Clinical trial NCT06980688: The PROTECT Trial: PROpofol Titration to Enhance haemodynamiC sTability
Official title: Multicentre Single-blinded, Expertise-based RCT Comparing Haemodynamic Parameters Between Titration and Conventional Induction of General Anaesthesia With Target-controlled Infusion System in Patients Undergoing Non-cardiac Surgery
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Anesthesia
Keywords: Target-controlled infusion
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
Collaborators: name: University of Basel
name: University of Zurich
First posted: 2025-05-20
Enrollment: 320
Sex: ALL
Minimum age (years): 55
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: The aim of this multicentre, single-blinded, expertise-based randomised controlled trial is evaluate whether slowly increasing the dose of the anaesthetic drug propofol based on a patient's needs leads to more stable blood pressure compared to giving a standard starting dose in patients aged 55 and older undergoing non-cardiac surgery.

Detailed description: Propofol is a widely used anaesthetic drug known to lower blood pressure (hypotension) by relaxing blood vessels. The extent of hypotension depends on the dose and speed of propofol administration. A significant drop in blood pressure after anaesthesia is started, known as post-induction hypotension (PIH), can damage organs like the heart and kidneys, especially in older and multimorbid patients.

Target-controlled infusion (TCI) systems are commonly used to deliver anaesthetic drugs like propofol and remifentanil in a controlled way. The standard approach for starting anaesthesia (induction) is to begin with a high dose to quickly make the patient unconscious and suppress the body's response to intubation. Titration is a potentially safer alternative, where the dose is slowly increased until the patient becomes unconscious.

However, current evidence comparing the two methods is limited, especially in older patients. A small retrospective study suggested that titration improves blood pressure stability, and a survey of Swiss anaesthetists showed strong interest in this approach.

This multicentre, single-blinded, expertise-based randomised controlled trial investigates whether titration using TCI systems improves blood pressure stability in patients aged 55 and older undergoing non-cardiac surgery. The results of this trial will help to evaluate the clinical applicability and economic impact of the titration method in routine anaesthesia care and may support its future implementation into standard practice.

Eligibility criteria: Inclusion Criteria:

* Adults ≥ 55 years old
* Patients undergoing any of the following planned surgery under general anaesthesia with intubation: Ear, nose and throat, gynaecological, maxillofacial, orthopedic, plastic and reconstructive, spine, urologic, vascular (varicose vein surgery, femoral endarterectomy, peripheral bypass surgery) and visceral surgery
* Standard procedure for anaesthesia with propofol Target-Controlled Infusion (TCI) using the Schnider model and remifentanil TCI using the Minto model
* American Society of Anesthesiologists Physical Status Classification system (ASA PS) I-IV
* Body mass index (BMI) ≥18.5 or \<35 kg/m2
* Signed written informed consent

Exclusion Criteria:

* Special forms of anaesthesia induction, specifically awake tracheal intubation and rapid sequence induction
* Combined anaesthesia procedures (general and regional anaesthesia combined)
* Special forms of general anaesthesia (opioid-free anaesthesia or any opioid-sparring modifications with lidocaine, magnesium, ketamine, clonidine or dexmedetomidine)
* Surgery in the prone position within the first 30 minutes
* Patients with known difficult airway
* Daily consumption of alcohol (\> one unit/day) or \> seven units/week
* Any regular recreational drug abuse
* Chronic use of benzodiazepines or opioids
* Allergy to propofol
* Patients with known brain pathologies, specifically seizure disorders, stroke within the past 9 months or dementia
* History of awareness
* Inability to follow procedures or insufficient knowledge in German

Primary outcomes:
measure: Area under the mean arterial pressure threshold (AUT)
timeFrame: 30 min after start of induction
Secondary outcomes:
measure: Maximum Deviance (maxDev)
timeFrame: 30 min after start of induction
measure: Use of vasoactive drugs
timeFrame: Up to 30 min after start of induction
measure: Use of Trendelenburg/ lithotomy positioning
timeFrame: Up to 30 min after start of induction
measure: Total propofol consumption
timeFrame: At LOC, up to 30 min after start of induction, and at skin incision
measure: Neurocognitive test
timeFrame: before surgery, 1 and 3-5 hours after recovery of consciousness (ROC)
measure: Brice Interview
timeFrame: 3-5 hours after ROC
measure: Time from induction start to LOC
timeFrame: From induction start to LOC
measure: Total remifentanil consumption
timeFrame: At LOC, up to 30 min after start of induction, and at skin incision
measure: Time from induction start to intubation
timeFrame: From induction start to intubation
measure: Signs of reaction to intubation
timeFrame: During intubation
measure: Effect-site concentration of propofol
timeFrame: At LOC and ROC
measure: Effect-site concentration (Ce) of remifentanil
timeFrame: At LOC and ROC
measure: Duration of MAP below threshold
timeFrame: Up to 30 min after start of induction
measure: Bispectral Index at skin incision
timeFrame: At skin incision
measure: Total opioid consumption
timeFrame: During PACU stay
Other outcomes:
measure: Health Economic Analysis
timeFrame: During the perioperative period
Locations:
city: Baden
country: Switzerland
facility: Kantonsspital Baden
city: Basel
country: Switzerland
facility: University Hospital Basel
city: Chur
country: Switzerland
facility: Cantonal Hospital Graubünden
city: Olten
country: Switzerland
facility: Kantonsspital Olten, soH
Study officials:
affiliation: University Hospital, Basel, Switzerland
name: Salome Dell-Kuster, Prof. Dr. med
role: PRINCIPAL_INVESTIGATOR
References: