Cholangiocarcinoma, Choledocholithiasis, Pancreatic Cancer, Pancreatitis
Conditions
Keywords
Endoscopic Retrograde Cholangiopancreatography (ERCP), Conscious Sedation, etomidate, midazolam
Brief summary
Recently up-coming drug, etomidate which is a modulator of GABA(gamma-Aminobutyric acid)-A receptor has been known that it maintains the appropriate sedative levels and affects little effects on respiratory system. The investigators are now trying to investigate that etomidate with meperidine combination regimen is superior to the midazolam with meperidine more effective and less harm on sedation during the ERCP procedure.
Detailed description
ERCP (Endoscopic retrograde cholangiopancreatogram) is an uncomfortable and time-consuming procedure compared to other endoscopic procedures. Most ERCP procedure had been performed in sedation using tranquilizers and pain-killers. Until recently, midazolam and opioid combination regimen recognized as a standard therapy is widely used, but the sedative effect is insufficient and intermittent paradoxical reaction has been questioned. Another drug, such as propofol, has been known that the sedative effect is superior one of the midazolam but disappointed due to narrow therapeutic range of respiratory distress and absence of antagonist. Meanwhile, recently up-coming drug, etomidate which is a modulator of GABA-A receptor has been known that it maintains the appropriate sedative levels and affects little effects on respiratory system. For these advantages, this short acting sedative drug has been widely used in the emergency room during minor operation and in the operation room for induction. However, research on the efficacy during ERCP was not yet published. In this regards, the purpose of the investigators study is to prove the efficacy of etomidate for sedation and to establish new evidence based sedation guidelines during ERCP procedure.
Interventions
DRUGEtomidate
This cohort would be administered etomidate with meperidine. The initial dose of etomidate is 0.1mg/kg IV and meperidine, 25mg. Additional dose of etomidate is 2mg(1cc). In old age cased, more than 65 years old, 30% of initial dose discounted.
DRUGMidazolam
This cohort would be administered midazolam with meperidine. The initial dose of midazolam is 0.06mg/kg IV and meperidine 50mg IV. Additional dose is 1mg of midazolam. In the elders, more than 65 years old, initial dose was declined to 70%.
DRUGMeperidine
Both groups were administered same dose of meperidinie 50mg. Then elders \> 80 years old were administered 25mg iv bolus.
Sponsors
Cheju Halla General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
20 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
* All patients who are scheduled diagnositic or therapeutic ERCP. * Age : more than 20 and less than 90 years old * ASA(American Society of Anesthesiologists) classificiation : I, II, III
Exclusion criteria
Patients following * Refuse to be enrolled * ASA American Society of Anesthesiologists)classification IV, V * Breast feeder * The mentally ill * Drug abuser * Hypersensitivity to sedative or opioids * Alcohol intoxication or dependency * Body mass index (BMI) 36kg/m2 or more * Unstable vital sign 1. tachypnea, respiration rate more than 25/min or less than 10/min 2. Oxygen saturation : 90% or less 3. Systolic blood pressure : less than 90 mmHg or more than 180 mmHg 4. Diastolic blood pressure : less than 50 mmHg or more than 100 mmHg 5. Heart rate : more than 120 beat/min or less than 50 beat/min.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Intervention | Throughout the whole ERCP procedure | The frequency of intervention which was defined as any restraint of the patient's head, arms, or legs if they became agitated, or if patient movement was not controlled with verbal instruction from the endoscopist during the whole intraoperative phases. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Event of Hypoxia | Every 5min in Preoperative, intraoperative phase and 15 min in Recovery phase | Hypoxia defined as peripheral blood oxygen saturation measured by pulse oxymeter \< 90% |
Countries
South Korea
Participant flow
Recruitment details
Eligibility was evaluated for all patients with a scheduled ERCP procedure in the Cheju Halla General Hospital during the study period from May 15 2013 to Aug 19 2013. Sample size estimated 26 of each groups for reject null hypothesis with probability (power) 0.8 and Type I error is 0.05.
Pre-assignment details
68 patients were enrolled and 35 were assigned in the MDZ group and 33 were in the ETM group. In ETM group, 1 case was dropped due to hypotension and 2 were desaturation. And 1 cases was dropped due to tachycardia and 1 were desaturation in MDZ group.
Participants by arm
| Arm | Count |
|---|---|
| Etomidate This cohort would be administered etomidate with meperidine. The initial dose of etomidate is 0.1mg/kg IV and meperidine, 25mg. Additional dose of etomidate is 2mg(1cc). In old age cased, more than 65 years old, 30% of initial dose discounted.
Etomidate: This cohort would be administered etomidate with meperidine. The initial dose of etomidate is 0.1mg/kg IV and meperidine, 25mg. Additional dose of etomidate is 2mg(1cc). In old age cased, more than 65 years old, 30% of initial dose discounted.
Meperidine: Both groups were administered same dose of meperidinie 50mg. Then elders \> 80 years old were administered 25mg iv bolus. | 30 |
| Midazolam This cohort would be administered midazolam with meperidine. The initial dose of midazolam is 0.06mg/kg IV and meperidine 50mg IV. Additional dose is 1mg of midazolam. In the elders, more than 65 years old, initial dose was declined to 70%.
Midazolam: This cohort would be administered midazolam with meperidine. The initial dose of midazolam is 0.06mg/kg IV and meperidine 50mg IV. Additional dose is 1mg of midazolam. In the elders, more than 65 years old, initial dose was declined to 70%.
Meperidine: Both groups were administered same dose of meperidinie 50mg. Then elders \> 80 years old were administered 25mg iv bolus. | 33 |
| Total | 63 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Protocol Violation | 3 | 2 |
Baseline characteristics
| Characteristic | Midazolam | Total | Etomidate |
|---|---|---|---|
| Age, Continuous | 71.6 years STANDARD_DEVIATION 11.5 | 70.9 years STANDARD_DEVIATION 13.8 | 70.3 years STANDARD_DEVIATION 15.7 |
| Body Mass Index (kg/square of m.) | 22.6 kg/square of m. STANDARD_DEVIATION 4.31 | 23.1 kg/square of m. STANDARD_DEVIATION 3.9 | 23.7 kg/square of m. STANDARD_DEVIATION 3.5 |
| Procedure Time (min) | 32.8 min STANDARD_DEVIATION 13.4 | 30.4 min STANDARD_DEVIATION 14.2 | 27.6 min STANDARD_DEVIATION 14.9 |
| Sex: Female, Male Female | 19 Participants | 35 Participants | 16 Participants |
| Sex: Female, Male Male | 14 Participants | 28 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 30 | 0 / 33 |
| serious Total, serious adverse events | 0 / 30 | 0 / 33 |
Outcome results
Primary
Number of Intervention
The frequency of intervention which was defined as any restraint of the patient's head, arms, or legs if they became agitated, or if patient movement was not controlled with verbal instruction from the endoscopist during the whole intraoperative phases.
Time frame: Throughout the whole ERCP procedure
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Etomidate | Number of Intervention | 1.9 Number of intervention | Standard Deviation 3.1 |
| Midazolam | Number of Intervention | 7.5 Number of intervention | Standard Deviation 6.8 |
Comparison: If the true difference in the experimental and control means is 4, total 26 experimental subjects and 26 control subjects was required to reject the null hypothesis that the means of the primary outcome values of experimental and control groups are equal with probability (power) 0.8. The Type I error probability associated with this test of this null hypothesis is 0.05.p-value: 0.05Regression, Logistic
Secondary
Event of Hypoxia
Hypoxia defined as peripheral blood oxygen saturation measured by pulse oxymeter \< 90%
Time frame: Every 5min in Preoperative, intraoperative phase and 15 min in Recovery phase
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Etomidate | Event of Hypoxia | 19 Hypoxia events |
| Midazolam | Event of Hypoxia | 27 Hypoxia events |
Comparison: All the continuous variables were compared using the Mann-Whitney U test and dichotomous categorical variables was used and the Pearson chi-square with Fisher exact test. We used the linear mixed model to compare the differences of paired data, such as mean values of RR, SpO2, MAP, HR, and RSS at different time points of the two different sedation groups. For two-sided tests, p \< 0.05 was considered statistically significant.p-value: 0.00295% CI: [2.41, 50.94]Regression, Logistic