January 17, 2017 — Two Pennsylvania hospitals in the fall of 2015 publicly linked infections of mycobacteria to the Stockert 3T Heater-Cooler device — yet a less commonly used heater-cooler device sold by another company also has been linked to these same types of infections, my research has found.

A third Pennsylvania hospital informed the FDA in Dec. 2015 and Jan. 2016 that at least four open-chest patients had been diagnosed with Mycobacterium abscessus months after the surgery performed using the Terumo HX2 Temperature Monitoring System.

At least two of this hospital’s four infected patients died, according to regulatory reports filed with the FDA.

The FDA had stopped the sale of this heater-cooler model in 2011 amid safety concerns, but then granted the company permission to begin re-selling it last June.

According to a regulatory report Terumo filed with the FDA, two of the Pennsylvania hospital’s physicians concluded that mycobacteria in the local water system were “the likely cause” of the M. abscessus infections linked to the heater-cooler device.

The name of the hospital that linked these four M. abscessus infections to the Terumo heater-cooler device was redacted from the regulatory reports I identified. The hospital’s name has not been publicly identified.

Last September, Penn Presbyterian Medical Center, a fourth Pennsylvania hospital, publicly disclosed that hundreds of patients were being notified about their potential exposure to mycobacteria during open-chest surgery. According to the Philadelphia Inquirer, all of this hospital’s infected patients recovered.

Wellspan York Hospital (York, PA) and Hershey Medical Center (Hershey, PA) were the other two hospitals in Pennsylvania that have linked a heater-cooler device to mycobacterial infections.

Six heater-cooler manufacturers

The HX2 heater-cooler device is manufactured by Terumo Cardiovascular Systems Corp (Ann Arbor, MI). It competes with the more-widely used Stockert 3T device, which is often also called the Sorin 3T.

LivaNova PLC (of Italy), formerly known as the Sorin Group Deutschland GmbH, manufactures the Stockert 3T model, which holds a significant share of the market for heater-cooler device used in the U.S. The purchase price one of these devices can be $35,000, or higher.

CardioQuip LLC (Bryan, TX), Cincinnati Sub Zero Products Inc. (Cincinnati, OH), Maquet Cardiovascular (Wayne, NJ), and Medtronic (Mounds View, MN) are the other four manufacturers who sell competing heater-cooler devices in the U.S.

These less frequently used heater-cooler models include: the MCH-1000, the Hemotherm 400CE Heater-Cooler, the HCU 40 Heater-Cooler, and the Bio-Cal 370 Blood Temperature Control Module, respectively.

The regulatory history and recalls of these heater-coolers are discussed in more detail in an accompanying article I wrote, “Infections Are Not Limited To The Sorin 3T Heater-Cooler Model.”

Nontuberculous mycobacteria (“NTM”)

The fast-growing M. abscessus and the much slower growing M. chimaera are examples of nontuberculous mycobacteria, also called “NTM.” Most outbreaks linked to a contaminated heater-cooler device, both in the U.S. and Europe, were caused by M. chimaera.

NTM are not transmitted from one patient to another. But they are “opportunistic,” generally causing infections only in patients who are already ill or have compromised immune systems.

These infections are usually treatable, although patients may not know they have been infected. Because M. chimaera is slow-growing, infected patients may not display symptoms until several months, or years, after exposure. Symptoms of infection include fever, pain, redness, and pus around the surgical incision.

Only those patients undergoing a surgical procedure that uses a heater-cooler device are potentially at risk of an NTM infection — for example, cardiopulmonary bypass surgery, lung transplants, and heart valve replacement surgery, among other complex cardiac procedures.

NTM-contaminated aerosols

Heater-cooler devices control the temperature of the patient’s blood during these procedures by circulating heated and cooled water within a “closed loop” of tubing. These devices may also be used to provide heated and cooled water to other medical equipment, including specifically designed patient blankets.

No matter the heater-cooler device’s manufacturer, its circulating water does not ordinarily directly contact the patient during surgery. But new findings now show that a heater-cooler device contaminated with mycobacteria and other types of bacteria can still infect patients, through indirect contact.

Researchers recently discovered that contaminated aerosols vented into the operating room’s air by the heater-cooler device appear responsible for at least some of the deadly mycobacterial outbreaks linked to these devices.

In response to this risk, the FDA now advises hospitals to direct the heater-cooler device’s exhaust vent away from the surgical field.

Quality, Safety and Legal Reviews:  Click here to read about Dr. Muscarella’s quality and safety services designed to help manufacturers, hospitals and patients reduce the risk of healthcare-associated infections, including mycobacterial outbreaks linked to contaminated heater-cooler devices.

A deadly outbreak of M. abscessus in 2014 

More than a year ago, in Oct. 2015, the FDA issued a safety alert warning healthcare providers for the first time that heater-cooler devices used in the U.S. and sold by a number of manufacturers could pose a risk of transmitting deadly mycobacterial infections.

The Centers for Disease Control and Prevention (CDC) issued a similar safety notice two weeks later, on Oct. 27, followed two weeks after that by a Pennsylvania Department of Health (PA-DOH) alert.

Greenville Memorial Hospital (Greenville, SC) — in 2014, almost 18 months earlier — was the first hospital in the U.S. to publicly link a contaminated heater-cooler device to a deadly outbreak of mycobacteria.

First in June 2016 and then again in the Oct. 2016, more than two years after investigators linked Greenville Memorial’s outbreak to a contaminated Sorin 3T device, the FDA warned patients that heater-cooler devices could pose a risk of transmitting life-threatening infections.

Also in Oct. 2016, the CDC issued a health advisory warning patients of this risk.

Other heater-cooler models are prone to contamination, infections too

Reports beginning in 2014 had initially linked only the Sorin 3T model to mycobacterial infections in patients undergoing open-heart surgery on cardiopulmonary bypass.

According to a clinical alert published last June by SpecialtyCare, “Due to design characteristics, all (heater-cooler devices), regardless of manufacturer, are susceptible to” the development of bacterial biofilms on some of their surfaces.

SpecialtyCare, which claims to be the largest provider of perfusion services in the U.S., further wrote in this clinical alert that, “The rate of reported incidents among different machine types is proportionate to the volume of market share of each manufacturer, and changing devices may not alleviate the problem. No device has been found to be less susceptible to biofilm deposition than another.”

Note: For clarification, “linking” a contaminated device to an infection, however, does not necessarily confirm that the device “caused” the infection. Additional data might be necessary to more precisely define the device’s role and confirm it more likely than not caused the infections.

An accompanying article I wrote, “Infections Are Not Limited To The Sorin 3T Heater-Cooler Model or to Mycobacteria chimaera,” discusses the regulatory history and recalls of heater-cooler devices.

Connecting the Dots:  Click here to read about Dr. Muscarella’s quality and safety services designed to reduce the risk of healthcare-associated infections. These services include his searching multiple databases to identify otherwise undisclosed infections linked to medical devices.

Terumo enters into consent decree with FDA in 2011 that’s lifted in June

Devices sold by Terumo have been the subject of a consent decree that the company entered with the FDA six years ago.

The FDA published a press release in March 2011 entitled, “FDA: Michigan heart-lung bypass machine manufacturer enters into consent decree.” This agreement prohibited Terumo from manufacturing and distributing to new customers several different cardiovascular devices, including the HX2 Temperature Management System.

Terumo entered into this consent decree with the FDA in 2011 because inspections of its facility in Ann Arbor (MI) the previous year revealed numerous violations and deficiencies in the company’s control of the design of its devices, including the HX2 heater-cooler model, according to the FDA.

Last June Terumo reported in a press release that the FDA had just lifted the 2011 consent decree, permitting the company to begin re-selling several cardiac devices, including the HX2 heater-cooler model.

Yet, six months before lifting this consent decree, the FDA had been notified by the company that the Terumo HX2 heater-cooler model had been linked to at last four mycobacterial infections and two deaths.

Some additional details about Terumo’s consent decree are discussed in my related article, “Infections Are Not Limited to the Sorin 3T Heater-Cooler Model or to Mycobacteria chimaera.”

4 patient infections, 2 deaths linked to the Terumo HX2 heater-cooler model 

A number of filed regulatory reports link the Terumo HX2 heater-cooler model to four mycobacterial infections in patients who underwent open-chest surgery.

These reports identify M. abscessus as the cause of the mycobacterial infections, although most of the mycobacterial outbreaks linked to a contaminated heater-cooler device in the U.S. and Europe were caused by M. chimaera.

More specifically, one of these regulatory reports, which the hospital filed on Dec. 17, 2015, links the Terumo HX2 heater-cooler device to a bloodstream infection identified in 2013 in a patient who had undergone a double lung transplant four months earlier, in 2012.

One month later, on Jan. 27, Terumo filed a report with the FDA apparently documenting this same apparent incident, stating that two of the hospital’s physicians concluded that “there is no connection or association between the heater-cooler unit and the patient infection.”

(I could not independently confirm that, or why, the physicians ruled out the heater-cooler device as a contributor to this infection. Whether their claim is conjecture or based on the findings of a complete investigation is unclear.)

This lung transplant patient survived the infection, according to Terumo’s filed regulatory report, which further noted that, “according to both (doctors), there is mycobacteria in the [redacted text] and [redacted text] water system and they theorize this was the likely cause of infection in these post-transplant and immunosuppressed patients.”

The FDA redacted, or removed, from this report the city and state where this hospital is located.

Another of these regulatory reports, also filed by a hospital on Dec. 17, 2015, similarly links the Terumo HX2 heater-cooler device to a M. abscessus bloodstream infection. This time, however, the infection was diagnosed 10 weeks after the patient underwent a left single lung transplant.

This hospital’s filed report is written using the same format, text and language as the earlier report (discussed above) that was filed on the same day by a hospital documenting a M. abscessus infection following a double lung transplant.

And, just as with the earlier report filed by a hospital, Terumo filed a report with the FDA one month later on Jan. 27 apparently documenting this same incident. This regulatory report states that two of the hospital’s physicians concluded that “there is no connection or association between the heater-cooler unit and the patient infection,” just as was reported in the manufacturer’s earlier report discussed above.

(Again, I could not independently confirm that, or why, these physicians similarly and summarily exclude the heater-cooler device as a contributor to this infection. Whether their claim is conjecture or based on the findings of a complete investigation is unclear.)

This second regulatory report filed by Terumo, however, acknowledges that the infected patient died.

And, just like Terumo’s other regulatory report discussed above, this report states too that, “according to both (doctors), there is mycobacteria in the [redacted] water system and they theorize this was the likely cause of infection in these post-transplant and immunosuppressed patients.”

Reasonably indicating the state where the hospital is located, Terumo’s regulatory report provides the following additional information: “The hospital was mandated by the state of pennsylvania to retrospectively look back the previous four years for patients that developed mycobacterium infections post cardiothoracic surgery where (cardiopulmonary bypass) was used and a heater cooler unit was used during the procedure.”

As discussed previously, the PA-DOH issued a safety alert in December 2015 that discussed the risk of heater-cooler devices infecting patients.

Likely explaining this regulatory report’s use of the word “mandate,” one section of this alert recommends that hospitals in Pennsylvania: “Conduct prospective and retrospective surveillance using proposed case definition (See Appendix A).”  This alert also reports that “In facilities in which open heart surgery on bypass is performed, conduct retrospective case finding by cross-referencing microbiology NTM culture data with operative databases. Report identified cases as noted below.”

Two more infections are linked to Terumo’s model, likely at this same hospital

Both Terumo and a hospital filed independent reports to the FDA almost a year ago, in early 2016, documenting yet two more cases of M. abscessus infection linked to the Terumo HX2 heater-cooler model.

One of these regulatory reports, the third of four likely filed by the same hospital, describes infection diagnosed in a patient who in 2012 underwent placement of a left ventricular assist device. Almost 3 years after the surgery was performed, the hospital reported that the patient was diagnosed with both M. abscessus and M. avium intracellulare (or, MAI) infections.

According to the manufacturer’s report that appears to correspond to this hospital report, the hospital’s two physicians concluded that, again using the identical text provided above, “there is no connection or association between the heater-cool device and the patient infection,” with the report adding that “according to both (physicians), there is mycobacteria in the [redacted] water system and they theorize this was the likley (sic) cause of infection …”

The fourth report filed by a hospital, once again on December 17, 2015, describes a patient who was diagnosed in 2014 with a mycotic aortic arch pseudoaneurysm with M. abscessus 2.5 years after undergoing orthotopic heart transplantation using the Terumo HX2 model.

Terumo’s report apparently documenting this same incident also refers to the “two doctors” who concluded that the heater-cooler device was not associated with the infection.

Unlike in the three previous reports, however, a crucial identifier — the city where the hospital is located — was not redacted from this report.

Instead, reasonably assuring that the hospital is in (or near) Philadelphia (PA), this regulatory report filed by Terumo discloses that, “there is mycobacteria in the philadelphia and delaware valley water system,” which the hospital’s two doctors suspect were the “likely cause” of the M. abscessus infection, according to this filed report.

This and other regulatory reports might suggest that the rapid-growing M. abscessus infections may not always be diagnosed within days or weeks after exposure, but, like the slow-growing M. chimaera, may instead not be diagnosed until months or years later.

Taken together, these eight regulatory reports — four filed ostensibly by a single hospital and four by Terumo — appear to suggest that a hospital in the Philadelphia area linked the HX2 heater-cooler model to a deadly M. abscessus cluster that infected four open-chest surgery patients, two of whom expired.

What’s more, according to each of the four regulatory reports that Terumo filed, the hospital’s two physicians, “would not have filed (this regulatory report) if this mandate was not in place, because there was no medical or laboratory data to associate the use of the heater cooler unit with these infections.

At least three hospitals in Philadelphia perform open-heart and lung-transplant surgeries.

Earlier this year, Terumo filed a report with the FDA linking another of its heater-cooler devices, the Sarns TCM II model, to NTM contamination. This report does not document any patient infections.

The reader is recommended to download the related article, “A Philadelphia Hospital Links Mycobacterial Infections to a Heater-Cooler Device.”

Summary and closing remarks

Infections linked to contaminated heater-cooler devices are not limited to one manufacturer, or to one type of nontuberculous mycobacteria. The risk of these devices infecting patients with bacteria may be significantly greater than publicly recognized.

Fore more details, review my related article, “Infections Are Not Limited to the LivaNova’s Sorin 3T Heater-Cooler Device or to Mycobacteria chimaera.”

More emphasis by manufacturers and the FDA on testing and validating the safety and effectiveness of heater-cooler device’s design — and decontamination procedure — is encouraged.

Further, mycobacterial infections linked to open-heart surgeries can be due to contamination of the tap water, not only to a flaw in the manufacturing of the heater-cooler device as the FDA has reported.

Implementation of mitigations shown to reduce the risk of tap water infecting hospitalized patients — for example, use of validated bacterial filtration systems — is recommended.

Hospitals are also now being urged to consider removing the heater-cooler device from the operating room (whenever feasible) to eliminate the risk of the device emitting aerosols of bacteria into the air and infecting patients during open-chest surgery.

Additional advice for the prevention of NTM transmissions due to contamination of a heater-cooler device is provided in both the aforementioned FDA October 2015 safety communication, the CDC’s safety notice issued the same month, and the PA-DOH December 2015 safety alert.

Update (Sept. 30, 2020): Consistent with this 2017 article’s findings, FDA reported almost three-and-a-half years later in an alert dated September 30, 2020, that “we are now aware of NTM patient infections, NTM device contamination, or both issues, for all the manufacturers of heater-cooler devices in the United States.”

Article by: Lawrence F Muscarella, PhD. Posted January 17, 2017. LFM Healthcare Solutions, LLC Copyright 2017. LFM Healthcare Solutions, LLC.  All rights reserved. 0003

Lawrence F Muscarella PhD is the owner of LFM Healthcare Solutions, LLC, a Pennsylvania-based quality improvement and consulting company that provides safety services for hospitals, manufacturers and the publicEmail Dr. Muscarella for more details.

E: Larry@LFM-HCS.com. Twitter: @MuskiePhD

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