Analgesia Efficacy and Haemodynamic Effects of Nefopam in Critically Ill Patients

Abstract

M anagement of pain is a challenge in intensive care unit (ICU) patients, because a description of the analgesic efficacy, tolerance, and hemodynamic effects of nefopam has never been available for such patients. Pain, Richmond Agitation Sedation Scale, respiratory parameters, and adverse drug reactions at T0 (baseline), T30 (end of infusion), T60, and T90 minutes were measured in consecutive medical-surgical ICU patients who received 20 mg of intravenous nefopam over 30 minutes. Hemodynamic variables were assessed every 15 minutes from T0 to T60 and T90. Evaluation of pain was made from a behavioral pain scale (BPS, 3Y12) or by a self-reported visual numeric rating scale (NRS, 0Y10) according to the capacity for communication. Data were analyzed for 59 patients. As early as T30, median NRS and BPS decreased markedly from T0 to a minimum level at T60 for NRS (5 [4Y7] vs 1 [1Y3]) and T90 for BPS (5 [5Y6] vs 3 [3Y4]). No marked changes were detected for Richmond Agitation Sedation Scale, ventilatory frequency, or oxygen saturation. An increase in heart rate and a decrease in mean arterial pressure, defined as a change of 15% or greater from baseline, were found in 29% and 27% of patients, respectively. For the 18 monitored patients, cardiac output increased by 19% (7%Y29%), and systemic vascular resistance decreased by 20% (8%Y28%), both maximally at T30. Heat sensation, nausea/vomiting, sweating, and mouth dryness were found in 6%, 9%, 22%, and 38% of patients, respectively.A single slow infusion of nefopam was found to be effective in critically ill patients who had moderate pain. To evaluate the risk-benefit ratio of prescribing nefopam, data on the risk of tachycardia, increased cardiac output, hypotension, and decreased systemic vascular resistance are needed. COMMENTNefopam, a centrally acting analgesic, has been used in the surgical setting in many European countries since the mid-1970s. It has been used as an opioid-sparing drug as well as a single therapy for postoperative pain relief. The current study evaluated the efficacy and adverse effects of nefopam in the critical care setting where nefopam is routinely used in France. Patients who were clinically stable received a 20 mg nefopam dose in slow infusion over 30 minutes. The efficacy of pain relief, as well as the presence of adverse effects during and after infusion, was evaluated at several time points. Nefopam decreased the level of pain substantially both in communicative and noncommunicative patients. Nefopam was associated with important hemodynamic changes in nearly 30% of the patients. Interestingly, 1 patient who received the drug rapidly developed severe adverse events.This study suffers from some limitations that preclude us from reaching definite conclusions. First, the number of patients studied was small. Even stable ICU patients are not that stable, and therefore some of the adverse event reports could be related to changes in patient condition rather than to the drug used. To evaluate the effect of the drug, a randomized double-blind st...