The Use of Midazolam and Remifentanil During Dialysis Access Procedures
Condition: Sedative Adverse Reaction; Analgesic Adverse Reaction; Midazolam Adverse Reaction; Adverse Reaction to Drug; Patient Satisfaction; Chronic Kidney Diseases; Arteriovenous Fistula
MeSH terms: Kidney Diseases; Renal Insufficiency, Chronic; Arteriovenous Fistula; Fistula; Drug-Related Side Effects and Adverse Reactions
Study type: Interventional

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.
    

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.
    

Intervention name(s): Midazolam intravenous injection; Remifentanil intravenous bolus dose
Intervention type(s): Drug; Drug
Intervention description(s): 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.; 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 intervention name(s): Dormicum, Deva Pharmaceutical, Turkey; Ultiva, Glaxo Smith Kline Pharmaceutical, England
Intervention MeSH terms: Midazolam; Remifentanil
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)
Primary purpose: Treatment
Keywords: Midazolam; Remifentanil; Benzodiazepine; Opioid; Chronic Kidney Diseases; Analgesia; Sedation; Adverse Reaction; Patient Satisfaction; Arteriovenous Fistula