Review article: registered nurse-administered propofol sedation for endoscopy

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1 Aliment Pharmacol Ther 2004; 19: doi: /j x Review article: registered nurse-administered propofol sedation for endoscopy S. C. CHEN & D. K. REX Department of Medicine, Division of Gastroenterology, Indiana University School of Medicine, Indianapolis, IN, USA Accepted for publication 5 November 2003 SUMMARY Propofol has several attractive properties that render it a potential alternative sedative agent for endoscopy. Compared with meperidine and midazolam, it has an ultra-short onset of action, short plasma half-life, short time to achieve sedation, faster time to recovery and discharge, and results in higher patient satisfaction. Shorter times to achieve sedation enhance efficiency in the endoscopy unit. Multiple studies have documented the safe administration of propofol by non-anaesthesiologists. Administration by registered nurses is more cost-effective than administration by anaesthesiologists. However, the administration of propofol by a registered nurse supervised only by the endoscopist is controversial because the drug has the potential to produce sudden and severe respiratory depression. More information is needed on how training nurses and endoscopists should proceed to give propofol, as well as the optimal level of monitoring to ensure the safety of nurse-administered propofol. INTRODUCTION Correspondence to: Dr D. K. Rex, Indiana University Hospital, #4100, 550 N. University Boulevard, Indianapolis, IN 46202, USA. drex@iupui.edu The pattern of sedation use for endoscopic procedures varies between countries more than any other aspect of endoscopic practice. These differences probably reflect cultural variation in the expectations of patients and the beliefs and preferences of endoscopists. Many patients prefer sedation, however, and sedation is routine in some countries, including the USA. 1 4 The routine sedative agents for gastrointestinal endoscopic procedures include a combination of benzodiazepines and narcotic analgesics. 5 7 Since its introduction in 1986, midazolam has become the most commonly chosen benzodiazepine for sedation. 7 9 It is a powerful anxiolytic agent, 10 which facilitates relaxation and patient co-operation. From an endoscopic perspective, it also has other useful properties, including antegrade amnesia and a short elimination half-life. Moreover, the cardiopulmonary effects of this agent are relatively minimal when the use of adjunctive agents is minimized. 9 With the addition of an opiate, the sedative and amnestic properties of midazolam are synergistically enhanced, thereby optimizing patient satisfaction. 3 Unfortunately, there are potential problems with the use of both benzodiazepines and narcotic analgesics. These include a variable onset of action, 5, 11 postprocedure residual effects that may delay the time to discharge and an increased risk of respiratory depression, particularly in the elderly population. 12 In certain groups of patients, e.g. alcoholics and chronic users of benzodiazepines or narcotics, the efficacy of midazolam and narcotics may be limited. 13 The ideal agent for sedation should have the following properties: rapid onset of action, analgesic and anxiolytic effects, immediate resolution of sedation without any lingering effects on mental and psychomotor functions, amnestic period long enough for the procedure and minimal associated risks or adverse effects. 3, 7 Ó 2004 Blackwell Publishing Ltd 147

2 148 S. C. CHEN & D. K. REX To that end, there has been increased attention focused on the use of propofol as an alternative sedative agent for gastrointestinal endoscopy. 14 Propofol has properties which may render it an attractive alternative to narcotics and benzodiazepines with regard to some of 1 3, 10, these desirable features. Propofol was introduced in 1989 as an intravenous sedative agent and is widely used for the induction of general anaesthesia and for the sedation of ventilated 16, 18, 19 patients in intensive care units. However, its use by non-anaesthesiologists is controversial. 20 Currently, the American Society of Anesthesiology (ASA) Task Force recommends that patients receiving propofol should receive care consistent with that required for deep sedation. 21 Personnel administering propofol should be able to rescue patients from general anaesthesia (Table 1). 16 Despite this, there is increasing evidence that propofol can be administered safely by specially trained registered nurses and gastroenterologists. 3, 4, 12, 14, 16 18, 22 PHARMACOLOGY AND PROPERTIES OF PROPOFOL Table 1. Continuum of sedation Minimal sedation (level 1): A drug-induced state, during which the patient responds normally to verbal commands. Cognitive function and co-ordination may be impaired. Ventilatory and cardiovascular functions are unaffected Moderate sedation/analgesia (level 2, conscious sedation ): A drug-induced depression of consciousness, during which patients respond purposefully to verbal commands, either alone or accompanied by light tactile stimulation. A patent airway is maintained without help. Spontaneous ventilation is adequate, and cardiovascular function is usually maintained Deep sedation/analgesia (level 3): A drug-induced depression of consciousness, during which patients cannot be easily aroused but respond purposefully to repeated stimulation. Patients may require assistance maintaining airway. Spontaneous ventilation may be inadequate and cardiovascular function is usually maintained General anaesthesia (level 4): Patients are not arousable, even by painful stimulation. Patients often require assistance in maintaining a patent airway. Positive pressure ventilation may be required owing to respiratory depression or neuromuscular blockade. Cardiovascular function may be impaired Propofol is a lipophilic alkyl phenol derivative (2,6- di-isopropyl phenol) with the potential to cause sedation, amnesia and hypnosis. 7, 23, 24 It provides minimal analgesia. 16 The drug is normally prepared as an oilin-water emulsion which consists of multiple components, including 1% propofol, 10% soybean oil, 2.25% glycerol and 1.2% egg lecithin. 24 It is therefore contraindicated in patients who have hypersensitivity to soybean or egg. Propofol has the potential to cross the placenta and therefore should not be given to pregnant or lactating women, 19 although lactating women may dispose of milk for 24 h after receiving propofol. It acts synergistically with benzodiazepines, barbiturates and opioids. 24 Sodium metabisulphite is also included in the generic formulation. Thus, the generic form is contraindicated in patients who are allergic to sulphite. 24 Diprivan (propofol; Astra Zeneca, Wilmington, DE, USA) can be obtained in vials of different quantities, including 20-, 50- and 100-mL vials. The average wholesale prices of Diprivan are as follows: a set of mL vials (10 mg/ml) costs $361.88, a set of mL vials (10 mg/ml) costs $ and a set of mL vials (10 mg/ml) costs $ In its generic formulation, a set of mL vials (10 mg/ml) costs $330, a set of mL vials (10 mg/ml) costs $660 and a set of mL vials costs $660. However, regardless of its formulation, the actual price of propofol varies and, most often, is a percentage of the average wholesale price, depending on the contract agreement between a supplier and a hospital. Propofol has some of the features noted above for the ideal sedative. It has an ultra-short onset of action, with the effect initially seen within s, or a single arm brain circulation. The plasma half-life ranges from 1.8 to 4.1 min. 25 It provides quick recovery within min after cessation of infusion or administration, via rapid tissue distribution, with initial distribution to well-perfused areas and subsequently to fat tissues and finally to hepatic metabolism. The effects of propofol may be prolonged in elderly patients. 12 The pharmacokinetics of propofol are not greatly affected in cirrhotic patients or patients with renal dysfunction. 25 In addition, it is associated with higher patient comfort and satisfaction when compared with conventional combinations of midazolam and meperidine. 3, 11, 23 Together with its many admirable qualities, there are a number of potential side-effects associated with propofol use. The drug is difficult to use for moderate sedation, because it has no analgesic effects, and patients who are moderately sedated with propofol may demonstrate confusion, agitation and marked withdrawal responses to painful stimuli. Patients may slip quickly from moderate to deep sedation and demonstrate no

3 REVIEW: PROPOFOL SEDATION FOR ENDOSCOPY 149 responses to painful stimulation (general anaesthesia). Although most patients maintain ventilatory effort even without a pain response, some will not, and respiratory depression is a major and potentially life-threatening risk. Concurrent use with narcotics may potentiate the effects of respiratory depression. 7 As a result of these risks, propofol use is controlled in many institutions by anaesthesia specialists. 3 Another concern about propofol is its depressant effect on cardiovascular function. By combining the effects of arterial and venous dilation, propofol induces a dose-dependent decrease in blood pressure. Accompanying this effect is a concurrent 4, 7, 8, 26 decline in heart rate and cardiac contractility. Therefore, its cautious and judicious use in patients with coronary artery disease or poor left ventricular 7, 12 function is recommended. Based on its side-effect profile, the administration of propofol requires diligent monitoring of vital signs and the availability of rescue agents and resuscitative equipment. Traditionally, the administration of propofol has been largely restricted to anaesthesiologists and nurse anaesthetists. 17 Therefore, propofol use may result in substantial additional costs to endoscopic procedures. Propofol can cause severe discomfort at the site of injection. 16 Up to 50% of patients may experience this type of injection pain, especially with injection into smaller peripheral veins. Using large veins (e.g. antecubital) for intravenous access or giving lignocaine (lidocaine) prior to propofol injection can reduce or prevent the pain. 7 Other factors which may limit support for propofol include its higher medication cost compared with other sedative regimens (e.g. midazolam and meperidine), 22 although the differences are smaller than many believe, and the drug can result in cost savings during the recovery phase of the procedures. Propofol can support contaminant microbial growth (propofol should be used no later than 6 h after being removed from the vial), 16 although sepsis essentially never occurs with proper use. Perhaps most importantly, there is no direct antagonist for the treatment of overdose. In such cases, patients may need assisted ventilation until their own spontaneous ventilation resumes. STUDIES ON THE SAFE USE OF PROPOFOL BY NON-ANAESTHESIOLOGISTS A recent study has shown that the administration of propofol by anaesthesiologists or nurse anaesthetists is not cost-effective compared with delivery by registered nurses. 22 Propofol can be administered by three methods: bolus titration, continuous infusion or patientcontrolled analgesia. 16 Most of the studies reviewed here have used the bolus titration method. Studies on safety A prospective study by Rex et al. found that, under the supervision of a physician-endoscopist, propofol was safely administered as sedation in 2000 endoscopic cases by registered nurses. 17 The patients were ASA class 1 2 (Table 2). Patients receiving propofol were monitored for oxygen saturation (whilst being given 4 L of oxygen continuously), blood pressure, heart rate and electrocardiogram. Registered nurses who administered propofol also monitored patients for chest excursion, respiratory effort and respiratory rate. Subjects were given an initial bolus of mg, followed by mg boluses as needed to maintain sedation. The results showed only five episodes (of the 2000 procedures) with oxygen saturation of less than 85%. One resulted from a coughing spasm during colonoscopy that responded well to increased inspired oxygen concentration and the remaining four from excessive propofol administration during upper endoscopy. All responded to mask ventilation for intervals of less than 1 min. Eleven other episodes of low oxygen saturation between 85% and 90% responded well to increased inspired oxygen fractions. No patient required endotracheal intubation or suffered from long-term sequelae as a result of oxygen desaturation, and no patient required specific treatment of hypotension. Table 2. Definition of American Society of Anesthesiology status Class 1: Patient has no organic, physiological, biochemical or psychiatric disturbance. The pathological process for which the operation is to be performed is localized and does not entail systemic disturbance Class 2: Mild to moderate systemic disturbance caused either by the condition to be treated surgically or by other pathophysiological processes Class 3: Severe, systemic disturbance or disease from whatever cause, even though it may not be possible to define the degree of disability with finality Class 4: Severe systemic disorders that are already life-threatening, not always correctable by operation Class 5: The moribund patient who has little chance of survival, but is submitted to operation in desperation

4 150 S. C. CHEN & D. K. REX A recent prospective observational study by Heuss et al. evaluated the safety of propofol administered by nurses in elderly patients. 12 The study consisted of three groups: patients less than 70 years of age (control group), patients between 70 and 85 years of age (group A) and patients more than 85 years of age (group B). Patients were from ASA class 1 4. Of the 1786 endoscopic procedures, 301 were performed without any sedation and 1485 were carried out with propofol sedation, with oesophagogastroduodenoscopy (EGD) (> 50% in each group) being the most common procedure performed. The endoscopic examinations were performed by 14 different endoscopists including seven board-certified gastroenterologists and seven residents in their last year of training. All patients were given a continuous infusion of normal saline and a minimum of 2 L of supplemental oxygen. Routine vital signs were monitored, including oxygen saturation, blood pressure and heart rate. For gastroscopies and colonoscopies, boluses of propofol were given, with an initial bolus of 20 mg, followed by mg boluses of propofol as needed. If the effect dissipated during the procedure, additional 10-mg boluses were also given as needed. For endoscopic retrograde cholangiopancreatography and endosonographies, propofol was delivered as a continuous infusion, with the dosage ranging from 100 to 200 mg/h. Additional 10-mg boluses of propofol were also given as needed. One patient each in group A and group B required bag ventilation, presumably secondary to the rapid administration of propofol, but both recovered without any sequelae or necessity for any further care. In addition, two cases in group A required emergent intervention, but recovered shortly after rescue manoeuvres without bag ventilation. Of note, a statistically significant increase in the risk of brief oxygen desaturation (< 90%) was noted in groups A and B. There was also a higher frequency of use of atropine that was not statistically significant in the elderly patients, but arterial hypotension occurred significantly more in the control group. Overall, there was no statistically significant difference between the groups in the parameters of mean changes in oxygen saturation, arterial blood pressure and heart rate. There was a reduced initial loading dose of propofol (up to 60%) given to patients over 85 years of age, and subsequent maintenance doses were also lowered to maintain adequate sedation during the examination. A separate prospective observational study was conducted by Heuss et al. to evaluate the safety of propofol administration by registered nurses under the supervision of gastroenterologists according to the ASA stratification. 4 Patients undergoing routine upper endoscopy or colonoscopy were free to choose between propofol and midazolam. The procedures were performed by 14 gastroenterologists. There was a total of 2574 patients included, with ASA class 1 4. All patients received a continuous infusion of normal saline and a minimum of 2 L of supplemental oxygen. Pulse oximetry, blood pressure and heart rate were monitored in all patients. Propofol was administered either as boluses or as a continuous infusion, depending on the endoscopic procedure. For upper endoscopy and colonoscopy, an intermittent bolus schedule was used, with an initial dose of 20 mg, followed by increments of mg as needed. Additional 10-mg propofol boluses were given if the drug effects dissipated during the procedure. For endoscopic retrograde cholangiopancreatography and endoscopic ultrasound (EUS), a continuous infusion of propofol was used at mg/h with 10-mg boluses as needed. In both schedules, the drug was administered by registered nurses. The results of the study showed that the average loading dose required for an adequate level of conscious sedation was 1.0 mg/kg of propofol, and the dose requirement was inversely related to the ASA classification. In terms of oxygen desaturation, 43 (1.7%) patients experienced desaturation thought to be induced by propofol sedation, with 37 of these having hypoxaemic episodes of less than 1 min that were easily reversed with simple stimulation and increased inspired oxygen. However, the other six (0.2%) patients required intervention, with three requiring nasopharyngeal tube placement and three brief mask ventilation. All recovered with no sequelae. In addition, this study revealed a tendency towards an increased risk of short-duration oxygen desaturation with increasing ASA classification. There was a total of 379 (14.6%) patients with a reduction of systolic blood pressure to below 90 mmhg. Ninety-five (3.7%) patients developed a pulse rate of < 50 which was thought to be related to propofol sedation. In addition, logistic regression analysis showed that four factors (the duration of sedation, total dose of propofol, ASA classification and patient height) significantly influenced the risk of oxygen desaturation below 90%. Walker et al. conducted a prospective study to investigate how nurse-administered propofol sedation, under the supervision of gastroenterologists but without the presence of either anaesthesiologists or nurse anaesthetists, affected the endoscopic experience with regard

5 REVIEW: PROPOFOL SEDATION FOR ENDOSCOPY 151 to patient safety and satisfaction in an ambulatory surgery centre. 14 Patients were ASA class 1 4, with the majority being ASA class 1 and 2. Propofol was administered with a loading dose of mg, followed by mg boluses as needed. Three procedures were performed in the endoscopy suite: upper endoscopy, colonoscopy and liver biopsy, with upper endoscopic procedures requiring a deeper level of sedation. Of the 9152 cases, the majority of the procedures were colonoscopies. The mean and range of propofol doses for the procedures were as follows: 150 mg ( mg) for upper endoscopy alone, 259 mg ( mg) for upper endoscopy and colonoscopy and 210 mg ( mg) for colonoscopy alone. Routine monitoring (pulse oximetry, blood pressure and electrocardiography) was used, but not capnography. There was a total of seven cases of respiratory compromise. All were associated with upper endoscopic procedures, with three cases of prolonged apnoea secondary to oversedation (two were mask ventilated for 30 s and the other recovered spontaneously), three cases of laryngospasm (mask ventilated for s) and one case of aspiration requiring hospitalization. Nine other patients were hospitalized for postprocedural complications, including seven with colonic perforations. Of those who had previous experience with sedation by both benzodiazepine and narcotics for endoscopy, at least 79% rated propofol as preferable, with a mean overall satisfaction with propofol sedation of 9.5 (on a scale of 10). The endoscopists also rated their experience with propofol, relative to midazolam and meperidine, with higher satisfaction. Overall, no patients needed endotracheal intubation, laryngeal mask airway or rescue by an anaesthesiologist. Another prospective controlled study by Heuss et al. investigated the safety of propofol administered by registered nurses in high-risk patients. 27 The study population consisted of two groups: the first group included 642 patients from ASA class 1 and 2 and the second group included 642 patients from ASA class 3 and 4. Both groups were matched for gender and age. However, the second group had a higher body mass index than the first group and their initial mean vital signs were slightly worse. All patients underwent either EGD or colonoscopy. The procedures were performed by 14 different endoscopists, with seven board-certified gastroenterologists and seven residents who were in their last year of training. All patients received a minimum of 2 L of supplemental oxygen and the continuous infusion of normal saline. Routine monitoring was carried out for heart rate, blood pressure and peripheral oxygen saturation. Propofol was given as boluses by registered nurses. All patients received an initial dose of 20 mg, followed by mg for patients in ASA class 1 and 2 and 10 mg for patients in ASA class 3 and 4, as needed. The results showed that patients from ASA class 3 and 4 had a statistically significant increased risk of brief oxygen desaturation below 90% (P ¼ 0.036). These patients responded well to increased oxygen. Six patients from ASA class 3 and 4 and one patient from ASA class 1 and 2 (P ¼ 0.12) required emergency interventions, including five brief mask ventilations. The investigators concluded that, with judicious monitoring and titration, nurse-administered propofol sedation was safe, even in patients with ASA class 3 and 4, but the total doses administered were, on average, 10 20% lower than those for patients with ASA class 1 and 2. To summarize these studies with regard to dosing, initial data with nurse-administered propofol have been accumulated almost entirely with bolus dosing for routine procedures 3, 4, 12, 14, 17, 27 and bolus or infusion for complex procedures, such as endoscopic retrograde cholangiopancreatography or EUS. Bolus doses should be reduced in patients with ASA class 3 12, 27 or 4 and in the elderly. To summarize these studies with regard to exclusion criteria for nurse-administered propofol, the selection of exclusion criteria has been based on the investigators assessment of risk rather than on the demonstration of adverse events in specific subgroups. Our own group has excluded patients who are ASA class 3 or 4, although, from anecdotal reports, we no longer exclude patients who are ASA class 3 unless the classification is based on cardiac or pulmonary disease. Others have not 4, 12, 14, 27 excluded patients who are ASA class 3 or 4. Exclusion criteria are probably applied more vigorously to upper endoscopy than colonoscopy, as the risk of respiratory depression appears to be higher during upper endoscopic procedures. 14, 16, 17 A detailed list of exclusion criteria has been provided by one group 3, 17 (Table 3), and constitutes the most conservative published approach to patient selection. Studies on monitoring Vargo et al. evaluated the role of capnography in 10 consecutive patients with ASA class 1 or 2 undergoing

6 152 S. C. CHEN & D. K. REX Table 3. Exclusion criteria for nurse-administered propofol sedation 1 Allergy to propofol or its components (eggs or soybeans) 2 Increased risk of aspiration: acute upper gastrointestinal bleeding known gastric outlet obstruction known delayed gastric emptying achalasia 3 Difficult airway management: sleep apnoea marked obesity inability to widely open the mouth short, thick neck 4 Patient co-morbidities* * Some studies have excluded patients of American Society of Anesthesiology class 3 or 4; others have not. advanced upper endoscopic examinations (endoscopic retrograde cholangiopancreatography, upper endoscopy with stent placement and EUS). 18 In addition to routine monitoring (oxygen saturation, blood pressure and electrocardiogram), graphic assessment of respiratory activity by capnography was performed. Patients were given propofol by a second gastroenterologist. The drug was delivered by an infusion pump with an initial rate of 25 lg.min/kg (1.5 mg.h/kg). The infusion rate could then be increased by an increment of 25 lg.min/kg every 2 min as needed, or decreased or transiently discontinued for apnoea or hypoventilation. The results showed that six of 10 patients experienced one or more episodes of apnoea. Continuous capnography was able to detect respiratory depression earlier than conventional pulse oximetry or clinical assessment of ventilation, allowing more timely infusion rate adjustments. There was excellent patient satisfaction with propofol sedation in nine of the 10 patients. All patients met the criteria for discharge 30 min after propofol infusion had been discontinued. A recent study by Heuss et al. investigated the use of a single ear sensor system combining digital pulse oximetry and transcutaneous carbon dioxide tension measurement. 28 The results showed that the single ear sensor system was able to detect oxygen saturation changes at a mean of 26 ± 8 s earlier than standard pulse oximetry, and was associated with fewer motion artefacts. P a co 2 measurements were used to monitor the level of sedation. In addition, the authors commented that the single ear sensor system may help gastroenterologists to titrate the sedation level during gastrointestinal procedures. Despite the detailed investigations on monitoring noted above, most data on nurse-administered propofol have been accumulated in the absence of capnography or 3, 4, 12, 14, 17, 27 transcutaneous CO 2 measurements. Authors have emphasized that the nurse administering propofol must monitor clinical evidence of ventilation continuously and must have no other tasks besides monitoring the patient and administering the drug. Studies on comparisons of propofol with traditional agents A prospective randomized study by Vargo et al. compared propofol (38 patients) and meperidine or midazolam (37 patients) for advanced upper endoscopies, with all drugs administered by a gastroenterologist. 22 Subjects were monitored by pulse oximetry, automated blood pressure cuff and capnography. Propofol was administered as a bolus of either 40 mg (< 60 kg body weight) or 50 mg (> 60 kg body weight). Additional 10-mg boluses of propofol were given as needed. For the meperidine/midazolam group, initial boluses of meperidine of 50 mg and of midazolam of 2 mg were given, followed by doses of meperidine ( mg) and midazolam ( mg) as needed. The propofol group had no events requiring the procedure to be terminated or ventilation assisted, whereas one patient on the meperidine/midazolam regimen required antagonists for prolonged desaturation immediately after the procedure. There were no differences between the groups in the incidence of oxygen desaturation, apnoea, hypotension or bradycardia, and no differences in patient satisfaction or procedural anxiety. The satisfaction of the endoscopist was noted to be higher when patients received propofol. At 30 min after the procedure, 100% of the propofol group had met the criteria for discharge vs. 16.2% of the meperidine/midazolam group (P < 0.001). In addition, the propofol group tended to recover pre-procedural levels of activity at a faster rate. The cost-effectiveness analysis showed that the propofol group incurred higher costs when the drug was administered by a gastroenterologist. However, the sensitivity analysis suggested that propofol administration would be more cost-effective if it were given by registered nurses. A prospective randomized study by Sipe et al. compared nurse-administered propofol with midazolam/ meperidine in 80 out-patients undergoing colonoscopy. 3 The patients were in ASA classes 1 2. The drugs were given by registered nurses who were under the

7 REVIEW: PROPOFOL SEDATION FOR ENDOSCOPY 153 supervision of endoscopists. Patient monitoring included pulse oximetry, blood pressure and electrocardiogram, and 4 L of supplemental oxygen was given to all patients. The initial bolus of propofol was 40 mg, followed by mg boluses of propofol as needed, and a reduced dose was given to elderly and smaller patients. In the midazolam/meperidine group, meperidine was given as a bolus of mg and midazolam as a mg bolus. The average time to reach full sedation was 2.1 min in the propofol group vs. 7.0 min in the midazolam/meperidine group (P < ). The relative depth of sedation was perceived to be greater in the propofol group (P < ). Only four of the 11 patients in the propofol group who were asked to change position responded to more than 10% of commands, whereas, in the midazolam/meperidine group, 13 of the 23 patients who were asked to change position were able to respond to most commands. Both groups had similar vital signs before sedation. During the procedure, patients in the midazolam/meperidine group (93.2%) had a significantly (P ¼ 0.002) lower mean nadir saturation than those in the propofol group (96.0%). Post-procedurally, propofol patients required a shorter mean time to leave the procedure room (9.7 min in the propofol group vs min in the midazolam/meperidine group, P < 0.038), were able to stand at the bedside sooner (14.2 min in the propofol group vs min in the midazolam/meperidine group, P < ) and attained full recovery at a faster rate (14.4 min in the propofol group vs. 33 min in the midazolam/meperidine group, P < ). Upon arrival in recovery, the propofol group s vital signs were similar to those at baseline. However, the midazolam/meperidine groups showed reduced blood pressure and oxygen saturation compared with baseline values. At the time of discharge, the vital signs of both groups were essentially similar to the baseline values. There was a total of five complications: one in the propofol group who responded well to increased inspired oxygen, and four in the midazolam/meperidine group who experienced isolated hypotension or a combination of tachycardia, hypotension and bradycardia requiring atropine. Recovery of neuropsychological function was compared in the two groups. In terms of the assessment of verbal learning and memory, on discharge, the propofol group showed a significantly higher verbal recall than the midazolam/ meperidine group (P < ). In addition, the propofol group performed better on delayed recall, defined as the recall of words 20 min after they were read. The patients in the propofol group also performed better in a discrimination test, in which they were able to discriminate between a greater number of words that had been read to them and those that had not been read. At the time of discharge and 48 h after discharge, more patients in the propofol group reported high satisfaction compared with those in the midazolam/ meperidine group. All the participants in the propofol group reported that they had received just the right amount of sedation on both surveys (at the time of discharge and 48 h after the procedure), whereas five patients in the midazolam/meperidine group stated that they would have liked some adjustment (more or less) in the amount of sedation they received. GUIDELINES PERTAINING TO NURSE- ADMINISTERED PROPOFOL The ASA guideline on sedation by non-anaesthesiologists characterizes propofol as an agent that is frequently associated with deep sedation. It does not preclude the administration of propofol by non-anaesthesiologists, but states that personnel administering agents targeted to a specific level of sedation should be able to rescue patients from the next deeper level of sedation, which in the case of propofol is general anaesthesia. 21 Thus, according to this guideline, the administration of propofol requires considerable comfort and skill with airway management. The ASA guideline recommends that capnography be considered when administering deep sedation, but does not mandate its use. It recommends oximetry, continuous electrocardiography and continuous measurement of blood pressure and pulse in patients receiving deep sedation. The American Society for Gastrointestinal Endoscopy guideline on deep sedation reiterates the opinions of the ASA guideline. 19 The American Society for Gastrointestinal Endoscopy guideline does not endorse the use of propofol for routine procedures and, furthermore, states that the routine assistance of an anesthesiologist for average risk patients undergoing standard upper and lower endoscopic procedures is not warranted and is cost prohibitive. The package insert for Diprivan includes the following warning regarding propofol: For general anaesthesia or monitored anaesthesia care (MAC) sedation, Diprivan Injectable Emulsion should be administered only by persons trained in the administration of

8 154 S. C. CHEN & D. K. REX general anaesthesia and not involved in the conduct of the surgical/diagnostic procedure. There is no published evidence base to support this statement. TRAINING FOR PROPOFOL ADMINISTRATION Little is known about the best methods of training of registered nurses in the administration of propofol. Brief descriptions of the processes used in two American 3, 14 centres have been provided. Briefly, nurses read written materials about the pharmacology, administration and risks of propofol and must take a written test. Both nurses and endoscopists must be certified in advanced cardiac life support. Nurses then observe the administration of propofol by another nurse trained in administration and then administer the agent under supervision until they are subjectively deemed to be ready to administer the drug independently, with only the supervision of the endoscopist. The optimal approach to training is a critical issue that has yet to be fully addressed. FUTURE OF NURSE-ADMINISTERED PROPOFOL SEDATION In order for the administration of propofol by registered nurses to become accepted on a widespread basis, a number of steps must be taken and hurdles must be overcome (Table 4). This process is likely to take time and to meet considerable resistance. First, additional reports of large experiences documenting safety should be obtained, as well as additional randomized controlled trials documenting the extent of clinical benefits Table 4. Necessary steps in the development of nurse-administered propofol sedation Continued development of safety databases and randomized controlled trials Endorsement of safety and effectiveness by gastrointestinal and anaesthesia societies Withdrawal of institutional rules and state laws restricting administration by non-anaesthesiologists Withdrawal of restrictive labelling Development of training recommendations for practitioners by gastrointestinal societies Development of centres of excellence in which practitioners can undergo training Systematic training of gastrointestinal fellows in propofol administration Ongoing assessment and reporting of complications compared with narcotics and benzodiazepines. This literature base should serve as evidence for the endorsement of the practice in principle by gastrointestinal societies, anaesthesia societies, local institutions and states. State laws will, in some cases, have to be challenged by in-state practitioners. Manufacturers will need to withdraw the labelling designating that propofol should only be given by anaesthesiologists, once the evidence base for safe administration by non-anaesthesiologists is sufficient. Finally, training recommendations for nurses and endoscopists must be developed and endorsed by gastrointestinal societies. The recommendations will probably encompass didactic material on propofol pharmacology and dosing, patient monitoring and airway management, exclusion criteria, numbers of anticipated supervised procedures prior to independent administration, etc. Training of gastroenterology fellows in administration will be critical to the dissemination of nurse-administered propofol. Centres of excellence in which practitioners can observe and obtain training will be critical, as the initiation of nurse-administered programmes without meeting training standards will quickly become unacceptable. Ongoing assessment of complications by all trained practitioners will be essential to a full understanding of safety. CONCLUSIONS Propofol offers certain advantages for endoscopy, including faster onset of sedation and faster recovery compared with narcotics and benzodiazepines. There is strong evidence for improved patient satisfaction with propofol compared with meperidine plus midazolam, as well as an improvement in physician satisfaction. Patient functioning post-procedure is improved with propofol and the recovery of neuropsychological function is faster than with narcotics and benzodiazepines. The principal potential toxicity of propofol use is respiratory depression and individuals administering propofol should be able to rescue patients from prolonged compromise of respiratory depression. Hypotension is also common, but less clinically significant. Rapidly accumulating data suggest that registered nurses supervised by endoscopists can safely administer propofol for routine endoscopic procedures. Additional data on the optimal methods of training are needed, as well as a careful study of what constitutes the optimal monitoring of patients receiving nurseadministered propofol sedation.

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