Linezolid in MRSA pneumonia: does it protect against tissue damage?

The debate concerning linezolid versus vancomycin as first line treatment for MRSA pneumonia is ongoing. This paper reports a mouse model of MRSA pneumonia in which linezolid may have a unique direct anti-inflammatory effect:

Results. Significant antibacterial activity was achieved after 48 hours of treatment for linezolid and vancomycin. Levels of interleukin 1β, a major proinflammatory cytokine, and macrophage inflammatory protein 2, a chemokine involved in the recruitment of neutrophils, were decreased by both antimicrobials. Only linezolid was able to dramatically reduce the production of tumor necrosis factor α. Analysis of myeloperoxidase activity and Ly6G immunostaining showed a dramatic decrease of neutrophil infiltration in infected lung tissues for linezolid-treated animals. A time-dependent increase of endothelial permeability was observed for the control and vancomycin regimens. Of interest, in the linezolid group, decreased endothelial permeability was detected 48 hours after infection.

Conclusions. Our results indicate that linezolid could be superior to vancomycin for the management of MRSA pneumonia by attenuating an excessive inflammatory reaction and protecting the lung from pathogen-associated damages.

Pulmonary alveolar proteinosis as a pneumonia mimic

I chose this abstract presentation from SHM 14 as a reminder that patients presenting with pulmonary radiographic opacities may have unusual parenchymal lung diseases masquerading as pneumonia. Over diagnosis of pneumonia is being increasingly recognized in today's increasingly performance driven, time constrained environment.

PICC associated bloodstream infections

From a recent paper in the American Journal of Medicine:

Results

During the study period, 966 PICCs were inserted in 747 unique patients for a total of 26,887 catheter days. Indications for PICC insertion included: long-term antibiotic administration (52%, n = 503), venous access (21%, n = 201), total parenteral nutrition (16%, n = 155), and chemotherapy (11%, n = 107). On bivariate analysis, intensive care unit (ICU) status (OR 3.23; 95% CI, 1.84-5.65), mechanical ventilation (OR 4.39; 95% CI, 2.46-7.82), length of stay (hospital, OR 1.04; 95% CI, 1.02-1.06 and ICU, OR 1.03; 95% CI, 1.02-1.04), PowerPICCs (C. R. Bard, Inc., Murray Hill, NJ; OR 2.58; 95% CI, 1.41-4.73), and devices placed by interventional radiology (OR 2.57; 95% CI, 1.41-4.68) were associated with PICC-bloodstream infection. Catheter lumens were strongly associated with this event (double lumen, OR 5.21; 95% CI, 2.46-11.04, and triple lumen, OR 10.84; 95% CI, 4.38-26.82). On multivariable analysis, only hospital length of stay, ICU status, and number of PICC lumens remained significantly associated with PICC bloodstream infection. Notably, the HR for PICC lumens increased substantially, suggesting earlier time to infection among patients with multi-lumen PICCs (HR 4.08; 95% CI, 1.51-11.02 and HR 8.52; 95% CI, 2.55-28.49 for double- and triple-lumen devices, respectively).

Conclusions

PICC-associated bloodstream infection is most associated with hospital length of stay, ICU status, and number of device lumens. Policy and procedural oversights targeting these factors may be necessary to reduce the risk of this adverse outcome.

Right ventricular outflow tract tachycardia: case presentation and discussion

From the green journal.

Sarcopenia in hospitalized patients: a risk factor for bad outcomes

From a paper in Clinical Nutrition. Via Hospital Medicine Virtual Journal Club.

Serotonin syndrome

Here is a review from BMJ.

Points of interest from the review:

SS has a wide spectrum of severity.
At the mild end the patient may only exhibit increased reflexes, mild hyperextitability and nausea.


Severe SS is usually (but not always) confined to cases in which a MAO inhibitor is used in combination with another serotonergic drug.
This may occur even when both are administered in “therapeutic” doses.


Moderate toxicity can occur with a variety of drug classes and sometimes with a single serotonergic agent.


It has been estimated that 15% of SSRI overdoses will lead to SS (moderate severity).


Some psychiatric drugs are serotonin antagonists and would not increase the risk of SS.


The list of drugs is long.
It is accessible in the article.

Remember the triad: CNS excitation (neuromuscular manifestations), altered mental status and autonomic excitation (including in some cases hyperthermia).

Ocular clonus is a frequently cited manifestation.
I always found this a little confusing because I could never find a satisfactory explanation of how this differs from nystagmus. But the review contains a link to this Wiki Tox page which has a good explanation and some videos.

Regional variation in STEMI care, costs and outcomes

From a recent study in Clinical Cardiology:

Methods

We used the 2003 to 2010 Nationwide Inpatient Sample databases to identify all patients age greater than or equal to 40 years hospitalized with STEMI. Patients were divided into 4 groups according to region: Northeast, Midwest, South, and West. Multivariable logistic regression was used to identify differences in treatment choice and outcomes (in-hospital mortality, acute stroke, and cardiogenic shock) among the 4 regions.

Results

Of 1 990 486 patients age greater than or equal to 40 years with STEMI, 350 073 (17.6%) were hospitalized in the Northeast, 483 323 (24.3%) in the Midwest, 784 869 (39.4%) in the South, and 372 222 (18.7%) in the West. Compared with the Northeast, patients in the Midwest, South, and West were less likely to receive medical therapy alone and more likely to receive percutaneous coronary intervention and coronary artery bypass grafting. Risk-adjusted in-hospital mortality was higher in the Midwest (odds ratio [OR]: 1.07, 95% confidence interval [CI]: 1.05-1.09, P less than 0.001), South (OR: 1.03, 95% CI: 1.01-1.05, P = 0.001), and West (OR: 1.06, 95% CI: 1.04-1.08, P less than 0.001), as compared with the Northeast. When adjusted further for regional variation in treatment selection, risk-adjusted in-hospital mortality was even higher in the Midwest, West, and South.

Conclusions

Despite higher reperfusion and revascularization rates, STEMI patients in the Midwest, West, and South have paradoxically higher risk-adjusted in-hospital mortality as compared with patients in the Northeast.

Let's try and make sense of these findings in view of what we already knew. We already knew that:

In general an early invasive reperfusion strategy for acute coronary occlusion leads to the best outcomes, and the earlier the better.

Invasive reperfusion strategies are costly.

But this study showed that by region in the US, decreased use of the early invasive strategy was associated with lower mortality and higher cost. It's the opposite of what we knew before. In fact it doesn't make any sense at all. In the discussion section of the paper the authors talk around the paradox but don't come up with a good answer.

I don't have a pat answer but I have an idea. Keep in mind that although STEMI is widely accepted as a surrogate for acute coronary occlusion it's not a very good one. Moreover this is from an administrative database, so the findings must have been captured from coding.

Coding has always been dubious as a way to capture research data but it's even worse in the current environment because it has been loaded with powerful incentives not only for payment but also for public reporting. Increasing the apparent severity through creative coding not only results in better reimbursement but it also makes you look like a better provider on public report cards. There's a lot of creative charting going on these days.

That means 1) there's no telling what these “STEMI” patients really had and 2) the severity adjustment for the mortality is questionable.

Coding has become corrupted. Dream on if you think ICD 10 is going to fix that.

Which patients post cardiac arrest should go to the cath lab?

This topic remains a little controversial, but according to a recent review:

The high rate of acute coronary occlusion, the lack of clear means to select ideal candidates, and the benefit associated with early PCI strongly encourage performing a systematic coronary angiography in all OHCA patients, providing that there is no obvious noncardiac cause of arrest. Several questions remain unsolved but at this time, this strategy appears to be the most secure and the best adapted in these patients.

Elevated troponin levels in sepsis

Independently associated with mortality.

What will be the impact of Obamacare on hospitals?

According to this piece in the Annals of Internal Medicine the ACA will not mean the decimation of hospitals as some have feared. The hospital has proven resilient and remarkably successful in its struggle with the ever changing payment environment over the past several decades. With every move of the target the hospital adapts to the changing rules of the game. There is no reason to think, according to the article, that that will change under ACA.

Yet another review of target specific oral anticoagulants (TSOACs)

There are so many reviews coming out on this topic that I'm beginning to wonder if there's any point in trying to compile them all here. I just found this one, though, that has a lot to add to what's already out there. It is one of the better nuts-and-bolts summaries I've seen. It also has some new information from Med Watch data on the bleeding risks of TSOACs.

Persuasion techniques to get patients admitted from the emergency department to the hospital

Here's a really fascinating paper from the journal Social Science & Medicine. From the abstract:

This paper reports a discourse analysis of the language doctors used as they talked about and engaged in patient handoffs between the emergency department (ED) and various inpatient services...Although interest in handoff improvement has grown considerably in recent years, progress has been hampered, perhaps in part, because of a widely used but limiting conceptual model of handoff as an information transmission.

That last phrase (my italics) is rich and insightful. The handoff between ED and inpatient is complex. Though purportedly a simple conveyance of clinical information, much more lies beneath the surface. Many times it's a case of competing agendas. The ED physician, dealing with department crowding and long wait times, wants to get the patient dispo'd ASAP. The hospitalist is already three admissions behind and doesn't need another bomb dropped on his work flow.

Here are the key points listed in the introduction:

Doctors use metaphors of sales, sports, packages, and teamwork to describe handoff.

These metaphors illuminate the complicated social interactions of handoff.

Findings implicate various organizational and social structures.

The information transmission conceptual model of handoff is challenged.

The specialty of emergency medicine has many parallels to hospital medicine, one of which is the problem of discontinuity. Back in the 70s primary physicians evaluated their own patients in the ED and decided whether to admit them or send them home. There was no disconnect at the transition, no competing agenda and no need for gamesmanship.

Via Hospital Medicine Virtual Journal Club.

The Medical Letter on warfarin versus TSOACs for atrial fibrillation

This Medical Letter summary was published in JAMA. The Medical Letter tends to be conservative when it comes to newer drugs. They were true to form on this issue. From the summary:

Patients with nonvalvular atrial fibrillation who are taking warfarin and whose INR generally remains within the therapeutic range should probably stay on it. New patients and those who are difficult to maintain in the therapeutic range of INR might benefit from treatment with dabigatran (Pradaxa), rivaroxaban (Xarelto), or apixaban (Eliquis). Of the three, apixaban was the only one shown to cause less overall bleeding than warfarin, but direct comparisons between the new drugs and long-term data on outcomes are lacking.

The summary outlines the advantages and disadvantages of TSOACs versus warfarin.

Useful science

Random evidence based intellectual burps.

Practice variation in fluid therapy for acute pancreatitis

–-was widespread in this study from New Zealand.

There are fluid therapy recommendations in pancreatitis guidelines but there is little evidence to back them up. That said, there is an emerging literature on this topic about which I have blogged extensively before.

Via Hospital Medicine Virtual Journal Club.

Transitions of care: should hospitalists reach outside the walls of the hospital or should PCPs reach in?

An editorial in American Family Physician, citing evidence that hospital initiated efforts to reduce readmissions have had limited success, recommends involvement by PCPs when patients are hospitalized, even though their care is delivered by hospitalists:

.. the primary care physician should have a prominent role at three times: at admission, immediately after discharge, and at the postdischarge follow-up visit...

At the time of hospitalization, the primary care physician should contact and maintain communication with hospital-based clinicians…The primary care physician should discuss any concerns about the care plan, medications, medical history, and any social or family dynamics that may affect care, and should obtain an estimated date and destination of discharge…

To bridge the gap between discharge and follow-up, the primary care physician or a staff member with clinical knowledge can contact the patient 24 to 72 hours after discharge…

If that seems like a radical idea, it’s not. In fact, it’s in keeping with guidelines published several years ago that even take it further, recommending that ED physicians should contact the patient’s PCP first, before calling the hospitalist to arrange admission.

Type 2 MI: addressing and resolving the confusion

A review article addressing this topic is available as free full text from the American Journal of Medicine.

The classification of MI into types 1-5 is linked here.

Confusion may exist between type 2 MI and elevated troponin due to non ischemic myocardial necrosis occurring in a variety of severe illnesses. Perhaps the most familiar example of the latter condition is the troponin elevation that accompanies sepsis. Though long recognized and purported to be due to a variety of mechanisms it remains poorly understood.


Troponin measurements in a variety of critical illnesses may be useful for prognostic stratification but elevated values do not always point to the need for coronary intervention, and must be correlated with other clinical findings.

The patient with type 2 MI may or may not have atherosclerotic coronary artery disease. Clinical judgment should determine whether the patient needs evaluation for CAD and the timing of such evaluation.

Want to know why performance measures fail?

Here's a big reason:

Objectives The aim of this study was to examine the prescribing patterns of medications quantified by the performance measures for acute myocardial infarction (AMI).

Background Current performance measures for AMI are designed to improve quality by quantifying the use of evidence-based treatments. However, these measures only assess medication prescription. Whether patients receive optimal dosing of secondary prevention medications at the time of and after discharge after AMI is unknown.

Methods We assessed treatment doses of beta-blockers, statins, and angiotensin-converting enzyme inhibitors (ACEI)/angiotensin II receptor blockers (ARBs) at discharge and 12 months after AMI among 6,748 patients from 31 hospitals enrolled in 2 U.S. registries (2003 to 2008)...

Results Most eligible patients (greater than 87%) were prescribed some dose of each medication at discharge, although only 1 in 3 patients were prescribed these medications at goal doses. Of patients not discharged on goal doses, up-titration during follow-up occurred infrequently (approximately 25% of patients for each medication). At 12 months, goal doses of beta-blockers, statins, and ACEI/ARBs were achieved in only 12%, 26%, and 32% of eligible patients, respectively...

Conclusions Although nearly all patients after an AMI are discharged on appropriate secondary prevention medications, dose increases occur infrequently, and most patients are prescribed doses below those with proven efficacy in clinical trials.

Despite the fact that these hospitals looked good on their public report cards few patients got treated to goal. I have always suspected this, and wondered when a study like this wold be done. The IOM talks about a quality chasm. The unappreciated chasm is between performance and quality.

VTE prophylaxis for medical patients with cancer: evidence of non-evidence

From a systematic review:

Methods 

A systematic literature search strategy was conducted using MEDLINE, EMBASE, and the Cochrane Register of Controlled Trials. Two reviewers independently extracted data onto standardized forms. The primary end points were all venous thromboembolic events. Secondary end points included major bleeding episodes and symptomatic venous thromboembolic events. Pooled analysis with relative risk using a random effect model was used as the primary measurement.

Results

A total of 242 citations were identified by the literature search. Of these, 3 placebo-controlled randomized trials included venous thromboembolic events as a primary outcome and were analyzed according to cancer subgroups. The pooled relative risk of venous thromboembolic events was 0.91 (95% confidence interval, 0.21-4.0; I2: 68%) among hospitalized patients with cancer who were receiving thromboprophylaxis compared with placebo. None of the trials reported the rates of symptomatic venous thromboembolic events or major bleeding episodes according to cancer status.

Conclusions

The risks and benefits of primary thromboprophylaxis with anticoagulant therapy in hospitalized patients with cancer are not known. This is especially relevant because numerous Medicare-type pay-for-performance incentives mandate prophylaxis specifically in patients with cancer.

The vicissitudes of mitral valve prolapse

MVP was once thought to be rare and was under recognized. It became much more commonly diagnosed in the 1970s due to a couple of developments. First, it was realized that early systolic clicks were commonly of mitral origin and not always of aortic origin. Secondly, M mode echocardiography was coming into common usage and criteria were developed. Fascination with the condition increased as it was purported to be associated with cardiomyopathy, cerebral ischemic events, arrhythmias, skeletal abnormalities, sudden cardiac death and a variety of minor maladies. For a while in the 1980s it seemed that the condition had increased to pandemic proportions. Was it a case of true increase in incidence or just increased recognition? Actually it was more complex than either of those. Interest in the condition rose then waned. This graphic from PubMed shows the number of citations by year through the span of 1966 through 2012. Publications peaked in 1985.

Over the last two decades we have achieved clarity due largely to two developments. First was refinement of the original echo criteria which lacked specificity for patients who truly had degenerative change of the valve leaflets or supporting structures. Second was the realization that we had been inappropriately lumping diverse groups of patients under the category of MVP. As our understanding of the condition evolved it became apparent that there were two main groups of patients, one with true MVP characterized by pathologic changes in the valve or supporting structures. The other group, perhaps the more commonly diagnosed, represented a dysautonomia, a hyperadrenergic state. The resulting hyperdynamic state of the heart could give the appearance of prolapse under the old echocardiographic criteria and be associated with clicks and murmurs. The current thinking is that, while there may be some overlap, many patients in this second group do not have valvular pathology.

So what is this hyperadrenergic state? It's a condition that's been recognized for over a century but under different names, as discussed in Wooley's classic paper from1976. These names included DaCosta's syndrome, effort syndrome and, by the early 70s, neurocirculatory asthenia. Over the following decade it became incorporated with MVP only to split off again as our understanding grew. Now many of these patients are labeled as postural orthostatic tachycardia syndrome (POTS).

The current thinking on true MVP is summarized in this paper. It makes the point that while the severity and complications of MVP are variable they depend, in our current understanding, almost entirely on the severity of mitral regurgitation.

H1N1 influenza ARDS versus non-influenza ARDS

There were substantial differences in clinical course in this small study:

Results

Twenty-one patients with H1N1-ARDS and 41 with non-H1N1-ARDS were identified. Gas exchange was more severely impaired in patients with H1N1-ARDS over course of time. Extracorporeal membrane oxygenation was more frequently needed in H1N1-ARDS. Despite significantly prolonged weaning off extracorporeal lung support and intensive care unit stay in H1N1 patients, the proportion of survivors did not differ significantly. Only Sepsis-Related Organ Failure Assessment score could be identified as an independent predictor of extracorporeal lung support.

Conclusions

Clinical course of H1N1-ARDS is substantially different from non-H1N1-ARDS. Affected patients may require extensive therapy including extracorporeal lung support in ARDS referral centers.

Head CT: low yield in evaluating hospitalized medical patients with delirium

Head CT is used almost universally in evaluating such patients. According to the results of this study, the yield is low. More selective use should be considered, though some patients may still benefit. Note that the study patients had no history of trauma and had no focal deficits. Via Hospital Medicine Virtual Journal Club.

Metrics, medical collectivism and the disenfranchisement of physicians

Recent changes in the culture of health care are undermining clinical excellence. Watch this grand rounds presentation from the University of Arizona!

Gallstone pancreatitis

A review on this topic recently appeared in NEJM's Clinical Therapeutics series. Key points below.


ERCP indications

Urgent intervention (within 24 hours) is favored in the presence of cholangitis or early intervention (within 72 hours) if suspicion of common duct obstruction exists (e.g. persistent elevation or worsening of LFTs) without cholangitis. The authors cite relevant guidelines and note that increasingly (and since much of the guideline informing research was done) MRCP and EUS have been used to help inform more precise use of ERCP.


Pathophysiology

The pathophysiology is not completely understood, but septal compression by a distended common bile duct or pancreatic duct obstruction and/or bile reflux due to obstruction of a common channel are suspected mechanisms. An unusually long common channel seen in some patients may explain severity of disease in a minority of patients with gallstone pancreatitis. All that being said it is well known, note the authors, that severe pancreatitis can occur with only microlithiasis.


Practical aspects of ERCP

In the presence of obstruction vitamin K absorption may be impaired putting the patient at risk for impaired coagulation, hence the importance of checking an INR, which should preferably be below 1.5 prior to ERCP. In addition the authors recommend that the platelet count exceed 75K. They recommend antibiotics (a quinolone or cephalosporin) pre-procedure.


Cholecystectomy timing

If a sphincterotomy was done the patient is not likely to have recurrent pancreatitis but remains at high short term risk for other biliary events. Thus the authors recommend, if the patient can be stabilized, cholecystectomy that same admission.

The choosing wisely list in neurology

There's one on the list that got my attention. I see it done pretty often:

Don’t perform imaging of the carotid arteries for simple syncope without other neurologic symptoms.

Occlusive carotid artery disease does not cause fainting but rather causes focal neurologic deficits such as unilateral weakness. Thus, carotid imaging will not identify the cause of the fainting and increases cost. Fainting is a frequent complaint, affecting 40% of people during their lifetime.

Bacteriuria and delirium in the elderly

The elderly patient presents “altered.” Urinalysis is abnormal. Evaluation over. Thinking stops.

But there's this from a recent review of the evidence:

..asymptomatic bacteriuria, by which we mean significant bacteriuria without local urinary tract symptoms or evidence of systemic infection, does not cause delirium and should not be treated with antibiotics. Stated differently, delirium is not a symptom of asymptomatic bacteriuria. The widespread belief that asymptomatic bacteriuria causes delirium is harmful. We propose strategies to mitigate this harm until better evidence is developed.

Available as free full text.

Antibiotic stewardship: Medical Grand Rounds at the University of Arizona

The term antibiotic stewardship has been tossed around and misused to the point of becoming nebulous. But there are some robust, evidence based processes that can be applied as brought out in this Grand Rounds presentation. Here are some of the key issues:


Overuse of antibiotics has consequences and it's not just about money

We're getting a handle on most health care associated infections but Clostridium difficile continues to rise at an alarming rate. There is a strong consensus that antibiotic overuse is driving the increase.


Prior antibiotic approval policies are not recommended

In dealing with really sick patients time is of the essence concerning the initiation of antibiotics. Moreover, the autonomy of the clinician is a key element in evidence based medicine. These objectives would be undermined by prior approval requirements and the grand rounds speakers do not recommend them, favoring other process improvements.


Sometimes it's just a matter of making the right diagnosis

Whether it's pseudocellulitis, pseudopneumonia or pseudoUTI antibiotic stewardship goes out the window if you don't make the right diagnosis. Over diagnosis of several infections is increasingly recognized and drives inappropriate antibiotic use.


Staph aureus bacteremia

There's a checklist of processes necessary for the best chance of a good outcome. These include:

Treating long enough (less is not necessarily more in this case).

Getting repeat blood cultures during treatment. The clock for duration of therapy starts on the day of the first negative culture. Contrast this with gram negative bacteremia, where it's not usually necessary.

Appropriate imaging for deep sites of infection.

Switching to a beta lactam if it turns out to be MSSA.

Considering alternatives to vancomycin for MRSA when the MIC is high even though below the breakpoint.

Appropriately addressing and removing lines.

Getting an ID consult. (Read here).


Candiduria

Candiduria is common but true candida UTI is uncommon. Candiduria does not usually warrant antifungal treatgment and when it does, special considerations apply.

The speaker gave some recommendations and drew from this article. From the article:

Treatment is indicated only for the following groups with asymptomatic candiduria: very low birth weight infants, patients undergoing urinary tract procedures, and neutropenic patients. The vast majority of patients should not be treated.

Patients who have symptoms of urinary tract infection should be treated. The treatment of choice is oral fluconazole. Amphotericin B and fluctyosine are less desirable alternatives, and there is little role for amphotericin B bladder irrigation.

Other antifungal agents, such as voriconazole, posaconazole, and the echinocandins, cannot be recommended for Candida urinary tract infections because very little active drug is found in the urine.

According to the speaker, if amphoterecin is used for candiduria it needs to be plain ampho, as lipid based amphoterecin does not get into the urinary tract. If candiduria is felt to represent candidemia or invasive disease elsewhere in the body, agents such as echinocandins might be justified if the goal is to treat the invasive disease in those areas, realizing that they will not clear the urinary tract.

Again, from the article, the approach to asymptomatic funguria would be as follows:

Repeat clean-catch urine culture to be sure not a contaminant

If cannot obtain clean-catch urine, obtain urine by catheterization

Candida grows on repeat culture: correct predisposing factors (stop antibiotics, remove catheter)

Repeat urine culture after correct predisposing factors

Culture remains positive: obtain ultrasound to look for obstruction

No obstruction: observe and do not treat

Obstruction present: urology consultation

Treat with fluconazole if procedure performed to correct obstruction

When to deescalate

In the case of gram negative infections it is largely a matter of clinical judgment. It can be guided by sensitivity results with the caveat that acquired gram negative resistance is a known issue in certain situations, eg infections with AmpC producing organisms. In the case of empiric MRSA coverage there is a pearl: if initial cultures do not grow staph within 48-72 hours the coverage can be discontinued. Staph aureus grows hardily. It declares itself or, in the words of the speaker, “doesn’t hide out.”


Duration of treatment: less may be more

The notable exception to this is Staph aureus as addressed above. For other types of infections we tend to treat too long. In pneumonia, for example, 5 days is enough for CAP, 8 days for HCAP.

Capnography as a diagnostic tool for pulmonary embolism

Here is an evidence summary of the test characteristics:

Methods

We performed a systematic search from 1990 to 2011, using MEDLINE, EMBASE, and the Cochrane Library, including studies evaluating capnography as a diagnostic tool alone or in conjunction with other tests. After study quality evaluation, we calculated the pooled sensitivity, specificity, likelihood ratios, and diagnostic odds ratios.

Results

We included 14 trials with 2,291 total subjects, with a 20% overall prevalence of pulmonary embolism. The pooled diagnostic accuracy for capnography was sensitivity 0.80 (95% confidence interval [CI] 0.76 to 0.83), specificity 0.49 (95% CI 0.47 to 0.51), negative likelihood ratio 0.32 (95% CI 0.23 to 0.45), positive likelihood ratio 2.43 (95% CI 1.70 to 3.46), and diagnostic odds ratio 10.4 (95% CI 6.33 to 17.1). The area under the summary receiver operating characteristic curve was 0.84. To reach pulmonary embolism posttest probabilities less than 1%, 2%, or 5%, pulmonary embolism prevalence or pretest probability had to be less than 3%, 5%, or 10% respectively. Because of interstudy differences in dead space measurements methodologies, the best cutoff in alveolar dead space or end tidal CO2 conferring the best negative likelihood ratio could not be evaluated.

Conclusion

Pooled data suggest a potential diagnostic role for capnography when the pulmonary embolism pretest probability is 10% or less, perhaps after a positive D-dimer test result.

Cognitive stop points in managing the patient with refractory hypotension

You know the patient. Profoundly hypotensive despite bolus after bolus, cranking the pressors up to ridiculously high doses and adding one on top of another. All too often we go through this sequence in knee jerk fashion but sometimes it helps to stop and think. Sort of a cognitive time out. Scott Weingart in a post at EMCrit calls it the stop point. A lot of what I'll say here is taken from that post. I'll add a few thoughts of my own. Here's a list of things to consider (not necessarily in this order) during your time outs to make your approach more systematic and less knee jerk.

Are your measurements accurate?
Troubleshoot the A line. Check a cuff pressure. Check the other arm.

Have you really given enough volume?

If the patient is on mechanical ventilation is autopeep present?

Is the ionized calcium low (leading to a negative inotropic effect)?

How about a stat echo?
Is there tamponade?
Is the heart hypodnamic (maybe the patient needs dobutamine)?
Is acquired outflow tract obstruction present (which would speak for a switch to a more pure pressor regimen)?

Is the patient bleeding?
Are you missing a big GI bleed because the patient hasn't vomited? Grab another H&H.

How about adrenal insufficiency?
There are several distinct ways this could present itself. First, however unlikely, the patient could have hypopituitarism or classic Addison's disease. A more common situation is the patient who is on chronic corticosteroid therapy and thus has decreased adrenal reserve. Finally, critical illness related corticosteroid insufficiency (CIRCI) is a real entity. The Surviving Sepsis guideline recommendation to address CIRCI is hydrocortisone therapy for patients refractory to volume and pressors.

Could it be abdominal compartment syndrome?
Check a bladder pressure.

Review the Hs and Ts of PEA
---just to be sure you haven't overlooked something.

Bleeding in patients taking target specific oral anticoagulants (TSOAC)

A review was recently published in the American Journal of Emergency Medicine.

Key points:

Effects on coagulation assays:

Readily available coag tests cannot precisely determine the intensity of anticoagulation. However, knowing the effects of the TSOACs on thest tests does help in assessing, qualititatively, “drug on board.”

Dabigatran

The PT has low sensitivity to the activity of dabigatran, and therapeutic plasma concentrations of dabigatran frequently reflect none to only modest elevations in the PT, and therefore, its use is not recommended… Dabigatran increases the aPTT in a curvilinear fashio. This test is rapidly available at most facilities and may be useful as a qualitative assessment of dabigatran's effects… Some clinical experts and guidelines have suggested that, in a patient who is taking dabigatran and experiences bleeding, if the aPTT is normal, then dabigatran is not likely to be present in significant amounts and contributing to the bleeding event [25]. However, a recent investigation demonstrated that depending on the aPTT reagent used, 15% to 35% of patients with a normal aPTT have plasma dabigatran concentrations greater than 100 ng/mL, well within the expected range of trough plasma concentrations on the standard 150 mg twice a day dose. As such, clinicians should use caution when interpreting aPTT results…

At the time of this publication, when faced with a dabigatran patient who is bleeding, the aPTT is the most readily available test; however, a normal test result cannot exclude expected plasma concentrations at standard dosing, although it does rule out supratherapeutic concentrations.

Rivaroxaban

At the time of this publication, when faced with a rivaroxaban patient who is bleeding, the PT is still the most available and useful assay to use; a prolonged PT simply represents that some drug is still present.

Apixaban

Less information is available for apixaban and its effect on a variety of coagulation assays. As a direct Xa inhibitor, apixaban's effect on various laboratory assays is similar to those of rivaroxaban. Prothrombin time is likely the most sensitive and widely available test to detect apixaban activity in plasma, but this test is limited by the high variability..

Attempted reversal in the severely bleeding patient:


Acknowledging the controversy and lack of high level evidence, the following tentative recommendations are made:

For dabigatran:

1. Consider activated charcoal if within 2-3 h of an overdose 2. Dialysis 3. Consider aPCC (Feiba VH 20-40 U/kg) 4. Or 4-PCC (25-50 IU/kg) a5. Or factor VIIa (20 U/kg) may repeat every 2 h

For rivaroxaban:

1. Consider activated charcoal if within 2-3 h of an overdose 2. Consider 4-PCC (25-50 IU/kg) over aPCC (Feiba VH 20-40 U/kg) a3. Or factor VIIa (20 U/kg) may repeat every 2 h

For apixaban:

1. Consider activated charcoal if within 2-3 h of an overdose 2. Consider 4-PCC (25-50 IU/kg) over aPCC (Feiba VH 20-40 U/kg) 3. Or factor VIIa (20 U/kg) may repeat every 2 h

The electronic medical record: from unbridled enthusiasm to sober assessment

The debate over the EMR, and the hype, are winding down. We've resigned to the fact that the EMR is here, and here to stay. It also appears that we've become more open about the unintended consequences. This is illustrated by a recent article in Wall Street Journal Market Watch.

One finding that surprised me a bit was that physician satisfaction with the EMR is declining. Policy makers and the general public like the idea of the EMR in the abstract. So apparently do many doctors, but later on they find that the EMR fails to live up to its promise in the real clinical world. From the article:

While most doctors like the idea of electronic health records, many are much less enamored with the reality. A survey released last year by the American College of Physicians and AmericanEHR Partners, a membership group for medical providers implementing electronic records, found that 34% of doctors using electronic records were “very dissatisfied” with the ability of their systems to decrease workload, up from 19% in 2010. What’s more, 32% of doctors said they couldn't return to their normal level of productivity after rolling out the systems, up from 20% in 2010. And the share of doctors who said they would not recommend electronic records to a colleague increased to 39% from 24% over that same time period.

A separate 2013 study of 30 physician practices by the Rand Corp. found that many doctors reported a dip in overall work satisfaction after implementing the electronic systems. Doctors said the systems increased their administrative workload, took away from time with patients and didn’t always mesh well with their other computer systems.

The article goes on to elaborate further about the decrease in the amount and the quality of time spent with patients. That's because the doctor now has two other jobs besides clinician: transcriptionist (due to the note functionality of the EMR) and secretary (due to CPOE).

Via Clinical Cases and Images.

Coagulation conundrums

Here's a podcast and some notes from an interview with hematologist Dr. Tom Deloughery presented at ercast.

Which antiplatelet agent for secondary stroke prevention?

Here is a review from CCJM.

Cefepime neurotoxicity

Here is an abstract presentation from SHM 2014 to remind us of cefepime neurotoxicity. As noted in the abstract it can occur even with appropriate renal dosing.

Anaphylaxis: definitions, classification, epidemiology

This article is available as free full text. Here are some highlights:

Criteria for diagnosis in emergency settings are listed in the article. The criteria necessary for the diagnosis are fewer if the offending allergen is suspected or known.

Non IgE mediated (e.g. from radiocontrast media) reactions are considered anaphylaxis although an alternate terminology labels them as anaphylactoid.

Among the cutaneous manifestations hives are the most characteristic but flushing, pruritis and angioedema are also listed.

A biphasic response occurs in up to 20% of patients. Observation for 8-12 hours is recommended.

Though antihistamines are the most common first line drugs used that is not a recommended practice. Epinephrine is first line treatment. As explained in the article:

Diphenhydramine is the most common drug given in the ED, even though it takes up to 80 minutes for 50% suppression of histamine flare and only affects the histamine mediator of anaphylaxis.28 Corticosteroids are the second most commonly administered drug in an emergency situation, but they also work slowly. Epinephrine is the treatment of choice as a first response because it acts on multiple receptors and has a maximal pharmacodynamic effect within 10 minutes of intramuscular (IM) administration into the thigh.29, 30 Multiple groups, including the NIAID, the WAO, the International Collaboration in Asthma and Allergy, and the Joint Task Force on Practice Parameters (representing several professional allergy/asthma organizations) state that epinephrine is an essential treatment for anaphylaxis.

Not all anaphylaxis is categorized as anaphylactic shock. The author says epinephrine should be given any time the diagnosis of anaphylaxis is made even in the absence of shock or severe respiratory manifestations.

Concerning the underlying triggers, the article states:

Foods (35%) represent the most common triggers for allergic reactions, followed by drugs and biologics (20%), insect stings (20%), exercise (5%), and vaccines (3%).22 Idiopathic or unknown causes account for approximately one fifth of remaining cases. Although triggers ultimately may be found for most cases of idiopathic anaphylaxis, there does seem to be an intrinsic disorder, currently unidentified, linked to some allergic reactions.

Aortic stenosis

The following Slide Share presentation is a little dated but has some good teaching points. It was created by Richard Whiting, MD, one of cardiology's great teachers.

Aortic Stenosis: A Review for the Internist, Hospitalist, and ... from yashika54

Missed diagnosis in anaphylaxis

It's largely due to non-textbook presentations according to this paper:

..the pathophysiology of anaphylaxis may cause patients to have symptoms that are consistent with anaphylaxis at the start of the reaction but may not be identified as such when seen later in the ED.

In addition, because anaphylaxis has such a wide range of possible symptoms, its differential diagnosis is lengthy and includes conditions such as asthma, vocal cord dysfunction, acute coronary syndrome (ACS), hereditary angioedema, vasovagal episode, and panic attack.5, 16 Atypical presentations make diagnosis particularly challenging.5 For example, acute airway obstruction during an anaphylactic event has sometimes been mislabeled as a “foreign body” in the airway. Vocal cord dysfunction also may present with a sensation of throat swelling and can be challenging to differentiate clinically from anaphylaxis, though fiberoptic laryngoscopy (if available) will determine whether swelling actually is present.

Exercise-induced anaphylaxis has been known to present as syncope and should be considered as part of the differential diagnosis in appropriate circumstances.5 Cardiac manifestations of anaphylaxis may mimic the symptoms of ACS, including arrhythmias in some cases, and this, in particular, takes time and effort to differentiate. Anaphylaxis can be especially low on the list of considerations when symptoms mimic ACS. Other conditions that may mimic anaphylaxis symptoms include flush syndromes (eg, carcinoid or disulfiram reactions), “restaurant syndromes” (eg, reactions to monosodium glutamate, sulfites, or scombroid), autonomic epilepsy, and vasomotor rhinitis. Additionally, anaphylaxis can sometimes cause nonspecific symptoms such as confusion, nausea, and dyspnea, which might be misattributed to more common conditions.