Anesthesia sTrategy foR Organ Procurement In braiN dEath

Official title

Impact of a Specific Anesthetic Strategy on Intraoperative Hemodynamic Stability During Organ Procurement in Brain Dead Donor: An Open-label Multicenter Randomized and Controlled Trial

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.

Detailed 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.

Interventions

• Drug Volatile anesthetic
  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.
• Drug Opioid Anesthesia
  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.
• Other Intraoperative brain-dead donor management
  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.

Primary outcome measures

• A hierarchical endpoint of hemodynamic stability during the organ procurement procedure [Time frame: Operative time]

Secondary outcome measures (12)

• 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 [Time frame: Operative time]
• Between-group comparaison of the proportion of intraoperative time spent in hypotention [Time frame: Operative time]
• Between-group comparaison of the proportion of brain-dead donors with a hemodynamic response at initial surgical incision [Time frame: Operative time]
• Between-group comparaison of the proportion of brain-dead donors with a hemodynamic response to sternotomy [Time frame: Operative time]
• Between-group comparaison of the mean arterial blood pressure variability during the organ procurement procedure [Time frame: Operative time]
• Between-group comparaison of the mean arterial blood pressure variability during the organ procurement procedure [Time frame: Operative time]
• Between-group comparaison of the mean dose of catecholamines administered during the organ procurement procedure [Time frame: Operative time]
• Between-group comparaison of the total intraoperative volume of vascular filling [Time frame: Operative time]
• Between-group comparaison of the total intraoperative volume of labile blood products [Time frame: Operative time]
• Between-group comparaison of the number of organs harvested and transplanted [Time frame: 24 hours]
• Between-group comparison of the rate of delayed graft function of the kidney [Time frame: 7 days post-transplant]
• Between-group comparison of the rate of primary lung graft dysfunction [Time frame: 72 hours]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

France · 1 center

• CHU Grenoble Alpes — Grenoble

Publications

• Fitzgerald RD, Dechtyar I, Templ E, Fridrich P, Lackner FX. Cardiovascular and catecholamine response to surgery in brain-dead organ donors. Anaesthesia. 1995 May;50(5):388-92. doi: 10.1111/j.1365-2044.1995.tb05989.x. PMID 7793540
• Conci F, Procaccio F, Arosio M, Boselli L. Viscero-somatic and viscero-visceral reflexes in brain death. J Neurol Neurosurg Psychiatry. 1986 Jun;49(6):695-8. doi: 10.1136/jnnp.49.6.695. PMID 3525756
• Wetzel RC, Setzer N, Stiff JL, Rogers MC. Hemodynamic responses in brain dead organ donor patients. Anesth Analg. 1985 Feb;64(2):125-8. PMID 3882020
• Fitzgerald RD, Hieber C, Schweitzer E, Luo A, Oczenski W, Lackner FX. Intraoperative catecholamine release in brain-dead organ donors is not suppressed by administration of fentanyl. Eur J Anaesthesiol. 2003 Dec;20(12):952-6. doi: 10.1017/s0265021503001534. PMID 14690096
• Elkins LJ. Inhalational anesthesia for organ procurement: potential indications for administering inhalational anesthesia in the brain-dead organ donor. AANA J. 2010 Aug;78(4):293-9. PMID 20879630
• Souter MJ, Eidbo E, Findlay JY, Lebovitz DJ, Moguilevitch M, Neidlinger NA, Wagener G, Paramesh AS, Niemann CU, Roberts PR, Pretto EA Jr. Organ Donor Management: Part 1. Toward a Consensus to Guide Anesthesia Services During Donation After Brain Death. Semin Cardiothorac Vasc Anesth. 2018 Jun;22(2):211-222. doi: 10.1177/1089253217749053. Epub 2017 Dec 24. PMID 29276852
• Boutin C, Vachiery-Lahaye F, Alonso S, Louart G, Bouju A, Lazarovici S, Perrigault PF, Capdevila X, Jaber S, Colson P, Jonquet O, Ripart J, Lefrant JY, Muller L; pour le groupe AzuRea. [Anaesthetic management of brain-dead for organ donation: impact on delayed graft function after kidney transplantation]. Ann Fr Anesth Reanim. 2012 May;31(5):427-36. doi: 10.1016/j.annfar.2011.11.027. Epub 2012 Apr PMID 22541983
• Perez-Protto S, Nazemian R, Matta M, Patel P, Wagner KJ, Latifi SQ, Lebovitz DJ, Reynolds JD. The effect of inhalational anaesthesia during deceased donor organ procurement on post-transplantation graft survival. Anaesth Intensive Care. 2018 Mar;46(2):178-184. doi: 10.1177/0310057X1804600206. PMID 29519220

Identifiers

NCT: NCT07166991 · 38RC24.0238

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗