Bill I. Wong

Metaanalysis of prophylactic drug treatment in the prevention of postoperative bleeding.

Prophylactic drug treatment is one of several strategies to reduce postoperative blood loss and potentially limit homologous blood use in open heart surgery. A computerized MEDLINE search supplemented with manual bibliography reviews was performed for randomized clinical trials published in peer-reviewed English-language journals from January 1980 to June 1993. A metaanalysis was conducted of trials evaluating desmopressin (group DD, n = 13), epsilon-aminocaproic acid or tranexamic acid (group EA, n = 4), and aprotinin (group AP, n = 16). Eligible studies used placebo controls and administered the drug in a prophylactic manner. The primary study end point was postoperative chest tube loss (mL, mean +/- standard deviation). There was a significant reduction in postoperative chest tube loss detected for each of the active treatments versus the placebo (DD versus controls: percent reduction 0.11, p = 0.0021; EA versus controls: percent reduction 0.30, p < 0.0001; and AP versus controls: percent reduction 0.36, p < 0.0001). Therapy with EA or AP was associated with a greater reduction in chest tube loss than DD (EA versus DD, p = 0.0033, and AP versus DD, p < 0.0001). Secondary study end points were transfusion requirements, chest reexploration, and perioperative mortality. The volume of postoperative red cell transfusion (mean +/- standard deviation) was reduced with EA (p < 0.0001) or AP treatment (p < 0.0001) compared with a placebo or DD, whereas the proportion of patients given transfusions was limited only in the AP-treated patients (odds ratio 0.23; 95% confidence interval, 0.16 to 0.33; p < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Comprehensive Canadian Review of the Off-Label Use of Recombinant Activated Factor VII in Cardiac Surgery

Background— This observational study sought to identify the off-label use pattern of recombinant activated factor VII (rFVIIa) in cardiac surgery and to identify predictors of its effectiveness and risk. Methods and Results— At 18 Canadian centers, 522 nonhemophiliac cardiac surgical patients received rFVIIa during the period 2003 through 2006; data were available, and retrospectively collected, on 503 patients. The median (quartile 1, quartile 3) units of red blood cells transfused from surgery to therapy and in the 24 hours after therapy were 8 (5, 12) and 2 (1, 5), respectively (P<0.0001). Mortality rate was 32%, and mortality or major morbidity rate was 44%. These rates were within expected ranges (mortality, 27% to 35%; mortality or morbidity, 39% to 48%), which were calculated with a separate cohort of cardiac surgical patients who did not receive rFVIIa used as reference. Independent predictors of complications included instability before therapy (multiple inotropes or intra-aortic balloon pump) and increasing red blood cell units transfused before and after therapy. Variables independently associated with nonresponse included abnormal coagulation parameters and >15 red blood cell units transfused before therapy. Conclusions— In Canada, rFVIIa is used primarily when standard interventions have failed to control bleeding. In this setting, rFVIIa is associated with reduced blood product transfusions and, after risk adjustment, does not appear to be associated with increased or decreased complication rates. The effectiveness of the drug may be enhanced if it is given early in the course of refractory blood loss in the setting of adequate amounts of circulating coagulation factors.

Central-nervous-system dysfunction after warm or hypothermic cardiopulmonary bypass

The increasing popularity of warm heart surgery led us to assess the effect of temperature during cardiopulmonary bypass (CPB) on neuropsychological function after coronary surgery. 34 patients enrolled in a randomised trial of normothermic versus hypothermic CPB were subjected to a battery of psychomotor and memory tests before and after their operations. The mean nasopharyngeal temperature for warm CPB was 34.7 (SD 0.5) degrees C and that for hypothermic CPB was 27.8 (2.0) degrees C. In all seven neuropsychological tests the postoperative scores were better in the warm CPB than in the hypothermic group, although only one difference achieved significance (trial-making test A; p less than 0.023). Thus, neurological function after normothermic CPB seems to be no worse than that after hypothermic procedures.

Aprotinin and tranexamic acid for high transfusion risk cardiac surgery

BACKGROUND Studies have shown that aprotinin and tranexamic acid can reduce postoperative blood loss after cardiac operation. However, which drug is more efficacious in a higher risk surgical group of patients, has yet to be defined in a randomized study. METHODS With informed consent, 80 patients undergoing elective high transfusion risk cardiac procedures (repeat sternotomy, multiple valve, combined procedures, or aortic arch operation) were randomized in a double-blind fashion, to receive either high dose aprotinin or tranexamic acid. Patient and operative characteristics, chest tube drainage and transfusion requirements were recorded. RESULTS There was no significant difference between the 2 treatment groups with respect to age, cardiopulmonary bypass time, complications (myocardial infarction, stroke, death), chest tube drainage (6, 12, or 24 hours), blood transfusions up to 24 hours postoperatively, total allogeneic blood transfusions for entire hospital stay, or induction/postoperative hemoglobin levels. However, multiple regression analysis revealed a positive relationship between cardiopulmonary bypass time and 24 hour blood loss in the tranexamic acid group (p = 0.001), unlike the aprotinin group where 24 hour blood loss is independent of cardiopulmonary bypass time (p = 0.423). CONCLUSIONS Overall, there was no significant difference in blood loss, or transfusion requirements, when patients received either aprotinin or tranexamic acid for high transfusion risk cardiac operation. Aprotinin, when given as an infusion in a high-dose regimen, was able to negate the usual positive effect of cardiopulmonary bypass time on chest tube blood loss.

The role of recombinant factor VIIa in on-pump cardiac surgery : Proceedings of the Canadian Consensus Conference

PurposeRecombinant activated factor VII (rFVIIa) is currently not approved by Health Canada or the Food and Drug Administration for treating excessive blood loss in nonhemophiliac patients undergoing on-pump cardiac surgery, but is increasingly being used “off-label” for this indication. A Canadian Consensus Conference was convened to generate recommendations for rFVIIa use in on-pump cardiac surgery.Methods: The panel undertook a literature review of the use of rFVIIa in both cardiac and non-cardiac surgery. Appropriateness, timing, and dosage considerations were addressed for three cardiac surgery indications: prophylactic, routine, and rescue uses. Recommendationswere based on evidencefromtheliterature and derived by consensus following recognized grading procedures.ResultsThe panel recommended against prophylactic or routine use of rFVIIa, as there is no evidence at this time that the benefits of rFVIIa outweigh its potential risks compared with standard hemostatic therapies. On the other hand, the panel made a weak recommendation (grade 2C) for the use of rFVIIa (one to two doses of 35–70 μg·kg-1) as rescue therapy for blood loss that is refractory to standard hemostatic therapies, despite the lack of randomized controlled trial data for this indication.ConclusionsIn cardiac surgery, the risks and benefits of rFVIIa are unclear, but current evidence suggests that its benefits may outweigh its risks for rescue therapy in selected patients. Methodologically rigorous studies are needed to clarify its risk-benefit profile in cardiac surgery patients.ObjectifLe facteur VII activé recombinant (rFVIIa) n’est actuellement approuvé ni par Santé Canada ni par la Food and Drug Administration (FDA) pour le traitement du saignement excessif chez les patients non-hémophiles subissant une chirurgie cardiaque avec circulation extra-corporelle (CEC); néanmoins, il est de plus en plus utilisé de manière ‘non conforme’ pour cette indication. Une Conférence canadienne de consensus s’est réunie afin de rédiger des recommandations quant à l’utilisation du rFVIIa lors de la chirurgie cardiaque avec CEC.MéthodeLe panel a entrepris une revue de la littérature traitant de l’utilisation du rFVIIa en chirurgies cardiaque et non cardiaque. Des considérations quant à la justification, au moment de l’administration et à la posologie ont été évaluées pour trois indications en chirurgie cardiaque: les utilisations prophylactique, de routine ou de sauvetage. Les recommandations, basées sur des données probantes tirées de la littérature, ont été interprétées par un consensus suivant des procédures de gradation reconnues.RésultatsLe panel s’est prononcé contre une utilisation prophylactique ou de routine du rFVIIa, étant donné qu’il n’existe actuellement pas de preuve que les bienfaits du rFVIIa l’emportent sur les risques potentiels encourus en comparaison des thérapies hémostatiques standard. En revanche, le panel a énoncé une recommandation faible (note 2C) en faveur de l’utilisation du rFVIIa (une à deux doses de 35–70 μg·kg-1) comme thérapie de sauvetage en cas de saignement réfractaire aux thérapies hémostatiques standard et ce, malgré le manque de données d’études randomisées contrôlées concernant cette indication.ConclusionEn chirurgie cardiaque, les risques et bienfaits du rFVIIa ne sont pas clairs; toutefois, les données actuelles suggèrent que ses bienfaits pourraient contrebalancer ses risques dans les cas de thérapie de sauvetage chez certains patients. Des études méthodologiquement rigoureuses sont nécessaires afin de clarifier le profil risque/bénéfice du rFVIIa pour les patients de chirurgie cardiaque.

Cardiopulmonary bypass, rewarming, and central nervous system dysfunction

BACKGROUND During cardiopulmonary bypass a nasopharyngeal temperature greater than 38 degrees C at the end of rewarming may indicate cerebral hyperthermia. This could exacerbate an ischemic brain injury incurred during cardiopulmonary bypass. METHODS In a cohort of 150 aortocoronary bypass patients neuropsychologic test scores of 66 patients whose rewarming temperature exceeded 38 degrees C were compared with those who did not. There were no differences between groups with respect to demographic and intraoperative variables. RESULTS A trend was seen for hyperthermic patients to do worse on all neuropsychologic tests in the early postoperative period but not at 3-month follow-up. By analysis of covariance hyperthermic patients did worse on the visual reproduction subtest of the Weschler memory scale at 3 months (p = 0.02), but this difference was not found by linear regression (p = 0.10). CONCLUSIONS We were unable to demonstrate any significant deterioration in patients rewarmed to greater than 38 degrees C in the early postoperative period. The poorer performance in the visual reproduction subtest of the Wechsler memory scale at 3 months in the group rewarmed to more than 38 degrees C is interesting but far from conclusive. Caution with rewarming is still advised pending more in-depth study of this issue.

Ketamine concentrations during cardiopulmonary bypass

PurposeTo describe the serum concentrations of ketamine following a clinically relevant dosing schedule during cardiopulmonary bypass (CPB).MethodsDesign: Prospective case series. Setting: Tertiarycare teaching hospital. Patients: Six patients undergoing coronary artery bypass grafting and over age 60 yr. Intervention: Following induction of anaesthesia each patient received a bolus of ketamine 2 mg· kg−1 followed by an infusion of 50 μg· kg−1 · min−1 which ran continuously until two hours after bypass. Main Outcome Measures: Ketamine serum concentrations were measured at five minutes after bolus, immediately following aortic cannulation, 10 and 20 min on CPB, termination of CPB, termination of the drug infusion and three and six hours after infusion termination.ResultsAt the time of aortic cannulation, ketamine concentrations were 3.11 ± 0.81μg · ml−1, these levels decreased by one third with the initiation of CPB. By the end of CPB the concentrations had returned to levels roughly equivalent to those observed at the time of aortic cannulation. Following cessation of the infusion, ketamine concentration declined in a log-linear fashion with a half-life averaging 2.12 hr. (range 1.38–3.09 hr).ConclusionsThis dosage regimen maintained general anaesthetic concentrations of ketamine throughout the operative period. These levels should result in brain tissue concentrations in excess of those previously shown to be neuroprotective in animals. Thus we conclude that this infusion regimen would be reasonable to use in order to assess the potential neuroprotective effects of ketamine in humans undergoing CPB.RésuméObjectifFaire connaître les concentrations sériques de la kétamine procurées par un schéma posologique approprié à la circulation extracorporelle (CEC).MéthodesType d’étude: Prospective. Endroit: Hôpital de soins tertiaires et d’enseignement. Patients: revascularisation du myocarde chez six patients âgés de plus de 60 ans. Intervention: Après l’induction de l’anesthésie chacun des patients a reçu un bolus de kétamine 2 mg· kg−1 suivi d’une perfusion de 50 μg· kg−1· h−1 en permanence, arrêtée deux heures après l’intervention. Principales mesures de résultats: Les concentrations sériques de kétamine mesurées après la canulation de l’aorte, 10 et 20 min après le début de la CEC, à l’arrêt de la CEC et trois et six heures après l’arrêt de la perfusion.RésultatsLes concentrations de kétamine qui étaient de 3,11 ± 0,81 μg· ml−1 au moment de la canulation de l’aorte ont diminué du tiers avec le début de la CEC. A la fin de la CEC, elles sont revenues à peu près à ce qu ’elles étaient au moment de la canulation de l’aorte. Après l’arrêt de la perfusion, la concentration de la kétamine a diminué de façon linéaire logarithmique avec une demi-vie moyenne de 2,12 h (écart de 1,38 à 3,09h).ConclusionsCe schéma posologique a permis de maintenir des concentrations anesthésiques de kétamine pendant l’intervention. Ces niveaux devraient produire des concentrationscérébrales plus élevées que celles qui ont été démontrées comme neuroprotectrices chez l’animal. Les auteurs concluent que ce schéma devrait être pertinent pour l’évaluation des propriété neuroprotectrices de la kétamine chez les humains qui subissent une CEC.

Cancer informatics in the post genomic era

Cancer informatics in the post genomic era : , Cancer informatics in the post genomic era : , کتابخانه دیجیتال جندی شاپور اهواز