|Year : 2022 | Volume
| Issue : 1 | Page : 25-30
Comparison of Intravenous Nefopam and Tramadol for Postoperative Analgesia in Adult Patients Scheduled for Laparoscopic Abdominal Surgeries under General Anesthesia: A Prospective, Randomized, Double-Blind Study
Yogesh Kumar Swarnkar1, Rajiv Gupta2, Anand Mohan Arora1, Tuhin Mistry3
1 Department of Anaesthesiology and Critical Care, Maharaja Agrasen Hospital, New Delhi, India
2 Department of Anaesthesiology and Critical Care, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India
3 Department of Anaesthesiology and Perioperative Care, Ganga Medical Centre and Hospitals Pvt Ltd, Coimbatore, Tamil Nadu, India
|Date of Submission||01-Dec-2021|
|Date of Decision||10-Jan-2022|
|Date of Acceptance||19-Jan-2022|
|Date of Web Publication||23-Mar-2022|
Dr. Tuhin Mistry
Department of Anaesthesiology and Perioperative Care, Ganga Medical Centre and Hospitals Pvt Ltd, Coimbatore, Tamil Nadu
Source of Support: None, Conflict of Interest: None
Background and Aims: Nefopam and tramadol have been used for postoperative analgesia in the various clinical settings. This study aims to evaluate and compare the postoperative analgesic effects of intravenous nefopam and tramadol in adult patients undergoing laparoscopic abdominal surgeries.
Materials and Methods: One hundred and twenty-six adult patients of the American Society of Anesthesiologists physical Status I and II, age group of 20–60 years undergoing elective or emergency laparoscopic abdominal surgeries under general anesthesia were allocated randomly into two groups. In the postanesthesia care unit, patients in Group A (n = 63) and Group B (n = 63) received Nefopam 20 mg and Tramadol 100 mg, respectively, as intravenous infusion in 100 ml 0.9% saline over 15 min. The same doses were repeated every 6th hour or if the Visual Analog Scale (VAS) score was ≥4. Postoperative VAS scores were recorded at 30 min, 1.5 h, 3 h, 6 h, 12 h, 18 h, and 24 h. The hemodynamic parameters were recorded just before and after the completion of the infusion of study drugs. P < 0.05 was considered statistically significant.
Results: The pain score was significantly lower in Group A (Nefopam) than in Group B (Tramadol). The difference in mean VAS scores between the two groups was statistically significant at 1.5 h, 3 h, 6 h, 12 h, 18 h, and 24 h after postoperatively (P < 0.05). There was no statistically significant difference in the incidence of side effects in both groups.
Conclusion: Intravenous nefopam provided better postoperative pain relief than Tramadol in patients undergoing laparoscopic surgeries under general anaesthesia.
Keywords: Abdominal surgery, acute pain management, analgesia, laparoscopic surgery, nefopam, postoperative, tramadol
|How to cite this article:|
Swarnkar YK, Gupta R, Arora AM, Mistry T. Comparison of Intravenous Nefopam and Tramadol for Postoperative Analgesia in Adult Patients Scheduled for Laparoscopic Abdominal Surgeries under General Anesthesia: A Prospective, Randomized, Double-Blind Study. Indian Anaesth Forum 2022;23:25-30
|How to cite this URL:|
Swarnkar YK, Gupta R, Arora AM, Mistry T. Comparison of Intravenous Nefopam and Tramadol for Postoperative Analgesia in Adult Patients Scheduled for Laparoscopic Abdominal Surgeries under General Anesthesia: A Prospective, Randomized, Double-Blind Study. Indian Anaesth Forum [serial online] 2022 [cited 2022 Dec 6];23:25-30. Available from: http://www.theiaforum.org/text.asp?2022/23/1/25/340478
| Introduction|| |
The optimal management of postoperative pain after laparoscopic surgery plays a vital role in a successful recovery. Although postoperative pain intensity following laparoscopic surgery is lesser than open surgery, many patients end up requiring a significant dose of analgesic medications, including both opioids and nonopioids. In a retrospective analysis, the incidence of chronic postsurgical pain after laparoscopic colorectal surgery was 17%, similar to those reported in the literature after laparotomy. After laparoscopic cholecystectomy, moderate-to-severe postoperative pain still occurs in 50%–70% of patients. Inadequate postoperative pain management could be associated with various systemic complications, restricted mobility, thromboembolic events, delayed recovery, prolonged hospital stay, and increasing overall cost.
Opioids are widely used to manage postoperative pain after laparoscopic surgery due to their proven efficacy. However, opioids are associated with various adverse effects, including gastrointestinal events, pruritus, respiratory depression, increasing hospital stay, and delay in discharge. Nonsteroidal anti-inflammatory drugs can provide good quality pain relief but may be associated with gastrointestinal side effects, interference with platelet aggregation, and delayed wound healing. Tramadol is an atypical opioid with less respiratory depression than morphine. It was reported to provide consistently lower pain scores than ketorolac and an insignificant difference in postoperative nausea vomiting (PONV) after laparoscopic sterilization.
Nefopam is a centrally acting nonopioid, nonsteroid analgesic that has been reported to provide a significant reduction in postoperative pain scores and opioid requirements in laparoscopic cholecystectomy. Nefopam or tramadol was used in a different subset of subjects who had undergone various abdominal surgeries. However, very few studies have been conducted on patients undergoing abdominal laparoscopic surgeries. Hence, the present study was conceived to compare the analgesic efficacy of intravenous (IV) nefopam and tramadol for postoperative analgesia in patients undergoing laparoscopic abdominal surgeries.
| Materials and Methods|| |
This prospective, randomized, double-blind study was conducted at a tertiary care center from November 2019 to June 2020. Due permission was taken from the institutional ethical committee and review board (Ref. No. MAH/ADMN/IEC/2019/3, dated October 11, 2019). Written informed consent was obtained from each patient following a detailed explanation of the study protocol. Visual Analog Scale (VAS) 0–10 was explained to the patient during preanesthetic check-up (PAC). The consort diagram indicating enrollment and progress is shown in [Figure 1].
Our study included 126 patients of either sex, aged 20–60 years, belonging to the American Society of Anesthesiologist (ASA) physical status Grade I and II, weighing 50–75 kg, who were scheduled for elective or emergency laparoscopic abdominal surgeries under general anesthesia (GA). Patients with a history of analgesics, sedatives, or antidepressant use within 24 h before surgery; opioid dependence, alcohol or drug abuse, motion sickness or PONV, convulsion, psychiatric illness, and known hypersensitivity to the study drugs were excluded from the study. Pregnant women, lactating mothers, and patients who refused to participate in the study were also excluded.
On arrival in the operation theater, fasting status, consent, and PAC were checked, and ASA standard monitors were attached. IV access was secured, and infusion of ringer's lactate was started as per the standard calculation of perioperative fluid replacement therapy. After preoxygenation with 100% O2 for 3 min, GA was induced with IV fentanyl 2 mcg/kg, propofol 2 mg/kg and cis-atracurium 0.2 mg/kg. Following induction and adequate paralysis, the trachea was intubated with an appropriate size cuffed endotracheal tube. GA was maintained with oxygen: Air (50:50), titrated Minimum alveolar concentration (MAC) of sevoflurane, the maintenance dose of cis-atracurium (0.03 mg/kg intermittent bolus every 20–40 min), and positive pressure ventilation. During laparoscopic surgery, intraabdominal pressure was maintained at 10–14 mm Hg. IV Ondansetron 4 mg was administered in all patients 45 min before the completion of surgery. All patients received IV paracetamol 1 g and an additional 1 mcg/kg/h fentanyl intraoperatively. Heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), respiratory rate (RR), oxygen saturation (SpO2), end-tidal carbon dioxide, and temperature were monitored throughout the operation. At the end of the surgery, patients were extubated following reversal of residual neuromuscular blockade and shifted to the post anesthesia care unit (PACU). By the time the patients arrived in the PACU, they were comfortable, pain-free, fully responsive, and oriented to any verbal command.
Using computer-generated random numbers, patients were randomly allocated into one of the two predefined Groups, A or B, with 63 patients in each. In PACU, all patients received the first dose of study drugs according to their group allocation, 30 min after completion of surgery. The principal investigator prepared the study drugs, and the co-investigators were blinded to the study drugs being administered to the patients. Both the patient and the co-investigators were blinded to group allocation. Participants received IV infusion (in 100 ml 0.9% saline) of 20 mg Nefopam hydrochloride (Nefosar, Abbott India Ltd, India) in Group A and 100 mg Tramadol hydrochloride (Tramazac, Zydus Cadila Health care Ltd, India) in Group B, respectively, over 15 min. The dose was repeated every 6th hour or if the VAS score was ≥4. The maximum dose of Nefopam and tramadol was set at 120 mg/day and 400 mg/day, respectively. The patients were asked to mark their pain intensity on a 0–100 mm VAS score scale. Pain scores equal to or above 5, despite the study drug administration, were considered breakthrough pain. It was managed with rescue analgesic IV Diclofenac sodium (1.5 mg/kg) and repeated if required. Postoperative VAS scores were recorded at 30 min, 1.5 h, 3 h, 6 h, 12 h, 18 h, and 24 h. The HR, SBP, DBP, and RR were recorded just before and after the infusion of study drugs. All the patients were observed for side effects such as nausea, vomiting, headache, dizziness, pruritus, skin rashes, and sweating during the 24 h postoperative period.
The sample size was calculated with the help of an online calculation tool (https://clincalc.com/stats/samplesize.aspx). The researcher had anticipated that the difference in VAS score between the two groups would be 20% or two points (on an 11-point scale). Assuming an alpha error of 0.05 and the power of the study to be 95%, a minimum of 63 patients were included in each group. So, owing to potential dropouts, a total of 130 patients were included in our study.
The raw data were entered into a Microsoft Excel Spreadsheet and analyzed using the standard statistical software SPSS® statistical package version 21.0 (SPSS Inc., Chicago, IL, USA). The continuous variables are presented as mean ± standard deviation, and categorical variables are presented as absolute numbers and percentages. The comparison of normally distributed continuous variables between the groups was performed using the Student's t-test. Nominal categorical data between the groups were compared using the Chi-squared test or Fisher's exact test as appropriate. P < 0.05 was considered statistically significant.
| Results|| |
We recruited a total of 126 patients, 63 each in Group A and Group B, and none were excluded from our study. Both the groups were comparable in terms of demographic profiles [Table 1]. The majority of the patients were from the mean age group of 31–40 years in both groups.
Different types of laparoscopic surgeries are shown in [Table 2].
[Table 3] shows patients vitals before and after administration of study drugs. The SBP and DBP were lower in group A (p <0.001) following IV infusion of Nefopam.
The mean VAS score was comparable in Group A and Group B, and the difference was not statistically significant at 30 min after infusion of study drugs [Table 2]. The mean VAS score at 1.5 h, 3 h, 6 h, 12 h, 18 h, and 24 h in Group A compared to Group B showed statistical significance [Figure 2] (P < 0.05). None of the patients in either group required rescue analgesic medication.
[Table 4] shows various side effects of study drugs in both groups. The difference was statistically not significant (P > 0.05). Nausea-vomiting was the most common side effect in both groups.
| Discussion|| |
The present randomized controlled trial showed that IV Nefopam provided a lower VAS score and better analgesia than IV tramadol in patients undergoing laparoscopic abdominal surgeries. Nefopam helped in a significant reduction in SBP and DBP following the infusion. The side effects profile of both the drugs was comparable.
Nefopam has been used for nociceptive pain, prevention, or treatment of postoperative shivering and hiccups. Nefopam 20 mg was reported to be equipotent to morphine 6–12 mg and meperidine 50 mg in surgical settings, and it has a morphine-sparing effect of 30%–50%. In our study, the mean VAS score (>5, moderate pain) was brought down to score < 3 (mild or tolerable pain) within 30 min of drug administration in both groups. However, nefopam showed better efficacy than tramadol (<0.05) for most of the follow-up intervals being studied. By 18–24 h, both groups had VAS scores in the range of mild and tolerable pain. Our findings well match with the study conducted by Ali Najeh Al-Awwady. The author observed that intraoperative paracetamol-Nefopam combinations were more effective in relieving immediate postoperative pain for elective laparoscopic cholecystectomy than paracetamol alone and paracetamol-tramadol combination without any side effects. McLintock et al. observed significant analgesic and morphine sparing effects of 20 mg nefopam on postoperative pain. Oh et al. also noticed comparable analgesia with equipotent doses of nefopam or fentanyl patient-controlled analgesia following laparoscopic gynecological surgery.
Nefopam reduced the HR after the administration of the first dose of the drug. However, this decrease was not statistically significant as compared to the tramadol group. Nefopam also decreased the SBP and DBP, which were statistically significant than Group B patients. Nefopam and tramadol both decreased the RR, but the difference was not statistically significant between the groups. The decrease in vitals parameters could be due to pain relief following the administration of study drugs or the expected side effect profile of the opioids on the respiratory and cardiovascular systems. Abeloos et al. also noticed minor changes in blood pressure, HR, and RR following IV administration of nefopam.
We observed a few side effects such as nausea-vomiting, headache, dizziness, dry mouth, pruritus, tachycardia, sweating in both groups. Skin rashes were observed in three patients who received Tramadol infusions, which were treated successfully using the drugs used for anaphylaxis like antihistaminics and steroids. One patient in Group A had hypertension. Pandit et al. compared nefopam with pentazocine and observed that patients in the Nefopam group (16%) experienced lesser side effects than the pentazocine group (40%) (P < 0.05). Ali Najeh Al-Awwady did not observe any significant side effects in patients receiving the Paracetamol-Nefopam combination.
Recently, opioid-free anesthesia has been gaining popularity, which is based on multimodal analgesic treatment. It is associated with lower postoperative opioid consumption and fewer adverse effects that result from opioid use while facilitating enhanced recovery and return of bowel function. Nefopam 20 mg has been proven to potentiate opioid analgesia and reduce the need for opioids by approximately 40%. It is a nonopioid analgesic that inhibits monoamine reuptake in the central nervous system and indirectly modulates the N-methyl-D-aspartate (NMDA) receptor. Thus, decreasing c-Fos expression in the dorsal horn of the spinal cord and relieving allodynia and opioid-related hyperalgesia. In our study, IV nefopam provided effective and better postoperative pain relief than IV tramadol.
Our study has a few limitations. We included all types of laparoscopic abdominal surgeries instead of any specific surgery. We did not compare the VAS score according to gender distribution. Male and female patients may have different pain thresholds. Further studies are required for optimal dosing regimen, comparison with other opioids and nonopioid analgesics, and feasibility of its application in ASA III and IV patients.
| Conclusion|| |
Intravenous nefopam provided better postoperative pain relief compared to Tramadol in adult patients undergoing elective or emergency laparoscopic abdominal surgeries. Hence, we are of the opinion that nefopam is a superior analgesic as compared to tramadol. The side effects profile of both drugs was comparable.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4]