Clinical trial NCT04839536: Comparing Sevoflurane With Propofol Sedation in ESRF Patients
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Sevoflurane
Kidney Diseases
Procedural Hypotension
Keywords: Sevoflurane Sedation, ESRF
Lead sponsor: University of Malaya
Sponsor class: OTHER
First posted: 2021-04-09
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: Inclusion Criteria:

* Patient with end stage renal failure, dialysis dependent undergoing transposition of brachiocephalic fistula repair
* American Society of Anesthesiology Physical Status Classification System (ASA) II or III

Exclusion Criteria:

* Patient refusal
* History or family history of malignant hyperthermia
* Known allergy to propofol or local anaesthetic agent
* Patients who have taken neuroleptics, benzodiazepine over 2 weeks within 1 month
* Chronic use of alcohols/ opioid
* Active lungs disease (eg. acute exacerbation of chronic obstructive pulmonary disease)
* Active and significant cardiac disease (eg. decompensated congestive cardiac failure, recent myocardial infarction)
* End-stage heart failure with left ventricular ejection fraction \< 30%
* Recent (\< 3 months) cerebrovascular accident

Primary outcomes:
measure: Change in mean arterial pressure from baseline following sedation
timeFrame: At baseline, pre-, and immediately after intervention
Secondary outcomes:
measure: Number of hemodynamic interventions required during sedation
timeFrame: At baseline, pre-, and immediately after intervention
measure: Duration of hemodynamic instability
timeFrame: At baseline, pre-, and immediately after intervention and surgery
measure: Onset time and recovery time
timeFrame: At baseline, pre-, and immediately after intervention and surgery
Other outcomes:
Locations:
Study officials:
affiliation: University of Malaya
name: Chao Chia Cheong, MMed Master
role: PRINCIPAL_INVESTIGATOR
References:
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