Postoperative analgesic efficacy of nefopam after anorectal surgery: a retrospective observational study

Objective: To examine the effectiveness of nefopam on postoperative pain control after anorectal surgeries. Methods: We retrospectively reviewed the electronic medical records of patients who underwent anorectal surgeries from January 2019 to March 2022 at two medical centers. The data were divided into nefopam and conventional groups. The primary outcome was the number of patients who requested additional opioids in the 24-h postoperative period. The secondary outcomes were numeric rating pain scores (NRPS) within a 24-h postoperative period and analgesic drugs-related side effects. Results: Eighty-seven patients in the conventional group and 60 in the nefopam group were recruited. The nefopam group reported less additional opioid consumption than the conventional group in all dimensions of analysis, including overall, adjusted to anesthetic techniques and types of surgery. However, these did not reach statistical significance (P = 0.093). Only patients in the nefopam group who underwent hemorrhoidectomy under TIVA or spinal anesthesia significantly required fewer additional opioids (P = 0.016, 60% mean difference). Similarly, the 24-h postoperative morphine consumption was lower in the nefopam group (mean difference = -3.4, 95%CI: 0.72,6.08). Furthermore, significantly lower NRPS were reported in the nefopam group during the 12-18 h postoperative period (P = 0.009). On the other hand, analgesic drugs related side effects were similar in both groups. Conclusions: The administration of nefopam after major anorectal surgery is beneficially evident in reducing postoperative opioid requirements. (AU)

Effect of Continuous Infusion of Intravenous Nefopam on Postoperative Opioid Consumption After Video-assisted Thoracic Surgery: A Double-blind Randomized Controlled Trial.

BACKGROUND: Although nefopam has been reported to have opioid-sparing and analgesic effects in postsurgical patients, its effectiveness in video-assisted thoracoscopic surgery (VATS) is unknown. OBJECTIVES: This study aimed to investigate the opioid-sparing and analgesic effects of perioperative nefopam infusion for lung resection. STUDY DESIGN: Double-blinded randomized controlled trial. SETTING: Operating room, postoperative recovery room, and ward at a single tertiary university hospital. METHODS: Ninety patients scheduled for elective VATS for lung resection were randomized to either the nefopam (group N) or control group (group C). Group N received 20 mg nefopam over 30 minutes immediately after the induction of anesthesia. Nefopam was administered continuously for 24 hours postoperative, using a dual-channel elastomeric infusion pump combined with fentanyl-based intravenous patient-controlled analgesia. Group C received the same volume of normal saline as nefopam solution administered in the same manner. The primary outcome measure was fentanyl consumption for the first postoperative 24 hours. The secondary outcome measures were the cumulative fentanyl consumption during the first postoperative 48 hours, pain intensity at rest and during coughing evaluated using an 11-point numeric rating scale, quality of recovery at postoperative time points 24 hours and 48 hours, and the occurrence of analgesic-related side effects during the first postoperative 24 hours and postoperative 24 to 48 hour period. Variables related to chronic postsurgical pain (CPSP) were also investigated by telephone interviews with patients at 3 months postoperative. This prospective randomized trial was approved by the appropriate institutional review board and was registered in the ClinicalTrials.gov registry. RESULTS: A total of 83 patients were enrolled. Group N showed significantly lower fentanyl consumption during the first postoperative 24 hours and 48 hours (24 hours: median difference: -270 µg [95%CI, -400 to -150 µg], P < 0.001); 48 hours: median difference: -365 µg [95% CI: -610 to -140 µg], P < 0.001). Group N also showed a significantly lower pain score during coughing at 24 hours postoperative (median difference, -1 [corrected 95% CI: -2.5 to 0], adjusted P = 0.040). However, there were no significant between-group differences in the postoperative quality of recovery, occurrence of analgesic-related side effects, length of hospital stay, and occurrence of CPSP. LIMITATIONS: Despite the significant opioid-sparing effect of perioperative nefopam infusion, it would have been difficult to observe significant improvements in other postoperative outcomes owing to the modest sample size. CONCLUSION: Perioperative nefopam infusion using a dual-channel elastomeric infusion pump has a significant opioid-sparing effect in patients undergoing VATS for lung resection. Therefore, it could be a feasible option for multimodal analgesia in these patients.

Effect of remifentanil on post-operative analgesic consumption in patients undergoing shoulder arthroplasty after interscalene brachial plexus block: a randomized controlled trial.

PURPOSE: Remifentanil is useful in balanced anesthesia; however, there is concern regarding opioid-induced hyperalgesia. The effect of remifentanil on rebound pain, characterized by hyperalgesia after peripheral nerve block has rarely been studied. This study evaluated whether intraoperative remifentanil infusion may increase postoperative analgesic requirement in patients receiving preoperative interscalene brachial plexus block (IBP). METHODS: Sixty-eight patients undergoing arthroscopic shoulder surgery under general anesthesia were randomly allocated to remifentanil (R) or control (C) group. Preoperative IBP with 0.5% ropivacaine 15 mL was performed in all patients. Intraoperative remifentanil was administered only in the R group. Postoperative pain was controlled using intravenous patient-controlled analgesia (IV-PCA) and rescue analgesics. The primary outcome was the dosage of fentanyl-nefopam IV-PCA infused over 24 h postoperatively. The secondary outcomes included the numeric rating scale (NRS) score recorded at 4-h intervals over 24 h, amount of rescue analgesics and total postoperative analgesics used over 24 h, occurrence of intraoperative hypotension, postoperative nausea and vomiting (PONV) and delirium. RESULTS: The dosage of fentanyl-nefopam IV-PCA was significantly less in C group than R group for postoperative 24 h. Fentanyl 101 [63-158] (median [interquartile range]) µg was used in the C group, while fentanyl 161 [103-285] µg was used in the R group (median difference 64 µg, 95% CI 10-121 µg, P = 0.02). Nefopam 8.1 [5.0-12.6] mg was used in the C group, while nefopam 12.9 [8.2-22.8] mg was used in the R group (median difference 5.1 mg, 95% CI 0.8-9.7 mg, P = 0.02). The total analgesic consumption: the sum of PCA consumption and administered rescue analgesic dose, converted to morphine milligram equivalents, was higher in the R group than C group (median difference 10.9 mg, 95% CI 3.0-19.0 mg, P = 0.01). The average NRS score, the incidence of PONV and delirium, were similar in both groups. The incidence of intraoperative hypotension was higher in R group than C group (47.1% vs. 20.6%, P = 0.005). CONCLUSIONS: Remifentanil administration during arthroscopic shoulder surgery in patients undergoing preoperative IBP increased postoperative analgesic consumption.

Does Nefopam Provide Analgesic Effect and Reduce Morphine Consumption After Primary Total Knee Arthroplasty? A Prospective, Double-Blind, Randomized Controlled Trial.

BACKGROUND: One of the most undesirable results after total knee arthroplasty (TKA) is severe immediate postoperative pain, resulting in patient dissatisfaction. We aimed to evaluate nefopam's analgesic efficacy after primary TKA along with related outcomes, including morphine consumption and adverse events. METHODS: We conducted a double-blind, randomized controlled trial of patients undergoing unilateral primary TKA, comparing 24 hours of 80 mg of continuous intravenous nefopam to placebo infusion. A 100-mm Visual Analog Scale (VAS) for pain-at-rest and in-motion ≤48 hours was the primary outcome measure. Secondary outcomes were morphine and antiemetic consumption, adverse events, and functional outcomes: time-to-walk, timed up-and-go test, postoperative knee range of motion at 24 and 48 hours, time-to-discharge, and patient satisfaction scores. RESULTS: Patients in the nefopam group had significantly lower VAS at rest 6 hours postop (20.3 ± 27.3 vs 35 ± 24.3, P = .01). Other timepoints and in-motion VAS did not significantly differ. Total morphine consumption (0-48 hours) was 37% less, significantly lower, in the nefopam group (5.3 ± 4.5 vs 8.4 ± 7.5 mg, P = .03). Antiemetic consumption was also 61% lower in the nefopam group but not statistically significant (0.8 ± 2.3 vs 2.0 ± 3.8 mg, P = .08). There were no variations in adverse events, functional outcomes, and satisfaction scores between groups. CONCLUSION: Continuous nefopam administration as part of multimodal analgesia for 24 hours post-TKA produced a significant analgesic effect but only within the first 6 hours. However, there was a notable reduction in morphine use 48 hours postop. Nefopam is a useful agent for contemporary pain control after TKA. LEVEL OF EVIDENCE: Therapeutic Level I.

Association of nefopam use with postoperative nausea and vomiting in gynecological patients receiving prophylactic ramosetron: A retrospective study.

BACKGROUND: Postoperative nausea and vomiting (PONV) is a common adverse effect of opioid-based intravenous patient-controlled analgesia (IV PCA). Nefopam has been considered as a good candidate for inclusion in multimodal analgesia because of its opioid sparing effect, but it can be emetic. This study aims to examine whether the use of nefopam combined with fentanyl in IV PCA was associated with the higher incidence of PONV in patients receiving prophylactic ramosetron after gynecological surgery. METHODS: Data from 296 patients who underwent gynecological surgery were retrospectively reviewed. The patients received IV PCA containing either fentanyl 1500 µg and ketorolac 90 mg (Group K) or fentanyl 1500 µg and nefopam 80 mg (Group N). All patients in both groups received 0.3 mg of ramosetron at the end of surgery. The primary outcome measure was the incidence of PONV during the 3-day postoperative period. RESULTS: No difference was observed in the incidence of PONV during the 3-day postoperative period between the two groups. However, the incidence of nausea on postoperative day 2 was significantly higher in Group N (10.3%) than in Group K (2.8%) (P = 0.016). Multivariable logistic regression analysis showed that the use of nefopam was not associated with a higher incidence of PONV (adjusted odds ratio, 1.616; 95% confidence interval, 0.952-2.743, P = 0.076). There were no differences in postoperative pain scores between the two groups. CONCLUSION: The combined use of nefopam with fentanyl in IV PCA was not associated with the higher incidence of PONV compared with the use of ketorolac and fentanyl combination in patients who received ramosetron as PONV prophylactic agent. However, prospective trials are required for a confirmative conclusion.

The effect of nefopam on lactation after caesarean section: a single-blind randomised trial.

BACKGROUND: Nefopam is a centrally acting analgesic which has a theoretical risk of stopping lactation due to its anticholinergic and dopaminergic effects. The aim of this study was to evaluate the effect of nefopam on lactation and to investigate potential adverse effects on newborns. METHODS: Seventy-two women, scheduled to undergo a caesarean delivery under spinal anaesthesia and wanting to breastfeed, were randomised to one of two groups: nefopam (20mg, six hourly) or paracetamol (1g, six hourly). In both groups, postoperative analgesia was supplemented with ketoprofen (50mg, six hourly) in conjunction with intrathecal morphine 0.1mg. The primary outcome was onset of lactation, estimated by weighing the newborns before and after feeding; by maternal perception of breast fullness and based on serum prolactin concentration 48hours postpartum. Secondary outcomes were neonatal adverse effects evaluated by neurobehavioural score at 12, 24, 48, and 72hours after birth. Statistical analyses were performed using Chi-squared, Fisher exact and Student t tests as appropriate. P<0.05 was considered statistically significant. RESULTS: The difference in the weight of the newborn before and after each feed, maternal perception of breast fullness and serum prolactin did not significantly differ between groups. The volume of artificial milk given to newborns of mothers in the nefopam group on days two and three was significantly greater than for the paracetamol group. Neurobehavioural scores were comparable at each time point. CONCLUSION: Nefopam does not appear to delay the onset of lactation or present any clear risk to the newborn.

Opioid sparing effect and safety of nefopam in patient controlled analgesia after laparotomy: A randomized, double blind study.

OBJECTIVES: A double-blind randomised study to evaluate the opioid sparing effect and safety of nefopam when administered via intravenous patient controlled analgesia (PCA) with fentanyl. METHODS: Patients planned for elective open laparotomy, were randomly assigned to receive into fentanyl 25 µg/ml (SF group) or nefopam 2.4 mg/ml plus fentanyl 25 µg/ml (NF group). Patients were assessed before surgery and for 24 h postoperatively. RESULTS: Total PCA fentanyl consumption was significantly lower in the NF group (n = 35) than the SF group (n = 36). Pain scores were significantly lower and patients' satisfaction with treatment significantly better in the NF group than the SF group. Dry mouth and dizziness were significantly more frequent in the NF group than the SF group. There were no other statistically significant between-group differences in the incidence of adverse events. CONCLUSIONS: Intravenous PCA using nefopam + fentanyl following laparotomy has an opioid sparing effect and is associated with a low incidence of some of the typical opioid related adverse events. TRIAL REGISTRY: Clinicaltrials.gov Registration No: NCT02596269.

Nefopam for the prevention of perioperative shivering: a meta-analysis of randomized controlled trials.

BACKGROUND: Shivering is a frequent complication following surgery and anaesthesia. A large variety of studies have been reported that nefopam may be efficacious for the prevention and treatment of perioperative shivering. Regrettably, there is still no conclusion of the efficacy and safety of nefopam for the prevention of perioperative shivering. The aim of this analysis is to evaluate the efficacy of nefopam for the prevention of perioperative shivering in patients undergoing different types of anaesthesia compared with placebo group and other active interventions. METHODS: PubMed, EMBASE, Cochrane Central Register of Control Trials were systematically searched for potentially relevant trials. Trial quality and extracted data were evaluated by two authors independently. Dichotomous data on the absence of shivering was extracted and analysed by using relative risk (RR) with 95% confidence interval (CI). Continuous outcome was abstracted and analysed by using weighted mean difference (WMD) with 95% confidence interval (CI). Outcome data was analysed by using random effect model or fixed effect model in accordance with heterogeneity. RESULTS: Compared with placebo, prophylactic administration of nefopam significantly reduced the risk of perioperative shivering not only in the patients under general anaesthesia but also neuraxial anaesthesia (RR 0.08; 95% CI 0.05-0.13). As compared with clonidine, nefopam was more efficacious in the prevention of perioperative shivering (RR 0.34; 95% CI 0.17-0.70). Nefopam has no influence on the extubation time (WMD 0.92; 95% CI -0.15-1.99). CONCLUSION: Our analysis has demonstrated that nefopam is associated with the decrease of risk of perioperative shivering following anaesthesia without influencing the extubation time.

Nefopam and meperidine are infra-additive on the shivering threshold in humans.

BACKGROUND: Induction of therapeutic hypothermia is often complicated by shivering. Nefopam, a nonsedative benzoxazocine analgesic, reduces the shivering threshold (triggering core temperature) with minimal side effects. Consequently, nefopam is an attractive drug for inducing therapeutic hypothermia. However, nefopam alone is insufficient and thus needs to be combined with another drug. Meperidine also reduces the shivering threshold. We therefore determined whether the combination of nefopam and meperidine is additive, infra-additive, or synergistic on the shivering threshold. METHODS: Ten volunteers were each studied on 4 randomly assigned days. In random order, they were given the following treatments: (1) control, no drug; (2) nefopam to a target concentration of 0.1 µg/mL; (3) meperidine to a target concentration of 0.1 µg/mL; and (4) both nefopam and meperidine at target concentrations of 0.1 µg/mL each. Lactated Ringer's solution at 4°C was infused to decrease core temperature while mean skin temperature was kept near 30.5°C. The core temperature that increased oxygen consumption >25% defined the shivering threshold. RESULTS: Nefopam reduced the shivering thresholds by 0.7°C ± 0.3°C compared with no drug. Meperidine reduced the shivering thresholds by 0.4°C ± 0.3°C compared with no drug. When combined, the shivering threshold decreased by only 0.6°C ± 0.4°C, which was about half what would have been expected based on the individual effects of each drug (P < 0.001). The effect of combined nefopam and meperidine on the shivering threshold was thus infra-additive. CONCLUSIONS: The combination of nefopam and meperidine should be avoided for induction of therapeutic hypothermia. Better options would be combinations of drugs that are at least additive or even synergistic.

[Postoperative analgesia with nefopam and non-steroidal anti-inflammatory drugs in patients after surgery for tumors of head and neck].

MATERIALS AND METHODS: 83 adult patients included in the study were divided into two groups. Patients of the group-1 (n-49) had medium level of pain after cancer head and neck surgery. Patients of the group-2 (n-34) had severe pain. Three first postoperative days their post-operative multimodal analgesia started with tenoxycam 20 mg i.m. after induction of anesthesia, then every 24 hour (58 patients). 25 patients got ketoprofen 100 mg i.m. every 8-12 hours instead of tenoxycam. All patients had nefopam 30 mg i.m. 30 min prior the end of surgery procedure, and every 8 hours afterwards. 7 patients of the group-1 had more than 4 pain scores (day 1), 4 patients--at the day 2. They received tramadol or paracetamol additionally. 7 patients (group-2) also had up to 5 pain scores on the day 1, 5 patients had 4 pain scores on the day 2, and 3 patients 4 pain scores on the day 3. All that patients received additional analgesia with tramadol or trimeperidine once a day. 8.4% of patients suffered from adverse reactions (tachycardia, PONV and sweating). CONCLUSION: This method of multimodal postoperative analgesia is very simple and fairly efficient.

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

OBJECTIVE: The efficacy and side-effects of nefopam were prospectively compared with those of fentanyl for patient-controlled analgesia (PCA) following cardiac surgery. METHODS: Patients scheduled to undergo cardiac surgery were randomly assigned between three PCA groups (nefopam, fentanyl or nefopam + fentanyl). Pain was assessed at rest and during movement at 12, 24, 36, 48 and 72 h after surgery using a visual analogue scale (VAS). Total infused PCA volume, number of rescue drug injections, duration of intubation and length of stay in the intensive care unit were recorded. The incidence of adverse effects was noted at 48 h postoperatively. RESULTS: There were no significant between-group differences in VAS score, total PCA infusion volume or number of rescue injections (n = 92 per group). Nausea was significantly more common in the fentanyl group compared with both other groups. CONCLUSIONS: PCA with nefopam alone provides suitable postoperative analgesia after cardiac surgery.

[Thrombocytopenia and postoperative analgesia].

OBJECTIVE: To develop effective and safe measures of postoperative multimodal analgesia (optimizing the use of narcotic analgesics) in surgical treatment of hematological patients with thrombocytopenia. DESIGN: A pilot and prospective comparative controlled study. METHODS: We studied 27 patients with acquired thrombocytopenia who underwent laparoscopic splenectomy. Three schemes of anesthesia were used: 1) Nefopam 20 mg/day + trimeperidin (n = 7); 2) Paracetamol 4 g/day + trimeperidin (n = 10); 3) paracetamol + trimeperidin + glucocorticosteroids (GC) (through treatment of the underlying disease) (n = 10). Analgesic properties and effect of each scheme were assessed according to a rating scale of pain NRS (10 points) and VAS (100 points) studied. Additionally we evaluated the effect of nefopam and paracetamol on the functional properties of platelets and hemostasis, platelet levels while monitoring and indicators of thromboelastogram (TEG). RESULTS: Application of paracetamol + trimeperidin accompanied with effectively reducing of postoperative pain (less than 5 points on the NRS). The level of postoperative pain was lower in patients who were treated with corticosteroids within the therapy of the underlying disease before surgery and who continued to receive it in postoperative period (2-3 points NRS). Nefopam use in the perioperative period is not only inferior to the analgesic effect of paracetamol, but also causes frequent side effects. Consumption of narcotic analgesic--trimeperidin when applying nefopam averaged 43 mg/day, the appointment of paracetamol--28 mg/day, using a combination of paracetamol + GC--20 mg/day. Thus, GC within the underlying disease treatment substantially reduces the need for opioid analgesics. A monitoring of the number of platelets and TEG did not shows negative effect of paracetamol and nefopam on platelet and plasma hemostasis. CONCLUSIONS: Nefopam and paracetamol may be used in patients with thrombocytopenia, as do not affect the hemostasis and platelet count. Application of postoperative analgesia scheme paracetamol + trimeperidin in patients receiving corticosteroids provides the maximum reduction of pain with the least consumption of narcotic analgesics.

Ondansetron does not attenuate the analgesic efficacy of nefopam.

OBJECTIVES: The aim of this study was to investigate if there is any interaction between ondansetron and nefopam when they are continuously co-administrated during patient-controlled intravenous analgesia (PCIA). METHODS: The study was a prospective, randomized, controlled, non-inferiority clinical trial comparing nefopam-plus-ondansetron to nefopam alone. A total of 230 postoperative patients using nefopam for PCIA, were randomly assigned either to a group receiving continuous infusion of ondansetron (Group O) or to the other group receiving the same volume of normal saline continuously (Group N). Postoperative pain intensity scores, the sum of pain intensity difference over 24 hours postoperatively (SPID24hr), the incidence of adverse events, and the total consumption of nefopam were evaluated respectively. RESULTS: Postoperative pain was treated successfully in both groups. The mean SPID24hr scores were 95.6 mm in Group N and 109.3mm in Group O [95% confidence interval (CI) -14.28, 24.32]. The lower margin of the 95% CI was above the pre-determined non-inferiority margin (-30mm) for SPID24hr, which indicated that nefopam-plus-ondansetron was not worse than the nefopam alone in term of analgesic efficacy. In addition, there was no statistical difference between the two groups in term of cumulative consumption of nefopam. Compared with Group N, postoperative vomiting was significantly reduced in Group O during the postoperative 24 hours (P < 0.05). Less rescue antiemetics were given to patients in Group O than those receiving nefopam alone (P < 0.05). There were no differences in postoperative nausea between the two groups. CONCLUSION: Nefopam-plus-ondansetron is not inferior to nefopam alone in relieving the pain in PCIA after minimally invasive surgery. In addition, adverse events are reduced without compromising analgesic efficacy.

[The use of central acting analgesic nefopam in postoperative analgesia in cardiac surgery patients].

A prospective, randomized, comparative study was conducted. 3 analgesia protocols were used: 1) patient controlled analgesia (PCA) with trimeperidine in combination with a nefopam constant infusion; 2) PCA with trimeperidine in combination with a nefopam bolus; 3) PCA with trimeperidine separately during early postoperative period in cardiac surgery patients. The study included 60 patients agedf rom 40 to 65 years of age (20 patients in each group). The analgesia efficacy was evaluated with a 5-point verbal rating scale (VRS) for pain intensity and inspiratory lung capacity (ILC), measured with incentive spirometer. The safety of nefopam during early postoperative period in cardiac surgery patients was shown. The combination of nefopam and trimeperidine led to a more pronounced analgetic effect. Trimeperidine consumption was significantly lower in nefopam groups than in the group of isolated PCA. Wholly adverse effects were associated with trimeperidine and were dose-related The incidence of nausea, vomiting, dizziness, weakness, bowel paresis was significantly higher in isolated PCA group than in the other two groups.

Unilateral permanent loss of vision after nefopam administration.

Acute glaucoma angle closure is a rare complication of anaesthesia and multimodal analgesia. However it is a medical emergency, hence any delay in its treatment may have catastrophic consequences. We present a case of postoperative glaucoma, which had evolved to permanent blindness. We also reviewed the French pharmacovigilance database between 1996 and 2006 and found four other cases of acute glaucoma angle closure in postoperative period possibly related to the administration of nefopam.

Median effective dose (ED50) of paracetamol and nefopam for postoperative pain: isobolographic analysis of their antinociceptive interaction.

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.

[Ketoprophen and nefopam combination for postoperative analgesia with minimal use of narcotic analgesics in cardio-surgical patients].

4 combinations of analgesia were studied: 1) Nefopam and patient-controlled analgesia (PCA) with Trimeperidine; 2) Ketoprofen (100 microg each 12 hours intramuscular) and PCA with Trimeperidine; 3) Nefopam, Ketoprofen and PCA with Trimeperidine; 4) PCA with Trimeperidine as monotherapy in early postoperative period in cardio-surgical patients. 80 patients (age from 40 to 70) were divided into 4 groups, 20 patients in each group. Administration of Nefopam and Ketoprofen before extubation reduced the intensity of pain syndrome (in average on 90%) and promoted the early stirring up of patients. Combination of Nefopam and Ketoprofen provided the most expressed analgesic and opioids-saving effects. In this group average amount of Trimeperidine per 24 hours was 14.7 microg that was 4.9 times less than in group of PCA with Trimeperidine as monotherapy. Dynamics of maximal inspiratory capacity of the lungs in the first three groups was better than in group of PCA with Trimeperidine as monotherapy beginning from 6th hour of study. In common undesirable effects was connected with Trimeperidine administration and depended on its dose. The frequency of nausea, vomit, dizziness and weakness was authentically higher in the group of PCA with Trimeperidine as monotherapy than in other groups.