Clinical trial NCT04622813: Nonopioid Analgesics and Cholecystectomy
Official title: The Effect of Intraoperative Nefopam, Ketoprofen and Paracetamol Combination vs Ketoprofen and Paracetamol Combination on Postoperative Morphine Requirements After Laparoscopic Cholecystectomy: A Randomized, Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cholecystectomy
Pain, Postoperative
Opioid Use
Lead sponsor: American University of Beirut Medical Center
Sponsor class: OTHER
First posted: 2020-11-10
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Total morphine consumption in the post anesthesia care unit
timeFrame: Throughout the patient's stay in the recovery room (average of 30 minutes after the surgery)
Secondary outcomes:
measure: Total fentanyl
timeFrame: Intraoperatively
measure: Total morphine
timeFrame: Throughout the patient's stay on the floor
measure: Ketoprofen consumption
timeFrame: Throughout the patient's stay on the floor
measure: Paracetamol consumption
timeFrame: Throughout the patient's stay on the floor
measure: Total morphine consumption at 24 hours after surgery
timeFrame: 24 hours after surgery
measure: Number of patients receiving morphine in PACU
timeFrame: Throughout the patient's stay in the recovery room (average of 30 minutes after the surgery)
measure: Number of patients receiving morphine on the floor
timeFrame: Throughout the patient's stay on the floor
measure: Number of patients receiving morphine during the first 24 hours after surgery
timeFrame: During the first 24 hours after surgery
measure: Number of patients receiving ketoprofen on the floor
timeFrame: On the floor
measure: Number of patients receiving paracetamol on the floor
timeFrame: On the floor
measure: NRS pain scores at rest in PACU
timeFrame: Throughout the patient's stay in the recovery room (average of 30 minutes after the surgery)
measure: NRS pain scores at 24 h after surgery
timeFrame: 24 hours after surgery
measure: sedation scores in PACU
timeFrame: Throughout the patient's stay in the recovery room (average of 30 minutes after the surgery)
measure: Time to first morphine requirement
timeFrame: From the time of arrival to PACU until discharge
measure: Time to discharge (readiness) from PACU
timeFrame: Throughout the patient's stay in the recovery room (average of 30 minutes after the surgery)
measure: Nausea and vomiting
timeFrame: Throughout the patient's stay in the recovery room (average of 30 minutes after the surgery)
measure: Rescue antiemetics
timeFrame: Throughout the patient's stay in the recovery room (average of 30 minutes after the surgery)
measure: Pruritus
timeFrame: Throughout the patient's stay in the recovery room (average of 30 minutes after the surgery)
measure: Respiratory depression
timeFrame: Throughout the patient's stay in the recovery room (average of 30 minutes after the surgery)
measure: Urinary retention
timeFrame: Throughout the patient's stay in the recovery room (average of 30 minutes after the surgery)
measure: Tachycardia
timeFrame: Intraoperatively and in PACU
measure: Sweating
timeFrame: Intraoperatively and in PACU
measure: Quality of recovery
timeFrame: At 24 hours after the surgery
measure: Overall satisfaction score
timeFrame: One month after surgery.
Other outcomes:
Locations:
city: Beirut
country: Lebanon
facility: American University of Beirut Medical center
Study officials:
affiliation: American University of Beirut Medical Center
name: Sahar Sayyid, MD
role: PRINCIPAL_INVESTIGATOR
References: