Applying nursing theory to the practice ofnurse anesthesiaSUSAN A. MARTIN, CRNA, MSNDestin, Florida

With the current movement of anesthesiaeducation into graduate programs, changesin curriculum are inevitable. These changeswill include advanced nursing theory. Howthe issues of nursing theory apply to thepractice of nurse anesthesia are examined.Applications of Betty Neuman's systemstheory are used in specific examples of theanesthesia role. The profession of nurseanesthesia may benefit significantly from thecontributions of nursing theory.

Key words: Graduate education,Neuman systems model, nursing,nursing theory.

IntroductionThe practice of nurse anesthesia has been histori-cally defined from a functional perspective. Thisis readily illustrated by reviewing the Scope ofNurse Anesthesia Practice as defined by the Amer-ican Association of Nurse Anesthetists. (AANA).P 2)

This publication summarizes 11 functions that out-line and define the scope of practice of the nurseanesthetist. The majority of functions describedare primarily "technical" in orientation, such asitem f, which states that the scope of nurse anesthe-sia practice includes managing a patient's airwayand pulmonary status using endotracheal intuba-tion, mechanical ventilation, pharmacological sup-port, respiratory therapy, or extubation.

Other functions addressed by the AANA re-flect judgment-related challenges for the nurse an-esthetist, such as selecting the appropriate anes-thetic technique. When compared with currentnursing practice acts, the scope of practice as de-fined by the AANA in 1992 is devoid of a concep-tual or theoretical framework. The AANA hasstated in its Standards for Nurse AnesthesiaPractice its belief that "Standards, based uponsound philosophy, theory, science and principles,serve to upgrade clinical practice."'1 p4)

The goal of this article is to explore existingtheoretical principles of nursing and their poten-tial application in nurse anesthesia education andpractice. The significance of this goal is accentu-ated by the Council on Accreditation of Nurse An-esthesia Educational Programs' Standards for Ac-creditation, which states that accredited programsmust "design a curriculum that will award a mas-ter's or higher degree level to students who willenter the program on or after January 1, 1998, andwho successfully complete graduation require-ments."2 The National Commission on Nurse An-esthesia Education explains that the AANA hasgradually increased the educational requirementsin response to the demand for more complex ser-vices [which require] expanded knowledge andtechnological capabilities."3 This Council furtherrequires that a program must adopt a curriculumplan and/or program design that is within the con-struct of graduate education. Requirements forgraduate nursing education as determined by the

August 1996/Vol. 64/No. 4 369

National League for Nursing include a mandate"to expand knowledge of nursing theory as a basisfor advanced nursing practice." 4 Subsequently,nursing theory courses are becoming mandatorycurriculum in nurse anesthesia programs that arehoused in colleges of nursing.

The appropriateness of the medical model tra-ditionally used as a framework in nurse anesthesiaprograms is now being questioned, just as in thepast nursing professionals and educators had ques-tioned the use of the medical model in nursing.The medical model is described by Englehardt as"rejecting philosophical speculation and givingway to rational or logical decision making. Physi-cians use their clinical experience and observationof patients as a basis for developing reliable diag-noses and treatments. The goal has been in the'tacit knowing' of medicine."5 Englehardt goes onto support the notion that medical practice, too,can benefit from a theoretical basis which may addan "analytic regard" to the tacit knowledge.

The question is simple: if the AANA feels thatgraduate education is important enough to man-date it as a curriculum requirement, should not wethen consider changes in the framework withinwhich CRNAs practice? Unfortunately, the answeror solution is not so simple because nurse anesthe-tists must first recognize a theoretical void in theirpractice (considering that one of the problems ourprofession faces is the notion that we are techni-cians and further considering that any professionmust, by definition, be supported by a conceptualframework) and decide that it may be filled by theinclusion of a theoretical framework. Developingtheory is not a simple undertaking. Perhaps theprofession of nurse anesthesia would be betterserved by adopting and adapting theoreticalnursing models on which the practice of nursinghas been based. To facilitate a better understand-ing of nursing theory and nursing practice, it isnecessary to review nursing theory in practice.

Review of literature: Nursing theory in practicePractice is sometimes viewed as the "down to

earth action carried out by the doers," while the-ory is viewed as somewhat esoteric, in some casesunnecessary or at best, marginal. 6 Nursing theoryinfluences nursing practice in a variety of ways.Fawcett suggests that nursing theory distinguishesnursing from medicine by directing our actionsand controlling the clinical environment. 7 This isaccomplished through the ability of the theory todefine the arena of nursing by defining clinicalproblems to be considered, settings in which nurs-ing practice occurs, legitimate recipients of nurs-ing care, and nursing process, format, and content.

370

Nursing models serve as the basis for clinical infor-mation systems (admission forms, care plans, anddischarge summaries, to name a few). Conceptualmodels also guide the development of patient clas-sification systems. Fawcett states emphatically that"nursing models were devised to move nursingaway from ritualistic and task-oriented care tothoughtful practice."7 They were created to "shapenursing into what it ought to be." 7

Speedy claims that nursing theory explainsour practice by changing the way nursing isunderstood. 6 This is accomplished through thetesting of nursing theory in the clinical arena.Adapting basic scientific knowledge (validated byresearch) is the primary determinant of nursingpractice. "Nursing practice so based in theory andresearch has a firm foundation far removed fromtrial and error, guesswork or intuition."6

Allen asserts that nursing theory empowersnurses to question the status quo. He points outthat the aim of critical theory is to expose the con-tradictions, oppression, and power imbalances thatinhibit the freedom and autonomy needed to de-velop as a profession. 8 This requires the establish-ment of open, unconstrained communications,which will better assist patients in making in-formed choices about their care.

Critics of nursing theory argue that the pro-cess of incorporating nursing theory into practicemay be too difficult to realistically achieve at thebedside. The application of theory may requiregreater conceptual sophistication of theoreticalideas,8 theories are often too vague and abstract toapply,8 the models are limited by the values andbeliefs of their originators,9 and the credibility ofnursing models is challenged when the patientssee no difference in nursing care when a theoreti-cal framework is used. 10 Although the criticismsmay be valid for generalists in nursing whose prac-tice incorporates a wide range of specialties andskills, advanced specialty practitioners may bene-fit from an easier application of conceptual framesof reference by virtue of the more narrow focus oftheir practice. Benner defends nursing theory inpractice by asserting that nurses are using theoryin their daily practice but are unaware of the basisfor their competence."

With these arguments and assertions in mind,Betty Neuman's nursing thoretical framework willbe applied to the practice of nurse anesthesia.Neuman's theory is only one of several nursingtheories that could be appropriately applied to an-esthesia. Neuman has been chosen due to her ori-entation with systems theory, an approach that in-volves processes and outcomes and, thus, seemsmost appropriate to the practice of anesthesia.

Journal of the American Association of Nurse A nesthetists

The Neuman systems modelNeuman's model is based on an individual's

relationship to stress, the reaction to it, and recon-stitution factors that are dynamic in nature. 12 Theaim of this model, called the total person approach,is to provide a unifying focus for approaching var-ied nursing problems and for understanding thebasic phenomenon: man and his environment.Neuman's theory is neatly classified as a systemstheory that evaluates processes and outcomes to-ward greater organization. The person is definedby Neuman as an open, holistic system interactingwith and to the environment. The environment isdefined as "all that interfaces with the person."' 2

The environment is the source of stressors forthe person that has the potential of disrupting theperson's normal lines of defense (a normal rangeof responses to stress). Stressors may be beneficialor noxious depending on the strength of the flexi-ble line of defense (an individual's combination ofresponses to stress). With humans in a constant stateof change, interacting with the environment, vary-ing degrees of wellness exist. If a person's totalneeds are met, that person is in a state of optimalwellness. Conversely, a reduced state of wellness isthe result of unmet needs.

Three key concepts in Neuman's theory arestress, homeostasis, and patient perceptions. Thenurse's role is to focus on variables affecting theperson's response to stressors, allaying risk factorsassociated with them. The nurse assesses, manages,and evaluates the patient, acting to impede statesof disorder. Interventions by the nurse, "can beginat any point at which a stressor is either suspectedor identified. One would carry out the interven-tion of primary prevention since a reaction hadnot yet occurred, though the degree of risk or haz-ard was known or present. The intervener wouldattempt to reduce the possibility of the individual'sencounter with the stressor or in some way attemptto strengthen the individual's flexible line of de-fense to decrease the possible reaction."12

The impact of multiple stressors can reducethe effectiveness of the person's buffer system al-lowing a reaction to a stressor to occur.

Discussion: Applying the Neuman systems modelto anesthesia

Nurse anesthetists are nurses first, and as suchview their role in terms of assessing, planning, im-plementing, and evaluating the care of the client.The unique scope of practice of the nurse anesthe-tist differs significantly from the other nursing spe-cialties in that its primary focus includes:

1. Preanesthetic preparation and evaluation.

2. Anesthesia induction, maintenance, andemergence.

3. Postanesthesia care.4. Perianesthetic and clinical support func-

tions. 2)These functions of the nurse anesthetist, when

considered in light of Neuman's framework, striveto support the normal line of defense of the clientby impeding the stressors the client experiences(or remembers). The majority of actions carriedout by the nurse anesthetist are directed at decreas-ing physical and emotional stress from the initialpreoperative counseling, through the administra-tion of anxiolytics, vagolytics, and anesthetics, tothe postoperative follow-up visit. Neuman's theoryalso emphasizes the promotion of homeostatic bal-ance in the maintenance of the person's whole sys-tem. Homeostasis is a concept that is well inte-grated in current anesthesia practice as evidencedby the constant vigilance required of the anesthe-tist during the delivery of anesthesia nursing care.

Neuman believes that although nurses receivetraining in the natural and behavioral sciences,they are expected to conceptualize it in their ownway. She has developed many applications of hertheory in order to provide meaningful ways of in-corporating conceptual frames of reference intopractice. One such way is in her assessment tool.This tool relates to the total person and considersthree basic principles:

1. Good assessment requires knowledge of allthe factors influencing a patient's perceptual field.(The identification of these factors takes place dur-ing the preanesthetic assessment.)

2. The meaning that a stressor has to the pa-tient is validated by the patient as well as by thecaregiver. (This is demonstrated in the preopera-tive classification of anxiety that serves to identifythree distinct coping patterns in patients facingsurgery. Nurse anesthetists may choose to give spe-cial counseling to patients classified with high- orlow-level anticipatory anxiety, since these are asso-ciated with lack of participation by the patient dur-ing the postoperative period.)

3. Factors in the caregiver's perceptual fieldthat influence assessment of the patient's situationshould become apparent. (This principle is obvi-ated by the use of the preanesthetic evaluation indeveloping the perioperative care plan.)

These few examples illustrate the ease andappropriateness of applying nursing theory to thepractice of anesthesia.

SummarySince nurse anesthesia programs have pro-

gressed to the realm of graduate education, it is

August 1996/ Vol. 64/No. 4 371

fitting that theoretical frames of reference be in-corporated into the practice of nurse anesthesia.As demonstrated in this article, this task can beeasily accomplished and appropriately applied tothe practice of nurse anesthesia. The primary ob-stacle with using nursing theory is not its complex-ity but the reluctance of the practitioners to acceptnursing theory as a vital part of their professionaldevelopment. This reluctance seems inconsistentwith the usual dialogue of professionalism. Astronger foundation in nursing and a conceptualframework from which to practice are only a cou-ple of the contributions made by nursing theory tonurse anesthesia. Further contributions have yet tobe explored in the new marriage of anesthesia andgraduate education.

REFERENCES(1) Guidelines and Standards for Nurse Anesthesia Practice. In: Pro-fessional Practice Manual for the Certified Registered Nurse Anesthetist. ParkRidge, Illinois: American Association of Nurse Anesthetists. 1992.(2) Annual Report of the President, 1989. 56th AANA Annual Meet-ing, Boston, Massachusetts. AANA NewsBulletin. Special Supplement.1989;43(10):11-15.(3) Report of the National Commission on Nurse Anesthesia Educa-tion. Introduction. AANA Journal. 1990;58:389-393.

(4) Council on Accreditation of Nurse Anesthesia Education Pro-grams. Official Council Listings. AANA Journal. 1993;61:630-638.(5) Engelhardt H. Tristam EH, Jr. Clinical Judgement: A Critical Ap-praisal Boston, Massachusetts: D. Riedel Publishing Company. 1979.(6) Speedy S. Theory-practice debate: Setting the scene. The Austra-lian Journal of Advanced Nursing. 1989;6:12-20.(7) Fawcett J, Archer CL, Becker D, et al. Guidelines for selecting aconceptual model of nursing: Focus on the individual patient. Dimen-sions of Critical Care Nursing. 1992;11:268-277.(8) Allen DG. Nursing research and social control: Alternative mod-els of science that emphasize understanding and emancipation. Image JNurs Sch. 1985;17:58-64.(9) McKenna HP. The selection by ward managers of an appropriatenursing model for long-stay psychiatric patient care. J Adv Nurs.1989;14:762-775.(10) Fawcett J. Conceptual models and nursing practice: The recipro-cal relationship. JAdv Nurs. 1992;17:224-228.(11) Benner P. From novice to expert. Am JNurs. 1982;82:402-407.(12) Neuman B. The Neuman Systems Model. Norwalk, Connecticut:Appleton-Century-Crofts. 1982.

AUTHORSusan A. Martin, CRNA, MSN, is a recent graduate of Southern

Illinois University at Edwardsville Nurse Anesthesia Program. Shecurrently practices at Ft. Walton Beach Medical Center and EmeraldCoast Day Surgery Center. She has earned two previous degrees innursing: A BSN from Abilene Christian University in Abilene, Texas,and an MSN from the University of Texas Health Science Center inHouston, Texas. Her work experience is primarily in intensive careunits, including cardiovascular, liver transplant, and pediatric units inHouston and Los Angeles.

Journal of the American Association of Nurse Anesthetists372

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DIPRIVAN" (propofol) Injectable EmlaionINJECTABLE EMULSION FOR IV ADMNISTRAION BRIEF SUMMARY (or Pull Prescribing Information, See Package Insert)

-UDICATIUSA AD USAGEDIPRr/AN Injectable Emulsion is an IV sedative-hypnoic agent that can be used for both induction and/or maintenance of anesthesiaas part of a balanced anesthetic technique for inpatient and outpatient surgery in adults and in children 3 years of age or olderDIPfVAN Injectable Emulsion, when administered intravenously us directed, car be used to initiate and maintain monitoredanesthesia care (MAC) sedation during diagnostic prcedures in adults. DIPRRIAN Injectable Emulson may also be used for MACsedation in conjunction with lecaregioeal anesthesia an patients undergoing surgical procedures. (See PRECAUTIONS.) DIPRIRNInjectable Emulsion should only be administered to intubated, mechanically ventilated adult patients in the Intensive Care Unit (ICU)to provide cotinuous sedation and control of stress responses In thls setting, DIPRMN Injectabe Emulsion should beadministered only by persons skilled in the medical management of critically ill patients and trained n cardiovascular resuscitationand airway manageeent DIPRAN Injectable Emulson is not recommended for obstetrics, incldig cesarean section deliveries.DIPRNAN Injectable Emu ion crosses the placetta, and us with other general anesthetic agents, the administration of DIPRNANInjectable Emulsion may be associated wieth neonatal depression (See PRECAUTIONS.) DIPRIN Injectable Emlson is notrecommended for use in nursing mothers because DIPRtrAN Injectable Emulsion has been reported to be excreted in human mlkand the effects of oral absorption of small amounts of propofol are not kown (See PRECAUTIONS) DIPRONN Injectable Emulsionis not recommended foranesthesia an children below the age of 3 years because safety and effectiveness have rot been established.DIPRIVAN Injectable Emulsion hr oot recommended for MAC sedation in children because safety and effectiveness have not beenestabshed. DIPRIVAN Injectable Emulsion is not recommended for pediatric ICU sedation because safety and effectiveness havenot been established.CONTRAINDICATIONSDIPRtAN Injectable Emulsion is contraindicated in patients with a known hypersensitivity to DIPRIRN Injectable Emulsion or itscomponents, or when general anesthesia or sedation are contraindicated

For general aneslhea erInernd aestela a eat(MAC) sedaion, DIRIIIN Injetae EulIon IbSd beadiebdaleredonly hy pesoa traleed ln the admstrall of - l aIsthele ma nd otWleneled cd of t e argia w sI cpounere. Patien s eNhe eenuoeenly - ida, Hales for maiane of a patndahway, artiicial lathne,ad oxygn eee e nrlebme md dredatey resuiatson meet be mmediteavalbe. Forudatiee of hItuhated, merbanlaSyvetltced adult paleels In tneete Care Unt(ICU),DPRIW Nnjectabl EElebdon bneld beadmsterednly hy personsdlled le tme mgeetud c at ritally III patendstied bleed l nariorascalar esnelatloe tid abmay mauageme. In tfo

elderly, debilitated, or ASA IIUIV patients, rapid (single or repeated) bolos administration should not be used during generalanesthesia or MAC sedation in order to minimize undesirable cardiorespiratory depression including hypotension, apnea, airwayobstruction, and/or oygen desatoration. MAC sedation patients should be continuously monitored by persons not involved in theconduct of the surgical or diagnostic procedure, oxygen supplementation should be immediatnly available and proided whereclinically indicated; and oxygee saturatin should be monitored in all patients. Patients should be continuously monitored for earlyigns of hypotension, apnea, airway obstruction,and/or oxygen desaturation. These cardiorespiratory effects amrelicelyto occurstlowing rapid initiation ( )ading) bouses or during supplemental maintenanc boluses, especialy in the elderly debilitated, or ASAIIVIV patients DIPRIVAN Injectable Emulsion should rot be coadministered through the same (V catheter with blood or pasmabecause compatibility has not been established. In vitro tests have shown that aggrngates of the globuhr component of the emulsionvehicle have uccurred with blod/plusma/serum from humans and animals. The clinical significance is not known

STRICT ASEPTIC TECIMOUE MUST AlWAYS BE MAINTAINED DURING HANDLING. DIPRIVAN INJECTABLE EMULSION IS ASIGLE-USE PARENTERAL PRODUCT WHICH CONTAIS D.NS% DSODII EDEITE TO RETARD THE RATE OF GROWTH OFMICROORGAISS IN THEEVENTOFACCIDEITAL EXTRINSIC COTANINATION. HOWEVER, DIPRIVAN IUEC1RILEEMULSIONCAN STILL SUPPORT THE GROWTH OF MICROORGANSNS AS IlS NOT AN ANTIMICROIALy PRESERVED PRODUCT UNDERUSP STANOARDS. ACCORDINGLY, STRICT ASEPTIC TECHNIQUE MUST STILL BE ADHERED TO. DO NOT USE IF CONTMINATIONIS SUSPECTED. DISCARD UNUSED PORTIONS AS DIRECTED WITHIN TlE REQIRED TIME UNITS (SEE DOSAGE ANDADMINISTRATION, HANDUIIG PROCEDURES). THERE HAE BEEN REPORTS U WHICH FAILURE TO USE ASEPTIC TECHINIUEWHEN HANDIG DINRIVAN NUIECTANLE EMULSION WAS ASSOCIATED WITH MICROBAL COITANINATION OTHE PRODUCTAND WITH FEVER, IFECTION/SEPSIS, OTHER LIFE-THREATENING ILNESS, AND/OR DEATH.PRECAUTIONS General: A lwer induction dose and a slower maintenance rate of administration should be used in eldedy,debilitated, or ASA IIUIV patients. (See CLINICAL PHARMACOLOGY- Individualzation of Dosage) Patients should be continuouslymonitored for eady sigs of significant hypotension and/or bradycardia. Treatment may include increasing the rate of intraveousuid, elevation of lwer extemiies, use of pressor agents, or administration of atropine. Apnea often occurs during induction and

may persist for morethan 60 seconds. Ventilatory support may be required. Because DIPR/AN Injectable Emulsion is an emulsion,caution should be exercised in patients with dsorders of lipid metabolism such an primary hyperlipoproteanemia, diabeticbypedipemia, and pancreatitls. The clinical criteriafor discharge from the recovery/day surgery ores established for each istitutionshould be satisfied before discharge of the patient from the care of 6w anesthespsiol t When DIPRIUN Injectable Emulsion isadministered to an epileptic patientwthere may be a risk of seizure during.nrecoveryphase.adults and children, attention shouldbe paid to minimize pain on adminrtration of DIPRtAN Injectable Emulsion. Trnsent local pan canbe minimized if the larger veinsof the forearm or antecubital fossa are used Pain during intravenous injecton may also be reduced by pror injection of IV lidocane(1 mltof a 1% solution). Pain or injection occurred frequently in pediatric patients (45%) when a small vein of the hand was utilizedwithout lidocaine pretreatment. With lidocalne pretreatment or when antecubital veins were utilized, pan wan minimal (incidenceless than 10%) and well tolerated. Venous sequelae (phetis or thrombosis) nave been reported rarely (<1%). In two well-controlledcliical studies using dedicated intravenous cathetrs, no intances of venous sequelae were observed up to 14 days followinginduction Intraartenal injection in animals did not induce local tissue effects Accidental itra-aiterial injection han been reported inpatients, and, other than pain, there were no major sequelae. Intentional injection into subcutaneous on perivascular tissues ofanimals caused minimal tissue reaction. During the potmadeting period, there have been rare reports of lecal pain, swelling,blisters, and/or tissue necrosis folowig accidental eoravasatios of DIPRIVAN Injectable Emulsion. Pan operative myoclonia, rarelyincluding conlsions and opisthotonos, has occurred in temporal relationship in canes in which DIPRPAN Injectable Emulsion hanbeen administered. Clinical features of anaphytuos, which may inclde angioedema, broechospasm, erythema, and hypatension,occur raNly following DIPRIVAN Injectable Emulsion administration, althogh use of other drugs in most instances makes therelationship to DIPRPAN Injectable Emulsion unclear There have beer rare repots of pulmonary edema in temporal relationship tothe administration of DIPRIVAN Injectable Emulsion, although a causal relationship is unknown. DIPRIVAN Injectable Emulsion hanno vagoytic activity. Reports of bradycardia, anysole, and rarely, cardiac arrest have been associated with DIPRPJAN InjectableEmulsion. The intravenos administation of antcholinergic agents (og, atropine or gycopynolale) should be considered to modifypotential increaes an vagal tone due to concomitant agents (a, succanyichotine) or surgical stimuli.

leeinle CregeH SedaiOn: (SeeWARNIMGS ad DOAGE ANDAMINISTRATION, Handling Prtcedre.)The administrationof DIPRIVAN Injectable Emulsion should be iitiated as a continuous infusion and changes in the rate of administration made slowly(>5 min) in order to minimize hypotension and avoid acute averdosage. (See CLINICAL PhARMACOLOGY - Individualiation ofDosage.) Patients should be monitored for early signs of ugniffantl i'V and/or cardiovascuar depression, which may beprofound. These effects are responsive to discontinuation of DIP RN Injectable Emulsion, / ffuid administration, and/orvasopressor therapy As with other sedative medications, there is wide interpatient variabilrty in DIPRPVAN Injectable Emulsiondosage requirements, and these requirements may change with time. Failure to reduce the infusion rate in patents receivingDIPR VAN Injectable Emulsion for extended periods may resuR in excessively high blond concentrations of the drug. Thus, titrationto clinical response and daily evaluation of sedation levels are important during use of DIPRIUAN Injectable Emulsion infusion forCU sedation, especiay of log duration. Opioids and paralytic agents should be dicontinued and respiratory function optimizedproto wens patients tram mechanical vestitation. Infusions of DIPRraAN ljectable Emubson shouts be adjusted to maintain aright level of sedation prior to weaning pahientu froes mechanical vesidatory support. Thmnughoid tw weaning process thhr level of

sedation may be maintained in the absence of respiratory depression. Because of the rapid clearance of DIPRIVAN InjectableEmulsion, abrupt discontinuation of a patient's infusion may result in rapid awaening of the patient with associated anxiety,agitation, and resistance to mechanical ventilation, making weaning from mechanical ventiation dificult. I is thereforerecommended that udministration of DIPRIVAN Injectable Emulsion be continued in order to maintain a tight level of sedationthroughout the weaning process until 10-15 minutes prior to extubation at which time the infusion can be discontinued. SinceDIPRIAN Injectable Emulsion as formulated in an oil-is-water emulsion, elevations in serum triglycerides may occur whenDIPRIVAN Injectable Emulsion is administered for extended periods of time. Patients at risk of hyperiipldemia should be monitoredfor increaes is serum triglycerides or serum tudidty. Administration of DIPRIVAN Injectable Emulsion should be adusted if fat isbeing loadequately cleared from the body.A redaction in the quatity of coecurrntly administered lipids is indicated to compensatefor the amount of lipid infused an part of the DIPRIVAN Injectable Emulsion formulation; 1 rt of DIPRIVAN Injectable Emulsioncontains approimately 0.1 g of fat (1.1 kcal). In patients who are predsposed to zinc deficiency such as those with bums, diarrhea,and/on major sepsis, the need for supplemeotal zinc should be considered during prolonged therapy with DIPRIVIt InjectableEmulsion. EDTA in a strong chetetor of trace metals - including zinc. Calcium disodiom edetate has been used in gram quantitiesto treat heavy metal toxicity. When used in this manner it is possible that an much as 10 mg of elemental zinc cabe lest pen dayvia this mechanism. Although with DIPRIVAN Injectable Emulsion there are so reports of decreaned zinc levels or zinc deficlency-related adverse events, DIPRPAN Injectable Emulsion should not be inused for loger than 5 days withoat providing a drug holidayto safely replace estimated on measured urine zinc losses. At high doses (2-3 grams per day), EDT has been reported, on rareoccasions, to be tosic to 6we rendl tubules. Studoes-to-date, in paents with normal un impaired rend lonction have nof shown anyahleration hr monat fuschion with DIPRIVAN Injectable Emulsion certaiig t.Ug5% dosodiom edetate. In pahiests at role for rendlimponrment urinalysle and urine sedenent shouts be dreckod befame ishtation of sedation and then be mositmred on atnmate daysduring sedation. The long-term admlehrtcahion of DIPRFAN Ijectable Emuo to pahients with omnal failure and/or hopaticinsidhicwncy han nothben evaluated.Nernnerglel Aseitesla: When DIPRIVAN Injectable Emulsion is used an patients with increaned istracranidl pressure sr

impaired corebodl carcutation, uigreticast decreanes in mean arterial pomssure shouts be avoided because of 6we omsuftat decreasesin cerebral perfusion premeure. To avoid uigodicairt hypoeensioe and decreases an cerebodl perfusion pressure, an iofusion or siowbolos of approoimately 2itmg evnry ig seconds shouts be uliand isstead of rapid, roam frequent, and/or tarpon bolases ofDIPRtrAN Injectable Emulsion. Slower induction titrated to clisical maspoeses will generally mshl in reduced inauto dosagerequirements (1 to 2 mgkg). When increused ICP hr suspected, hyperenbiation and hypocathia shouts accompany theadmioistrahion of DIPRIVAN Inectable Emulsion. (See DOSAGE AND ADMINISTRATION.)Can Ameslteel: Slower rates of adminstation shoots be utiloed an premedicated pahierts, gesuatric pahients, pahients with

recant Void sthat, or pahiests who are hemodynarocally unstable. Any ffuid deticits shouts be conoected prior to adminstrahion ofDIPRIVAN lsjectable Emulsion. In thmse paherts where addithooal ffuld foerapy may be coetmaiodicated, other messuoms, ng,elevation of lower eotremeties, or mae of premser agents, may be useful to offoet 6we hypatenoior which is ansociated with 6weinduction of asesthesia with DIPRIVAN Intale Emulsion.leemnose ler aPees: Patients shouts be advhred that performance of activities requiring reetl aletes, such us operaigm otor vehicle or hacardoos machionry or signing legal documents, may be imparred fur rome time afton geneodl anesthesia

oronedaion.Drg bieretleem: The induction dose requiaements of DIPRIVAN ljectatile Emubsion may be reduced in pahients with

intramuocuter on intravenous paemedication, partiuladyl with narcotics lng, murphine, ronpedidine, and fnntaoyl, etc.) andceestileaboes of opleids and sedatives )ng, bensodiazepenes, badiurates, chleral hydrate, dropenidol, etc.) These agents mayincremse 6we anesthetic or sedative effects of DIPRIVAN Islectable Emulsion and may ahso resuht in more pronounced decreanes ansystolic, diastolic, and mean arterial pressures and cardiac output During mainenance of anesthesia or sedation, the rate ofDIPRIVAN Injectable Emulsion administration should be adjusted according to the desired level of aesthesia orsedation and maybe reduced in the presence of supplemental analgesic agents (eg, nitrous oide or opioids). The concurrent administration of potentinhalational agents )ng, leoffurane, enflurane, and halethane) during maintenance with DIPRIVAN Injectable Emulsion has not beenedeesively evaluated. These ishatational agents can also be expected to increase the anesthetic or sedative and cardiorespiratory

wuvirniv (prpuiuj tlwcjUei* wmus ioneffects of DIPRIVAN Injectable Emulsion. DIPRIVAN Injectable Emulsion does rot cause a clinically significant change in onsetintensity, or duration of action of the commonly used neuromuscular bloclog agents leg, succinytchotise aod nondepotaringmuscle relaxants). No significat adverse interactions with commonly used premedications or drugs used during anesthesia orsedation (induding a range of muscle relaxants, inhatational agents, analgesic agents, and local anesthetic agents) havebeen obervedCerciuegeuss, Mutugmeses, Imparuaen of FertWlf Animal carcinogenicity studies have not been performed with propofol. In

vitro and n vvo animal tests failed to show any potential for mutagesicity ty propofof Tents for mutagesicity incfuded the Ames(using Samonela sp) mutation test gene mutation/gene conversion using Saccharomyces erievnine, in vitro cytsgeneic studiesin Chinese hamsters, and a mouse micronucleus test Studes in female rats at intravenous doses up to 15 mg/hg/day (6 tmes themaximum recommended human induction dose) for 2 weeks before pregnacy to day 7 of gestation did not show impared fertility.Male fertility in rats wan not affected in a dominant lethal study at intravenous doses up to 15 mg/ltglday for 5 daysPregany Category B: Reproductior studies have been performed in rats and rabbits at intravenous doses of 15 mg/kg/day (i

times the recommended human induction dose) and have revealed no nvidencn of impaired fertility or harm to the fntus due topropofol. Ropfol, however, has been shown to cause matemal deaths in rats and rabbits and decreased pup survival during thelactating period in dams treated with 15 mg/kg/day (or 6 times the recommended human induction dose). The pharmacologicalactivity (anesthesia) of the drug on the mother is probably responsible for the adverse effects seen in the offspring. There are,however, no adequate and well-controlled studies in pregnant women. Becuse animal reproduction studes are not always predictiveof human responses, this drug should be used during pregnacy only ifclearly needed.

Lakr a nDueBe: DIPRIVAN Injectable Emulsion is not recommended for obstetrics, including cesarean section deiveriesDIPRJAN Injectable Emulsion crosses the placenta, and us with other general anesthetic agents, the adminitration of DIPRRPPNEmulsion may be associated with neonatal depression.Nusing Mntern: DIPRIVAN Injectable Emulsion is not recommended for use in nursing mothers because DIPRIVAN Injectable

Emulsion has been reported to be ecreted in human milk, and the effects of oral absorption of small amounts of propofol arenot known.

Phdiaics: DIPRIVAN Injectable Emulsion is net recommended for use in pediatric patients for ICU or MAC sedation. In addition,DIPRIVAN Injectable Emulsion is not recommended for general anesthesia for children blow the age of 3 years bncause safety andeffectiveness have not been established. Althongh no causal relationship has been established, senous adverse events (includingfatalities) have been repoited in children given DIPRIVAN Injectable Emulsion for ICU sedation. Thnse events were seen most oftenin children with respiratory tract infections given doses in excess of those recommended for adults.ADVERSE REACTIONS

Geeralf:Adverse event information is derived from cotrolled clinical trials and worldwide marketing experience. In the descriptionbelow, rates of the more common events represent US/Canadian clinical study results. Less frequent events are also derived frompublications and marketing eperienco in over 8 million patients, there are insufficinnt data ts support an accurate estimate of theirincidenc rates These studies were conducted using a variety of premedicants, varying lengths of surgicatrdiagnostic prcedures,and various other anestheticlsedative agents. Most adverse events were mild and transient

AesdhesutaudMAC Seda inu Aduk: The following estimates of adverse events for DIPRrAN Injectable Emulsion include datafrom cliical trials in general anesthesia/MAC sedation (N=2889 adult patents). The adverse events listed below as probably causallyrelated are those events in which the actual incidenco rate in patients treated with DIPRIVAN Injectable Emulsion wan greater thanthe comparatur incidenco rate in these trials. Therefore, incidence rates fur anesthesia and MAC sedation in adults geerallyrepresent estimates of the percentage of clinical trial patients whch appeared to have probable causal reationship. The adverseexpeience profile trom reports of 150 patients in the MAC sedation clinical trials is simiiar to the profile established with DIPRViInjectableEmulsion during anesthesia (see belw). During MAC sedation clinicaltrials, sgnificant respiratory events included cough,upper airway obstruction, apne, hypoventilahon, and dyspnea.Anesthesla In Childree: Generally the adverse expeence profile from repoits of 349 DIPRIVAN Injectable Emulsion pediatric

patients behween the ages of 3 and 12 years in the US/Canadan anesthesia clinical trials is similar to the profile established withDIPRIVAN Injectable Emulsion during anesthesia in adults (see Pediatric percentages [Peds %] below). Although not repoted as anadverse event in clinical trials, apnea is frequently obsered in pediatric patients.

ICU Sedaton in A lts: Thefollwing estimates of adverse events include data from clnical trials in ICU sedation (N=159) patients.Probably related incidenco rates for ICU sedation were determined by individual case report form revlew. Probable causality wanbased upon an apparent dose response reationship and/or positive responses no rechallenge. In many instances the presence ofconcomitant dlsease and concomitant therapy made the causal relationship unknown. Therefore, incidenco rates for ICU sedationgenerally represent estimates of the perentage of clinical trial patients which appeared to have a probable causal relationship.

Incidence greater tan 1% -Probay Casally Related

Sedation ICU SedationCardiovascuiar Bradycardia Bradycordia,

Hyoeso' Decreased

Pd:17%/] Cardiac Output,SHypertension HpotensionPnds:8% %(see also CLINICAL

PHARMACOLOGY)Central NervousSystem: Movement [Peds 17%)Injection Site: Buming/Stinging

or Pan, 17.6%(Pods. 1(1%)

Metaholic/Nutritional: Hyperipomia'Respiratory: Anes Respiratory

(see also CLINICAL AcidosisPHARMACOLOGY) During

Weaning*Skin andAppendages: Rush [Peds: 5%]

Events without an 'or % had an incidence of 1%-3%Incidence of events 3% to 10%

Incideese less thn 1%- ProbabhCausally Related

Anesthesia/MAC

Sedation ICU SedationBody as a Whole. Anaphyaxis/

AnaphylactoidReaction,Perinatal Disorder

Cardiovacuar Premature AtrialContractions,Syncope

Central NerousSystem: iypertonialDystoria,

Paresthesia AgitationDigestive: pemalivahonMucculosknletal: MalgiaRespiratory: Wenng Decreased

Lung FunctionSkin andAppedages: ushing, PruritusSpecial Senses: AmblyopiaUrugenital: Cloudy Unine Grnen Urine

Incideece estleoan 1% -Caual Relatnship Unidowe

AnesthesialMAC

Sedation ICU Sedation

BodyasaWhole. Asthenia, Awareness, Fever, Sepsis,Chest Pain, Trunk Pan,Extremitles Pain, Whole BodyFever, WeaknessIncreased Drug Effect,Neck Rigidity/Stiffness,Trunk Pain

Cardiovacuar Arhythmia, Atrial Arrhythmia,Fibrilahtion, AdialAtrioventricularHeart Fibrilation,Block. Bgeminy, Bgeminy,Bleeding, Bundle Cardiac AnstBranch Block, Extrasystole,Cardiac Arrest, RightECG Abnormal, Heart Failure,

Manufactured forZeneca PharmaceuticalsA Business Unit of Zeneca Inc.Wilmington, DE 19850-5437

Cardiavascutar Edema, Etrasystole, Vntricuar(continued) Heart Block, Tachycardia

Hypertension,Myocardial Infarction,Myocrdial Ichomia,Premature VntricuiarContractions, STSegment Depression,SupraventricularTachycardia, Tchycardia,Ventricuiar Fibrillation

Central NerousSystem Abnormal Dreams, Chills/Shivering,

Agitation, Amorous IntracranialBehavior, Anxiety, Hypertension,

BcigJri Seus,Thrashing, Chil g Somnolence,Shivering, Clonic/ ThinkingMyoclonic Movement, AbnormalCombativeness,Confusion, Delirium,Depression, Dziness,Emotional Lability,Euhoria, Fatigue,Hallucinations,

Headache, Hypotonia,Hysteria, Insomnia,Moaning, Neuropathy,Opisthotonos, Rigidity,Seizures, Somnolence,Tremor, Twitching

Digestive: Cramping, Diarrhea, linus, LiverDry Mouth, Eniarged FunctionParotid, Nausea, AbnormalSwallowing, Vomiting

Hematolugic/Lymphatic: Coaguation Disorder,

LeukocytssisInjection Site: Hives/ltching, Phlebitis,

Redness/DiscolorationMetabolic/Nutritional: Hyperkalemia, BUN Increased,

Hyperipemia CreatinineIncreased,Dehydration,Hyperglycemia,

Acdosis,OsmolalityIncreased

Respiraory: Bronchospasm, HypoxiaBurning in Throat,Cough, Dyspnea,Hiccough,Hypervnntilation,Hypoventitation,Hypooia, Laryngospasro,Pharyngitis, Snoozing,Tachypnna, UpperAirway Obstruction

Skin andAppendages: Conunctival Rush

Hyperemia,Daphoresis, Urticaria

Special Senses: Diplopia, Ear Pain,Eye Pain, Nytagmus,Taste Perversion,Tinnitus

Urogenital: Olagunia, Urine Kidney FailureRetention

Rev D06/96