Nafamostat mesilate reduces blood cell adhesion to cardiopulmonary bypass circuits: an in-vitro study

Nafamostat mesilate (FUT-175) is a protease inhibitor, working as an inactivator of coagulation, fibrinolysis and platelet aggregation. Although FUT-175 directly blocks contact factors in coagulation, it also may decrease activation of humoral cascade systems when used in cardiopulmonary bypass circuits. We performed an in vitro study using fresh human blood in the following cardiopulmonary bypass circuits: standard circuit (C), biosurfaced circuit (B) and standard circuit containing FUT-175 (F). Each circuit was primed with 500 ml of electrolyte solution and 500 ml of fresh blood. Cardiopulmonary bypass was performed using a roller pump for four hours in two sets of each circuit configuration. Platelet factors (platelet count and beta-thromboglobulin), coagulation factors (thrombin-antithrombin III complex and fibrinopeptide A), fibrinolysis factors (alpha 2-plasmin inhibitor complex and alpha 2-plasmin inhibitor), complement factors (C3a, C4a), free hemoglobin, and granulocyte elastase were measured at the beginning and end of the study. Hemocytograms were measured concurrently. The FUT-175 group showed significantly lower levels of the measured indices than the biosurfaced group in thrombin-antithrombin III complex (7.4 +/- 2.1 vs. 54.9 +/- 38.1 ng/ml), fibrinopeptide A (7.2 +/- 2.0 vs. 20.2 +/- 14.6 ng/ml), beta-thromboglobulin (1940 +/- 250 vs. 2438 +/- 314 ng/ml) and free hemoglobin (25.2 +/- 14.3 vs. 73.8 +/- 18.4 mg/dl). There were no significant differences between Group F and Group B in platelet count, C3a, C4a and granulocyte elastase, although these indices were significantly lower in Groups F and B when compared to Group C.(ABSTRACT TRUNCATED AT 250 WORDS)     

Reduction of the inflammatory response following coronary bypass grafting with total minimal extracorporeal circulation.

OBJECTIVE: Cardiopulmonary bypass (CPB) is known to cause part of the systemic inflammatory reaction after cardiac surgery that can be responsible for organ failure. A novel technique based on a minimal extracorporeal circulation (MECC(R)) system has been evaluated with regard to the inflammatory response in a prospective study involving patients undergoing coronary artery bypass grafting. METHODS: Sixty consecutive patients were randomly assigned to either standard normothermic CPB (n=30) or the MECC system, with a reduced priming volume, no aortic venting and no venous reservoir, excluding the blood-air interface (n=30). Specific evaluation of cytokine release (IL-1beta, IL-6, TNF-alpha), as well as neutrophil elastase secretion and beta-thromboglobulin release from platelets and S100 protein assay were performed. Serial blood samples were taken prior to the onset, after initiation, at the end and after weaning of the CPB; further samples were collected 6 and 24h after the end of the CPB. RESULTS: All patients were similar with regards to pre- and intra-operative characteristics and clinical outcomes were comparable for both groups. MECC system allowed a reduced hemodilution with a mean drop of the hematocrit of 8.5 vs. 15.3% (P<0.05). Mononuclear phagocytes dropped in a more important manner under standard CPB conditions (247+/-151 vs. 419+/-168, P=0.002), but both groups demonstrated a rise in monocyte count at the end of the CBP. No significant release of IL-1beta was observed in either group. By the end of CPB, IL-6 levels were significantly lower in the MECC group (38.8+/-19.6 vs. 87.9+/-78.9, P=0.04), despite a higher monocyte count. Plasma levels of TNF-alpha rised significantly more during standard CPB than with the MECC system (17.8+/-15.4 vs. 10.1+/-5.6, P=0.002). With MECC, the neutrophil elastase release was reduced (72.7+/-47.9 vs. 219.6+/-103.4, P=0.001). Platelet count remained at higher values with the minimal compared to standard CPB. It is noteworthy to consider that beta-thromboglobulin levels showed slightly lower platelet activation in the MECC group at all times of CPB (110.5+/-55.6 vs. 134.7+/-46.8, P=0.10). The pattern of release of S100 protein showed higher values in patients undergoing standard CPB than after MECC. CONCLUSIONS: The MECC system is suitable to maintain total extracorporeal circulation and demonstrates a lower inflammatory reaction when compared to standard CPB.     

Off-pump coronary artery bypass operation does not increase procoagulant and fibrinolytic activity: preliminary results

BACKGROUND: This study analyzes the effects on coagulation and fibrinolysis comparing off-pump coronary artery bypass (OPCAB) and on-pump CABG operations. METHODS: In a prospective, nonrandomized, comparative evaluation, patients scheduled for elective myocardial revascularization were studied. Due to possible confounding factors patients with postoperative retransfusion of mediastinal shed blood were excluded. Nine patients underwent OPCAB operation and 16 underwent on-pump CABG. Activated clotting time (ACT) was adjusted to 250 seconds in OPCAB (81 +/- 18 [mean +/- SD] IU/kg heparin) and to more than 480 seconds in on-pump CABG (400 IU/kg heparin, additional 10,000 IU in pump prime). Perioperatively blood samples were collected and hematologic and hemostatic variables including fibrinopeptide A (FPA), fibrin monomer (FM), thrombin-antithrombin complex (TAT), and D-dimer were analyzed. RESULTS: Both groups showed comparable demographic variables. Number of grafts per patient was slightly higher in the on-pump group (3.6 +/- 0.6 versus 3.0 +/- 1.1, p = 0.23). The FPA levels did not differ significantly between the groups. The FM, TAT, and D-dimer values were significantly higher in on-pump CABG (p < 0.0001, p < 0.01, and p < 0.0001, respectively), reflecting increased coagulant and fibrinolytic activity. This was also the case when values were corrected for hemodilution. CONCLUSIONS: Despite lower systemic anticoagulation activation of coagulation and fibrinolysis is reduced in OPCAB compared with on-pump CABG. Reduced thrombin generation and reduced fibrinolytic activity in OPCAB indicates better preservation of hemostasis. We suggest the term "preserved hemostasis" instead of "hypercoagulant activity" with respect to OPCAB.     

Platelet aggregation and beta-thromboglobulin levels in nephrotic patients with and without thrombosis

Platelet aggregation and beta-thromboglobulin levels were studied in 17 patients with the nephrotic syndrome. Thrombosis or thromboembolic complications occurred in 4 of these patients with serum albumin levels below 2 g/100 ml. Pathologic platelet aggregation assessed by estimating alpha 2-angle values derived from platelet aggregation curves was seen in the 4 patients with thromboembolic complications (alpha 2-angle 69.5 degrees +/- 10.1 degrees), whereas patients without thrombosis showed normal alpha 2-angle values (less than 30 degrees) with only one exception. In addition, patients with thromboembolic complications demonstrated significantly elevated beta-thromboglobulin levels, when compared with those not having thrombosis or thromboembolic complications (76.8 +/- 14.3 ng/ml vs 44.8 +/- 8.6 ng/ml, P less than 0.001). The decrease in serum albumin concentration showed an inverse relationship with both, alpha 2-angle values (r = -0.82, P less than 0.001) and beta-thromboglobulin levels (r = -0.83, P less than 0.001) indicating a regulatory role of serum albumin in platelet aggregation. We conclude, that altered platelet aggregation as well as hypercoagulability may be involved in the pathogenesis of thrombosis and thromboembolic complications in the course of the nephrotic syndrome.     

The effect of hemodilution on blood flow regulation in normal and postischemic intestine

We investigated the effect of hemodilution on intestinal blood flow and oxygen consumption (VO2) in denervated rat small intestinal preparations. In one series of experiments, intestinal blood flow (IBF) and intestinal oxygen extraction (A-VO2) were measured during graded decreases in perfusion pressure. Control animals underwent consecutive studies without hemodilution; experimental animals were studied before and after isovolemic hemodilution. In a second series of experiments, normovolemic hemodilution was performed in experimental animals NH while hematocrit was maintained in controls, C. Preparations were then subjected to 30 min of complete ischemia followed by 30 min of reperfusion. Hemodilution (40.5 +/- 0.8% to 17.2 +/- 2.5%) decreased A-VO2 (3.9 +/- 0.5 to 2.1 +/- 0.4 ml/dl; P less than 0.05) but increased IBF (77.5 +/- 9.8 to 132.1 +/- 15.0 ml/min/100 gm; P less than 0.01). IBF was maintained to the limit of pressure:flow autoregulation (69 mmHg). Below this point, decreases in IBF were accompanied by increases in A-VO2 thus maintaining VO2. At a much lower "critical pressure" (42 mmHg) maximal oxygen extraction was reached and VO2 decreased with IBF. In the second series of experiments, hemodiluted animals (hematocrit 25 +/- 1%) studied during the reperfusion period maintained higher O2 consumption [30 min values (ml/min/100 gm): 4.8 +/- 0.9 NH vs 1.6 +/- 0.2 C, P less than 0.01] and A-VO2 difference [30 min values (vol%): 3.9 +/- 0.4 NH vs 2.1 +/- 0.4 C, P less than 0.005] than control animals (hct 33 +/- 2%). Hemodilution does not impair the intestine's ability to maintain O2 consumption during hypotension and hypoperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Activated coagulation during open and endovascular abdominal aortic aneurysm repair

OBJECTIVE: The study was conducted to determine activation of coagulation in patients undergoing open and endovascular infrarenal abdominal aortic aneurysm repair (EVAR). METHODS: In a prospective, comparative study, 30 consecutive patients undergoing open repair (n = 15) or EVAR (n = 15) were investigated. Blood samples to determine fibrinopeptide A, fibrin monomer, thrombin-antithrombin complex, and D-dimer were taken up to 5 days postoperatively. Routine hematologic and hematochemical parameters as well as clinical data were collected. RESULTS: Both groups showed comparable demographic variables. Operating time was longer in open repair (249 +/- 77 minutes vs 186 +/- 69 minutes, P < .05). Perioperatively elevated markers of coagulation were measured in both groups. Fibrinopeptide A levels did not differ significantly between the groups (P = .55). The levels of fibrin monomer and thrombin-antithrombin complex were significantly higher in patients undergoing EVAR (P < .0001), reflecting increased thrombin activity and thrombin formation compared with open surgery. The D-dimer level did not differ significantly between the groups. These results were also valid after correction for hemodilution. CONCLUSION: These data suggest increased procoagulant activity in EVAR compared with open surgery. A procoagulant state may favor possible morbidity derived from micro- and macrovascular thrombosis, such as in myocardial infarction, multiple organ dysfunction, venous thrombosis and thromboembolism, or disseminated intravascular coagulation.     

Cold continuous antegrade blood cardioplegia: high versus low hematocrit.

OBJECTIVE: Cold continuous antegrade blood cardioplegia (CCABCP) is used with different hematocrit values. We investigated the consequences of CCABCP with low hematocrit (LH: 20-25%) versus high hematocrit (HH: 40-45%). METHODS: Anesthetized open chest pigs (25 kg) were placed on cardiopulmonary bypass (CPB). The hearts were arrested for 30 min by 6 degrees C CCABCP with either LH or HH (n=8, each): After an initial 3 min application of high potassium (20 mEq) BCP the hearts were arrested for subsequent 27 min by normokalemic 6 degrees C cold blood delivered continuously antegradely. Thereafter the hearts underwent perfusion with warm systemic blood for an additional 30 min on CPB. Biochemical cardiac data (MVO(2) (ml min(-1)100 g(-1)), release of creatine kinase (CK; units min(-1)100 g(-1))) and lactate (mg min(-1)100 g(-1))) and the coronary vascular resistance index (CVRI (mmHg ml(-1)ming)) were measured during CPB. Total tissue water content (%) and left and right ventricular stroke work indices (LV-and RV-SWI (g m kg(-1))) were assessed 30 min after discontinuation of CPB and compared to pre-CPB controls. RESULTS: The hearts of the LH group had no biochemical or functional disturbance. The HH group showed marked CK leakage (0.6+/-0.2* vs. 0.1+/-0.1, *P<0.05 for comparison of LH vs. HH with Student's t-test for unpaired data), impaired initial oxygen consumption (4+/-1* vs. 7+/-1) after cardiac arrest, an increased CVRI (82+/-12* vs. 50+/-8), the formation of myocardial edema (81.0+/-1.3* vs. 77.5+/-1.2), and poor functional recovery (LVSWI 0.2+/-0.1* vs. 1.0+/-0.1; RVSWI 0.1+/-0.1* vs. 0.5+/-0.1). The absence of lactate production in both groups was in accord with the non-ischemic protocol. CONCLUSIONS: CCABCP with a low hematocrit of 20-25% is cardioprotective. In contrast, CCABCP with a high hematocrit of 40-45% jeopardizes the heart despite avoiding ischemic periods, and should be avoided.     

Effects of continuous haemofiltration vs intermittent haemodialysis on systemic haemodynamics and splanchnic regional perfusion in septic shock patients: a prospective, randomized clinical trial.

BACKGROUND: Parameters of splanchnic regional perfusion, like intramucosal pH (pHi) and pCO(2) (pCO(2)i), may predict outcome in septic shock patients. Continuous venovenous haemofiltration (CVVH) has been considered beneficial in haemodynamically unstable septic shock patients. In a prospective, randomized, clinical study, we investigated whether CVVH, in comparison to intermittent haemodialysis (IHD), is able to improve splanchnic regional perfusion in critically ill patients. METHODS: Thirty septic shock patients with acute renal failure were randomized to either CVVH (n=20) or IHD (n=10) groups for renal replacement therapy. Patient characteristics at baseline were not different in terms of severity of illness (APACHE II scores), haemodynamics, and pHi/pCO(2)i values. Systemic haemodynamics, oxygen transport variables, and splanchnic regional perfusion parameters were measured at 0.5, 2, 4 and 24 h after initiation of renal replacement therapy. There were no major changes in vasopressor support throughout the 24-h study period. RESULTS: In contrast to IHD, CVVH caused a decrease in heart rate (-3+/-11 vs +9+/-8/min, P<0.01) and an increase in systolic blood pressure (+12+/-1 vs -5+/-17 mmHg, P<0.05) after 2 h. After 24 h, increased systemic vascular resistance was found in the CVVH group in comparison with the IHD group (+312+/-755 vs -29+/-89 dyne/cm(5), P<0.05) and was accompanied by a decrease in cardiac output (-1.54+/-1.4 vs -0.25+/-0.9 l/min, P<0.01). However pHi values remained constant throughout the 24-h study period in both groups and were not different between the groups (CVVH 7.19+/-0.1 vs IHD 7.19+/-0.1, n.s.) as did the pCO(2)i values (CVVH +7+/-17 vs IHD 0+/-15 mmHg, n.s.) and pCO(2) gap values (CVVH +6+/-15 vs IHD +5+/-12 mmHg, n.s.). CONCLUSIONS: Despite different changes of systemic haemodynamics between CVVH and IHD, CVVH did not improve parameters of splanchnic regional perfusion like pHi, pCO(2)i or pCO(2) gap in septic shock patients.     

Influence of hematocrit on cardiopulmonary function after acute hemorrhage

The 'optimal' hematocrit to which patients should be resuscitated after shock and trauma is controversial. To test the hypothesis that sufficient oxygen delivery can be provided at a lower hematocrit without impairing oxygen consumption or hemodynamic function, 25 patients were prospectively studied immediately following injury and/or acute hemorrhage. Patients were randomized to have their hematocrits (HCT) maintained near 30% (29.7 +/- 0.4% (M +/- SEM); n = 12) or 40% (38.4 +/- 0.6%, n = 13). Cardiopulmonary parameters were measured twice a day for 3 days. Statistical analysis used a repeated measures analysis of variance with patient age, and ventilator parameters (FIO2, PEEP, and ventilator mode) as covariates. Arterial and venous O2 saturations were not significantly different at different hematocrits, although arterial and venous O2 contents were lower at 30% HCT (a = 14.1 +/- 0.2 m10(2)/dl, v = 10.1 +/- 0.3 m10(2)/dl; vs. a = 17.4 +/- 0.4 m10(2)/dl, v = 13.6 +/- 0.6 m10(2)/dl; p less than 0.05). This resulted in a lower oxygen delivery at the lower HCT. Between the two groups, there also was no significant difference in cardiac index (overall mean, 3.64 +/- 0.16 ml/min/m2), heart rate (99 +/- 4 bpm), systemic vascular resistance (1,058 +/- 55 dyne-sec/cm5), or left ventricular stroke work index (4.3 +/- 0.3 X 10(6) dyne-cm/m2). Intrapulmonary shunt was higher with higher hematocrit (22.6 +/- 2.4% at 40% HCT vs. 14.6 +/- 1.6% at 30% HCT; p less than 0.05) with no difference in end-expiratory pressure.(ABSTRACT TRUNCATED AT 250 WORDS)     

Influence of hemodialysis on the mean blood flow velocity in the middle cerebral artery

BACKGROUND: Several effects of hemodialysis, including hemoconcentration, alterations of hemostasis or hemorheology and endothelial activation, could potentially interfere with cerebral blood flow (CBF) regulation. These treatment-specific changes may also be crucial for the enhanced incidence of stroke in uremic patients. Nevertheless, the influence of hemodialysis on CBF has not been yet adequately studied. PATIENTS AND METHODS: We registered mean blood flow velocity (MFV) in the middle cerebral artery (MCA) during hemodialysis treatment in order to evaluate its contribution on CBF changes. Transcranial Doppler ultrasonography (TCD) of the MCA was performed continuously during hemodialysis treatment in 18 stable patients (10 males and 8 females, mean age 62 +/- 11 years) with end-stage renal disease of various origin. Blood pressure (mmHg), heart rate (/min), ultrafiltration volume (ml), BV changes (deltaBV by hemoglobinometry, %), arterial blood gases (pO2, blood oxygen content, pCO2), hemostasis activation (thrombin-antithrombin III complex, ELISA) and fibrinogen (Clauss) were measured simultaneously at the beginning of treatment and every hour thereafter. RESULTS: Before the hemodialysis session the MFV in the MCA was within normal range (57.5 +/- 13.0 cm/s, ref. 60 +/- 12) and was mainly dependent on the patients' age (r = -0.697, p < 0.01). The blood flow velocity in the MCA decreased significantly from 57.5 +/- 13.0 cm/s before the beginning to 48.3 +/- 11.1 cm/s after four hours (n = 18, p < 0.05) and to 43.9 +/- 8.9 cm/s after five hours (n = 9, p < 0.05) of hemodialysis treatment. During hemodialysis treatment, the percentual changes of MFV in the MCA (delta%MFV) were interrelated to the ultrafiltration volume (r = -0.486, p < 0.01), the blood volume (BV%, r = 0.369, p < 0.01) and the percentual changes of the hematocrit (r = -0.358, p < 0.01), of the arterial blood oxygen content (delta%acO2, r = -0.420, p < 0.01) and of the plasma fibrinogen levels (delta%fibrinogen, r = 0.244, p < 0.05). CONCLUSION: A significant continuous decrease of the MFV in the MCA was observed during hemodialysis treatment, which inversely correlated both with ultrafiltration volume, BV changes and changes of plasma fibrinogen. The ultrafiltration-induced hemoconcentration with concomitant rise of hematocrit and oxygen transport capacity, may partly explain the alterations in the cerebral MFV observed during hemodialysis.     

Continuous renal replacement therapy: does technique influence azotemic control?

BACKGROUND AND OBJECTIVES: Different techniques of continuous renal replacement therapy (CRRT) might have different effects on azotemic control. Accordingly, we tested whether continuous veno-venous hemodiafiltration (CVVHDF) or continuous veno-venous hemofiltration (CVVH) would achieve better control of serum creatinine and plasma urea levels. DESIGN: Retrospective controlled study. SETTING: Two tertiary Intensive Care Units. PATIENTS: Critically ill patients with acute renal failure (ARF) treated with CVVHDF (n = 49) or CVVH (n = 50). Interventions: Retrieval of daily morning urea and creatinine values before and after the initiation of CRRT for up to 2 weeks of treatment. MEASUREMENTS AND RESULTS: Before treatment, serum urea and creatinine concentrations were significantly lower in the CVVH group than in CVVHDF group (urea: 31.0 +/- 15.0 mmol/L for CVVHDF and 24.7 +/- 16.1 mmol/L for CVVH, p = 0.01, creatinine: 547 +/- 308 micromol/L vs. 326 +/- 250 micromol/L, p < 0.0001). These differences were still significant after 48 h of treatment (urea: 20.1 +/- 8.3 mmol/L vs. 14.1 +/- 6.1 mmol/L; p = 0.0003, creatinine: 360 +/- 189pmol/L vs. 215 +/- 118 micromol/L; p < 0.0001). Throughout the duration of therapy, mean urea levels (22.3 +/- 9.0 mmol/L for CVVHDF vs. 16.7 +/- 7.8 mmol/L for CVVH, p < 0.0001) and mean creatinine levels (302 +/- 167 vs. 211 +/- 103 micromol/L, p < 0.0001) were better controlled in the CVVH group. CONCLUSIONS: CRRT strategies based on different techniques might have a significantly different impact on azotemic control.     

Physiological changes during hemodialysis in patients with intradialysis hypertension

Intradialysis hypertension is a frustrating complication among hemodialysis (HD) patients. This study was conducted to investigate the physiological changes during intradialytic hypertension. The beat-to-beat continuous heart rate, hematocrit (Hct) changes during HD, serum levels of nitric oxide, plasma levels of catecholamine, renin, endothelin (ET-1), cardiac output (CO), and peripheral vascular resistance (PVR) were measured before and after HD in patients prone to develop intradialysis hypertension (n = 30) and from age, sex-matched control HD subjects (n = 30). It was found that the baseline values of Hct, serum levels of nitric oxide, plasma levels of catecholamine, renin, and ET-1, CO, PVR, and power index (low frequency/high frequency ratios) of heart rate variability were not significantly different between the patients and control subjects. In the hypertension-prone group, the plasma levels of catecholamine, renin, and the serial measurements of power index, did not show significant changes. However, the patients showed a significant elevation of systemic vascular resistance (56.8 +/- 9.2% vs 17.7 +/- 9.5; P < 0.05), ET-1 (510.9 +/- 43.3 vs 276.7 +/- 30.1 pg/ml; P < 0.05) and a significant decrease of nitric oxide (NO)/ET-1 balance (0.018 +/- 0.003 vs 0.034 +/- 0.005; P < 0.05) at the end of HD compared with the control patients. It was found that the physiological changes in intradialysis hypertension patients were characterized by inappropriately increased PVR through mechanisms that did not involve sympathetic stimulation or renin activation but might be related with altered NO/ET-1 balance.     

Autotransfusion after cardiac operation. Assessment of hemostatic factors

Reinfusion of mediastinal blood after coronary bypass grafting reduces the need for homologous transfusion with its hazards. To determine the efficacy of autotransfusion using the cardiotomy reservoir used during operation as a postoperative collection system, we studied the characteristics of reservoir blood (minimum 500 ml, mean 810 ml) and compared the hematologic profiles of 21 patients before and after blood infusion. The mean hematocrit value of the shed blood was 25% +/- 7%, platelet count 60,000 +/- 39,000/microliter, fibrinogen 19 +/- 25 mg/dl, and factor VIII 11% +/- 7%. The fibrinopeptide A concentration was 400 ng/ml, and the B beta 15-42 peptide was 28 +/- 14 pmol/ml. These values indicate defibrination of the blood before collection (no clots were found in the reservoirs), and no significant differences were detected between the types of reservoirs used (Bentley, n = 10, Shiley, n = 11). Infusion of reservoir blood between 500 and 1860 ml did not significantly affect the factor VIII, fibrinopeptide A, or B beta 15-42 peptide levels. Fibrinogen levels increased from 254 to 395 mg/dl (p less than 0.001). Only six of 21 patients received bank blood before discharge. These findings indicate that extensive coagulation occurs within the mediastinum before the blood is collected, that mediastinal blood can be safely infused without inducing fibrinolysis or disseminated intravascular coagulation, and that use of the cardiotomy reservoir is a safe and inexpensive method of autotransfusion after coronary artery bypass grafting.     

A simple mathematical approach to calculate blood loss in radical prostatectomy

INTRODUCTION: The aim of this study was to apply a simple mathematical approach to calculate blood loss in 126 patients undergoing radical retropubic prostatectomy (RRP). MATERIALS AND METHODS: Perioperative red blood cell loss (RBCL) was estimated by adding the difference in circulating red blood cells from before to after surgery to the allogeneic red blood cells transfused in the same period. RESULTS: Mean preoperative hematocrit was 45 +/- 4% and mean perioperative RBCL was 574 +/- 297 ml, corresponding to a mean equivalent whole blood loss (WBL) of 1,479 +/- 831 ml. Twenty of 126 patients (15.9%) received 42 units of allogeneic packed red blood cells (PRBC), for a mean of 2.1 +/- 1.2 U/patient. The transfusion rate was higher in patients with a preoperative hematocrit of 40% or less (45 vs. 13%, p = 0.014). CONCLUSIONS: Anatomical RRP is still associated with appreciable operative blood loss. Owing to the high preoperative hematocrit values, the allogeneic blood transfusion rate is low and the transfusion requirement of the majority of patients is limited to about 2 units of PRBC. Preoperative autologous blood augmentation strategies may not be routinely needed for patients with a basal hematocrit of >40%.     

Intraperitoneal fibrin-formation and its inhibition in CAPD

The intraperitoneal fibrin formation and its inhibition by intraperitoneal heparin (5000 U) was investigated in six patients on CAPD. The intraperitoneal heparin concentration decreased linearily from 1.78 U/ml to 1.13 U/ml during a 4-hour dwell time. The antithrombin III-concentration increased to 0.56 +/- 0.1 mg/dl, reaching 1.87% of normal plasma values. The antithrombin III-portion of total protein was 0.62% in plasma and 0.79% in dialysate. The fibrinopeptide A-concentration, a specific product of thrombin action on fibrinogen was 37.1 +/- 11.8 ng/ml in plasma (normal range: less than 2.5 ng/ml) and 153.4 +/- 16.8 ng/ml in dialysate during regular CAPD. After the addition of 5000 U heparin the fibrinopeptide A-concentration in dialysate decreased to 11.6 +/- 2.6 ng/ml during a 4-hour dwell time. In vitro experiments showed no remarkable inhibition of fibrin formation by heparin without antithrombin III in dialysate. We suggest that the fibrinopeptide A is produced intraperitoneally and the antithrombin III-concentration in dialysate is sufficient to inhibit the fibrin formation after acceleration by heparin.     

Assessment of hemostatic activation during cardiopulmonary bypass for coronary artery bypass grafting with bivalirudin: results of a pilot study

OBJECTIVE: Bivalirudin has been successfully used as a replacement for heparin during on-pump coronary artery bypass grafting. This study was conducted to assess the effects of the currently suggested protocol for bivalirudin on hemostatic activation during cardiopulmonary bypass with and without cardiotomy suction. METHODS: Ten patients scheduled for coronary artery bypass grafting were enrolled. Bivalirudin was given with a bolus of 50 mg in the priming solution and 1.0 mg/kg for the patient, followed by an infusion of 2.5 mg . kg(-1) . h(-1) until 15 minutes before the conclusion of cardiopulmonary bypass. Cardiopulmonary bypass was performed with a closed system in 5 patients with and in 5 patients without the use of cardiotomy suction. Blood samples were obtained before and after cardiopulmonary bypass. D-dimers, fibrinopeptide A, prothrombin 1 and 2 fragments, thrombin-antithrombin, and factor XIIa were determined. RESULTS: Values for factor XIIa remained almost unchanged in both groups, indicating a minor effect of contact activation. In patients without cardiotomy suction, post-cardiopulmonary bypass values for D-dimers, fibrinopeptide A, prothrombin 1 and 2 fragments, and thrombin-antithrombin were not significantly increased compared with pre-cardiopulmonary bypass values. In patients with cardiotomy suction, values obtained for these parameters had significantly increased compared with pre-cardiopulmonary bypass values and the values obtained in the group without cardiotomy suction after cardiopulmonary bypass. CONCLUSIONS: With this protocol, hemostatic activation during cardiopulmonary bypass was almost completely attenuated when cardiotomy suction was avoided. Cardiotomy suction results in considerable activation of the coagulation system and should therefore be restricted and replaced by cell saving whenever possible.     

Effects of bicarbonate- and lactate-buffered replacement fluids on cardiovascular outcome in CVVH patients

BACKGROUND: Bicarbonate-buffered replacement fluid (RF-bic) in continuous venovenous hemofiltration (CVVH) may be superior to lactate-buffered replacement fluid (RF-lac) in acute renal failure. In an open, randomized, multicenter study, we investigated the effects of RF-bic and RF-lac on cardiovascular outcome in patients requiring CVVH following acute renal failure. METHODS: One hundred seventeen patients between the age of 18 and 80 years were randomized to CVVH either with RF-bic (N = 61) or RF-lac (N = 56). Patients were treated with CVVH for five days or until either renal function was restored or the patient was removed from the study. Data were analyzed on day 5 or according to the "last observation carried forward" (LOCF) option. Adverse events were classified according to the WHO-Adverse Reaction Terminology system. RESULTS: Blood lactate levels were significantly lower and blood bicarbonate levels were significantly higher in patients treated with RF-bic than in those treated with RF-lac (lactate, 17.4 +/- 8.5 vs. 28.7 +/- 10.4 mg/dL, P < 0.05; bicarbonate, 23.7 +/- 0.4 vs. 21.8 +/- 0.5 mmol/L, P < 0. 01). The number of hypotensive crises was lower in RF-bic-treated patients than in RF-lac-treated patients (RF-bic 14 out of 61 patients, RF-lac in 29 out of 56 patients; 0.26 +/- 0.09 vs. 0.60 +/- 0.31 episodes per 24 h, P < 0.05). Nine out of 61 patients (15%) treated with RF-bic and 21 out of 56 patients (38%) treated with RF-lac developed cardiovascular events during CVVH therapy (P < 0. 01). A multiple regression analysis showed that the occurrence of cardiovascular events was dependent on replacement fluid and previous cardiovascular disease and not on age or blood pressure. Patients with cardiac failure died less frequently in the group treated with RF-bic (7 out of 24, 29%) than in the group treated with RF-lac (12 out of 21, 57%, P = 0.058). In patients with septic shock, lethality was comparable in both groups (RF-bic, 10 out of 27, 37%; RF-lac, 7 out of 20, 35%, P = NS). CONCLUSIONS: The results show that the administration of RF-bic solution was superior in normalizing acidosis of patients without the risk of alkalosis. The data also suggest that the use of RF-bic during CVVH reduces cardiovascular events in critically ill patients with acute renal failure, particularly those with previous cardiovascular disease or heart failure.     

Echocardiographic findings in patients on maintenance hemodialysis substituted with recombinant human erythropoietin

Cardiomegaly and impaired myocardial function are frequent in patients on maintenance hemodialysis. One important reason is probably severe renal anemia. Substitution with recombinant human erythropoietin (rhEPO) results in long-term correction of renal anemia. We investigated the changes in cardiac function under rhEPO therapy using echocardiography. 13 patients with severe renal anemia (hct less than 26%) but independent of regular blood transfusions during the last six months were treated with 40-120 IU/kg rhEPO intravenously three times/week. Echocardiographic studies were performed in the anemic state and when hematocrit values were stable at levels above 30%. Left ventricular end-diastolic diameter (LVEDD) and end-systolic diameter (LVESD) were reduced (LVEDD: 53.9 +/- 4.2 mm vs. 51.4 +/- 5.8 mm; LVESD: 35.7 +/- 5 mm vs. 32.8 +/- 5 mm). Mean end-diastolic volume (LVEDV) and end-systolic volume (LVESV) were also diminished (LVEDV: 141.9 +/- 25.4 ml vs. 128.1 +/- 32.5 ml; LVESV: 54.8 +/- 18.6 ml vs. 45.1 +/- 17 ml). Stroke volume (SV) fell slightly from 87.1 ml to 83 ml resulting in a decrease of cardiac output (CO) from 6.9 +/- 1.6 l/min to 6.2 +/- 1.7 l/min. The thickness of the left ventricular posterior wall (LVPW) and of the septum interventriculare (IVS) remained constant. Myocardial contractility indicated by ejection fraction (EF), fractional shortening (FS) and the velocity of circumferential fiber shortening (VCF) frequently improved. Our data indicate that correction of renal anemia by rhEPO can improve myocardial function in patients on maintenance hemodialysis.     

Critical hematocrit in intestinal tissue oxygenation during severe normovolemic hemodilution

BACKGROUND: A critical point in oxygen supply for microvascular oxygenation during normovolemic hemodilution has not been identified. The relation between organ microvascular oxygen partial pressure (microPO2) and organ oxygen consumption (VO2) during a decreasing oxygen delivery (DO2) is not well understood. The present study was designed to determine the systemic hematocrit and organ DO2 values below which organ microPO2 and VO2 cannot be preserved by regulatory mechanisms during normovolemic hemodilution. METHODS: Eighteen male Wistar rats were randomized between an experimental group (n = 12), in which normovolemic hemodilution was performed with pasteurized protein solution (PPS), and a control group (n = 6). Systemic hemodynamic and intestinal oxygenation parameters were monitored. Intestinal microPO2 was measured using the oxygen-dependent quenching of palladium-porphyrin phosphorescence. RESULTS: Baseline values in hemodilution and control group were similar. Hemodilution decreased hematocrit to 6.2 +/- 0.8% (mean +/- SD). Constant central venous pressure measurements suggested maintenance of isovolemia. Despite an increasing mesenteric blood flow, intestinal DO2 decreased immediately. Initially, microPO2 was preserved, whereas mesenteric venous PO2 (P(mv)O2) decreased; below a hematocrit of 15%, microPO2 decreased significantly below P(mv)O2. Critical DO2 was 1.5 +/- 0.5 ml x kg(-1) x min(-1) for VO2, and 1.6 +/- 0.5 ml x kg(-1) x min(-1) for microPO2. Critical hematocrit values for VO2 and microPO2 were 15.8 +/- 4.6% and 16.0 +/- 3.5%, respectively. CONCLUSIONS: Intestinal microPO2 and VO2 were limited by a critical decrease in DO2 and hematocrit at the same time. Beyond these critical points not only shunting of oxygen from the microcirculation could be demonstrated, but also a significant correlation between intestinal microPO2 and VO2.     

High serum soluble CD30 does not predict acute rejection in liver transplant patients

Increased pre- and posttransplantation values of soluble CD30 (sCD30) have been shown to be associated with acute kidney transplant rejection. We sought to study whether high sCD30 could predict rejection early after liver transplantation. The study population included 54 consecutive liver transplant patients, whose samples were collected before liver transplantation and at discharge, which was at a mean time of 3 weeks after transplantation. During the first 6 months posttransplantation, 22 patients experienced an acute rejection episode. Serum sCD30 concentrations were measured by an enzyme-linked immunoassay; changes in serum sCD30 levels posttransplantation were also expressed as relative values compared with pretransplantation results. Liver patients before transplantation displayed higher serum sCD30 values compared with healthy controls: mean values +/- SD were 93 +/- 58 IU/mL vs 17 +/- 8 IU/mL, respectively. At 3 weeks after transplantation the mean sCD30 concentration in liver transplant patients decreased to 59 +/- 42 IU/mL (P = .005). The mean pretransplantation serum sCD30 value was slightly lower among rejecting vs nonrejecting patients: 78 +/- 43 IU/mL vs 104 +/- 65 IU/mL (P = NS). Posttransplantation values in both groups decreased significantly: 47 +/- 34 IU/mL in patients with rejection (P = .014) vs 69 +/- 45 IU/mL in patients without rejection (P = .012). The relative value at 3 weeks posttransplantation decreased slightly more among patients with vs without rejection (70% vs 88%; NS). No correlation was found between serum sCD30 and anti-HLA class I antibodies or crossmatch positivity. In conclusion, neither pre- nor posttransplantation sCD30 levels were associated with acute rejection in liver transplant patients.