[Individualized use of levosimendan in cardiac surgery]. / Individualisierter Einsatz von Levosimendan in der Herzchirurgie.

BACKGROUND: Levosimendan is a cardiac inotrope that augments myocardial contractility without increasing myocyte oxygen consumption. Additionally, levosimendan has been shown to exhibit anti-inflammatory, antioxidative, and other cardioprotective properties and is approved for treatment of heart failure. Recent studies indicated that these beneficial effects can be achieved with doses lower than the standard dose of 12.5 mg. Patients with preoperatively diagnosed left ventricular ejection fraction (LVEF) ≤40% received 1.25 mg levosimendan after induction of anesthesia. After surgery, administration of low-dose levosimendan was repeated until cardiovascular stability was achieved. OBJECTIVE: This study aimed to evaluate if pharmacological preconditioning with 1.25 mg levosimendan in patients with LVEF ≤40% altered the postoperative need for inotropic agents, the incidence of newly occurring atrial fibrillation, renal replacement therapy, mechanical circulatory support and 30-day mortality. The cumulative dosage of levosimendan was recorded to assess the required dosage in the context of individualized treatment. MATERIAL AND METHODS: This retrospective study included patients with preoperatively diagnosed LVEF ≤40% who underwent cardiac surgery at this institution between January 2015 and December 2018 and who received 1.25 mg levosimendan after induction of anesthesia to prevent postoperative low cardiac output syndrome. Based on echocardiography results, invasive hemodynamic monitoring, and central venous or mixed venous oxygen saturation and lactate clearance, repetitive doses of levosimendan in 1.25 mg increments could be postoperatively administered until cardiovascular stability was achieved. The results were compared to the current literature. RESULTS: We identified 183 patients with LVEF <40% who received pharmacological preconditioning with 1.25 mg levosimendan. Maximum doses of epinephrine, incidence of atrial fibrillation, need for renal replacement therapy and 30-day mortality were found to be below the published rates of comparable patient collectives. In 73.2% of patients, a cumulative dosage of 5 mg levosimendan or less was considered sufficient. CONCLUSION: The presented concept of pharmacological preconditioning with 1.25 mg levosimendan followed by individualized additional dosing in cardiac surgery patients with preoperative LVEF ≤40% suggests that this concept is safe, with possible advantages regarding the need of inotropic agents, renal replacement therapy, and 30-day mortality, compared to the current literature. Individualized treatment with levosimendan to support hemodynamics and a timely reduction of inotropic agents needs further confirmation in randomized trials.

[Vasopressin in distributive shock : Brief summary of the guidelines of the Canadian Critical Care Society published in December 2019]. / Vasopressin im distributiven Schock : Kurzzusammenfassung der im Dezember 2019 veröffentlichten Guideline der Canadian Critical Care Society.

The Canadian Critical Care Society performed a meta- analysis to assess the benefits and risks of the application of vasopressin and vasopressin- analogues in distributive shock. Their results were formulated as a Guideline in 2019. In the meta- analysis mainly included were studies with patients suffering from sepsis causing the distributive shock. The recommendations of the Surviving Sepsis Campaign 2016 concerning catecholamine therapy clearly prefer norepinephrin as the first- choice vasopressor, the use of vasopressin as an additionally administered drug is rated more tentative. Also the Canadian guideline now, implicating recently published studies, argues for the use of vasopressin or vasopressin- analogues in addition to an existing norepinephrine therapy, even though the level of evidence remains still low and there's no simple therapeutic algorithm formulated. This is based on a lowered incidence of newly- diagnosed atrial fibrillation and decreased mortality rate while administration remains safe.

[Noninvasive Mechanical Ventilation in Acute Respiratory Failure]. / Nicht-invasive Beatmung als Therapie der akuten respiratorischen Insuffizienz.

The non-invasive ventilation (NIV) is widespread in the clinical medicine and has attained meanwhile a high value in the clinical daily routine. The application of NIV reduces the length of ICU stay and hospitalization as well as mortality of patients with hypercapnic acute respiratory failure. Patients with acute respiratory failure in context of a cardiopulmonary edema should be treated in addition to necessary cardiological interventions with continuous positive airway pressure (CPAP) or NIV. In case of other forms of acute hypoxaemic respiratory failure it is recommended the application of NIV to be limited to mild forms of ARDS as the application of NIV in severe forms of ARDS is associated with higher rates of treatment failure and mortality. In weaning process from invasive ventilation the NIV reduces the risk of reintubation essentially in hypercapnic patients. A delayed intubation of patients with NIV failure leads to an increase of mortality and should therefore be avoided. With appropriate monitoring in intensive care NIV can also be successfully applied in pediatric patients with acute respiratory insufficiency. Furthermore NIV can be useful within palliative care for reduction of dyspnea and improving quality of life. The aim of the guideline update is, taking into account the growing scientific evidence, to outline the advantages as well as the limitations of NIV in the treatment of acute respiratory failure in daily clinical practice and in different indications.

Platelet factor 4-positive thrombi adhering to the ventricles of a ventricular assist device in patients with heparin-induced thrombocytopenia type II.

BACKGROUND: Thromboembolism is a major complication in patients with ventricular assist devices (VADs). Drug anticoagulation and the use of biocompatible surfaces, such as coating with heparin, aim to reduce thromboembolism in these patients. Administration of heparin can lead to heparin-induced thrombocytopenia (HIT) type II, mainly through heparin/platelet factor 4 (PF4) antibodies. We assessed the presence of PF4 antibodies in VAD thrombi of patients with heparin-coated VADs and HIT II. METHODS: Thrombi (n = 6) were obtained from the replaced Excor ventricles of patients with HIT II after biventricular VAD implantation (Excor Adult; Berlin Heart, Germany). Excor ventricles were changed after clinical examination and suspicion of thrombi in the polyurethane valves. Expression of PF4- antibodies was assessed with the use of a polyclonal rabbit antibody (anti-PF4 antibody; Abcam, USA). Expression was assessed by 2 independent observers. RESULTS: Biopsies of all thrombi showed an extreme positive immunoreaction for PF4. No differences between the different thrombi and localization (left/right Excor ventricle) were observed. The thrombi were organized, without lamination of fibrin and cellular layers. CONCLUSIONS: Platelet surface expression of PF4 in the thrombi reflects HIT antigen presentation. The physical relationship between the PF4-positive thrombi and the heparin-coated surface suggests that onset of HIT II could be influenced by the immobilized heparin coating.

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.

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.

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.

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).

Assessing fluid responsiveness during open chest conditions.

BACKGROUND: Measurement of ventilation-induced left ventricular stroke volume variations (SVV) or pulse pressure variations (PPV) is useful to optimize preload in patients after cardiac surgery. The aim of this study was to investigate the ability of SVV and PPV measured by arterial pulse contour analysis to assess fluid responsiveness in patients undergoing coronary artery bypass surgery during open-chest conditions. METHODS: We studied 22 patients immediately after midline sternotomy. We determined SVV, PPV, left ventricular end-diastolic area index by transoesophageal echocardiography, global end-diastolic volume index and cardiac index by thermodilution before and after removal of blood 500 ml and after volume substitution with hydroxyethyl starch 6%, 500 ml. RESULTS: Blood removal resulted in a significant increase in SVV from 6.7 (2.2) to 12.7 (3.8)%. PPV increased from 5.2 (2.5) to 11.9 (4.6)% (both P<0.001). Cardiac index decreased from 2.9 (0.6) to 2.3 (0.5) litres min(-1) m(-2) and global end-diastolic volume index decreased from 650 (98) to 565 (98) ml m(-2) (both P<0.025). Left ventricular end-diastolic area index did not change significantly. After fluid loading SVV decreased significantly to 6.8 (2.2)% and PPV decreased to 5.4 (2.1)% (both P<0.001). Concomitantly, cardiac index increased significantly to 3.3 (0.5) litres min(-1) m(-2) (P<0.001) and global end-diastolic volume index increased significantly to 663 (104) ml m(-2) (P<0.005). Left ventricular end-diastolic area index did not change significantly. We found a significant correlation between the increase in cardiac index caused by fluid loading and SVV as well as PPV before fluid loading (SVV, R=0.74, P<0.001; PPV, R=0.61, P<0.005). No correlations were found between values of global end-diastolic volume index or left ventricular end-diastolic area index before fluid loading and the increase in cardiac index. CONCLUSION: Measurement of SVV or PPV allows assessment of fluid responsiveness in hypovolaemic patients under open-chest and open-pericardium conditions. Thus, measuring heart-lung interactions may improve haemodynamic management during surgical procedures requiring mid-line sternotomy.

Effects of mid-line thoracotomy on the interaction between mechanical ventilation and cardiac filling during cardiac surgery.

BACKGROUND: Mid-line thoracotomy is a standard approach for cardiac surgery. However, little is known how this surgical approach affects the interaction between the circulation and mechanical ventilation. We studied how mid-line thoracotomy affects cardiac filling volumes and cardiovascular haemodynamics, particularly variations in stroke volume and pulse pressure caused by mechanical ventilation. METHODS: We studied 19 patients during elective coronary artery bypass surgery. Before and after mid-line thoracotomy, we measured arterial pressure, cardiac index (CI) and global end-diastolic volume index (GEDVI) by thermodilution, left ventricular end-diastolic area index (LVEDAI) by transoesophageal echocardiography and the variations in left ventricular stroke volume and pulse pressure during ventilation by arterial pulse contour analysis. RESULTS: After thoracotomy, CI increased from 2.3 (0.4) to 2.9 (0.6) litre min(-1) m(-2), GEDVI increased from 605 (110) to 640 (94) litre min(-1) m(-2), and LVEDAI increased from 9.2 (3.7) to 11.2 (4.1) cm(2) m(-2). All these changes were significant. In contrast, stroke volume variation (SVV) decreased from 10 (3) to 6 (2)% and pulse pressure variation (PPV) decreased from 11 (3) to 5 (3)%. Before thoracotomy, SVV and PPV significantly correlated with GEDVI (both P<0.01). When the chest was open, similar significant correlations of SVV (P<0.001) and PPV (P<0.01) were found with GEDVI. CONCLUSION: Thoracotomy increases cardiac filling and preload. Further, thoracotomy reduces the effect of mechanical ventilation on left ventricular stroke volume. However, also under open chest conditions, SVV and PPV are preload-dependent.

Surgical treatment of permanent atrial fibrillation using microwave energy ablation: a prospective randomized clinical trial.

OBJECTIVE: Radiofrequency or the use of microwave energy in combination with atrial size reduction during open heart surgery have been reported to be effective in up to 75% in the treatment of permanent atrial fibrillation. However, no data from prospective randomized trials using microwave energy are available. METHODS: Forty-three patients with permanent atrial fibrillation undergoing open-heart surgery were randomly stratified into treatment group receiving microwave ablation and atrial size reduction (n=24) or control group (n=19). Patients in either group were treated with amiodarone or sotalol for 3 months if sinus rhythm or any atrioventricular rhythm was successfully restored. Follow-up time points were at 3, 6 and 12 month after surgery. RESULTS: In the treatment group 22 out of 24 patients (91,7%) were successfully converted to sinus rhythm by using intraoperative microwave ablation therapy whereas only six out of 19 (31.5%) patients converted to sinus rhythm directly after surgery. At 12-month follow-up there were still a significantly higher percentage of patients in the treatment group free from atrial fibrillation when compared to control (80 vs. 33.3%, P=0.036). CONCLUSION: The preliminary data from this first prospectively randomized trial indicate that microwave ablation combined with atrial size reduction is a safe and highly efficient treatment in permanent atrial fibrillation.

Trendelenburg positioning after cardiac surgery: effects on intrathoracic blood volume index and cardiac performance.

BACKGROUND AND OBJECTIVE: The efficacy of the Trendelenburg position, a common first step to treat suspected hypovolaemia, remains controversial. We evaluated its haemodynamic effects on cardiac preload and performance in patients after cardiac surgery. METHODS: Twelve patients undergoing mechanical ventilation of the lungs who demonstrated left ventricular 'kissing papillary muscles' by transoesophageal echocardiography, thus suggesting hypovolaemia, were positioned 30 degrees head down for 15 min immediately after cardiac surgery. Cardiac output by thermodilution, central venous pressure, pulmonary artery occlusion pressure, left ventricular end-diastolic area by transoesophageal echocardiography and intrathoracic blood volume by thermo- and dye dilution were determined before, during and after this Trendelenburg manoeuvre. RESULTS: Trendelenburg's manoeuvre was associated with increases in central venous pressure (9 +/- 2 to 12 +/- 3 mmHg) and pulmonary artery occlusion pressure (8 +/- 2 to 11 +/- 3 mmHg). The intrathoracic blood volume index increased slightly (dye dilution from 836 +/- 129 to 872 +/- 112 mL m(-2); thermodilution from 823 +/- 129 to 850 +/- 131 mL m(-2)) as did the left ventricular end-diastolic area index (7.5 +/- 2.1 to 8.1 +/- 1.7 cm2 m(-2)), whereas mean arterial pressure and the cardiac index did not change significantly. After supine repositioning, the cardiac index decreased significantly below baseline (3.0 +/- 0.6 versus 3.5 +/- 0.8 L min(-1) m(-2)) as did mean arterial pressure (76 +/- 12 versus 85 +/- 11 mmHg), central venous pressure (8 +/- 2 mmHg) and pulmonary artery occlusion pressure (6 +/- 4 mmHg). The intrathoracic blood volume index and left ventricular end-diastolic area index did not differ significantly from baseline. CONCLUSIONS: Trendelenburg's manoeuvre caused only a slight increase of preload volume, despite marked increases in cardiac-filling pressures, without significantly improving cardiac performance.

Optimizing fluid therapy in mechanically ventilated patients after cardiac surgery by on-line monitoring of left ventricular stroke volume variations. Comparison with aortic systolic pressure variations.

BACKGROUND: Mechanical ventilation causes changes in left ventricular preload leading to distinct variations in left ventricular stroke volume and systolic arterial pressure. Retrospective off-line quantification of systolic arterial pressure variations (SPV) has been validated as a sensitive method of predicting left ventricular response to volume administration. We report the real-time measurement of left ventricular stroke volume variations (SVV) by continuous arterial pulse contour analysis and compare it with off-line measurements of SPV in patients after cardiac surgery. METHODS: SVV and SPV were determined before and after volume loading with colloids in 20 mechanically ventilated patients. RESULTS: SVV and SPV decreased significantly after volume loading and were correlated (r=0.89; P<0.001). Changes in SVV and changes in SPV as a result of volume loading were also significantly correlated (r=0.85; P<0.005). Changes in SVV correlated significantly with changes in stroke volume index (SVI) (r=0.67; P<0.005) as did changes in SPV (r=0.56; P<0.05). SVV determined before volume loading correlated significantly with changes in SVI (R=0.67; P <0.005). Using receiver operating characteristics curves, the area under the curve was statistically greater for SVV (0.824; 95% confidence interval: [CI] 0.64-1.0) and SPV (0.81; CI: 0.62-1.0) than for central venous pressure (0.451; CI: 0.17-0.74). CONCLUSIONS: Monitoring of SVV enables real-time prediction and monitoring of the left ventricular response to preload enhancement in patients after cardiac surgery and is helpful for guiding volume therapy.

Continuous cardiac output measurements do not agree with conventional bolus thermodilution cardiac output determination.

PURPOSE: To evaluate the performance of two different continuous cardiac output monitoring systems based on the thermodilution principle in critically ill patients. METHODS: Nineteen cardiac surgical patients were randomly assigned to continuous cardiac output monitoring using one of the two systems under study (group I, IntelliCath(TM) catheter, n=9; group II, Opti-Q(TM) catheter, n=10). Each patient was studied over a period of three hours. Conventional bolus thermodilution cardiac output measurements were carried out every 15 min leading to 13 measurements in each patient. The continuous cardiac output values were compared with the bolus thermodilution measurements. Bias (mean difference between continuous and bolus thermodilution) and precision (SD of differences) were calculated as a measure of agreement between the respective continuous method and conventional bolus thermodilution. RESULTS: The range of measured cardiac outputs was 3.8-15.4 L*min(-1) (IntelliCath(TM)) and 3.5-8.3 L*min(-1) (OptiQ(TM)). Bias and precision was 0.06 +/- 0.76 L*min(-1) (IntelliCath(TM)) and -0.04 +/- 0.74 L*min(-1) (OptiQ(TM)), respectively. There was no difference in bias between the two systems (P=0.38). +/- 2 SD of the differences (i.e., 95% of the differences) did not fall within the predetermined limits of agreement of +/- 0.5 L*min(-1). CONCLUSIONS: There was no difference between the two systems regarding the agreement with conventional bolus thermodilution as the standard. A discrepancy between bolus and continuous thermodilution cardiac output measurement techniques above the clinically acceptable limits suggest that they are not interchangeable.

[Perioperative antiarrhythmic drug management]. / Perioperative antiarrhythmische Therapie.

Perioperative arrhythmias are common. In 2.5 % they result in a severe adverse outcome. This review discusses the normal physiology of the myocardial conduction system and the etiology and pathophysiology of the most common perioperative dysrhythmias. Subsequently some important antiarrhythmic drugs are described and treatment plans for the most frequent dysrhythmias are presented.