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.

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.

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.

A propensity score analysis on the effect of eliminating cardiopulmonary bypass for coronary artery bypass grafting.

AIM: The aim of the study was to investigate if the off-pump technique could reduce the hospital mortality after coronary artery bypass grafting when compared to the standard cardiopulmonary bypass (CPB) technique. METHODS: An observational study with propensity score matching analysis was performed in a university teaching hospital in 2,899 consecutive patients undergoing elective coronary artery bypass grafting. No intervention was performed. Major perioperative complications and hospital mortality were noted. RESULTS: The overall hospital mortality was 1.3% (39/2,899) with no difference between the off-pump (16/802, 2.0%) and the CPB group (23/2,097, 1.1%) P=0.09. Since the off-pump group included patients at high risk, a propensity score analysis was then performed and off-pump patients matched 1:1 to CPB patients in order to have the same preoperative variables identified by a multivariate analysis as associated to surgeon propensity to operate off-pump: (age, chronic renal failure and low ejection fraction) and the same number of graft performed. The results of the propensity matching still showed no difference in hospital mortality between off-pump and CPB group (1.6% vs 1.1% P=0.6). The off-pump technique showed advantages in terms of transfusion of blood products (P<0.001) and reduction of surgical re-exploration (P=0.04). CONCLUSIONS: No difference in hospital mortality in coronary artery bypass grafting patients could be observed between patients operated off-pump or with the standard CPB technique.

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.

The outcome of patients requiring emergency conversion from off-pump to on-pump coronary artery bypass grafting.

BACKGROUND AND OBJECTIVE: Patients undergoing off-pump coronary artery bypass grafting (CABG) may need emergent institution of cardiopulmonary bypass (CPB) for circulatory collapse during the operation. Our aim was to evaluate outcome in such patients and identify preoperative and intraoperative risk factors. METHODS: This is an observational study in a University Hospital setting. In the period June 2001-July 2003, data from 988 consecutive patients undergoing CABG in our institution were prospectively collected. No interventions were made. Prolonged hospital stay (>7 days), hospital mortality, temporal trends and risk factors for conversion from off-pump to on-pump surgery were studied. RESULTS: Fifty-four patients with emergency operations and six with associated carotid artery surgery were excluded. Of the remaining 928 patients, 450 (48.5%) were planned for off-pump surgery. Thirty-seven (8.2%) of them required conversion to CPB on an emergency basis. These patients had higher mortality (5.4%) than the off-pump group (1.5%) and the CPB group (0.4%), P = 0.02. The incidence of prolonged hospital stay was also higher (conversion group = 27%, off-pump group = 12.3%, CPB group = 17.6%; P = 0.02). We did not identify any perioperative characteristics significantly associated with the risk of requiring conversion. The conversion rate was uniformly distributed over the study period. CONCLUSIONS: Patients who are emergently converted to CPB during attempted off-pump procedures are at higher risk of death and prolonged hospital stay; this population should be included in comparative studies as "intention to treat" in the off-pump group.

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.

Anesthesiological management and outcome of 100 ''beating heart'' coronary artery bypass grafting.

AIM: The aim of this paper is to describe the anesthesiological management and the outcome of beating heart revascularization. METHODS: A prospective study has been performed in a tertiary teaching hospital on 100 consecutive patients undergoing off-pump coronary artery revascularization. The main features of anesthetic technique are the maintenance hemodynamic stability and atrial kick. RESULTS: Mechanical stabilisers shunts have improved the management of these patients. In hospital mortality was 1%, acute myocardial infarction 3%, low output syndrome 2%, atrial fibrillation 16%. Only 2% of patients had acute renal failure, but no patient needed renal replacement treatment. No neurologic event was noted. Only 19% of patients received blood transfusion. Ninety-seven % of patients were extubated within 12 h. CONCLUSIONS: The application of this anesthetic strategy combined with surgical skillful and new devices makes off-pump surgery safe also in high risk patients.

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.

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.

Inhibition by Interleukin-4 of stromelysin expression in human skin fibroblasts: role of PKC.

This study explores novel aspects of the interaction between inflammatory mediators and extracellular matrix degradation. Here we have evaluated the effects of a T-cell cytokine interleukin-4 (IL-4) on the expression and activity of a metalloprotease, stromelysin, and its tissue inhibitor (TIMP-1) in human skin fibroblasts. IL-4 strongly decreased stromelysin mRNA levels and stromelysin-producing activity induced by IL-1 beta-treated and untreated cells. Under the same experimental conditions, TIMP-1 mRNA expression was slightly modified. Phorbol ester (PMA), a PKC activator, induced stromelysin gene expression, an effect enhanced by the addition of IL-1 beta. IL-4 was not able to decrease the PMA and PMA + IL1 beta effects. Calphostin, a specific PKC inhibitor, inhibited stromelysin mRNA expression induced by IL-1 beta. Forskolin, a PKA activator, did not modify mRNA levels and was not able to reduce the effect of IL-4 on IL-1 beta-induced stromelysin expression. These data suggest that in human dermal fibroblasts, activation of PKC abolishes the observed IL-4 effect on both basal and IL-1 beta-induced stromelysin gene expression. It therefore appears that lack of PKC activation is a prerequisite for the inhibitory effect of IL-4 in the system.

[Clinical considerations in the use of nifedipine in patients with "HELLP syndrome"]. / Considerazioni cliniche sull'uso della nifedipina nelle pazienti affette da "Hellp syndrome".

The authors report eleven cases of patients having pregnancy induced hypertension, and two cases of patients having severe pregnancy induced hypertension complicated by thrombocytopenia, and elevated liver enzymes. Nifedipine has been used in treatment of blood hypertension. Moreover, nifedipine appeared to reverse thrombocytopenia and serum liver enzymes. The authors discuss the significance of Hellp syndrome (haemolysis, elevated liver Enzymes, and low platelet count).

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.

Biochemical changes in central nervous system membranes in chronic-relapsing experimental allergic encephalomyelitis.

Biochemical studies of myelin fractions were undertaken on Lewis rats during various time-points in the development of chronic-relapsing experimental allergic encephalomyelitis (CR-EAE). Lipid and protein composition of myelin fractions obtained by sucrose density gradient centrifugation at 10, 19, 24, and 66 d postinduction (pi) were determined by high-performance thin-layer chromatography (HPTLC) and sodium dodecyl sulfate-polyacrilamide gel electrophoresis (SDS PAGE), respectively. When comparing the myelin fractions of CR-EAE affected animals with those of controls, main differences were observed at 10 d pi. These changes were particularly evident in the light myelin fraction, where a decrease in the percentage of phosphatidylethanolamine and small basic protein relative to the total lipids and proteins of the fraction were observed. At 19 and 24 d pi no biochemical differences were present in both fractions. At 66 d pi, differences in the lipid composition were observed again only in the light myelin fraction. These findings suggest that the light myelin fraction is the most sensitive, particularly at the early stages of the disease, and must play a key role in demyelinating processes.

Lipid profile of rat myelin subfractions.

Myelin from adult rat brains was separated on a discontinuous sucrose gradient into three subfractions. Analysis of "light", "heavy" and "membrane fraction" lipid classes was performed by HPTLC and densitometry while fatty acid composition was determinated by GLC. The more interesting results observed are: i) the "membrane fraction" resembles in its lipid and fatty acid composition other cell membranes (particularly oligodentrocytes); ii) "light" and "heavy" myelin are quite similar between them but the former has a higher content of sphingomyelin, a lower hydroxy/nonhydroxy cerebrosides ratio and a lower content of monoenoic fatty acids than the "heavy" subfraction. The results obtained could explain the different structures observed in each myelin subfraction since fatty acid composition, hydroxy fatty acids, sphingomyelin and cholesterol play a key role in the stability and structure of membranes.

Analysis of brain and myelin lipids by high-performance thin layer chromatography and densitometry.

We have developed a simple method involving high-performance thin layer chromatographic separation of total brain and myelin lipids. Only two solvent systems consisting of chloroform: methanol:acetic acid and water at different concentrations were needed. The plate was then stained with three sequential procedures to visualize phospholipids, cholesterol and galactolipids. Densitometric procedure at each step of staining was utilized to obtain quantitative analysis of brain and myelin samples.