epoetin-alfa and Sepsis

Catheter-related infection (CRI) is a major cause of morbidity and mortality in patients receiving hemodialysis. Antibiotic locking of these catheters has been shown to increase both the success of systemic antibiotic treatment in line sepsis, and to reduce the incidence of sepsis. We have studied the use of gentamicin locking of catheters (in combination with standard heparin rather than previously reported citrate) to reduce CRI rates. Furthermore, we have investigated the effects of this strategy on epoetin requirements and vascular access function.. Fifty patients were studied. Patients were randomized to catheter-restricted filling with either standard heparin (5000 IU/mL) alone, or gentamicin and heparin (5 mg/mL). Epoetin requirements and hemoglobin response were monitored over the study period.. The gentamicin-locked group suffered only one infective episode (0.3/1000 catheter days) compared to 10 episodes in six patients in the heparin alone group (4/1000 catheter days, P= 0.02). The isolated organisms were equally split between Staphylococcal species and coliforms. There were no statistically significant differences in delivered dialysis dose (Kt/V) or QA between the two groups. Use of antibiotic locking was associated with both a higher mean hemoglobin (10.1 +/-0.14 g/dL vs. 9.2 +/- 0.17 g/dL in the heparin group, P= 0.003) and a lower mean epoetin dose (9000 +/- 734 IU/week vs. 10790 +/-615 IU/week in the heparin group, P= 0.04).. The practice of locking newly inserted tunneled central venous catheters with gentamicin and heparin is an effective strategy to reduce line sepsis rates, and is associated with beneficial effects on epoetin requirements.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Anti-Bacterial Agents; Anticoagulants; Catheterization; Cross Infection; Epoetin Alfa; Erythropoietin; Female; Gentamicins; Hematinics; Heparin; Humans; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Sepsis

A prospective, randomized trial comparing Epoetin alfa (Procrit) with placebo saline injection to determine effectiveness in increasing erythropoietic recovery in complex spine deformity surgery.. To determine if Epoetin alfa can allow preoperative autologous donation completion more effectively and reduce perioperative homologous blood transfusion.. The use of Epoetin alfa has been studied, primarily in the arthroplasty literature, for its effectiveness in decreasing transfusion requirements and increasing hemoglobin levels. It has not been studied in patients undergoing complex spine deformity surgery.. A total of 48 patients were prospectively randomized into an Epoetin alfa group and a control group. All patients attempted to donate 4 units of preoperative autologous donation at weekly intervals; 40,000 units of Epoetin alfa were injected subcutaneously at the time of preoperative autologous donation in the Epoetin alfa group. Hematocrit levels were recorded weekly during the donation process and daily in the preoperative period.. Preoperative autologous donation was completed more effectively in the patients receiving Epoetin alfa. Epoetin alfa resulted in statistically higher hematocrit levels during preoperative autologous donation and perioperatively (P < 0.005). Homologous transfusion was decreased by 2.4 units and hospital stay was 1.8 days shorter in patients receiving Epoetin alfa.. Patients who received Epoetin alfa were able to complete preoperative autologous donation more effectively, increase erythropoietic recovery, decrease homologous transfusion requirements, and had shorter hospital stays.

Topics: Adult; Aged; Blood Donors; Blood Loss, Surgical; Blood Transfusion, Autologous; Constipation; Contraindications; Epoetin Alfa; Erythropoietin; Female; Fever; Hematocrit; Humans; Injections, Subcutaneous; Length of Stay; Male; Middle Aged; Postoperative Complications; Postoperative Nausea and Vomiting; Preoperative Care; Prospective Studies; Recombinant Proteins; Sepsis; Spinal Curvatures; Spinal Fusion; Treatment Outcome

Sepsis is one of the most common causes of mortality in intensive care units. Although sepsis-associated encephalopathy (SAE) is reported to be a leading manifestation of sepsis, its pathogenesis remains to be elucidated. In this study, we investigated whether exogenous recombinant human erythropoietin (rhEPO) could protect brain from neuronal apoptosis in the model of SAE. We showed that application of rhEPO enhanced Bcl-2, decreased Bad in lipopolysaccharide treated neuronal cultures, and improved neuronal apoptosis in hippocampus of cecal ligation and peroration rats. We also found that rhEPO increased the expression of phosphorylated AKT, and the antiapoptotic role of rhEPO could be abolished by phosphoinositide 3-kinase (PI3K)/AKT inhibitor LY294002 or SH-5. In addition, systemic sepsis inhibited the hippocampal-phosphorylated mammalian target of rapamycin (mTOR) and p70S6K (downstream substrates of PKB/AKT signaling), which were restored by administration of exogenous rhEPO. Moreover, treatment with mTOR-signaling inhibitor rapamycin or transfection of mTOR siRNA reversed the neuronal protective effects of rhEPO. Finally, exogenous rhEPO rescued the emotional and spatial cognitive defects without any influence on locomotive activity. These results illustrated that exogenous rhEPO improves brain dysfunction by reducing neuronal apoptosis, and AKT/mTOR signaling is likely to be involved in this process. Application of rhEPO may serve as a potential therapy for the treatment of SAE.

Topics: Animals; Apoptosis; bcl-Associated Death Protein; Brain; Cecum; Cognition; Emotions; Epoetin Alfa; Erythropoietin; Humans; Ligation; Male; Neurons; Neuroprotective Agents; Phosphorylation; Proto-Oncogene Proteins c-akt; Punctures; Rats; Rats, Sprague-Dawley; Recombinant Proteins; Sepsis; Signal Transduction; TOR Serine-Threonine Kinases