Levamisole associated ANCA vasculitis

Here is an abstract from SHM 2014 containing a case presentation and brief discussion of ANCA positive vasculitis associated with levamisole-adulterated cocaine. Levamisole is one of several culprit drugs (see here). Once thought of as a drug induced “false positive ANCA” it is now widely recognized that the problem can involve a fully developed vasculitis, the management of which may require more than just stopping the offending drug, as illustrated in the abstract.

Agile MD

A collection of quick reference medical resources. Most are free after registration. It is optimized for smart phone use but you can also access it from a desktop or laptop.  

Abstract presentations, SHM 2014

The abstract presentations at the 2014 Society of Hospital Medicine annual meeting can be accessed here. I will blog individual presentations of interest in the near future. After my disappointment in the plenary sessions I was encouraged to see so many clinically focused abstracts. Though SHM as a whole has lost its clinical emphasis, clearly there are hospitalists on the ground who are still passionate about clinical medicine. The abstract  collection contains some of the gems of SHM 2014. It's too bad this type of content wasn't given center stage.

SHM 2014: scientific assembly or rally?

Being a clinician, as I sat in the plenary sessions of our 2014 national meeting I started to wonder. Was I in the right place? There was some clinical content at the conference (I'll blog a bit of that later) but, unless you paid extra to attend a precourse, it was largely relegated to the breakout and poster sessions.

I attended the plenary sessions in hopes I'd get a better idea of the vision of our leaders and where they are taking the field of hospital medicine. It wasn't encouraging. The highlights below centered around Ian Morrison's talk and some elaboration in a panel discussion.


Consolidation and increased centrality of care

Morrison said:

Doctors discretion in selection of specific technologies and clinical protocols
will be increasingly constrained by large motivated health systems that employ
them..

He might as well have said “prepare for the decimation of evidence based medicine.” I'll explain. EBM takes the external evidence and applies it to the individual patient's attributes, preferences and values, as directed by the judgment and expertise of the individual clinician. It's incompatible with medicine by central control. That point seems widely misunderstood about EBM but it was taught by the founders and still applies today.


The transitions of care

Morrison said:

Care coordination of transitions will be at a premium.

The hospitalist model is a deliberate disruption in the continuum of care. Hospitalists created these artificial transitions and have been trying, with little success, to undo the consequences ever since. Don't expect them to suddenly fix it now.


Renewed focus on primary care

What will that mean for patients? It will mean limited choice and limited access to specialists. We've been there before. With heavy managed care in the 90s patients found it very difficult to access specialty care. It backfired. It was a patient satisfaction disaster. Are we going to try again?


The second curve

By that he means, broadly, the future demands of the economic and regulatory environment of health care.

Components of the second curve, according to Morrison, include the following:

A shift toward population health.

As important as that is, what do hospitalists have to do with it?


A shift from volume to value as the compensation incentive .

Value based purchasing is the latest term for P4P, based on performance surrogates that do not equate to real quality and to date have had no proven beneficial impact. [1] [2] The principal effect of the incentive has been to drive elaborate charting and coding games to create the appearance of delivering quality care to very sick patients. It's difficult for me to see how any of that can be good.


Morrison ended with some remarks about how hospitalists can “lead the redesign of acute care” to achieve the triple aim. If inpatient medicine's place in health care is about to diminish precipitously (see Bob Wachter's post here and if you're still skeptical about the incredible shrinking hospital see here) why, of all people, would hospitalists emerge to be the reformers? We would do that by “reaching out beyond the walls” of the hospital according to Morrison. In other words we wouldn't be hospitalists anymore.

So Morrison is predicting the demise of EBM and the demise of the hospitalist model, at least as originally conceived. I'm not criticizing him. He's a health care futurist and is just the messenger. The disturbing thing is that the leadership of SHM doesn't seem to mind.

Rare and emerging viral infections in transplant recipients

Recent review.

Thyroid storm

The clinical approach to thyroid storm was well covered in a recent post at Academic Life in Emergency Medicine. Though it's a quick, concise read and just a click away I'll mention here a few points deserving emphasis, made by the peer reviewer:

Thyroid storm is a clinical diagnosis

Despite difficulty in the fact that many patients have vague and undifferentiated features the urgency of the situation may not allow time for laboratory confirmation. If you suspect it, treat it.


The presentation may be deceptive

The peer reviewer goes so far as to say:

The diagnosis of thyrotoxicosis can be subtle and will absolutely be missed by the clinician who has not considered it on his or her differential.

The Burch-Wartofsky score may be helpful

It's a clinical tool for evaluation of the probability of thyroid storm independent of lab results and can be accessed here.


Order and timing of medications

Wait at least an hour after giving the thionamide before giving iodine to avoid exacerbation of storm as a consequence of iodine.


Understand the relationship to infection

Infection is one of several known stressors that can convert ordinary thyrotoxicosis into storm. So in the patient presenting with storm evaluate for underlying infection and have a low threshold for starting antibiotics. It works in the other direction. Since the manifestations of sepsis and storm overlap considerably, avoid premature closure and consider the thyroid in patients presenting as sepsis.

The binary classification of ACS into STEMI and NSTEMI can be misleading

There, I said it again. I've said it here before in various ways and offered many examples [1] [2] [3] [4] [5] [6] [7], encountering a little resistance along the way.

This review makes the case again and provides some examples of why it's true, including hyperacute T waves, de Winter T waves and Wellen syndrome.

VTE and cancer

This review in Circulation compliments another review on this topic that I linked recently and makes the following additional points of interest:

Tissue factor expression and activation of the coagulation system by tumor cells facilitate tumor growth and metastasis.

Pulmonary embolism incidentally discovered on cancer imaging studies is not benign as was once thought.


The other points are similar to the review linked in the previous post. The Circulation review is available as free full text.

Weight reduction as a treatment modality in atrial fibrillation

Obesity has become increasingly recognized as a driver of atrial fibrillation. The topic was recently reviewed in this paper and I provided some background here. Now for the first time a study in JAMA suggests that weight reduction lowers the arrhythmia burden in obese patients who have atrial fibrillation:

Design, Setting, and Patients Single-center, partially blinded, randomized controlled study conducted between June 2010 and December 2011 in Adelaide, Australia, among overweight and obese ambulatory patients (N = 150) with symptomatic atrial fibrillation. Patients underwent a median of 15 months of follow-up.

Interventions Patients were randomized to weight management (intervention) or general lifestyle advice (control). Both groups underwent intensive management of cardiometabolic risk factors...

Results Of 248 patients screened, 150 were randomized (75 per group) and underwent follow-up. The intervention group showed a significantly greater reduction, compared with the control group, in weight (14.3 and 3.6 kg, respectively; P less than .001) and in atrial fibrillation symptom burden scores (11.8 and 2.6 points, P less than .001), symptom severity scores (8.4 and 1.7 points, P less than .001), number of episodes (2.5 and no change, P = .01), and cumulative duration (692-minute decline and 419-minute increase, P = .002). Additionally, there was a reduction in interventricular septal thickness in the intervention and control groups (1.1 and 0.6 mm, P = .02) and left atrial area (3.5 and 1.9 cm2, P = .02).

More about the study from Medscape Cardiology.

SHM 2014: What was all the excitement about?

To answer that question let’s take another look at Bob Wachter’s post about the conference. Bob, after all, is tuned in to the hospital medicine zeitgeist if anyone is. So what was Bob excited about? Well, the incredible growth of our field, hospitalists “taking over the world” of inpatient care, and the fact that the CMS Chief Medical Officer and the nominee for surgeon general are hospitalists. Wonderful. So where was the excitement about the latest in critical care, nephrology and cardiovascular disease? There’s been some real cool stuff that’s come out in the past year!

I’m not picking on Bob these days but chose to center my discussion points around his comments because I believe they reflect the overall focus of our professional society (which I think is misguided) and he articulates them well.

The problem illustrated here is that we're losing our clinical focus. If we want value why not focus on being the best clinicians available to care for these incredibly sick and complex patients? It’s not measurable in any meaningful way but something we could embrace.

SHM 2014: the prevailing winds of hospital medicine

This is my second post about the 2014 Society of Hospital Medicine national meeting in Las Vegas. I decided to use Bob Wachter's blog form April 14 as a starting point. I intended to review his entire post on Saturday but got stuck on the first paragraph. But Bob had a good deal more to say. My reactions were all over the map (agree, disagree, hope you're wrong, I told you so) so let's dive right in.

One of the big topics for discussion in the plenary sessions was the impact of the ever changing regulatory environment on hospital medicine. Bob predicts a major trend toward closure of hospitals in just the next few years as if it's something new. But we've seen this before, haven't we? In fact it's been going on ever since Medicare enacted the Prospective Payment System (DRGs) in 1983.

Consider this paper for example. According to the report many hospitals closed in the 1980s due at least in part to the advent of Medicare's Prospective Payment System:

Throughout the 1980s a tremendous number of rural hospitals closed their doors nationwide due to the impact of rural outmigration, shifting demographics and changes in Medicare payment methodologies.

This section of the report elaborates on the impact of DRGs:

Early on, Medicare and many other third party insurers simply paid what the hospital charged for the care received by the beneficiary. Then, in 1982, as a result of the TaxEquity and Fiscal Responsibility Act8 (TEFRA), Medicare started transitioning over to a new reimbursement methodology called the prospective payment system in an effort tocontrol costs. For inpatient services, Medicare would pay a set amount per diagnosis related group (DRG)9

As McGuire et al. (1993) point out, PPS was designed to reward efficiency. If a hospital could find a way to keep its costs below the rate of payment, the difference could be considered a profit. This concept was problematic for many rural hospitals because costs were usually well above these generally determined reimbursement rates. Fluctuations in the cost of providing care were not taken nto account by Medicare and were skewed toward urban providers. Medicare has saved a lot of money over the years but cost rural America a lot of hospitals as well.

A lot of hospitals did close and those that stayed open shifted inpatient beds to other lines of service. Things only got worse through the years as Medicare tightened its noose and private payers adopted the DRG model. We've been on a trajectory of more and more regulatory baggage ever since but it has been smooth. Obamacare means we'll progress along that continuum. It'll be disruptive but not nearly so much as with DRGs unless I miss my guess.

So what, says Bob, does this mean for hospitalists? Why, value! It's been Bob's mantra for years and it goes something like this: the hospitalist model has proven its value (in terms of resource utilization and outcomes) up to now and will have to work even harder to do so in order to thrive as a specialty in the future. I'm sure Bob would have some nuance to add but it's certainly the group think at SHM these days. So we have two ideas in need of critical examination.

First, have we proven our value by any measure? Bob says in his post:

The point here is that, just as hospitalists took over the world of hospital care because they demonstrated that they could provide high-quality care at a lower cost, the increasing financial pressures that hospitals are under will create, in turn, pressures on hospitalist programs to achieve quality, safety, patient satisfaction, and efficiency outcomes at the lowest possible cost to the hospital...

The reason the hospitalist field thrived was that it demonstrated that it delivered better value than traditional models.

Well, that's debatable. As I've blogged time and time again the evidence is mixed. I'll not rehash it all here other than to say that one of the best and largest studies ever to address this question showed no benefit of the model. It can be accessed on page 25 of this issue of The Hospitalist but as far as I know has never been published in a Medline indexed journal. So it's been tossed down the memory hole and has contributed to the publication bias that has plagued this literature ever since. I'm happy to listen to arguments on both sides of the question but you can't take it for granted that the hospitalist model has been proven superior to the traditional model. There's just not a clean evidential case to be made.

In terms of demonstrating our value to secure our future, how about just showing up? Outside of our ranks fewer and fewer doctors are willing to take care of hospitalized patients. There’s no reason to think the increasingly harsh regulatory environment will do anything other than drive the rest of the non-hospitalists out of the building.

Consider emergency medicine and its parallels with our specialty. Though under the same economic and regulatory pressures as we are you don’t find them crowing about their value. Their emphasis is clinical which is why I have so many of EM blogs linked here. They’re thriving quite well with that singular focus. There are lessons we can learn from them.

What's the optimal duration of antibiotic treatment for ventilator associated pneumonia?

Short duration of treatment was as good as long duration in this systematic review. Keep in mind though that short duration was defined as 7-8 days.

SHM 2014: visceral reactions

The 2014 national meeting of the Society of Hospital Medicine was held March 25-27. I've been busy since I got back and am just now getting around to “blogging the conference.” This, I hope, will be but one of a series of posts about the meeting.

Bob Wachter shared some of his thoughts the other day. I thought I'd read his post before starting. Bob can be a little provocative and sure enough his comments got me going.  In Bob's opening I was struck by this:

As Win Whitcomb, who co-founded SHM, wrote to me, the meeting is “a mix of love, deep sense of purpose, community, mission, changing-the world, and just plain sizzle,” and I completely agree.

Unfortunately that quote matches my own observations concerning what the sizzle was about: community, mission, changing the world. But what happened to the clinical care of the individual hospitalized patient? Sadly, there didn't seem to be a lot of energy focused on that aspect. Sure there were clinical break out sessions (yes, they were good and will be the subject of future posts here) but they seemed to be relegated to a lesser status. It was as if the clinical content was incidental. That seems to be the general direction of the organization.

It wasn't always that way. It was different when I first attended our national meeting about a decade ago (when we were known as NAIP, the National Association of Inpatient Physicians). The buzz as I remember it back then was about things like sepsis, pneumonia, mystery cases and complex cases of thromboembolic disease. The focus was clinical.

Not so much nowadays. In the plenary sessions I got the feeling this was a meeting for hospital administrators, policy makers and public health professionals rather than doctors. The “patients” they talked about were the hospitals, the health care systems and the larger communities, not the individuals populating the hospital wards.

We need the leaders of our field to go back to promoting hospitalists as clinicians. Unfortunately I didn't see that happening at SHM 14.

EM talks from Vanderbilt

By Corey Slovis and others.

Wiki Tox

An open source toxicology site. Lots of good resources here.

Update on serotonin syndrome

Free full text review.

Brain dysfunction in sepsis

A review.

The Z-drugs: zolpidem, zopiclone, and zaleplon

From a recent review:

The Z-drugs zolpidem, zopiclone, and zaleplon were hailed as the innovative hypnotics of the new millennium, an improvement to traditional benzodiazepines in the management of insomnia. Increasing reports of adverse events including bizarre behavior and falls in the elderly have prompted calls for caution and regulation..Z-drugs exert their effects through increased γ-aminobutyric acid (GABA) transmission at the same GABA-type A receptor as benzodiazepines..Poisoning with Z-drugs involves predominantly sedation and coma with supportive management being adequate in the majority. Flumazenil has been reported to reverse sedation from all three Z-drugs. Deaths from Z-drugs are rare and more likely to occur with polydrug overdose.

The Magic Eye method of ECG rhythm assessment

Magic Eye posters were quite the rage a couple of decades ago. I got pretty good at stereoviewing so I'll have to try this. It might come in handy if there are no calipers around.

Via RESUS ME

A simple clinical prediction rule for the presence of CAD in patients presenting with heart failure

Published here in AJC. This may help in selecting those patients who need coronary angiography. The new ACC heart failure guidelines do not make a strong statement on coronary angiography or non invasive imaging indications, leaving it to clinical assessment.

Chlorine gas inhalation

Here is a post at The Poison Review on this topic focusing on important management questions including the use of steroids and nebulized sodium bicarb. There is a link to an Emedicine article.

Acute LAD occlusion

Some nuances on the electrocardiographic findings along with a discussion of the relevant coronary anatomy can be found in this post at the blog ECG interpretation.

Orthostatic vital signs: evidence based or not?

An evidence rundown is presented in the video below. The test characteristics are poor.


 

HT to LITFL. 

A history of the hospitalist movement in song

Well, Bob Wachter promised us something different for his keynote at HM 2014 but I wasn't expecting this.




I had to catch an early flight and missed this session. Thanks to Medicina Hospitalar for pointing it out to me.

Hospitalists and heart failure outcomes

JACC Heart Failure has published data from a large heart failure registry:

Results The analysis included 31,505 Medicare beneficiaries in 166 hospitals. Across hospitals, the use of hospitalists varied from 0% to 83%. After multivariable adjustment, a 10% increase in the use of hospitalists was associated with a slight increase in mortality (risk ratio: 1.03; 95% confidence interval [CI]: 1.00 to 1.06) and decrease in length of stay (0.09 days; 95% CI: 0.02 to 0.16). There was no association with 30-day readmission. Increased use of hospitalists in hospitals with high use of cardiologists was associated with improved defect-free adherence to a composite of heart failure performance measures (risk ratio: 1.03; 95% CI: 1.01 to 1.06).

Hospitalist care was associated with a slight reduction in LOS and a slight increase in mortality (borderline statistical significance) despite higher adherence to performance measures. The findings are not surprising. Hospitalists are doing what they are incented to do: get patients out faster and score better on various metrics. The benefit to patients is dubious.

Via Hospital Medicine Virtual Journal Club.

The ProCESS trial---discussing the fine points

Here's a podcast interview with Dr. Derek Angus over at the EMCrit Blog. It offers some nuanced insights on how you might apply the findings to your practice. Before you run with the findings, though, remember that two more sepsis trials asking similar questions are about to be published. I first blogged ProCESS here.

Stroke care: nuances, practical aspects and pearls

These are some points from S. Andrew Josephson 's talk at the 17th Annual UCSF hospital medicine course.

Timeline for interventions

Acute ischemic stroke time windows:

0-4.5 hr IV thrombolysis (I acknowledge the controversy that still rages about this. I'll save it for another discussion).

0-6 hours intra arterial thrombolysis (stroke guideline class I for MCA occlusions not otherwise eligible for IV lysis).

0-8 hours mechanical embolectomy (class IIa for those not eligible for lytics).


And here's what the 2013 stroke guidelines say about the interventional treatments including rescue:

Intra-arterial fibrinolysis is beneficial for treatment of carefully selected patients with major ischemic strokes of less than 6 hours’ duration caused by occlusions of the MCA who are not otherwise candidates for intravenous rtPA (Class I; Level of Evidence B). The optimal dose of intra-arterial rtPA is not well established, and rtPA does not have FDA approval for intra-arterial use. (Revised from the previous guideline13) 

As with intravenous fibrinolytic therapy, reduced time from symptom onset to reperfusion with intra-arterial therapies is highly correlated with better clinical outcomes, and all efforts must be undertaken to minimize delays to definitive therapy (Class I; Level of Evidence B). (New recommendation)

Intra-arterial treatment requires the patient to be at an experienced stroke center with rapid access to cerebral angiography and qualified interventionalists. An emphasis on expeditious assessment and treatment should be made. Facilities are encouraged to define criteria that can be used to credential individuals who can perform intra-arterial revascularization procedures. Outcomes on all patients should be tracked (Class I; Level of Evidence C). (Revised from the previous guideline13)

When mechanical thrombectomy is pursued, stent retrievers such as Solitaire FR and Trevo are generally preferred to coil retrievers such as Merci (Class I; Level of Evidence A). The relative effectiveness of the Penumbra System versus stent retrievers is not yet characterized. (New recommendation)

The Merci, Penumbra System, Solitaire FR, and Trevo thrombectomy devices can be useful in achieving recanalization alone or in combination with pharmacological fibrinolysis in carefully selected patients (Class IIa; Level of Evidence B). Their ability to improve patient outcomes has not yet been established. These devices should continue to be studied in randomized controlled trials to determine the efficacy of such treatments in improving patient outcomes. (Revised from the previous guideline13)

Intra-arterial fibrinolysis or mechanical thrombectomy is reasonable in patients who have contraindications to the use of intravenous fibrinolysis (Class IIa; Level of Evidence C). (Revised from the previous guideline13)

Rescue intra-arterial fibrinolysis or mechanical thrombectomy may be reasonable approaches to recanalization in patients with large-artery occlusion who have not responded to intravenous fibrinolysis. Additional randomized trial data are needed (Class IIb; Level of Evidence B). (New recommendation)

Note that the rescue therapies are IIb and the speaker said we should “probably not” be using them at present with the exception of basilar lesions.


Informed consent

Informed consent for IV thrombolysis is vital. Because time for discussion is limited, graphics such as this one are useful (from this paper).


Who needs a TEE? When is TTE enough?

TEE is far superior to TTE for detection of an indication for systemic anticoagulation. For practical purposes, according to the speaker, a selective approach can be used and he presented UCSF's protocol:

Cryptogenic clinically large vessel stroke, age under 55, no known a fib: TEE.

For patients 55 and older with cryptogenic clinically large vessel stroke and no a fib get a TTE. Stop there if no LV systolic dysfunction, LVH, left sided valvular stenosis, left sided valvular regurgitation (or only mild), prosthetic valve or LAE (over 40mm). Otherwise TEE. If TTE shows intracardiac mass or veg TEE may still be necessary if warfarin indication unclear.


A fib detection

In cryptogenic stroke if echo eval is negative and inpatient telemetry shows no a fib: extended day outpatient event monitor. The cost effectiveness of such an approach was shown in this analysis.


Indications for anticoagulation are diminishing

Chronic: A fib, thrombus seen in heart. For PFO (even with atrial septal aneurysm): questionable. For artery dissection: maybe. For hypercoagulable states: only if antiphospholipid syndrome.

Acute: none. Not even if the patient has a fib (in such a case just put them on warfarin and let the INR drift out).

What about target specific oral anticoagulants in this setting (secondary prevention)? Data are scant.


Antiplatelet therapy 

What about the CHANCE study? The speaker says this approach is not ready for prime time and we need to wait for the POINT trial results.

What if the patient with acute stroke is already on aspirin? He recommends a switch to plavix or aggrenox. If the patient is already on plavix or aggrenox there is no published experience to guide us.


Lipid management

80 mg atorvastatin for almost everyone.


Permissive hypertension in CVA

In the non-TPA ischemic stroke patient treat 220/120 but not anything lower initially, unless their's some other indication (e.g. cardiac emergency). What if it's just a TIA? He still advocates for permissive HT but says sometimes he “fudges” a little.


TIA

Treatment approach essentially same as stroke, conceptually. 30-50% will have infarct on MRI.

Sepsis: changing definitions and recommendations

At UCSF's 17th annual hospital medicine conference Michael A. Gropper, MD, PhD summarized the changes, focusing mainly on changes from 2008 in the 2012 Surviving Sepsis guidelines. Here's my quick and dirty rundown.

Definitions

Sepsis was formerly defined as documented or suspected infection plus two sirs criteria. In contrast, the 2012 guidelines define it as documented or suspected infection plus “some” of a long list of conditions:

Fever (greater than 38.3°C)

Hypothermia (core temperature less than 36°C)

Heart rate greater than 90/min–1 or more than two sd above the normal value for age

Tachypnea

Altered mental status

Significant edema or positive fluid balance (greater than 20 mL/kg over 24 hr)

Hyperglycemia (plasma glucose greater than 140 mg/dL or 7.7 mmol/L) in the absence of diabetes

Leukocytosis (WBC count greater than 12,000 μL–1)

Leukopenia (WBC count less than 4000 μL–1)

Normal WBC count with greater than 10% immature forms

Plasma C-reactive protein more than two sd above the normal value

Plasma procalcitonin more than two sd above the normal value

Arterial hypotension (SBP less than 90 mm Hg, MAP less than 70 mm Hg, or an SBP decrease greater than 40 mm Hg in adults or less than two sd below normal for age) 

Arterial hypoxemia (Pao2/Fio2 less than 300)

Acute oliguria (urine output less than 0.5 mL/kg/hr for at least 2 hrs despite adequate fluid resuscitation)

Creatinine increase greater than 0.5 mg/dL or 44.2 μmol/L

Coagulation abnormalities (INR greater than 1.5 or aPTT greater than 60 s)

Ileus (absent bowel sounds)

Thrombocytopenia (platelet count less than 100,000 μL–1)

Hyperbilirubinemia (plasma total bilirubin greater than 4 mg/dL or 70 μmol/L)

Tissue perfusion variables

Hyperlactatemia (greater than 1 mmol/L)

Management

Crystalloid as the initial resuscitation fluid of choice (former guidelines did not specify crystalloid versus colloid). Initial crystalloid amount of 30 ml//kg.

Norepinephrine as the first choice pressor (former guidelines did not specify norepi versus dopamine).

Note that norepinephrine is not always to be delayed until volume resuscitation is complete. From the guideline document:

Vasopressor therapy is required to sustain life and maintain perfusion in the face of life-threatening hypotension, even when hypovolemia has not yet been resolved. Below a threshold MAP, autoregulation in critical vascular beds can be lost, and perfusion can become linearly dependent on pressure. Thus, some patients may require vasopressor therapy to achieve a minimal perfusion pressure and maintain adequate flow (133, 134).

What if norepi isn't enough? The implication is that epinephrine is next followed by vasopressin, but the guidelines lack clarity as to which to use first and why. Again, quoting from the document:

We recommend norepinephrine as the first-choice vaso-pressor (grade 1B).

We suggest epinephrine (added to and potentially substituted for norepinephrine) when an additional agent is needed to maintain adequate blood pressure (grade 2B).

Vasopressin (up to 0.03 U/min) can be added to norepinephrine with the intent of raising MAP to target or decreasing norepinephrine dosage (UG).

Neuromuscular blockers for ARDS but only early, only if PO2/FiO2 below 150 and only for up to 48 hours. The 2008 guidelines suggested blanket avoidance of neuromuscular blockers.

Relaxed glycemic control targets (180 in the new guidelines as opposed to 150).

Feeding (oral or enteral) within 48 hours onset of severe sepsis or septic shock. Previous guidelines didn't address feeding.

Advance care planning addressed within 72 hours. Previous guidelines did not set a time frame for this.


The guidelines make several additional recommendations about sepsis induced ARDS which are (or will be) addressed in separate posts on that topic.

Anti-TNF therapy and the risk for Legionella pneumophila

We don't ordinarily think of Legionella pneumophila as an opportunist but findings of a recent study indicate that patients undergoing anti-TNF therapy are at special risk. The paper concludes:

The incidence rate of legionellosis for patients receiving TNF-α antagonists is high, and the risk is higher for patients receiving anti-TNF-α monoclonal antibodies than soluble TNF-receptor therapy. In case of pneumonia occurring during TNF-α antagonist therapy, specific urine antigen detection should be performed and antibiotic therapy should cover legionellosis.

The CAP guidelines recommend legionella coverage for all patients. Urinary antigen testing, however, is only recommended for select groups (e.g. ICU admissions, outpatient treatment failure) with no mention made of anti-TNF treatment status.

COPD versus asthma

Although there is overlap between these two conditions there are important distinctions to keep in mind when patients are hospitalized. The points below were drawn from a talk given by Prescott Woodruff, MD, MPH at the 17th annual UCSF hospital medicine course.

General differences
As compared to asthma, COPD patients have more structural lung disease, are weaker with more comorbid conditions and are more likely to have bacterial infections when they present with exacerbations.

Oxygen administration
In COPD as opposed to asthma, greater cautions apply with more reliance on ABGs over pulse oximetry.

Corticosteroids
Some nuanced differences but for the most part similar dosing and rationale.

Inhaled bronchodilators
Beta agonists for both. Greater role of ipratropium in COPD but probably also helpful in asthma.

Antibiotics
Generally used for COPD, selectively used for asthma.

NIPPV
Well established for COPD. Patient selection based on blood gases and clinical assessment. Less well established for asthma but may be helpful in some instances.

Target specific (novel) oral anticoagulants: lessons and pearls from clinical trials

This post draws on some of the information provided in Dr. Tracy Minichiello's talk at the 17th annual UCSF conference on hospital medicine with particular focus on some less well appreciated findings form the clinical trials that led to approval of the three target specific oral anticoagulants (TSOACs) currently in use.

Dabigatran (Pradaxa)

Compared to warfarin in RE-LY. Below in reference to the 150 mg bid dose.

Dabigatran favored, established superiority , RR 0.66 (0.53-0.82), for the primary outcome stroke or systemic embolism. NNT 172.

Dabigatran associated with borderline statistically significant reduction in all cause mortality, RR 0.88 (0.77 to 1.00) P=0.051.

Dabigatran associated with less ICH, RR 0.4 (0.27-0.6). NNT 227.

Dabigatran associated with increased GI bleed, RR 1.5 (1.19-1.89). NNH=204.

Dabigatran associated with trend toward higher risk of MI, not statistically significant, RR 1.27 (0.94-1.71). Absolute risk very low. NNH for the point estimates would be 588.

For the other safety outcomes the two drugs were comparable.

Pradaxa product labeling.

Comment: the trend toward a difference in MI risk suggests caution in the selection of anticoagulants in patients with coronary disease particularly taking into account that warfarin has an FDA approved indication for secondary prevention post MI. Consider avoidance in patient with history of GI bleed.


Rivaroxaban (Xarelto)

Compared to warfarin in ROCKET AF.

For the primary outcome of stroke/systemic embolism rivaroxaban, in the per protocol, as treated population, was non-inferior with HR 0.79 (0.66-0.96).

Overall bleeding rates comparable.

Critical (see the body of the paper for definition) and fatal bleeding rates were less with rivaroxaban, and the differences were statistically significant, HR 0.69 (0.53-0.91) and 0.50 (0.31-0.79) respectively.

ICH rates were statistically significantly less with rivaroxaban, HR 0.67 (0.47-0.93).

Rivaroxaban was associated with a statistically significant increase in GI bleeds, NNH 101.

There was no difference in MI.

At the end of the study treatment period there was a spike in the primary outcome in rivaroxaban patients transitioning to warfarin related to a long (13 day) time to reach target INR.

Xarelto labeling.


Apixaban (Eliquis)

Compared to warfarin in ARISTOTLE.

Note the primary outcome: ischemic or hemorrhagic stroke or systemic embolism.

Apixaban was favored, HR 0.79 (0.66-0.95) p=.01 for superiority.

For ischemic or unknown mechanism stroke HR 0.97 (0.74-1.13).

For ICH HR 0.51 (0.35-0.75).

All cause mortality HR 0.89 (0.80-0.99).

Non-statistically significant trend toward reduced MI.

No significant difference in GI bleeds.

Eliquis labeling.



Concluding comments:

The labeling for all three agents carries warnings to consider bridging with discontinuation or transition to warfarin.

When selecting an anticoagulant for stroke prevention in a fib for patients with CAD consider 1) warfarin has an approved indication for secondary prevention in CAD patients; 2) a possible increased risk of MI with dabigatran; and 3) that we have a long experience using various combinations of warfarin and antiplatelet agents.

Consider avoidance of dabigatran and rivaroxaban in patients with GI bleed history or risk.

The true practice of EBM honors the preferences and values of an informed patient. Carve out time for a long discussion with your patient when you start them on an oral anticoagulant for stroke prevention in atrial fibrillation.

Statin use and delirium risk in critical illness

According to this study statin administration the previous evening was associated with reduced delirium in critically ill patients. It was also associated with lower CRP and when adjusted for CRP the effect was no longer statistically significant, suggesting a role of inflammation. This was a prospective cohort analysis. A clinical trial is now in progress to evaluate statin therapy as an intervention for delirium.

More from Medpage Today.

Outpatient pulmonary embolism treatment: what does the evidence say?

From a recent meta-analysis:

 We identified 13 studies (1657 patients) with outpatients (discharge less than 24 h), three studies (256 patients) with early discharge patients (discharged within 72 h) and five studies (383 patients) with inpatients. The pooled incidence of recurrent venous thromboembolism was 1.7% (95% CI 0.92–3.1%) in outpatients, 1.1% (0.22–5.4%) in patients discharged early and 1.2% (0.16–8.1%) in inpatients. The pooled incidence of major bleeding was 0.97% (0.58–1.6%) in outpatients, 0.78% (0.16–3.7%) in early discharge patients and 1.0% (0.39–2.8%) in inpatients. The pooled incidence of mortality was 1.9% (0.79–4.6%) in outpatients, 2.3% (1.1–5.1%) in early discharge patients and 0.74% (0.04–11%) in inpatients.

Incidences of recurrent venous thromboembolism, major bleeding and, after correction for malignancies, mortality were comparable between outpatients, patients discharged early and inpatients. We conclude that home treatment or early discharge of selected low-risk patients with pulmonary embolism is as safe as inpatient treatment.

Via Hospital Medicine Virtual Journal Club.

The ECG findings in massive and submassive pulmonary embolism

Here is a review, available as free full text, along with a presentation of four cases.

Although the ECG lacks sensitivity and specificity and is not a “rule in” or “rule out” test for PE it is important for several reasons.

If the PE is massive or submassive it may provide diagnostic clues.

Massive and submassive PEs may be cause troponin elevation and electrocardiographic findings that superficially mimic MI. There are differences, however, that are worth knowing.

Here are a couple of my previous posts on the ECG in pulmonary embolism: [1] [2]

Here is a post on the electrocardiographic distinction between ACS and PE.

Perioperative management of patients with long QT

Little has been written about this topic. Here is a review which provides background and compiles what is known to date. Key points to remember are the management of K and Mg levels as well as the avoidance of certain drugs commonly used in the anesthesia suite such as droperidol and ondansetron. Hospitalists involved in the care of such patients can leverage the EMR by flagging such drugs as contraindicated in the allergy section.

SARS ten years later

From Emerging Infectious Diseases.