Nonopioid Analgesics and Cholecystectomy

Pain, Postoperative Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04622813
• Other study ID #: BIO-2020-0375
• Status: Completed
• Phase: Phase 3
• Start date: April 8, 2021
• Est. completion date: October 19, 2022

Study information

• Verified date: May 2023
• Source: American University of Beirut Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 90
• Est. completion date: October 19, 2022
• Est. primary completion date: October 19, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 64 Years

Eligibility

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)

Related Conditions & MeSH terms

• Cholecystectomy
• Opioid Use
• Pain, Postoperative

Intervention

Drug:
• nefopam, 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
• saline 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

Locations

Country	Name	City	State
Lebanon	American University of Beirut Medical center	Beirut

Sponsors (1)

Lead Sponsor	Collaborator
American University of Beirut Medical Center

Country where clinical trial is conducted

Lebanon, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Total morphine consumption in the post anesthesia care unit	Total morphine doses consumed after the surgery during the post anesthesia care unit stay of the patient	Throughout the patient's stay in the recovery room (average of 30 minutes after the surgery)
Secondary	Total fentanyl	Total fentanyl given intraoperatively.	Intraoperatively
Secondary	Total morphine	Total morphine on the floor	Throughout the patient's stay on the floor
Secondary	Ketoprofen consumption	Ketoprofen consumption on the floor	Throughout the patient's stay on the floor
Secondary	Paracetamol consumption	Paracetamol consumption on the floor	Throughout the patient's stay on the floor
Secondary	Total morphine consumption at 24 hours after surgery	Total morphine doses consumed at 24 hours after surgery	24 hours after surgery
Secondary	Number of patients receiving morphine in PACU	Number of patients receiving morphine in post anesthesia care unit	Throughout the patient's stay in the recovery room (average of 30 minutes after the surgery)
Secondary	Number of patients receiving morphine on the floor	Number of patients receiving morphine on the floor	Throughout the patient's stay on the floor
Secondary	Number of patients receiving morphine during the first 24 hours after surgery	Number of patients receiving morphine during the first 24 hours after surgery	During the first 24 hours after surgery
Secondary	Number of patients receiving ketoprofen on the floor	Number of patients receiving ketoprofen on the floor	On the floor
Secondary	Number of patients receiving paracetamol on the floor	Number of patients receiving paracetamol on the floor	On the floor
Secondary	NRS pain scores at rest in PACU	NRS pain scores at rest in post anesthesia care unit	Throughout the patient's stay in the recovery room (average of 30 minutes after the surgery)
Secondary	NRS pain scores at 24 h after surgery	NRS pain scores at 24 hours after surgery	24 hours after surgery
Secondary	sedation scores in PACU	sedation scores in post anesthesia care unit	Throughout the patient's stay in the recovery room (average of 30 minutes after the surgery)
Secondary	Time to first morphine requirement	Time to first morphine requirement	From the time of arrival to PACU until discharge
Secondary	Time to discharge (readiness) from PACU	Time to discharge (readiness) from post anesthesia care unit	Throughout the patient's stay in the recovery room (average of 30 minutes after the surgery)
Secondary	Nausea and vomiting	Incidence and severity of nausea and vomiting	Throughout the patient's stay in the recovery room (average of 30 minutes after the surgery)
Secondary	Rescue antiemetics	Need for rescue antiemetics	Throughout the patient's stay in the recovery room (average of 30 minutes after the surgery)
Secondary	Pruritus	Incidence of pruritus	Throughout the patient's stay in the recovery room (average of 30 minutes after the surgery)
Secondary	Respiratory depression	Incidence of respiratory depression	Throughout the patient's stay in the recovery room (average of 30 minutes after the surgery)
Secondary	Urinary retention	Incidence of urinary retention	Throughout the patient's stay in the recovery room (average of 30 minutes after the surgery)
Secondary	Tachycardia	Episodes of tachycardia	Intraoperatively and in PACU
Secondary	Sweating	Episodes of sweating	Intraoperatively and in PACU
Secondary	Quality of recovery	Quality of recovery at 24 h using the QoR-40	At 24 hours after the surgery
Secondary	Overall satisfaction score	Overall satisfaction score collected one month after surgery.	One month after surgery.