Glutaradehyde及其衍生物之消毒效果與監測

中華民國防疫學會

王任賢 秘書長

Spaulding’s Classifications

Critical (Sterilize) Semi-critical (Disinfect) Non-critical (Clean)

Endoscopes:

A flexible device used to visualize the interior of a hollow organ such as the GI tract, respiratory tract, urinary tract etc.

Flexible endoscopes are considered semi-critical devices because they come into contact with mucus membranes but do not ordinarily enter sterile tissue or the vascular system. At a minimum, endoscopes are to be cleaned, decontaminated and high level disinfected prior to re-use.

High Level Disinfection

An EPA registered chemical agent with a label claim as a high level disinfectant/sterilant is used per the manufacturer’s instructions for appropriate concentration, submersion and contact time to kill all microorganisms except high numbers of bacterial spores or prions that cause CJD.

Glutaraldehyde

Glut History

Tanning agent for leather Tissue fixative Preservative in cosmetics Therapeutic agent for warts & other infections X-ray processing solution & film emulsion

Uses of CIDEX A disinfectant A tanning agent in leather To sterilize endoscopic instruments,

thermometers, rubber or plastic equipment which cannot be heat sterilized

Glutaraldehyde Disinfection

•Broad spectrum antimicrobial “cold” disinfectant

•Glut action – bonds protein

•Device preparation – thorough cleaning and rinsing

•Efficacy monitoring

•Soak time controversy

Controversy

FDA45 min soak25 degrees C.

Prof. Org20 min soakRoom temp.

Chemical Description Synonyms-- glutaric dialdehyde chemical

formula – C5H8O2

Poisonous, colorless liquid or powder salt Pungent odor Stable Non-flammable when in solution with water Turns green when activated

Glut Advantages

Effective for HLD Highly compatible Sterilization with long soak times Low cost, convenient

Glut Limitations Unstable - Effective life 2-4 weeks Thorough rinsing - mandatory Skin, respiratory hazards Glut bonds proteins

Options for alternatives: Other soaking solutions (Cidex OPA) or sterilization methods

Glut Hazards Skin & mucous membrane hazards Ingestion hazards Respiratory hazards Chronic exposure hazards

Exposure Levels

0.04 ppm Detect odor 0.2 ppm Exposure level 0.3 ppm Irritant 0.4 ppm Pouring

AAMI Document

“Safe use and handling of glutaraldehyde-based products in health care facilities”

AAMI: Association for the Advancement of Medical Instrumentation

New methods in disinfection and sterilization

Regulatory agency actionAgentProcess

FDA cleared, October 1999Ortho-phthalaldehyde (Cidex OPA)

Disinfection

Not FDA/EPA clearedAntimicrobial coating (Surfacine)

Not FDA/EPA clearedSuperoxidized water (Sterilox)

Not FDA clearedLiquid sterilization process (Endoclens)

Sterilization

Not FDA clearedRapid readout ethylene oxide biological indicator (Attest)

FDA cleared, January 1999New plasma sterilizer (Sterrad 50)

Ortho-Phthal-aldehyde (OPA)

Chemical Sterilizaer Advantages:

not eye and nasal passages irritant has excellent stability over a wide range of pH (3 to 9) has a barely perceptible odor Like glutaric aldehyde, it has excellent material compatibility

Disadvantage: It stains proteins gray (including unprotected skin)

OPA vs. Glutaric Aldehyde

Activity of glutaraldehyde and ortho-phthalaldehyde against Mycobacterium bovis

Time for 6-log10 reductionaDisinfectant 28-36 minutes1.5% glutaraldehyde14-18 minutes2.5% glutaraldehyde4.8-6.3 minutes0.21% ortho-phthalaldehyde

aRange of values from two different laboratories .

High Level Disinfection of “Semicritical Objects”

Exposure Time > 12 m-30m, 20oCGermicide Concentration_____Glutaraldehyde > 2.0%Ortho-phthalaldehyde (12 m) 0.55%Hydrogen peroxide* 7.5%Hydrogen peroxide and peracetic acid* 1.0%/0.08%Hydrogen peroxide and peracetic acid* 7.5%/0.23%Hypochlorite (free chlorine)* 650-675 ppmGlut and phenol/phenate** 1.21%/1.93%___*May cause cosmetic and functional damage; **efficacy not verified

New FDA-Cleared Sterilants “Old” > 2% Glut, 7.5% HP, 1.0% HP and 0.08% PA

New 1.21% glut and 1.93% phenol/phenate (HLD-20 m at

25oC) 0.55% ortho-phthalaldehyde (HLD-12 m) 7.35% HP and 0.23% PA (HLD-15 m) 2.5% Glut (HLD-5 m at 35oC) Hypochlorite (650-675ppm free chlorine)

Ensure antimicrobial activity and material compatibility

Ideal HLD/Chemical Sterilant Rapid HLD (< 10 min) No disinfectant residue after rinsing Excellent material compatibility Long shelf-life Nontoxic (no odor or irritation issues) No disposal problems Monitor minimum effective concentration

Glutaraldehyde Advantages Numerous use studies published Relatively inexpensive Excellent materials compatibility

Disadvantages Respiratory irritation from vapor Pungent and irritating odor Relatively slow mycobactericidal activity Coagulate blood and fix tissues to surfaces Allergic contact dermatitis

Ortho-phthalaldehyde

Advantages Fast acting HLD No activation Excellent materials

compatibility Not a known irritant to

eyes and nasal passages

Weak odor No ACGIH or OSHA limit

Disadvantages Stains protein gray Cost ($30/gal); but lower

reprocessing costs-soak time, devices per gal

Slow sporicidal activity Hypersensitivity in some

patients with a history of bladder cancer

Comparison of Glutaraldehyde and OPA>2.0% Glutaraldehyde HLD: 45 min at 25oC Needs activator 14 day use life 2 year shelf life ACGIH ceiling limit,

0.05ppm Strong odor MEC, 1.5% Cost - $12/gallon

0.55% Ortho-phthalaldehyde HLD: 12 min at 20oC No activator needed 14 day use life 2 year shelf life No ACGIH or OSHA limit Weak odor MEC, 0.3% Cost - $30/gallon

OPA Research Alfa and Sitter, 1994. OPA eliminated all

microorganisms from 100 different endoscopes used in a clinical setting.

Gregory et al, 1999. OPA achieved a 6 log10 reduction of M. bovis in 5.5 min compared to 32 min for glutaraldehyde

Walsh et al, 1999. OPA effective against glutaraldehyde-resistant M. chelonae strains

OPA Label Claims Worldwide

1. Europe, Asia, Latin America5 min at 20oC

2. Canada and Australia10 min at 20oC

3. United States12 min at 20oC

1. Antimicrobial tests support 5 min exposure time.

2. Canadian regulatory authority requires 6-log reduction in mycobacteria (5.5 m) and only 5 min intervals.

3. FDA requires 6-log reduction of mycobacteria suspended in organics and dried onto scope without cleaning

Ortho-phthalaldehyde (OPA)New Contraindications for OPA

Repeated exposure to OPA, following manual reprocessing of urological instruments, may have resulted in hypersensitivity in some patients with a history of bladder cancer undergoing repeated cystoscopy.

Out of approximately 1 million urological procedures, there have been reports of 24 patients who have experience ‘anaphylaxis-like’ reactions after repeated cystoscopy (typically after 4-9 treatments).

Risk control measures: residues of OPA minimized; and contraindicated for reprocessing of urological instruments used on patients with history of bladder cancer.

Minimum Effective Concentration (MEC)High Level Disinfectant (HLD)

Dilution of HLD occurs during use Test strips are available for monitoring MEC For example, test strips for glutaraldehyde

monitor 1.5% Test strip not used to extend the use-life beyond

the expiration date (date test strips when opened)

Testing frequency based on how frequently the solutions are used (used daily, test at least daily)

Record results

Hazardous Component The active ingredient is glutaraldehyde. CIDEX 14-day solution contains 2.4% CIDEX 28-day solution contains 3.2%

Occupational Exposure to Cidex (Glutaraldehyde)

Routes of Exposure

Absorption Most common route of exposure for

Cidex Inhalation Ingestion Injection

Effects of Acute Exposure to Glutaraldehyde Inhalation – Low to mild irritant; nose and throat

irritation, nausea & headaches Eye Contact – Vapors irritating to eyes & may

cause eye damage on contact Skin Contact/Absorption – Mild to moderate

irritant. Ingestion – Toxic. Irritation if consumed in small

amounts; Toxic effects similar to alcohol poisoning; including CNS depression, nausea & vomiting if consumed in large amounts

Effects of Acute Exposure (Continued)

Chronic Exposure – repeated skin contact may cause dermatitis

Sensitization to Product – Limited evidence to support possible skin and respiratory sensitization

NO reported evidence of carcinogenicity. Glutaraldehyde is metabolized in the body predominantly to carbon dioxide and is exhaled via the respiratory tract. There is little potential for accumulation of the product in the body.

How EH&S Monitors Employee Exposure An Assay Technology ChemDisk Monitor for

aldehydes is worn on the lapel to represent the breathing zone for no less than 15 minutes or the duration of the procedure.

The disk is collected and sent to AIHA accredited lab for testing.

A report of the results is distributed to the supervisor and employee.

Exposure Monitoring

Initial monitoring Annual monitoring Periodic monitoring; where initial results are

above the TLV-C or there is a change in procedure.

Employee Exposure to Glutaraldehyde

ACGIH TLV-C 0.05 ppm, instantaneous limit NIOSH REL 0.2 ppm TWA for 10 hours OSHA does not have a PEL

ACGIH TLV-C Threshold Limit Value-Ceiling (TLV-C) is the

concentration that should not be exceeded at any time when working with glutaraldehyde or glutaraldehyde containing products.

EH&S compares your exposure to the TLV-C.

Protective Work Clothing and Equipment Nitrile rubber or butyl rubber gloves Splash-proof safety goggles with side shields Lab coat

Personal Protective Equipment

Face Shield OR Safety glasses with a general surgical mask to protect eyes & mucus membranes

Nitrile gloves with long cuffs Cover gowns – waterproof to protect clothing

from splashes Respirators may be used, but not required. N-95

are ONLY used during endoscopic procedures on patients requiring airborne isolation. N-95 masks are not to be used while performing high level disinfection.

Engineering Controls Room large enough to ensure

adequate dilution of vapors 10 Air changes per hour Exhaust that pulls vapors away

from the user’s breathing zone Fresh air entering at ceiling Routine maintenance of system OR ductless fume ventilation

devices that contain filters to absorb glutaraldehyde vapors from the air

Examples of Ductless Fume Ventilation Devices that contain filters to absorb glutaraldehyde vapors from the air

Management of Glutaraldehyde Spills or Leaks

Stop discharge and contain spill Keep others at a safe distance Don PPE ASAP Absorb any product with an inert absorbent

or use absorbent paper to pick up all liquids Seal absorbent paper along with any

contaminated clothing in a vapor-tight plastic bag and place in biohazardous container.

Call Operation of Plant to assist with large spills

Waste Disposal Discard remaining solution in container

down sink drain Flush well with large quantity of water. For

every 1-qt of CIDEX use 2-gal of water. Rinse container well with water Put container in trash can DO NOT

reuse empty container

Storage Requirements for Glutaraldehyde Keep containers tightly closed Room temperature between 59-86oF Store in a cool dry, well ventilated area (not under sinks!) Do not store with acids, alkalines or oxidizers Do not store with incompatible products Protect containers from damage Avoid skin & eye contact (don’t store the bottle above

eye level) No food or drink in the area

Secondary Containers The name of the chemical without

abbreviations and symbols The name of the responsible party The expiration date The hazard class

Example:

First Aid Skin – wash skin with soap & water Eyes – Use emergency eyewash station to

flush eyes for 15 min Inhalation – move to fresh air

After first aid is given, follow-up with Employee Health Services as needed or Emergency Care Center if after hours

Manual Cleaning Meticulous manual cleaning of all instruments

must precede exposure to any high-level disinfectant or sterilant. Inadequate cleaning of instruments has been one factor cited in transmission of infection by flexible endoscopes.

Appropriate cleaning reduces the number of microorganisms by 99.9%.

Always follow the manufacturer’s guidelines for design features that are unique to a particular instrument

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