Safe Injection Practices forAdministration of Propofol

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

ices in thes of infec-wth in or

reuse ofultiple pa-n control

ided addi-ations. Inontrol andthe issues

articipantsevelopinge-specific,es to helpd to med-2012. doi:

n prac-

ABSTRACT

Sepsis and postoperative infection can occur as a result of unsafe practadministration of propofol and other injectable medications. Investigationtion outbreaks have revealed the causes to be related to bacterial grocontamination of propofol and unsafe medication practices, includingsyringes on multiple patients, use of single-use medication vials for mtients, and failure to practice aseptic technique and adhere to infectiopractices. Surveys conducted by AORN and other researchers have provtional information on perioperative practices related to injectable medic2009, the US Food and Drug Administration and the Centers for Disease CPrevention convened a group of clinicians to gain a better understanding ofrelated to infection outbreaks and injectable medications. The meeting pproposed collecting data to persuade clinicians to adopt new practices, dguiding principles for propofol use, and describing propofol-specific, sitand practitioner-specific injection techniques. AORN provides resourcperioperative nurses reduce the incidence of postoperative infection relateication administration. AORN J 95 (March 2012) 365-372. © AORN, Inc,10.1016/j.aorn.2011.06.009

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

e has

ostop

e han

ally, c

have1 Pro

esthe

od an

as bee

e tha

ation

was ap-

ease Control

four clusters

thermic re-

e infections

luding ex-

hat resulted

ring the han-

ofol by in-

infusion

he same

During the past 10 years, ther

growing concern regarding p

infections associated with th

injectable medications; more specific

of sepsis and postoperative infections

curred related to the use of propofol.

a sterile, IV, lipid-based, emulsive an

agent. It was approved by the US Fo

Administration (FDA) in 1989 and h

widely used in the United States sinc

As a lipid-based emulsion, this medic

known to support bacterial growth.3

doi: 10.1016/j.aorn.2011.06.009

© AORN, Inc, 2012

been

erative

dling of

lusters

oc-

pofol is

tic

d Drug

n

t time.2

is

In 1990, one year after propofol

proved for use, the Centers for Dis

and Prevention (CDC) investigated

of postsurgical infections and hyper

actions.4 The investigators traced th

and reactions to several factors, inc

trinsic contamination of the agent t

from lapses in aseptic technique du

dling of the medication, use of prop

fusion pump, and preparation of the

pump by one anesthesia provider. T

infusion pump, syringe, and provider were

March 2012 Vol 95 No 3 ● AORN Journal 365

he in

ptedcturercular

aysprep

suedn recon Soca Patthe

mariased

that

rapid

or vithe

dicati

terialresultions w

8 to 2008, 35curred inpain clinics,

ers), whichfor develop-

1 These out-

ents,or multiple

e, andinfection

ent ofutbreak ofpatients had

patient clinic.s able to testeen treatedt 71 patients

tracted hepa-taff mem-

ealed thatnd syringen medica-

es

en handling

ticulatef the

administration

alcohol.syringes or 12.

ta.fda.gov/

March 2012 Vol 95 No 3 KING—OGG

identified as risk factors in two of tpatients.4

These outbreaks of infection prompharmaceutical company that manufafol to add language to the product cithat “strict aseptic technique must alwmaintained during handling . . .”5 andof propofol for injection. The FDA isfol administration guidelines based odations from the CDC,4 the AmericaAnesthesiologists,6 and the AnesthesiSafety Foundation7 that are similar tomanufacturer’s recommendations sumTable 1. All recommendations were bfollowing facts:

� Propofol is a lipid-based emulsionports bacterial growth.8

� Bacterial contamination increasestime.9

� Disinfection of propofol ampulesfore opening considerably reducesbacterial contamination of the me

Disodium edetate, which inhibits bacwas added to propofol in 1996; as aincidence of propofol injection infect

TABLE 1. Propofol Handling Guid

US Food and Drug Administrrecommendations

� Vials of propofol and prefilled syringes arfor single (ie, one patient) use.

� Begin infusion immediately after drawingopening the vial of medication.

� Infusion from prefilled syringes or vials mwithin 6 hours of opening/filling the syring

� Propofol that is infused directly from a lar(eg, 100 mL) vial is to be limited to one pmust be infused within 12 hours of openor spiking the stopper.

1. DIPRIVAN® (propofol) Injectable Emulsion. 45109drugsatfda_docs/label/2008/019627s046lbl.pdf. Acc

reduced but not eliminated.10

366 AORN Journal

fected

thes propo-stating

bearationpropo-mmen-

iety ofient

zed inon the

sup-

ly over

als be-risk ofon.8

growth,, the

as

During a 10-year period from 199documented outbreaks of hepatitis ocnonhospital health care facilities (eg,endoscopy clinics, hemodialysis centput more than 60,000 patients at risking bloodborne pathogen infections.1

breaks were traced to

� reuse of syringes on multiple pati� single-use medication vials used f

patients,� failure to practice aseptic techniqu� failure to follow fundamentals of

control practices.11

In 2002, the Oklahoma State DepartmHealth investigated an unexplained ohepatitis C (HCV).12 All the infectedbeen treated for pain at the same outThe Oklahoma health department wa795 (88%) of the patients who had bsince the clinic opened and found thahad contracted HCV and 31 had contitis B during 2002. Interviews with sbers regarding injection practices revcare providers used a single needle ato administer three different sedatio

s1

General product insert guidelin

ded

in

mendvial

� Strict aseptic technique must always be used whsterile injectable medications.

� Propofol should be inspected before use for parmatter, discoloration, or evidence of separation oemulsion.

� Do not use if contaminated.� Fill syringes or spike the vial immediately before

to each patient.� Disinfect the rubber stopper with 70% isopropyl� Discard unused portions within 6 hours of filling

hours after spiking a large volume vial for infusion

ed: February 2008. US Food and Drug Administration. http://www.accessdaecember 8, 2011.

eline

ation

e inten

up or

ust bege.ge voluatient aing the

4A/Issuessed D

tions. In addition, these providers used the

ter theatedggest

patge anis ando admThe og syr

ak offive oroced

f theppropmediles ation fdicatore

e witore mflowve cocontan wa

into tfectios that

stoperative

techniqueated by thes.

EYSdom elec-mbers to

andlingmpleted theeventy-twoin a hospitalal), and 28%latory sur-highest per-ked in facili-nd mostan average

e performedrity of the

heir facilities,certified RNation prod-hen askedpically ac-

44% reportedsed two tots reportedg accessed

en asked if

periopera-ards and:605-611.

spring

s module

SAFE INJECTION PRACTICES www.aornjournal.org

same needle and syringe to adminismedications to all of the patients trday. Results of the investigation suthe infections were transmitted frompatient after a provider used a syrindle on a patient positive for hepatitused the same syringe and needle tmedication to subsequent patients.stopped when the practice of reusinand needles stopped.12

In 2007, investigation of an outbreat an endoscopy center revealed thatsix infected patients had undergone pthe same day.13 Direct observation opersonnel demonstrated that they inareused syringes and used single-dosevials on multiple patients. Clean needringes were used to withdraw medicasingle-use bottle of propofol. The meinjected through the patient’s IV. If mfol was needed, then the same syringclean needle was used to withdraw mtion. Investigators theorized that backthe patient’s IV or the needle may hanated the syringe with HCV, therebying the vial. The remaining medicatioon subsequent patients.13,14

The findings of the investigationsvarious outbreaks of postoperative inbe summarized into four major pointto safe injection practices.

� Propofol is a lipophilicIV injection that isknown to supportthe growth ofmicroorganisms.

� The addition of a preser-vative to propofol onlyinhibits microbial growth,it will not prevent it.

� There is quantitative evi-dence that extrinsic mi-crobial contamination

A

AtiR

WaSAP

and cross contamination

esethatthat

ient tod nee-then

inisterutbreakinges

HCVf theures on

center’sriatelycationnd sy-rom a

ion waspropo-h a

edica-fromntami-minat-s used

hesens mayrelate

has led to outbreaks of serious pohealth care-associated infections.

� It is essential to use strict asepticwhen handling propofol, as mandmanufacturer’s written instruction

MEDICATION PRACTICES SURVIn July 2009, AORN conducted a rantronic survey of 500 of its 40,000 medetermine their current practice for hpropofol. A total of 410 members cosurvey for a response rate of 82%. Spercent of the respondents practicedsetting (ie, academic, community, rurof the respondents practiced in ambugery centers or endoscopy units. Thecentage of respondents (ie, 36%) worties with five to 10 ORs (Figure 1), arespondents worked in ORs in whichof 51 to 100 surgical procedures werper week (25%) (Figure 2). The majorespondents (87%) reported that, in tanesthesia providers (eg, physicians,anesthetists) draw up propofol medicucts for administration (Figure 3). Whow often the vial of propofol was tycessed, 50% reported once, whereaswitnessing the same vial being accesthree times. Six percent of respondenseeing the same vial of propofol beinmore than four times (Figure 4). Wh

N Resources

guidance statement: safe medication practices inttings across the life span. In: Perioperative Standmended Practices. Denver, CO: AORN, Inc; 2011

for these new and updated AORN resources inmmer 2012edication Administration Tool KitMedication Safety video101: A Core Curriculum™ Medication and Fluid

OR

ORNve seecom

atchnd suafe MORNeriop

AORN Journal 367

l of pyes”respoto th

not o(44%

the miffered outtepsopofotion

steps wereifty-eight

their facilityprevent con-

oducts.e survey oft differenttotal of

ians, anes-al technolo-cluded

d parental

March 2012 Vol 95 No 3 KING—OGG

there were multiple accesses to a viafor the same patient, 68% answered “32% answered “no.” The majority of(82%) reported that multiple accessesof propofol for different patients didMost facilities routinely stock 20 mL50 mL (39%) vials of propofol, andof respondents (70%) reported that dumes of propofol were not being usethe OR. When asked the number of svolved from initially accessing the prcontainer to administering the medica

Figure 1. The number of ORs.

Figure 2. The average number of cases per

368 AORN Journal

ropofolandndentse vialccur.) and

ajoritynt vol-side ofin-l

to the

patient, 62% noted that one to threeinvolved in this process (Figure 5). Fpercent of respondents reported thathad a policy or procedure in place totamination of propofol medication pr

Pugliese et al15 conducted an onlinmultidisciplinary clinicians in 2010 atypes of health care organizations. A8,035 clinicians (eg, nurses, physicthesia professionals, dentists, surgicgists) responded. The researchers in5,446 respondents who administere

week.

d excminisinedy of pnts obsurv

inglee 50%witne. Theusing

ient. R

using a sy-re than onereusing thesame multi-

L) HEALTH

issues re-FDA and

ans on Julyattendance

o adm

SAFE INJECTION PRACTICES www.aornjournal.org

medications in the final analysis anclinicians who do not prepare or adrental medications. The survey contations about injection safety, frequencing injections, and how the respondeinjection safety information.15 In thisof respondents reported accessing a svial more than once, in contrast to thAORN survey respondents who hadthis practice in perioperative settingsity of respondents (ie, 66%) reportedmultidose vial for more than one pat

Figure 3. Health care professionals wh

Figure 4. The number of times that the prop

ludedter pa-

ques-erform-tained

ey, 30%-dose

of thessedmajor-ae-

searchers calculated the practice of reringe but changing the needle for mopatient to be 1% and the practice ofsyringe for additional doses from thedose vial to be 15%.15

THE FDA SAFE USE (PROPOFOPROFESSIONALS MEETINGTo gain a better understanding of thelated to the outbreak of infection, thethe CDC convened a group of clinici29, 2009, to assess the problem.16 In

inister propofol.

ofol vial is accessed.

AORN Journal 369

anesth

gastr

enter

nding

issues

dicati

ards

eline

deve

l setti

c adm

ipline

able m

nition

edicat

, sing

t guid

ssure

in fr

ompl

chnique,s) and

eparation and

g the manu-information

ional associ-ion of Nursen Society ofPatienttice

harmacopeiaications re-

the nextta to per-ices; devel-ol use thatsetting; andwould bepractitioner

the FDAto some of

in ac

March 2012 Vol 95 No 3 KING—OGG

were FDA and CDC staff members,

gists, nurse anesthetists, pharmacists,

ologists, and perioperative and gastro

nurses. Health care professionals atte

conference identified and prioritized

to the safe handling of injectable me

needed to be addressed, including

� implementation of universal stand

tice as they relate to practice guid

collection of evidence-based data,

ment of practice guidelines for al

description or definition of specifi

tion techniques).

� education across cultures and disc

what are acceptable and unaccept

tion administration practices.

� clearly defined meanings and defi

practice terminology related to m

ministration (eg, product labeling

single access).

� site-specific handling managemen

that address the issues of cost, pre

efficacy, and quick turnover times

standing ambulatory facilities.

� direct observations that monitor c

Figure 5. The number of steps involved

and competency related to following b

370 AORN Journal

esiolo-

oenter-

ological

the

related

ons that

of prac-

s (eg,

lop-

ngs,

inistra-

s as to

edica-

s of

ion ad-

le use,

elines

for

ee-

iance

practices guidelines (eg, aseptic tehand hygiene, standard precautionmanufacturer’s instructions for prhandling of medications.

� resolution of confusion surroundinfacturer’s written instructions and(eg, single access, single use).

� a coordinated policy from professations (eg, the American AssociatAnesthetists, AORN, the AmericaAnesthesiologists, the AnesthesiaSafety Foundation) regarding pracguidelines.

� practical applications of the US Pthat address the use of sterile medlated to anesthesia practice.17

The meeting participants proposedsteps, which included collecting dasuade clinicians to adopt new practoping guiding principles for propofwould be adaptable to any practicedescribing injection techniques thatpropofol specific, site specific, andspecific.

As a result of the 2009 meeting,has taken a broader-based approach

cessing a vial of propofol.

est the issues that were raised. As a regulatory

angu

ow w

by th

to reking

ed on

rms a

rms w

naly

stry a

that

w m

FDA

es on

ould

sed.18

n Nov

tuatio

nd rec

of qu

arginUnit

regula

ence o

he ris

e he

ation

ith i

at is

linic

ust bmay b

repar

in a

for ev

hen prepar-ns for

ts;hdraw medi-

ule, or

y patient;

to adminis-ts.19

al,15 60% ofional organi-f practice

vide educa-sources tosafe medica-and adminis-

patients andofessionals:generic prod-fety/Postmarketviders/

Accessed No-

ith therapeuticand Drug Ad-

gov/scripts/cder/r 29, 2011.

ofol for IV ad-n, DE: Astratrazeneca-us18, 2011.l infectionsnated intrave-is, Maine, andkly Rep. 1990;

n. RxList Inter-iprivan-drug

h of Operatingion of medica-n Control forPark Ridge, IL:

SAFE INJECTION PRACTICES www.aornjournal.org

agency, the FDA is looking at the l

is used on various products to see h

communicates to and is understood

health care professionals who need

use it.18 In addition, the FDA is loo

issue of standardization of terms us

facturer labels, evaluating which te

erable and whether standardizing te

be beneficial. After completing its a

FDA may provide guidance to indu

FDA reviewers on additional issues

should consider when evaluating ne

tion applications. For example, the

been evaluating fill amounts, closur

injectables, and other factors that c

ute to the way these products are uShortages of propofol that began i

2009 have further complicated the si

ufacturers have stopped production a

several lots. The shortage is a result

control issues and decreasing profit mpresent, only one manufacturer in the

States is producing propofol. Future

initiatives may develop as a consequ

issues.

CONCLUSIONThere is a growing concern about t

transmitting infections during routin

care procedures requiring IV medic

breaks of infection have occurred w

ing regularity. The gap between wh

mended and what is actually done c

regarding safe injection practices mdressed. Safe medication practices

marized as

� performing hand hygiene before pmedications for administration,

� storing and preparing medications

area,� using a clean syringe and needle

patient, and

age that

ell it

e

ad andat the

manu-

re pref-

ould

ses, the

nd to

they

edica-

has

liquid

contrib-

ember

n. Man-

alled

ality

s.19 At

ed

tory

f these

ks for

alth

s. Out-

ncreas-

recom-

ally

e ad-e sum-

ing

clean

ery

� implementing aseptic technique wing sterile medications and solutioinjection.

Unsafe practices include

� pooling or combining vial conten� reusing a syringe or needle to wit

cation from a multidose vial;� re-entering a single-use vial, amp

solution;� reusing a syringe or needle on an

and� using the same syringe or needles

ter medications to multiple patien

In the 2010 survey by Pugliese etthe respondents selected their professzation as their most frequent source oinformation. AORN continues to protional and evidence-based practice remembers and the industry related totion practices related to the handlingtration of medications and solutions.

References1. Postmarket drug safety information for

providers. Information for healthcare prpropofol (marketed as Diprivan and asucts). http://www.fda.gov/Drugs/DrugSaDrugSafetyInformationforPatientsandProucm125817.htm#.TtUiFvNryTw.email.vember 29, 2011.

2. Orange Book: approved drug products wequivalence evaluations. 2011. US Foodministration. http://www.accessdata.fda.ob/docs/temptn.cfm. Accessed Novembe

3. Diprivan® 1% injectable emulsion propministration [product insert]. WilmingtoZeneca Pharmaceuticals. http://www1.as.com/pi/diprivan.pdf. Accessed October

4. Centers for Disease Control. Postsurgicaassociated with an extrinsically contaminous anesthetic agent—California, IllinoMichigan, 1990. MMWR Morb Mortal W39(25):426-427, 433.

5. Diprivan® (propofol) injectable emulsionet Drug Index. http://www.rxlist.com/d.htm. Accessed May 16, 2011.

6. ASA Committee on Occupational HealtRoom Personnel. Preventing contaminattions. In: Recommendations for Infectiothe Practice of Anesthesiology. 3rd ed.

American Society of Anesthesiologists; 2011:11-22.

AORN Journal 371

ndlingnd Se

ty Fou

g contlogy. 1

phylocnesth

a T. Pon. An

Holmbtitis B08. An

l. A latitis B

tments6-583.tion. Asafe inda, 2007(19):5wrhtml, 2011rict Neadaheased N

insond State38(10)A) Saf. July

Compacope

. Rockv007.stions

-content/.pdf. Accessed

: Clinicians ad-d lots. CDC

.cdc.gov/HAN/2011.

ractices. Onelycampaign

and Prevention.sed November

ealth Organiza-ign/meetings/

December 8,

enters for Dis-dc.gov/November 28,

nd Prevention.ovember 28,

nurse atcetown,ation thatntial con-this article.

periopera-c, Denver,tion thatntial con-this article.

March 2012 Vol 95 No 3 KING—OGG

7. Berry AJ, ed. Recommendations for Hateral Medications Used for Anesthesia aPittsburgh, PA: Anesthesia Patient Safe1995.

8. Zacher AN, Zornow MH, Evans G. Drufrom opening glass ampules. Anesthesio75(5):893-895.

9. Sosis MD, Braverman B. Growth of Staaureus in four intravenous anesthetics. A1993;77(4):766-768.

10. Jansson JR, Ozaki M, Kimura S, FukadEDTA and reduced incidence of infectiIntensive Care. 2006;34(3):362-368.

11. Thompson ND, Perz JF, Moorman AC,Nonhospital health care-associated heparus transmission: United States, 1998-20Med. 2009;150(1):33-39.

12. Comstock RD, Mallonee S, Fox JL, et acomial outbreak of hepatitis C and hepapatients receiving pain remediation treaControl Hosp Epidemiol. 2004;25(7):57

13. Centers for Disease Control and Prevenatitis C virus infections attributed to unpractices at an endoscopy clinic—NevaMMWR Morb Mortal Wkly Rep. 2008;5http://www.cdc.gov/mmwr/preview/mmmm5719a2.htm. Accessed November 28

14. Hepatitis C investigation. Southern DistHealth District. http://www.southernnev.org/hepc-investigation/index.php. Acces28, 2011.

15. Pugliese G, Gosnell C, Bartley JM, Robtion practices among clinicians in Unitecare settings. Am J Infect Contol. 2010;

16. US Food and Drug Administration (FD(Propofol) Health Professionals MeetingRockville MD.

17. USP �797� Guidebook to PharmaceuticalSterile Preparations. In: United States PharmNational Formulary (USP30-NF 25). Vol 2United States Pharmacopeial Convention; 2

18. US Food and Drug Administration. Que

swers on propofol shortage. International Phar

372 AORN Journal

Paren-dation.ndation;

amination991;

occusAnalg.

ropofolesthes

erg SD.& C vi-n Intern

rge noso-among

. Infect

cute hep-jection7.13-517./.vadalthdistrictovember

S. Injec-s health:789-798.e Use29, 2009.

ounding—ia andille, MD:

and an-

cal Quality. http://www.ipqpubs.com/wpuploads/2010/05/Propofol_Shortage_QADecember 8, 2011.

19. CDC Health Advisory of July 13, 2009vised to halt use of propofol from tainteHealth Alert Network. http://emergencyhan00296.asp. Accessed November 28,

Resources1 Syringe, 1 Patient, 1 time: Safe Injection P

and Only Campaign. http://www.oneandon.org/. Accessed November 28, 2011.

Injection safety. Centers for Disease Controlhttp://www.cdc.gov/injectionsafety/. Acces28, 2011.

Safe Injection Global Network. The World Htion. http://www.who.int/injection_safety/spast/en/InitialMeetingReport.pdf. Accessed2011.

The CDC’s role in safe injection practices. Cease Control and Prevention. http://www.cinjectionsafety/CDCsRole.html. Accessed2011.

Viral hepatitis. Centers for Disease Control ahttp://www.cdc.gov/hepatitis/. Accessed N2011.

Cecil A. King, MS, RN, is a chargeOuter Cape Health Services, ProvinMA. Mr King has no declared affilicould be perceived as posing a poteflict of interest in the publication of

Mary Ogg, MSN, RN, CNOR, is ative nursing specialist for AORN, InCO. Ms Ogg has no declared affiliacould be perceived as posing a poteflict of interest in the publication of

maceuti-