Effective dose of nefopam in 80% of patients (ED80): a study using the continual reassessment method

Abstract

The effective dose in 50% of patients (ED(50)) is far from being relevant for clinical purposes. We used the continual reassessment method (CRM) to determine the effective dose of nefopam in 80% of the patients suffering from moderate pain in the postoperative period (ED(80)). Patients with a pain intensity >3 on a 1-10 numerical pain score (NPS) received increasing or decreasing doses of nefopam (20, 30, 40, 60, 80 mg) postoperatively. The criterion of success was a NPS <or=3, 30 min after the beginning of infusion. The initial dose was 20 mg and the subsequent doses were determined by the continuous reassessment method (CRM). The data were also fitted a posteriori with the maximum likelihood technique. Twenty-four patients were enrolled. Nefopam 60 mg gave a probability of success of 0.818 (95% credibility interval 0.606-0.941). Using the maximum likelihood technique, we determined an ED(50) of 27.3 mg and a dose leading to a probability of 0.8 (ED(80)) of 74.4 mg. We did not observe a high incidence of side-effects. The ED(80) of nefopam, close to 60 mg is higher than the usual dose of 20 mg. The CRM allowed us to determine the ED(80) of nefopam with reasonable accuracy in a small number of patients as compared with the classical dose-probability curve fitting. We did not observe an increased incidence of side-effects when compared with the literature or to our previous studies.