DC Medical Malpractice & Patient Safety Blog

The blood-thinning drug Pradaxa has starred in a long-running drama with hundreds of adverse event reports, scores of lawsuits and more than 500 deaths. Introduced in 2010 as an option to Coumadin (warfarin), Pradaxa is under fire for dire side effects including hemorrhage and internal bleeding, as we wrote earlier this year. Unlike older anti-clotting drugs, Pradaxa has no antidote for uncontrolled bleeding.

The latest chapter in this tale was told earlier this month by the New York Times, when the FDA released a report concluding that Pradaxa did not show a higher risk of bleeding than warfarin. As The Times noted, the report did not mention the lack of an antidote.

Medical professionals and patients alike have complained about Pradaxa, expressing concern that the approval process was insufficient, and that such a potentially dangerous drug should not be on the market without a way to reverse its unwanted effects. Pradaxa has made $1 billion for its manufacturer, Boehringer Ingelheim, but critics say it’s exemplary, as The Times puts it, “of what can happen when a drug that performs well in tightly controlled trials is released into the messy world of real-life medicine.”

The FDA report says that bleeding rates associated with Pradaxa don’t appear to be higher than those associated with warfarin. At the American Heart Association Scientific Session a week after the FDA report, Boehringer Ingelheim presented findings that, according to its news release, an antidote in development shows promise, and clinical trials are being initiated.

We have to ask: Didn’t they put the cart so far in front that you can’t even see the horse?

When reports began to surface of bleeding problems, Boehringer Ingelheim recommended dialysis to flush the drug out. Dialysis involves bypassing the kidneys to purify the blood through a machine. But the company, according to The Times, acknowledges that “the amount of data supporting this approach is limited.”

The boneheaded dialysis advice was described perfectly by one doctor in The Times’ story: “People that are bleeding to death aren’t going to tolerate being put on dialysis.”

The problem is compounded, according to The Times, if doctors prescribe the drug to the wrong patients. Older people and people with kidney problems are not good candidates for Pradaxa—their bleeding risks are higher than for other people. Boehringer Ingelheim advises testing a patient’s kidney function before prescribing Pradaxa, and notes that the risk of bleeding increases with age.

“The problem is that the people that prescribe this, as a general rule, are cardiologists and family practitioners,” Dr. Mark L. Mosley, director of the emergency room at Wesley Medical Center in Wichita, Kan., told The Times. “The people that see the harm are your E.R. docs and your trauma docs.”

When Pradaxa was approved, its lower maintenance seemed superior to the nearly 60-year-old warfarin (Coumadin) for preventing prevent strokes in people with atrial fibrillation (a heart-rhythm disorder commonly called A-fib). Warfarin patients must be carefully monitored for diet and drugs, and must have frequent blood tests. Not so for Pradaxa patients.

In little more than a year, The Times reports, 17 in 100 a-fib patients got Pradaxa; 44 in 100 got warfarin. The FDA estimates that in the U.S., about 725,000 patients have taken Pradaxa.

But in 2011, according to The Times, Pradaxa “was linked to more reports of injury or death than any of the more than 800 drugs regularly monitored by the Institute for Safe Medication Practices.”

Other new drugs intended as an option to warfarin (Xarelto, which has been approved to treat blot clots, and Eliquis, for which FDA approval is pending) also lack antidotes, but they haven’t shown the same bleeding-death risk as Pradaxa.

All medicine carries a risk of side effects; some can be life-threatening. Sometimes, the risk is worth it, which is the position adopted by medical professionals who believe in Pradaxa. The Times referred to a recent study showing that about 4 in 10 people with atrial fibrillation don’t take any drugs, leaving them at risk for strokes. Many cardiologists say the risk of stroke is more dangerous than the risk of bleeding complications.

Maybe. But if you’re an A-fib patient whose doctor recommends Pradaxa, find out why he or she prefers it to warfarin, which also can cause a host of side effects, some of them serious. If you’re older or have a history of kidney problems, beware, and seek a second opinion.

For people whose kidneys no longer function well enough to process waste products or maintain proper levels of certain chemicals in the bloodstream, kidney dialysis is the only treatment except for transplant. But kidneys -- and the dialysis procedure -- are complicated, and a few recent stories are a heads-up for people affected by kidney failure or disease.

A patient in dialysis is hooked up to a machine that replaces the body's natural filtration system, removing waste and excess fluid and maintaining chemical balance. Beginning this treatment too early in the disease process is not a good idea. As discussed in John James’ Patient Safety newsletter, participants in the Consumer Union Safe Patient Project are wary of the growing commercial takeover of dialysis facilities in part because of the rush to treat. “The truth,” James writes, “is that many patients have already suffered because they were steered into dialysis far too early.”

The danger is especially acute for patients older than 75. The glomerular filtration rate (GFR) quantifies the rate at which filtered fluids are processed by the kidneys. By medical consensus, a GFR of 10 is deemed “early” for dialysis. But from 1996 to 2009, the number of elderly people who started dialysis when their GFR was lower than 10 increased from 1 in 4 to more than 6 in 10.

Patients with GFRs below 20, as noted in a commentary in the Journal of the American Medical Association (JAMA), often are referred to kidney specialists, who often have financial incentives to prescribe dialysis. This is a recipe for conflict of interest, not to mention overtreatment and its adverse outcomes.

Premature kidney dialysis puts the patient at risk for life-threatening infections and even sudden death. As the JAMA article said, “Many patients with advanced chronic kidney disease have stable renal function for years and their rate of decline of renal function may vary inversely with age.” That means that the rate of kidney function decline in older people might be lower than the rate in younger people.

More bad news in kidney dialysis was depicted in the New York Times and in the Bangor Daily News. The Times recounted an FDA investigation over concerns that one national operator of dialysis centers failed to inform patients of a potentially lethal problem in one of its dialysis products. The story from Maine concerned a dialysis patient-turned-whistleblower who was tossed out of treatment when the center didn't care for his complaints about shoddy care.

About 400,000 people in the U.S. are on kidney dialysis, and, according to The Times, Fresenius Medical Care treats more than 1 in 3 of them. It’s also the leading supplier of dialysis machines and disposable products to other operators.

Although Fresenius informed doctors practicing at its dialysis centers that failure to use GranuFlo properly seemed to be contributing to a marked increase of patient deaths from cardiac arrest, the company was tardy in warning other centers that used the concentrate. The FDA found out when someone leaked the internal memo.

The immoral, if not illegal, corporate behavior was reported first by RenalWEB, a neutral, nonaffiliated website for the dialysis industry and community. The site estimated that 125,000 patients in non-Fresenius clinics are treated with GranuFlo.

Dialysis involves bicarbonate, which neutralizes acid that builds up in the blood. GranuFlo contains more than similar products of a component the body converts into bicarbonate. Too much, however, appears to present heart problems. Doctors, apparently have not been accounting for the overdose potential GranuFlo presents.

The FDA issued an alert about GranuFlo and similar products, and dialysis centers now must check patient bicarbonate levels.

As quoted in the The Times, Dr. Daniel Coyne, director of hemodialysis at Washington University in St. Louis, said nearly 1 in 3 of its patients had elevated bicarbonate levels. “A four- to sixfold increased risk of in-center cardiac arrest is very concerning. My partners are all trying to figure out a fix to this problem.”

Kidney dialysis, it seems, is fraught with peril for patients who need or one day might need this life-saving procedure. If this describes you or a loved one, know your GFR levels, find out who owns and operates the dialysis facility you use or might use, and have a frank discussion with your doctor about age-appropriate treatment.

The number of bloodstream infections in intensive care units (ICUs) caused by tubes inserted into major blood vessels decreased significantly between 2001 to 2009, but unacceptably high rates of infection are still occurring for patients in other hospital units and for dialysis patients, government researchers say.

Central lines are tubes that are usually placed in the large veins of the neck or chest to deliver medicines and nutrition. Infections of these lines, which are largely preventable, can become serious problems, with death rates of 12-25%.

An estimated 18,000 ICU central-line infections were recorded in 2009, down from 43,000 in 2001, according to a report by the Centers for Disease Control and Prevention (CDC). This 58% decrease means that in 2009, between 3,000 and 6,000 deaths were prevented and as much as $414 million saved. And if the decrease in these ICU infections was steady from 2001 to 2009, as many as 27,000 lives and as much as $1.8 billion may have been saved.

(Note: These numbers are rough estimates. The 2001 figure of 43,000 infections could have been as low as 27,000 and as high as 67,000.)

According to the CDC, much of the decrease resulted from campaigns to improve techniques for managing the lines in ICUs, where they are most frequently used. Infections involving bacteria such as staphylococcus can be avoided with simple measures like washing hands, wearing sterile gowns and drapes, and following the proper techniques for inserting and maintaining the lines.

However, researchers noted that central line infections still occurred far too often, affecting 80,000 patients a year and killing at least 10,000. In addition, of the 350,000 patients who received dialysis in the U.S. in 2008, about 37,000 suffered central-line infections. Such infections are the second leading cause of hospital stays and death in people on dialysis after cardiovascular problems.

Peter Pronovost, MD of Johns Hopkins Hospital, a pioneer in patient safety, developed the simple "checklist" for using central lines in ICU patients, which was proven in a landmark study in the New England Journal of Medicine to cut the infection risk to close to zero.

Source: The New York Times

You can read an abstract of the study here.

ProPublica, the investigative reporting group, is publishing a series on the quality of care the nation's 400,000 dialysis patients get, and it's not pretty. The basic conclusion:

"Taxpayers spend more than $20 billion a year to care for those on dialysis -- about $77,000 per patient, more, by some accounts, than any other nation. Yet the United States continues to have one of the industrialized world's highest mortality rates for dialysis care. ...

"At clinics from coast to coast, patients commonly receive treatment in settings that are unsanitary and prone to perilous lapses in care. Regulators have few tools and little will to enforce quality standards. Industry consolidation has left patients with fewer choices of provider. The government has withheld critical data about clinics' performance from patients, the very people who need it most. Meanwhile, the two corporate chains that dominate the dialysis-care system are consistently profitable, together making about $2 billion in operating profits a year."

The ProPublica reporters go on to say that: "One reason the system's problems have evolved out of the health care spotlight is that kidney failure disproportionately afflicts minorities and the dispossessed."

Read more about this emerging malpractice and safety scandal here.

And here is part 2 of the series, which opens with a horrifying story about a woman who lost a quarter of her blood because the dialysis tube delivering the cleansed blood back to her body became dislodged and the technicians didn't notice until it was too late.

Here is one more piece of it, an important footnote about how the ProPublica reporters got the hard data on patient deaths that the government keeps hidden from the public.