Wednesday, May 04, 2016

Neurocritical care of patients with cerebral vein thrombosis

From a review:

Recent findings: The mainstay of treatment in CVT is systemic anticoagulation even in the setting of intracerebral hemorrhage. Nonrandomized studies and case series suggest that endovascular therapy in CVT is relatively safe, and can improve outcomes in the small subset of CVT patients with neurologic deterioration despite anticoagulation.

Summary: Despite a generally favorable prognosis, one in four patients with CVT develop neurological deterioration in the acute phase. Predisposing factors include a neurological deficit or seizures at onset, deep venous thrombosis, venous infarctions, or intracranial hemorrhage with mass effect and an underlying thrombophilia. More randomized trials are needed to compare the benefits of anticoagulation and endovascular therapy.

Tuesday, May 03, 2016

Will the computer someday replace the physician as diagnostician?

With the growing enthusiasm over Watson and other forms of high technology decision support has come the nutty idea that computers may eventually surpass clinicians in the diagnostic process. Taking that idea to its full extent, in such a world the role of doctors would be restricted. The need for clinicians would be gone though we would still need providers to navigate the EMR and coordinate care (essentially secretarial duties), do procedures and maintain a “human touch” in healthcare through education, counselling and other types of social interaction. Could this ever come to pass?

It has already been the subject of an experiment, the conditions of which gave the idea the best possible chance to work in two ways. First, the experiment was conducted in what is arguably one of the most mechanistic and formulaic areas of diagnostic medicine. Second, it's been going on, repeated time and time again with generation after generation of software “improvement,” for decades. I am referring, of course, to computerized interpretation of electrocardiograms. Despite being given every conceivable chance it has failed. From a recent review on the topic:

The use of digital computers for ECG processing was pioneered in the early 1960s by two immigrants to the US, Hubert Pipberger, who initiated a collaborative VA project to collect an ECG-independent Frank lead data base, and Cesar Caceres at NIH who selected for his ECAN program standard 12-lead ECGs processed as single leads. Ray Bonner in the early 1970s placed his IBM 5880 program in a cart to print ECGs with interpretation, and computer-ECG programs were developed by Telemed, Marquette, HP-Philips and Mortara. The “Common Standards for quantitative Electrocardiography (CSE)” directed by Jos Willems evaluated nine ECG programs and eight cardiologists in clinically-defined categories. The total accuracy by a representative “average” cardiologist (75.5%) was 5.8% higher than that of the average program (69.7, p less than 0.001).

Those results don't say much for the cardiologists either but that's a topic for another discussion.  In a green journal editorial in 2012 Dr. Joseph Alpert cited additional research from the 1970s:

In 1976, I was involved in one of the earliest evaluations of 5 competing computer programs that interpreted electrocardiograms (ECGs).1 At that time, computer interpretation of ECGs was just beginning to make its way into hospitals in the United States and abroad. Dr Arthur Hagan and I evaluated the accuracy of the different computer interpretations compared with our own experienced analysis of more than 100 ECGs with various well defined abnormalities.

The results were illuminating. The computer interpretations were often wrong, particularly with respect to arrhythmia identification. Furthermore, the different computer ECG readings from the 5 programs often were surprisingly different. The conclusion of this early study was that computers were not as accurate in reading ECGs when compared with experienced cardiologists. We suggested that all computer-read ECGs should be over-read by an experienced physician. In the end, this study showed that the overall accuracy score for the computer ECG programs was approximately 80%, and as already noted, the computer was particularly poor on arrhythmia interpretation.

Of note, Alpert cites no improvement in over 30 years. Again from the editorial:

This is still the situation today with all ECGs with computer diagnoses over-read by an experienced physician, usually a cardiologist. Of note, when I am the over-reading cardiologist in our hospital, I still find that the computer reading of the ECG is incorrect approximately 20% of the time.

Because we often rely on the ECG to supply the critical data to guide decision making in very ill patients, this is unacceptable. And it hasn't improved in decades. These numbers were derived using artificial conventions. The results would certainly be even worse against more nuanced standards based on subtle ECG patterns.

Alpert suggests the reason for such poor results:

What is the reason that the most sophisticated computer ECG interpreting software makes so many mistakes? I think the answer lies in the remarkable and extensive capacity of the human brain to recognize visual patterns. This capacity is the reason that a person with minimal prior instruction can recognize a van Gogh painting without looking at the accompanying label. The distinctive style of van Gogh is easily recognized by the highly complex visual pattern recognition system of our central nervous system... Today, we apply this ability in a variety of areas, including athletic endeavors, police investigations, aesthetics, and many other venues, including the interpretation of ECGs.

Based on this explanation and the lack of progress over time it would appear unlikely that the computer will supplant the clinician in ECG interpretation let alone in other areas of diagnostic evaluation that are far more complex and less mechanistic.

Cardiac manifestations in ankylosing spondylitis

From a recent paper:


Transthoracic echocardiography was performed in 187 patients (105 men), mean age (SD) 50 (13) years, and mean disease duration 24 (13) years, and was related to demographic, clinical, radiographic, electrocardiographic, and laboratory data.


Aortic regurgitation was found in 34 patients (18%; 95% confidence interval [CI], 12%-24%): mild in 24, moderate in 9, and severe in one. The prevalence was significantly higher than expected from population data. Conduction system abnormalities were documented in 25 patients (13%; 95% CI, 8%-18%), and significantly more likely in the presence of aortic regurgitation (P = .005), which was related to increasing age and longstanding disease, and increased from ∼20% in the 50s to 55% in the 70s. It was also independently associated with disease duration, with higher modified Stoke Ankylosing Spondylitis Spine Score, and with a history of anterior uveitis. HLA-B27 was present in similar proportions in the presence vs absence of aortic regurgitation. For comparison, clinically significant coronary artery disease was present in 9 patients (5%; 95% CI, 2%-8%).


Patients with ankylosing spondylitis frequently have cardiac abnormalities, but they more often consist of disease-related aortic regurgitation or conduction system abnormalities than manifestations of atherosclerotic heart disease. Because aortic regurgitation or conduction abnormalities might cause insidious symptoms not easily interpreted as of cardiac origin, we suggest that both electrocardiography and echocardiography evaluation should be part of the routine management of patients with ankylosing spondylitis.

Monday, May 02, 2016

Brugada syndrome: the essentials

A free full text review was recently published on this topic. Some of the key questions addressed:

What is it?

Brugada syndrome is a genetically heterogeneous channelopathy, first described in 1992, capable of causing arrhythmia, syncope and sudden cardiac death.

What is the presenting arrhythmia?

PMVT or VF. Less commonly MMVT.

When should you suspect it?

In a patient with characteristic ECG findings inquire about syncope or a family history of syncope, drowning or SCD. In a patient with such a personal or family history look for characteristic ECG findings. Know the typical patterns (see below).

How do you make the definitive diagnosis?

Although features from the clinical history are said to strengthen the diagnosis the new (2013) criteria are purely electrocardiographic. From the article:


BrS is diagnosed in patients with ST-segment elevation with type I morphology greater than or equal to 2 mm in greater than or equal to 1 lead among the right precordial leads V1,V2 positioned in the 2nd, 3rd, or 4th intercostal space occurring either spontaneously or after provocative drug test with intravenous administration of Class I antiarrhythmic drugs.


BrS is diagnosed in patients with Type 2 or Type 3 ST-segment elevation in greater than or equal to1 lead among the right precordial leads V1,V2 positioned in the 2nd, 3rd, or 4th intercostal space when a provocative drug test with intravenous administration of Class I antiarrhythmic drugs induces a Type 1 ECG morphology.

Note that you explore along three intercostal spaces with the V1-2 electrodes in attempting to elicit the pattern. Also note that drug challenge is contraindicated in patients who spontaneously exhibit the type 1 pattern. This is because it is unnecessary according to present diagnostic criteria and may provoke arrhythmia.

What electrophysiologic mechanisms are at play?

Inhomogeneous sodium channel defects cause transmyocardial voltage gradients and inhomogeneous repolarization, leading to the arrhythmia substrate. Triggering PVCs are close coupled and arise from the RVOT and thus can be ablated as an option for patients who suffer from electrical storm.

What are the genetics of Brugada syndrome?

At least 16 genes have been identified but no known mutation is present in the majority of cases. Most of the mutations are novel, found in isolated individuals or families. It has been traditionally thought to be autosomal dominant but recent evidence indicates that the genetic picture is more complex and some cases may be polygenic.

What are the management recommendations?

For symptomatic Brugada syndrome patients (syncope, cardiac arrest) : ICD implantation.

For asymptomatic patients meeting electrocardiographic criteria: avoidance of contraindicated drugs (see this list) and management of aggravating conditions such as fever and hypokalemia.

Note: quinidine can reverse the Brugada pattern and reduce arrhythmias but is not generally recommended due to a lack of high level evidence that it improves clinical outcomes, proarrhythmic effects of its own and a lack of general availability.

Asymptomatic patients who exhibit the pattern only during certain acute illnesses or exposure to sodium channel blocking drugs are considered at very low risk.

Sunday, May 01, 2016

Bacterial translocation peri cardiac arrest

This paper reviews issues related to peri arrest infection. From the abstract:

During the periarrest period, intestinal ischemia may result in barrier dysfunction and bacterial translocation, which has clear mechanistic links to inflammation and cascade stimulation, especially in patients who are treated with therapeutic hypothermia. Despite optimal management, periarrest bacterial translocation may worsen the outcome of cardiac arrest victims.

But the relationship between infection and cardiac arrest is more complex than we might imagine. Emerging evidence is beginning to suggest that antibiotics may be indicated in non-shockable out of hospital cardiac arrest. From the body of the paper:

One of the main goals both during CPR and postresuscitation period is hemodynamic optimization to preserve adequate coronary and cerebral perfusion. However, intestinal ischemia, a neglected consequence of circulatory collapse, and subsequent reperfusion may be extremely detrimental by enhancing bacterial translocation [3] . This phenomenon is likely more common in patients presenting with asystole or pulseless electrical activity (PEA) rather than ventricular fibrillation or pulseless ventricular tachycardia due to the prolongation of whole-body ischemia in nonshockable cardiac arrest. Asystole has been reported as the most common presenting rhythm in OHCA victims with bacteremia followed by PEA and ventricular fibrillation [4] , whereas, in a retrospective analysis, shockable rhythms were uncommon among patients with preexisting pneumonia compared with initial arrest rhythms in patients without pneumonia [5] . Although the initial rhythm in OHCA is rarely recorded and may have evolved to asystole at the time of the recording, we have also reported PEA as the initial cardiac arrest rhythm in severe sepsis and septic shock [6] .

Research so far has shown that more than one third of OHCA victims are bacteremic upon presentation [4] ; however, it is difficult to know if sepsis is the reason for cardiac arrest or bacteremia is a downstream effect of intestinal hypoperfusion.

Multiple purported mechanisms are discussed including the use of saline as resuscitation fluid and the use of therapeutic hypothermia.

Saturday, April 30, 2016

Non cardiac surgery in patients with aortic stenosis

Advances in perioperative management and the availability of transcutaneous techniques have improved the outlook for patients but have made decision making more complex. The topic is reviewed in this recent paper. Here is a key passage:

Emergency noncardiac surgery (NCS) obviously needs to be performed without consideration of the AS; these patients are at the highest risk of perioperative morbidity and mortality. Aortic balloon valvuloplasty (ABV) can be considered in patients needing urgent noncardiac surgery; transcatheter aortic valve replacement (TAVR) is an alternative, but the necessary assessment of vascular access and LVOT sizing cannot usually be performed in due time. Asymptomatic patients can in general proceed with elective noncardiac surgery; however, surgical aortic valve replacement (SAVR) or TAVR should be considered before high-risk surgical interventions, or in patients with revised cardiac risk index (RCRI) greater than or equal to 2. Symptomatic patients should in general undergo TAVR or SAVR before noncardiac surgery, unless the need for antithrombotic therapy required after TAVR or SAVR unduly delays or increases the risk of noncardiac surgery, or when the noncardiac surgery could decrease the risk of anticipated SAVR or TAVR for severe symptomatic aortic stenosis. Concomitant SAVR and noncardiac surgery can also be considered in selected patients (see the text for details).

The full text of the article is recommended.

Friday, April 29, 2016

Arrhythmic versus asphyxial cardiac arrest

We are comfortable thinking of cardiac arrest as one entity. That thinking is simplistic and flawed.  A recent review article highlights differences between two major categories of arrest. First some definitions. Arrhythmic cardiac arrest is primary cardiac arrest. It is caused by structural, electrical (channelopathy) or metabolic (eg electrolyte disturbance) disorders and the presenting rhythm is usually (though not always) VF or pulseless VT. Asphyxial arrest is the “respiratory code” which occurs as a result of respiratory failure and consequent hypoxemia or hypercapnia. VF may occur but it is almost never the presenting rhythm. These represent the main two causes of arrest. A third category, cardiac arrest as the end result of progressive circulatory shock, was not covered in the review.

The following sections from the body of the paper highlight key points:

Asphyxial CA is characterized by a prolonged time course and an important prearrest period where hypoxia (defined as critical reduction in arterial oxygen saturation or arterial oxygen tension), and hypercapnia (defined as increases in arterial carbon dioxide tension), progressively advance along with maintained but gradually deteriorating cardiopulmonary function...

Contrary to asphyxial, dysrhythmic CA leads to sudden and complete cessation of blood flow...

Although VF is a lethal tachyarrhythmia often associated with underlying cardiac disturbances and considered to be the immediate cause of CA, it can also occur during the asphyxial process. Ventricular fibrillation in this setting is uncommon, but not rare [15] . Asphyxia-induced or secondary VF has different underlying pathophysiologic mechanisms with regard to myocardial bioenergetics and electrophysiology...

The conversion of PEA and nonshockable rhythms to shockable during asphyxia is an interesting phenomenon and it seems that outcomes after asphyxial CA with asystole/PEA with subsequent VF are worse than after asystole/PEA without subsequent VF [20] . This is probably attributed to the fact that subsequent VF might be a marker of more severe myocardial dysfunction...

At cellular level, sudden CA of cardiac origin causes an immediate no-flow state with global ischemia, where high-energy phosphates are depleted rapidly. Especially in the brain, adenosine triphosphate (ATP) depletion is thought to occur within a few minutes [23] . On the contrary, asphyxial CA is characterized by progressive and global hypoxia with incomplete ischemia and results in gradually with the length of asphyxia ATP and phosphocreatine reduction. If ATP is depleted during hypoxia, necrosis occurs because of mitochondria transmembrane potential disruption, leading to cell swelling and ultimately to apoptosis and necrosis [24 25] . Depletion of cellular energy initiates biochemical cascades that lead to cell damage and death prior to the no-flow state...

Finally, maintained cardiovascular function during asphyxia prior to cardiac standstill results in CO 2 tissue production and accumulation in the alveoli, as there is no alveolar gas exchange. There are at least 5 laboratory studies that showed different patterns of end-tidal carbon dioxide ( et CO 2 ) levels during cardiopulmonary resuscitation (CPR) betpathophysiologic role. In particular, organ perfusion with hypoxemic blood during asphyxia prior to complete circulatory collapse may contribute to a different degree of reperfusion injury after ROSC compared with sudden dysrhythmic CA, affecting overall prognosis...

Although both asphyxial and dysrhythmic CAs lead to brain damage through global ischemia, it seems that significant histopathologic differences exist between the 2 conditions...

In summary, all available data support the assumption that the ischemic degree and final brain damage are greater and more severe after asphyxial CA than after dysrhythmic CA...

Myocardial dysfunction after resuscitated CA is a well-recognized and described component of the post-CA syndrome...

As for treatment implications based on the type of cardiac arrest, the authors suggest a traditional guideline based approach to asphyxial arrest versus cardiocerebral resuscitation as originally promulgated by the Arizona investigators for arrhythmic arrest. Post arrest hypothermia is recommended for both forms of arrest although it is more firmly established for arrhythmic arrest.

Tuesday, April 26, 2016

Advances in the treatment of acute liver failure

From a review:

Recent findings: As the treatment of ALF has evolved, there is an increasing recognition regarding the risk of intracranial hypertension related to advanced hepatic encephalopathy. Therefore, there is an enhanced emphasis on neuromonitoring and therapies targeting intracranial hypertension. Also, new evidence implicates systemic proinflammatory cytokines as an etiology for the development of multiorgan system dysfunction in ALF; the recent finding of a survival benefit in ALF with high-volume plasmapheresis further supports this theory.

Summary: Advances in the critical care management of ALF have translated to a substantial decrease in mortality related to this disease process. The extrapolation of therapies from general neurocritical care to the treatment of ALF-induced intracranial hypertension has resulted in improved neurologic outcomes. In addition, recognition of the systemic inflammatory response and multiorgan dysfunction in ALF has guided current treatment recommendations, and will provide avenues for future research endeavors. With respect to extracorporeal liver support systems, further randomized studies are required to assess their efficacy in ALF, with attention to nonsurvival end points such as bridging to liver transplantation.