Are biomarkers additive to pulmonary embolism severity index for severity assessment in normotensive patients with acute pulmonary embolism?

BACKGROUND: Biomarkers and clinical prediction rules have been proposed for severity assessment in acute pulmonary embolism (PE). AIM: The aim of this study was to compare biomarkers with the PE Severity Index (PESI), a validated scoring system for predicting 30-day mortality and to determine if addition of biomarkers to PESI would improve its predictive accuracy. STUDY DESIGN AND METHODS: We conducted a retrospective analysis of normotensive patients admitted with PE confirmed by CT pulmonary angiogram, to three teaching hospitals between January 2005 and July 2007. All patients had admission levels of D-dimer and Troponin I and calculation of PESI score on admission. The outcome of interest was 30-day mortality. RESULTS: There were 411 patients included in the study. Patients who died had higher levels of D-dimer (median 2947 ng/ml vs. 1464 ng/ml; P=0.02), Troponin (57.1% positive vs. 13.8%; P<0.0001) and higher PESI scores [median 109 vs. 83; P<0.0001], compared to survivors. PESI had superior accuracy for predicting 30-day mortality than a combination of Troponin and D-dimer (AUC 0.80 vs. 0.75). Addition of Troponin to PESI further improved the predictive value of the score (AUC 0.85 for vs. AUC 0.80 for PESI alone). CONCLUSION: Biomarkers and clinical prediction rules predict outcome in acute PE. Addition of troponin to the PESI scoring system improves the predictive value for 30-day mortality and may be useful for guiding initial management of patients presenting with PE.

Multiple binding sites for local anesthetics in membranes: characterization of the sites and their equilibria by deuterium NMR of specifically deuterated procaine and tetracaine.

Anesthetics bound to model membranes were observed directly by means of deuterium nuclear magnetic resonance (NMR). The specifically deuterated local anesthetics procaine and tetracaine were synthesized, and their partition coefficients (water:phosphatidylcholine) and pKa values determined. The interaction of these anesthetics with lamellar dispersions of egg phosphatidylcholine was studied by 2H nuclear magnetic resonance and by electron spin resonance (ESR) of a spin-labelled phospholipid at low (5.5) and high (9.5) pH. The ESR experiments suggest that tetracaine intercalates in the membrane and that it equilibrates between water and the phospholipid bilayers of the multilamellar system. The NMR results are consistent with a model where the anesthetic is (1) free in water, (2) weakly bound, and (3) strongly bound to the membrane. A fast exchange exists between the two first sites, but exchange is slow with the third site. Binding of type 3 is observed only at high pH for procaine, whereas it is found both at low and high pH for tetracaine. Calculations of the partition coefficients for the charged and uncharged forms of tetracaine indicate that both sites, 2 and 3, are occupied by the charged form at low pH and by the uncharged form at high pH. The partition coefficient for the weakly bound species was estimated from an analysis of the dependence of line width on the lipid to water ratio. The NMR data suggest that the binding sites for the strongly bound charged and uncharged species are different, the former probably being closer to the membrane-water interface. Estimates of molecular order parameters for the strongly bound species indicate that it is located with its long molecular axis approximately parallel to the director for ordering of the fatty acyl chains. A small increase in lipid ordering by tetracaine is observed at low pH, as evidenced by 2H NMR of the deuterated N-methyl groups of phosphatidylcholine; the reverse occurs at high pH.