Anesthesia sTrategy foR Organ Procurement In braiN dEath (ATROPINE)

Grenoble Alpes University Hospital Center (CHU)

Status and phase: Not yet enrolling; Phase 3

Conditions: Brain-dead Organ Donors

Treatments: Drug: Opioid Anesthesia; Other: Intraoperative brain-dead donor management; Drug: Volatile anesthetic

Study type: Interventional

Funder types: Other

Identifiers

NCT07166991

38RC24.0238

Details and patient eligibility

About

The optimal anesthetic strategy during organ procurement in brain-dead donors remains unknown. The administration of anesthetic drugs in this setting aims to preserve hemodynamic stability in the face of reflex responses mediated by preserved spinal activity. Volatile anesthetics may blunt these reflexes, but their potential benefits in this context have never been investigated.

This randomized trial evaluates the effects of volatile anesthesia (sevoflurane), opioid administration (sufentanil), or no anesthetic drugs on intraoperative hemodynamic stability during organ procurement in brain-dead donors. The primary outcome is the proportion of operative time within a predefined arterial blood pressure range.

Full description

Brain-dead donors (BDD) remain the primary source of grafts for organ transplantation in France and worldwide. The main objective of BDD management, from the diagnosis of brain death in the intensive care unit (ICU) to organ procurement (OP) in the operating room, is to restore or maintain physiological homeostasis in order to preserve graft viability and improve long-term recipient outcomes. ICU management of potential BDD-particularly through donor management goals-has been shown to increase both the number and the quality of transplanted organs.

In contrast, anesthetic management of BDD during OP is less standardized, although surgical manipulation may jeopardize donor homeostasis. Hemodynamic responses to surgical stimuli (e.g., incision and visceral manipulation), such as tachycardia and marked increases in arterial blood pressure, are well described and result from preserved spinal reflexes. These reflexes, and the vasoactive drugs administered to counteract them, may cause intraoperative hemodynamic instability potentially detrimental to grafts.

Opioids have been proposed to attenuate these responses, but they have proven ineffective in suppressing catecholamine release induced by nociceptive surgical stimulation. Volatile anesthetics (in addition to potential protective effects against ischemia-reperfusion injury) may more effectively blunt these reflex responses. However, their benefits during OP in BDD have not been demonstrated. In the absence of evidence, retrospective studies and surveys in the USA and France report wide heterogeneity in anesthetic strategies used during graft harvesting. Volatile anesthetics and opioids remain the most common agents despite the lack of proven benefit compared with no anesthetic use.

This randomized controlled trial is designed to evaluate whether volatile anesthetics (sevoflurane) improve intraoperative hemodynamic stability during OP in BDD, compared with either no anesthetic use or opioid (sufentanil) administration. The hypothesis is that halogenated agents, by blunting spinally mediated hemodynamic responses to surgical stimuli, will provide greater intraoperative hemodynamic stability than no anesthetic or an opioid-based strategy.

Enrollment: 270 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Eligible adult brain-dead donor hospitalized in intensive care unit in one of the participating center:

  • Confirmed diagnosis of brain death according to French public health code.
  • Ongoing organ donation procedure managed by the local organ procurement coordination team with confirmation of the potential procurement of at least one intra-abdominal or intra-thoracic organ.
  • Transfer to the operating room for the organ procurement procedure scheduled for the next 6 hours and anesthesia team alerted.

• Information of the patient's next of kin by the investigator and absence of opposition to research confirmed by the testimony of the next of kin according to French public health code.

Exclusion criteria

• Age < 18 years.

• DCD (donation after circulatory death) donors.

• Ongoing extracorporeal circulation at the time of death.

• Hemodynamic instability at the screening visit defined by a noradrenalin dose > 1 µg/kg/min.

• Contraindication to the implementation of the anesthetic interventions evaluated in the trial:

  • Prior history of opioid or volatil anesthetic agents allergy.
  • Prior personal or family history of malignant hyperthermia or history of myopathy at risk of malignant hyperthermia.

• Opposition to the research expressed by the patient during his or her lifetime and documented by the next of kin.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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270 participants in 3 patient groups

Volatile anesthetic group

Experimental group

Description:

Sevoflurane administration during the organ procurement procedure

Treatment:

Other: Intraoperative brain-dead donor management

Drug: Volatile anesthetic

Opioid anesthetic group

Active Comparator group

Description:

Sufentanil administration during the organ procurement procedure

Treatment:

Other: Intraoperative brain-dead donor management

Drug: Opioid Anesthesia

No anesthetic drug group

Active Comparator group

Description:

No hypnotic (volatil anesthetics or intravenous anesthetics) or analgesic (opioid agents) drug administration during the organ procurement procedure

Treatment:

Other: Intraoperative brain-dead donor management