C Knothe

Justus-Liebig-Universität Gießen, Gieben, Hesse, Germany

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Publications (35)134.02 Total impact

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    ABSTRACT: 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.
    Thrombosis Research 10/1998; 92(1):1-9. DOI:10.1016/S0049-3848(98)00095-4 · 2.45 Impact Factor
  • C Knothe · G Hempelmann ·

    ains · Anästhesiologie · Intensivmedizin 08/1998; 33(7):409-10. · 0.44 Impact Factor
  • C Knothe · G Hempelmann ·

    ains · Anästhesiologie · Intensivmedizin 01/1998; 32(12):707. DOI:10.1055/s-2007-995139 · 0.44 Impact Factor
  • J Bauer · F Dapper · S Demirakça · C Knothe · J Thul · K J Hagel ·
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    ABSTRACT: Pulmonary hypertension is responsible for a substantial part of perioperative and postoperative mortality and morbidity after cardiac transplantation. Treatment of right ventricular failure after increased pulmonary vascular resistance is difficult especially in infants and children. Therefore we started a preventive therapy of pulmonary hypertension after cardiac transplantation to avoid right ventricular failure and compared the results with a group of patients with conventional therapy. Group 1 (n = 13), with transplantation from 1988 to 1991, was treated with vasodilators when symptoms of right ventricular failure developed. Group 2 (n = 19) had preventive treatment with prostaglandin E1 (PGE1), the phosphodiesterase-III inhibitor enoximone, and alkalinazation starting during weaning from cardiopulmonary bypass. Six patients in group 1 died; four of them as the result of right ventricular failure in the immediate postoperative course despite aggressive treatment. In group 2 there were three deaths as the results of rejection (2) and infection (1). None of these patients developed right ventricular failure (p = 0.02). Cold ischemic time, extracorporeal circulation time, and waiting time before transplantation were significantly longer in group 2. Side effects of this preventive therapy were not observed. We conclude that prophylactic therapy of pulmonary hypertension with vasodilators in infants and children after heart transplantation is safe and effective in preventing right ventricular failure in the postoperative course.
    The Journal of Heart and Lung Transplantation 01/1998; 16(12):1238-47. · 6.65 Impact Factor
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    ABSTRACT: Methemoglobinemia is a well-known side effect of nitric oxide inhalation. We tested the hypothesis whether cardiopulmonary bypass increases methemoglobin formation by nitric oxide. A two-phase study: a) a controlled, prospective in vivo study of inhaled nitric oxide treatment followed by b) a second, prospective and controlled in vitro study. Pediatric intensive care unit and research laboratory in a university hospital. The in vivo study consisted of 25 patients following open-heart surgery and 19 children with acute respiratory distress syndrome (ARDS) or persistent pulmonary hypertension of the newborn. The in vitro study consisted of 20 patients with and 20 patients without cardiopulmonary bypass. For the in vivo study, methemoglobin measurements were taken before and after application of 20 parts per million (ppm) of nitric oxide. For the in vitro study, red blood cells of patients were incubated with 32 ppm nitric oxide before and after surgery. Methemoglobin, glutathione, adenosine triphosphate (ATP), and nicotinamide adenine dinucleotide/nicotinamide adenine dinucleotide phosphate (NADH/NADHP) concentrations were compared. For the in vivo study, nitric oxide inhalation increased methemoglobin from 0.2 +/- 0.1% to 1.2 +/- 0.7% in patients receiving nitric oxide after open-heart surgery and from 0.2 +/- 0.1% to 0.5 +/- 0.4% in ARDS/persistent pulmonary hypertension of the newborn patients (p < .01). For the in vitro study, nitric oxide incubation of red blood cells increased methemoglobin concentration from 3.7 +/- 1.9% preoperatively to 7.4 +/- 2.4% after open-heart surgery. This increase was not observed in patients who did not undergo cardiopulmonary bypass (3.6 +/- 1.6% vs. 3.6 +/- 1.9%; p < .001). In erythrocytes of patients undergoing extracorporeal circulation, there was no difference between pre- and postoperative glutathione, ATP, and NADH/NADPH concentrations. Cardiopulmonary bypass is an important risk factor for methemoglobinemia when inhaled nitric oxide is applied. This risk is not secondary to diminished concentrations of energetic substrates.
    Critical Care Medicine 07/1997; 25(7):1153-8. DOI:10.1097/00003246-199707000-00016 · 6.31 Impact Factor
  • Stefan E Scholz · Christoph Knothe · Achim Thiel · Gunter Hempelmann ·

    The Lancet 06/1997; 349(9061):1295-6. DOI:10.1016/S0140-6736(05)62507-X · 45.22 Impact Factor
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    ABSTRACT: Inhaled nitric oxide is a potent and selective pulmonary artery vasodilator. We studied the effects of nitric oxide inhalation in neonatal and pediatric acute respiratory distress syndrome (ARDS) patients with respect to dosage, prolonged inhalation, and weaning. Prospective, open-label study. Neonatal and pediatric intensive care units of a level three university hospital. Seventeen patients with severe ARDS (1 day to 6 yrs of age [mean 1.75]; oxygenation index of > 20 cm H2O/torr) were enrolled. To identify the optimal dosage for continuous nitric oxide inhalation, doses between 1 and 80 parts per million (ppm) of nitric oxide were tested after the patients had stabilized. Daily withdrawals of nitric oxide were made, according to predetermined criteria. Nine neonatal and eight pediatric ARDS patients (mean Pediatric Risk of Mortality score 28.4 +/- 6.1; mortality risk 54 +/- 15%) were studied. The following variables changed within 24 hrs of nitric oxide inhalation: mean oxygenation index decreased by 56% (from 34 +/- 12 to 15 +/- 7 cm H2O/torr, p = .0004); alveolar-arterial O2 gradient decreased by 31% (from 579 +/- 71 to 399 +/- 102 torr (77.2 +/- 9.5 to 53.2 +/- 13.6 kPa), p = .0004); and mean systemic arterial pressure increased by 15% (from 49 +/- 10 to 57 +/- 12 mm Hg, p = .0029). The optimal dose of nitric oxide was 20 ppm in neonates (with additional persistent pulmonary hypertension of the newborn) and 10 ppm in pediatric patients. Prolonged inhalation (4 to 21 days) was associated with continuous improvement of oxygenation. An oxygenation index of < 5 cm H2O/torr predicted successful withdrawal, with a sensitivity of 75% and a specificity of 89%. None of the patients had to be rescued with extracorporeal membrane oxygenation and 16 of the 17 patients survived. Inhaled nitric oxide enhances pulmonary gas exchange, with concomitant hemodynamic stabilization, in neonatal and pediatric ARDS. Best effective doses were 10 ppm of nitric oxide in pediatric ARDS and 20 ppm in neonates. Treatment should be continued until an oxygenation index of < or = 5 cm H2O/torr is achieved. Effects on outcome need verification in larger controlled trials.
    Critical Care Medicine 11/1996; 24(11):1913-9. DOI:10.1097/00003246-199611000-00024 · 6.31 Impact Factor
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    ABSTRACT: 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. Prospective, randomized. A university hospital. Forty consecutive cardiac surgical patients. 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. 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. Parameters of HRV suggest that induction with fentanyl, midazolam, and pancuronium decreases sympathetic but not parasympathetic autonomic system activity. The anesthetic induction technique's 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.
    Journal of Cardiothoracic and Vascular Anesthesia 09/1996; 10(5):609-13. DOI:10.1016/S1053-0770(96)80138-8 · 1.46 Impact Factor
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    ABSTRACT: 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. 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). 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. 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.
    The Annals of Thoracic Surgery 07/1996; 62(1):130-5. DOI:10.1016/0003-4975(96)00239-1 · 3.85 Impact Factor
  • Ch. Knothe · G Hempelmann ·

    ains · Anästhesiologie · Intensivmedizin 06/1996; 31(4):197-9. DOI:10.1055/s-2007-995901 · 0.44 Impact Factor
  • C Knothe · S Scholz · B Zickmann · B Marquart · F Dapper · G Hempelmann ·
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    ABSTRACT: The right ventricle is more jeopardized by a cardiopulmonary bypass than the left one. Impaired right ventricular performance may profit from an afterload reduction. A selective reduction in pulmonary artery pressure (PAP) or pulmonary vascular resistance (PVR) without impairment of the systemic circulation seems to be possible by inhalation of nitric oxide (NO). Therefore in the present study we looked for influences of NO inhalation on PAP, PVR and right heart parameters immediately after weaning from the bypass. The dependence of endothelial function on age, preoperative heart function and extracorporeal circulation is well established. The relevance of such parameters on NO inhalation was also investigated. After ethical approval and informed consent were obtained, 20 patients with moderately increased PAP were included in the study. Ten patients inhaled NO at a concentration of 30 ppm; the other group served as a control group. Measurement points were 10 min after the end of extracorporeal circulation (baseline), 3, 10, and 20 min after the start, as well as 10 min after the end of NO inhalation. NO was injected near the tube into the tubing system during inspiration; dosage and monitoring of the concentration were achieved by means of a chemiluminometer. Measured parameters consisted of PAP, PVR, right ventricular ejection fraction and volumes, systemic blood pressure and resistance, central venous pressure, pulmonary capillary wedge pressure, and oxygenation parameters (paO2, pvO2, paCO2). The decrease in PAP (from 29.7 +/- 3.9 to a minimal 25.4 +/- 4.3 mm Hg, P < 0.005) and in PVR (from 169.4 +/- 51.9 to a minimal 116.3 +/- 60.9 dyn.s.cm-5, P.0.05) did not improve right heart function. A similar significant increase in SVR was observed in the NO group and in the control group. Age, haemodynamic parameters or duration of the ischaemic phase of the cardiopulmonary bypass did not influence the course of PAP or PVR. Changes in PAP (from 30.0 +/- 4.0 to a minimal 26.7 +/- 3.6 mm Hg, P < 0.05) and PVR (from 149.0 +/- 41.5 to a minimal 125.2 +/- 51.5 dyn.s.cm-5, in the control group were not statistically different from those in the NO group. Indicators of intoxication like an increase in NO2 or methaemoglobin concentrations or changes in compliance or resistance were not observed. Patients with moderate pulmonary hypertension did not profit from NO inhalation immediately after weaning from the cardiopulmonary bypass. The decreases in PAP and PVR found in the NO or control group did not improve right-heart function. When the NO and control group were compared, specific effects of NO inhalation on PAP and PVR must be questioned. This could perhaps be explained by data from animal experiments, which found high endogenous NO levels in situations with elevated cytokine levels. Cytokines are increased after extracorporeal circulation. Oxygenation was not impaired by inhalation of relatively high concentrations of NO. For all investigations with NO inhalation not preceded by steady-state conditions, a control group is recommended.
    Der Anaesthesist 03/1996; 45(3):240-8. · 0.76 Impact Factor
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    ABSTRACT: Zusammenfassung Der rechte Ventrikel ist durch extrakorporale Zirkulation (EKZ) mehr gefährdet als der linke. Eine beeinträchtigte rechtsventrikuläre Funktion kann von einer Senkung der Nachlast profitieren. Durch Inhalation von Stickstoffmonoxid (NO) kann ein pulmonaler Hypertonus ohne Auswirkungen auf den Systemkreislauf gesenkt werden. In der vorliegenden Arbeit wurde deshalb der Einfluß einer NO-Inhalation auf pulmonalarteriellen Druck (PAP), pulmonalvaskulären Widerstand (PVR) und Rechtsherzparameter unmittelbar nach EKZ untersucht. An der Studie nahmen 20 Patienten mit mäßiggradigem pulmonalen Hochdruck teil. 10 Patienten inhalierten 30 ppm NO, die anderen dienten als Kontrollgruppe. Meßzeitpunkte lagen 10 min nach EKZ (Ausgangswerte), 3, 10 und 20 min nach Start sowie 10 min nach Beendigung der NO-Inhalation. Es fand sich ein signifikanter Abfall von PAP und PVR ohne begleitende Verbesserung der Rechtsherzfunktion. In der Kontrollgruppe wurden Veränderungen von PAP und PVR in vergleichbarer Größenordnung beobachtet. Es ist somit fraglich, ob die beobachteten Effekte spezifisch für die NO-Inhalation sind. Hohe endogene NO-Konzentrationen in dieser Phase, wie im Tierexperiment gefunden, könnten dieses Verhalten erklären. Eine klinische Verbesserung der Rechtsherzfunktion nach EKZ konnte bei unseren Patienten durch NO-Inhalation nicht erreicht werden.
    Der Anaesthesist 03/1996; 45(3):240-248. DOI:10.1007/s001010050259 · 0.76 Impact Factor
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    ABSTRACT: Some studies found endothelin-1 to be a trigger for pulmonary hypertension. Endothelin-1 is an endothelial derived substance with generally vasoconstrictive properties, but probably vasodilatory effects on pulmonary arteries. The aim of the present study was to look for influences of endothelin-1 plasma values on pulmonary artery pressure. Endothelin-1 levels during and after cardiac surgery and correlations to pulmonary artery pressure were tested in 10 control patients and 21 patients with pulmonary hypertension (mean pulmonary arterial pressure > 20 mmHg, systolic pulmonary arterial pressure > 30 mmHg). According to endothelin-1 values before anaesthesia (normal value below 4 pg/ml) patients with pulmonary hypertension could be divided into a "high endothelin-1" (10 patients, mean 8.25 +/- 2.06 pg/ml) and a "normal endothelin-1" (11 patients, mean 2.13 +/- 0.86 pg/ml) subgroup (p < 0.01). Values of the "high endothelin-1" group decreased until end of operation (from 7.58 +/- 2.35 to 2.95 +/- 1.44 pg/ml, n = 6) when pulmonary artery pressure returned to normal. Otherwise they slightly increased (from 9.43 +/- 2.24 to 11.07 +/- 1.96 pg/ml, n = 4). Levels of the "normal endothelin-1" group increased (to 2.55 pg/ml). Endothelin-1 values peaked on the intensive care unit (ICU) in all patients. Baseline endothelin-1 and systolic pulmonary artery pressure values correlated well with each other (r = 0.73, p < 0.001). Endothelin-1 decreased after extracorporeal circulation in all patients in whom pulmonary artery pressure tended to normalise, whereas no rise in pulmonary artery pressure paralleled the marked increase in endothelin-1 on the ICU. Vasodilatory effects of endothelin on pulmonary arteries can attribute to this course. Endothelin-1 seems not to trigger pulmonary hypertension but rather to vasodilate pulmonary vasculature.
    European Journal of Cardio-Thoracic Surgery 02/1996; 10(7):579-84. DOI:10.1016/S1010-7940(96)80428-3 · 3.30 Impact Factor
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    S Scholz · J Sticher · C Knothe · G Hempelmann ·
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    ABSTRACT: The usefulness of body plethysmography in the assessment of thoracotomy candidates is not well documented. Reported thresholds for operability are generally expressed in absolute values, which do not take into account a patient's size, age or gender. Spirometric and plethysmographic data of 103 patients undergoing thoracotomy were examined for their ability to predict death due to cardiopulmonary insufficiency, pneumonia, and atelectasis during the first 30 postoperative days. Neither plethysmographic nor spirometric parameters could predict atelectasis. Patients who underwent lobectomy were susceptible to the development of atelectasis. A weak correlation between elevated functional residual capacity (FRC) and occurrence of postoperative pneumonia was found. Lung function testing was not able to separate survivors from non-survivors. Patients with pneumonia were at high risk of death in their postoperative course. Because of the non-linear relationship, a correlation coefficient between spirometric and plethysmographic variables was not calculated. The prevalence of cardiac risk factors was high, so the decision for invasive hemodynamic studies should rather be based upon a patient's history than restricted to patients with impaired lung function. Because of methodological differences, and probably insuitable reference values, body plethysmography cannot substitute for spirometry. For FRC and FRC to total lung capacity (FRC/ TLC) ratio, further investigations must be undertaken to establish a correct reference value.
    European Journal of Cardio-Thoracic Surgery 02/1996; 10(5):312-9. DOI:10.1016/S1010-7940(96)80088-1 · 3.30 Impact Factor
  • B Zickmann · J Boldt · C Knothe · J Bauer · F Dapper · G Hempelmann ·
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    ABSTRACT: Paediatric cardiac transplantation (pHTX) has gained widespread acceptance as a therapy in end-stage myocardial failure and some forms of congenital heart disease, particularly hypoplastic left heart syndrome (HLHS). The major problems to the anaesthesiologist in these patients are induction of anaesthesia in infants with HLHS and treatment of pulmonary hypertension in the early post-bypass period. PATIENTS AND METHODS. Anaesthesia for pHTX was performed in 15 children < 1 year of age (4-237 days); 12 suffered from HLHS, 2 from endocardial fibroelastosis, and 1 from dilatative cardiomyopathy. Induction of anaesthesia in patients with HLHS IS a challenge to the anaesthesiologist, as he has to maintain the delicate balance between pulmonary and systemic blood flow. Anaesthesia was induced with fentanyl (10-15 micrograms/kg) and pancuronium (0.2-0.4 mg/kg) and maintained with fentanyl (total dosage 70-100 micrograms/kg). Modification of ventilatory parameters such as FiO2, PaCO2, and airway pressure (PEEP, I:E ratio) was used to influence systemic and pulmonary blood distribution in the pre-bypass period according to changes in haemodynamics (target: O2 saturation approximately 75%-80%, PaCO2 45-50 mmHg). Treatment of pulmonary hypertension in the weaning and early post-bypass period consisted of respiratory (PaCO2 < 30 mmHg) and metabolic alkalinisation (pH 7.45-7.55, BE > +3 mmol/l), the use of prostaglandin E1 (3-6-12 micrograms/kg.h), and the phosphodiesterase inhibitor enoximone (10-15 micrograms/kg.min). Additional positive inotropic support was achieved with dobutamine (5-10 micrograms/kg.min), adrenaline (0.1-0.5 micrograms/kg.min), and/or orciprenaline (0.1-0.2 micrograms/kg.min) and calcium chloride (25-100 mg/kg). RESULTS. Two children died intraoperatively and 1 on the 1st postoperative day from overwhelming pulmonary vascular resistance and right ventricular failure. Three children died between 3 and 4 weeks postoperatively, 1 from cytomegalovirus infection, 1 from sepsis, and 1 from acute rejection. Nine patients survived and are well up to 5.5 years after transplantation. CONCLUSION. Pulmonary hypertension in the weaning and early post-bypass period is the main anaesthesiological problem of pHTX, particularly in children with HLHS. A polypragmatic approach to this problem consisting of alkalinisation, pulmonary vasodilatation, and inotropic support is presented and seems to be effective. Further improvements in concepts of pHTX are limited by the lack of donor organs. Though the experience with pHTX in neonates and infants is growing slowly, it might be a routine procedure from the anaesthesiological point of view within a few years in some selected centres.
    Der Anaesthesist 05/1995; 44(4):250-6. · 0.76 Impact Factor
  • M Ballesteros · J Boldt · B Zickmann · C Knothe · G Hempelmann ·
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    ABSTRACT: To describe the changes in cardiac function after administration of three different solutions infused after anesthetic induction. Thirty-six patients scheduled for elective aortocoronary bypass surgery were randomly distributed into three groups. Over a period of 25 min after anesthetic induction, 12 received 10 ml/kg of Ringer solution (low dose crystalloid group), 12 received 20 ml/kg of Ringer solution (high dose crystalloid group), and 12 received 10 ml/kg of Ringer solution with 10 ml/kg of hydroxi-ethyl-almidon solution 450,000 D, 0.7 substitution grade (group C-HEA). Minute volume, systemic and pulmonary pressures, osmolality of blood and urine, and plasma and urine sodium concentrations were measured before and after infusion of the assigned liquid. In spite of the volume infused, low dose crystalloid group showed a high incidence of oliguria, increased urinary osmolality and decreased sodium in urine. Cardiac and systolic indices and left ventricular work load remained stable after infusion of the assigned liquid in low and high dose crystalloid groups, whereas they increased significantly ion group C-HEA (+23%, +16% and +20%). Administration of restricted doses of crystalloids after anesthetic induction favors the retention of water and sodium. Higher doses of crystalloids weaken this effect. However, neither of these two regimens leads to a more effective cardiac work load. A combination of crystalloids and colloids administered immediately after anesthetic induction temporarily improves cardiac performance during surgery.
    Revista espanola de anestesiologia y reanimacion 02/1995; 42(1):9-14.
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    ABSTRACT: Is intravenous iron therapy as efficient as oral iron supplementation in patients undergoing autologous blood donation? Prospective, randomized study. 30 male and 30 female patients, separated into two groups were examined prior to total hip replacement. Patients of group O were given 6 x 50 mg Fe2+ aspartate/day orally, and patients of group P were given 0.75 mg/kg BW complex-bound Fe3+ once a week by infusion. In both groups therapy was started two weeks prior to the first donation. The substitution was continued the following six weeks until surgery. Hemoglobin, ferritin plasma concentrations and reticulocytes were monitored. The appearance of unwanted side effects was studied by questionnaire. Hb decreased significantly in both groups. A difference was seen in the reticulocyte count and in the ferritin levels. Here we found a significant increase in group P compared with group O. 40% of the patients who took the iron orally complained about unwanted side effects such as obstipation and diarrhoea, whereas none of the patients of the parenteral group had any complaints. Stimulation of the erythropoiesis appeared to be more efficient with intravenous iron therapy than with oral iron supplementation. The oral dose has in about 40% unwanted side effects. For this reason a parenteral iron therapy can be considered, but one must be aware that in some cases dangerous anaphylactic reactions could appear.
    Infusionstherapie und Transfusionsmedizin 09/1994; 21(4):236-41.
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    ABSTRACT: 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)
    The Annals of Thoracic Surgery 07/1994; 57(6):1584-9. DOI:10.1016/0003-4975(94)90128-7 · 3.85 Impact Factor
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    ABSTRACT: 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)
    Journal of Cardiothoracic and Vascular Anesthesia 06/1994; 8(3):317-23. DOI:10.1016/1053-0770(94)90244-5 · 1.46 Impact Factor
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    J Boldt · C Knothe · F Schindler · WA Stertmann · G Hempelmann ·
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    ABSTRACT: The isolated vascular effects of intravenous administration of the angiotensin converting enzyme (ACE) inhibitor enalaprilat were investigated. Thirty male patients undergoing cardiopulmonary bypass (CPB) were studied. According to a randomized sequence, 0.04 mg kg-1 enalaprilat (low-dose, n = 10), 0.08 mg kg-1 (high-dose, n = 10) enalaprilat or saline solution as placebo (control group, n = 10) was given as an i.v. bolus during CPB. Changes in mean arterial pressure (MAP) and venous reservoir (RV) of the extracorporeal circulation were studied as indices of arterial resistance and venous capacitance. Mean arterial blood pressure (MAP) and peripheral vascular resistance (SVR) were significantly more reduced in the high-dose enalaprilat group (MAP: -36 mm Hg after 9 min; SVR: -836 dyn s cm-5) than in the low-dose group (MAP: -13 mm Hg after 10 min). Volume of the reservoir (RV) decreased in both enalaprilat treated groups indicating additional (dose-dependent) venous pooling effects of the substance (low-dose: -300 ml; high-dose: -520 ml; control group: -100 ml). Skin capillary blood flow measured by laser Doppler flowmetry (LDF) increased after injection of 0.04 mg kg-1 enalaprilat, whereas it decreased significantly when MAP fell markedly in patients treated with high-dose enalaprilat. I.v. enalaprilat had dose-dependent vasodilating properties in the arterial and venous vessel system indicating reduction in pre- and afterload. Microcirculation in both enalaprilat treated groups improved as long as reduction in blood pressure was not limited.
    British Journal of Clinical Pharmacology 05/1994; 37(4):341-6. DOI:10.1111/j.1365-2125.1994.tb04287.x · 3.88 Impact Factor