Comparing Sevoflurane With Propofol Sedation in ESRF Patients

Kidney Diseases Clinical Trial

Official title: A Comparative Study of Sevoflurane Sedation With TCI Propofol Sedation in Dialysis Dependent End Stage Renal Failure Patients for Transposition of Brachiocephalic Fistula Repair

Status Not yet recruiting

Clinical Trial Summary

End-stage renal failure (ESRF) cohorts undergo brachiocephalic fistula(BCF) transposition with supraclavicular block. However, this is inadequate because the incision may extend to the axillary region which requires intercostobrachial (T2) dermatome blockage. Sedation is commonly indicated to allay anxiety whilst allowing intraprocedural lignocaine infiltration. It is challenging to administer safe sedation to ESRF patients due to multiple comorbidities, polypharmacy, altered pharmacokinetic drug handling. Intraoperative hypotension can be common and evident from the residual effect of antihypertensive and intravascular hypovolemia from regular hemodialysis. Midazolam is metabolized to an active metabolite which can accumulate causes apnea and delayed recovery. TCI propofol needs higher induction doses to achieve hypnosis causes exaggerated hypotension which may jeopardize organ perfusion. The investigators are exploring the potential benefit of sevoflurane sedation which are independent of renal clearance, rapid onset and offset, and ischemic preconditioning property in ESRF cohorts.

Clinical Trial Description

Regional anesthesia has been shown to be superior to general anesthesia in end-stage renal disease (ESRF) patients undergoing brachiocephalic transposition by ensuring graft patency, reducing pharmacokinetic (pK) and pharmacodynamic (pD) unpredictability, and minimize hemodynamic instability. However, a supraclavicular nerve block is inadequate in BCF transposition where surgical incision may extend to the axillary region which requires intercostobrachial nerve (T2) dermatome to be blocked. Intraprocedural lignocaine infiltration or pectoralis minor (PEC 2) block may be required to anaesthetize this region. Hence, sedation is commonly indicated to allay anxiety and to blunt sympathetic stress response to surgery.

ESRF patient is a challenging cohort to administer safe sedation due to multiple comorbidities, polypharmacy, altered pK handling of drug with a high proportion of total body water, the altered volume of distribution, protein binding, drug metabolism and excretion[3]. Commonly used intravenous midazolam causes delayed recovery and apnoea due to loss of renal ability to clear active metabolite α1-hydroxymidazolam. Target controlled infusion (TCI) propofol needs a higher induction dose to achieve clinical end-point of hypnosis in ESRF patient and causes hemodynamic disturbances.

Dialysis dependent ESRF patients are commonly hypertensive and adapted to a higher baseline blood pressure. Intraoperative hypotension is exaggerated from residual effect of antihypertensive, relative intravascular hypovolemia from pre-op haemodialysis and pre-operative fasting with no replacement fluid. Blood pressure determine perfusion, and existing evidence suggests intraoperative hypotension is associated with stroke, myocardial injury and delirium. Major hypertension guidelines have recommended target blood pressure level of 140/90 mm Hg for patients with renal disease.

Volatile sedation with sevoflurane in intensive care has been widely appraised for significant shorten and superior awakening time and reduced incidence of delirium compared with conventional midazolam/ propofol intravenous sedation. Sevoflurane has rapid onset of action with no significant concern of tolerance and tachyphylaxis. Drug clearance is via pulmonary exhalation which is independent of hepatic and renal function. Volatile agent is a mild analgesia with opioid sparing effect via N methyl-D-aspartate receptor blockade, thus provide a more stable sedation profile.ESRF patients are prone to develop ischemic heart disease due to calcification of intima. Sevoflurane also possess ischemic preconditioning and end organ cytoprotective properties along with anti-inflammatory mechanism. ;

Related Conditions & MeSH terms

• Hypotension
• Kidney Diseases
• Procedural Hypotension
• Sevoflurane

• NCT number: NCT04839536
• Study type: Interventional
• Source: University of Malaya
• Contact: Chao Chia Cheong, MMed Master
• Phone: +60163113597
• Email: chaochia@um.edu.my
• Status: Not yet recruiting
• Phase: Phase 4
• Start date: April 1, 2021
• Completion date: April 30, 2022