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Postresuscitation Seizure Prophylaxis

Question Type:
Full Question:
Among adults with ROSC after cardiac arrest in any setting (P), does seizure prophylaxis  (I), compared with compared with no prophylaxis  (C), change  (O)?
Consensus on Science:
For the critical outcome of survival with favorable neurologic/functional outcome, moderate-quality evidence (downgraded for indirectness) from 2 prospective double-blinded randomized clinical trials involving a total of 312 subjects(1986, 397; Longstreth 2002, 506) and 1 nonrandomized prospective clinical trial that used historic controls with 107 subjects(Monsalve 1987, 244) detected no benefit of seizure prophylaxis. In 1 block randomized trial,(Longstreth 2002, 506) OHCA patients with ROSC received either placebo, diazepam, magnesium sulfate, or diazepam plus magnesium sulfate. The percentage of patients independent at 3 months was 25.3% (19/75) in the placebo group, 34.7% (26/75) in the magnesium group, 17.3% (13/75) in the diazepam group, and 17.3% (13/75) in the diazepam plus magnesium group (for magnesium: RR, 1.22; 95% CI, 0.81–1.83). After adjusting for baseline imbalances, outcomes did not differ between groups. In a trial of thiopental versus placebo within 1 hour of ROSC,(1986, 397-403) 1-year survival with good cerebral function was 15% (20/131) in the placebo group and 18% (24/131) in the thiopental group (RR, 1.20; 95% CI, 0.70–2.06). After multivariate adjustment, groups did not differ (OR, 1.18; 95% CI, 0.76–1.84). A nonrandomized clinical trial(Monsalve 1987, 244) showed no benefit of barbiturate therapy in comatose post–cardiac arrest patients using a combination of thiopental and phenobarbital when compared with historic controls. In this study, survival to hospital discharge with favorable neurologic outcome was 38% (20/53) in the barbiturate group and 26% (14/54) in the historic control group (ARR, 11.8%; 95% CI, −5.8 to 28.5; or 118 more patients/1000; 95% CI, 58 fewer to 285 more patients/1000). One case series showed that 9 of 10 patients with anesthesia-associated cardiac arrest survived with good neurologic outcome when single-dose phenytoin was administered early after ROSC.(Aldrete 1981, 474) For the important outcome of seizure prevention, we identified low-quality evidence downgraded for indirectness from 2 prospective double-blinded RCTs(BRCT Study Group 1986, 397; Longstreth 2002, 506) showing no benefit of seizure prophylaxis. In 1 trial of thiopental treatment,( BRCT Study Group 1986, 397-403) 21% (28/131) of control subjects and 13% (17/131) of thiopental-treated subjects had seizures (ARR, −8.4%; 95% CI, −17.5 to 0.8; 84 fewer patients/1000; 95% CI, 175 fewer to 8 more patients/1000). The incidence of seizures in a second trial(Longstreth 2002, 506) was 11.9% in all treatment groups (double placebo, magnesium plus placebo, diazepam plus placebo, and diazepam plus magnesium).
Treatment Recommendation:
We suggest against routine seizure prophylaxis in post–cardiac arrest patients (weak recommendation, very-low-quality evidence). Values, Preferences, and Task Force Insights In making this recommendation, the task force acknowledged the lack of confidence in a treatment effect on the critical outcome of survival with good neurologic function treatment. The task force also considered that seizure prophylaxis in other forms of acute brain injuries is not associated with improved outcomes, and that most drugs have significant side effects.
CoSTR Attachments:
Copy of Geocadin and Stacey Papers-ILCOR SZ PR and TR review.xlsx    
Copy of Geocadin and Stacey-Bias-ILCOR SZ PR and TR.xlsx    

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