Ch. Knothe

Does aprotinin influence endothelial-associated coagulation in cardiac surgery?

Aprotinin has been reported to reduce bleeding in cardiac surgery patients. Its mechanisms of action on coagulation have not been fully elucidated. In a prospectively randomized study of 40 patients undergoing elective aortocoronary bypass grafting, the influence of high-dose aprotinin (2 million IU of aprotinin before CPB, 500,000 IU/h until the end of operation, 2 million IU added to the prime) (N = 20) on endothelial-related coagulation was compared to a nontreated control group (N = 20). Thrombomodulin (TM), protein C and (free) protein S as well as thrombin/antithrombin-III (TAT) plasma concentrations were measured by enzyme-linked immunosorbent assays (ELISA) before the aprotinin infusion, before cardiopulmonary bypass (CPB), during CPB and after CPB, at the end of surgery, 5 hours after CPB, and on the first postoperative day. All standard coagulation parameters (AT-III and fibrinogen plasma levels, platelet count, partial thromboplastin time) did not differ between the two groups. At baseline, TM plasma levels were within the normal range (< 40 ng/mL) and similar in both groups. During CPB, TM plasma concentrations decreased similarly in both groups (aprotinin: 18 +/- 6 ng/mL, control: 17 +/- 7 ng/mL) followed by a comparable increase in the postbypass period until the first postoperative day (aprotinin: 60 +/- 10 ng/mL, control: 53 +/- 11 ng/mL). Protein C and (free) protein S plasma levels also showed no differences between the two groups. On the first postoperative day, baseline values for protein C and protein S had not yet been reached.(ABSTRACT TRUNCATED AT 250 WORDS)

Phosphodiesterase-inhibitors enoximone and piroximone in cardiac surgery: influence on platelet count and function.

ObjectiveSome phosphodiesterase (PDE)-inhibitors are believed to alter platelet count and function due to changes in intracellular cAMP. Whether newly developed (specific) PDE-inhibitors negatively influence platelet function in cardiac surgery should be investigated in a randomized study.MethodsEighty patients undergoing aorto-coronary bypass grafting were divided into 4 groups and received either the new PDE-III-inhibitor piroximone (group 1), the PDE-III-inhibitor enoximone (group 2), epinephrine (group 3) or no inotropic support (control). PDE-III-inhibitors were given as a bolus followed by infusion until starting of cardiopulmonary bypass (CPB). In addition to platelet count and a thrombelastogram, platelet function was assessed by aggregometry (ADP, epinephrine, collagen). Measurements were done before, during and after CPB until the 1st postoperative day.ResultsPlatelet count and postoperative blood loss did not differ between the groups within the entire investigation period. Maximum aggregation and maximum gradient of platelet aggregation to all stimuli were not changed by either PDE-inhibitor enoximone or piroximone. CPB resulted in a significant decrease of all aggregation variables which was without differences due to treatment. Platelet aggregation recovered in the post-bypass period and exceeded baseline values on the 1st postoperative day.ConclusionIt is concluded that enoximone and the new PDE-III-inhibitor piroximone do not affect platelet function and can be used before CPB without risking plateletrelated bleeding in cardiosurgical patients in the perioperative period.

NO-Inhalation bei herzchirurgischen Eingriffen: Relevanz für die Rechtsherzfunktion?

ZusammenfassungDer 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.AbstractThe 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. Methods. 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). Results. The decrease in PAP (from 29.7±3.9 to a minimal 25.4±4.3 mm Hg, P<0.05) 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. Conclusions. 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.

Anästhesie bei Herztransplantationen im Neugeborenenund Säuglingsalter

ZusammenfassungDie orthotope Herztransplantation hat sich auch für das Neugeborenen- und Säuglingsalter zu einer akzeptierten Behandlungsmethode bei hypoplastischem Linksherzsyndrom (HLHS) oder Kardiomyopathien (CM) entwickelt. Das anästhesiologische Vorgehen bei 15 Transplantationen bei Kindern unter einem Jahr wird beschrieben. 12 Kinder litten unter HLHS, die anderen unter CM. Fentanyl wurde zur Narkoseeinleitung (10–15 μg/kg) und -führung (70–100 μg/kg) als Mononarkotikum eingesetzt. Die Stabilität der Hämodynamik in dieser Phase ist stark von Beatmungskonzepten abhängig. In der Phase der Beendigung der extrakorporalen Zirkulation wurden zur Therapie der rechtsventrikulären Nachlasterhöhung nach konsequenter respiratorischer und metabolischer Alkalisierung Prostaglandin E1 (3–6–12 μg/kg/h), Enoximon (10–15 μg/kg/min) und in zwei Fällen Tolazolin (0,025 μg/kg/min) eingesetzt. Positiv inotrope Unterstützung erfolgte in allen Fällen. Eingesetzt wurden Dobutamin (5–10 μg/kg/min), Adrenalin (0,1–0,5 μg/kg/min) und Orciprenalin (0,1–0,2 μg/kg/min). In 3 Fällen war eine passagere, in einem Fall eine permanente (A-V-)-Schrittmachertherapie erforderlich. 2 Patienten konnten aufgrund eines rechtsventrikulären Versagens nicht von der EKZ entwöhnt werden. Ein weiterer Patient starb am ersten postoperativen Tag an einem Rechtsherzversagen. Die derzeitige Überlebensrate beträgt 60% bei einem Beobachtungszeitraum bis zu 51/2 Jahren.AbstractPaediatric 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 μg/kg) and pancuronium (0.2–0.4 mg/kg) and maintained with fentanyl (total dosage 70–100 μg/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 ∼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 μg/kg·h), and the phosphodiesterase inhibitor enoximone (10–15 μg/kg·min). Additional positive inotropic support was achieved with dobutamine (5–10 μg/kg·min), adrenaline (0.1–0.5 μg/kg·min), and/or orciprenaline (0.1–0.2 μg/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.

Wirkung oraler versus parenteraler Eisensubstitution bei Eigenblutspendern

Ziel: Die Frage zu beantworten, ob die parenterale Substitution von Eisen Vorteile gegenuber der bisher ublichen oralen Gabe bei Eigenblutspendern bietet. Design: Prospektiv, randomisierte Studie. Rahmen und Patienten: 30 mannliche und 30 weibliche Patienten, getrennt in zwei Gruppen, vor einer elektiven Huftgelenksoperation. Interventionen: Patienten der Gruppe·erhielten oral 6 × 50 mg Fe2+-Aspartat/Tag und Patienten der Gruppe P bekamen 0,75 mg/kg KG komplexgebundenes Fe3+ ein-mal wochentlich nach der Eigenblutspende (EBS) infundiert. In beiden Gruppen wurde die Substitution 2 Wochen vor Beginn der ersten Spende begonnen und uber 6 Wochen bis zur Operation fortgefuhrt. Insgesamt wurden bei jedem Patienten drei EBS durchgefuhrt. Die Therapiekontrolle erfolgte durch Messung des Hamoglobin-gehaltes, der Ferritin-Plasmakonzentration und der Retikulozytenzahl. Das Auf-treten von Nebenwirkungen wurde durch einen Fragebogen ermittelt. Ergebnisse: Im Hamoglobin-Verlauf beider Gruppen bestand kein Unterschied. Deutlich unterschiedlich waren die Ergebnisse bezuglich der Retikulozytenzahl und des Ferritinverlaufs. Hier kam es in Gruppe P zu einem signifikanten Anstieg im Vergleich zur Gruppe O. 38,9% der Patienten in Gruppe·zeigten unerwunschte Nebenwirkungen der Eisentherapie, wie Obstipation oder Diarrhoe. Bei Patienten der Gruppe P wurden keine Nebenwirkungen der Eisensubstitution beobachtet. Schluβfolgerungen: Da die Anzahl der zu gewinnenden Eigenblutkonserven zu einem groβen Teil vom Fullungszustand der Eisenspeicher abhangt, ist eine fruhzeitige, suffiziente Eisengabe sinnvoll. Da die orale Eisengabe haufig mit unerwunschten Nebenwirkungen einhergeht, kann bei diesen Patienten eine parenterale Gabe er-wogen werden, die jedoch unter strenger arztlicher Kontrolle zu erfolgen hat, da in seltenen Fallen mit schweren anaphylaktischen Reaktionen gerechnet werden muβ.