Patient Safety Tip of the Week
May 25, 2010 Propofol Issues
Propofol, of course, recently hit the headlines for its likely role in the death of pop star Michael Jackson in 2009. But it has also been generating controversy off the front pages of standard media.
Propofol has several characteristics that make it attractive as a sedating agent for procedures. It has a rapid onset of action and short duration of action so patients wake up sooner and can resume normal activities faster compared to most other sedating agents. It also reduces the need for adjunctive opioids. And the ability to control the level of sedation also makes it attractive for use in procedures.
But numerous safety issuees have surrounded propofol use. Propofol has long been on ISMP’s list of high alert medications and ISMP has published medication safety alerts about propofol. They include multiple examples of patients developing respiratory arrest or hypotension during propofol sedation for procedures. A sense of complacency or lack of fear because “we use it all the time in the ICU” may be factors predisposing to dangerous practices. But they also noted the sometime unpredictable and profound effects of propofol (noting that a patient can go from breathing normally to full respiratory arrest in seconds, even at low doses). Importantly, there is no reversal agent available like there is for other sedating agents or opioids.
Yet propofol has quietly become the procedural sedating agent of choice in many venues, particularly when dealing with pediatric patients. In fact, at the recent Pediatric Academic Societies meeting research was presented on over 25, 000 cases using propofol sedation in areas outside the OR by emergency physicians. That abstract (Mallory et al 2010) presented data from the Pediatric Sedation Research Consortium. The vast majority of these (22,068) were performed in radiology.
Controversy really erupted when CMS issued new interpretive guidelines regarding anesthesia services, which must be followed by hospitals who accept Medicare or Medicaid patients. The revised CMS guidelines point out that propofol is only indicated for general anesthesia, MAC (monitored anesthesia care) and for the sedation of the mechanically-ventilated patient. The guidelines essentially mean that propofol can only be administered by those with credentials to provide deep sedation or general anesthesia and many or most emergency physicians only possess privileges for moderate sedation (Klauer 2010). The CMS guidelines do not preclude emergency physicians from administering propofol. Rather they clearly specify that the Department of Anesthesiology has responsibility to oversee performance of anesthesia or deep sedation throughout the hospital (or healthcare organization). They would be responsible for ensuring that all clinicians administering propofol are appropriately trained and credentialed and oversee the quality improvement monitoring of such use. A key point of contention is the issue of having one physician vs. two during the administration of propofol. In most cases where an anesthesiologist is involved, there is one person (the anesthesiologist or CRNA) overseeing the anesthesia or deep sedation and the second who is performing the procedure. In the ER (or other venue where the emergency physician is involved), there might be only one physician who is attempting to do both.
As you’d expect, specialty societies representing ER personnel have been active in opposing the new CMS guidelines. The American College of Emergency Physicians (ACEP), the Emergency Nurses Association (ENA), and the American Association of Emergency Medicine (AAEM) sent a joint letter to CMS on anesthesia issues in March and met with CMS officials in April to express their concerns. There are numerous position papers on use of sedating agents by emergency physicians as well (see Mace 2008 and Goodwin 2005)
The abstract presented by Mallory et al documented airway and respiratory adverse events in 3.9% of cases of the pediatric cases. Cases included two aspirations and one cardiac arrest but there were no deaths. In 2.4% of cases interventions beyond simple airway repositioning were required. They performed regression analysis and found the following variables to be independently associated with complications: age less than 2 months, ASA class greater than 2, use of adjunctive opioids or midazolam, or adjunctive use of anticholinergics.
Another recent study (Larsen 2009) looked at the safety of propofol administration by pediatric intensivists for pediatric outpatient procedures in a single institution over a 6-year period. In over 4700 cases, major complications occurred in only 0.1% of cases, though minor complications were noted in 15% of cases.
Frequencies of complications in adults undergoing procedures with propofol sedation are a bit harder to come by because of varying types of procedure, varying personnel administering and monitoring the sedation, varying depth of sedation, and varying concomitant use of opioids or other sedating agents. For routine endoscopic procedures (colonoscopies and upper endoscopies), the safety of nurse-administered propofol sedation has generally been accepted and position papers from most endoscopy-oriented specialty societies support nurse-administered propofol procedural sedation. However, studies from more advanced endoscopic procedures, where deep sedation or anesthesia are often produced, provide some insight into the risks of propofol sedation. A recent study (Cote et al 2010) looked at propofol sedation administered by CRNA’s under the supervision of an anesthesiologist for patients undergoing advanced endoscopic procedures such as ERCP. Of these, 87.2% showed no response to endoscopic intubation, an indication they were probably in deep sedation or frank anesthesia. Of the 799 patients, hypoxemia developed in 12.8%, hypotension in 0.5%, and procedures were terminated prematurely in 0.5%. Airway modifications had to be performed in 14.4% (mostly chin lifts but sometimes modified face mask ventilation or nasal airways). Independent predictors of the need for airway modifications were male sex, ASA class 3 or higher, and high BMI (Mallampati score of 4 or higher was also more frequently associated with need for airway modifications but the small number precluded reaching statistical significance). Though the authors conclude that propofol can be used safely for advanced endoscopic procedures, they stress that this was done under the supervision of very well qualified professionals.
The accompanying editorial (Vargo 2010) stresses the importance that the sedation team maintain constant vigilance during the procedure. Vargo also makes the case for using capnography as a key component of such vigilance, at least in that setting. In our March 2, 2010 Patient Safety Tip of the Week “Alarm Sensitivity: Early Detection vs. Alarm Fatigue” we discussed an article (Deitch et al 2010) which looked at use of capnography during procedural sedation in the emergency department. Monitoring end-tidal CO2 during procedures in which IV sedation or IV opioids are used is theoretically very attractive since it is a better indicator of respiratory depression in such cases and should identify patients at risk before they develop oxygen desaturation. Their randomized controlled trial in adults undergoing propofol sedation showed significantly fewer patients with hypoxia in the group monitored by capnography. The 17% absolute risk reduction translates to a number needed to treat (NNT) of 6 cases to prevent one episode of hypoxia. Capnography recognized 100% of the patients who developed hypoxia and did so a median time of 60 seconds before hypoxia developed. That delay meant the physicians usually had adequate time to intervene.
We have previously pointed out that it is extremely difficult to identify respiratory depression just by watching a patient. We have had medical students, residents, and attendings all observe patients on whom we had arterial blood gases and they did little better than chance at picking out which patients had respiratory depression. So the ability to identify patients with respiratory depression before they become hypoxic is a major potential advantage.
The editorial (Green & Pershad 2010) accompanying the Deitch study describes the pros and cons of adopting capnography routinely for such procedural sedation. The editorial notes that capnography clearly identifies respiratory failure before it is apparent by either clinical examination or pulse oximetry. And it acknowledges the significant contribution of the Deitch study, though it points out that some methodological issues (eg. using O2 at a flow rate of only 3L/minute and using an O2 saturation of 93% as the definition of hypoxia) may have overestimated the frequency of hypoxic events. And many episodes of hypoxia are self-limited and resolve without any intervention. In fact, 41% of the episodes in the Deitch study resolved without any intervention.
Recent court cases have also involved propofol. A suit in one case alleges that a patient with sleep apnea died during routine colonoscopy when the CRNA was unable to intubate the patient when he deteriorated after a reduced dose of propofol was administered.
In another court case a jury found that the makers of propofol products failed to adequately warn not to reuse 50 ml vials of propofol on multiple patients. Use of such vials was found in an outbreak of hepatitis C linked to 2 Las Vegas endoscopy centers. Apparently such use of vials for multiple patients has occurred because of the nationwide shortage of propofol. The FDA has been cautioning against such usage and addresses a variety of issues related to the propofol shortage on its website.
And propofol is one of those drugs that often goes “unlabeled” in syringes in OR’s or other sites because staff think it is the only “cloudy” or “milky” drug likely to be in the field. Remember: all drugs in syringes must be labeled.
So there remain many unanswered questions about the safety of propofol for procedural sedation and the best ways to minimize risk of adverse events if it is used. Until we have more complete answers we recommend:
- Include propofol as one of the drugs on your high-alert medication list
- Anesthesiology must oversee all use of propofol, regardless of setting
- All providers who are allowed to use propofol sedation must be appropriately trained and credentialed (with appropriate updates) for deep sedation or anesthesia by the department of anesthesiology regardless of whether they are anesthesiologists or non-anesthesiologists (including demonstrated continued competence in intubating patients)
- Find out where propofol is being used (it may pop up in places you did not expect it!)
- You need good monitoring protocols and flowsheets for all cases (including vital signs, level of arousal, oxygen saturation)
- Strongly consider using capnography as an additional monitoring tool
- A good monitoring protocol also includes some assessment of cumulative doses of all drugs given
- A single individual is not likely to be able to monitor and respond to airway/respiratory complications if he/she is also doing the procedure. Therefore, always having at least 2 individuals functioning as a team during such procedures is important.
- If you allow non-anesthesiologists to perform propofol administration for procedures, develop some sort of screening tool that would flag high risk cases (eg. the very young or very old, obese patients, those with high Mallampati scores, those with ASA levels 3 or higher, those with known sleep apnea, those requiring concomitant use of other sedating agents, opioids, anticholinergics, etc.) that should only be done by anesthesiologists
- A good risk:benefit analysis should be done when considering a procedure that will require propofol sedation (especially important for pediatric imaging procedures which tend to be overordered)
- Anesthesiology must do the quality improvement assessments for all such cases regardless of where they are performed (but results must be shared with all disciplines involved)
- Never use the same vials of propofol for more than one patient
- Label all syringes
- Don’t let your “turf” battles get in the way of patient safety
Note that today’s article does not address use of propofol sedation in the intubated, mechanically ventilated patient in the ICU setting. However, even there we know that propofol sedation is likely overused (see our What’s New in the Patient Safety World column “March 2010 If Sedation Vacations Work, Why Not Eliminate Sedation All Together?”). Every attempt should be made to assess the continued need for such sedation. Daily sedation “vacations” are a key component of the IHI VAP Bundle and other bundles designed to prevent ventilator-associated pneumonia. Minimizing sedation also helps reduce the incidence of delirium in the intubated, mechanically-ventilated patient. But the article by Strem 2010 found that patients who received no sedation had significantly fewer days on ventilators, shorter ICU stays, and shorter total hospital LOS. There was no difference in accidental extubations or VAP, though more patients in the no sedation group had agitated delirium. Those results are actually quite encouraging and the practice of eliminating sedation all together may become more widely accepted if these results can be replicated in other settings.
Propofol can be a very useful drug in a variety of settings. But it may have a small margin for error and there are safety issues lurking whenever it is used. Treat it with respect.
References:
ISMP’s list of high alert medications
http://www.ismp.org/Tools/highalertmedications.pdf
ISMP. Propofol sedation: Who should administer? ISMP Medication Safety Alert (Acute Care Edition). November 3, 2005
http://www.ismp.org/Newsletters/acutecare/articles/20051103.asp
Smith M. PAS: Propofol Widely Used to Sedate Children. MedPageToday.com. May 3, 2010
http://www.medpagetoday.com/MeetingCoverage/PAS/19892
Mallory MD, Baxter AL, Yanosky DJ, Cravero. JP. Use of Propofol for Sedation of Pediatric Patients by Emergency Physicians: A Report from the Pediatric Sedation Research Consortium (abstract). Pediatric Academic Societies meeting May 1, 2010
http://www.abstracts2view.com/pas/view.php?nu=PAS10L1_3860
Phillion M. New CMS Anesthesia Guidelines Completely Rewrite Former Standard. HealthLeaders Media, April 13, 2010
CMS. Revised Hospital
Anesthesia Services Interpretive Guidelines – State Operations Manual (SOM)
Appendix A. Revision 2/05/2010
http://www.cms.gov/SurveyCertificationGenInfo/downloads/SCLetter10_09.pdf
Klauer K. Is Propofol Gone? CMS Releases New Guidelines. Emergency Physicians Monthly March 24, 2010
http://www.epmonthly.com/features/current-features/is-propofol-gone-cms-releases-new-guidelines/
Mace SE, Brown LA, Francis L, et al for the EMSC Panel (Writing Committee) on Critical Issues in the Sedation of Pediatric Patients in the Emergency
Department. Clinical Policy: Critical Issues in the Sedation of Pediatric Patients in the Emergency Department. Ann Emerg Med 2008; 51(4): 378-399
http://www.acep.org/WorkArea/DownloadAsset.aspx?id=33726
Goodwin SA, Caro DA, Wolf SJ, et al. from the American College of Emergency Physicians Clinical Policies Subcommittee (Writing Committee) on
Procedural Sedation and Analgesia. Clinical Policy: Procedural Sedation and Analgesia in the Emergency Department. Ann Emerg Med. 2005; 45:177-196
http://www.acep.org/WorkArea/DownloadAsset.aspx?id=8818
Joint Letter from the American College of Emergency Physicians (ACEP), the Emergency Nurses Association (ENA), and the American Association of Emergency Medicine (AAEM) to CMS on anesthesia issues. March 22, 2010
http://www.acep.org/WorkArea/linkit.aspx?LinkIdentifier=id&ItemID=48060&libID=48089
American College of Emergency Physicians. ACEP, Other EM
Groups Meet With CMS About Anesthesia Interpretation. May 5, 2010 http://www.acep.org/acepnews.aspx?id=48402
Larsen R,Galloway D, Wadera S, et al. Safety of Propofol Sedation for Pediatric Outpatient Procedures. Clin Pediatr (Phila) 2009; 48: 819-823
http://cpj.sagepub.com/cgi/content/abstract/48/8/819
Coté GA, Hovis RM, Ansstas MA et al. Incidence of Sedation-related Complications with Propofol Use during Advanced Endoscopic Procedures. Clin Gastroenterol Hepatol. 2010; 8(2):137-142
http://download.journals.elsevierhealth.com/pdfs/journals/1542-3565/PIIS1542356509006569.pdf
Vargo JJ. Anesthesia-Mediated Sedation for Advanced Endoscopic Procedures and Cardiopulmonary Complications: Of Mountains and Molehills. Clin Gastroenterol Hepatol. 2010; 8(2):103-104
http://download.journals.elsevierhealth.com/pdfs/journals/1542-3565/PIIS1542356509011380.pdf
Outpatient Surgery Magazine. After Death in the GI Suite, Patient's Family Sues CRNA. Outpatientsurgery.net May 19, 2010
http://www.outpatientsurgery.net/news/2010/05/12
Outpatient Surgery Magazine. Jury Finds Propofol Makers Liable in Las Vegas Hepatitis C Outbreak. Outpatientsurgery.net May 6, 2010
http://www.outpatientsurgery.net/news/2010/05/3
FDA. Questions and Answers on the Propofol Shortage.
http://www.fda.gov/Drugs/DrugSafety/DrugShortages/ucm209227.htm
Deitch K, Miner J, Chudnofsky CR, Dominici P, Latta P. Does End Tidal CO2 Monitoring During Emergency Department Procedural Sedation and Analgesia With Propofol Decrease the Incidence of Hypoxic Events? A Randomized, Controlled Trial. Annals of Emergency Medicine 2010; 55(3): 258-264
http://www.annemergmed.com/article/S0196-0644%2809%2901429-2/abstract
Green SM, Pershad J. Should Capnographic Monitoring Be Standard Practice During Emergency Department Procedural Sedation and Analgesia? Pro and Con. Annals of Emergency Medicine 2010; 55(3): 265-267
http://download.journals.elsevierhealth.com/pdfs/journals/0196-0644/PIIS0196064409014462.pdf
Strem T, Martinussen T, Toft P. A protocol of no sedation for critically ill patients receiving mechanical ventilation: a randomised trial. The Lancet 2010; 375: 475 - 480
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2809%2962072-9/abstract
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