Intraoperative haemodynamic monitoring and management of adults having non-cardiac surgery: Guidelines of the German Society of Anaesthesiology and Intensive Care Medicine in collaboration with the German Association of the Scientific Medical Societies.

Haemodynamic monitoring and management are cornerstones of perioperative care. The goal of haemodynamic management is to maintain organ function by ensuring adequate perfusion pressure, blood flow, and oxygen delivery. We here present guidelines on "Intraoperative haemodynamic monitoring and management of adults having non-cardiac surgery" that were prepared by 18 experts on behalf of the German Society of Anaesthesiology and Intensive Care Medicine (Deutsche Gesellschaft für Anästhesiologie und lntensivmedizin; DGAI).

German Patient Blood Management Network: effectiveness and safety analysis in 1.2 million patients.

BACKGROUND: Patient Blood Management (PBM) is a patient-centred, systematic, evidence-based approach to improve patient outcomes by managing and preserving a patient's own blood whilst promoting patient safety and empowerment. The effectiveness and safety of PBM over a longer period have not yet been investigated. METHODS: We performed a prospectively designed, multicentre follow-up study with non-inferiority design. Data were retrospectively extracted case-based from electronic hospital information systems. All in-hospital patients (≥18 yr) undergoing surgery and discharged between January 1, 2010 and December 31, 2019 were included in the analysis. The PBM programme focused on three domains: preoperative optimisation of haemoglobin concentrations, blood-sparing techniques, and guideline adherence/standardisation of allogeneic blood product transfusions. The outcomes were utilisation of blood products, composite endpoint of in-hospital mortality and postoperative complications (myocardial infarction/ischaemic stroke/acute renal failure with renal replacement therapy/sepsis/pneumonia), anaemia rate at admission and discharge, and hospital length of stay. RESULTS: A total of 1 201 817 (pre-PBM: n=441 082 vs PBM: n=760 735) patients from 14 (five university/nine non-university) hospitals were analysed. Implementation of PBM resulted in a substantial reduction of red blood cell utilisation. The mean number of red blood cell units transfused per 1000 patients was 547 in the PBM cohort vs 635 in the pre-PBM cohort (relative reduction of 13.9%). The red blood cell transfusion rate was significantly lower (P<0.001) with odds ratio 0.86 (0.85-0.87). The composite endpoint was 5.8% in the PBM vs 5.6% in the pre-PBM cohort. The non-inferiority aim (safety of PBM) was achieved (P<0.001). CONCLUSIONS: Analysis of >1 million surgical patients showed that the non-inferiority condition (safety of Patient Blood Management) was fulfilled, and PBM was superior with respect to red blood cell transfusion. CLINICAL TRIAL REGISTRATION: NCT02147795.

Association of anaemia, co-morbidities and red blood cell transfusion according to age groups: multicentre sub-analysis of the German Patient Blood Management Network Registry.

BACKGROUND: Blood transfusions are common medical procedures and every age group requires detailed insights and treatment bundles. The aim of this study was to examine the association of anaemia, co-morbidities, complications, in-hospital mortality, and transfusion according to age groups to identify patient groups who are particularly at risk when undergoing surgery. METHODS: Data from 21 Hospitals of the Patient Blood Management Network Registry were analysed. Patients were divided into age subgroups. The incidence of preoperative anaemia, co-morbidities, surgical disciplines, hospital length of stay, complications, in-hospital mortality rate, and transfusions were analysed by descriptive and multivariate regression analysis. RESULTS: A total of 1 117 919 patients aged 18-108 years were included. With increasing age, the number of co-morbidities and incidence of preoperative anaemia increased. Complications, hospital length of stay, and in-hospital mortality increased with age and were higher in patients with preoperative anaemia. The mean number of transfused red blood cells (RBCs) peaked, whereas the transfusion rate increased continuously. Multivariate regression analysis showed that increasing age, co-morbidities, and preoperative anaemia were independent risk factors for complications, longer hospital length of stay, in-hospital mortality, and the need for RBC transfusion. CONCLUSION: Increasing age, co-morbidities, and preoperative anaemia are independent risk factors for complications, longer hospital length of stay, in-hospital mortality, and the need for RBC transfusion. Anaemia diagnosis and treatment should be established in all patients.

Comparison of oscillometric, non-invasive and invasive arterial pressure monitoring in patients undergoing laparoscopic bariatric surgery - a secondary analysis of a prospective observational study.

BACKGROUND: Oscillometric, non-invasive blood pressure measurement (NIBP) is the first choice of blood pressure monitoring in the majority of low and moderate risk surgeries. In patients with morbid obesity, however, it is subject to several limitations. The aim was to compare arterial pressure monitoring by NIBP and a non-invasive finger-cuff technology (Nexfin®) with the gold-standard invasive arterial pressure (IAP). METHODS: In this secondary analysis of a prospective observational, single centre cohort study, systolic (SAP), diastolic (DAP) and mean arterial pressure (MAP) were measured at 16 defined perioperative time points including posture changes, fluid bolus administration and pneumoperitoneum (PP) in patients undergoing laparoscopic bariatric surgery. Absolute arterial pressures by NIBP, Nexfin® and IAP were compared using correlation and Bland Altman analyses. Interchangeability was defined by a mean difference ≤ 5 mmHg (SD ≤8 mmHg). Percentage error (PE) was calculated as an additional statistical estimate. For hemodynamic trending, concordance rates were analysed according to the Critchley criterion. RESULTS: Sixty patients (mean body mass index of 49.2 kg/m2) were enrolled and data from 56 finally analysed. Pooled blood pressure values of all time points showed a significant positive correlation for both NIPB and Nexfin® versus IAP. Pooled PE for NIBP versus IAP was 37% (SAP), 35% (DAP) and 30% (MAP), for Nexfin versus IAP 23% (SAP), 26% (DAP) and 22% (MAP). Correlation of MAP was best and PE lowest before induction of anesthesia for NIBP versus IAP (r = 0.72; PE 24%) and after intraoperative fluid bolus administration for Nexfin® versus IAP (r = 0.88; PE: 17.2%). Concordance of MAP trending was 90% (SAP 85%, DAP 89%) for NIBP and 91% (SAP 90%, DAP 86%) for Nexfin®. MAP trending was best during intraoperative ATP positioning for NIBP (97%) and at induction of anesthesia for Nexfin® (97%). CONCLUSION: As compared with IAP, interchangeability of absolute pressure values could neither be shown for NIBP nor Nexfin®, however, NIBP showed poorer overall correlation and precision. Overall trending ability was generally high with Nexfin® surpassing NIBP. Nexfin® may likely render individualized decision-making in the management of different hemodynamic stresses during laparoscopic bariatric surgery, particularly where NIBP cannot be reliably established. TRIAL REGISTRATION: The non-interventional, observational study was registered retrospectively at ( NCT03184285 ) on June 12, 2017.

Prospective, randomized, controlled, double-blind, multi-center, multinational study on the safety and efficacy of 6% Hydroxyethyl starch (HES) sOlution versus an Electrolyte solutioN In patients undergoing eleCtive abdominal Surgery: study protocol for the PHOENICS study.

BACKGROUND: Hydroxyethyl starch (HES) solutions are used for volume therapy to treat hypovolemia due to acute blood loss and to maintain hemodynamic stability. This study was requested by the European Medicines Agency (EMA) to provide more evidence on the long-term safety and efficacy of HES solutions in the perioperative setting. METHODS: PHOENICS is a randomized, controlled, double-blind, multi-center, multinational phase IV (IIIb) study with two parallel groups to investigate non-inferiority regarding the safety of a 6% HES 130 solution (Volulyte 6%, Fresenius Kabi, Germany) compared with a crystalloid solution (Ionolyte, Fresenius Kabi, Germany) for infusion in patients with acute blood loss during elective abdominal surgery. A total of 2280 eligible patients (male and female patients willing to participate, with expected blood loss ≥ 500 ml, aged > 40 and ≤ 85 years, and ASA Physical status II-III) are randomly assigned to receive either HES or crystalloid solution for the treatment of hypovolemia due to surgery-induced acute blood loss in hospitals in up to 11 European countries. The dosing of investigational products (IP) is individualized to patients' volume needs and guided by a volume algorithm. Patients are treated with IP for maximally 24 h or until the maximum daily dose of 30 ml/kg body weight is reached. The primary endpoint is the treatment group mean difference in the change from the pre-operative baseline value in cystatin-C-based estimated glomerular filtration rate (eGFR), to the eGFR value calculated from the highest cystatin-C level measured during post-operative days 1-3. Further safety and efficacy parameters include, e.g., combined mortality/major post-operative complications until day 90, renal function, coagulation, inflammation, hemodynamic variables, hospital length of stay, major post-operative complications, and 28-day, 90-day, and 1-year mortality. DISCUSSION: The study will provide important information on the long-term safety and efficacy of HES 130/0.4 when administered according to the approved European product information. The results will be relevant for volume therapy of surgical patients. TRIAL REGISTRATION: EudraCT 2016-002162-30 . ClinicalTrials.gov NCT03278548.

Preoperative Predictors of Adverse Clinical Outcome in Emergent Repair of Acute Type A Aortic Dissection in 15 Year Follow Up.

BACKGROUND: Acute type A aortic dissection (AAAD) has high mortality. Improvements in surgical technique have lowered mortality but postoperative functional status and decreased quality of life due to debilitating deficits remain of concern. Our study aims to identify preoperative conditions predictive of undesirable outcome to help guide perioperative management. METHODS: We performed retrospective analysis of 394 cases of AAAD who underwent repair in our institution between 2001 and 2018. A combined endpoint of parameters was defined as (1) 30-day versus hospital mortality, (2) new neurological deficit, (3) new acute renal insufficiency requiring postoperative renal replacement, and (4) prolonged mechanical ventilation with need for tracheostomy. RESULTS: Total survival/ follow-up time averaged 3.2 years with follow-up completeness of 94%. Endpoint was reached by 52.8%. Those had higher EuroSCORE II (7.5 versus 5.5), higher incidence of coronary artery disease (CAD) (9.2% versus 3.2%), neurological deficit (ND) upon presentation (26.4% versus 11.8%), cardiopulmonary resuscitation (CPR) (14.4% versus 1.6%) and intubation (RF) before surgery (16.9% versus 4.8%). 7-day mortality was 21.6% versus 0%. Hospital mortality 30.8% versus 0%. CONCLUSIONS: This 15-year follow up shows, that unfavorable postoperative clinical outcome is related to ND, CAD, CPR and RF on arrival.

High-dose spironolactone lacks effectiveness in treatment of fibromyalgia (RCT).

BACKGROUND: Spironolactone (SPL) is a reversible mineralocorticoid receptor (MR) and androgen receptor (AR) antagonist which attracts pharmacotherapeutic interest not only because of its beneficial effects in heart failure but also because of the pathogenetic roles of MR and AR activities in neuropsychiatric diseases. Recently, beneficial and rapid-onset effects of SPL have been documented in a case series of women with fibromyalgia syndrome (FMS). To reaffirm this observation, we performed a double-blind placebo-controlled randomized clinical trial (RCT). METHODS: A total of 69 patients were screened, 56 patients were eligible and randomized to SPL or placebo (each n = 28). Forty-three patients completed the clinical trial to the last visit (n = 21 and n = 22). After a run-in phase of 50 and 100 mg/day, 200 mg/day SPL or placebo were applied between days 7 and 28. Primary outcome was the change in the FIQ-G score (Fibromyalgia Impact Questionnaire, German version). Secondary outcome parameters were the changes in pain (numeric rating scale, NRS), mood (ADS), quality of life (SF-36) and change in FIQ scores 14 days after the end of the medication. RESULTS: SPL of 200 mg/day did not change significantly either the primary or the secondary end points. SPL evoked a transient rise in serum potassium and a transient fall in GFR maximal after 2 weeks, but without clinical relevance. CONCLUSIONS: SPL at 200 mg/day does not improve symptoms in women with FMS, but was considered not to cause harm. SIGNIFICANCE: The mineralocorticoid receptor and androgen receptor antagonist spironolactone is repeatedly tested for its therapeutic effectivity against neuropsychiatric disorders. The present RCT demonstrated that 200 mg spironolactone does not change the symptoms of the fibromyalgia syndrome (FMS) in adult women. Between 2 and 4 weeks, spironolactone evokes a transient decrease in GFR and increase in serum potassium. Spironolactone cannot be recommended for the treatment of FMS.

Comparison of adequacy of anaesthesia monitoring with standard clinical practice monitoring during routine general anaesthesia: An international, multicentre, single-blinded randomised controlled trial.

BACKGROUND: Previous studies have suggested that monitoring the levels of both hypnosis and antinociception could reduce periods of inadequate anaesthesia. However, the evidence regarding associated benefits of this monitoring is still limited. OBJECTIVE: The primary objective of this study was to confirm that guidance of anaesthesia by depth of hypnosis and antinociception monitoring decreases the number of inadequate anaesthesia events in comparison with standard clinical practice. DESIGN: A multicentre, single-blinded, randomised controlled trial. SETTING: The study was conducted in four European University hospitals in four different countries between December 2013 and November 2016. PATIENTS: The study population consisted of a total of 494 adult patients undergoing elective surgery requiring tracheal intubation. INTERVENTIONS: The patients were allocated to one of two groups. The first group was treated using Entropy for depth of hypnosis and surgical pleth index to determine depth of antinociception (adequacy of anaesthesia group; AoA group). The second group was monitored using standard monitoring alone (control group). Anaesthesia was conducted with target-controlled infusions of propofol and remifentanil. MAIN OUTCOME MEASURES: The primary outcome of the study was the number of total unwanted events for example signs of inadequately light or unintentionally deep anaesthesia. RESULTS: Evidence of inadequate anaesthesia had an incidence of around 0.7 events per patient in both groups with no difference between groups (P = 0.519). In the AoA group, the overall consumption of propofol was significantly reduced (6.9 vs. 7.5 mg kg h, P = 0.008) in comparison with the control group. The consumption of remifentanil was equal in both groups. The times to emergence [8.0 vs. 9.6 min (P = 0.005)] and full recovery in the postanaesthesia care unit (P = 0.043) were significantly shorter in the AoA group. No differences were seen in postoperative pain scores or in the use of analgesics. CONCLUSION: In the current study, the guidance of total intravenous anaesthesia by Entropy and surgical pleth index in comparison with standard monitoring alone was not able to validate reduction of unwanted anaesthesia events. However, there was a reduction in the use of propofol, and shorter times for emergence and time spent in the postanaesthesia care unit. TRIAL REGISTRATION: at ClinicalTrials.gov NCT01928875.

Continuous noninvasive monitoring of arterial pressure using the vascular unloading technique in comparison to the invasive gold standard in elderly comorbid patients: A prospective observational study.

BACKGROUND AND AIMS: Elderly patients aged ≥65 years represent a growing population in the perioperative field, particularly orthopedic and vascular surgery. The higher degree of age-related or comorbid-dependent vascular alterations renders these patients at risk for hemodynamic complications and likely denote a possible limitation for modern, non-invasive arterial pressure monitoring devices. The aim was to compare vascular unloading technique-derived to invasive measurements of systolic (SAP), diastolic (DAP), and mean arterial pressure (MAP) in elderly perioperative patients. METHODS: This prospective observational study included patients aged ≥65 years scheduled for orthopedic and patients ≥50 years with peripheral artery disease Fontaine stage ≥ II scheduled for vascular surgery, respectively. Invasive radial artery and non-invasive finger-cuff (Nexfin system) arterial pressures were recorded before and after induction of general anesthesia and during surgery. Correlation, Bland-Altman, and concordance analyses were performed. Measurements of arterial pressure were also compared during intraoperative hypotension (MAP <70 mm Hg) and hypertension (MAP >105 mm Hg). RESULTS: Sixty patients with orthopedic (N = 25, mean (SD) age 77 (5) years) and vascular surgery (N = 35, age 69 [10] years) were enrolled. Seven hundred data pairs of all patients were analysed and pooled bias and percentage error were: SAP: 14.43 mm Hg, 43.79%; DAP: -2.40 mm Hg, 53.78% and MAP: 1.73 mm Hg, 45.05%. Concordance rates were 84.01% for SAP, 77.87% for DAP, and 86.47% for MAP. Predefined criteria for interchangeability of absolute and trending values could neither be reached in the overall nor in the subgroup analyses orthopedic vs vascular surgery. During hypertension, percentage error was found to be lowest for all pressure values, still not reaching predefined criteria. CONCLUSION: Arterial pressure monitoring with the vascular unloading technique did not reach criteria of interchangeability for absolute and trending values. Nevertheless, the putatively beneficial use of noninvasive arterial pressure measurements should be further evaluated in the elderly perioperative patient.

Perioperative non-invasive versus semi-invasive cardiac index monitoring in patients with bariatric surgery - a prospective observational study.

BACKGROUND: In morbidly obese patients undergoing laparoscopic bariatric surgery, the combination of obesity-related comorbidities, pneumoperitoneum and extreme posture changes constitutes a high risk of perioperative hemodynamic complications. Thus, an advanced hemodynamic monitoring including continuous cardiac index (CI) assessment is desirable. While invasive catheterization may bear technical difficulties, transesophageal echocardiography is contraindicated due to the surgical procedure. Evidence on the clinical reliability of alternative semi- or non-invasive cardiac monitoring devices is limited. The aim was to compare the non-invasive vascular unloading to a semi-invasive pulse contour analysis reference technique for continuous CI measurements in bariatric surgical patients. METHODS: This prospective observational study included adult patients scheduled for elective, laparoscopic bariatric surgery after obtained institutional ethics approval and written informed consent. CI measurements were performed using the vascular unloading technique (Nexfin®) and semi-invasive reference method (FloTrac™). At 10 defined measurement time points, the influence of clinically indicated body posture changes, passive leg raising, fluid bolus administration and pneumoperitoneum was evaluated pre- and intraoperatively. Correlation, Bland-Altman and concordance analyses were performed. RESULTS: Sixty patients (mean BMI 49.2 kg/m2) were enrolled into the study and data from 54 patients could be entered in the final analysis. Baseline CI was 3.2 ± 0.9 and 3.3 ± 0.8 l/min/m2, respectively. Pooled absolute CI values showed a positive correlation (rs = 0.76, P < 0.001) and mean bias of of - 0.16 l/min/m2 (limits of agreement: - 1.48 to 1.15 l/min/m2) between the two methods. Pooled percentage error was 56.51%, missing the criteria of interchangeability (< 30%). Preoperatively, bias ranged from - 0.33 to 0.08 l/min/m2 with wide limits of agreement. Correlation of CI was best (rs = 0.82, P < 0.001) and percentage error lowest (46.34%) during anesthesia and after fluid bolus administration. Intraoperatively, bias ranged from - 0.34 to - 0.03 l/min/m2 with wide limits of agreement. CI measurements correlated best during pneumoperitoneum and after fluid bolus administration (rs = 0.77, P < 0.001; percentage error 35.95%). Trending ability for all 10 measurement points showed a concordance rate of 85.12%, not reaching the predefined Critchley criterion (> 92%). CONCLUSION: Non-invasive as compared to semi-invasive CI measurements did not reach criteria of interchangeability for monitoring absolute and trending values of CI in morbidly obese patients undergoing bariatric surgery. TRIAL REGISTRATION: The study was registered retrospectively on June 12, 2017 with the registration number NCT03184272 .

The Extended Postoperative Care-Score (EXPO-Score)-An Objective Tool for Early Identification of Indication for Extended Postoperative Care.

Extended postoperative care and intensive care unit capacity is limited and efficient patient allocation is mandatory. This study aims to develop an effective yet simple score to predict indication for extended postoperative care, as there is a lack of objective criteria for early prediction of admission to extended care in surgical patients. This prospective observational study was divided into two periods (Period 1: Extended Postoperative Care-Score (EXPO)-Score generation; Period 2: EXPO-Score validation) and it was performed at a tertiary university center in Germany. A total of 4042 (Period 1) and 2198 (Period 2) adult patients ≥ 18 years old receiving elective or emergency surgery were included in this study. After identifying patient- and surgery-related risk factors by an expert panel, the EXPO-Score was developed through logistic regression from data of Period 1 and validated in Period 2. Three risk factors are sufficient for generating a reliable predictive EXPO-Score: (1) the American Society of Anesthesiologists' (ASA) physical status, (2) cardiopulmonary physical exercise status expressed in metabolic equivalents (MET), and (3) the type of surgery. The score threshold (0.23) has a sensitivity of 0.87, a specificity of 0.91, and an accuracy of 0.90 for predicting indication for extended postoperative care. The EXPO-Score provides a validated, early collectable, and easy-to-use tool for predicting indication of extended postoperative care in adult surgical patients.

Remote ischemic preconditioning attenuates intestinal mucosal damage: insight from a rat model of ischemia-reperfusion injury.

BACKGROUND: Remote ischemic preconditioning (RIPC) is a phenomenon, whereby repeated, non-lethal episodes of ischemia to an organ or limb exert protection against ischemia-reperfusion (I/R) injury in distant organs. Despite intensive research, there is still an apparent lack of knowledge concerning the RIPC-mediated mechanisms, especially in the intestine. Aim of this study was to evaluate possible protective effects RIPC on intestinal I/R injury. METHODS: Thirty rats were randomly assigned to four groups: I/R; I/R + RIPC; Sham; Sham + RIPC. Animals were anesthetized and the superior mesenteric artery was clamped for 30 min, followed by 60 min of reperfusion. RIPC-treated rats received 3 × 5 min of bilateral hindlimb I/R prior to surgery, sham groups obtained laparotomy without clamping. After I/R injury serum/tissue was analyzed for: Mucosal damage, Caspase-3/7 activity, expression of cell stress proteins, hydrogen peroxide (H2O2) and malondialdehyde (MDA) production, Hypoxia-inducible factor-1α (HIF-1α) protein expression and matrix metalloproteinase (MMP) activity. RESULTS: Intestinal I/R resulted in increased mucosal injury (P < 0.001) and elevated Caspase-3/7 activity (P < 0.001). RIPC significantly reduced the histological signs of intestinal I/R injury (P < 0.01), but did not affect Caspase-3/7 activity. Proteome profiling suggested a RIPC-mediated regulation of several cell stress proteins after I/R injury: Cytochrome C (+ 157%); Cited-2 (- 39%), ADAMTS1 (+ 74%). Serum concentrations of H2O2 and MDA remained unchanged after RIPC, while the reduced intestinal injury was associated with increased HIF-1α levels. Measurements of MMP activities in serum and intestinal tissue revealed an attenuated gelatinase activity at 130 kDa within the serum samples (P < 0.001) after RIPC, while the activity of MMPs within the intestinal tissue was not affected by I/R injury or RIPC. CONCLUSIONS: RIPC ameliorates intestinal I/R injury in rats. The underlying mechanisms may involve HIF-1α protein expression and a decreased serum activity of a 130 kDa factor with gelatinase activity.

Liberal transfusion strategy to prevent mortality and anaemia-associated, ischaemic events in elderly non-cardiac surgical patients - the study design of the LIBERAL-Trial.

BACKGROUND: Perioperative anaemia leads to impaired oxygen supply with a risk of vital organ ischaemia. In healthy and fit individuals, anaemia can be compensated by several mechanisms. Elderly patients, however, have less compensatory mechanisms because of multiple co-morbidities and age-related decline of functional reserves. The purpose of the study is to evaluate whether elderly surgical patients may benefit from a liberal red blood cell (RBC) transfusion strategy compared to a restrictive transfusion strategy. METHODS: The LIBERAL Trial is a prospective, randomized, multicentre, controlled clinical phase IV trial randomising 2470 elderly (≥ 70 years) patients undergoing intermediate- or high-risk non-cardiac surgery. Registered patients will be randomised only if Haemoglobin (Hb) reaches ≤9 g/dl during surgery or within 3 days after surgery either to the LIBERAL group (transfusion of a single RBC unit when Hb ≤ 9 g/dl with a target range for the post-transfusion Hb level of 9-10.5 g/dl) or the RESTRICTIVE group (transfusion of a single RBC unit when Hb ≤ 7.5 g/dl with a target range for the post-transfusion Hb level of 7.5-9 g/dl). The intervention per patient will be followed until hospital discharge or up to 30 days after surgery, whichever occurs first. The primary efficacy outcome is defined as a composite of all-cause mortality, acute myocardial infarction, acute ischaemic stroke, acute kidney injury (stage III), acute mesenteric ischaemia and acute peripheral vascular ischaemia within 90 days after surgery. Infections requiring iv antibiotics with re-hospitalisation are assessed as important secondary endpoint. The primary endpoint will be analysed by logistic regression adjusting for age, cancer surgery (y/n), type of surgery (intermediate- or high-risk), and incorporating centres as random effect. DISCUSSION: The LIBERAL-Trial will evaluate whether a liberal transfusion strategy reduces the occurrence of major adverse events after non-cardiac surgery in the geriatric population compared to a restrictive strategy within 90 days after surgery. TRIAL REGISTRATION: ClinicalTrials.gov (identifier: NCT03369210 ).

Genome-wide association study of myocardial infarction, atrial fibrillation, acute stroke, acute kidney injury and delirium after cardiac surgery - a sub-analysis of the RIPHeart-Study.

BACKGROUND: The aim of our study was the identification of genetic variants associated with postoperative complications after cardiac surgery. METHODS: We conducted a prospective, double-blind, multicenter, randomized trial (RIPHeart). We performed a genome-wide association study (GWAS) in 1170 patients of both genders (871 males, 299 females) from the RIPHeart-Study cohort. Patients undergoing non-emergent cardiac surgery were included. Primary endpoint comprises a binary composite complication rate covering atrial fibrillation, delirium, non-fatal myocardial infarction, acute renal failure and/or any new stroke until hospital discharge with a maximum of fourteen days after surgery. RESULTS: A total of 547,644 genotyped markers were available for analysis. Following quality control and adjustment for clinical covariate, one SNP reached genome-wide significance (PHLPP2, rs78064607, p = 3.77 × 10- 8) and 139 (adjusted for all other outcomes) SNPs showed promising association with p < 1 × 10- 5 from the GWAS. CONCLUSIONS: We identified several potential loci, in particular PHLPP2, BBS9, RyR2, DUSP4 and HSPA8, associated with new-onset of atrial fibrillation, delirium, myocardial infarction, acute kidney injury and stroke after cardiac surgery. TRIAL REGISTRATION: The study was registered with ClinicalTrials.gov NCT01067703, prospectively registered on 11 Feb 2010.

RIPHeart (Remote Ischemic Preconditioning for Heart Surgery) Study: Myocardial Dysfunction, Postoperative Neurocognitive Dysfunction, and 1 Year Follow-Up.

BACKGROUND: Remote ischemic preconditioning (RIPC) has been suggested to protect against certain forms of organ injury after cardiac surgery. Previously, we reported the main results of RIPHeart (Remote Ischemic Preconditioning for Heart Surgery) Study, a multicenter trial randomizing 1403 cardiac surgery patients receiving either RIPC or sham-RIPC. METHODS AND RESULTS: In this follow-up paper, we present 1-year follow-up of the composite primary end point and its individual components (all-cause mortality, myocardial infarction, stroke and acute renal failure), in a sub-group of patients, intraoperative myocardial dysfunction assessed by transesophageal echocardiography and the incidence of postoperative neurocognitive dysfunction 5 to 7 days and 3 months after surgery. RIPC neither showed any beneficial effect on the 1-year composite primary end point (RIPC versus sham-RIPC 16.4% versus 16.9%) and its individual components (all-cause mortality [3.4% versus 2.5%], myocardial infarction [7.0% versus 9.4%], stroke [2.2% versus 3.1%], acute renal failure [7.0% versus 5.7%]) nor improved intraoperative myocardial dysfunction or incidence of postoperative neurocognitive dysfunction 5 to 7 days (67 [47.5%] versus 71 [53.8%] patients) and 3 months after surgery (17 [27.9%] versus 18 [27.7%] patients), respectively. CONCLUSIONS: Similar to our main study, RIPC had no effect on intraoperative myocardial dysfunction, neurocognitive function and long-term outcome in cardiac surgery patients undergoing propofol anesthesia. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01067703.

Immobilization during anesthesia for vitrectomy using a laryngeal mask without neuromuscular blockade versus endotracheal intubation and neuromuscular blockade.

BACKGROUND: For intraocular surgery, most authors recommend general anesthesia including intubation and neuromuscular blockade to avoid complications by patient movements. However, anesthesia using a laryngeal mask and avoidance of muscle relaxants is common clinical practice. Purpose of this prospective observational study was to compare the incidence of eye movement and deviation of the eye axis during general anesthesia adjusted to minimal alveolar concentration (MAC) for pars plana-vitrectomy (PPV) using a laryngeal mask without neuromuscular blockade (LM) versus endotracheal intubation and neuromuscular blockade (INT). METHODS: The patients (N.=148) who underwent PPV for vitreoretinal disorders received MAC adjusted general anesthesia by volatile anesthetics. Seventy-four patients were subjected to LM and 74 to INT. In both groups the patient's lungs were mechanically ventilated without allowing spontaneous ventilation. Eye movements and upward deviations were judged and documented during surgery. Postoperatively quality of immobilization was assessed by a standardized questionnaire. RESULTS: Intraoperative movements were not observed in either group. Upward eye deviation was observed in nine (12%) patients in the LM group, but not in patients in the INT group (0%; P=0.003). The standardized questionnaire revealed no clinically relevant difference in quality of immobilization between groups, especially eye deviations did not lead to any relevant surgical complications or difficulties. CONCLUSIONS: For PPV, MAC adjusted balanced anesthesia using a laryngeal mask without neuromuscular blockade was associated with more, but clinically irrelevant upward eye deviations and may be an alternative to intubation with neuromuscular blockade. However, adequate depth of anesthesia must be assured to avoid unwanted injuries during surgery.

Effect of Xenon Anesthesia Compared to Sevoflurane and Total Intravenous Anesthesia for Coronary Artery Bypass Graft Surgery on Postoperative Cardiac Troponin Release: An International, Multicenter, Phase 3, Single-blinded, Randomized Noninferiority Trial.

BACKGROUND: Ischemic myocardial damage accompanying coronary artery bypass graft surgery remains a clinical challenge. We investigated whether xenon anesthesia could limit myocardial damage in coronary artery bypass graft surgery patients, as has been reported for animal ischemia models. METHODS: In 17 university hospitals in France, Germany, Italy, and The Netherlands, low-risk elective, on-pump coronary artery bypass graft surgery patients were randomized to receive xenon, sevoflurane, or propofol-based total intravenous anesthesia for anesthesia maintenance. The primary outcome was the cardiac troponin I concentration in the blood 24 h postsurgery. The noninferiority margin for the mean difference in cardiac troponin I release between the xenon and sevoflurane groups was less than 0.15 ng/ml. Secondary outcomes were the safety and feasibility of xenon anesthesia. RESULTS: The first patient included at each center received xenon anesthesia for practical reasons. For all other patients, anesthesia maintenance was randomized (intention-to-treat: n = 492; per-protocol/without major protocol deviation: n = 446). Median 24-h postoperative cardiac troponin I concentrations (ng/ml [interquartile range]) were 1.14 [0.76 to 2.10] with xenon, 1.30 [0.78 to 2.67] with sevoflurane, and 1.48 [0.94 to 2.78] with total intravenous anesthesia [per-protocol]). The mean difference in cardiac troponin I release between xenon and sevoflurane was -0.09 ng/ml (95% CI, -0.30 to 0.11; per-protocol: P = 0.02). Postoperative cardiac troponin I release was significantly less with xenon than with total intravenous anesthesia (intention-to-treat: P = 0.05; per-protocol: P = 0.02). Perioperative variables and postoperative outcomes were comparable across all groups, with no safety concerns. CONCLUSIONS: In postoperative cardiac troponin I release, xenon was noninferior to sevoflurane in low-risk, on-pump coronary artery bypass graft surgery patients. Only with xenon was cardiac troponin I release less than with total intravenous anesthesia. Xenon anesthesia appeared safe and feasible.

Non-invasive hemodynamic optimization in major abdominal surgery: a feasibility study.

BACKGROUND: Today, most of the pre-emptive hemodynamic optimization algorithms are based on variables associated with invasive techniques like arterial cannulation. The non-invasive Nexfin™ technology is able to estimate continuous Cardiac Index (CI) and pulse pressure variation (PPV). However, the efficiency of an early goal directed therapy (EGDT) algorithm based on non-invasive variables has to be proven. The aim of our study was to investigate the feasibility of a non-invasive driven EGDT protocol and its impact on patient's outcome. METHODS: Seventy-nine patients (ASA II-III) undergoing elective major abdominal surgery were randomized to either study group (SG, N.=39) or control group (CG, N.=40). The SG was treated according to an algorithm based on non-invasive CI and PPV, whereas the CG received standard of care. Postoperative complications up to 28 days and length of hospital stay (LOS) in both groups were recorded. RESULTS: There was no significant difference between the groups regarding demographics, hemodynamic variables, preoperative risk scores and duration of surgery. The total amount of complications was higher in the CG (SG 94 vs. CG 132 complications, P=0.22) without reaching statistical significance. LOS revealed no difference between both groups (SG, 9 [7-15] vs. CG, 9 [7-15.25] days, P=0.82). We have seen no impact of the non-invasive optimization protocol with respect to postoperative mortality. CONCLUSIONS: In this patient collective, we could demonstrate the feasibility of a non-invasive approach for hemodynamic optimization. However, EGDT based on non-invasive variables was not able to significantly improve outcome.

Patient Blood Management is Associated With a Substantial Reduction of Red Blood Cell Utilization and Safe for Patient's Outcome: A Prospective, Multicenter Cohort Study With a Noninferiority Design.

OBJECTIVE: To determine whether the implementation of patient blood management (PBM) is effective to decrease the use of red blood cell without impairment of patient's safety. BACKGROUND: The World Health Organization encouraged all member states to implement PBM programs employing multiple combined strategies to increase and preserve autologous erythrocyte volume to minimize red blood cell transfusions. Data regarding safety issues are not sufficiently available. METHODS: In this prospective, multicenter study, surgical inpatients from four German University Hospitals were analyzed before (pre-PBM) and after the implementation of PBM. PBM program included multiple measures (ie, preoperative optimization of hemoglobin levels, blood-sparing techniques, and standardization of transfusion practice). Primary aim was to show noninferiority of the PBM cohort with a margin of 0.5%. Secondary endpoints included red blood cell utilization. RESULTS: A total of 129,719 patients discharged between July 2012 and June 2015 with different inclusion periods for pre-PBM (54,513 patients) and PBM (75,206 patients) were analyzed. The primary endpoint was 6.53% in the pre-PBM versus 6.34% in the PBM cohort. The noninferiority aim was achieved (P < 0.001). Incidence of acute renal failure decreased in the PBM cohort (2.39% vs 1.67%; P < 0.001, regression model). The mean number of red blood cell transfused per patient was reduced from 1.21 ±â€Š0.05 to 1.00 ±â€Š0.05 (relative change by 17%, P < 0.001). CONCLUSIONS: The data presented show that implementation of PBM with a more conscious handling of transfusion practice can be achieved even in large hospitals without impairment of patient's safety. Further studies should elucidate which PBM measures are most clinically and cost effective. TRIAL REGISTRATION: PBM-Study ClinicalTrials.gov, NCT01820949.