June 20, 2018

Much Ado About CPR

Two short essays in this week’s New England Journal of Medicine present differing perspectives on how to treat a desperately ill woman w in the ICU of an American hospital, a woman who is unable to make her own decisions and has no advance directive. One author responded that the right course of action was to “institute a DNR order” and the other that it was to “continue full resuscitative measures,” setting up a quasi-debate. I say a quasi-debate because the two authors, as per the editor’s instructions, simply laid out their own arguments without responding to the other’s point of view. I know, because I am one of the two.

I asserted that the physician should declare the patient DNR—a woman with no written advance directive and no designated health care surrogate who was dying of multiple organ failure triggered by sepsis and unresponsive to maximal medical therapy. Attempted CPR in this setting, I argued, was as close to futile as medical treatment ever is; moreover, the patient had clearly stated to a friend and neighbor that she would not want aggressive measures when facing overwhelming odds. I stand by my arguments, which I won’t repeat here, but I regret that the discussion focused on the wrong question.

The wrong question is whether the patient should have a DNR status; the right question asks about the general treatment strategy rather than a specific medical intervention and about the process for deciding, not just the outcome of the process. It moves the discussion beyond considerations of futility—a debated that raged in the 1980s and ultimately led to the recognition that futility is meaningless without reference to what treatment is intended to accomplish. Maintaining a patient who is in a persistent vegetative state on artificial nutrition is futile if the goal is to restore her to full functioning as a thinking human being. But it’s entirely appropriate if the goal is to sustain life in the sense of a heart that beats and lungs that respire. Discussing how to make medical decisions for patients who have lost capacity and how to think about treatment for those who are dying allows us to discuss much more important decisions than whether or not to attempt CPR.

Ever since 1984, when a New York hospital was found guilty of putting purple dots on patients’ charts signaling that they were not to be resuscitated—without their knowledge or input or that of their next of kin—we’ve been obsessed with DNR orders. I suspect that more ink has been spilled on whether, when and why to write a DNR order than on any other medical decision. The reason, presumably, is that it seems irreversible: if a patient sustains a cardiac arrest and CPR isn’t performed, the patient will surely die. Other seemingly momentous decisions often prove not quite so momentous—even Karen Ann Quinlan, the first patient to bring the possibility of not intervening medically to public attention, lingered for nine years after her “life-sustaining” ventilator had been disconnected. A choice not to resuscitate is far more unambiguous—although CPR, it should be pointed out, is hardly a guarantee of life.

Cardiac arrest may have special cachet because it seems to divide the living from the dead. But in fact, for older patients who are critically ill, it is often merely the last step in what is often a relentless progression of markers on the way to death. From the perspective of human suffering and of doing good (and avoiding harm), other steps along the way are often far more significant. After all, a person whose heart has stopped and who is not breathing is no longer able to experience anything, neither the existential angst from awareness of imminent death nor the physical discomfort of aggressive treatment. The nurses and doctors who attempt CPR in a dying patient may feel guilty of assault; they often regard intubation, chest compressions, and electrical shocks as an undignified way to end life, but they are the ones experiencing malaise, not the patient.

Subjecting a patient who is in the final phase of life to dialysis for four hours a day, three times a week, or to major surgery to repair a damaged heart valve, or to ventilator care for advanced lung disease, by contrast, may cause pain and suffering to the person receiving treatment. Both the potential benefit of treatment (longer life) and its potential burdens (ranging from delirium and functional decline to a shorter life) are difficult to assess quantitatively. These decisions, which are difficult to make with a competent patient and correspondingly more fraught with an incapacitated patient, are the ones we should be discussing, not CPR.

Ironically, despite the now 42-year history of DNR orders, there is still confusion about whether DNR indicates that CPR will not be performed in the event of a cardiopulmonary arrest (as it is defined by the American College of Cardiology and other authorities) or something more. Indeed, the opposing piece in the New England Journal of Medicine talks about a time-limited trial of “continued resuscitative measures,” which presumably refers to ongoing ventilator treatment for respiratory failure, dialysis for kidney failure, and fluids and antibiotics for sepsis, rather than for a few minutes of attempted CPR. This uncertainty about what DNR means reflects another problem with the obsession with “getting the DNR order,” and that is the widespread belief that treatment decisions must be all-or-nothing: if you don’t want CPR, then surely you don’t want any potentially life-prolonging medical interventions. The reality is that many people don’t want burdensome treatments that are extremely unlikely to be beneficial, but that doesn’t mean they want to focus exclusively on comfort. 

There’s much more to discuss—I haven’t even touched on the process for making medical decisions. That includes not only who the surrogate should be in the event of decisional incapacity and what standard that surrogate should use for making decisions (substituted judgment is the usual standard, with best interests the back-up if no information about the patient’s preferences is available), but also how the discussion should unfold. Typically, physicians are so eager to reach a decision about what to do that they jump to this step in the process without first clarifying the patient’s underlying health state (in the NEJM vignette, the crucial bit of information is that the patient was dying), as though preferences are independent of any broader context. But for now, let me leave you with the thought that both medical decision-making and advance care planning involve much more than checking off items on a menu, and that if we do engage in intervention-specific planning, CPR should be low on the list of what we discuss.

June 07, 2018

The Sting of the Jellyfish

Several years ago, the public health community launched an initiative to persuade pharmacies to stop selling cigarettes. Responding to steady pressure, CVS announced in 2014 that it was pulling all tobacco products from the shelves of its approximately 7700 stores. The result? Overall sales of cigarettes dropped, with fewer teens starting to smoke and more people quitting. The other chains, such as Walgreen’s and Rite Aid, have not yet followed suit, but the precedent has been set: retailers dedicated to the promotion of health should not be in the business of peddling death—and cigarettes are the leading cause of preventable death in the U.S., accounting for over half a million deaths per year.

In the same vein, we might ask why news organizations that are dedicated to ferreting out the truth continue to allow ads that peddle falsehoods. And that’s exactly what CNN, Fox News and MSNBC are doing when they advertise Prevagen, a protein that its manufacturer, Quincy Bioscience (a company that seems to be devoted almost exclusively to making and selling Prevagen) touts as “clinically shown to improve memory,” exhorting aging individuals to “try Prevagen for yourself today” in order to “support healthier brain function, a sharper mind and clearer thinking.”

These claims are untrue. The FDA issued a warning letter to the company in 2012, arguing that the company’s unverified health claims indicate that it is selling a drug and not a “supplement” (as the company calls Prevagen) and thus must go through the rigorous approval process for new drugs. Today, the manufacturer continues to call Prevagen a “supplement” because it is a synthetic version of a protein found in jellyfish and continues to make the same claims about its effectiveness, though with the disclaimer in small print that “these statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat cure or prevent any disease.” 

In 2016, the Federal Trade Commission’s Bureau of Consumer Protection and the NY State Attorney General filed a lawsuit arguing that, contrary to its manufacturer's claims, Prevagen has not been shown to improve memory in 90 days; it has not been shown to reduce memory problems associated with aging; and it has not been shown to produce other cognitive benefits.That lawsuit, incidentally, was dismissed because the judge failed to understand that the methodology used in the clinical trial on which the company’s assertions are based is irredeemably flawed. With the added support of AARP, the case has been appealed to the Second Circuit Court of Appeals. 

Why anyone should be motivated to take Prevagen based on its activity in jellyfish, which are not known for their cognitive abilities, is a mystery to me. 

Why anyone should think that the active ingredient, Apoaequorin, could possibly do anything when it is destroyed in the stomach by the enzyme pepsin and therefore doesn’t even make it into the circulation is another puzzle. And why anyone should believe that Apoaequorin could affect brain function (if it somehow managed to elude stomach enzymes and find its way into the blood stream) when it is 40 times too large to cross the blood-brain barrier is also unknown. But what is clear is that Quincy Bioscience has been successful in earning $165 million between 2007 and 2015. It is willing to spend big bucks on advertising on national television to promote its product because it knows the strategy works.

Followers of CNN, MSNBC, or Fox trust the news they hear from commentators on those stations. Because they trust the station, they tend to trust its advertisers. News programs have an ethical responsibility to vet the ads they run; they don’t have to like the products, they don’t have to want the products themselves, but they should be committed to fact-checking their veracity.

A separate question is why FDA regulation of “supplements” is confined to assuring that they are accurately labeled—that is, that the ingredients are correctly listed on the bottle. Manufacturers of dietary supplements do not have to prove them safe nor do they have to make claims about efficacy that are accurate or truthful. A related question is why products such as Prevagen can bypass the FDA's regulatory process for new drugs by calling themselves “supplements,” a term primarily applied to vitamins and minerals but increasingly used for all sorts of “herbs and botanicals” as well as other substances found in nature, or their synthetic analogs. 

In today’s anti-regulatory climate, we cannot realistically expect increased government protection for vulnerable consumers. We can expect—and demand—ethical behavior from any organization dedicated to promulgating the truth.