Tuesday, November 30, 2010

Nonalcoholic fatty liver disease

Pearls from the NEJM blog:


Nonalcoholic fatty liver disease — especially its necroinflammatory variant, nonalcoholic steatohepatitis — not only is a marker of cardiovascular disease but also may be involved in its pathogenesis. This might occur through the systemic release of proatherogenic mediators from the steatotic or inflamed liver as well as through the contribution of nonalcoholic fatty liver disease itself to insulin resistance and atherogenic dyslipidemia...


And more.

Even more evidence on the importance of lead aVR

From the Annals of Noninvasive Electrocardiography:


We found that lead aVR may provide important additional information in the diagnosis of coronary artery disease. It may provide a clue to the location of a lesion as well as the possibility of three vessel disease during an acute coronary syndrome. Lead aVR was found useful in the locus of arrhythmias and in differentiation of narrow and wide QRS complex tachycardias. It provides useful prognostic information for patients with the Brugada syndrome and tricyclic antidepressant toxicity. Lead aVR provides alternative criteria for the electrocardiographic diagnosis of left ventricular hypertrophy and left anterior fascicular block.

Diagnosis of acute MI in the presence of left bundle branch block

In my training we were taught that the electrocardiographic diagnosis of MI was impossible in the presence of LBBB. That thinking has changed. Now we have criteria for the diagnosis of MI in LBBB which, although lacking in sensitivity, have high specificity. Here are the Sgarbossa criteria. They are somewhat arbitrary, and are best applied with a more basic understanding of what happens to the ST segments.


In bundle branch block the ST segments deviate in the opposite direction from the major portion of the QRS complex. This is known as secondary ST segment change, also known as discordant ST segment deviation. It is intuitively obvious that such ST deviations can obscure ST segment changes resulting from an ischemic process. If the ischemic process alters the ST segment in the same direction as the secondary ST change attributable to the bundle branch block, an exaggerated discordant ST deviation results. This may be difficult to “eyeball” on the ECG and generally requires some form of measurement or quantitative analysis. If the ischemic process moves the ST segment in the opposite direction from the secondary ST change, a “tug-o'-war on the stylus”, as Barney Marriott affectionately called it, results. This may merely blunt the discordant ST deviation, again necessitating measurement. Sometimes the ischemic force wins the tug-o'-war and produces ST deviation in the same direction as the QRS complex, so called concordant ST segment deviations. Those are evident at a glance and require no measurement.


Quantitative analysis of the ST segment displacement in left bundle branch block (determining whether the discordant ST segment deviation is too much or too little for the LBBB thereby representing an ischemic process) is most formally and precisely done via determination of the left ventricular gradient, a process involving vector analysis which is time consuming and beyond the skill level of many clinicians. One of the criteria in the link above employs a simple measurement to determine “too much discordance” in leads with a negative QRS (> 5mm elevation). A post by Dr. Smith on this topic provides criteria based on the ST/S wave ratio in V1-3 and discusses other important aspects of the electrocardiographic diagnosis of MI in LBBB.

Linezolid or vanc for MRSA coverage in nosocomial pneumonia?

In a meta-analysis of 7 trials there was no significant difference in cure rate or mortality. Not surprising was double the incidence of thrombocytopenia with linezolid. Somewhat surprising was a marked increase in “GI events” with linezolid. The authors did not indicate what the events were. There was more renal failure in the vanc group but the difference was not statistically significant (very wide confidence interval). Vancomycin MICs were not reported. That would have been of great interest in view of all the troubling reports of frequent vancomycin treatment failures associated with higher MICs even when in the “sensitive” range.


Via the Medicine for Residents blog.

Net Biochem

Available here.

Monday, November 29, 2010

VTE prophylaxis for hospitalized medical patients

This review summarizes the major clinical trials and addresses controversial areas such as extended (post-discharge) VTE prophylaxis and unfractionated versus low molecular weight heparin.


Key points:


Pharmacologic VTE prophylaxis is associated with relative risk reductions for VTE in the neighborhood of 50-60%.


LMWH has a slight edge over UFH. Some studies were beset with design issues and had non statistically significant differences, but the signal consistently favored LMWH for efficacy with a suggestion of less bleeding risk.


While extended duration (post-discharge) VTE prophylaxis has been well validated for orthopedic and cancer surgery patients it is less well validated for medical patients. Benefits appear to be confined to particularly high risk patients at the price of increased bleeding risk.

On line medical school pathology course

YouTubes and Power points.


Links to the resource here, here and here.

Metformin fifteen years later

Since this original NEJM review metformin has turned out to be better and safer than we anticipated. Early fears were driven by the dismal track record of its cousin phenformin. Lactic acidosis is rare and heart failure no longer seems to be a contraindication according to this recent review. After 15 years it looks like a keeper.

Can you diagnose acute MI from a paced ECG?

Sometimes, yes. The rules for doing so are similar to the rules for LBBB. Via Dr. Smith's ECG Blog.

Hyponatremia and hypokalemia due to thiazides

A report and mini-review on this topic from the American Journal of Kidney Diseases Acid-Base and Electrolyte Teaching Case series deserves a place in every hospitalist's library. If you don't have access via subscription or MD Consult it would be worth the effort to see if you can get your hospital librarian to get you a reprint. I'll try to summarize a few key points.


The case in question involves a patient with severe hyponatremia and hypokalemia complicating thiazide use (Na 96 meq/l, K 1.6 meq/l).


What are the mechanisms of hyponatremia in patients taking thiazide diuretics?
The mechanisms are multiple and involve more than a simple case of electrolyte depletion. While thiazides are relatively weak diuretics, to the extent that volume depletion does occur, volume signals for vasopressin trump osmoregulation and lead to increases in vasopressin levels despite normal or even low serum sodium concentrations.


The degree and rapidity of development of hyponatremia in patients taking thiazides often cannot be explained by volume depletion. Other mechanisms have to be operative. In animal models, thiazides up regulate aquaporin channels in the renal collecting ducts---that is, they have a direct vasopressin like effect. That may explain the beneficial effects of thiazides in the treatment of nephrogenic diabetes indipidus.


In some patients, apparently, the hyponatremia is physiologic whereas in others it is idiosyncratic, as illustrated in this statement from the article:


Friedman et al,[7] studying the effect of a single dose of hydrochlorothiazide-amiloride tablet in patients with a history of hydrochlorothiazide-induced hyponatremia, noted a decrease in sodium level of 5.5 mEq/L (5.5 mmol/L) in 6 hours associated with mild weight gain.


But that's not the whole story. Potassium is involved as illustrated below.


How does thiazide induced potassium depletion impact the development and treatment of hyponatremia?
The impact of hypokalemia and the effect of potassium repletion on hyponatremia are underappreciated. Hypokalemia of any etiology can contribute to hyponatremia. Potassium depletion is one of the mechanisms by which thiazides produce hyponatremia, as was true in the case under discussion. Repletion of potassium can raise the serum sodium. In this case aggressive potassium repletion was responsible for over correction of the patient's hyponatremia and consequent neurologic damage due to osmotic demyelination despite the fact that the clinicians caring for her made no deliberate attempt to aggressively raise the serum sodium.


To understand how depletion and repletion of potassium cause changes in serum sodium it is necessary to recall that osmolarity is the same in the intra- and extracellular compartments because water is permeable across call membranes. Thus changes in the intracellular compartment induced by shifts in potassium balance will result in changes in serum sodium concentration.


Are patients with thiazide induced hyponatremia at unique risk for over correction and myelinolysis compared to patients with hyponatremia due to other causes?
Maybe, for two reasons. One is the usual accompaniment of hypokalemia, as illustrated in the discussion above. The other is the fact that patients on thiazide diuretics tend to be volume depleted. Thus volume signals drive excess vasopressin secretion. Even modest efforts toward volume repletion of such patients, with no deliberate effort to normalize the sodium, will turn off volume signals for vasopressin secretion. Then, because of the prevailing hyponatremia, vasopressin levels will quickly fall to zero and a brisk free water diuresis will endue, leading to rapid correction.


Do NSAIDs have a role in causing hyponatremia?
The patient under discussion was taking NSAIDs. The authors discuss two mechanisms by which NSAIDs may cause or contribute to hyponatremia. First, in the loop of Henle, locally produced PGE2 regulates the Na+-K+-2Cl- cotransporter. NSAIDs inhibit the PGE2 resulting in increased activity of the pump, increasing medullary tonicity. In the presence of vasopressin this enables greater reabsorption of free water. Secondly, in the collecting duct, the presence of vasopressin stimulates local production of PGE2 which inhibits its antidiuretic action, thus providing a self regulating negative feedback loop. By inhibiting PGE2 synthesis NSAIDs disrupt that loop, thus enabling excessive vasopressin action.


Could anything have been done differently in this case?
Because of the risk of cardiac arrhythmias and respiratory muscle weakness there was no alternative but to replete the potassium. The authors suggest that once the serum sodium was seen to rise at too rapid a rate hypotonic fluids could have been given.


More on this topic from Precious Bodily Fluids.

Friday, November 26, 2010

Another use for the QT interval

It can help differentiate between benign and ischemic T wave inversion as well as benign early repolarization and ischemic ST elevation. It's short in the benign variants, long in ischemia.


Via Dr. Smith's ECG Blog.

Did you say revascularization is no better than medical therapy for stable CAD? Not so fast!

In an era when it's fashionable to point the finger of shame at cardiologists for being greedy and doing too many procedures this new study is of interest. It seems that the intuitive idea that some patients will do better with their plumbing fixed is correct after all.


MASS II is one of many examples of comparative effectiveness research conceived years before policy wonks coined the term. In this study of patients with stable multivessel disease and preserved ventricular function CABG won hands down. There was a strong signal that PCI was better than medical therapy for multiple outcomes but the differences were not quite statistically significant. The patient numbers were somewhat small and the study may not have been adequately powered. Also, it must be kept in mind that the PCI methods were not optimal by today's standards:


 Devices used for catheter-based therapeutic strategies included stents, lasers, directional atherectomy, and balloon angioplasty. Angioplasty was performed according to a standard protocol.7 Glycoprotein IIb/IIIa agents were not used. 


The study differed from COURAGE and BARI 2D in that the patients probably represented more severe disease and the follow up was longer.


Related editorial here.


Via Medicine for Residents.

The office visit is a dinosaur: Berwick

Yes, he really said it. Blog post and link to the primary source here.

A unique “non-STEMI” pattern of acute proximal LAD occlusion

I just ran across this via a post at Dr. Smith's blog. In 2% of acute LAD occlusions in a large database the authors observed, in the indicative precordial leads, upsloping ST segment (J point) depression leading into the more typical broad based high amplitude hyperacute T waves. The ST depression was static---it didn't evolve into the more typical ST elevations. It was a little noticed letter to the editor of the NEJM by a major league group. Free full text access allows viewing of eight of these fascinating tracings.

Wednesday, November 24, 2010

An easily missed inferior STEMI equivalent

---was presented a while back at Dr. Smith's ECG blog.


Inferiorly there were broad based upright T waves without frank ST elevation. In addition there was ST depression in AVL. The lesson here is that reciprocal ST depression in AVL may be the major clue to acute inferior MI.


This pattern, though probably under recognized, has been known for decades.

Neuroanatomy

---web atlas resource.

Tb or not Tb?

The Xpert MTB/RIF test can help answer the question in a matter of minutes according to this study. It's an automated nucleic acid amplification test.


Via the NEJM blog.

University of Michigan anatomy resources

Great links here.

Immunology and Micro text

University of South Carolina.

Tuesday, November 23, 2010

Hyperkalemia induced by non-selective beta blockers

It's far more common than you might think, although not always clinically significant. From the Medicine for Residents blog:


I recently had a Chronic kidney diesease patient on low dose Ramipril with a stable potassium level for many months, got admitted to the hospital for an hypertensive urgency.Her renal function & K were stable on admission. She was started on a Labetalol infusion overnight.Next day her potassium level was 6.9mEq/L, and she needed two Insulin dextrose treatment( couple of hours apart) to get that back to normal. Her TTKG(transtubular potassium gradient) was 4. This is hyperkalemia due to Labetalol.




Via Nephron Power.

Virtual histo lab

From Iowa.

Left ventricular dysfunction in critical illness

---is common and may occur in the absence of prior known heart disease. Acute coronary syndrome, takotsubo cardiomyopathy (probably under-recognized in critical illness), global LV dysfunction due to inflammatory mediators and other ill-understood causes are responsible. Here is a new review in Chest.

McGill ECG tutorial

Nice.

Inotropes in critically ill patients

A review in Current Opinion in Critical Care.

Monday, November 22, 2010

Saturday, November 20, 2010

Sarah Jackman

I tried to find the original Allan Sherman version of this song, but couldn't. These folks nailed it pretty well.


Friday, November 19, 2010

Another podcast on the new ACLS guidelines

This one is from the EMS Garage. The participants expressed some disappointment that the guidelines didn't go far enough toward implementing Ewy's cardiocerebral resuscitation. The podcast is a great example of how the new guidelines are rapidly being disseminated and discussed through social networking. Traditionally, implementation of guidelines has taken years. Social media may change that.

Hypertensive emergencies

The nuts and bolts. Via The Hospitalist.

Toxicology core curriculum

A great resource for hospitalists from AJKD. Free full text.

Hypophosphatemia in the ICU

A review of clinical manifestations and treatment.

Lessons from the IMPROVE HF registry

You can look at IMPROVE HF as the outpatient version of OPTIMIZE. This Medscape CME activity summarizes information from the database, the quality improvement tools used to increase guideline adherence and the results of the quality improvement efforts.


Not surprisingly at baseline only 20 some odd percent of patients were completely guideline adherent. After intervention it was just over 40%. And these were cardiology practices. For single measures, of course, the percentages were higher.


The CME presentation makes unfortunate use of the term performance. This was not really a performance initiative. It went far beyond that to address total guideline adherence.


The IMPROVE HF website has some useful resources and guideline adherence tools.

Thursday, November 18, 2010

Is this the health care system we're supposed to be romantic about?

New findings on health outcomes in the US and England.

Criticize death panel alarmists out of one side of your mouth and advocate death panels out of the other? Oops!



Via Secondhand Smoke.

The impact of state midterm elections on the future of health care reform

Republican gains in the US House and Senate were impressive enough, but the sweep was even more massive in the state races. Much of the machinery of reform will play out at the state level where it could get gummed up or even grind to a halt, as Wesley Smith explains:


This isn’t healthy for America.  But when you pass a profoundly unpopular law over the pronounced objections of the American people–in a system that requires the consent of the governed– it is naive (at best) to think people will just shrug and go along.

Emory internal medicine residents blog

This blog is a series of posts driven by topics arising at Emory's intern and resident morning reports.

Emergency Medicine Handbook

This site is reasonably up to date and has some useful links.

Ventilator-induced respiratory muscle weakness

---an emerging issue in mechanical ventilation with inadequate research evidence to make definitive recommendations for change in practice. From a review in Annals of Internal Medicine:


Scientific understanding of ventilator-induced respiratory muscle injury has not reached the stage where meaningful controlled trials can be done, and thus, it is not possible to give concrete recommendations for patient management. In the meantime, clinicians are advised to select ventilator settings that avoid both excessive patient effort and excessive respiratory muscle rest. The contour of the airway pressure waveform on a ventilator screen provides the most practical indication of patient effort, and clinicians are advised to pay close attention to the waveform as they titrate ventilator settings.

Emergency medicine audio lectures

---including several talks by Amal Attu (he's awesome). The slides are missing but hey, it's free.

Wednesday, November 17, 2010

Paul Krugman on death panels

Via Drugwonks:


The media’s favorite economist Paul Krugman is under fire for these comments he made this past weekend on ABC regarding federal spending on health care.
 
“Some years down the pike, we’re going to get the real solution, which is going to be a combination of death panels and sales taxes.”


He says he really didn't mean it the way it sounded. Just a slip of the tongue, I guess.

Evidence based medicine ≠ science based medicine

David Gorski explains in a recent post.


The apologists for science based medicine have for some time been pointing out a shortcoming of EBM: its utter failure in the evaluation of certain claims of complementary and alternative medicine. The reason for this failure, the apologists point out, is that EBM ignores biologic plausibility.


The science based medicine (SBM) movement has been criticized by some EBM proponents. The criticism (and this may be an oversimplification) is that there's no need for SBM as a new discipline to address plausibility because EBM already does that. Those proponents might say it's inherent in David Sackett's original description of EBM:


It's about integrating individual clinical expertise and the best external evidence...

Evidence based medicine is the conscientious, explicit, and judicious use of current best evidence in making decisions about the care of individual patients. 


I say that because as a proponent of EBM myself I thought so, until fairly recently. I was aware of EBM's multiple failures to evaluate quackery but I just dismissed them as occasional unintended consequences. I naively believed that EBM in its true notion, as advanced by those who really understood it, appropriately took scientific plausibility into account.


I began to wonder, though, as I saw more and more failures, even instances in which EBM appeared to promote quackery. Then yesterday I ran across the above referenced post by Gorski. That did it for me. It explained in a way I hadn't realized before that this failure of EBM is more than just one of occasional unintended consequences. While it may have been unintended in the minds of the original founders, now it's systematic.


The problem is illustrated by the evidence pyramids, which are at the very core of the teaching about EBM. There are numerous versions of these pyramids, and Gorski links to a few examples, but what they have in common is that they put biologic plausibility (variously termed basic science, physiologic rationale, etc) at the bottom if they include it at all.


A casual observer might think that putting basic scientific rationale at the bottom means it's intended to be foundational (remember the old stepped care diagrams for treatment of hypertension and rheumatoid arthritis?). But that's not the way the EBM hierarchies of evidence are designed. Instead, higher levels on the pyramid trump those below. Students of EBM are taught to start at the top of the pyramid and “drill down,” level-by-level, until they find the evidence they want, and stop there.


Gorski includes an interesting quote from SBM blogger Kimball Atwood. Atwood uses homeopathy as an absurd example of EBM's pyramid approach, in which occasional equivocal results of clinical trials favoring homeopathy, easily explained by chance variation, are valued above the overwhelming basic science case against it (my italics):


When this sort of evidence is weighed against the equivocal clinical trial literature, it is abundantly clear that homeopathic “remedies” have no specific, biological effects. Yet EBM relegates such evidence to “Level 5”: the lowest in the scheme. How persuasive is the evidence that EBM dismisses? The “infinitesimals” claim alone is the equivalent of a proposal for a perpetual motion machine. The same medical academics who call for more studies of homeopathy would be embarrassed, one hopes, to be found insisting upon “studies” of perpetual motion machines. Basic chemistry is still a prerequisite for medical school, as far as I’m aware.


As to that last sentence, well, maybe not for long.

EKG World Encyclopedia

With this resource you can browse by condition or category, or view tracings in the quiz mode. A wide range of difficulty is represented.

Don't overlook vocal cord dysfunction

It can be an asthma mimic or can complicate asthma itself.


Via Medscape.

The EKG in pulmonary embolism

I've linked to numerous papers on this subject in the past. This recent review may be the best I've seen. It includes a case report of a patient with a strong clinical prior probability of PE who, due to clinical and external factors, could not be imaged. She had several electrocardiographic features suggestive of PE. Based on clinical suspicion and the ECG features the authors treated her, with a satisfactory outcome. Later on clinical circumstances enabled her to be imaged and the diagnosis was confirmed.


There are two potential uses of electrocardiography in pulmonary embolism. One is in severity assessment. The electrocardiogram is helpful in predicting complications of PE because it detects right ventricular strain, and an emerging literature is helping define its most effective use in this area. The other use, the diagnosis of PE itself, is more problematic. No single abnormality has high specificity. Several studies, as summarized in the paper, suggest that combinations of abnormalities have high specificity and positive predictive value.

Concealed junctional extrasystoles---a cause of pseudo AV block

Here's a case report and brief review.


Barney Marriott used to cite these red flags for the condition:


Abrupt, unexplaind (non-physiologic) lengthening in the PR interval.


Apparent “Mobitz II” AV block but with a normal conducted QRS (but intrahisian AV block can cause this too).


Manifest junctional extrasystoles seen elsewhere.


Electrophysiology at the bedside. Fascinating stuff.

Tuesday, November 16, 2010

What kind of physicians do government policy makers want?

---asks Edwin Leap, guest blogging at Kevin MD:


I’m just asking; I don’t know the answer.  We used to choose physicians for their autonomy and individuality.  For their willingness to open their practices, do what they thought was right and serve within the context of their own morals.  The reward for their autonomy, and for their service to the sick, was their relative freedom.

What does the future of reform hold?  I don’t know.  But I do know it may require an entirely new species of physician.  Myself, I have a chilling sense of impending extinction.

If you're a malpractice defendant

---here are some deposition tips. It's all pretty counterintuitive.

Management of DKA in hemodialysis patients

What do you the hospitalist need to know aside from the fact that you should manage the patient in concert with his or her nephrologist? Well, as explained in this post at Nephron Power, in some respects your job may be easier than when you manage DKA in patients with working kidneys.

Early prediction of contrast nephropathy

Check another creatinine 12 hours post procedure. It predicts both AKI and 30 day renal impairment.

Communication gaps between doctors and hospitalized patients

This study showed a discrepancy between how physicians believe they inform patients and how patients perceive they are informed. When I ask patients about a previous hospitalization I have a recurring experience. I ask “What did they say was wrong with you?” Answer: “They didn't say.” Are we really that bad?

Monday, November 15, 2010

Retired Doc on Don Berwick's leaders with plans

By all means read the entire post, but here's the opening:


Dr. Don Berwick,head of the Center for Medicare/Medicaid Services (CMS),has made clear his views on how medical decisions should be made and on what kind of health care system the United states should have.This quote from a book he co-authored with Dr. Troyen Brennan,entitled New Rules leaves little room for ambiguity:
"Today, this isolated relationship[ he is speaking of the physician patient relationship] is no longer tenable or possible… Traditional medical ethics, based on the doctor-patient dyad must be reformulated to fit the new mold of the delivery of health care...Regulation must evolve. Regulating for improved medical care involves designing appropriate rules with authority...Health care is being rationalized through critical pathways and guidelines. The primary function of regulation in health care, especially as it affects the quality of medical care, is to constrain decentralized individualized decision making.



Spoken as only a true policy wonk (and one, I'd wager, who hasn't been involved in direct patient care in decades) could.

Why did you order that echo?

It was a case of CYA. It's a compelling anecdote about an academic cardiologist who, after a thoughtful and thorough clinical evaluation, orders an unnecessary echo “just in case.”


The last thing I did was order an echocardiogram—then came the fellow's question.

The answer was simple but painful: I was practicing defensive medicine. “If she has a familial hypertrophic cardiomyopathy or arrhythmogenic right ventricular dysplasia and I don't diagnose it, what do you think would happen to me?” I was embarrassed to admit it, but I had fallen prey to the most miserable excuse for test-ordering. The fellow was kind (or smart) enough not to point out there was nothing to suggest either diagnosis, the pretest probability was abysmally low, and the test would cost the healthcare system at least $500.


The author points out the tremendous waste in this approach. But in today's practice environment he'd do it again, and so would you. This is a compelling case for tort reform, something we didn't get in the recently passed health care reform legislation.

Cat bites

What to worry about, what to do. Via the NEJM blog.

Cardiac catheterization---not just a luminogram

A concise discussion by C. Richard Conti, MD, about physiologic information that can be gained at cardiac catheterization using such techniques as IVUS and FFR.

Amyloidosis

Clinical pearls from the NEJM blog.

Sunday, November 14, 2010

Cerebral salt wasting versus SIADH

According to a recent review in Neurosurgical Clinics of North America: Cerebral salt wasting (CSW) is a syndrome of hypovolemic hyponatremia caused by natriuresis and diuresis.


SIADH and CSW have similar urine chemistries, so the differentiation lies in volume assessment, which is often difficult. But distinction is important because the treatments differ. To further complicate matters, not all salt wasting syndromes are cerebral, leading to increasing popularity of the more general term renal salt wasting (RSW).


Related articles can be found here and here.

Thursday, November 11, 2010

The use of neuromuscular blockers in ARDS---is the pendulum swinging back?

You're no doubt aware of the hype surrounding this issue as a result of a new NEJM study. From the study:


...340 patients presenting to the intensive care unit (ICU) with an onset of severe ARDS within the previous 48 hours were randomly assigned to receive, for 48 hours, either cisatracurium besylate (178 patients) or placebo...

The hazard ratio for death at 90 days in the cisatracurium group, as compared with the placebo group, was 0.68 (95% confidence interval [CI], 0.48 to 0.98; P=0.04), after adjustment for both the baseline PaO2:FIO2 and plateau pressure and the Simplified Acute Physiology II score. The crude 90-day mortality was 31.6% (95% CI, 25.2 to 38.8) in the cisatracurium group and 40.7% (95% CI, 33.5 to 48.4) in the placebo group (P=0.08). Mortality at 28 days was 23.7% (95% CI, 18.1 to 30.5) with cisatracurium and 33.3% (95% CI, 26.5 to 40.9) with placebo (P=0.05). The rate of ICU-acquired paresis did not differ significantly between the two groups.

CONCLUSIONS
In patients with severe ARDS, early administration of a neuromuscular blocking agent improved the adjusted 90-day survival and increased the time off the ventilator without increasing muscle weakness.


And how did they define severe ARDS?


Severe ARDS was defined as a ratio of the partial pressure of arterial oxygen (PaO2) to the fraction of inspired oxygen (FIO2) of less than 150, with a positive end-expiratory pressure of 5 cm or more of water and a tidal volume of 6 to 8 ml per kilogram of predicted body weight. 


So this is a select group of patients among those presenting with ALI/ARDS. It's not for everyone. We haven't come full circle, back to the days when it seems we paralyzed nearly everyone.


There's some insightful discussion over at the NEJM blog. First, it must be recognized that it's difficult to ventilate patients on the ARDSnet protocol without heavy sedation, or, on occasion, paralysis. That's because ARDSnet tidal volumes don't satisfy the dyspnea of some patients. Aside from that, in other patients who matched the conditions of this study, the findings must be interpreted with caution. It must be kept in mind that there was a significant reduction in the adjusted, though not the crude 90 day mortality with the intervention. Further study may be warranted before we routinely change practice in patients, even those with a PO2/FiO2 of less than 150, who otherwise are “cruising” and able to tolerate ARDSnet tidal volumes with sedation alone.

When one P wave begets two QRS complexes: 1:2 AV conduction

The cause is dual AV nodal pathways where the slow pathway is so much slower than the fast pathway that by the time the impulse traverses it the infranodal tissues are no longer refractory. Although it is believed to be rare its true frequency is unknown, and the surface electrocardiac patterns it produces are common, often called by the computer or the casual observer “supraventricular bigeminy.” It may also be considered to be “narrow complex tachycardia with alternating RR intervals.” If the second impulse experiences aberrant conduction it may present as “ventricular bigeminy.” It may also be mistaken for atrial fibrillation. Case report here, editorial here, blog post here.

Tumor lysis syndrome and the use of Rasburicase

If you can't access the full text of this review there's a nice summary post at Renal Fellow Network.

Tylenol and the kidney

Three issues are raised at Renal Fellow Network, one with overdose (ATN, which can happen with or without hepatotoxicity) and two with long term use (analgesic nephropathy and wide gap acidosis). But let's not forget a possible future protective role for acetaminophen in the kidney, (ordinary therapeutic doses) in the setting of rhabdomyolysis, too early for prime time right now.

Wednesday, November 10, 2010

Celera responds to JACC article claiming to debunk statin check

I blogged about this the other day. Celera markets the KIF6 statin check. They responded:


"We believe that the case-control study of coronary artery disease published by Assimes et al., is not a replication study of the published prospective studies of KIF6 Trp719Arg, which involved rigorous prospective and randomized controlled trial designs," said Thomas White, Ph.D., Chief Scientific Officer at Celera. "Moreover, Celera and others have previously reported1-4 the finding that in case-control studies there was no association between KIF6 and nonfatal MI or CAD, and thus we see little that is new or relevant to the association between KIF6 and statin benefit." 


They also pointed out a conflict of interest in the JACC paper: multiple authors work for a competing genetics company.

90% of the risk of stroke was attributable to 10 conditions

---in this Lancet study:


... significant risk factors for all stroke were: history of hypertension (OR 2·64, 99% CI 2·26—3·08; PAR 34·6%, 99% CI 30·4—39·1); current smoking (2·09, 1·75—2·51; 18·9%, 15·3—23·1); waist-to-hip ratio (1·65, 1·36—1·99 for highest vs lowest tertile; 26·5%, 18·8—36·0); diet risk score (1·35, 1·11—1·64 for highest vs lowest tertile; 18·8%, 11·2—29·7); regular physical activity (0·69, 0·53—0·90; 28·5%, 14·5—48·5); diabetes mellitus (1·36, 1·10—1·68; 5·0%, 2·6—9·5); alcohol intake (1·51, 1·18—1·92 for more than 30 drinks per month or binge drinking; 3·8%, 0·9—14·4); psychosocial stress (1·30, 1·06—1·60; 4·6%, 2·1—9·6) and depression (1·35, 1·10—1·66; 5·2%, 2·7—9·8); cardiac causes (2·38, 1·77—3·20; 6·7%, 4·8—9·1); and ratio of apolipoproteins B to A1 (1·89, 1·49—2·40 for highest vs lowest tertile; 24·9%, 15·7—37·1). Collectively, these risk factors accounted for 88·1% (99% CI 82·3—92·2) of the PAR for all stroke. When an alternate definition of hypertension was used (history of hypertension or blood pressure greater than 160/90 mm Hg), the combined PAR was 90·3% (85·3—93·7) for all stroke. These risk factors were all significant for ischaemic stroke, whereas hypertension, smoking, waist-to-hip ratio, diet, and alcohol intake were significant risk factors for intracerebral haemorrhagic stroke.
Interpretation
Our findings suggest that ten risk factors are associated with 90% of the risk of stroke. Targeted interventions that reduce blood pressure and smoking, and promote physical activity and a healthy diet, could substantially reduce the burden of stroke.


Via Clinical Cases and Images.

Restrictive antibiotic policies in hospitals---beware the unintended consequences

This study didn't look at clinical outcomes but restrictive policies were associated with ORs of 1.49 and 1.78, respectively, for 1 and 2 hour delays. This would be very worrisome in sepsis where the big guns are routinely used initially and where mortality increases of 7% per hour of delay have been cited.

Urine, pre- and post-tolvaptan

A picture is worth a thousand words. Via Precious Bodily Fluids.

Monday, November 08, 2010

Aortic stenosis and intestinal angiodysplasia (Heyde Syndrome): Fact or myth?

Although the subject of controversy, the association is probably real. Moreover, AS appears to cause a coagulopathy resembling vWD-2a.


Via the Clinical Correlations blog.

Is the KIF6 statin test debunked?

KIF6 codes for a kinesin, which transports cargo along intracellular microtubules.

A recent paper and accompanying editorial in JACC are sure to spark controversy. The paper was an analysis of 19 case-control studies, looking at the association of the KIF6 polymorphism with CAD risk. The findings:


Results: A total of 17,000 cases and 39,369 controls of European descent as well as a modest number of South Asians, African Americans, Hispanics, East Asians, and admixed cases and controls were successfully genotyped. None of the 19 studies demonstrated an increased risk of CAD in carriers of the 719Arg allele compared with noncarriers. 


The somewhat overhyped editorial, titled The KIF6 Collapse, declared not only that KIF6 is not a marker of increased coronary risk, but also that it cannot be relied upon to predict statin responsiveness.


There are several flaws in this analysis, not the least of which is the fact that a significant number of patients in these case-control studies were undoubtedly taking statins. Given the evidence that the KIF6 polymorphism predicts both risk and the ability of statins to reduce that same risk, a valid study would have to be confined to patients not taking statins. The editorial writers anticipated and made an unconvincing attempt to refute that objection (unconvincing to me, anyway).


A little background. KIF6 is a common genetic variation (polymorphism). There is a commercially available test. The claim that it is a marker of risk is based on analysis of sera from multiple randomized controlled trials. In these studies it proved to be a modest predictor of risk, with hazard ratios on the order of 1.2, similar to traditional risk factors. More important is the ability of the test to predict statin responsiveness. Given the current debates over the cost effectiveness of statins in primary prevention, particularly in low risk populations, the utility of such a test would be enormous.


Here are some estimates of statin effectiveness in KIF6 non-carriers versus carriers. (These findings were presented by Dr. H. Robert Superko at the 36th Annual Tutorials in the Tetons Update in Cardiovascular Disease):


In terms of numbers needed to treat (NNT) to prevent one event, in KIF6 non-carriers versus carriers, respectively, in various statin trials:


CARE 72 vs 20
WOSCOPS greater than 100 vs 18
PROSPER 83 vs 16
PROVE IT 125 vs 10


Note that WOSCOPS was a primary prevention study, but with high lipid entry criteria. Specimens from the JUPITER trial are currently being analyzed for KIF6. Those results should shed light on the utility of the KIF6 test in low risk populations.


These results are impressive. Pending the results of the JUPITER analysis, I would consider taking the KIF6 test if faced with a less than clear choice as to whether to take a statin.

Review of augmentation therapy for alpha-1 antitrypsin deficiency

Augmentation therapy has become somewhat controversial. A recent Cochrane review, concluding that augmentation therapy was ineffective, was simplistic and heavily criticized. A new review published in Therapeutic Advances in Respiratory Disease provides a careful look at the evidence. The level of evidence regarding augmentation therapy is not as high as we might like. We have to go with the best evidence we have, which suggests that augmentation therapy does impact the progression of the disease and provides meaningful clinical benefits for selected patients. As the review pointed out there are areas of controversy:


Areas where controversy exists regarding the use of AAT augmentation therapy include: (1) indications for treatment, (2) selection of specific AAT augmentation therapy, (3) appropriate dose and interval of administration, (4) cost effectiveness, (5) frequency and mode of follow up of treated patients, (6) use of augmentation therapy after lung transplantation, (7) use of recombinant AAT supplementation, (8) alternative delivery routes, and (9) genetic therapy. 


These are decisions that require special expertise, suggesting to me that patients with COPD who might have AAT should be screened and appropriate candidates referred to centers where such expertise is available.

Process issues in the evaluation and management of patients with alpha-1 antitrypsin deficiency

---were examined in this recent study. Not surprisingly, delays in diagnosis were considerable. (That's also the case for COPD in general). Augmentation therapy and vaccinations did decrease ER visits and exacerbations. This was not a randomized controlled trial and the role of augmentation therapy is likely to remain controversial.


The recently emerging controversy regarding augmentation therapy raises two questions: What is the precise role for augmentation therapy today? Should we still screen all COPD and unremitting asthma patients as the guidelines recommend?


Given the complexity of management and multiple process issues involved in the management of patients with AAT, the controversy has not dampened my enthusiasm for screening. Those patients identified as having AAT can then be referred to appropriate centers of expertise.

Friday, November 05, 2010

A novel, but physiologically sound, method of treatment of profound hyponatremia

The abstract of an article in the American Journal of Kidney Diseases reads:


An alcoholic patient presented with profound hyponatremia (serum sodium concentration, 96 mEq/L) caused by the combined effects of a thiazide diuretic, serotonin reuptake inhibitor, beer potomania, and hypovolemia. A computed tomographic scan of the brain was indistinguishable from one obtained 3 weeks earlier when he was normonatremic. Concurrent administration of 3% saline solution and desmopressin controlled the rate of correction to an average of 6 mEq/L daily and resulted in full neurologic recovery without evidence of osmotic demyelination. This case illustrates the value of controlled correction of profound hyponatremia.


This is a very tough situation. What do you do? No matter what you give the patient you have no control over how fast the serum sodium rises. The patient, depending on his volume status, may have volume signals for vasopressin which could be shut off by the administration of volume in any form, resulting in a free water diuresis and uncontrollable rise in the serum sodium. The solution to this case was to make sure, while 3% saline was given, to maintain sufficient antidiuretic effect via administration of desmopressin to prevent that outcome.


I first read about the use of desmopressin to avoid over correction of hyponatremia in UptoDate several years ago. At that time it was advocated as a reactionary move---something to do when you saw the sodium rising too fast. Later on I blogged about a paper describing the use of desmopressin as a preemptive strike in certain clinical circumstances. This AJKD paper is the first I've seen to advocate desmopressin as part of the initial therapy, but it makes sense. Although the authors didn't give the precise recipe for desmopressin, the full text is worth the read. This paragraph from the body of the paper explains why the rise of serum sodium with any therapy would be impossible to predict or control:


Impaired diluting ability due to a thiazide diuretic and syndrome of inappropriate secretion of antidiuretic hormone caused by an SSRI will resolve soon after these medications are cleared, [9] , [10] , [11] and our patient most likely stopped taking these medications many hours before admission. Similarly, vasopressin secretion in response to hypovolemia ceases when the volume deficit is corrected using saline. Our patient had a very low urine sodium concentration (Table 1), consistent with hypovolemia. Transient vasopressin secretion related to alcohol withdrawal and the stress of a seizure will resolve spontaneously. Our patient had a history of alcohol withdrawal seizures and was delirious despite an undetectable blood alcohol level (Table 1). When nonosmotic stimuli for vasopressin secretion are eliminated, hypothalamic vasopressin-secreting neurons respond to the low plasma sodium concentration, and plasma vasopressin levels rapidly become undetectable. This results in excretion of up to 1 L/h of maximally dilute urine that will increase serum sodium concentration by greater than 2 mEq/L/h.


H/T to DB's MedRants.

Alignments between hospitals and physicians: where are things headed?

Patrice Villemure, Vice President of the Heart and Vascular Institute at St. Joseph's Hospital of Atlanta, gave a talk on the ever changing relationships between physicians and hospitals at the 36th Annual Tutorials in the Tetons Update in Cardiovascular Disease.


I'm late blogging about this talk (it was given last August) and we've since had a midterm election which is likely to impact the future of health care reform. Some of the talk was premised on the consequences of the Affordable Care Act (AKA Obamacare), the future of which is now uncertain.


If Obamacare survives the lawsuits, the state initiatives, the new congress and the 2012 election it may emerge beaten down and barely recognizable. Even so, the external pressures and the conversation surrounding health care reform will continue to shape the relationships between physicians and hospitals. The premise of her talk remains true no matter what happens with health care legislation: that hospitals and clinics, once able to function as separate entities, have since been forced into changing relationships under various tensions, not all of which are healthy.


So here's the time line. In the 60s, 70s and early 80s things were simple. The hospital was the “doctor's workshop.” There were no conflicting financial incentives as a cause of tension. Even with the advent of Medicare in 1965 things didn't change too much, at least at first. Medicare paid the bills and otherwise didn't intrude.


When rising costs became an increasing concern Medicare implemented the PSROs in the early 70s to monitor utilization and try and contain costs. For the first time doctors began to feel the pressure of government intrusion and administrative push back. PSROs, while intrusive, ultimately proved a failure and were discontinued in the early 80s.


Then in 1984 Medicare's implementation of the Prospective Payment System pitted doctors against hospitals by eliminating fee-for-service payments for inpatients and creating negative cost incentives.


Managed care was not a new idea but it gained traction in the 1990s as a result of the conversation surrounding the health care reform proposal of the day (often referred to as Hillarycare) which was based on a model of nationally regulated managed care. In anticipation of passage, insurance companies shifted toward the model. By the time of the bill's defeat in 1994 the wave of managed care was already well underway. This fueled many trends aimed at increased efficiency including integrated medical groups (in which hospitals purchased physician practices) and quite possibly the hospitalist movement.


Heavy managed care turned out to be a public relations disaster and only a temporary financial success. Its influence began to wane within a decade. While non-economic factors continued to drive the hospitalist movement the push for integration went on hiatus. Easing of the economic pressure of managed care was just one reason. Doctors and hospital administrators were at odds. Administrators didn't understand the ingredients of professional satisfaction. Docs valued autonomy and administrators didn't get it. And the economic advantages of integration were less than anticipated. Health care systems gave up on the model. Some ran from it.


But the retreat from integration may only be a hiatus. Since the conversation about health care reform has resurfaced 15 years after the defeat of HillaryCare there's been a renewed interest. Dartmouth Atlas data, talk of accountable care organizations and Atul Gawande's profoundly influential article on health care variation have sparked renewed enthusiasm for integration. Most importantly, the economic pressures are back with a vengeance in the form of threats, such as bundling, to fee-for-service medicine. (One of the health care wonks at SHM 2010 declared that private practice is dead).


Whether Obamacare survives, is decimated or goes down in flames the push toward integration of healh care services will likely continue. If it happens without more government intrusion it might be a good thing.

When psych patients leave AMA

---are you off the hook?


It's more complicated than you might think.

Understanding referral bias

Part of a series of essays by Jerome Hoffman, MD, in Emergency Physicians Monthly.

Thursday, November 04, 2010

STEMI criteria, STEMI equivalents and Takotsubo cardiomyopathy

There's a great case discussion over at the 12 lead ECG blog. The patient, while not meeting the official criteria for STEMI, had tell-tale electrocardiographic signs of acute coronary occlusion (what I'm calling STEMI equivalent these days). The blogger gives a brilliant discussion of the findings. Then when the patient actually turned out to have Takotsubo cardiomyopathy he provides an equally brilliant discussion of that entity. Go read the entire three part post which ends with the link above.


By the way Takotsubo cardiomyopathy, while originally presented as a cardiomyopathy that followed well defined emotional stress, is now being described in a wider variety of settings, including patients admitted with other diagnoses, in which, presumably, the initial non-cardiac diagnosis is the triggering stress. See, for example, this review. It may even be a factor in some patients experiencing the well known “cardiopathy of sepsis” in which patients with severe sepsis experience troponin bumps and drop their ejection fractions transiently. Because it's identified with increasing frequency and is soooo cool to diagnose I wonder if it's on a trajectory from under appreciated entity to wastebasket diagnosis for any cardiomyopathy when the clinician doesn't know what else to call it.

Wide anion gap metabolic acidosis from acetaminophen in therapeutic use

According to this review I found recently (H/T to Renal Fellow Network) the mechanism is an accumulation of 5-oxoproline (pyroglutamic acid) due to depletion of glutathione. It is believed to be rare although the true incidence is unknown and it may be under recognized. Malnourished individuals seem more susceptible.


The take-home message? Once in a while the search for the usual suspects in a case of wide gap acidosis (ketones, lactate, toxic alcohols, salicylates, etc) is unrevealing. Consider this entity in appropriate clinical circumstances. Stop the acetaminophen and the acidosis may resolve.

Initial and emergent resistance of Pseudomonas to Imipenem in pneumonia

This systematic review showed an alarming rate of both initial and acquired Pseudomonas resistance to Imipenem in the treatment of pneumonia, in comparison to several other antibiotics.

ICUroom.net

Up to date and loaded with resources for hospitalists, emergency medicine and critical care physicians.

EMRAP TV

Brief emergency medicine video podcasts. Free.

Wednesday, November 03, 2010

On the loss of a great mentor---Coy Fitch


I just learned that Coy Fitch, MD, former Chair of Internal Medicine at St. Louis University School of Medicine, died last May. When I was in my residency at SLU back in the late 70s Dr. Fitch was a ward attending and one of the leaders of the residency program.

When he stepped onto the ward for attending rounds my first week there I was fooled by his soft spoken, unassuming manner. But I soon experienced for myself the sense of reverential fear I'd heard about from the other house staff. What was it about him in all that humility? He wasn't abusive. He didn't yell and rant and rave and he wasn't into “pimping.” I think it was his utter, uncompromising sincerity about excellence in patient care and the fact that he expected the same of you. If you were dumb and green that was understandable but he couldn't tolerate sloppiness or carelessness. You wanted to please him more than anything but that sigh or that Coy Fitch scowl reminded you when you didn't measure up.

He wasn't gratuitous in his praise or criticism, but a little bit went a long way. He said what he meant and meant what he said, and that was that. I think he was the straightest shooter I ever knew in my training. One time after a case presentation at professor's rounds he said “that was a well worked up, well presented case.” That was the highest praise I think I ever heard him give anybody. It didn't sound like much but the team knew it meant a lot coming from Fitch, and probably gloated for a week.

All the same we knew he cared about our personal lives and professional development. I was always welcome to call him at home. He once expressed concern to me about whether I was getting enough sleep, strange as that may seem now as we look back on an era when education was punishment.

He was one of that dying breed, the physician-scientist. He had joint appointments in Medicine and Biochemistry. Although his subspecialty was endocrinology he also maintained a career long basic research interest in malaria. Despite that academic bent he exhibited great common sense and extraordinary clinical instincts on the wards. He imparted many pearls of wisdom which I never forgot and have yet to prove wrong. One time after listening to a presentation in morning report about a patient with unexplained dyspnea he remarked that any time you catch yourself saying “I wonder why this patient is dyspneic” think pulmonary embolism. That was prescient. It's essentially Wells criterion #2, and Fitch predated it by 20 years!

Dr. Fitch talked some time ago about retiring and moving back to Arkansas but as far as I know he continued to work until shortly before his death at age 75. He loved the teaching and practice of medicine and was devoted to the University. SLU will never be the same, and Coy Fitch stories will no doubt circulate among alumni for years to come.


How will the 2010 elections affect health care reform?

Health care reform may be Obama's Iraq. Wesley Smith at Secondhand Smoke has this take:


The political debacle suffered by the Democratic Party tonight–it was not a validation of Republicans–had two major causes.  One, beyond our scope here, was the economy and the president’s handling thereof. The second, unquestionably, was Obamacare.  The American people resent how it was passed over their clear and abundantly expressed objections.  The American people loathe the corrupt political process that led to its enactment. The American people don’t want it.  The American people want it repealed, or at the very least, substantially changed.


That won’t happen–yet–what with the president owning the veto pen and the Senate remaining narrowly Democratic.  But it can be badly undermined, indeed, so badly damaged all that will remain will be a husk to blow over in the electoral wind of 2012.  Its regulatory machine can now be defunded before it sinks deeply into the bedrock of American society. The House can–and should–repeatedly pass major modifications and repeals, which will probably be stopped in the Senate,  thereby setting up 2012 for the coup de grace.

Should we be recommending vitamin D supplementation?

And for whom?


There's biologic plausibility and lots of indirect evidence, but the jury is still out.


Via the Clinical Correlations blog.