Propofol Infusion versus Intermittent Meperidine and Midazolam Injection for Conscious Sedation in ERCP

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1 Propofol Infusion versus Intermittent Meperidine and Midazolam Injection for Conscious Sedation in ERCP Pradermchai Kongkam 1, Rungsun Rerknimitr 1, Sahadol Punyathavorn 2, Chitr Sitthi-Amorn 3, Yuwadee Ponauthai 1, Narongrit Prempracha ], Pinit Kullavanijaya 1 1) Division of Gastroenterology, Department of Internal Medicine; 2) Department of Anesthesiology, Faculty of Medicine, Chulalongkorn. University; 3) Division of Medical Epidemiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand Abstract Background and aim: ERCP generally requires longer time than standard endoscopy. Only few studies have shown benefit of intermittent propofol over conventional sedation. This study was conducted to compare satisfaction, recovery score, and recovery/safety profiles for ERCP sedation between continuous infusion of propofol and conventional sedation. Patients and methods: One hundred thirtyfour patients with ASA I-III underwent ERCP and were randomly assigned into two groups (n=67 each). Patients underwent propofol sedation or meperidine/midazolam sedation. Supplemental oxygen was offered only when oxygen saturation was lower than 90 %. Oxygen saturation, blood pressure, heart rate, recovery score, times for recovery and satisfaction score after procedure were recorded and analyzed. Results: Average amount of meperidine, midazolam and propofol per each patient were (± 27.29), 7.80 (± 3.73), (± ) mg, respectively. Time to regain full consciousness in the propofol arm was significantly shorter than in the conventional arm (17.24 ± 5.99 versus ± min, p<0.001). The rates of desaturation, bradycardia and hypotension in both arms were low and comparable. Propofol provided higher level of recovery scores at 15, 30, 45 and 60 min after the procedure (p < 0.001). Conclusion: Continuous infusion of propofol for ERCP by direction of gastroenterologist yields no difference in the completion rate and adverse profiles when compared with conventional technique but it provides a better recovery profile. The maintainance of appropriate level of sedation by well trained personnel is the key to achieve this success. Key words Sedation ERCP propofol midazolam Received: Accepted: J Gastrointestin Liver Dis September 2008 Vol.17 No 3, Address for correspondence: Rungsun Rerknimitr, M.D. Division of Gastroenterology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand rungsun@pol.net Introduction Generally, a prolonged and potentially uncomfortable endoscopic procedure like ERCP requires at least conscious sedation. In addition, a guideline from the American Society of Anesthesiology (ASA) [1] for sedation by nonanesthesiologists recommended an accurate titration of sedation at conscious level for patients undergoing ERCP. Sedation using intermittent intravenous administration of benzodiazepine combined with an opioid showed variable outcome due to the difficulty in maintaining level of sedation [2]. In addition, titration of these medications requires meticulous attention to adjust the appropriate dose for different age, sex and medical backgrounds. Therefore, over- and under-sedation can still frequently happen [3]. This in turn may lead to the unsatisfactory perception of the patients. Moreover, recovery period is prolonged in elderly who is prone to over-sedation [4]. Lately, propofol, an ultrashort-acting agent with rapid recovery profile has been increasingly used worldwide as a sedative agent for standard endoscopy [5]. Many studies [6-13] have compared propofol versus conventional sedation for gastroscopy and colonoscopy and demonstrated the benefit of propofol over conventional sedation. However, few studies have compared propofol sedation with meperidine and midazolam for ERCP [14-16]. Our study was aimed to compare recovery/safety profiles, satisfaction, and recovery score between propofol versus conventional agents for ERCP. Material and methods Patients At King Chulalongkorn Memorial Hospital between December 2003 and May 2005, all eligible ERCP inpatients were recruited. Exclusion criteria were: age < 18 or >70 years; pregnancy; those whose informed consent could not be obtained; emergency situations (i.e., concomitant upper gastrointestinal bleeding, acute cholangitis); patients receiving intravenous narcotic analgesia; patients within less than 72 hours from an operative intervention; mechanically ventilated patients; a history of sulfite, egg, or soybean

2 292 Kongkam et al allergy; a baseline oxyhemoglobin saturation (SaO 2 ) less than 90%; a baseline systolic blood pressure less than 90 mmhg; and an American Society of Anesthesiologists (ASA) physical status class IV or V. Each patient entered the study only once. The process of randomization was performed after ERCP scheduling. Patients were alternately assigned with one of the regimens by using block randomization. The procedure was performed with patients in prone position. After the procedure, patients were observed in the recovery unit for at least 60 minutes or until they gained full level of consciousness. Discomfort, gagging, and satisfaction scores from both patients and endoscopists were recorded by another assistant who was blinded to the method of sedation. Monitoring There was an independent non-physician assistant observing and recording vital signs during and after the procedure. An Advanced Cardiopulmonary Life Support (ACLS) trained physician (PK, a gastroenterologist) controlled the sedation process and instructed the assistant in administrating sedation to these patients according to their conscious level, movement, and vital signs. The goal of sedation was to maintain patient sedation level between moderate (patients respond purposefully to verbal commands, either alone or accompanied by light tactile stimulation) and deep sedation level (patients can not be easily aroused but may respond purposefully to repeated or painful stimulation) [17,18]. Patient requiring more than 3 episodes of personal restrain by the assistant during the procedure was noted. Vital signs and oxygen saturation were continuously monitored and recorded every 5-10 minutes. Routine supplemental oxygen was not given. If patient developed desaturation (< 90 %) for longer than 10 sec or developed 3 shorter periods of desaturation, then supplemental oxygen was administered immediately. If the supplemental oxygen was not able to improve patient oxygenation within 3 minutes, the procedure was terminated. Securing airway and reversal agents were given as necessary. If the oxygenation improved, then the patient was maintained with continuous oxygen for 8 minutes and then closed observation was continued. Hypotension (systolic blood pressure < 90 mm Hg or a decrease in blood pressure of < 25% of the baseline value) or bradycardia (heart rate <50 beats/min) and apnea (the cessation of respiratory activity for >10 seconds by observation) were recorded as serious adverse events (SAE). The procedure was terminated whenever SAE occurred. Medication In the meperidine/midazolam arm, patients were given the initial bolus of 50 mg or less of meperidine (Abbott Laboratories, North Chicago, IL) plus 2.5 mg or less of midazolam (Ben Venue Laboratories, Bedford, OH). Then sedation was maintained by intravenous intermittent bolus dose of meperidine ( mg/each dose) or midazolam ( mg/each dose) to keep patients at sedation level as described. In the propofol arm, patients were given an initial intravenous bolus of 40 mg (body weight (BW) equal or less than 60 kg) or 50 mg (BW more than 60 kg) of 1% propofol emulsion (Baxter Healthcare Corp., Irvine, CA) followed by continuous intravenous drip of 1% propofol (0.5-1 mg/kg/hr) titrating to maintain the same level of sedation. An automate pump (Terufusion syringe pump TE-331, Terrumo Corporation, Tokyo, Japan) was used for propofol infusion. When optimal level of sedation was not achieved, the additional bolus of mg 1% propofol was given intermittently. If necessary, additional personal restrain by the assistant was provided before achieving the level of designed sedation. Lag time was measured by the time between finishing injection of the combination agents or the white-color propofol fluid running into patient arm and the time for duodenoscope intubation. Recovery phase After the procedure, vital signs and recovery score (modified Aldrete score) were recorded every 15 minutes. Patient who woke up earlier than 15 minutes was also recorded and the time for this earlier wake up was also used for the calculation of recovery time. At 60 minutes post procedure or when full conscious was gained, visual analogue score for gagging reflex, abdominal discomfort score (0, none; 100, severe), satisfaction to sedative method score (0, unsatisfied; 100, satisfied) was evaluated by the assistant who was blinded to the given sedation, the patient was then discharged back the floor. The technical difficulty score (0, easy; 100, very demanding) was evaluated by the endoscopist (RR). Follow up After the procedure, a physician (P.K.) visited the patient to evaluate complication and use visual analogue score to grade daily activity score (0, no activity; 100, baseline activity) and food intake score (0, no food intake; 100, diet before endoscopic procedure). Statistical Analysis Due to the nature of our study protocol that was not double blinded, this study was conducted as a randomized case series/ observational study. One of our main objectives was to study the safety profile. We used the difference of percentage in patients whose oxygen saturation dropped significantly to lower than 90 % as our primary parameter for sample size calculation. The sample size was calculated based on our pilot study result that showed desaturation rates in the propofol and conventional arms to be 0.15 and 0.38 respectively [19]. For two sided test, the sample size required for an Alpha of 0.05 and 80 % power is 67 patients per arm. Categorical outcomes were analyzed with the Continuity Correction or Fisher exact test or Chi-square where appropriate. Continuous outcomes were analyzed with independent sample t test for normally distributed data or the Wilcoxon rank sum test for nonparametric data. The protocol was submitted and approved by Chulalongkorn Medical School Ethical Committee. Results One hundred and thirty-four patients were recruited. Baseline characteristics are shown in Table I. There was

3 Propofol for conscious sedation in ERCP 293 no statistical difference between the two groups. Average amount of meperidine, midazolam and propofol in each patient were (SD 27.29), 7.80 (SD 3.73), and (SD ) mg, respectively. Lag time after starting sedation before the procedure, duration of the procedure, recovery time, baseline oxygen saturation, baseline blood pressure and baseline heart rate are shown in Table II. Recovery time in propofol arm was significantly shorter than in the meperidine/midazolam arm (p<0.001). Number of patients with desaturation, of patients who required supplemental oxygen, with hypotension or Table I. Baseline characteristics. Parameters Meperidine/Midazolam Propofol p value Sex (M:F) 41:26 40: a Age (SD) (13.55) (11.91) 0.777d BMI (SD) (4.67) (5.66) 0.178d Dosage (SD) Meperidine 1.86 (1.30) 9.38 (4.03) (mg/kg/hr) Midazolam 0.24 (0.18) ASA class 0.060c I 32 (47.8%) 26 (38.8%) II 27 (40.3%) 22 (32.8%) III 8 (11.9%) 19 (28.4%) Education level 0.397c Elementary 40 (59.7%) 31 (46.3%) Junior School 4 (6.0%) 8 (11.9%) High School 10 (14.9%) 12 (17.9%) University 13 (19.4%) 16 (23.9%) a. Continuity Correction, b. Fisher s Exact Test; c. Pearson Chi-Square; d. t Test, NS Non significant Table II. Time to intubation, duration of the procedure, recovery time, oxygen saturation baseline, systolic blood pressure baseline and heart rate baseline Parameters Time to intubation (min) Duration of the procedure (min) Recovery time (min) Baseline oxygen saturation (%) Systolic blood pressure baseline (mmhg) Heart rate baseline (per min) Meperidine/ Midazolam Propofol p value (t test) 4.09 (1.64) 4.36 (1.96) (21.75) (32.49) (16.06) (5.99) < (7.79) (1.48) (21.52) (22.57) (17.06) (15.07) with bradycardia are shown in Table III. There was no statistical difference between the two groups regarding these parameters. Some patients from propofol and meperidine/midazolam arms required more than three episodes of additional control and personal restrain by the assistant during the procedure (20.9% and 11.9%, p =NS). Scores of discomfort, gagging reflex scores and satisfaction to sedation scores from both patients and endoscopists by using visual analogue scale showed no statistical difference between the two groups. Scores of discomfort, gagging reflex scores and satisfaction scores evaluated by endoscopist were significantly different (p<0.001) between patients with and without addition control and personal restrain (22.86 vs , vs , vs , respectively) The results of modified Aldrete score at 15, 30, 45 and 60 min are shown in Table IV. Patients in propofol arm had significantly higher level of recovery score at every point of time, p < There was no difference in both arms regarding the rate of post ERCP pancreatitis. Three patients from meperidine/midazolam group developed perforations (one with guidewire perforation; two with scope related perforation). One from propofol arm developed post sphincterotomy bleeding. Two scope perforations underwent surgical repair without long term sequel. All, except 4 patients with procedure related complications were able to resume expected baseline activity within the next day. Uncontrolled agitation during sedation occurred in three patients, of these, two patients were from propofol group and another was from meperidine/midazolam group. The Table III. Percentages of oxygen desaturation and hypotension Parameters Meperidine/ Propofol p value Midazolam Number of patients with oxygen saturation lower than 90 % (%) (any episode) 21 (31.3%) 15 (22.4%) 0.330a Mean % decrease in oxygen saturation Number of patients who required supplemental oxygen via nasal cannula (%) (any episode) Number of patients whose SBP was lower than 75 % of initial value (%) (any episode) 9.60% (15.83%) Mean % decrease in SBP (18.97) Number of patients whose SBP was lower than 90 mmhg (%)(any episode) Number of patients whose heart rate was lower than 75 % of baseline rate (%) (any episode) 9.72% (18.36) 0.968d 17 (25.4%) 11 (16.4%) (16.4%) 13 (19.4%) 0.822a (26.99) 0.356d 6 (9%) 6 (9%) 1.000a 7 (10.4%) 2 (3.0%) 0.165b a. Continuity Correction, b. Fisher s Exact Test; c. Pearson Chi-Square; d. t Test, NS Non significant. SBP = systolic blood pressure

4 294 Kongkam et al uncontrolled movements in these three patients were severe enough to terminate the procedure. Another patient from the propofol group required supplemental nasal airway oxygen in order to maintain oxygen saturation and the procedure was continued until completion. One patient from propofol Table IV. Recovery profile and rate of pancreatitis Parameters Meperidine/ Propofol p value Midazolam Recovery score at (1.60) 9.84 (0.45) 0.001a** Recovery score at (1.39) 9.99 (0.12) 0.001d** Recovery score at (1.27) (0.00) 0.001d** Recovery score at (1.01) (0.00) 0.001d** Patients who were able 53 (79.1%) 54 (80.6%) NS to do daily activity as usual (%) Patients with post ERCP pancreatitis (%) 7 (10.4%) 5 (7.5%) 0.762a a. Continuity Correction, b. Fisher s Exact Test; c. Pearson Chi- Square; d. t Test, NS Non significant group developed apnea and another patient from meperidine/ midazolam group developed aspiration during the procedure and the procedures were terminated in both; these cases were recorded as SAEs. Of note, these episodes were not related to uncontrolled agitation that required additional bolus of medications. Discussion Over the last 5 years, propofol has been used increasingly in many gastrointestinal endoscopic procedures [6-13, 20-24]. Many studies in standard endoscopy have demonstrated lower risk of complications related to propofol sedation when compared with conventional sedation [6, 7, 9, 10, 13, 23]. However, there are few reports documenting the safety of propofol for prolonged procedures like ERCP. To date, there have been thus far only 5 eligible studies using intermittent propofol administration alone compared with conventional agent (Table V). These studies [4, 14-16, 25] showed no significant difference between the propofol and conventional arm in terms of oxygen desaturation and cardiovascular events despite different type of measurement. Studies with additional monitoring equipments [14, 16, 25, 26] appeared to use lesser amount of propofol than those without Table V. Results of propofol for ERCP sedation in the present and previous studies Study Criteria Meperidine/midazolam Propofol group p value group N (%) N (%) Present study O 2 saturation < 90 % 21/67 (31.3%) 15/67 (22.4%) NS Mean decline in O 2 saturation 9.60% (15.83%) 9.72% (18.36) NS SBP < 75 % baseline 11/67 (16.4%) 13/67 (19.4%) NS SBP < 90 mmhg 6 (9%) 6 (9%) NS HR < 75 % baseline 7/67 (10.4%) 2/67 (3.0%) NS Vargo et al [14] O 2 saturation < 90 % 21/37 (57%) 14/38 (37%) NS SBP < 75 % baseline 7/37 (18.9%) 6/38 (15.8%) NS SBP < 75 % baseline 7/37 (18.9%) 6/38 (15.8%) NS HR < 75 % baseline 3/37 (8.1%) 0/38 (0.0%) NS Riphaus et al [4] O 2 saturation < 90 % 7/75 (9.0%) 8/75 (11%) NS Mean decline in O 2 saturation 3 % (2%) 6 % (3%) <0.01 SBP < 90 mmhg 4/75 (5.3%) 6/75 (8%) NS HR < 50 bpm 4/75 (5.3%) 3/75 (4%) NS Wehrmann et al [15] O 2 saturation < 90 % 8/98 (8.2%) 11/99 (11%) NS Mean decline in O 2 saturation 3% (2%) 5% (3%) <0.01 SBP < 90 mmhg 2/98 (2.0%) 7/99 (7.1%) NS HR < 50 bpm 2/98 (2.0%) 5/99 (5.1%) NS Krugliak P et al [16] N Mean arterial events 37.0± ±18.6 NS Heart rate events 48.2± ±25.0 <0.01 Jung M et al [25] N Oxygen desaturation (%) -2-4 NS Mean arterial pressure NS decrease (%) Pulse change (%) NS SBP: systolic blood pressure - HR: heart rate

5 Propofol for conscious sedation in ERCP 295 Table VI. Dosages of propofol in different studies First author Number of pts. Special equipment mg/patient mg/kg/hr Vargo et al [14] 38 Capnography monitoring Wehrmann et al [26] 40 EEG monitoring 290(±158) 7.8 Krugliak et al [16] 15 EEG monitoring NA NA Jung et al [25] 40 No Fanti et al [28] 205 No 465± Wehrmann et al [26] 40 Without EEG monitoring 374 ± Wehrmann et al [15] 99 None 388± Riphaus et al [4] 75 No 322±208 NA Present study 67 No equipments [4, 15, 26] (Table VI). Sedation with propofol demonstrated a low incidence of serious adverse events (0% to 1.9%) [4, 14, 15, 27, 28]. The most important statement from these studies is that propofol provides significant shorter recovery time than conventional sedation [4, 6, 14, 16, 25]. Our series has confirmed that the recovery profiles in the propofol arm were better than conventional method at any period of measurement. In addition, the amount of propofol requirement by continuous infusion method in our study was comparable to others that used intermittent injection of propofol [4, 14-16, 25]. Oxygen supplementation is essential for patient undergoing propofol sedation [18]. We did not routinely give supplemental oxygen unless it was necessary. Supplemental oxygen plays a significant role for a safer sedation however it may decrease the chance to detect early desaturation. The number of patients with desaturation in our series was comparable to other series [14]. However, our rate was higher than the series reported by Riphaus et al [4] and of Wehrmann et al [15, 26] (Table V). We speculate that baseline oxygen supplementation in their series may have played a role in the better results. In addition, a study by Wehrmann et al [26] showed the benefit of EEG monitoring to maintain adequate sedation by using a lower dose of propofol and demonstrated a faster recovery time. In retrospect, we would mandate supplemental oxygen as our protocol for all patients who underwent ERCP in this study. Some studies that used additional monitoring equipments including capnography and EEG monitoring [14, 16, 25, 26] required lower doses of propofol, while other three studies [4, 15, 26], without additional monitoring equipment, used higher amount of propofol than ours (Table VI). Fanti et al [28], with target controlled monitoring and oxygen supplementation, used a small dose of propofol quite equivalent to ours (9.38 vs 9.4 mg/ kg/ hour) (Table VI). In this study, the target-controlled concentration of propofol was titrated by the anesthesiologist in increments of 0.5 μg/ ml (target concentration ranging between 2 and 5 μg/ml) to maintain adequate patient cooperation. The mean dosage of propofol administered was 465±245 mg. Of note, they also administered fentanyl in bolus as an adjunctive agent for insufficient analgesia. We speculate that the additive effect from fentanyl would account for the achievement of deep sedation in their study since with similar dose of pure propofol infusion, we were able to maintain sedation at the moderate level. In addition, our infusion technique may have played an important role for maintaining the constant level of sedation. These data provide indirect support to the notion that the propofol dosage and the sedation level achieved in our patients are comparable to other studies in which oxygen and analgesic agent were given. To minimize the dose of propofol, we hypothesize that a combination of continuous propofol infusion and monitoring with capnography plus EEG may be of benefit. No study showed significant difference in the rate of cardiovascular complications between propofol and conventional sedation (Table V). The clinical practice guidelines developed by the ASA task force [1] supported that cardiopulmonary function is usually maintained even at the stage of deep sedation whereas at the stage of general anesthesia, the cardiopulmonary system may be impaired, often requiring airway intervention. Given these facts, cardiopulmonary function is safe if we are able to avoid over-sedation [27]. Our goal for sedation was to maintain the sedation level between moderate and deep sedation. However, maintaining this level of sedation remains a challenge. Often, the onset of sedation was slightly deep (at the onset of sedation) with moderate sedation following with time. With a narrow therapeutic window of propofol, fluctuations in the depth of sedation may occur. In our study, two procedures had to be terminated because of SAE. The percentage of patients using propofol requiring procedural termination or assisted ventilation in our series was low. Our conventional arm had similar rate of procedural termination, which sometimes required reversal agent to correct hypoventilation. However, one important issue is that reversal agent has a shorter half life time than meperidine/midazolam, hence, even after reversal agents are given, these patients still require a careful monitoring. Since propofol is a short acting agent, episode of apnea requiring intubation does rarely occur. However, with no reversal agents available, well trained personnel in airway rescue is mandatory. In our series, no one from both arms required an endotracheal intubation. Four patients developed procedure related complications. One patient from propofol arm had post sphincterotomy

6 296 Kongkam et al bleeding, controlled by endoscopic treatment. Three patients from the conventional arm had perforations. Of theses, one guide-wire related perforation healed with conservative treatment. Those two patients with scope related perforation underwent surgical repair without sequel. We speculate that frozen duodenum from the underlying pancreatic carcinoma contributed to this complication. We have to admit that our rate of complication was higher than standard published studies [29,30]. Non anesthetist administered propofol [4, 14] causes a concern to some physicians regarding detail monitoring. The presence of an anesthesiologist with or without special monitoring equipment such as EEG [26], capnography [14], target controlled infusion system [10, 28] would incur a higher cost. It has been shown in our study that propofol infusion without special monitoring system did not cause more SAEs when compared with series that used advance monitoring [14, 16, 26, 28]. We speculate that the infusion technique used in our series was the key factor to protect the development of complications from over-sedation. In addition, the physician who administered propofol was well aware to maintain sedation only at the moderation level. However, with its narrow therapeutic window the maintainance of moderate sedation remains a challenge. Most studies on sedation for general endoscopy reported the post procedural satisfaction score in the propofol arm as better than in the conventional arm [6, 8-10, 31]. However, in many studies focusing on advanced endoscopy including ERCP, they reported these scores as not different [4, 14, 15]. In the present series, the overall post procedure satisfactory score given by both sides was not statistically different. We did not perform a cost-effectiveness analysis in our study. Roughly, adding the anesthesiologist for this type of sedation in Thailand will cost $ more. For the purpose of this study, we used a gastroenterologist to administer the sedation agents. However, this protocol could not be applied for a standard practice since adding the cost of another gastroenterologist for sedation would cost more even in our country where the cost of medical practice is not high. Perhaps, registered nurse administered propofol may be a better option. In the US, the cost-effectiveness of nonanesthesiologist administered propofol was well explained by Vargo et al [14]. They showed that the incremental costeffectiveness analysis for a gastroenterologist-administered propofol costed $403 more per additional patient at 100% of baseline when compared with conventional sedation. In contrast, their sensitivity analysis indicated that if a registered nurse could be used, the cost could be quite comparable to the conventional sedation ($59.8 vs. 66.8, P=0.65). In conclusion, gastroenterologist directed administration of propofol for ERCP has a better recovery profile than conventional sedation. It also provides comparable safety profiles and outcome including the adverse event, numbers of procedure interruptions, and physician/patient satisfaction. Well trained personnel in propofol administration is the key for the success. If future studies could show a similar effectiveness of nurse directed administration of propofol for ERCP, perhaps translation into clinical practice is more feasible. Conflicts of interest The authors have no conflict of interest in relation to this article. References 1. American Society of Anesthesiologists Task Force on Sedation and Analgesia by Non-Anesthesiologists. Practice guidelines for sedation and analgesia by non-anesthesiologists. Anesthesiology 2002; 96: Diab FH, King PD, Barthel JS, Marshall JB. Efficacy and safety of combined meperidine and midazolam for EGD sedation compared with midazolam alone. Am J Gastroenterol 1996; 91: Patel S, Vargo JJ, Khandwala F, et al. Deep sedation occurs frequently during elective endoscopy with meperidine and midazolam. Am J Gastroenterol 2005; 100: Riphaus A, Stergiou N, Wehrmann T. Sedation with propofol for routine ERCP in high-risk octogenarians: a randomized, controlled study. Am J Gastroenterol 2005; 100: Ladas SD, Aabakken L, Rey JF, et al. Use of sedation for routine diagnostic upper gastrointestinal endoscopy: a European Society of Gastrointestinal Endoscopy Survey of National Endoscopy Society Members. Digestion 2006; 74: Koshy G, Nair S, Norkus EP, Hertan HI, Pitchumoni CS. Propofol versus midazolam and meperidine for conscious sedation in GI endoscopy. Am J Gastroenterol 2000; 95: Ulmer BJ, Hansen JJ, Overley CA, et al. Propofol versus midazolam/ fentanyl for outpatient colonoscopy: administration by nurses supervised by endoscopists. Clin Gastroenterol Hepatol 2003; 1: Moerman AT, Foubert LA, Herregods LL, et al. Propofol versus remifentanil for monitored anaesthesia care during colonoscopy. Eur J Anaesthesiol 2003; 20: Sipe BW, Rex DK, Latinovich D, et al. Propofol versus midazolam/ meperidine for outpatient colonoscopy: administration by nurses supervised by endoscopists. Gastrointest Endosc 2002; 55: Ng JM, Kong CF, Nyam D. Patient-controlled sedation with propofol for colonoscopy. Gastrointest Endosc 2001; 54: Carlsson U, Grattidge P. Sedation for upper gastrointestinal endoscopy: a comparative study of propofol and midazolam. Endoscopy 1995; 27: Patterson KW, Casey PB, Murray JP, O Boyle CA, Cunningham AJ. Propofol sedation for outpatient upper gastrointestinal endoscopy: comparison with midazolam. Br J Anaesth 1991; 67: Gasparovic S, Rustemovic N, Opacic M, Bates M, Petrovecki M. Comparison of colonoscopies performed under sedation with propofol or with midazolam or without sedation. Acta Med Austr 2003; 30: Vargo JJ, Zuccaro G Jr, Dumot JA, et al. Gastroenterologistadministered propofol versus meperidine and midazolam for advanced upper endoscopy: a prospective, randomized trial. Gastroenterology 2002; 123: Wehrmann T, Kokabpick S, Lembcke B, Caspary WF, Seifert H. Efficacy and safety of intravenous propofol sedation during routine ERCP: a prospective, controlled study. Gastrointest Endosc 1999; 49: Krugliak P, Ziff B, Rusabrov Y, Rosenthal A, Fich A, Gurman

7 Propofol for conscious sedation in ERCP 297 GM. Propofol versus midazolam for conscious sedation guided by processed EEG during endoscopic retrograde cholangiopancreatog raphy: a prospective, randomized, double-blind study. Endoscopy 2000; 32: Qadeer MA, Vargo JJ, Khandwala F, Lopez R, Zuccaro G. Propofol versus traditional sedative agents for gastrointestinal endoscopy: a meta-analysis. Clin Gastroenterol Hepatol 2005; 3: Training Committee. American Society for Gastrointestinal Endoscopy. Training guideline for use of propofol in gastrointestinal endoscopy. Gastrointest Endosc 2004; 60: Kongkam P, Pornphisarn B, Rerknimitr R. Non-anesthetist administered propofol for ERCP; efficacy, safety profile and side effect: A prospective randomized trial. Gastrointest Endosc 2004; 59: P Oei-Lim VLB, Kalkman CJ, Bartelsman J, Res JC, van Wezel HB. Cardiovascular responses, arterial oxygen saturation and plasma catecholamine concentration during upper gastrointestinal endoscopy using conscious sedation with midazolam or propofol. Eur J Anaesthesiol 1998; 15 : Carlsson U, Grattidge P. Sedation for upper gastrointestinal endoscopy - a comparative-study of propofol and midazolam. Endoscopy 1995; 27: Hofmann C, Kiesslich R, Brackertz A, Jung M. Propofol for sedation in gastroscopy - a randomized comparison to midazolam. Z Gastroenterol 1999; 37: Rex DK, Overley C, Kinser K, et al. Safety of propofol administered by registered nurses with gastroenterologist supervision in 2000 endoscopic cases. Am J Gastroenterol 2002; 97: Kulling D, Fantin AC, Biro P, Bauerfeind P, Fried M. Safer colonoscopy with patient-controlled analgesia and sedation with propofol and alfentanil. Gastrointest Endosc 2001; 54: Jung M, Hofmann C, Kiesslich R, Brackertz A. Improved sedation in diagnostic and therapeutic ERCP: propofol is an alternative to midazolam. Endoscopy 2000; 32: Wehrmann T, Grotkamp J, Stergiou N, et al. Electroencephalogram monitoring facilitates sedation with propofol for routine ERCP: a randomized, controlled trial. Gastrointest Endosc 2002; 56: Heuss LT, Schnieper P, Drewe J, Pflimlin E, Beglinger C. Safety of propofol for conscious sedation during endoscopic procedures in high-risk patients - a prospective, controlled study. Am J Gastroenterol 2003; 98: Fanti L, Agostoni M, Casati A, et al. Target-controlled propofol infusion during monitored anesthesia in patients undergoing ERCP. Gastrointest Endosc 2004; 60: Masci E, Toti G, Mariani A, et al. Complications of diagnostic and therapeutic ERCP: a prospective multicenter study. Am J Gastroenterol 2001; 96: Freeman ML, Nelson DB, Sherman S, et al. Complications of endoscopic biliary sphincterotomy. N Engl J Med 1996; 335: Kulling D, Fantin AC, Biro P, Bauerfeind P, Fried M. Safer colonoscopy with patient-controlled analgesia and sedation with propofol and alfentanil. Gastrointest Endosc 2001; 54: 1-7.