Explore the vast range of titles available.

In this clinical trial involving patients undergoing high-risk cardiac surgery, aprotinin was somewhat more effective than either aminocaproic acid or tranexamic acid in reducing massive perioperative bleeding but at the expense of a higher rate of death, mainly from cardiac causes. Aprotinin cannot be recommended to control blood loss in this clinical setting. In patients undergoing high-risk cardiac surgery, aprotinin was somewhat more effective than either aminocaproic acid or tranexamic acid in reducing massive perioperative bleeding but at the expense of a higher rate of death, mainly from cardiac causes. Every year an estimated 1 million to 1.25 million patients worldwide undergo cardiac surgery, including high-risk procedures such as repeat coronary-artery bypass grafting (CABG), valve replacements, and combined procedures. 1 High-risk procedures present an increased risk of death, massive bleeding, renal failure, and thrombotic complications, as compared with first-time isolated CABG. 2 – 4 Three antifibrinolytic agents have been used in cardiac surgery to minimize bleeding and reduce the need for transfusion: aprotinin, a naturally occurring serine protease inhibitor, and two lysine analogues, tranexamic acid and aminocaproic acid. 5 In clinical trials, all three drugs have been shown to be effective in reducing the . . .

The antifibrinolytic agent aprotinin is often used to control blood loss in patients undergoing cardiac surgery. This observational study found that the use of aprotinin is associated with an increased risk of serious end-organ damage. In patients undergoing cardiac surgery, aprotinin should be replaced by aminocaproic acid or tranexamic acid. Aprotinin is often used to control blood loss in patients undergoing cardiac surgery. This observational study found that the use of aprotinin is associated with an increased risk of serious end-organ damage. The mainstay of medical therapy for patients with an acute coronary syndrome — when accompanied by myocardial infarction with ST-segment elevation — includes fibrinolytic and antiplatelet agents to mitigate thrombosis-related events. 1 However, if surgical therapy (coronary-artery surgery) is elected, fibrinolytic agents are not used before, during, or after surgery because of concerns regarding excessive bleeding. In fact, these bleeding-related concerns have given rise to the testing, regulatory approval, and widespread use of two classes of agents, both proven to mitigate bleeding: the lysine analogues (aminocaproic acid and tranexamic acid) and the serine protease inhibitors (aprotinin). Consequently, the majority of patients . . .

In this single-center study, the use of aprotinin in coronary-artery bypass grafting (CABG) was associated with an increase in mortality and worsening renal function. The results concur with those of Schneeweiss et al. in this issue of the Journal, and together these studies raise concern about the safety of aprotinin in CABG. In this single-center study, the use of aprotinin in coronary-artery bypass grafting was associated with an increase in mortality and worsening renal function. Aprotinin (Trasylol, Bayer HealthCare) is an antifibrinolytic agent in widespread use during cardiac surgery around the world, particularly in high-risk patients. Aprotinin was approved by the Food and Drug Administration on December 29, 1993, for use during cardiac surgery, to reduce the risk of blood transfusion. The literature on aprotinin contains reports of single studies ranging in size from 22 patients 1 to 12,403 patients, 2 as well as several meta-analyses and systematic reviews. Dozens of clinical trials have been conducted with this agent since the original report of efficacy of the high-dose regimen was published, 1 yet, as pointed out in a . . .

When bleeding is the consequence of a specific defect of hemostasis, the goal of treatment is to correct the defect. A typical example is the replacement of factor VIII by transfusion in patients with hemophilia. Specific treatment may be impossible, however, because bleeding may result from multiple defects or because no cause can be identified. In such situations, nontransfusional drugs that help to stop bleeding are indicated. 1 These drugs may also be indicated for patients who refuse blood transfusion or for those who undergo surgical procedures associated with large blood losses necessitating many transfusions of donated blood. Many nontransfusional hemostatic . . .

Twenty-four patients with refractory epilepsy on one or more antiepileptic drugs were given additional vigabatrin (1 g twice daily for six weeks, followed by 1.5 g twice daily for a further six weeks) and matched placebo in a double blind, randomised, crossover study. A battery of neuropsychological tests was administered at baseline and at weeks two, six and 12 of both treatment periods. No significant differences were found between vigabatrin and placebo at any time point for any of the objective tests of cognitive function. Patients, however, reported a greater degree of sedation after two and six weeks on vigabatrin than during the equivalent placebo phase (p < 0.01), although no such difference was apparent at 12 weeks. Follow up over a mean of 14.75 months in 12 responders, who continued on vigabatrin, revealed a significant improvement (all p < 0.01) on each of three composite scales (three psychomotor tests, four memory tests, three self rating scales) compared with their scores during the double blind trial. Vigabatrin did not cause cognitive impairment either acutely or in the long term. Phased introduction, however, seems a prudent policy to allow tolerance to early subjective sedation.

Excessive bleeding may complicate cardiac surgery, and is associated with increased morbidity and mortality. Pharmacological strategies to decrease perioperative bleeding have been investigated in a large number of controlled trials, most of which have shown a decrease in blood loss. However, most studies lacked sufficient power to detect a beneficial effect on clinically more relevant outcomes. We did a meta-analysis of all randomised, controlled trials of the three most frequently used pharmacological strategies to decrease perioperative blood loss (aprotinin, lysine analogues [aminocaproic acid and tranexamic acid], and desmopressin). Studies were included if they reported at least one clinically relevant outcome (mortality, rethoracotomy, proportion of patients receiving a transfusion, or perioperative myocardial infarction) in addition to perioperative blood loss. In addition, a separate meta-analysis was done for studies concerning complicated cardiac surgery. We identified 72 trials (8409 patients) that met the inclusion criteria. Treatment with aprotinin decreased mortality almost two-fold (odds ratio 0·55 [95% CI 0·34-0·90]) compared with placebo. Treatment with aprotinin and with lysine analogues decreased the frequency of surgical re-exploration (0·37 [0·25-0·55], and 0·44 [0·22-0·90], respectively). These two treatments also significantly decreased the proportion of patients receiving any allogeneic blood transfusion. By contrast, the use of desmopressin resulted in a small decrease in perioperative blood loss, but was not associated with a beneficial effect on other clinical outcomes. Aprotinin and lysine analogues did not increase the risk of perioperative myocardial infarction; however, desmopressin was associated with a 2·4-fold increase in the risk of this complication. Studies in patients undergoing complicated cardiac surgery showed similar results. Pharmacological strategies that decrease perioperative blood loss in cardiac surgery, in particular aprotinin and lysine analogues, also decrease mortality, the need for rethoracotomy, and the proportion of patients receiving a blood transfusion.

We report a series of 14 cases of psychosis occurring in patients with severe intractable epilepsy, following the prescription of vigabatrin, a new antiepileptic drug. Nine patients had no previous history of psychosis. In eight patients the psychosis occurred following a change in the habitual pattern of seizure activity; in four it developed after a period of seizure freedom followed by a cluster of seizures, and in the other four patients an alternating psychosis was observed. In five patients there was no clear relationship to seizure pattern. Another patient developed psychosis after taking an overdose of between eight and 12 g of vigabatrin. A further three patients, who developed psychosis following vigabatrin withdrawal, were not included in this series. The mean dose at onset of the psychosis (excluding the patient who took an overdose) was 2580 mg, and the period from initiation of therapy to the onset of psychosis varied from five days to 32 weeks (and occurred 24 hours after the overdose of vigabatrin). In all cases the psychosis resolved, but necessitated the withdrawal of vigabatrin, except in the single patient who took the overdose. The mechanism of this behaviour change is unclear, but in some instances may reflect vigabatrin's powerful anti-epileptic action. This is clearly not the case for all patients. Vigabatrin should be started with caution in patients with severe epilepsy, particularly in the presence of a previous history of psychosis, and such patients should be carefully monitored.

A controlled study of the effect of aminocaproic acid 3 g six-hourly taken by mouth during menstruation was carried out on 56 women for eight months from the time of insertion of a Lippes D intrauterine device (IUD). Thirty-five women presenting with menorrhagia in association with an IUD were also treated during three out of six consecutive menses. A highly significant reduction in menstrual loss was observed during treatment in both groups.

Ten patients who developed a major depressive episode in association with vigabatrin treatment for intractable epilepsy are reported. The depression usually occurred early in the course of treatment, but when delayed followed a recent increase in dose. Depressive symptoms occurred at doses varying between 1.5 g and 4 g a day, often but not always when patients were experiencing a decrease in their seizure frequency. Most patients had a history of affective disturbance, sometimes in association with other GABAergic drugs. The observations support a possible role for GABAergic mechanisms in the biology of mood disorders.