Thursday, January 14, 2010

Please, Dr. Gupta, I Don’t Want to Go, Part 1

(With apologies and gratitude to the music of Ray Stevens.)

I have certainly written before about my concerns when research studies get reported, and often misunderstood, by the popular press. I suppose I shouldn’t be surprised that the reporter is interested in getting a good story. But that’s precisely the problem. The reporter gets so excited about the good story that he or she fails to recognize, much less convey, the limitations of the story he or she wants to tell. Unfortunately, those limitations are important. Like adding all those disclaimers in a television pharmacy ad, appreciating the limitations of studies that get reported are really in the best interest of the reading public. However, they aren’t nearly as much fun as the good story.

Which brings me to Dr. Sanjay Gupta. I’ve been reading his book, Cheating Death, and I’m afraid that I’m left with the same impression: that Dr. Gupta the reporter has overcome Dr. Gupta the physician in his effort to tell the story.

I’m not suggesting this is easy. Indeed, I think a central aspect of the book highlights the difficulty of providing information on research in the public sphere. The book is certainly readable. However, in the interest of being readable the book centers on the stories of individuals. These individuals are exceptional, usually in more ways than one. At the most important level, they are exceptions because they have survived in circumstances when almost no one would have predicted it. In addition to that (and I think related to that), most of them were in good health before the event that made their stories interesting.

As I suggested, that makes for good writing and good journalism. However, it’s not really all that good as reporting about health care. Each case serves to illustrate an area of research in health care at the extremes that Dr. Gupta finds worthwhile, but each is an individual case. That is, each of them is, in the language of research, anecdotal evidence. They are meant to be illustrative and even significant of the new procedures under discussion; but in research terms it takes more than one case to be significant. Over and above the number of his examples who were in other excellent health, and so good risks, we have no way of knowing other ways in which these cases were exceptional, more likely to survive than others in the same conditions. Anecdotal evidence is interesting, but it’s not necessarily significant. But once you’ve published in the book, how clear will that be to the reading public?

Now, to address that issue the book is extensively footnoted. That could give one a good sense of reliability. However, when I read the footnotes, I had questions. Certainly, Dr. Gupta quotes valid resources, including both peer reviewed publications and conversations with the professionals involved. At the same time, a fair number of the citations are simple of other news reports. That offers some confirmation that these events really happened, but no additional assurance that these events are really meaningful.

And even the peer reviewed publications weren’t always as confirming as Dr. Gupta thought. Part of what got me into the book was its first chapter. That chapter is devoted to therapeutic hypothermia, a treatment I’ve written about before. A major part of the chapter is a historical review of efforts to establish therapeutic hypothermia as the standard of care for patients who’ve had a heart attack. He speaks of the enthusiasm of the proponents, and of the questions of the opponents, and especially about difficulties with the results in research. At one point, Dr. Gupta writes, “In 2005, the AHA’s [American Heart Association] guidelines for treating cardiac arrest were rewritten, as they are every five years, and they did list therapeutic hypothermia as a recommended treatment – but still not that elusive standard of care.”

The problem for me is that this statement is not accurate, or at least not as reliable as one migh think. The publication that Dr. Gupta cites is “2005 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care” (Circulation 112, no. 24 (December, 2005): IV-136 – IV-138). Unfortunately, the pages don’t say that hypothermia is a “recommended treatment.” In fact, that section of the report isn’t really about hyperthermia as treatment at all. It’s about appropriate treatment when a victim is found who is already hypothermic. It does note (twice, actually) that “hypothermia may exert a protective effect on the brain and organs in cardiac arrest;” but it isn’t advocating cooling patients who are already cool, and it isn’t commenting on hypothermia as treatment.

Now, there is a section on “Postresuscitation Support” (pp. IV-84 – IV-88). That includes several paragraphs on “Temperature Regulation,” and they do address induced hypothermia. This section does recommend therapeutic hypothermia, but not broadly. Rather,

In a select subset of patients who were initially comatose but hemodynamically stable after a witnessed VF [ventricular fibrillation] arrest of presumed cardiac etiology, active induction of hypothermia was beneficial. Thus, unconscious patients with ROSC [recovery of spontaneous circulation – the heart restarted] after out-of-hospital cardiac arrest should be cooled… for 12 to 24 hours when the initial rhythm was VF…. (emphasis mine)
This limited recommendation is based on two studies, at least as cited in the text. In both studies more patients did well among those who received hypothermia than among those who didn’t. However, it’s important to look at the exclusion criteria – that is, to know what cardiac patients they didn’t include in the study. In one (1),

Patients were excluded if they met any of the following criteria: a tympanic-membrane temperature below 30°C on admission, a comatose state before the cardiac arrest due to the administration of drugs that depress the central nervous system, pregnancy, response to verbal commands after the return of spontaneous circulation and before randomization, evidence of hypotension (mean arterial pressure, less than 60 mm Hg) for more than 30 minutes after the return of spontaneous circulation and before randomization, evidence of hypoxemia (arterial oxygen saturation, less than 85 percent) for more than 15 minutes after the return of spontaneous circulation and before randomization, a terminal illness that preceded the arrest, factors that made participation in follow-up unlikely, enrollment in another study, the occurrence of cardiac arrest after the arrival of emergency medical personnel, or a known preexisting coagulopathy.
In the other (2),

The exclusion criteria were an age of less than 18 years for men, an age of less than 50 years for women (because of the possibility of pregnancy), cardiogenic shock (a systolic blood pressure of less than 90 mm Hg despite epinephrine infusion), or possible causes of coma other than cardiac arrest (drug overdose, head trauma, or cerebrovascular accident). Patients were also excluded if an intensive care bed was not available at a participating institution.

Two things strike me about these sets of exclusion criteria. One is that they differ, making it more difficult to connect their data and generalize from it. The second is how carefully they narrow the types of patients with possible heart attacks who were actually studied. So, as the AHA Report says, “a select subset” showed benefit, and not a broad spectrum of patient unconscious after heart attacks. This is, of course, a common step in research. However, each exclusion adds another group of patients for whom it’s hard to argue the benefits of induced hypothermia.

Perhaps that progressive narrowing of “a select subset” is the reason for this comment in the last section of the AHA guidelines, “Major Changes in the 2005 AHA Guidelines for CPR and ECC,” by Hazinski et al (Circulation 112, no. 24 (December, 2005): IV-206 – IV-211): “Because of the challenges in the practical application of therapeutic hypothermia, further research is needed to identify optimal methods of cooling and optimal timing, duration, and intensity of cooling that is likely to be effective.” (p. 209)

So, it’s clear from what research we have that there are definitely patients who can benefit from therapeutic hypothermia. What we don’t know yet is how to determine who will and who won’t. It’s that lack of clarity that calls for more research before this could become the standard of care in postresuscitation care.

Now, for Dr. Gupta the physician that should be obvious. However, for Dr. Gupta the journalist it’s glossed over, in the interest of the story.  That's unfortunate, because it's particularly important for the wider reading public in understanding when this might be appropriate and available, and when it might not - specifically, when it might not be appropriate for someone they love.

An notethat I raised the question of availability.  Availability is one of the "challenges" cited in the "Major Changes" article by Hazinski et al.  For not only hypothermia, but also for almost all the new and "miraculous" procedures Dr. Gupta reports on, availability is a major issue (changes in standards for CPR are the noteworthy exception).  In his anecdotal reports, patients have access to major research hospitals, whether by proximity, by insurance, or by the interest an individual physician takes in the case.  For most patients, and certainly for most who might read this book, those resources are simply not going to be available.

As I said, this is an interesting and readable book.  Unfortunately, for all the qualifications of Dr. Gupta the doctor, this book from Dr. Gupta the reporter shows all the shortcomings of health journalism.  It brings out possibilities well before they're going to be generally accepted, much less available.  It highlights the successes without making clear the limitations, and especially the limitations in how many patients might actually be appropriate recipients of the therapies.  Finally, while it uses research to support the story, it does so poorly, relying primarily on anecdotal reports and using published research imprecisely.  Yeah, it's an interesting read.  Unfortunately, it might just create more problems than it solves.

(1) “Therapeutic Hypothermia after Cardiac Arrest,” the Hypothermia after Cardiac Arrest Study Group , Bernard S. A., et al, New England Journal of Medicine 346: 549-556, February 21, 2002.

(2) “Treatment of Comatose Survivors of Out-of-Hospital Cardiac Arrest with Induced Hypothermia, Stephen A. Bernard, M.B., B.S., et al, New England Journal of Medicine 346: 557-563, February 21, 2002.


Christian Sinclair, MD said...

Great post. You really looked into the details of this, which I commend since many people just would read it superficially and think they too could 'cheat death.'

GeriPal has a great take on this book as well.

Marshall Scott said...

Christian, thanks for the comment. And I do also appreciate your post on this. The related issues raised when he writes about "cheating death," and about changing (or wanting to change) means of determining death, can make for difficulties in both your work and mine.