The Use of Midazolam and Remifentanil During Dialysis Access Procedures

NCT04226443 | Completed DMC

• 1 other identifier: 2013.1/28(#)
• Study Type: interventional
• Target: 99
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Sedative Adverse Reaction; Analgesic Adverse Reaction; Midazolam Adverse Reaction; Adverse Reaction to Drug; Patient Satisfaction; Chronic Kidney Diseases; Arteriovenous Fistula

Keywords

Midazolam; Remifentanil; Benzodiazepine; Opioid; Chronic Kidney Diseases; Analgesia; Sedation; Adverse Reaction; Patient Satisfaction; Arteriovenous Fistula

Outcome Measures

Primary Outcomes (12)

• The amount of total use of midazolam and remifentanil drug consumptions in milligrams during operation time period.

  The comparison of total use of midazolam and remifentanil drug consumptions in milligrams during operation time period between the two groups.

  Through the operative time period up to two hours of time.

• The evaluation of satisfaction of patient and surgeon by a questionnaire at the end of operation.

  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.

  The collection of questionnaire at the end of operation in recovery room after recovery from sedation in a total of ten minutes time.

• Modified Observer's Assessment of Alertness/Sedation Scale (MOSS/A) Scale

  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.

  Through the operative time period up to two hours of time.

• Modified Observer's Assessment of Alertness/Sedation Scale (MOSS/A) Scale

  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.

  Through the operative time period up to two hours of time.

• Verbal Numerical Rating Scale

  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.

  Through the operative time period up to two hours of time.

• Verbal Numerical Rating Scale

  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.

  Through the operative time period up to two hours of time.

• Recovery time

  The comparison of recovery time duration presented in minutes unit of time between the two groups.

  Through the recovery room time period before discharge up to one hour time.

• Hospital stay

  The comparison of hospital stay duration presented in hours unit of time between the two groups.

  Through the duration of stay in hospital before discharge up to seventy two hours time.

• Systolic blood pressure values during operation and in the recovery room.

  The comparison of systolic blood pressure in mmHg unit values every 15 minutes between the two groups.

  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.

• Heart rate values during operation and in the recovery room.

  The comparison of heart rate values in beats per minute unit every fifteen minutes between the two groups.

  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.

• Pulse oximetry values during operation and in the recovery room.

  The comparison of pulse oximetry values in percent unit every fifteen minutes between the two groups.

  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.

• Adverse events during operation and in the recovery room.

  Number of Participants With Adverse Events as Assessed by CTCAE Version 4.03.

  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.

Study Arms (2)

Group 1

ACTIVE COMPARATOR

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; Drug: Remifentanil intravenous bolus dose

Group 2

ACTIVE COMPARATOR

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; Drug: Remifentanil intravenous bolus dose

Interventions

Midazolam intravenous injection DRUG

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.

Also known as: Dormicum, Deva Pharmaceutical, Turkey

Group 1; Group 2

Remifentanil intravenous bolus dose DRUG

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.

Also known as: Ultiva, Glaxo Smith Kline Pharmaceutical, England

Group 1; Group 2

Eligibility Criteria

• Age: 43 Years - 81 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Kartal Kosuyolu Yuksek Ihtisas Education and Research Hospital: lead
• Trakya University: collaborator

Related Publications (12)

• Cole NM, Vlassakov K, Brovman EY, Heydarpour M, Urman RD. Regional Anesthesia for Arteriovenous Fistula Surgery May Reduce Hospital Length of Stay and Reoperation Rates. Vasc Endovascular Surg. 2018 Aug;52(6):418-426. doi: 10.1177/1538574418772451. Epub 2018 Apr 29.

  PMID: 29706126 BACKGROUND

• Sa Rego MM, Inagaki Y, White PF. Remifentanil administration during monitored anesthesia care: are intermittent boluses an effective alternative to a continuous infusion? Anesth Analg. 1999 Mar;88(3):518-22. doi: 10.1097/00000539-199903000-00009.

  PMID: 10071997 BACKGROUND

• Sun GQ, Gao BF, Li GJ, Lei YL, Li J. Application of remifentanil for conscious sedation and analgesia in short-term ERCP and EST surgery. Medicine (Baltimore). 2017 Apr;96(16):e6567. doi: 10.1097/MD.0000000000006567.

  PMID: 28422846 BACKGROUND

• Wyne A, Rai R, Cuerden M, Clark WF, Suri RS. Opioid and benzodiazepine use in end-stage renal disease: a systematic review. Clin J Am Soc Nephrol. 2011 Feb;6(2):326-33. doi: 10.2215/CJN.04770610. Epub 2010 Nov 11.

  PMID: 21071517 BACKGROUND

• Ahuja V, Mitra S, Kazal S, Huria A. Comparison of analgesic efficacy of flupirtine maleate and ibuprofen in gynaecological ambulatory surgeries: A randomized controlled trial. Indian J Anaesth. 2015 Jul;59(7):411-5. doi: 10.4103/0019-5049.160937.

  PMID: 26257413 BACKGROUND

• Levey AS, Eckardt KU, Tsukamoto Y, Levin A, Coresh J, Rossert J, De Zeeuw D, Hostetter TH, Lameire N, Eknoyan G. Definition and classification of chronic kidney disease: a position statement from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int. 2005 Jun;67(6):2089-100. doi: 10.1111/j.1523-1755.2005.00365.x.

  PMID: 15882252 BACKGROUND

• Boonstra AM, Stewart RE, Koke AJ, Oosterwijk RF, Swaan JL, Schreurs KM, Schiphorst Preuper HR. Cut-Off Points for Mild, Moderate, and Severe Pain on the Numeric Rating Scale for Pain in Patients with Chronic Musculoskeletal Pain: Variability and Influence of Sex and Catastrophizing. Front Psychol. 2016 Sep 30;7:1466. doi: 10.3389/fpsyg.2016.01466. eCollection 2016.

  PMID: 27746750 RESULT

• Beathard GA, Urbanes A, Litchfield T, Weinstein A. The risk of sedation/analgesia in hemodialysis patients undergoing interventional procedures. Semin Dial. 2011 Jan-Feb;24(1):97-103. doi: 10.1111/j.1525-139X.2011.00844.x.

  PMID: 21338400 RESULT

• Son A, Mannoia K, Herrera A, Chizari M, Hagdoost M, Molkara A. Dialysis Access Surgery: Does Anesthesia Type Affect Maturation and Complication Rates? Ann Vasc Surg. 2016 May;33:116-9. doi: 10.1016/j.avsg.2015.12.005. Epub 2016 Mar 8.

  PMID: 26965819 RESULT

• Niscola P, Scaramucci L, Vischini G, Giovannini M, Ferrannini M, Massa P, Tatangelo P, Galletti M, Palumbo R. The use of major analgesics in patients with renal dysfunction. Curr Drug Targets. 2010 Jun;11(6):752-8. doi: 10.2174/138945010791170879.

  PMID: 20041843 RESULT

• Hatzidakis AA, Charonitakis E, Athanasiou A, Tsetis D, Chlouverakis G, Papamastorakis G, Roussopoulou G, Gourtsoyiannis NC. Sedations and analgesia in patients undergoing percutaneous transhepatic biliary drainage. Clin Radiol. 2003 Feb;58(2):121-7. doi: 10.1053/crad.2002.1128.

  PMID: 12623040 RESULT

• Coyle TT, Helfrick JF, Gonzalez ML, Andresen RV, Perrott DH. Office-based ambulatory anesthesia: Factors that influence patient satisfaction or dissatisfaction with deep sedation/general anesthesia. J Oral Maxillofac Surg. 2005 Feb;63(2):163-72. doi: 10.1016/j.joms.2004.10.003.

  PMID: 15690283 RESULT

MeSH Terms

Conditions

Drug-Related Side Effects and Adverse Reactions; Patient Satisfaction; Renal Insufficiency, Chronic; Arteriovenous Fistula; Agnosia

Interventions

Midazolam; Remifentanil

Condition Hierarchy (Ancestors)

Chemically-Induced Disorders; Treatment Adherence and Compliance; Health Behavior; Behavior; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Arteriovenous Malformations; Vascular Malformations; Cardiovascular Abnormalities; Cardiovascular Diseases; Vascular Fistula; Vascular Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Fistula; Pathological Conditions, Anatomical; Perceptual Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Propionates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Piperidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Gonul Sagiroglu, MD

  Trakya University

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: 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.

Study Record Dates

• First Submitted: November 28, 2019
• First Posted: January 13, 2020
• Study Start: August 28, 2012
• Primary Completion: April 15, 2016
• Study Completion: April 30, 2016
• Last Updated: January 13, 2020

Record last verified: 2020-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, 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.