Systemic matrix metalloproteinase-8 and tissue inhibitor of metalloproteinases-1 levels in severe sepsis-associated coagulopathy.

BACKGROUND: Matrix metalloproteinase-8 (MMP-8) and tissue inhibitor of metalloproteinases-1 (TIMP-1) have recently been suggested to be involved in coagulation process. Our objectives were to observe systemic MMP-8 and TIMP-1 levels in patients with severe sepsis with or without disseminated intravascular coagulation (DIC) and to study their relationship with coagulation markers over time. METHODS: Our prospective pilot study included 22 patients with severe sepsis, nine (41%) of whom had overt DIC. We analysed MMP-8 and TIMP-1 serum concentrations by time-resolved immunofluorometric and enzyme-linked immunosorbent assays, respectively, on days 1, 2, 4 and 7 after the intensive care unit admission. Traditional coagulation tests were taken at the same time points. The results were compared between patients with and without DIC. Blood samples from 10 healthy volunteers were used to demonstrate normal levels. RESULTS: Both patient groups had elevated levels of MMP-8 and TIMP-1 as compared with healthy controls. TIMP-1 concentration was almost twofold in DIC patients compared with those without DIC on the first 2 days. MMP-8 was elevated only on day 2. TIMP-1 correlated positively with the severity of coagulation disturbance and with disease severity scores. MMP-8 correlated negatively only with platelet count. CONCLUSION: In this first human study, we could show that TIMP-1 is elevated in the early phase of sepsis-induced overt DIC, and it correlates both with degree of coagulopathy and disease severity. These findings suggest that TIMP-1 may play a role in the pathogenesis of DIC in septic patients.

The use of balanced HES 130/0.42 during complex cardiac surgery; effect on blood coagulation and fluid balance: a randomized controlled trial.

INTRODUCTION: Colloids and crystalloid are used during cardiac surgery for priming of the cardiopulmonary bypass (CPB) circuit. Colloids may decrease postoperative fluid balance because of their high oncotic pressure and low risk of fluid extravasation. On the other hand, colloids have been shown to impair blood coagulation. MATERIALS AND METHODS: In a prospective, randomized, double-blinded study, 50 patients scheduled for coronary artery bypass grafting or a valve procedure were planned to be randomized to receive either balanced 6% HES130/0.42 or Ringer-acetate solution for CPB priming. Randomization was stopped prematurely after 35 randomized patients (19 in the HES and 16 in the Ringer groups) because of the published report where HES130/0.42 was associated with impaired renal function. Effects on haemostasis and fluid balance were investigated. RESULTS: The rotational thromboelastometry (ROTEM®) parameters and chest tube drainage on the first postoperative morning (1POM) were comparable between the groups (p>0.05). However, patients in the HES group needed more blood and blood product transfusions. The total volume administered into the CPB circuit was lower in the HES than in the Ringer (RIN) group, 2905±1049 mL versus 3973±1207 mL (p=0.011), but there was no statistically significant difference in total fluid balance on the 1POM (5086±1660 mL in the HES group versus 5850±1514 mL in the RIN group, respectively). CONCLUSIONS: After complex cardiac surgery, the use of balanced 6% HES130/0.42 solution for CPB circuit priming did not impair haemostasis measured by ROTEM®, but it increased the need for transfusions. Fluid balance after CPB was less positive in the HES group, but, on the 1POM, it was comparable between the groups.

Fluid responsiveness predicted by elevation of PEEP in patients with septic shock.

BACKGROUND: The assessment of whether a patient is fluid responsive can be difficult in clinical practice. Invasive filling pressures are inadequate indicators of preload and fluid responsiveness in critically ill patients. Dynamic indices may be unreliable in clinical practice because of arrhythmias or spontaneous breathing efforts. Elevation of positive end-expiratory pressure (PEEP) causes cardiorespiratory interactions, which may produce signs of hypovolaemia. Our aim was to assess whether haemodynamic changes during a short elevation of PEEP would predict fluid responsiveness in patients with septic shock. METHODS: We performed a prospective observational study in 20 patients with septic shock on mechanical ventilation. We assessed the following changes in haemodynamic variables during a temporary elevation of PEEP from 10 cm H2O to 20 cm H2O during an end-expiratory pause: mean arterial pressure (MAP), systolic arterial pressure, pulse pressure, central venous pressure, pulmonary artery occlusion pressure, left ventricular end diastolic area and aortic velocity-time integral. We defined fluid responsiveness as an increase in cardiac output of 15% to a subsequent fluid challenge. RESULTS: Decrease in MAP related to elevation of PEEP predicted fluid responsiveness (P = 0.003). The best cut-off value of ΔMAP for clinical use was -8%, with a negative predictive value for fluid responsiveness of 100%. CONCLUSION: In patients with septic shock, the absence of decrease in MAP during an elevation of PEEP may be used to identify patients who will not increase their cardiac output in response to fluid challenge.

Association between inotrope treatment and 90-day mortality in patients with septic shock.

BACKGROUND: Administration of inotropes in septic patients with low cardiac output or low central/mixed venous saturation is recommended in current guidelines. However, the impact of inotrope use on the outcome of these patients is controversial. We aimed to analyse the association of inotrope treatment with 90-day mortality. METHODS: Data from 420 consecutive patients with septic shock were retrospectively collected from the intensive care unit (ICU) data management system. Factors associated with inotrope treatment were assessed. The association of 90-day mortality with inotrope treatment was first analysed using logistic regression analysis, and second including propensity score based on observed variables for selection to inotrope treatment. A subgroup analysis was performed for the 252 patients with pulmonary artery catheter. RESULTS: One hundred eighty-six (44.3%) patients received inotrope treatment during the first 24 h in ICU. Of those, 168 (90.3%) received dobutamine, 29 (15.6%) levosimendan, and 23 (12.4%) epinephrine. Blood lactate (P < 0.001), central venous pressure, (P < 0.001), and norepinephrine dose (P = 0.03) were independently associated with inotrope treatment. Patients with inotrope treatment had a higher 90-day mortality (42.5% vs. 23.9%, P < 0.001). Age (P < 0.001), Acute Physiology and Chronic Health Evaluation II score (P < 0.001), and inotrope treatment (P = 0.003) were independently associated with 90-day mortality also after adjustment with propensity score. CONCLUSION: The use of inotrope treatment in septic shock was associated with increased 90-day mortality without and after adjustment with propensity to receive inotrope. To differentiate between non-observed biases of severity of septic shock and an unfavourable effect of inotropes, prospective studies are needed.

Plasma neutrophil gelatinase-associated lipocalin and adverse outcome in critically ill patients with ventilatory support.

OBJECTIVE: Plasma neutrophil gelatinase-associated lipocalin (pNGAL) has been introduced as an early and sensitive biomarker of acute kidney injury (AKI), with an increased risk for renal replacement therapy (RRT) and adverse outcome in selected critically ill patient groups. Acute respiratory failure is the most common organ dysfunction in critically ill patients with an increased risk for AKI. Accordingly, we hypothesized that pNGAL would independently predict adverse outcome in a heterogeneous group of critically ill adult patients with acute respiratory failure. DESIGN AND SETTING: Prospective, multi-centre study in 25 Finnish intensive care units. PATIENTS AND METHODS: pNGAL was measured from critically ill patients with acute respiratory failure. We evaluated the predictive value of pNGAL for RRT, and hospital and 90-day mortality first separately, second in addition to the Simplified Acute Physiology Score (SAPS II), and third to RIFLE (Risk, Injury, Failure, Loss, End-Stage Renal Disease) AKI classification. Additionally, we assessed the factors associated with pNGAL by linear regression analysis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We included 369 patients. Median (interquartile range) baseline pNGAL was 169 (92-370) ng/ml. The areas under receiver operating characteristic curves of baseline pNGAL were as follows: 0.733 [95% confidence interval (CI) 0.656-0.810] for RRT, 0.627 (95% CI 0.561-0.693) for hospital, and 0.582 (95% CI 0.520-0.645) for 90-day mortality. Present infection, baseline creatinine, operative status, and pancreatitis were independently associated with baseline pNGAL. CONCLUSIONS: Baseline pNGAL gives no additional value into prediction of hospital and 90-day mortality compared with RIFLE or SAPS II, and has only moderate predictive power regarding RRT in critically ill adult patients with acute respiratory failure.

Hydroxyethylstarch and gelatin solutions impair blood coagulation after cardiac surgery: a prospective randomized trial.

BACKGROUND: Colloids are often used after cardiac surgery as intravascular volume replacement therapy. Cardiac surgical patients have an increased risk of bleeding. Both hydroxyethylstarch (HES) and gelatin solutions impair haemostasis. We examined the impact and dose effect on coagulation of HES 130/0.4, gelatin, or Ringer's acetate solutions after cardiac surgery. METHODS: Forty-five patients received three boluses (each 7 ml kg(-1)) of either 6% HES 130/0.4, 4% gelatin, or Ringer's acetate solution after elective cardiac surgery. The infusion of study solution was continued in the dose 7 ml kg(-1) over the following 12 h. The total dose of study solution was 28 ml kg(-1). Hypovolaemia was treated with Ringer's acetate. Modified thromboelastometry was performed to detect coagulation disorders. RESULTS: Clot formation time was prolonged and clot strength decreased after infusion of 7, 14, and 21 ml kg(-1) of either colloid compared with the Ringer's acetate group. After infusion of 14 and 21 ml kg(-1) of Ringer's acetate, clot strength was slightly, but significantly, increased. On the first postoperative morning, clot strength was still decreased in the gelatin group in comparison with the Ringer's acetate group. Neither HES nor gelatin induced fibrinolysis. Chest tube drainage was comparable between all groups. CONCLUSIONS: Even a small dose of HES 130/0.4 or gelatin impaired clot strength after cardiac surgery in a dose-dependent fashion, but neither colloid increased blood loss.

Role of fibrinogen-, factor VIII- and XIII-mediated clot propagation in gelatin haemodilution.

BACKGROUND: Gelatin solution impairs coagulation. The mechanism of coagulopathy is incompletely defined. The purpose of this study was to evaluate the capacity of single coagulation factors to reverse gelatin-promoted whole-blood coagulation disorders in vitro. METHODS: Venous blood was withdrawn from 12 volunteers in a crossover study. Four percent succinylated gelatin was added to citrated whole-blood samples to make a 40 vol% end-concentration of gelatin. The baseline and 40 vol% samples, and samples with addition of fresh-frozen plasma (FFP), fibrinogen, coagulation factors XIII (FXIII) or VIII, together with the von Willebrand factor (FVIII+vWF), were analysed by thromboelastometry (ROTEM. Coagulation was initiated by tissue thromboplastin (ExTEM with and without cytochalasin to determine the functional component of fibrinogen (FibTEM. RESULTS: Initiation of coagulation and fibrin formation were delayed at 40 vol% gelatin dilution. At this stage, the median (25th-75th percentiles) maximum clot firmness (MCF) was 76.3 (65.9-80.0) and 32.5 (27.4-45.0)% of the pre-dilution value in ExTEM and FibTEM thromboelastometry, respectively. Coagulation time was corrected by addition of fibrinogen and FFP in ExTEM and FibTEM analysis, whereas FVIII or FXIII had minimal effects. MCF was partly restored only by FFP in ExTEM. In FibTEM analysis, MCF improved more by fibrinogen than by FVIII+VWF, FXIII or FFP. CONCLUSIONS: Gelatin-induced whole-blood coagulation disorder in vitro is mainly dependent on the initial fibrinogen-fibrin interaction. The proposed mechanism might suggest not to reverse gelatin coagulopathy solely by fibrinogen administration. The administration of FFP, a mixture of different coagulation factors, reversed the gelatin-induced in vitro coagulopathy the best.

Haemodynamics and acid-base equilibrium after cardiac surgery: comparison of rapidly degradable hydroxyethyl starch solutions and albumin.

BACKGROUND: Stable haemodynamics is often achieved by administration of colloids after cardiac surgery. We conducted a prospective, randomized, open-label study comparing haemodynamics and acid-base equilibrium after infusion of two rapidly degradable hydroxyethyl starch (HES) solutions or human albumin (HA) to cardiac surgical patients. MATERIALS AND METHODS: 45 patients received a predetermined fixed dose of 15 ml kg(-1) of either 6% HES (mW 130 kDa, n = 15), 6% HES (MW 200 kDa, n = 15) or 4% HA (MW 69 kDa, n = 15) after on-pump cardiac surgery. RESULTS: Left ventricular filling pressures assessed using pulmonary artery catheter responded similarly in all groups. mean (SD) cardiac index was higher in HES130 [3.5 l min(-1) m(-2) (0.7) ] and HES200 [3.5 l min(-1) m(-2) (0.5)] than in HA [2.8 l min(-1) m(-2) (0.6)] group after completion of infusion (P = 0.002) but no differences were detected at 2 and 18 hours. Oxygen delivery increased in both HES groups but not in HA group. After cessation of infusion base excess was the most negative in Ha group. At 2 hours mean (SD) base excess was higher in HES130 [0 (1.32)] than in HES200 [-1.32 (2.27) ] and HA [-2.3 (1.3)] group (P = 0.002, between the groups). CONCLUSIONS: We conclude that the effect of albumin on cardiac performance is inferior than that of HES130 or HES200 in early postoperative phase after cardiac surgery. HES130 induces no alterations in acid-base equilibrium whereas a negative base excess was observed after HA infusion.

A comparison of the haemodynamic effects of 4% succinylated gelatin, 6% hydroxyethyl starch (200/0.5) and 4% human albumin after cardiac surgery.

BACKGROUND AND AIMS: The goal for volume replacement therapy is to maintain stable haemodynamics after cardiac surgery. We hypothesized that a short term infusion of hydroxyethyl starch results in better haemodynamic response than an infusion of lower molecular weight gelatin. MATERIAL AND METHODS: 45 patients received a predetermined fixed dose of 15 ml kg(-1) of either 4% succinylated gelatin (GEL) or 6% hydroxyethyl starch (HES) or 4% human albumin (HA) after cardiac surgery. RESULTS AND CONCLUSIONS: Pulmonary capillary wedge pressure was more increased in GEL and HES groups [mean (SD) 153% (54) and 168% (57) of pre-infusion value] than in HA group [122% (23)] (P = 0.031) after completion of infusion, but no differences in cardiac index (CI) and stroke volume index (SVI) were observed. At 2 and 18 hours after end of study infusions SVI was more increased in HES [143% (38) and 148% (41) of pre-infusion values] and HA [143% (35) and 163% (42) of pre-infusion values] groups than in GEL [116% (23) and 125% (30)] group (P = 0.047 at 2 hours and P = 0.033 at 18 hours). In early postoperative phase after cardiac surgery, HES and HA infusions improve haemodynamics more and longer period than GEL infusion.

Thrombin generation during reperfusion after coronary artery bypass surgery associates with postoperative myocardial damage.

BACKGROUND: Cardiopulmonary bypass and coronary artery bypass grafting (CABG) result in significant thrombin generation and activation of fibrinolysis. Thrombin contributes to myocardial ischemia-reperfusion injury in animal studies, but the role of thrombin in myocardial damage after CABG is unknown. OBJECTIVES: We measured thrombin generation and fibrin turnover during reperfusion after CABG to evaluate their associations with postoperative hemodynamic changes and myocardial damage. METHODS: One hundred patients undergoing primary, elective, on-pump CABG were prospectively enrolled. Plasma prothrombin fragment F(1+2) and D-dimer were measured preoperatively and at seven time points thereafter. Mass of the Mb fraction of creatine kinase (Ck-Mbm) and troponin T (TnT) were measured on the first postoperative day. RESULTS: Reperfusion induced an escalation of thrombin generation and fibrin turnover despite full heparinization. F(1+2) during early reperfusion associated with postoperative pulmonary vascular resistance index. F(1+2) at 6 h after protamine administration correlated with Ck-Mbm (r = 0.40, P < 0.001) and TnT (r = 0.44, P < 0.001) at 18 h postoperatively. Patients with evidence of myocardial damage (highest quintiles of plasma Ck-Mbm and TnT) had significantly higher F(1+2) during reperfusion than others (P < 0.002). Logistic regression models identified F(1+2) during reperfusion to independently associate with postoperative myocardial damage (odds ratios 2.5-4.4, 95% confidence intervals 1.04-15.7). CONCLUSIONS: Reperfusion caused a burst in thrombin generation and fibrin turnover despite generous heparinization. Thrombin generation during reperfusion after CABG associated with pulmonary vascular resistance and postoperative myocardial damage.

Red blood cell transfusions in patients undergoing lower extremity artery bypass surgery.

BACKGROUND AND AIMS: The purpose of this study was to search predictors of red blood cell transfusions in peripheral vascular surgical patients. MATERIAL AND METHODS: All the patients who undergone infrainguinal bypass surgery at Helsinki University Hospital in the year 2000 were included. Of 266 records 261 (98%) were available for data review. Multiple stepwise regression model was created to identify independent predictors of blood use. RESULTS AND CONCLUSIONS: 174 (67%) of the patients received red blood cell transfusion. The lowest measured mean (SD) haemoglobin was 94 (11) g/l intraoperatively and 92 (+/- 10) g/l on the first two postoperative days. The median (range) number of units was 3 (1-19). Multivariate analysis showed that high age (p = 0.019), small body surface area (p = 0.017), low preoperative haemoglobin (p < 0.001), blood loss (p < 0.001), long lasting surgery (p<0.001), reoperation (p=0.018), femoro-distal reconstruction (p=0.048) and chronic obstructive pulmonary disease (p = 0.023) increased the risk to receive red blood cell transfusion. The frequent use of antithrombotic medication (72% of the patients) did not significantly increase red blood cell administration. The generous use of red blood cells despite relative safe haemoglobin levels indicates a need for a standardized multidisciplinary transfusion strategy in this patient population. Otherwise, most of the predictors for red blood cell administration were nonmodifiable.

Cardiopulmonary bypass with heparin-coated circuits and reduced systemic anticoagulation.

BACKGROUND: The improved biocompatibility of the cardiopulmonary bypass circuits made possible by the use of surface-immobilized heparin may allow for a reduction in the amount of heparin administered systemically. This study was performed to elucidate the effects of cardiopulmonary bypass using heparin-coated circuits and reduced heparinization on hemostatic variables and clinical outcome. METHODS: Thirty patients scheduled to undergo myocardial revascularization were randomized to have either a heparin-coated or an uncoated cardiopulmonary bypass circuit. Anticoagulation was induced with heparin (100 IU/kg in the coated group and 300 IU/kg in the uncoated group) and the activated clotting time was kept over 200 and 480 seconds in the coated and uncoated groups, respectively. RESULTS: The postoperative overnight loss of hemoglobin through the drains was lower in the heparin-coated group (43.6 g; range, 18.5-69.0 g) than in the uncoated group (73.0 g; range, 32.2-137.7 g) (p = 0.0015). Plasma concentrations of prothrombin fragment 1 + 2 and D-dimer were significantly more elevated after cardiopulmonary bypass in the coated group than they were in the uncoated group. Two patients in the coated group had a stroke postoperatively. CONCLUSIONS: The reduction in systemic heparinization was associated with thrombin formation, which may predispose to intravascular and cardiopulmonary bypass circuit clotting. Therefore, generous systemic heparinization may still be prudent despite the improved biocompatibility offered by heparin-coated surface.

Auditory stream segregation in children with Asperger syndrome.

Individuals with Asperger syndrome (AS) often have difficulties in perceiving speech in noisy environments. The present study investigated whether this might be explained by deficient auditory stream segregation ability, that is, by a more basic difficulty in separating simultaneous sound sources from each other. To this end, auditory event-related brain potentials were recorded from a group of school-aged children with AS and a group of age-matched controls using a paradigm specifically developed for studying stream segregation. Differences in the amplitudes of ERP components were found between groups only in the stream segregation conditions and not for simple feature discrimination. The results indicated that children with AS have difficulties in segregating concurrent sound streams, which ultimately may contribute to the difficulties in speech-in-noise perception.

Lack of renoprotective effect of i.v. N-acetylcysteine in patients with chronic renal failure undergoing cardiac surgery.

BACKGROUND: Pre-existing chronic renal failure is a significant risk factor for acute renal failure (ARF) after cardiac surgery. N-acetylcysteine (NAC) has been shown to prevent contrast media-induced ARF. Our objective was to evaluate whether i.v. NAC has renoprotective effects in patients with mild renal failure undergoing cardiac surgery. METHODS: In this prospective, randomized, double-blind study, 80 patients with mild to moderate renal failure undergoing elective heart surgery with cardiopulmonary bypass were recruited. All received either i.v. NAC (n=38) or placebo (n=39) at induction of anaesthesia and then up to 20 h. Urine N-acetyl-beta-D-glucosaminidase (NAG) and urine creatinine ratio, plasma creatinine, and serum cystatin C levels indicated renal function. RESULTS: Levels of urinary NAG/creatinine ratio, plasma creatinine and serum cystatin C did not significantly differ between NAC and placebo groups during five postoperative days. Urine NAG/creatinine ratio increased over 30% in 100% of patients in the NAC group vs 92.3% in the placebo group (P=0.081). Plasma creatinine increased by 25% from baseline or over 44 mumol litre(-1) in 42.1% in NAC group vs 48.7% in placebo group (P=0.560). Serum cystatin C exceeded 1.4 mg litre(-1) in 78.9% in NAC group vs 61.5% in placebo group (P=0.096). CONCLUSIONS: Prophylactic treatment with i.v. N-acetylcysteine had no renoprotective effect in patients with pre-existing renal failure undergoing cardiac surgery.

Artificial colloids impair haemostasis. An in vitro study using thromboelastometry coagulation analysis.

BACKGROUND: Hydroxyethyl starch (HES) solutions impair haemostatic mechanisms. The impact of the degree of substitution (DS) of a HES solution on thromboelastometry tracings is unclear. Therefore we tested the hypothesis of whether the DS has an effect on the haemostatic defect caused by HES, and assessed whole blood coagulation by thromboelastometry coagulation analysis (ROTEM, Pentapharm Co., Munich, Germany) in serial in vitro haemodilutions of colloids. METHODS: Whole blood was withdrawn from 12 volunteers in a crossover study. Six per cent low-molecular weight HES with a high (HES MW 120 kDa/degree of substitution 0.7) and low (HES MW 130 kDa/0.4) degree of substitution, 4% succinylated gelatin (GEL) or 4% albumin (ALB) was added to citrated venous whole blood samples to make 20, 40, 60 vol.% end-concentrations of each of the solutions. Samples were analyzed by ROTEM. RESULTS: There was a comparable decrease in maximum clot firmness (MCF) and shear elastic modulus [G = 5000 x MCF/(100-MCF)] by HES 120/0.7 and HES 130/0.4 at 20 and 40 vol.% dilutions. At 60 vol.% dilution HES 120/0.7 decreased less alpha-angle and MCF than HES 130/0.4 (P < 0.05). With moderate dilutions all colloids shortened coagulation time (CT). At 20, 40 and 60 vol.% dilutions MCF and G were more decreased in both HES groups than in the ALB and GEL groups (P < 0.05). Furthermore, at 40 and 60 vol.% dilutions G deteriorated more in the GEL than in the ALB group (P < 0.05). CONCLUSION: In vitro the impact of the degree of substitution of HES solution on thromboelastometry coagulation analysis was modest. Haemodilution with gelatin and albumin induced fewer coagulation abnormalities than HES. In addition, the haemodilution with gelatin impaired coagulation more than albumin solution.

The effects of aprotinin and tranexamic acid on thrombin generation and fibrinolytic response after cardiac surgery.

BACKGROUND: Thrombin formation during cardiac surgery could result in disordered hemostasis and thrombosis. The aim of the study was to examine the effects of aprotinin and tranexamic acid on thrombin generation and fibrinolytic activity in patients undergoing cardiac surgery. METHODS: Data were collected prospectively from 60 patients undergoing coronary artery bypass grafting using cardiopulmonary bypass (CPB). In a randomized sequence, 20 patients received aprotinin, 20 patients received tranexamic acid, and in 20 patients placebo was used. RESULTS: Significant thrombin activity was found in all the studied patients. Thrombin generation was less in the aprotinin group than in the tranexamic acid and the placebo group (thrombin/anti-thrombin III complexes 33.7 +/- 3.6, 53.6 +/- 7.0 and 44.2 +/- 5.3 microg/l 2 h after CPB and F1 + 2 fragment 1.50 +/- 0.10, 2.37 +/- 0.37 and 2.04 +/- 0.20 nmol/l 6 h after surgery, respectively). The inhibition of fibrinolysis was significant with both anti-fibrinolytic drugs (D-dimers 0.427 +/- 0.032, 0.394 +/- 0.039 and 2.808 +/- 0.037 mg/l 2 h after CPB, respectively). The generation of d-dimers was inhibited until 16 h after CPB in the aprotinin group. The plasminogen activation was significantly less in the aprotinin group (plasmin/anti-plasmin complexes 0.884 +/- 0.095, 2.764 +/- 0.254 and 1.574 +/- 0.185 mg/l 2 h after CPB, respectively). CONCLUSION: Thrombin formation is inevitable in coronary artery bypass surgery when CPB is used. The suppression of fibrinolytic activity, either with aprotinin or with tranexamic acid interferes with the hemostatic balance as evaluated by biochemical markers. Further investigations are needed to define the role of hemostatic activation in ischemic complications associated with cardiac surgery.

Haemostatic responses to desmopressin acetate after primary coronary artery bypass surgery.

Previous studies have suggested that the administration of desmopressin (DDAVP) may reduce blood loss after cardiac surgery. The present double-blind, randomized, placebo-controlled trial was performed to determine the effect of DDAVP on haemostasis during and after primary coronary artery bypass surgery. Fifteen patients received an infusion of DDAVP 0.3 microgram/kg and 15 patients received a placebo infusion over 15 min after cardiopulmonary bypass. Following DDAVP administration, the increase in factor VIII:C plasma level was greater than after placebo (the increase at 90 min after treatment 1.10 +/- 0.11 vs. 0.45 +/- 0.09 IU/ml, P less than 0.01). A difference between the treatments tended to occur also in the increase of von Willebrand antigen (0.64 +/- 0.08 vs. 0.23 +/- 0.07 IU/ml, P = 0.0556). A detailed evaluation of various haemostatic parameters showed no significant changes towards hypercoagulability or fibrinolysis. Inspite of the observed potential haemostatic effect of DDAVP, patients treated with DDAVP and placebo had similar postoperative blood losses (950 +/- 185 vs. 1034 +/- 321 ml), similar total haemoglobin losses (45.9 +/- 11.1 vs. 54.7 +/- 25.9 g) and similar red cell transfusion requirements (1.3 (range 0-2) vs. 1.1 (range 0-3) units). The plasma concentrations of factor F VIII:C and von Willebrand factor antigen after cardiopulmonary bypass may explain the failure to achieve a therapeutic effect with DDAVP.