TREM2hi resident macrophages protect the septic heart by maintaining cardiomyocyte homeostasis.

Sepsis-induced cardiomyopathy (SICM) is common in septic patients with a high mortality and is characterized by an abnormal immune response. Owing to cellular heterogeneity, understanding the roles of immune cell subsets in SICM has been challenging. Here we identify a unique subpopulation of cardiac-resident macrophages termed CD163+RETNLA+ (Mac1), which undergoes self-renewal during sepsis and can be targeted to prevent SICM. By combining single-cell RNA sequencing with fate mapping in a mouse model of sepsis, we demonstrate that the Mac1 subpopulation has distinct transcriptomic signatures enriched in endocytosis and displays high expression of TREM2 (TREM2hi). TREM2hi Mac1 cells actively scavenge cardiomyocyte-ejected dysfunctional mitochondria. Trem2 deficiency in macrophages impairs the self-renewal capability of the Mac1 subpopulation and consequently results in defective elimination of damaged mitochondria, excessive inflammatory response in cardiac tissue, exacerbated cardiac dysfunction and decreased survival. Notably, intrapericardial administration of TREM2hi Mac1 cells prevents SICM. Our findings suggest that the modulation of TREM2hi Mac1 cells could serve as a therapeutic strategy for SICM.

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.

Do alterations in pulmonary vascular tone result in changes in central blood volumes? An experimental study.

BACKGROUND: The effects of selective pulmonary vascular tone alterations on cardiac preload have not been previously examined. Therefore, we evaluated whether changing pulmonary vascular tone either by hypoxia or the inhalation of aerosolized prostacyclin (PGI2) altered intrathoracic or pulmonary blood volume (ITBV, PBV, respectively), both as surrogate for left ventricular preload. Additionally, the mean systemic filling pressure analogue (Pmsa) and pressure for venous return (Pvr) were calculated as surrogate of right ventricular preload. METHODS: In a randomized controlled animal study in 6 spontaneously breathing dogs, pulmonary vascular tone was increased by controlled moderate hypoxia (FiO2 about 0.10) and decreased by aerosolized PGI2. Also, inhalation of PGI2 was instituted to induce pulmonary vasodilation during normoxia and hypoxia. PBV, ITBV and circulating blood volume (Vdcirc) were measured using transpulmonary thermo-dye dilution. Pmsa and Pvr were calculated post hoc. Either the Wilcoxon-signed rank test or Friedman ANOVA test was performed. RESULTS: During hypoxia, mean pulmonary artery pressure (PAP) increased from median [IQR] 12 [8-15] to 19 [17-25] mmHg (p < 0.05). ITBV, PBV and their ratio with Vdcirc remained unaltered, which was also true for Pmsa, Pvr and cardiac output. PGI2 co-inhalation during hypoxia normalized mean PAP to 13 (12-16) mmHg (p < 0.05), but left cardiac preload surrogates unaltered. PGI2 inhalation during normoxia further decreased mean PAP to 10 (9-13) mmHg (p < 0.05) without changing any of the other investigated hemodynamic variables. CONCLUSIONS: In spontaneously breathing dogs, changes in pulmonary vascular tone altered PAP but had no effect on cardiac output, central blood volumes or their relation to circulating blood volume, nor on Pmsa and Pvr. These observations suggest that cardiac preload is preserved despite substantial alterations in right ventricular afterload.

Clinical Evaluation of a High-fidelity Upper Arm Cuff to Measure Arterial Blood Pressure during Noncardiac Surgery.

BACKGROUND: In most patients having noncardiac surgery, blood pressure is measured with the oscillometric upper arm cuff method. Although the method is noninvasive and practical, it is known to overestimate intraarterial pressure in hypotension and to underestimate it in hypertension. A high-fidelity upper arm cuff incorporating a hydraulic sensor pad was recently developed. The aim of the present study was to investigate whether noninvasive blood pressure measurements with the new high-fidelity cuff correspond to invasive measurements with a femoral artery catheter, especially at low blood pressure. METHODS: Simultaneous measurements of blood pressure recorded from a femoral arterial catheter and from the high-fidelity upper arm cuff were compared in 110 patients having major abdominal surgery or neurosurgery. RESULTS: 550 pairs of blood pressure measurements (5 pairs per patient) were considered for analysis. For mean arterial pressure measurements, the average bias was 0 mmHg, and the precision was 3 mmHg. The Pearson correlation coefficient was 0.96 (P < 0.0001; 95% CI, 0.96 to 0.97), and the percentage error was 9%. Error grid analysis showed that the proportions of mean arterial pressure measurements done with the high-fidelity cuff method were 98.4% in zone A (no risk), 1.6% in zone B (low risk) and 0% in zones C, D, and E (moderate, significant, and dangerous risk, respectively). The high-fidelity cuff method detected mean arterial pressure values less than 65 mmHg with a sensitivity of 84% (95% CI, 74 to 92%) and a specificity of 97% (95% CI, 95% to 98%). To detect changes in mean arterial pressure of more than 5 mmHg, the concordance rate between the two methods was 99.7%. Comparable accuracy and precision were observed for systolic and diastolic blood pressure measurements. CONCLUSIONS: The new high-fidelity upper arm cuff method met the current international standards in terms of accuracy and precision. It was also very accurate to track changes in blood pressure and reliably detect severe hypotension during noncardiac surgery.

Sustained Immunoparalysis in Endotoxin-Tolerized Monocytic Cells.

Sepsis is associated with a strong inflammatory reaction triggering a complex and prolonged immune response. Septic patients have been shown to develop sustained immunosuppression due to a reduced responsiveness of leukocytes to pathogens. Changes in cellular metabolism of leukocytes have been linked to this phenomenon and contribute to the ongoing immunological derangement. However, the underlying mechanisms of these phenomena are incompletely understood. In cell culture models, we mimicked LPS tolerance conditions to provide evidence that epigenetic modifications account for monocyte metabolic changes which cause immune paralysis in restimulated septic monocytes. In detail, we observed differential methylation of CpG sites related to metabolic activity in human PBMCs 18 h after septic challenge. The examination of changes in immune function and metabolic pathways was performed in LPS-tolerized monocytic THP-1 cells. Passaged THP-1 cells, inheriting initial LPS challenge, presented with dysregulation of cytokine expression and oxygen consumption for up to 7 days after the initial LPS treatment. Proinflammatory cytokine concentrations of TNFα and IL1ß were significantly suppressed following a second LPS challenge (p < 0.001) on day 7 after first LPS stimulation. However, the analysis of cellular metabolism did not reveal any noteworthy alterations between tolerant and nontolerant THP-1 monocytes. No quantitative differences in ATP and NADH synthesis or participating enzymes of energy metabolism occurred. Our data demonstrate that the function and epigenetic modifications of septic and tolerized monocytes can be examined in vitro with the help of our LPS model. Changes in CpG site methylation and monocyte function point to a correlation between epigenetic modification in metabolic pathways and reduced monocyte function under postseptic conditions.

Differential modulation of endothelial cell function by fresh frozen plasma.

AIMS: In vivo studies suggest a positive influence of fresh frozen plasma (FFP) on endothelial properties and vascular barrier function, leading to improved outcomes in animal sepsis models as well as in major abdominal surgery. However, those effects are incompletely described. It was our aim to evaluate in vitro effects of FFP on endothelial key functions and to identify underlying mechanisms. MATERIALS AND METHODS: Human pulmonary microvascular endothelial cells (HPMECs) were prestimulated with LPS, followed by incubation with FFP. Permeability for FITC-dextran was assessed, and intercellular gap formation was visualized. NF-κB nuclear translocation and expression of pro-inflammatory, pro-adhesion, and leakage-related genes were evaluated, and monocyte adhesion to ECs was assessed. Intracellular cAMP levels as well as phosphorylation of functional proteins were analyzed. In patients undergoing major abdominal surgery, Syndecan-1 serum levels were assessed prior to and following FFP transfusion. KEY FINDINGS: Post-incubation of HPMVECs with FFP increased intracellular cAMP levels that had been decreased by preceding LPS stimulation. On one hand, this reduced endotoxin-mediated upregulation of IL-8, ICAM-1, VCAM-1, VEGF, and ANG-2. Impaired phosphorylation of functional proteins was restored, and intercellular cohesion and barrier function were rescued. On the other hand, NF-κB nuclear translocation as well as monocyte adhesion was markedly increased by the combination of LPS and FFP. Syndecan-1 serum levels were lower in surgery patients that were transfused with FFP compared to those that were not. SIGNIFICANCE: Our data provide evidence for a differential modulation of crucial endothelial properties by FFP, potentially mediated by elevation of intracellular cAMP levels.

Dynamic changes of angiopoietins and endothelial nitric oxide supply during fluid resuscitation for major gyn-oncological surgery: a prospective observation.

BACKGROUND: Despite goal-directed hemodynamic therapy, vascular function may deteriorate during surgery for advanced abdominal tumor masses. Fluid administration has been shown to be associated with distinct changes in serum levels of functional proteins. We sought to determine how serum total protein and angiopoietin (ANG) levels change during major abdominal tumor surgery. In addition, ex vivo endothelial nitric oxide synthase (eNOS) activation as well as NO bioavailability in vivo were assessed. METHODS: 30 patients scheduled for laparotomy for late-stage ovarian or uterine cancer were prospectively included. Advanced hemodynamic monitoring as well as protocol-driven goal-directed fluid optimization were performed. Total serum protein, ANG-1, -2, and soluble TIE2 were determined pre-, intra-, and postoperatively. Phosphorylation of eNOS was assessed in microvascular endothelial cells after incubation with patient serum, and microvascular reactivity was determined in vivo by near-infrared spectroscopy and arterial vascular occlusion. RESULTS: Cardiac output as well as preload gradually decreased during surgery and were associated with a median total fluid intake of 12.8 (9.7-15.4) mL/kg*h and a postoperative fluid balance of 6710 (4113-9271) mL. Total serum protein decreased significantly from baseline (66.5 (56.4-73.3) mg/mL) by almost half intraoperatively (42.7 (36.8-51.5) mg/mL, p < 0.0001) and remained at low level. While ANG-1 showed no significant dilutional change (baseline: 12.7 (11.9-13.9) ng/mL, postop.: 11.6 (10.8 -13.5) ng/mL, p = 0.06), serum levels of ANG-2 were even increased postoperatively (baseline: 2.2 (1.6-2.6) ng/mL vs. postop.: 3.4 (2.3-3.8) ng/mL, p < 0.0001), resulting in a significant shift in ANG-2 to ANG-1 ratio. Ex vivo phosphorylation of eNOS was decreased depending on increased ANG-2 levels and ANG-2/1 ratio (Spearman r = - 0.37, p = 0.007). In vivo, increased ANG-2 levels were associated with impaired capillary recruitment and NO bioavailability (Spearman r = - 0.83, p = 0.01). CONCLUSIONS: Fluid resuscitation-associated changes in serum vascular mediator profile during abdominal tumor surgery were accompanied by impaired eNOS activity ex vivo as well as reduced NO bioavailability in vivo. Our results may explain disturbed microvascular function in major surgery despite goal-directed hemodynamic optimization.

Accuracy of the non-invasive Tcore™ temperature monitoring system to measure body core temperature in abdominal surgery.

An accurate determination of body core temperature is crucial during surgery in order to avoid and treat hypothermia, which is associated with poor outcome. In a prospective observational study, we evaluated the suitability of the Tcore™ device (Drägerwerk AG & Co. KGaA, Lübeck, Germany)-a non-invasive thermometer-to accurately determine core body temperature. In patients undergoing surgery for ovarian cancer, core body temperature (CBT) was determined with the Tcore™ sensor attached to the forehead and compared with blood temperature (Tblood) as measured within the femoro-iliacal artery. Both temperatures were recorded every 10 s and the measurement error was calculated. 57,302 data pairs of CBT and Tblood were obtained in 22 patients. In a repeated-measurements version of the Bland and Altman test, a bias of - 0.02 °C and 95% limits of agreement of - 0.48 to 0.44 °C were calculated. In a population analysis, a median absolute error of 0 [- 0.1; + 0.1] °C, a bias of 0 [- 0.276; 0.271] % and an inaccuracy of 0.276 [0.274; 0.354] % was determined. Although the Tcore™ sensor was attached to the frontal skin, it provided an accurate measurement of core body temperature in the investigated intraoperative setting.

Network of Mediators for Vascular Inflammation and Leakage Is Dysbalanced during Cytoreductive Surgery for Late-Stage Ovarian Cancer.

BACKGROUND: Cytoreductive surgery (CS) in late-stage ovarian cancer patients is often challenging due to extensive volume shifts, and high fluid intake may provoke postoperative complications. Expression of vasoactive mediators is altered in cancer patients, which may affect systemic vascular function. We sought to assess how serum levels of vasoactive markers and mediators change during CS in ovarian cancer. METHODS: Following IRB approval and informed consent, pre- and postoperative serum samples were analyzed in 26 late-stage ovarian cancer patients using multiplex protein arrays and ELISA. RESULTS: The proinflammatory cytokines and chemokines IL-6, IL-8, and CCL2 were significantly elevated after 24 hrs compared to the baseline values, with IL-6 and IL-8 being most prominently increased. While ANGPT1 remained unchanged after surgery, its competitive antagonist ANGPT2 was significantly increased. In contrast, serum levels of the ANGPT receptor TIE2 were decreased to 0.6 of the baseline values. While VEGF-D, E-selectin, P-selectin, ICAM-1, and PECAM-1 remained unchanged, serum activity of both thrombomodulin and syndecan-1 was significantly increased following surgery. CONCLUSION: We identified a regulatory network of acute-phase reaction during CS in late-stage ovarian cancer. This suggests that IL-6 exerts positive regulation of other proinflammatory mediators and, by upregulating ANGPT2 and suppressing ANGPT1, induces a serum profile that promotes vascular leakage. This may contribute to the observed hemodynamic alterations during CS procedures.

Perioperative Quality Initiative consensus statement on preoperative blood pressure, risk and outcomes for elective surgery.

BACKGROUND: A multidisciplinary international working subgroup of the third Perioperative Quality Initiative consensus meeting appraised the evidence on the influence of preoperative arterial blood pressure and community cardiovascular medications on perioperative risk. METHODS: A modified Delphi technique was used, evaluating papers published in MEDLINE on associations between preoperative numerical arterial pressure values or cardiovascular medications and perioperative outcomes. The strength of the recommendations was graded by National Institute for Health and Care Excellence guidelines. RESULTS: Significant heterogeneity in study design, including arterial pressure measures and perioperative outcomes, hampered the comparison of studies. Nonetheless, consensus recommendations were that (i) preoperative arterial pressure measures may be used to define targets for perioperative management; (ii) elective surgery should not be cancelled based solely upon a preoperative arterial pressure value; (iii) there is insufficient evidence to support lowering arterial pressure in the immediate preoperative period to minimise perioperative risk; and (iv) there is insufficient evidence that any one measure of arterial pressure (systolic, diastolic, mean, or pulse) is better than any other for risk prediction of adverse perioperative events. CONCLUSIONS: Future research should define which preoperative arterial pressure values best correlate with adverse outcomes, and whether modifying arterial pressure in the preoperative setting will change the perioperative morbidity or mortality. Additional research should define optimum strategies for continuation or discontinuation of preoperative cardiovascular medications.

Post-anaesthesia pulmonary complications after use of muscle relaxants (POPULAR): a multicentre, prospective observational study.

BACKGROUND: Results from retrospective studies suggest that use of neuromuscular blocking agents during general anaesthesia might be linked to postoperative pulmonary complications. We therefore aimed to assess whether the use of neuromuscular blocking agents is associated with postoperative pulmonary complications. METHODS: We did a multicentre, prospective observational cohort study. Patients were recruited from 211 hospitals in 28 European countries. We included patients (aged ≥18 years) who received general anaesthesia for any in-hospital procedure except cardiac surgery. Patient characteristics, surgical and anaesthetic details, and chart review at discharge were prospectively collected over 2 weeks. Additionally, each patient underwent postoperative physical examination within 3 days of surgery to check for adverse pulmonary events. The study outcome was the incidence of postoperative pulmonary complications from the end of surgery up to postoperative day 28. Logistic regression analyses were adjusted for surgical factors and patients' preoperative physical status, providing adjusted odds ratios (ORadj) and adjusted absolute risk reduction (ARRadj). This study is registered with ClinicalTrials.gov, number NCT01865513. FINDINGS: Between June 16, 2014, and April 29, 2015, data from 22 803 patients were collected. The use of neuromuscular blocking agents was associated with an increased incidence of postoperative pulmonary complications in patients who had undergone general anaesthesia (1658 [7·6%] of 21 694); ORadj 1·86, 95% CI 1·53-2·26; ARRadj -4·4%, 95% CI -5·5 to -3·2). Only 2·3% of high-risk surgical patients and those with adverse respiratory profiles were anaesthetised without neuromuscular blocking agents. The use of neuromuscular monitoring (ORadj 1·31, 95% CI 1·15-1·49; ARRadj -2·6%, 95% CI -3·9 to -1·4) and the administration of reversal agents (1·23, 1·07-1·41; -1·9%, -3·2 to -0·7) were not associated with a decreased risk of postoperative pulmonary complications. Neither the choice of sugammadex instead of neostigmine for reversal (ORadj 1·03, 95% CI 0·85-1·25; ARRadj -0·3%, 95% CI -2·4 to 1·5) nor extubation at a train-of-four ratio of 0·9 or more (1·03, 0·82-1·31; -0·4%, -3·5 to 2·2) was associated with better pulmonary outcomes. INTERPRETATION: We showed that the use of neuromuscular blocking drugs in general anaesthesia is associated with an increased risk of postoperative pulmonary complications. Anaesthetists must balance the potential benefits of neuromuscular blockade against the increased risk of postoperative pulmonary complications. FUNDING: European Society of Anaesthesiology.

Improve hip fracture outcome in the elderly patient (iHOPE): a study protocol for a pragmatic, multicentre randomised controlled trial to test the efficacy of spinal versus general anaesthesia.

INTRODUCTION: Hip fracture surgery is associated with high in-hospital and 30-day mortality rates and serious adverse patient outcomes. Evidence from randomised controlled trials regarding effectiveness of spinal versus general anaesthesia on patient-centred outcomes after hip fracture surgery is sparse. METHODS AND ANALYSIS: The iHOPE study is a pragmatic national, multicentre, randomised controlled, open-label clinical trial with a two-arm parallel group design. In total, 1032 patients with hip fracture (>65 years) will be randomised in an intended 1:1 allocation ratio to receive spinal anaesthesia (n=516) or general anaesthesia (n=516). Outcome assessment will occur in a blinded manner after hospital discharge and inhospital. The primary endpoint will be assessed by telephone interview and comprises the time to the first occurring event of the binary composite outcome of all-cause mortality or new-onset serious cardiac and pulmonary complications within 30 postoperative days. In-hospital secondary endpoints, assessed via in-person interviews and medical record review, include mortality, perioperative adverse events, delirium, satisfaction, walking independently, length of hospital stay and discharge destination. Telephone interviews will be performed for long-term endpoints (all-cause mortality, independence in walking, chronic pain, ability to return home cognitive function and overall health and disability) at postoperative day 30±3, 180±45 and 365±60. ETHICS AND DISSEMINATION: iHOPE has been approved by the leading Ethics Committee of the Medical Faculty of the RWTH Aachen University on 14 March 2018 (EK 022/18). Approval from all other involved local Ethical Committees was subsequently requested and obtained. Study started in April 2018 with a total recruitment period of 24 months. iHOPE will be disseminated via presentations at national and international scientific meetings or conferences and publication in peer-reviewed international scientific journals. TRIAL REGISTRATION NUMBER: DRKS00013644; Pre-results.

Dabigatran in patients with myocardial injury after non-cardiac surgery (MANAGE): an international, randomised, placebo-controlled trial.

BACKGROUND: Myocardial injury after non-cardiac surgery (MINS) increases the risk of cardiovascular events and deaths, which anticoagulation therapy could prevent. Dabigatran prevents perioperative venous thromboembolism, but whether this drug can prevent a broader range of vascular complications in patients with MINS is unknown. The MANAGE trial assessed the potential of dabigatran to prevent major vascular complications among such patients. METHODS: In this international, randomised, placebo-controlled trial, we recruited patients from 84 hospitals in 19 countries. Eligible patients were aged at least 45 years, had undergone non-cardiac surgery, and were within 35 days of MINS. Patients were randomly assigned (1:1) to receive dabigatran 110 mg orally twice daily or matched placebo for a maximum of 2 years or until termination of the trial and, using a partial 2-by-2 factorial design, patients not taking a proton-pump inhibitor were also randomly assigned (1:1) to omeprazole 20 mg once daily, for which results will be reported elsewhere, or matched placebo to measure its effect on major upper gastrointestinal complications. Research personnel randomised patients through a central 24 h computerised randomisation system using block randomisation, stratified by centre. Patients, health-care providers, data collectors, and outcome adjudicators were masked to treatment allocation. The primary efficacy outcome was the occurrence of a major vascular complication, a composite of vascular mortality and non-fatal myocardial infarction, non-haemorrhagic stroke, peripheral arterial thrombosis, amputation, and symptomatic venous thromboembolism. The primary safety outcome was a composite of life-threatening, major, and critical organ bleeding. Analyses were done according to the intention-to-treat principle. This trial is registered with ClinicalTrials.gov, number NCT01661101. FINDINGS: Between Jan 10, 2013, and July 17, 2017, we randomly assigned 1754 patients to receive dabigatran (n=877) or placebo (n=877); 556 patients were also randomised in the omeprazole partial factorial component. Study drug was permanently discontinued in 401 (46%) of 877 patients allocated to dabigatran and 380 (43%) of 877 patients allocated to placebo. The composite primary efficacy outcome occurred in fewer patients randomised to dabigatran than placebo (97 [11%] of 877 patients assigned to dabigatran vs 133 [15%] of 877 patients assigned to placebo; hazard ratio [HR] 0·72, 95% CI 0·55-0·93; p=0·0115). The primary safety composite outcome occurred in 29 patients (3%) randomised to dabigatran and 31 patients (4%) randomised to placebo (HR 0·92, 95% CI 0·55-1·53; p=0·76). INTERPRETATION: Among patients who had MINS, dabigatran 110 mg twice daily lowered the risk of major vascular complications, with no significant increase in major bleeding. Patients with MINS have a poor prognosis; dabigatran 110 mg twice daily has the potential to help many of the 8 million adults globally who have MINS to reduce their risk of a major vascular complication [corrected]. FUNDING: Boehringer Ingelheim and Canadian Institutes of Health Research.

Electrocardiography-controlled central venous catheter tip positioning in patients with atrial fibrillation.

INTRODUCTION:: A significant increase of the p-wave of a real-time intracavitary electrocardiography is a reliable and safe method to confirm the central venous catheter tip position close to the atrium. However, conflicting data about the feasibility of electrocardiography exist in patients with atrial fibrillation. METHODS:: An observational prospective case-control cohort study was set up to study the feasibility and accuracy of the electrocardiography-controlled central venous catheter tip placement in 13 patients with atrial fibrillation versus 10 patients with sinus rhythm scheduled for elective surgery. Each intervention was crosschecked with ultrasound-guided positioning via right supraclavicular fossa view and chest radiography. Ultrasound-guided supraclavicular venipuncture of the right subclavian vein and guidewire advancement were performed. A B-mode view of the superior vena cava and the right pulmonary artery was obtained to visualize the J-tip of the guidewire. The central venous catheter was advanced over the guidewire and the electrocardiography was derived from the J-tip of the guidewire protruding from the central venous catheter tip. Electrocardiography was read for increased p- and atrial fibrillation waves, respectively, and insertion depth was compared with the ultrasound method. RESULTS:: Electrocardiography indicated significantly increasing fibrillation and p-waves, respectively, in all patients and ultrasound-guided central venous catheter positioning confirmed a tip position within the lower third of the superior vena cava. CONCLUSION:: Electrocardiography-guided central venous catheter tip positioning is a feasible real-time method for patients with atrial fibrillation. Combined with ultrasound, the electrocardiography-controlled central venous catheter placement may eliminate the need for postinterventional radiation exposure.

Effects of Intraoperative Fluid Management on Postoperative Outcomes: A Hospital Registry Study.

OBJECTIVE: Evaluate the dose-response relationship between intraoperative fluid administration and postoperative outcomes in a large cohort of surgical patients. BACKGROUND: Healthy humans may live in a state of fluid responsiveness without the need for fluid supplementation. Goal-directed protocols driven by such measures are limited in their ability to define the optimal fluid state during surgery. METHODS: This analysis of data on file included 92,094 adult patients undergoing noncardiac surgery with endotracheal intubation between 2007 and 2014 at an academic tertiary care hospital and two affiliated community hospitals. The primary exposure variable was total intraoperative volume of crystalloid and colloid administered. The primary outcome was 30-day survival. Secondary outcomes were respiratory complications within three postoperative days (pulmonary edema, reintubation, pneumonia, or respiratory failure) and acute kidney injury. Exploratory outcomes were postoperative length of stay and total cost of care. Our models were adjusted for patient-, procedure-, and anesthesia-related factors. RESULTS: A U-shaped association was observed between the volume of fluid administered intraoperatively and 30-day mortality, costs, and postoperative length of stay. Liberal fluid volumes (highest quintile of fluid administration practice) were significantly associated with respiratory complications whereas both liberal and restrictive (lowest quintile) volumes were significantly associated with acute kidney injury. Moderately restrictive volumes (second quintile) were consistently associated with optimal postoperative outcomes and were characterized by volumes approximately 40% less than traditional textbook estimates: infusion rates of approximately 6-7 mL/kg/hr or 1 L of fluid for a 3-hour case. CONCLUSIONS: Intraoperative fluid dosing at the liberal and restrictive margins of observed practice is associated with increased morbidity, mortality, cost, and length of stay.

Propofol Pharmacodynamics and Bispectral Index During Key Moments of Awake Craniotomy.

BACKGROUND: During awake craniotomy, the patient's language centers are identified by neurological testing requiring a fully awake and cooperative patient. Hence, anesthesia aims for an unconscious patient at the beginning and end of surgery but an awake and responsive patient in between. We investigated the plasma (Cplasma) and effect-site (Ceffect-site) propofol concentration as well as the related Bispectral Index (BIS) required for intraoperative return of consciousness and begin of neurological testing. MATERIALS AND METHODS: In 13 patients, arterial Cplasma were measured by high-pressure liquid chromatography and Ceffect-site was estimated based on the Marsh and Schnider pharmacokinetic/dynamic (pk/pd) models. The BIS, Cplasma and Ceffect-site were compared during the intraoperative awakening period at designated time points such as return of consciousness and start of the Boston Naming Test (neurological test). RESULTS: Return of consciousness occurred at a BIS of 77±7 (mean±SD) and a measured Cplasma of 1.2±0.4 µg/mL. The Marsh model predicted a significantly (P<0.001) higher Cplasma of 1.9±0.4 µg/mL as compared with the Schnider model (Cplasma=1.4±0.4 µg/mL) at return of consciousness. Neurological testing was possible as soon as the BIS had increased to 92±6 and measured Cplasma had decreased to 0.8±0.3 µg/mL. This translated into a time delay of 23±12 minutes between return of consciousness and begin of neurological testing. At begin of neurological testing, Cplasma according to Marsh (Cplasma=1.3±0.5 µg/mL) was significantly (P=0.002) higher as compared with the Schnider model (Cplasma=1.0±0.4 µg/mL). CONCLUSIONS: To perform intraoperative neurological testing, patients are required to be fully awake with plasma propofol concentrations as low as 0.8 µg/mL. Following our clinical setup, the Schnider pk/pd model estimates propofol concentrations significantly more accurate as compared with the Marsh model at this neurologically crucial time point.

The provision of pediatric cardiac anesthesia services in Germany: current status of structural and personnel organization.

BACKGROUND: Anesthesia for pediatric cardiac surgery requires a high level of expert knowledge. There are currently no recommendations and standards for anesthetic management for congenital cardiac surgery in Germany. AIM: The aim of the present study was to assess the current status of structural and personnel anesthetic standards at pediatric cardiac surgery centers in Germany. METHODS: All cardiac surgical centers in Germany were reviewed for an active program for congenital heart surgery. Centers with an active program were invited to respond to an online survey. The questionnaire containing 55 items in 16 categories assessed current practice in pediatric cardiac anesthesia. RESULTS: An active program for pediatric cardiac surgery was identified at 27 centers. The response rate to the survey was 96.3%. A specialized group of anesthesiologists for pediatric cardiac anesthesia was reported from 26 centers (92.3%). The mean size of this group was 4.8 anesthesiologists per center. However, the annual case load of centers and relative annual case load per specialized anesthesiologist varied considerably between 12.5 and 250. Nonanesthesiologists performed sedation and general anesthesia for diagnostic and therapeutic interventions outside the operating theater in children with congenital heart diseases in 24 centers (77%). Although special equipment, for example, pediatric TEE, near-infrared spectroscopy, and devices for mechanical auto transfusion were available in most centers, their routine use was not always part of standard operating procedures. The proposal for mean adequate training in pediatric cardiac anesthesia as estimated by the participating centers was 10.8 months. CONCLUSION: The present study represents the current structural situation for anesthesia at German pediatric cardiac surgery centers.