Source of effectiveness data The evidence for the final outcomes and resource use were derived from a single study.

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1 Gastroenterologist-administered propofol versus meperidine and midazolam for advanced upper endoscopy: a prospective, randomized trial Vargo J J, Zuccaro G, Dumot J A, Shermock K M, Morrow J B, Conwell D L, Trolli P A, Maurer W G Record Status This is a critical abstract of an economic evaluation that meets the criteria for inclusion on NHS EED. Each abstract contains a brief summary of the methods, the results and conclusions followed by a detailed critical assessment on the reliability of the study and the conclusions drawn. Health technology The use of propofol for gastrointestinal endoscopy compared with meperidine and midazolam. A propofol 1% emulsion (Baxter Healthcare Corp.) was given as a loading dose of either 40 mg (less than 60 kg body weight) or 50 mg (greater than 60 kg body weight). If the patient showed signs of discomfort, restlessness or agitation, repeated intravenous 10-mg boluses of propofol were administered without limiting the total dose given. In the meperidine-midazolam group, intravenous sedation and analgesia were initiated with meperidine (Abbot Laboratories) at an initial dose of less than 50 mg and midazolam (Ben Venue Laboratories) at an initial dose of less than 2 mg, administered through an indwelling intravenous catheter. Increments of meperidine ( mg) and midazolam ( mg) were given if the patient showed signs of discomfort, restlessness or agitation. Type of intervention Palliative care. Economic study type Cost-effectiveness analysis. Study population The study population comprised patients presenting for endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasonography (EUS) of the oesophagus, stomach or retro peritoneum, as these procedures were frequently prolonged and required multiple doses of agents for sedation and analgesia. Any patient undergoing ERCP or EUS was randomised only once (i.e. re-examinations were not included). Patients were excluded if they were aged younger than 18 years, were pregnant, if informed consent could not be obtained, or if they were in an emergency situation (i.e. upper gastrointestinal bleeding or cholangitis). Also excluded were patients receiving intravenous narcotic analgesia, patients less than 72 hours from an operation, and mechanically ventilated patients. Patients with a history of sulphite, egg or soybean allergy, a baseline systolic pressure of less than 90 mmhg, or an American Society of Anaesthesiologists (ASA) physical status classification of IV or V were also excluded. Setting The setting was secondary care. The economic study was undertaken in the Cleveland Clinic Foundation, Cleveland, USA. Dates to which data relate The dates to which the effectiveness and resource use data related were not stated. The price year was also not reported. Source of effectiveness data The evidence for the final outcomes and resource use were derived from a single study. Page: 1 / 6

2 Link between effectiveness and cost data The costing was undertaken prospectively on the same patient sample as that used in the effectiveness study. Study sample Before the trial, sample size calculations were performed using standard deviations from trials assessing pain and tolerance of endoscopic procedures on a visual analogue scale (VAS). With a 100-mm VAS, the authors believed that a difference of 10 mm in pain, gagging, or anxiety scores between the study groups would be clinically relevant. Enrolling 37 patients in each group achieved a power of 0.82 to detect this difference (t-test, alpha error of 0.05). Of the 86 patients invited to enrol in the trial, 75 agreed to participate. Thirty-eight of these were randomised to the propofol group and 37 to the meperidine-midazolam group. The patients in the propofol group had a mean age of 52.9 (+/- 2.4) years, and 21 were male and 17 female. The patients in the meperidine-midazolam group had a mean age of 55.7 (+/- 2.6) years, and 17 were male and 20 female. Study design The study was a prospective randomised controlled trial that was carried out in a single centre. A 1:1 randomisation was used, with the randomisation blocks supplied by the biostatistics department of the Cleveland Clinic Foundation. The patients, the research nurse who conducted all the pre- and post-procedural patient assessments, and the recovery room personnel were blinded to the type of medication used for sedation. As the randomisation was conducted in the procedure room, the endoscopist and procedure room personnel were not blinded to the patient's sedation regimen. The patients in both groups were followed until discharge. No patient was lost to follow-up. Analysis of effectiveness It was not stated whether the clinical study was analysed on an intention to treat basis or on treatment completers only. However, this was not entirely relevant since all the patients completed the treatment. The outcomes used in the analysis were as follows. The time patients needed to achieve an adequate level of sedation. Cardio respiratory activity, for example oxygen saturation levels, need for supplemental oxygen, changes in systolic blood pressure, add decrease in the baseline heart rate. Respiratory activity was assessed graphically using a side-stream carbon dioxide detector (Microcap Plus; Ordion Corp.). Patient tolerance and satisfaction. Patient assessments of pain, gagging, anxiety and satisfaction were obtained before the procedure and in the recovery suite at the time of discharge, using a VAS. The patients were asked to place a vertical mark on a 100-mm line to represent pain, gagging and anxiety, with 0 representing none and 100 representing severe. The degree of technical difficulty, gagging and discomfort associated with the two procedures, the average time to full recovery, and next-day activity. Immediately after the procedure, endoscopists were given a VAS to rate patient discomfort (0, none; 100, severe), patient gagging (0, none; 100, severe), overall satisfaction with the patient's sedation (0, very dissatisfied; 100, very satisfied), and technical difficulty (0, easy; 100, very demanding). The average time to full recovery and ability to transfer from the procedure table to a transport gurney immediately after the procedure. The research nurse blinded to the type of sedation conducted the discharge assessments. Next-day activity. The patients were interviewed 24 hours after the procedure, either in person or by phone, to assess the return to normal activity (0, no activity; 100, baseline activity) and food intake (0, no food intake; 100, diet before endoscopic procedure). At analysis, the groups were shown to be comparable in terms of their age, gender, body mass index, ASA physical status classification, education level, and history of difficulty with sedation for endoscopic procedures. There was no difference between the groups in their use of ethanol, narcotics or tobacco, and in the duration of the procedure. Page: 2 / 6

3 Effectiveness results Patients in the propofol group achieved an adequate level of sedation more rapidly (3.9 versus 8.0 minutes), allowing for earlier endoscopic intubation, (p<0.001). There were no significant differences between the two groups in adverse events requiring termination of the procedure or temporary ventilatory assistance. No differences were detected between the groups for patients with oxygen saturation values less than 90% or less than 85%, or for the need for supplemental oxygen. Changes in systolic blood pressure between the two groups were equivalent. The incidence of apnoea was higher in the meperidine-midazolam group, but the difference was not significant. The mean percentage decrease in the baseline heart rate was the same for both groups. Both groups reported similar low levels of perceived post-procedural gagging and discomfort. High satisfaction levels were seen with both sedation groups, 90.1 for propofol versus 84.9 for meperidine-midazolam, (p=0.72). Similar high satisfaction levels were seen with both sedation groups, 90.1 versus Post-procedural anxiety tended to be higher in patients receiving propofol (26.3 versus 20.0), but this difference was not statistically significant. The endoscopist judged the degree of technical difficulty, gagging and discomfort associated with the procedure to be equivalent between the two groups. The average time to full recovery was significantly shorter in the propofol group (18.6 minutes) than in the meperidinemidazolam group (70.5 minutes), (p<0.001). More patients receiving propofol were able to independently transfer from the procedure table to a transport gurney immediately after the procedure than those receiving meperidine and midazolam (71.1% versus 29.7%; p<0.001). The propofol group tended to have better recovery of overall activity (93.8 versus 81.8) and food intake (92.8 versus 80.3) than the meperidine-midazolam group, although these differences were not statistically significant. Clinical conclusions The authors concluded that propofol led to a significantly shorter recovery room time and a significantly higher return to baseline activity and food intake. Measure of benefits used in the economic analysis The effectiveness measure used was the proportion of patients who returned to 100% of food intake and activity level on the day after the procedure. Direct costs The resource quantities and the costs were not reported separately. The direct costs included were those of the hospital. Only those costs that differed between the treatment groups were included in the analysis. These were the costs of medication and personnel involved in the procedure and recovery. The only difference in procedure personnel between the two groups was a person dedicated to the administration of propofol and continuous monitoring of the patient. The cost of medication was determined by multiplying the amount of medication used (mg) by the unit average wholesale price. The cost of personnel dedicated to propofol administration and physiological monitoring was estimated by using the Medicare allowable charge for each procedure. Nursing costs were calculated by multiplying the length of time spent in the recovery suite by US national average salary data for nurses. Discounting was not relevant, as all the costs were incurred during a short time, and hence was not performed. The study reported the average costs. The dates to which the price data referred were not reported. Statistical analysis of costs The costs were treated stochastically. Statistical analyses were conducted using Student's t-test for parametric data and the Mann-Whitney rank sum test for nonparametric data, as appropriate on the basis of the distribution of the data, to compare the component and total costs of the two regimens. Page: 3 / 6

4 Indirect Costs The indirect costs were not included in the analysis. Currency US dollars ($). Sensitivity analysis Sensitivity analyses were conducted to determine the effect of variations in the cost estimates on the results of the basecase analysis. The cost estimates were varied 50% either way. The authors also analysed the effect of using generic medications, the use of different personnel dedicated to propofol administration (anaesthesiologist, gastroenterologist, nurse anaesthetist or registered nurse), and the use of licensed practical nurses instead of registered nurses in the recovery suite. Estimated benefits used in the economic analysis The proportion of patients who returned to 100% of food intake and activity level on the day after procedure was 71% for the propofol group and 43% for the meperidine-midazolam group, (p=0.028). Cost results The propofol group was associated with significantly higher anaesthesia personnel costs ($144) than the meperidinemidazolam group ($0), p<0.001). The drug costs were similar between the groups ($27 versus $29). The recovery room costs were significantly lower in the propofol group ($9) than in the meperidine-midazolam group ($38), p<0.001), because of the significantly shorter stay in the recovery room after the procedure. The total costs, however, were significantly higher in the propofol group ($180) than in the meperidine-midazolam group ($67), (p<0.001). Synthesis of costs and benefits Compared with the meperidine-midazolam group, individuals randomised to propofol cost $403 more per additional patient at 100% of baseline for both activity level and food intake. The results from the sensitivity analysis were insensitive to the variation of costs estimates by 50% and to the use of generic medications. The results also indicated that if a registered nurse could be used to administer propofol, the propofol group would be as costly as the meperidine-midazolam group ($59.80 versus $66.80; p=0.65), with propofol becoming the dominant strategy (i.e. no more costly but more effective). Authors' conclusions The administration of propofol for endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasonography (EUS) by a trained gastroenterologist using extended monitoring with capnography was safe. It provided superior immediate and delayed recovery parameters, but similar levels of patient and endoscopist satisfaction, when compared with meperidine and midazolam. CRD COMMENTARY - Selection of comparators The comparator used was justified on the ground that it represented current practice in the authors' setting. You should decide if the comparator represents current practice in your own setting. Page: 4 / 6

5 Validity of estimate of measure of effectiveness The basis of the analysis was a randomised controlled trial, which was appropriate for the study question. An external body supplied the randomisation blocks. The patients, research nurse conducting patient assessments, and the recovery room personnel were blinded to the type of medication used for sedation. These factors minimise the potential of any biases being introduced into the study. However, the endoscopist and procedural personnel were not blinded because, in the authors' opinion, it was impossible to suitably accomplish this given the rapid onset of action and short half-life of propofol. The authors also pointed out that it was unlikely that assessment bias from the endoscopists was present because the VAS scores were no different between the two sedation regimens. The study sample was representative of the study population. However, since the exclusion criteria were numerous it might be difficult to generalise the authors' findings to other settings and patients. The patient groups were shown to be comparable at analysis in terms of their age, gender, body mass index, ASA classification, educational level, and history of difficulty with sedation for endoscopic procedures. The analysis was handled in a credible way, with appropriate statistical analyses being undertaken to test for any statistically significant differences. Validity of estimate of measure of benefit The estimation of benefit was obtained directly from the effectiveness analysis. The justified their choice of the number of patients at 100% recovery of activity level and food intake 24 hours after the procedure, as they believed it would highlight important pharmacodynamic differences between the agents. Validity of estimate of costs All the categories of cost relevant to the perspective adopted were included in the analysis. Costs that did not differ between the groups, such as the costs of procedure personnel (e.g. endoscopist and nurse), were excluded from the analysis. As these costs were common to both regimens, these omissions will not affect the authors' conclusions. The costs and the quantities were not reported separately, which will hamper the generalisability of the results. A sensitivity analysis of costs was performed using very wide ranges, to account for variability and uncertainty in the data. The authors also performed statistical tests of significance. Discounting was unnecessary since all the costs were incurred during a very short time period. Charges were used to proxy prices in order to estimate the cost of personnel dedicated to propofol administration. The dates to which the prices related were not reported, which will hamper any possible reflation exercises. Other issues The authors did not compare their findings with those from similar studies, as theirs was the first prospective, randomised trial to compare gastroenterologist-administered propofol with meperidine and midazolam for advanced upper endoscopic procedures such as ERCP and EUS. It was also the first trial addressing the cost-effectiveness of propofol in the endoscopy suite. The issue of generalisability to other settings was partially addressed through the sensitivity analysis. The authors do not appear to have presented their results selectively and their conclusions reflected the scope of the analysis. The authors reported a number of further limitations to their study. For example, the administration of boluses of propofol rather than a continuous infusion, as bolus administration is usually used in addition to infusion to achieve a more rapid effect. However, the authors pointed out that a recent series using computer-controlled administration to achieve a steady-state plasma level resulted in both under- and oversedation. The authors also pointed out that their study did not focus on hospitalised patients with an ASA physical status of IV or V which, according to the authors, would merit a more extensive evaluation. Implications of the study The authors reported that for propofol to become a viable alternative to standard sedation and analgesia administration, further studies using nurse-administered propofol are needed. In addition, the policies governing this practice must be carefully reviewed. The authors also stated that, because of the pharmacokinetics of propofol and its narrow therapeutic window, they do not currently recommend the use of propofol unless it is given by specially trained personnel who are Page: 5 / 6

6 Powered by TCPDF ( independent of the procedural team. Source of funding Supported by an American Digestive Health Foundation/Olympus Endoscopic Career Development Award. Bibliographic details Vargo J J, Zuccaro G, Dumot J A, Shermock K M, Morrow J B, Conwell D L, Trolli P A, Maurer W G. Gastroenterologist-administered propofol versus meperidine and midazolam for advanced upper endoscopy: a prospective, randomized trial. Gastroenterology 2002; 123(1): 8-16 PubMedID Other publications of related interest Morrow JB, Zuccaro G, Conwell DL, et al. Sedation for colonoscopy using a single bolus is safe, effective, and efficient: a prospective, randomised, double-blind trial. American Journal of Gastroenterology 2000;95: Weinbroum AA, Halpern P, Rudick V, et al. Midazolam versus propofol for long-term sedation in the ICU: a randomized prospective comparison. Intensive Care Medicine 1997;23: Koshy G, Nair S, Norkus E, et al. Propofol versus midazolam and meperidine for conscious sedation in GI endoscopy. American Journal of Gastroenterology 2000;95: Indexing Status Subject indexing assigned by NLM MeSH Analgesics, Opioid /administration & dosage /economics /therapeutic use; Cholangiopancreatography, Endoscopic Retrograde; Cost-Benefit Analysis; Endosonography; Female; Gastroenterology /methods; Health Care Costs; Heart /drug effects; Humans; Hypnotics and Sedatives /administration & dosage /economics /therapeutic use; Male; Meperidine /administration & dosage /economics /therapeutic use; Midazolam /administration & dosage /economics /therapeutic use; Middle Aged; Patient Satisfaction; Propofol /administration & dosage /economics /therapeutic use; Prospective Studies; Respiration /drug effects AccessionNumber Date bibliographic record published 30/09/2004 Date abstract record published 30/09/2004 Page: 6 / 6