Continuous vs. Bolus Administration of NSAIDs After Laparoscopic Surgery for Multimodal Analgesia

Continuous vs. Bolus Administration of NSAIDs After Laparoscopic Surgery for Multimodal Analgesia: Pilot Randomized Controlled Trial

Currently the prevalent approach to perioperative management of patients is ERAS (Enhanced Recovery After Surgery) concept. This approach includes numerous aspects, among which the perioperative use of multimodal analgesia takes one of the leading places. Within the ERAS guidelines all sorts of minimization of opioid analgesics use in schemes of postoperative analgesia are appreciated. Thus, new pharmacological approaches are being actively developed currently in order to achieve adequate analgesia and to minimize the use of this group of drugs.

One of the most perspective trends within the multimodal analgesia concept is continuous infusion of non-steroidal anti-inflammatory drugs (NSAID). Up to date there are papers that both confirm the effectiveness of this method for maintaining adequate postoperative analgesia and show its limitations and deny the advantages of the continuous use of NSAID.

Up to this time the main attention of the medical community was paid for such drugs as paracetamol and ketoprofen. Nevertheless, one of the most common and safe NSAID is ibuprofen. In spite of this, there are no studies that explore the effectiveness of the continuous infusion of this drug. Thus, the lack of even low-quality evidence led to setting up a study of effectiveness and safety of continuous infusion of ibuprofen in comparison to its bolus injection.

Study Overview

• Status: Recruiting
• Conditions: Pain Management; Analgesic Efficacy; Postoperative Care; Analgesic Drugs; Analgesic, Nonopioid; Analgetic Consumption
• Intervention / Treatment: Drug: Ibuprofen bolus injection; Drug: Ibuprofen continuous infusion

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Valery Likhvantsev, PhD; Phone Number: +79036235982; Email: lik0704@gmail.com
• Study Contact Backup: Name: Kristina Kadantseva, PhD; Phone Number: +79168306947; Email: kristina161093@gmail.com

Study Locations

• Russian Federation
  • Moscow region
    • Moscow, Moscow region, Russian Federation, 115446
      • Recruiting
      • City Clinical Hospital named after S.S. Yudin
      • Contact: Maria Shemetova, PhD; Phone Number: +79055617910; Email: mshemetova@mail.ru
      • Principal Investigator: Maria Shemetova, PhD
      • Sub-Investigator: Natalia Smirnova

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age > 18 years old
• Elective laparoscopic surgery
• General anesthesia
• Signed informed consent from the patient to participate in the study
• RASS scale from -2 to +1 on admission to a surgical department or ICU

Exclusion Criteria:

• History of ibuprofen allergy
• Active erosive or ulcerative lesions of the gastrointestinal tract
• Chronic use of opioid analgesics or NSAIDs prior to enrollment
• Chronic kidney disease ≥ 3b stage according to the KDIGO classification
• Liver dysfunction (three times exceeding the upper reference limit of ALT or AST)
• A history of bronchial asthma
• A history of hereditary coagulopathies
• A history of use of anticoagulants

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: NSAID bolus injection	Drug: Ibuprofen bolus injection; The first bolus: ibuprofen 400 mg diluted in 0, 9% NaCl 200 ml is intravenous injected during the first hour right after the admission to the department. The drug is injected during the first hour at the rate of 4 mg/kg/h for the ideal body weight.; Bolus injection:Every 8 hours a intravenous bolus of ibuprofen 800 mg diluted in 0,9% NaCl 200 ml is injected during 1 hour (3 boluses per day in total).On the second day the every 8 hours intravenous bolus of ibuprofen 800 mg diluted in 0, 9% NaCl 200 ml is injected during 1 hour (3 boluses per day in total).; Placebo continuous infusion: Between the boluses a placebo (0,9% NaCl) continuous intravenous infusion is performed with the speed imitating the speed of ibuprofen infusion in the experimental group.
Experimental: NSAID continuous infusion	Drug: Ibuprofen continuous infusion; The first bolus: ibuprofen 400 mg diluted in 0,9% NaCl 200 ml is intravenous injected during the first hour right after the admission to the department. The drug is injected during the first hour at the rate of 4 mg/kg/h for the ideal body weight.; Continuous infusion:Ibuprofen 1200 mg diluted in 0,9% NaCl 300 ml is intravenous injected on the first day with the speed of 1 mg/kg/h (for the ideal body weight) during the remaining 23 hours.On the second day the intravenous infusion of ibuprofen 1600 mg diluted in 0,9% NaCl 400 ml with the speed of 1 mg/kg/h is continued during the 24 hours.; Imitation of bolus: Every 8 hours placebo (0, 9% NaCl 200 ml) is intravenous injected to create an imitation of bolus injection. Placebo is injected during the first hour.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Opioid consumption	Evaluation of the overall consumption of opioid analgesics after surgery during the whole postoperative period	up to 28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain intensity assessment	Evaluation of postoperative pain intensity using the Numerical Rating Scale (NRS); measurements at regular intervals and before rescue analgesia if pain exceeds NRS >5. The maximum value is 10, the minimum value is 0. The higher the value, the more severe patient's pain (worse).	From admission to ICU until 48 hours postoperatively

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
NSAID-related Adverse Effects	Incidence and severity of adverse effects including respiratory depression, gastrointestinal dysfunction, hepatotoxicity, renal dysfunction, allergic reactions, and CNS effects.	up to 28 days
Length of ICU stay	The number of days between the day of discharge from the ICU (or in-hospital death) after initial admission and the day of randomization.	1 year
Length of Hospital Stay	The number of days between the day of discharge from the hospital (or in-hospital death) after initial admission and the day of randomization.	1 year
ICU Readmission	Incidence of readmission to the intensive care unit within 28 days from the day of randomization.	Within 28 days from randomization
In-hospital mortality	Number of patients who die from any cause during initial hospitalization	1 year
28-days mortality	Number of patients who die from any cause within28 days after randomization	From randomization to 28 days
6-month mortality	Number of patients who die from any cause within 6 months after randomization	From randomization to 6 months

Collaborators and Investigators

• Sponsor: Federal Research and Clinical Centre of Intensive Care Medicine and Rehabilitology
• Investigators: Principal Investigator: Valery Likhvantsev, PhD, Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology

Study record dates

Study Major Dates

• Study Start (Actual): May 5, 2025
• Primary Completion (Estimated): May 20, 2026
• Study Completion (Estimated): November 20, 2026

Study Registration Dates

• First Submitted: June 30, 2025
• First Submitted That Met QC Criteria: July 7, 2025
• First Posted (Actual): July 17, 2025

Study Record Updates

• Last Update Posted (Actual): July 17, 2025
• Last Update Submitted That Met QC Criteria: July 7, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: analgesia; NSAID; postoperative care; pain management; analgesic drug
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Inflammatory Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Antirheumatic Agents; Sensory System Agents; Analgesics, Non-Narcotic; Analgesics; Anti-Inflammatory Agents, Non-Steroidal; Cyclooxygenase Inhibitors; Ibuprofen
• Other Study ID Numbers: CALM

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No