Key summary of German national treatment guidance for hospitalized COVID-19 patients : Key pharmacologic recommendations from a national German living guideline using an Evidence to Decision Framework (last updated 17.05.2021).

PURPOSE: This executive summary of a national living guideline aims to provide rapid evidence based recommendations on the role of drug interventions in the treatment of hospitalized patients with COVID-19. METHODS: The guideline makes use of a systematic assessment and decision process using an evidence to decision framework (GRADE) as recommended standard WHO (2021). Recommendations are consented by an interdisciplinary panel. Evidence analysis and interpretation is supported by the CEOsys project providing extensive literature searches and living (meta-) analyses. For this executive summary, selected key recommendations on drug therapy are presented including the quality of the evidence and rationale for the level of recommendation. RESULTS: The guideline contains 11 key recommendations for COVID-19 drug therapy, eight of which are based on systematic review and/or meta-analysis, while three recommendations represent consensus expert opinion. Based on current evidence, the panel makes strong recommendations for corticosteroids (WHO scale 5-9) and prophylactic anticoagulation (all hospitalized patients with COVID-19) as standard of care. Intensified anticoagulation may be considered for patients with additional risk factors for venous thromboembolisms (VTE) and a low bleeding risk. The IL-6 antagonist tocilizumab may be added in case of high supplemental oxygen requirement and progressive disease (WHO scale 5-6). Treatment with nMABs may be considered for selected inpatients with an early SARS-CoV-2 infection that are not hospitalized for COVID-19. Convalescent plasma, azithromycin, ivermectin or vitamin D3 should not be used in COVID-19 routine care. CONCLUSION: For COVID-19 drug therapy, there are several options that are sufficiently supported by evidence. The living guidance will be updated as new evidence emerges.

General Anesthesia Leads to Underestimation of Regurgitation Severity in Patients With Secondary Mitral Regurgitation Undergoing Transcatheter Mitral Valve Repair.

OBJECTIVES: To evaluate the effect of general anesthesia (GA) on severity of mitral regurgitation (MR) in patients undergoing transcatheter mitral valve repair (TMVR). DESIGN: Retrospective cohort study. SETTING: Tertiary care university hospital. PARTICIPANTS: Fifty consecutive patients with symptomatic severe MR and extremely high surgical risk. INTERVENTION: TMVR under GA. MEASUREMENTS AND RESULTS: Transesophageal echocardiography was performed during the preprocedural workup under conscious sedation and during TMVR under GA. After the parameters of MR were assessed, color-flow jet area (CJA), vena contracta (VC), effective regurgitant orifice area (EROA), regurgitant volume (RVOL), three-dimensional (3D) vena contracta area (VCA), and severity of MR were compared between the two examinations. In patients with primary MR (n = 11), there were no significant differences in CJA, VC, EROA, RVOL, or 3D-VCA between pre- and intraprocedural transesophageal echocardiography. In patients with secondary MR (n = 39), GA led to significant decreases of CJA (10 ± 7 v 7 ± 3 cm², p < 0.001), VC (5.5 ± 1.6 v 4.7 ± 1.5 mm, p = 0.002), EROA (30 ± 11 v 24 ± 10 mm², p < 0.001), and RVOL (47 ± 17 v 34 ± 13 mL/beat, p < 0.001). Consequently, GA led to a downgrade of regurgitation severity classification in 44% of patients when assessed by two-dimensional analysis. When evaluated by 3D analysis, GA also led to a significant but less extensive decrease of MR (3D-VCA: 66 ± 27 v 60 ± 29 mm², p = 0.002), and subsequent downgrade of MR classification in 20% of patients. CONCLUSIONS: GA underestimates regurgitation severity in patients with secondary, but not primary MR, undergoing TMVR. This effect must be considered when evaluating the immediate result of the procedure.

Increase of urinary TIMP-2 and IGFBP7 as potential predictor of acute kidney injury requiring renal replacement therapy and patients' outcome following complex endovascular and open thoracic abdominal aortic aneurysm surgery - a prospective observational study.

Background: Acute kidney injury (AKI) as complication after open and endovascular repair of thoracoabdominal aortic aneurysm (TAAA) is one major predictor of mortality and postoperative complications. We evaluated tissue inhibitor of metalloproteinase 2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) as combined early biomarker for AKI detection and predictor of patients' outcome. Patients and methods: Between 2014 and 2015, 52 patients have been enrolled in this observational study, of whom 29 (55.8%) underwent elective open repair and 23 (44.2%) endovascular repair. TIMP2 × IGFBP7 were measured until 48 hours after admission on intensive-care unit (ICU) and were analyzed regarding their predictive ability for AKI (defined according to the KDIGO criteria) requiring temporary renal replacement therapy (RRT) and 90-day mortality using ROC curves. Results: Mean patient age was 64.5 years (Min: 43, Max: 85), endovascular treated patients were older (p <0.0001). 40.4% (n = 21) developed AKI, and 21.2% (n = 11) required renal replacement therapy. In-hospital and total mortality rates were 7.7% (n = 4) and 9.6% (n = 5), respectively. At no time a significant difference in TIMP2 × IGFB7 levels between patients undergoing open or endovascular surgery was observed. The predictive quality of the TIMP2 × IGFBP7 value on ICU admission was sound regarding AKI requiring temporary renal replacement therapy (sensitivity: 55.56% [38.1-72.1%], specificity: 90.91% [58.7-99.8%] with an area under the curve [AUC]: 0.694 [0.543-0.820]). Mean follow-up was 13.2 months (Min: 2, Max: 20), regarding the 90-day mortality, the predictive property of the TIMP2 × IGFBP7 value was not sufficient (sensitivity: 80% [28.4-99.5%], specificity: 52.38% [36.4-68%], and AUC: 0.607 [0.454-0.746]). Conclusions: TIMP2 × IGFBP7 level measured 6-12 hrs postoperatively may be useful as an early detectable biomarker for AKI requiring temporary renal replacement therapy. It seems not suited to predict patients' outcome following complex thoracoabdominal aortic surgery, regardless if performed by open or endovascular repair.

[Recommendations for emergency management of patients with permanent mechanical circulatory support : Consensus statement of DGTHG, DIVI, DGIIN, DGAI, DGINA, DGfK and DGK]. / Empfehlungen zum Notfallmanagement von Patienten mit permanenten Herzunterstützungssystemen : Konsensuspapier der DGTHG, DIVI, DGIIN, DGAI, DGINA, DGfK und DGK.

The prevalence of patients living with long-term mechanical circulatory support (MCS) is rapidly increasing due to improved technology, improved survival, reduced adverse event profiles, greater reliability and mechanical durability, and limited numbers of organs available for donation. Patients with long-term MCS are very likely to require emergency medical support due to MCS-associated complications (e.g., right heart failure, left ventricular assist device malfunction, hemorrhage and pump thrombosis) but also due to non-MCS-associated conditions. Because of the unique characteristics of mechanical support, management of these patients is complicated and there is very little literature on emergency care for these patients. The purpose of this national scientific statement is to present consensus-based recommendations for the initial evaluation and resuscitation of adult patients with long-term MCS.

Tyrosine kinase inhibitors relax pulmonary arteries in human and murine precision-cut lung slices.

BACKGROUND: Tyrosine kinase inhibitors (TKIs) inhibit the platelet derived growth factor receptor (PDGFR) and gain increasing significance in the therapy of proliferative diseases, e.g. pulmonary arterial hypertension (PAH). Moreover, TKIs relax pulmonary vessels of rats and guinea pigs. So far, it is unknown, whether TKIs exert relaxation in human and murine pulmonary vessels. Thus, we studied the effects of TKIs and the PDGFR-agonist PDGF-BB in precision-cut lung slices (PCLS) from both species. METHODS: The vascular effects of imatinib (mice/human) or nilotinib (human) were studied in Endothelin-1 (ET-1) pre-constricted pulmonary arteries (PAs) or veins (PVs) by videomicroscopy. Baseline initial vessel area (IVA) was defined as 100%. With regard to TKI-induced relaxation, K+-channel activation was studied in human PAs (PCLS) and imatinib/nilotinib-related changes of cAMP and cGMP were analysed in human PAs/PVs (ELISA). Finally, the contractile potency of PDGF-BB was explored in PCLS (mice/human). RESULTS: Murine PCLS: Imatinib (10 µM) relaxed ET-1-pre-constricted PAs to 167% of IVA. Vice versa, 100 nM PDGF-BB contracted PAs to 60% of IVA and pre-treatment with imatinib or amlodipine prevented PDGF-BB-induced contraction. Murine PVs reacted only slightly to imatinib or PDGF-BB. Human PCLS: 100 µM imatinib or nilotinib relaxed ET-1-pre-constricted PAs to 166% or 145% of IVA, respectively, due to the activation of KATP-, BKCa2+- or Kv-channels. In PVs, imatinib exerted only slight relaxation and nilotinib had no effect. Imatinib and nilotinib increased cAMP in human PAs, but not in PVs. In addition, PDGF-BB contracted human PAs/PVs, which was prevented by imatinib. CONCLUSIONS: TKIs relax pre-constricted PAs/PVs from both, mice and humans. In human PAs, the activation of K+-channels and the generation of cAMP are relevant for TKI-induced relaxation. Vice versa, PDGF-BB contracts PAs/PVs (human/mice) due to PDGFR. In murine PAs, PDGF-BB-induced contraction depends on intracellular calcium. So, PDGFR regulates the tone of PAs/PVs. Since TKIs combine relaxant and antiproliferative effects, they may be promising in therapy of PAH.

Cardiac stress after electroconvulsive therapy and spontaneous generalized convulsive seizures: A prospective echocardiographic and blood biomarker study.

AIM: Knowledge about cardiac stress related to seizures in electroconvulsive therapy (ECT) and spontaneously occurring generalized convulsive seizures (GCS) is limited. The aim of the present study was to analyze cardiac function and circulating markers of cardiac stress in the early postictal period after ECT and GCS. METHODS: Patients undergoing ECT in the Department of Psychiatry, Psychotherapy and Psychosomatics and patients undergoing diagnostic video-EEG monitoring (VEM) in the Department of Neurology were prospectively enrolled between November 2017 and November 2018. Cardiac function was examined twice using transthoracic echocardiography within 60 min and >4 h after ECT or GCS. Established blood markers (troponin T high-sensitive, N-terminal pro brain natriuretic peptide) of cardiac stress or injury were collected within 30 min, 4 to 6 h, and 24 h after ECT or GCS. In the ECT group, the troponin T values were also correlated with periprocedural heart rate and blood pressure values. Because of organizational or technical reasons, the measurement was not performed in all patients. RESULTS: Twenty patients undergoing ECT and 6 patients with epilepsy with a GCS during VEM were included. Postictal echocardiography showed no wall motion disorders and no change in left ventricular and right ventricular functions. Four of 17 patients displayed a transient increase in high-sensitive cardiac troponin T 4-6 h after the seizure (3 patients with ECT-induced seizure). None of these 4 patients had signs of an acute cardiac event, and periprocedural blood pressure or heart rate peaks during ECT did not significantly differ in patients with and without troponin T elevation. CONCLUSIONS: Signs of mild cardiac stress can occur in some patients following ECT or GCS without clinical complications, probably related to excessive catecholamine release during the seizure.

Macrophage Migration Inhibitory Factor Predicts Outcome in Complex Aortic Surgery.

The perioperative inflammatory response is associated with outcome after complex aortic repair. Macrophage migration inhibitory factor (MIF) shows protective effects in ischemia-reperfusion (IR), but also adverse pro-inflammatory effects in acute inflammation, potentially leading to adverse outcome, which should be investigated in this trial. This prospective study enrolled 52 patients, of whom 29 (55.7%) underwent open repair (OR) and 23 (44.3%) underwent endovascular repair (ER) between 2014 and 2015. MIF serum levels were measured until 72 h post-operatively. We used linear mixed models and ROC analysis to analyze the MIF time-course and its diagnostic ability. Compared to ER, OR induced higher MIF release perioperatively; at 12 h after ICU admission, MIF levels were similar between groups. MIF course was significantly influenced by baseline MIF level (P = 0.0016) and acute physiology and chronic health evaluation (APACHE) II score (P = 0.0005). MIF level at 24 h after ICU admission showed good diagnostic value regarding patient survival [sensitivity, 80.0% (28.4-99.5%); specificity, 51.2% (35.1-67.1%); AUC, 0.688 (0.534-0.816)] and discharge modality [sensitivity, 87.5% (47.3-99.7%); specificity, 73.7% (56.9-86.6%), AUC, 0.789 (0.644-0.896)]. Increased perioperative MIF-levels are related to an increased risk of adverse outcome in complex aortic surgery and may represent a biomarker for risk stratification in complex aortic surgery.

Xenon triggers pro-inflammatory effects and suppresses the anti-inflammatory response compared to sevoflurane in patients undergoing cardiac surgery.

INTRODUCTION: Cardiac surgery encompasses various stimuli that trigger pro-inflammatory mediators, reactive oxygen species and mobilization of leucocytes. The aim of this study was to evaluate the effect of xenon on the inflammatory response during cardiac surgery. METHODS: This randomized trial enrolled 30 patients who underwent elective on-pump coronary-artery bypass grafting in balanced anaesthesia of either xenon or sevoflurane. For this secondary analysis, blood samples were drawn prior to the operation, intra-operatively and on the first post-operative day to measure the pro- and anti-inflammatory cytokines interleukin-6 (IL-6), interleukin-8/C-X-C motif ligand 8 (IL-8/CXCL8), and interleukin-10 (IL-10). Chemokines such as C-X-C motif ligand 12/ stromal cell-derived factor-1α (CXCL12/SDF-1α) and macrophage migration inhibitory factor (MIF) were measured to characterize xenon's perioperative inflammatory profile and its impact on migration of peripheral blood mononuclear cells (PBMC). RESULTS: Xenon enhanced the postoperative increase of IL-6 compared to sevoflurane (Xenon: 90.7 versus sevoflurane: 33.7 pg/ml; p = 0.035) and attenuated the increase of IL-10 (Xenon: 127.9 versus sevoflurane: 548.3 pg/ml; p = 0.028). Both groups demonstrated a comparable intraoperative increase of oxidative stress (intra-OP: p = 0.29; post-OP: p = 0.65). While both groups showed an intraoperative increase of the cardioprotective mediators MIF and CXCL12/SDF-1α, only MIF levels decreased in the xenon group on the first postoperative day (50.0 ng/ml compared to 23.3 ng/ml; p = 0.012), whereas it remained elevated after sevoflurane anaesthesia (58.3 ng/ml to 53.6 ng/ml). Effects of patients' serum on chemotactic migration of peripheral mononuclear blood cells taken from healthy volunteers indicated a tendency towards enhanced migration after sevoflurane anaesthesia (p = 0.07). CONCLUSIONS: Compared to sevoflurane, balanced xenon anaesthesia triggers pro-inflammatory effects and suppresses the anti-inflammatory response in cardiac surgery patients even though the clinical significance remains unknown. TRIAL REGISTRATION: This clinical trial was approved by the European Medicines Agency (EudraCT-number: 2010-023942-63) and at ClinicalTrials.gov ( NCT01285271 ; first received: January 24, 2011).

Tissue oxygen saturation as an early indicator of delayed lactate clearance after cardiac surgery: a prospective observational study.

BACKGROUND: In this observational study near infrared spectroscopy (NIRS) was evaluated as a non-invasive monitor of impaired tissue oxygenation (StO2) after cardiac surgery. StO2, cardiac output, mixed venous oxygen saturation and mean arterial pressure were compared with lactate clearance as established measure for sufficient tissue perfusion and oxygen metabolism. METHODS: Forty patients after cardiac surgery (24 aortocoronary bypass grafting, 5 heart valve, 3 ascending aorta and 8 combined procedures) were monitored until postoperative day 1 with NIRS of the thenar muscle (InSpectra™ StO2-monitor, Hutchinson Technology), a pulmonary-artery catheter and intermittent blood gas analyses for the assessment of lactate clearance. RESULTS: StO2 was reduced 4 h after surgery (75 ± 6 %), but recovered at day 1 (84 ± 5 %), while lactate concentration remained increased. Using uni- and multivariate regression analysis, minimum StO2 (r = 0.46, p <0.01) and cardiac index (r = 0.40, p <0.05) correlated with lactate clearance at day 1, while minimum mixed venous saturation and mean arterial pressure did not. In a receiver-operating characteristics (ROC) analysis, minimum StO2 (with a threshold of 75 %) predicted a lactate clearance <10 % at day 1 with an area under the ROC-curve of 0.83, a sensitivity of 78 % and a specificity of 88 %. In the subgroup with StO2 <75 %, troponin and creatine kinase MB were significantly increased at day 1. CONCLUSIONS: StO2 below 75 % in the first hours after surgery was a better early indicator of persistent impaired lactate clearance at day 1 than cardiac index, mixed venous oxygen saturation or mean arterial pressure.

[The correct way to deal with the definitive surgical airway]. / Der richtige Umgang mit dem definitiven chirurgischen Atemweg.

Dealing with a difficult airway is familiar to emergency care providers in both the prehospital and clinical settings. In anesthesiology and emergency medical care different algorithms almost equal in their wording have been introduced, indicating that an emergency front of neck airway access (eFONA) has to be established in the case of a cannot ventilate-cannot oxygenate situation. In a survey (Surveymonkey®) data concerning the level of experience with eFONA, devices required, previous training and complications were allocated among acute and emergency care providers of different backgrounds (doctors and paramedics). Furthermore, we asked about individual attitudes to and frequency of previous situations, in which an eFONA was not established despite strong indications. Of the respondents 15% (n = 63) answered that they had experienced this type of situation. eFONA had been performed by 28% of the interviewed (n = 117), reflecting the high number of military and EMT (emergency medical team) physicians participating in the survey. The number of experiences are rarely representative for the civilian setting. Different adjuncts may be helpful to detect the cricothyroid ligament. To use ultrasound seems obvious but it doubles the time for the detection of the cricothyroid ligament. Laryngeal masks can be employed as a supraglottic airway device (SAD) during "plan B". Stabilizing the airway with a SAD almost doubles the success of identifying laryngeal landmarks in females. The crew resource management (CRM) guidelines are more than essential in threatening situations demanding measures like eFONA. Providers should anticipate emerging problems and whenever feasible call for help and finally speak up. Naming a failed airway should be avoided as it implies a failure of the provider or of the entire airway team. In fact, the term non-accessible airway should be introduced. This might help to avoid the implication of a major failure. So far, an ideal simulator to train eFONA has not been introduced but it is mandatory to train procedures and algorithms on different types of simulators and manikins to achieve mastery.

[Cricothyrotomy : Data situation, guidelines and techniques for the definitive surgical airway]. / Koniotomie : Datenlage, Leitlinien und Techniken zum definitiven chirurgischen Atemweg.

Cricothyrotomy represents the final approach to secure the airway, in the course of which less invasive measures have failed. It can also primarily be carried out to establish a secure airway. This is essential to protect the patient from a significant hypoxia. This is a cannot ventilate-cannot oxygenate (CVCO) situation, which presumably all colleagues in emergency intensive care medicine and anesthesia have already been confronted with. Evidence-based algorithms for the management of a difficult airway and CVCO have been established. If oxygenation using an endotracheal tube, an extraglottic airway device or bag-valve mask ventilation all fail, the airway must be surgically secured, i.e. using cricothyrotomy. The prevalence of the CVCO situation in a prehospital setting is ca. 1%. No valid prospective randomized in vivo studies have been carried with respect to the question of the best method.

The Spread of Exhaled Air and Aerosols during Physical Exercise.

Physical exercise demonstrates a special case of aerosol emission due to its associated elevated breathing rate. This can lead to a faster spread of airborne viruses and respiratory diseases. Therefore, this study investigates cross-infection risk during training. Twelve human subjects exercised on a cycle ergometer under three mask scenarios: no mask, surgical mask, and FFP2 mask. The emitted aerosols were measured in a grey room with a measurement setup equipped with an optical particle sensor. The spread of expired air was qualitatively and quantitatively assessed using schlieren imaging. Moreover, user satisfaction surveys were conducted to evaluate the comfort of wearing face masks during training. The results indicated that both surgical and FFP2 masks significantly reduced particles emission with a reduction efficiency of 87.1% and 91.3% of all particle sizes, respectively. However, compared to surgical masks, FFP2 masks provided a nearly tenfold greater reduction of the particle size range with long residence time in the air (0.3-0.5 µm). Furthermore, the investigated masks reduced exhalation spreading distances to less than 0.15 m and 0.1 m in the case of the surgical mask and FFP2 mask, respectively. User satisfaction solely differed with respect to perceived dyspnea between no mask and FFP2 mask conditions.

Cerebral oxygen saturation in the prefrontal cortex during electroconvulsive therapy and its relation with the postictal reorientation time.

The therapeutic effect of Electroconvulsive Therapy (ECT) has been attributed to generalised seizure. Although patients are well oxygenated prior to and during treatment, critics have associated ECT with brain tissue hypoxemia. In this study, the regional oxygen saturation (rSO2) was measured continuously during ECT in the prefrontal cortex (PFC) of both hemispheres using 2-channel Near Infrared Spectroscopy (NIRS). Additionally, the postictal reorientation time (PRT) was determined and related to the rSO2 course. We evaluated 72 ECT treatments in 22 adult patients who were treated for a therapy-resistant depressive syndrome. The therapy was performed according to our standard clinical procedures deploying right unilateral (RUL) and left anterior versus right temporal (LART) electrode placements. According to our results, the rSO2 courses showed an increase during hyperventilation, a sharp drop immediately after the stimulus, and a long recovery period with values far exceeding the baseline. In 55,6% of treatments the rSO2 course stayed above the baseline. In the others, the drop fell below it for an average of 12.6 s. According to a cardio surgical standard no signs of hypoxemia occurred during ECT treatments. The rSO2 drop at seizure onset was the only parameter of the oxygen course related to the PRT in the multivariate analysis and might therefore be a characteristic feature of the seizure. It could reflect its physiological intensity and thereby be involved in the mechanism of action of ECT. NIRS seems to be an interesting non-invasive tool for monitoring and studying ECT.

The intraoperative decrease of selenium is associated with the postoperative development of multiorgan dysfunction in cardiac surgical patients.

OBJECTIVE: The trace elements selenium, copper, and zinc are essential for maintaining the oxidative balance. A depletion of antioxidative trace elements has been observed in critically ill patients and is associated with the development of multiorgan dysfunction and an increased mortality. Cardiac surgery using cardiopulmonary bypass provokes ischemia-reperfusion-mediated oxidative stress. We hypothesized that an intraoperative decrease of circulating trace elements may be involved in this response. DESIGN: Prospective observational clinical study. SETTING: University hospital cardiothoracic operation theater and intensive care unit. PATIENTS: Sixty patients (age 65 ± 14 yrs) undergoing cardiac surgery with the use of cardiopulmonary bypass. MEASUREMENTS AND MAIN RESULTS: Whole blood concentrations of selenium, copper, and zinc were measured after induction of anesthesia and 1 hr after admission to the intensive care unit. All patients were separated in a priori defined subgroups according to the development of no organ failure, single organ failure, and ≥ 2 organ failures in the postoperative period. RESULTS: Fifty patients exhibited a significant selenium deficiency already before surgery, whereas copper and zinc concentrations were within the reference range. In all patients, blood levels of selenium, copper, and zinc were significantly reduced after end of surgery when compared to preoperative values (selenium: 89.05 ± 12.65 to 70.84 ± 10.46 µg/L; zinc: 5.15 ± 0.68 to 4.19 ± 0.73 mg/L; copper: 0.86 ± 0.15 to 0.65 ± 0.14 mg/L; p < .001). During their intensive care unit stay, 17 patients were free from any organ failure, while 31 patients developed single-organ failure and 12 patients multiple organ failure. Multilogistic regression analysis showed that selenium concentrations at end of surgery were independently associated with the postoperative occurrence of multiorgan failure (p = .0026, odds ratio 0.8479, 95% confidence interval 0.7617 to 0.9440). CONCLUSIONS: Cardiac surgery using cardiopulmonary bypass resulted in a profound intraoperative decrease of whole blood levels of antioxidant trace elements. Low selenium concentrations at end of surgery were an independent predictor for the postoperative development of multiorgan failure.

[Recommendations for emergency management of patients with permanent mechanical circulatory support : Consensus statement of DGTHG, DIVI, DGIIN, DGAI, DGINA, DGfK and DGK]. / Empfehlungen zum Notfallmanagement von Patienten mit permanenten Herzunterstützungssystemen : Konsensuspapier der DGTHG, DIVI, DGIIN, DGAI, DGINA, DGfK und DGK.

The prevalence of patients living with long-term mechanical circulatory support (MCS) is rapidly increasing due to improved technology, improved survival, reduced adverse event profiles, greater reliability and mechanical durability, and limited numbers of organs available for donation. Patients with long-term MCS are very likely to require emergency medical support due to MCS-associated complications (e.g., right heart failure, left ventricular assist device malfunction, hemorrhage and pump thrombosis) but also due to non-MCS-associated conditions. Because of the unique characteristics of mechanical support, management of these patients is complicated and there is very little literature on emergency care for these patients. The purpose of this national scientific statement is to present consensus-based recommendations for the initial evaluation and resuscitation of adult patients with long-term MCS.

Levosimendan reduces segmental pulmonary vascular resistance in isolated perfused rat lungs and relaxes human pulmonary vessels.

INTRODUCTION: Levosimendan is approved for acute heart failure. Within this context, pulmonary hypertension represents a frequent co-morbidity. Hence, the effects of levosimendan on segmental pulmonary vascular resistance (PVR) are relevant. So far, this issue has been not studied. Beyond that the relaxant effects of levosimendan in human pulmonary vessel are unknown. We addressed these topics in rats' isolated perfused lungs (IPL) and human precision-cut lung slices (PCLS). MATERIAL AND METHODS: In IPL, levosimendan (10 µM) was perfused in untreated and endothelin-1 pre-contracted lungs. The pulmonary arterial pressure (PPA) was continuously recorded and the capillary pressure (Pcap) was determined by the double-occlusion method. Thereafter, segmental PVR, expressed as precapillary (Rpre) and postcapillary resistance (Rpost) and PVR were calculated. Human PCLS were prepared from patients undergoing lobectomy. Levosimendan-induced relaxation was studied in naïve and endothelin-1 pre-contracted PAs and PVs. In endothelin-1 pre-contracted PAs, the role of K+-channels was studied by inhibition of KATP-channels (glibenclamide), BKCa2+-channels (iberiotoxin) and Kv-channels (4-aminopyridine). All changes of the vascular tone were measured by videomicroscopy. In addition, the increase of cAMP/GMP due to levosimendan was measured by ELISA. RESULTS: Levosimendan did not relax untreated lungs or naïve PAs and PVs. In IPL, levosimendan attenuated the endothelin-1 induced increase of PPA, PVR, Rpre and Rpost. In human PCLS, levosimendan relaxed pre-contracted PAs or PVs to 137% or 127%, respectively. In pre-contracted PAs, the relaxant effect of levosimendan was reduced, if KATP- and Kv-channels were inhibited. Further, levosimendan increased cGMP in PAs/PVs, but cAMP only in PVs. DISCUSSION: Levosimendan reduces rats' segmental PVR and relaxes human PAs or PVs, if the pulmonary vascular tone is enhanced by endothelin-1. Regarding levosimendan-induced relaxation, the activation of KATP- and Kv-channels is of impact, as well as the formation of cAMP and cGMP. In conclusion, our results suggest that levosimendan improves pulmonary haemodynamics, if PVR is increased as it is the case in pulmonary hypertension.

Neurophysiological and paraspinal oximetry monitoring to detect spinal cord ischemia in patients during and after descending aortic repair: An international multicenter explorative study.

BACKGROUND: During descending aortic repair, critically decreased blood flow to the myelum can result in ischemic spinal cord injury and transient or permanent paraplegia. Assessment of motor evoked potentials (MEPs) has been shown to be a valuable tool which allows to detect spinal cord ischemia (SCI) intraoperatively within a therapeutic window suitable to prevent progression to paraparesis or paraplegia. MEP monitoring is not feasible during postoperative care in the awakening patient. Therefore, ancillary techniques to monitor integrity of spinal cord function are needed to detect delayed spinal cord ischemia. OBJECTIVE: The purpose of this study is to evaluate whether assessment of long loop reflexes (LLR; F-waves) and paraspinal muscle oximetry using Near-Infrared Spectroscopy (NIRS) are feasible and valid in detecting delayed SCI. METHODS: We aim to include patients from three tertiary referral centers undergoing aortic repair with MEP monitoring in this study.F-wave measurements and paraspinal NIRS oximetry will be operated intra- and postoperatively. Measurement characteristics and feasibility will be assessed in the first 25 patients. Subsequently, a second cohort of 75 patients will be investigated to determine the sensitivity and specificity of F-waves and NIRS in detecting perioperative SCI. In this context for the MEP group SCI is defined intraoperatively as significant MEP changes and postoperatively as newly developed paraplegia. CONCLUSIONS: A clinical study design and protocol is proposed to assess if F-waves and/or NIRS-based paraspinal oximetry are feasible and valid in detecting and monitoring for occurrences of delayed SCI.

Influence of temperature on the positive inotropic effect of levosimendan, dobutamine and milrinone.

BACKGROUND AND OBJECTIVE: Patients in cardiac surgery and critically ill patients often demonstrate either hypothermia or fever. In addition, owing to heart failure, they frequently require inotropic support. The relative effectiveness of modern inotropic agents at various temperatures has not yet been evaluated. Therefore, we investigated the influence of levosimendan, dobutamine and milrinone on the contractile response of myocardial trabeculae at various temperatures. METHODS: A total of 120 guinea pig ventricular trabeculae were placed in oxygenated 4-(2-hydroxyethyl)-1-piperazineethanesulphonic acid (HEPES) buffer, stimulated at a frequency of 1.3 Hz and randomly assigned to a temperature of 31 degrees C, 34 degrees C, 37 degrees C or 40 degrees C. Concentrations of all substances were increased stepwise from 10(-9) to 10(-5) mol l(-1) (milrinone up to 10(-4) mol l(-1)). Maximum developed force, time to peak tension, Tsystolic(50%) and Tdiastolic(50%) were continuously recorded. RESULTS: All agents showed a dose-dependent positive inotropic effect (P < 0.0001 for all). Levosimendan acted at every temperature as a positive inotrope (P = 0.0643). Dobutamine-related inotropy showed a clear trend towards temperature dependence, although statistical evaluation did not prove this (P = 0.0624). Milrinone-related inotropy was abolished at 31 degrees C and 34 degrees C, and temperature dependence was significant (P < 0.0001). Hypothermia induced a positive inotropic effect. CONCLUSION: Our results suggest no modulation of levosimendan-induced inotropy under the experimental temperatures tested. This observation is possibly due to its Ca2+-sensitizing mechanism, which might not be influenced by temperature-related changes in intracellular Ca2+ levels. In contrast, the inotropic effect of cyclic AMP-coupled dobutamine and milrinone is suppressed under hypothermia-related interaction with intracellular Ca2+ homeostasis. Hence, levosimendan might prove to be the preferred inotropic drug in hypothermic patients.