Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The protease inhibitor aprotinin was given a) in experimental septic shock, and b) in patients with hepatic cirrhosis and ascites, since in both conditions, activation of the plasma kallikrein-kinin system is associated with pathological systemic vasodilatation, which may trigger reflex neuroendocrine activation and renal solute retention. Given early in experimental sepsis, aprotinin maintained the arterial pressure, systemic vascular resistance (SVR), creatinine clearance and sodium excretion, all of which fell in controls. Aprotinin also blocked increases in pulmonary artery pressure and plasma renin activity (PRA). Given late in sepsis, aprotinin caused a rapid rise in arterial pressure and SVR towards baseline levels. In cirrhosis, aprotinin increased SVR in patients with low baseline values, and improved glomerular filtration rate, renal plasma flow and sodium excretion in all subjects; PRA was suppressed by aprotinin. Aprotinin reverses pathological systemic vasodilatation in these two conditions, and this is associated with a reduction in renin release and improved renal function.
 ...
PMID:Vasoactive effects of aprotinin. 128 72

Previous studies of experimental sepsis suggested that excessive systemic vasodilatation might be the stimulus to renal hypofiltration and fluid retention in sepsis. Successful therapy for this syndrome requires agents that either act to improve systemic haemodynamics without adverse renal effects, or that act directly on the kidney without impairing circulatory homeostasis. The plasma kallikrein-kinin system is a potent vasodilator pathway, activated by endotoxin. We studied the effect of aprotinin (Trasylol), which inhibits plasma kallikrein, in an ovine model of surgically-induced intra-abdominal sepsis. Given either as an early or late intervention, aprotinin was associated with increased mean arterial pressure and systemic vascular resistance, improved glomerular filtration rate, and increased urinary sodium excretion. In further studies, treatment with the thromboxane synthetase inhibitor, U63,557A (Upjohn), either before or after the surgical induction of peritonitis, was associated with increased glomerular filtration rate and sodium excretion, without any effect on systemic haemodynamics. Logical use of specific antagonists, based on an understanding of the pathophysiology of the septic ARF syndrome, is a desirable strategy.
 ...
PMID:Acute renal failure and sepsis: therapeutic approaches. 752 64

Transfusion risks include the possibility of ABO/Rh incompatibility, sepsis, febrile reactions, immunosuppression, and viral transmission; incidences and consequences of these complications are reviewed. Predonation of autologous blood generally reduces the need for homologous blood by about 30% to 40%, but relatively few coronary artery bypass surgery (CABG) patients predonate blood. Drug products to decrease blood use include 1-deamino-8-D-arginine vasopressin (DDAVP), tranexamic acid, epsilon-aminocaproic acid, and aprotinin. A recent study suggests that a subgroup of patients with abnormal platelet function may benefit from a platelet therapy such as DDAVP. The prophylactic use of tranexamic acid reduces cardiac surgery postoperative blood loss, as measured by chest-tube output, by about 30%; unfortunately, data demonstrating a reduction in transfusion requirements are not available. Aprotinin use is associated with major reductions in blood transfusion requirements. Aprotinin provides platelet protection during cardiopulmonary bypass. Duration of stay in the intensive care unit was not increased by use of aprotinin, thus alleviating some concerns that aprotinin might promote coronary thrombosis. A recent report cites early graft closure as a major concern with aprotinin therapy, but data from other studies show no significant differences in rates of graft closure between patients receiving and those not receiving aprotinin. Routine use of a thromboelastogram with all cardiopulmonary bypass surgery at the University of Washington Hospital has reduced use of blood products by 30%.
 ...
PMID:Cardiac anesthesia risk management. Hemorrhage, coagulation, and transfusion: a risk-benefit analysis. 816 99

Aprotinin is an important member of a family of related protease inhibitors and has many clinically beneficial activities. These inhibitors have multiple functions, but not all of them are mediated by enzyme inhibition. Aprotinin has complex effects on many homeostatic functions including coagulation, platelet function and inflammation. It also has complex interactions with other drug therapies including angiotensin-converting enzyme inhibitors. Since patients with cardiovascular diseases are treated frequently with angiotensin-converting enzyme inhibitors and also often need cardiopulmonary bypass surgery and receive aprotinin, these interactions are potentially significant but often overlooked. Aprotinin is currently used to reduce the amount of transfused homologous blood (during cardiopulmonary bypass surgery) and thus, the risks associated with homologous blood transfusion. Aprotinin also has potential uses in acute pancreatitis, carcinoid tumors, sepsis, and other clinical situations. Future research will provide a definitive answer for the need to employ this inhibitor therapeutically in these situations. Aprotinin also has some potentially adverse effects in the kidney in special circumstances. For example, the use of aprotinin in diabetic patients may be related with an increased risk for renal dysfunction. It has also been associated with thrombosis, inadequate coagulation, and allergic reactions. In balance, the available information indicates that the advantages of its application outweigh its disadvantages in most patients.
 ...
PMID:Aprotinin: a serine protease inhibitor with therapeutic actions: its interaction with ACE inhibitors. 1257 Jul 94

Aprotinin is a potent pharmacological agent that reduces bleeding and limits blood transfusion requirements in current surgical practice. Many studies have been conducted in orthopedic surgery. In several trials performed in total hip replacement (THR) and total knee replacement (TKN) patients, aprotinin only moderately decreased blood-loss-replacement requirements. Conversely, when aprotinin was used in patients at high risk for bleeding (cancer, sepsis, redone surgery), it developed a potent hemostatic activity and decreased blood transfusion significantly. No increase in deep vein thrombosis and pulmonary embolism was observed. The only major side effect could be the potential occurrence of an anaphylactoid reaction. Prophylactic administration of aprotinin should be considered in extensive spine surgery and in high-risk major orthopedic operations. The decision to use aprotinin should be guided by a risk/benefit analysis.
 ...
PMID:Aprotinin and major orthopedic surgery. 1523 43

Aprotinin is a potent pharmacological agent that reduces bleeding. In current surgical practices, the rate of blood transfusions has decreased with the use of aprotinin. Recently, studies using aprotinin have been conducted in orthopedic surgery. Several trials have been performed in patients undergoing total hip replacement and total knee replacement. Aprotinin moderately decreased blood loss in these patients. When aprotinin was used in patients with a high-risk of bleeding (ie, patients with cancer, sepsis, or undergoing reoperation), potent hemostatic activity occurred and the rate of blood transfusions significantly decreased. No increase in deep vein thrombosis and pulmonary embolism was observed. One adverse effect was the potential occurrence of an anaphylactoid reaction. Prophylactic administration of aprotinin should be considered in extensive spine surgery and in high-risk orthopedic operations. The decision to use aprotinin can be guided by a risk/benefit analysis.
 ...
PMID:A direct antifibrinolytic agent in major orthopedic surgery. 1523 56

Studies have shown that antifibrinolytic (aprotinin, tranexamic acid, epsilon-aminocaproic acid) reduce blood loss in orthopedic surgery. However, most lacked sufficient power to evaluate the efficacy and safety on clinical outcomes. This meta-analysis aims to evaluate whether intravenous antifibrinolytics, when compared with placebo, reduce perioperative allogeneic erythrocyte transfusion requirement in adults undergoing orthopedic surgery and whether it might increase the risk of venous thromboembolism. From MEDLINE, EMBASE, and the Cochrane Controlled Trials Register, the authors identified 43 randomized controlled trials in total hip and knee arthroplasty, spine fusion, musculoskeletal sepsis, or tumor surgery performed to July 2005 (for aprotinin, 23 trials with 1,268 participants; tranexamic acid, 20 with 1,084; epsilon-aminocaproic acid, 4 with 171). Aprotinin and tranexamic acid reduced significantly the proportion of patients requiring allogeneic erythrocyte transfusion according to a transfusion protocol. The odds ratio was 0.43 (95% confidence interval, 0.28-0.64) for aprotinin and 0.17 (0.11-0.24) for tranexamic acid. Results suggest a dose-effect relation with tranexamic acid. Epsilon-aminocaproic acid was not efficacious. Unfortunately, data were too limited for any conclusions regarding safety. Although the results suggest that aprotinin and tranexamic acid significantly reduce allogeneic erythrocyte transfusion, further evaluation of safety is required before recommending the use of antifibrinolytics in orthopedic surgery.
 ...
PMID:Do antifibrinolytics reduce allogeneic blood transfusion in orthopedic surgery? 1706 78