Christoph Knothe

Influence of different intravascular volume therapies on platelet function in patients undergoing cardiopulmonary bypass

The influence of four different kinds of intravascular volume replacement on platelet function was investigated in 60 patients undergoing elective aortocoronary bypass grafting using cardiopulmonary bypass (CPB). In a randomized sequence, high-molecular weight hydroxyethyl starch solution (HMW-HES, mean molecular weight [Mw] 450,000 d), low-molecular weight HES (LMW-HES, Mw 200,000 d), 3.5% gelatin or 5% albumin were infused preoperatively to double reduced filling pressure (pulmonary capillary wedge pressure [PCWP] < 5 mm Hg). Fifteen untreated patients served as a control. Platelet function was assessed by aggregometry using turbidometric technique (inductors: ADP, epinephrine, collagen). Maximum aggregation, maximum gradient of aggregation, and platelet volume were measured before, during, and after CPB until the first postoperative day. HMW-HES 840 +/- 90 mL, LMW 850 +/- 100 mL, gelatin 950 +/- 110 mL, and albumin 810 +/- 100 mL were given preoperatively. Maximum platelet aggregation (ranging from -23% to -44% relative from baseline value) and maximum gradient of platelet aggregation (ranging from -26% to -45% relative from baseline values) were reduced only in the HMW-HES patients. After CPB, aggregometry also was impaired most markedly in these patients. The other volume groups showed less reduction in platelet aggregation and were similar to the untreated control. On the first postoperative day, aggregation variables had returned almost to baseline in all patients. Platelet volume was the same among the groups within the investigation period. Postbypass blood loss was highest in the HMW-HES group (890 +/- 180 mL). There was significant (P < 0.04) correlation in this group between blood loss and change in platelet aggregation.(ABSTRACT TRUNCATED AT 250 WORDS)

Normothermic versus hypothermic cardiopulmonary bypass: Do changes in coagulation differ?

BACKGROUND The differences between hypothermic and normothermic cardiopulmonary bypass (CPB) on platelet function and endothelial-related coagulation (eg, the thrombomodulin/protein C/protein S system) should be investigated. METHODS According to a randomized sequence, 30 patients undergoing aortocoronary bypass grafting underwent either hypothermic (rectal temperature, 27 degrees C to 28 degrees C, n = 15) or normothermic CPB (rectal temperature, more than 35 degrees C, n = 15). Arterial blood samples were taken after induction of anesthesia (baseline values), before, during, and immediately after CPB, 5 hours after CPB, and on the morning of the first postoperative day. Circulating thrombomodulin, (free) protein S, protein C, and thrombin/antithrombin III complex were measured from these samples. Platelet function was assessed by aggregometry (turbidometric technique) induced by adenosine diphosphate (2 mumol/L), collagen (4 micrograms/L), and epinephrine (25 mumol/L). RESULTS Hypothermic patients showed a significantly higher blood loss and need for homologous blood than the normothermic patients. Thrombomodulin plasma level increased more in the hypothermic (from 28 +/- 5 ng/mL to 60 +/- 10 ng/mL) than in the normothermic group (from 28 +/- 7 ng/mL to 41 ng/mL); p < 0.05). Both protein C and (free) protein S were reduced significantly in the hypothermic (protein C, from 88% +/- 25% to 60% +/- 11%; protein S, from 71% +/- 10% to 40% +/- 8%) than in the normothermic patients. Platelet aggregation was significantly more decreased in the hypothermic (adenosine diphosphate, maximum decrease by -43% relative to baseline) than in the normothermic patients (adenosine diphosphate, maximum decrease by -22% relative to baseline). In the hypothermic CPB group, platelet aggregation had recovered incompletely, whereas in the normothermic patients platelet aggregation even slightly exceeded baseline values. CONCLUSIONS Hypothermic CPB resulted in more pronounced alterations of platelet aggregation and endothelial-related coagulation than normothermic CPB. Plasma levels of soluble thrombomodulin were more increased in hypothermic than in normothermic CPB indicating more extensive endothelial damage or activation associated with hypothermic CPB.

Platelet function in cardiac surgery: Influence of temperature and aprotinin

Hypothermic cardiopulmonary bypass (CPB) has been associated with both coagulation defects and hemorrhage. The influence of temperature on platelet function and the benefits of aprotinin in this situation were studied in 60 patients undergoing elective aortocoronary bypass grafting. The patients were randomly divided into four groups (15 patients per group): group 1, normothermic CPB (nasopharyngeal temperature > 34 degrees C); group 2, normothermic bypass and administration of high-dose aprotinin (2 million IU before CPB, 500,000 IU/h until the end of the operation, and 2 million IU added to the prime); group 3, hypothermic CPB (nasopharyngeal temperature < 28 degrees C); and group 4, hypothermic CPB and aprotinin. Platelet function was evaluated by aggregometry (turbidimetric technique), and aggregation was induced by adenosine diphosphate (1 and 2 mumol/L), collagen (4 micrograms/L), and epinephrine (25 mumol/L) before, during, and after CPB into the first postoperative day. Starting from comparable baseline values, maximum platelet aggregation and maximum gradient of platelet aggregation were significantly most reduced after CPB in group 3 (hypothermic CPB without aprotinin) (ranging from -30% to -53% relative to baseline values). In comparison with the other groups, platelet function in this group also recovered less quickly in the later post-bypass period. Hypothermic CPB with aprotinin resulted in less-altered platelet function than hypothermic CPB without aprotinin. Platelet aggregation in aprotinin-treated patients was comparable overall with that in patients undergoing normothermic CPB. On the first postoperative day, aggregation variables had returned to or exceeded baseline values.(ABSTRACT TRUNCATED AT 250 WORDS)

Aprotinin in pediatric cardiac operations: Platelet function, blood loss, and use of homologous blood

Excessive hemorrhage secondary to cardiopulmonary bypass may be encountered after pediatric cardiac operations. Platelet dysfunction appears to be especially responsible for this problem. The proteinase inhibitor aprotinin is suggested to possess platelet preservation properties and reduce blood loss in this situation. The effects of aprotinin (25,000 U/kg after induction of anesthesia, 25,000 U/kg added to the prime, 25,000 U/kg every hour of cardiopulmonary bypass) on platelet function were randomly studied in 12 children with a weight of less than 10 kg (group 2) and 12 children weighing more than 10 kg (group 4), who were compared with two groups of children without aprotinin (group 1, < 10 kg; group 3, > 10 kg). Twelve children undergoing major vessel operations without cardiopulmonary bypass and aprotinin served as a control. Platelet function was assessed using aggregometry (turbidometric technique with adenosine diphosphate, 2.0 mumol/L; collagen, 4 micrograms/mL; epinephrine, 25 mumol/L; NaCl [control]). Platelet function was not altered in the control patients within the entire investigation period. Maximum aggregation in the small children was already lower at baseline in comparison with that of the children > 10 kg. Cardiopulmonary bypass was followed by a significant reduction in platelet aggregation in all groups. Treatment with aprotinin did not improve platelet function (maximum aggregation and maximum gradient of aggregation) in any group. On the first postoperative day, maximum aggregation in the small children exceeded baseline values, whereas in both groups of children > 10 kg baseline values had almost been established. Postoperative blood loss was not reduced by treatment with aprotinin.(ABSTRACT TRUNCATED AT 250 WORDS)

Changes in Heart Rate Variability During Induction of Anesthesia With Fentanyl and Midazolam

OBJECTIVE The study was designed to evaluate changes in autonomic nervous system function during induction of anesthesia with fentanyl, midazolam, and pancuronium and to answer the question of dose-dependency of these effects. DESIGN Prospective, randomized. SETTING A university hospital. PARTICIPANTS Forty consecutive cardiac surgical patients. INTERVENTIONS Anesthesia was induced with fentanyl, midazolam, and pancuronium. The patients were assigned to four groups differing in dosages of fentanyl plus midazolam and speed of injection. Fentanyl, 7.5 micrograms/kg (group A), 12.5 micrograms/kg (group B), and 20.0 micrograms/kg (group C) plus midazolam, 0.075 mg/kg (group A), 0.125 mg/kg (group B), and 0.200 mg/kg (group C) were administered over 10 minutes; in group D, fentanyl, 7.5 micrograms/kg, and midazolam, 0.075 mg/kg, were administered within 1 minute. MEASUREMENTS AND MAIN RESULTS Heart rate variability (HRV) was measured using parameters in the time domain and the frequency domain. The comparison of preinduction HRV with the intra-anesthetic epochs did not show significant differences with respect to heart rate, coefficient of variation, and root mean squared successive differences. Spectral analysis showed significant reductions of power in the vasomotor band (0.01 to 0.05 Hz) and the low-frequency band (0.05 to 0.15 Hz) in all groups. Power in the high-frequency band (0.15 to 0.50 Hz) decreased slightly, but this did not reach the significance level. A dose dependency of these changes was found in the low-frequency band only. CONCLUSIONS Parameters of HRV suggest that induction with fentanyl, midazolam, and pancuronium decreases sympathetic but not parasympathetic autonomic system activity. The anesthetic induction techniques modulation of autonomic nervous system balance is better represented by means of spectral analysis than by analysis in the time domain. This modulation was largely independent of the doses administered and independent of the speed of injection.

Thrombomodulin in pediatric cardiac surgery

In 30 consecutive children with congenital heart disease scheduled for pediatric cardiac operations, thrombomodulin, protein C, free protein S, and thrombin-antithrombin complex were measured by enzyme-linked immunosorbent assay after the induction of anesthesia (baseline value), and then before, during, and after cardiopulmonary bypass until the first postoperative day. The patients were divided prospectively into two groups: children weighing less than 10 kg (group 1; n = 15) and those weighing more than 10 kg (group 2; n = 15). At baseline, the plasma concentration of thrombomodulin was significantly higher in the children in group 1 than in those in group 2 (83.1 +/- 11.0 ng/mL versus 29.2 +/- 12.1 ng/mL). During cardiopulmonary bypass, the thrombomodulin level was reduced in both groups without showing any significant group differences. Five hours after cardiopulmonary bypass and on the first postoperative day, the thrombomodulin level exceeded normal values only in the children weighing less than 10 kg. In both groups, the protein C levels were already below normal at the beginning of the study. The baseline protein S concentration was higher in the smaller children (80% +/- 18%) than in the larger children (66% +/- 11%). It was reduced by cardiopulmonary bypass in both groups; however, postoperatively it did not return to normal in group 1 (45.1% +/- 10%). Plasma levels of the thrombin-antithrombin complex were similar in both groups, with a marked increase at the end of cardiopulmonary bypass, and returned to near-normal levels by 5 hours after bypass.(ABSTRACT TRUNCATED AT 250 WORDS)

Thrombin Generation and Activation of the Thrombomodulin Protein C System in Open Heart Surgery Depend on the Underlying Cardiac Disease

The exposure of blood to foreign surfaces during extracorporeal circulation (ECC) leads to an activation of the coagulation system. In arteriosclerotic patients thrombin activation is increased and plasma fibrinogen is elevated, while protein C levels are reduced. In this study we investigated the influence of different cardiac diseases on ECC-induced thrombin generation and activation of the thrombomodulin-protein C system. Twenty-four patients undergoing either elective coronary artery bypass grafting (CABG) or elective aortic valve replacement (AVR) were included in the study. Blood samples were taken at different time intervals before, during and after ECC, and in the postoperative period. Plasma concentrations of thrombin-antithrombin III-complex (TAT), modified antithrombin (ATM), prothrombin fragment F1+2, free protein S, thrombomodulin, and protein C-antigen were determined by ELISA. Fibrinogen and antithrombin III levels were detected by nephelometry. Both groups were comparable with respect to biometric and ECC-related data. TAT concentrations were elevated in both groups after induction and increased during surgery (p<0.001). As a marker of thrombin generation levels of F1+2 were higher in the CABG group during cardiopulmonary bypass (p=0.003). In CABG patients ATM peaks were higher during ECC (p=0.0024). Significantly higher plasma thrombomodulin concentrations were found in CABG patients after induction (p<0.001), while protein S concentrations were higher in the AVR group (p=0.002). Protein C levels and antithrombin III concentrations did not differ between the groups. Patients undergoing CABG were found to have lower protein S levels and increased plasma thrombomodulin concentrations as markers of endothelial damage. In these patients contact activation and as a consequence thrombin generation takes place at a higher level, indicating a hypercoagulable state. Thromboembolic events in the perioperative period may be caused by different hemostatic changes in CABG patients.

Volume Loading With Hypertonic Saline Solution: Endocrinologic and Circulatory Responses

Hypertonic saline solution appears to be an attractive method of volume expansion. In 45 patients undergoing elective aorto-coronary bypass grafting, endocrinologic and circulatory responses to volume loading with hypertonic saline solution prepared in low molecular weight (MW) hydroxyethyl starch (HES) solution (72 g/L NaCl, HES concentration: 6%; MW: 200,000 D; degree of substitution [DS]: 0.5) (HS-HES) was compared randomly to patients who had received low molecular weight HES solution (LMW-HES). A group of patients without volume loading served as a control. Volume was infused to double the low pulmonary capillary wedge pressure (PCWP < 5 mmHg) after induction of anesthesia. Plasma levels of atrial natriuretic peptide (ANP), endothelin, vasopressin, and catecholamines were measured before, during, and after cardiopulmonary bypass (CPB) until the first postoperative day. In addition to systemic circulatory changes, capillary skin blood flow was measured by laser Doppler flowmetry. ANP plasma concentration increased in both volume groups (HS-HES: +79%; HES: +32%), whereas it decreased in the control (-20%). Infusion of HS-HES resulted in an increase in plasma endothelin concentration before and after CPB (from 3 to 6 pg/mL). Five hours after CPB, both treatment groups had higher endothelin plasma concentrations than the control patients (P < 0.05). Epinephrine and norepinephrine plasma levels increased most markedly in the control patients and were highest in the postbypass period in these patients. CI increased most after infusion of HS-HES (+65%) (P < 0.05). In the postbypass period, CI remained significantly higher in both volume groups than in the controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of different glucose-insulin-potassium regimes on glucose homeostasis and hormonal response in cardiac surgery patients

Intravenous infusion of glucose/insulin in combination with potassium (GIK) is an often used technique to improve myocardial preservation in cardiac surgery. In a randomized study in 50 patients undergoing elective aortocoronary bypass grafting with good ventricular function, the influence on glucose homeostasis and hormonal response to four different glucose/insulin regimes were compared to an untreated control: 1) 50 g of glucose mixed with 100 U of human insulin (HI/100); 2) 50 g of glucose mixed with 100 U of bovine insulin (BI/100); 3) 50 g of glucose mixed with 50 U of human insulin (HI/50); and 4) 50 g of glucose mixed with 50 U of bovine insulin (BI/50) [corrected]. Glucose/insulin were given in combination with 70 mmol of potassium 40 min before beginning the operation. In addition to blood glucose concentrations various endocrine variables were studied before, during and after cardiopulmonary bypass (CPB). Hemodynamic data (arterial blood pressure, heart rate, cardiac index, systemic vascular resistance) were similar in all five groups. Inotropic support after CPB was necessary in none of the patients. Blood glucose levels showed no differences among all GIK groups (groups 1-4) but were significantly higher than in the control patients. The incidence of severely reduced (< 50 mg/dL) or elevated blood glucose level (> 300 mg/dL) did not differ between HI- and BI-treated patients but was significantly lower in the untreated control. Insulin plasma level increased significantly after infusion of GIK with higher levels in HI- than BI-treated patients (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)