Levosimendan in intensive care and emergency medicine: literature update and expert recommendations for optimal efficacy and safety.

The inodilator levosimendan, in clinical use for over two decades, has been the subject of extensive clinical and experimental evaluation in various clinical settings beyond its principal indication in the management of acutely decompensated chronic heart failure. Critical care and emergency medicine applications for levosimendan have included postoperative settings, septic shock, and cardiogenic shock. As the experience in these areas continues to expand, an international task force of experts from 15 countries (Austria, Belgium, China, Croatia, Finland, France, Germany, Greece, Hungary, Italy, the Netherlands, Spain, Sweden, Switzerland, and the USA) reviewed and appraised the latest additions to the database of levosimendan use in critical care, considering all the clinical studies, meta-analyses, and guidelines published from September 2019 to November 2021. Overall, the authors of this opinion paper give levosimendan a "should be considered" recommendation in critical care and emergency medicine settings, with different levels of evidence in postoperative settings, septic shock, weaning from mechanical ventilation, weaning from veno-arterial extracorporeal membrane oxygenation, cardiogenic shock, and Takotsubo syndrome, in all cases when an inodilator is needed to restore acute severely reduced left or right ventricular ejection fraction and overall haemodynamic balance, and also in the presence of renal dysfunction/failure.

[Hemodynamic target variables in the intensive care unit]. / Hämodynamische Zielvariablen auf der Intensivstation.

Despite broad availability, extended hemodynamic monitoring is used in practice only in the minority of critical care patients. Pathophysiological reasoning suggests that systemic perfusion pressure (and thereby arterial as well as central venous pressure), cardiac stroke volume, and the systemic oxygen balance are key variables in maintaining adequate organ perfusion. In line with these assumptions, several studies support that a goal-directed optimization of these hemodynamic variables leads to a reduction in morbidity and mortality. The appropriate monitoring modality should be selected following echocardiographic evaluation of biventricular function. Ideally, high-risk patients with limited right ventricular function should be monitored with a pulmonary artery catheter. In patients with preserved right ventricular function, transpulmonary thermodilution with special consideration of extravascular lung water seems to be sufficient to guide hemodynamic therapy.

[S3 guidelines on intensive medical care of cardiac surgery patients : Hemodynamic monitoring and cardiovascular system-an update]. / S3-Leitlinie zur intensivmedizinischen Versorgung herzchirurgischer Patienten : Hämodynamisches Monitoring und Herz-Kreislauf ­ ein Update.

An update of the S3- guidelines for treatment of cardiac surgery patients in the intensive care unit, hemodynamic monitoring and cardiovascular system was published by the Association of Scientific Medical Societies in Germany (AWMF) in January 2018. This publication updates the guidelines from 2006 and 2011. The guidelines include nine sections that in addition to different methods of hemodynamic monitoring also reviews the topic of volume therapy as well as vasoactive and inotropic drugs. Furthermore, the guidelines also define the goals for cardiovascular treatment. This article describes the most important innovations of these comprehensive guidelines.

Positive end-expiratory pressure titration at bedside using electrical impedance tomography in post-operative cardiac surgery patients.

BACKGROUND: Post-operative positive end-expiratory pressure (PEEP) setting to minimize the risk of ventilator-associated lung injury is still controversial. Assessment of regional ventilation distribution by electrical impedance tomography (EIT) might be superior as compared with global parameters. The aim of this prospective observational study was to compare global dynamic compliance (CRS ) with different EIT indices during a short clinical applicable descending PEEP trial. METHODS: Twenty mechanically ventilated patients after elective cardiac surgery received a standard recruitment manoeuvre (RM) following descending PEEP trial in steps of 2 cmH2 O from PEEP 14 cmH2 O to 6 cmH2 O. During baseline and all PEEP steps, CRS was assessed and regional ventilation distribution was measured by means of EIT. The individual 'best' PEEP values for the derived EIT indices and CRS were calculated and compared. RESULTS: The descending PEEP trial lasted less than 10 min. CRS increased after the RM and showed a maximum value at PEEP 8 cmH2 O. Ventilation distribution shifted more to dependent lung regions after RM and back to more non-dependent regions during the PEEP trial. Individual 'best' PEEP by CRS showed significantly lower values than 'best' PEEP by ventilation distribution measured with EIT indices. CONCLUSION: During a short descending PEEP trial at bedside, EIT is capable of following the status of regional ventilation distribution in ventilated patients. The 'best' PEEP value identified by individual maximum CRS was lower than optimal PEEP levels as determined by means of EIT indices. EIT could help setting PEEP in post-operative ventilated patients.

Preoperative and perioperative use of levosimendan in cardiac surgery: European expert opinion.

In cardiac surgery, postoperative low cardiac output has been shown to correlate with increased rates of organ failure and mortality. Catecholamines have been the standard therapy for many years, although they carry substantial risk for adverse cardiac and systemic effects, and have been reported to be associated with increased mortality. On the other hand, the calcium sensitiser and potassium channel opener levosimendan has been shown to improve cardiac function with no imbalance in oxygen consumption, and to have protective effects in other organs. Numerous clinical trials have indicated favourable cardiac and non-cardiac effects of preoperative and perioperative administration of levosimendan. A panel of 27 experts from 18 countries has now reviewed the literature on the use of levosimendan in on-pump and off-pump coronary artery bypass grafting and in heart valve surgery. This panel discussed the published evidence in these various settings, and agreed to vote on a set of questions related to the cardioprotective effects of levosimendan when administered preoperatively, with the purpose of reaching a consensus on which patients could benefit from the preoperative use of levosimendan and in which kind of procedures, and at which doses and timing should levosimendan be administered. Here, we present a systematic review of the literature to report on the completed and ongoing studies on levosimendan, including the newly commenced LEVO-CTS phase III study (NCT02025621), and on the consensus reached on the recommendations proposed for the use of preoperative levosimendan.

[Cerebral oximetry: clinical importance for cardiac surgery patients]. / Zerebrale Oxymetrie : Klinischer Stellenwert bei kardiochirurgischen Patienten.

The determination of cerebral oxygen saturation (S(c)O(2)) by means of near-infrared spectroscopy allows non-invasive assessment of the cerebral oxygen delivery and demand ratio in the frontal cortex region. Studies in cardiac as well as non-cardiac patients have shown that maintaining S(c)O(2) in the preoperative range reduces the incidence of postoperative cognitive dysfunction and general morbidity; however, S(c)O(2) is not only reflective of cerebral but also of systemic oxygen balance, is inversely related to cardiopulmonary function and has prognostic relevance in cardiac surgery patients. This suggests that cerebral oximetry is not only useful for neurological but also for hemodynamic monitoring and preoperative risk stratification of cardiac surgery patients.

Relationship between mixed venous oxygen saturation and regional cerebral oxygenation in awake, spontaneously breathing cardiac surgery patients.

BACKGROUND: In search of a non-invasive method for estimation of the oxygen balance this prospective study evaluates the relationship between regional cerebral oxygenation (rScO2) and mixed venous oxygen saturation in awake, spontaneously breathing patients after cardiac surgery. METHODS: After approval by the local ethical committee and written informed consent, 26 consecutive patients after cardiac surgery with cardiopulmonary bypass were enrolled. On intensive care unit (ICU), several hours after extubation, patients were connected to the INVOS 5100 cerebral monitor. Blood samples for determination of mixed venous oxygen saturation (SvO2) and central venous oxygen saturation (ScvO2) were drawn successively and rScO2 was documented. Patients were studied twice, breathing room air for the first measurement cycle, and breathing 4L/min supplemental oxygen by face mask, achieving a transcutaneous oxygen saturation above 98%, for a second measurement. RESULTS: Hemodynamic variables, hemoglobin and arterial carbon dioxide tension (PaCO2) remained stable between the two measurement cycles. Without oxygen, SvO2 and rScO2 showed a bias of -2.0%, limits of agreement (LOA) of -15.0 to 10.9% and a percentage error (PE) of 20.3%. SvO2 and ScvO2 showed a bias of -3.9%, LOA of -13.9 to 6.2% and PE 15.7%. With oxygen, the bias between SvO2 and rScO2 was -2.5%, LOA -14.2 to 9.2%, PE 17.2%. Between SvO2 and ScvO2 the bias was -4.1%, LOA -10.2 to 2.1%, PE 9.0%. CONCLUSION: The rScO2 measured by near infrared spectroscopy was sufficiently representing mixed venous oxygen saturation in awake, hemodynamically stable, spontaneously breathing patients after cardiac surgery. The agreement was comparable to the agreement between SvO2 and ScvO2 with smaller differences in the lower ranges of SvO2.

Cognitive function after sevoflurane- vs propofol-based anaesthesia for on-pump cardiac surgery: a randomized controlled trial.

BACKGROUND: Cognitive dysfunction is a frequent complication after cardiac surgery and has been found to be associated with decreases in cerebral oxygen saturation measured with near-infrared spectroscopy. Sevoflurane has neuroprotective properties in vitro and in animal models. This study was designed to determine cognitive and clinical outcomes after sevoflurane- compared with propofol-based anaesthesia for on-pump cardiac surgery and the impact of decreases in under different anaesthesia regimens. METHODS: One hundred and twenty-eight patients were randomly assigned to either i.v. anaesthesia with propofol- (PROP) or sevoflurane-based anaesthesia (SEVO). An intraoperative was defined as desaturation. The Abbreviated Mental Test, Stroop Test, Trail-Making Test, Word Lists, and mood-assessment tests were performed before, 2, 4, and 6 days after cardiac surgery. Markers of general outcome were obtained. RESULTS: The analysis groups had differences in baseline cognitive performance. Analysis of variance for repeated measures (incorporating covariance of baseline scores) showed that in three of four cognitive tests, patients with cerebral desaturation showed worse results than patients without desaturation. Patients assigned to sevoflurane-based anaesthesia showed better results in all cognitive tests than patients after propofol. Interactions between the anaesthetic regimen and desaturation were found in all four cognitive tests. There were no differences in markers of organ dysfunction or general clinical outcome. CONCLUSIONS: Patients with impaired cognitive performance before operation may be at particular risk for intraoperative cerebral insult. A sevoflurane-based anaesthesia was associated with better short-term postoperative cognitive performance than propofol.

Lack of agreement between pulmonary arterial thermodilution cardiac output and the pressure recording analytical method in postoperative cardiac surgery patients.

BACKGROUND: Pulse-contour analysis method (PCM) cardiac output (CO) monitors are increasingly used for CO monitoring during anaesthesia and in the critically ill. Very recently, several systems have been introduced that do not need calibration; among them the pressure recording analytical method (PRAM). Sparse data comparing the accuracy of the PRAM-CO with conventional thermodilution CO (ThD-CO) in cardiac surgery patients are available. METHODS: In this prospective comparison study, paired CO measurements with a pulmonary artery catheter and a PRAM monitoring set were obtained 20-30 min apart (t1, t2) in 23 extubated patients on the first postoperative day after cardiac surgery. Data were analysed by the Bland-Altman method. RESULTS: A total of 46 paired CO measurements (23 for each interval) were collected. The Bland-Altman analysis showed a mean difference (bias) of 0.0 litre min(-1) and limits of agreement (1.96 sd) of 4.53 to -4.54 litre min(-1) [upper 95% confidence interval (CI), 3.26-5.80; lower 95% CI, -5.8 to -3.27]. The percentage error (1.96 sd/mean of the reference method) was 87%. CONCLUSIONS: These results question the reliability of the PRAM technology for the determination of CO in postoperative cardiac surgery patients.

S3 guidelines for intensive care in cardiac surgery patients: hemodynamic monitoring and cardiocirculary system.

Hemodynamic monitoring and adequate volume-therapy, as well as the treatment with positive inotropic drugs and vasopressors are the basic principles of the postoperative intensive care treatment of patient after cardiothoracic surgery. The goal of these S3 guidelines is to evaluate the recommendations in regard to evidence based medicine and to define therapy goals for monitoring and therapy. In context with the clinical situation the evaluation of the different hemodynamic parameters allows the development of a therapeutic concept and the definition of goal criteria to evaluate the effect of treatment. Up to now there are only guidelines for subareas of postoperative treatment of cardiothoracic surgical patients, like the use of a pulmonary artery catheter or the transesophageal echocardiography. The German Society for Thoracic and Cardiovascular Surgery (Deutsche Gesellschaft für Thorax-, Herz- und Gefässchirurgie, DGTHG) and the German Society for Anaesthesiology and Intensive Care Medicine (Deutsche Gesellschaft für Anästhesiologie und lntensivmedizin, DGAI) made an approach to ensure and improve the quality of the postoperative intensive care medicine after cardiothoracic surgery by the development of S3 consensus-based treatment guidelines. Goal of this guideline is to assess the available monitoring methods with regard to indication, procedures, predication, limits, contraindications and risks for use. The differentiated therapy of volume-replacement, positive inotropic support and vasoactive drugs, the therapy with vasodilatators, inodilatators and calcium sensitizers and the use of intra-aortic balloon pumps will also be addressed. The guideline has been developed following the recommendations for the development of guidelines by the Association of the Scientific Medical Societies in Germany (AWMF). The presented key messages of the guidelines were approved after two consensus meetings under the moderation of the Association of the Scientific Medical Societies in Germany (AWMF).

[Anti-inflammatory effects of pentoxifylline: importance in cardiac surgery]. / Antiinflammatorische Effekte von Pentoxifyllin : Bedeutung bei herzchirurgischen Eingriffen.

Initially introduced as a rheologic agent for use in intermittent claudication due to peripheral artery disease and in ischemic cerebrovascular disease, the methylxanthine derivative pentoxifylline (PTX) has been shown to possess several anti-inflammatory properties which make this drug an interesting immunomodulating adjunct for the management of patients undergoing cardiac surgery. As an unspecific phosphodiesterase inhibitor PTX ameliorates the inflammatory response following a septic stimulus and blunts organ dysfunction after ischemia-reperfusion injury. Apart from this several small clinical studies have shown that the use of PTX may blunt the inflammatory response induced by cardiac surgery using a cardiopulmonary bypass. Additionally it has been shown that the perioperative application of this drug may improve postoperative function of organs at risk, such as the kidneys and liver.

Goal-directed hemodynamic optimization in high-risk cardiac surgery patients: a tale from the past or a future obligation?

The present manuscript summarizes the available evidence on outcome-related hemodynamic variables and ''goal-directed hemodynamic optimization'' strategies in patients undergoing cardiac surgery.

Respiratory protection during high-fidelity simulated resuscitation of casualties contaminated with chemical warfare agents.

Emergency room personnel are threatened by secondary poisoning when treating victims affected by chemical warfare agents. Therefore, resuscitation skills practised with respiratory protection equipment in place require evaluation. We investigated the influence of wearing air-purifying respirators on the simulated resuscitation of chemical warfare agent casualties. We studied 22 anaesthetic trainees in a simulated resuscitation scenario requiring five set tasks, either unprotected, wearing a binocular visor respirator or a panoramic visor respirator in a randomised, crossover study. Treatment times did not differ between the three groups, with mean (SD) times to complete the tasks being 122 (8) s without a mask, 126 (7) s when wearing the panoramic visor mask and 129 (8) s when wearing the binocular respirator mask. All anaesthetists preferred the panoramic visor in terms of visual orientation but 88% of them rated the binocular mask as being more comfortable. Modern respirators have a negligible effect on simulated resuscitation scenarios for victims affected by chemical warfare agents. Panoramic visor respirators allow better visual orientation for anaesthetists during simulated resuscitation.

[Guidelines for intensive care in cardiac surgery patients: haemodynamic monitoring and cardio-circulatory treatment guidelines of the German Society for Thoracic and Cardiovascular Surgery and the German Society of Anaesthesiology and Intensive Care Medicine]. / Die intensivmedizinische Versorgung herzchirurgischer Patienten: Hämodynamisches Monitoring und Herz-Kreislauf-Therapie S3-Leitlinie der Deutschen Gesellschaft für Thorax-, Herz- und Gefässchirurgie (DGTHG) und der Deutschen Gesellschaft für Anästhesiologie und Intensivmedizin (DGAI).

Hemodynamic monitoring and adequate volume-therapy, as well as the treatment with positive inotropic drugs and vasopressors, are the basic principles of the postoperative intensive care treatment of patient after cardiothoracic surgery. The goal of these S3 guidelines is to evaluate the recommendations in regard to evidence based medicine and to define therapy goals for monitoring and therapy. In context with the clinical situation the evaluation of the different hemodynamic parameters allows the development of a therapeutic concept and the definition of goal criteria to evaluate the effect of treatment. Up to now there are only guidelines for subareas of postoperative treatment of cardiothoracic surgical patients, like the use of a pulmonary artery catheter or the transesophageal echocardiography. The German Society for Thoracic and Cardiovascular Surgery and the German Society for Anaesthesiology and Intensive Care Medicine made an approach to ensure and improve the quality of the postoperative intensive care medicine after cardiothoracic surgery by the development of S3 consensus-based treatment guidelines. Goal of this guideline is to assess available monitoring methods and their risks as well as the differentiated therapy of volume-replacement, positive inotropic support and vasoactive drugs, the therapy with vasodilators, inodilators and calcium-sensitizers and the use of intra-aortic balloon pumps. The guideline has been developed according to the recommendations for the development of guidelines by the Association of the Scientific Medical Societies in Germany (AWMF). The presented key messages of the guidelines were approved after two consensus meetings under the moderation of the Association of the Scientific Medical Societies in Germany (AWMF).

Focussing cellular function. Metabolic monitoring in perioperative and Intensive Care Medicine.

In the clinical field microdialysis today is a routine technique for monitoring the chemistry of tissues and organs in physiological and pharmacological research on animals. In more than 10.000 papers on microdialysis research it is used to uncover physiological mechanisms and the influence of drugs in almost every organ of the body. Since the first papers describing microdialysis in the human brain microdialysis has become a technique for routine monitoring of energy metabolism especially in neurointensive care. This paper gives an account of the microdialysis technique describing its practical use and interpretation in monitoring energy metabolism and ischemia in different organs with respect to the field of perioperative and intensive care medicine. This article gives an overview over current results of clinical studies using microdialysis in critical care medicine and tries to focus on possible indications for clinical biochemical monitoring. However, despite numerous publications available microdialysis has not been shown to improve outcome of the patients yet.