pituitrin and Pneumonia--Bacterial

To determine if the selective vasopressin type 1a receptor agonist selepressin (FE 202158) is as effective as the mixed vasopressin type 1a receptor/vasopressin V2 receptor agonist vasopressor hormone arginine vasopressin when used as a titrated first-line vasopressor therapy in an ovine model of Pseudomonas aeruginosa pneumonia-induced severe sepsis.. Prospective, randomized, controlled laboratory experiment.. University animal research facility.. Forty-five chronically instrumented sheep.. Sheep were anesthetized, insufflated with cooled cotton smoke via tracheostomy, and P. aeruginosa were instilled into their airways. They were then placed on assisted ventilation, awakened, and resuscitated with lactated Ringer's solution titrated to maintain hematocrit ± 3% from baseline levels. If, despite fluid management, mean arterial pressure fell by more than 10 mm Hg from baseline level, an additional continuous IV infusion of arginine vasopressin or selepressin was titrated to raise and maintain mean arterial pressure within no less than 10 mm Hg from baseline level. Effects of combination treatment of selepressin with the selective vasopressin V2 receptor agonist desmopressin were similarly investigated.. In septic sheep, MAP fell by ~30 mm Hg, systemic vascular resistance index decreased by ~50%, and ~7 L of fluid were retained over 24 hours; this fluid accumulation was partially reduced by arginine vasopressin and almost completely blocked by selepressin; and combined infusion of selepressin and desmopressin increased fluid accumulation to levels similar to arginine vasopressin treatment.. Resuscitation with the selective vasopressin type 1a receptor agonist selepressin blocked vascular leak more effectively than the mixed vasopressin type 1a receptor/vasopressin V2 receptor agonist arginine vasopressin because of its lack of agonist activity at the vasopressin V2 receptor.

Topics: Animals; Arginine Vasopressin; Drug Therapy, Combination; Hemodynamics; Pneumonia, Bacterial; Pseudomonas aeruginosa; Random Allocation; Receptors, Vasopressin; Respiratory Mechanics; Sepsis; Sheep; Vasoconstrictor Agents; Vasopressins

Markers to better assess severity of disease in patients with community-acquired pneumonia (CAP) would help improve medical care of this condition. The hemodynamic biomarkers carboxy-terminal provasopressin (CT-proAVP; copeptin) and midregional proatrial natriuretic peptide (MR-proANP) are increased under septic conditions, in which MR-proANP has been described as a prognostic predictor. We aimed to explore the diagnostic accuracy of MR-proANP and CT-proAVP to predict mortality in patients with CAP.. We conducted a prospective observational study of patients with CAP. We measured biomarkers in serum samples obtained at diagnosis and performed univariate and multivariate analyses to identify potential predictors of mortality.. CT-proAVP and MR-proANP concentrations were measured in 173 patients. We found a positive correlation between pneumonia severity index (PSI) and MR-proANP (r(s) = 0.68, P <0.0001) and between PSI and CT-proAVP (r(s) = 0.44, P <0.0001). Median (interquartile range) CT-proAVP and MR-proANP values were 8.2 (5.3-16.8) and 73.6 (44.6-144.0) pmol/L, respectively. Nonsurvivors had significantly higher MR-proANP and CT-proAVP than survivors (median 259.0 vs 71.8 pmol/L, P = 0.01, and 24.9 vs 8.1 pmol/L, P = 0.03, respectively). In multivariate analysis including PSI, procalcitonin, C-reactive protein, lipopolysaccharide-binding protein, CT-proAVP, and MR-proANP concentrations, only CT-proAVP remained an independent predictor of death (odds ratio 1.05, P = 0.007). Cutoff values of >18.9 pmol/L for CT-proAVP and >227 pmol/L for MR-proANP showed the highest diagnostic accuracy to predict mortality.. CT-proAVP and MR-proANP may be used to predict prognosis in patients with CAP.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Atrial Natriuretic Factor; Biomarkers; Community-Acquired Infections; Female; Glycopeptides; Humans; Male; Middle Aged; Pneumonia, Bacterial; Pneumonia, Viral; Predictive Value of Tests; Prognosis; Prospective Studies; Protein Precursors; Vasopressins