Anticoagulant properties of drotrecogin alfa (activated) during hemofiltration in patients with severe sepsis

Abstract

In a retrospective study among 35 severely septic patients treated with drotrecogin alfa (activated) (DrotAA) and renal replacement therapy (RRT), Camporota and colleagues demonstrated that the addition of heparin, epoprostenol, or both to DrotAA during RRT did not improve filter survival. Furthermore, in a multivariate logistic regression analysis, they identified the minimum value in platelet count as the only predictive factor of filter clotting during DrotAA infusion. These findings are in line with the previously formulated suggestion that DrotAA alone is as effective as heparin in the prevention of coagulation in the extracorporeal circuit. They also confirm the importance of baseline platelet count in the pathogenesis of extracorporeal circuit thrombosis. In the study by Camporata and colleagues, DrotAA treatment was not associated with an increase in red blood cell requirements. The results of this study supply a background to clinical decision making when choosing an anticoagulant for RRT in septic patients.In the last 2008 issue of Critical Care, Camporota and colleagues [1] reported the results of a retrospective study analyzing filter survival time and transfusion requirements among 35 severely septic patients treated with drotrecogin alfa (activated) (DrotAA) and renal replacement therapy (RRT). DrotAA is capable of reducing mortality in severely septic patients [2] and the international guidelines for management of severe sepsis and septic shock recommend considering its use in adult patients with sepsis-induced organ dysfunction and high risk of death [3]. Among septic patients, acute renal failure (ARF) is common: its incidence ranges from 19% in moderate sepsis to 51% in septic shock [4]. ARF patients have an increased risk of mortality and this risk is even higher among patients treated with RRT [5]. As the annual incidence of sepsis ranges from 100 to 300 per 100,000 inhabitants and 30% to 40% of septic patients develop severe sepsis [6], the number of patients meeting the indications for treatment with both DrotAA and RRT is considerable.As DrotAA is an anticoagulant itself, the risk of bleeding during its use might be increased by the addition of other anticoagulants during RRT. Until now, only one report of three cases has been published on this topic. This report suggested that Drot AA alone is as effective as heparin in the prevention of coagulation in the extracorporeal circuit [7].The current study demonstrates that the addition of heparin, epoprostenol, or both to DrotAA during RRT does not prolong filter survival. The lack of an additional effect of heparin on filter survival is not surprising since the antithrombotic effect of DrotAA is not enhanced by the addition of heparin [8]. However, since epoprostenol is a potent inhibitor of platelet function and DrotAA does not seem to have a direct inhibitory effect on platelet aggregation [9], one might have expected prolongation of filter survival during treatment with both DrotAA and epoprostenol.Notably, multivariate logistic re...

Effects of Carnosine (Beta-Alanyl-L-Histidine) in an Experimental Rat Model of Acute Kidney Injury Due to Septic Shock

“…The antioxidative activity of carnosine and 16 related compounds, both synthetic and natural, has been determined [ 15 – 18 ]. Antioxidative effects were estimated by the ability of the dipeptides to prevent MDA accumulation over the course of lipid peroxidation (LPO) induced in rabbit sarcoplasmic reticulum membranes by the Fe 2+ ascorbate system [ 18 ].…”

“…The antioxidative activity of carnosine and 16 related compounds, both synthetic and natural, has been determined [ 15 – 18 ]. Antioxidative effects were estimated by the ability of the dipeptides to prevent MDA accumulation over the course of lipid peroxidation (LPO) induced in rabbit sarcoplasmic reticulum membranes by the Fe 2+ ascorbate system [ 18 ]. It was found that an antioxidative effect comparable to that of carnosine was exerted by water- soluble (cyclo-L-histidyl-L-proline) and alcohol-soluble (cyclo-L-histidyl-L-phenylalanine) dipeptides, as well as by the histidine-free cyclodipeptides (cyclo-L-tyrosyl-L-proline) [ 18 ].…”

“…Antioxidative effects were estimated by the ability of the dipeptides to prevent MDA accumulation over the course of lipid peroxidation (LPO) induced in rabbit sarcoplasmic reticulum membranes by the Fe 2+ ascorbate system [ 18 ]. It was found that an antioxidative effect comparable to that of carnosine was exerted by water- soluble (cyclo-L-histidyl-L-proline) and alcohol-soluble (cyclo-L-histidyl-L-phenylalanine) dipeptides, as well as by the histidine-free cyclodipeptides (cyclo-L-tyrosyl-L-proline) [ 18 ]. However, in contrast to its synthetic analogues, carnosine not only inhibited LPO but also diminished the level of products accumulating during membrane LPO [ 15 – 18 ].…”

“…In a previous study that used a rat sepsis model, there was a statistically significant improvement in renal function, as assessed by increased urine output, renal blood flow, and decreased serum creatinine, in an arginine vasopressin (AVP) treatment group, when compared with a norepinephrine-treated group (p<0.05) [ 18 ]. Similarly, in our study, urine output volume and creatinine clearance rate decreased significantly, and blood urea nitrogen (BUN) and creatinine (Cr) levels increased significantly in rats exposed to sepsis.…”

“…In another previously reported study, Vassal et al obtained hemodynamic improvement with amino acid infusion in an experimental porcine model of septic shock [ 17 ]. Simon et al showed decreased mean arterial blood pressure in rats exposed to septic shock [ 18 ]. In our study, mean arterial blood pressure also decreased significantly after surgery in Group 2, compared with Groups 1 and 3.…”