Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

The Use of Midazolam and Remifentanil During Dialysis Access Procedures

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04226443
Recruitment Status : Completed
First Posted : January 13, 2020
Last Update Posted : January 13, 2020
Sponsor:
Collaborator:
Trakya University
Information provided by (Responsible Party):
Ayse Baysal, Kartal Kosuyolu Yuksek Ihtisas Education and Research Hospital

Brief Summary:

BACKGROUND: Sedation and analgesia are related to unexpected adverse events in chronic renal failure patients undergoing arteriovenous fistula placement procedures under monitored anesthesia care (MAC).

OBJECTIVE: Our goal was to investigate and compare the sedation and analgesia related effects and adverse effects of continuous intravenous use of midazolam and intermittent bolus doses of midazolam while intravenous remifentanil is used as a rescue medication in patients with chronic renal failure.


Condition or disease Intervention/treatment Phase
Sedative Adverse Reaction Analgesic Adverse Reaction Midazolam Adverse Reaction Adverse Reaction to Drug Patient Satisfaction Chronic Kidney Diseases Arteriovenous Fistula Drug: Midazolam intravenous injection Drug: Remifentanil intravenous bolus dose Not Applicable

Detailed Description:

BACKGROUND: Sedation and analgesia are related to unexpected adverse events in chronic renal failure patients undergoing arteriovenous fistula placement procedures under monitored anesthesia care (MAC).

OBJECTIVE: Our goal was to investigate and compare the sedation and analgesia related effects and adverse effects of continuous intravenous use of midazolam to intermittent bolus doses of midazolam while intravenous remifentanil is used as a rescue medication in patients with chronic renal failure.

DESIGN: From a total of 116 patients, 99 patients with chronic renal failure undergoing arteriovenous fistula procedures were included in a prospective randomized study.

SETTINGS: Two tertiary care hospitals. PATIENTS: The patients were divided into Group 1 (continuous)(n=50); patients receiving intravenous midazolam infusion at a dose of 0.02 to 0.04 mg/kg/h and Group 2 (intermittent)(n=49); patients receiving intermittent intravenous bolus doses of 0.015 mg/kg every 10 minutes.

MAIN OUTCOME MEASURES: Primary outcomes were; 1- The total amount of doses of the use of midazolam and remifentanil in both groups of patients, 2- The evaluation of satisfaction of patient and surgeon at the end of the operation, in the recovery room during the period of recovery from sedation and before discharge. Other outcome measures include; the sedative, analgesic and hemodynamical effects of sedative medications that were compared in both groups of patients during the operation time period. The hospital stay duration was recorded and compared between groups. The maximum dose of midazolam was limited to 4 mg intravenously. The intensity of pain was assessed using a verbal numerical sedation scale (range 1 to 10) (VNRS) and the sedation level was recorded by Modified Observer's Assessment of Alertness/Sedation Scale (MOSS/A) (range 0 to 6). MOSS/A Scale includes; Score 0: Does not respond to deep stimulus, Score 1: Does not respond to mild prodding or shaking, Score 2: Responds only after mild prodding or shaking, Score 3: Responds only after name is called loudly and/or repeatedly, Score 4: Lethargic response to name spoken in normal tone, Score 5: Responds readily to name spoken in normal tone, Score 6: Agitated. An intravenous bolus dose of remifentanil as a rescue medication was administered for pain scores greater than 3 at a dose of 5µg/mL. Adverse events were recorded. Patient satisfaction level depending on the experience in general were evaluated at discharge from 0 to 4 point numerical scale: 0 = extremely dissatisfied; 1 = dissatisfied; 2 = neither satisfied nor dissatisfied; 3 = satisfied; 4 = extremely satisfied. Surgeon satisfaction level depending on the experience in general were evaluated at discharge from five-point numerical scale: 0 = extremely poor; 1 = poor; 2 = fair; 3 = good; 4 = excellent.

SAMPLE SIZE: The sample size was calculated based on a power of 80% and a 5% type-I error and for each group, thirty patients were required.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 99 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: This is a prospective, randomized clinical study. The patients were divided into two groups with a 1: 1 allocation and sealed envelope randomization method. Both groups of patients received intravenous midazolam, in Group 1, intravenous midazolam was administered continuously whereas, in Group 2, intravenous midazolam was administered as intermittent bolus doses. Both groups received intravenous remifentanil bolus doses as a rescue medication.
Masking: Double (Participant, Care Provider)
Masking Description: This study was a single-blinded controlled study because the sedation and analgesia were administered by anesthesiology residents who were unaware of the technique and the study protocol, however, the protocol was known by the experienced anesthesiologist who was attending the case and collecting the data during the procedure. The preparation of midazolam and remifentanil solutions and installation of the infusion devices were done by an anesthesiologist who was blinded for the study groups.
Primary Purpose: Treatment
Official Title: The Use of Midazolam and Remifentanil During Arteriovenous Fistula Placement Procedure and Monitored Anesthesia Care
Actual Study Start Date : August 28, 2012
Actual Primary Completion Date : April 15, 2016
Actual Study Completion Date : April 30, 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Fistulas

Arm Intervention/treatment
Active Comparator: Group 1
In Group 1(n=50); continuous infusion of intravenous midazolam (Dormicum, Deva Pharmaceutical, Turkey) at a dose of 0.02 to 0.04 mg/kg/h was started at the beginning of the operation and the dose was adjusted depending on pain level and sedation level using appropriate scales for monitoring throughout the surgical time period. An intravenous bolus dose of midazolam at a dose of 0.015 mg/kg was administered before the start of the surgery. A rescue medication of intravenous bolus dose of remifentanil at a concentration of 5 μg/mL was used every 5 to 10 minutes in doses of 1 to 3 mL if necessary for pain scores greater than 3. The medications were stopped prior to the end of the surgery.
Drug: Midazolam intravenous injection
The midazolam was prepared as 5 mg midazolam in 20 mL syringe of 5% dextrose water solution (0.25 mg/mL) in both arms. Both groups of patients received an intravenous bolus dose of midazolam was administered before the start of the surgery. In Group 1, continuous infusion of intravenous midazolam was started and in Group 2, intravenous bolus doses of midazolam were administered. The doses were adjusted depending on pain level and sedation level using appropriate scales for monitoring during the surgical time period. The drip rate was adjusted according to pain intensity. The infusion of drugs was discontinued at the end of the procedure.
Other Name: Dormicum, Deva Pharmaceutical, Turkey

Drug: Remifentanil intravenous bolus dose
A remifentanil infusion was prepared as follows; 0.5 mg remifentanil was added into 100 mL of 0.9% saline at a concentration of 5 μg/mL. The preparation of remifentanil solution and installation of the device was done by an anesthesiologist who was blinded for the study groups. The dose and number of patients that required remifentanil were recorded. The infusion of drugs was discontinued at the end of the procedure. A rescue medication of intravenous remifentanil bolus dose was used as 1 to 3 mL (5 μg or 15 μg) every 5 minutes if necessary for pain scores greater than 3. This infusion was prepared prior to the use during the study and was discontinued at the end of the procedure.
Other Name: Ultiva, Glaxo Smith Kline Pharmaceutical, England

Active Comparator: Group 2
in Group 2 (n=49), intravenous bolus doses of midazolam at a dose of 0.015 mg/kg every 10 minutes were administered at the beginning of the operation and the dose was adjusted depending on pain level and sedation level using appropriate scales for monitoring throughout the surgical time period. An intravenous bolus dose of midazolam at a dose of 0.015 mg/kg was administered before the start of the surgery. A rescue medication of intravenous bolus dose of remifentanil at a concentration of 5 μg/mL was used every 5 to 10 minutes in doses of 1 to 3 mL if necessary for pain scores greater than 3. The medications were stopped prior to the end of the surgery.
Drug: Midazolam intravenous injection
The midazolam was prepared as 5 mg midazolam in 20 mL syringe of 5% dextrose water solution (0.25 mg/mL) in both arms. Both groups of patients received an intravenous bolus dose of midazolam was administered before the start of the surgery. In Group 1, continuous infusion of intravenous midazolam was started and in Group 2, intravenous bolus doses of midazolam were administered. The doses were adjusted depending on pain level and sedation level using appropriate scales for monitoring during the surgical time period. The drip rate was adjusted according to pain intensity. The infusion of drugs was discontinued at the end of the procedure.
Other Name: Dormicum, Deva Pharmaceutical, Turkey

Drug: Remifentanil intravenous bolus dose
A remifentanil infusion was prepared as follows; 0.5 mg remifentanil was added into 100 mL of 0.9% saline at a concentration of 5 μg/mL. The preparation of remifentanil solution and installation of the device was done by an anesthesiologist who was blinded for the study groups. The dose and number of patients that required remifentanil were recorded. The infusion of drugs was discontinued at the end of the procedure. A rescue medication of intravenous remifentanil bolus dose was used as 1 to 3 mL (5 μg or 15 μg) every 5 minutes if necessary for pain scores greater than 3. This infusion was prepared prior to the use during the study and was discontinued at the end of the procedure.
Other Name: Ultiva, Glaxo Smith Kline Pharmaceutical, England




Primary Outcome Measures :
  1. The amount of total use of midazolam and remifentanil drug consumptions in milligrams during operation time period. [ Time Frame: Through the operative time period up to two hours of time. ]
    The comparison of total use of midazolam and remifentanil drug consumptions in milligrams during operation time period between the two groups.

  2. The evaluation of satisfaction of patient and surgeon by a questionnaire at the end of operation. [ Time Frame: The collection of questionnaire at the end of operation in recovery room after recovery from sedation in a total of ten minutes time. ]
    The evaluation and comparison of satisfaction of patient and surgeon at the end of operation by a questionnaire between the two groups. Patient satisfaction level depending on the experience in general was evaluated at discharge from 0 to 4 point numerical scale: 0 = extremely dissatisfied; 1 = dissatisfied; 2 = neither satisfied nor dissatisfied; 3 = satisfied; 4 = extremely satisfied. Surgeon satisfaction level depending on the experience in general was evaluated at discharge from five point numerical scale: 0 = extremely poor; 1 = poor; 2 = fair; 3 = good; 4 = excellent.

  3. Modified Observer's Assessment of Alertness/Sedation Scale (MOSS/A) Scale [ Time Frame: Through the operative time period up to two hours of time. ]
    The comparison of level of sedation using MOSS/A scale that ranges from 0 to 6, with a score of 6 defined as awake or minimally sedated, and a score of 0 defined as general anesthesia every 10 to 15 minutes between the two groups.

  4. Modified Observer's Assessment of Alertness/Sedation Scale (MOSS/A) Scale [ Time Frame: Through the operative time period up to two hours of time. ]
    Repeated measure analysis of level of sedation by the use of the collected MOSS/A scale that ranges from 0 to 6, with a score of 6 defined as awake or minimally sedated, and a score of 0 defined as general anesthesia every 10 to 15 minutes within groups.

  5. Verbal Numerical Rating Scale [ Time Frame: Through the operative time period up to two hours of time. ]
    The comparison of level of pain using Verbal Numerical Rating Scale (VNRS; 0= no pain, 10=the worst possible pain imaginable) scale every 10 to 15 minutes between the two groups.

  6. Verbal Numerical Rating Scale [ Time Frame: Through the operative time period up to two hours of time. ]
    Repeated measure analysis of level of sedation by the use of the collected Verbal Numerical Rating Scale (VNRS; 0= no pain, 10=the worst possible pain imaginable) scale every 10 to 15 minutes between the two groups.

  7. Recovery time [ Time Frame: Through the recovery room time period before discharge up to one hour time. ]
    The comparison of recovery time duration presented in minutes unit of time between the two groups.

  8. Hospital stay [ Time Frame: Through the duration of stay in hospital before discharge up to seventy two hours time. ]
    The comparison of hospital stay duration presented in hours unit of time between the two groups.

  9. Systolic blood pressure values during operation and in the recovery room. [ Time Frame: Through the operative time period up to two hours of time and through the recovery room time period before discharge up to one hour time. ]
    The comparison of systolic blood pressure in mmHg unit values every 15 minutes between the two groups.

  10. Heart rate values during operation and in the recovery room. [ Time Frame: Through the operative time period up to two hours of time and through the recovery room time period before discharge up to one hour time. ]
    The comparison of heart rate values in beats per minute unit every fifteen minutes between the two groups.

  11. Pulse oximetry values during operation and in the recovery room. [ Time Frame: Through the operative time period up to two hours of time and through the recovery room time period before discharge up to one hour time. ]
    The comparison of pulse oximetry values in percent unit every fifteen minutes between the two groups.

  12. Adverse events during operation and in the recovery room. [ Time Frame: Through the operative time period up to two hours of time and through the recovery room time period before discharge up to one hour time. ]
    Number of Participants With Adverse Events as Assessed by CTCAE Version 4.03.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   43 Years to 81 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age: Forty-three to eighty-one years of age,
  2. ASA status: American Society of Anesthesiologist (ASA) status I-III,
  3. The diagnosis: A diagnosis of chronic renal failure,
  4. The operation type: An arteriovenous fistula procedure

Exclusion Criteria:

  1. Body mass index greater than 40 that are considered morbidly obese patients,
  2. Lung disorders leading to severe respiratory insufficiency such as; severe asthma, chronic obstructive lung disease,
  3. Severe cardiovascular insufficiency or dysfunction,
  4. Insulin-dependent diabetes mellitus,
  5. Severe hepatic diseases,
  6. ASA status of 4 and 5,
  7. Neurologic disorders such as; the presence of epilepsy, arterial aneurysm, intracranial mass,
  8. Patients complaining about intense pain before the procedure and patients with a history of long term opioid use or chronic pain,
  9. Patients with a history of allergy to the study drugs,
  10. Patients without written informed consent.

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): NCT04226443


Sponsors and Collaborators
Kartal Kosuyolu Yuksek Ihtisas Education and Research Hospital
Trakya University
Investigators
Layout table for investigator information
Study Director: Gonul Sagiroglu, MD Trakya University, Faculty of Medicine, Edirne, Turkey
Publications of Results:

Other Publications:
Layout table for additonal information
Responsible Party: Ayse Baysal, Associate Professor, Kartal Kosuyolu Yuksek Ihtisas Education and Research Hospital
ClinicalTrials.gov Identifier: NCT04226443    
Other Study ID Numbers: 2013.1/28(#)
First Posted: January 13, 2020    Key Record Dates
Last Update Posted: January 13, 2020
Last Verified: January 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: This is a prospective, randomized clinical study. Both groups of patients received intravenous midazolam in two different methods. The groups were assigned depending on the use of intravenous midazolam as a continuous infusion or intermittent bolus doses. In both groups, as a rescue medication, intravenous bolus doses of remifentanil was used. The titration of the doses of midazolam and remifentanil was done according to the use of pain intensity level and the sedation level evaluations. The primary outcome was the comparison of the total amount of doses of the use of midazolam and remifentanil in milligrams in both groups of patients and the comparison of the satisfaction of patients and surgeons using an appropriate questionnaire. The pain intensity and sedation level, hemodynamical effects, as well as adverse events, were compared in both groups of patients. The recovery time and hospital stay duration were compared between the two groups of patients.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
Time Frame: The data will become available after registration and will be available upon request from the Clinical Study Director at any time after registration.
Access Criteria: Study Protocol and Statistical Package for the Social Sciences computer program data.

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Ayse Baysal, Kartal Kosuyolu Yuksek Ihtisas Education and Research Hospital:
Midazolam
Remifentanil
Benzodiazepine
Opioid
Chronic Kidney Diseases
Analgesia
Sedation
Adverse Reaction
Patient Satisfaction
Arteriovenous Fistula
Additional relevant MeSH terms:
Layout table for MeSH terms
Kidney Diseases
Renal Insufficiency, Chronic
Arteriovenous Fistula
Fistula
Drug-Related Side Effects and Adverse Reactions
Urologic Diseases
Renal Insufficiency
Pathological Conditions, Anatomical
Arteriovenous Malformations
Vascular Malformations
Cardiovascular Abnormalities
Cardiovascular Diseases
Vascular Fistula
Vascular Diseases
Congenital Abnormalities
Chemically-Induced Disorders
Midazolam
Remifentanil
Adjuvants, Anesthesia
Hypnotics and Sedatives
Central Nervous System Depressants
Physiological Effects of Drugs
Anti-Anxiety Agents
Tranquilizing Agents
Psychotropic Drugs
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
GABA Modulators
GABA Agents