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Endoscopist-directed propofol
Techniques in Gastrointestinal Endoscopy (2009) 11, 177-180
Techniques in GASTROINTESTINAL ENDOSCOPY www.techgiendoscopy.com
Endoscopist-directed propofol Douglas K. Rex, MD Indiana University Medical Center, Indianapolis, Indiana. KEYWORDS: Propofol; Nurse-administered propofol sedation; Balanced sedation
This is a review of basic principles applicable to the use of propofol by trained endoscopists and nurses for endoscopy, without the involvement of an anesthesia specialist (an anesthesiologist or certified registered nurse anesthetist). The review also explicitly describes the nature of the current controversy surrounding the use of propofol by endoscopists, implies its origins in financial incentives, and outlines obstacles to the use of endoscopist-directed propofol. © 2009 Elsevier Inc. All rights reserved.
A variety of terms have been used in the literature on endoscopist-directed propofol (EDP). Nurse-administered propofol sedation (NAPS) in its literal sense refers simply to the administration of propofol by a trained registered nurse under the supervision of an endoscopist; however, it has evolved in the language of some experts to mean the use of propofol as a single agent for endoscopy. Balanced propofol sedation (BPS) refers to the administration of propofol in combination with low doses of opioids and/or benzodiazepines and typically with titration to moderate, rather than deep, sedation. The distinction between single-agent propofol and combination regimens is not trivial. Some experts, including anesthesiologists, are of the opinion that combination regimens are inherently more dangerous than singleagent regimens because there is synergism in the sedative effects of different agents. Although there is unquestionably synergism in the sedative effects of propofol with both opioids and benzodiazepines, the realities of propofol pharmacology result in single-agent propofol being inherently more dangerous than combination therapy in some circumstances. This is because it is difficult to titrate single-agent propofol to moderate sedation for endoscopy.1,2 During upper endoscopy, patients being given single-agent propofol titrated to moderate sedation may have severe coughing and gagging if intubation is attempted, resulting in the need to push patients into deep sedation or general anesthesia to
The author reports no direct financial interests that might pose a conflict of interest in connection with the submitted manuscript. Address reprint requests to Douglas K. Rex, MD, Indiana University Medical Center, 550 N. University Blvd., #4100, Indianapolis, IN 46202. E-mail: [email protected] 1096-2883/09/$-see front matter © 2009 Elsevier Inc. All rights reserved. doi:10.1016/j.tgie.2009.09.003
complete the procedure. Similarly, the use of single-agent propofol titrated to moderate sedation for colonoscopy will result in movement and posturing by the patient that precipitates additional propofol administration to achieve deep sedation; thus, single-agent propofol is best used in deep sedation or general anesthesia, which requires higher skills to safely manage than moderate sedation. The administration of very low doses of opioids (eg, 50 g of fentanyl) or benzodiazepines (eg, midazolam, 1 mg) block the coughing and gagging effects during upper endoscopy and the posturing during lower endoscopy and allow propofol to be titrated to moderate sedation.1-3 Therefore, in the case of propofol administration for endoscopy, only BPS consistently targets moderate sedation. Most of the available literature on EDP, which encompasses both NAPS and BPS, has been done with NAPS.4 Some users of EDP are strong proponents of NAPS as preferable to BPS, because the pharmacologic advantages of propofol are partly lost when benzodiazepines and opioids are administered. However, several experts in EDP are strong proponents of BPS, because BPS is inherently safer if propofol is titrated to moderate sedation, and the track records of some practices in using BPS and avoiding bag mask ventilation are remarkable.1,2 In reality, low doses of opioids and benzodiazepines have almost no negative effects in comparison with NAPS, at least with regard to patient recovery time and satisfaction.3 This review considers EDP to encompass both NAPS and BPS, and NAPS and BPS both satisfy the economic goals of EDP. Monitored anesthesia care (MAC) refers to the administration of sedation by anesthesia specialists to nonintubated patients for medical procedures and, in this
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paper, for endoscopy. Although MAC is not synonymous with propofol, because technically it refers to sedation by an anesthesia specialist using any agents and to any level of sedation, it involves the use of propofol in the overwhelming majority of cases. Importantly, MAC generates an additional fee for the completion of the endoscopy, as opposed to EDP, for which there is no additional fee generated, because payment for the administration of sedation is considered part of the professional fee for performance of endoscopy.
The real arbiters of the controversy should be medical evidence and an analysis of the relative cost-effectiveness of MAC. In an era of exploding health care costs without an improvement in outcomes relative to other countries, the United States stands to incur new costs of $5 billion per year as payment for MAC if the transition from endoscopistdelivered sedation to MAC is completed.9 The goal of EDP is to avoid the use of health care dollars associated with MAC for endoscopy while providing safe and effective sedation.
The problems and the controversy
Propofol administration in EDP
The only rationales for EDP are that MAC is not costeffective and that the use of propofol on a national scale by MAC is not possible with regard to anesthesia manpower in the USA. The basis for the controversy is the package insert for propofol, which states that propofol should only be administered by persons trained in rescue from unintended general anesthesia. The fact that this insert was written long before the evidence emerged that EDP is safe has not changed the package insert as the fundamental source of the controversy. The American Society of Anesthesiology,5 individual anesthesiologists, and lawyers all cite the package insert as well as the pharmacologic properties of propofol as to why non-anesthesiologists should not use propofol. The policies of the American Society of Anesthesiology and the opinions of individual anesthesiologists cannot be separated from their financial incentives and the enormous profitability of MAC. As noted recently by anesthesiologist Richard Dworkin in The Wall Street Journal, there is no specialty that approaches anesthesiology in the discrepancy between fees paid by private insurance companies and those paid by the federal government. Thus, while Centers for Medicare and Medicaid Services (CMS) pays a bit more than $100 per case of MAC, private insurers average payments are as much as $700 per case. These high fees paid by private insurers are based partly on the success of anesthesiologists in staying out of insurance plans and therefore being able to negotiate with private insurers. There is no specialty in medicine that is more organized from a business perspective than anesthesiology. The American Society of Anesthesiologists has one of the largest political action committees of any medical specialty and contributes consistently to a broad range of senators and congressmen.6,7 To many observers, fees of this magnitude for MAC, which is a service that practitioners of EDP can consistently train registered nurses to provide the equivalent of in about 2 weeks,8 seem an obvious target for reduction. To some members of the anesthesia community, MAC for endoscopy is a remarkably attractive revenue stream; practitioners can charge high fees for the performance of a relatively simple service on healthy outpatients and make more money than anesthesiologists providing general anesthesia for complicated hospital cases.
There are no mysteries involved in the administration of propofol.10 The principles of the administration of propofol are the same as those for the administration of opioids, benzodiazepines, and other sedative and analgesic agents. First, the sedationist must understand the pharmacokinetics of the agent being used. In the case of propofol, the drug has a time to peak effect of 90 seconds. It also has a rapid offset of action, although this is extended with cumulative dosing. The individual administering the drug must continually observe and measure the patient’s level of sedation and ventilatory effort, as well as their airway patency and level of sedation. An attitude of caution and vigilance will result in an appropriate level of sedation, an open airway, and protection from aspiration. The second principle of endoscopic sedation with propofol is titration.10 EDP is usually done by giving boluses, in the same fashion that other agents for endoscopist-delivered sedation are given. The size of the bolus is chosen based on the patient’s size, age, and comorbidities, as well as whether the patient has received adjunctive opioids and/or benzodiazepines and their respective doses. Sedationists in EDP administer propofol in a fashion very different from that commonly used by anesthesiologists using propofol to induce general anesthesia. The goal of EDP is to ease gradually into an appropriate level of sedation. An initial bolus of 20-40 mg is followed by repeated boluses of 10-20 mg, typically never given at an interval closer than 20 seconds apart. Pretreatment with low doses of benzodiazepines and opioids (eg, midazolam 1 mg and fentanyl 50 g) will reduce the size of boluses, frequency of administration, and total dose of propofol required by more than half.3 The principles of titration include the recognition that there is a 3- to–5-fold variability between individuals in their pharmacologic response to sedative agents, including propofol. Therefore, as titration proceeds, the need for and size of additional boluses is determined by observation of the patient’s level of sedation and ventilatory effort. These principles are no different from those used for opioids and benzodiazepines, but the frequency of administration of propofol is greater than traditional agents because the duration of action of the drug is shorter. The level of sedation required for upper endoscopic procedures is slightly deeper than that required for colonoscopy, and patients tend to have more oropharyngeal secre-
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tions during upper endoscopic procedures, and to be more subject to coughing and gagging. In our unit, we use BPS for all upper endoscopic procedures but only for a portion of colonoscopy procedures (NAPS is used for many colonoscopy procedures). BPS has allowed us to reduce our rate of bag mask ventilation during upper endoscopic procedures from around 1 in 300 procedures during the era where we used single-agent propofol for endoscopy to around 1 per 1000 during the era of BPS in our unit. The need for bag mask ventilation during propofol sedation is expected to be 4-10 times higher for upper endoscopic procedures than for colonoscopy.4 Most EDP has been performed without capnography, but capnography provides additional information about ventilation.11 It is not a substitute for continuous monitoring of ventilation and airway patency. Bispectral monitoring typically lags too far behind the sedation level to be useful in the titration process for short procedures, such as endoscopy.12,13 Continuous monitoring of ventilation by clinical means as well as monitoring of pulse oximetry, blood pressure, heart rate, and cardiac rhythm are required.14
of the patients who died appears to have expired because of unsuccessful resuscitation efforts by the endoscopist. The overall death rate of EDP was 1 per 161,515 cases, a death rate lower than that published for opioids and benzodiazepines delivered by endoscopists, comparable to older studies of general anesthesia performed by anesthesiologists, and lower than recent studies published by anesthesiologists regarding general anesthesia. There are no data available on the safety of MAC for endoscopy or other medical procedures. Therefore, no direct comparison of EDP and MAC with regard to safety is available. Rates of bag mask ventilation were available for 569,220 cases, for which the overall bag mask ventilation rate was 0.1%. When procedure-specific rates of bag mask ventilation were available, the need for bag mask ventilation was 10 times higher for upper endoscopic procedures than for colonoscopy.4 In summary then, available evidence indicates that trained registered nurses supervised by endoscopists have a complication rate equivalent to or better than that of other accepted sedation practices.
Safety of EDP
Cost-effectiveness of MAC for endoscopy
A summary of the safety of EDP identified 223,656 previously published cases of EDP and presented 422,424 new cases of EDP that were previously unpublished and were collected by 28 centers, including 17 in the USA, 2 in Japan, 2 in Germany, and single centers in Switzerland, Australia, Peru, the Bahamas, Italy, Saudi Arabia, and Canada.4 Among the 646,080 total endoscopic cases, data on endotracheal intubation, neurologic injury, and death were available in all series, and all but 1 center had collected data prospectively on these endpoints. There were 11 patients who underwent endotracheal intubation, none who had permanent neurologic sequelae, and there were 4 deaths, all of which occurred in the previously unpublished cases. The 4 deaths occurred in 4 patients with ASA Class III or higher, including 2 patients with metastatic pancreatic cancer, 1 with severe mental retardation, and 1 with severe alcoholic cardiomyopathy as well as substance abuse that was unknown to the endoscopist. One of the patients with metastatic pancreatic cancer appeared to have suffered a pulmonary embolism shortly after completion of placement of 2 small bowel enteral stents for obstruction, and the other required endotracheal intubation to prevent aspiration from an upper GI hemorrhage and died several days postprocedure of exsanguination from pancreatic cancer eroding into the duodenum. The patient with alcoholic cardiomyopathy developed refractory ventricular arrhythmias shortly after initiation of sedation and prior to initiation of the endoscopic procedure. The patient with severe mental retardation developed hypoxia and apnea in the recovery area after successful completion of a percutaneous endoscopic gastrostomy tube. The patient was successfully resuscitated, but life support was withdrawn at the family’s request. None
In the safety summary described above, a “back of the envelope” analysis was used to estimate the cost-effectiveness of substituting MAC for EDP in the 646,080 cases with safety data available.4 Assuming that anesthesia specialists’ administration of propofol would not have resulted in any other deaths and that anesthesia specialists could have prevented all 4 of the deaths that occurred, the cost per life year saved of MAC would be $5.3 million. The cost of MAC would have to drop to $2.70 to $5.40 to reach accepted cost-effectiveness thresholds of $50,000 to $100,000 per life year saved. In a sensitivity analysis that assumed that all 4 patients would have lived to age 85 years, the cost per life year saved was $2.7 million. If it was assumed that anesthesia specialists would have been involved only in ASA III cases, and assuming that they were 10% of the study population, the cost per life year saved was $527,000. If the assumptions were that all 4 decedents would have lived to age 85 years, and anesthesia specialists had been involved only with ASA III patients, the cost per life year saved was $257,000.
Training in EDP The American Society for Anesthesiologists published an evidence-based document on recommended monitoring for non-anesthesiologists using propofol in 2002,14 but has declined to participate in efforts to ensure safe training in EDP. The American Society for Gastrointestinal Endoscopy (ASGE) has made broad recommendations regarding the content of EDP training programs.15 The ASGE and the American College of Gastroenterology have initiated didactic training courses that include information on propofol
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administration. Dr. John Walker, though his “Dr. NAPS” program,16 offers training and credentialing in EDP, as does Dr. John Goff’s group in Colorado. Of the 28 centers providing previously unpublished cases in the above safety report, 23 centers had didactic training sessions, and 13 required physicians and nurses performing EDP to pass a written test. Twenty-seven centers required hands-on supervised training in administration of propofol, and 1 used a simulator for training. All centers included training in airway assessment and management, and 5 had sessions with an anesthesiologist. All the centers required physicians and nurses to have certification in Advanced Cardiac Life Support or an equivalent certification for those outside the USA. All the centers used continuous measurement of pulse oximetry, blood pressure, heart rate, and cardiac rhythm, and 2 of the centers used routine capnography. In one report, three centers with extensive experience indicated that the training interval for nurses involved in administration of propofol typically lasted 2 weeks or less.8 Training was typically accomplished by a didactic session on propofol pharmacology and airway assessment and management, observation of propofol administration by a nurse mentor, and administration of propofol under supervision of a nurse mentor and the endoscopist until the individual was judged competent to administer propofol directly under the supervision of the endoscopist.
Impediments to EDP The use of EDP has expanded rapidly only in Switzerland and Germany, where the safety of EDP and its costeffectiveness have been recognized early-on, and there has not been organized resistance by anesthesia specialists. In the USA, at least 12 states have laws or regulations regarding nursing practice that prevent the administration of propofol to nonintubated patients. The expansion of EDP in the numerous states that do not have specific laws forbidding it has been held back by concerns over medical–legal risk and local institutional policies.
Summary The use of propofol by endoscopists and trained registered nurses for endoscopy has been demystified by a large body of evidence indicating its safety. Propofol, like all sedative agents, has inherent risks when it is misused. However, relatively modest training allows responsible and appropriately cautious individuals to titrate propofol as competently and safely as they
can administer opioids, benzodiazepines, and other agents. The benefits to patients of EDP are obvious, and the cost savings of EDP compared with MAC are enormous. The growth of EDP is inhibited by a lack of cooperation from the anesthesia community. The evidence produced by endoscopists dedicated to the safe and cost-effective administration of moderate sedation for endoscopy is growing, and evidence is a powerful harbinger of change.
References 1. Cohen LB, Hightower CD, Wood DA, et al: Moderate level sedation during endoscopy: a prospective study using low-dose propofol, meperidine/fentanyl, and midazolam. Gastrointest Endosc 59:795-803, 2004 2. 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 3. VanNatta ME, Rex DK: Propofol alone titrated to deep sedation versus propofol in combination with opioids and/or benzodiazepines and titrated to moderate sedation for colonoscopy. Am J Gastroenterol 101:2209-2217, 2006 4. Rex DK, Deenadayalu VP, Eid E, et al: Endoscopist-directed administration of propofol: a worldwide safety experience. Gastroenterology 2009, in press 5. AANA-ASA joint statement regarding propofol administration. Available at: http://www.asahq.org/. Accessed August 15, 2008 6. http://webapps.org/docs/asapac.asp. Accessed September 4, 2009 7. http://opensecrets.org. Accessed September 4, 2009 8. Rex DK, Heuss LT, Walker JA, et al: Trained registered nurses/ endoscopy teams can administer propofol safely for endoscopy. Gastroenterology 129:1384-1391, 2005 9. Aisenberg J, Brill JV, Ladabaum U, et al: Sedation for gastrointestinal endoscopy: new practices, new economics. Am J Gastroenterol 100: 996-1000, 2005 10. Rex DK: Review article: moderate sedation for endoscopy: sedation regimens for non-anaesthesiologists. Aliment Pharmacol Ther 24:163171, 2006 11. Vargo JJ, Zuccaro G Jr, Dumot JA, et al: Gastroenterologist-administered propofol for therapeutic upper endoscopy with graphic assessment of respiratory activity: a case series. Gastrointest Endosc 52:250255, 2000 12. Chen SC, Rex DK: An initial investigation of bispectral monitoring as an adjunct to nurse-administered propofol sedation for colonoscopy. Am J Gastroenterol 99:1081-1086, 2004 13. Drake LM, Chen SC, Rex DK: Efficacy of bispectral monitoring as an adjunct to nurse-administered propofol sedation for colonoscopy: a randomized controlled trial. Am J Gastroenterol 101:2003-2007, 2006 14. American Society of Anesthesiologists Task Force on Sedation and Analgesia by Non-Anesthesiologists: practice guidelines for sedation and analgesia by non-anesthesiologists. Anesthesiology 96:1004-1017, 2002 15. American Society for Gastrointestinal Endoscopy: training guideline for use of propofol in gastrointestinal endoscopy. Gastrointest Endosc 60:167-172, 2004 16. NAPS. Available at: http://www.drnaps.org/index.htm. Accessed September 8, 2009
Techniques in GASTROINTESTINAL ENDOSCOPY www.techgiendoscopy.com
Endoscopist-directed propofol Douglas K. Rex, MD Indiana University Medical Center, Indianapolis, Indiana. KEYWORDS: Propofol; Nurse-administered propofol sedation; Balanced sedation
This is a review of basic principles applicable to the use of propofol by trained endoscopists and nurses for endoscopy, without the involvement of an anesthesia specialist (an anesthesiologist or certified registered nurse anesthetist). The review also explicitly describes the nature of the current controversy surrounding the use of propofol by endoscopists, implies its origins in financial incentives, and outlines obstacles to the use of endoscopist-directed propofol. © 2009 Elsevier Inc. All rights reserved.
A variety of terms have been used in the literature on endoscopist-directed propofol (EDP). Nurse-administered propofol sedation (NAPS) in its literal sense refers simply to the administration of propofol by a trained registered nurse under the supervision of an endoscopist; however, it has evolved in the language of some experts to mean the use of propofol as a single agent for endoscopy. Balanced propofol sedation (BPS) refers to the administration of propofol in combination with low doses of opioids and/or benzodiazepines and typically with titration to moderate, rather than deep, sedation. The distinction between single-agent propofol and combination regimens is not trivial. Some experts, including anesthesiologists, are of the opinion that combination regimens are inherently more dangerous than singleagent regimens because there is synergism in the sedative effects of different agents. Although there is unquestionably synergism in the sedative effects of propofol with both opioids and benzodiazepines, the realities of propofol pharmacology result in single-agent propofol being inherently more dangerous than combination therapy in some circumstances. This is because it is difficult to titrate single-agent propofol to moderate sedation for endoscopy.1,2 During upper endoscopy, patients being given single-agent propofol titrated to moderate sedation may have severe coughing and gagging if intubation is attempted, resulting in the need to push patients into deep sedation or general anesthesia to
The author reports no direct financial interests that might pose a conflict of interest in connection with the submitted manuscript. Address reprint requests to Douglas K. Rex, MD, Indiana University Medical Center, 550 N. University Blvd., #4100, Indianapolis, IN 46202. E-mail: [email protected] 1096-2883/09/$-see front matter © 2009 Elsevier Inc. All rights reserved. doi:10.1016/j.tgie.2009.09.003
complete the procedure. Similarly, the use of single-agent propofol titrated to moderate sedation for colonoscopy will result in movement and posturing by the patient that precipitates additional propofol administration to achieve deep sedation; thus, single-agent propofol is best used in deep sedation or general anesthesia, which requires higher skills to safely manage than moderate sedation. The administration of very low doses of opioids (eg, 50 g of fentanyl) or benzodiazepines (eg, midazolam, 1 mg) block the coughing and gagging effects during upper endoscopy and the posturing during lower endoscopy and allow propofol to be titrated to moderate sedation.1-3 Therefore, in the case of propofol administration for endoscopy, only BPS consistently targets moderate sedation. Most of the available literature on EDP, which encompasses both NAPS and BPS, has been done with NAPS.4 Some users of EDP are strong proponents of NAPS as preferable to BPS, because the pharmacologic advantages of propofol are partly lost when benzodiazepines and opioids are administered. However, several experts in EDP are strong proponents of BPS, because BPS is inherently safer if propofol is titrated to moderate sedation, and the track records of some practices in using BPS and avoiding bag mask ventilation are remarkable.1,2 In reality, low doses of opioids and benzodiazepines have almost no negative effects in comparison with NAPS, at least with regard to patient recovery time and satisfaction.3 This review considers EDP to encompass both NAPS and BPS, and NAPS and BPS both satisfy the economic goals of EDP. Monitored anesthesia care (MAC) refers to the administration of sedation by anesthesia specialists to nonintubated patients for medical procedures and, in this
178
Techniques in Gastrointestinal Endoscopy, Vol 11, No 4, October 2009
paper, for endoscopy. Although MAC is not synonymous with propofol, because technically it refers to sedation by an anesthesia specialist using any agents and to any level of sedation, it involves the use of propofol in the overwhelming majority of cases. Importantly, MAC generates an additional fee for the completion of the endoscopy, as opposed to EDP, for which there is no additional fee generated, because payment for the administration of sedation is considered part of the professional fee for performance of endoscopy.
The real arbiters of the controversy should be medical evidence and an analysis of the relative cost-effectiveness of MAC. In an era of exploding health care costs without an improvement in outcomes relative to other countries, the United States stands to incur new costs of $5 billion per year as payment for MAC if the transition from endoscopistdelivered sedation to MAC is completed.9 The goal of EDP is to avoid the use of health care dollars associated with MAC for endoscopy while providing safe and effective sedation.
The problems and the controversy
Propofol administration in EDP
The only rationales for EDP are that MAC is not costeffective and that the use of propofol on a national scale by MAC is not possible with regard to anesthesia manpower in the USA. The basis for the controversy is the package insert for propofol, which states that propofol should only be administered by persons trained in rescue from unintended general anesthesia. The fact that this insert was written long before the evidence emerged that EDP is safe has not changed the package insert as the fundamental source of the controversy. The American Society of Anesthesiology,5 individual anesthesiologists, and lawyers all cite the package insert as well as the pharmacologic properties of propofol as to why non-anesthesiologists should not use propofol. The policies of the American Society of Anesthesiology and the opinions of individual anesthesiologists cannot be separated from their financial incentives and the enormous profitability of MAC. As noted recently by anesthesiologist Richard Dworkin in The Wall Street Journal, there is no specialty that approaches anesthesiology in the discrepancy between fees paid by private insurance companies and those paid by the federal government. Thus, while Centers for Medicare and Medicaid Services (CMS) pays a bit more than $100 per case of MAC, private insurers average payments are as much as $700 per case. These high fees paid by private insurers are based partly on the success of anesthesiologists in staying out of insurance plans and therefore being able to negotiate with private insurers. There is no specialty in medicine that is more organized from a business perspective than anesthesiology. The American Society of Anesthesiologists has one of the largest political action committees of any medical specialty and contributes consistently to a broad range of senators and congressmen.6,7 To many observers, fees of this magnitude for MAC, which is a service that practitioners of EDP can consistently train registered nurses to provide the equivalent of in about 2 weeks,8 seem an obvious target for reduction. To some members of the anesthesia community, MAC for endoscopy is a remarkably attractive revenue stream; practitioners can charge high fees for the performance of a relatively simple service on healthy outpatients and make more money than anesthesiologists providing general anesthesia for complicated hospital cases.
There are no mysteries involved in the administration of propofol.10 The principles of the administration of propofol are the same as those for the administration of opioids, benzodiazepines, and other sedative and analgesic agents. First, the sedationist must understand the pharmacokinetics of the agent being used. In the case of propofol, the drug has a time to peak effect of 90 seconds. It also has a rapid offset of action, although this is extended with cumulative dosing. The individual administering the drug must continually observe and measure the patient’s level of sedation and ventilatory effort, as well as their airway patency and level of sedation. An attitude of caution and vigilance will result in an appropriate level of sedation, an open airway, and protection from aspiration. The second principle of endoscopic sedation with propofol is titration.10 EDP is usually done by giving boluses, in the same fashion that other agents for endoscopist-delivered sedation are given. The size of the bolus is chosen based on the patient’s size, age, and comorbidities, as well as whether the patient has received adjunctive opioids and/or benzodiazepines and their respective doses. Sedationists in EDP administer propofol in a fashion very different from that commonly used by anesthesiologists using propofol to induce general anesthesia. The goal of EDP is to ease gradually into an appropriate level of sedation. An initial bolus of 20-40 mg is followed by repeated boluses of 10-20 mg, typically never given at an interval closer than 20 seconds apart. Pretreatment with low doses of benzodiazepines and opioids (eg, midazolam 1 mg and fentanyl 50 g) will reduce the size of boluses, frequency of administration, and total dose of propofol required by more than half.3 The principles of titration include the recognition that there is a 3- to–5-fold variability between individuals in their pharmacologic response to sedative agents, including propofol. Therefore, as titration proceeds, the need for and size of additional boluses is determined by observation of the patient’s level of sedation and ventilatory effort. These principles are no different from those used for opioids and benzodiazepines, but the frequency of administration of propofol is greater than traditional agents because the duration of action of the drug is shorter. The level of sedation required for upper endoscopic procedures is slightly deeper than that required for colonoscopy, and patients tend to have more oropharyngeal secre-
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179
tions during upper endoscopic procedures, and to be more subject to coughing and gagging. In our unit, we use BPS for all upper endoscopic procedures but only for a portion of colonoscopy procedures (NAPS is used for many colonoscopy procedures). BPS has allowed us to reduce our rate of bag mask ventilation during upper endoscopic procedures from around 1 in 300 procedures during the era where we used single-agent propofol for endoscopy to around 1 per 1000 during the era of BPS in our unit. The need for bag mask ventilation during propofol sedation is expected to be 4-10 times higher for upper endoscopic procedures than for colonoscopy.4 Most EDP has been performed without capnography, but capnography provides additional information about ventilation.11 It is not a substitute for continuous monitoring of ventilation and airway patency. Bispectral monitoring typically lags too far behind the sedation level to be useful in the titration process for short procedures, such as endoscopy.12,13 Continuous monitoring of ventilation by clinical means as well as monitoring of pulse oximetry, blood pressure, heart rate, and cardiac rhythm are required.14
of the patients who died appears to have expired because of unsuccessful resuscitation efforts by the endoscopist. The overall death rate of EDP was 1 per 161,515 cases, a death rate lower than that published for opioids and benzodiazepines delivered by endoscopists, comparable to older studies of general anesthesia performed by anesthesiologists, and lower than recent studies published by anesthesiologists regarding general anesthesia. There are no data available on the safety of MAC for endoscopy or other medical procedures. Therefore, no direct comparison of EDP and MAC with regard to safety is available. Rates of bag mask ventilation were available for 569,220 cases, for which the overall bag mask ventilation rate was 0.1%. When procedure-specific rates of bag mask ventilation were available, the need for bag mask ventilation was 10 times higher for upper endoscopic procedures than for colonoscopy.4 In summary then, available evidence indicates that trained registered nurses supervised by endoscopists have a complication rate equivalent to or better than that of other accepted sedation practices.
Safety of EDP
Cost-effectiveness of MAC for endoscopy
A summary of the safety of EDP identified 223,656 previously published cases of EDP and presented 422,424 new cases of EDP that were previously unpublished and were collected by 28 centers, including 17 in the USA, 2 in Japan, 2 in Germany, and single centers in Switzerland, Australia, Peru, the Bahamas, Italy, Saudi Arabia, and Canada.4 Among the 646,080 total endoscopic cases, data on endotracheal intubation, neurologic injury, and death were available in all series, and all but 1 center had collected data prospectively on these endpoints. There were 11 patients who underwent endotracheal intubation, none who had permanent neurologic sequelae, and there were 4 deaths, all of which occurred in the previously unpublished cases. The 4 deaths occurred in 4 patients with ASA Class III or higher, including 2 patients with metastatic pancreatic cancer, 1 with severe mental retardation, and 1 with severe alcoholic cardiomyopathy as well as substance abuse that was unknown to the endoscopist. One of the patients with metastatic pancreatic cancer appeared to have suffered a pulmonary embolism shortly after completion of placement of 2 small bowel enteral stents for obstruction, and the other required endotracheal intubation to prevent aspiration from an upper GI hemorrhage and died several days postprocedure of exsanguination from pancreatic cancer eroding into the duodenum. The patient with alcoholic cardiomyopathy developed refractory ventricular arrhythmias shortly after initiation of sedation and prior to initiation of the endoscopic procedure. The patient with severe mental retardation developed hypoxia and apnea in the recovery area after successful completion of a percutaneous endoscopic gastrostomy tube. The patient was successfully resuscitated, but life support was withdrawn at the family’s request. None
In the safety summary described above, a “back of the envelope” analysis was used to estimate the cost-effectiveness of substituting MAC for EDP in the 646,080 cases with safety data available.4 Assuming that anesthesia specialists’ administration of propofol would not have resulted in any other deaths and that anesthesia specialists could have prevented all 4 of the deaths that occurred, the cost per life year saved of MAC would be $5.3 million. The cost of MAC would have to drop to $2.70 to $5.40 to reach accepted cost-effectiveness thresholds of $50,000 to $100,000 per life year saved. In a sensitivity analysis that assumed that all 4 patients would have lived to age 85 years, the cost per life year saved was $2.7 million. If it was assumed that anesthesia specialists would have been involved only in ASA III cases, and assuming that they were 10% of the study population, the cost per life year saved was $527,000. If the assumptions were that all 4 decedents would have lived to age 85 years, and anesthesia specialists had been involved only with ASA III patients, the cost per life year saved was $257,000.
Training in EDP The American Society for Anesthesiologists published an evidence-based document on recommended monitoring for non-anesthesiologists using propofol in 2002,14 but has declined to participate in efforts to ensure safe training in EDP. The American Society for Gastrointestinal Endoscopy (ASGE) has made broad recommendations regarding the content of EDP training programs.15 The ASGE and the American College of Gastroenterology have initiated didactic training courses that include information on propofol
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administration. Dr. John Walker, though his “Dr. NAPS” program,16 offers training and credentialing in EDP, as does Dr. John Goff’s group in Colorado. Of the 28 centers providing previously unpublished cases in the above safety report, 23 centers had didactic training sessions, and 13 required physicians and nurses performing EDP to pass a written test. Twenty-seven centers required hands-on supervised training in administration of propofol, and 1 used a simulator for training. All centers included training in airway assessment and management, and 5 had sessions with an anesthesiologist. All the centers required physicians and nurses to have certification in Advanced Cardiac Life Support or an equivalent certification for those outside the USA. All the centers used continuous measurement of pulse oximetry, blood pressure, heart rate, and cardiac rhythm, and 2 of the centers used routine capnography. In one report, three centers with extensive experience indicated that the training interval for nurses involved in administration of propofol typically lasted 2 weeks or less.8 Training was typically accomplished by a didactic session on propofol pharmacology and airway assessment and management, observation of propofol administration by a nurse mentor, and administration of propofol under supervision of a nurse mentor and the endoscopist until the individual was judged competent to administer propofol directly under the supervision of the endoscopist.
Impediments to EDP The use of EDP has expanded rapidly only in Switzerland and Germany, where the safety of EDP and its costeffectiveness have been recognized early-on, and there has not been organized resistance by anesthesia specialists. In the USA, at least 12 states have laws or regulations regarding nursing practice that prevent the administration of propofol to nonintubated patients. The expansion of EDP in the numerous states that do not have specific laws forbidding it has been held back by concerns over medical–legal risk and local institutional policies.
Summary The use of propofol by endoscopists and trained registered nurses for endoscopy has been demystified by a large body of evidence indicating its safety. Propofol, like all sedative agents, has inherent risks when it is misused. However, relatively modest training allows responsible and appropriately cautious individuals to titrate propofol as competently and safely as they
can administer opioids, benzodiazepines, and other agents. The benefits to patients of EDP are obvious, and the cost savings of EDP compared with MAC are enormous. The growth of EDP is inhibited by a lack of cooperation from the anesthesia community. The evidence produced by endoscopists dedicated to the safe and cost-effective administration of moderate sedation for endoscopy is growing, and evidence is a powerful harbinger of change.
References 1. Cohen LB, Hightower CD, Wood DA, et al: Moderate level sedation during endoscopy: a prospective study using low-dose propofol, meperidine/fentanyl, and midazolam. Gastrointest Endosc 59:795-803, 2004 2. 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 3. VanNatta ME, Rex DK: Propofol alone titrated to deep sedation versus propofol in combination with opioids and/or benzodiazepines and titrated to moderate sedation for colonoscopy. Am J Gastroenterol 101:2209-2217, 2006 4. Rex DK, Deenadayalu VP, Eid E, et al: Endoscopist-directed administration of propofol: a worldwide safety experience. Gastroenterology 2009, in press 5. AANA-ASA joint statement regarding propofol administration. Available at: http://www.asahq.org/. Accessed August 15, 2008 6. http://webapps.org/docs/asapac.asp. Accessed September 4, 2009 7. http://opensecrets.org. Accessed September 4, 2009 8. Rex DK, Heuss LT, Walker JA, et al: Trained registered nurses/ endoscopy teams can administer propofol safely for endoscopy. Gastroenterology 129:1384-1391, 2005 9. Aisenberg J, Brill JV, Ladabaum U, et al: Sedation for gastrointestinal endoscopy: new practices, new economics. Am J Gastroenterol 100: 996-1000, 2005 10. Rex DK: Review article: moderate sedation for endoscopy: sedation regimens for non-anaesthesiologists. Aliment Pharmacol Ther 24:163171, 2006 11. Vargo JJ, Zuccaro G Jr, Dumot JA, et al: Gastroenterologist-administered propofol for therapeutic upper endoscopy with graphic assessment of respiratory activity: a case series. Gastrointest Endosc 52:250255, 2000 12. Chen SC, Rex DK: An initial investigation of bispectral monitoring as an adjunct to nurse-administered propofol sedation for colonoscopy. Am J Gastroenterol 99:1081-1086, 2004 13. Drake LM, Chen SC, Rex DK: Efficacy of bispectral monitoring as an adjunct to nurse-administered propofol sedation for colonoscopy: a randomized controlled trial. Am J Gastroenterol 101:2003-2007, 2006 14. American Society of Anesthesiologists Task Force on Sedation and Analgesia by Non-Anesthesiologists: practice guidelines for sedation and analgesia by non-anesthesiologists. Anesthesiology 96:1004-1017, 2002 15. American Society for Gastrointestinal Endoscopy: training guideline for use of propofol in gastrointestinal endoscopy. Gastrointest Endosc 60:167-172, 2004 16. NAPS. Available at: http://www.drnaps.org/index.htm. Accessed September 8, 2009