Oliver, William C.

Background The US Food and Drug Administration issued a black box warning regarding the use of droperidol and the potential for torsade de pointes (TdP). Methods The primary objective of this retrospective study was to determine whether low-dose droperidol administration increased the incidence of TdP in the general surgical population during a 3-yr time period before and after the Food and Drug Administration black box warning. A random sample of 150 surgical patients during each time interval was selected to estimate the droperidol use for each time period. Results During the time period before the black box warning (July 1, 1998 to June 30, 2001), 2,321/139,932 patients (1.66%) had QT prolongation, TdP, or death within 48 h after surgery. We could identify no patients who clearly developed TdP before the black box warning. There was one patient for whom the cause of death could not positively be ruled out as due to TdP. In the time period after the black box warning (July 1, 2002 to June 30, 2005), 2,207 patients (1.46%) had documented QT prolongation, TdP, or death within 48 h after surgery, including only two cases (<0.1%) of TdP. The incidence of droperidol exposure was approximately 12% (exact 95% confidence interval, 7.3-18.3%) before the black box warning and 0% after placement of the black box warning on droperidol. Therefore, we estimate that approximately 16,791 patients (95% confidence interval, 10,173-25,607) were exposed to droperidol, none of whom experienced documented TdP. Conclusions This indicates that the Food and Drug Administration black box warning for low dose droperidol is excessive and unnecessary.

Compared with adults, infants and children who undergo cardiopulmonary bypass for cardiac surgery present with a myriad of anticoagulation considerations. Inadequate anticoagulation during cardiopulmonary bypass may cause “subclinical” or “overt” thrombosis, while effective anticoagulation decreases excessive bleeding and transfusions. Current strategies for heparinization and its neutralization in pediatric patients undergoing congenital heart repair requiring cardiopulmonary bypass are examined. The coagulation system of the neonate and infant is immature and is further weakened by congenital heart disease. Changes in coagulation and fibrinolytic activity occur during cardiopulmonary bypass as a result of hemodilution and exposure of the blood to the extracorporeal circuit. Adequate anticoagulation is essential to minimize the thrombin generation that will result. The extent of excessive thrombin formation in pediatric patients undergoing cardiopulmonary bypass is better appreciated today than in the past, but no controlled study defines the optimal dose or technique for heparin dosing in these patients. Heparin concentration may even fall to 1.5 U/mL during cardiopulmonary bypass. However, the activated clotting time and heparin concentration correlate poorly. The ideal method to achieve adequate thrombin inhibition is unknown. Additionally, the dangers of excessive protamine are becoming more apparent. Heparin continues to be the most effective agent to achieve anticoagulation and protamine the most effective agent to neutralize it. A technique for heparin and protamine dosing with determination of heparin concentrations, may remove many variables associated with pediatric cardiac surgery that requires cardiopulmonary bypass and may provide clinicians with new therapies to achieve better anticoagulation for patients and consequently better outcomes.

Background Activation of the inflammatory cascade is thought to account for some of the respiratory dysfunction and prolonged mechanical ventilation associated with cardiopulmonary bypass. The objective of this investigation was to identify whether perioperative steroids or hemofiltration during cardiopulmonary bypass, by their attenuation of inflammation, would reduce duration of mechanical ventilation after cardiac surgery. Methods After Institutional Review Board approval and informed consent, 192 patients scheduled to undergo elective primary coronary artery bypass grafting or valvular replacement or repair were randomized in a double-blind prospective study into three groups. One group (Control) received saline at induction and at 6-h intervals for four doses. Another group (Hemofil) received saline and hemofiltration to obtain 27 ml/kg of hemofiltrate. The final group (Steroid) received 1 g methylprednisolone before anesthesia induction and then 4 mg of dexamethasone at 6-h intervals for four doses. All patients underwent normothermic cardiopulmonary bypass and received propofol for postoperative sedation. Separate two-sample comparisons were performed to compare each experimental group versus the control group using the Wilcoxon rank sum test for continuous variables and Fisher exact test for categorical variables. In all cases, two-tailed P values </= 0.05 were considered statistically significant. Results The median time until the patient reached an intermittent mandatory ventilation of 4/min (258.5 versus 385.0 min, respectively; P = 0.02) and tracheal extubation (352.0 versus 518.0 min; P = 0.03) was significantly reduced for group Hemofil but no different for Steroid compared to Control. Conclusions Hemofiltration and steroids are both previously reported to attenuate the inflammatory response but only hemofiltration reduced time to tracheal extubation for adults after cardiopulmonary bypass in this study.

Background Aprotinin and tranexamic acid are routinely used to reduce bleeding in cardiac surgery. There is a large difference in agent price and perhaps in efficacy. Methods In a prospective, randomized, partially blinded study, 168 cardiac surgery patients at high risk for bleeding received either a full-dose aprotinin infusion, tranexamic acid (10-mg/kg load, 1-mg x kg(-1) x h(-1) infusion), tranexamic acid with pre-cardiopulmonary bypass autologous whole-blood collection (12.5% blood volume) and reinfusion after cardiopulmonary bypass (combined therapy), or saline infusion (placebo group). Results There were complete data in 160 patients. The aprotinin (n = 40) and combined therapy (n = 32) groups (data are median [range]) had similar reductions in blood loss in the first 4 h in the intensive care unit (225 [40-761] and 163 [25-760] ml, respectively; P = 0.014), erythrocyte transfusion requirements in the first 24 h in the intensive care unit (0 [0-3] and 0 [0-3] U, respectively; P = 0.004), and durations of time from end of cardiopulmonary bypass to discharge from the operating room (92 [57-215] and 94 [37, 186] min, respectively; P = 0.01) compared with the placebo group (n = 43). Ten patients in the combined therapy group (30.3%) required transfusion of the autologous blood during cardiopulmonary bypass for anemia. Conclusions The combination therapy of tranexamic acid and intraoperative autologous blood collection provided similar reduction in blood loss and transfusion requirements as aprotinin. Cost analyses revealed that combined therapy and tranexamic acid therapy were the least costly therapies.