Cholecystectomy, Opioid Use, Pain, Postoperative
Conditions
Brief summary
The goal of this clinical trial is to evaluate the effect of the addition of nefopam to a multimodal analgesic regimen consisting of ketoprofen and paracetamol during sevoflurane- dexmedetomidine-based anesthesia on postoperative morphine requirements in patients undergoing laparoscopic cholecystectomy.
Detailed description
Nefopam is a centrally-acting anti-nociceptive compound with supraspinal and spinal sites of action. It inhibits monoamine reuptake, modulates descending serotoninergic pain, and may also interact with a dopaminergic pathway. Because its mechanism of action is distinct from that of other analgesic opioids, nefopam may well have a role in analgesic protocols. The role of nefopam in multimodal analgesia has been extensively investigated in laparoscopic cholecystectomy. However, there is general agreement that more studies are needed to determine the ideal multimodal strategy. No previous study has investigated a combination regimen of the three most commonly prescribed non-opioid analgesics (NOA) (nefopam, ketoprofen, and paracetamol) vs ketoprofen and paracetamol combination during sevoflurane-dexmedetomidine based anesthesia on pain control after laparoscopic cholecystectomy. The aim of our study is to compare a combination regimen of three NOA (nefopam, ketoprofen, and paracetamol) vs ketoprofen and paracetamol combination during sevoflurane-dexmedetomidine based anesthesia on pain control after laparoscopic cholecystectomy. We will try to demonstrate the benefit with the addition of a third NOA, which is the nefopam, to the double-drug regimen including ketoprofen and paracetamol. Our hypothesis is that this combination regimen of three NOA is associated with less postoperative pain, less opioid consumption, shorter length of post-anesthesia care unit (PACU) stay, and fewer opioid-related adverse effects and postoperative complications compared to the double-drug regimen of ketoprofen and paracetamol. In this prospective randomized double-blind study, 90 patients aged 18 to 64 years, with American Society of Anesthesiologists (ASA) physical status I and II, will be randomly assigned using a computer-generated random number table to one of two treatment groups. Group A will receive sevoflurane-dexmedetomidine based anesthesia with ketoprofen and paracetamol for postoperative pain control, and group B will receive sevoflurane-dexmedetomidine based anesthesia with nefopam, ketoprofen, and paracetamol for postoperative pain control. The primary outcome measure of this study is total morphine consumption in PACU. Normally distributed data will be summarized as mean ± SD and non-normally distributed data will be summarized as median \[interquartile range\]. This study would have an impact on our current practice and may help find out the best multimodal analgesic strategy to control postoperative pain after laparoscopic cholecystectomy.
Interventions
DRUGnefopam, ketoprofen, paracetamol
Patients in this group will receive Nefopam and Ketoprofen in addition to the paracetamol intraoperatively prior to the anticipated end of the surgery
DRUGsaline infusion, ketoprofen, paracetamol
Patients in this group will receive one placebo infusion (saline infusion) in addition to the ketoprofen and paracetamol intraoperatively prior to the anticipated end of the surgery
Sponsors
American University of Beirut Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 64 Years
Healthy volunteers
No
Inclusion criteria
* ASA physical status I-II * Age between 18 and 64 years * Patients able to give consent
Exclusion criteria
* ASA physical status III to V * History of chronic pain * Use of an opioid analgesic within 12 hours prior to surgery * Alcohol or drug abuse * Chronic opioid intake * Morbid obesity * Psychiatric disorder * Pregnancy or breast-feeding * Intolerance to NSAIDSs * Allergy or contraindication to nefopam (acute angle-closure glaucoma, epilepsy, coronary artery disease, prostate adenoma), to morphine or paracetamol (liver failure), to ketoprofen (increased risk of bleeding, stomach or intestinal ulcer, chronic kidney disease) or to dexmedetomidine (uncontrolled hypertension, heart block greater than first degree, or other clinically significant morbidities)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total morphine consumption in the post anesthesia care unit | Throughout the patient's stay in the recovery room (average of 30 minutes after the surgery) | Total morphine doses consumed after the surgery during the post anesthesia care unit stay of the patient |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Urinary retention | Throughout the patient's stay in the recovery room (average of 30 minutes after the surgery) | Incidence of urinary retention |
| Tachycardia | Intraoperatively and in PACU | Episodes of tachycardia |
| Number of patients receiving morphine during the first 24 hours after surgery | During the first 24 hours after surgery | Number of patients receiving morphine during the first 24 hours after surgery |
| Number of patients receiving ketoprofen on the floor | On the floor | Number of patients receiving ketoprofen on the floor |
| Total fentanyl | Intraoperatively | Total fentanyl given intraoperatively. |
| Total morphine | Throughout the patient's stay on the floor | Total morphine on the floor |
| Ketoprofen consumption | Throughout the patient's stay on the floor | Ketoprofen consumption on the floor |
| Paracetamol consumption | Throughout the patient's stay on the floor | Paracetamol consumption on the floor |
| Total morphine consumption at 24 hours after surgery | 24 hours after surgery | Total morphine doses consumed at 24 hours after surgery |
| Number of patients receiving morphine in PACU | Throughout the patient's stay in the recovery room (average of 30 minutes after the surgery) | Number of patients receiving morphine in post anesthesia care unit |
| Number of patients receiving morphine on the floor | Throughout the patient's stay on the floor | Number of patients receiving morphine on the floor |
| Number of patients receiving paracetamol on the floor | On the floor | Number of patients receiving paracetamol on the floor |
| NRS pain scores at 24 h after surgery | 24 hours after surgery | NRS pain scores at 24 hours after surgery |
| sedation scores in PACU | Throughout the patient's stay in the recovery room (average of 30 minutes after the surgery) | sedation scores in post anesthesia care unit |
| Time to first morphine requirement | From the time of arrival to PACU until discharge | Time to first morphine requirement |
| Time to discharge (readiness) from PACU | Throughout the patient's stay in the recovery room (average of 30 minutes after the surgery) | Time to discharge (readiness) from post anesthesia care unit |
| Nausea and vomiting | Throughout the patient's stay in the recovery room (average of 30 minutes after the surgery) | Incidence and severity of nausea and vomiting |
| Rescue antiemetics | Throughout the patient's stay in the recovery room (average of 30 minutes after the surgery) | Need for rescue antiemetics |
| Pruritus | Throughout the patient's stay in the recovery room (average of 30 minutes after the surgery) | Incidence of pruritus |
| Respiratory depression | Throughout the patient's stay in the recovery room (average of 30 minutes after the surgery) | Incidence of respiratory depression |
| Sweating | Intraoperatively and in PACU | Episodes of sweating |
| Quality of recovery | At 24 hours after the surgery | Quality of recovery at 24 h using the QoR-40 |
| Overall satisfaction score | One month after surgery. | Overall satisfaction score collected one month after surgery. |
| NRS pain scores at rest in PACU | Throughout the patient's stay in the recovery room (average of 30 minutes after the surgery) | NRS pain scores at rest in post anesthesia care unit |
Countries
Lebanon
Outcome results
None listed