Genetic variants are associated with severe cutaneous reactions to phenytoin

A number of SNPs were identified in this study:

Design, Setting, and Participants Case-control study conducted in 2002-2014 among 105 cases with phenytoin-related severe cutaneous adverse reactions (n=61 Stevens-Johnson syndrome/toxic epidermal necrolysis and n=44 drug reactions with eosinophilia and systemic symptoms), 78 cases with maculopapular exanthema, 130 phenytoin-tolerant control participants, and 3655 population controls from Taiwan, Japan, and Malaysia. A genome-wide association study (GWAS), direct sequencing of the associated loci, and replication analysis were conducted using the samples from Taiwan. The initial GWAS included samples of 60 cases with phenytoin-related severe cutaneous adverse reactions and 412 population controls from Taiwan. The results were validated in (1) 30 cases with severe cutaneous adverse reactions and 130 phenytoin-tolerant controls from Taiwan, (2) 9 patients with Stevens-Johnson syndrome/toxic epidermal necrolysis and 2869 population controls from Japan, and (3) 6 cases and 374 population controls from Malaysia.

Main Outcomes and Measures Specific genetic factors associated with phenytoin-related severe cutaneous adverse reactions.

Results The GWAS discovered a cluster of 16 single-nucleotide polymorphisms in CYP2C genes at 10q23.33 that reached genome-wide significance. Direct sequencing of CYP2C identified missense variant rs1057910 (CYP2C9*3) that showed significant association with phenytoin-related severe cutaneous adverse reactions (odds ratio, 12; 95% CI, 6.6-20; P=1.1 × 10−17). The statistically significant association between CYP2C9*3 and phenytoin-related severe cutaneous adverse reactions was observed in additional samples from Taiwan, Japan, and Malaysia. A meta-analysis using the data from the 3 populations showed an overall odds ratio of 11 (95% CI, 6.2-18; z=8.58; P less than .00001) for CYP2C9*3 association with phenytoin-related severe cutaneous adverse reactions. Delayed clearance of plasma phenytoin was detected in patients with severe cutaneous adverse reactions, especially CYP2C9*3 carriers, providing a functional link of the associated variants to the disease.

Fruit and vegetable servings and mortality

From a recent BMJ meta-analysis:

Results Sixteen prospective cohort studies were eligible in this meta-analysis. During follow-up periods ranging from 4.6 to 26 years there were 56 423 deaths (11 512 from cardiovascular disease and 16 817 from cancer) among 833 234 participants. Higher consumption of fruit and vegetables was significantly associated with a lower risk of all cause mortality. Pooled hazard ratios of all cause mortality were 0.95 (95% confidence interval 0.92 to 0.98) for an increment of one serving a day of fruit and vegetables (P=0.001), 0.94 (0.90 to 0.98) for fruit (P=0.002), and 0.95 (0.92 to 0.99) for vegetables (P=0.006). There was a threshold around five servings of fruit and vegetables a day, after which the risk of all cause mortality did not reduce further. A significant inverse association was observed for cardiovascular mortality (hazard ratio for each additional serving a day of fruit and vegetables 0.96, 95% confidence interval 0.92 to 0.99), while higher consumption of fruit and vegetables was not appreciably associated with risk of cancer mortality.

It looks like the five serving rule still holds!

Volume controlled versus pressure controlled ventilation in ARDS

Given that treatment needs to be individualized, there is insufficient evidence to tell whether one is better than the other across the board according to a Cochrane review.

Via Hospital Medicine Virtual Journal Club.

Relationships between exercise, hunger and energy balance

Interesting article in the American Journal of Lifestyle Medicine:

High-intensity exercise causes a short-term suppression of hunger of approximately 15 to 60 minutes. Although there is evidence for compensatory food consumption, it usually does not make up for the energy deficit created by exercise. The exception occurs when individuals consume or reward themselves with energy-dense foods or drink. Because people tend to eat the same volume of food each day, on days when they exercise, they will remain in an energy deficit. However, on sedentary days, a positive energy balance is likely if caloric restriction is not imposed, which could result in weight gain. Caloric restriction alone leads to loss of lean body mass, while the inclusion of exercise with an energy deficit helps conserve lean tissue.

What’s new in the management of acute severe asthma?

From a recently published update:

Recent findings: β2-agonist heliox-driven nebulization significantly increased by 17% [95% confidence interval (CI) 5.2–29.4] peak expiratory flow, and decreased the rate of hospital admissions (risk ratio 0.77, 95% CI 0.62–0.98), compared with oxygen-driven nebulization. Other findings indicate that there is no robust evidence to support the use of intravenous or nebulized magnesium sulphate in adults with severe acute asthma, and that levalbuterol was not superior to albuterol regarding efficacy and safety in individuals with acute asthma. Finally, hyperlactatemia developed during the first hours of acute asthma treatment has a high prevalence, is related with the use of β2-agonists and had no clinical consequences.

Exercise to improve cognitive function

This review focuses on the cognitive impairment associated with heart failure. Neurophysiologic mechanisms are discussed.

When hypersensitivity pneumonitis enters the fibrotic stage

---it can mimic many other diffuse ILDs as outlined in this review.

Via Hospital Medicine Virtual Journal Club.

Whole bowel irrigation for overdose patients

A recent literature review found that it may facilitate removal in selected patients but is not supported by convincing evidence of improved outcomes.

Exercise as treatment for depression

From a JAMAClinical Evidence Synopsis:

Bottom Line Exercise is associated with a greater reduction in depression symptoms compared with no treatment, placebo, or active control interventions, such as relaxation or meditation. However, analysis of high-quality studies alone suggests only small benefits.

Endurance exercise and atrial fibrillation risk

From a recent review:

Endurance exercise, despite a plethora of proven health benefits, is increasingly recognized as a potential cause of lone atrial fibrillation. Moderate exercise reduces all-cause mortality and protects against developing atrial fibrillation. However, more intense exercise regimes confer modest incremental health benefits, induce cardiac remodelling and negate some of the cardiovascular benefits of exercise. The implications of endurance exercise and athletic heart are becoming increasingly relevant as the popularity of endurance exercise has increased 20-fold within a generation.

Recent findings: An apparent dose–response relationship exists between endurance exercise and left atrial dilatation. Repeated strenuous endurance exercise overloads atria, resulting in stretch-induced ‘microtears’, inflammation and endocardial scarring. Although these findings are observational in humans, similar mechanisms have recently been confirmed in animal models suggesting causation.

The toxic alcohol work up

A case presentation and some tips from Emergency Physicians Monthly.

Is therapeutic hypothermia associated with more bleeding after cardiac arrest?

Not according to this systematicreview and meta-analysis.

Toxic epidermal necrolysis

A brief review in the American Journal of Medicine. Free full text.

TB or not TB? Tips for the evaluation of hospitalized patients

Here is a recent update from CCJM.

Adult cases of group A strep meningitis

From a recent report:

RESULTS:

GAS was identified in 26 of 1322 patients with community-acquired bacterial meningitis (2%); 9 cases (35%) occurred in the first four months of 2013. GAS meningitis was often preceded by otitis or sinusitis (24 of 26 [92%]) and a high proportion of patients developed complications during clinical course (19 of 26 [73%]). Subdural empyema occurred in 8 of 26 patients (35%). Nine patients underwent mastoidectomy and in 5 patients neurosurgical evacuation of the subdural empyema was performed. Five of 26 patients (19%) died and 11 of 21 surviving patient had neurologic sequelae (52%). Infection with the emm1 and cc28 GAS genotype was associated with subdural empyema (both 4 of 6 [67%] vs. 2 of 14 [14%]; P = 0.037).

CONCLUSIONS:

GAS meningitis is an uncommon but severe disease. Patients are at risk for empyema, which is associated with infection with the emm1 and cc28 genotype.

Via Hospital Medicine VirtualJournal Club.

Is statin myalgia associated with decreased muscle strength?

Not in this study.

Carbamazepine poisoning

Here is a systematic review with a focus on extracorporeal removal. From the review:

The workgroup concluded that carbamazepine is moderately dialyzable and made the following recommendations: ECTR is suggested in severe carbamazepine poisoning (2D). ECTR is recommended if multiple seizures occur and are refractory to treatment (1D), or if life-threatening dysrhythmias occur (1D). ECTR is suggested if prolonged coma or respiratory depression requiring mechanical ventilation are present (2D) or if significant toxicity persists, particularly when carbamazepine concentrations rise or remain elevated, despite using multiple-dose activated charcoal (MDAC) and supportive measures (2D). ECTR should be continued until clinical improvement is apparent (1D) or the serum carbamazepine concentration is below 10 mg/L (42 the μ in μmol/L looks weird.) (2D). Intermittent hemodialysis is the preferred ECTR (1D), but both intermittent hemoperfusion (1D) or continuous renal replacement therapies (3D) are alternatives if hemodialysis is not available. MDAC therapy should be continued during ECTR (1D). Conclusion. Despite the low quality of the available clinical evidence and the high protein binding capacity of carbamazepine, the workgroup suggested extracorporeal removal in cases of severe carbamazepine poisoning.

Tylenol and benadryl before transfusions

Very commonly done but not evidence based in the least. If this is not on someone’s choosing wisely list it should be.

Sleep deprivation caused endothelial dysfunction

---in this small study.

Tigecycline activity against Clostridium difficile

New study here.

Via Hospital Medicine Virtual Journal Club.

Skin and soft tissue infections: what the hospitalist needs to know

Here's a nice free full text review form Mayo Clinic Proceedings.

Non invasive ventilation in a variety of settings: an update

From a recent evidence summary:

Recent findings: The efficacy of NIV is variable depending on the cause of the episode of ARF. In community-acquired pneumonia, NIV is often associated with poor response, with better response in patients with preexisting cardiac or respiratory disease. In patients with pandemic influenza H1N1 and severe ARF, NIV has been associated with high failure rates but relatively favorable mortality. In acute respiratory distress syndrome, NIV should be used very cautiously and restricted to patients with mild–moderate acute respiratory distress syndrome without shock or metabolic acidosis due to the high failure rate observed in several reports. Despite limited evidence, NIV may improve the outcomes of patients with chest trauma and severe ARF. In postoperative ARF, both continuous positive airway pressure and NIV are effective to improve clinical outcomes, particularly in those with abdominal, cardiac, and thoracic surgery.

Summary: Although patients with severe hypoxemic ARF are, in general, less likely to be intubated when NIV is used, the efficacy is different among these heterogeneous populations. Therefore, NIV is not routinely recommended in all patients with severe hypoxemic ARF.

Sibbitt's Diagonal Line Lead Rule for electrocardiography

A simple, easy to remember rule for basic interpretation of the electrocardiogram developed years ago was validated in this study. It's a memory trick to help apply the basic rules of electorcardiography to the detection of myocardial disease. It does not apply to patients with wide QRS other than RBBB and it ignores many important nuances of interpretation.

Stanford Septris

Test your sepsis management skills with this free on line game.

Bob Wachter on the American Board of Internal Medicine

The deafening silence from Bob Wachter on the concerns swirling around the ABIM was finally broken in a recent post titled The ABIM Controversy: Where the Critics are Right, Where They’re Wrong, and Why I Feel the Need to Speak Out. Well, I have to take issue with Bob right off the bat. There is no controversy about what's happened at the ABIM. The discussion has been overwhelmingly one sided. No one (well, at least not until Bob's post) has offered much of a defense or counter argument; not that people haven't been given the chance.

But indeed he did need to speak out. Though Bob has been a booster of the ABIM we look to him to provide healthy skepticism. After all he describes his blog as a series of “Lively and iconoclastic ruminations..” But his post is hardly iconoclastic concerning the ABIM. From the post:

This is not to say that the Board has made perfect choices – it hasn’t, and ABIM’s CEO, Dr. Rich Baron, courageously admitted as much in a February statement of apology, in which he announced the suspension of certain parts of the program. But these were mistakes born of trying to do good but challenging work for the right reason: to ensure to our patients that their physicians are competent. Painting the organization – and particularly Rich, one of the finest people I know – as corrupt and nefarious is wrong.

I haven't seen much in the way of personal attacks on Dr. Baron and will accept Bob's statement that he's a great guy. The focus of the outrage has been, as it should be, about where the ABIM has gone wrong and the consequences to practicing physicians and, ultimately, patients.

There's a lot to unpack from Bob's next paragraph:

Here’s what’s at stake: we physicians are granted an extraordinary amount of autonomy by the public and the government.

An extraordinary amount of autonomy? Really Bob? Decades ago maybe but not the last time I checked. He goes on:

We ask people to disrobe in our presence; we prescribe medications that can kill; we perform procedures that would be labeled as assault if done by the non-credentialed. If we prove ourselves incapable of self-governance, we are violating this trust, and society will – and should – step into the breach with standards and regulations that will be more onerous, more politically driven, and less informed by science. That is the road we may be headed down. It is why this fight matters.

Well, society has already done just that. And apparently Bob has no problem with some of the baggage imposed on medicine by politically driven initiatives not well informed by science, as evidenced, for example, by his repeated praise of the IOM's egregious spin on patient safety (you know, the one about how medical errors result in patient deaths equivalent to a jumbo jet crash a day). I, for one, do have a problem with such grandstanding and have seen more negative consequences from the IOM report than benefits, but I digress. What's really telling in that paragraph is the strongly implied premise that resuscitation of the Board will help protect patients against an out of control, incompetent medical profession. That's apparently why, in his view, this particular fight matters. There's no evidence, of course, that the MOC program helps patients at all. To be clear, I wouldn't demand evidence were it not for all the negative consequences. After all, there is not, and probably never will be, good evidence concerning regular CME. But the negative consequences of the MOC program, as it has recently existed, abound.

Much of the rest of Bob's post was more thoughtful and nuanced, though I partially disagree with his ideas on the demonstration of competence. His attempt to offer a defense, point by point, against the various accusations was unconvincing to me, though it is clear Bob believes passionately in the Board.

He makes the point that regulation should come from within the profession, which was part of the Board's original mission, with which I heartily agree (that's why I am a tad concerned that he said they are about to add non-physician members to their governance structure). And I can't make an argument against doctors having to take a test now and again (though I remain displeased that the Board recently told grandfathered diplomats, in effect, concerning that requirement, Sorry, we lied).

Bob points out changes that are being made to the process. I, like many physicians in the community, am skeptical as to whether this will be enough. I am even skeptical as to whether trust can be restored at all. The reputation of the ABIM is on a downward trajectory like a freight train rolling down hill. It is largely, though probably not entirely, of their own making. I find this unfortunate because I used to have a good feeling about the Board. Bob concludes with a valid concern. If the Board meets its demise something worse may emerge to fill a perceived vacuum.

The selective outrage of the conscience of medicine now focuses on Medscape

When Bob Doherty, representing the American College of Physicians as the conscience of medicine, was called out for his silence on the serious ethical concerns surrounding the American Board of Internal Medicine, he said:

..it is not within my area of expertise or responsibilities for at ACP. I am responsible for the ACP's governmental affairs efforts (federal and state legislation, regulations by CMS and other regulatory agencies, payment policies by third party payers, the Affordable Care Act, etc), and while I am generally aware of the controversies relating to ABIM, I as a matter of sound practice and policy do not express my opinion, or purport to speak for ACP, on other issues that fall outside my direct governmental affairs responsibilities.

But just a couple of weeks later Doherty seems to have departed form said practice and policy in  this scathing criticism of Medscape's article on the best and worst places to practice in the United States:

I would think that when physicians decide where to set up practice, there are things that they would want to think about other than how much money they’ll make. Yet if one reads Medscape’s current list of the best and worst places to practice, it would appear that money trumps everything else (although Medscape said it also considered factors like “cultural attractions”). What Medscape apparently did not consider at all are factors like the percent of the population that is uninsured, mortality and morbidity rates, rates of chronic disease, per capita healthcare spending, that is, anything having to do with patients.

He goes on to talk around this issue and gives examples of other ways Medscape might have ranked states, but never makes a cogent argument. How, exactly, might a different approach to the ranking of states have helped patients? Doherty never explains. In fact, as he implies, the Medscape article, if anything, points doctors to states where patients are underserved. How could the article better serve patients than to direct doctors where they're needed most?

The entire post seemed incoherent to me until I realized the premise behind Doherty's argument which finally became apparent in this paragraph from the post:

No, my beef is only with Medscape, and the sources (recruiters, interviews, surveys) they used that looked mostly at the economics of practice, not the environment affecting the care of patients. As a result, there is an inherently conservative bias built into Medscape’s analysis, because by emphasizing higher physician earnings, lower cost of living, fewer malpractice suits and lower taxes over health outcomes and the percentage uninsured, its rates more favorably the states that are hostile to government programs to help cover people and reduce healthcare disparities, and less favorably the states that have more activist governmental programs to reduce the ranks of the uninsured and healthcare disparities, often requiring higher taxes to pay for such programs.

According to that premise things that promote the interests of physicians have to be contrary to the interests of patients and, as a corollary, so do things that deviate from the political views of the ACP which is, after all, the new conscience of medicine.

Neurally adjusted mechanical ventilation

Like many other techniques in critical care pulmonology, it’s promising but not yet supported by high level data.

Pharmacologic agents to prevent stress cardiomyopathy recurrence: do they work?

Here are the findings of a recent meta-analysis:

Methods

After a PubMed search, we conducted a meta-analysis of available studies (clinical nonrandomized registries) on efficacy of drug therapy in preventing recurrence of TTC.

Results

A total of 23 (4.5%) TTC recurrences occurred in the 511 patients included in the analysis. Seven studies on the effects of β-blockers on prevention of TTC recurrence were evaluated; the odds ratio (OR) was 0.44 and the 95% confidence interval (CI) was 0.15-1.31. In 5 studies on the effects of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, the OR was 0.42 and the 95% CI was 0.08-2.36; in 3 studies on statins, the OR was 0.74 and the 95% CI was 0.07-7.3; and in 4 studies on aspirin, the OR was 0.33 with a 95% CI of 0.05-2.17 (P value not significant in all cases).

Conclusions

A meta-analysis of the efficacy of different medications through the clinical TTC registries available showed no clinical evidence for a standard drug treatment in the chronic management of TTC. β-Blockers, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, statins, and aspirin do not seem to significantly reduce recurrences of TTC. Randomized, adequately powered studies are needed to further assess this issue.

Only low level data were available for this meta-analysis and better studies are needed.

Nonleg venous thrombosis in critically ill patients

From a recent systematic review:

Results Of 3746 trial patients, 84 (2.2%) developed 1 or more non–leg vein thromboses (superficial or deep, proximal or distal). Thromboses were more commonly incident (n = 75 [2.0%]) than prevalent (n = 9 [0.2%]) (P less than .001) and more often deep (n = 67 [1.8%]) than superficial (n = 31 [0.8%]) (P < .001). Cancer was the only independent predictor of incident NLDVT (hazard ratio [HR], 2.22; 95% CI, 1.06-4.65). After adjusting for Acute Physiology and Chronic Health Evaluation (APACHE) II scores, personal or family history of venous thromboembolism, body mass index, vasopressor use, type of thromboprophylaxis, and presence of leg DVT, NLDVTs were associated with an increased risk of PE (HR, 11.83; 95% CI, 4.80-29.18). Nonleg DVTs were not associated with ICU mortality (HR, 1.09; 95% CI, 0.62-1.92) in a model adjusting for age, APACHE II, vasopressor use, mechanical ventilation, renal replacement therapy, and platelet count below 50 × 109/L.

Conclusions and Relevance Despite universal heparin thromboprophylaxis, nonleg thromboses are found in 2.2% of medical-surgical critically ill patients, primarily in deep veins and proximal veins. Patients who have a malignant condition may have a significantly higher risk of developing NLDVT, and patients with NLDVT, compared with those without, appeared to be at higher risk of PE but not higher risk of death.

Nasal high flow oxygen post extubation

From the blue journal:

OBJECTIVES:

To compare the effects of the Venturi mask and the nasal high-flow (NHF) therapy on PaO2/FiO2SET ratio after extubation. Secondary endpoints were to assess effects on patient discomfort, adverse events, and clinical outcomes.

METHODS:

Randomized, controlled, open-label trial on 105 patients with a PaO2/FiO2 ratio less than or equal to 300 immediately before extubation. The Venturi mask (n = 52) or NHF (n = 53) were applied for 48 hours postextubation.

MEASUREMENTS AND MAIN RESULTS:

PaO2/FiO2SET, patient discomfort caused by the interface and by symptoms of airways dryness (on a 10-point numerical rating scale), interface displacements, oxygen desaturations, need for ventilator support, and reintubation were assessed up to 48 hours after extubation. From the 24th hour, PaO2/FiO2SET was higher with the NHF (287 ± 74 vs. 247 ± 81 at 24 h; P = 0.03). Discomfort related both to the interface and to airways dryness was better with NHF (respectively, 2.6 ± 2.2 vs. 5.1 ± 3.3 at 24 h, P = 0.006; 2.2 ± 1.8 vs. 3.7 ± 2.4 at 24 h, P = 0.002). Fewer patients had interface displacements (32% vs. 56%; P = 0.01), oxygen desaturations (40% vs. 75%; P less than 0.001), required reintubation (4% vs. 21%; P = 0.01), or any form of ventilator support (7% vs. 35%; P less than 0.001) in the NHF group.

CONCLUSIONS:

Compared with the Venturi mask, NHF results in better oxygenation for the same set FiO2 after extubation. Use of NHF is associated with better comfort, fewer desaturations and interface displacements, and a lower reintubation rate. Clinical trial registered with www.clinicaltrials.gov (NCT 01575353).

Via Intensive care medicine worth knowing.

Non-alcoholic fatty liver disease review

Here's a great review in BMJ.

From the article:

Non-alcoholic fatty liver disease (NAFLD) represents a spectrum of liver disease with key stages consisting of hepatic steatosis (NAFL), steatohepatitis (NASH), fibrosis, and eventual cirrhosis

NAFLD affects more than 20% of populations worldwide and most patients with type 2 diabetes mellitus

The risk of progressive liver disease in the earliest stage of NAFLD, hepatic steatosis, is low but patients with NASH are at far higher risk...

Owing to the slow progression of NAFLD, randomised clinical trials have been unable to identify drugs that conclusively reduce progression to cirrhosis, but sustained weight loss has been shown to improve liver function test results and liver histology and thus lifestyle improvement remains the key intervention

There is no convincing evidence that NAFLD independently increases a patient’s cardiovascular risk but there is also no reason to withhold statins in patients with NAFLD who are at high cardiovascular risk unless transaminase levels are more than three times the upper limit of normal.

Some of my previous posts on this topic:

[1] [2] [3]

Resting heart rage correlates with incident heart failure

---and other nasty cardiovascular indicators in this study.

What is reflex anuria?

Apparently it's an old concept not considered very often today. From a recent article:

In summary, RA is a cessation of urine production caused by stimuli on kidney, ureter or other organs, through a mechanism of reflex spasm of intrarenal arterioles or ureters, leading to acute renal failure. It is a functional rather than parenchymal disease.

Via Hospital Medicine VirtualJournal Club.

How do the interpretation rules for ST segment proportionality, concordance and discordance apply to right bundle branch block in patients with chest pain?

Here is a case with several teaching points from Dr. Smith's ECG blog.

Proton pump inhibitors increase the risk of AKI

See here. This is an under appreciated association and is driven by acute interstitial nephritis due to PPI administration.

Via The Poison Review.

Temperature management post cardiac arrest: therapeutic hypothermia or strict normothermia?

Recent findings have raised this question, which is examined in a recent Circulation article:

Current guidelines from the American Heart Association recommend use of therapeutic hypothermia (TH) after witnessed cardiac arrest (CA) to mitigate posthypoxic injuries. This is based on results of 3 randomized, controlled trials (RCTs) enrolling 385 patients, 43 before–after studies enrolling 10 442 patients, and supporting evidence from the field of neonatal asphyxia where 7 RCTs enrolling 1329 patients also demonstrated neuroprotective effects of hypothermia. However, this has been called into question by a recently published RCT enrolling 939 patients, which found no benefit of cooling to 33°C compared with maintaining 36°C. In this article we review the literature, with extra attention for strengths and weaknesses of the recently published RCT. In view of potential weaknesses in the new study (including a possibility of selection bias, long delays before initiation of cooling, a time to target temperature of 10 hours, and a rapid rewarming rate), we conclude that there are sufficient grounds to continue using hypothermia in most patients with witnessed ventricular fibrillation (VF)/ventricular tachycardia (VT) arrest, pending results of further studies which should examine multiple temperature levels (32–36°C) and multiple treatment durations (24–72 hours).

Tramadol has not lived up to its promise

Not only is it a weak analgesic but there are under appreciated risks including hypoglycemia, seizures and serotonin syndrome.

Via Emergency Medicine PharmD.

When the left main coronary artery is the culprit in acute myocardial ischemia

When you think of acute left main coronary syndrome the electrocardiographic picture that probably comes to mind is that of multi-lead ST depression with elevation in aVR. At least that's what I tend to think and have blogged the concept many times. It's true but it's not the whole story. It applies to left main ischemia but what about occlusion or near total occlusion of the left main? Well, that's a different pattern altogether and not often seen. How many of those folks make it to the hospital, after all? It's a unique and frightening combination of electrocardiographic features with a few variations an the theme. Here's a post at EMS 12 Lead with some examples and links.

Point of care echo to evaluate patients with non shockable rhythm cardiac arrest

From a recent paper in Resuscitation:

Methods

This prospective and observational cohort study evaluated ICU patients with CPA in asystole or pulseless electrical activity (PEA). Intensivists performed TTE during intervals of up to 10 s as established in the treatment protocol. Myocardial contractility was defined as intrinsic movement of the myocardium coordinated with cardiac valve movement. PEA without contractility was classified as electromechanical dissociation (EMD), and with contractility as pseudo-EMD. The images, the rates of return of spontaneous circulation (ROSC) and the survival upon hospital discharge and after 180 days were evaluated.

Results

A total of 49 patients were included. Image quality was considered adequate in all cases and contributed to the diagnosis of CPA in 51.0% of the patients. Of the 49 patients included, 17 (34.7%) were in asystole and 32 (65.3%) in PEA, among which 5 (10.2%) were in EMD and 27 (55.1%) in pseudo-EMD. The rates of ROSC were 70.4% for those in pseudo-EMD, 20.0% for those in EMD, and 23.5% for those in asystole. Survival upon hospital discharge and after 180 days occurred only in patients in pseudo-EMD (22.2% and 14.8%, respectively).

Conclusions

TTE conducted during cardiopulmonary resuscitation in ICU patients can be performed without interfering with care protocols and can contribute to the differential diagnosis of CPA and to the identification of a subgroup of patients with better prognosis.

Via Hospital Medicine VirtualJournal Club.

Comparison of temperature targets in patients with non shockable rhythm cardiac arrest

From a recent study:

Purpose

Despite a lack of randomized trials in comatose survivors of out-of-hospital cardiac arrest (OHCA) with an initial non-shockable rhythm (NSR), guidelines recommend induced hypothermia to be considered in these patients. We assessed the effect on outcome of two levels of induced hypothermia in comatose patient resuscitated from NSR.

Methods

Hundred and seventy-eight patients out of 950 in the TTM trial with an initial NSR were randomly assigned to targeted temperature management at either 33 °C (TTM33, n = 96) or 36 °C (TTM36, n = 82). We assessed mortality, neurologic function (Cerebral Performance Score (CPC) and modified Rankin Scale (mRS)), and organ dysfunction (Sequential Organ Failure Assessment (SOFA) score).

Results

Patients with NSR were older, had longer time to ROSC, less frequently had bystander CPR and had higher lactate levels at admission compared to patients with shockable rhythm, p less than  0.001 for all. Mortality in patients with NSR was 84% in both temperature groups (unadjusted HR 0.92, adjusted HR 0.75; 95% CI 0.53–1.08, p = 0.12). In the TTM33 group 3% survived with poor neurological outcome (CPC 3–4, mRS 4–5), compared to 2% in the TTM36 group (adjusted OR 0.67; 95% CI 0.08–4.73, p = 0.69 for both). Thirteen percent in the TTM33 group and 15% in the TTM36 group had good neurologic outcome (CPC 1–2, mRS 0–3, OR 1.5, CI 0.21–12.5, p = 0.69). The SOFA-score did not differ between temperature groups.

Conclusion

Comatose patients after OHCA with initial NSR continue to have a poor prognosis. We found no effect of targeted temperature management at 33 °C compared to 36 °C in these patients.

STEMI: now you see it, now you don't!

The STEMI versus non-STEMI distinction is unreliable in emergency decision making in patients with ACS for several reasons I have posted before. This study illustrates yet another reason:

Objective. To determine the prevalence and significance of ST-segment elevation resolution between prehospital and first hospital ECG...Results. We reviewed 24,197 prehospital ECGs and identified 293 cases of prehospital STEMI. Complete hospital and prehospital records were available for 83 cases (28%)...STR occurred in 18 cases (22%, CI 14–32%). There were no differences between STR and non-STR cases in prehospital vital signs or treatments. 95% of patients underwent cardiac catheterization with a mean door-to-needle time of 57 minutes (interquartile range 43–71). Comparing STR and non-STR cases, significant lesions (greater than or equal to 50%) were found in 94 and 97% of patients (p = 0.6), and subtotal or total lesions (greater than or equal to 95%) were found in 63 and 85% (p = 0.1), respectively. Conclusions. We found that ST-segment resolution occurred prior to catheterization in 1 of 5 patients with prehospital STEMI, emphasizing the necessity of prehospital ECG in risk stratification of patients with suspected coronary disease. Coronary lesions and intervention rates did not differ between STR and non-STR, suggesting that catheterization is warranted even when STEMI criteria are no longer met in-hospital.

Acute coronary syndromes, as we've known ever since studies involving coronary angioscopy in the 1980s, are dynamic states of thrombus, lysis and reformation. What presents as NSTEMI to the ER may have been a STEMI only moments prior.

Via Life in the Fast Lane.

Obesity and CKD: a newly emerging association

From a recent review:

Recent findings: It is well established that excessive caloric intake contributes to organ injury. The associated increased adiposity initiates a cascade of cellular events that leads to progressive obesity-associated diseases such as kidney disease. Recent evidence has indicated that adipose tissue produces bioactive substances that contribute to obesity-related kidney disease, altering the renal function and structure. In parallel, proinflammatory processes within the adipose tissue can also lead to pathophysiological changes in the kidney during the obese state.

Summary: Despite considerable efforts to better characterize the pathophysiology of obesity-related metabolic disease, there are still a lack of efficient therapeutic strategies. New strategies focused on regulating adipose function with respect to AMP-activated protein kinase activation, NADPH oxidase function, and TGF-β may contribute to reducing adipose inflammation that may also provide renoprotection.

TIA: the essentials

A brief review in the American Journal of Medicine. Free full text.

Statins in the prevention of contrast induced acute kidney injury

Earlier I linked a couple of studies that showed promise. Now here's a new meta-analysis that shows benefit:

A systematic review and meta-analysis was performed including randomized controlled trials of short-term high-dose statins (compared with either low-dose statin or placebo) for CIAKI prevention in patients undergoing coronary angiography. Study-specific odds ratios (ORs) were calculated, and between-study heterogeneity was assessed using the I2 statistic. We used a random-effects model meta-analysis to pool the OR. Twelve RCTs, including 5,564 patients, were included. CIAKI occurred in 94 of 2,769 patients (3.4%) pretreated with high-dose statins and 213 of 2,795 patients (7.6%) in the low-dose or no-statin group (OR 0.43, 95% confidence interval [CI] 0.33 to 0.55, I2 = 19%, p less than 0.001). Subgroup analysis showed that the occurrence of CIAKI did not differ in patients with diabetes (OR 0.60, 95% CI 0.43 to 0.85, I2 = 0%, p = 0.004) or in patients with documented renal insufficiency (creatinine clearance les than 60 ml/min/m2; OR 0.66, 95% CI 0.45 to 0.96, I2 = 0%, p = 0.03). In conclusion, pretreatment with high-dose statins, compared with low-dose statins or placebo, in patients undergoing coronary angiography reduces the incidence of CIAKI. This benefit was seen irrespective of the presence of diabetes and chronic kidney disease. Future studies should identify optimum dosing protocols for each statin.

Statin-associated autoimmune necrotizing myopathy

This recently emerging entity is the topic of a review in the Cleveland Clinic Journal of Medicine.

Some points of interest:

The principal cause is autoantibody to HMG coenzyme A reductase, the site of action of statins.

Unlike other statin associated myopathies it does not resolve with stopping the drug and requires immunosuppression.

In the spectrum of statin associated myopathy three principal entities have emerged: 1) simple myalgias without CK elevation; 2) myositis with elevated CK which resolves on drug discontinuation; and 3) the autoimmune entity just described.

Another example of a “non-STEMI” that needed to go to the cath lab

Via Dr. Smith's ECG blog.

Increased T wave amplitude was the only finding on the initial ECG and highlights the rule of proportionality.

Statins for the prevention of contrast associated AKI

Here's a systematic review that provides more evidence of benefit.