Hemodynamic effects of Vernakalant in cardio-surgical ICU-patients treated for recent-onset postoperative atrial fibrillation.

Postoperative atrial fibrillation (POAF) is one of the most frequent complications after cardiothoracic surgery and a predictor for postoperative mortality and prolonged ICU-stay. Current guidelines suggest the multi-channel inhibitor Vernakalant as a treatment option for rhythm control. However, rare cases of severe hypotension and cardiogenic shock following drug administration have been reported. To elucidate the impact of Vernakalant on hemodynamics, we included ten ICU patients developing POAF after elective cardiac surgery, all of them awake and breathing spontaneously, in this prospective trial. Patients received the recommended dosage of Vernakalant and were clinically observed and monitored (heart rate, invasive blood pressure, pulse oximetry, central venous pressure) in 1-minute-intervals for 20 minutes before- and 120 minutes after the first dose of Vernakalant. The median time from the end of surgery until occurrence of POAF amounted up to 52.8 [45.9-77.4] hours, it took 3.5 [1.2-10.1] hours from occurrence of POAF until the first application of Vernakalant. All patients received catecholamine support with epinephrine that was held steady and not dynamic throughout the observational phase. We noted stable hemodynamic conditions, with a trend towards a reduction in heart rate throughout the 120 minutes after drug administration. In 7 patients (70%), conversion to sustained sinus rhythm (SR) occurred within 8.0 minutes [6.0-9.0]. No serious adverse events (SAEs) were noted during the observation period. In this prospective trial in ICU-patients showing POAF after cardiac surgery, intravenous Vernakalant did not induce clinically relevant negative effects on patients' hemodynamics but resulted in conversion to sustained SR after a median of 8.0 minutes in 7 out of ten patients.

Beneficial effects of levosimendan on survival in patients undergoing extracorporeal membrane oxygenation after cardiovascular surgery.

BACKGROUND: The impact of levosimendan treatment on clinical outcome in patients undergoing extracorporeal membrane oxygenation (ECMO) support after cardiovascular surgery is unknown. We hypothesized that the beneficial effects of levosimendan might improve survival when adequate end-organ perfusion is ensured by concomitant ECMO therapy. We therefore studied the impact of levosimendan treatment on survival and failure of ECMO weaning in patients after cardiovascular surgery. METHODS: We enrolled a total of 240 patients undergoing veno-arterial ECMO therapy after cardiovascular surgery at a university-affiliated tertiary care centre into our observational single-centre registry. RESULTS: During a median follow-up period of 37 months (interquartile range 19-67 months), 65% of patients died. Seventy-five per cent of patients received levosimendan treatment within the first 24 h after initiation of ECMO therapy. Cox regression analysis showed an association between levosimendan treatment and successful ECMO weaning [adjusted hazard ratio (HR) 0.41; 95% confience interval (CI) 0.22-0.80; P=0.008], 30 day mortality (adjusted HR 0.52; 95% CI 0.30-0.89; P=0.016), and long-term mortality (adjusted HR 0.64; 95% CI 0.42-0.98; P=0.04). CONCLUSIONS: These data suggest an association between levosimendan treatment and improved short- and long-term survival in patients undergoing ECMO support after cardiovascular surgery.

[Intensive care treatment of patients with left ventricular assist devices]. / Intensivbehandlung von Kranken mit Linksherzersatz.

Apart from heart transplantation, implantation of a left ventricular assist device (LVAD) is the only established surgical treatment for therapy-refractory terminal left heart failure, The specific intensive care unit (ICU) management of these patients depends on the reason for the ICU admission and requires understanding of the characteristic hemodynamics of non-pulsatile LVADs as well as of the inherent problems. Knowledge about the specific features in hemodynamic monitoring, understanding of pump characteristics, management of anticoagulation and hemostasis and the handling of problems, such as right heart failure, aortic valve insufficiency and infections is essential. The management of unconscious LVAD patients can be challenging. It requires a sophisticated transthoracic and transesophageal echocardiography (TTE/TEE) examination, targeted laboratory diagnostics and consideration of possible alternative diagnoses. Professional interdisciplinary cooperation and exchange of current knowledge is crucial.

A pilot study on reparixin, a CXCR1/2 antagonist, to assess safety and efficacy in attenuating ischaemia-reperfusion injury and inflammation after on-pump coronary artery bypass graft surgery.

Reparixin, a CXCR 1/2 antagonist, has been shown to mitigate ischaemia-reperfusion injury (IRI) in various organ systems in animals, but data in humans are scarce. The aim of this double-blinded, placebo-controlled pilot study was to evaluate the safety and efficacy of reparixin to suppress IRI and inflammation in patients undergoing on-pump coronary artery bypass grafting (CABG). Patients received either reparixin or placebo (n = 16 in each group) after induction of anaesthesia until 8 h after cardiopulmonary bypass (CPB). We compared markers of systemic and pulmonary inflammation, surrogates of myocardial IRI and clinical outcomes using Mann-Whitney U- and Fisher's exact tests. Thirty- and 90-day mortality was 0% in both groups. No side effects were observed in the treatment group. Surgical revision, pleural and pericardial effusion, infection and atrial fibrillation rates were not different between groups. Reparixin significantly reduced the proportion of neutrophil granulocytes in blood at the beginning [49%, interquartile range (IQR) = 45-57 versus 58%, IQR = 53-66, P = 0·035], end (71%, IQR = 67-76 versus 79%, IQR = 71-83, P = 0·023) and 1 h after CPB (73%, IQR = 71-75 versus 77%, IQR = 72-80, P = 0·035). Reparixin patients required a lesser positive fluid balance during surgery (2575 ml, IQR = 2027-3080 versus 3200 ml, IQR = 2928-3778, P = 0·029) and during ICU stay (2603 ml, IQR = 1023-4288 versus 4200 ml, IQR = 2313-8160, P = 0·021). Numerically, more control patients required noradrenaline ≥ 0·11 µg/kg/min (50 versus 19%, P = 0·063) and dobutamine (50 versus 25%, P = 0·14). Therefore, administration of reparixin in CABG patients appears to be feasible and safe. It concurrently attenuated postoperative granulocytosis in peripheral blood.

Emergency ambulance transport induces stress in patients with acute coronary syndrome.

BACKGROUND: Trials with healthy volunteers have shown that emergency ambulance transportation induces stress, which becomes evident by an increase in heart rate, blood pressure and plasma levels of stress hormones such as adrenaline, noradrenaline, cortisol and prolactin. A study was undertaken to test the hypothesis that emergency ambulance transportation may also lead to stress in patients with acute coronary syndrome. METHODS: Venous plasma levels of epinephrine, norepinephrine and lactate as well as visual analogue scale (VAS) scores for pain and anxiety were measured in 32 patients with defined clinical signs of acute coronary syndrome before and after transportation. Heart rate, blood pressure and transcutaneous oxygen saturation levels were recorded every 3 min. RESULTS: Mean (SD) plasma levels of epinephrine and norepinephrine increased significantly (p<0.01) during transportation (159.29 (55.34) ng/l and 632.53 (156.32) ng/l before transportation vs 211.03 (70.12) ng/l and 782.93 (173.95) ng/l after transportation), while lactate levels, heart rate and mean blood pressure remained almost stable. There was no significant change in mean (SD) VAS scores for pain and anxiety (3.79 (3.70) and 2.89 (3.01) vs 2.13 (3.30) and 1.57 (2.78)). CONCLUSION: Emergency ambulance transportation induces a rise in plasma catecholamine levels and therefore stress in patients with acute coronary syndrome, but does not result in cardiac shock as lactate levels and haemodynamic parameters remain normal.

Intravenous immunoglobulins induce CD32-mediated platelet aggregation in vitro.

BACKGROUND: Intravenous immunoglobulins (IVIg) and cytomegalovirus immunoglobulins (CMVIg) are currently finding increased acceptance in clinical states of high immune activity and in transplant recipients. A rare side-effect of their application is intravascular thrombosis, which is thought to be related to pre-existing hyperviscosity. In a previous study we have shown that rabbit antithymocyte globulin causes platelet aggregation in vitro via the Fc IgG receptor (CD32). OBJECTIVES: To investigate if IVIg and CMVIg have the potential to cause CD32-dependent platelet aggregation. METHODS: The influence of CMVIg or IVIg on platelets pre-incubated with or without monoclonal antibody AT10 was studied in an aggregometer. Expression of platelet surface activation marker CD62P was determined by fluorescence-activated cell sorting analysis and presence of soluble CD40L (sCD40L) was evaluated by enzyme-linked immunosorbent assay. All in vitro experiments were performed using platelet concentrates from the blood bank, at therapeutic concentrations of immunoglobulins. Results Incubation of platelets with CMVIg and IVIg markedly induced platelet aggregation, and increased expression of CD62P and secretion of sCD40L. The capacity of CMVIg and IVIg to induce platelet aggregation was completely abrogated by adding the blocking antibody AT10 directed against the low-affinity Fc IgG receptor (CD32). CONCLUSIONS: Our results suggest that CMVIg and IVIg solutions with activating Fc domains are able to bind CD32 on platelets and cause platelet aggregation in vitro. These results indicate a mechanism by which in vivo intravascular thrombosis may be explained and suggest caution with concomitant use of packed platelets and IVIg in autoimmune diseases in the clinical setting.

Low-dose remifentanil to suppress haemodynamic responses to noxious stimuli in cardiac surgery: a dose-finding study.

BACKGROUND: High-dose remifentanil (1-5 microg kg-1 min-1), commonly used for cardiac surgery, has been associated with muscle rigidity, hypotension, bradycardia, and reduced cardiac output. The aim of this study was to determine an optimal lower remifentanil dose, which should be accompanied by fewer adverse events, that still effectively suppresses haemodynamic responses to typical stressful stimuli (i.e. intubation, skin incision, and sternotomy). METHODS: Total i.v. anaesthesia consisted of a target-controlled propofol (2 microg ml-1) and a remifentanil infusion. Forty patients were allocated to receive either a constant infusion of remifentanil at 0.1 microg kg-1 min-1 or up-titrations to 0.2, 0.3, or 0.4 microg kg-1 min-1, respectively, 5 min before each stimulus. Subsequently, changes in heart rate and mean arterial blood pressure were recorded for 8 min. Increases exceeding 20% of baseline were considered to be of clinical relevance. Patients who exhibited these alterations were termed responders. RESULTS: The number of responders was less with the two higher remifentanil dosages (P<0.05) while propofol target doses could either be kept at the same level or even be reduced without affecting the plane of anaesthesia. Although single phenylephrine bolus had to be applied more frequently in these two groups (P<0.05), no severe haemodynamic depression was observed. CONCLUSIONS: Remifentanil at 0.3 and 0.4 microg kg-1 min-1 in combination with a target-controlled propofol infusion in the pre-bypass period is well tolerated. It appears to mitigate potentially hazardous haemodynamic responses from stressful stimuli equally well as higher doses when compared with data from the literature.

Reparixin, a specific interleukin-8 inhibitor, has no effects on inflammation during endotoxemia.

Reparixin antagonizes interleukin-8 (IL-8) on the level of signal transduction in vitro. We hypothesized that IL-8 mediates some of the reactions occurring during acute inflammation and specifically that IL-8 may be a mediator of endotoxin induced neutrophilia. We therefore tested the effects of reparixin on humoral and cellular parameters in LPS-induced acute systemic inflammation. The study is a randomized (3:2 active:placebo), double-blind, placebo-controlled parallel group trial. Twenty healthy male volunteers randomly received either reparixin (12) or placebo (8) intravenously. One hour after the start of reparixin/placebo infusion a bolus of 2 ng/kg endotoxin was infused over 1-2 min. Blood samples were obtained over 24 h. Reparixin, being metabolized to ibuprofen, suppressed serum thromboxane B2 levels by 78 percent compared to baseline and control at 8 h. LPS-induced neutrophilia was not significantly affected by reparixin in human volunteers. Consistently, reparixin did not alter the lymphocyte or monocyte counts and had no effect on LPS-induced systemic inflammation as measured by tumor necrosis factor alpha (TNF-alpha) or interleukin-6 (IL-6) release. Regulation of IL-8 receptors CXCR1 and 2 and the degranulation marker CD11b showed the expected kinetics. Reparixin had no effect on thrombin formation as measured by prothrombin fragment (F1+2). In conclusion, our study showed that reparixin was safe but had no impact on endotoxin induced inflammation. In contrast to previous studies with its metabolite ibuprofen, reparixin does not enhance inflammation in this model.

Magnesium moderately decreases remifentanil dosage required for pain management after cardiac surgery.

BACKGROUND: Magnesium is a calcium and an NMDA-receptor antagonist and can modify important mechanisms of nociception. We evaluated the co-analgesic effect of magnesium in the postoperative setting after on-pump cardiac surgery. METHODS: Forty patients randomly received either magnesium gluconate as an i.v. bolus of 0.21 mmol kg(-1) (86.5 mg kg(-1)) followed by a continuous infusion of 0.03 mmol(-1) kg(-1) h(-1) (13.8 mg kg(-1) h(-1)) or placebo for 12 h after tracheal extubation. After surgery, remifentanil was decreased to 0.05 microg kg(-1) min(-1) and titrated according to a pain intensity score (PIS, range 1-6) in the intubated, awake patient and a VAS scale (range 1-100) after extubation. If PIS was > or =3 or VAS > or =30, the infusion was increased by 0.01 microg kg(-1) min(-1); if ventilatory frequency was < or =10 min(-1) it was decreased by the same magnitude. RESULTS: Magnesium lowered the cumulative remifentanil requirement after surgery (P<0.05). PIS > or =3 was more frequent in the placebo group (P<0.05). Despite increased remifentanil demand, VAS scores were also higher in the placebo group at 8 (2 vs 8) and 9 h after extubation (2 vs 7) (P<0.05). Dose reductions attributable to a ventilatory frequency < or =10 min(-1) occurred more often in the magnesium group (17 vs 6; P<0.05). However, time to tracheal extubation was not prolonged. CONCLUSIONS: Magnesium gluconate moderately reduced the remifentanil consumption without serious side-effects. The opioid-sparing effect of magnesium may be greater at higher pain intensities and with increased dosages.