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Background: The endocannabinoid system (ECS) is an endogenous signalling system which includes the endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG) and specific G-protein-coupled endocannabinoid receptors (CB1 and CB2). Recent studies have described important roles of the peripheral ECS in human atherosclerosis, cardiometabolic disorders, heart failure, and systemic inflammation. We sought to study changes in plasma endocannabinoid concentrations during cardiac surgery (CS) under general anaesthesia with isoflurane/sufentanil, and during cardiopulmonary bypass (CPB). [ABSTRACT FROM PUBLISHER]

Arterial hypotension with vasopressor dependence is a major problem after cardiac surgery. We evaluated the early postoperative course of 1558 consecutive patients scheduled for cardiac surgery, and compared the outcome of patients with and without vasopressor dependence (defined as the need for > 0.1 μg.kg−1.h−1 noradrenaline for > 3 h in the face of normovolaemia). Vasopressor dependence was diagnosed in 424 patients (27%) and was associated with a higher incidence of postoperative renal failure (67 (15.7%) vs 7 (0.6%), respectively; p < 0.0001), a longer duration of ventilation (median IQR [range]) 14 (8–26 [6–39]) h vs 8 (5–11 [4–32]) h; p < 0.0001), a greater need for red cell transfusion (3 (1–5 [0–10]) units vs 1 (0–2 [0–4]) units; p < 0.001) and a longer length of stay in the ICU (4 (2–6 [2–9] days) vs 2 (1–3 [1–6] days; p < 0.001). Vasopressor dependence could be predicted from a combination of factors, including pre-operative ejection fraction < 37%, cardiopulmonary bypass lasting > 94 min, and postoperative interleukin-6 > 837 pg.ml−1. [ABSTRACT FROM AUTHOR]

Background: We studied the feasibility of using patient-controlled anesthesia (PCA) for conscious sedation during colonoscopy.Methods: Patients having elective colonoscopy had medications delivered in bolus fashion by PCA pump (Abbot Lifecare Provider 5500 Infusion System). Four patients received propofol as 20 mg/dose boluses, and four patients received propofol in a 0.3 mg/kg/dose. Twelve patients received propofol at 0.2 mg/kg/dose with alfentanil at 4 microg/kg/dose.Results: There were no clinically unacceptable changes in continuously monitored blood pressure, pulse rate, ECG, or respiratory rate. There were no adverse effects from the sedation and no complications due to colonoscopy. Recovery time was rapid, but recall persisted in most subjects. Pain and overall discomfort in patients given propofol only were rated as moderate by most subjects.Conclusion: Patient-controlled anesthesia is feasible for use in endoscopic sedation. Propofol alone did not allow adequate pain relief, but propofol and alfentanil together seemed to provide good control of pain. [ABSTRACT FROM AUTHOR]

A response by F. Weis and A. Beiras-Fernandez to a letter to the editor about their article "Risk and outcome analysis of renal replacement therapies in patients after cardiac surgery with pre-operatively normal renal function" in the 2009 issue is presented.

Replies to a commentary on a case report concerning temporary hypoxemia from right-to-left shunting in a patient during support with a left ventricular assist device and a patent foramen ovale previously published in the periodical 'Acta Anaesthesiological Scandinavia' in 2000. Shunting triggered by the device; Causes of the closure of the patent foramen ovale.

The Palaeogene layered ultrabasic intrusion of the Isle of Rum forms the hearth of the Rum Igneous Centre in NW-Scotland. The regional Long Loch Fault, which is widely held to represent the feeder system to the layered magma reservoir, dissects the intrusion and is marked by extensive ultrabasic breccias of various types. Here we explore the connection between the layered ultrabasic cumulate rocks and breccias of central Rum that characterize the fault zone (the 'Central Series') and evaluate their relationship with the Long Loch Fault system. We show that fault splays in the Central Series define a transtensional graben above the Long Loch Fault into which portions of the layered units subsided and collapsed to form the extensive breccias of central Rum. The destabilization of the cumulate pile was aided by intrusion of Ca-rich ultrabasic magmas along the faults, fractures and existing bedding planes, creating a widespread network of veins and dykelets that provided a further means of disintegration and block detachment. Enrichment in LREE and compositional zoning in intra cumulate interstices suggest that the collapsed cumulates were infiltrated by relatively evolved plagioclase-rich melt, which led to extensive re-crystallization of interstices. Clinopyroxene compositions in Ca-rich gabbro and feldspathic peridotite veins suggest that the intruding magma was also relatively water-rich, and that pyroxene crystallized dominantly below the current level of exposure. We propose that the Long Loch Fault opened and closed repeatedly to furnish the Rum volcano with a pulsing magma conduit. When the conduit was shut, pressure built up in the underlying plumbing system, but was released during renewed fault movements to permit dense and often crystal-rich ultrabasic magmas to ascend rapidly from depth. These spread laterally on arrival in the shallow Rum magma reservoir, supplying repetitive recharges of crystal-rich magma to assemble the rhythmic layering of the Rum layered intrusion. [ABSTRACT FROM AUTHOR]

Background: Infection is a main cause of morbidity and mortality after heart surgery, with multi-resistant pathogens increasingly representing a challenge. Daptomycin provides bactericidal activity against gram-positive organisms that are resistant to standard treatment including vancomycin.Methods: A cohort of cardiac surgical patients, treated with daptomycin for major infection at two tertiary care centers, were retrospectively studied with a particular focus on the type of infection, causative pathogens and co-infections, daptomycin dosage, adverse events and outcome in order to provide evidence for the efficiency and safety of daptomycin in a distinct high-risk patient population.Results: Sixty-five patients (87.7 % males, 60.4 ± 13.5 years) who had undergone aortic surgery (20.0 %), ventricular assist device (VAD) implantation (21.5 %), combined procedures (21.5 %), coronary artery bypass grafting (12.3 %), isolated valve surgery (15.4 %) and heart transplantation (7.7 %) were diagnosed with catheter-related infection (26.1 %), valve endocarditis (18.8 %), sternal wound (13.0 %), VAD-associated (11.6 %), cardiac implantable electrophysiological device (CIED)-associated (4.1 %), respiratory tract (4.3 %), bloodstream (4.3 %) and other infection (4.3 %). In 13.0 %, no focus of infection was identified though symptoms of severe infection were present. The most frequent pathogens were Staphylococcus epidermidis (30.4 %), Staphylococcus aureus (23.1 %) and Enterococcus species (10.1 %). Daptomycin doses ranging from 3 mg/kg every 48 h to 10 mg/kg every 24 h were administered for 15.4 ± 11.8 days. 87.0 % of the cases were classified as success, 7.2 % as treatment failure and 5.8 as non-evaluable. Adverse events were limited to one case of mild and one case of moderate neutropenia with recovery upon termination of treatment.Conclusion: Daptomycin proved safe and effective in major infection in high-risk cardiac surgical patients. [ABSTRACT FROM AUTHOR]

OBJECTIVE: : Acquired glucocorticoid resistance frequently complicates the therapy of sepsis. It leads to an exaggerated proinflammatory response and has been related to altered expression profiles of glucocorticoid receptor isoforms glucocorticoid receptor-[alpha] (mediating anti-inflammatory effects) and glucocorticoid receptor-[beta] (acting as a dominant negative inhibitor). We investigated the impact of glucocorticoid receptor isoforms on glucocorticoid effects in human T-cells. We hypothesized that 1) changes of the ratio of glucocorticoid receptor isoforms impact glucocorticoid resistance and 2) glucocorticoid receptor-[alpha] expression is controlled by microRNA-mediated gene silencing. DESIGN: : Laboratory-based study. SETTING: : University research laboratory. SUBJECTS AND PATIENTS:: Healthy volunteers, sepsis patients. METHODS: : First, T-cells from healthy volunteers (native and CD3/CD28-stimulated cells with or without addition of hydrocortisone) were analyzed for the expression of glucocorticoid receptor-isoforms by quantitative polymerase chain reaction. Additionally, effects of gene silencing of glucocorticoid receptor-[beta] by siRNA transfection were determined. Secondly, microRNA-mediated silencing was evaluated by cloning of a glucocorticoid receptor-[alpha]-specific 3'-untranslated-region reporter construct and subsequent transfection experiments in cell cultures. Effects of miRNA transfection on glucocorticoid receptor-[alpha] expression were analyzed in Jurkat T-cells and in T-cells from healthy volunteers (quantitative polymerase chain reaction and Western blotting). Finally, expression of glucocorticoid receptor-[alpha], glucocorticoid receptor-[beta], and miR-124 was tested in T-cells of sepsis patients (n = 24). MEASUREMENTS AND MAIN RESULTS: : Stimulation of T-cells induced a significant upregulation of glucocorticoid receptor-[alpha] (not glucocorticoid receptor-[beta]) thereby possibly rendering T-cells more sensitive to glucocorticoids; this T-cell response was hindered by hydrocortisone. Silencing of glucocorticoid receptor-[beta] doubled the inhibitory effects of glucocorticoids on interleukin-2 production. MicroRNA-124 was proved to specifically downregulate glucocorticoid receptor-[alpha]. Furthermore, a glucocorticoid-induced three-fold upregulation of microRNA-124 was found. T-cells of sepsis patients exhibited slightly decreased glucocorticoid receptor-[alpha] and slightly increased miR-124 expression levels, whereas glucocorticoid receptor-[beta] expression was two-fold upregulated (p < .01) and exhibited a remarkable interindividual variability. CONCLUSIONS: : Glucocorticoid treatment induces expression of miR-124, which downregulates glucocorticoid receptor-[alpha] thereby limiting anti-inflammatory effects of glucocorticoids. Steroid treatment might aggravate glucocorticoid resistance in patients with high glucocorticoid receptor-[beta] levels. [ABSTRACT FROM AUTHOR]

Plasma clearance of indocyanine green has recently been established as a tool to monitor hepatic function and perfusion non-invasively. Reduced indocyanine green clearance has been associated with adverse outcome in cardiac surgery patients, and cardiopulmonary bypass has been hypothesized to be one important triggering factor. We performed a prospective observational study comparing the influence of off-pump and on-pump coronary surgery on perioperative indocyanine green clearance. Twenty-five consecutive adult patients without known pre-existing hepatic diseases scheduled for off-pump coronary artery bypass grafting were evaluated for hepatic dysfunction pre- and postoperatively with serial measurements of indocyanine green plasma clearance, specific laboratory values and liver function scores. Twenty-five matched patients who underwent coronary artery bypass grafting surgery with cardiopulmonary bypass in the same period served as controls. Parameters of postoperative hepatic function, including measurements of indocyanine green plasma clearance and specific laboratory values and scores, did not differ significantly between patients undergoing off-pump coronary artery bypass grafting and patients undergoing coronary artery bypass grafting with extracorporeal circulation. In patients without pre-existing hepatic diseases, a significant influence of cardiopulmonary bypass on perioperative indocyanine green plasma clearance as well as on liver specific laboratory parameters and scores cannot be proven. [ABSTRACT FROM AUTHOR]

BACKGROUND: Epinephrine enhances emotional memory whereas beta-adrenoceptor antagonists (beta-blockers, BBs) impair it. However, the effects of BB administration on memory are sex dependent. Therefore, we predicted differential effects of epinephrine and the BB metoprolol given to male and female patients after cardiac surgery (CS) on traumatic memories and post-traumatic stress disorder (PTSD) symptoms. METHOD: We performed a prospective observational study and determined the number of standardized traumatic memories (NTRM) and PTSD symptom intensity in cardiac surgical patients at 1 day before surgery, and at 1 week and 6 months after the procedure. PTSD symptoms and NTRM were quantified using validated questionnaires. Metoprolol could be administered any time post-operatively. RESULTS: Baseline NTRM was not significantly different between male (n=95) and female patients (n=33). One week after CS, the NTRM in male patients was significantly higher. Metoprolol had no significant effect in either sex. At 6 months, females with metoprolol (n=18) showed a significantly lower NTRM and significantly lower PTSD symptom scores than females without BBs (n=15, p=0.02). By contrast, the totally administered dosage of epinephrine correlated with NTRM in males (r=0.33, p<0.01) but not in females (r=0.21, p=0.29). CONCLUSIONS: beta-Adrenergic stimulation with epinephrine enhances memory for adverse experiences in males but not in females whereas beta-blockade selectively reduces memory for post-operative adverse events and PTSD symptoms in females. [ABSTRACT FROM AUTHOR]

Background. Epinephrine enhances emotional memory whereas b-adrenoceptor antagonists (β-blockers, BBs) impair it. However, the effects of BB administration on memory are sex dependent. Therefore, we predicted differential effects of epinephrine and the BB metoprolol given to male and female patients after cardiac surgery (CS) on traumatic memories and post-traumatic stress disorder (PTSD) symptoms. Method. We performed a prospective observational study and determined the number of standardized traumatic memories (NTRM) and PTSD symptom intensity in cardiac surgical patients at 1 day before surgery, and at 1 week and 6 months after the procedure. PTSD symptoms and NTRM were quantified using validated questionnaires. Metoprolol could be administered any time post-operatively. Results. Baseline NTRM was not significantly different between male (n=95) and female patients (n=33). One week after CS, the NTRM in male patients was significantly higher. Metoprolol had no significant effect in either sex. At 6 months, females with metoprolol (n=18) showed a significantly lower NTRM and significantly lower PTSD symptom scores than females without BBs (n=15, p=0.02). By contrast, the totally administered dosage of epinephrine correlated with NTRM in males (r=0.33, p<0.01) but not in females (r=0.21, p=0.29). Conclusions. β-Adrenergic stimulation with epinephrine enhances memory for adverse experiences in males but not in females whereas β-blockade selectively reduces memory for post-operative adverse events and PTSD symptoms in females. [ABSTRACT FROM AUTHOR]

Peri-operative acute renal failure requiring renal replacement therapy is common (5–30%) after cardiac surgery and associated with a mortality of ∼50%. Pre-operative renal impairment seems to be the most important risk factor for frank postoperative renal failure. To help evaluate the risk factors, we conducted a prospective observational trial of 1574 consecutive patients with normal pre-operative renal function (creatinine < 110 μmol.l−1). Renal failure was defined as the need for renal replacement therapy. After univariate analysis of previously described risk factors, those who differed significantly between patients with or without renal failure were enrolled into a multivariate classification and regression tree (CART) statistical model that identifies the most ‘predictive’ risk factors and creates a ranked list of these. In patients with pre-operatively normal renal function, a serum level of lactate > 1.1 mmol.l−1 in the first 24 h after the operation was the strongest predictor for the development of renal failure. [ABSTRACT FROM AUTHOR]

Abstract: Background: Primary graft failure (PGF) is a severe complication responsible for 42% of the in-hospital mortality after heart transplantation. It has been postulated that once 30-day survival is achieved, patients with PGF have no increased risk of death. Levosimendan increases the 30-day survival among patients with PGF. Herein we have reported a 3-year follow-up at a single center of a patient cohort including PGF cases treated with levosimendan. Methods: From September 2005 to December 2006 53 patients underwent heart transplantation at our institution, including 12 patients (22.6%) who presented with PGF and were treated with levosimendan using a 24-hour continuous infusion (0.10 μg/kg/min). Risk factors for 1-year and three-year mortality were analyzed using 30-day as well as 1 and 3-year survivals comparing patients with versus without PGF (n = 41). Results: There were no significant differences in donor age, weight, height, and serum sodium between the groups. However, the ischemia time (259 ± 53 vs 227 ± 50 min; P = .06) and recipient age (51.6 ± 15 vs 41.5 ± 21 years; P = .07) were greater among the PGF patients. The 30-day survival rate was 92% in both groups. After 1 and 3 years, the survival rate was significantly lower among the PGF cohort (50% vs 80.6% and 41.7% vs 80.6%; P < .05) with 86.5% of PGF patients succunding due to non cardiac reasons, predominantly infections. Conclusions: Although treatment of PGF with levosimendan increased the 30-day survival, the 1 year and 3-year rates were reduced among this cohort of patients. PGF was associated with poor long-term outcomes, which may be a consequence of systemic malperfusion during the stage of cardiac low-output after transplantation. [Copyright &y& Elsevier]

We report a 56-year-old male patient developing hypoxemia after surgical replacement of infected valves of a left ventricular assist device (LVAD, Novacor) which had supported him during the previous 15 months. Contrast transesophageal echocardiography (TEE) revealed an atrial septal defect with intermittent right-to-left shunt across a patent foramen ovale. We postulate that the shunt detected in this patient occurred as a consequence of reduced pulmonary vascular compliance due to positive end-expiratory pressure (PEEP) and an increase of mean intrathoracic pressure. Furthermore, we hypothesize that synchronized LVAD operation exacerbates any potential right-to-left shunt due to the profound left ventricular unloading which occurs during LVAD support. In this first report of a right-to-left shunt from a previously unrecognized patent foramen ovale in a Novacor patient, the subsequent transient hypoxemia could be managed by avoiding PEEP of more than 3 mmHg, and mean airway pressure of more than 11 mmHg and by careful volume replacement in order to prevent the pump from completely emptying the left ventricle (LV) and the left atrium (LA). Thus, prior to every LVAD implantation a transesophageal contrast echocardiography with Valsalva maneuver should be performed to identify intracardiac right-to-left shunt. [ABSTRACT FROM AUTHOR]