Study design of the DAS-OLT trial: a randomized controlled trial to evaluate the impact of dexmedetomidine on early allograft dysfunction following liver transplantation

Abstract

Background: Perioperative ischemia/reperfusion (I/R) injury during liver transplantation is strongly associated with early allograft dysfunction (EAD), graft loss, and mortality. Hepatic I/R injury also causes remote damage to other organs including the renal and pulmonary systems. Dexmedetomidine (DEX), a selective α2-adrenoceptor agonist which is used as an adjuvant to general anesthesia, has been shown in preclinical studies to provide organ protection by ameliorating the effects of I/R injury in a range of tissues (including the liver). However, prospective clinical evidence of any potential benefits in improving outcomes in liver transplantation is lacking. This study aimed to verify the hypothesis that the application of dexmedetomidine during the perioperative period of liver transplantation can reduce the incidence of EAD and primary graft non-function (PNF). At the same time, the effects of dexmedetomidine application on perioperative renal function and lung function were studied. Methods: This is a prospective, single-center, randomized, parallel-group study. Two hundred participants (18-65 years) scheduled to undergo liver transplantation under general anesthesia will be included in this study. For participants in the treatment group, a loading dose of DEX will be given after induction of anesthesia (1 μg/kg over 10 min) followed by a continuous infusion (0.5 μg/kg /h) until the end of surgery. For participants in the placebo group, an equal volume loading dose of 0.9% saline will be given after the induction of anesthesia followed by an equal volume continuous infusion until the end of surgery. All other supplements, e.g., opioids, sedatives, and muscle relaxant, will be identical in both arms and administered according to routine clinical practice. Discussion: The present trial will examine whether DEX confers organoprotective effects in the liver, in terms of reducing the incidence of EAD and PNF in orthotopic liver transplantation recipients.

Intraoperative Low-Dose Dexmedetomidine Administration Associated with Reduced Hepatic Ischemia-Reperfusion Injury in Pediatric Deceased Liver Transplantation: A Retrospective Cohort Study

“…Although there were concerns of potential risks of delayed awakening and extubation due to the accumulation of DEX in patients with impaired liver function, no studies [ 9 , 38 ], including ours, have demonstrated any increase in the durations of mechanical ventilation, ICU stay, and hospital stay. This could be because the infusion rate and total dose of DEX in our study were lower than those of previous reports [ 9 , 27 , 28 , 35 , 38 , 39 ]. We used a dose of 0.4 μg/kg/h for approximately 8 h without a loading dose, and DEX infusion was well tolerated by the patients, without noticeable adverse effects attributable to the infusion.…”

Effect of intraoperative dexmedetomidine on hepatic ischemia-reperfusion injury in pediatric living-related liver transplantation: A propensity score matching analysis

“…A recent retrospective study showed that intraoperative low-dose DEX was associated with reduced HIRI in pediatric deceased LT ( 10 ). Another ongoing randomized controlled trial (NCT03770130) is currently investigating the effects of intraoperative DEX compared to placebo on EAD and PNF in adult deceased LT ( 31 ).…”

Effect of patient-controlled intravenous analgesia combined with flurbiprofen axetil and dezocine on postoperative analgesia for lobectomy (EPIC-FAD): a trial protocol

“…Patients who, at the time of enrolment, meet any of the following criteria are not eligible for the study: Body mass index (BMI) > 30 kg/m 2 Last smoked < 2 weeks prior to surgery for current smokers Pregnant or breastfeeding females (females aged 18 to 55 will receive pregnancy test) Hepatic (presence of ≥ 3 times the reference value of alanine aminotransferase/aspartate aminotransferase), renal (undergoing renal replacement therapy before surgery), or cardiac (the left ventricular ejection fraction < 30%) dysfunction [ 22 , 23 ] History of gastrointestinal disease (e.g., peptic disease, intestinal perforation) Severe or unstable mental illness (presence of mental illness in International Classification of Diseases-10 diagnosis groups F2, F3, F4, F5, or F6) [ 24 ] Severe or unstable physical conditions in which the selective surgery would not be considered (e.g., cerebral stroke, cardiac ischemia, congestive heart failure, hepatic failure, grade 3 hypertension) Patient with known allergies to opioids or NSAIDs Current or recent (within 1 month prior to surgery) administration of opioids or NSAIDs. Intake of any analgesics within 48 h prior to surgery History of alcohol, opioids or other drugs abuse, or chronic use of opioids Patients with contradictions to the use of PCIA Preoperative pain diagnosis (e.g., chronic pain, cancer-causing pain in site of surgery) Emergency surgery Reoperations for severe postoperative complications (e.g., severe bleeding, bronchopleural fistula) …”

“…Hepatic (presence of ≥ 3 times the reference value of alanine aminotransferase/aspartate aminotransferase), renal (undergoing renal replacement therapy before surgery), or cardiac (the left ventricular ejection fraction < 30%) dysfunction [ 22 , 23 ]…”