How did lorazepam come to be a first-line agent for treating status epilepticus?
A Comparison of Four Treatments for Generalized Convulsive Status Epilepticus
Treiman D et al. NEJM (September 1998)
Bottom line: This five-year randomized, double-blind, multicenter trial compared initial treatment of generalized convulsive status epilepticus. Four intravenous regimens were evaluated: diazepam (0.15 mg per kilogram of body weight) followed by phenytoin (18 mg per kilogram), lorazepam (0.1 mg per kilogram), phenobarbital (15 mg per kilogram), and phenytoin (18 mg per kilogram). The 570 enrolled patients were classified as having either overt status epilepticus (defined as easily visible generalized convulsions) or subtle status epilepticus (indicated by coma and ictal discharges on EEG, with or without subtle convulsive movements). Treatment success was defined as cessation of motor and electroencephalographic seizure activity within 20 minutes of drug infusion and no return of seizure activity within 40 minutes. Among the 384 patients with overt status epilepticus, lorazepam resulted in treatment success in 64.9% of patients as compared to 58.2% for phenobarbitol, 55.8% for diazepam and phenytoin, and 43.6% for phenytoin alone (P=0.02). No significant differences were found among the treatments for the 134 patients with subtle status epilepticus and there were no differences among treatments with respect to recurrence during the 12-hour study period, incidence of adverse reactions, or outcome at 30 days. Overall, lorazepam was found to be more effective than phenytoin in patients with overt status epilepticus (P=0.002). Although it was no more efficacious than phenobarbital or diazepam and phenytoin, it is easier to use.
Why isn’t preoperative prophylactic revascularization recommended for stable CAD prior to non-cardiac surgery?
Coronary-Artery Revascularization before Elective Major Vascular Surgery (CARP)
McFalls E et al. NEJM (December 2004)
Bottom Line: This randomized controlled trial, conducted at 18 Veterans Affairs medical centers, aimed to determine the benefit of coronary-artery revascularization before elective major vascular surgery. Indications for a vascular operation included expanding abdominal aortic aneurysm (33%) or arterial occlusive disease of the legs (67%). Patients at increased risk for perioperative cardiac complications and clinically significant coronary artery disease were randomly assigned to undergo either revascularization, via percutaneous coronary intervention or bypass, or no revascularization before surgery. The primary outcome was long-term mortality at 2.7 years after randomization, at which time mortality in the revascularization group was 22% compared to 23% in the non-revascularization group (relative risk, 0.98; 95 percent confidence interval, 0.70 to 1.37; P=0.92). Results showed no significant difference in mortality between the intervention and comparator groups. However, a postoperative myocardial infarction occurred in 12% of the intervention group and 14% of the comparator group within 30 days after surgery (P=0.37). Based on these findings, the authors do not recommend a strategy of coronary-artery revascularization before elective vascular surgery in patients with stable cardiac symptoms.
What’s the evidence for using hydroxyurea to reduce pain crises in sickle cell anemia?
Effect of Hydroxyurea on the Frequency of Painful Crises in Sickle Cell Anemia (MSH)
Charache S et al. NEJM (May 1995)
Bottom Line: This double-blind, randomized clinical trial studied the efficacy of hydroxyurea therapy in reducing the frequency of painful crises in adults with sickle cell anemia. The study included 299 patients with sickle cell anemia and a history of three or more painful crises per year. Patients were randomized to receive either hydroxyurea (n = 152) or placebo (n = 147) and it was found that those treated with hydroxyurea had a lower annual rate of crises compared to those given placebo (median, 2.5 vs. 4.5 crises per year, P<0.001). The median times to the first and second crises were also longer with hydroxyurea treatment, at 3.0 vs. 1.5 months for hydroxyurea vs. placebo respectively for the first crisis (P = 0.01) and 8.8 vs. 4.6 months for the second crisis (P<0.001). Fewer patients in the hydroxyurea group experienced chest syndrome or required transfusions and the therapy was well-tolerated with no significant adverse effects. The study suggested that hydroxyurea therapy can improve the clinical course of sickle cell anemia. However, it was suggested that maximum tolerated doses may not be necessary for therapeutic effect and careful monitoring and use of lower doses was recommended.
