The PROTECT Trial: PROpofol Titration to Enhance haemodynamiC sTability

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Процедура Propofol titration
  Induction starts with propofol target-controlled Infusion (TCI) (Schnider model) at target effect-site drug concentration (Cet) 0.5-1.0 µg/mL and remifentanil TCI (Minto model) at Cet 0.5 ng/mL. If loss of consciousness (LOC) is not reached, propofol Cet is increased in 0.5-1.0 µg/mL steps. For intubation, remifentanil Cet increases up to 6.0 ng/mL.
• Процедура Conventional propofol induction
  Induction starts with propofol TCI at Cet 4-8 µg/mL and remifentanil TCI at Cet 2.5-3.5 ng/mL.

Первичные конечные точки

• Area under the mean arterial pressure threshold (AUT) [Срок оценки: 30 min after start of induction]

Вторичные конечные точки (12)

• Maximum Deviance (maxDev) [Срок оценки: 30 min after start of induction]
• Use of vasoactive drugs [Срок оценки: Up to 30 min after start of induction]
• Use of Trendelenburg/ lithotomy positioning [Срок оценки: Up to 30 min after start of induction]
• Total propofol consumption [Срок оценки: At LOC, up to 30 min after start of induction, and at skin incision]
• Neurocognitive test [Срок оценки: before surgery, 1 and 3-5 hours after recovery of consciousness (ROC)]
• Brice Interview [Срок оценки: 3-5 hours after ROC]
• Time from induction start to LOC [Срок оценки: From induction start to LOC]
• Total remifentanil consumption [Срок оценки: At LOC, up to 30 min after start of induction, and at skin incision]
• Time from induction start to intubation [Срок оценки: From induction start to intubation]
• Signs of reaction to intubation [Срок оценки: During intubation]
• Effect-site concentration of propofol [Срок оценки: At LOC and ROC]
• Effect-site concentration (Ce) of remifentanil [Срок оценки: At LOC and ROC]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Простое слепое

Основная цель

Другое

Центры проведения

Швейцария · 4 центра

• Kantonsspital Baden — Baden
• University Hospital Basel — Basel
• Cantonal Hospital Graubünden — Chur
• Kantonsspital Olten, soH — Olten

Публикации

• Funk S, Lohri MD, Kopp Lugli A, Schindler C, Wiencierz A, Mnich K, Schlapfer M, Gaberdiel AP, Puhan MA, Steiner LA, Gomes NV, Dell-Kuster S. The PROTECT trial: Effect of titrated versus conventional induction of general anaesthesia using a target-controlled infusion system on haemodynamics in patients undergoing non-cardiac surgery - protocol for a multicentre, expertise-based randomised controlle PMID 41605589

Идентификаторы

NCT: NCT06980688 · am24DellKuster

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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