[Tranexamic acid for bleeding prophylaxis in orthopedic surgery and trauma-standard or customized therapy?] / Tranexamsäure zur Blutungsprophylaxe bei Trauma und orthopädischen Eingriffen ­ Standard oder individualisierte Anwendung?

The use of tranexamic acid (TXA) is established in the treatment of bleeding, especially of bleeding due to hyperfibrinolysis. In recent years the prophylactic use of TXA in trauma and orthopedic surgery has increased leading to open questions regarding potentially associated risks and a possible classification as off label use. The available literature provides a sound basis for the recommendation that TXA can be used in these indications provided that an individual risk assessment is done in patients with increased risks for thromboembolic complications. Although the prophylactic use of TXA in orthopedic surgery and trauma is not explicitly listed in the product characteristics, it should not be regarded as an off label use.

Perioperative Management of a Patient with Severe Factor V Deficiency Presenting with Chronic Subdural Hematoma: A Clinical Report.

BACKGROUND: Severe factor V deficiency is an extremely rare coagulation disorder. Patients with factor V activity <5% usually become symptomatic in early childhood. CASE DESCRIPTION: We report the case of an 82-year-old woman with incidentally diagnosed severe factor V deficiency, who developed a symptomatic chronic subdural hematoma, requiring burr hole craniostomy. Successful management was achieved by a multidisciplinary approach. Preoperatively, factor V activity was increased from 2% to 50% by administration of 25 mL/kg body weight of fresh frozen plasma over 30 minutes under close cardiopulmonary monitoring in the intensive care unit. Straight afterward, the patient was transferred to the operating room where surgery was performed under general anesthesia. Burr hole craniostomy could be performed without perioperative complications. In the postoperative days, there was no relevant recurrence of the subdural hematoma in the follow-up computed tomography scans under frequent control of coagulation parameters. However, despite further transfusion of fresh frozen plasma, factor V activity did not increase >16%. The patient was discharged without any neurologic deficits. In a hemostaseologic follow-up 2 months after surgery, factor V activity <1% was confirmed with evidence of a factor V inhibitor in the modified Bethesda assay. Most likely, the patient suffered from an acquired form of factor V deficiency with preformed antibodies that had been boosted by the initial treatment with fresh frozen plasma. CONCLUSIONS: We conclude that in this rare bleeding disorder, intracranial surgery was successfully managed because of a thoroughly planned perioperative therapeutic strategy. However, if there is time prior to surgery, a full checkup of the bleeding disorder is advisable.

Alternative polyadenylation allows differential negative feedback of human miRNA miR-579 on its host gene ZFR.

About half of the known miRNA genes are located within protein-coding host genes, and are thus subject to co-transcription. Accumulating data indicate that this coupling may be an intrinsic mechanism to directly regulate the host gene's expression, constituting a negative feedback loop. Inevitably, the cell requires a yet largely unknown repertoire of methods to regulate this control mechanism. We propose APA as one possible mechanism by which negative feedback of intronic miRNA on their host genes might be regulated. Using in-silico analyses, we found that host genes that contain seed matching sites for their intronic miRNAs yield longer 32UTRs with more polyadenylation sites. Additionally, the distribution of polyadenylation signals differed significantly between these host genes and host genes of miRNAs that do not contain potential miRNA binding sites. We then transferred these in-silico results to a biological example and investigated the relationship between ZFR and its intronic miRNA miR-579 in a U87 cell line model. We found that ZFR is targeted by its intronic miRNA miR-579 and that alternative polyadenylation allows differential targeting. We additionally used bioinformatics analyses and RNA-Seq to evaluate a potential cross-talk between intronic miRNAs and alternative polyadenylation. CPSF2, a gene previously associated with alternative polyadenylation signal recognition, might be linked to intronic miRNA negative feedback by altering polyadenylation signal utilization.

Indocyanine green clearance as an outcome prediction tool in cardiac surgery: a prospective study.

PURPOSE: To evaluate the role of plasma disappearance rate of indocyanine green (PDR-ICG) as an outcome prediction tool in cardiac surgery. PATIENTS AND METHODS: One hundred ninety patients undergoing coronary artery bypass grafting, valve surgery or combined procedures were enrolled. PDR-ICG measurements along with standard lab values were performed preoperative and on postoperative days 1, 2, and on discharge from the intensive care unit. Adverse outcomes were defined as prolonged length of stay in the intensive care unit and/or mortality. Two groups were defined according to length of stay in the intensive care unit (≤ 3 days vs >3 days). RESULTS: PDR-ICG values differed significantly for all time points between the groups. In a multivariate model, in patients over 65 years with a EuroSCORE below 8.5, a preoperative PDR-ICG value below 12.85%/min was the strongest independent predictor for prolonged intensive care unit stay (>3 days). A preoperative PDR-ICG value below 8.2%/min was the strongest independent predictor for mortality in a multivariate analysis including age, cardiac function, and EuroSCORE. CONCLUSIONS: In addition to the established scores, PDR-ICG may provide valuable information for the assessment of perioperative morbidity and mortality in cardiac surgery. Pre- and early postoperative measurements may help to identify patients at risk for developing perioperative complications.

Routine use of corticosteroids to prevent inflammation response in cardiac surgery.

Cardiac surgery, especially if it involves cardiopulmonary bypass, is associated with a severe systemic inflammatory response. It is characterized by complement activation and initiation of coagulation, fibrinolysis and kallikrein cascades. Consecutive activation of immunoregulatory cells results in an extensive release of pro- and anti-inflammatory cytokines. This inflammatory storm is related to organ dysfunction or failure and correlates with postoperative morbidity. In order to attenuate this deleterious inflammatory response in the perioperative period alternative surgical techniques, novel extracorporeal circulation devices and immunomodulatory pharmacological strategies are in focus of contemporary research. Since decades corticosteroids have been used and studied in patients undergoing cardiac surgery. Although it could be shown that glucocorticoids seem to change the pro-inflammatory cytokine profile in a favourable manner, it still remains controversial if this effect translates into a better clinical outcome. Several clinical trials have proclaimed an association between this inflammatory response and the incidence of major complications i.e, myocardial infarction and pulmonary complications, but until now they have failed to show conclusive results. This article describes the different types and recommended dose schemes of corticosteroids in the perioperative period of cardiac surgery along with the discussion of few patents. It will comment on potential side effects and review the effect on the postoperative outcome.

Adenosine A2A receptor upregulation in human PMNs is controlled by miRNA-214, miRNA-15, and miRNA-16.

Immunosuppressive signaling via the adenosine A2A receptor (A2AR) is an important pathway to control inflammation. In immune cells, expression levels of A2ARs influence responsiveness to inflammatory stimuli. However, mechanisms driving expressional changes of A2ARs are still largely elusive. In the current study, we have investigated the impact of microRNAs (miRNAs) on A2AR expression in human polymorphonuclear leukocytes (PMNs) and T cells. Bioinformatic analyses and reporter gene assays revealed that A2AR expression is controlled by miRNA-214, miRNA-15, and miRNA-16. We detected all three miRNAs in both human PMNs and T cells. However, in PMNs, up to 10-fold higher levels of miRNA-16 and miRNA-214 were detected as compared with T cells. Upon in vitro stimulation, no significant expressional changes occurred. Expression levels of all three miRNAs strongly differed between individuals. A2AR expression also exhibited significant differences between PMNs and T cells: In PMNs, more than a 60-fold increase was seen upon LPS stimulation, whereas in T cells only a 2-fold increase was observed upon anti-CD3/CD28 activation. The extent of A2AR upregulation in PMNs strongly differed between individuals (from less than 10-fold to more than 100-fold). In PMNs, the increase in A2AR mRNA expression upon stimulation was inversely correlated with the expression levels of miRNA-214, miRNA-15, and miRNA-16 (R = -0.87, P < 0.0001); no correlation was found in human T cells. These results indicate that individual miRNA profiles gain important influence on A2AR expression regulation in PMNs upon stimulation. Determination of miRNA expression levels may help to identify patients with an increased risk for severe inflammation.

Lack of effectiveness of the pulmonary artery catheter in cardiac surgery.

BACKGROUND: The pulmonary artery catheter (PAC) continues to be used for monitoring of hemodynamics in patients undergoing coronary artery bypass graft (CABG) surgery despite concerns raised in other settings regarding both effectiveness and safety. Given the relative paucity of data regarding its use in CABG patients, and given entrenched practice patterns, we assessed the impact of PAC use on fatal and nonfatal CABG outcomes as practiced at a diverse set of medical centers. METHODS: Using a formal prospective observational study design, 5065 CABG patients from 70 centers were enrolled between November 1996 and June 2000 using a systemic sampling protocol. Propensity score matched-pair analysis was used to adjust for differences in likelihood of PAC insertion. The predefined composite endpoint was the occurrence of any of the following: death (any cause), cardiac dysfunction (myocardial infarction or congestive heart failure), cerebral dysfunction (stroke or encephalopathy), renal dysfunction (dysfunction or failure), or pulmonary dysfunction (acute respiratory distress syndrome). Secondary variables included treatment indices (inotrope use, fluid administration), duration of postoperative intubation, and intensive care unit length of stay. After categorization based on PAC and transesophageal echocardiography use (both, neither, PAC only, transesophageal echocardiography only), we performed the primary analysis contrasting PAC only and neither (total, 3321 patients), from which propensity paring yielded 1273 matched pairs. RESULTS: The primary endpoint occurred in 271 PAC patients versus 196 without PAC (21.3% vs.15.4%; adjusted odds ratio [AOR], 1.68; 95% confidence interval [CI], 1.24 to 2.26; P<0.001). The PAC group had an increased risk of all-cause mortality, 3.5% vs 1.7% (AOR, 2.08; 95% CI, 1.11 to 3.88; P=0.02) and an increased risk of cardiac (AOR, 1.58; 95% CI, 1.14 to 2.20; P=0.007), cerebral (AOR, 2.02; 95% CI, 1.08 to 3.77; P=0.03) and renal (AOR, 2.47; 95% CI, 1.68 to 3.62; P<0.001) morbid outcomes. PAC patients received inotropic drugs more frequently (57.8% vs 50.0%; P<0.001), had a larger positive IV fluid balance after surgery (3220 mL vs 3022 mL; P=0.003), and experienced longer time to tracheal extubation (15.40 hours [11.28/20.80] versus 13.18 hours [9.58/19.33], median plus Q1/Q3 interquartile range; P<0.0001). Use of PAC was also associated with prolonged intensive care unit stay (14.5% vs 10.1%; AOR, 1.55; 95% CI, 1.06 to 2.27; P=0.02). CONCLUSIONS: Use of a PAC during CABG surgery was associated with increased mortality and a higher risk of severe end-organ complications in this propensity-matched observational study. A randomized controlled trial with defined hemodynamic goals would be ideal to either confirm or refute our findings.

An uncommon cause of myocardial ischemia after coronary artery bypass grafting: "the dangerous drainage".

The most common causes of myocardial ischemia and myocardial infarction early after coronary artery bypass grafting surgery are early graft occlusion/thrombosis or occlusion/ thrombosis of coronary arteries due to advanced coronary heart disease. We describe a case of postoperative myocardial ischemia due to an uncommon and quickly reversible cause: mechanical compression of a vein graft by a 19F flexible silicone mediastinal drainage tube.

Postoperative red blood cell transfusion and morbid outcome in uncomplicated cardiac surgery patients.

OBJECTIVE: To evaluate postoperative red blood cell (RBC) transfusion and its association with postoperative cardiac events and multiorgan morbidity in uncomplicated cardiac surgery patients. METHODS: A cohort of 945 patients from the 5,436 coronary artery bypass grafting patients enrolled in the international Multicenter Study of Perioperative Ischemia (McSPI) Epidemiology II (EPI II) study was investigated. Inclusion criteria were low to moderate risk profile, postoperative hemoglobin level ≥ 10 g/dl, minimal postoperative blood loss, and no evidence of any morbid event on the day of surgery. RBC transfusion was assessed during the first 24 postoperative hours and cardiac as well as multiorgan outcomes from postoperative day 2 to hospital discharge. Multivariate analysis was applied to assess the effect of RBC transfusion on multiorgan outcomes. A secondary propensity score analysis was performed in 4,465 patients without early postoperative morbid outcomes. RESULTS: Transfused patients (193/945, 20.4%) were more likely to suffer cardiac events (P = 0.03), harvest-site infection (P = 0.002), and composite morbidity outcome (P = 0.04). RBC transfusion was associated with cardiac events on multivariate as well as on propensity score analysis (adjusted odds ratio, 1.39; 95% confidence interval, 1.01-1.92; P = 0.04), and with harvest-site infection on multivariate analysis. Additionally, propensity score analysis suggested possible associations of RBC transfusion with increased risks for composite morbidity outcome and in-hospital mortality, renal morbidity, pneumonia, and mediastinitis. CONCLUSIONS: The data suggest a potential association between postoperative RBC transfusion and increased morbidity for cardiac surgery patients with low to moderate mortality risk profiles, adequate hemoglobin levels, and low bleeding rates.

Noninvasive mechanical ventilation in patients with acute respiratory failure after cardiac surgery.

OBJECTIVE: To evaluate the feasibility and outcomes of protocol-driven noninvasive mechanical ventilation in patients with acute respiratory failure (ARF) after cardiac surgery. METHODS: From 2001 to 2004, a total of 2428 cardiac surgery patients admitted to our intensive care unit were observed. After exclusion of patients who received tracheostomy or were discharged while still on mechanical ventilation, 2261 patients with spontaneous breathing were further evaluated for ARF. Patients diagnosed with ARF were treated with intermittent noninvasive mechanical ventilation (NIV) if possible. Risk factors for the development of postoperative ARF as well as outcomes in patients with and without ARF were analyzed. RESULTS: In 2261 spontaneously breathing postoperative cardiac surgical patients after primarily successful extubation, 799 patients (35%) were diagnosed with ARF. Fifty-six patients (7%) did not tolerate NIV treatment. In 743 patients (33%) intermittent NIV was performed. In patients with ARF, ejection fraction was lower, combined cardiac surgical procedures were more frequent, postoperative mechanical ventilation time was longer, and the severity of illness score (SAPS II) was higher (P < .05). The duration of catecholamine support was longer, and the transfusion rate was higher in the NIV group (P < .05); however, mortality did not differ between patients with ARF treated by NIV and patients without ARF. CONCLUSION: Our study demonstrates the feasibility of NIV in patients after cardiac surgery. These results might suggest that NIV should be considered as first-line ventilatory support in ARF after cardiac surgery. A large randomized trial is warranted to confirm these findings.

The ongoing variability in blood transfusion practices in cardiac surgery.

BACKGROUND: Although blood utilization has been under considerable scrutiny for the past two decades, particularly for surgery, studies comparing perioperative blood transfusion practices between countries are rare, and the evolution of international standards remains unknown. Therefore, the objective of this evaluation was to compare the perioperative transfusion of blood components in cardiac surgery in multiple centers in different countries. STUDY DESIGN AND METHODS: Transfusion practice was investigated prospectively in 70 centers among 16 countries. A total of 5065 randomly selected cardiac surgery patients of the Multicenter Study of Perioperative Ischemia Epidemiology II (EPI II) Study were evaluated. Utilization of red blood cells (RBCs), fresh-frozen plasma (FFP), and platelets (PLTs) was assessed daily, before, during, and after surgery until hospital discharge. RESULTS: Intraoperative RBC transfusion varied from 9 to 100 percent among the 16 countries, and 25 to 87 percent postoperatively (percentage of transfused patients). Similarly, frequency of transfusion of FFP varied from 0 to 98 percent intraoperatively and 3 to 95 percent postoperatively, and PLT transfusion from 0 to 51 and 0 to 39 percent, respectively. Moreover, there were not only marked differences in transfusion rates between centers in different countries but also in interinstitutional comparison of multiple centers within countries. CONCLUSION: In cardiac surgical patients, marked variability in transfusion practice exists between centers in various countries and suggests differences in perioperative practice patterns as well as possible inappropriate use. International standardization of perioperative practice patterns as well as transfusion regimes appears necessary.

Coronary artery bypass graft surgery--care globalization: the impact of national care on fatal and nonfatal outcome.

OBJECTIVE: In an international, prospective, observational study, we contrasted adverse vascular outcomes among four countries and then assessed practice pattern differences that may have contributed to these outcomes. METHODS: A total of 5065 patients undergoing coronary artery bypass graft surgery were analyzed at 70 international medical centers, and from this pool, 3180 patients from the 4 highest enrolling countries were selected. Fatal and nonfatal postoperative ischemic complications related to the heart, brain, kidney, and gastrointestinal tract were assessed by blinded investigators. RESULTS: In-hospital mortality was 1.5% (9/619) in the United Kingdom, 2.0% (9/444) in Canada, 2.7% (34/1283) in the United States, and 3.8% (32/834) in Germany (P = .03). The rates of the composite outcome (morbidity and mortality) were 12% in the United Kingdom, 16% in Canada, 18% in the United States, and 24% in Germany (P < .001). After adjustment for difference in case-mix (using the European System for Cardiac Operative Risk Evaluation) and practice, country was not an independent predictor for mortality. However, there was an independent effect of country on composite outcome. The practices that were associated with adverse outcomes were the intraoperative use of aprotinin, intraoperative transfusion of fresh-frozen plasma or platelets, lack of use of early postoperative aspirin, and use of postoperative heparin. CONCLUSIONS: Significant between-country differences in perioperative outcome exist and appear to be related to hematologic practices, including administration of antifibrinolytics, fresh-frozen plasma, platelets, heparin, and aspirin. Understanding the mechanisms for these observations and selection of practices associated with improved outcomes may result in significant patient benefit.

Perturbations in laboratory values after coronary artery bypass graft surgery with cardiopulmonary bypass.

OBJECTIVE: The purpose of this study was to describe the sequential changes in commonly obtained laboratory values after coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB). METHODS: The authors examined laboratory data from 375 patients who underwent uncomplicated CABG with CPB in a multicenter clinical trial of a medication for postoperative pain. Data were obtained preoperatively, at the time of postoperative extubation, and at 4 subsequent intervals ending 14 days after extubation. Data obtained before study drug administration are reported for all patients; thereafter, only data from placebo patients without perioperative complications (n=123) are reported. RESULTS: Mean postoperative coagulation values remained within their reference ranges at the time of extubation. However, platelet counts increased to a peak value well above the reference range by the end of the study. Postoperative white blood cell counts rose above the reference range, mainly because of increased neutrophils. Serum chemistries were also altered; most patients showed a persistent postoperative hyperglycemia. Creatine kinase levels rose to nearly 4 times the upper limit of the reference range in the early postoperative period. Lactate dehydrogenase, serum aspartate aminotransferase, and alanine aminotransferase levels also increased above the reference range. Total protein and albumin values were below the reference range throughout the postoperative period. CONCLUSIONS: Laboratory values for hematology, blood coagulation, and serum chemistry change substantially after uncomplicated CABG with CPB. Recognition of these changes will facilitate the conduct of clinical research and may prevent inappropriate treatment based on abnormal laboratory findings that have no clinical significance.