Increased anticoagulation during cardiopulmonary bypass by prostaglandin E1.

UNLABELLED: Prostaglandin E1 (PGE1) inhibits tissue factor/factor VIIa-dependent thrombin formation and platelet procoagulant activity. These pathways may trigger thrombin generation during cardiopulmonary bypass (CPB). We hypothesized that the therapeutic combination of PGE1 and heparin increases the degree of anticoagulation as measured by reduced thrombin generation during CPB. Patients undergoing primary coronary artery bypass grafting using CPB were anticoagulated with unfractionated porcine heparin and 12.5 ng x kg(-1) x min(-1) PGE1 (n = 20) or placebo (n = 20). Plasma markers that reflect thrombin generation (prothrombin fragment F1+2, thrombin-antithrombin complex) were determined, and postoperative bleeding was documented. Thrombin generation gradually increased in both groups during and after CPB but was lower in the PGE1 group. After CPB, the difference between mean levels of prothrombin fragment F1+2 was 1.9 nmol/L (95% confidence interval for difference 1.1 to 2.8; P = 0.001). The difference between mean levels of thrombin-antithrombin complex was 43.6 ng/mL (21.2 to 66.1; P = 0.001). A trend in reduced postoperative bleeding was observed in the PGE1 group with a difference of sample means of 183 mL (-5 to 371; P = 0.056). Adding PGE1 to unfractionated heparin enhances anticoagulation during CPB. The results suggest that reduced thrombin generation during surgery may decrease postoperative bleeding. IMPLICATIONS: Cardiopulmonary bypass is associated with extensive thrombin generation even in the presence of clinically sufficient heparin anticoagulation. The addition of prostaglandin E1 to heparin enhances the degree of anticoagulation as measured by reduced thrombin formation during cardiopulmonary bypass.

Emergency aortic valve replacement for critical aortic stenosis. A lifesaving treatment for patients with cardiogenic shock and multiple organ failure.

OBJECTIVE: To demonstrate that emergency aortic valve replacement can be successfully performed in patients with critical aortic stenosis and reduced left ventricular function even in cardiogenic shock with associated severe multiple organ failure. DESIGN: Retrospective, consecutive case series. SETTING: Multidisciplinary intensive care unit of a tertiary care university hospital. PATIENTS: Five patients admitted to the intensive care unit with critical aortic stenosis (aortic valve area 0.56 +/- 0.13 cm2) and greatly reduced left ventricular ejection fraction (20 +/- 3%) in prolonged cardiogenic shock and associated multiple organ failure (Multiple organ failure score 6.8 +/- 0.5; Acute Physiology, Age, and Chronic Health Evaluation III score 91 +/- 27). INTERVENTION: Emergency aortic valve replacement. RESULTS: All patients survived with full recovery of organ function. At follow-up (18 +/- 10 months) all patients were in New York Heart Association functional class I or II with improvement of left ventricular ejection fraction to 48 +/- 25%. CONCLUSIONS: This excellent outcome suggests that emergency aortic valve replacement should be strongly considered in patients with critical aortic stenosis even in cardiogenic shock and multiple organ failure.

Measurement of inotropic effects by a newly developed guinea pig papillary muscle bioassay.

In order to measure inotropic influences of physiologically occurring substances and drugs we used a newly developed guinea pig papillary muscle (GPPM) bioassay. GPPM were suspended in air and surface coated with buffer (Krebs-Henseleit solution). The muscles were stimulated (pulsating direct current, 1.5 V; 0.5 Hz, 20 ms duration) which led to contraction. This method enables measurements of inotropic effects up to 5 days, contrary to previous studies (1 day), in which immersions of GPPM in buffer were performed. In order to investigate the comparability of the new method we measured the effect of metabolites (citric acid cycle), lactic acid, lactate, and extracellular pH on muscle contractility. The H(+)-dependent decrease of the contractile force of the GPPM can be compensated by an increased Ca(2+)-concentration. Further, the influence of catecholamines (isoproterenol) on the contractility was investigated. As a result, isoproterenol caused arrhythmias and extrasystoles as it was observed in clinical studies. Several pharmaceutical substances were tested to show the reproducibility and repeatability of the bioassay.

Effects of dobutamine versus insulin on cardiac performance, myocardial oxygen demand, and total body metabolism after coronary artery bypass grafting.

OBJECTIVE: The purpose was to study whether the hemodynamic benefit of a catabolic catecholamine (dobutamine) induces a certain oxygen cost for the myocardial energy demand and whether this effect would be less pronounced if an anabolic intervention, such as the administration of insulin, was used. DESIGN: A prospective and randomized study. SETTING: A university hospital. PARTICIPANTS: Investigation of two comparable groups of cardiac patients. INTERVENTIONS: The interventions were postoperative infusions of dobutamine, 7 micrograms/kg/min, and of insulin, 1.5 U/kg/h, respectively, over a period of 30 minutes. MEASUREMENTS AND MAIN RESULTS: The effects of the interventions were measured using parameters relating to cardiac work and myocardial oxygen demand. Moreover, parameters relating to total body metabolism were also recorded. In the dobutamine group, cardiac index (CI) and left ventricular stroke work index (LVSWI) increased significantly (p < 0.05) during therapy by 30% and 40%, respectively. Cardiac effort index (CEI) and tension time index (TTI) also increased (p < 0.05) during therapy by 41% and 30%, respectively. However, in the insulin group, CI and LVSWI also increased (p < 0.01 and p < 0.05) during therapy, although to a lesser extent (16% and 14%), but CEI and TTI did not change at all during therapy. Total body CO2 production (VCO2) and O2 consumption (VO2) in the dobutamine group increased (p < 0.05) during therapy by 9% and 11%, respectively, whereas in the insulin group only CO2 production increased (p < 0.05) by 13%. O2 consumption remained unchanged in this group. CONCLUSIONS: It is concluded that dobutamine as well as insulin administration increase cardiac performance. However, in contrast to dobutamine, insulin does not appear to increase myocardial oxygen demand. Therefore, the anabolic insulin administration may represent a more economic pattern of energy-consuming hemodynamic intervention than does the catabolic catecholamine administration.

Continuous hemofiltration for the failing heart.

The effect of hemofiltration (HF) was studied in three different groups of patients with severe heart failure refractory to inotropic support. Group I consisted of 72 patients who were treated preoperatively with HF. In 1,350 patients (group II) undergoing several kinds of open heart surgery, HF was performed during cardiopulmonary bypass. In a third group (520 patients), HF was used postcardiotomy cardiogenic shock. Hemodynamic, metabolic, and PO2 measurements were obtained before, during, and after continuous HF. During 2 to 24 hrs of continuous HF, an increase in mean arterial pressure left ventricular stroke work index, and total peripheral resistance, as well as a decrease in left atrial pressure, were seen in groups II and III. In group I, all hemodynamic variables improved significantly; afterload and preload decreased, reversing cardiac dysfunction and restoring renal function. Continuous HF eliminates cardiopulmonary toxic metabolites (partly responsible for multiorgan dysfunction) from the plasma of patients with severe cardiac failure. The preliminary results indicate that the early use of HF offers an effective treatment which prolongs life in acute and severe congestive heart failure.

Improved cardiac performance and reduced pulmonary vascular constriction by epinephrine administration via a left atrial catheter in cardiac surgical patients.

Diminished left ventricular contractility and increased right ventricular afterload are issues in cardiac surgery. The usual administration of catecholamines (epinephrine) via the central venous (CV) catheter increases cardiac output, but also may increase pulmonary vascular constriction. Epinephrine was, therefore, administered via the left atrial (LA) catheter or the CV catheter in 8 cardiac surgery patients, each serving as his or her own control. The LA administration of epinephrine has an advantage with its immediate effect on the coronary circulation, while avoiding associated pulmonary vasoconstriction by passing through the systemic capillary bed before reaching the lung. It was found in this study that administration of epinephrine via an LA catheter increased the average cardiac output by 1.05 L/min, which was significantly (P < 0.05) greater than with administration via the CV catheter. With LA administration of epinephrine, systemic arterial pressure (systolic arterial pressure and diastolic arterial pressure) (SAP, DAP) were also elevated to a greater extent than by CV administration. On the other hand, pulmonary arterial pressures (systolic pulmonary arterial pressure and diastolic pulmonary arterial pressure) (SPAP, DPAP) were less elevated than by administration via the CV catheter. This produced increased coronary perfusion and a smaller increase in pulmonary vascular tone by LA administration in contrast to CV administration of epinephrine. It is concluded that epinephrine administration via an LA catheter improved myocardial performance and pulmonary perfusion due to direct entry of the agent into the coronary circulation and partial metabolism while passing through the systemic capillary bed before reaching the lung.

[Myocardial metabolism during the pre-ischemic administration of metabolic myocardial protection in coronary surgical patients]. / Myokardialer Stoffwechsel während präischämischer Verabreichung einer metabolischen Myokardprotektion bei koronarchirurgischen Patienten.

Metabolic myocardial preservation by means of preischemic insulin administration (glucose-potassium-insulin, GPI; acute parenteral alimentation, APA) with the aim of a preischemic myocardial glycogen enrichment was performed in 20 consecutive CABG patients (12 in the APA group, 8 in the control group). Before and after 30 min of an infusion (APA or 0.9% NaCl solution), blood levels of potassium, glucose, NEFA (non-esterified fatty acids) and lactate were determined from arterial (a), central venous (cv) and coronary sinus (cs) blood. The cs potassium level in the APA group decreased from 4.06 to 3.56 mmol/l, whereas in the control group an increase from 3.78 to 4.36 mmol/l occurred. The difference between the two groups (interaction) was significant, p less than 0.002. The myocardial glucose extraction (a-cs difference) in the APA group increased from 3.83 to 10.08 mg/dl, whereas in the control group a change from 3.37 to 0.87 mg/dl occurred (p less than 0.0003). The myocardial NEFA (non-esterified fatty acids) extraction in the APA group decreased from 0.25 to -0.06 mmol/l, whereas in the control group no change (0.08 to 0.13 mmol/l) occurred (p less than 0.05). The myocardial lactate extraction in the APA group increased from 0.13 to 0.70 mmol/l, whereas in the control group no change occurred (0.47 to 0.51 mmol/l), interaction p less than 0.0001. It is concluded that a preischemic insulin administration (APA) for metabolic preservation leads to: (1) myocardial potassium extraction, obviously caused by intracellular potassium shifting; (2) increased myocardial glucose extraction; (3) decreased myocardial NEFA extraction, the last two obviously caused by a shift of the myocardial metabolism from predominant lipolysis to predominantly glycolysis; and (4) surprisingly, increased myocardial lactate extraction (decreased lactate production), obviously caused by the avoidance of a myocardial lactate accumulation by way of stimulated pyruvate oxidation. Increased anaerobically, available ATP without myocardial lactate production must be considered a metabolic contribution to myocardial protection against ischemic damage.

Infusion of nifedipine after coronary artery bypass grafting decreases the incidence of early postoperative myocardial ischemia.

We performed a randomized study on patients undergoing elective coronary bypass grafting to examine whether postoperative infusion of nifedipine (n = 25) could reduce the incidence of isolated transient myocardial ischemia, myocardial infarction, or both. The control group (n = 25) received nitroglycerin. Hemodynamic and Holter monitoring and serial assessment of enzymatic and electrocardiographic changes were performed for all patients. Both groups showed comparable preoperative and operative data. The incidence of myocardial infarction was significantly lower in the nifedipine group (n = 1) as compared with the control group (n = 4), whereas the number of patients with isolated transient myocardial ischemia was similar in both groups (nifedipine, 3; control, 4). At the time of peak activity, levels of creatine kinase (350 +/- 129 versus 511 +/- 287 IU/mL), creatine kinase-MB (8.4 +/- 5.4 versus 17.1 +/- 11.0 IU/mL), and glutamate-oxaloacetate-transaminase (30.4 +/- 4.4 versus 41.0 +/- 7.9 IU/mL) were markedly lower in the nifedipine group (p less than 0.05). We conclude that infusion of nifedipine after elective coronary artery bypass grafting effectively decreases the incidence of myocardial infarction and the extent of myocardial necrosis during the early postoperative period.

Control of the total artificial heart: new aspects in human versus animal experience.

Control strategies for total artificial heart application have generally been based on experience with healthy animals. Human patients in a bad state of health who have impaired organ functions and who are subjected to intensive care procedures can develop atypical hemodynamic behavior. In these patients, both unstable and hyperstable behavior of the vascular resistance were observed. Therefore, regulation of cardiac output (CO) by pressure parameters only was avoided and CO was adjusted to obtain an appropriate O2-utilization (O2U). Intending to keep the O2U within ranges of 20-25%, we obtained cardiac indexes between 3.3 and 4.4 L/m2/min (CO 6-8 L/min), which is higher than other cardiac indexes reported. A CO of 10.5 L/min was even necessary to obtain an O2U of 30% in a septic patient. This strategy caused a stable driving management and led to a rapid hemodynamic stabilization and general improvement of the patients' condition. Results indicate that it is also very important to monitor metabolic parameters for appropriate driver adjustment as well, especially in the early postoperative phase, and that O2-U is a sensitive and useful parameter for this purpose.

Total artificial heart bridging: a temporary support for deteriorating heart transplantation-candidates--methods and results.

Since 1975 at the 2. Dept. of Surgery, University of Vienna, Austria, artificial circulation devices and artificial hearts have been constructed and in experimental use. We started a clinical heart transplantation (HTX) program in 1984, and up to now more than 40 HTXs have been performed. Since May 1986, 3 patients--all suffering from end stage dilatative cardiomyopathy--received total artificial heart (TAH) as a temporary support until HTX was possible. Two of them were transplanted after 9 and 10 days. The third patient, who additionally suffered from a postinfarctial lung abscess and had to undergo an indispensable lobectomy contemporary with TAH implantation, could not be transplanted due to an incurable infection, which he died of after 22 days on TAH. The temporary TAH implantation proved to be a valuable measure preventing life-threatening circulatory deterioration. After restoration of a sufficient circulation by the implanted system, the patients' general conditions improved and the concomitant dysfunctions of kidneys, brain, and other vital organs, due to cardiogenic shock, could be rectified in those two patients, who underwent transplantation. Thromboembolic complications were observed only in the third patient, who developed a small infarction in the anterior lobe of the left hemisphere caused by cerebral embolism after 3 weeks of TAH pumping. The use of TAH is liable to severe, even lethal, complications. At present it should be used only as a last resort. If a donor heart is not available, this measure can be a real chance to save the patient's life.

Acute respiratory failure after cardiac surgery: clinical experience with the application of continuous arteriovenous hemofiltration.

Hemodynamic and oxygen measurements were obtained before and during 24 h of continuous arteriovenous hemofiltration (CAVH) in 36 postoperative cardiac surgery patients with severe acute pulmonary failure. During the first 6 h, the low mean arterial pressure averaged only 50 +/- 7 mm Hg; PaO2 was 90 torr on an inspired oxygen fraction of 0.86 +/- 0.03; and lactic acid was 10.5 +/- 6 mmol/L. Of the 34 patients recovering from shock within 12 h, only 24 (67%) were hospital survivors. Cardiac index, oxygen availability index, oxygen consumption, and PaO2 increased during CAVH. This treatment decreased serum levels of the myocardial depressant factor, thus allowing catecholamine support to be reduced. We conclude that CAVH eliminates cardiopulmonary toxic substances partly responsible for shock. Our patients' improved hemodynamic and respiratory function suggests that CAVH may be useful in postoperative cardiac surgery patients with respiratory and hemodynamic failure.

[Hemofiltration as therapy in acute pulmonary failure in cardiogenic shock]. / Hämofiltration als Therapie des akuten Lungenversagens im kardiogenen Schock.

In 29 cardiosurgical patients in cardiogenic shock after extracorporal circulation complicated by acute pulmonary failure, it was impossible to restore normal postoperative arterial oxygen tension, in-spite of optimal pharmacotherapy and ideal conditions with a conventional volume-controlled respirator. These patients were subject to continuous arteriovenous haemofiltration; in all of them the start of haemofiltration immediately led to a significant reduction of respiratory oxygen supply with an increase in arterial oxygen tension. Pulmonary shunt volume decreased. At the same time there was an increase in arteriovenous oxygen difference, arterial oxygen content and oxygen transport capacity. Pulmonary artery pressure as well as pulmonary vascular resistance decreased noticeably, whereas there was an increase in total peripheral vascular resistance. Starting haemofiltration with decreasing left ventricular filling pressure, accompanied by a rise in blood pressure and an increase in total peripheral resistance, led to an improvement of the haemodynamic situation as well as pulmonary oxygen diffusion, thereby ensuring oxygen perfusion of peripheral tissue. The results suggest a causal relation between the improvement of the clinical condition of the patient and the elimination of cardiopulmonary toxic agents like myocardial depressant factor (MDF) and shock mediators due to arteriovenous haemofiltration.

[Positive modification of hemodynamics in post cardiac surgery patients by hemofiltration. Improved method for the demonstration of myocardial depressant factor (MDF) in hemofiltrate]. / Positive Beeinflussung der Hämodynamik bei postkardiochirurgischen Patienten durch die Hämofiltration. Eine verbesserte Methodik zur Darstellung des Myocardial Depressant Factor's (MDF) in Hämofiltrat.

The method of haemofiltration was used in 29 postoperative cardio-surgical patients with low blood pressure, high left ventricular filling pressure and low total peripheral resistance, which did not respond to the use of the intraaortic balloon pump or pharmaco-therapy. In severe low-output syndrome hemodynamic parameters are: reduced mean arterial pressure, increased left ventricular filling pressure, increased mean arterial pulmonary pressure as well as significantly reduced total peripheral resistance [4-6, 28]. Inspite of pharmaco-therapy, cardiac performance regarding peripheral perfusion is insufficient; this leads to a vicious cycle of irreversible O2-debt and severe cellular damage. After haemofiltration there was a significant improvement in the haemodynamic parameters, which in our opinion was due to the elimination of toxic peptides such as Myocardial Depressant Factor (MDF). In 27 of a total of 29 patients, haemodynamic parameters returned to normal after treatment. 19 patients were discharged, eight patients died after a number of days or weeks from causes not related to the original cardiogenic shock (cerebral embolism, reinfarction, myocardiopathy and pneumonia).