Continuous infusion of midazolam in the treatment of refractory generalized convulsive status epilepticus

Abstract

We studied the efficacy and safety of midazolam given as a continuous infusion in the treatment of refractory generalized convulsive status epilepticus (RGCSE). We carried out a prospective, open study, in 19 patients (11 men) with RGCSE in the intensive care unit at Firat Medical Center in Elazig. When intravenous administration of 0.3 mg/kg diazepam (three times at 5-min intervals), 20 mg/kg phenytoin, and 20 mg/kg phenobarbital failed to bring the episode under control, patients were administered an intravenous bolus of midazolam (200 microg/kg) followed by a continuous infusion at 1 microg/kg min. The dose was increased by 1 microg/kg min every 15 min until the episode of seizure was brought under control. The time from beginning of treatment to control of seizures, infusion rate, and side-effects were monitored. The mean age of the patients was 40.4 years (range 16-87 years). The clinical etiology of RGCSE was idiopathic epilepsy (6 cases), anoxicischemic cerebral insult due to cardiac arrest (3), viral encephalitis (2), intrahemispheric hematoma due to hemorrhagic stroke (1), cerebral infarct due to ischemic stroke (1), pituitary adenoma (1), post-traumatic epilepsy (1), renal failure (1), tuberculous meningitis (1), and unknown (2). In eighteen (94.7%) patients, seizures were completely controlled in a mean time of 45 min (range, 5-120 min) at a mean infusion rate of 8 microg/kg min (range, 3-21 microg/kg min). In one patient seizures did not stop. Midazolam administration did not cause any significant change in blood pressure, heart rate, oxygen saturation, or respiratory status. The mean time to full consciousness for patients after stopping the infusion was 1.6 hours (range, 2.0-8.5 hours). The mean infusion duration of midazolam was 14.5 hours (range, 12-25 hours). Midazolam is an effective and safe drug to control RGCSE, and may represent a substantial improvement over current therapeutic approaches such as pentobarbital anesthesia.

High-dose midazolam infusion for refractory status epilepticus

“…7,[12][13][14][15] The suggested maximum MDZ infusion rate of 0.4 mg/kg/h in the low-dose group compares well to the typically reported doses in contemporary reports from that time (0.39-0.8 mg/kg/h). [16][17][18][19] In subsequent reports, isolated cases received high cIV-MDZ doses in adult (1.26 and 4.0 mg/kg/h) 20,21 and pediatric (1.92 mg/kg/h) RSE, 22 but no large series has investigated this approach. Recent guidelines advocate for Ischemic stroke 2 (7) 3 (3) Trauma 2 (7) 11 (11) Tumor 2 (7) 6 (6) Toxic-metabolic 5 (17) 6 (6) higher maximum cIV-MDZ doses 2,23 despite a lack of evidence showing the benefit and safety of this approach.…”

Admissions to paediatric intensive care units (PICU) with refractory convulsive status epilepticus (RCSE): A two-year multi-centre study

“…In general, cIV therapy to treat RCSE is associated with an increased risk of hypotension and respiratory depression, regardless of drug [43,[54][55][56][57]. This risk may be lower with diazepam or midazolam than with thiopentone [14,30,[58][59][60].…”

The anaesthesiologist in the intensive care unit

“…In a recent trial a midazolam bolus of 0.2 mg/kg followed by an infusion range of 3-21 mg/kg per min continued for 12-25 h controlled 18 of 19 patients with refractory status epilepticus (RSE) [44]. The regimen for propofol use in RSE is an initial bolus of 2 mg/kg repeated if seizures continue followed by an infusion of 5-10 mg/kg per h maintained for 12-24 h [43 . ].…”