Anesthesia sTrategy foR Organ Procurement In braiN dEath

Phase 3Not Yet RecruitingNCT07166991

University Hospital, Grenoble270 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

270

Interventions

Volatile anestheticDRUG

In the volatile anesthetic group, sevoflurane will be administrated during the organ procurement procedure. Administration will be initiated progressively after moving in the operating room and will be pursued until aortic clamping (targeted end-expiratory concentration suggested between 1 and 2%). No opioid agent (or intravenous hypnotic agent) will be allowed in this group.

Opioid AnesthesiaDRUG

In the opioid anesthetic group, intravenous sufentanil will be administrated during the organ procurement procedure. Continuous administration will be initiated after moving in the operating room (suggested dosage : 0,3 µg/kg/h) with supplemental dose if needed (at the discretion of the anesthesia team) and will be pursued until aortic clamping. No hypnotic drug administration will be allowed in this group.

Intraoperative brain-dead donor managementOTHER

In all groups (experimental and control groups), neuromuscular blocking agents will be administered during the entire procedure, according to national guidelines. In all groups, hemodynamic management (use of vasoactive agents as vasopressors or anti-hypertensive drugs) will be done according to the discretion of the anesthesia team. In all groups, all the others aspects of the donor management will be not modified by the study protocol.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

A hierarchical endpoint of hemodynamic stability during the organ procurement procedure

Proportion of intraoperative time (between initial skin incision and aortic clamping) with a mean arterial blood pressure between 65 and 75 mmHg, between the volatile anesthetic group of brain-dead donors and : 1. The no anesthetic drug group of brain-dead donors. 2. The opioid anesthetic group of brain-dead donors.

Time frame: Operative time

Secondary Outcomes

Comparaison of the hemodynamic stability during the organ procurement procedure between the no anesthetic drug group and the opioid anesthetic group of brain-dead donors

Proportion of intraoperative time (between initial skin incision and aortic clamping) with a mean arterial blood pressure between 65 and 75 mmHg.

Time frame: Operative time

Between-group comparaison of the proportion of intraoperative time spent in hypotention

Relative duration of intraoperative time (from initial skin incision to aortic clamping) spent with a mean arterial pressure \< 60 mmHg.

Time frame: Operative time

Between-group comparaison of the proportion of brain-dead donors with a hemodynamic response at initial surgical incision

Occurrence of an increase in systolic blood pressure ≥ 20%, within 5 minutes of the initial surgical incision, compared with the mean systolic blood pressure registered in the 1 to 5 min preceding the initial surgical incision.

Time frame: Operative time

Between-group comparaison of the proportion of brain-dead donors with a hemodynamic response to sternotomy

Occurrence of an increase in systolic blood pressure ≥ 20%, in the 5 minutes following sternotomy, compared with the mean systolic blood pressure measured in the 1 to 5 min preceding sternotomy, in the subgroup of brain-death donors who underwent an intra-thoracic organ harvesting.

Time frame: Operative time

Between-group comparaison of the mean arterial blood pressure variability during the organ procurement procedure

Intraoperative variability of the mean arterial pressure measuring using the average real variability (ARV) index of mean arterial pressure.

Time frame: Operative time

Between-group comparaison of the mean arterial blood pressure variability during the organ procurement procedure

Intraoperative variability of the mean arterial pressure measuring using the intra-individual standard deviation of mean arterial pressure measurements (SD-MAP).

Time frame: Operative time

Between-group comparaison of the mean dose of catecholamines administered during the organ procurement procedure

Intraoperative mean dose (µg/kg/min or U/min) of each catecholamine administered (noradrenaline, adrenaline, dobutamine, vasopressin) and intraoperative mean norepinephrine equivalent score.

Time frame: Operative time

Between-group comparaison of the total intraoperative volume of vascular filling

Volume by type of feeling solution during the organ procurement procedure

Time frame: Operative time

Between-group comparaison of the total intraoperative volume of labile blood products

Volume of labile blood products by type during the organ procurement procedure

Time frame: Operative time

Between-group comparaison of the number of organs harvested and transplanted

Number of solid organs (heart, lungs, liver, kidneys) harvested and effectivelly transplanted by brain-dead donors.

Time frame: 24 hours

Between-group comparison of the rate of delayed graft function of the kidney

Delayed graft function of the kidney in the recipient defined as the need for dialysis within 7 days post-transplant.

Time frame: 7 days post-transplant

Between-group comparison of the rate of primary lung graft dysfunction

Primary lung graft dysfunction in the recipient, as defined by the French Biomedicine Agency: Existence within 72 hours post-transplant of diffuse pulmonary opacities, the severity of which is graded from 1 to 3, depending on the PaO2/FiO2 ratio (\< 200, 200-300, \>300) or the need for extracorporeal oxygenation (grade 3).

Time frame: 72 hours

Between-group comparison of the rate of primary heart graft dysfunction

Primary heart graft dysfunction in the recipient, as defined by the French Biomedicine Agency: left ventricular ejection fraction \< 30% (ultrasound), and/or need for mechanical circulatory assistance, re-transplantation or death of the recipient within 24 hours post-transplant.

Time frame: 24 hours

Between-group comparison of the rate of primary liver graft dysfunction

Primary liver graft dysfunction in the recipient, as defined by the French Biomedicine Agency: bilirubin ≥ 10mg/dL on day 7, international normalized ratio ≥ 1.6 on day 7, and alanine or aspartate aminotransferases \>2000 IU/L within the first 7 days

Time frame: 7 days post-transplant

Describe the number of donor management goals achieved in the 12 hours prior and during the organ procurement procedure

Describe the number of donor management goals achieved in the 12 hours prior and during the organ procurement procedure, including the following: * Heart rate between 60 and 120 /min, * Diuresis between 1 and 1.5 mL/kg/h, * PaO2 / FiO2 ratio \> 250 (if lung harvested), * Hemoglobin \> 7 g/dL (10 g/dL if intrathoracic harvesting), * Blood glucose between 5 and 8 mmol/L, * Natremia \< 155 mmol/L, * Core temperature \> 35°C.

Time frame: 24 hours