Risk stratification-based thromboprophylaxis does not affect mortality after fast-track hip and knee arthroplasty.

BACKGROUND AND PURPOSE: Use of thromboprophylaxis effectively prevents pulmonary embolism (PE) and deaths after total hip and knee arthroplasty (THA and TKA). The optimum length of thromboprophylaxis is not known and has traditionally been based on the type of operation. Nowadays, a more individualized approach is preferred. This study analyzed if risk stratification-based planning of thromboprophylaxis has an association with the all-cause mortality after fast-track THA and TKA. PATIENTS AND METHODS: We compared fast-track THAs and TKAs operated between 2015-2016 and 2020-2021. Between 2015 and 2016, all patients received a routine length of thromboprophylaxis. From 2020 onwards, thromboprophylaxis was planned by risk stratification, and patients at low risk for venous thromboembolism received thromboprophylaxis only during hospitalization. All causes of death within 90 days of surgery were identified and the incidence of mortality was calculated. Mortality rates between the two periods were then compared. RESULTS: Between 2015 and 2016, 3192 arthroplasties were performed. A total of eight deaths occurred within 90 days of surgery, yielding an incidence of all-cause mortality of 0.3% (95% CI 0.1-0.5). Between 2020 and 2021, a total of 3713 arthroplasties were performed to patients who received risk stratification-based thromboprophylaxis. Thirteen of these patients died within 90 days of surgery, yielding an all-cause mortality incidence of 0.4% (95% CI 0.2-0.6). Cardiovascular diseases were the main cause of death during both study periods. None of the deaths were caused by PEs. INTERPRETATION: Risk stratification-based thromboprophylaxis was not associated with increased all-cause mortality within 90 days of fast-track THA and TKA.

Venous thromboembolism is rare after total hip and knee joint arthroplasty with long thromboprophylaxis in Finnish fast-track hospitals.

INTRODUCTION: Pharmacological thromboprophylaxis effectively prevents venous thromboembolism (VTE) after total knee (TKA) and total hip arthroplasty (THA). Less is known about the influence of fast-track arthroplasty on VTE risk. We conducted a register-based study to determine the incidence of VTE after fast-track TKA and THA in Finland using long thromboprophylaxis. MATERIALS AND METHODS: All primary TKAs and THAs operated during 2015-2016 in 3 fast-track hospitals were identified from the Finnish Arthroplasty Register. Pulmonary embolism (PE) and deep vein thrombosis (DVT) diagnosed in this patient cohort within 90 days of surgery were identified from the Finnish Hospital Discharge Register. The recommended length of thromboprophylaxis was 10 to 14 days for TKA and 28 days for THA during study period. RESULTS: During the study period, 3 831 THAs, 4 394 TKAs and 286 bilateral TKAs (BTKAs) were performed. Of all these patients, 60% were females. Venous thromboembolism (VTE) incidence within 90 days of surgery was 0.3% (95% CI 0.2-0.4). These VTEs comprised 10 PEs and 15 DVTs. None of the VTE patients´ died within the 90-day period. CONCLUSION: VTE incidence is low in Finnish fast-track TKA and THA patients with long thromboprophylaxis.

Anti-factor X activity levels with continuous intravenous infusion and subcutaneous administration of enoxaparin after coronary artery bypass grafting: A randomized clinical trial.

BACKGROUND: Low-molecular-weight heparin enoxaparin is widely used in pharmacological thromboprophylaxis after coronary artery bypass grafting (CABG). The aim of this study was to compare anti-factor X activity (anti-Xa) levels when the thromboprophylactic dose of enoxaparin was provided after CABG, with two different administration routes: continuous intravenous infusion (CIV) and subcutaneous bolus (SCB) injection. We hypothesized that the current standard method of SCB administration might lead to lower anti-Xa levels than recommended in other patient groups, due to reduced bioavailability. METHODS: In this prospective, randomized, controlled clinical trial, 40 patients scheduled for elective CABG were randomized to receive 40 mg of enoxaparin per day either as CIV or SCB for 72 h. Enoxaparin was initiated 6-10 h after CABG. Anti-Xa levels were measured 12-14 times during the study period. The primary outcome, that is, the maximum anti-Xa concentration over 0-24 h (Cmax0-24h ), was calculated from these measured values. Secondary outcomes were Cmax25-72h and the trough concentration of anti-Xa after 72 h of enoxaparin initiation (C72h ). RESULTS: Twenty patients were randomized to the CIV-group and 19 to the SCB-group. The median anti-Xa Cmax0-24h was significantly lower in the CIV-group than in the SCB-group: 0.15 [interquartile range (IQR) 0.13-0.19] IU/ml versus 0.25 (IQR 0.18-0.32) IU/ml, p < .005. The median anti-Xa Cmax25-72h was 0.12 (IQR, 0.1-0.17) IU/ml versus 0.23 (IQR 0.19-0.31) IU/ml, respectively, p < .005. At 72 h, there was no difference between the groups in their anti-Xa levels. CONCLUSIONS: In this low-risk CABG patient population, SCB administration of a thromboprophylactic dose of enoxaparin provided anti-Xa levels that are considered sufficient for thromboprophylaxis in other patient groups. CIV administration resulted in lower anti-Xa levels compared to the SCB route.

Low incidence of clinically relevant bleeding complications after fast-track arthroplasty: a register study of 8,511 arthroplasties.

BACKGROUND AND PURPOSE: Fast-track total joint replacement (TJR) has become increasingly common. Routine thromboprophylaxis for pulmonary embolism and deep venous thrombosis prevention lasts from 2 to 5 weeks. This retrospective registry study focused on clinically relevant bleeding complications 90 days after fast-track primary TJR. PATIENTS AND METHODS: All primary fast-track total hip (THA) and knee arthroplasties (TKA) performed between 2015 and 2016 were extracted from the Finnish Arthroplasty Register and Finnish Hospital Discharge Register. Type of arthroplasty and indication for the operation were combined with diagnoses of clinically relevant bleeding complications within 90 days of surgery. The incidence of these bleedings was the primary outcome measure. RESULTS: Of the total of 8,511 patients (mean age 67 years (SD 10); 60% female), 45% underwent unilateral THA, 52% unilateral TKA, and 3% bilateral TKA. The incidence of clinically relevant bleeding complications within 90 days was 1% (95% CI 0.8-1.3). No difference was observed in bleeding incidence between the groups. The 87 bleedings comprised 57 operative site bleedings, 17 gastrointestinal bleedings, 6 intracranial non-traumatic bleedings, 5 bleedings from the nose or another undetermined site, and 2 intraocular bleedings. 1 death due to intracranial bleeding was recorded, and hence clinically relevant bleeding-specific 90-day mortality was 0.01%. INTERPRETATION: The incidence of clinically relevant bleeding complications was low. However, they cause patient discomfort, increase the use of healthcare services, and can be life-threatening and even fatal.

Diagnosis and outcome of acute respiratory failure in immunocompromised patients after bronchoscopy.

OBJECTIVE: We wished to explore the use, diagnostic capability and outcomes of bronchoscopy added to noninvasive testing in immunocompromised patients. In this setting, an inability to identify the cause of acute hypoxaemic respiratory failure is associated with worse outcome. Every effort should be made to obtain a diagnosis, either with noninvasive testing alone or combined with bronchoscopy. However, our understanding of the risks and benefits of bronchoscopy remains uncertain. PATIENTS AND METHODS: This was a pre-planned secondary analysis of Efraim, a prospective, multinational, observational study of 1611 immunocompromised patients with acute respiratory failure admitted to the intensive care unit (ICU). We compared patients with noninvasive testing only to those who had also received bronchoscopy by bivariate analysis and after propensity score matching. RESULTS: Bronchoscopy was performed in 618 (39%) patients who were more likely to have haematological malignancy and a higher severity of illness score. Bronchoscopy alone achieved a diagnosis in 165 patients (27% adjusted diagnostic yield). Bronchoscopy resulted in a management change in 236 patients (38% therapeutic yield). Bronchoscopy was associated with worsening of respiratory status in 69 (11%) patients. Bronchoscopy was associated with higher ICU (40% versus 28%; p<0.0001) and hospital mortality (49% versus 41%; p=0.003). The overall rate of undiagnosed causes was 13%. After propensity score matching, bronchoscopy remained associated with increased risk of hospital mortality (OR 1.41, 95% CI 1.08-1.81). CONCLUSIONS: Bronchoscopy was associated with improved diagnosis and changes in management, but also increased hospital mortality. Balancing risk and benefit in individualised cases should be investigated further.

The urine protein NGAL predicts renal replacement therapy, but not acute kidney injury or 90-day mortality in critically ill adult patients.

BACKGROUND: Urine neutrophil gelatinase-associated lipocalin (uNGAL) is increasingly used as a biomarker for acute kidney injury (AKI). However, the clinical value of uNGAL with respect to AKI, renal replacement therapy (RRT), or 90-day mortality in critically ill patients is unclear. Accordingly, we tested the hypothesis that uNGAL is a clinically relevant biomarker for these end points in a large, nonselected cohort of critically ill adult patients. METHODS: We prospectively obtained urine samples from 1042 adult patients admitted to 15 Finnish intensive care units. We analyzed 3 samples (on admission, at 12 hours, and at 24 hours) with NGAL ELISA Rapid Kits (BioPorto® Diagnostics, Gentofte, Denmark). We chose the highest uNGAL (uNGAL24) for statistical analyses. We calculated the areas under receiver operating characteristics curves (AUC) with 95% confidence intervals (95% CIs), the best cutoff points with the Youden index, positive likelihood ratios (LR+), continuous net reclassification improvement (NRI), and the integrated discrimination improvement (IDI). We performed sensitivity analyses excluding patients with AKI or RRT on day 1, sepsis, or with missing baseline serum creatinine concentration. RESULTS: In this study population, the AUC of uNGAL24 (95% CI) for development of AKI (defined by the Kidney Disease: Improving Global Outcomes [KDIGO] criteria) was 0.733 (0.701-0.765), and the continuous NRI for AKI was 56.9%. For RRT, the AUC of uNGAL24 (95% CI) was 0.839 (0.797-0.880), and NRI 56.3%. For 90-day mortality, the AUC of uNGAL24 (95% CI) was 0.634 (0.593 to 0.675), and NRI 15.3%. The LR+ (95% CI) for RRT was 3.81 (3.26-4.47). CONCLUSION: In this study, we found that uNGAL associated well with the initiation of RRT but did not provide additional predictive value regarding AKI or 90-day mortality in critically ill patients.

Increased preoperative thrombin generation and low protein S level associated with unfavorable postoperative hemodynamics after coronary artery bypass grafting.

In a previous study, preoperative levels of activated protein C (APC) were associated with unfavorable postoperative hemodynamics after coronary artery bypass grafting (CABG). Protein C is activated by thrombin. Protein S, the cofactor of activated protein C, has activated protein C-independent anticoagulant activity and cytoprotective effects. Therefore, the objective of this study was to test whether preoperative, baseline levels of either thrombin or protein S were associated with hemodynamic performance or markers of myocardial damage after CABG. One hundred patients undergoing elective on-pump CABG were prospectively studied. Prothrombin fragment F1+2 (a marker of thrombin generation) and free protein S were measured preoperatively and cardiac index, systemic vascular resistance index (SVRI), and pulmonary vascular resistance index (PVRI) were measured serially thereafter at fixed time points. Cardiac biomarkers CK-MBm and TnT were measured postoperatively. There was an inverse correlation between preoperative F1+2 and free protein S levels (r= -0.30, p=0.003). High preoperative F1+2 and low preoperative protein S levels were associated with a less favorable hemodynamic profile postoperatively. Patients with F1+2 in the highest decile (≥0.85 nmol/l) and patients with preoperative protein S in the lowest decile (≤63%) had lower CI values, and higher pulmonary and systemic vascular resistance index values postoperatively than comparison patients. Preoperative F1+2 or protein S did not correlate with postoperative cardiac biomarker levels. Baseline activation of coagulation and the balance between pro-coagulant and anti-coagulant factors preoperatively might have implications for postoperative hemodynamic recovery after CABG.

Comparison of the effect of 6% hydroxyethyl starch and gelatine on cardiac and stroke volume index: a randomized, controlled trial after cardiac surgery.

BACKGROUND AND AIMS: The objective of this study was to find out the effect of various doses of hydroxyethyl starch (HES), gelatine or Ringer's acetate on cardiac and stroke volume index after cardiac surgery. MATERIAL AND METHODS: Three consecutive boluses (each 7 mL·kg(-1)) of either 6% HES 130/0.4, 4% gelatine, or Ringer's acetate solutions were administered to 45 patients postoperatively. The rate of infusions was adjusted according to haemodynamic measurements. Thereafter, infusion of the study solution (7 mL·kg(-1)) was continued for the following 12 hours. The total dose of study solution was 28 mL·kg(-1). RESULTS AND CONCLUSION: Mean (SD) cardiac and stroke volume indices were greater in the HES group [2.8 L·min(-1)·m(-2) (0.7), 34.1 (6.7) ml·m( -2)] than in the gelatine group [2.2 L·min(-1)·m( -2) (0.6), 25.8 (7.2) ml·m(-2)] after completion of 7 mL·kg(-1) of study solution. At this stage, the effect of gelatine did not differ from Ringer's acetate. After completion of 14 mL·kg(-1) and 21 mL·kg(-1) of colloids, similar cardiac and stroke volume indices were observed and the haemodynamic response was better in both colloid groups than in the Ringer's acetate group. No differences between groups were detected on the first postoperative morning. In the early postoperative phase after cardiac surgery, the effect of a single dose of HES solution on the haemodynamics was superior to the effect of gelatine or Ringer's acetate. However, after repeated administration of the study solutions, the haemodynamics in the two colloid groups appeared to be similar, but superior to the Ringer's acetate group.

Serum cystatin C in elderly cardiac surgery patients.

BACKGROUND: Elderly cardiac surgery patients are more prone to develop postoperative acute kidney injury (AKI). The common clinical glomerular filtration marker, plasma creatinine, is considered to be inadequate to discover AKI in its early stage. The aim of this study was to determine if serum cystatin C can detect mild renal failure earlier than plasma creatinine. METHODS: From 110 cardiac surgery patients aged 70 or greater years, serum cystatin C and plasma creatinine samples were collected preoperatively and on postoperative days 1 to 5. Their urine output, creatinine, and estimated glomerular filtration rate were calculated and AKI was determined by the risk-injury-failure-loss-end-stage kidney disease criteria (RIFLE). The correlation of plasma creatinine and serum cystatin C to AKI was calculated. RESULTS: After cardiac surgery, 62 of the 110 patients (56.4%) developed AKI according to the RIFLE classification. In this group, both serum cystatin C and plasma creatinine peaked on postoperative day 3. Cystatin C and creatinine correlated equally with AKI at different time points calculated with receiver operating characteristic curves. On postoperative day 1 the area under the curve (AUC) for creatinine was 0.66 (0.55 to 0.76) and for cystatin C 0.71 (0.61 to 0.81); Delta AUC 0.05 (0.01 to 0.12), p = 0.11. On postoperative day 2 the AUC for creatinine was 0.74 (0.64 to 0.83) and for cystatin was C 0.77 (0.68 to 0.86); Delta AUC -0.03 (-0.09 to 0.03), p = 0.32. CONCLUSIONS: Elderly cardiac surgery patients have a high incidence of AKI, as defined by the RIFLE criteria. After cardiac surgery serum cystatin C and plasma creatinine detected AKI similarly.

Levosimendan facilitates weaning from cardiopulmonary bypass in patients undergoing coronary artery bypass grafting with impaired left ventricular function.

BACKGROUND: Levosimendan is a compound with vasodilatory and inotropic properties. Experimental data suggest effective reversal of stunning and cardioprotective properties. METHODS: This prospective, randomized, placebo-controlled, double-blind study included 60 patients with 3-vessel coronary disease and left ventricular ejection fraction (LVEF) of less than 0.50. Levosimendan administration (12 microg/kg bolus, followed by an infusion of 0.2 microg/kg/min) was started immediately after induction anesthesia. Predefined strict hemodynamic criteria were used to assess the success of weaning. If weaning was not successful, CPB was reinstituted and an epinephrine infusion was started. If the second weaning attempt failed, intraaortic balloon pumping (IABP) was instituted. RESULTS: The groups had comparable demographics. The mean (standard deviation) preoperative LVEF was 0.36 (0.8) in both groups. The baseline cardiac index was 1.8 (0.3) L/min/m(2) in the levosimendan group and 1.9 (0.4) L/min/m(2) in the placebo group. The mean duration of CPB to primary weaning attempt was 104 (25) minutes in the levosimendan and 109 (22) minutes in the placebo group. Primary weaning was successful in 22 patients (73%) in the levosimendan group and in 10 (33%) in the placebo group (p = 0.002). The odds ratio for failure in primary weaning was 0.182 (95% confidence interval, 0.060 to 0.552). Four patients in the placebo group failed the second weaning and underwent IABP compared with none in the levosimendan group (p = 0.112). CONCLUSIONS: Levosimendan significantly enhanced primary weaning from CPB compared with placebo in patients undergoing 3-vessel on-pump coronary artery bypass grafting. The need for additional inotropic or mechanical therapy was decreased.

Rapidly degradable hydroxyethyl starch solutions impair blood coagulation after cardiac surgery: a prospective randomized trial.

BACKGROUND: There is continuing concern about the effect of hydroxyethyl starch (HES) solutions on blood coagulation. Rapidly degradable HES solutions with more favorable effects on clot strength have therefore been developed. Because the risk of bleeding is increased after cardiopulmonary bypass, we examined whether these types of HES solutions could be administered after cardiac surgery without an alteration of coagulation. METHODS: Two new rapidly degradable HES solutions were compared with human albumin in 45 patients scheduled for elective primary cardiac surgery. After admission to the cardiac surgical intensive care unit, the patients were allocated in random order to receive either 15 mL/kg of HES solution with low molecular weight and low molar substitution (either 6% HES200/0.5 or 6% HES130/0.4) or 4% human albumin solution as a short-time (70-240 min) infusion. RESULTS: Clot formation time was prolonged and maximum clot firmness was decreased in thromboelastometry tracings after infusion of both HES solutions. This impairment in thromboelastometry tracings partly recovered (using InTEM and ExTEM coagulation activators) at 2 h after the completion of the study infusion. Platelet contribution to maximum clot firmness remained unaffected in all of the study groups. HES did not induce fibrinolysis. No changes in thromboelastometry tracings were observed after human albumin infusion. Chest tube drainage was comparable in the study groups. CONCLUSIONS: We conclude that a short-time infusion of rapidly degradable HES solutions after cardiac surgery produces impairment in fibrin formation and clot strength in thromboelastometry tracings. In this clinical setting, human albumin does not impair hemostasis.

Monitoring high-dose heparinization during cardiopulmonary by-pass--a comparison between prothrombinase-induced clotting time (PiCT) and two chromogenic anti-factor Xa activity assays.

Heparinization requires monitoring, but optimal methods for measuring the anticoagulant effects of heparin remain to be determined. We compared prothrombinase-induced clotting time (PiCT) and two chromogenic anti-factor Xa activity (anti-Xa) assays in monitoring high-dose heparinization during cardiopulmonary by-pass (CPB). Heparin effects were serially measured with PiCT and two anti-Xa assays in 100 patients. Antithrombin and protein C activities were measured preoperatively, and antithrombin activity was measured during CPB. Activation of coagulation was assessed with measurements of prothrombin fragment F1+2, soluble fibrin complexes, and D-dimer before, during, and after CPB. During CPB mean ranges of PiCT and of anti-Xa heparin levels measured with (anti-Xa A) and without (anti-Xa B) dextran sulfate and antithrombin supplementation were 5.0-5.2, 4.7-5.0, and 4.5-4.9 IU/ml, respectively. There was poor agreement between PiCT and anti-Xa and between the two anti-Xa assays (r = 0.32-0.65 and broad limits of agreement). Patients with low preoperative antithrombin or protein C levels had lower PiCT (p = 0.028 and p = 0.01) and anti-Xa A (both p<0.001) levels during CPB than others. Patients with the lowest heparin activities during CPB (lowest deciles of PiCT and anti-Xa A) had higher subsequent F1+2 after CPB (p = 0.002 and p = 0.02), and patients with high heparin levels required fewer transfusions of packed red blood cells than others. In conclusion, in the challenging setting of CPB there is poor agreement between anti-Xa assays and PiCT. However, coagulation-based PiCT could provide an alternative to the chromogenic anti-Xa assays. Higher heparin levels during CPB were confirmed to associate with reduced transfusion requirements.

Thrombophilic variables do not increase the generation or procoagulant activity of thrombin during cardiopulmonary bypass.

BACKGROUND: The generation of thrombin and its procoagulant activity are upregulated during cardiopulmonary bypass (CPB). Thrombophilia associates with increased basal thrombin generation and might therefore propagate thrombin generation during CPB. The objective of this study was to test whether preoperative thrombophilic variables associate with increased generation of thrombin or its procoagulant activity during and after CPB. METHODS: Comprehensive thrombophilia screening was performed in patients (n = 100) before elective coronary artery bypass grafting (CABG) with CPB. Markers of thrombin generation (prothrombin fragment F1+2), its procoagulant activity (soluble fibrin complexes), and a marker of fibrin degradation (D-dimer) were measured serially at eight time points before, during, and after CABG. RESULTS: Abnormal thrombophilia screening was common (44%). While patients with thrombophilic variables had higher preoperative prothrombin fragment F1+2 than others (median [interquartile range] 0.55 [0.34] vs 0.45 (0.21) nmol/L, p = 0.009) they did not have higher F1+2, D-dimer, or soluble fibrin complex levels during CPB or postoperatively than patients without thrombophilic variables. CONCLUSIONS: Preoperative thrombophilic variables do not associate with perioperative thrombin generation or its procoagulant activity in patients undergoing CABG. Our results do not support routine thrombophilia screening before CABG.

Universal leukocyte reduction of transfused red cells does not provide benefit to patients undergoing cardiac surgery.

OBJECTIVE: A policy of universal leukocyte reduction of the blood supply in Finland was implemented at the beginning of 2003. The aim of the present evaluation was to determine the potential role of leukocyte-reduced red blood cells in decreasing postoperative infections. DESIGN: A retrospective cohort study. SETTING: A major university clinic. PARTICIPANTS: Consecutive patients undergoing cardiac surgery during the years 2002 and 2003. INTERVENTIONS: Transfused patients received either buffy-coat-depleted red blood cells before leukocyte reduction (n = 782) or leukocyte-reduced red blood cells after leukocyte reduction (n = 632). MEASUREMENTS AND MAIN RESULTS: The evaluated outcome parameters were culture-proven postoperative infections, 90-day mortality, and length of stay in the intensive care unit. The percentage of patients transfused with red blood cells (56% v 53%, p = 0.16) and amounts of transfused red blood cells (4.3 +/- 6.7 [3.0] units v 4.3 +/- 6.6 [2.0] units, means +/- standard deviation [median], p = 0.48) were comparable between the study groups (buffy-coat-depleted group and leukocyte-reduced group, respectively). The 90-day mortality (6.6% v 6.3%, p = 0.28), the length of intensive care stay (3.6 +/- 4.7 [2.0] days v 4.3 +/- 7.1 [2.0] days, p = 0.34), and the number of patients with culture-proven infections (8.8% v 10.9%, p = 0.19) were unchanged after universal leukocyte reduction. In multivariate comparisons, the leukocyte reduction was not associated with culture-proven postoperative infections and 90-day mortality. CONCLUSION: No beneficial effect of the universal leukocyte reduction in cardiac surgery was found for culture-positive infection rates, 90-day mortality, or length of intensive care stay.

Heparin-induced thrombocytopenia following cardiac surgery is associated with poor outcome.

OBJECTIVE: The outcome of cardiac surgical patients with clinically diagnosed heparin-induced thrombocytopenia (HIT) was studied. DESIGN: Retrospective, observational study. SETTING: University hospital. PARTICIPANTS: All cardiac surgical patients with diagnosed HIT after cardiac surgery between January 2002 and December 2004, and concurrently, consecutive patients without HIT. INTERVENTIONS: None Measurements and Main Results: 3465 patients were treated postoperatively in the cardiac surgical intensive care unit during the study period. Clinical suspicion of HIT arose when platelet count markedly fell several days after surgery and HIT was proven by a positive enzyme immunoassay in 20 patients. Thrombocytopenia (35.5 [22] x 10(9)/L, median [interquartile range]) developed within 7 (6) days. HIT patients received significantly more platelet transfusions perioperatively than controls (p < 0.001). Thromboembolic complications occurred in 70% of HIT patients, but in none of non-HIT patients (14/20 v 0/20, p = 0.001). Intensive care unit stay was longer in HIT patients than in controls (16.5 [11.0] v 1.0 [3.0] days, p < 0.001). Nine HIT patients died (45%), while all control patients survived. Mortality was related to thrombotic complications in seven HIT patients (35%). CONCLUSIONS: The incidence of HIT in association with low-molecular-weight heparin use after cardiac surgery was low. HIT was associated with perioperative platelet transfusions and carried a remarkably high risk of thromboembolic complications and death. In order to reduce morbidity and mortality, early recognition of heparin-associated antiplatelet antibodies and alternative anticoagulation strategies need to be implemented.

Activation of protein C and hemodynamic recovery after coronary artery bypass surgery.

OBJECTIVES: Activated protein C is a physiologic anticoagulant that is activated by thrombin and upregulated during coronary artery bypass grafting. We studied the balance between thrombin generation and activated protein C levels during coronary artery bypass grafting and hypothesized that protein C activation during reperfusion is associated with hemodynamic recovery or postoperative myocardial damage. METHODS: One hundred patients undergoing elective on-pump coronary artery bypass grafting were prospectively studied. Activated protein C, protein C, prothrombin fragment F1+2 (a marker of thrombin generation), and D-dimer (a marker of fibrinolysis) levels were measured preoperatively and at 7 time points during cardiopulmonary bypass and reperfusion and postoperatively. Hemodynamic parameters were measured serially. Cardiac biomarkers (mass of the Mb fraction of creatine kinase and troponin T) were measured postoperatively. RESULTS: Reperfusion induced a significant increase in thrombin generation. Activated protein C levels peaked after heparin neutralization, when they increased more than 3-fold. Activated protein C levels correlated with F1+2 and D-dimer levels during cardiopulmonary bypass and reperfusion. Even though this correlation peaked during early reperfusion (r = 0.55, P < .001), the ratio of activated protein C to F1+2 decreased during surgical intervention and early reperfusion by 70% from the preoperative level, indicating a marked delay in protein C activation in relation to thrombin generation. Patients in the highest quintile of activated protein C levels during this period had a higher postoperative cardiac index (mean, 3.1 vs 2.5 L x min(-1) x m(-2); P < .05) and lower systemic vascular resistance (mean, 2137 vs 2429 dyne x s x cm(-5) x m(-2); P < .05). Conversely, levels of preoperative activated protein C and activated protein C measured after heparin neutralization were associated with unfavorable hemodynamic recovery postoperatively. Activated protein C or protein C levels were not associated with increased postoperative cardiac biomarkers. CONCLUSIONS: Reperfusion caused significant thrombin generation that was followed by activation of protein C. The balance of activated protein C with thrombin is associated dynamically with postoperative hemodynamic recovery.

Tranexamic acid does not correct the haemostatic impairment caused by hydroxyethyl starch (200 kDa/0.5) after cardiac surgery.

We investigated the effect of intravenous tranexamic acid on hydroxyethyl starch (HES)-induced clot strength impairment after cardiac surgery. Patients were randomized to receive either 1 g tranexamic acid or the same volume of 0.9% saline after administration of 15 ml/kg of 6% HES (molecular weight, 200 kDa; degree of substitution, 0.5) in the immediate postoperative period. Modified thromboelastometry (ROTEM) using different activators [intrinsic ROTEM (InTEM), extrinsic ROTEM (ExTEM), fibrinogen ROTEM (FibTEM)] was carried out to evaluate clot formation and lysis. The clot formation time was prolonged, and the maximum clot firmness (MCF) and shear elastic modulus [G = 5000 x MCF / (100-MCF), dynes/cm(2)] decreased (all activators of ROTEM) after completion of HES (P < 0.001, two-factor analysis of variance). These abnormalities in blood coagulation persisted despite tranexamic acid. Maximal lysis (FibTEM), indicative of fibrinolytic activity, was increased after HES but no effect of tranexamic acid was observed. The cumulative chest tube drainage until the first postoperative morning was not different between the groups (1008 +/- 251 and 1081 +/- 654 ml, P = 0.698, respectively). We conclude that after cardiopulmonary bypass, HES-induced impairment in clot formation and strength, or increased fibrinolytic capacity, is not reversed by the administration of tranexamic acid.

Treatment of abdominal compartment syndrome with subcutaneous anterior abdominal fasciotomy in severe acute pancreatitis.

BACKGROUND: Managing the abdominal compartment syndrome associated with severe acute pancreatitis by the open abdomen method is associated with considerable morbidity and resource utilization. METHODS: A technique of subcutaneous anterior abdominal fasciotomy is described for the first time in two patients with severe acute pancreatitis. RESULTS: Following the procedure, the intra-abdominal pressure decreased from 30 mmHg immediately to 23 mmHg and to a sustained level of 12-14 mmHg in the first patient, and from 35 mmHg immediately to 23 mmHg and to a sustained level of 14-19 mmHg in the second patient. CONCLUSIONS: The subcutaneous anterior abdominal fasciotomy is a promising method for safe and effective abdominal decompression with sustained effect and avoiding the morbidity associated with the alternative open abdomen techniques.

Risk evaluation of cardiac surgery in octogenarians.

OBJECTIVE: To assess the predictive value of risk factors in the European System for Cardiac Operative Risk Evaluation (EuroSCORE) for cardiac surgery on octogenarians. DESIGN: An observational study of octogenarians undergoing cardiac surgery and average-aged controls matched according to the cardiac surgical procedure. SETTING: A university hospital. PARTICIPANTS: One hundred sixty-two consecutive patients 80 years or older who underwent cardiac surgery between January 1, 2001, and June 30, 2003, and 162 average-aged controls. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Risk factors according to the EuroSCORE (The European System for Cardiac Risk Evaluation) model and EuroScore algorithm without an age component (EuroSCOREex) were evaluated. The EuroSCORE model and EuroSCOREex predicted mortality (odds ratio 1.4) and morbidity (odds ratio 1.2 and 1.3, respectively) equally well in both age groups. Adding age group information into the EuroSCOREex model in combined data, the odds ratio estimate was 3.5 for age group. The 30-day mortality of octogenarians was 8.6% versus 1.9% in controls (p < 0.01). Incidences of organ-related complications were comparable. Octogenarians spent more days in the hospital's intensive care unit and surgical ward than did controls (3.4 +/- 3.3 days v 2.7 +/- 3.1 days, p < 0.01; 9.9 +/- 5.8 days v 8.6 +/- 3.8 days, p = 0.02). Only 31 (19.1%) octogenarians were discharged home, whereas the corresponding number was 66 (40.7%) in controls (p < 0.01). CONCLUSIONS: Risk factors other than age were not higher in octogenarians, and the EuroSCORE model predicted mortality and morbidity. Age was an important single risk factor predicting mortality.

Gelatin and hydroxyethyl starch, but not albumin, impair hemostasis after cardiac surgery.

We investigated the effect of postoperative administration of colloids on hemostasis in 45 patients after cardiac surgery. Patients were randomized to receive 15 mL kg(-1) of either 4% albumin, 4% succinylated gelatin, or 6% hydroxyethyl starch (molecular weight of 200 kDa/degree of substitution 0.5) as a short-term infusion. There was a comparable decrease in maximum clot firmness of thromboelastometry tracings in gelatin and hydroxyethyl starch groups immediately after completion of the infusion, whereas these values remained unchanged in the albumin group. The impairment in clot strength persisted up to 2 h, although the values partly recovered. Postoperative bleeding correlated inversely with the clot strength in pooled data of the artificial colloids. Fibrin formation (clot formation time, alpha-angle) and fibrinogen-dependent clot strength (maximum clot firmness and shear elastic modulus) were more disturbed in the hydroxyethyl starch group than in the gelatin group. We conclude that after cardiopulmonary bypass surgery, both gelatin and hydroxyethyl starch impair clot strength and fibrin buildup, which may predispose patients to increased blood loss. The greatest impairment in hemostasis was seen after hydroxyethyl starch administration, whereas albumin appeared to have the least effect on hemostatic variables.