ABSTRACT
BACKGROUND AND AIMS: Vasopressin (VP) in sepsis apart from vasoconstrictive effect may have some immunomodulatory effects. The aim of this study was to evaluate the effect of VP on different aspect of sepsis by measuring of sepsis biomarkers. MATERIALS AND METHODS: In this trial, a total number of 42 septic shock patients were included. The first group received norepinephrine (NE) infusion to reach the target mean arterial pressure (MAP) of ≥ 65 mm Hg and the second group received arginine vasopressin (AVP) infusion in addition to NE. Serum lactate, C-reactive protein (CRP), interleukin-6 (IL-6), IL-10, pentraxin 3 (PTX3), angiopoietin 1 and 2 (Ang 1 and 2) levels were assessed. RESULTS: Level of IL-6 and IL-10 decreased, but there was no significant difference between the two groups after 48 h. CRP and PTX3 levels were not also significantly different between groups. Although Angs were not statistically different, there was a trend toward higher Ang-1 in and lower Ang 2 in AVP group after 24 and 48 h. In addition, lactate level did not differ between NE and AVP groups. There was no interaction between VP and hydrocortisone use on IL-6, IL-10, and PTX3, but a significant statistical interaction on Ang 1 and Ang 2 were observed. CONCLUSIONS: Although analysis of sepsis biomarkers showed no significant difference between two groups, no immunomodulatory effect for VP alone, subgroup analysis of hydrocortisone used in this study showed that the combination of glucocorticoids and AVP had a significant effect on Angs level which eventually causes less endothelial permeability and higher MAP in this group of patients.
ABSTRACT
BACKGROUND: Sepsis is the result of the interaction between inflammatory mediators and coagulation pathway. Unfractionated heparin may play a role as an anti-inflammatory agent beyond its anticoagulatory effect in sepsis. As a result, it may cause reduction in organ failure rate in patients with sepsis due to its impact on both inflammatory and coagulation process. OBJECTIVES: The aim of this study was to evaluate the anti-inflammatory effects of heparin in sepsis. Plasma plasminogen activator inhibitor-1 (PAI-1) as an inflammatory mediator and urinary necoutrophil gelatinase-associated lipocalin (NGAL) as a marker of kidney injury were investigated. PATIENTS AND METHODS: This prospective, randomized controlled trial was conducted in a 32-bed intensive care unit. Thirty patients with sepsis were randomized to receive heparin infusion of 500 units/hour or 5000 units of heparin three times a day, subcutaneously. The plasma level of PAI-1 and urinary level of NGAL were determined at day 0, 2 and 7. RESULTS: The infusion group had a lower plasma PAI-1 level compared to the subcutaneous group at day 7 (11.3 ± 1.6 vs. 16.5 ± 4.2; P = 0.003). The urinary NGAL level was lower in the infusion group at day 2 (131.3 ± 11.9 vs. 151.2 ± 20.6; P = 0.014); however, at day 7 the NGAL level was decreased in the subcutaneous group as much as the infusion group and there was no significant difference between the two groups. There was no significant difference in the acute physiology and chronic health evaluation (APACHE) II and sequential organ failure assessment (SOFA) scores between the two groups at day 0, 2 and 7. CONCLUSIONS: Low-dose heparin infusion compared to subcutaneous heparin can decrease the plasma PAI-1 and urinary NGAL levels more rapidly. It can be related to anti-inflammatory effects of heparin, which may be more prominent in infusion route.
ABSTRACT
Arginine vasopressin as a supplementary vasopressor in septic shock restores vascular tone and mean arterial pressure, meanwhile decreases dose and exposure time to catecholamines. The objective of this study was to evaluate the effect of vasopressin on lactate and lactate clearance as markers of tissue perfusion during septic shock. In this prospective, randomized, controlled trial, 30 patients with septic shock were enrolled in two groups. One group received norepinephrine infusion (titrated to reach the target MAP of ≥65 mm Hg) and the other group in addition to norepinephrine, received vasopressin at a constant rate of 0.03 u/min. Serum lactate levels were assessed at baseline, 24 and 48 hours after randomization. Lactate clearance was estimated for each patient at 24 and 48 hours. Venous lactate was measured in both groups. Despite a tendency toward higher venous lactate at 24 and 48 hours in the norepinephrine group (3.1 vs. 2.5, P=0.67 and 1.7 vs. 1.1, P=0.47), the conflict was not statistically significant among them. While lactate clearance after 24 hours was significantly higher in vasopressin treatment group (46% vs. 20%, respectively; P=0.048), the 48-hour lactate clearance did not differ from statistic viewpoints despite their clinical values (66% vs. 40%, P=0.17). Although lactate levels did not significantly differ between treatment groups, lactate clearance at 24 hours was significantly higher in vasopressin group. This may be the effect of vasopressin effect on microcirculation and tissue hypoperfusion or its catecholamine sparing effect.
