or during hospitalization, which found improved survival with administration of nifekalant (loading dose 0.27 mg/kg followed by infusion of 0.26 mg/kg/h) compared with no drug in historic controls (OR for cardiac death, 0.26; 95% CI, 0.07–0.95; P=0.041).(Ando 2005, 647)
Treatment Recommendation:
We suggest the use of amiodarone in adult patients with refractory VF/pVT to improve rates of ROSC (weak recommendation, moderate-quality evidence).

We suggest the use of lidocaine or nifekalant as an alternative to amiodarone in adult patients with refractory VF/pVT (weak recommendation, very-low-quality evidence).

We recommend against the routine use of magnesium in adult patients (strong recommendation, low-quality evidence).

Values, Preferences, and Task Force Insights

In making these recommendations, we considered the reported beneficial effects of amiodarone on the important outcome of survival to hospital admission. We acknowledged that there was the uncertainty about any beneficial or harmful effects of these drugs on the critical outcomes of survival or favorable neurologic survival. Although the evidence supporting their use is weaker, in making a recommendation for lidocaine and nifekalant as alternatives to amiodarone, the task force recognized that amiodarone is not available or currently used in some countries. The small quantity of new data made the task force place value on not changing current clinical practice.
CoSTR Attachments:
AAs section of the COSTR document for steve lin- SLin edits 20150223.docx    
ALS 428 should-amiodarone-vs-placebo-be-used-for-adults-who-are-in-cardiac-arrest-in-any-setting.pdf    
ALS 428 should-lidocaine-vs-no-lidocaine-be-used-for-adults-who-are-in-cardiac-arrest-in-any-setting.pdf    
ALS 428 should-magnesium-vs-no-magnesium-be-used-for-adults-who-are-in-cardiac-arrest-in-any-setting.pdf    
ALS 428 should-nifekalant-vs-no-nifekalant-be-used-for-adults-who-are-in-cardiac-arrest-in-any-setting.pdf    

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