Tuesday, January 31, 2006
Oxygen transport in critical illness
These two articles in November’s Chest belong in the libraries of hospitalists and critical care specialists. [1] [2] They outline theory, practices and controversies concerning oxygen delivery.
Thursday, January 26, 2006
Medical searching secrets
Told by Mohammad Al-Ubaydli in this article from PLOS Medicine. Although Google medical searching has been well covered by the med bloggers I found some new tips here. There’s also good information about some of the other search engines and a caveat: handy as Google is it lacks the precision of Pub Med. Pub Med’s a must if your search has to be comprehensive, or if you need to know exactly how the search was executed. Ovid Medline works similarly but it’s not free.
Wednesday, January 25, 2006
And speaking of conflicts of interest-----
The country’s most popular alt med guru may have a few of his own. Though receiving far less publicity than mainstream docs and Big Pharma it has been exposed by the Center for Science in the Public Interest and is covered here and here. Thanks to the Health Fraud List for the links.
Medical professionalism and Big Pharma
An article in today’s JAMA received heavy coverage in the media and around the blogosphere. (Via DB’s Medical Rants). The authors, concerned that the pharmaceutical industry corrupts medical ethics, want stringent regulations. My first read was the New York Times coverage which hypes the issue in the opening paragraph: “The free gifts, drugs and classes that pharmaceutical and medical device makers routinely give doctors undermine good medical care, hurt patients and should be banned, a group of influential doctors say in The Journal of the American Medical Association.” (Italics mine). So--- pens, note pads, drug samples and sponsored CME activities hurt patients! The JAMA authors, to their credit, said no such thing. And, as I have blogged previously, there’s not a shred of evidence to support that assertion.
I agree with some of the points in the JAMA article. However the authors are inconsistent on their position concerning conflict of interest. Out of concern for conflict of interest they argue for elimination of small gifts yet acknowledge the token nature of such gifts under existing regulations.
They assert: “Arguably, the most challenging and extensive of these conflicts emanate from relationships between physicians and pharmaceutical companies and medical device manufacturers.” Yet, as Health Care Renewal pointed out today, our profession is faced with many conflicts of interest other than those created by the pharmaceutical industry. Perhaps the most pervasive, at least in primary care, is the perverse financial incentive to spend less time with individual patients due to an ill conceived compensation system, as recently pointed out by DB.
Finally, I think their restrictions on CME support are ill advised. I’m afraid if they have their way we can say good bye to Medscape, emedicine, and CME as we now know it.
I agree with some of the points in the JAMA article. However the authors are inconsistent on their position concerning conflict of interest. Out of concern for conflict of interest they argue for elimination of small gifts yet acknowledge the token nature of such gifts under existing regulations.
They assert: “Arguably, the most challenging and extensive of these conflicts emanate from relationships between physicians and pharmaceutical companies and medical device manufacturers.” Yet, as Health Care Renewal pointed out today, our profession is faced with many conflicts of interest other than those created by the pharmaceutical industry. Perhaps the most pervasive, at least in primary care, is the perverse financial incentive to spend less time with individual patients due to an ill conceived compensation system, as recently pointed out by DB.
Finally, I think their restrictions on CME support are ill advised. I’m afraid if they have their way we can say good bye to Medscape, emedicine, and CME as we now know it.
Tuesday, January 24, 2006
Evidence based mechanical ventilation
For years technological advances in respiratory care have outpaced clinical evidence, resulting in a confusing array of opinions about the best way to deliver and “wean” from mechanical ventilation (MV). But evidence based medicine is here, enabling a systematic approach. This approach is nicely summarized in a review by Neil MacIntyre in the November issue of Chest. The article is worth reading in the original. A few summary points are made below.
The review pertains primarily to acute respiratory distress syndrome (ARDS) and acute lung injury (ALI) but many of the principles are applicable to other forms of respiratory failure. MV itself can injure the lungs, a concept known as ventilator induced lung injury (VILI). There are two well known mechanisms of this injury: volutrauma (over distension of alveoli) and atelectrauma (alveolar shearing caused by repetitive opening and closing of marginal or “recruitable” alveoli). These mechanisms of injury suggest a rationale for the prevention of both forms of VILI by maintaining tidal ventilation between the lower and upper inflection points of the pressure volume curve. Theoretically this means utilization of low tidal volumes combined with high levels of peep designed to recruit alveoli. However, somewhat surprisingly, only one of these strategies—low tidal volumes—is supported by high level clinical evidence. As for the use of peep, the best approach may be that outlined by the ARDS net peep scale.
The current synthesis of evidence also enables a systematic, almost algorhythmic, approach to discontinuation of MV. The process of discontinuation has traditionally been termed “weaning”, a misconception, since it implies that liberation from mechanical ventilation is done gradually. This concept was the basis for the now outmoded approaches of gradual reduction in levels of pressure support or frequency of machine delivered breaths in the SIMV mode. (Patients with poor cardiovascular reserve may occasionally constitute an exception to the rule that true weaning is not necessary. Because resumption of spontaneous breathing is a cardiovascular stress, patients with marginal reserve may experience ischemia and pulmonary edema upon abrupt withdrawal of ventilatory support. That issue is addressed briefly in another review in the same issue of Chest).
The process has two phases, the first of which consists of clinical assessment for readiness, and which should be done daily. The criteria that must be met are 1) evidence of stabilization and/or improvement in the original disease process; 2) blood gas parameters reflecting PO2/FiO2 > 150, peep level of less than 8, FiO2 less than 0.5, and ph greater than 7.25; 3) hemodynamic stability; and 4) ability to make an inspiratory effort. This assessment must also take into account the patient's general condition and neurologic status.
Once those criteria are met the patient may be considered for advancement to the second phase, the spontaneous breathing trial, which can be done with the patient on a T-tube, C-pap, or pressure support. If the patient maintains a frequency/tidal volume ratio under105 over the first several minutes, the trial is continued for 30 minutes to 2 hours. Tolerance of the period of spontaneous breathing without adverse clinical signs generally indicates readiness for withdrawal from MV, tempered by clinical judgment. Patients who fail the trial should have their disease process, nutrition, pain control, fluid balance and overall management reviewed and breathing trials repeated as appropriate.
The review pertains primarily to acute respiratory distress syndrome (ARDS) and acute lung injury (ALI) but many of the principles are applicable to other forms of respiratory failure. MV itself can injure the lungs, a concept known as ventilator induced lung injury (VILI). There are two well known mechanisms of this injury: volutrauma (over distension of alveoli) and atelectrauma (alveolar shearing caused by repetitive opening and closing of marginal or “recruitable” alveoli). These mechanisms of injury suggest a rationale for the prevention of both forms of VILI by maintaining tidal ventilation between the lower and upper inflection points of the pressure volume curve. Theoretically this means utilization of low tidal volumes combined with high levels of peep designed to recruit alveoli. However, somewhat surprisingly, only one of these strategies—low tidal volumes—is supported by high level clinical evidence. As for the use of peep, the best approach may be that outlined by the ARDS net peep scale.
The current synthesis of evidence also enables a systematic, almost algorhythmic, approach to discontinuation of MV. The process of discontinuation has traditionally been termed “weaning”, a misconception, since it implies that liberation from mechanical ventilation is done gradually. This concept was the basis for the now outmoded approaches of gradual reduction in levels of pressure support or frequency of machine delivered breaths in the SIMV mode. (Patients with poor cardiovascular reserve may occasionally constitute an exception to the rule that true weaning is not necessary. Because resumption of spontaneous breathing is a cardiovascular stress, patients with marginal reserve may experience ischemia and pulmonary edema upon abrupt withdrawal of ventilatory support. That issue is addressed briefly in another review in the same issue of Chest).
The process has two phases, the first of which consists of clinical assessment for readiness, and which should be done daily. The criteria that must be met are 1) evidence of stabilization and/or improvement in the original disease process; 2) blood gas parameters reflecting PO2/FiO2 > 150, peep level of less than 8, FiO2 less than 0.5, and ph greater than 7.25; 3) hemodynamic stability; and 4) ability to make an inspiratory effort. This assessment must also take into account the patient's general condition and neurologic status.
Once those criteria are met the patient may be considered for advancement to the second phase, the spontaneous breathing trial, which can be done with the patient on a T-tube, C-pap, or pressure support. If the patient maintains a frequency/tidal volume ratio under105 over the first several minutes, the trial is continued for 30 minutes to 2 hours. Tolerance of the period of spontaneous breathing without adverse clinical signs generally indicates readiness for withdrawal from MV, tempered by clinical judgment. Patients who fail the trial should have their disease process, nutrition, pain control, fluid balance and overall management reviewed and breathing trials repeated as appropriate.
Monday, January 23, 2006
Hyponatremia, hypokalemia and thiazide diuretics, part 2
Click here for part 1.
“Thiazide diuretic prescription and electrolyte abnormalities in primary care”, published in the January issue of the British Journal of Clinical Pharmacology, has several important lessons on the use of thiazides. Thiazide induced hypokalemia is generally known to be dose related, and the better safety profile with chlorthalidone in ALLHAT compared to MRFIT is believed to reflect the lower doses used in ALLHAT. However, low doses of thiazides were used in the current British study. No patient whose electrolyte disturbance was categorized as severe exceeded the usual starting dose of the thiazide, and 75% of patients with severe disturbances received only half the starting dose. So, while lower doses of thiazides are safer they do not eliminate the problem. Unfortunately the British study does not address mortality, nor does it tell us how many patients were hospitalized as a result of electrolyte disturbances.
Hyponatremia deserves special mention. Unlike hypokalemia, thiazide induced hyponatremia is less predictable. It appears to be an idiosyncratic reaction. This complication of thiazide treatment can have severe clinical consequences: lasting neurologic sequelae and deaths have been documented. This is the subject of a fascinating editorial from last August’s issue of Nephrology Dialysis Transplantation which reviews several unique clinical characteristics and risk factors for the syndrome. The principal mechanism of thiazide induced hyponatremia is probably not mineral depletion. There is evidence to suggest that thiazides promote retention of free water by up regulation of aquaporin channels in the renal collecting ducts.
While the British study informs us about electrolyte disturbances we desperately need data on the frequency with which such disturbances lead to clinical consequences. Such information is elusive in the case of hypokalemia given the difficulty in knowing the prevailing potassium concentration at the time of sudden cardiac death. The link between severe hyponatremia and neurologic sequelae is more easily established. Although multiple instances have been documented in the literature we don’t know the true frequency because we lack a denominator. Clinical events related to electrolyte disturbances, though they must have occurred, were not reported in ALLHAT.
These observations have implications for clinical practice and research.
1) As DB pointed out, electrolytes should be monitored regularly in patients taking thiazides.
2) Because thiazide induced hyponatremia is idiosyncratic and may occur early, the first electrolyte panel should be obtained within two weeks of the start of treatment.
3) Though normal electrolyte levels would seem a reasonable goal for most patients this recent paper from the Journal of the American College of Cardiology suggests that for patients with underlying heart disease normal is not enough. The authors recommend a potassium target of 4.5.
4) If the data are available the ALLHAT investigators should report the frequency of clinical sequelae and hospitalization related to thiazide induced electrolyte disturbances.
“Thiazide diuretic prescription and electrolyte abnormalities in primary care”, published in the January issue of the British Journal of Clinical Pharmacology, has several important lessons on the use of thiazides. Thiazide induced hypokalemia is generally known to be dose related, and the better safety profile with chlorthalidone in ALLHAT compared to MRFIT is believed to reflect the lower doses used in ALLHAT. However, low doses of thiazides were used in the current British study. No patient whose electrolyte disturbance was categorized as severe exceeded the usual starting dose of the thiazide, and 75% of patients with severe disturbances received only half the starting dose. So, while lower doses of thiazides are safer they do not eliminate the problem. Unfortunately the British study does not address mortality, nor does it tell us how many patients were hospitalized as a result of electrolyte disturbances.
Hyponatremia deserves special mention. Unlike hypokalemia, thiazide induced hyponatremia is less predictable. It appears to be an idiosyncratic reaction. This complication of thiazide treatment can have severe clinical consequences: lasting neurologic sequelae and deaths have been documented. This is the subject of a fascinating editorial from last August’s issue of Nephrology Dialysis Transplantation which reviews several unique clinical characteristics and risk factors for the syndrome. The principal mechanism of thiazide induced hyponatremia is probably not mineral depletion. There is evidence to suggest that thiazides promote retention of free water by up regulation of aquaporin channels in the renal collecting ducts.
While the British study informs us about electrolyte disturbances we desperately need data on the frequency with which such disturbances lead to clinical consequences. Such information is elusive in the case of hypokalemia given the difficulty in knowing the prevailing potassium concentration at the time of sudden cardiac death. The link between severe hyponatremia and neurologic sequelae is more easily established. Although multiple instances have been documented in the literature we don’t know the true frequency because we lack a denominator. Clinical events related to electrolyte disturbances, though they must have occurred, were not reported in ALLHAT.
These observations have implications for clinical practice and research.
1) As DB pointed out, electrolytes should be monitored regularly in patients taking thiazides.
2) Because thiazide induced hyponatremia is idiosyncratic and may occur early, the first electrolyte panel should be obtained within two weeks of the start of treatment.
3) Though normal electrolyte levels would seem a reasonable goal for most patients this recent paper from the Journal of the American College of Cardiology suggests that for patients with underlying heart disease normal is not enough. The authors recommend a potassium target of 4.5.
4) If the data are available the ALLHAT investigators should report the frequency of clinical sequelae and hospitalization related to thiazide induced electrolyte disturbances.
Sunday, January 22, 2006
Defending scientific medicine
I have blogged critically about alternative medicine. This post is driven by readers’ comments. They follow several general themes to which I offer this response.
They laughed when researchers claimed a bacterial infection could cause ulcers. Those researchers just won the Nobel Prize.
Several readers made this point after I criticized “research” that was not based on biologic plausibility. This premise, that the mainstream rejected the bacterial theory, is false. A Pub Med search yields a spate of favorable articles within several years of the 1983 Helicobacter paper. There’s a distinction to be made. The notion of a bacterial cause of peptic ulcer was novel but not implausible. Furthermore it had an evidentiary basis. (Those researchers could actually look in the microscope and see the critters inhabiting the stomach lining). Contrast that with homeopathy---the idea that once all molecules are diluted out of solution a force is left behind which imparts clinical effects. I would be the first to urge research funding for homeopathy if there was even a shred of evidence that such a force exists. If it’s powerful enough to cure multiple ailments why hasn’t it been measured in the more than 200 years since Samuel Hahnemann advanced the theory? Wouldn’t it alter the physical properties of water in some way---maybe alter the electrostatic charges or the hydrogen bond configuration? I think the folks at MIT would have demonstrated something by now.
Mainstream medicine ignores the psychosocial dimensions of health and disease.Moof said it well: “I think that the reason the general public is so keen on that sort of thing is because the pseudo-scientific 'medicines' are more in the business of connecting with people on an emotive level than they are on a medical level. To counter this, serious medicine may have to try a bit harder to relate to more than just the physical aspects of illnesses.” Although a scientific underpinning doesn’t preclude an emotional connection doctors, for a variety or reasons, don’t spend enough time with patients. The unfortunate consequence is that alternative practitioners have hijacked the concept of “treating the whole person.”
Mainstream medicine doesn’t have all the answers.Of course not. Tune up your baloney detector and run from any medical system that claims to have all the answers.
Mainstream medicine is just following the money.
That’s partially true, and maybe it’s why the mainstream increasingly embraces quackery. It sells.
If patients think it works, what’s the harm?Patients have the right to choose. They are and should be free to go to the local herbalist or purchase the latest colon cleanse remedy. It’s quite another thing for us in the mainstream to endorse invalid methods. We claim to base our practices on good science and that’s what the public expects of us. If we accommodate unscientific practices through some sort of “integration” we endorse those practices, either explicitly or implicitly. Our science then becomes pretense. That’s pseudoscience. It betrays the public’s expectation and is, in my opinion, unethical.
They laughed when researchers claimed a bacterial infection could cause ulcers. Those researchers just won the Nobel Prize.
Several readers made this point after I criticized “research” that was not based on biologic plausibility. This premise, that the mainstream rejected the bacterial theory, is false. A Pub Med search yields a spate of favorable articles within several years of the 1983 Helicobacter paper. There’s a distinction to be made. The notion of a bacterial cause of peptic ulcer was novel but not implausible. Furthermore it had an evidentiary basis. (Those researchers could actually look in the microscope and see the critters inhabiting the stomach lining). Contrast that with homeopathy---the idea that once all molecules are diluted out of solution a force is left behind which imparts clinical effects. I would be the first to urge research funding for homeopathy if there was even a shred of evidence that such a force exists. If it’s powerful enough to cure multiple ailments why hasn’t it been measured in the more than 200 years since Samuel Hahnemann advanced the theory? Wouldn’t it alter the physical properties of water in some way---maybe alter the electrostatic charges or the hydrogen bond configuration? I think the folks at MIT would have demonstrated something by now.
Mainstream medicine ignores the psychosocial dimensions of health and disease.Moof said it well: “I think that the reason the general public is so keen on that sort of thing is because the pseudo-scientific 'medicines' are more in the business of connecting with people on an emotive level than they are on a medical level. To counter this, serious medicine may have to try a bit harder to relate to more than just the physical aspects of illnesses.” Although a scientific underpinning doesn’t preclude an emotional connection doctors, for a variety or reasons, don’t spend enough time with patients. The unfortunate consequence is that alternative practitioners have hijacked the concept of “treating the whole person.”
Mainstream medicine doesn’t have all the answers.Of course not. Tune up your baloney detector and run from any medical system that claims to have all the answers.
Mainstream medicine is just following the money.
That’s partially true, and maybe it’s why the mainstream increasingly embraces quackery. It sells.
If patients think it works, what’s the harm?Patients have the right to choose. They are and should be free to go to the local herbalist or purchase the latest colon cleanse remedy. It’s quite another thing for us in the mainstream to endorse invalid methods. We claim to base our practices on good science and that’s what the public expects of us. If we accommodate unscientific practices through some sort of “integration” we endorse those practices, either explicitly or implicitly. Our science then becomes pretense. That’s pseudoscience. It betrays the public’s expectation and is, in my opinion, unethical.
Saturday, January 21, 2006
Arnold Relman versus Andrew Weil
April 9, 1999 marked a defining moment in the alt med controversy. The future of “integrative medicine” was the subject of a debate between Arnold Relman, editor emeritus of the New England Journal of Medicine and Andrew Weil, director of the University of Arizona program in Integrative Medicine. A partial transcript of the debate was published several months later in the Archives of Internal Medicine. Relman took the skeptical side, arguing that pseudoscience and mysticism cannot be meaningfully “integrated” with Western science.
Now you can watch the debate in its entirety here (scroll to April 9, 1999 and choose Real Player or Windows Media Player format). It was recently posted at the Video Archives of the University of Arizona. (Gotta go with Relman on this).
Now you can watch the debate in its entirety here (scroll to April 9, 1999 and choose Real Player or Windows Media Player format). It was recently posted at the Video Archives of the University of Arizona. (Gotta go with Relman on this).
Thursday, January 19, 2006
A verbal spanking from Jacob
My remarks on alternative medicine evidently pushed some buttons. Jacob of Family Medicine Notes commented on yesterday’s post: "You are joking right? These people are doing research. I don't get why you would discount something just because it is not mainstream big-pharma funded. If a well-researched alternative to the traditional treatments turns out to be effective - I would call this SCIENCE .. and your knee-jerk rejection of all things "integrative" to be the pseudo-science. Shame on you!"
Wow. Where to begin. Jacob reminds us that research is being done. I acknowledge and applaud high quality research in CAM. Note the proviso high quality. If, for example, the large NIH sponsored placebo controlled chelation therapy trial demonstrates benefits for patients with coronary artery disease I’ll accept chelation as something that works. Mainstream or not the real distinction is between health claims which have been scientifically proven to work and those which have not.
Other notions proffered for “research” are, in my considered opinion, exercises in pseudoscience---attempts to validate claims that have been debunked and have no biologic plausibility. What’s the point of looking for clinical effects of energy fields undetectable by instruments of physicists and Star Wars forces left behind in water after active ingredients are diluted out?
A strict empiricist might object to my requirement of biologic plausibility, but I maintain a line must be drawn. Otherwise we might as well burn the chemistry and physics books and study every claim that comes along. Why stop with Therapeutic Touch, Homeopathy and Reiki? Let’s go on down the slippery slope and fund studies of astrology, telekinesis and shamanism. And while we’re on the subject of energy medicine why not resurrect Franz Mesmer’s theory of animal magnetism? If only we do enough research his claims will surely be validated. (Discredited in the 18th century, Mesmer would likely be on faculty at a medical school today).
But it’s not so much the research I criticize as the uncritical promotion of baseless methods. Jacob thinks I'm pseudoscientific. Is it pseudoscientific to be skeptical, ask questions or require proof? Having now elaborated on the basis for my objections I hope Jacob and other readers will not regard my opinions as knee-jerk. Finally, I’m afraid I’m missing Jacob’s point about big-pharma funding---it hasn’t entered into my opinions on pseudoscience.
If it seems I’m beating the drum on pseudoscience, I have a distinct purpose: exposure. People who expect institutions of medical education and health care to be based on rigorous science and intellectual integrity need to know what’s going on. Or maybe I’m just full of negative energy.
Wow. Where to begin. Jacob reminds us that research is being done. I acknowledge and applaud high quality research in CAM. Note the proviso high quality. If, for example, the large NIH sponsored placebo controlled chelation therapy trial demonstrates benefits for patients with coronary artery disease I’ll accept chelation as something that works. Mainstream or not the real distinction is between health claims which have been scientifically proven to work and those which have not.
Other notions proffered for “research” are, in my considered opinion, exercises in pseudoscience---attempts to validate claims that have been debunked and have no biologic plausibility. What’s the point of looking for clinical effects of energy fields undetectable by instruments of physicists and Star Wars forces left behind in water after active ingredients are diluted out?
A strict empiricist might object to my requirement of biologic plausibility, but I maintain a line must be drawn. Otherwise we might as well burn the chemistry and physics books and study every claim that comes along. Why stop with Therapeutic Touch, Homeopathy and Reiki? Let’s go on down the slippery slope and fund studies of astrology, telekinesis and shamanism. And while we’re on the subject of energy medicine why not resurrect Franz Mesmer’s theory of animal magnetism? If only we do enough research his claims will surely be validated. (Discredited in the 18th century, Mesmer would likely be on faculty at a medical school today).
But it’s not so much the research I criticize as the uncritical promotion of baseless methods. Jacob thinks I'm pseudoscientific. Is it pseudoscientific to be skeptical, ask questions or require proof? Having now elaborated on the basis for my objections I hope Jacob and other readers will not regard my opinions as knee-jerk. Finally, I’m afraid I’m missing Jacob’s point about big-pharma funding---it hasn’t entered into my opinions on pseudoscience.
If it seems I’m beating the drum on pseudoscience, I have a distinct purpose: exposure. People who expect institutions of medical education and health care to be based on rigorous science and intellectual integrity need to know what’s going on. Or maybe I’m just full of negative energy.
Pseudoscience promotion by hospitals
Memorial Herman Katy Hospital is hosting a workshop this week on ancient healing methods. Participants will be taught “how to use sound and movement to cleanse and recharge the internal organs of stagnant energy, standing meditation and other postures that drive qi or ‘pure energy’ through the bones, increasing strength and balancing the immune system.”
Wednesday, January 18, 2006
Medical school pseudoscience is pervasive
When I first began researching the antiscientific agenda in medical education I thought it was confined to isolated examples popping up here and there. I was wrong. It’s become organized. There’s a consortium of academic medical centers pushing for more pseudoscience in the curriculum. Is your favorite med school on the list?
Tuesday, January 17, 2006
Hyponatremia, hypokalemia and thiazide diuretics, part 1
DB of DB’s Medical Rants recently posted a discussion of a study highlighting hyponatremia and hypokalemia in patients taking thiazides. The metabolic effects of thiazides have long been controversial and this paper adds to our understanding of the problem. My interest in the topic of thiazide safety was piqued by the controversies in the field of hypertension in the wake of ALLHAT. DB’s post prompted me to review the literature.
Although the true magnitude of the metabolic consequences of thiazide diuretics is not known it is likely to be increasing with heavier use of the drugs following the publication and promotion of ALLHAT. Upon release of the ALLHAT results an aggressive media campaign, which pushed thiazide diuretics, was launched. Less than a year later the boosters of ALLHAT announced plans (Lancet, subscription required) to enlist hundreds of doctors as a sales force and train them in the techniques used by drug companies to market products. The goal was to get out the message that thiazides should be the “first step” drugs for most patients in hypertension treatment. A recent increase in the thiazide market share suggests that the message was effective.
The message recommended a stepped care approach to hypertension similar to one popularized decades ago, which was used for the intervention group in the Multiple Risk Factor Intervention Trial (MRFIT). That study, published in 1982, was important because it first raised awareness of the metabolic hazzards of thiazides. In a subset of the MRFIT cohort (patients with electrocardiographic abnormalities) thiazide use was associated with sudden cardiac death. It was believed to be due to hypokalemia and perhaps activation of the renin angiotensin system.
Starting in 1982 the rate of thiazide prescribing began to decline. Although this finding has been spun to reflect on industry promotion of newer more expensive brands of antihypertensives, the new safety concerns raised by MRFIT undoubtedly had a negative impact on thiazide use. (In 1982 the only angiotensin converting enzyme inhibitor available was captopril. Although three calcium channel blockers were being marketed at the time for angina and arrhythmias, none were yet approved for hypertension).
Subsequent studies such as the SHEP trial suggested a better safety profile for thiazides as did ALLHAT. But the latest article cited by DB suggests the pendulum once again swinging towards heightened safety concerns. The paper appeared in the January issue of the British Journal of Clinical Pharmacology, and an open access full text version is available here.
In part two I will review this paper in some detail and discuss practical clinical implications of the metabolic hazards of thiazide diuretics.
Although the true magnitude of the metabolic consequences of thiazide diuretics is not known it is likely to be increasing with heavier use of the drugs following the publication and promotion of ALLHAT. Upon release of the ALLHAT results an aggressive media campaign, which pushed thiazide diuretics, was launched. Less than a year later the boosters of ALLHAT announced plans (Lancet, subscription required) to enlist hundreds of doctors as a sales force and train them in the techniques used by drug companies to market products. The goal was to get out the message that thiazides should be the “first step” drugs for most patients in hypertension treatment. A recent increase in the thiazide market share suggests that the message was effective.
The message recommended a stepped care approach to hypertension similar to one popularized decades ago, which was used for the intervention group in the Multiple Risk Factor Intervention Trial (MRFIT). That study, published in 1982, was important because it first raised awareness of the metabolic hazzards of thiazides. In a subset of the MRFIT cohort (patients with electrocardiographic abnormalities) thiazide use was associated with sudden cardiac death. It was believed to be due to hypokalemia and perhaps activation of the renin angiotensin system.
Starting in 1982 the rate of thiazide prescribing began to decline. Although this finding has been spun to reflect on industry promotion of newer more expensive brands of antihypertensives, the new safety concerns raised by MRFIT undoubtedly had a negative impact on thiazide use. (In 1982 the only angiotensin converting enzyme inhibitor available was captopril. Although three calcium channel blockers were being marketed at the time for angina and arrhythmias, none were yet approved for hypertension).
Subsequent studies such as the SHEP trial suggested a better safety profile for thiazides as did ALLHAT. But the latest article cited by DB suggests the pendulum once again swinging towards heightened safety concerns. The paper appeared in the January issue of the British Journal of Clinical Pharmacology, and an open access full text version is available here.
In part two I will review this paper in some detail and discuss practical clinical implications of the metabolic hazards of thiazide diuretics.
Monday, January 16, 2006
Hygienic measures to avert dementia
Gardening, walking and modest alcohol intake according to this Australian study.
And, just today emedicine reports a soundbite version of a study due out in tomorrow’s Annals of Internal Medicine with similar implications.
And, just today emedicine reports a soundbite version of a study due out in tomorrow’s Annals of Internal Medicine with similar implications.
Evidence based medicine--- old ideas recycled
It’s widely believed that evidence based medicine is a new idea. I’m not so sure. Although the general view is that the concept originated with Gordon Guyatt in 1992 I found something interesting in the almost century old Flexner Report (large pdf download).
The promoters of EBM say we need to replace dogma with evidence, tradition with science and physiologic assumptions with empiric observations. They tell us that old practice patterns need continual re-evaluation in the light of new evidence.
Great new ideas, right? Well, page 156 of the Flexner Report says-- “The modern point of view may be restated as follows: medicine is a discipline, in which the effort is made to use knowledge procured in various ways in order to effect certain practical ends. With abstract general propositions it has nothing to do. It harbors no preconceptions as to diseases or their cure. Instead of starting with a finished and supposedly adequate dogma or principle, it has progressively become less cocksure and more modest. It distrusts general propositions, a priori explanations, grandiose and comforting generalizations.” So this, Flexner’s view of the scientific basis of medicine, reads like a defense of EBM today.
A few sentences later Flexner issues a plea for evidence in medicine stating “It wants not dogma, but facts.” And, sounding again like an EBM apologist he says this concerning bias and conflict of interest in research: “The sectarian, on the other hand, begins with his mind made up. He possesses in advance a general formula, which the particular instance is going to illustrate, verify, reaffirm, even though he may not know just how. One may be sure that facts so read will make good what is expected of them; that only that will be seen which will sustain its expected function; that every aspect noted will be dutifully loyal to the revelation in whose favor the observer is predisposed: the human mind is so constituted.”
Another supposedly new tenet of EBM is the destruction of medical myths. But Flexner long ago recognized the hazard of medical myth: “Scientific medicine therefore brushes aside all historic dogma.” Finally, we all know how EMB decries reliance on experts. Flexner anticipated the problem, declaring “No man is asked in whose name he comes—whether that of Hahnemann, Rush, or of some more recent prophet. But all are required to undergo rigorous cross-examination.”
In these prescient words of Abraham Flexner we read the principles of EBM articulated some 95 years ago. (The full Flexner report is an interesting read, but long. A more easily accessible html page containing the section of the report referenced above can be found in this article from HomeoWatch).
The promoters of EBM say we need to replace dogma with evidence, tradition with science and physiologic assumptions with empiric observations. They tell us that old practice patterns need continual re-evaluation in the light of new evidence.
Great new ideas, right? Well, page 156 of the Flexner Report says-- “The modern point of view may be restated as follows: medicine is a discipline, in which the effort is made to use knowledge procured in various ways in order to effect certain practical ends. With abstract general propositions it has nothing to do. It harbors no preconceptions as to diseases or their cure. Instead of starting with a finished and supposedly adequate dogma or principle, it has progressively become less cocksure and more modest. It distrusts general propositions, a priori explanations, grandiose and comforting generalizations.” So this, Flexner’s view of the scientific basis of medicine, reads like a defense of EBM today.
A few sentences later Flexner issues a plea for evidence in medicine stating “It wants not dogma, but facts.” And, sounding again like an EBM apologist he says this concerning bias and conflict of interest in research: “The sectarian, on the other hand, begins with his mind made up. He possesses in advance a general formula, which the particular instance is going to illustrate, verify, reaffirm, even though he may not know just how. One may be sure that facts so read will make good what is expected of them; that only that will be seen which will sustain its expected function; that every aspect noted will be dutifully loyal to the revelation in whose favor the observer is predisposed: the human mind is so constituted.”
Another supposedly new tenet of EBM is the destruction of medical myths. But Flexner long ago recognized the hazard of medical myth: “Scientific medicine therefore brushes aside all historic dogma.” Finally, we all know how EMB decries reliance on experts. Flexner anticipated the problem, declaring “No man is asked in whose name he comes—whether that of Hahnemann, Rush, or of some more recent prophet. But all are required to undergo rigorous cross-examination.”
In these prescient words of Abraham Flexner we read the principles of EBM articulated some 95 years ago. (The full Flexner report is an interesting read, but long. A more easily accessible html page containing the section of the report referenced above can be found in this article from HomeoWatch).
Sunday, January 15, 2006
Is it OK to give cardioselective beta blockers to patients with COPD?
This Cochrane review, which looked at studies using single doses or longer durations of administration, says yes. The beta blockers did not affect the patients’ symptoms, spirometry measurements or their response to bronchodilators.
Examples of cardioselective beta blockers include atenolol, metoprolol, esmolol, bisoprolol and acebutolol. Propranolol, timolol, carvedilol, labetalol and sotolol are non-selective beta blockers.
As I posted previously there is considerable overlap between COPD and cardiovascular disease so that many patients with COPD could obtain cardiovascular benefits from beta blockers. This review suggests that we should not consider them contraindicated in patients who need them for cardiovascular disease. I would caution that cardioselectivity is not absolute, and cardiovascular benefit is often obtained at higher dose ranges in which selectivity is lost. These conclusions should not be applied to patients with asthma.
Examples of cardioselective beta blockers include atenolol, metoprolol, esmolol, bisoprolol and acebutolol. Propranolol, timolol, carvedilol, labetalol and sotolol are non-selective beta blockers.
As I posted previously there is considerable overlap between COPD and cardiovascular disease so that many patients with COPD could obtain cardiovascular benefits from beta blockers. This review suggests that we should not consider them contraindicated in patients who need them for cardiovascular disease. I would caution that cardioselectivity is not absolute, and cardiovascular benefit is often obtained at higher dose ranges in which selectivity is lost. These conclusions should not be applied to patients with asthma.
Grand Rounds (the traditional kind)
Wednesday, January 11, 2006
Another useful avian flu resource
A concise review in CMAJ provides more useful information on avian flu. It briefly sketches the history of the infection since the 1997 outbreak in Hong Kong. Unique clinical features are primary viral pneumonia (as opposed to secondary bacterial pneumonia more characteristic of ordinary flu) and the occurrence of severe infections in young healthy hosts. Unique features of influenza promote genetic shift: 1) the lack of a proofreading mechanism during replication, thus allowing easier mutation and 2) organization of its RNA in the form of 8 separate strands which enables swapping of genetic material between strains when co infection occurs.
Is there evidence that we are actually moving toward a pandemic? The article cites evidence from observations of animal infections that the virus may be changing. The significance of these observations concerning the risk of a pandemic is far from clear. Links to WHO guidelines for infection control and treatment of avian flu cases are provided.
Is there evidence that we are actually moving toward a pandemic? The article cites evidence from observations of animal infections that the virus may be changing. The significance of these observations concerning the risk of a pandemic is far from clear. Links to WHO guidelines for infection control and treatment of avian flu cases are provided.
Tuesday, January 10, 2006
Hepatitis C—a multisystem disease
The extrahepatic manifestations of hepatitis C were reviewed in the November issue of Cleveland Clinic Journal of Medicine. The review points out that cryoglobulinemia is the most strongly associated manifestation. Most cases of what was formerly called essential mixed cryoglobulinemia are in fact due to hepatitis C. Most patients with circulating cryoglobulins are asymptomatic, with about 10% manifesting the typical features of purpura, arthralgia, renal disease and neuropathy, according to the review.
Other disease associations mentioned were Sjogren syndrome (an autoimmune exocrinitis differing from classic Sjogren syndrome in the lack of antibodies to SSA/Ro and SSB/La), lymphoproliferative disorders, prophyria cutanea tarda and membranoproliferative glomerulonephritis (which can occur with or without cryoglobulinemia).
Antiviral treatment for the underlying hepatitis C seems to be the most effective treatment for cryoglobulinemia and some of the other manifestations.
Other disease associations mentioned were Sjogren syndrome (an autoimmune exocrinitis differing from classic Sjogren syndrome in the lack of antibodies to SSA/Ro and SSB/La), lymphoproliferative disorders, prophyria cutanea tarda and membranoproliferative glomerulonephritis (which can occur with or without cryoglobulinemia).
Antiviral treatment for the underlying hepatitis C seems to be the most effective treatment for cryoglobulinemia and some of the other manifestations.
Monday, January 09, 2006
American Medical Massage Association takes firm stand against fringe massage therapy
Pseudoscience is rampant in the field, and AMMA has had enough.
Their position is outlined here. Fringe methods are rampant in the massage community and take up between 20% and 65% of the curriculum in message schools. According to the document “Some subjects taught in massage schools and practices of the general massage community are so extreme in nature as to constitute health care fraud.” Among the methods condemned by AMMA are metaphysical practices such as Reiki, Polarity Therapy and Therapeutic Touch. Others mentioned are those that have no rationale in known physiology such Myofacial Release.
Now why don’t the American Medical Association, the American College of Physicians and the Association of American Medical Colleges have the courage to take a similar stand?
Their position is outlined here. Fringe methods are rampant in the massage community and take up between 20% and 65% of the curriculum in message schools. According to the document “Some subjects taught in massage schools and practices of the general massage community are so extreme in nature as to constitute health care fraud.” Among the methods condemned by AMMA are metaphysical practices such as Reiki, Polarity Therapy and Therapeutic Touch. Others mentioned are those that have no rationale in known physiology such Myofacial Release.
Now why don’t the American Medical Association, the American College of Physicians and the Association of American Medical Colleges have the courage to take a similar stand?
Which CT protocol for appendicitis?
A systematic review in the American Journal of Surgery compared various combinations of oral, rectal and IV contrast for CT scanning to evaluate patients for appendicitis. All protocols performed well including imaging without oral, rectal or IV contrast. The authors believe a prospective comparative trial is needed.
A related commentary in Internal Medicine News mentions some caveats, suggesting that increased experience in interpretation may be necessary for non contrast exams, that non contrast imaging is particularly challenging in lean individuals and that non contrast exams sacrifice some ability to detect other pathology that may cause pain.
This information could prove useful for those patients with possible appendicitis in whom contrast administration is contraindicated.
A related commentary in Internal Medicine News mentions some caveats, suggesting that increased experience in interpretation may be necessary for non contrast exams, that non contrast imaging is particularly challenging in lean individuals and that non contrast exams sacrifice some ability to detect other pathology that may cause pain.
This information could prove useful for those patients with possible appendicitis in whom contrast administration is contraindicated.
Sunday, January 08, 2006
Goodpasture syndrome and Spanish Flu
There is an under appreciated historical connection between Goodpasture syndrome and the 1918 pandemic (Spanish) flu. We are traditionally taught that Goodpasture syndrome is a pulmonary-renal syndrome characterized by pulmonary hemorrhage and rapidly progressive glomerulonephritis due to antiglomerular basement membrane (anti-GBM) antibodies. But “Goodpasture syndrome” is a misnomer. The patient with pulmonary and renal disease described by Ernest Goodpasture in 1919 (Goodpasture EW. The significance of certain pulmonary lesions in relation to the etiology of influenza. Am J Med Sci 1919;158:863-70) was presented as a case of influenza and probably did not have anti-GBM disease. Yet the myth of Goodpasture syndrome persists. It was a particularly unfortunate misattribution because it diverted attention from Goodpasture’s most monumental work at Vanderbilt in 1931, the development of a chick embryo technique for viral culture. Although this ground breaking work spurred a revolution in virology and brought fame to the Pathology department at Vanderbilt, [1] over time it tended to be forgotten, being overshadowed by the eponymic association with anti-GBM disease.
The story of Ernest Goodpasture, pandemic influenza and anti-GBM disease is controversial and seems to vary with every telling. Perhaps the most reliable account can be found in the biography by Robert D. Collins, “Ernest William Goodpasture—Scientist, Scholar, Gentleman.” On pp. 64-67 we find Goodpasture in the Navy Medical Corps in 1918-19, stationed at the Chelsea Naval Hospital near Boston. There he was responsible for performing autopsies of victims of the influenza pandemic. Because many patients with the disease developed secondary bacterial pneumonia it was widely believed that influenza had a bacterial etiology. But Goodpasture postulated a viral etiology and believed that the primary etiologic agent could cause pneumonia. Therefore he was interested in finding cases of influenza pneumonia with negative bacterial cultures. Two such cases formed the basis of his 1919 paper. One of the two was described as unusual in that while the pulmonary pathologic findings were consistent with influenza the pulmonary hemorrhage was profuse and glomerular inflammation was found. It is unclear what underlying disease other than influenza this patient may have had. Attempts to retrieve the slides from Chelsea years later for further study were unsuccessful. According to Collins, Goodpasture did not approve of the association of his name with this syndrome. He writes “In this case, good intentions---recognizing Dr. Goodpasture---paved the road to inaccuracy and inappropriateness.”
And so, with apologies to Paul Harvey: Now you know the rest of the story.
The story of Ernest Goodpasture, pandemic influenza and anti-GBM disease is controversial and seems to vary with every telling. Perhaps the most reliable account can be found in the biography by Robert D. Collins, “Ernest William Goodpasture—Scientist, Scholar, Gentleman.” On pp. 64-67 we find Goodpasture in the Navy Medical Corps in 1918-19, stationed at the Chelsea Naval Hospital near Boston. There he was responsible for performing autopsies of victims of the influenza pandemic. Because many patients with the disease developed secondary bacterial pneumonia it was widely believed that influenza had a bacterial etiology. But Goodpasture postulated a viral etiology and believed that the primary etiologic agent could cause pneumonia. Therefore he was interested in finding cases of influenza pneumonia with negative bacterial cultures. Two such cases formed the basis of his 1919 paper. One of the two was described as unusual in that while the pulmonary pathologic findings were consistent with influenza the pulmonary hemorrhage was profuse and glomerular inflammation was found. It is unclear what underlying disease other than influenza this patient may have had. Attempts to retrieve the slides from Chelsea years later for further study were unsuccessful. According to Collins, Goodpasture did not approve of the association of his name with this syndrome. He writes “In this case, good intentions---recognizing Dr. Goodpasture---paved the road to inaccuracy and inappropriateness.”
And so, with apologies to Paul Harvey: Now you know the rest of the story.
AMSA and PharmFree
A commenter gently cautioned me against the ad hominem fallacy in my recent blog post on this topic. He wrote: “I just wanted to state the point of view that although AMSA may not be the best practitioner of its message that should not take away from the validity of the message.” Regular readers of this blog know my view of the message, which is about the relationship between physicians and the pharmaceutical industry. While I agree partially with their concerns I think the position of PharmFree and organizations like No Free Lunch is extreme. I have expressed a more moderate view in the pages of this blog, filed under the Medicine and Public Debate category.
Although the commenter correctly points out that PharmFree should be judged on its own merits, he may have missed my larger point. The AMSA seems to be claiming the moral high ground in matters of ethics, evidence and doing what’s best for patients. But the claim is baseless when they actively promote bogus (and in my opinion fraudulent) health claims. Moreover, they accuse the profession of engaging in conflicts of interest when they themselves accept money in return for distributing promotional material from an organization which advocates shamanism, ritual healing and New Age fluff. So, it kind of ruffles my feathers when they point the accusing finger and besmirch the ethics of the medical profession. This inconsistency also begs the question of motivation: what is the real agenda of PharmFree?
Although the commenter correctly points out that PharmFree should be judged on its own merits, he may have missed my larger point. The AMSA seems to be claiming the moral high ground in matters of ethics, evidence and doing what’s best for patients. But the claim is baseless when they actively promote bogus (and in my opinion fraudulent) health claims. Moreover, they accuse the profession of engaging in conflicts of interest when they themselves accept money in return for distributing promotional material from an organization which advocates shamanism, ritual healing and New Age fluff. So, it kind of ruffles my feathers when they point the accusing finger and besmirch the ethics of the medical profession. This inconsistency also begs the question of motivation: what is the real agenda of PharmFree?
Friday, January 06, 2006
Is it any wonder so many consumers flock to alternative medicine?
It seems folks will believe anything if it has the trappings of science. Here’s a study of credulity in action.
Wednesday, January 04, 2006
Should residency programs accept support from pharmaceutical companies?
A point-counterpoint appeared in Skin and Allergy News. Dr. Raymond Comelison Jr., chief of dermatology at the University of Oklahoma and past president of the American Academy of Dermatology says yes, in some circumstances. Dr. Jeffrey Meffert, staff dermatologist at Wilford Hall Air force Medical Center says “just say no”, regardless of the circumstance.
I agree with Dr. Comelison. It is unfair to paint all industry supported activities with the same brush. There is extreme variation in quality. At one end of the spectrum are events amounting to little more than infomercials for a single product. These drug company dinners and junkets of low educational value are easy to spot. Both discussants agree that such activities are not of value. But drug companies also provide support for academic programs to send house staff to high quality CME offerings at national specialty organizations. Here the discussants disagree, and Dr. Comelison points out that if pharmaceutical support disappeared far fewer residents would be able to attend such meetings.
Most would agree with the need for caution in accepting industry support. Dr. Comelison applies the maxim “everything in moderation.” While increasing numbers of people subscribe to Dr. Meffert’s position, it is simplistic and extreme.
I agree with Dr. Comelison. It is unfair to paint all industry supported activities with the same brush. There is extreme variation in quality. At one end of the spectrum are events amounting to little more than infomercials for a single product. These drug company dinners and junkets of low educational value are easy to spot. Both discussants agree that such activities are not of value. But drug companies also provide support for academic programs to send house staff to high quality CME offerings at national specialty organizations. Here the discussants disagree, and Dr. Comelison points out that if pharmaceutical support disappeared far fewer residents would be able to attend such meetings.
Most would agree with the need for caution in accepting industry support. Dr. Comelison applies the maxim “everything in moderation.” While increasing numbers of people subscribe to Dr. Meffert’s position, it is simplistic and extreme.
Monday, January 02, 2006
AMSA claims to take moral high ground
The American Medical Student Association’s PharmFree campaign was featured in USA Today. The campaign encourages doctors and medical students to distance themselves from the pharmaceutical industry by refusing to accept gifts or support from drug companies. They say it’s all about ethics, evidence and doing what’s best for patients. But, as I have recently demonstrated, [1] [2] this grandstanding belies an agenda which promotes pseudoscience and bogus health claims.
It’s also supposedly about conflicts of interest. Says the USA Today article: “Behind the modest rebellion is the belief that taking gifts from drug companies creates a conflict of interest for doctors. The argument: To accept handouts is to feel indebted, and doctors indebted to drug firms may not be prescribing medicines based solely on what's best for their patients.” If that’s the argument, why does the AMSA accept support from the anti-science based American Holistic Medical Association? The AMSA document “Successful Ways Past Retreats Found Moola” (which can be downloaded from the AMSA web site’s section on Humanistic Medicine) says the American Holistic Medical Association gives out grants for humanistic medicine “retreats.” Moreover, according to the document, in return for the grant “You have to contact the student rep and agree to give out AHMA (American Holistic Medical Association) materials at the retreat….”
So the AMSA, champions of ethics and professional integrity apparently have no problem accepting money in return for distributing “holistic” propaganda. The USA Today piece goes on to say that student representatives plan to visit 40,000 practicing physicians this year hoping to “pique the consciences of future colleagues.” I hope they pay me a visit. I have some questions to ask.
The link to the USA Today story was via Kevin MD.
It’s also supposedly about conflicts of interest. Says the USA Today article: “Behind the modest rebellion is the belief that taking gifts from drug companies creates a conflict of interest for doctors. The argument: To accept handouts is to feel indebted, and doctors indebted to drug firms may not be prescribing medicines based solely on what's best for their patients.” If that’s the argument, why does the AMSA accept support from the anti-science based American Holistic Medical Association? The AMSA document “Successful Ways Past Retreats Found Moola” (which can be downloaded from the AMSA web site’s section on Humanistic Medicine) says the American Holistic Medical Association gives out grants for humanistic medicine “retreats.” Moreover, according to the document, in return for the grant “You have to contact the student rep and agree to give out AHMA (American Holistic Medical Association) materials at the retreat….”
So the AMSA, champions of ethics and professional integrity apparently have no problem accepting money in return for distributing “holistic” propaganda. The USA Today piece goes on to say that student representatives plan to visit 40,000 practicing physicians this year hoping to “pique the consciences of future colleagues.” I hope they pay me a visit. I have some questions to ask.
The link to the USA Today story was via Kevin MD.
Sunday, January 01, 2006
Top 10 issues in hospital medicine for 2005------issue 1
State of the hospitalist movement
The hospitalist movement is growing. It is estimated that there were 15,000 hospitalists in North America in 2005. That number is projected to double in 5 years. There are multiple forces driving this growth, but this year there was the somewhat surprising multi-center study which failed to show that hospitalists had better clinical or economic outcomes than their non-hospitalist peers. This made the rounds in the blogosphere and I commented about it here.
Meanwhile there are signs that hospital medicine is moving toward establishment as a formal subspecialty. Robert Wachter, one of the founders and boosters of the movement, has been appointed to the board of directors of the American Board of Internal Medicine. A subspecialty textbook of hospital medicine is now in its second edition. Finally, there’s even a Wikipedia article about hospital medicine!
The hospitalist movement is growing. It is estimated that there were 15,000 hospitalists in North America in 2005. That number is projected to double in 5 years. There are multiple forces driving this growth, but this year there was the somewhat surprising multi-center study which failed to show that hospitalists had better clinical or economic outcomes than their non-hospitalist peers. This made the rounds in the blogosphere and I commented about it here.
Meanwhile there are signs that hospital medicine is moving toward establishment as a formal subspecialty. Robert Wachter, one of the founders and boosters of the movement, has been appointed to the board of directors of the American Board of Internal Medicine. A subspecialty textbook of hospital medicine is now in its second edition. Finally, there’s even a Wikipedia article about hospital medicine!
Top 10 issues in hospital medicine for 2005------issue 2
The Natrecor controversy
Nesiritide (Natrecor) was approved in 2001 for intravenous treatment of acutely decompensated heart failure. Short term results in the VMAC study showed superiority over nitroglycerine, mainly in terms of wedge pressure reduction, with more modest improvement in clinical endpoints. The drug appeared promising for rapid reversal of acute severe decompensation of heart failure and had a better safety profile than dobutamine.
Controversy was sparked, however, with the publication of this pooled analysis in JAMA last April which suggested a trend toward increased 30 day mortality with the use of Nesiritide. Opinion writers and bloggers reacted with harsh criticism of the makers of Natrecor for their promotions, and many called for a ban of its use.
How can we put the findings of the pooled analysis in perspective? First of all it must be noted that of 12 randomized controlled trials of Neseritide only 3 were chosen for inclusion in the analysis and the results were driven mainly by one study (PROACTION) which looked only at the use of Nesiritide in emergency department observation units. Moreover, the trend toward increased mortality was not statistically significant. Nesiritide’s effects on mortality deserve systematic study, and pending the results of such studies it should be used with caution. Nitroglycerine may be a safer alternative. In considering adjunctive infusion treatments alongside intravenous diuretics for acutely decompensated heart failure Nesiritide might occupy a position on the hierarchy between nitroglycerine and inotropes. The swift and contentious reactions to the paper were surprising and, in my view, irresponsible. For over a decade it was known that dobutamine was associated with increased mortality, yet clinicians continued to use it. Where was the outrage?
A reasoned and balanced recommendation on Natrecor is contained in this document from an expert panel chaired by Eugene Braunwald. Any clinician with an interest in treating acute heart failure should be thoroughly familiar with this report.
Nesiritide (Natrecor) was approved in 2001 for intravenous treatment of acutely decompensated heart failure. Short term results in the VMAC study showed superiority over nitroglycerine, mainly in terms of wedge pressure reduction, with more modest improvement in clinical endpoints. The drug appeared promising for rapid reversal of acute severe decompensation of heart failure and had a better safety profile than dobutamine.
Controversy was sparked, however, with the publication of this pooled analysis in JAMA last April which suggested a trend toward increased 30 day mortality with the use of Nesiritide. Opinion writers and bloggers reacted with harsh criticism of the makers of Natrecor for their promotions, and many called for a ban of its use.
How can we put the findings of the pooled analysis in perspective? First of all it must be noted that of 12 randomized controlled trials of Neseritide only 3 were chosen for inclusion in the analysis and the results were driven mainly by one study (PROACTION) which looked only at the use of Nesiritide in emergency department observation units. Moreover, the trend toward increased mortality was not statistically significant. Nesiritide’s effects on mortality deserve systematic study, and pending the results of such studies it should be used with caution. Nitroglycerine may be a safer alternative. In considering adjunctive infusion treatments alongside intravenous diuretics for acutely decompensated heart failure Nesiritide might occupy a position on the hierarchy between nitroglycerine and inotropes. The swift and contentious reactions to the paper were surprising and, in my view, irresponsible. For over a decade it was known that dobutamine was associated with increased mortality, yet clinicians continued to use it. Where was the outrage?
A reasoned and balanced recommendation on Natrecor is contained in this document from an expert panel chaired by Eugene Braunwald. Any clinician with an interest in treating acute heart failure should be thoroughly familiar with this report.
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