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.

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.

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.

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.

The data will become available after registration and will be available upon request from the Clinical Study Director at any time after registration.

Study Protocol and Statistical Package for the Social Sciences computer program data.

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.