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.

Monday, April 25, 2016

Spironolactone superior as an add on drug for resistant hypertension


Optimal drug treatment for patients with resistant hypertension is undefined. We aimed to test the hypotheses that resistant hypertension is most often caused by excessive sodium retention, and that spironolactone would therefore be superior to non-diuretic add-on drugs at lowering blood pressure.


In this double-blind, placebo-controlled, crossover trial, we enrolled patients aged 18–79 years with seated clinic systolic blood pressure 140 mm Hg or greater (or greater than or equal to135 mm Hg for patients with diabetes) and home systolic blood pressure (18 readings over 4 days) 130 mm Hg or greater, despite treatment for at least 3 months with maximally tolerated doses of three drugs, from 12 secondary and two primary care sites in the UK. Patients rotated, in a preassigned, randomised order, through 12 weeks of once daily treatment with each of spironolactone (25–50 mg), bisoprolol (5–10 mg), doxazosin modified release (4–8 mg), and placebo, in addition to their baseline blood pressure drugs. Random assignment was done via a central computer system. Investigators and patients were masked to the identity of drugs, and to their sequence allocation. The dose was doubled after 6 weeks of each cycle. The hierarchical primary endpoints were the difference in averaged home systolic blood pressure between spironolactone and placebo, followed (if significant) by the difference in home systolic blood pressure between spironolactone and the average of the other two active drugs, followed by the difference in home systolic blood pressure between spironolactone and each of the other two drugs. Analysis was by intention to treat. The trial is registered with EudraCT number 2008-007149-30, and number, NCT02369081.


Between May 15, 2009, and July 8, 2014, we screened 436 patients, of whom 335 were randomly assigned. After 21 were excluded, 285 patients received spironolactone, 282 doxazosin, 285 bisoprolol, and 274 placebo; 230 patients completed all treatment cycles. The average reduction in home systolic blood pressure by spironolactone was superior to placebo (–8·70 mm Hg [95% CI −9·72 to −7·69]; p less than 0·0001), superior to the mean of the other two active treatments (doxazosin and bisoprolol; −4·26 [–5·13 to −3·38]; p less than 0·0001), and superior when compared with the individual treatments; versus doxazosin (–4·03 [–5·04 to −3·02]; p<0 0="" 285="" 6="" all="" and="" baseline="" being="" best="" bisoprolol="" blood="" but="" distribution.="" distribution="" drug="" effective="" ends="" exceeded="" for="" greater="" higher="" in="" individual="" its="" less="" likelihood="" lower="" many-fold="" margin="" mmol="" most="" occasion.="" of="" on="" one="" p="" patient="" patients="" plasma="" potassium="" pressure-lowering="" received="" renin="" serum="" six="" span="" spironolactone="" superiority="" than="" the="" throughout="" to="" tolerated.="" treatment="" treatments="" versus="" was="" well="" were="" who="">


Spironolactone was the most effective add-on drug for the treatment of resistant hypertension. The superiority of spironolactone supports a primary role of sodium retention in this condition.

Sunday, April 24, 2016

Fitness level and a fib risk: finding the sweet spot

From a recent study:


CRF, as assessed by maximal oxygen uptake (VO2max) during exercise testing, was measured at baseline in 1950 middle-aged men (mean age 52.6 years, SD 5.1) from the Kuopio Ischaemic Heart Disease (KIHD) study.


During average follow-up of 19.5 years, there were 305 incident AF cases (annual AF rate of 65.1/1000 person-years, 95% confidence interval [CI] 58.2–72.8). Overall, a nonlinear association was observed between CRF and incident AF. The rate of incident AF varied from 11.5 (95% CI 9.4–14.0) for the first quartile of CRF, to 9.1 (95% CI 7.4–11.2) for the second quartile, 5.7 (95% CI 4.4–7.4) for the third quartile, and 6.3 (95% CI 5.0–8.0) for the fourth quartile. Age-adjusted hazard ratio comparing top vs bottom fourth of usual CRF levels was 0.67 (95% CI 0.48–0.95), attenuated to 0.98 (95% CI 0.66–1.43) upon further adjustment for risk factors. These findings were comparable across age, body mass index, history of smoking, diabetes, and cardiovascular disease status at baseline.


Improved fitness as indicated by higher levels of CRF is protective of AF within a certain range, beyond which the risk of AF rises again. These findings warrant further replication.

Saturday, April 23, 2016

Augmented renal clearance of antibiotics in critically ill patients

From a recent review:


Augmented renal clearance (ARC) is a prevalent condition in the critically ill.

ARC may result in sub-therapeutic exposure of renally eliminated antibiotics.

Beta-lactams are particularly affected due to their pharmacokinetic and pharmacodynamic characteristics.

Dose optimization is necessary to circumvent the influence of ARC.

Therapeutic drug monitoring may be necessary to guide dose optimization.

Dose optimization might consist, in the case of beta lactam antibiotics and their congeners, of extended or continuous infusion dosing. Although ARC is defined by a creatinine clearance of greater than 130 mL/min/173 m2 routine clinical estimates may not be reliable. Moreover, enhanced tubular secretion or diminished reabsorption may account for ARC of some antibiotics. Less severely ill patients tend to be at greater risk for ARC.

Friday, April 22, 2016

Ca-125 levels may indicate perforation in acute appendicitis

From a recent report:


Sixty patients with acute appendicitis were recruited prospectively in this study between May 2014 and March 2015. Blood samples were obtained to measure CA-125 levels before appendectomy. Of the 57 patients, 10 had perforated or gangrenous appendicitis intraoperatively. The CA-125 levels were significantly higher in patients with perforated or gangrenous appendicitis than patients with uncomplicated appendicitis (49.9 vs 10.5 U/mL, P = .000).


Cancer antigen 125 levels in patients with highly suspected or confirmed appendicitis could help clinicians determine the severity of the disease.

Thursday, April 21, 2016

Should you screen your patient for alpha 1?

A recent paper, linked here, outlines the indications for screening and the reasons why. This has been a bit controversial, since gene product replacement has been supported only by clinical data on surrogate endpoints. However, the article makes a compelling case for screening based on several reasons. First, the surrogate based evidence is mounting. Second, there are multiple reasons beyond product replacement to justify screening.