Desmopressin after cardiac surgery in bleeding patients. A multicenter randomized trial.

BACKGROUND: Previous studies showed that desmopressin decreases post-operative blood loss in patients undergoing cardiac surgery. These studies were small and never studied the effect of desmopressin in patients with active bleeding. Objective of the study was to determine whether desmopressin reduces red blood cells transfusion requirements in patients with active bleeding after cardiac surgery who had been pre-treated with tranexamic acid. METHODS: This multicenter, randomized, double-blind, placebo-controlled, parallel-group study randomized elective patients with bleeding after cardiac surgery despite pre-treatment with tranexamic acid, to receive placebo (saline solution) or a single administration of desmopressin (0.3 µg/kg in saline solution). The primary endpoint was the number of patients requiring red blood cells transfusion after randomization and during hospital stay. Secondary end points were: blood loss from chest tubes during the first 24 h after study drug administration, hours of mechanical ventilation, intensive care unit stay, and in-hospital mortality. RESULTS: The study was interrupted after inclusion of 67% of the planned patients for futility. The number of patients requiring red blood cells transfusion after randomization was 37/68 (54%) in desmopressin group and 33/67 (49%) in placebo group (P = 0.34) with no difference in blood loss: 575 (interquartile 422-770) ml in desmopressin group and 590 (476-1013) ml in placebo group (P = 0.42), mechanical ventilation, intensive care unit stay or mortality. CONCLUSIONS: This multicenter randomized trial demonstrated that, in patients pre-treated with tranexamic acid, desmopressin should not be expected to improve treatment of patients who experience bleeding after cardiac surgery.

Antimitochondrial effect of saturated medium chain length (C8-C13) dicarboxylic acids.

In isolated rat liver mitochondria, respiration was competitively inhibited by medium chain length (C8 to C13) dicarboxylic acids to different extents: the higher the number of carbon atoms up to C12, the greater the inhibition. In particular, experiments on submitochondrial particles showed that the competitive inhibition concerned the following enzymes: NADH dehydrogenase, succinic dehydrogenase and reduced ubiquinone: cytochrome c oxido-reductase. These results tend to confirm the suggestion that the melanocytotoxic effect of dicarboxylic acids, which are also competitive inhibitors of tyrosinase, may be primarily due to an antimitochondrial effect rather than being tyrosinase-dependent.

Effects of dietary phospholipids and odd-chain fatty acids on the behavioural maturation of mice.

Five groups of female mice were fed from day 14 of pregnancy and throughout lactation on synthetic diets differing only in the lipid component, which constituted 10% of the diet and was derived from (a) the lipid fraction extracted from yeast grown on n-alkanes, (b) commercial soya lecithin, (c) fatty acids isolated from yeast lipids (off-chain fatty acids), (d) lipids extracted from yeast grown on glucose or (e) margarine (8%), corn oil (1%) and the unsaponifiable fraction (1%) from yeast grown on n-alkanes. A control diet (9% margarine and 1% corn oil) was fed to a sixth group of pregnant mice and to the offspring of all the groups from weaning to 60 days after birth. A battery of behavioural tests was performed on the offspring of the six groups between days 1 and 16 after birth (reflex activities), between days 2 and 21 (locomotor activity) and at 60 days of age (avoidance learning). An acceleration of postnatal behavioural maturation was evident in the pups of animals fed lipids from yeast grown on n-alkanes and of those fed soya lecithin, indicating the involvement of phospholipids and odd-chain fatty acids in the aspects of development studied.

Fluconazole and ketoconazole in the treatment of oral and esophageal candidiasis in AIDS patients.

In our study 77 AIDS patients suffering from oral and/or esophageal candidiasis were evaluated: 38 received fluconazole, 39 ketoconazole. We analyzed the rates of clinical and mycological responses, relapses and toxicities. In vitro susceptibility tests for both antifungal drugs were performed by evaluating their Minimal Inhibitory Concentrations (MICs). The azole drugs investigated show a good activity in the treatment of oropharyngeal and esophageal candidiasis also in advanced stages of HIV infection. Clinical cure or improvement were achieved in 29 (76.3%) and 31 (79.4%) of the patients treated with fluconazole or ketoconazole respectively. Clinical or laboratory adverse experiences related to fluconazole were seen in 7 (21.2%) patients while ketoconazole provoked adverse experiences in 9 (26.4%) patients. In vitro susceptibility tests, if repeated more than once, both in primary infection and relapses, could be important to demonstrate a probable sensitivity change or resistance of the tested strains.

Children exposed to chronic contamination after the Chernobyl accident: cytogenetic and radiotoxicological analyses.

In this study, we describe cytogenetic studies of lymphocytes obtained from children who were exposed after the Chernobyl accident to low doses of ionizing radiation. We sought to determine possible chromosomal damage relative to internal contamination, as measured by whole-body counter and urine radiotoxicological analyses. The study was performed during a 1-mo period on the peripheral blood of children hosted in Italy, but who resided in contaminated regions of the Russian Federation and Belarus. We used conventional cytogenetics to detect chromosomal aberrations. In some cases, we also used "chromosome painting" to look for stable aberrations. There were more acentric fragments in subjects than in controls; a few chromosome and chromatid breaks werefound in the subjects, but this finding did not differ significantly between subjects and controls.

Health status and internal radiocontamination assessment in children exposed to the fallout of the Chernobyl accident.

The Chernobyl fallout caused release of radioisotope contaminants in a very large area that includes Belarus, the Ukraine, and the Russian Federation. In this study, the authors monitored the health status and level of internal contamination in 422 children who resided in the aforementioned areas and who were < or = 10 y of age at the time of the accident. The children came to Italy for a 1-mo period between 1991 and 1992. During this time, the children underwent pediatric checkups and biochemical, immunological, and thyroid analyses. All children underwent whole-body counter measurements, and urine radiotoxicological analysis was performed for 224 of them. The 24 children evacuated from Pripiat, a village very close to the Chernobyl reactor site, were selected for cytogenetic analysis. All of these children continue to have a detectable internal contamination of caesium radioisotopes. This condition is likely the result of ground and foodstuff contamination in the various areas. The children did not evidence overt pathologies related to ionizing radiation. However, minor alterations in immunological and thyroid parameters were observed in the group of the evacuated children. Traditional cytogenetic dosimetry was not possible, but the occurrence of acentric fragments was observed-indicating a persistent effect of continuous exposure to low doses of radiation.

Tricks and pitfalls regarding the hemodynamics of patients undergoing non-transplantation surgery for heart failure.

This paper aims to address the mechanisms responsible for poor perioperative cardiac performance, analyzing the pathophysiology of heart failure and the main hemodynamic parameters (contractility, preload, afterload, systemic vascular resistance, and pulmonary artery pressure) used in diagnosing patients and assessing their response to therapy. It will also discuss potential therapeutic approaches to cardiac surgery patients. With advances in monitoring and life support, our critically ill patients often become trapped in a sheer, impenetrable net of wires and tubes. Unfortunately, technology can seriously compromise patient safety if the data obtained is misinterpreted. While advanced technology has become a part of daily life in the Intensive Care Unit (ICU), there remains a crucial step that cannot be performed by computers: the link from sensors to patient status. We should always remember to look past the cables and monitors and to look at the patient. This would not only reduce the number of ever-present wires, but would also help improve patient outcome. The field of non-transplant cardiac surgery for heart failure is extremely challenging for the cardiac anesthesiologist. The high incidence of postoperative low cardiac output syndrome should mandate aggressive monitoring and therapy. Nevertheless, a comprehensive understanding of the pathophysiology of heart failure and the hemodynamic implications of surgical therapies is mandatory for optimal patient management. In particular, the presence of systolic dysfunction should not automatically rule out other potential causes of poor global cardiac performance.

Reduction of hemodilution in small adults undergoing open heart surgery: a prospective, randomized trial.

BACKGROUND: Given that there is an association between the degree of hemodilution during cardiopulmonary bypass (CPB) and postoperative complications, patients-outcome might be improved if the nadir hematocrit concentration is kept within an optimal range. Smaller patients are more likely to have a low hematocrit during CPB: this phenomenon may be related, at least partially, to the extreme hemodilution induced by a large fixed CPB priming volume. METHODS: Forty patients with a body surface area (BSA) < 1.7 m2 undergoing open heart operations were randomized to either standard CPB with full prime volume (control group) or reduced prime extracorporeal circuit and vacuum-assisted venous drainage (VAVD) (study group). RESULTS: There were no significant differences between the groups with respect to baseline characteristics, body surface area, hematologic profile and operative data. Clinical outcomes were similar. Nadir hematocrit and hemoglobin on bypass were significantly lower in the control group (22 +/- 2.3 vs. 24 +/- 2.5%, p < 0.02 and 7.4 +/- 0.7 vs. 8 +/- 0.9 g/dl, p < 0.04, respectively). Postoperative chest tube drainage was significantly higher in the control group (272 +/- 253 vs. 139 +/- 84 ml, p < 0.04). There was no difference in blood transfusion in the two groups (0.5 +/- 1.14 vs. 1.0 +/- 1.77 units of packed red blood cells (PRBC), p = 0.29). CONCLUSIONS: Lowering CPB priming volume by means of using a small oxygenator and vacuum-assisted venous drainage (VAVD) resulted in a significant decrease of intraoperative hemodilution. This technique should be strongly considered for patients with a small BSA (<1.7 m2) undergoing open heart surgery.

Myocardial necrosis biomarkers after different cardiac surgical operations.

AIM: A high postoperative peak of cardiac Troponin I is associated to an increased risk of morbidity and mortality after cardiac operations. The aim of this study was to investigate the release of cardiac Troponin I in different cardiac surgical procedures. METHODS: This was a prospective, single-centre study performed at the IRCCS San Raffaele Hospital in Milan, Italy. The study group consisted of 194 consecutive patients undergoing cardiac surgery. For each of them creatinkinase MB and cardiac Troponin I were assayed preoperatively, at ICU arrival, 4 h and 18 h postoperatively. RESULTS: Different cardiac surgical procedures were characterized by different release of cardiac biomarkers (P<0.001, ANOVA test). Off-pump coronary artery bypass grafting (CABG) was associated to the smallest amount of myocardial injury while mitral valve replacement produced the largest amount of biomarkers release. Patients who suffered a postoperative cardiac event released more myocardial necrosis biomarkers than those with an uneventful course (P=0.01). CONCLUSION: We showed that each type of cardiac operation has a peculiar amount of myocardial necrosis biomarkers: mitral valve replacement in particular is associated to the highest release of cardiac biomarkers.

Successful use of bivalirudin for cardiopulmonary bypass in a patient with heparin allergy.

Heparin-induced IgE-mediated hypersensitivity and anaphylactoid reactions, although rare, can pose a serious clinical problem for patients requiring cardiopulmonary bypass (CPB). Bivalirudin is a bivalent reversible direct thrombin inhibitor, with a half-life of 25 min, eliminated mostly by proteolytic cleavage. There are some reports on the use of bivalirudin for cardiac surgery, particularly for heparin-induced thrombocytopenia (HIT), but none on cases of heparin allergy. We report a case of heparin allergy successfully managed for CPB with bivalirudin anticoagulation.