Comparison of the Analgesic Dose‐Effect Relationships of Nefopam and Oxycodone in Postoperative Pain

Abstract

The analgesic dose-effect relationship of nefopam was compared in a double-blind randomised trial with that of oxycodone in immediate postoperative pain. Nefopam 15 mg or oxycodone 4 mg was given every 10 min i.v. (maximum six times) to patients in pain after upper abdominal surgery until their wound pain (scored 0-3) disappeared. The mean pain intensity (PI), initially 2.2 in both groups, descreased by approximately the same extent for up to two doses in both groups (to 1.5 after nefopam 30 mg and to 1.1 after oxycodone 8 mg). Thereafter PI was significantly less in the oxycodone group and diminished almost linearily to 0.1 after the sixth dose (24 mg). In the nefopam group, the PI score fell to 1.1 after the fourth dose (60 mg). This seemed to be the "ceiling" effect since additional doses up to 90 mg did not result in greater pain relief. In the oxycodone group, only two patients (12%) needed maximal dosage (6 x 4 mg), one of them requiring 32 mg of oxycodone. In the nefopam group, 12 patients (75%) needed further pain relief after the maximal dosage (6 x 15 mg). In these patients, oxycodone (maximally 16 mg) gave satisfactory analgesia. Drowsiness and a decrease in the respiratory rate were the principal side-effects of oxycodone, whereas tachycardia, restlessness, sweating and nausea were more frequent after nefopam.

Respiratory and metabolic effects of oral nefopam in human volunteers.

“…This contrasts with reports conceming the parenteral use ofthe drug where increases in pulse rate (Tigerstedt et al, 1977;Tigerstedt et al, 1979) and blood pressure (Dodson, 1980) have been observed.…”

“…However increasing the dose of nefopam did not increase the severity of the respiratory depression. Clinical studies on the analgesic action of nefopam have also suggested that increasing the dose of nefopam does not necessarily increase its maximum effect (Tigerstedt et al, 1977;Tigerstedt et al, 1979). Depression of the CO2 response by nefopam suggests that it might enhance the respiratory depressant effects of other drugs, for example the narcotic analgesics.…”

“…Since other investigators have reported sweating and flushing with nefopam (De Thibault de Boesinghe et al, 1976;Tigerstedt et al, 1979;Schietzel, 1977) it may be that nefopam causes an imbalance on the side of heat loss mechanisms. This requires more detailed investigation.…”

“…Some clinical trials have compared the analgesic activity of nefopam to the narcotic analgesics (Sunshine & Laska, 1975;Tigerstedt, Sipponen, Tammisto & Turunen, 1977) and thus interest has been focused on possible respiratory depressant effects of nefopam, since this is the principal disadvantage of opioid analgesics. Gasser & Bellville (1975) Severen, 1976;Tigerstedt, Tammisto & Leander, 1979;Schietzel, 1977) and so the effects of nefopam on oral temperature were monitored.…”

The analgesic efficacy and safety of nefopam in patient-controlled analgesia after cardiac surgery: A randomized, double-blind, prospective study

“…It has been reported that 10-30% of patients given a low dose of nefopam experience nausea, usually after its first administration. 25 Nefopam may affect the incidence of nausea by modulating chemical mediators such as serotonin.…”