ASK YOUR ENDOSCOPY CLINIC
DO YOU STERILIZE WITH PERACTETIC ACID?
By age fifty, everyone should be routinely screened for colorectal cancer. I am, and fortunately have been cancer free so far. Colon cancer is one of the easiest cancers to cure when it’s caught in time. Flexible fiber optic endoscopes, which are long flexible tubes with a camera lens at the end, are technological marvels. It’s pretty amazing how doctors today can routinely inspect internal areas of the body such as the colon and lungs, collect biopsies, and perform corrective surgery. The only problem is that flexible endoscopes cannot withstand heat-sterilization, and most models aren’t infection-control friendly. For example, internal air and water channels in most flexible endoscopes are too small to insert brushes all the way through them to clean out blood, feces, and tissue that collect inside.
Pentax flexible endoscope with all channels fully accessible to brushing. Photo courtesy of Walker Montgomery.
Insertion tip of an Olympus colonoscope with lubricants and live bacteria (fluorescing under U.V. light) leaking from a non-brushable air-water channel after preparing the scope for the next patient according to the CDC’s current disinfection guidelines. Courtesy David Lewis.
Tips on Choosing the Best Endoscopy Clinic1
1. Sterilization is better than disinfection. Although most doctors assure patients that the flexible endoscope used on them will be sterilized, most endoscopy units (approximately 80 percent) only disinfect them. Disinfection doesn’t kill spores, which are produced by some very important pathogens such as Clostridium difficile (“C diff”) and Mycobacterium. In 2012, the CDC estimated that C diff, which causes an increasingly fatal form of severe diarrhea, is linked to fourteen thousand American deaths each year.2 Currently, Steris Corporation’s process using buffered peracetic acid is the only FDA-approved process in common use for sterilizing flexible endoscopes. It is used in approximately 20 percent of the endoscopy clinics in the United States.3
2. Flushing is better than soaking. Liquid chemical germicides used to disinfect or sterilize flexible endoscopes are mass-transport limited. That means disinfection and sterilization rates increase proportionally to the solution flow rates. In other words, doubling the flow rate of a disinfectant solution doubles the rate of disinfection. That’s critically important with flexible endoscopes because their internal channels are contaminated with biofilms, and particles of blood, feces, and other patient materials hide in nooks and crannies. Doubling the flow rate doubles the chances that the disinfectant will penetrate this type of contamination. While many endoscopy clinics use machines that automatically circulate germicide solutions over the internal and external surfaces of flexible endoscopes, most are only soaked for short periods of time (approximately ten minutes).
3. Sporadic infections are underreported. Your doctor may reassure you that only one patient is infected per 1.8 million procedures using flexible endoscopes. But bear in mind that this information is based on surveys of practitioners and reported outbreaks, where numerous patients are infected at or about the same time at the same facility. Outbreaks are relatively easy to detect and report compared with sporadic cases involving a single patient; also, outbreaks are caused by egregious lapses in infection control. Most infections associated with flexible endoscopes, by far, are sporadic. Patients are unlikely to suspect endoscopes as the culprit, especially when doctors falsely reassure patients that endoscopes are sterilized when most (80 percent) have only been treated with disinfectants. Most flexible endoscopes are only soaked in disinfectant for ten minutes, and it would take hours to reach sterilization conditions. And, if you test positive for hepatitis C, anal HPV infection, or other infectious agents transmitted by flexible endoscopes, the last thing any doctor will ask is “Have you had a colonoscopy done?”
4. Don’t avoid endoscopy. The risks associated with ignoring colorectal cancer and other serious diseases far outweigh the risks of infection whenever CDC guidelines are followed for disinfecting flexible endoscopes. Just be smart about it when it comes to choosing where you have endoscopy done and what kind of disinfection or sterilization process is used. If you still have concerns, you should talk with your doctor about alternatives, such as radiology.
Disinfection versus Sterilization
Infection-control guidelines are based on E. H. Spaulding’s classification system, which recommends high-level disinfection as the minimum standard for flexible endoscopes. Spaulding considered endoscopes to be semi-critical devices, which enter unsterile areas of the body and contact only intact mucous membranes.4 Some bleeding, however, occurs in half or more of all colonoscopies, for example, when biopsies are taken. Also, the inner lining of the intestine is easily damaged when flexible endoscopes turn corners, press against hemorrhoids, and contact weakened or injured tissues. Currently, buffered peracetic acid and ethylene oxide gas (ETO) are the only FDA-approved sterilization processes available for flexible endoscopes.5
The Spaulding classification system provided a rationale for not sterilizing flexible endoscopes at a time when ethylene oxide sterilization, an overnight process, was the only sterilization process available for flexible endoscopes. It gave rise to some irrational distinctions. For example, biopsy forceps must be sterilized, while the biopsy channels through which the forceps are inserted in flexible endoscopes require only high-level disinfection. This makes little, if any, sense when biopsy channels are contaminated with the same patient materials as the forceps during endoscopic procedures.
Most physicians still think it’s unnecessary to sterilize a device that’s inserted in unsterile areas of the body, especially the colon where large numbers of fecal coliform bacteria proliferate. The presence of fecal matter, however, offers little if any protection from hepatitis B, HIV, and other pathogens that contaminate flexible endoscopes. Otherwise, sexually transmitted diseases among homosexual men would be less of a public health concern.
Also, when the Spaulding classification system was published in 1968, the ease by which some viruses can pass through intact mucous membranes was unknown. Now, it is widely recognized that viral transmission across mucous membranes, such as HIV transmission via breast-feeding, is an efficient mechanism of disease transmission.
More importantly, few individuals with severely compromised immune systems survived long enough to be treated with endoscopes when the Spaulding system was put into practice. Now, organ transplant recipients, patients undergoing chemotherapy, diabetics, AIDS patients, and people with a host of other conditions that compromise their immune systems are surviving for many years and receiving frequent endoscopic examinations. Introducing new strains of organisms into immune-compromised patients can lead to severe disease or death. Therefore, it is no longer safe to assume that patients can fend off low numbers of opportunistic pathogens known to escape high-level disinfection. Moreover, because resistance to antibiotics has become a widespread problem, many endoscope-related infections that were once easily treated are now life-threatening.
Although the amount of infectious matter potentially passed patient to patient by flexible endoscopes is small, we found that even a few microliters of HIV-positive blood contaminating lubricants used in endoscopes and dental handpieces can efficiently transmit the virus to human lymphocytes.6 Admittedly, the risk of HIV infection from endoscopes is very low. Endoscopic procedures, however, may be a far more common, yet largely undocumented, source of infection with other viruses, such as human papillomavirus and cytomegalovirus.
Hidden Problems
In the United States, Europe, and elsewhere throughout the world, current guidelines for reprocessing flexible endoscopes recommend pre-cleaning followed by high-level disinfection.7 The adequacy of these guidelines, according to their authors and proponents, rests on the efficacy of high-level disinfectants in laboratory tests and the low numbers of documented cases of infection. Experimental designs of the tests cited, however, bear little resemblance to the practice of endoscopy, where pathogens lodge in difficult-to-clean areas in bits of flesh, blood, and feces hardened with glutaraldehyde and mixed with viscous lubricants. Moreover, a patient infected by an endoscope has almost no chance of having his case documented in the peer-reviewed medical literature.
Endoscope manufacturers admit that visible traces of blood, feces, and other patient materials remain in internal areas of flexible endoscopes, serving as a potential source of infection despite our best efforts to clean the devices.8 Even a cursory application of the fundamental laws of physics reveals the challenge this presents to infection control. It would take at least fifty-eight hours for 2 percent glutaraldehyde, the germicide most commonly used on endoscopes, to diffuse through even barely visible traces of patient material.9 For germicides to reach pathogens buried in such material in less than an hour, the concentration and temperature of the germicide would have to be so high that it would quickly destroy endoscopes and be far too hazardous to handle. Microbiologists have long recognized this limitation and stressed that all surfaces must be thoroughly cleaned for disinfection to work properly.
What has not been appreciated, however, are the pitfalls of testing chemical germicides using standard techniques for culturing microbes. When germicides contact residual patient debris inside endoscopes, they kill microorganisms only on surfaces of the debris. This can leave large numbers of viable organisms hidden inside. Whenever such superficially disinfected material is submerged in nutrient solutions to test for live organisms, nutrients fail to penetrate the material. Few, if any, colonies of microorganisms are revealed. What appears to be adequately disinfected material can actually harbor large numbers of pathogens buried inside, waiting to be dislodged from air/water and biopsy channels during endoscopic procedures. Once the material enters patients and is broken down, these stowaway microorganisms can begin multiplying and cause infection.
Lubricants used on external surfaces and mechanical parts of endoscopes add yet another dimension to the problem. Even the most fragile viruses, including human immunodeficiency virus (HIV), can survive a two-hour exposure to 2 percent glutaraldehyde when entrapped in lubricants.10 Once again, large numbers of microorganisms can go undetected by conventional microbiological tests.11
Poor Compliance
Only about one in ten endoscopy units follow FDA requirements for properly disinfecting and sterilizing endoscopes.12 These requirements are supported by endoscope and disinfectant manufacturers, and no infections have been reported when complying with these requirements. Most health-care facilities (84 percent) currently follow less stringent recommendations of the Centers for Disease Control and Prevention and professional endoscopy societies. These recommendations are inadequate for achieving the minimum conditions of exposure time and temperature required to kill Mycobacterium tuberculosis and other germicide-resistant pathogens with 2 percent glutaraldehyde. Outbreaks involving Mycobacterium and other pathogens have occurred when applying these less stringent guidelines.
One national survey found that most physicians (66 percent) reprocess flexible endoscopes in considerably less time than is required to perform the cleaning and disinfection steps recommended in infection control guidelines.13 While every effort should be made to improve compliance, appropriate recommendations should provide the widest margin of safety practical to protect patients when the performance of reprocessing procedures is less than perfect. With this in mind, the following general approach to reprocessing endoscopes provides the best margin of safety in current practice.
Flexible endoscopes should be meticulously cleaned according to manufacturers’ instructions as soon as they are removed from patients, and then subjected to a sterilization procedure. All germicides approved by the FDA for use on flexible endoscopes are chemical sterilants; that is, they have the potential to achieve sterilization, given sufficient exposure times. For example, the most common liquid chemical germicide used, 2 percent glutaraldehyde, can achieve sterilization with a minimum of ten hours of exposure time. But the maximum exposure time used in practice is only forty-five minutes, and most facilities use only ten minutes of exposure.
Another important point is that liquid chemical germicides that facilitate rather than frustrate the cleaning process should be chosen. Two of the most common germicides used on endoscopes, glutaraldehyde and peracetic acid, are used for other purposes that illustrate an important difference between these two chemicals. Like its first cousin formaldehyde, glutaraldehyde is used to prevent decomposition. To preserve a frog so that it can be dissected and studied fifty or one hundred years later, just treat it with glutaraldehyde. But, when scientists want to dissolve organic matter instead of preserve it, peracetic acid is used. For years, researchers have employed this powerful oxidizing agent to render inaccessible areas of intricate laboratory glassware completely clean of even baked-on organic matter.
The ability of buffered peracetic acid to remove glutaraldehyde-hardened patient material from biopsy channels has been demonstrated using surface infrared spectroscopy.14 What has long been common knowledge to laboratory researchers wanting to either preserve organic material with glutaraldehyde or remove it with peracetic acid can be easily visualized by even the most casual observer.
Some health-care practitioners switching from soaking endoscopes in glutaraldehyde to purging the devices with buffered peracetic acid have experienced an initial increase in repairs. The oxidizing power of peracetic acid causes it to completely break down proteins and other organic matter. As hardened patient material begins to dissolve away, leaks are exposed in internal channels. Incredibly (or disgustingly), many flexible endoscopes now in use apparently are literally held together by potentially infectious patient material, sealed by a “superglue” containing microorganisms buried between layers of glutaraldehyde-hardened surfaces.
The oxidizing action of peracetic acid is short-lived. Just as hydrogen peroxide decomposes into innocuous byproducts (water and oxygen), peracetic acid quickly breaks down to oxygen and dilute acetic acid—a weak vinegar solution. Peracetic acid in the dilute buffered solution used for sterilization does not require fume hoods and can be disposed of down the drain after the solution exits the sterilization unit. Glutaraldehyde, on the other hand, is persistent, and breathing its vapors tends to preserve human lungs, like frogs, only not in working condition.
Sheath Technology
Another method of rendering flexible endoscopes safer for reuse is newly developed sheath technology.15 Rather than trying to clean contaminated surfaces, they are simply discarded after each use of the flexible endoscope. Discarded portions include all external surfaces that directly contact the patient as well as internal channels that can retain bodily fluids and other patient matter. Optical and mechanical workings of sheathed endoscopes are designed as a separate unit that is re-sheathed and supplied with sterile, disposable biopsy and air/water channels after each use. Although Vision-Sciences, Inc., developed the basic technology, a number of other endoscope manufacturers, including Olympus Optical Co., Ltd., have considered sheathed endoscopes.16
No Documented Cases
Proponents of high-level disinfection of endoscopes point out that only one infection has been reported in the medical literature for an estimated 1.8 million endoscopic procedures.17 In most cases, failure to follow all of the recommended steps for pre-cleaning and high-level disinfection is blamed for causing these infections. These numbers are meaningless, however, considering that the likelihood that any endoscope-induced infection will be published in the medical literature is probably also on the order of one in a million.
When proponents of disinfection refer to reported cases, they often fail to point out that a number of infections have been documented where adherence to guidelines for pre-cleaning and high-level disinfection were followed. By comparison, no infections have been reported with proper pre-cleaning and sterilization. Sterilization, microbiologists agree, offers a higher degree of assurance that microorganisms are killed. Mycobacterium passed patient to patient via bronchoscopes in a Roanoke, Virginia, hospital, for example, could not be eliminated by even the most rigorous pre-cleaning followed by high-level disinfection with 2 percent glutaraldehyde, but was eliminated with peracetic acid sterilization.18 Even manufacturers of high-level disinfectants acknowledge that bacteria have demonstrated an increasing resistance to glutaraldehyde while remaining susceptible to peracetic acid.19
A 1992 survey found that 6 percent of US nurses were knowledgeable of outbreaks of infections attributed to flexible endoscopes at their institutions.20 Recent advances in DNA fingerprinting enabled several cases of tuberculosis transmission via endoscopes treated with 2 percent glutaraldehyde to be detected in separate hospitals.21 One patient died from the nosocomial transmission. If this new science of molecular epidemiology were to be widely applied in the area of endoscopy, I expect that the numbers of infections uncovered and scope of organisms involved would quickly precipitate an upgrading of federal guidelines to a sterilization standard.
In my own work, I have encountered scores of unreported cases where patients with no other identified risk factors have developed life-threatening infections within expected incubation times after both dental and endoscopic procedures.22 For example, I have investigated several cases where male patients developed human papillomavirus (HPV) infections of the anus, which began to appear four to five weeks after routine colorectal examinations in separate medical facilities. The flexible endoscopes used on these patients had been cleaned and subjected to high-level disinfection with 2 percent glutaraldehyde. Most strains (types 6, 11, 16, 18) of HPV, the virus causing genital warts, place patients at high risk of developing anal cancer when the virus infects this area of the body. Ironically, these patients submitted to endoscopic examinations after being encouraged by their physicians to have annual screening tests for colorectal cancer.
Patient Concerns
While patients should not be frightened away from needed medical care, neither should they be kept uninformed. Physicians should encourage candidates for endoscopy to discuss any concerns they may have about infection control and address their questions fully and honestly. Just as physicians tell patients that paralysis from surgery or death from anesthesia is a remote but real possibility, they should make patients aware of the risks of infection from endoscopy. Until sterilization becomes the standard of practice, patients should be fully informed and afforded the opportunity to decide whether to disregard the small chance of infection from unsterilized endoscopes or seek the added assurance of safety provided by sterilization.
Recommended guidelines for reprocessing endoscopes should be upgraded from high-level disinfection to the exclusive employment of sterilization methods and sterile disposable products. The federal Centers for Disease Control and Prevention has already instituted this change in dentistry with regard to dental handpieces and similar devices retaining blood and other patient materials in difficult-to-clean areas.23 There, the standard is simple and can be understood by any patient. Any device entering the oral cavity must be either subjected to an approved sterilization procedure after each use or discarded.
There is no reason why government agencies and medical associations should not adopt this same high standard for endoscopy in response to the rapidly changing world of medical technology and increasing microbial resistance to high-level disinfectants. Sterilization is the standard of care that most physicians already tell their patients they are receiving for endoscopy, and the majority of patients mistakenly believe this is the standard of care they are receiving.24
Muzzling the Messenger
As was the case with my research on dental infection control, the CDC and FDA were both supportive of my efforts to improve infection control standards regarding endoscopy. My research published in Nature Medicine demonstrated that lubricants used with flexible endoscopes could thwart disinfection with glutaraldehyde, the most common germicide used by endoscopy clinics.25 A cover story about my research on disinfectants by Hippocrates magazine (Time Inc.) won a national award, and lengthy articles focusing on problems with using glutaraldehyde to disinfect flexible endoscopes were published by USA Today, Newsweek, and others.26 Also, network television news programs, including Dr. Timothy Johnson with ABC’s Good Morning America, NBC’s Nightly News, and PBS’s Healthweek, interviewed me on the subject.27 Thus, the threshold for silencing me—causing widespread public concerns—was passed.
Nevertheless, the medical community responded appropriately. For example, Practical Gastroenterology, a peer-reviewed medical journal, devoted two issues to covering the debate by inviting me to contribute an article, and others to argue that it isn’t necessary to sterilize flexible endoscopes.28 Only one company, Custom Ultrasonics, Inc., which manufactures a washer-disinfector that uses glutaraldehyde, retaliated. After the Los Angeles Times refused to publish the company’s false allegations of research and ethics misconduct against me, its infection-control chief, Lawrence Muscarella, published them in the company’s newsletter.29 Specifically, the company alleged that I failed to disclose a “financial relationship” with Steris Corporation when I published our paper in Nature Medicine.
As editors of Hippocrates magazine pointed out, Steris Corporation had once donated funds to a community church that David Gattie and others, including myself, built in Oconee County, Georgia, in 1993. The church, called Saxon Road Church, held regular Sunday services until 2013, when David retired as pastor. It had an all-volunteer staff, and didn’t solicit tithes or offerings. Custom Ultrasonics refused to publish a brief response I submitted regarding its allegations. In it, I stated that I did, in fact, disclose the donations, which were approved by EPA ethics officials. But, because I could not financially benefit from the church, editors at Nature Medicine didn’t consider the donations to represent a financial conflict of interest. All I can do is disclose any possible conflicts of interest. It’s up to the editors whether they choose to publish them.
