The Future of Low-Te m p e r a t u r eSterilization Te c h n o l o g y

Safety, Economics, and the Environment

Published by Communicore under an educational grant from Advanced Sterilization Products, a division of Johnson & Johnson Medical, Inc. Copyright © 1996, Communicore, 220 Newport Center Drive,

Suite 8, Newport Beach, CA 92660 U.S.A. E-mail: admin@communicore.comAny reproduction without permission is prohibited.

Table of Contents

O v e rview of the Issues . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1

Historical Background . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3

The Development of Sterilization Te c h n i q u e s . . . . . . . . . . . . . . . . . . . . . . . . . . 3

Medical Sterilization: Definitions and Guidelines . . . . . . . . . . . . . . . . . . . . . 5

Guidelines for Device Classification . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5

Guidelines for Sterilization Va l i d a t i o n . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6

Strengths and Limitations of Traditional Sterilization Te c h n o l o g i e s. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8

H i g h - Temperature and/or High-Humidity Te c h n o l o g i e s. . . . . . . . . . . . . . . 8

Dry Heat . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8

S t e a m . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9

L o w - Temperature and/or Low-Humidity Te c h n o l o g i e s. . . . . . . . . . . . . . . . 9

Liquid Chemical Germicides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9

Ethylene Oxide . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10

Emerging Issues with Traditional Low-Temperature Sterilization Te c h n o l o g y . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11

New Demands . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11

Health and Safety Issues . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12

Occupational Health Risks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12

Patient Health and Safety . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13

Environmental Issues . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14

Economic Issues. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16

Taxes and Regulation of Carrier Gases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16

Monitoring Costs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16

Instrument Processing and Inventory Management. . . . . . . . . . . . . . . . 16

Sterilization vs. Disinfection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17

Newer Low-Temperature Sterilization Te c h n o l o g i e s . . . . . . . . . . . . . . 18

Vapor Phase Hydrogen Peroxide . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18

O z o n e . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19

Liquid Chemical Sterilants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19

Gas Plasma Systems . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20

Mixed Chemical Plasma. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20

L o w - Temperature Hydrogen Peroxide Gas Plasma . . . . . . . . . . . . . . . . . 21

Summary and Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23

R e f e r e n c e s . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25

5

Preventing patient exposure to disease-causing microbial organisms on instru-ments utilized during their care is ofgreat importance in fulfilling the basicHippocratic ideal: do no harm. As a

result, sterilization is an important technologi-cal component in the success of all surgicalprocedures. The field of medical sterilizationhas become increasingly complex, however,due to advances in medical instruments and devices. This complexity has raised seri-ous safety, economic, and environmental con-cerns about traditional low-temperaturesterilization technologies. Important to thisdiscussion is the expected role emerging tech-nologies will play in medical sterilization inthe near future.

Sterilization may be defined as a process thatrenders medical devices and surgical instru-ments devoid of all life forms, including fungi,viruses, active bacteria, and heat- and chemi-cal-resistant bacterial spores. Disinfection—often used erroneously as an interchangeableterm for sterilization—is a process that isdesigned to kill actively growing and vegeta-tive microbial organisms; spores will com-monly survive this process. Importantly,disinfection is not a substitute for sterilization.Instruments that are used invasively generallyrequire sterilization, not just disinfection.

Medical sterilization technology has remainedessentially unchanged over the last 40 yearsor more. Traditional methods used to sterilizemedical devices and surgical instruments canbe categorized by the temperature at which

they are effective. Those that use high heatand/or humidity include dry heat and steam techniques. Low-temperature methodsinclude liquid chemical germicides and ethyl-ene oxide (EtO) gas. Dry heat and steam arecommonly used to sterilize liquids, linens,wood-containing items, metals, and heat-stable plastics. Liquid chemical germicidesare used in certain specialty applications due to questions of sterilization efficacy.

For the majority of heat- and moisture-sensi-tive medical devices and surgical instruments,EtO has been the most useful sterilizationtechnology available. This is particularly tru efor those sensitive materials that have beenutilized over the last 40 years, as EtO is aneffective sterilant in relatively less harsh environments than dry heat or steam. It canbe stated with relative assurance that thewidespread use of low-temperature EtO sterilization has contributed significantly to the revolution in medical device and surgi-cal instrumentation development—delicate,sophisticated instruments do not fare well in the environments of intense heat and highhumidity required for sterilization with other methods.

While EtO and other traditional sterilizationtechnologies have been shown to be eff i c a c i o u sfor medical sterilization applications, they are not without significant safety problems.For example, liquid chemical germicides,while functional at low temperatures, have no established method to ensure a sterileresult. The use of EtO raises significant

O v e rview of the Issues

6

concerns of compromised employee health andsafety as a result of exposure to the gas duringthe sterilization process. Even at extraordi-narily low levels of exposure allowed foremployees, the gas has been linked to cancer,fetal abnormalities, and chronic medical prob-lems. In addition, the carrier gases currentlyused in most EtO sterilizers to render the system relatively safe (i.e., not overly explo-sive or flammable) no longer can be producedlegally due to overt environmental concerns.Replacement carrier gases are costly and donot alleviate any of the safety problems foremployees that are associated with EtO.Finally, for patient safety reasons, extendedcycle times are required to eliminate toxic gas residue, which eff e c t i v e l y limits the num-ber of times a device or instrument can beused to no more than once per day. This limitation demands that hospitals carry excessi n v e n t o r y, which can create problems for eff e c-tive budget management.

In the last five years, low-temperature sterili-zation technologies, particularly EtO, havecome under increased scrutiny. Issues ofemployee and patient safety, economics, andenvironmental mandates have all coalesced increating a crisis with increasing momentum:the well-accepted method to achieve low-temperature sterilization, EtO, fails to addressthese problems. The questions then arise:W h a t will replace EtO? What sterilizationmethod can ensure patient safety? How candelicate and expensive surgical and medicalinstruments be sterilized without damage?These are difficult questions to address asthey require a fundamental change in the wayin which sterilization has been considered formore than 40 years.

Recently, several new sterilization technolo-gies have been cleared for marketing by the United States Food and Drug Administra-tion (FDA). These technologies represent the first attempts to meet the strict criteria for efficacy and safety of medical sterilizersset forth by the FDA. The anticipated rolethese emerging sterilization technologies will play in the future of sterile medical pro-cessing is expected to be significant as tradi-tional sterilization technologies are retired or relegated to disuse.

With more than 100 years of sterilizationknowledge, the medical community generallyagrees on the components necessary for an ideal sterilization technology. These include demonstrated efficacy against allpotential disease-producing microbial lifeforms, rapid sterilization cycle times, cost-effective operation, established safety for both patients and s t a ff, inexpensive installationand maintenance, non-corrosiveness and compatibility with instruments and devices,and environmental safety. Traditional low-temperature sterilization technology fails toaddress a number of these issues and may nolonger be appropriate for healthcare institu-tions. With the introduction of novel low-temperature sterilization technologies thathave been specifically designed to addresssafety, economic, and environmental con-cerns, it may now be possible to better protecthealthcare employees, patients, and the environment in a cost-effective manner. Athorough understanding of the relationshipamong safety, economic, and environmentalissues is essential to appropriately evaluatethe options available in medical sterilizationtoday and into the 21st century.

7

For much of human existence, the under-lying cause of microbe-induced diseasewas unknown. Common explanationspromulgated by folklore and early prac-titioners of medicine included angry gods,

bad air, various spells, and the odd demon ortwo—all apparently capricious in both thechoice of who suffered and who recovered.

Beginning in the early 1800s, however, the bat-t l e against the unseen microbial world beganto shift with the application of the scientificmethod to the practice of medicine. By themid-19th century, the fundamental disciplinesof biomedical research—physiology, anatomy,and biochemistry—had been established.

During this period of dramatic change, thepractice of surgery evolved rapidly, due mainlyto the advent of anesthesia (ether and chloro-form) that made possible significant advancesin surgical technique. Surgeons now had themeans to perform more invasive operationsthat lasted for extended periods of time. Sim-ply surviving a surgical procedure, however,was not sufficient to ensure recovery—therewas one significant hurdle left to overcome.

Microbial contamination of surgical woundsbecame a significant source of both postopera-tive morbidity and mortality; the gains madewith better surgical procedures were oftenmore than offset by massive infections in thedays and weeks following surgery. Through-out this time, the underlying source of theselife-threatening complications remained poorly understood, if at all.

With the development of the germ theory ofdisease, first promulgated by Agostino Bassi,an Italian biologist, in 1836, and later extendedby Louis Pasteur with the demonstration thatmicroorganisms were responsible for produc-ing disease in silkworms, the stage was set fora more thorough understanding of the natureof postoperative complications due to micro-bial contamination.1 With extrapolation ofthese early studies to humans in 1863, againby Pasteur, both the cause and effect of surgi-cal wound contamination by microbial organ-isms were gradually recognized.

Developing methods to achieve asepsis, or thelack of microbial contamination of a surgicalwound, became the goal of a number of med-ical scientists and surgeons during this time.By 1865, Joseph Lister, a British surgeon, beganusing carbolic acid (phenol) as a surgical dis-infectant. His work, and that of Robert Koch,a German bacteriologist, and others, broughtaseptic techniques into widespread surgicalpractice by the early 1870s.2

The Development of Sterilization Techniques

The identification of the microbial basis ofinfectious disease provided a rational basis to improve the success rates of developingsurgical techniques and procedures. Earlyattempts to prevent infection in contaminatedwounds used chemicals such as sodium

Historical Background

8

hypochlorite, other chlorine-containing solu-tions, strong acids and bases, and alcohols.Some chemicals were more effective than others—some even achieved a moderatedegree of asepsis. All, however, were notablefor their toxicity to the patient. This series oftrial-and-error studies culminated with thepublication, in 1881, of a classic monographby Koch of the relative abilities of more than70 different chemicals to kill the spores of thebacteria that caused anthrax.2 This identifica-tion of chemicals capable of destroying spores was an important advance in the evolution of sterilization and disinfection.

Limited use for medical applications of steri-lization by heat and steam began by the early1880s. Intere s t i n g l y, the steam pre s s u re cooker,an early version of the autoclave, had beeninvented in 1681 and used solely for culinarypurposes until Charles Chamberland, a col-league of Pasteur’ s , began to use it 200 yearslater for sterilization in the l a b o r a t o r y.3 T h efirst commercial steam sterilization systemintended for use on medical products wasdeveloped in 1889.

Until the introduction of EtO sterilization inthe late 1950s, dry heat and steam were theonly methods available to routinely sterilize

surgical instruments. With EtO, increasinglysophisticated and delicate instruments couldbe sterilized at low temperatures, reducingthe damage to these instruments that wouldotherwise result if more aggressive forms ofsterilization were used.

Together, dry heat, steam, liquid chemical germicides, and EtO represent the range oftraditional medical sterilization technologies.Each technique functions differently to eliminate microbial life from medical devicesand surgical instruments. Each has its advan-tages and disadvantages. Low-temperaturesterilization—liquid chemical germicides andEtO—has come under increased scrutiny over the last 10 years due to significant problems with employee, patient, and environmental safety. These problems have,however, created opportunities to implementnovel methods to achieve both safe and complete sterilization in the healthcare set-ting. While it is essential that effective, low-temperature sterilization methods remain available for the ever-increasing number of heat- and moisture-sensitive medical devices and surgical instruments, traditional methods to meet these expecta-tions are no longer viable within today’shealthcare environment.

9

As a procedure, sterilization uses e i t h e rphysical or chemical methods to destro yall microbial life, including viruses andbacterial spores.4

In contrast, disinfection is a process that elim-inates virtually all forms of microbial life exceptbacterial spores, a difficult-to-kill form of cer-tain pathogenic bacteria that often can resistharsh environments such as heat and chemicaldisinfectants.5 Less lethal than sterilization,disinfection lacks the level of safety provided bysterilization, and failure to properly disinfectan instrument can be the source of potentialinfections by disease-causing bacterial spores.

Cleaning is the process of removing organicmatter—in which microorganisms may findfavorable conditions for continued life andgrowth—from an instrument or device thathas been in contact with a patient or the envi-ronment. It is usually accomplished by wash-ing with a cleanser and hot water. No matterhow extensive, instrument cleaning is not asubstitute for either sterilization or disinfec-tion—but it should always be performed priorto either procedure to ensure efficacy.

Guidelines for Device Classification

The Centers for Disease Control and Pre v e n t i o nrecommends that medical devices, surgicalinstruments, and environmental surfaces

be divided into three general categories todetermine whether sterilization or disinfec-tion is appropriate.4,6,7

• Critical devices. These are items that are introduced into the body orare attached to devices that are indirect contact with the patient’s inter-nal tissues, such as scalpel blades, car-diac catheters, and laparoscopes. TheAssociation of Operating Room Nurses(AORN) recommends that criticaldevices be sterilized, not disinfected.8

• Semicritical devices. These are itemsthat come into direct contact withintact mucous membranes, and includesuch devices as endotracheal tubes,cystoscopes, and proctoscopes. Whilemany hospitals accept intermediate-level disinfection for semicriticaldevices, other hospitals prefer dispos-able instruments in this category.

• Noncritical devices. These items only require low-level disinfection, asthey only come in contact with intactskin, if they touch the patient at all.Examples include humidifiers, bed-side tables, and similar equipment.

Professional societies and government agen-cies have promulgated recommendations and guidelines in an attempt to ensure ade-quate decontamination of medical and surgi-cal instruments and devices, yet in practice,hospitals determine which protocols to employ,

Medical Sterilization: Definitions and Guidelines

10

and sterilization and/or disinfection practicesmay differ significantly among institutions.

Guidelines for Sterilization Va l i d a t i o n

There is no such thing as “partial sterility” or “degree of sterility.” Items are either sterileor nonsterile. Sterilization technologies canbe deemed effective only when methods existto ascertain the success or lack of success ofeach sterilization cycle. Absolute sterilityassurance would require laboratory testing todetect the presence of single microorganisms,viruses, and bacterial spores—a goal that notest method can actually achieve. Instead,guidelines have been developed for assessingdegrees of microbial contamination.

In the United States, the widely acceptedAssociation for the Advancement of MedicalInstrumentation (AAMI) guidelines recom-mend that steam and EtO equipment (repre-senting the majority of healthcare sterilizers)demonstrate at least a 10-6 sterility assurancelevel (SAL), i.e., that the probability of a definedbioburden (selected bacterial spores on a par-ticular object or volume of liquid) survivingafter exposure to the sterilization process is nogreater than one chance in one million.9 TheAAMI guidelines dictate that the organismused in the biological challenge should be asresistant as possible to the sterilization pro c e s sbeing monitored, and recommend specificbacteria for use as biological indicators.

The AAMI guidelines also discuss the “overkillmethod” of assuring sterility. In this method,sterilization conditions are established that will

kill highly resistant bacterial spores, followedby an additional safety factor of sterilizationtime or intensity appropriate to the steriliza-tion method that is added to the cycle. T h econditions re q u i red for “overkill” are thus farmore severe than those established for inacti-vation of the most resistant organisms.

In the evaluation of new sterilization technol-ogy, the FDA has established a number of validation tests designed to demonstrate anacceptable level of efficacy and safety beforenew sterilizer technologies are approved.Sterilizers that use technology available prior to1976 are grandfathered under the MedicalDevice Amendments of 1976, allowing t h e i rcontinued marketing. Sterilizer technologiesdeveloped since that time, however, mustshow evidence of extensive sterility validationtesting to gain FDA clearance to market.

Among the important efficacy requirementsfor FDA marketing clearance are:

• Spectrum of activity. The manufac-t u rer must demonstrate that the s t e r i l i z e r is effective against a widerange of clinically important micro-bial organisms.

• Efficacy against most resistantstrains. Efficacy validation must beperformed using organisms (usuallybacterial spores) that have beenshown to be the most resistant to thenew technology.

• Appropriate SAL level. The manu-facturer must demonstrate that theinstrument is capable of killing adefined b i o b u rden in one-half the usual cycle time.

11

• Biological indicators. A validatedand reliable biological indicator mustbe developed (liquid chemical germi-cides still do not have this require-ment) and cleared for marketing.

• Critical process parameter study. Astudy is required, with appropriate

statistical analyses, which establishesthat sterility will be consistentlyachieved when critical process para-meters operate within a defined r a n g e . This assures the operator that as long as there is no operationalerror or equipment failure, sterility is achieved.

12

Although the vast majority of microor-ganisms do not pose a risk to humans, a few do cause illness, including seriousdisease and death. Avenues of researchin the field of sterilization have focused

on the development of technologies that canensure the absence of microbial life forms onmedical and surgical instruments, thus pre-venting the transmission of potentially life-threatening organisms to the patient.

Medical sterilization technologies can bebroadly placed into two categories: high-temperature and/or high-humidity or low-temperature and/or low-humidity. The following represents a brief overview of theprimary technologies used in healthcare insti-tutions today to sterilize medical devices andsurgical instruments.

H i g h - Temperature and/or High-Humidity Te c h n o l o g i e s

Dry Heat

Dry heat sterilization is a general term for anumber of different technologies having incommon only that water is not added to thesterilization chamber.10 In fact, dry heat canbe viewed as any sterilization process wherethe amount of moisture is less than 100% (i.e., below 100% relative humidity). Dry heat sterilization often is considered the system of

choice for sterilizing heat-stable items andsurgical instruments that may be damaged bymoisture or are of a design that moisture failsto penetrate. Examples of such materialscommonly used in the healthcare settinginclude powders and certain liquids.11

Materials to be sterilized are placed in an oven-like chamber and are subjected to temperature sthat range from 160–180°C (320–356°F) for 60–180minutes (not including the heat-up and cool-down cycle times, which can be significant).1 2 , 1 3

Dry heat sterilization technology has severaladvantages over other general-use methods.It is less destructive to many materials thansteam, which can be corrosive to metal objectsand damaging to certain glass surfaces.14

Unlike EtO sterilizers, dry heat systems donot leave toxic gas residuals on sterilizeditems following the completion of a s t e r i l i z a-tion cycle—an important consideration forboth staff and patients.13 Furthermore, sincethe items to be sterilized are directly e x p o s e dto the heat, wrapping of the materials often isnot necessary.11 Finally, dry heat sterilizersand protocols are relatively straightforwardwith minimal danger to staff if they are main-tained well and operated correctly.

Dry heat sterilization also has a number ofsignificant disadvantages.14 For example, theheating and cooling times of dry heat sterilizersoften are lengthy (2–5 hours) because air is apoor conductor of heat.12 The killing rate ofbacteria and bacterial spores also is slow withdry heat technology, so that the time required

Strengths and Limitations of Traditional Sterilization Te c h n o l o g i e s

13

to effectively sterilize instruments is relativelylong. Finally, dry heat sterilization requireshigh temperatures; many materials are unableto withstand these temperatures because ofthermal decomposition that leads to damageor destruction of the instrument or device,requiring premature replacement.

S t e a m

Steam sterilization (often referred to as auto-claving) is a traditional and dependablemethod of sterilization for many applicationsin healthcare.15,16 Steam sterilization is per-formed under high pressure at temperaturesthat range from 121–140°C (250–284°F), which is lower than temperatures required for dry heat sterilization. Sterilization timesrange from 5–45 minutes, depending on theitems to be sterilized.

Many solids and some aqueous liquids (e.g.,saline) can be sterilized by steam techniques.For solids, proper packaging is important inorder to allow the steam to contact all surfacesand condense while simultaneously allowingfor the removal of air—failure to completelysterilize an item due to entrapped air orimpervious surfaces is common.12 Whenwater condenses on the surface of an instru-ment, the latent heat that is re l e a s e d brings thetemperature of the object rapidly to tempera-tures that ensure sterilization.10

The main advantages of steam include the relatively short processing times and the lackof toxic residues following sterilization.The main disadvantages of steam are the relatively high temperatures necessary forsterilization and the inability to sterilize products that are either moisture-sensitive or moisture-impermeable.13 In addition, a

number of important variables—temperature,time, steam saturation, steam purity, and s t e a m availability (within the object to be s t e r i l i z e d ) —can adversely affect the efficacy ofthe sterilization process.17 Finally, employeesare at risk for burns due to the high tempera-tures involved with the process.

L o w - Temperature and/or Low-Humidity Te c h n o l o g i e s

Liquid Chemical Germicides

Liquid chemical germicides (LCGs) are com-monly used agents in the healthcare setting.While dry heat, steam, and EtO sterilizationmethods are used for the majority of health-care sterilization applications, LCGs do find appropriate, albeit limited uses with asmall number of delicate medical devices,including endoscopes.

A few LCGs—glutaraldehyde, hydrogen per-oxide, formaldehyde, chlorine dioxide, andperacetic acid—have been approved by theFDA for use as sterilants, but most LCGs aredisinfectants, not sterilants.4 Chemical steri-lants have few advantages other than conven-ience. The disadvantages generally outweighthe benefits when a rigorous analysis is per-formed. For example, each of the approvedsterilants also can be used as a disinfectant,depending on how long the device is exposedto the LCG, thus raising the possibility ofinadvertent substitution of less effective disin-fection protocols (concentration of sterilant,soaking time, proper cleaning, etc.) when steri-lization was intended. Thus, the potential foruntrained or busy personnel to disinfect,rather than sterilize, an instrument is high.

14

This is particularly troublesome in light of the fact that LCGs do not have establishedmethods to monitor sterilization success.

Patient and employee safety issues with LCGsalso are worth considering. For example, dire c tcontact with glutaraldehyde can be very irri-tating to the skin, causing chemical dermatitisor exacerbating an existing case of eczema.18

Breathing glutaraldehyde vapors can irritatethe nose and mouth as well as induce cough-ing and bronchospasm even in previouslyunexposed individuals.18

Ethylene Oxide

Ethylene oxide is a small, simple organic molecule that has, in many ways, revolution-ized the medical and surgical product mar-kets over the last 40 years. Compared withdry heat and steam sterilization technologies,the conditions under which EtO is used leadto relatively little damage to delicate andcomplex surgical instruments.10

For healthcare applications, EtO can be usedeither in a pure form or, more commonly, as amixture with a “carrier” gas. The carrier gasis usually chlorofluoromethane—a chlorofluo-rocarbon (CFC)—in a 12% EtO, 88% CFCratio.19 The “12/88” blend is used more

commonly than pure EtO in healthcare facili-ties because it reduces the flammability andexplosiveness of EtO. In addition, systemsthat use blended gases have lower overallcapital acquisition costs than those that useunblended gases.

The chief advantages of EtO sterilization ofhealthcare products are the low temperaturestypically employed (25–75°C or 77–167°F) and the wide range of EtO-compatible med-ical and surgical instruments and devices.Microorganisms (including spore-formingbacteria, fungi, and viruses) are effectivelydestroyed by chemical reactions with the EtOmolecules—both cellular components andgenetic material are destroyed or alteredbeyond the ability to function following exposure to EtO.19

Ethylene oxide is not without problems, how-ever, some of which are difficult to overcome.For example, EtO is a very toxic gas withpotentially significant risks to both employeesand patients (see: Issues of Safety with Tradi-tional Low-Temperature Sterilization Technol-ogy, page 12). In addition, most EtO systemsuse the 12/88 mixture to decrease the flam-mability and explosiveness of EtO, but theproduction of CFCs in the United Statesceased at the end of 1995 for environmentalreasons (issues pertaining to the use of CFCswill be discussed in a later section).

15

Progress in medical care often is drivenby advances in technology. In the fieldof sterilization, advances in medical ands u rgical devices are placing new demandson sterilization pro c e d u res and personnel.

In addition, issues of patient and employeesafety, costs associated with traditional tech-nologies, and environmental hazards are creating pressure for new technologies.

New Demands

The primary goal of medical sterilization is top revent infections during medical and surg i c a lp ro c e d u res. The complexity of the process thatsurrounds this goal, however, often obscuresthe role sterilization must play in protectingpatients’ health. As noted previously, disin-fection is not a substitute for sterilization. Ster-i l i z a t i o n is the ideal procedure for all medicaldevices and surgical instruments used for inva-s i v e procedures that place a patient at risk ofinfection. As a result, diligence in the choice ofsterilization methods provides the greatest mar-gin of safety for every patient that receives care .

A significant problem for infection controlspecialists arises from the frequent intro d u c t i o ninto medical practice of sophisticated, hard-to-sterilize instru m e n t s .2 0 While these devicesplay an important role in the treatment of dis-ease, it is important that they also do not con-tribute to disease. A thorough evaluation andexamination of the sterilization requirem e n t s

for each new, invasive item purchased by theinstitution is important to maintain controlover the spread of increasingly dangerousand difficult-to-treat microbial diseases.

Minimally invasive surgery has initiated arevolution in the manner in which surgery isperformed. Originally, minimally invasivesurgical techniques were almost exclusivelyused by gynecologic and orthopedic sur-geons. Since the late 1980s, minimally inva-sive surgery has gained rapid acceptance inthe general surgical environment as an alter-native to traditional, and more expensive, surgical techniques. The driving force behindthe growth of minimally invasive surgery has been a juxtaposition of technology andeconomics. In the mid- to late-1980s, endo-scopes became sufficiently advanced to allowsurgeons to perform such operations as gallbladder and appendix removal, and to perform a wide variety of diagnostic and therapeutic procedures with minimally inva-sive techniques. Hospitals also were undergreat pressure during this time to reduce theaverage length of stay of all patients; thosewho did not need to recover from the largeincisions associated with many forms of traditional surgery could be discharged more rapidly.

In most endoscopic procedures, the instru-ments (either flexible or rigid) come into contact with mucous membranes or are placedinto sterile areas of the body. As such, endo-scopes are considered semicritical or criticaldevices.4 Depending on the intended use,

Emerging Issues with Traditional L o w - Temperature Sterilization Te c h n o l o g y

16

endoscopes must be either disinfected or steri-lized prior to their next use. Though steriliza-tion rather than disinfection of endoscopeswould be ideal, in practice many endoscopesare only disinfected.20 In a recent survey ofmore than 100 hospitals in North Carolina, 57%p e r f o r m e d “high level” disinfection (with 2%glutaraldehyde) while only 17% sterilizedtheir endoscopes with EtO.21

There are numerous descriptions in the litera-t u re of serious, and sometimes fatal, infectionsbelieved to be associated with improper endo-scope decontamination.22,23,24,25,26 The majortechnical barrier to adequate sterilization ofendoscopes is inherent in their design. Endo-scopes are complicated devices that containnumerous channels and crevices that arepoorly accessed by sterilizing chemicals andg a s e s .2 7 In addition, sterilization by traditionalmethods—dry heat, steam, EtO, and liquidchemical germicides—can damage or destroythe delicate mirrors and cables commonlyfound in endoscopes.28,29,30

There are a number of incentives to choosedisinfection over sterilization for these com-plicated instruments, the most significant per-haps being economic. Sterilization with EtOoften requires a turnaround time of 12 hoursor more. This slow turnaround time eff e c t i v e l yremoves a particular instrument from surgicaluse for the rest of the day. Limiting the avail-ability of these expensive devices because of slow sterilization cycle times adds to thecost of providing patient care.27,31,32 With thecost of equipment inventories placing increas-ing pressures on hospitals, the use of rapiddisinfection instead of sterilization, thoughpotentially subjecting patients to increasedrisk, is a choice that is increasingly made.

Choices in sterilization technology acquisitionmust account for the ever- i n c reasing complexity

of emerging surgical and medical instrumen-tation. The level of sophistication in i n v a s i v ei n s t ruments often outpaces the ability of traditional sterilization technologies to meet the requirements of both sterilizationand instrument protection. Damaging anitem while sterilizing it, however, is not a reasonable choice. New technologies thatcome closer to accomplishing the goal of sterilization of a wide range of medicaldevices and surgical instruments should beevaluated to address this problem.

Health and Safety Issues

In hospitals today, ethylene oxide is consid-ered the sterilization technology of choice forheat- and moisture-sensitive medical devicesand surgical instruments. The other traditionalsterilization technologies—dry heat, steam,and liquid chemical germicides—are usedmore for specialty applications. As a result,the significant issue of safety is focused onEtO as a stand-alone technology rather thanon the other, less-utilized methods.

The healthcare institution is charged withensuring, to the best of its ability, the safety of its patients, visitors, and employees. In an ever-litigious society, much effort goes into reducing the potential for liability, thusprotecting the institution from avoidable andcostly litigation.

Occupational Health Risks

In the healthcare setting, there are numerousand often unseen hazards that may be encoun-t e red by employees on a daily basis. In hospital

17

a reas that perform sterilization, occupationalh a z a rds include exposure to high-temperaturesterilizers, liquid chemical sterilants, andespecially ethylene oxide, a very toxic gas.

In the most recent United States governmentstudy on the effects of ethylene oxide expo-sure, an estimated 90,000 hospital workerswere exposed annually, either directly or indirectly, to EtO.33 Although acute exposureto high levels of EtO is rare in the healthcaresetting, low-level exposure is more common.The long-term effects of low-level exposureare only just beginning to be fully understoodand appreciated.34,35 Acute and chronic exposure to EtO can cause respiratory tractirritation, central nervous system disorders,gastrointestinal problems, and chemicalburns.36,37 In addition, occupational exposureto EtO has been linked to changes in the structure of human chromosomes, anincreased risk of cancer, and an increased rate of spontaneous abortions and birthdefects.38,39,40,41,42,43,44,45

The significant potential for harm to hospitalpersonnel prompted the Occupational Safetyand Health Administration (OSHA) in 1984 to place tight restrictions on occupationalexposure: 1 part per million (ppm) over an 8-hour time period.46 This directive, updatedin 1988, is monitored through EtO detectors(EtO is odorless to humans up to a thresholdof 100 ppm—a dangerous level) and medicalmonitoring of employees.47 Importantly, anumber of studies have demonstrated bio-chemical and biologic effects on healthcareworkers at or below the limits for EtO expo-sure. As noted by Schulte and colleagues:

…[T]he results indicate that workplacelevels which meet the current OSHA standard do not protect against certain

biologic changes associated with ethyleneoxide exposure.44

The respected International Agency forResearch on Cancer has recommended thatEtO be reclassified from a Class IIA (probablehuman carcinogen) to a Class IA (recognizedhuman carcinogen).48 As noted by Siegel and Bunn:

Hospitals are under increased scrutiny forall hazardous exposures under OSHA’s‘general duty’ clause….In the standard[Occupational Exposure to EthyleneOxide, 1984, OSHA], OSHA acknowl-edges the potential risks to health posed byethylene oxide exposure. This acknowl-edgment of risk provides a legal basis for lawsuits.49

Clearly, the risks to employees as a result ofthe use of EtO as a sterilant can be significant.Every institution that continues to use a technology with such well-documented short- and long-term harmful effects runs therisk of substantial financial burden in com-pensation to those who can demonstrate per-sonal damage. Some of the tests for geneticdamage are relatively simple to perform, and are accessible to any employee who may request them. The continued exposure of employees to EtO can thus damage an institution in two ways: by harming its valued employees and, possibly, its financial well-being.

Patient Health and Safety

The acute toxicity associated with low-levele x p o s u re of patients to EtO was first re c o g n i z e din the 1970s. Patients suff e red chemical burns,

18

inflammatory reactions, and even death dueto improper aeration pro c e d u re s .5 0 , 5 1 N a t i o n a lguidelines for aeration were defined in thelate 1970s, aimed at reducing the risk of EtOresidual-associated patient injuries. Recentreports, however, have underscored the factthat despite strict regulations regarding EtOaeration cycles, patient injuries still occur.

Anaphylaxis, an allergic reaction that can be fatal, has been reported in patients under-going renal dialysis with EtO-sterilizedhemodialysis equipment.52,53,54 In addition,EtO-sterilized tissues commonly used inorthopedic surgery have been implicated inpostoperative adverse reactions.55 Whilereports in the literature would indicate thatEtO-associated adverse reactions are uncom-mon, the actual rate of injury may be muchhigher, as pointed out by McGreevy Steelman:

Because of the seriousness of the issue andconcerns about accreditation and publicimage, hospitals may be unwilling to pub-lish manuscripts indicating noncompli-ance….[P]erioperative nurse managers…indicated that patients who came into con-tact with improperly aerated instrumentswere not followed to see if injuries weresustained. This poses a very serious concern for the quality of care in operating rooms.51

As the role of EtO residue in nosocomial disease becomes better understood, risk management in this area will be increasinglyimportant. With the long sterilization pro-cessing times associated with EtO—some-times approaching 24 hours—the temptationto speed up the process increases. In thesec a s e s , sterility cannot be guaranteed. Eachtime an i n s t rument or device whose sterility isin doubt is used on a patient, the possibility

exists of an adverse event occurring. Theevaluation of traditional sterilization tech-nologies and the newer methods that havefewer opportunities to cause patient harm canhelp to address the issue of providing betterpatient care without the risk of serious adverseevents. The decreased potential for inadver-tent patient harm can have a positive bearingon the financial well-being of the institutionand the general level of care in the hospital.

Environmental Issues

High-temperature and/or high-humidity sterilization methods pose little environmen-tal danger if they are kept in proper workingorder. Liquid chemical germicides, whileexhibiting environmental toxicities muchgreater than dry heat or steam, n e v e r t h e l e s sa re considered reasonably safe due to adequatedisposal mechanisms. Ethylene oxide, however,is toxic to all living things even at extremelylow concentrations; because of this, it wasconsidered as a potential chemical warfareagent during World War I.56 It is preciselythis property of EtO that makes it an excellentsterilant, and a dangerous chemical to all who may inadvertently come in contact withit. In order to achieve a degree of safety forhospital staff during a sterilization cycle, EtOmust be released directly into the atmospherethrough a complicated series of pipes andvents to ensure no possibility of a leak. Thisprocess is under increasing attack due to its toxicity to all forms of life, just as CFCemissions were attacked due to their effect on the atmospheric ozone layer.

The Environmental Protection Agency (EPA) recently has proposed a set of national

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regulations under the Clean Air Act to curbthe release of EtO into the atmosphere byl a rge-scale industrial sterilizer sites.5 7 , 5 8 W h i l ethere is cause for concern by healthcare insti-tutions regarding these new regulations, theEPA currently considers the discharge levelsof EtO by individual hospitals too low to bea ffected by the proposed abatement re g u l a t i o n s .Once full implementation of the strict discharg eregulations occurs at the large-scale industrialsterilization units, however, healthcare insti-tutions could be targeted for enforcementsince they are not excluded from the regula-tions, only considered too small at this partic-ular time to be worthy of regulatory oversight.

Of more concern to hospitals is the likelihoodthat state and local regulatory agencies, usingEPA regulations as a model, will require EtOgas abatement. In states such as California,Michigan, New York, Texas, Wisconsin, andlocal areas such as the Puget Sound Basin ofWashington state, regulatory agencies gener-ally have required a 95–99.9% reduction in allEtO emissions.59 Any large metropolitan areanot in compliance with the EPA’s limits onenvironmental pollution can reasonablyexpect to be placed under similar restrictionswithin the next several years.

Scientists have recently confirmed that the CFCsused with EtO sterilizers are contributing tothe destruction of the ozone layer in the upperatmosphere.60,61 In an unusual display of sci-entific, political, and economic unity, the UnitedStates and the European Community (EC)signed the Montreal Protocol in 1987, whichbanned the manufacture (and, ultimately, theuse) of CFCs by the end of 1995 in the UnitedStates, and by 2003 in EC countries.62

H y d ro c h l o ro f l u o rocarbons (HCFCs), a re p l a c e-m e n t for CFCs used with EtO sterilizers thatare claimed to be less harmful to the ozonelayer, also are subject to the internationalagreement.63 Although the EC originally proposed the year 2015 for the completion of a phase-out of all substances other thanCFCs that deplete the ozone layer, includingHCFCs, the governing body of the EC has infact recently voted for stricter controls with aview toward phasing out production by theyear 2003.

Once CFCs and HCFCs are unavailable, somehospitals may re t rofit their EtO sterilizers to use100% EtO—an expensive option that does notaddress worker and patient safety issues andonly partially addresses the environmentalconcerns. In fact, as the number of institutionsusing EtO declines, and those that remain beginto utilize 100% systems, the EPA may find itmuch easier to closely monitor those hospitalsthat made the choice to continue to use EtO.In addition, because 100% EtO systems will usem o re EtO each year, federally imposed storagesafety requirements for the larger quantitiesof the flammable gas will place a further eco-nomic and space burden on hospitals.

Other hospitals may opt to retrofit their steri-lizers to accept a different carrier gas, such ascarbon dioxide (CO2) in a mixture of 90% CO2

and 10% EtO (“90/10” systems). Aside fromthe cost of the retrofit—which includes theinstallation of new cylinders that can handlehigher pressure gas—additional tanks of car-bon dioxide will have to be stored and han-dled. More o v e r, the sterilant would still be EtOand the concerns about employee, patient,and environmental safety would remain.

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Economic Issues

Taxes and Regulation of Carrier Gases

To curb CFC use prior to the production cut-off date at the end of 1995, the United StatesCongress levied a punitive excise tax on CFC use in 1989 that escalated annually to ahigh in 1995 of $5.35 per pound.64 The tradepublication OR Manager reports that, as aresult, a typical 300-bed hospital using an esti-mated 5,280 pounds of CFCs per year wouldhave paid $28,000 in taxes in 1995, comparedwith $8,800 for the same level of usage in1993.65 If the United States follows the lead of the EC, the date of 2030 for HCFC phase-out in the United States mandated by theClean Air Act may be revised, and healthcarefacilities could soon be facing a similar tax forHCFC usage.

Monitoring Costs

The degree of medical monitoring required byOSHA of employees potentially exposed toEtO is extensive, and includes medical andwork history, an annual physical examinationwith particular attention paid to organ sys-tems known to be affected by EtO exposure,and a complete blood work-up.47 The costsassociated with this medical monitoring canbe significant. In fact, in 1985, they were esti-mated to exceed $70 million per year.49 Sincemedical surveillance is a mandated functionthat must be performed if an institution usesEtO gas sterilization, these costs must be con-sidered as direct costs associated with EtOsterilization equipment.

Medical monitoring of employees exposed to EtO is not the only monitoring cost associ-ated with EtO technology. OSHA regulationsrequire environmental monitoring before,during, and after each sterilization run.47

Environmental monitoring, which must beavailable to employees at all sites of potentialEtO exposure, can be one of a number oftypes of tests including personal dosimetry(monitoring) and direct-reading continuousanalysis of the area where EtO is used. Con-sidering methods to comply with OSHA’smandate, Gschwandtner and colleaguesreported that there was probably no singlebest method for monitoring personal expo-sure to ethylene oxide in all situations. Theyrecommended that a combination of proce-dures should be used for effective monitoringof the environment.66

These EtO monitoring costs, including insur-ance premiums that have been estimated at$4,000 per year or more per EtO sterilizer, and those associated with general and emer-gency training of staff, can add a significantfinancial burden to the department responsi-ble for sterilization and to the healthcare institution as a whole.67

Instrument Processing and Inventory Management

Hospitals are under increasing pressure tocontrol the costs of performing surgery, which include staffing and maintaining the operating suite, central supply, surgicalpathology, and recovery. This pressure comesnot only from within, but also from emerg i n gn o n - t r a d i t i o n a l venues such as off-site surg i c a llocations. These sites can compete for the surgical dollar in a number of ways important

21

to this discussion, including the ability to con-centrate selectively on high-volume, low-costsurgical practices.

In an effort to reduce surgical costs, institu-tions are beginning to look more closely at the time required to complete sterilizationcycles of surgical instruments. As alreadymentioned, EtO sterilization can take 12–24hours to complete, due mainly to the extendedaeration cycle required to eliminate residualEtO on the instruments. In a recent HealthDevices report, it was noted that, comparedwith EtO sterilization systems, an emergingsterilization technology demonstrated:

…[a] throughput…about five times higher…than in the larger EtO sterilizer(if aeration time is included). The largerthroughput translates to faster instrumentturnaround and potentially places lessdemand on instrument inventory.68

As noted in this report, less demand on instrument inventory can be expected totranslate into lower inventory carrying costs, with a commensurate decrease ininventory budgets. The reduction of expen-sive surgical instrument budgets is one goalmany institutions now have in a global

program to lower operating room costs and increase competitiveness for managedcare contracts.

Sterilization vs. Disinfection

Utilizing disinfection inappropriately as asubstitute for sterilization without writtenpolicy and procedure guidelines, training,and other safeguards can pose a significantfinancial risk in the event of litigation. Evenwith guidelines, successful high-level disin-fection depends on trained staff, sterilityassurance monitoring, and other difficult-to-control variables.

Presumably, hospitals would gladly sterilizeinstruments instead of merely disinfectingthem, so long as a new technique was fast,effective, and at least as harmless to instru-ments as EtO or steam. In addition, any new sterilization technology must not be haz-ardous to employees, patients, or the environ-ment. Finally, ideal technology for fiscallyconstrained healthcare institutions shouldhave a significantly shorter cycle time andcost substantially less to purchase, install, andoperate than existing sterilization technology.

22

The inherent toxicity and danger of tradi-tional sterilization processes argue forthe development and adoption of bettersterilization technologies. Any newtechnology should be safe for employ-

ees and patients throughout the sterilizationprocess and the subsequent use of the steri-lized instruments and equipment. Ideally, thesterilant should be effective at low tempera-tures and packaged in such a way that spillsand leaks would be virtually impossible,eliminating the need for protective garments,badges, and monitoring equipment. Janssenand Schneider have suggested several addi-tional attributes of an ideal sterilization tech-nology for hospital use, including:20,69,70

• High efficacy—must be shown to bebactericidal, sporicidal, fungicidal,and virucidal

• Cost—must have reasonable equip-ment, operating, and installation costs

• Rapid activity—resulting in shortcycle times to reduce instrument carrying costs

• Strong penetrability—to ensure sterilization of device lumens as wellas packaging materials

• Materials compatibility—the sterilization process should be non-damaging to devices and packagingmaterials and should not alter theappearance of instruments

• Nontoxic—must be safe for workers,patients, and the environment

• Adaptability—should require little orno site modification for installation atpoint of use

• Organic material resistance—shouldbe able to withstand reasonable challenge (bioburden) without loss of efficacy

• Monitoring capability—should beeasy and accurate, with approvedchemical and biological indicators

Several new technologies have been devel-oped to more effectively address these safety,efficacy, installation, operation, and environ-mental goals, to varying degrees of success.

Vapor Phase Hydrogen Peroxide

Liquid hydrogen peroxide solutions have beenused to disinfect instruments for many years.6 9

Vapor phase hydrogen peroxide sterilizationbegan in the food industry and reached thehealthcare market in the mid-1980s.71

Two approaches for the use of vapor phasehydrogen peroxide in medical settings havebeen developed. The first uses a deep vacuumto pull liquid hydrogen peroxide (30%) from

Newer Low-Temperature Sterilization Te c h n o l o g i e s

23

a cartridge through a heated vaporizer andinto the sterilization chamber.72 This processoperates at temperatures of 55–60°C. The sec-ond method uses a flow-through approach, inwhich the vaporized hydrogen peroxide isbrought into the sterilization chamber by acarrier gas.

Although vapor phase hydrogen peroxide sys-tems meet several of the criteria for an idealsterilization technology, t h e y cannot be usedwith highly absorptive materials such as cel-lulosic materials, nylon, and certain types ofrubber.6 9 Moreover, polypropylene/polyesterpackaging has been shown to retain hydrogenperoxide residues, necessitating post-steriliza-tion aeration.73 Because of exposure concernswith the 30% hydrogen peroxide during loadingof the cartridges, operators must wear pro t e c t i v egarb and installation requires special ventingand emission monitoring considerations.

O z o n e

Ozone, used for many years to disinfectdrinking water, is created by producing anelectrical discharge in the presence of oxygenor air.7 4 Ozone is a naturally occurring, highlyreactive form of oxygen that is very unstable.Ozone quickly converts back to stable oxygen.

The medical sterilizer combines ozone with humid air which is passed through thesterilization chamber.7 0 Sterilization cycles takeup to two hours to complete. At the completionof a cycle, the sterilizer is purged by the flowof regular oxygen or air and residual ozone iscatalytically converted back to oxygen.75

The ozone-based system has the advantage of nontoxic by-products, low operational tem-peratures (25°C) and a relatively short (com-pared with EtO) cycle time of 1–3 hours.69,76

Although the cycle time is relatively fast anddoes not require prolonged aeration, ozonesterilization is unsuitable for moisture-sensi-tive instruments. Moreover, some packagingmaterials, certain types of rubber, and manyplastics may be damaged by exposure to thehighly reactive gas. Also, the gas must begenerated on-site at the time of the reactionfrom oxygen stored in large containers,adding to the complexity of the operation.Finally, concerns about penetrability intomaterials also exist.

Liquid Chemical Sterilants

A liquid peracetic acid (peroxyacetic acid)sterilizer was introduced for commercial use in the late 1980s. The technology uses0.2% peracetic acid (an oxidizing agent) inwhich the instruments are immersed forapproximately 30 minutes. Although fast, the system can only sterilize immersible items and requires the use of filter-sterilizedwater and sterile air since the items to be sterilized are not wrapped or otherwise protected while in the immersion chamber.

Liquid chemical sterilizers using peraceticacid have two main advantages over traditionalchemical sterilizer technologies: no overtlytoxic end-products (peracetic acid breaksdown into acetic acid [vinegar] and oxygen)and a short cycle time.20

24

The disadvantages of current liquid peraceticacid systems include limited capacity (currentmodels can only sterilize one large endoscopeat a time) and no available biological indica-tor.20 As discussed earlier, because a biologi-cal indicator is not available to monitor liquidchemical sterilizers, there is considerable debateas to whether items are truly sterilized or onlydisinfected.77 In addition, exposure to liquidperacetic acid has been linked to skin and eyeirritation as well as occupational asthma, nau-sea, and headache.78 Liquid sterilants alsomust be monitored daily to ensure that theyhave not become contaminated or diluted.

Gas Plasma Systems

Scientists refer to gaseous plasma, not to beconfused with blood plasma, as the fourthstate of matter, different from solids, liquids,and gases. Plasmas are cloud-like collectionsof ions, free electrons, and neutral atomic andmolecular species that occur naturally in outerspace. One of the more prominent plasmas in nature is the aurora borealis, or “northernlights.” An everyday example of a gas plasmais a neon light—its glow is the result of elec-trical energy applied to a reactive gas.

Forming a low-temperature plasma requires aclosed chamber, a deep vacuum, a chemicalprecursor from which to derive the plasma,and a source of electromagnetic energy, suchas radio frequency (RF) energy, to create anelectromagnetic field to generate the plasma.The electromagnetic field interacts with thechemical—hydrogen peroxide, for example—and creates a number of highly reactive species.Hydrogen peroxide and the highly reactiveagents are capable of quickly destroying the

difficult-to-kill bacterial spores with no toxic residues.

Mixed Chemical Plasma

A mixed chemical plasma (MCP) devicebecame available in January 1995. The MCP system uses a two-phase process that is repeated for a total of six times during the 4-hour sterilization cycle to achieve fullsterilization.79 In the first phase, a 5% liquidperacetic acid is infused into the sterilizationchamber and vaporized. This vapor then diffuses throughout the sterilization chamberfor a period of time.68 It is during this phasethat the majority of vegetative bacteria isdestroyed. The remaining vapor is venteddirectly into the atmosphere.

In the second phase, a plasma is formed in aseparate reaction chamber when vaporizedhydrogen, oxygen, and argon are exposed toan electromagnetic field. The products of thisreaction then flow into the sterilization cham-ber to complete the sterilization cycle.

Currently, the MCP method has been clearedby the FDA to sterilize stainless steel surgicalinstruments. One advantage of this system isthat it can be used with Tyvek® and Tyvek/Mylar packaging.

While considerably faster than EtO, the MCPsystem still has a relatively slow sterilizationtime—over four hours.79 In addition, the sys-tem must be permanently placed with a ventto the exterior of the building to allow theremoval of the vaporized peracetic aciddirectly into the atmosphere. Finally, theMCP system requires the storage of large,high-pressure gas cylinders and smaller

25

bottles for the peracetic acid solution—each contributing to toxic materials storageand handling (workers with bottles andtanks) requirements that must be addressedby the hospital.

L o w - Temperature Hydrogen Peroxide Gas Plasma

Low-temperature hydrogen peroxide gasplasma sterilization, available in the UnitedStates since 1993, is different from the MCPtechnology described above. In this process,hydrogen peroxide plasma is formed directlyin the sterilization chamber rather than in aseparate reaction chamber.

During low-temperature hydrogen peroxidegas plasma sterilization, medical devices and surgical instruments are placed in thesterilization chamber and a vacuum is applied to remove the air. A solution of 58%hydrogen peroxide in water is injected into an outer chamber from a self-contained cassetteinserted by the operator at the beginning of every 10 sterilization cycles. The solution is then vaporized and allowed to diffusethroughout the sterilization chamber, sur-rounding the items to be sterilized. Radio frequency (RF) energy is then applied to create an electromagnetic field, which in turninitiates the generation of the plasma. At theconclusion of the sterilization cycle afterapproximately one hour, the electromagneticfield is turned off, and the reactive hydrogenperoxide species rapidly revert to primarilywater vapor and oxygen. The sterilizationchamber is repressurized and the air is passedthrough an activated charcoal filter to removeany residual hydrogen peroxide.80,81

Advantages of the low-temperature hydrogenperoxide gas plasma system include an excellent safety profile for employees. UnlikeEtO, liquid chemical sterilants, and otheralternative sterilization technologies, the low-temperature hydrogen peroxide gas plasmasterilizer poses little risk to operators and theenvironment. Exposure to hydrogen peroxidehas been limited to 1 ppm over eight hours byOSHA. Monitoring by OSHA of the externalenvironment of the sterilizer during operationdemonstrated that the average concentrationof hydrogen peroxide in the atmosphere over eight hours was 0.018 ppm while thepersonal sample exposure was determined to be 0.013 ppm.82

Safety for patients has been establishedthrough laboratory tests of the low-tempera-t u re hydrogen peroxide gas plasma technologyprior to marketing clearance in 1993. Thesetests demonstrated that this technologydestroys a broad spectrum of microorganisms,including Gram-negative and Gram-positivevegetative bacteria, mycobacteria, yeasts, fungi, and viruses, as well as highly resistantaerobic and anaerobic bacterial spores.81,83

In addition, as the hydro g e n peroxide breaksdown into water and oxygen, there are noconcerns about toxic residues following thecompletion of a sterilization cycle. Studieshave demonstrated that items processed bythis technology are nonirritating and nontoxicto cells and tissues.8 1 , 8 4

Significant economic advantages have beenassociated with low-temperature gas plasmasterilization as well. For example, because ofits extremely rapid cycle time (about one hour),inventory of expensive surgical instrumentssuch as rigid endoscopes can be reduced whilestill ensuring that every patient receives a

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sterilized—not just disinfected—device at anygiven time of the day. In addition, for a widerange of medical and surgical instrumentsprocessed by low-temperature hydrogen p e roxide gas plasma sterilization, significantlyless deleterious effects on metal items havebeen observed compared with steam steriliza-tion, reducing replacement costs of expensivesurgical instruments.81,84 Since there are noinstallation requirements except a modified208-volt electrical outlet, the system can beplaced almost anywhere—including the sur-gical suite—to facilitate the distribution ofsterile instruments.85 Finally, since prepara-tion of items for sterilization is similar to EtO processing, consisting of instrumentcleaning, reassembly, and packaging in c o m-m e rcially available, nonwoven polypro p y l e n ewraps, employee training costs can be kept to a minimum.

Environmental concerns are addressed in thefundamental manner in which the technologyoperates: self-contained ampoules of hydro-gen peroxide are used that virtually eliminateconcerns about exposure to the chemical. In addition, following the completion of thesterilization cycle, the hydrogen peroxide

degrades primarily into vaporized water andoxygen, free of toxic materials associated withother low-temperature technologies.

Disadvantages of this technology include theinability to sterilize linens and other cellu-losic-containing materials, as the hydrogenperoxide reacts with the organic materialfound in these items.86 In addition, becausethe technology relies upon diffusion, materialssuch as powders and liquids cannot be steri-lized. The technology currently has restrictedapplications for n a r row-lumen devices in theU n i t e d States.

As the shift occurs away from traditional low-temperature sterilization technologiessuch as EtO and liquid chemical germicides to the newer methods, the full spectrum ofmedical sterilization technology comes intofocus. While no single technology can hopeto fulfill all the sterilization needs of a hospi-tal, a range of safe, economical choices isimperative. Dry heat and steam will probablyalways have an appropriate place in the pro-vision of this service. Low-temperature sys-tems that are potentially dangerous and costly will not.

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Sterilization is a fundamental link in theprevention, and thus control, of hospi-tal-acquired infections. Modern steri-lization technology provides the marginof safety necessary to allow physicians

and other healthcare professionals to diag-nose and treat the wide range of diseases andinjuries that can affect us all.

In the 1990s, those who are involved withdecisions that affect the way in which steri-lization is performed in the healthcare institu-tion must evaluate three main issues: safety,economics, and the environment. These issuesa re neither simple nor are they fully addre s s e dby traditional sterilization technologies.

Safety of the sterilization equipment andprocesses for employees and patients cannot be underestimated. Employees should not be placed at risk from dangero u sgases, chemicals, or the hazard of potentialexplosions during their work day. Patientsneed to be assured that the instruments anddevices used on them for diagnostic and ther-apeutic procedures are not potential sourcesof harm, and that, in particular, they do notbecome victims of lowered safety margins ininstitutions struggling with economic pro b-lems. As has been demonstrated, the cost toan institution to address these risk manage-ment issues can be substantial with traditionallow-temperature technology.

In an era of increasingly lowered revenueexpectations for healthcare institutions, theeconomics of sterilization are very important.

All sterilization technologies have hiddenc o s t s —training, facilities management, storage,and monitoring, for example—that must beconsidered and compared. Environmentalregulations add significant burdens to theoperating costs of ethylene oxide sterilizationequipment. Abatement, personnel monitor-ing, taxes, and even fines affect the economicsof both the department responsible for steriliza-t i o n and the institution itself. All major fore-casts of the future of surgery suggest thatminimally invasive procedures will grow innumber. Instruments designed for these pro-cedures are delicate and often expensive.New sterilization technologies should be ableto effectively and rapidly sterilize theseinstruments without damage.

Finally, environmental concerns are increasingat every level in this country, and safety for thecommunity becomes an important considerationwhen evaluating new sterilization technolo-gies. The release of overtly toxic gas or otherby-products of sterilization into the environ-ment has become increasingly difficult to jus-tify. Choices in low-temperature sterilizationtechnology must be made with a completeunderstanding of these problems at the local,state, and federal levels.

Summary and Conclusion

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The complexities of modern medical technol-ogy preclude a single form of sterilization;therefore, dry heat, steam, and low-tempera-ture technologies will continue to coexist inthe hospital to ensure that patient care is not compromised.

Ethylene oxide, for many years the mainstay ofl o w - t e m p e r a t u re medical sterilization, has anumber of significant liabilities that hospitalscannot easily ignore. Fortunately, the synerg i s mbetween low-temperature sterilization andthe provision of safe medical and surgical caredoes not need to suffer. Newly availabletechnologies, relying on novel engineering con-c e p t s , have been shown to be capable of meet-ing most, if not all, requirements identified by

hospitals for low-temperature sterilization oftheir medical devices and surgical instruments.

Ethylene oxide sterilization has contributedgreatly to advancements in medical care overthe last 40 years. The liabilities directly asso-ciated with EtO sterilization, however, callinto question its continued use as a medicalsterilant. Low-temperature sterilization is notunsafe or expensive, however, when alterna-tive technologies are utilized. As healthcareinstitutions rapidly move away from the dan-gers of EtO, the problems with burdensomeenvironmental regulations, and the protractedcycle times associated with its use, hospitalsare increasingly relying on safe, economicalalternatives to ethylene oxide sterilization.

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