Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Between September 1992 and April 1995, 19 patients at the authors' institution received pneumatic, pulsatile left ventricular assist devices (LVADs) for bridging to cardiac transplantation. The mean (+/- SD) age of the patients was 51 +/- 14 years (range, 19-64 years). Nine (47%) patients had end-stage idiopathic cardiomyopathy, five (26%) had ischemic cardiomyopathy, and five (26%) other recipients were in cardiogenic shock caused by acute myocardial infarction (AMI). Fifteen (79%) patients were supported with an intraaortic balloon pump or centrifugal LVAD at the time of LVAD insertion (duration, 5.5 +/- 4.1 days). Aprotinin was given to limit bleeding; heparin, followed by warfarin sodium, was used for anticoagulation. A vigorous exercise and nutrition protocol was followed. Cardiac index averaged 2.94 +/- 0.87 L/min/m2 immediately after the implantation procedure. No patient required placement of a right VAD. Average duration of LVAD support was 45 +/- 39 days (range, 3-153 days). Major complications included bleeding requiring reoperation (three patients); cerebrovascular accident (three patients); and severe dysrhythmias requiring direct current cardioversion (four patients). Fourteen (74%) patients underwent transplantation, with one patient still being mechanically supported. All of the patients receiving transplants were discharged from the hospital. Of the individuals who died while supported with the LVAD, 75% were patients with AMI. Timely application of LVADs as part of the interdisciplinary management of end-stage heart disease has generated excellent results for transplant candidates. Right ventricular dysfunction has not necessitated right VAD placement in the authors' experience. Patients with AMI have a higher risk of death while being supported with the device than do more chronically ill recipients.
 ...
PMID:Long-term left ventricular assist device use before transplantation. 857 61

The frequency and severity of central nervous system complications in patients undergoing cardiopulmonary bypass (CPB) may be greater than previously thought, particularly in the older population. The risks of embolic neurologic complications and stroke in the population older than 70 years from a severely atherosclerotic ascending aorta are well documented. Moreover, while the majority of CPB patients do not experience perioperative stroke, a high incidence of more subtle central nervous system dysfunction has been demonstrated to persist for up to 1 year after surgery. This report reviews the incidence and severity of cerebral injury during CPB and the effects of both age and the severely atherosclerotic ascending aorta on adverse neurologic outcomes. It discusses perioperative diagnostic methods, including transesophageal echocardiography, periaortic echocardiography, transcranial Doppler, and retinal fluorescein angiography, and the benefit of pH management. Ischemic brain injury resulting from activation of injury-related enzymes as part of the systemic inflammatory response is briefly reviewed. Age has been shown to be the strongest predictor of neurologic sequelae in patients undergoing CPB. The risk of embolic complications in the brain also increases in proportion to the degree of atherosclerosis in the ascending aorta, which is age-related. Transesophageal echocardiography has been found to be only partly useful in diagnosing these lesions or in guiding surgical manipulations in comparison with epiaortic imaging, which is more discreet. Transcranial Doppler and retinal fluorescein angiography have provided further evidence of microemboli during surgical manipulations. In a 316-patient prospective study, we found no differences in outcome between pH-stat and alpha-stat strategies during moderate hypothermic CPB, except in patients who were on bypass for more than 90 minutes. Approximately 90% of these had a significant reduction in cognitive impairment with the alpha-stat method. Aprotinin, a serine protease inhibitor, has been found in two separate, randomized, placebo-controlled trials to significantly lower incidences of perioperative stroke. Further study to develop therapeutic and preemptive strategies for prevention of brain injury is required, especially in the elderly. Aprotinin and other modalities aimed at suppressing the inflammatory response to CPB may offer hope because they act to suppress injury-provoking enzymes and leukocyte activation that are, in part, responsible for organ system dysfunction following CPB.
 ...
PMID:Etiology and incidence of brain dysfunction after cardiac surgery. 1046 44

This article discusses evidence for the role of pharmacological interventions such as the protease inhibitor aprotinin (Trasylol), lysine analogue anti-fibrinolytics [tranexamic acid (Cyclokapron) and epsilon aminocaproic acid (Amicar)], DDAVP (Desmopressin) and recombinant Factor VIIa (NovoSeven), in preventing the need for blood and blood-component therapies after major (cardiac, hepatic and orthopaedic/trauma) surgery. The data show that aprotinin is consistently effective in reducing globally the transfusion burden in cardiac and hepatic surgical procedures. However, there are little data to support its use in routine elective orthopaedic surgery. Multiple studies have failed to show an increased risk for myocardial ischaemia or infarction with aprotinin, and there may even be a reduced incidence of perioperative stroke in patients undergoing cardiac surgery. An increased probability of a hypersensitivity reaction when the drug is readministered within a 6-month period remains a significant issue. The data for the lysine analogue anti-fibrinolytics show no evidence of efficacy in reducing the transfusion burden for epsilon aminocaproic acid and inconsistent results with tranexamic acid in cardiac and hepatic surgery. As with aprotinin therapy, there is a paucity of data to support their use in routine elective orthopaedic surgery. There are no data to support the routine use of DDAVP to reduce the transfusion burden. Limited data suggest that this drug may be effective when a defect in platelet function is demonstrated. This aspect deserves further investigation. Recombinant activated Factor VII (rFVIIa) has proven benefit for its licensed indication to reduce bleeding in haemophiliacs with inhibitors to Factors VIII and IX. Reports of benefit in other instances are largely anecdotal. Hence, at this time it is therefore speculative and premature to suggest whether there is a place for this agent in routine clinical practice. No adequately powered, placebo-controlled prospective studies are available to investigate the safety of the lysine analogues, DDAVP or rFVIIa in cardiac, hepatic or orthopaedic surgery.
 ...
PMID:Pharmacological approaches to reducing allogeneic blood exposure. 1254 28

Aprotinin is a serine protease inhibitor with antithrombotic, antifibrinolytic, and antiinflammatory effects. It is effective in reducing bleeding and the need for blood transfusions after cardiac surgery with cardiopulmonary bypass. Additional benefits, such as cerebral protection, are hypothesized but not yet thoroughly substantiated. The safety of aprotinin has been questioned based on a phase IV analysis of large data sets, including patients undergoing cardiac surgery. Potential risks including increased occurrences of stroke, myocardial infarction, renal failure, and death are implied by these analyses; however, adequate study group matching is lacking from these nonrandomized, retrospective studies. In October 2007, a large randomized controlled trial comparing antifibrinolytics in patients undergoing cardiac surgery was stopped after a preliminary analysis suggested a trend toward an increase in all-cause 30-day mortality associated with aprotinin. Subsequently, the manufacturer of aprotinin temporarily suspended marketing and halted all shipment of aprotinin on a worldwide basis. Pending a complete analysis of this study, the use of aprotinin could be considered as one component of a blood conservation strategy. After contemplating the benefits and risks of this controversial drug, clinicians should reserve its use for patients at high risk for postoperative blood loss.
 ...
PMID:Benefits and risks of aprotinin use during cardiac surgery. 1815 81

The use of aprotinin in cardiac surgery to reduce perioperative bleeding and transfusion is controversial. We assessed the effect of aprotinin on the risk of acute renal failure in 423 patients who underwent on-pump cardiac surgery between January 1, 2005 and December 31, 2006. Of these 423 patients, 318 (75.2%) received aprotinin (median dose=3.0 million KIU, standard deviation=2.8 million KIU; interquartile range: 2 million KIU to 4 million KIU). Aprotinin was more likely to be used in patients who did not cease aspirin before surgery, in urgent or emergency surgery, who had impaired left ventricular function, a longer period of bypass and aortic cross-clamp time, and with both coronary artery bypass graft and valvular surgery performed. The overall incidence of acute renal failure requiring dialysis was 2.8%. The use of aprotinin was not associated with a reduction in transfusion nor an increased risk of renal failure requiring dialysis, atrial fibrillation, cerebrovascular accident or mortality in the univarate analyses. In the multivariate analysis, only preoperative serum creatinine concentration (odds ratio [OR] 1.06 per 10 micromol/l increment in creatinine, 95% confidence interval [CI]: 1.01 to 1.14, P=0.029) and urgency of the surgery (urgent vs. scheduled surgery: OR 12.8, CI: 2.3 to 70.8, P=0.004; emergency vs. scheduled surgery: OR 23.1, CI: 3.0 to 180.2, P=0.003) were significantly associated with an increased risk of acute renal failure requiring dialysis. The use of low-dose aprotinin did not significantly reduce perioperative transfusion requirements and was not a significant risk factor for acute renal failure requiring dialysis in our patients.
 ...
PMID:The effect of aprotinin on risk of acute renal failure requiring dialysis after on-pump cardiac surgery. 1856 98