A Novel Two-Step Dosing Induction Strategy (The Propofol Challenge Test) to Minimize Propofol Injection Pain

NCT07763548 | Not Yet Recruiting Phase 4

• 1 other identifier: HUB20260364
• Study Type: interventional
• Target: 2,000
• Locations: 0 countries
• Sites: N/A

Brief Summary

Propofol is the most widely used intravenous hypnotic agent for the induction of general anesthesia owing to its rapid onset and short duration of action. Despite its favorable pharmacokinetics and widespread use, a notable drawback persists: the incidence of pain on injection. Statistics on the matter are widely variable, but some estimates indicate that the incidence of pain with propofol injection is around 70%1. To date, no studies have systematically evaluated whether dividing the induction dose of propofol-starting with a small sub-induction bolus (e.g., 20 mg) followed by the remainder-can reduce pain perception. We hypothesize that a two-step administration of propofol-consisting of a small initial dose followed by the remaining dose-may serve as a nociceptive preconditioning stimulus and reduce postoperative patient-recalled injection pain compared to standard single-bolus administration.

Conditions

Any Patient Under General Anesthesia With Propofol Induction

Keywords

Propofol, pain,

Outcome Measures

Primary Outcomes (1)

• Pain on injection

  To compare the incidence of postoperative patient-recalled injection pain compared to standard single-bolus administration.

  6 hour

Secondary Outcomes (1)

• Intensity of pain

  6 hours

Study Arms (2)

Single bolus injection

ACTIVE COMPARATOR

Patient will receive their propofol induction dose in a single bolus injection.

Other: Bolus injection

Fractionned injection

EXPERIMENTAL

Patients will receive 20 mg of propofol followed by the remaining dose of propofol 30-40 seconds later.

Other: Fractionned onjection

Interventions

Bolus injection OTHER

During Months 1, 3, 5 and 7 patients will receive a full single bolus of propofol

Single bolus injection

Fractionned onjection OTHER

During Months 2, 4, 6 and 8 patients will receive the same total dose but delivered in two sequential injections: an initial subdose (e.g., 20 mg), followed by the remainder of the dose after a brief interval (e.g., 30 seconds).

Fractionned injection

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults ≥18 years old.
• Undergoing non cardiac surgery under general anesthesia.
• Receiving propofol for induction.
• No midazolam premedication
• g IV Catheter below the antecubital fossa used for induction of anesthesia

You may not qualify if:

• Emergency surgery.
• Inability to communicate (language or cognitive impairment).
• Pre-induction IV analgesia administration or patients under preoperatively
• Patient with dementia, Alzheimer or other uncontrolled psychiatric diseases that would impact their ability to willingly participate

Sponsors & Collaborators

• Erasme University Hospital: lead

Related Publications (5)

• Euasobhon P, Dej-Arkom S, Siriussawakul A, Muangman S, Sriraj W, Pattanittum P, Lumbiganon P. Lidocaine for reducing propofol-induced pain on induction of anaesthesia in adults. Cochrane Database Syst Rev. 2016 Feb 18;2(2):CD007874. doi: 10.1002/14651858.CD007874.pub2.

  PMID: 26888026 BACKGROUND

• Picard P, Tramer MR. Prevention of pain on injection with propofol: a quantitative systematic review. Anesth Analg. 2000 Apr;90(4):963-9. doi: 10.1097/00000539-200004000-00035.

  PMID: 10735808 BACKGROUND

• Nakane M, Iwama H. A potential mechanism of propofol-induced pain on injection based on studies using nafamostat mesilate. Br J Anaesth. 1999 Sep;83(3):397-404. doi: 10.1093/bja/83.3.397.

  PMID: 10655909 BACKGROUND

• Jalota L, Kalira V, George E, Shi YY, Hornuss C, Radke O, Pace NL, Apfel CC; Perioperative Clinical Research Core. Prevention of pain on injection of propofol: systematic review and meta-analysis. BMJ. 2011 Mar 15;342:d1110. doi: 10.1136/bmj.d1110.

  PMID: 21406529 BACKGROUND

• Bellouni G, Clanet M, Touihri K, Delaporte A, Boulos NM, Kim K, Grogan T, Alexander B, Coeckelenbergh S, Joosten A. Incidence and predictors of postoperative recall of propofol injection pain: a prospective observational cohort pilot study. BJA Open. 2026 Feb 27;17:100537. doi: 10.1016/j.bjao.2026.100537. eCollection 2026 Mar.

  PMID: 41798321 BACKGROUND

MeSH Terms

Conditions

Pain

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Alexandre Joosten, MD, PhD

  Department of Anesthesiology & Perioperative Medecine, Ronald Reagan Medical Center, University of California Los Angeles, USA

  STUDY DIRECTOR

Central Study Contacts

Denis Schmartz, MD

CONTACT

+3225553324; denis.schmartz@hubruxelles.be

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Pain will be assessed by a blinded member of the team, not aware of the group.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This will be a pragmatic prospective, time-block-allocated comparative effectiveness trial which will take place over an eight-month period. To assess the impact of injection technique on recall pain, the method of propofol administration will alternate monthly. * During Months 1, 3, 5 and 7 patients will receive a full single bolus of propofol * During Months 2, 4, 6 and 8 patients will receive the same total dose but delivered in two sequential injections: an initial subdose (e.g., 20 mg), followed by the remainder of the dose after a brief interval (e.g., 30 seconds). All other aspects of anesthesia induction will follow standard clinical protocols.

Study Record Dates

• First Submitted: August 10, 2026
• First Posted: August 13, 2026
• Study Start (Estimated): October 2, 2026
• Primary Completion (Estimated): May 31, 2028
• Study Completion (Estimated): June 30, 2028
• Last Updated: August 13, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will not share