Remifentanil Only vs. Midazolam and Meperidine During Elective Colonoscopy (remifentanil)

• ClinicalTrials.gov Identifier: NCT01693185
• Recruitment Status: Completed
• First Posted: September 26, 2012
• Results First Posted: June 18, 2014
• Last Update Posted: June 18, 2014
• Sponsor: Konkuk University Medical Center
• Collaborator: GlaxoSmithKline
• Information provided by (Responsible Party): Tae-Yop Kim, MD PhD, Konkuk University Medical Center

Study Description

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

Condition or disease	Intervention/treatment	Phase
Diagnostic Colonoscopy Screening	Drug: Remifentanil; Drug: Midazolam; Drug: Meperidine; Drug: placebo (for remifentanil); Drug: placebo (for midazolam); Drug: placebo (for meperidine)	Phase 4

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

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Remifentanil Only vs. Combination Group Midazolam + Meperidine During Elective Colonoscopy
• Study Start Date: December 2012
• Actual Primary Completion Date: February 2013
• Actual Study Completion Date: August 2013

Arms and Interventions

Arm	Intervention/treatment
Experimental: Remifentanil; remifentanil of 0.04 mcg/kg/min with placebo (for midazolam) and placebo (for meperidine)	Drug: Remifentanil; continuous infusion 0.4 mcg/kg/min; Other Name: Ultiva; Drug: placebo (for midazolam); normal saline mimic to midazolam injection; Other Name: normal saline; Drug: placebo (for meperidine); normal saline mimic meperidine injection; Other Name: normal saline
Active Comparator: midazolam and meperidine; a bolus midazolam of 0.03 mg/kg a bolus meperidine of 1.0 mg/kg placebo (for remifentanil)	Drug: Midazolam; bolus injection; Other Name: dormicum; Drug: Meperidine; bolus injection for 30 sec 1.0 mg/kg; Other Name: Pethidine Injection; Drug: placebo (for remifentanil); normal saline mimic diluted remifentanil; Other Name: normal saline

Outcome Measures

Primary Outcome Measures :

1. The Recovery Time [ Time Frame: every 5 minutes after completing colonoscopy up to 30 min ]

   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.

Secondary Outcome Measures :

1. Participants Assumed to Feel Frequent Pain [ Time Frame: during and after colonoscopy ]
   patients sound "Ah" at feeling pain during colonosocpy: if a patients sounds "Ah" > 6 times, the patient was assumed to feel frequent pain.
2. Bispectra Lindex Score [ Time Frame: every 5 min during and after colonoscopy ]
   Bispectral index (BIS) score 0-100 maximal sedation=0, maximal sedation=100
3. Patient's Distress Score [ Time Frame: 5 min after the end of colonoscopy ]
   patients' distress in visual analogue scale 100 mm minimal distress=0, maximal distress=100
4. Endoscopist Satisfaction [ Time Frame: 5 min after the colonoscopy ]
   endoscopist's satisfaction after colonoscopy in visual analogue scale 100 mm
5. Indigence of Patient's Recall [ Time Frame: after colonoscopy ]
   The numbers of patients who recalled instructions and explanations given during colonoscopy

Eligibility Criteria

• Ages Eligible for Study: 19 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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 exclusion criteria are refusal or inability to provide written informed consent
• Age < 18 years
• Pregnancy
• Previous large bowel surgery
• Psychiatric disorders
• History of addiction to opiates and / or sedatives, and previous adverse reaction to any drug used in the study.

Contacts and Locations

Locations

Korea, Republic of

Konkuk University Medical Center

Seoul, Korea, Republic of, 143-729

Sponsors and Collaborators

Konkuk University Medical Center

GlaxoSmithKline

Investigators

• Principal Investigator: Tae-Yop Kim, MD, PhD; Konkuk University

More Information

• Responsible Party: Tae-Yop Kim, MD PhD, Professor of Anesthesiology, Konkuk University Medical Center
• ClinicalTrials.gov Identifier: NCT01693185
• Other Study ID Numbers: KUH1160048
• First Posted: September 26, 2012
• Results First Posted: June 18, 2014
• Last Update Posted: June 18, 2014
• Last Verified: May 2014

Keywords provided by Tae-Yop Kim, MD PhD, Konkuk University Medical Center:

colonoscopy; remifentanil; midazolam; meperidine

Additional relevant MeSH terms:

Midazolam; Meperidine; Remifentanil; Adjuvants, Anesthesia; Hypnotics and Sedatives; Central Nervous System Depressants; Physiological Effects of Drugs; Anti-Anxiety Agents; Tranquilizing Agents; Psychotropic Drugs; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; GABA Modulators; GABA Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Analgesics, Opioid; Narcotics; Analgesics; Sensory System Agents; Peripheral Nervous System Agents