Midazolam With Meperidine and Dexmedetomidine vs. Midazolam With Meperidine and Propofol for Sedation During ERCP

NCT ID: NCT02475824

Last Updated: 2018-04-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 258 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-05-31
• Study Completion Date: 2017-01-30

Brief Summary

This is a single-center, prospective, randomized, double-blinded study of consecutive patients referred for ERCP. A recent study suggested that the addition of dexmedetomidine to the midazolam-meperidine regimen (MMD)provided better sedative efficacy and a superior safety profile during ERCP compared with a midazolam-meperidine regimen. Further study is warranted to compare an MMD regimen with propofol-based regimen.

Randomization is performed by use of a computer-generated random allocations in a ratio of 1:1 in balanced blocks of 4. A separate sedating nurse, who don't participate in the study, is the only person with knowledge of the sedation regimen. This separate nurse repeated the injection of propofol and completed questionnaires.

Detailed Description

Study design This is a single-center, prospective, randomized, double-blinded study of consecutive patients referred for ERCP. Randomization is performed by use of a computer-generated random allocations in a ratio of 1:1 in balanced blocks of 4. A separate sedating nurse, who don't participate in the study, is the only person with knowledge of the sedation regimen. This separate nurse repeated the injection of propofol and completed questionnaires.

Inclusion criteria include consecutive patients who are scheduled for ERCP and those are aged 18-80 years. (ASA class I-III) Exclusion criteria are as follows;

1) patient age < 18years, 2) pregnancy, 3) American Society of Anesthesiology (ASA) physical status class IV, V, 4) history of allergies to drug used, 6) history of complications with previous sedation, 5) hypoxemia (baseline SaO2) <90%, 6) hypotension (baseline systolic blood pressure <90mmHg), 7) severe bradycardia (heart rate <50/min) and/or brady-dysrhythmias (e.g. advanced heart block), 8) impaired ventricular function (left ventricular ejection fraction <30%), 9) baseline respiratory rate >25 or <10 breaths/min, and 10) inability to provide informed consent. Patients are excluded from the final analysis if the procedure is terminated early or abandoned for anatomical reasons (i.e., duodenal obstruction or gastrectomy).

Sedation protocols After randomization patients are allocated to group 1 or 2, and prepared for endoscopy.

All sedatives and analgesics used for the study are administered by trained sedative nurse under endoscopist supervision. All participants receive an IV bolus dose of midazolam (0.06mg/kg, 50% reduction for patients if age ≥70 or ASA class III-IV; Bukwang Pharm Co., Seoul, Republic of Korea) and meperidine (50mg. 25mg for patients aged ≥70 years; pethidine HCL, Hana Pharm Co., Seoul, Republic of Korea). Repeated doses of 10-20 mg propofol are titrated to achieve the target level of sedation. Maintenance of sedation is achieved with repeated doses of 5 to 20 mg propofol. The total dosage of propofol (including additional doses) is limited by lower and upper bounds of 10mg and 100mg, respectively. The target level of sedation is moderate sedation based on the ASA levels.

For the patients allocated to the midazolam-meperidine-dexmedetomidine (MMD) group, both midazolam (0.05 mg/kg, 30% reduction for patients if age ≥70 or ASA class III-IV; Bukwang Pharm Co., Seoul, Republic of Korea) and meperidine (50mg. 25mg for patients aged ≥70 years; pethidine HCL, Hana Pharm Co., Seoul, Republic of Korea) are given intravenously at the initiation of sedation. In addition, a continuous IV infusion of dexmedetomidine (1ug/kg/h, Precedex; Hospira, Seoul, Republic of Korea) is administered 15 min before the ERCP till complete the procedure. Thereafter, repeated doses of 1 to 2 mg midazolam are administered to maintain a moderate level of sedation. For the patients allocated to the midazolam-meperidine-propofol (BPS) group, both midazolam and meperidine are given at the initiation of sedation in the same manner as in the MMD group.

Thereafter, repeated doses of 10-20 mg propofol are titrated to achieve the target level of sedation. Maintenance of sedation is achieved with repeated doses of 5 to 20 mg propofol. The total dosage of propofol (including additional doses) is limited by lower and upper bounds of 10mg and 100mg, respectively. The target level of sedation is moderate sedation based on the ASA levels.

Medications and monitoring Intranasal supplemental oxygen (2L/min) is provided to all participants at the initiation of sedation. Heart rate, electrocardiogram, peripheral oxygen saturation (SaO2), respiratory rate, and end-tidal carbon dioxide (EtCo2) are constantly monitored. Non-invasive blood pressure (NIBP) is automatically measured at 3-minute intervals. Sedation level is assessed and recorded every 3 minutes throughout the procedure with the Modified Observer's Assessment of Alertness and Sedation (MOAA/S). Patients are considered to be oversedated at MOAA/S score 1.

MOAA/S, Modified Observe's Assessment of Alertness and Sedation: 5-responds readily to name spoken in normal tone, 4-lethargic response to name spoken in normal tone, 3-responds only after name is called loudly and/or repeatedly, 2-responds only after mild prodding or shaking, 1-does not respond to mild prodding or shaking, 0-does not respond to noxious stimulus.

If hypoxemia (SpO2<90%) is observed during sedation in either group, O2 supplementation is increased by 2L/min until oxygen saturation is restored. If the SpO2 dropped to < 85% for >30 sec, despite patient stimulation and interruption of sedatives and jaw thrust maneuver, an antagonist to midazolam (flumazenil) could be injected and the procedure is interrupted until normalization of oxygen saturation occurred again.

During recovery, the patient's vital signs (NIBP, SpO2, heart rate), sedation level (Gillham scale), and speed of recovery (modified Aldrete score) are recorded at 5-minute intervals until discharge from the recovery room.

Gillham sedation scale; 1-awake and anxious, 2-awake not anxious, 3-speech slurred, 4-eyes closed, responds to speech, 5-eye closed, responds to shaking, 6-unresponsive.

Outcome measurements and definitions The primary endpoint of the study is the rates of cardiopulmonary complications and the frequency of interruption of the ERCP procedures because of complications included (1) hypoxemia (pulse oximeter oxygen saturation below 90% on supplemental oxygen), (2) hypotension (systolic blood pressure below 90 mmHg), (3) bradycardia (heart rate below 50 beats/min). Procedure quality is evaluated based on therapeutic procedure outcomes, including technical success and total procedure time, and procedure-related adverse events. If transient interruptions of the procedure occurred because of sedation-related complications, that time is subtracted from the procedure time.

The endoscopist, blinded to the method of sedation, The secondary endpoints are the ease of ERCP performance, speed of recovery, and patient satisfaction with sedation.

At the end of the procedure, the ease of performance of ERCP is evaluated by the endoscopist using structured questionnaires.

If full recovery is confirmed in the inpatient setting, patient satisfaction with sedation and pain intensity during ERCP are assessed by another independent assistant using a 10-cm VAS scale (0=no pain/no satisfaction, 10=worst pain/full satisfaction)

Conditions

Complication

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

MMD arm

Both midazolam® (0.05 mg/kg, 30% reduction for patients if age ≥70 or ASA class III-IV; Bukwang Pharm Co., Seoul, Republic of Korea) and meperidine (50mg. 25mg for patients aged ≥70 years; pethidine HCL, Hana Pharm Co., Seoul, Republic of Korea) are given intravenously at the initiation of sedation. In addition, a continuous IV infusion of dexmedetomidine (1ug/kg/h, Precedex; Hospira, Seoul, Republic of Korea) is administered 15 min before the ERCP till complete procedure

Group Type: EXPERIMENTAL

Midazolam®

Intervention Type: DRUG

midazolam (0.05 mg/kg, 30% reduction for patients if age ≥70 or ASA class III-IV; Bukwang Pharm Co., Seoul, Republic of Korea)

"Meperidine" (pethidine®)

Intervention Type: DRUG

Meperidine (50mg. 25mg for patients aged ≥70 years; pethidine HCL, Hana Pharm Co., Seoul, Republic of Korea).

Dexmedetomidine (Precedex®)

Intervention Type: DRUG

Dexmedetomidine (1μg/kg/h, Precedex; Hospira, Seoul, Republic of Korea) or the same volume of normal saline were administered in the MMD and midazolam-meperidine group

BPS arm

IV bolus dose of midazolam® (0.06mg/kg, 50% reduction for patients if age ≥70 or ASA class III-IV; Bukwang Pharm Co., Seoul, Republic of Korea) and meperidine (50mg. 25mg for patients aged ≥70 years; pethidine HCL, Hana Pharm Co., Seoul, Republic of Korea). Repeated doses of 10-20 mg propofol® are titrated to achieve the target level of sedation. 0.9% NaCl 1μg/Kg•hr IV continuous infusion, initiated 15 min before the procedure (ERCP) till complete procedure

Group Type: ACTIVE_COMPARATOR

Midazolam®

Intervention Type: DRUG

midazolam (0.05 mg/kg, 30% reduction for patients if age ≥70 or ASA class III-IV; Bukwang Pharm Co., Seoul, Republic of Korea)

"Meperidine" (pethidine®)

Intervention Type: DRUG

Meperidine (50mg. 25mg for patients aged ≥70 years; pethidine HCL, Hana Pharm Co., Seoul, Republic of Korea).

Propofol®

Intervention Type: DRUG

Repeated doses of 10-20 mg propofol are titrated to achieve the target level of sedation.

Interventions

Midazolam®

midazolam (0.05 mg/kg, 30% reduction for patients if age ≥70 or ASA class III-IV; Bukwang Pharm Co., Seoul, Republic of Korea)

Intervention Type: DRUG

"Meperidine" (pethidine®)

Meperidine (50mg. 25mg for patients aged ≥70 years; pethidine HCL, Hana Pharm Co., Seoul, Republic of Korea).

Intervention Type: DRUG

Propofol®

Repeated doses of 10-20 mg propofol are titrated to achieve the target level of sedation.

Intervention Type: DRUG

Dexmedetomidine (Precedex®)

Dexmedetomidine (1μg/kg/h, Precedex; Hospira, Seoul, Republic of Korea) or the same volume of normal saline were administered in the MMD and midazolam-meperidine group

Intervention Type: DRUG

Other Intervention Names

Midazolam; meperidine; Propofol; Dexmedetomidine

Eligibility Criteria

Inclusion Criteria

• Those who are scheduled for ERCPs
• aged 18 to 80 years
• American Society of Anesthesiologists (ASA) classification I to III

Exclusion Criteria

• ASA IV and V
• History of allergies to drug used
• refuse to participate the study

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Dankook University

OTHER

Sponsor Role: lead

Responsible Party

Jun Ho Choi

Assistant professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jun Ho Choi, MD

Role: PRINCIPAL_INVESTIGATOR

Dankook University

Locations

Dankook University College of Medicine

Cheonan, Chungcheongnam-do, South Korea

Countries

South Korea

Other Identifiers

DankookU

Identifier Type: -

Identifier Source: org_study_id