Medications approved for adults often have additional uses in pediatric patients. Such is the case — as described by Wessel and colleagues — for clopidogrel, an agent that blocks the P2Y12 component of adenosine diphosphate (ADP) receptors on the surface of platelets. ADP receptors prevent the activation of the glycoprotein IIb/IIIa receptor complex, thereby reducing aggregation. Clopidogrel is used most commonly as a prophylactic antiplatelet therapy in adults with atherosclerotic cardiovascular disease, but is increasingly employed in the pediatric population, particularly in those with cardiac disease. Pediatric cardiovascular practitioners are using clopidogrel (along with the standard aspirin) to prevent the thrombosis of systemic-to-pulmonary-artery shunts in patients with complex cyanotic heart disease; however, the safety and efficacy of this practice have never been looked at prospectively. In the June 20 issue of The New England Journal of Medicine, investigators created a multicenter, event-driven trial to evaluate clopidogrel’s effect on infants.

The study, Clopidogrel to Lower Arterial Thrombotic Risk in Neonates and Infants Trial (CLARINET), was a double-blinded, randomized, placebo-controlled trial. Infants of 92 days or younger were recruited from one of 134 sites all over the world if they had cyanotic congenital heart disease that was palliated with a systemic-to-pulmonary-artery shunt. These infants were then randomly assigned to receive clopidogrel or placebo (most subjects in both groups were taking aspirin). The primary end point was defined as the earliest occurrence of any of the following: death or heart transplant, shunt thrombosis, or a cardiac procedure performed before 120 days of age because of a thrombotic event.  Adverse events, particularly bleeding episodes, also were tracked. Although this study was sponsored by the drug’s manufacturers Sanofi-Aventis and Bristol-Myers Squibb, the authors noted that statisticians not employed by either company were responsible for validating the final end point. Read the rest of this entry »

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In two meta-analyses and one previous observational study, prone positioning was associated with improved survival for patients with severely hypoxemic acute respiratory distress syndrome (ARDS). However, the findings in these studies were in contradistinction to previously conducted randomized trials. To further evaluate the effectiveness of early prone positioning in severe ARDS, Guerin and colleagues from the PROSEVA Study Group designed a randomized controlled trial comparing early application of prone positioning versus supine positioning for patients with severe ARDS. Results were published in a recent issue of The New England Journal of Medicine.

The pre-Berlin definition of ARDS was used to screen 3,449 patients from 26 intensive care units (ICU) in France and one in Spain. After a stabilization period of 12 to 24 hours, patients were randomly assigned to a prone or supine positioning study group. Patients in the prone group were placed in a prone position for at least 16 consecutive hours every day for up to 28 days. Outcomes assessors were blinded to group assignments. The primary outcome of interest was mortality at day 28. Secondary end points were rate of extubation, ICU length of stay, complications, and several other outcomes. Data were analyzed according to the intention-to-treat principle; patient survival was assessed with the Kaplan-Meier method and Cox proportional-hazards regression. Read the rest of this entry »

Metabolomics is a relatively new technology that involves the measurement of an organism’s global metabolic response to some physiologic stress. The study of this technology is gaining momentum, as measurement of a person’s metabolic profile in easily accessible biological fluids can help distinguish disease states from non-disease states earlier. Thus, patients could receive appropriate therapies earlier, which can improve outcomes in cases such as pneumonia and sepsis. In the May 2013 issue of Respiratory and Critical Care Medicine, the authors used 1H proton nuclear magnetic resonance spectroscopy to measure the concentrations of 58 different metabolites in serum samples taken from 140 pediatric subjects from 11 different institutions.

The subjects were divided into healthy controls, children with septic shock, and children with systemic inflammatory response syndrome (SIRS) who were admitted to a pediatric intensive care unit. They were also further divided into age groups (neonates, infants, toddlers, and school age children) to determine if the metabolic profiles changed with age. Once the samples were obtained and metabolites measured by spectroscopy, multivariate statistical analyses were applied to separate metabolic variation in the subjects to detect patterns in metabolic profiles. For example, principal component analysis (PCA) was used to reduce the number of variables by removing redundancies. Other statistical methods that were then used included partial least squares discriminant analysis (PLS-DA) and orthogonal partial least squares discriminant analysis (OPLS-DA). Read the rest of this entry »

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Critically ill patients are at risk for significant oxidative stress; however, several small analyses have proposed that supplementation with glutamine, with or without antioxidants, may improve survival. Heyland and colleagues from the Canadian Critical Care Trials Group conducted an international, multicenter study to test the hypothesis that 28-day mortality in critically ill adults would be reduced by supplementation with glutamine, with or without antioxidants. Results were published in a recent issue of The New England Journal of Medicine.

In a randomized factorial, double-blinded, multicenter trial, consecutive adults admitted to an intensive care unit (ICU) and receiving mechanical ventilation were enrolled. Additionally, patients were required to have two or more organ failures related to their critical illness. Subjects were randomized to one of four groups: placebo, glutamine, antioxidants (selenium, beta carotene, vitamins E and C), or antioxidants plus glutamine. The primary outcome was 28-day mortality; several secondary outcomes were also studied.  Read the rest of this entry »

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Permissive hypercapnia is a well-accepted ventilator strategy for the management of acute respiratory distress syndrome as well as other causes of respiratory failure, such as the respiratory distress syndrome seen in premature infants.  Multiple studies have demonstrated that both myocardial contractility and systemic vascular resistance (SVR) decrease with hypercapnic acidosis, the ultimate effect being that cardiac function is maintained or even augmented. The effects of hypercapnic acidosis on cardiac function in the preterm infant have not been elucidated. In a prospective observational study, published in the May issue of The Journal of Pediatrics, the authors analyzed paired blood gases and echocardiograms from 29 hemodynamically stable preterm infants at 30 weeks’ gestation or less. 

Samples were taken within the first two weeks of life, either during the transitional period (days 1-3) or post-transitional period (days 4-14). In all, there were 103 paired blood gases and echocardiograms from 21 subjects in the transitional period and 44 paired studies from 15 subjects in the post-transitional period. Each echocardiographic examination included measurements for shortening fraction (which is a load-dependent measure of contractility), stress-velocity index (which is a load-independent measure of contractility), left and right ventricular output, assessment of the ductus arteriosus, myocardial performance index, and SVR. Read the rest of this entry »

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