Propofol-mediated gastrointestinal endoscopy

Propofol-mediated gastrointestinal endoscopy

Propofol-mediated Gastrointestinal Endoscopy John J. Vargo, MD, MPH Propofol-mediated gastrointestinal endoscopy (PME) has become a hotly debated and...

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Propofol-mediated Gastrointestinal Endoscopy John J. Vargo, MD, MPH

Propofol-mediated gastrointestinal endoscopy (PME) has become a hotly debated and rapidly evolving topic. Supporters tout the agent’s rapidity of onset, superior recovery profile and enhanced patient and endoscopist satisfaction. Its detractors point to the fact that propofol is an anesthesia induction agent with a narrow therapeutic window which should only be used by anesthesia personnel. Another evolving issue is the training and regulatory aspects of PME. Is it appropriate for a registered nurse of gastroenterologist to administer propofol? How (and who) should sanction the training and competency issues? The purpose of this discussion is to provide an evidence-based approach to PME, with careful attention to administration techniques and clinical outcomes. © 2004 Elsevier Inc. All rights reserved.

Pharmacology and Definitions ropofol (2-6 diisopropylphenol) is classified as an ultra short acting sedative hypnotic agent that provides amnesia, but minimal levels of analgesia.1,2 Because of its lipophilic nature, the drug is prepared in an emulsion consisting of 1% propofol, 10% soybean oil, 2.25% glycerol, and 1.2% egg lecithin.3,4 A generic formulation also contains sodium metabisulfite.5 The medication is therefore contraindicated in patients with allergies to eggs, soybeans, or sulfites. Propofol rapidly crosses the blood-brain barrier, and causes a depression in consciousness that is theorized to result from the potentiation of ␥-aminobutyric acid (GABA) activity in the brain. Typically, the time from injection to the onset of hypnosis is 30 to 60 seconds, which is essentially the time for one arm-brain circulatory pass.2 The plasma half-life ranges from 1.3 to 4.13 minutes. It is 98% plasma bound and undergoes primarily a hepatic degradation.2 Dose reduction is required in patients with cardiac dysfunction and in the elderly due decreased clearance of the drug.6 Propofol potentiates the effects of narcotic analgesics and sedatives such as benzodiazepines, barbiturates and droperidol, and therefore, the dose requirements may be reduced.1,2,4 Interestingly, the pharmacokinetics of propofol are not significantly changed in the setting of moderate hepatic or renal dysfunction.1,2,4 Practice guidelines put forth by the American Society of Anesthesiologists Committee for Sedation and Analgesia by Non-Anesthesiologists, have classified both moderate and deep

P

From the Division of Gastroenterology and Hepatology, Cleveland Clinic Foundation, Cleveland, OH. Address reprint requests to John J. Vargo, MD, MPH, Section of Therapeutic Endoscopy, Division of Gastroenterology and Hepatology, Cleveland Clinic Foundation, 9500 Euclid Ave, Cleveland, OH 44195; e-mail: [email protected] © 2004 Elsevier Inc. All rights reserved. 1096-2883/04/0602-0004$30.00/0 doi:10.1053/j.tgie.2004.03.004

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sedation and analgesia in a continuum of sedation (Table 1).7 It is important to emphasize that candidacy for sedation and analgesia still must take into account a thorough pre-procedure assessment including a history of present illness, past medical history and a physical examination.8 In most endoscopic cases, moderate sedation is the goal, which is defined as a purposeful response after verbal or tactile (not painful) sensation, and no compromise of the patient’s airway, ventilation or cardiovascular function. In comparison, deep sedation/analgesia may require the use of painful stimuli to elicit responsiveness. Additionally, the patient’s airway and spontaneous ventilation may become compromised, and hence, personnel must be designated for the complete and uninterrupted observation of the patient’s respiratory and cardiovascular status. An important component of these guidelines is that the endoscopy team must have the ability to rescue the patient from deeper than expected levels of sedation/analgesia.7 Propofol has a narrow therapeutic window-its administration, even in the hands of an anesthesiologist, does not prevent the occurrence of severe respiratory compromise.7 It cannot be overemphasized enough that personnel specifically trained in the administration of propofol with expertise in emergency airway management need to be present during the procedure, constantly monitoring the patient’s physiologic parameters. In this author’s opinion, the use of propofol usually results in a state of deep sedation and analgesia. It is our practice to utilize nasopharyngeal capnography to detect early signs of respiratory depression such as apnea, which would otherwise, go undetected by standard pulse oximetry.9,10 The presence of a person who is dedicated to the administration of propofol and the uninterrupted monitoring of the patient’s physiologic parameters is another important requirement.7,9,10 Specific contraindications to propofol administration include allergies to propofol or any of the emulsion components, pregnant or lactating females, and patients with an American Society of Anesthesiologists IV or V physical status classification.11 Pain at the injection site is the most frequent local complication, occurring in up to 5% of patients. Respiratory depression necessitating temporary ventilatory support have occurred in large series utilizing propofol for endoscopic procedures.12-14 Capnography has been successfully used to graphically assess the respiratory activity in patients receiving gastroenterologistadministered propofol for therapeutic upper endoscopy.9,10 Monitoring with graphic assessment of respiratory activity detected early phases of respiratory depression, resulting in a timely decrease in the propofol infusion without significant hypoxemia, hypercapnea, hypotension or arrhythmias.

Case Series Table 2 summarizes selected case series in which propofol was used for sedation and analgesia for a variety of endoscopic procedures.13,15-18 In general, these are much larger than the

Techniques in Gastrointestinal Endoscopy, Vol 6, No 2 (April), 2004: pp 60-64

TABLE 1. Continuum of the Depth of Sedation Moderate Sedation/Analgesia (conscious sedation)

Minimal Sedation (anxiolysis)

Deep Sedation/Analgesia

Responsiveness

Normal response to verbal stimulation

Airway

Unaffected

Purposeful response to verbal or tactile stimulation Unaffected

Spontaneous Respiration Cardiovascular Function

Unaffected

Unaffected

Purposeful response after repeated/ painful stimulation Intervention may be required May be inadequate

Unaffected

Usually maintained

Usually maintained

General Anesthesia No response, event with painful stimulation Intervention often required Intervention often required May require intervention

Adapted and reprinted with permission.7

randomized, controlled trials. The vast majority of these trials employ a bolus delivery technique. A loading dose of 20-50 mg is employed which is based on ASA classification, age, concurrent medical conditions, or a combination thereof. Typically, additional 10-20 mg doses are given as needed to achieve and maintain the desired depth of sedation. Walker et al. has published the largest case series encompassing 9,152 procedures in which propofol was administered by a specially trained registered nurses in the setting of an ambulatory surgical center.17 Seven instances of respiratory compromise were noted (0.7%) which included prolonged apnea, laryngospasm, and aspiration. Temporary support with mask ventilation for 30 seconds was employed and no patient required endotracheal intubation. It is important to point out that all respiratory complications occurred in patients undergoing

upper endoscopy. In a subset of 440 patients who has received the combination of a narcotic and benzodiazepine with previous endoscopic procedures, 79% preferred sedation with propofol. The safety and experience with propofol administered by registered nurses has been addressed in a case series including 2,000 patients undergoing elective EGD and/or colonoscopy.13 All patients were ASA class I or II. No extended monitoring was used and all patients received 3L of nasal cannula oxygenation. The propofol dosage was an initial bolus of 20-40 mg, followed by 10-20 mg to maintain sedation. Five episodes of oxygen desaturation to ⬍ 85%, four of which required temporary mask ventilation. Four of these episodes occurred during upper endoscopy. In a case series of 2,574 patients undergoing a total of 3,475 procedures. Heuss et al. employed either bolus dosing for upper endoscopy or colonos-

TABLE 2. Propofol Case Series

Author

Procedure

Koshy et al.15 Rex et al.13

EGD Colonoscopy EGD Colonoscopy Sigmoidoscopy Enteroscopy Ileoscopy EGD Colonoscopy ERCP EUS

Heuss et al.16

No. of Patients 274

Sedation

Propofol Administration

P bolus/F vs. M/Md P bolus

Nurse anesthetist Registered nurse

2,574

P Bolus: EGD/ Colonoscopy Infusion: ERCP/EUS

Registered nurse

P bolus

Registered nurse

M/Md/P bolus

Physician

2,000

Walker et al.17

EGD Colonoscopy Liver biopsy

9,152

Cohen et al.18

EGD Colonoscopy

819

Safety NS Airway support* 0.2% Bradycardia 0.05% Airway support* 0.2% Hypotension 14.6% Bradycardia 3.7% Apnea (0.3%) Laryngospasm (0.3%) Aspiration (0.1%) Hypotension 27% Hypoxemia 9%

Patient Satisfaction/ Comfort§

Recovery Time

Cost Effectiveness

NS

Not addressed

Not addressed

Not addressed

Not addressed

Not addressed

Not addressed

79% preference rate for P over M/Md

Not addressed

Not addressed

Not Addressed

26 min

Not addressed

P/F superior comfort Not addressed

P ⫽ propofol F ⫽ fentanyl M ⫽ meperidine Md ⫽ Midazolam R ⫽ remifentanil Pz ⫽ pentazocine NS ⫽ not statistically significant *temporary airway support, not intubation §Satisfaction and comfort from patient standpoint PROPOFOL-MEDIATED GI ENDOSCOPY

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TABLE 3. Propofol Randomized Controlled Trials Study No. of Design Patients Sedation

Author

Procedure

Sipe et al.14

Colonoscopy

RCT

80

P bolus vs. M/Md

Vargo et al.10

ERCP EUS

RCT

75

P bolus vs. M/Md

Wehrmann ERCP et al.12

RCT

198

P bolus vs. Md/Pz

Wehrmann ERCP et al.20

RCT

80

Umer et al.19 Weston et al.21

RCT

100

Colonoscopy EGD

RCT

20

Propofol Administration

Safety

Patient Satisfaction/ Comfort§

Recovery Time

P: Hypotension P ⬎ M/Md P 1.25% satisfaction M/Md: Hypotension 3.75% Arrhythmia 2.5% Gastroenterologist P ⫽ M/Md P ⫽ M/Md P Satisfaction Discomfort Not stated P ⫽ Md/Pz Not P SaO2 ⬍ 85% addressed P: airway support * 1% “Assisting P ⫹ EEG ⫽ P Not P physician” ⫺ EEG addressed Registered nurse

P bolus ⫹/ ⫺ EEG# titration P bolus vs. Registered nurse F/Md M/Md vs. P Registered nurse Bolus

P ⫽ Md/F P ⫽ M/Md

P ⫽ F/Md P ⬎ M/Md

Cost Effectiveness

⬍ M/Md

Not addressed

⬍ M/Md

P more cost effective if nurseadministered Not addressed

⬍ M/Pz

⫹ EEG ⬍ Not addressed P ⫺ EEG

P ⬍ F/Md

Not addressed }

P ⬍ M/Md

Not addressed

P ⫽ propofol F ⫽ fentanyl M ⫽ meperidine Md ⫽ Midazolam R ⫽ remifentanil Pz ⫽ pentazocine NS ⫽ not statistically significant *temporary airway support, not intubation #EEG: electroencephalogram §Satisfaction and comfort from patient standpoint } Quality of sedation

copy or an infusion with as-needed bolus administration for ERCP and endoscopic retrograde cholangiopancreatography.16 Propofol was administered by a registered nurse under the direction of a gastroenterologist. Overall, hypoxemia (SaO2 ⬍ 90%) occurred in 43 (1.7%) patients. In six of these cases, temporary airway support was required. As in the previous series, the majority of patients requiring emergency airway intervention underwent an upper endoscopy. Logistic regression analysis defined the following as independent risk factors for hypoxemia: duration of sedation, total dose of propofol, ASA classification, and patient height. Hypotension (systolic blood pressure ⬍ 90 mm Hg) occurred in 379 (14.6%) patients. Koshy et al compared the combination of propofol and fentanyl to midazolam and meperidine in a non-randomized group of 274 patients undergoing upper endoscopy and colonoscopy.15 The group receiving propofol and fentanyl led to better patient comfort and deeper sedation without an increase in untoward side effects. There was not however, a significant difference in the recovery times between the two groups. Cohen et al. utilized the combination of propofol, meperidine or fentanyl and midazolam for 638 colonoscopies and 181 upper endoscopies.18 An aged-based dosing nomogram was used to administer the narcotic and benozodiazepine. Propofol was administered in 5-15 mg boluses at 30-60 second interval based on oxygen saturation and end-expiratory carbon dioxide levels. No procedure was terminated due to inadequate sedation. A 9% incidence of hypoxemia, which responded to supplemental oxygen and the chin, thrust maneuver. The time for full recovery for colonoscopy patients was similar to that seen in patients receiving midazolam and meperidine in a randomized, controlled trial.19

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Randomized Trials Table 3 summarizes selected randomized controlled trials in which propofol was used for sedation and analgesia for a variety of endoscopic procedures.10,12,14,19-21 A prospective, randomized trial compared the efficacy of propofol alone to the combination of midazolam and propofol in 239 patients undergoing therapeutic upper endoscopy or ERCP.22 While sedation efficacy and the incidence of hypotension and hypoxemia were comparable in both groups, patients receiving midazolam and propofol exhibited a significantly longer mean recovery time. Propofol has been compared in a prospective, randomized trial to midazolam and meperidine in 80 ASA Class I or II outpatients undergoing elective colonoscopy.14 Propofol was superior in terms of the rapidity and depth of sedation, recovery times and overall satisfaction. Additionally, patients receiving propofol exhibited improved recovery of psychometric function. In a randomized study, 90 patients received a bolus administration of propofol or midazolam both before and during upper endoscopy.23 The propofol treatment arm was superior in terms of patient tolerance, maximum level of sedation achieved, and shorter recovery room times. In contrast, a smaller series of 40 patients randomized to receive the same medications before upper endoscopy found that propofol provided a more rapid recovery room time, but was also associated with pain at the injection site, reduced patient acceptance, and a shorter amnesia span.24 Ulmer et al. randomized 100 outpatients undergoing elective colonoscopy to either bolus propofol or fentanyl and midazolam.19 Patients receiving propofol exhibited a faster time to effective sedation, full recovery and JOHN J. VARGO

discharge. Additionally, recovery of psychomotoric function appeared to be enhanced in the propofol group. Overall patient satisfaction was similar between the two sedation groups. Two trials have compared propofol alone to midazolam for ERCP.12,25 In one study, an anesthesiologist administered propofol; in the second study, an assisting physician who was not involved in the endoscopic procedure administered propofol. In both studies, patients receiving propofol exhibited significantly improved quality of sedation and shorter recovery times. Untoward effects such as hypotension and hypoxemia occurred equally in both treatment groups. However, it is important to point out that in both series, one patient in the propofol group developed prolonged apnea that necessitated discontinuation of the procedure and temporary ventilatory support. The use of electroencephalographic monitoring was used in a randomized controlled trial of 80 consecutive patients undergoing elective ERCP.20 Patients receiving propofol titrated to EEG waveforms exhibited a significantly less decrease in the intraprocedural mean arterial blood pressure and a shorter recovery time. Gastroenterologist-administered bolus propofol administration has been compared to meperidine and midazolam for elective ERCP and EUS.10 A separate gastroenterologist, who was trained in propofol administration, was utilized. Additionally, capnography was used to detect apnea or hypercapnea, and thus adjust the propofol dosing accordingly. This study was also the first to address issues of cost effectiveness from an institutional standpoint. Visual analog scales (VAS) were used to address patient and endoscopist satisfaction. Patients randomized to propofol exhibited a faster mean recovery time (18.6 vs. 70.5 min), could perform independent transfer following the procedure and were able to achieve a baseline return to a baseline food intake and activity level (71% vs. 16%). Cost effectiveness data with a sensitivity analysis found that nurseadministered propofol to be the dominant strategy, when compared to standard sedation and analgesia.10

Infusion Administration Patient-controlled sedation and analgesia (PCS) with propofol has recently gained in popularity. Kulling et al. randomized 150 patients to three sedation arms: PCS with propofol/alfentanil (group I), continuous propofol/alfentanil infusion (Group II), and nurse-administered midazolam/meperidine (Group III).26 Group I exhibited a higher degree of patient satisfaction and more of a complete recovery at 45 minutes when compared to conventional sedation and analgesia. In a similar study, Ng and colleagues randomized 88 patients undergoing colonoscopy to PCS with propofol alone or midazolam.27 Patients receiving propofol PCS exhibited significantly shorter recovery times (43.3 min vs. 61.0 min) and improved satisfaction with overall level of comfort. PCS for ERCP however, has not been as successful. In a pilot study utilizing a software system designed to deliver a “ceiling” for the plasma propofol concentration, only 80% of patients received a safe and fully effective sedation.28 Rudner et al. compared the use of remifentanil infusion with propofol bolus dosing to achieve moderate sedation and analgesia to a regimen of fentanyl, midazolam and propofol to achieve a state of “total intravenous general anesthesia” (TIVA) in fifty ASA class I and II patients undergoing elective colonoscopy.29 In the TIVA group, bispectral index (BIS) monitoring was used to achieve a stable level of anesthesia and the “jaw PROPOFOL-MEDIATED GI ENDOSCOPY

TABLE 4. Critical Components for Propofol Administration in the Endoscopy Suite Equipment for airway management and resuscitation readily available Personnel trained in the administration of propofol Personnel dedicated to the continuous and uninterrupted monitoring of the patient’s physiologic parameters At least one person who is qualified in both basic and advanced life support skills (BLS and ACLS) Physiologic monitoring with pulse oximetry, electrocardiography, and automated blood pressure measurement Extended monitoring with capnography should be considered as it may decrease risks during deep sedation Adapted and reprinted with permission.30

thrust” maneuver was applied to minimize the risk of airway obstruction. Patients receiving the sedation and analgesia regimen exhibited a superior recovery time (4 vs. 25.7 minutes). The TIVA group exhibited significant decrements in the mean arterial pressure, heart rate, oxygen saturation, respiratory rate and end-expiratory carbon dioxide. No serious adverse events were noted.

Training Propofol-mediated sedation for endoscopy is a rapidly evolving and contentious issue. In its most recent statement, the American Society of Anesthesiologists Task Force on Sedation and Analgesia by Non-Anesthesiologists concluded that there was insufficient evidence to determine whether moderate or deep sedation with propofol resulted improved efficacy over standard medications for moderate sedation.7 However, since the publication of these guidelines, the literature has burgeoned with randomized controlled trials and case series which include over 17,000 patients12-29 it is becoming evident that with properly trained personnel and meticulous patient selection that safety and efficacy have been demonstrated. The American Society of Gastrointestinal Endoscopy’s guidelines on the use of deep sedation and anesthesia for endoscopy recommends that the following personnel and equipment be present in a procedure room where propofol is used (Table 4).

Summary Popofol-mediated sedation for gastrointestinal endoscopy is a proven alternative to standard sedation and analgesia. In the hands of appropriately trained personnel and in the appropriate clinical setting, propofol has been shown to superior to standard sedation and analgesia in terms of patient satisfaction, comfort, and recovery parameters. Comparative studies have found it to be as safe as the traditional combination of an opioid and benzodiazepine. Cost effectiveness data suggest that propofol is superior to conventional sedation and analgesia, even with the use of added personnel. As with any procedure or sedation regimen, the endoscopy team must have a thorough knowledge of the pharmacology of the agents used for sedation and the training necessary to recognize and manage oversedation. What does the future hold for the dissemination of propofol mediated sedation? The dilemma of added personnel in the endoscopy suite with its resultant cost issues may be answered in the future with the development of “smart machines” which will administer propofol and utilize physiological feedback to

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determine the depth of sedation and to alert endoscopy personnel of potential oversedation. could be a possible solution to this dilemma. Alternatively, the use of a centrally located anesthesia personnel in an endoscopy unit may be another way of maintaining safety while defraying the cost of extra personnel in each room.

References 1. Marinella JA: Propofol for sedation in the intensive care unit: essentials for the clinician. Resp Med 91:505-510, 1997 2. Smith I, White PF, Nathansonn M, et al: Propofol: An update on its clinical use. Anesthesiology 81:1005-1043, 1994 3. Diprivan 1%. Package insert, Astra-Zeneca, Wilmington, DE, 2003. 4. Bryson HM, Fulton BR, Faulds D: Propofol: An update of its use in anaesthesia and conscious sedation. Drugs 50:513-519, 1995 5. Propofol. Package insert, Baxter Pharmaceutical Products, Inc., New Providence, NJ, 2003. 6. Kirkpatrick T, Cockshott ID, Douglas EJ, et al: Pharmacokinetics of propofol (diprivan). Br J Anaesth 60:146-150, 1988 7. Gross JB, Bailey PL, Caplan RA, et al: Practice guidelines for sedation and analgesia by non-anesthesiologists. Anesthesiology 96: 1004-1017, 2002 8. ASGE Standards of Practice Committee: Sedation and monitoring of patients undergoing gastrointestinal endoscopic procedures. Gastrointest Endosc 42:626-629, 1995 9. Vargo JJ, Zuccaro G, Dumot JA, et al: Gastroenterologist-administered propofol for therapeutic upper endoscopy with graphic assessment of respiratory activity: a case series. Gastrointest Endosc 52:250-255, 2000 10. Vargo JJ, Zuccaro G, Dumot J, et al: Gastroenterologist-administered propofol versus meperidine and midazolam for ERCP and EUS: A randomized, controlled trial with cost effectiveness analysis. Gastroenterology 123:8-16, 2002 11. Vargo JJ: Propofol in the endoscopy suite: Panacea or Pandora’s box? Clin Pers Gastroenterol 2:117-119, 2001 12. Wehrmann T, Kokapick S, Lembcke B, et al: Efficacy and safety of intravenous propofol sedation for routine ERCP: a prospective, controlled study. Gastrointest Endsoc 49:677-683, 1999 13. Rex DK, Sipe BW, Kinser KM, et al: Safety of propofol administered by registered nurses with gastroenterologist supervision in 2,000 endoscopic cases. Am J Gastroenerol 97:1159-1163, 2002 14. Sipe BW, Rex DK, Latinovich D, et al: Propofol versus midazolam/ meperidine for outpatient colonoscopy: Administration by nurses supervised by endoscopists. Gastrointest Endosc 55:815-825, 2002 15. Koshy G, Nair S, Norkus EP, et al: Propofol versus midazolam and meperidine for conscious sedation in GI endoscopy. Am J Gastroenterol 95:1476-1479, 2000

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16. Heuss LT, Schieper P, Drewe J, et al: Risk stratification and safe administration of propofol by registered nurses supervised by the gastroenterologist: a prospective observational study of more than 2000 cases. Gastrointest Endosc 57:664-671, 2003 17. Walker JA, McIntyre RD, Scleinitz PF, et al: Nurse-administered propofol sedation without anesthesia specialists in 9152 endoscopic cases in an ambulatory surgery center. Am J Gastroneterol 98:17441750, 2003 18. Cohen LB, Dubovsky AN, Aisenberg J, et al: Propofol for endoscopic sedation: A protocol for safe and effective administration by the gastroenterologist. Gastrointest Endosc 58:725-732, 2003 19. Ulmer BJ, Hansen JJ, Overly CA, et al: Propofol versus midazolam/ fentanyl for outpatient colonoscopy: administration by nurses supervised by endoscopists. Clin Gastroenterol Hepatol 1:425-423, 2003 20. Wehrmann T, Grotkamp J, Stergiou N, et al: Electroencephalogram monitoring facilitates sedation with propofol for routine ERCP: A randomized, controlled trial. Gastrointest Endosc 56:817-824, 2002 21. Weston BR, Chadalawada V, Chalasani N, et al: Nurse-administered propofol versus midazolam and meperidine for upper endoscopy in cirrhotic patients. Am J Gastroenterol 98:2440-2447, 2003 22. Seifert H, Schmitt T, Gultekin T, et al: Sedation with propofol plus midazolam versus propofol alone for interventional endoscopic procedures: A prospective, randomized study. Aliment Pharmacol Ther 14:1207-1214, 2000 23. Carlsson U, Grattidge P: Sedation for upper gastrointestinal endoscopy: A comparative study of propofol and midazolam. Endoscopy 27:240-243, 1995 24. Patterson KW, Casey PB, Murray JP, et al: Propofol sedation for outpatient upper gastrointestinal endoscopy: comparison with midazolam. Br J Anaesth 67:108-111, 1991 25. Jung M, Hofmann C, Kiesslich R, et al: Improved sedation in diagnostic and therapeutic ERCP: Propofol is an alternative to midazolam. Endoscopy 32:233-238, 2000 26. Kulling D, Fantin AC, Biro P, et al: Safer colonoscopy with patientcontrolled analgesia and sedation with propofol and alfentanil. Gastrointest Endosc 54:1-7, 2001 27. Ng JM, Kong CF, Nyam D: Patient-controlled sedation with propofol for colonoscopy. Gastrointest Endosc 54:8-13, 2001 28. Gillham M, Hutchinson R, Carter R, et al. Patient—maintained sedation for ERCP with a target-controlled infusion of propofol: A pilot study. Gastrointest Endosc 5414-5417, 2001 29. Rudner R, Jalowiecki P, Kawecki P, et al: Conscious sedation/ analgesia with remifentanil and propofol versus total intravenous anesthesia with fentanyl, midazolam, and propofol for outpatient colonoscopy. Gastrointest Endosc 57:657-663, 2003 30. Vargo J, Waring P, Faigel D, et al: Guidelines for the use of deep sedation and anesthesia for GI endoscopy. Gastroinest Endosc 56:613-617, 2002

JOHN J. VARGO