Are the risk factors listed in warfarin prescribing information associated with anticoagulation-related bleeding? A systematic literature review.

Warfarin significantly reduces thromboembolic risk, but perceptions of associated bleeding risk limit its use. The evidence supporting the association between bleeding and individual patient risks factors is unclear. This systematic review aims to determine the strength of evidence supporting an accentuated bleeding risk when patients with risk factors listed in the warfarin prescribing information are prescribed the drug. A systematic literature search of MEDLINE and Cochrane CENTRAL was conducted to identify studies reporting multivariate relationships between prespecified covariates and the risk of bleeding in patients receiving warfarin. The prespecified covariates were identified based on patient characteristics for bleeding listed in the warfarin package insert. Each covariate was evaluated for its association with specific types of bleeding. The quality of individual evaluations was rated as 'good', 'fair' or 'poor' using methods consistent with those recommended by the Agency for Healthcare Research and Quality (AHRQ). Overall strength of evidence was determined using the Grading of Recommendations Assessment, Development (GRADE) criteria and categorised as 'insufficient', 'very low', 'low', 'moderate' or 'high'. Thirty-four studies, reporting 134 multivariate evaluations of the association between a covariate and bleeding risk were identified. The majority of evaluations had a low strength of evidence for the association between covariates and bleeding and none had a high strength of evidence. Malignancy and renal insufficiency were the only two covariates that had a moderate strength of evidence for their association with major and minor bleeding respectively. The associations between covariates listed in the warfarin prescribing information and increased bleeding risk are not well supported by the medical literature.

Changes in P-wave dispersion and P-wave duration after open heart surgery are associated with the peak incidence of atrial fibrillation.

BACKGROUND: Increased P-wave dispersion (P-disp) and maximum P-wave duration (P-max) predict the development of atrial fibrillation (AF) in the general population. The present study evaluates the time-dependent relationship of P-disp and P-max after open heart surgery. METHODS AND RESULTS: P-disp and P-max were measured in the perioperative period of open heart surgery (one day before surgery through postoperative day 4). Compared with the baseline, P-max decreased immediately after open heart surgery (112.63 +/- 7.4 ms vs 106.9 +/- 8.2 ms, P =.005). An increase in P-disp was observed between postoperative days 1 and 2 (37.5 +/- 6.8 ms vs 43.1 +/- 4.5 ms, P <.05), and postoperative days 1 and 3 (37.5 +/- 6.8 ms vs 44.1 +/- 6.6 ms, P <.05). There was also an increase in the P-max between postoperative day 1 and 3 (103 +/- 8.3 ms vs 110 +/- 7.7 ms, P <.05). CONCLUSIONS: Nonuniform atrial conduction (P-disp) is greatest on days 2 and 3 after open heart surgery, and the longest atrial conduction time (P-max) is greatest on day 3 after open heart surgery, findings that coincide with the time of greatest risk for AF. (Heart Lung((R)) 2001;30:466-71.)

Oral amiodarone for prevention of atrial fibrillation after open heart surgery, the Atrial Fibrillation Suppression Trial (AFIST): a randomised placebo-controlled trial.

BACKGROUND: Beta-blockers and amiodarone reduce the frequency of atrial fibrillation after open-heart surgery but the effectiveness of oral amiodarone in older patients already receiving beta-blockers is unknown. We have assessed the efficacy of oral amiodarone in preventing atrial fibrillation in patients aged 60 years or older undergoing open-heart surgery. METHODS: We did a randomised, double-blind placebo-controlled trial in which patients undergoing open-heart surgery (n=220, average age 73 years) received amiodarone (n=120) or placebo (n=100). Patients enrolled less than 5 days before surgery received 6 g of amiodarone or placebo over 6 days beginning on preoperative day 1. Patients enrolled at least 5 days before surgery received 7 g over 10 days beginning on preoperative day 5. FINDINGS: Patients on amiodarone had a lower frequency of any atrial fibrillation (22.5% vs 38.0%; p=0.01; absolute difference 15.5% [95% CI 3.4-27.6%]), and there were significant differences in favour of the active drug for symptomatic atrial fibrillation (4.2% vs 18.0%, p=0.001), cerebrovascular accident (1.7% vs 7.0%, p=0.04), and postoperative ventricular tachycardia (1.7% vs 7.0%, p=0.04). Beta-blocker use (87.5% amiodarone vs 91.0% placebo), nausea (26.7% vs 16.0%), 30-day mortality (3.3% vs 4.0%), symptomatic bradycardia (7.5% vs 7.0%), and hypotension (14.2% vs 10.0%) were similar. INTERPRETATION: Oral amiodarone prophylaxis in combination with beta-blockers prevents atrial fibrillation and symptomatic fibrillation and reduces the risk of cerebrovascular accidents and ventricular tachycardia.

An assessment of the safety of short-term amiodarone therapy in cardiac surgical patients with fentanyl-isoflurane anesthesia.

UNLABELLED: In previously published case reports and a retrospective study, investigators have noted that amiodarone may cause substantial hemodynamic instability when combined with fentanyl-containing anesthesia regimens. We performed the present study to evaluate the safety of short-term amiodarone therapy when combined with a fentanyl-containing anesthesia regimen in a randomized, double-blinded, placebo-controlled format. After institutional approval and written informed consent, patients scheduled to undergo coronary artery bypass grafting or valvular surgery were randomly allocated to receive amiodarone (3.4 g over 5 days or 2.2 g over 24 hours) or placebo before surgery. Four indicators for hemodynamic instability were assessed: 1) a net increase in fluid balance during surgery of >2 L; 2) use of dopamine at a rate >10 microg x kg(-1) x min(-1); 3) use of other vasopressive catecholamines; and 4) use of a phosphodiesterase inhibitor or intraaortic balloon pump. Systolic, diastolic, and central venous pressures were measured before fentanyl administration, before cardiopulmonary bypass (CPB), and after separation from CPB. Overall, 84 patients (45 patients in the amiodarone group, 39 in the placebo group) were enrolled and completed the study. There were no significant differences between the two groups in any indicator for hemodynamic instability or the indicators of instability combined. After CPB, there was a significantly lower systolic blood pressure in the amiodarone group compared with the placebo group (112 +/- 12 vs 117 +/- 14 mm Hg; P = 0.049). However, there was a trend toward smaller IV fluid requirements during surgery in the amiodarone group compared with the placebo group (438 +/- 867 vs 907 +/- 1640 mL; P = 0.09). We found no increased risk of hemodynamic compromise after short-term amiodarone therapy among patients receiving a fentanyl-containing anesthesia regimen during open heart surgery. IMPLICATIONS: In previous retrospective studies and case reports, investigators have identified a possible risk of hemodynamic compromise when patients receiving chronic amiodarone therapy are given anesthesia regimens containing fentanyl. We performed a prospective, randomized, double-blinded study to evaluate the hemodynamic effects of short-term amiodarone therapy during fentanyl-isoflurane anesthesia for open heart surgery. No adverse hemodynamic effects of amiodarone were identified.

De novo monomorphic and polymorphic ventricular tachycardia following coronary artery bypass grafting.

We compared de novo monomorphic and polymorphic ventricular tachycardia (VT) occurring after coronary artery bypass graft surgery in 21 patients. Our findings support an underlying arrhythmogenic substrate for de novo monomorphic VT, whereas polymorphic VT is more likely related to transient perioperative abnormalities.

Preoperative immunostimulation with propionibacterium avidum KP-40 in patients with gastric carcinoma: a prospective randomized study.

Sixty-eight patients admitted for resection of gastric carcinoma entered a prospectively randomized trial. Patients in the therapy group (n = 34) received a preoperative controlled infusion of 10 mg Propionibacterium avidum KP-40. The therapy and control group did not differ with regard to postoperative complications, tumor recurrence rates (therapy group: 41%, control group: 38%), and patient survival rates (survival rate in the therapy group after 25 months: 53%, in the control group after 25 months: 50%).

Combination high dose amrinone and dopamine in the management of moribund cardiogenic shock after open heart surgery.

Two patients who suffered severe cardiogenic shock after open-heart surgery were successfully resuscitated with high doses of amrinone and dopamine. Both patients had required cardiopulmonary resuscitation and neither was responsive to more conventional mechanical and pharmacologic intervention. Neither patient suffered any serious side effects and both were eventually discharged from the hospital in good condition. These two case reports suggest the potential for using higher than previously reported doses of amrinone in combination with dopamine for the successful treatment of moribund cardiogenic shock in the post open-heart surgical patient. Further studies are needed to assess whether this high-dose drug combination will be successful in patients who present with severe cardiogenic shock unrelated to the post open-heart surgical setting.

[Preoperative nonspecific immunostimulation with Propionibacterium granulosum KP-45 in patients with colorectal cancer. A prospective randomized study]. / Präoperative unspezifische Immunstimulation mit Propionibacterium granulosum KP-45 bei Patienten mit colorectalem Carcinom. Eine prospektiv randomisierte Studie.

The effect of preoperative unspecific immunomodulation with Propionibacterium granulosum KP-45 (P.g.) on postoperative complications and patient survival was evaluated in a prospectively randomized trial in patients with colorectal tumor resection. Patients of the therapy group (n = 51) received at least 3 days before operation an infusion of 10 mg P.g., patients of the control group (n = 49) were not treated at all. The wound infection rate and the number of re-explorations were significantly lower in the therapy group, however, patient survival and tumor recurrence rates were not positively affected by this P.g. pre-treatment.

Possible recurrence of amiodarone pulmonary toxicity following corticosteroid therapy.

Amiodarone hydrochloride, a new antiarrhythmic agent, has been associated with pulmonary toxicity characterized by cough, dyspnea and diffuse pulmonary infiltrates. We describe a case of fibrosing alveolitis, diagnosed by lung biopsy, in a patient receiving amiodarone which responded to corticosteroid therapy. The pulmonary symptoms recurred after discontinuing corticosteroids, five months after amiodarone was stopped, and were associated with a persistent amiodarone level. To our knowledge, this recurrence of amiodarone pulmonary toxicity has not been reported previously.

Anterior S-T segment depression in acute inferior myocardial infarction: indicator of posterolateral infarction.

Although patients with acute inferior myocardial infarction often manifest S-T segment depression in precordial electrocardiographic leads, the pathophysiologic abnormalities associated with this finding are poorly understood. To examine this problem, electrocardiographic findings on admission were compared with results of radionuclide cineangiography performed within 38 hours of the onset of symptoms in 25 patients with inferior infarction. Summation of S-T depression in leads V1 through V4 permitted the separation of patients into two groups: Group A (11 patients with 0.20 mV or less of S-T depression) and Group B (14 patients with 0.45 vM or more of S-T depression). The radionuclide cineangiogram revealed inferior wall dysfunction in all patients. Additional posterolateral dysfunction was seen in 13 patients, all in Group B. Patients in Group B had a relatively larger infarction (peak creatine kinase Units - 756 +2- 358 in Group A versus 1,566 +/- 983 units in Group B, p less than 0.01) and greater functional impairment (ejection fraction - 45 +/- 12 in Group A versus 33 +/- 12 in Group B, p less than 0.01). The relation between precordial S-T segment depression and posterolateral dysfunction appears to be largely independent of electrocardiographic evidence of "true posterior infarction." Thus moderate or severe anterior precordial S-T depression in patients with acute inferior infarction is a sensitive and specific indicator of relatively extensive myocardial damage, primarily involving the posterolateral region.