Status Epilepticus ================== þ Midazolam IM is better than Valium IV for Status Epilepticus - McMullan, J., C. Sasson, et al. (2010). "Midazolam versus diazepam for the treatment of status epilepticus in children and young adults: a meta-analysis." Academic emergency medicine : official journal of the Society for Academic Emergency Medicine 17(6): 575-582. BACKGROUND: Rapid treatment of status epilepticus (SE) is associated with better outcomes. Diazepam and midazolam are commonly used, but the optimal agent and administration route is unclear. OBJECTIVES: The objective was to determine by systematic review if nonintravenous (non-IV) midazolam is as effective as diazepam, by any route, in terminating SE seizures in children and adults. Time to seizure cessation and respiratory complications was examined. METHODS: We performed a search of PubMed, Web of Knowledge, Embase, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, American College of Physicians Journal Club, Cochrane Central Register of Controlled Trials, the Cumulative Index to Nursing and Allied Health Literature, and International Pharmaceutical Abstracts for studies published January 1, 1950, through July 4, 2009. English language quasi-experimental or randomized controlled trials comparing midazolam and diazepam as first-line treatment for SE, and meeting the Consolidated Standards of Reporting Trials (CONSORT)-based quality measures, were eligible. Two reviewers independently screened studies for inclusion and extracted outcomes data. Administration routes were stratified as non-IV (buccal, intranasal, intramuscular, rectal) or IV. Fixed-effects models generated pooled statistics. RESULTS: Six studies with 774 subjects were included. For seizure cessation, midazolam, by any route, was superior to diazepam, by any route (relative risk [RR] = 1.52; 95% confidence interval [CI] = 1.27 to 1.82). Non-IV midazolam is as effective as IV diazepam (RR = 0.79; 95% CI = 0.19 to 3.36), and buccal midazolam is superior to rectal diazepam in achieving seizure control (RR = 1.54; 95% CI = 1.29 to 1.85). Midazolam was administered faster than diazepam (mean difference = 2.46 minutes; 95% CI = 1.52 to 3.39 minutes) and had similar times between drug administration and seizure cessation. Respiratory complications requiring intervention were similar, regardless of administration route (RR = 1.49; 95% CI = 0.25 to 8.72). CONCLUSIONS: Non-IV midazolam, compared to non-IV or IV diazepam, is safe and effective in treating SE. Comparison to lorazepam, evaluation in adults, and prospective confirmation of safety and efficacy is needed. MIDAZOLAM DRIP -------------- Study found no failures with IV midazolam drip: about 0.22 mg/kg bolus (10-15 mg. bolus for adult) and about 0.17 mg/kg/hr (12 mg/hr for adult). All stopped seizing in <100 seconds. Mean of 30 hours on this, max of 70 hours. Used as alternative to barbiturate coma. Even worked well with theophylline and tricyclic overdose seizures. [Kumar A, Black T. Intravenous midazolam for the treatment of refractory status epilepticus. Crit Care Med 1992;20:483 et seq] Treiman DM. The role of benzodiazepines in the managememt of status epilepticus. Neurology 1990; 40:32. ------------------------------------------------------------------------------ benzodiazepines have complex effects; they enhance GABA-ergic inhibition and thus decrease rate of neuron firing. Benzodiazepine receptors are surmised to be close to GABA receptors on the neuron. 47 studies since 1965 attest to efficacy and safety of BZD's for status (about 80% respond). Suggests treating seizures with GLUCOSE and THIAMINE then Ativan 0.1 mg/kg IV (1-2 mg; can go up to 10-12 mg) then loading with Dilantin 20 mg/kg. Give up to two extra 5 mg/kg. doses of Dilantin if needed, then go to Phenobarb at 20 mg/kg. Pentobarb coma is last resort. Shaner et al. Neurology 1988; 38:202. And: Gabor J Epilepsy 1990; 3:3 ------------------------------------------------------------------------------ Recommends using phenbarb first instead of benzodiazepines; just as effective. (Give 12-15mg/kg; can give at 100mg/min IV) Lacey. J Ped 1986; 108:771 ----------------------------------------------------------------------------- Ativan is drug of choice for peds in status. (81-92% success with 0.05 mg/kg) Chiulli et al. JEM 1991; 9:13 ----------------------------------------------------------------------------- Argues for Ativan over Valium; less likely to need intubation (27% vs. 73%) Rashkin MC et al. Pentobarbital treatment of refractory status epilepticus ----------------------------------------------------------------------------- Hoppu et al. Acta Pediatr Scand 1981; 70:369 ----------------------------------------------------------------------------- Rectal use of IV formulation of Valium 0.5mg/kg; might be useful when can't get an IV right away; reported to work in 1-15'. Morris HH. Lidocaine, a neglected anticonvulsant? South Med J 1979; 72:1564 ----------------------------------------------------------------------------- Case report of standard cardiac doses and drips of lidocaine effective for refractory seizures.