Endoscopic retrograde cholangiopancreatography (ERCP) is an uncomfortable procedure that requires adequate sedation for its successful conduction. We investigated the efficacy and safety of the combined use of intravenous midazolam and propofol for sedation during ERCP.
A retrospective review of patient records from a single tertiary care hospital was performed. Ninety-four patients undergoing ERCP received one of the two medication regimens, which was administered by a nurse under the supervision of a gastroenterologist. Patients in the midazolam (M) group (
The time to the initial sedation was shorter in the MP group than in the M group (1.13 minutes vs. 1.84 minutes, respectively;
The combined use of intravenous midazolam and propofol for sedation during ERCP is more effective than midazolam alone. There is no difference in the safety of the procedure.
Endoscopic retrograde cholangiopancreatography (ERCP) is a very highly advanced upper endoscopic procedure, and is very useful for the diagnosis and treatment of pancreatobiliary disorders. Therefore, it has a great role as an alternative laparotomy method. ERCP is frequently a prolonged and potentially uncomfortable procedure; therefore, it requires adequate patient sedation for successful completion.
Midazolam is a fast-acting benzodiazepine with a short elimination half-life. It has sedative, anxiolytic, hypnotic, and anterograde amnesic properties.
Propofol is a more recently developed ultrashort-acting intravenous anesthetic agent that rapidly produces sleep, followed by a prompt recovery.
Previous studies prove that propofol is superior to benzodiazepines for sedation during an ERCP procedure, even in high-risk octogenarians.
There are adequate safety results for the administration of propofol by nonanesthesiologists.
We performed a retrospective review of patient records from a single tertiary care hospital. Ninety-four patients were included in this study. Between June 2010 and September 2010, the patients underwent ERCP procedures at the Asan Medical Center, a tertiary referral hospital in Seoul, Korea. All procedures were performed by one gastroenterologist. All patients were graded in accordance with the American Society of Anesthesiologists (ASA) physical status classification. Patients were excluded from this study if they were younger than 20 years or older than 60 years; if they were graded as ASA class III to V; if they had psychological disorders; or if they had a history of chronic benzodiazepine or opiate use. Each patient was included in the study only once. Forty-four patients received midazolam (i.e., the M group) and 50 received midazolam and propofol (i.e., the MP group).
The patients in the M group were administered an initial intravenous bolus of 3 to 4 mg of midazolam. Unless patients achieved adequate sedation within 1 minute after initial loading, repeated intravenous 1 mg boluses of midazolam were administered every 1 minute until the patients achieved adequate sedation. Sedation was then maintained by an intermittent intravenous bolus of 1 mg of midazolam to maintain patients at an adequate sedation level. In the MP group, patients were administered an initial intravenous bolus of 2 mg of midazolam and 20 or 30 mg of propofol if the patient's body weight was less than 60 kg, or they were administered 3 mg of midazolam and 40 mg of propofol if the patient's body weight was 60 kg or greater. Repeated intravenous 10-mg boluses of propofol were administered every minute without limitation of the total dose until patients achieved adequate sedation. The sedation was then maintained by an intermittent intravenous 10-mg bolus of propofol. When patients had achieved deep sedation, intubation of endoscopy was initiated. In this study, propofol was administered by a nurse under the supervision of a gastroenterologist.
We considered a score of 2 on the modified Observer's Assessment of Alertness/Sedation (OAA/S) scale as deep sedation (i.e., the state at which the patient can respond, but only after mild prodding or shaking); we then checked the time it took for the patient to reach deep sedation after receiving the initial sedative administration.
Heart rate, electrocardiogram, oxygen saturation, and blood pressure were in stable condition before the procedure. These parameters were then monitored at 5-minute intervals throughout the procedure. If the pulse oximeter oxygen saturation (SpO2) decreased below 90%, we initially conducted the triple airway maneuver (i.e., head-tilt, jaw-thrust, and mouth opening) on the patient. If the SpO2 recovered for more than 90% within 10 seconds, we continued the ERCP procedure without any additional measures. Unless the SpO2 had recovered, we applied oxygen by nasal cannula at 6 L/min. An SpO2 of less than 90% for more than 10 seconds was recorded as a significant adverse event. In addition, changes in blood pressure greater than 20% of the baseline value and changes in the pulse rate greater than 50% were regarded as significant adverse events.
Recovery from sedation was assessed by using a modified Aldrete scoring system, which was evaluated every 5 minutes after the removal of the endoscope (i.e., at 5, 10, and 15 minutes). This scoring system is an established postanesthetic recovery score that takes into account the color of the patient, respiratory and circulatory parameters, and the level of consciousness and patient activity.
Immediately after the ERCP procedure, the endoscopist was administered a visual analog scale (VAS) to rate the patient's cooperation for the procedure (0 to 3, fair; 4 to 7, average; 8 to 10, excellent) and the patient's gag reflex (0 to 3, no; 4 to 7, mild; 8 to 10, severe). Patients were interviewed 24 hours after the procedure by phone to assess their pain during the procedure (0 to 3, no; 4 to 7, mild; 8 to 10, severe); the degree of amnesia (0 to 3, total recall; 4 to 7, partial recall; 8 to 10, total amnesia); and discomfort (0 to 3, no; 4 to 7, mild; 8 to 10, severe).
Categorical outcomes were analyzed by the chi-square test or Fisher exact tests, when appropriate. Continuous outcomes were analyzed with Student
Ninety-four patients were included, out of which 60 were men and 34 women. The sex ratio was 1.7:1, and the mean age was 48.5 years. There were no significant differences between the two groups with regard to age, sex, weight, total procedure duration, and baseline cardiorespiratory parameters (
Patients in the MP group achieved an adequate level of sedation more rapidly, which allowed for earlier endoscopic intubation (1.84 minutes [M group] vs. 1.13 minutes [MP group];
An SpO2 of less than 90% for more than 10 seconds was observed in only one patient in the MP group. The patient immediately recovered after receiving oxygen (6 L/min) via a nasal cannula with the triple airway maneuver. There was no significant difference between the two groups with regard to events of respiratory depression. Changes in blood pressure of more than ±20% after the administration of the drug regimen occurred in 23 patients in the M group and 28 in the MP group. There was no significant difference between the two groups with regard to a change in blood pressure. Changes greater than ±50% in the pulse rate after the administration of the drug regimen occurred in 19 patients in the M group and 20 in the MP group. There was no significant difference between the two groups with regard to changes in the pulse rate (
The modified Aldrete scores that were obtained 5 and 10 minutes after the procedure were 9.02±0.76 and 9.22±0.67, respectively, in the M group and 8.84±1.03 and 9.14±0.98, respectively, in the MP group. The scores at 5 minutes and 10 minutes were higher in the M group than in the MP group; however, there were no statistical differences between the two groups. The modified Aldrete score at 15 minutes after the procedure was 9.43±0.54 in the M group and 9.68±0.55 in the MP group and was significantly higher in the MP group than in the M group (
The aim of this retrospective study was to compare the two groups with respect to efficacy and safety in sedation for ERCP. Patients in the MP group achieved an adequate level of sedation more rapidly as compared to patients in the M group; therefore, earlier endoscopic intubation was possible in the MP group. Two well-designed randomized controlled studies that compared propofol with the combined administration of midazolam and meperidine for sedation during ERCP have demonstrated that the time to the onset of sedation was shorter in the propofol group.
For most patients in the MP group, the intubation of endoscopy could start with adequate sedation without additional dosage after the initial loading injection. We believe this is a great advantage for procedures that require prolonged and extreme concentration such as therapeutic ERCP.
The total dose of propofol required for the ERCP procedure was far smaller in the MP group in our study than in other randomized controlled studies that compared propofol with midazolam plus meperidine.
Compared to other sedatives, propofol is associated with a relatively higher incidence of cardiovascular and respiratory complications such as hypotension, bradycardia, and respiratory depression.
Recovery from sedation, as assessed by the modified Aldrete scoring system, was faster in the MP group than in the M group. Nearly all well-designed randomized controlled studies that compare propofol and midazolam show that recovery is significantly faster with propofol than with midazolam.
There were no differences between the MP group and the M group with regard to pain, discomfort, amnesia, and gag reflex in our study. Patient cooperation rated as excellent by the endoscopist was significantly greater in the MP group than in the M group. In the Paspatis et al.
Our study did not use advanced monitoring equipment, such as capnography. In studies by Vargo et al.
There are some limitations in our study. The most important limitations are that this was a retrospective study and the sample size was relatively small. The result of our study may not be applicable to an older age group, because the patients who participated were relatively young with an age range of 20 to 60 years. Our data are only the results of a single-center study, and it may not be possible to generalize our results. Therefore, multicenter randomized trials are required to confirm these findings.
In conclusion, our data showed that the combined use of midazolam and propofol is a more effective sedation method for ERCP compared to midazolam alone. There was no difference in safety. The combined use resulted in a shorter time to initial effective sedation and a quicker recovery. There were no significant differences between the two regimens with respect to the rate of adverse events. Patient cooperation rated as excellent by the endoscopist was greater in the MP group. Our results suggest that the combined use of propofol and intravenous midazolam is useful and safe for the ERCP procedure. We believe that future studies that compare the use of propofol alone with the combined use of propofol and midazolam are needed to demonstrate the superiority of the combined use of propofol and midazolam for sedation during an ERCP.
The authors have no financial conflicts of interest.
Pain of patient during endoscopic retrograde cholangiopancreatography under sedation. There is no statistical significance between the midazolam (M) group and the midazolam plus propofol (MP) group
Degree of amnesia during endoscopic retrograde cholangiopancreatography under sedation. There is no statistical significance between the midazolam (M) group and the midazolam plus propofol (MP) group.
Discomfort of patient during endoscopic retrograde cholangiopancreatography under sedation. There is no statistical significance between the midazolam (M) group and the midazolam plus propofol (MP) group.
Gag reflex during endoscopic retrograde cholangiopancreatography under sedation. There is no statistical significance between the midazolam (M) group and the midazolam plus propofol (MP) group
Patient cooperation assessed by the endoscopist during endoscopic retrograde cholangiopancreatography under sedation. Patient cooperation rated as excellent by the endoscopist is significantly greater in the midazolam plus propofol (MP) group than in the midazolam (M) group (
Demogaphic and Clinical Dates
Values are presented as mean±SD. All parameters are no significant difference between the two groups
M, midazolam; MP, midazolam pulse propofol; SBP, systolic blood pressure; DBP, diastolic blood pressure; SpO2, saturation of partial pressure oxyzen.
Drug Dosage and Time to Initial Sedation
Values are presented as mean±SD.
M, midazolam; MP, midazolam pulse propofol; ERCP, endoscopic retrograde cholangiopancreatography.
a)
Frequency of Adverse Events for Endoscopic Retrograde Cholangiopancreatography
Values are presented as number (%). All parameters are no significant difference between the two groups.
M, midazolam; MP, midazolam pulse propofol; SpO2, saturation of partial pressure oxyzen; BP, blood pressure; PR, pulse rate.
Recovery Score after Endoscopic Retrograde Cholangiopancreatography
Values are presented as mean±SD.
M, midazolam; MP, midazolam pulse propofol.
a)