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ZusammenfassungDieses zweite Positionspapier der Sektion Metabolismus und Ernährung der Deutschen Interdisziplinären Vereinigung für Intensiv- und Notfallmedizin (DIVI) gibt Empfehlungen zum laborchemischen Monitoring der Makro- und Mikronährstoffzufuhr sowie zum Einsatz der indirekten Kalorimetrie im Rahmen der medizinischen Ernährungstherapie erwachsener Intensivpatient:innen. Zusätzlich werden Empfehlungen zur krankheitsbezogenen bzw. individuellen (Spiegelbestimmung) Substitution und (Hochdosis‑)Pharmakotherapie von Vitaminen und Spurenelementen vorgenommen.

Background A recent landmark randomized controlled trial (RCT) in septic patients demonstrated an increased risk of death and persistent organ dysfunction with intravenous Vitamin C (IVVC) monotherapy, which represents a disparate result from previous systematic reviews and meta-analyses (SRMA). We performed an updated SRMA of IVVC monotherapy to summarize and explore heterogeneity across current trials and conduct trial sequential analysis (TSA) to guard against type-I or type-II statistical errors. Methods RCTs evaluating IVVC in adult critically ill patients were included. Four databases were searched from inception to 22 June 2022 without language restrictions. The primary outcome was overall mortality. Random effect meta-analysis was performed to estimate the pooled risk ratio. TSA for mortality was performed using the DerSimonian–Laird random effect model, alpha 5%, beta 10%, and relative risk reduction (RRR) of 30%, 25%, and 20%. Results We included 16 RCTs (n = 2130). IVVC monotherapy is associated with significant reduction in overall mortality [risk ratio (RR) 0.73, 95% confidence interval (CI) 0.60–0.89; p = 0.002; I2 = 42%]. This finding is supported by TSA using RRR of 30% and 25%, and sensitivity analysis using fixed-effect meta-analysis. However, the certainty of our mortality finding was rated low using GRADE due to the serious risk of bias and inconsistency. In a priori subgroup analyses, we found no differences between single vs multicenter, higher (≥ 10,000 mg/day) vs lower dose and sepsis vs non-sepsis trials. Post-hoc, we found no differences in subgroup analysis of earlier ( 4 days) vs shorter treatment duration, and low vs other risk of bias studies. IVVC may have the greatest benefit in trials that enrolled patients above (i.e., > 37.5%; RR 0.65, 95% CI 0.54–0.79) vs below (i.e., ≤ 37.5%; RR 0.89, 95% CI 0.68–1.16) median control group mortality (test for subgroup differences: p = 0.06), and TSA supported this. Conclusions IVVC monotherapy may be associated with mortality benefits in critically ill patients, particularly in patients with a high risk of dying. Given the low certainty of evidence, this potentially life-saving therapy warrants further studies to identify the optimal timing, dosage, treatment duration, and patient population that will benefit most from IVVC monotherapy. PROSPERO Registration ID: CRD42022323880. Registered 7th May 2022.

Der ethische Bezugsrahmen zur Durchfuhrung einer Flussigkeitstherapie in der palliativmedizinischen Versorgung am Lebensende kann sehr unterschiedlich gewahlt werden. Welche ethischen Implikationen gilt es wahrend einer Dehydration am Lebensende zu beachten und gibt es besondere Anforderungen im Umgang mit der „terminalen“ Dehydration? Es wurde eine umfassende Literatursuche durchgefuhrt, um relevante Artikel in englischer und deutscher Sprache zu identifizieren. Unsere Schlussfolgerungen reprasentieren eher eine Haltung als eine evidenzbasierte Position – eine Tatsache, die auf den zugrunde liegenden normativen und ethischen Bezugen basiert, die einer statistischen Auswertung kaum zuganglich sind. Unsere ethischen Erwagungen werden vom Fehlen einer klaren Evidenzlage gepragt, die es nach unserer Auffassung auch am Lebensende nicht rechtfertigt, sich von etablierten Konzepten der klinisch assistierten Flussigkeitszufuhr („clinically assisted hydration“, CAH) zu entfernen, solange therapeutische Masnahmen wirksam umgesetzt werden konnen. Die „permissive“ Dehydration darf am Lebensende nicht als eine Option zur Verkurzung des Sterbeprozesses betrachtet werden. In der Palliativmedizin ist die Dehydration auch weiterhin als „Symptom“ zu betrachten, das zu „kontrollieren“ ist, solange dieses mit therapeutischen Mitteln beherrscht werden kann und solange der Patient diesem Vorgehen nicht ablehnend gegenubersteht. Bleibt die Dehydration aber therapeutisch refraktar, ist es gerechtfertigt, die CAH entweder nicht zu initiieren oder die laufende Therapie zu stoppen.

Der rechtliche Bezugsrahmen zur Durchfuhrung einer Flussigkeitstherapie in der palliativmedizinischen Versorgung am Lebensende kann auf verschiedenen Kontinenten und sogar in benachbarten Landern sehr unterschiedlich sein. Welche rechtlichen Implikationen mussen in Deutschland im Umgang mit der „terminalen“ Dehydration beachtet werden? Es wurden relevante Publikationen in englischer und deutscher Sprache identifiziert. Insbesondere wurden die in Deutschland gultigen Empfehlungen herangezogen und mit den Vorgehensweisen in England und Kanada verglichen. Unsere rechtlichen Erwagungen entsprechen den Empfehlungen der Bundesarztekammer. Als zentrale Bestandteile sind die Patientenautonomie, die bestmogliche Symptomkontrolle und die standige therapeutische Nutzen-Risiko-Abschatzung zu nennen. Die Dehydration ist danach auch weiterhin als „Symptom“ zu betrachten, das zu „kontrollieren“ ist, solange dieses mit therapeutischen Mitteln beherrscht werden kann und solange der Patient diesem Vorgehen nicht ablehnend gegenubersteht. Bleibt die Dehydration aber therapeutisch refraktar, ist es gerechtfertigt, die klinisch assistierte („Clinically assisted hydration“, CAH) entweder nicht zu initiieren oder die laufende Therapie zu stoppen. Diesem Vorgehen steht das in Kanada praktizierte „shared decision-making model“ diametral gegenuber, bei dem eine paternalistische Entscheidungsfindung moglich ist, sofern die Patienten oder Angehorigen schlecht informiert und unvorbereitet erscheinen, um nach Expertenmeinung „richtig“ zu entscheiden. Eine nichtrefraktare Dehydration am Lebensende darf nach deutschem Recht nicht untherapiert bleiben und darf nicht als Option zur Verkurzung des Sterbeprozesses genutzt werden, wenn die Entstehung einer Dehydration nicht dem Patientenwillen entspricht oder dieser Wille nicht ermittelbar ist.

Perioperative right ventricular (RV) failure due to pressure overload from pulmonary hypertension (PH) worsens postoperative outcomes after cardiac surgery. Inhaled iloprost is a potent pulmonary vasodilator improving RV performance, ameliorating myocardial and pulmonary ischemia-reperfusion injury and attenuating inflammation. We hypothesized that the prophylactic inhalation of iloprost would reduce postoperative ventilation times after cardiac surgery. In this phase III, multicentre, randomized, double-blind, placebo-controlled trial, we randomly assigned 253 cardiac surgical patients at high risk of perioperative RV failure to the prophylactic inhalation of 20 µg iloprost or placebo before and during weaning from extracorporeal circulation. The primary endpoint was the duration of postoperative ventilation. Secondary endpoints included perioperative hemodynamics, intensive care unit and hospital length of stay, and 90-day mortality. Safety was assessed by the incidence of adverse events. Iloprost had no significant effect on the median [interquartile range] duration of postoperative ventilation compared with placebo (720 [470–1170] min vs 778 [541–1219] min, respectively; median decrease, 65 min; 95% confidence interval [CI], − 77 to 210; P = 0.37). While the nebulization of iloprost decreased RV afterload and improved cardiac index, major secondary endpoints were not significantly affected. Ninety-day mortality occurred in 14% of the iloprost patients compared with 14% of the placebo patients (hazard ratio, 0.97; 95% CI, 0.50 to 1.89; P = 0.93). The incidence of adverse events was comparable in both groups. The prophylactic inhalation of iloprost did not meaningfully improve the outcome in high-risk cardiac surgical patients. www.clinicaltrials.gov (NCT00927654); registered 25 June, 2009.

The goal of nutrition support is to provide the substrates required to match the bioenergetic needs of the patient and promote the net synthesis of macromolecules required for the preservation of lean mass, organ function, and immunity. Contemporary observational studies have exposed the pervasive undernutrition of critically ill patients and its association with adverse clinical outcomes. The intuitive hypothesis is that optimization of nutrition delivery should improve ICU clinical outcomes. It is therefore surprising that multiple large randomized controlled trials have failed to demonstrate the clinical benefit of restoring or maximizing nutrient intake. This may be in part due to the absence of biological markers that identify patients who are most likely to benefit from nutrition interventions and that monitor the effects of nutrition support. Here, we discuss the need for practical risk stratification tools in critical care nutrition, a proposed rationale for targeted biomarker development, and potential approaches that can be adopted for biomarker identification and validation in the field., SCOPUS: re.j, info:eu-repo/semantics/published

In the present observational study, we measured serum levels of the chemokine stromal cell-derived factor-1α (SDF-1α) in 100 patients undergoing cardiac surgery with cardiopulmonary bypass at seven distinct time points including preoperative values, myocardial ischemia, reperfusion, and the postoperative course. Myocardial ischemia triggered a marked increase of SDF-1α serum levels whereas cardiac reperfusion had no significant influence. Perioperative SDF-1α serum levels were influenced by patients' characteristics (e.g., age, gender, aspirin intake). In an explorative analysis, we observed an inverse association between SDF-1α serum levels and the incidence of organ dysfunction. In conclusion, time of myocardial ischemia was identified as the key stimulus for a significant upregulation of SDF-1α, indicating its role as a marker of myocardial injury. The inverse association between SDF-1α levels and organ dysfunction association encourages further studies to evaluate its organoprotective properties in cardiac surgery patients.

The licensed anesthetic xenon, which exerts organ protective properties, was recently added by the World Anti-Doping Agency to the list of prohibited substances. Xenon is supposed to trigger the production of hypoxia-inducible factor 1α (HIF-1α) and subsequently erythropoietin, but data are limited to in vivo experimental work. Therefore we evaluated the effect of xenon on erythropoietin levels in healthy persons. Twenty-four healthy volunteers were randomly assigned either to a group spontaneously breathing xenon 30 % (Xe/O2 30 %/60 %) or a group breathing control gas (N2/O2 40 %/60 %) for 45 min. Primary outcome parameters were erythropoietin levels at several time-points after exposure. Secondary outcome parameters were serum levels of testosterone, cytokines, and growth factors as well as concentrations of xenon in blood and exhalation samples measured at several time-points after exposure. In addition, hemodynamic safety parameters were monitored during exposure. The administration of xenon significantly increased erythropoietin levels 8 h after exposure (1.34 [±0.368]; p = 0.008), peaking at 24 h compared to the baseline values (1.45 [±0.498]; p = 0.01) and remained traceable in blood and exhalation probes until 24 h after exposure. In contrast, no significant change was observed in the control group. Measurement of stromal cell-derived factor 1 (SDF-1) revealed a significant increase of SDF-1 levels (p = 0.005), whereas no differences were observed with respect to growth factors, cytokines, or androgens. In an in vitro chemotaxis assay, endothelial progenitor cells (EPCs) showed a trend towards increased migration in serum samples received from participants after xenon exposure (p = 0.080). The present study presents first evidence about a xenon-induced effect on increased erythropoietin levels in healthy volunteers. The study was registered at the European Medicines Agency (EudraCT-number: 2014-000973-38) and at ClinicalTrials.gov (NCT number: 02129400).

Background Despite substantial success in the anesthetic and surgical management of cardiac surgery, patients frequently show postoperative complications and organ dysfunctions. This is highly relevant for mid- to long-term outcomes. Objectives To evaluate cardioprotective strategies that may offer effective protection in vulnerable cardiac surgery patients. Methods To demonstrate recent cardioprotective approaches for cardiac surgery patients, aiming to modulate the body's own protective mechanisms in cardiac surgery patients. Results Both cardioplegia and hypothermia belong to the well-established protective strategies during myocardial ischemia. Volatile anesthetics have been repeatedly shown to improve the left ventricular function and reduce the extent of myocardial injury compared to a control group with intravenous anesthesia. Furthermore, patients receiving volatile anesthetics showed a significantly shortened stay in the ICU and in hospital after cardiac surgery. In contrast, numerous other protective strategies failed translation into the clinical practice. Despite the published reduction of troponin release after remote ischemic preconditioning, two recent large-scale randomized multicenter trials were unable to demonstrate a clinical benefit. Conclusions Beside the use of cardioplegia and hypothermia, the use of volatile anesthetics is well-established during cardiac surgery because of its conditioning and protective properties. Regardless of the promising results derived from experimental studies and small clinical trials, the majority of other approaches failed to translate their findings into the clinic. Therefore, systematic experimental studies are needed to identify potential confounding factors that may affect the protective effects.

Der demografische Wandel bringt eine stetige Zunahme der Patienten in der Alterstraumatologie mit sich. Diese Patienten weisen eine hohe Zahl an Komorbiditaten auf und haben folglich ein entsprechend hohes perioperatives Risiko fur postoperative Morbiditat und Letalitat. Die Dreisigtageletalitat dieser Patienten ist hoch. Es soll eine Ubersicht uber wichtige Aspekte des anasthesiologischen Managements in der Alterstraumatologie gegeben werden. Dies kann dazu dienen, das perioperative Outcome dieser Hochrisikopatienten zu verbessern. Es erfolgte eine Analyse der aktuellen Literatur als Grundlage fur eine Darstellung des pra-, intra- und postoperativen anasthesiologischen Managements in der Alterstraumatologie. Eine zeitnahe Versorgung der alterstraumatologischen Patienten ist wichtig. Viele dieser Patienten weisen ein hohes perioperatives Risikoprofil auf. Dieses kann mithilfe von Scores berechnet werden, um Aussagen uber die Prognose der Patienten zu ermoglichen. Entsprechend kann die Aufklarung der Patienten erfolgen. Der Behandlungspfad bedarf einer multidisziplinaren Planung. Viele Fragestellungen des perioperativen Managements, wie z. B. nach dem bestgeeigneten Anasthesieverfahren, dem idealen individuellen Transfusionstrigger, dem Volumenmanagement u.v.m., sind noch nicht ausreichend durch Studien geklart. Der Evidenzgrad der perioperativen Versorgung in der Alterstraumatologie ist schwach. Aufgrund dessen sind grose prospektive Studien ein dringendes Forschungsziel, um einheitliche Standards und Richtlinien zu definieren.

BACKGROUND Postoperative hypoxemia is a common complication in the anesthesia recovery room (ARR), which is predominantly based on the development of atelectasis, excessive intraoperative fluid shift and insufficient ventilation. The goal of this prospective observational study was to compare the effect of standard oxygen administration via a face mask with oxygen administration using the EzPAP® system, a device which additionally provides a positive end-expiratory pressure (PEEP). METHODS This study included 210 patients with postoperative hypoxemia (S(p)O(2) 5 min), the oxygen therapy was restarted in both groups via a facemask. Both groups were compared using repeat measurement analysis of variance (ANOVA), the unpaired t-test, the Mann-Whitney U-test, Fisher's exact test and the χ(2)-test. The correlation of O(2) flow and PEEP was evaluated by regression analysis and p < 0.05 was considered to be statistically significant. Apart from this a subgroup analysis was performed depending on body-mass index (BMI), American Society of Anesthesiologists (ASA) classification, intraoperative airway management, the use of neuromuscular blocking agents and co-existing disorders, e.g. chronic obstructive lung disease (COLD), obesity and chronic heart failure. RESULTS All patients were equally distributed between both groups with respect to demographic data, ASA classification, BMI, co-existing disorders and surgical procedures. The S(p)O(2) values did not differ between the EzPAP patients and the control group, except for 0.5 min after initiation of oxygen therapy: EzPAP group 96 ± 3.7% (mean ± standard deviation) versus the control group 93.8 ± 4.4% (p < 0.001). However, restarting oxygen therapy was less common in the EzPAP group (EzPAP group 25 versus control group 41, p = 0.03), as well as the occurrence of postoperative complications (EzPAP group 13 versus control group 25, p = 0.02), e.g. nosocomial pneumonia (0 versus 4) and wound infections (2 versus 3). Furthermore, patients with obesity and pulmonary disorders, such as COLD had a benefit from oxygen administration using the EzPAP device and showed higher postoperative than preoperative S(p)O(2) values. In contrast, the subgroup analysis of patients with heart failure did not reveal any differences between both groups and both groups did not differ in terms of time spent in the recovery room (EzPAP group 113 min versus control group 174.8 min, p = 0.2). CONCLUSIONS In this observational study oxygen supply using the EzPAP® system appeared to be at least equally as effective in the therapy of postoperative hypoxemia compared to standard oxygen supply using a face mask. In patients with a high risk of postoperative hypoxemia, such as patients with obesity and/or pulmonary disorders, oxygen administration using the EzPAP® system possibly improves pulmonary oxygenation more effectively and is longer lasting compared to standard oxygen supply via a face mask. Hence, the EzPAP® system represents a well-tolerated, effective, cost-effective and easily operated tool to improve postoperative oxygenation. In order to investigate the possibilities of this promising tool more intensively, randomized clinical trials are warranted.

Macrophage migration inhibitory factor (MIF) is an inflammatory cytokine that exerts protective effects during myocardial ischemia/reperfusion injury. We hypothesized that elevated MIF levels in the early postoperative time course might be inversely associated with postoperative organ dysfunction as assessed by the simplified acute physiology score (SAPS) II and sequential organ failure assessment (SOFA) score in patients after cardiac surgery. A total of 52 cardiac surgical patients (mean age [± SD] 67 ± 10 years; EuroScore: 7 [2–11]) were enrolled in this monocenter, prospective observational study. Serum levels of MIF and clinical data were obtained after induction of anesthesia, at admission to the intensive care unit (ICU), 4 h after admission and at the first and second postoperative day. To characterize the magnitude of MIF release, we compared blood levels of samples from cardiac surgical patients with those obtained from healthy volunteers. We assessed patient outcomes using the SAPS II at postoperative d 1 and SOFA score for the first 3 d of the eventual ICU stay. Compared to healthy volunteers, patients had already exhibited elevated MIF levels prior to surgery (64 ± 50 versus 13 ± 17 ng/mL; p < 0.05). At admission to the ICU, MIF levels reached peak values (107 ± 95 ng/mL; p < 0.01 versus baseline) that decreased throughout the observation period and had already reached preoperative values 4 h later. Postoperative MIF values were inversely correlated with SAPS II and SOFA scores during the early postoperative stay. Moreover, MIF values on postoperative d 1 were related to the calculated cardiac power index (r = 0.420, p < 0.05). Elevated postoperative MIF levels are inversely correlated with organ dysfunction in patients after cardiac surgery.

Background Cardiovascular disease (CVD) is a major contributor to the burden of disease and the number one cause of death worldwide. From 1990 until today, more people have died from coronary heart disease than from any other cause. CVD is regularly treated with minimal or non-minimalinvasive offor on-pump cardiothoracic surgery and interventions related to the outcome of the surgical procedures are regularly evaluated in clinical trials, but heterogeneity in outcome reporting hinders comparison of interventions and limits the ability of research synthesis. This problem is encountered by core outcome sets (COS) that should be measured and reported – as a minimum – in all clinical trials for a specific clinical field.

Page 1764, Column 2, `Acknowledgements' section: The first sentence, which previously read.

Macrophage migration inhibitory factor (MIF) is a structurally unique inflammatory cytokine [1] that exerts protective effects during ischemia and reperfusion [2]. We hypothesized that elevated MIF levels in the early postoperative time course might be inversely associated with postoperative organ dysfunction as assessed by SAPS II and SOFA score in patients after cardiac surgery.

Medical Gas Research 3(1), 12,11 S. (2013). doi:10.1186/2045-9912-3-12, Published by BioMed Central, London

Medical gas research 1(1), 9 (2011). doi:10.1186/2045-9912-1-9, Published by BioMed Central, London