The PROTECT Trial: PROpofol Titration to Enhance haemodynamiC sTability

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

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.

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.

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