Sedation: propofol versus conscious sedation. Who should administer it?|
"Sedation and analgesia" in gastrointestinal endoscopy ranges from minimal sedation to general anesthesia, and is used to relieve anxiety and diminish pain, discomfort, and memory of the procedure. While endoscopy can be successfully performed without sedation, many endoscopic procedures are performed under moderate sedation and analgesia, often referred to as "conscious sedation".
In conscious sedation, patients are able to make purposeful responses to auditory and tactile clues, and both vascular and ventilatory status are maintained. With deep sedation, patients respond only to painful stimuli, and airway support may be required. At the level of general anesthesia, patients are unresponsive, and airway support is necessary [1-3].
The degree of sedation should be titrated to achieve patient comfort and a successful procedure. Patients may require different levels of sedation for the same procedure and may attain varying levels of sedation during a single procedure. In general, diagnostic and uncomplicated therapeutic upper endoscopy and colonoscopy are successfully performed using moderate (conscious) sedation. Deeper levels of sedation may be considered for longer and more complex procedures, such as ERCP and EUS, and also may be appropriate for patients difficult to sedate with those medications usually employed to achieve conscious sedation [4-6].
Short acting anesthetic agents, such as propofol, may be used to achieve deep sedation. Routine use of short acting anesthetics (e.g. propofol) has been advocated by some authors as a means to improve patient comfort during standard and routine endoscopic procedures, and may result in shortened procedure and recovery time [7-15]. It may be of particular use for patients who have a history or likelihood of being difficult to sedate using standard agents .
Deep sedation in endoscopy
The combination of a benzodiazipine and narcotic can be used to achieve deep sedation. Such combinations may require higher doses than those used for moderate sedation alone. Agents that have been added to the benzodiazipine/narcotic combination include diphenhydramine, promethazine and droperidol. These potentiate the action of the benzodiazipine/narcotic, and may lead to a deeper level of sedation. Anesthetic agents have been used for endoscopic procedures, and include propofol and the inhalation agents such as nitrous oxide, enflurane, isoflurane, and sevoflurane. The inhalation agents will not be further considered here.
Propofol is an FDA approved anesthetic agent used for the induction and maintenance of general anesthesia and for sedation in ventilated patients . It is classified as an ultrashort-acting hypnotic agent. Propofol possesses sedative, amnestic, and hypnotic properties, but minimal levels of analgesia .
Propofol is 98% plasma-protein bound, and is metabolized primarily in the liver. The drug is lipophilic and is prepared as an oil/water emulsion consisting of 1% propofol, 10% soybean oil, 2.25% glycerol, and 1.2% egg lecithin. Propofol is contraindicated in patients with hypersensitivity to eggs or soybean. In addition, a generic formulation contains sodium metabisulfite and is contraindicated in patients with sulfite allergies [18, 19].
Propofol increases the likelihood of satisfactory deep sedation as well as the risk of rapid and profound decreases in the level of consciousness and cardiorespiratory function, which may culminate in general anesthesia. Propofol rapidly crosses the blood-brain barrier, and causes a depression in consciousness that is thought to be related to potentiation of the gamma-aminobutyric acid activity in the brain. Typically, the time from injection to the onset of sedation is very short, i.e. 30 to 60 seconds. The plasma half-life ranges from 1.3 to 4.13 minutes.
Propofol potentiates the effects of benzodiazepines, barbiturates, and opioids [17, 20]. The pharmacokinetic properties do not significantly change in patients with moderate chronic liver disease or renal failure [17, 20]. Dose reduction is required in patients with cardiac dysfunction and in the elderly due to decreased clearance of the drug .
The narrow therapeutic window of propofol separates it from "conventional" sedation used in endoscopy and increases the risk for complications if it is not administered appropriately. Hence, additional training and monitoring may be needed to allow the safe administration of propofol.
Efficacy of propofol for endoscopic procedures
The use of propofol in "standard" endoscopic procedures, such as upper and lower endoscopy, has been investigated in several studies. Conflicting results have been reported [8-10, 23-24]. Carlsson randomized 90 patients to receive a bolus administration of propofol or midazolam both before and during upper endoscopy. Those in the propofol treatment arm found it to be superior in terms of patient tolerance, maximum level of sedation achieved, and shorter recovery room times. However, amnesia for the procedure and perceived patient discomfort were not different . Patterson reported a smaller series of 40 patients randomized to receive midazolam or propofol titrated to the same level of sedation before upper endoscopy found that while propofol provided for a shorter recovery room time, it was associated with pain at the injection site, reduced patient acceptance, and a shorter amnesia span .
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 . The group receiving propofol and fentanyl had 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. Sipe et al. randomized 80 patients undergoing colonoscopy to combination midazolam/meperidine versus propofol. The propofol group had a greater depth of sedation, modest improvement in satisfaction scores and faster post-procedure recovery times, all of which were statistically significant . However, a prior randomized study of sedation for colonoscopy in 57 patients did not find a benefit for propofol/fentanyl over diazepam/meperidine or midazolam/fentanyl in terms of sedation, analgesia, recovery rate or incidence of side effects. The largest experience to date, compiled in 9152 endoscopic cases in an ambulatory surgery center, demonstrated that of patients who had previously received narcotics or benzodiazepines sedation, 84% preferred propofol sedation . Taken together, these studies have not shown a convincing benefit for propofol when used for standard upper and lower endoscopy. The published studies are heterogeneous with respect to propofol dose, use of a narcotic and method of administration. Further randomized controlled trials are needed.
Propofol may have more clinically significant advantages when used for prolonged and therapeutic procedures. Two randomized, controlled trials in 80 and 196 patients compared propofol alone to midazolam for ERCP [4, 5]. Both studies found improved levels of sedation and faster recovery room times with propofol. In one study, an anesthesiologist administered propofol; in the second study, an assisting physician who was not involved in the endoscopic procedure administered propofol. A study of propofol that included EUS in addition to ERCP found that patients receiving propofol exhibited significantly improved quality of sedation and shorter recovery times as compared to meperidine/midazolam . In these studies untoward effects such as hypotension and hypoxemia occurred equally in both treatment groups. However, in both of the ERCP series, one patient in the propofol group developed prolonged apnea that necessitated discontinuation of the procedure and temporary ventilatory support [4, 5]. The addition of midazolam to propofol in 239 patients undergoing therapeutic upper endoscopy or ERCP significantly lengthened mean recovery time without conferring other clinical benefits over propofol alone .
Administration of propofol by non-anesthesiologists
Propofol has been administered by non-anesthesiologists in endoscopic series, including physicians not participating in the endoscopic procedure, registered nurses and patient-controlled systems. Vargo et al. conducted a randomized, controlled trial of gastroenterologist-administered propofol versus meperidine and midazolam for elective ERCP and EUS . In this study, a gastroenterologist not otherwise participating in the procedure who was trained in propofol administration was utilized. Additionally, capnography was used to detect apnea or hypercapnea, in order to adjust the propofol dosing accordingly. Patients randomized to propofol exhibited a faster mean recovery time (18.6 versus 70.5 min), could perform independent transfer following the procedure and were able to achieve a return to a baseline food intake and activity level (71% versus 16%) more quickly.
The safety and experience with propofol administered by registered nurses has been reported in several studies [8, 9, 14]. In general, all patients were ASA class I or II, monitored with "standard" automated blood pressure, EKG and oximetry devices, and all patients received 3-4L/min of nasal cannula oxygenation. The propofol dosage typically was an initial bolus of 20 to 40 mg, followed by 10 to 20 mg boluses to maintain sedation. Sipe reported that propofol achieved faster time to sedation, greater depth of sedation and faster recovery than midazolam/meperidine sedation. Complication rates were similar. Patient satisfaction was high in both groups but better in those receiving propofol . Walker reported the safe administration of propofol by a registered nurse supervised by a physician in over 9000 patients . Rex reported a similar safety profile for administration of propofol by "appropriately trained nurses" in over 2000 standard endoscopic procedures . Heuss concluded that delivery of propofol by RNs with "careful monitoring under the supervision of gastroenterologists" was safe and effective in 3475 procedures in 2574 patients . In a separate report, cost effectiveness modeling with a sensitivity analysis found nurse-administered propofol to be the dominant strategy, when compared to standard sedation and analgesia .
Patient-controlled sedation and analgesia (PCS) with propofol has also been reported. Kulling et al. randomized 150 patients, and the PCS using propofol/alfentanil had a higher degree of patient satisfaction and more of a complete recovery at 45 minutes when compared to conventional sedation and analgesia . Ng and colleagues randomized 88 patients undergoing colonoscopy to PCS with propofol alone or midazolam . Patients receiving propofol PCS exhibited significantly shorter recovery times (43.3 min versus 61.0 min) and improved satisfaction with overall level of comfort. PCS for ERCP however, has not been as successful .
It is important to remember that while properly trained physicians can administer propofol, regulations governing its administration by non-physician personnel are variable on a state-by-state basis. This leaves the options of utilizing physician or nurse-anesthetist administered propofol. Some authors have found that this does not represent the most cost-effective strategy.
Extended monitoring techniques
Transcutaneous CO2 and end tidal CO2 monitoring are noninvasive methods for measuring respiratory activity, and provide different information from standard oximetry. Capnography, based on the principle that carbon dioxide absorbs light in the infrared region of the electromagnetic spectrum, provides real-time information about the patient's respiratory activity. Capnography more readily identifies patients with apneic episodes . Capnography has been employed to allow the safe titration of propofol by a qualified gastroenterologist during ERCP and EUS [29, 30]. Whether capnography improves outcome has not been demonstrated and would likely require a prohibitively large study.
Who should be qualified to give propofol?
Clinicians administering propofol should have:
- Familiarity with the various levels of sedation and analgesia .
- Familiarity with the principles of deep sedation and resuscitation.
- Current Advanced Cardiac Life Support certification (or Pediatric Advanced Life Support as appropriate).
- Training in the administration of deep sedation
- Ability to recognize a patient who has progressed to a deeper level in the continuum of sedation than was intended, and the ability to rescue a patient who becomes unresponsive, unable to protect their airway, or who loses spontaneous respiratory or cardiovascular function.
Use of anesthesiologist assistance for endoscopic procedures
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Anesthesiologist assistance may be appropriate in the following situations:
- Prolonged or complicated endoscopic procedures.
- Increased risk for complications due to severe co-morbidity.
- Increased risk for airway obstruction due to anatomic variant.
A task force of the American Society for Anesthesiologists recommended that airway management may be difficult in the following situations :
- Patients with previous problems with anesthesia or sedation.
- Patients with a history of stridor, snoring, or sleep apnea.
- Patients with dysmorphic facial features.
Patients with oral abnormalities, such as a small opening (< 3 cm in an adult), edentulous, protruding incisors, loose or capped teeth, high, arched palate, macroglossia, tonsillar hypertrophy or a non-visible uvula.
- Patients with neck abnormalities, such as obesity involving the neck and facial structures, short neck, limited neck extension, decreased hyoid-mental distance (< 3 cm in an adult), neck mass, cervical spine disease or trauma, tracheal deviation or advanced rheumatoid arthritis.
- Patients with jaw abnormalities such as micrognathia, retrognathia, trismus, significant malocclusion.
The ASA Taskforce guidelines recommend that the presence of one or more of sedation-related risk factor, coupled with the potential for deep sedation will increase the likelihood of adverse, sedation-related events . In this situation, if the practitioner is not trained in the rescue of patients from general anesthesia, an anesthesiologist should be consulted. The routine assistance of an anesthesiologist for average risk patients undergoing standard upper and lower endoscopic procedures is not warranted and is cost-prohibitive.
Propofol may be useful in certain patients undergoing endoscopic procedures. Propofol administration provides faster onset and may lead to deeper sedation than "standard" benzodiazepines and narcotics, and is associated with as faster recovery times. However, clinically important benefits have not been consistently demonstrated in average-risk patients undergoing standard upper and lower endoscopy in all studies. In prolonged therapeutic procedures such as ERCP and EUS, propofol has been demonstrated to be superior to standard benzodiazepine/narcotic sedation and its use should be considered. Safe administration of propofol by non-anesthesiologists has been demonstrated in several large reports. Given the more rapid onset of sedation and faster recovery times, cost savings in the endoscopy suite through increased efficiency may be possible through the use of propofol. Further studies in this area are forthcoming.
Deep sedation requires more intensive monitoring by trained individuals. Clinicians considering using propofol in clinical practice should meet criteria listed above. The assistance of anesthesiologists may be appropriate in patients undergoing prolonged or complicated endoscopic procedures, for those at increased risk for sedation-related complications such as patients with severe comorbidities or with anatomic variants increasing the risk of airway obstruction, and in those anticipated to be intolerant of standard sedatives.
This "Soapbox" was published as part of the syllabus for the New York Society for Gastrointestinal Endoscopy 27th Annual Postgraduate Course - Endoscopic Decision Making 2003, held in New York, NY. 15 and 16 December 2003. See the NYSGE website.
- Faigel DO, Baron TH, Goldstein JL, et al. ASGE Standards of Practice Committee. Guidelines for the use of deep sedation and anesthesia for gastrointestinal endoscopy. Gastrointest Endosc 2002; 56: 613-7 (Erratum: Gastrointest Endosc 2003; 57: 440).
- American Society of Anesthesiologists Task Force on Sedation and Analgesia by Non-Anesthesiologists. Practice guidelines for sedation and analgesia by non-anesthesiologists. Anesthesiology 2002; 96: 1004-17.
- ASGE Standards of Practice Committee. Sedation and monitoring of patients undergoing gastrointestinal endoscopic procedures. Gastrointest Endosc 1995; 42: 626-9.
- Jung M, Hofmann C, Kiesslich R, et al. Improved sedation in diagnostic and therapeutic ERCP: propofol is an alternative to midazolam. Endoscopy 2000;32: 233-8.
- Wehrmann T, Kokabpick S, Lembcke B, et al. Efficacy and safety of intravenous propofol sedation for routine ERCP: a prospective, controlled study. Gastrointest Endsoc 1999; 49: 677-83.
- Vargo JJ, Zuccaro G, Dumot JA, et al. Gastroenterologist-administered propofol versus meperidine and midazolam for advanced upper endoscopy: a prospective randomized trial. Gastroenterol 2002; 123: 8-16.
- Lazzaroni M, Porro GB. Preparation, premedication, surveillance. Endoscopy 2001; 33: 103-8.
- Walker JA, McIntyre RD, Schleinitz PF, et al. Nurse-administered propofol sedation without anesthesia specialists in 9152 endoscopic cases in an ambulatory surgery center. Am J Gastroenterol 2003; 98: 1744-50.
- Sipe BW, Rex DK, Latinovich D, et al. Propofol versus midzolam/meperidine for outpatient colonoscopy: administration by nurses supervised by endoscopists. Gastrointest Endosc 2002; 55: 815-25.
- Koshy G, Nair S, Norkus EP, et al. Propofol versus midazolam and meperidine for conscious sedation in GI endoscopy. Am J Gastroenterol 2000; 95: 1476-9.
- Bhardwaj G, Conlon S, Bowles J, et al. Use of midazolam and propofol during colonoscopy: 7 years of experience. Am J Gastroenterol 2002; 97: 495-7.
- Kaddu R, Bhattacharya D, Metriyakool K, et al. Propofol compared with general anesthesia for pediatric GI endoscopy: is propofol better? Gastrointest Endosc 2002; 55: 27-32.
- Rex DK, Overley C, Kinser K, et al. Safety of propofol administered by registered nurses with gastroenterologist's supervision in 2000 endoscopic cases. Am J Gastroenterol 2002; 97: 1159-63.
- Heuss LT, Schnieper P, Drewe J, et al. Risk stratification and safe administration of propofol by registered nurses supervised by the gastroenterologists: a prospective observational study of more than 2000 cases. Gastrointest Endosc 2003; 57: 664-71.
- 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 2000; 14: 1207-14.
- Nelson DB, Barkun AN, Block KP, et al. Propofol use during gastrointestinal endoscopy. Gastrointest Endosc 2001; 53: 876-9.
- Bryson HM, Fulton BR, Faulds D. Propofol: an update of its use in anesthesia and conscious sedation. Drugs 1995; 50: 513-19.
- Diprivan 1%. Astra-Zeneca, Wilmington, DL, 2000 (package insert).
- Propofol. Baxter Pharmaceutical Products, Inc. New providence, New Jersey, 2002 (package insert).
- Vuyk J. Pharmacokinetics and pharmacodynamic interactions between opioids and propofol. J Clin Anesth 1997: 9; 23S-26S.
- Marinella MA. Propofol for sedation in the intensive care unit: essentials for the clinician. Respir Med 1997; 91: 505-10.
- Kirkpatrick T, Cockshott ID, Douglas EJ, et al. Pharmacokinetics of propofol in elderly patients. Br J Anesth 1988; 60: 146-50.
- Carlsson U, Grattidge P. Sedation for upper gastrointestinal endoscopy: a comparative study of propofol and midazolam. Endoscopy 1995; 27: 240-3.
- Patterson KW, Casey PB, Murray JP, et al. Propofol sedation for outpatient upper gastrointestinal endoscopy: comparison with midazolam. Br J Anaesth 1991; 67: 108-11.
- Kulling D, Fantin AC, Biro P, et al. Safer colonoscopy with patient-controlled analgesia and sedation with propofol and alfentanil. Gastrointest Endosc 2001; 54: 1-7.
- Ng JM, Kong CF, Nyam D. Patient-controlled sedation with propofol for colonoscopy. Gastrointest Endosc 2001; 54: 8-13.
- Gillham MJ, Hutchinson RC, Carter R, et al. Patient-maintained sedation for ERCP with a target-controlled infusion of propofol: a pilot study. Gastrointest Endosc 2001; 54: 14-17.
- Nelson DB, Freeman ML, Silvis SE, et al. A randomized, controlled trial of transcutaneous carbon dioxide monitoring during ERCP. Gastrointest Endosc 2000; 51: 288-95.
- Vargo JJ, Zuccaro G, Dumot JA, et al. Automated graphic assessment of respiratory activity is superior to pulse oximetry and visual assessment for the detection of early respiratory depression during therapeutic upper endoscopy. Gastrointest Endosc 2002; 55: 826-31.
- 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 2000; 52: 250-5.