Daptomycin for the treatment of major gram-positive infections after cardiac surgery.

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.

[Daptomycin for the treatment of gram-positive infections after cardiac surgery]. / Daptomycin zur Behandlung grampositiver Infektionen nach herzchirurgischen Eingriffen.

BACKGROUND AND METHOD: Surgical infection remains a main cause of death after heart surgery, despite advances in pharmacological therapy. Daptomycin is a cyclic lipopeptide antibiotic, useful in gram-positive organisms resistant to standard treatment, including vancomycin. The aim of this study was to describe the use of daptomycin regarding efficacy, efficiency and safety in patients with gram-positive infections after heart surgery using a retrospective analysis on 49 adult patients. CONCLUSION: Daptomycin shows excellent in vitro and in vivo activity against gram-positive organisms, such as Enterococcus faecalis, Enterococcus faecium, Staphylococcus aureus, especially MRSA. Daptomycin is also effective against increasing vancomycin-resistant or vancomycin-intermediate S. aureus.

Indocyanine green clearance after cardiac surgery: the impact of cardiopulmonary bypass.

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.

Levosimendan for primary graft failure after heart transplantation: a 3-year follow-up.

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.

Stress doses of hydrocortisone reduce systemic inflammatory response in patients undergoing cardiac surgery without cardiopulmonary bypass.

BACKGROUND: Systemic inflammatory response occurs after cardiac surgery (CS) and leads to a worse outcome in many cases. Stress doses of hydrocortisone have been successfully used to reduce SIRS and to improve outcome of patients after CS with cardiopulmonary bypass grafting (on-pump CABG), but the effect of hydrocortisone on patients undergoing CS without cardiopulmonary bypass grafting (off-pump CABG) is unclear. Therefore, we evaluated the effect of stress doses of hydrocortisone in this group of patients. METHODS: A total of 305 patients undergoing off-pump CABG were enrolled in a prospective randomized trial according to the study protocol. The patients either received stress doses of hydrocortisone or placebo. We measured various laboratory and clinical variables characterizing the patients' outcomes. RESULTS: The two study groups did not differ with regard to demographic data. Patients receiving hydrocortisone had an increased Higgins score and a decreased ejection fraction. Furthermore, patients from the hydrocortisone group had significantly lower levels of IL-6 (275 [162/677] pg/mL vs. 450 [320/660] pg/mL, P=0.001) and a shorter stay in the ICU (1 [1/3] day vs. 2 [2/3] days, P=0.04). Both groups did not differ in regard to catecholamine support, duration of mechanical ventilation, incidence of postoperative atrial fibrillation, blood loss, and mortality rate. CONCLUSION: We conclude that intravenous stress doses of hydrocortisone lead to a reduction of systemic inflammation and to a potential improvement in the early outcome of patients undergoing off-pump CABG.

Effect of anaesthesia and cardiopulmonary bypass on blood endocannabinoid concentrations during cardiac surgery.

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). METHODS: We studied 30 patients undergoing CS with CPB. All patients received midazolam and sufentanil for induction and isoflurane and sufentanil for maintenance of general anaesthesia. Blood samples were drawn before and after induction of general anaesthesia, after the beginning of surgery, during and after weaning from CPB, and after admission to intensive care unit (ICU) after surgery. Endocannabinoid measurements were performed by HPLC-tandem mass spectrometry. RESULTS: Induction of general anaesthesia led to a significant decline in plasma AEA concentrations [from mean (sd) 0.39 (0.03) to 0.27 (0.03) ng ml(-1), P<0.01]. CPB induced a pronounced increase in 2-AG concentrations [from 112.5 (163.5) to 321.0 (120.4) ng ml(-1), P<0.01], whereas AEA concentrations remained persistently low until admission to the ICU. 2-AG concentrations returned to preoperative values after surgery. CONCLUSIONS: General anaesthesia with isoflurane significantly reduces plasma AEA concentrations. This could be a consequence of stress reduction after loss of consciousness. The significant increase in 2-AG after initiation of CPB may be part of an inflammatory response. These findings suggest that anaesthesia and surgery have differential effects on the ECS which could have substantial clinical consequences.

A beta-adrenergic antagonist reduces traumatic memories and PTSD symptoms in female but not in male patients after cardiac surgery.

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.

Multidrug-resistant gram-positive infections in patients with ventricular assist devices: the role of daptomycin.

OBJECTIVES: The rate of infection in patients who require ventricular assist devices (VADs) is estimated at more than 35%. Infections with multidrug-resistant (MDR) organisms in VAD recipients present a high mortality rate. Daptomycin (Cubicin, Novartis, Nuremberg, Germany), a new cyclic lipopeptide antibiotic, is useful for MDR gram-positive organisms. We report the successful use of daptomycin in patients presenting with MDR gram-positive infections after VAD implantation. METHODS: We retrospectively studied nine consecutive patients presenting with resistant gram-positive infections after VAD implantation treated with daptomycin. We analyzed type of VAD, type of infection, responsible microorganism, outcome, and adverse events. RESULTS: We studied nine patients (eight males, one female), of overall mean age of 51 +/- 8 years; 78% required a biventricular assist device or a left VAD (Berlin Heart, Berlin, Germany), 22% received other ventricular support. Sixty-six percent presented with catheter-related infections (CRIs). Therapy with daptomycin was empirically initiated in all cases. The initial dose was 6 mg/kg, continued at 4 mg/kg. The mean duration of therapy was 16 +/- 5 days. The reported pathogens were MRSA, 33%; E. faecium, 25%; methicillin-resistant staphylococcus epidermidis, 12.5%; methicillin-sensitive staphylococcus aureus, 12.5%; others, 17%. Successful outcomes were reported in seven subjects (78%), with two patients succumbing due to multiorgan failure related to their heart condition prior completing antibiotic therapy. No adverse events were reported. CONCLUSIONS: Among our VAD patients, daptomycin proved efficient as a therapy for CRI with bacteremia. However, controlled studies are necessary to evaluate this antibiotic in patients presenting with VAD and MDR bacteremia.

Risk and outcome analysis of renal replacement therapies in patients after cardiac surgery with pre-operatively normal renal function.

Peri-operative acute renal failure requiring renal replacement therapy is common (5-30%) after cardiac surgery and associated with a mortality of approximately 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 micromol.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.

Primary graft failure and Ca2+ sensitizers after heart transplantation.

Primary organ failure after heart transplantation is a severe complication generally related to prolonged ischemia time, poor quality of the organ, or rejection. Ca(2+) sensitisers increase cardiac contractility without altering intracellular Ca(2+) levels. Our aim was to evaluate the influence of levosimendan in the therapy of primary failure after heart transplantation. Five patients presenting with reduced ejection fraction (EF<30%) and high dosed catecholamines after heart transplantation were treated with levosimendan (Simdax, Abbot GesmbH, Vienna, Austria) in a 24-hour continuous infusion (0.10 microg/kg*min) postoperatively. We assessed hemodynamic measurements including MAP, CVP, and PAP as well as heart function. Pharmacologic support with catecholamines could be halved at 24 hours and terminated in four of the patients 72 hours after levosimendan administration. Hemodynamics (MAP 70 +/- 11 vs 85 +/- 6 mm Hg; CI 2.5 +/- 0.4 vs 3.6 +/- 0.4 L/min/m(2)) and EF (28 +/- 10 vs 54 +/- 4%) improved at 48 hours after treatment. Acute graft failure after cardiac transplantation is associated with poor short- and long-term outcomes. Among our patients, levosimendan reduced the need for catecholamine support as well as improved ventricular performance.

Association between vasopressor dependence and early outcome in patients after cardiac surgery.

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 microg x kg(-1) x 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 x ml(-1).

Intensive care after minimally invasive and conventional coronary surgery: a prospective comparison.

OBJECTIVE: The purpose of this study was to compare the intensive care course of patients after minimally invasive coronary surgery to conventional coronary artery bypass grafting. DESIGN: Prospective observational study. SETTING: Intensive care unit of a university hospital. PATIENTS AND PARTICIPANTS: One hundred and five patients with two-vessel disease consecutively scheduled for elective coronary bypass surgery were enrolled. INTERVENTIONS: Two techniques of revascularization were performed: the Octopus procedure via median sternotomy without cardiopulmonary bypass (n = 52) and conventional coronary artery bypass grafting CABG (n = 53). MEASUREMENTS AND RESULTS: Three major categories describing the patients' postoperative course were defined: (1) clinical and laboratory findings, i.e., transfusion rate, catecholamine support, duration of ventilation, Simplified Acute Physiology Score II (SAPS II), serum levels of cardiac enzymes and lactic acid; (2) postoperative complications, i.e., incidence of myocardial infarction (MI), atrial fibrillation (AF), and neurological deficits; (3) this category was defined as "the extent of care" as represented by the Therapeutic Intervention Scoring System (TISS), and the length of stay in the ICU and in the hospital. In the Octopus group significantly lower figures were noted for duration of ventilation [6.1(5.5/9.5) vs 10.2(8.2/11.8) h], cardiac enzymes (CK-MB-Mass [5.1(2.0/8.3) vs 31.3(21.4/39.3) ng/ml], and lactic acid [2.0(1.5/3.3) vs 3.2(2.2/6.5) mmol/l]), incidence of AF (2/52 vs 9/53), and neurological deficits (0/52 vs 4/53), TISS score [72(44/83) vs 84(73/93)], LOS in the ICU [2(1/2) vs 2(2/2) days], and in the hospital [6(5/9) vs 9(8/12) days]. Catecholamine support, SAPS II scores, and incidence of MI of each group did not differ significantly. CONCLUSIONS: Off-pump coronary surgery via the Octopus technique was superior to conventional CABG regarding the course of patients in the early postoperative period. This implies benefits for the patients and the entire healthcare system.

Intermittent atrial level right-to-left shunt with temporary hypoxemia in a patient during support with a left ventricular assist device.

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.

Markers of myocardial ischemia after minimally invasive and conventional coronary operation.

BACKGROUND: The purpose of this study was to evaluate the course of serum markers of myocardial tissue damage after two different types of minimally invasive coronary surgical procedures (MICS) as compared with conventional coronary artery bypass grafting (CABG). METHODS: We enrolled 87 patients with one- or two-vessel disease scheduled for one of the three procedures: minimally invasive direct coronary artery bypass grafting (MIDCABG) by lateral thoracotomy (n = 29), the OCTOPUS method by median sternotomy (n = 27), and CABG (n = 31). Creatine kinase activity (CK), creatine kinase MB activity (CK-MB act), creatine kinase MB mass concentration (CK-MB mass), myoglobin concentration (MG), and cardiac troponin I concentration (cTnI) were measured perioperatively until the second postoperative day. RESULTS: Creatine kinase-MB, CK-MB mass, and cTnI were significantly higher after CABG and were nearly maintained within the normal range in MICS. Creatine kinase and MG were significantly lower in the OCTOPUS group than in the MIDCABG or CABG groups. CONCLUSIONS: Minimally invasive coronary surgical procedures cause less myocardial injury than CABG as indicated by specific serum markers. However, higher CK and MG reflect more substantial skeletal muscle trauma during MIDCABG operation compared with OCTOPUS procedures.

XTrR-I is a TGFbeta receptor and overexpression of truncated form of the receptor inhibits axis formation and dorsalising activity.

We have previously cloned a type I serine/threonine kinase receptor from Xenopus, namely XTrR-I. We show here that XTrR-I is able to bind and mediate the activity of TGFbeta1, but is unable to mediate response to activin or BMP-4. We have made a truncated receptor construct that can act as a dominant negative mutant receptor, and this can block the activity of TGFbeta2 but not that of activin. Overexpression of either the full-length or truncated receptor has a drastic effect on mesoderm differentiation. The truncated receptor inhibits expression of notochord and muscle in mesodermalised animal caps, while the full-length receptor greatly increases the amount of notochord. In addition, the truncated receptor blocks the axis duplicating activity of both siamois and Xwnt8. We conclude that XTrR-I is involved in mediating a dorsalising activity important for mesoderm differentiation.

Patient-controlled anesthesia for colonoscopy using propofol: results of a pilot study.

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.