Outcomes Following Three-Factor Inactive Prothrombin Complex Concentrate Versus Recombinant Activated Factor VII Administration During Cardiac Surgery.

OBJECTIVE: To compare outcomes following inactive prothrombin complex concentrate (PCC) or recombinant activated factor VII (rFVIIa) administration during cardiac surgery. DESIGN: Retrospective propensity-matched analysis. SETTING: Academic tertiary-care center. PARTICIPANTS: Patients undergoing cardiac surgery requiring cardiopulmonary bypass who received either rFVIIa or the inactive 3-factor PCC. INTERVENTIONS: Outcomes following intraoperative administration of rFVIIa (263) or factor IX complex (72) as rescue therapy to treat bleeding. MEASUREMENTS AND MAIN RESULTS: In the 24 hours after surgery, propensity-matched patients receiving PCC versus rFVIIa had significantly less chest tube outputs (median difference -464 mL, 95% confidence interval [CI] -819 mL to -110 mL), fresh frozen plasma transfusion rates (17% v 38%, p = 0.028), and platelet transfusion rates (26% v 49%, p = 0.027). There were no significant differences between propensity-matched groups in postoperative stroke, deep venous thrombosis, pulmonary embolism, myocardial infarction, or intracardiac thrombus. Postoperative dialysis was significantly less likely in patients administered PCC versus rFVIIa following propensity matching (odds ratio = 0.3, 95% CI 0.1-0.7). No significant difference in 30-day mortality in patients receiving PCC versus rFVIIa was present following propensity matching. CONCLUSIONS: Use of rFVIIa versus inactive PCCs was significantly associated with renal failure requiring dialysis and increased postoperative bleeding and transfusions.

Surgical and Patient Risk Factors for Severe Arterial Line Complications in Adults.

BACKGROUND: Prior research has provided inconsistent data regarding the risk factors associated with complications from arterial cannulation. The goal of this study was to clearly define the incidence and risks factors associated with arterial cannulation complications. METHODS: After obtaining institutional review board approval, all patients requiring arterial line placement with documentation were included in this retrospective study between January 1, 2006, and December 31, 2012. Leveraging two robust data warehouses, the Perioperative DataMart and the Mayo Clinic Life Silences System, the authors cross-matched arterial line cannulation with a documented vascular consult, neurologic consult, infection, or return to surgery within 30 days in order to identify the initial patient population. RESULTS: A total of 62,626 arterial lines were placed in 57,787 patients, and 90.1% of the catheters placed were 20-gauge catheters. The radial artery was cannulated in 94.5% of patients. A total of 21 patients were identified as having experienced vascular complications or nerve injuries, resulting in a complication rate of 3.4 per 10,000 (95% CI, 2.1 to 5.1). Cardiac surgery had the largest number of catheters placed (n = 15,419) with 12 complications (complication rate = 7.8 per 10,000; 95% CI, 4.0 to 13.6). The rate of complications differed significantly (P < 0.001) across the three most common catheter sizes (2.7 per 10,000 [95% CI, 1.5 to 4.4] for 20 gauge, 17.2 per 10,000 [95% CI, 4.7 to 43.9] for 18 gauge, and 9.4 per 10,000 [95% CI, 1.1 to 34.1] for 5 French). CONCLUSION: In a large retrospective study, the authors document a very low rate of complications with arterial line placement.

Coagulation Parameter Thresholds Associated with Non-Bleeding in the Eighth Hour of Adult Cardiac Surgical Post-Cardiotomy Extracorporeal Membrane Oxygenation.

Excessive bleeding and allogeneic transfusion during adult post-cardiotomy venoarterial extracorporeal membrane oxygenation (ECMO) are potentially harmful and expensive. Balancing the inhibition of clotting and distinguishing surgical from non-surgical bleeding in post-operative period is difficult. The sensitivity of coagulation tests including Thromboelastography(®) (TEG) to predict chest tube drainage in the early hours of ECMO was examined with the use of receiver-operating characteristics (ROC). The results are useful to incorporate in clinical evidence-based algorithms to guide management decisions. In the eighth hour of ECMO, 26 of the 53 adult patients (49%) studied were identified as non-bleeders (less than 2.0 mL/kg/h). All had experienced various types of cardiac surgical procedures. Fifty-two percent were female and the group was 54 ± 19 (mean ± 1 SD) years old. The coagulation parameter threshold with the maximum sensitivity and specificity to predict non-bleeding at 8 hours on ECMO was the kaolin plus heparinase TEG maximum amplitude (KH-TEG MA) at a significant ROC threshold (t) > 50 mm. The activated partial thromboplastin time (aPTT) t < 49 seconds, KH-TEG alpha-angle t > 51°, and the kaolin activated clotting time (ACT) t < 148 seconds were sensitive predictors of non-bleeders. The whole-blood KH-TEG MA was superior to the plasma-based aPTT or International Normalization Ratio (INR) to predict bleeding in the eighth hour of ECMO. Using coagulation laboratory thresholds that predict non-bleeding can begin a process of identifying patients earlier that are likely to bleed. Awareness of these parameter thresholds may improve care through patient protection from unnecessary transfusion and prolonging the life of the ECMO circuit. An algorithm incorporating the ROC thresholds was created to help recognize surgical bleeding to minimize unnecessary transfusions.

Transfusion errors: causes, incidence, and strategies for prevention.

PURPOSE OF REVIEW: Miss-transfusion of blood has become one of the leading causes of death related to blood transfusion. New technology is able to better prevent miss-transfusions than older methods. RECENT FINDINGS: New computer-based technology is available and is very effective in preventing miss-transfusion of blood. SUMMARY: Humans make errors. New technology can prevent those errors.

Does low-dose droperidol increase the risk of polymorphic ventricular tachycardia or death in the surgical patient?

BACKGROUND: The Food and Drug Administration issued a black box warning regarding the use of droperidol and the potential for torsade de pointes. METHODS: The primary objective of this retrospective study was to determine if low-dose (0.625 mg) droperidol administration was associated with episodes of torsade de pointes in the general surgical population during the 3-yr period following the reinstitution of droperidol to our institutional formulary. RESULTS: The authors identified 20,122 surgical patients who received 35,536 doses of droperidol. These patients were cross-matched with an electrocardiogram database and an adverse outcome database. The charts of 858 patients were reviewed, including patients with documentation of prolonged QTc (>440 ms) from March 2007 to February 2011, polymorphic ventricular tachycardia (VT) within 48 h of receiving droperidol, or death within 7 days of receiving droperidol. Twelve surgical patients had VT (n = 4) or death (n = 8) documented within 48 h of droperidol administration. No patients developed polymorphic VT or death due to droperidol administration (n = 0). The eight patients that died were on palliative care. The four patients with documented VT had previous cardiac conditions: two had pre-existing implantable cardiac defibrillators, three had episodes of VT before receiving droperidol, and another had pre-existing hypertrophic obstructive cardiomyopathy. The authors found 523 patients with a documented QTc >440 ms before receiving droperidol. No patients developed VT or death as a direct result of droperidol administration. CONCLUSIONS: Our evidence suggests that low-dose droperidol does not increase the incidence of polymorphic VT or death when used to treat postoperative nausea and vomiting in the surgical population.

Outcomes of general anesthesia for noncardiac surgery in a series of patients with Fontan palliation.

OBJECTIVES: To describe the experience of a single, tertiary care institution in the care of patients with Fontan physiology undergoing anesthesia for noncardiac surgery. BACKGROUND: The Fontan procedure was developed in 1971 to palliate patients with univentricular cardiac physiology leading to long-term survival of these patients, who may now present as adults for noncardiac surgery. METHODS: We retrospectively reviewed the medical records of Fontan patients 16 years and older who underwent general anesthesia for noncardiac surgery at Mayo Clinic in Rochester, Minnesota. Preoperative data, perioperative course, intraoperative and postoperative hemodynamic, pulmonary, cardiovascular, and renal complications were described. RESULTS: Thirty-nine general anesthetics were administered to 31 patients for noncardiac surgery after Fontan palliation. Perioperative complications occurred in 12 of the 39 (31%) noncardiac surgeries, and there was one postoperative death that occurred on day 13 after ventral hernia repair. The two patients who had complications that did not resolve (long-term dialysis and death) had ejection fractions well below the mean for the group (22% and 28%). CONCLUSION: It may be more appropriate for Fontan patients to undergo anesthesia for noncardiac surgery in a tertiary institution, particularly patients with an ejection fraction of <30%. Intraoperative arterial blood pressure monitoring and overnight admission are likely appropriate for most cases.

A prospective, randomized, double-blind trial of 3 regimens for sedation and analgesia after cardiac surgery.

OBJECTIVE: The aim of this study was to evaluate cardiac risk as a consideration for selecting postoperative sedation and analgesia regimens used for cardiac surgical patients requiring cardiopulmonary bypass and early extubation. DESIGN: An observer-blind, randomized, controlled trial. SETTING: A tertiary referral medical center involving an intensive care unit. PARTICIPANTS: One hundred forty-five adults requiring elective cardiac surgery. INTERVENTIONS: Patients were stratified preoperatively as low, moderate, or high cardiac risk based on established criteria and then assigned to 1 of 3 postoperative regimens: propofol infusion beginning at 25 µg/kg/min and morphine boluses (P), fentanyl infusion beginning at 2 µg/kg/h and midazolam boluses (F), or propofol and fentanyl infusions beginning at 25 µg/kg/min and 0.5 µg/kg/h (PF), respectively. MEASUREMENTS AND MAIN RESULTS: Postoperative regimen P was associated with a significantly reduced time to extubation (median value, 264 minutes; p = 0.05) compared with F (295 minutes) but not PF (278 minutes) in patients characterized as low cardiac risk. The time to extubation did not differ among regimens in patients of moderate/high cardiac risk. CONCLUSION: Patients with low cardiac risk undergoing cardiac surgery had statistically significantly shorter times to extubation with propofol infusion and intermittent morphine than a fentanyl infusion and intermittent midazolam. These differences were not sustained in patients considered at higher cardiac risk. The time to extubation after cardiac surgery may further improve if postoperative sedation and analgesia are not administered uniformly to all patients but selected based on individual characteristics.

Hemofiltration during cardiopulmonary bypass does not decrease the incidence of atrial fibrillation after cardiac surgery.

BACKGROUND: Atrial fibrillation (AF) occurs in 20%-50% of patients after cardiac surgery and is associated with increased morbidity and mortality. Corticosteroids are reported to decrease the incidence of postoperative AF, presumably by attenuating inflammation caused by surgery and cardiopulmonary bypass (CPB). We hypothesized that hemofiltration during CPB, which may attenuate inflammation, might decrease the incidence of AF after cardiac surgery. METHODS: This was a retrospective review of patients previously enrolled in a double-blind, placebo-controlled trial evaluating the effects of perioperative steroid therapy and hemofiltration during CPB on duration of postoperative mechanical ventilation. In that study, 192 patients undergoing cardiac surgery were randomized to 1 of 3 groups: controls (placebo), hemofiltration during CPB, or perioperative steroid therapy. Patient records were reviewed to determine the incidence of new onset AF defined as any electrocardiogram evidence of AF or AF diagnosed by the patients' clinicians. RESULTS: Of the 192 enrolled patients, 3 were excluded for protocol violations and 4 were excluded for history of chronic AF. Data from 185 patients from the original study were available for review. Sixty patients (32%) had new onset AF after cardiac surgery. There was no difference among groups in the incidence of AF (control group, 21%; steroid group, 41%; hemofiltration group, 36%; P = 0.057 among groups). The only risk factor for the development of AF was age (mean age of patients with AF, 65.4 +/- 10.1 yr vs patients without AF, 61.4 +/- 11.5 yr; P = 0.024). When age, procedure type, and presence or absence of chronic obstructive pulmonary disease were controlled for in multivariate analysis, the difference among study groups remained nonsignificant (P = 0.108). CONCLUSIONS: Perioperative corticosteroids or the use of hemofiltration during CPB did not decrease the incidence of AF after cardiac surgery. Further studies evaluating the efficacy and safety of perioperative corticosteroids for prevention of postoperative AF are warranted before their routine use can be recommended.

Anticoagulation and coagulation management for ECMO.

Advances in extracorporeal membrane oxygenation (ECMO) management have helped to reduce complications compared with its inception but they remain high. The principal causes of mortality and morbidity are bleeding and thrombosis. The nonbiologic surface of an extracorporeal circuit provokes a massive inflammatory response leading to consumption and activation of procoagulant and anticoagulant components. The vast differences in neonatal and adult anticoagulation and transfusion requirements demands tremendous clinical knowledge to provide the best care. Increased use of thrombelastogram will complement other methods currently being used to improved care. Methods to recognize the level of thrombin formation at the bedside could help reduce neurologic complications. ECMO requires a multidisciplinary team approach to achieve the best outcomes.

Cardiac risk of noncardiac surgery after percutaneous coronary intervention with drug-eluting stents.

BACKGROUND: The American College of Cardiology released a scientific advisory that included a recommendation to delay elective of noncardiac surgery (NCS) for 1 yr after percutaneous coronary intervention (PCI) with a drug-eluting stent (DES). METHODS: This single-center, retrospective study examined the risk for complications of NCS performed within 2 yr after DES placement and examined whether this risk changed based on the time between procedures. The primary endpoint was major adverse cardiac events (MACEs) during the hospitalization for NCS. Bleeding events were analyzed as a secondary endpoint. RESULTS: From April 22, 2003, to December 31, 2006, a total of 520 patients underwent NCS within 2 yr after PCI with a DES at Mayo Clinic. The majority, 84%, of the DES placed were Cypher stents. The frequency of MACE was not found to be significantly associated with the time between PCI and NCS (rate of MACEs 6.4, 5.7, 5.9, and 3.3% at 0-90, 91-180, 181-365, and 366-730 days after PCI with DES, respectively; P = 0.727 for comparison across groups). Characteristics found to be associated with MACEs in univariate analysis were advanced age (P = 0.031), emergent NCS (P = 0.006), shock at time of PCI (P = 0.035), previous history of myocardial infarction (P = 0.046), and continuation of a thienopyridine (ticlopidine or clopidogrel) into the preoperative period (P = 0.040). The rate of transfusion did not seem to be associated with antiplatelet therapy use. CONCLUSIONS: The risk of MACEs with NCS after DES placement was not significantly associated with time from stenting to surgery, but observed rates of MACEs were lowest after 1 yr.

Time and cardiac risk of surgery after bare-metal stent percutaneous coronary intervention.

BACKGROUND: The duration of time that elective noncardiac surgery (NCS) should be delayed after percutaneous coronary intervention (PCI) with bare metal stents (BMSs) is unknown. METHODS: This large, single-center, retrospective study examined the relation between complication rate in patients with BMSs undergoing NCS and the duration of time between PCI and NCS. Primary endpoints included in-hospital major adverse cardiac events (death, myocardial infarction, stent thrombosis, or repeat revascularization with either coronary artery bypass grafting or PCI of the target vessel) and bleeding events. The relation between the events and the timing of noncardiac surgery after PCI with BMS was assessed using univariate analysis and multiple logistic regression. RESULTS: From January 1, 1990, to January 1, 2005, a total of 899 patients were identified. The frequency of major adverse cardiac events was 10.5% when NCS was performed less than 30 days after PCI with BMS, 3.8% when NCS was performed between 31 and 90 days after PCI with BMS, and 2.8% when NCS was performed more than 90 days after PCI with BMS. In univariate and multivariate analyses, a shorter time interval between PCI with BMS and noncardiac surgery was significantly associated with increased incidence of major adverse cardiac events (univariate: P < 0.001; odds ratio = 4.0; 95% confidence interval, 2.0-8.3; multivariate: P = 0.006; odds ratio = 3.2; 95% confidence interval, 1.5-6.9). Bleeding events were not associated with time between PCI with BMS and NCS or with the use of antiplatelet therapy in the week before NCS. CONCLUSIONS: The incidence of major adverse cardiac events is lowest when NCS is performed at least 90 days after PCI with BMS.

A preliminary study of a new tranexamic acid dosing schedule for cardiac surgery.

OBJECTIVE(S): The authors have developed an alternative dosing schedule for tranexamic acid that incorporates the effects of renal function on tranexamic acid concentrations. The objectives of this study were to determine if this new dosing schedule can achieve the desired plasma concentration of tranexamic acid and reduce intra- and interpatient variability in tranexamic acid plasma concentrations relative to the current dosing schedule. DESIGN: A prospective randomized trial. SETTING: A tertiary referral medical center hospital. PARTICIPANTS: Cardiac surgery patients. INTERVENTIONS: Cardiac surgery patients were randomly assigned to receive the authors' standard tranexamic acid loading dosage of 10 mg/kg given over 20 minutes, followed by an infusion of 1 mg/kg/h (9 patients), or the new drug dosage schedule described later (11 patients). MEASUREMENTS AND MAIN RESULTS: Perioperative plasma tranexamic acid concentrations were measured using high-performance liquid chromatography. From repeated-measures analysis of variance, a significant (p < 0.001) time-by-treatment interaction effect was detected indicating that differences in mean tranexamic acid concentration between treatment groups were dependent on time period. Among patients receiving the standard dosing regimen, those with renal insufficiency had lower tranexamic acid concentration at 5 minutes on cardiopulmonary bypass (p = 0.003). For patients receiving the experimental regimen, the mean tranexamic acid concentration did not differ significantly at any time point between patients with and without renal insufficiency (p > 0.20 at all time points). CONCLUSIONS: The new dosing protocol for tranexamic acid resulted in more consistent blood concentrations of tranexamic acid, but not stable tranexamic acid levels >20 microg/mL on cardiopulmonary bypass.

A prospective study on anesthesia machine fault identification.

BACKGROUND: Although few studies have been performed recently, several have suggested that some practitioners are not well able to detect preset anesthesia machine faults. METHODS: We performed a prospective study to determine whether there is a correlation between duration of anesthesia practice and the ability to detect anesthesia machine faults. Our hypothesis was that more anesthesia practice would increase the ability to detect anesthesia machine faults. This study was performed during a nationally attended anesthesia meeting held at a large academic medical center, where 87 anesthesia providers were observed performing anesthesia machine checkouts. The participants were asked to individually check out an anesthesia machine with an unspecified number of preset faults. The primary outcome measures were the written listing of faults detected during an anesthesia machine checkout. RESULTS: Of the five faults preset into the test machine, participants with 0-2 yr experience detected a mean of 3.7 faults, participants with 2-7 yr experience detected a mean of 3.6 faults, and participants with more than 7 yr experience detected a mean of 2.3 faults (P < 0.001). CONCLUSIONS: Our prospective study demonstrated that anesthesia machine checkout continues to be a problem.

Aprotinin does not prolong the Sonoclot aprotinin-insensitive activated clotting time.

STUDY OBJECTIVE: To determine whether a new Sonoclot-based, aprotinin-insensitive activated clotting time (aiACT) assay yields stable results over a broad range of aprotinin concentrations. DESIGN: Prospective trial conducted on in vitro blood samples. SETTING: Tertiary-care teaching medical center. PARTICIPANTS: 19 healthy adult volunteers. INTERVENTIONS: Whole blood samples were collected from volunteers. Heparin (2 U/mL) and escalating concentrations of aprotinin of 160 to 500 kallikrein inhibitory units (KIU)/mL were added in vitro. MEASUREMENTS AND MAIN RESULTS: Celite ACT, kaolin ACT, and aiACT assays were completed. The aiACT showed stable activated clotting time (ACT) results on heparinized, noncitrated blood with added aprotinin (P = nonsignificant). In contrast, celite ACT and kaolin ACT were greatly prolonged when aprotinin was added to heparinized, noncitrated, and citrated blood (P < 0.05). The aiACT had consistent results at all aprotinin concentrations (P = nonsignificant). CONCLUSIONS: Aprotinin (160, 320, and 500 KIU/mL) significantly prolongs the ACT value with celite and kaolin activators but not with the aprotinin-insensitive activator.

Total and free cortisol responses and their relation to outcomes after cardiopulmonary bypass in infants.

BACKGROUND: Hypothalamic-pituitary-adrenal (HPA) axis dysfunction may be partially responsible for the hemodynamic instability experienced by infants after cardiopulmonary bypass (CPB). We report the full spectrum of the HPA response surrounding CPB for infant congenital cardiac surgery. METHODS: We enrolled 84 infants who received 1 mg/kg of dexamethasone before initiation of CPB. Total cortisol (TC), free cortisol (FC), adrenocorticotropic hormone (ACTH), and corticosteroid-binding globulin (CBG) were measured at 3 time points: immediately before CPB (TP1), on intensive care unit arrival (TP2), and at 24 hours after surgery (TP3). A 1-µg ACTH stimulation test was performed at each time point to evaluate adrenal responsiveness. RESULTS: Sixty-eight infants completed all study procedures. Levels of TC, FC, CBG, and ACTH decreased significantly between the preoperative and 24-hour postoperative measurements. There were no significant associations between preoperative FC responses and clinical outcomes after adjusting for weight and Risk-Adjusted Scores for Congenital Heart Surgery. Infants with subnormal TC responses to ACTH stimulation (<9 µg/dL) at TP2 had greater fluid requirements (P < .001) and greater chest tube output (P < .001) during the first 24 hours, as well as longer length of stay (LOS) (P = .007). Except for LOS, these differences persisted for infants with subnormal stimulation tests at TP3. CONCLUSIONS: We observed a significant decline in all aspects of the HPA axis throughout the first 24 hours after infant CPB. TC and FC levels were not associated with clinical outcomes. Subnormal (Δ <9 µg/dL) TC response to cosyntropin stimulation during the postoperative period was associated with increased fluid resuscitation and greater LOS.

Predictors of procedural complications in adult Fontan patients undergoing non-cardiac procedures.

OBJECTIVE: Limited data exist regarding the outcomes of non-cardiac procedures (NCPs) in adult patients after Fontan operations (Fontan patients). METHODS: To compare procedural outcomes after NCPs in Fontan patients with outcomes for two matched control groups: patients with repaired congenital heart disease and biventricular circulation (CHD-BiV) and patients with no heart disease (NHD). We defined cyanosis as oxygen saturation <90% and procedural hypoxia as saturation <80% or a decrease in saturation >10% from baseline. RESULTS: There were 538 NCPs in 154 Fontan patients (mean age, 30 years) performed in 1990-2015. Sedation and anaesthesia types were monitored anaesthesia care (256,48%), general anaesthesia (51,9%), minimal sedation (105,20%), local anaesthesia (75,14%) and regional anaesthesia (51,9%). Ninety-three complications occurred in 79 procedures (15%) and included arrhythmia requiring intervention (9), hypotension (14), bradycardia (8), hypoxia (38), heart failure requiring intravenous diuretics (2), acute kidney injury (3), bleeding requiring blood transfusion (1), unplanned procedures for dialysis catheter placement (2), readmission (2), unplanned hospitalisation for hypoxia (8) and unplanned transfer to intensive care unit (1). Baseline cyanosis was the only multivariable risk factor for complications (HR, 1.87 (95% CI 1.14 to 3.67), p=0.04). Procedural complications were more common in the Fontan group (18%) than in the CHD-BiV (5%) and NHD groups (1.4%) (p=0.001). CONCLUSIONS: Complications after NCPs were more common in Fontan patients, and baseline cyanosis was a risk factor for complications. All-cause mortality was low and may be related to the multidisciplinary care approach used for Fontan patients at our centre.

Prothrombin Complex Concentrates in Pediatric Cardiac Surgery: The Current State and the Future.

BACKGROUND: After decades of practice of pediatric cardiac surgery, postoperative bleeding due to the immaturity of hemostasis, hemodilution, and hypothermia remains a concern. Recently, a new approach for adult coagulopathy after bypass has emerged. Prothrombin complex concentrates (PCCs), designed to treat bleeding in hemophilia patients, are safely and efficiently used off label for hemorrhage after bypass. However, optimal dosing, indications and contraindications, and laboratory tests to assess the efficacy of PCC use in children have not yet been established. This literature review outlines the challenges of bypass-related coagulopathy, the pharmacology, and the experience in use of PCCs, with a focus on their potential in pediatric cardiac surgery. METHODS: After a thorough literature search of MEDLINE, Scopus, and Ovid databases using the term "prothrombin complex concentrate AND pediatric," 23 relevant articles were selected. RESULTS: The data supporting successful use of PCCs in acquired coagulopathy after cardiac surgery in adults have been increasing. Although small volume, low immunogenicity, efficiency, and speed in correcting coagulopathy are attractive qualities of PCCs for pediatric practice, current evidence is only anecdotal. The main concerns are unknown dosing regimens, the inability to closely monitor the effects of PCCs in real time, and a possibility of thrombotic complications, which can be particularly devastating in young congenital cardiac patients whose lives frequently depend upon the patency of artificial shunts. CONCLUSIONS: Extensive, high-quality research is warranted to fill in the gaps of knowledge regarding using PCCs in pediatric cardiac practice.

A comparison of fenoldopam with dopamine and sodium nitroprusside in patients undergoing cross-clamping of the abdominal aorta.

Fenoldopam, a selective dopamine-1-receptor agonist, decreases arterial blood pressure rapidly, with a brief duration of action similar to sodium nitroprusside (SNP), but in contrast to SNP, it increases renal blood flow. We compared the hemodynamic and renal effects of fenoldopam in patients undergoing abdominal aortic surgery requiring cross-clamping of the aorta with another therapeutic option, dopamine and SNP. Fenoldopam or 2 mcg x kg(-1) x min(-1) of dopamine and SNP was infused before incision in 60 randomly selected patients in a double-blind fashion. Hemodynamic variables were recorded before incision, immediately before clamping the aorta, 5 min after cross-clamp release and upon completion of surgery. Urine output, serum creatinine, and creatinine clearance were measured intraoperatively and postoperatively. Characteristics were compared between groups using two-sample rank sum test for continuous variables and Fisher's exact test for discrete variables. The occurrence of severe hypotension, maximum systolic blood pressure, and need for additional antihypertensive drugs were not different between the groups. Most intraoperative hemodynamic variables and all indices of renal function did not differ according to treatment. Therefore, fenoldopam has no therapeutic advantage compared with similar therapies in patients undergoing major vascular surgery involving cross-clamping of the aorta.

Excessive bleeding and transfusion in a prior cardiac surgery is associated with excessive bleeding and transfusion in the next surgery.

If there is a genetic predisposition to excessive bleeding, there should be an association in excessive blood loss between multiple cardiac surgeries. We retrospectively determined in 174 patients the association of excessive bleeding between 2 cardiac surgeries with cardiopulmonary bypass between January 19, 1990 and June 25, 2002. Excessive bleeding was defined by 2 criteria: (a) postoperating room chest tube blood loss over 24 h more than or equal to 750 mL (chest tube drainage [CTD] > or = 750) and (b) transfusion of any non-red blood cell (RBC) blood products. Logistic regression was used to estimate the association between excessive bleeding at the first and second cardiac procedures. The logistic regression models for CTD > or = 750 in the second surgery determined that CTD > or = 750 in the first surgery compared to CTD < 750 had an unadjusted odds ratio of 2.18 (P = 0.03) and an odds ratio of 2.42 (P = 0.03) when adjusted for age, sex, body surface area, preoperative anticoagulant use, cardiopulmonary bypass duration, and procedure type at second surgery. The logistic regression model for any non-RBC use in the second surgery determined that any non-RBC use in the first surgery compared with no non-RBC use had an unadjusted odds ratio of 2.32 (P = 0.02) and an odds ratio of 2.55 (P = 0.02) when adjusted for age, sex, body surface area, preoperative anticoagulant use, cardiopulmonary bypass duration, and procedure type at second surgery. We conclude that a history of excessive bleeding during the first operation is associated with more than two times increased risk for excessive bleeding in the second surgery.

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.