The use of balanced HES 130/0.42 during complex cardiac surgery; effect on blood coagulation and fluid balance: a randomized controlled trial.

INTRODUCTION: Colloids and crystalloid are used during cardiac surgery for priming of the cardiopulmonary bypass (CPB) circuit. Colloids may decrease postoperative fluid balance because of their high oncotic pressure and low risk of fluid extravasation. On the other hand, colloids have been shown to impair blood coagulation. MATERIALS AND METHODS: In a prospective, randomized, double-blinded study, 50 patients scheduled for coronary artery bypass grafting or a valve procedure were planned to be randomized to receive either balanced 6% HES130/0.42 or Ringer-acetate solution for CPB priming. Randomization was stopped prematurely after 35 randomized patients (19 in the HES and 16 in the Ringer groups) because of the published report where HES130/0.42 was associated with impaired renal function. Effects on haemostasis and fluid balance were investigated. RESULTS: The rotational thromboelastometry (ROTEM®) parameters and chest tube drainage on the first postoperative morning (1POM) were comparable between the groups (p>0.05). However, patients in the HES group needed more blood and blood product transfusions. The total volume administered into the CPB circuit was lower in the HES than in the Ringer (RIN) group, 2905±1049 mL versus 3973±1207 mL (p=0.011), but there was no statistically significant difference in total fluid balance on the 1POM (5086±1660 mL in the HES group versus 5850±1514 mL in the RIN group, respectively). CONCLUSIONS: After complex cardiac surgery, the use of balanced 6% HES130/0.42 solution for CPB circuit priming did not impair haemostasis measured by ROTEM®, but it increased the need for transfusions. Fluid balance after CPB was less positive in the HES group, but, on the 1POM, it was comparable between the groups.

Platelet transfusions in adult patients with particular reference to patients undergoing surgery.

Descriptive information on platelet (PLT) recipients, particularly during surgery, is limited. A description of the current epidemiology of PLT-transfused patients is required to optimize platelet transfusion care and to follow trends in PLT use. In 2004 and 2005, information was combined from several computerized medical systems. Participating hospitals (9 hospital districts of 21) handled approximately 64% of annual Finnish hospital admissions. A total of 6321 adult patients were transfused with 37,761 PLT products. Most PLT products (43.1%) were transfused to patients suffering from haematological malignancies. Only 1.0% of all surgical patients received PLTs (53.8% of PLT recipients and 35.8% of transfused PLTs). The most common single operation connected with PLT transfusion was coronary artery bypass while 27.1% of surgery-related PLTs were given to patients having an operation involving the digestive system or spleen. Only 36.4% of all PLT-transfused (operated and conservatively treated) patients were discharged directly home; in-hospital mortality was 9.5%. PLTs were given 40 products per 1000 hospital admissions requiring an operation in 2004, and 38 products in 2005. Perioperative PLT use is slightly decreasing in adult patients. As a single-operation type, coronary artery bypass patients receive most of the PLT products and have experienced no decline in PLT use over the years. Overall, PLT recipients have high in-hospital mortality.

Effects of 5-bromodeoxyuridine on the ACTH-dependent mitochondrial biogenesis in cortical cells of fetal rat adrenals in tissue culture.

Cortical cells of fetal rat adrenals in tissue culture were treated with 5-bromodeoxyuridine (BrdU) during their proliferative phase and during ACTH stimulation when nuclear DNA synthesis has almost ceased. Pretreatment with 0.5 mug/ml/day of BrdU inhibited the ACTH-induced differentiation of cortical cells as well as the secretion of corticosterone and 18-OH-deoxycorticosterone (18-OHDOC). When nuclear DNA synthesis was suppressed and mitochondrial DNA synthesis was stimulated by ACTH BrdU addition (30 mug/ml/day) permitted normal untrastructural differentiation of cortical cells, except that the development of mitochondrial inner membranes was inhibited. Simultaneously mitochondrial inner membranes was inhibited. Simultaneously mitochondrial 11beta- and 18-hydroxylations were strongly inhibited while cytoplasmic 21-hydroxylation was not affected.

Perioperative Myocardial Infarction in Non-Cardiac Surgery Patients: A Prospective Observational Study.

BACKGROUND AND AIMS: Perioperative myocardial infarction is an underdiagnosed complication causing morbidity, mortality, and considerable costs. However, evidence of preventive and therapeutic options is scarce. We investigated the incidence and outcome of perioperative myocardial infarction in non-cardiac surgery patients in order to define a target population for future interventional trials. MATERIAL AND METHODS: We conducted a prospective single-center study on non-cardiac surgery patients aged 50 years or older. High-sensitivity troponin T and electrocardiograph were obtained five times perioperatively. Perioperative myocardial infarction diagnosis required a significant troponin T release and an ischemic sign or symptom. Perioperative risk calculator was used for risk assessment. RESULTS: Of 385 patients with systematic ischemia screening, 27 patients (7.0%) had perioperative myocardial infarction. The incidence was highest in vascular surgery-19 of 172 patients (11.0%). The 90-day mortality was 29.6% in patients with perioperative myocardial infarction and 5.6% in non-perioperative myocardial infarction patients ( p < 0.001). Perioperative risk calculator predicted perioperative myocardial infarction with an area under curve of 0.73 (95% confidence interval: 0.64-0.81). CONCLUSION: Perioperative myocardial infarction is a common complication associated with a 90-day mortality of 30%. The ability of the perioperative risk calculator to predict perioperative myocardial infarction was fair supporting its routine use.

Preoperative and perioperative use of levosimendan in cardiac surgery: European expert opinion.

In cardiac surgery, postoperative low cardiac output has been shown to correlate with increased rates of organ failure and mortality. Catecholamines have been the standard therapy for many years, although they carry substantial risk for adverse cardiac and systemic effects, and have been reported to be associated with increased mortality. On the other hand, the calcium sensitiser and potassium channel opener levosimendan has been shown to improve cardiac function with no imbalance in oxygen consumption, and to have protective effects in other organs. Numerous clinical trials have indicated favourable cardiac and non-cardiac effects of preoperative and perioperative administration of levosimendan. A panel of 27 experts from 18 countries has now reviewed the literature on the use of levosimendan in on-pump and off-pump coronary artery bypass grafting and in heart valve surgery. This panel discussed the published evidence in these various settings, and agreed to vote on a set of questions related to the cardioprotective effects of levosimendan when administered preoperatively, with the purpose of reaching a consensus on which patients could benefit from the preoperative use of levosimendan and in which kind of procedures, and at which doses and timing should levosimendan be administered. Here, we present a systematic review of the literature to report on the completed and ongoing studies on levosimendan, including the newly commenced LEVO-CTS phase III study (NCT02025621), and on the consensus reached on the recommendations proposed for the use of preoperative levosimendan.

Steroid formation and differentiation of cortical cells in tissue culture of human fetal adrenals in the presence and absence of ACTH.

Steroid secretion and ultrastructural differentiation of human fetal adrenal cortical cells were analyzed in tissue culture with and without ACTH. The unconjugated and sulfated endogenous neutral steroids were analyzed by gas-liquid chromatography and gas chromatography-mass spectrometry. A fetal pattern of neutral steroids, including high concentrations of sulfate conjugates, was found during the first five days of the cultivation. At 6 to 11 days of cultivation, a decrease was seen in concentrations of these steroids. However, when stimulated with ACTH, an increasing amount of steroids was secreted during days 6 to 11 and their pattern was transformed into the adult type with a 30-200 times higher secretion rate of cortisol. Cortical cells capable of proliferation in the culture had the ultrastructure of the permanent zone cells of the fetal adrenal or adult zona glomerulosa type. ACTH stimulation induced a differentiation of these cells into zona fasciculata type. The results suggest that ACTH is the main hormonal regulator in the genesis of the adult human adrenal cortex and that there is a factor during fetal life which inhibits the synthesis of the 3beta-hydroxysteroid dehydrogenase system.

Single lung allotransplantation in pigs. A morphologic study of tissue preservation with modified Euro-Collins and fluorocarbon solutions.

In the present study the functional and morphologic effects of two pulmoplegic solutions are evaluated. Single left-lung allotransplantation with ligation of the right pulmonary artery was performed in 15 piglets (13-20 kg). The lungs were preserved after donor prostaglandin E-1 treatment with single pulmonary artery flush with either modified Euro-Collins solution (mECS) (9 pigs) or oxygenated fluorocarbon emulsion (FC-43) (6 pigs) and transplanted after 6-hr storage in cold Physiosol solution. Tidal volumes of 15 ml/kg x fr (18) with 40% inspired oxygen were used for ventilation during reperfusion. Function of the transplanted lung was monitored for 4 hr postoperatively by determining pa CO2 and pa O2 levels from arterial samples and by noninvasive monitoring of end-tidal CO2 values and arterial oxygen saturations. Sequential morphologic changes in pulmonary artery flow surface and lung tissue were studied after 6-hr storage and 4-hr reperfusion, using light, scanning, and transmission electron microscopy (LM, SEM, TEM). There was no mortality. After transplantation the mECS group experienced significant hypoxia and hypercarbia and had low end-tidal CO2 values as signs of defective oxygenation and gas exchange, whereas the FC-43 group was normoxic and normoventilated without disturbed elimination of carbon dioxide. After storage and reperfusion, LM showed signs of increased vascular permeability and reperfusion damage--more evident in the mECS group compared with the FC-43 group--while the lymphoid cell population was more intensely activated in the latter group. Electron microscopy after storage showed good overall preservation of structures in both groups. After reperfusion preservation of pulmonary artery flow surface and lung tissue was estimated to be moderate in the mECS group, whereas it was good-to-moderate in the FC-43 group by SEM (NS). TEM of lung tissue, however, showed significantly better-preserved alveolar epithelial lining in the FC-43 group compared with the mECS group. In conclusion, oxygenated fluorocarbon (FC-43) pulmoplegia gave better functional and morphologic preservation of lung grafts compared with modified Euro-Collins solution.

Effects of corticosterone on adrenocorticotrophin-induced mitochondrial differentiation with special reference to 11 beta- and 18-hydroxylation.

The effects of corticosterone in concentrations found in adrenal venous plasma on ACTH-induced changes in cultured cortical cells derived from foetal rat adrenals were studied. Corticosterone at a concentration of 5-7 X 10(-5) mol/l completely inhibited mitochondrial differentiation to fasciculte-like morphology. The same cultures revealed significant inhibition of 11beta- and 18-hydroxylation compared with cultures treated with ACTH only. This was shown by the reduced formation of corticosterone and 18-OH-deoxycorticosterone (48%, P less than 0-001) and simultaneous enhancement of deoxycorticosterone formation (33%, P less than 0-05) from added [4-14C]progesterone. Similar inhibition was observed when dibutyryl cyclic AMP replaced ACTH as an inducer of differentiation. Lower concentrations of corticosterone (1-2 X 10(-5) and 2-4 X 10(-5) mol/l) inhibited ACTH-stimulated formation of corticosterone and 18-OH-deoxycorticosterone from endogenous precursors. The results demonstrate that corticosterone regulates the stage of differentiation in cultured adrenocortical cells. The possible role of corticosterone in the regulation of growth and steroidogenic capacity of the adrenal cortex is discussed.

Hemodynamic responses to beta-adrenergic blockade with metoprolol and pindolol after coronary artery bypass surgery.

Varying ancillary properties of beta-adrenergic blocking drugs, such as intrinsic sympathomimetic activity or beta 1-selectivity, are known to evoke different hemodynamic effects. These differences may be relevant during hemodynamically unstable conditions. Twenty patients undergoing elective coronary artery bypass surgery were matched in two groups and given either metoprolol tartrate (0.03 mg/kg) or pindolol (0.003 mg/kg) intravenously during recovery from surgery. Heart rate (p less than 0.01) and the rate-pressure product (p less than 0.05) were equally reduced by both beta-blocking drugs. Pindolol also caused a minor decrease in cardiac output (p less than 0.05) and a respective increase in the systemic vascular resistance; all other variables remained stable. It is plausible that in the presence of significant adrenalinemia, which constantly develops after coronary artery surgery, the nonselective pindolol blocks both beta 1-receptors and vascular dilatory beta 2-receptors and thereby increases systemic vascular resistance despite its intrinsic sympathetic activity. Thus, if the use of a beta-blocking agent is considered during the immediate recovery stage following coronary artery bypass surgery, a beta 1-selective drug is more desirable than one with an intrinsic sympathomimetic property.

Pulmonary vascular resistance before and after cardiopulmonary bypass. The effect of PaCO2.

To examine whether CPB influences pulmonary vascular sensitivity to CO2, we compared the effect of slight induced hypocarbia and hypercarbia on pulmonary circulation before and after CPB in ten mechanically ventilated patients undergoing CABG. Hypocarbia was produced by increasing tidal volume slightly and hypercarbia was then induced by adding CO2 to the inspired gas mixture. In another ten patients, hypercarbia was produced after CPB by decreasing ventilator rate and the cardiopulmonary responses to hypercarbia, produced by the two methods of CO2 elevation, were compared. Slight respiratory acidosis induced by CO2 inhalation did not change PVR before CPB but effected a 50 percent increase after CPB. Hypercarbia induced by alveolar hypoventilation after CPB increased PVR by 40 percent. During the increased CO2 production after hypothermic CPB, pulmonary vasoconstriction would be expected to occur and impair right ventricular performance. Therefore, tight control of PaCO2 with appropriate adjustment of ventilatory support is mandatory.

Endothelial cell damage following crystalloid cardioplegic solution infusion. Scanning electron microscope study of coronary bypass grafts.

Scanning electron microscope studies of coronary bypass grafts were carried out in six routine bypass operations. Infusion of the initial crystalloid cardioplegic medium into the aortic root after aortic cross clamping was performed in every case. In two cases, pieces of aorta below and above the cross-clamped site, le, having and not having had contact with the crystalloid cardioplegic medium, were studied. The endothelial lining of the veins showed normal structure following distention with blood. Following infusion with a crystalloid cardioplegic solution, the endothelial cells had almost completely vanished and the flow surface was composed mainly of collagen fibers. The aortic samples taken from below the cross-clamp site showed similar destruction of the endothelium that was observed in vein grafts after crystalloid cardioplegic solution infusion, whereas the aortic samples taken from above the cross-clamp site disclosed normal endothelium.

Cardiopulmonary bypass with heparin-coated circuits and reduced systemic anticoagulation.

BACKGROUND: The improved biocompatibility of the cardiopulmonary bypass circuits made possible by the use of surface-immobilized heparin may allow for a reduction in the amount of heparin administered systemically. This study was performed to elucidate the effects of cardiopulmonary bypass using heparin-coated circuits and reduced heparinization on hemostatic variables and clinical outcome. METHODS: Thirty patients scheduled to undergo myocardial revascularization were randomized to have either a heparin-coated or an uncoated cardiopulmonary bypass circuit. Anticoagulation was induced with heparin (100 IU/kg in the coated group and 300 IU/kg in the uncoated group) and the activated clotting time was kept over 200 and 480 seconds in the coated and uncoated groups, respectively. RESULTS: The postoperative overnight loss of hemoglobin through the drains was lower in the heparin-coated group (43.6 g; range, 18.5-69.0 g) than in the uncoated group (73.0 g; range, 32.2-137.7 g) (p = 0.0015). Plasma concentrations of prothrombin fragment 1 + 2 and D-dimer were significantly more elevated after cardiopulmonary bypass in the coated group than they were in the uncoated group. Two patients in the coated group had a stroke postoperatively. CONCLUSIONS: The reduction in systemic heparinization was associated with thrombin formation, which may predispose to intravascular and cardiopulmonary bypass circuit clotting. Therefore, generous systemic heparinization may still be prudent despite the improved biocompatibility offered by heparin-coated surface.

Atrial pressure and hormonal and renal responses to acute cardiac tamponade.

The effect of acute cardiac tamponade on atrial pressures, plasma atrial natriuretic factor concentration and renin activity, and renal water and electrolyte excretion was studied in pigs loaded intravenously with hydroxyethyl starch and maintained on a continuous intravenous infusion of isotonic saline solution. Saline solution was infused into the pericardial space in 6 anesthetized pigs until a predetermined decrease of 20% in mean arterial pressure was achieved. Another 6 sham-treated pigs served as controls. Tamponade increased atrial intracavitary pressures but decreased atrial transmural (distending) pressures. These changes in atrial pressures were reversed after release of tamponade. Changes in plasma atrial natriuretic factor concentration correlated positively with changes in atrial transmural pressures. Tamponade increased plasma renin activity and decreased urine flow and renal sodium and potassium excretion, and release of tamponade reversed these changes. Thus, the tamponade-induced reduction in atrial distention is associated with hormonal changes, which may contribute to the reductions in diuresis and natriuresis observed in this connection.

Effect of addition of magnesium to potassium-containing fluorocarbon cardioplegic preparations. An experimental study.

The effect of magnesium on potassium fluorocarbon cardioplegia was studied in 20 rabbits. Isolated hearts with ascending aortas were perfused with oxygenated and cooled (+4 degrees C) fluorocarbon solutions. In 10 experiments, the solution contained 20 mmol/l of potassium, in 10 further experiments, 20 mmol/l of potassium and 15 mmol/l of magnesium. Ultrastructural preservation of the myocardium was studied using transmission electron microscopy. In addition, the cation contents of the myocardium were studied by flame atomic absorption spectrophotometry (calcium, magnesium) or electrothermal atomic absorption spectrophotometry (copper). After 120 minutes of ischaemia, areas of moderate or severe ultrastructural myocardial cell damage were observed in both groups but severe damage was more extensive and commoner in the group with no access to magnesium. Preservation of the capillary endothelium was also worse in that group. There was a highly significant increase in magnesium content, a decrease in calcium content and an increase in the magnesium/calcium ratio following magnesium-potassium fluorocarbon infusion. The copper content remained unchanged. A protective effect of magnesium was observed. The electrolyte content of cardioplegic solutions also alters the electrolyte content of the myocardium. This may be important in reperfusion.