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Comparing Sevoflurane With Propofol Sedation in ESRF Patients

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ClinicalTrials.gov Identifier: NCT04839536
Recruitment Status : Not yet recruiting
First Posted : April 9, 2021
Last Update Posted : April 9, 2021
Sponsor:
Information provided by (Responsible Party):
University of Malaya

Study Description
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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.

Condition or disease Intervention/treatment Phase
Sevoflurane Kidney Diseases Procedural Hypotension Drug: Sevoflurane inhalant product Phase 4

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 Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 36 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Estimated Study Start Date : April 1, 2021
Estimated Primary Completion Date : March 31, 2022
Estimated Study Completion Date : April 30, 2022

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Arms and Interventions
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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 Name: 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 Name: Ultane, 74412392


Outcome Measures
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Primary Outcome Measures :
  1. 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)



Secondary Outcome Measures :
  1. 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)

  2. 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%

  3. 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


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04839536


Contacts
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Contact: Chao Chia Cheong, MMed Master +60163113597 chaochia@um.edu.my
Contact: Chew Yin Y Wang, FRCA +60192340232 wangcy1836@gmail.com

Sponsors and Collaborators
University of Malaya
Investigators
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Principal Investigator: Chao Chia Cheong, MMed Master University Malaya
More Information
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Publications:

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Responsible Party: University of Malaya
ClinicalTrials.gov Identifier: NCT04839536    
Other Study ID Numbers: MREC: 2021116-9722
First Posted: April 9, 2021    Key Record Dates
Last Update Posted: April 9, 2021
Last Verified: April 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: All collected individual participant data (IPD) and all IPD that underlie results in a publication
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: Starting 6 months after publication
Access Criteria: Personal enquiry via email

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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
Keywords provided by University of Malaya:
Sevoflurane Sedation, ESRF
Additional relevant MeSH terms:
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Kidney Diseases
Hypotension
Urologic Diseases
Vascular Diseases
Cardiovascular Diseases
Sevoflurane
 Platelet Aggregation Inhibitors
Anesthetics, Inhalation
Anesthetics, General
Anesthetics
Central Nervous System Depressants
Physiological Effects of Drugs