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Remifentanil Only vs. Midazolam and Meperidine During Elective Colonoscopy

Remifentanil Only vs. Combination Group Midazolam + Meperidine During Elective Colonoscopy

Status
Completed
Phases
Phase 4
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT01693185
Acronym
remifentanil
Enrollment
60
Registered
2012-09-26
Start date
2012-12-31
Completion date
2013-08-31
Last updated
2014-06-18

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Diagnostic Colonoscopy Screening

Keywords

colonoscopy, remifentanil, midazolam, meperidine

Brief summary

The aim of the present study is to compare patient's recovery times after elective colonoscopy employing remifentanil only vs conventional combination of midazolam and meperidine

Detailed description

A regimen with combined administration of midazolam and meperidine has been widely used and provides quite satisfactory sedation as well as analgesia during colonoscopy. However, the relatively long duration of midazolam and meperidine often prolongs the recovery time after colonoscopy and delays discharge time. (Reimann FM , Samson U , Derad I et al. Synergistic sedation with low-dose midazolam and propofol for colonoscopies . Endoscopy 2000 ; 32 : 239 - 44). Remifentanil, an ultra-short-acting opioid, provides excellent pain control during colonoscopy and its rapid onset and offset times are advantages over other conventional opioids including meperidine, in avoiding prolonged discharge time after the colonoscopy. A total 54 patients, aged 18-65 years in American Society of Anesthesiologists physical status (ASA PS)1 and 2, scheduled for elective colonoscopy under Monitored Anesthesia Care in a University Hospital, will be recruited after obtaining written informed consent during the patients' first visit to outpatient/inpatient clinic for interview. Predetermined patient identification numbers (PIN) and enrolment order were placed in sealed envelopes, and all patients were randomly assigned, at recruitment, to the midazolam-meperidine combination (group-MM) or remifentanil alone (group-R). If a patient was excluded during the study, the following patient assumed the status of the excluded patient. Patients are allocated into one of two groups, Group 1 and Group 2 (27 patients each) according to the PIN at the recruitment. The exclusion criteria were as follows: refusal or inability to provide written informed consent, age \<19 years, pregnancy, previous history of large bowel surgery, a psychiatric disorder, an addictions to opiates or sedatives, a previous history of adverse events to any drug used in the present study, and performance of any additional diagnostic procedure after completion of colonoscopy. All colonoscopic procedure is going to be performed by one Gastroenterologist (endoscopist). On arriving in the endoscopy room, supplemental oxygen (2 L/min) was given through the mouth and both nostrils via a specially designed nasal prong which could monitor the end-tidal CO2 (ETCO2) level. Before drug administration, the basal values of mean blood pressure (MBP), heart rate (HR), peripheral O2 saturation (SpO2), respiratory rate (RR), end-expiratory CO2 level (ETCO2), and the bispectral index (BIS), were recorded by a single observer, who also monitored these values every 5 min during entire colonoscopy procedures. Supplemental oxygen (3 L/min) is given through nasal prong with capnography transducer in all patients. Two min before the colonoscopy procedure, a bolus midazolam of 0.03 mg/kg with a bolus meperidine of 1.0 mg/kg are given intravenously over 60 sec in Group 1 or those of comparable amount of diluted remifentanil 0.4 mcg/kg are given in Group 2 at the colonoscopy room, and a continuous infusion of diluted remifentanil of 0.04 mcg/kg/min is followed in Group 2 or that of comparable amount of normal saline (placebo) is followed in Group 1. The patients are asked to rate the degree of pain and distress (reverse satisfaction) by a 100 mm Visual analogue scale (VAS; 0 = minimum, 100 = maximum) just after passing the scope, during the scope, just after the completion of the colonoscopy and at the discharge from the recovery unit. After colonoscopy, the patients are transferred to the recovery unit and evaluated every 5 min until ready for discharge from the 30 min stay in the recovery unit. The patients are considered recovered if when they achieved an Aldrete score of 10 (Aldrete JA , Kroulik D . A postanesthetic recovery score. Anesth Analg 1970; 49: 924 - 34), have stable vital signs, are able to tolerate oral fluids, have no nausea, vomiting, or itching, and can walk unaided. Assessment of readiness to ambulate is made by a blinded observer who remained with the patient for the duration of recovery unit stay. The observer is instructed that the patients are required to walk as if they were leaving the recovery unit unescorted. Aldrete score, patient pain and satisfaction (distress score) were determined every 5 min during colonoscopy and after colonoscopy up to 30 min. Time for achieving Aldrete score 10, patient's degree of pain, patient's satisfaction during and after colonoscopy, patient's ability to recall the explanations and instructions given during and before colonoscopy are determined and compared. Aldrete score Respiration: Able to take deep breath and cough = 2, Dyspnea/shallow breathing = 1, Apnea = 0 O2 saturation: Maintains \> 92% on room air =2, Needs O2 inhalation to maintain O2 saturation \> 90% =1 , O2 saturation \< 90% even with supplemental oxygen =0 Consciousness: Fully awake= 2, Arousable on calling = 1, Not responding = 0 Circulation: BP +/- 20 mm Hg preop =2, BP +/- 20-50 mm Hg preop =1, BP +/- 50 mm Hg preop =0 Activity: Able to move 4 extremities = 2, Able to move 2 extremities = 1, Able to move 0 extremities = 0

Interventions

DRUGRemifentanil

continuous infusion 0.4 mcg/kg/min

DRUGMidazolam

bolus injection

DRUGMeperidine

bolus injection for 30 sec 1.0 mg/kg

normal saline mimic diluted remifentanil

DRUGplacebo (for midazolam)

normal saline mimic to midazolam injection

DRUGplacebo (for meperidine)

normal saline mimic meperidine injection

Sponsors

GlaxoSmithKline
CollaboratorINDUSTRY
Konkuk University Medical Center
Lead SponsorOTHER

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)

Eligibility

Sex/Gender
ALL
Age
19 Years to 65 Years
Healthy volunteers
No

Inclusion criteria

* Aged 19-65 years * American Society of Anesthesiologists physical status (ASA PS) 1-2 * Patients scheduled for elective colonoscopy under Monitored Anesthesia Care in a University Hospital * Patients who signed on written informed consent.

Exclusion criteria

* The

Design outcomes

Primary

MeasureTime frameDescription
The Recovery Timeevery 5 minutes after completing colonoscopy up to 30 minTime from completing the colonoscopy to achieving Aldrete score 10 in the recovery unit Aldrete score * Respiration: Able to take deep breath and cough = 2, Dyspnea/shallow breathing = 1, Apnea = 0 * O2 saturation: Maintains \> 92% on room air =2, Needs O2 inhalation to maintain O2 saturation \> 90% =1 , O2 saturation \< 90% even with supplemental oxygen =0 * Consciousness: Fully awake= 2, Arousable on calling = 1, Not responding = 0 * Circulation: BP +/- 20 mm Hg preop =2, BP +/- 20-50 mm Hg preop =1, BP +/- 50 mm Hg preop =0 * Activity: Able to move 4 extremities = 2, Able to move 2 extremities = 1, Able to move 0 extremities = 0 To estimate the required sample size, we conducted a pilot study to measure the recovery of 10 patients in each of groups-MM and -R before the present study. The means and standard deviations were 22.5 ± 9.5 and 7.5 ± 9.2 min respectively. We wished to be able to distinguish a difference of 7.5 min, thus half of the observed difference.

Secondary

MeasureTime frameDescription
Participants Assumed to Feel Frequent Painduring and after colonoscopypatients sound Ah at feeling pain during colonosocpy: if a patients sounds Ah \> 6 times, the patient was assumed to feel frequent pain.
Bispectra Lindex Scoreevery 5 min during and after colonoscopyBispectral index (BIS) score 0-100 maximal sedation=0, maximal sedation=100
Patient's Distress Score5 min after the end of colonoscopypatients' distress in visual analogue scale 100 mm minimal distress=0, maximal distress=100
Endoscopist Satisfaction5 min after the colonoscopyendoscopist's satisfaction after colonoscopy in visual analogue scale 100 mm
Indigence of Patient's Recallafter colonoscopyThe numbers of patients who recalled instructions and explanations given during colonoscopy

Countries

South Korea

Participant flow

Recruitment details

Predetermined patient identification numbers and enrolment order were placed in sealed envelopes, and all patients were randomly assigned, at recruitment, to the midazolam-meperidine combination (group-MM) or remifentanil alone (group-R). If a patient was excluded during the study, the following patient assumed the status of the excluded patient.

Pre-assignment details

The exclusion criteria were applied. If a patient was excluded after recruitment and enrollment into the study, the following new patient assumed the status of the excluded patient.

Participants by arm

ArmCount
Remifentanil
remifentanil of 0.04 mcg/kg/min with placebo (for midazolam) and placebo (for meperidine) Remifentanil: continuous infusion 0.4 mcg/kg/min placebo (for midazolam): normal saline mimic to midazolam injection placebo (for meperidine): normal saline mimic meperidine injection
27
Midazolam and Meperidine
a bolus midazolam of 0.03 mg/kg a bolus meperidine of 1.0 mg/kg placebo (for remifentanil) Midazolam: bolus injection Meperidine: bolus injection for 30 sec 1.0 mg/kg placebo (for remifentanil): normal saline mimic diluted remifentanil
27
Total54

Withdrawals & dropouts

PeriodReasonFG000FG001
Overall Studydiagnostic procedure after colonoscopy06

Baseline characteristics

CharacteristicRemifentanilMidazolam and MeperidineTotal
Age, Continuous56.6 years
STANDARD_DEVIATION 12.7
53.0 years
STANDARD_DEVIATION 10.7
54.8 years
STANDARD_DEVIATION 11.8
Sex: Female, Male
Female
16 Participants17 Participants33 Participants
Sex: Female, Male
Male
11 Participants10 Participants21 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
deaths
Total, all-cause mortality
— / —— / —
other
Total, other adverse events
0 / 270 / 27
serious
Total, serious adverse events
0 / 270 / 27

Outcome results

Primary

The Recovery Time

Time from completing the colonoscopy to achieving Aldrete score 10 in the recovery unit Aldrete score * Respiration: Able to take deep breath and cough = 2, Dyspnea/shallow breathing = 1, Apnea = 0 * O2 saturation: Maintains \> 92% on room air =2, Needs O2 inhalation to maintain O2 saturation \> 90% =1 , O2 saturation \< 90% even with supplemental oxygen =0 * Consciousness: Fully awake= 2, Arousable on calling = 1, Not responding = 0 * Circulation: BP +/- 20 mm Hg preop =2, BP +/- 20-50 mm Hg preop =1, BP +/- 50 mm Hg preop =0 * Activity: Able to move 4 extremities = 2, Able to move 2 extremities = 1, Able to move 0 extremities = 0 To estimate the required sample size, we conducted a pilot study to measure the recovery of 10 patients in each of groups-MM and -R before the present study. The means and standard deviations were 22.5 ± 9.5 and 7.5 ± 9.2 min respectively. We wished to be able to distinguish a difference of 7.5 min, thus half of the observed difference.

Time frame: every 5 minutes after completing colonoscopy up to 30 min

ArmMeasureValue (MEDIAN)
RemifentanilThe Recovery Time0 minute
Midazolam and MeperidineThe Recovery Time30 minute
Comparison: Recovery time in patients administered remifentanil alone will be significantly shorter than that in patients administered midazolam-meperidine combination for colonoscopy.p-value: <0.001Wilcoxon (Mann-Whitney)
Secondary

Bispectra Lindex Score

Bispectral index (BIS) score 0-100 maximal sedation=0, maximal sedation=100

Time frame: every 5 min during and after colonoscopy

ArmMeasureValue (MEDIAN)
RemifentanilBispectra Lindex Score92 units on a scale
Midazolam and MeperidineBispectra Lindex Score84 units on a scale
Secondary

Endoscopist Satisfaction

endoscopist's satisfaction after colonoscopy in visual analogue scale 100 mm

Time frame: 5 min after the colonoscopy

ArmMeasureValue (MEDIAN)
RemifentanilEndoscopist Satisfaction5 units on a scale
Midazolam and MeperidineEndoscopist Satisfaction20 units on a scale
Secondary

Indigence of Patient's Recall

The numbers of patients who recalled instructions and explanations given during colonoscopy

Time frame: after colonoscopy

ArmMeasureValue (NUMBER)
RemifentanilIndigence of Patient's Recall27 participants
Midazolam and MeperidineIndigence of Patient's Recall13 participants
Secondary

Participants Assumed to Feel Frequent Pain

patients sound Ah at feeling pain during colonosocpy: if a patients sounds Ah \> 6 times, the patient was assumed to feel frequent pain.

Time frame: during and after colonoscopy

ArmMeasureValue (NUMBER)
RemifentanilParticipants Assumed to Feel Frequent Pain4 participants
Midazolam and MeperidineParticipants Assumed to Feel Frequent Pain7 participants
Secondary

Patient's Distress Score

patients' distress in visual analogue scale 100 mm minimal distress=0, maximal distress=100

Time frame: 5 min after the end of colonoscopy

ArmMeasureValue (MEDIAN)
RemifentanilPatient's Distress Score37 units on a scale
Midazolam and MeperidinePatient's Distress Score30 units on a scale

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026