Can N-acetylcysteine reverse the antiplatelet effects of clopidogrel? An in vivo and vitro study.

BACKGROUND: The active metabolite of clopidogrel binds the P2Y12 ADP receptor on the platelet surface via a disulfide bond. N-Acetylcysteine (NAC) is able to reduce disulfide bonds. We postulated that NAC might reverse clopidogrel's effect on platelets. METHODS: Two groups of patients were investigated. Group 1 included 11 patients with stable coronary disease who, after discontinuation of aspirin, received 14 days of clopidogrel, 75 mg/day. Bleeding time and whole-blood platelet aggregometry (with 5 micromol/L ADP) were compared before and after the 14 days. Patients were then treated with 6 g of NAC orally, followed by repeat measurement of bleeding time and aggregometry. In group 2, 14 patients were treated with clopidogrel (300 mg) and aspirin before a percutaneous coronary intervention. Blood was drawn 22 +/- 3 hours later and divided into 2 samples. One was sent immediately for platelet-rich plasma aggregometry (using 5 and 2 micromol/L ADP, collagen, and arachidonic acid as agonists), thromboelastography, and aggregometry using the Plateletworks assay (Helena Laboratories, Beaumont, Tex). The other sample was treated with NAC (500 mg/L), after which these same platelet function tests were performed. RESULTS: In group 1, NAC therapy did not significantly change the bleeding time or results of aggregometry. In group 2, neither aggregometry nor the Plateletworks assay suggested reversal of inhibition by NAC. CONCLUSIONS: These studies reveal that a large dose of NAC does not reduce inhibition of platelet aggregation by clopidogrel in vitro or in vivo.

Intraoperative hyperglycemia and perioperative outcomes in cardiac surgery patients.

OBJECTIVE: To estimate the magnitude of association between intraoperative hyperglycemia and perioperative outcomes in patients who underwent cardiac surgery. PATIENTS AND METHODS: We conducted a retrospective observational study of consecutive adult patients who underwent cardiac surgery between June 10, 2002, and August 30, 2002, at the Mayo Clinic, a tertiary care center in Rochester, Minn. The primary independent variable was the mean intraoperative glucose concentration. The primary end point was a composite of death and infectious (sternal wound, urinary tract, sepsis), neurologic (stroke, coma, delirium), renal (acute renal failure), cardiac (new-onset atrial fibrillation, heart block, cardiac arrest), and pulmonary (prolonged pulmonary ventilation, pneumonia) complications developing within 30 days after cardiac surgery. RESULTS: Among 409 patients who underwent cardiac surgery, those experiencing a primary end point were more likely to be male and older, have diabetes mellitus, undergo coronary artery bypass grafting, and receive insulin during surgery (P< or =.05 for all comparisons). Atrial fibrillation (n=105), prolonged pulmonary ventilation (n=53), delirium (n=22), and urinary tract infection (n=16) were the most common complications. The initial, mean, and maximal intraoperative glucose concentrations were significantly higher in patients experiencing the primary end point (P<.01 for all comparisons). In multivariable analyses, mean and maximal glucose levels remained significantly associated with outcomes after adjusting for potentially confounding variables, including postoperative glucose concentration. Logistic regression analyses indicated that a 20-mg/dL increase in the mean intraoperative glucose level was associated with an increase of more than 30% in outcomes (adjusted odds ratio, 1.34; 95% confidence Interval, 1.10-1.62). CONCLUSION: Intraoperative hyperglycemia is an independent risk factor for complications, including death, after cardiac surgery.

Approaching patient engagement in research: what do patients with cardiovascular disease think?

Movement toward patient-centered health care must be supported by an evidence base informed by greater patient engagement in research. Efforts to better understand patients' interest in and perspectives on involvement in the research process are fundamental to supporting movement of research programs toward greater patient engagement. We describe preliminary efforts to engage members of a community group of patients living with heart disease to better understand their interest and perspectives on involvement in research. A semi-structured focus group guide was developed to probe willingness to participate in the following three phases of research: preparation, execution, and translation. The focus group discussion, and our summary of key messages gleaned from said discussion, was organized around the phases of research that patients may be involved in, with the goal of delineating degrees of interest expressed for engagement in each phase. Consistent with what is known from the literature, a clear preference for engagement during the preparation and translation phase of the research process emerged. This preliminary conversation will guide our ongoing research efforts toward greater inclusion of patients throughout the research process.

Variability of plasma aprotinin concentrations in pediatric patients undergoing cardiac surgery.

OBJECTIVES: Infants and children undergoing cardiopulmonary bypass for repair of congenital heart defects are at substantial risk for excessive bleeding, contributing greatly to morbidity and mortality. Aprotinin significantly reduces bleeding and transfusion requirements in adults but is of indeterminate value for pediatric patients. The aim of this study was to determine plasma aprotinin concentrations in these patients with a functional aprotinin assay. METHODS: Thirty patients less than 16 years of age scheduled for cardiac surgery with aprotinin were enrolled. Aprotinin was administered as a 25,000 KIU/kg bolus, 35,000 KIU/kg cardiopulmonary bypass prime, and 12,500 KIU.kg(-1).h(-1) continuous infusion. Blood samples for aprotinin concentrations (kallikrein-inhibiting units/milliliter) were obtained before aprotinin; 5 minutes post-bolus; 5 minutes after cardiopulmonary bypass initiation; 30 and 60 minutes on cardiopulmonary bypass; on discontinuation of aprotinin; 1 hour after aprotinin discontinuation; and 4 hours after permanent separation from cardiopulmonary bypass. For analysis, patients were grouped according to weight (<10 kg, 10-20 kg, >20 kg). Differences between weight groups were assessed using an exact test for categoric variables and 1-way analysis of variance for continuous variables. RESULTS: Aprotinin concentrations differed significantly across weight groups. Five minutes after aprotinin bolus and initiation of cardiopulmonary bypass, there was significant correlation between weight and aprotinin concentration (r =.57, P =.003; r =.69, P =.001, respectively). CONCLUSION: A functional assay reveals significant variability in aprotinin concentration for pediatric patients using current weight-based aprotinin dosing. Additional investigation is necessary to determine target aprotinin concentration dosing regimens to provide better efficacy.

Microporous Polysaccharide Hemospheres do not enhance abdominal infection in a rat model compared with gelatin matrix.

BACKGROUND: Residual topical hemostatic material can serve as a nidus for infection or enhance infection in an already contaminated wound. A newly approved agent, Microporous Polysaccharide Hemospheres (MPH) (Arista AH), has rapid degradation properties, which may reduce the chance of surgical site infection. MATERIALS AND METHODS: With institutional approval, 170 Wister rats underwent standardized anesthesia and abdominal surgery. An Echerichia coli inoculum was added to the incision, and MPH, gelatin matrix, or no agent (control) was placed in the site. After 72 h, the animals were sacrificed, and colony-forming units (cfu)/g were counted in the harvested tissue. RESULTS: Application of gelatin matrix resulted in more cfu/g of tissue and an 87% infection rate, with fewer cfu/g of tissue and a 14% and 24% infection rate in the control and MPH groups, respectively. CONCLUSION: The use of MPH in this rat abdominal infection model did not enhance infection. Gelatin matrix was associated with a greater infection rate than MPH. The rapid degradation of MPH may account for these results, making it a good hemostat in the presence of infective sources.

An in vitro study comparing the effects of Hextend, Hespan, normal saline, and lactated ringer's solution on thrombelastography and the activated partial thromboplastin time.

OBJECTIVE: The purpose of this study was to determine if 6% HES 450/0.7 (hydroxyethyl starch 450/0.7) in normal saline (Hespan) and 6% HES 450/0.7 in lactated Ringer's solution (Hextend) have the same inhibition of the intrinsic coagulation pathway and platelet function. Multiple studies have suggested that 6% Hespan inhibits coagulation and increases chest tube drainage and transfusion requirements in cardiac surgical patients. There have been few studies of the effects of 6% Hextend, a relatively new plasma volume expander, on coagulation and the results thus far have been mixed. DESIGN: A prospective in vitro study. SETTING: A large academic medical center. PARTICIPANTS: Blood was collected from 30 healthy volunteers. Interventions : The blood was fractionated and diluted by 30% with Hextend, Hespan, normal saline, and lactated Ringer's solutions, with a native sample for a control. MEASUREMENTS AND MAIN RESULTS: Primary outcome measures were thromboelastography and activated partial thromboplastin time (APTT). For each of the TEG parameters, there was no difference between samples diluted with Hextend compared with Hespan (p > or = 0.112 in all cases). APTT did not differ significantly between samples diluted with Hextend compared with Hespan (p = 0.562). CONCLUSIONS: This prospective in vitro study suggests that Hextend and Hespan, hydroxyethyl starch 450/0.7 in different base solutions, exhibit the same effect on platelet function as measured by the TEG.