Nefopam is a non-opioid analgesic agent with a central mode of action involving activation of descending pain-modulating pathways and inhibition of synaptosomal uptake of hydroxytryptamine, norepinephrine and dopamine. Adverse effects during therapeutic use and after overdose of nefopam are known to involve the central nervous system (confusion and convulsions), the cardiovascular system (tachycardia and palpitations) and the kidneys (oliguria and renal failure). We report a death after nefopam overdose in a young woman who exhibited many of these features. It is only the second case of death after nefopam overdose in the literature. (+info)
Fatal overdosage with nefopam (Acupan).
This paper presents a fatality due to massive, intravenous self-administration of nefopam (Acupan), a non-opiate central analgesic, in a 37-year-old female. Nefopam was measured in various postmortem samples by means of high-pressure liquid chromatography coupled to mass spectrometry via an ionspray interface. Heart blood concentration was 4.38 microg/mL and exceeded by approximately 30 times the highest therapeutic levels with the usual reservations concerning possible postmortem redistribution. This is only the third case of death following nefopam overdose reported in the literature. (+info)
Randomized prospective study of the analgesic effect of nefopam after orthopaedic surgery.
BACKGROUND: Balanced postoperative analgesia combines non-narcotic drugs and opioids. We organized a large study to evaluate nefopam analgesia and tolerance in combination with morphine for patient-controlled analgesia (PCA) after orthopaedic surgery. METHODS: Two hundred and one patients scheduled to undergo hip arthroplasty were included in this multicentre (n=24), double-blind, randomized study comparing nefopam (20 mg every 4 h for 24 h) with placebo, the first dose being infused peroperatively. The primary outcome measure was the cumulative morphine dose received postoperatively by PCA over 24 h. Secondary outcome measures were the amount of morphine received as a loading dose in the postanaesthesia care unit (PACU) and during the 24-h observation period, and pain assessments using a visual analogue scale (VAS) and a verbal pain scale (VPS), patient's satisfaction with analgesia and treatment tolerance. RESULTS: The two groups were comparable with respect to their characteristics and preoperative pain assessment. PCA-administered morphine over 24 h was significantly less for the nefopam group than the control group (21.2 (15.3) and 27.3 (19.2) mg respectively; P=0.02). This morphine-sparing effect was greater (35.1%) for patients with severe preoperative pain (VAS>30/100). For the entire study period (loading dose and PCA), morphine use was less for the nefopam group (34.5 (19.6) vs 42.7 (23.6) mg; P=0.01). Pain VAS at PACU arrival and during the whole PACU period was significantly lower for the nefopam than for the placebo group (P=0.002 and 0.04 respectively). Patient satisfaction was similar for the nefopam and placebo groups. CONCLUSION: In combination with PCA morphine, nefopam gives significant morphine-sparing with lower immediate postoperative pain scores without major side-effects. This analgesic effect seems to be particularly notable for patients with intense preoperative pain. (+info)
Nefopam, a nonsedative benzoxazocine analgesic, selectively reduces the shivering threshold in unanesthetized subjects.
BACKGROUND: The analgesic nefopam does not compromise ventilation, is minimally sedating, and is effective as a treatment for postoperative shivering. The authors evaluated the effects of nefopam on the major thermoregulatory responses in humans: sweating, vasoconstriction, and shivering. METHODS: Nine volunteers were studied on three randomly assigned days: (1) control (saline), (2) nefopam at a target plasma concentration of 35 ng/ml (low dose), and (3) nefopam at a target concentration of 70 ng/ml (high dose, approximately 20 mg total). Each day, skin and core temperatures were increased to provoke sweating and then reduced to elicit peripheral vasoconstriction and shivering. The authors determined the thresholds (triggering core temperature at a designated skin temperature of 34 degrees C) by mathematically compensating for changes in skin temperature using the established linear cutaneous contributions to control of each response. RESULTS: Nefopam did not significantly modify the slopes for sweating (0.0 +/- 4.9 degrees C. microg-1. ml; r2 = 0.73 +/- 0.32) or vasoconstriction (-3.6 +/- 5.0 degrees C. microg-1. ml; r2 = -0.47 +/- 0.41). In contrast, nefopam significantly reduced the slope of shivering (-16.8 +/- 9.3 degrees C. microg-1. ml; r2 = 0.92 +/- 0.06). Therefore, high-dose nefopam reduced the shivering threshold by 0.9 +/- 0.4 degrees C (P < 0.001) without any discernible effect on the sweating or vasoconstriction thresholds. CONCLUSIONS: Most drugs with thermoregulatory actions-including anesthetics, sedatives, and opioids-synchronously reduce the vasoconstriction and shivering thresholds. However, nefopam reduced only the shivering threshold. This pattern has not previously been reported for a centrally acting drug. That pharmacologic modulations of vasoconstriction and shivering can be separated is of clinical and physiologic interest. (+info)
Nefopam and ketamine comparably enhance postoperative analgesia.
Opioids alone sometimes provide insufficient postoperative analgesia. Coadministration of drugs may reduce opioid use and improve opioid efficacy. We therefore tested the hypothesis that the administration of ketamine or nefopam to postoperative patients with pain only partly alleviated by morphine reduces the amount of subsequent opioid necessary to produce adequate analgesia. Patients (n=77) recovering from major surgery were given up to 9 mg of IV morphine. Those who still had pain were randomly assigned to blinded administration of 1) isotonic saline (control group; n=21), 2) ketamine 10 mg (ketamine group; n=22), or 3) nefopam 20 mg (nefopam group; n=22). Three-milligram morphine boluses were subsequently given at 5-min intervals until adequate analgesia was obtained, until 60 min elapsed after the beginning of study drug administration, or until ventilation became insufficient (respiratory rate <10 breaths/min or saturation by pulse oximetry <95%). Supplemental morphine (i.e., after test drug administration) requirements were significantly more in the control group (mean +/- sd; 17 +/- 10 mg) than in the nefopam (10 +/- 5 mg; P <0.005) or ketamine (9 +/- 5 mg; P <0.001) groups. Morphine titration was successful in all ketamine and nefopam patients but failed in four control patients (two because of respiratory toxicity and two because of persistent pain). Tachycardia and profuse sweating were more frequent in patients given nefopam, and sedation was more intense with ketamine; however, the incidence of other potential complications did not differ among groups. (+info)
Median effective dose (ED50) of nefopam and ketoprofen in postoperative patients: a study of interaction using sequential analysis and isobolographic analysis.
BACKGROUND: The analgesic efficacy of ketoprofen has been shown after moderate- and severe-pain surgery, and the analgesic efficacy of nefopam has been shown after moderate-pain surgery. The aim of this study was to define the median effective analgesic doses of each drug and to determine whether the interaction of nefopam and of ketoprofen is synergistic. METHODS: Seventy-two patients scheduled to undergo moderately painful surgery were enrolled in one of three groups. The dose of nefopam and ketoprofen received by a particular patient was determined by the response of the previous patient of the same group, using an up-and-down technique. Initial doses were 18 and 40 mg, with dose adjustment intervals of 2 and 5 mg, in the nefopam and ketoprofen groups, respectively. The initial doses of nefopam and ketoprofen were 8 and 20 mg, respectively, in the nefopam-ketoprofen group, with the same dose adjustment intervals. Analgesic efficacy was defined as a decrease to less than 3 on a 0-10 numeric pain scale, 45 min after the beginning of drug infusion. RESULTS: The median effective analgesic dose (median value and 95% confidence interval) of nefopam and ketoprofen were, respectively, 28 mg (17-39 mg) and 30 mg (14-46 mg). The median effective analgesic dose of the combination was 1.75 mg (0.9-2.3 mg) for nefopam and 4.3 mg (2.2-6.5 mg) for ketoprofen. CONCLUSION: The isobolographic analysis demonstrated that the combination of the two drugs produces effective analgesia with an important synergistic interaction. (+info)
Effective dose of nefopam in 80% of patients (ED80): a study using the continual reassessment method.
AIMS: 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)). METHODS: 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 +info)
Analgesic efficacy of bilateral superficial cervical plexus block administered before thyroid surgery under general anaesthesia.
BACKGROUND: The use of regional anaesthesia in thyroid surgery remains controversial. This double-blind, randomized controlled study was conducted to evaluate the analgesic efficacy of bilateral superficial cervical plexus block (BSCPB) performed under general anaesthesia in patients undergoing total thyroidectomy. METHODS: Eighty-seven consecutive consenting patients were randomized to receive a BSCPB with saline (Group P, n = 29), ropivacaine 0.487% (Group R, n = 29), or ropivacaine 0.487% plus clonidine 5 microg ml(-1) (Group RC, n = 29). Sufentanil was given during the intraoperative period for a 20% increase in arterial mean pressure or heart rate in a patient with a bispectral index between 40 and 60. All patients received 4 g of acetaminophen during the first 24 h after operation. The pain score was checked every 4 h and nefopam was given for pain score >4 on a numeric pain scale. RESULTS: During surgery, the median sufentanil requirements were significantly reduced in Group RC compared with Groups R and P (0.32 vs 0.47 and 0.62 microg kg(-1); P < 0.0001). After surgery, the number of patients requiring nefopam within 24 h of surgery was significantly lower in Groups R and RC than in Group P (16 and 19 vs 25; P = 0.03). At post-anaesthetic care unit admission, median (range) pain scores were significantly lower in Groups R [3 (0-10)] and RC [3 (0-8)] than in Group P [5 (0-8), P = 0.03]. No major complications of BSCPB occurred during study. CONCLUSIONS: BSCPB with ropivacaine and clonidine improved intraoperative analgesia. BSCPB with ropivacaine or ropivaciane and clonidine was effective in reducing analgesic requirements after thyroid surgery. (+info)