Comparing Sevoflurane With Propofol Sedation in ESRF Patients

April 7, 2021 updated by: University of Malaya

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

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

36

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Chao Chia Cheong, MMed Master
  • Phone Number: +60163113597
  • Email: chaochia@um.edu.my

Study Contact Backup

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: DOUBLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
ACTIVE_COMPARATOR: Target controlled infusion (TCI) propofol
For TCI propofol group, all patients will receive nasal CPAP mask and nasal breathing with oxygen of 3 litre/min. We will utilize the Schneider model to target effect-site (Cet) starting from 0.5 mcg/ml and with a gradual 0.5mcg/ml increment every 30s until OAAS score of 3 is achieved. For any patients with OAAS score < 3, Cet will be decreased by a decremental 0.5 mcg/ml. The deepest level of sedation will be recorded.
Drug: Sevoflurane inhalant product
Sevoflurane will be delivered in an incremental dose to throughout procedure to achieve clinical sedation endpoint OAAS 3.
Other Names:
  • Ultane, 74412392
EXPERIMENTAL: Sevoflurane sedation
Patients randomised to this arm will be given time to familiarise with the nasal continuous positive airway pressure (CPAP) mask and nasal breathing with oxygen 3 litre/min via a Bain anaesthetic circuit before the introduction of sevoflurane. Once the patient starts to adapt to nasal CPAP mask, sevoflurane will be delivered, starting with a concentration of 0.2% and increase stepwise by 0.2% every 30s until sedation score of OAAS of 3 is achieved. Anaesthetist in charge will assess and maintain sedation endpoint to OAAS 3. If patient is over sedated, sevoflurane concentration will be reduced by 0.2% until OAAS 3. The deepest level of sedation will be recorded.
Drug: Sevoflurane inhalant product
Sevoflurane will be delivered in an incremental dose to throughout procedure to achieve clinical sedation endpoint OAAS 3.
Other Names:
  • Ultane, 74412392

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in mean arterial pressure from baseline following sedation
Time Frame: At baseline, pre-, and immediately after intervention

Hemodynamic instability is defined as event below:

Hypotension- Drop in mean arterial pressure (MAP) from baseline by more than 20% Hypotension - Drop in systolic blood pressure (sBP < 140 mmHg) and diastolic blood pressure (dBP < 90 mmHg)
At baseline, pre-, and immediately after intervention

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of hemodynamic interventions required during sedation
Time Frame: At baseline, pre-, and immediately after intervention
administration of vasoactive drugs to maintain hemodynamic within target (sBP> 140 mmHg, dBP > 80 mmHg, MAP within 20% baseline)
At baseline, pre-, and immediately after intervention
Duration of hemodynamic instability
Time Frame: At baseline, pre-, and immediately after intervention and surgery
Time course of drop in mean arterial pressure more than 20%
At baseline, pre-, and immediately after intervention and surgery
Onset time and recovery time
Time Frame: At baseline, pre-, and immediately after intervention and surgery
Onset time: time from starting sedation to Observer Assessment of Alertness/ Sedation (OAAS) score 3 (maintain at 3 for a consecutive 15 mins) Recovery time: Time from cessation of sedation to return to OAAS score 5
At baseline, pre-, and immediately after intervention and surgery

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Malaya

Investigators

  • Principal Investigator: Chao Chia Cheong, MMed Master, University Malaya

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ANTICIPATED)

April 1, 2021

Primary Completion (ANTICIPATED)

March 31, 2022

Study Completion (ANTICIPATED)

April 30, 2022

Study Registration Dates

First Submitted

March 28, 2021

First Submitted That Met QC Criteria

April 7, 2021

First Posted (ACTUAL)

April 9, 2021

Study Record Updates

Last Update Posted (ACTUAL)

April 9, 2021

Last Update Submitted That Met QC Criteria

April 7, 2021

Last Verified

April 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MREC: 2021116-9722

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

All collected individual participant data (IPD) and all IPD that underlie results in a publication

IPD Sharing Time Frame

Starting 6 months after publication

IPD Sharing Access Criteria

Personal enquiry via email

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Kidney Diseases

Clinical Trials on Sevoflurane inhalant product

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Italy

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe