Article

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

A. P.-H. P. Hôpital Bicêtre, Département d'Anaesthésie-Réanimation, F-94275, Le Kremlin-Bicêtre, University Paris-Sud, Laboratoire d'anaesthésie, Faculté de Médecine de Bicêtre, F-94275, Le Kremlin-Bicêtre, France.
British Journal of Clinical Pharmacology (impact factor: 2.96). 12/2007; 64(5):686-93. DOI:10.1111/j.0306-5251.2007.02960.x pp.686-93
Source: PubMed

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.

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    Article: Median effective dose (ED50) of paracetamoland nefopam for postoperative pain: isobolographic analysis of their antinociceptive interaction
    Van Elstraete Alain, Sitbon Philippe
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    ABSTRACT: Background. The analgesic efficacy of nefopam and of paracetamol has been shown in the postoperative period after mild- and moderate-pain surgery. The aim of this study was to define the median effective analgesic doses of each drug and of their combination, in order to determine the nature of their interaction.Methods. Ninety adult patients scheduled to undergo tonsillectomy under general anesthesia were enrolled in one out of three groups: nefopam group, or paracetamol group, or nefopam-paracetamol group. The median effective dose for each drug and also for their combination was defined using an up-and-down sequential allocation technique. The analgesic interaction of their combination was assessed using an isobolographic analysis.Results. The median effective analgesic dose (median value and 95% confidence interval) of nefopam and paracetamol were 21.7 mg (21.1-22.3 mg) and 628 mg (600-656 mg), respectively. The median effective analgesic doses of the combination were 8.9 mg (8.7-9.1 mg) for nefopam and 265 mg (256-274 mg) for paracetamol. The isobolographic analysis demonstrated a supra-additive interaction of the two drugs.Conclusion. The combination of nefopam and paracetamol produces effective analgesia with a synergistic interaction.
    Minerva anestesiologica 03/2013; 79(3):232-9. · 2.66 Impact Factor
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Keywords

1-10 numerical pain score
 
classical dose-probability curve fitting
 
clinical purposes
 
continual reassessment method
 
continuous reassessment method
 
decreasing doses
 
effective dose
 
increased incidence
 
infusion
 
initial dose
 
maximum likelihood technique
 
moderate pain
 
nefopam
 
Nefopam 60 mg
 
pain intensity >3
 
Patients
 
postoperative period
 
reasonable accuracy
 
subsequent doses
 
usual dose