Assessing efficacy and safety of buccally inoculated midazolam and intravenously administered diazepam for relieving pediatric primary generalized epileptic seizures

Objective: to confirm a therapeutic equivalence and similar safety profile of “Midazolam, oromucosal (buccal) solution” and “Sibazon, solution for intravenous and intramuscular administration” used in children aged from 1 year to 18 years suffering from primary generalized and bilateral tonic, clonic and tonic-clonic seizures.Material and methods. An open-label, randomized clinical trial on efficacy and safety was conducted with 25 patients having primary generalized and bilateral tonic, clonic and tonic-clonic seizures due to epilepsy or epileptic syndrome. The study used age-appropriate doses of Midazolam with a single buccal administration as well as diazepam (Sibazon) for single intramuscular administration. Midazolam dosing was as follows: 5 mg for children of the younger age group (1 tube-dropper 5 mg/ml), 7.5 mg for children of the middle age group (1 tube-dropper 5 mg/ml and 1 tube-dropper 2.5 mg/ml), 10 mg for older children (2 tube-droppers 5 mg/ml). The drug effectiveness was assessed by primary and secondary criteria. The number of cases of drug administration in each group was used as the primary criteria, in which the convulsions ended up within 10 minutes after using the drug and did not resume within 60 minutes after drug administration. The following criteria were used as secondary: no repeated convulsive seizures within 24 hours after drug administration, no repeated convulsive seizure within 48 hours after drug administration, time before repeated convulsive seizure within 48 hours after drug administration. Clinical assessment was carried out according to clinical data, electroneurophysiologic (electroencephalographic) studies, electrocardiography, clinical blood and urine tests, aswell as biochemical blood tests by measuring glucose, total protein, albumin, total bilirubin, cholesterol, aspartate aminotransferase, alanine aminotransferase, creatine phosphokinase, alkaline phosphatase, creatinine, urea, and creatinine clearance level.Results. Compliance with the first efficacy criterion after using Midazolam and Sibazon was observed in 11 (84.6%) and 9 (75%) patients in Group 1 and Group 2, respectively, showing insignificant differences (Fisher's exact test (FET): p=0.645). The number of no cases of repeated convulsive seizure within 24 hours after drug administration differed significantly and was 12 (92.3%) and 6 (50%), respectively (FET: p=0.030). The number of cases with no second seizures within 48 hours after drug administration in Group 1 and Group 2 was 12 (92.3%) and 5 (41.7%), respectively, showing insignificant differences (FET: p=0.0112). No serious adverse events were reported during the study. No patients cancelled participation in the study due to developed adverse event.Conclusion. The data obtained evidence about compatibility of therapeutic efficacy profile and similar safety profile for “Midazolam, oromucosal (buccal) solution” and “Sibazon, solution for intravenous and intramuscular administration” that agrees with multiple data of earlier studies.

Intraoperative tranexamic acid use in patients undergoing excision of intracranial meningioma: Randomized, placebo-controlled trial

Background: Intracranial meningioma resection is associated with substantial intraoperative bleeding. Intraoperative tranexamic acid (TXA) use can reduce bleeding in a variety of surgical procedures. The objective of this study was to evaluate the effects of TXA treatment on blood loss and transfusion requirements in patient undergoing resection of intracranial meningioma. Methods: We conducted a prospective, randomized double-blind clinical study. The patient scheduled to undergo excision of intracranial meningioma were randomly assigned to receive intraoperatively either intravenous TXA or placebo. Patients in the TXA group received intravenous bolus of 20 mg/kg over 20 min followed by an infusion of 1 mg/kg/h up to surgical wound closure. Efficacy was evaluated based on total blood loss and transfusion requirements. Postoperatively, thrombotic complications, convulsive seizure, and hematoma formation were noted. Results: Ninety-one patients were enrolled and randomized: 45 received TXA (TXA group) and 46 received placebo (group placebo). Total blood loss was significantly decreased in TXA group compared to placebo (283 ml vs. 576 ml; P < 0.001). Transfusion requirements were comparable in the two groups (P = 0.95). The incidence of thrombotic complications, convulsive seizure, and hematoma formation was similar in the two groups. Conclusion: TXA significantly reduces intraoperative blood loss, but did not significantly reduced transfusion requirements in adults undergoing resection of intracranial meningioma.