Safe Injection Practices for Administration of Propofol

CECIL A. KING, MS, RN; MARY OGG, MSN, RN, CNOR

ABSTRACT

Sepsis and postoperative infection can occur as a result of unsafe practices in the administration of propofol and other injectable medications. Investigations of infection outbreaks have revealed the causes to be related to bacterial growth in or contamination of propofol and unsafe medication practices, including reuse of syringes on multiple patients, use of single-use medication vials for multiple patients, and failure to practice aseptic technique and adhere to infection control practices. Surveys conducted by AORN and other researchers have provided additional information on perioperative practices related to injectable medications. In 2009, the US Food and Drug Administration and the Centers for Disease Control and Prevention convened a group of clinicians to gain a better understanding of the issues related to infection outbreaks and injectable medications. The meeting participants proposed collecting data to persuade clinicians to adopt new practices, developing guiding principles for propofol use, and describing propofol-specific, site-specific, and practitioner-specific injection techniques. AORN provides resources to help perioperative nurses reduce the incidence of postoperative infection related to medication administration. AORN J 95 (March 2012) 365-372. © AORN, Inc, 2012. doi: 10.1016/j.aorn.2011.06.009

Key words: sterile injectable medications, propofol, sepsis, safe injection practices, safe medication administration.

uring the past 10 years, there has been In 1990, one year after propofol was ap- growing concern regarding postoperative proved for use, the Centers for Disease Control Dinfections associated with the handling of and Prevention (CDC) investigated four clusters injectable medications; more speciﬁcally, clusters of postsurgical infections and hyperthermic re- of sepsis and postoperative infections have oc- actions.4 The investigators traced the infections curred related to the use of propofol.1 Propofol is and reactions to several factors, including ex- a sterile, IV, lipid-based, emulsive anesthetic trinsic contamination of the agent that resulted agent. It was approved by the US Food and Drug from lapses in aseptic technique during the han- Administration (FDA) in 1989 and has been dling of the medication, use of propofol by in- widely used in the United States since that time.2 fusion pump, and preparation of the infusion As a lipid-based emulsion, this medication is pump by one anesthesia provider. The same known to support bacterial growth.3 infusion pump, syringe, and provider were doi: 10.1016/j.aorn.2011.06.009 © AORN, Inc, 2012 March 2012 Vol 95 No 3 ● AORN Journal 365 March 2012 Vol 95 No 3 KING—OGG

TABLE 1. Propofol Handling Guidelines1

US Food and Drug Administration recommendations General product insert guidelines

Vials of propofol and prefilled syringes are intended Strict aseptic technique must always be used when handling for single (ie, one patient) use. sterile injectable medications. Begin infusion immediately after drawing up or Propofol should be inspected before use for particulate opening the vial of medication. matter, discoloration, or evidence of separation of the Infusion from prefilled syringes or vials must begin emulsion. within 6 hours of opening/filling the syringe. Do not use if contaminated. Propofol that is infused directly from a large volume Fill syringes or spike the vial immediately before administration (eg, 100 mL) vial is to be limited to one patient and to each patient. must be infused within 12 hours of opening the vial Disinfect the rubber stopper with 70% isopropyl alcohol. or spiking the stopper. Discard unused portions within 6 hours of filling syringes or 12 hours after spiking a large volume vial for infusion.

1. DIPRIVAN® (propofol) Injectable Emulsion. 451094A/Issued: February 2008. US Food and Drug Administration. http://www.accessdata.fda.gov/ drugsatfda_docs/label/2008/019627s046lbl.pdf. Accessed December 8, 2011. identiﬁed as risk factors in two of the infected During a 10-year period from 1998 to 2008, 35 patients.4 documented outbreaks of hepatitis occurred in These outbreaks of infection prompted the nonhospital health care facilities (eg, pain clinics, pharmaceutical company that manufactures propo- endoscopy clinics, hemodialysis centers), which fol to add language to the product circular stating put more than 60,000 patients at risk for develop- that “strict aseptic technique must always be ing bloodborne pathogen infections.11 These out- maintained during handling . . .”5 and preparation breaks were traced to of propofol for injection. The FDA issued propo- reuse of syringes on multiple patients, fol administration guidelines based on recommen- single-use medication vials used for multiple dations from the CDC,4 the American Society of patients, Anesthesiologists,6 and the Anesthesia Patient failure to practice aseptic technique, and Safety Foundation7 that are similar to the failure to follow fundamentals of infection manufacturer’s recommendations summarized in control practices.11 Table 1. All recommendations were based on the following facts: In 2002, the Oklahoma State Department of Health investigated an unexplained outbreak of Propofol is a lipid-based emulsion that sup- hepatitis C (HCV).12 All the infected patients had ports bacterial growth.8 been treated for pain at the same outpatient clinic. Bacterial contamination increases rapidly over The Oklahoma health department was able to test time.9 795 (88%) of the patients who had been treated Disinfection of propofol ampules or vials be- since the clinic opened and found that 71 patients fore opening considerably reduces the risk of had contracted HCV and 31 had contracted hepa- bacterial contamination of the medication.8 titis B during 2002. Interviews with staff mem- Disodium edetate, which inhibits bacterial growth, bers regarding injection practices revealed that was added to propofol in 1996; as a result, the care providers used a single needle and syringe incidence of propofol injection infections was to administer three different sedation medica- reduced but not eliminated.10 tions. In addition, these providers used the

366 AORN Journal SAFE INJECTION PRACTICES www.aornjournal.org same needle and syringe to administer these has led to outbreaks of serious postoperative medications to all of the patients treated that health care-associated infections. day. Results of the investigation suggest that It is essential to use strict aseptic technique the infections were transmitted from patient to when handling propofol, as mandated by the patient after a provider used a syringe and nee- manufacturer’s written instructions. dle on a patient positive for hepatitis and then used the same syringe and needle to administer MEDICATION PRACTICES SURVEYS medication to subsequent patients. The outbreak In July 2009, AORN conducted a random elec- stopped when the practice of reusing syringes tronic survey of 500 of its 40,000 members to and needles stopped.12 determine their current practice for handling In 2007, investigation of an outbreak of HCV propofol. A total of 410 members completed the at an endoscopy center revealed that five of the survey for a response rate of 82%. Seventy-two six infected patients had undergone procedures on percent of the respondents practiced in a hospital the same day.13 Direct observation of the center’s setting (ie, academic, community, rural), and 28% personnel demonstrated that they inappropriately of the respondents practiced in ambulatory sur- reused syringes and used single-dose medication gery centers or endoscopy units. The highest per- vials on multiple patients. Clean needles and sy- centage of respondents (ie, 36%) worked in facili- ringes were used to withdraw medication from a ties with five to 10 ORs (Figure 1), and most single-use bottle of propofol. The medication was respondents worked in ORs in which an average injected through the patient’s IV. If more propo- of 51 to 100 surgical procedures were performed fol was needed, then the same syringe with a per week (25%) (Figure 2). The majority of the clean needle was used to withdraw more medica- respondents (87%) reported that, in their facilities, tion. Investigators theorized that backflow from anesthesia providers (eg, physicians, certified RN the patient’s IV or the needle may have contami- anesthetists) draw up propofol medication prod- nated the syringe with HCV, thereby contaminat- ucts for administration (Figure 3). When asked ing the vial. The remaining medication was used how often the vial of propofol was typically ac- on subsequent patients.13,14 cessed, 50% reported once, whereas 44% reported The findings of the investigations into these witnessing the same vial being accessed two to various outbreaks of postoperative infections may three times. Six percent of respondents reported be summarized into four major points that relate seeing the same vial of propofol being accessed to safe injection practices. more than four times (Figure 4). When asked if Propofol is a lipophilic IV injection that is known to support AORN Resources the growth of AORN guidance statement: safe medication practices in periopera- microorganisms. tive settings across the life span. In: Perioperative Standards and The addition of a preser- Recommended Practices. Denver, CO: AORN, Inc; 2011:605-611. vative to propofol only inhibits microbial growth, Watch for these new and updated AORN resources in spring it will not prevent it. and summer 2012 There is quantitative evi- Safe Medication Administration Tool Kit dence that extrinsic mi- AORN Medication Safety video crobial contamination Periop 101: A Core Curriculum™ Medication and Fluids module and cross contamination

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Figure 1. The number of ORs. there were multiple accesses to a vial of propofol patient, 62% noted that one to three steps were for the same patient, 68% answered “yes” and involved in this process (Figure 5). Fifty-eight 32% answered “no.” The majority of respondents percent of respondents reported that their facility (82%) reported that multiple accesses to the vial had a policy or procedure in place to prevent con- of propofol for different patients did not occur. tamination of propofol medication products. Most facilities routinely stock 20 mL (44%) and Pugliese et al15 conducted an online survey of 50 mL (39%) vials of propofol, and the majority multidisciplinary clinicians in 2010 at different of respondents (70%) reported that different vol- types of health care organizations. A total of umes of propofol were not being used outside of 8,035 clinicians (eg, nurses, physicians, anes- the OR. When asked the number of steps in- thesia professionals, dentists, surgical technolo- volved from initially accessing the propofol gists) responded. The researchers included container to administering the medication to the 5,446 respondents who administered parental

Figure 2. The average number of cases per week.

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Figure 3. Health care professionals who administer propofol. medications in the ﬁnal analysis and excluded searchers calculated the practice of reusing a sy- clinicians who do not prepare or administer pa- ringe but changing the needle for more than one rental medications. The survey contained ques- patient to be 1% and the practice of reusing the tions about injection safety, frequency of perform- syringe for additional doses from the same multi- ing injections, and how the respondents obtained dose vial to be 15%.15 injection safety information.15 In this survey, 30% of respondents reported accessing a single-dose THE FDA SAFE USE (PROPOFOL) HEALTH vial more than once, in contrast to the 50% of the PROFESSIONALS MEETING AORN survey respondents who had witnessed To gain a better understanding of the issues re- this practice in perioperative settings. The major- lated to the outbreak of infection, the FDA and ity of respondents (ie, 66%) reported using a the CDC convened a group of clinicians on July multidose vial for more than one patient. Re- 29, 2009, to assess the problem.16 In attendance

Figure 4. The number of times that the propofol vial is accessed.

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Figure 5. The number of steps involved in accessing a vial of propofol.

were FDA and CDC staff members, anesthesiolo- practices guidelines (eg, aseptic technique, gists, nurse anesthetists, pharmacists, gastroenter- hand hygiene, standard precautions) and ologists, and perioperative and gastroenterological manufacturer’s instructions for preparation and nurses. Health care professionals attending the handling of medications. conference identified and prioritized issues related resolution of confusion surrounding the manu- to the safe handling of injectable medications that facturer’s written instructions and information needed to be addressed, including (eg, single access, single use). a coordinated policy from professional associ- implementation of universal standards of prac- ations (eg, the American Association of Nurse tice as they relate to practice guidelines (eg, Anesthetists, AORN, the American Society of collection of evidence-based data, develop- Anesthesiologists, the Anesthesia Patient ment of practice guidelines for all settings, Safety Foundation) regarding practice description or definition of specific administra- guidelines. tion techniques). practical applications of the US Pharmacopeia education across cultures and disciplines as to that address the use of sterile medications re- what are acceptable and unacceptable medica- lated to anesthesia practice.17 tion administration practices. The meeting participants proposed the next clearly defined meanings and definitions of steps, which included collecting data to per- practice terminology related to medication ad- suade clinicians to adopt new practices; devel- ministration (eg, product labeling, single use, oping guiding principles for propofol use that single access). would be adaptable to any practice setting; and site-specific handling management guidelines describing injection techniques that would be that address the issues of cost, pressure for propofol specific, site specific, and practitioner efficacy, and quick turnover times in free- specific. standing ambulatory facilities. As a result of the 2009 meeting, the FDA direct observations that monitor compliance has taken a broader-based approach to some of and competency related to following best the issues that were raised. As a regulatory

370 AORN Journal SAFE INJECTION PRACTICES www.aornjournal.org agency, the FDA is looking at the language that implementing aseptic technique when prepar- is used on various products to see how well it ing sterile medications and solutions for communicates to and is understood by the injection. health care professionals who need to read and Unsafe practices include use it.18 In addition, the FDA is looking at the pooling or combining vial contents; issue of standardization of terms used on manu- reusing a syringe or needle to withdraw medi- facturer labels, evaluating which terms are pref- cation from a multidose vial; erable and whether standardizing terms would re-entering a single-use vial, ampule, or be beneficial. After completing its analyses, the solution; FDA may provide guidance to industry and to reusing a syringe or needle on any patient; FDA reviewers on additional issues that they and should consider when evaluating new medica- using the same syringe or needles to adminis- tion applications. For example, the FDA has ter medications to multiple patients.19 been evaluating fill amounts, closures on liquid In the 2010 survey by Pugliese et al,15 60% of injectables, and other factors that could contrib- the respondents selected their professional organi- ute to the way these products are used.18 zation as their most frequent source of practice Shortages of propofol that began in November information. AORN continues to provide educa- 2009 have further complicated the situation. Man- tional and evidence-based practice resources to ufacturers have stopped production and recalled members and the industry related to safe medica- several lots. The shortage is a result of quality tion practices related to the handling and adminis- 19 control issues and decreasing profit margins. At tration of medications and solutions. present, only one manufacturer in the United States is producing propofol. Future regulatory initiatives may develop as a consequence of these References 1. Postmarket drug safety information for patients and issues. providers. Information for healthcare professionals: propofol (marketed as Diprivan and as generic products). http://www.fda.gov/Drugs/DrugSafety/Postmarket DrugSafetyInformationforPatientsandProviders/ CONCLUSION ucm125817.htm#.TtUiFvNryTw.email. Accessed No- There is a growing concern about the risks for vember 29, 2011. transmitting infections during routine health 2. Orange Book: approved drug products with therapeutic equivalence evaluations. 2011. US Food and Drug Ad- care procedures requiring IV medications. Out- ministration. http://www.accessdata.fda.gov/scripts/cder/ breaks of infection have occurred with increas- ob/docs/temptn.cfm. Accessed November 29, 2011. 3. Diprivan® 1% injectable emulsion propofol for IV ad- ing regularity. The gap between what is recom- ministration [product insert]. Wilmington, DE: Astra mended and what is actually done clinically Zeneca Pharmaceuticals. http://www1.astrazeneca-us .com/pi/diprivan.pdf. Accessed October 18, 2011. regarding safe injection practices must be ad- 4. Centers for Disease Control. Postsurgical infections dressed. Safe medication practices may be sum- associated with an extrinsically contaminated intravenous anesthetic agent—California, Illinois, Maine, and marized as Michigan, 1990. MMWR Morb Mortal Wkly Rep. 1990; 39(25):426-427, 433. performing hand hygiene before preparing 5. Diprivan® (propofol) injectable emulsion. RxList Inter- medications for administration, net Drug Index. http://www.rxlist.com/diprivan-drug .htm. Accessed May 16, 2011. storing and preparing medications in a clean 6. ASA Committee on Occupational Health of Operating area, Room Personnel. Preventing contamination of medications. In: Recommendations for Infection Control for using a clean syringe and needle for every the Practice of Anesthesiology. 3rd ed. Park Ridge, IL: patient, and American Society of Anesthesiologists; 2011:11-22.

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7. Berry AJ, ed. Recommendations for Handling Paren- cal Quality. http://www.ipqpubs.com/wp-content/ teral Medications Used for Anesthesia and Sedation. uploads/2010/05/Propofol_Shortage_QA.pdf. Accessed Pittsburgh, PA: Anesthesia Patient Safety Foundation; December 8, 2011. 1995. 19. CDC Health Advisory of July 13, 2009: Clinicians ad- 8. Zacher AN, Zornow MH, Evans G. Drug contamination vised to halt use of propofol from tainted lots. CDC from opening glass ampules. Anesthesiology. 1991; Health Alert Network. http://emergency.cdc.gov/HAN/ 75(5):893-895. han00296.asp. Accessed November 28, 2011. 9. Sosis MD, Braverman B. Growth of Staphylococcus aureus in four intravenous anesthetics. Anesth Analg. Resources 1993;77(4):766-768. 1 Syringe, 1 Patient, 1 time: Safe Injection Practices. One 10. Jansson JR, Ozaki M, Kimura S, Fukada T. Propofol and Only Campaign. http://www.oneandonlycampaign EDTA and reduced incidence of infection. Anesthes .org/. Accessed November 28, 2011. Intensive Care. 2006;34(3):362-368. Injection safety. Centers for Disease Control and Prevention. 11. Thompson ND, Perz JF, Moorman AC, Holmberg SD. http://www.cdc.gov/injectionsafety/. Accessed November Nonhospital health care-associated hepatitisB&Cvi- 28, 2011. rus transmission: United States, 1998-2008. Ann Intern Safe Injection Global Network. The World Health Organiza- Med. 2009;150(1):33-39. tion. http://www.who.int/injection_safety/sign/meetings/ 12. Comstock RD, Mallonee S, Fox JL, et al. A large noso- past/en/InitialMeetingReport.pdf. Accessed December 8, comial outbreak of hepatitis C and hepatitis B among 2011. patients receiving pain remediation treatments. Infect The CDC’s role in safe injection practices. Centers for Dis- Control Hosp Epidemiol. 2004;25(7):576-583. ease Control and Prevention. http://www.cdc.gov/ 13. Centers for Disease Control and Prevention. Acute hep- injectionsafety/CDCsRole.html. Accessed November 28, atitis C virus infections attributed to unsafe injection 2011. practices at an endoscopy clinic—Nevada, 2007. Viral hepatitis. Centers for Disease Control and Prevention. MMWR Morb Mortal Wkly Rep. 2008;57(19):513-517. http://www.cdc.gov/hepatitis/. Accessed November 28, http://www.cdc.gov/mmwr/preview/mmwrhtml/ 2011. mm5719a2.htm. Accessed November 28, 2011. 14. Hepatitis C investigation. Southern District Nevada Health District. http://www.southernnevadahealthdistrict Cecil A. King, MS, RN, is a charge nurse at .org/hepc-investigation/index.php. Accessed November Outer Cape Health Services, Provincetown, 28, 2011. 15. Pugliese G, Gosnell C, Bartley JM, Robinson S. Injec- MA. Mr King has no declared affiliation that tion practices among clinicians in United States health could be perceived as posing a potential con- care settings. Am J Infect Contol. 2010;38(10):789-798. 16. US Food and Drug Administration (FDA) Safe Use flict of interest in the publication of this article. (Propofol) Health Professionals Meeting. July 29, 2009. Mary Ogg, MSN, RN, CNOR, is a periopera- Rockville MD. 17. USP Ͻ797Ͼ Guidebook to Pharmaceutical Compounding— tive nursing specialist for AORN, Inc, Denver, Sterile Preparations. In: United States Pharmacopeia and CO. Ms Ogg has no declared affiliation that National Formulary (USP30-NF 25). Vol 2. Rockville, MD: United States Pharmacopeial Convention; 2007. could be perceived as posing a potential con- 18. US Food and Drug Administration. Questions and an- flict of interest in the publication of this article. swers on propofol shortage. International Pharmaceuti-

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