Adjustment of positive end-expiratory pressure to body mass index during mechanical ventilation in general anesthesia: BodyVent, a randomized controlled trial.

BACKGROUND: In patients requiring general anesthesia, lung-protective ventilation can prevent postoperative pulmonary complications, which are associated with higher morbidity, mortality, and prolonged hospital stay. Application of positive end-expiratory pressure (PEEP) is one component of lung-protective ventilation. The correct strategy for setting adequate PEEP, however, remains controversial. PEEP settings that lead to a lower pressure difference between end-inspiratory plateau pressure and end-expiratory pressure ("driving pressure," ΔP) may reduce the risk of postoperative pulmonary complications. Preliminary data suggests that the PEEP required to prevent both end-inspiratory overdistension and end-expiratory alveolar collapse, thereby reducing ΔP, correlates positively with the body mass index (BMI) of patients, with PEEP values corresponding to approximately 1/3 of patient's respective BMI. Thus, we hypothesize that adjusting PEEP according to patient BMI reduces ΔP and may result in less postoperative pulmonary complications. METHODS: Patients undergoing general anesthesia and endotracheal intubation with volume-controlled ventilation with a tidal volume of 7 ml per kg predicted body weight will be randomized and assigned to either an intervention group with PEEP adjusted according to BMI or a control group with a standardized PEEP of 5 mbar. Pre- and postoperatively, lung ultrasound will be performed to determine the lung aeration score, and hemodynamic and respiratory vital signs will be recorded for subsequent evaluation. The primary outcome is the difference in ΔP as a surrogate parameter for lung-protective ventilation. Secondary outcomes include change in lung aeration score, intraoperative occurrence of hemodynamic and respiratory events, oxygen requirements and postoperative pulmonary complications. DISCUSSION: The study results will show whether an intraoperative ventilation strategy with PEEP adjustment based on BMI has the potential of reducing the risk for postoperative pulmonary complications as an easy-to-implement intervention that does not require lengthy ventilator maneuvers nor additional equipment. TRIAL REGISTRATION: German Clinical Trials Register (DRKS), DRKS00031336. Registered 21st February 2023. TRIAL STATUS: The study protocol was approved by the ethics committee of the Christian-Albrechts-Universität Kiel, Germany, on 1st February 2023. Recruitment began in March 2023 and is expected to end in September 2023.

Pulmonary function testing in preoperative high-risk patients.

BACKGROUND: Postoperative respiratory failure is the most frequent complication in postsurgical patients. The purpose of this study is to assess whether pulmonary function testing in high-risk patients during preoperative assessment detects previously unknown respiratory impairments which may influence patient outcomes. METHODS: A targeted patient screening by spirometry and the measurement of the diffusing capacity of the lung for carbon monoxide (DLCO) was implemented in the anesthesia department of a tertiary university hospital. Patients of all surgical disciplines who were at least 75 years old or exhibited reduced exercise tolerance with the metabolic equivalent of task less than four (MET < 4) were examined. Clinical characteristics, history of lung diseases, and smoking status were also recorded. The statistical analysis entailed t-tests, one-way ANOVA, and multiple linear regression with backward elimination for group comparisons. RESULTS: Among 256 included patients, 230 fulfilled the test quality criteria. Eighty-one (35.2%) patients presented obstructive ventilatory disorders, out of which 65 were previously unknown. 38 of the newly diagnosed obstructive disorders were mild, 18 moderate, and 9 severe. One hundred forty-five DLCO measurements revealed 40 (27.6%) previously unknown gas exchange impairments; 21 were mild, 17 moderate, and 2 severe. The pulmonary function parameters of forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and DLCO were significantly lower than the international reference values of a healthy population. Patients with a lower ASA class and no history of smoking exhibited higher FVC, FEV1, and DLCO values. Reduced exercise tolerance with MET < 4 was strongly associated with lower spirometry values. CONCLUSIONS: Our screening program detected a relevant number of patients with previously unknown obstructive ventilatory disorders and impaired pulmonary gas exchange. This newly discovered sickness is associated with low metabolic equivalents and may influence perioperative outcomes. Whether optimized management of patients with previously unknown impaired lung function leads to a better outcome should be evaluated in multicenter studies. TRIAL REGISTRATION: German Registry of Clinical Studies (DRKS00029337), registered on: June 22nd, 2022.

Setting positive end-expiratory pressure by using electrical impedance tomography.

PURPOSE OF REVIEW: This review presents the principles and possibilities of setting positive end-expiratory pressure (PEEP) using electrical impedance tomography (EIT). It summarizes the major findings of recent studies where EIT was applied to monitor the effects of PEEP on regional lung function and to guide the selection of individualized PEEP setting. RECENT FINDINGS: The most frequent approach of utilizing EIT for the assessment of PEEP effects and the PEEP setting during the time period from January 2022 till June 2023 was based on the analysis of pixel tidal impedance variation, typically acquired during stepwise incremental and/or decremental PEEP variation. The most common EIT parameters were the fraction of ventilation in various regions of interest, global inhomogeneity index, center of ventilation, silent spaces, and regional compliance of the respiratory system. The studies focused mainly on the spatial and less on the temporal distribution of ventilation. Contrast-enhanced EIT was applied in a few studies for the estimation of ventilation/perfusion matching. SUMMARY: The availability of commercial EIT devices resulted in an increase in clinical studies using this bedside imaging technology in neonatal, pediatric and adult critically ill patients. The clinical interest in EIT became evident but the potential of this method in clinical decision-making still needs to be fully exploited.

Pressure- and time-dependent alveolar recruitment/derecruitment in a spatially resolved patient-specific computational model for injured human lungs.

We present a novel computational model for the dynamics of alveolar recruitment/derecruitment (RD), which reproduces the underlying characteristics typically observed in injured lungs. The basic idea is a pressure- and time-dependent variation of the stress-free reference volume in reduced dimensional viscoelastic elements representing the acinar tissue. We choose a variable reference volume triggered by critical opening and closing pressures in a time-dependent manner from a straightforward mechanical point of view. In the case of (partially and progressively) collapsing alveolar structures, the volume available for expansion during breathing reduces and vice versa, eventually enabling consideration of alveolar collapse and reopening in our model. We further introduce a method for patient-specific determination of the underlying critical parameters of the new alveolar RD dynamics when integrated into the tissue elements, referred to as terminal units, of a spatially resolved physics-based lung model that simulates the human respiratory system in an anatomically correct manner. Relevant patient-specific parameters of the terminal units are herein determined based on medical image data and the macromechanical behavior of the lung during artificial ventilation. We test the whole modeling approach for a real-life scenario by applying it to the clinical data of a mechanically ventilated patient. The generated lung model is capable of reproducing clinical measurements such as tidal volume and pleural pressure during various ventilation maneuvers. We conclude that this new model is an important step toward personalized treatment of ARDS patients by considering potentially harmful mechanisms-such as cyclic RD and overdistension-and might help in the development of relevant protective ventilation strategies to reduce ventilator-induced lung injury (VILI).

The role of PEEP for cannulation of the subclavian vein: A prospective observational study.

PURPOSE: The role of positive endexpiratory pressure (PEEP) for successful cannulation of the subclavian vein (SCV) remains inconclusive. The aim of our study was to assess the effect of different levels of PEEP on distance from SCV to parietal pleura (DVP) and on the cross-sectional area (CSA) of the SCV. METHODS: Invasive mechanically ventilated adult patients with a clinical indication for a stepwise PEEP-trial (0, 5, 10, and 15 cm H2O) were included in this prospective observational single-center study. Ultrasound examinations of SCV were performed with a linear ultrasound probe using the infraclavicular view. DVP and CSA were measured on the right and left bodyside. Examinations were repeated at each PEEP step. RESULTS: 27 patients were enrolled (12 female; 60±21 years; BMI 24.6±4.9 kg/m2; 20 patients on controlled, 7 on assisted ventilation). A statistically significant increase of DVP in the in-plane view was found on the left side which was not clinically relevant. No significant differences of DVP were observed in all other views. PEEP induced changes in CSAs were statistically significant but clinically not relevant on both sides. The largest change in CSA (2mm2) was observed when comparing PEEP 10 with PEEP 0 cm H2O. CONCLUSION: A stepwise PEEP increase was not associated with clinically relevant changes of the DVP and CSA. Thus, a PEEP-optimization for the cannulation of the subclavian vein is not indicated.

Recruitable alveolar collapse and overdistension during laparoscopic gynecological surgery and mechanical ventilation: a prospective clinical study.

BACKGROUND: Laparoscopic surgery in Trendelenburg position may impede mechanical ventilation (MV) due to positioning and high intra-abdominal pressure. We sought to identify the positive end-expiratory pressure (PEEP) levels necessary to counteract atelectasis formation ("Open-Lung-PEEP") and to provide an equal balance between overdistension and alveolar collapse ("Best-Compromise-PEEP"). METHODS: In 30 patients undergoing laparoscopic gynecological surgery, relative overdistension and alveolar collapse were assessed with electrical impedance tomography (EIT) during a decremental PEEP trial ranging from 20 to 4 cmH2O in supine position without capnoperitoneum and in Trendelenburg position with capnoperitoneum. RESULTS: In supine position, the median Open-Lung-PEEP was 12 (8-14) cmH2O with 8.7 (4.7-15.5)% of overdistension and 1.7 (0.4-2.2)% of collapse. Best-Compromise-PEEP was 8 (6.5-10) cmH2O with 4.2 (2.4-7.2)% of overdistension and 5.1 (3.9-6.5)% of collapse. In Trendelenburg position with capnoperitoneum, Open-Lung-PEEP was 18 (18-20) cmH 2 O (p < 0.0001 vs supine position) with 1.8 (0.5-3.9)% of overdistension and 0 (0-1.2)% of collapse and Best-Compromise-PEEP was 18 (16-20) cmH2O (p < 0.0001 vs supine position) with 1.5 (0.7-3.0)% of overdistension and 0.2 (0-2.7)% of collapse. Open-Lung-PEEP and Best-Compromise-PEEP were positively correlated with body mass index during MV in supine position but not in Trendelenburg position. CONCLUSION: The PEEP levels required for preventing alveolar collapse and for balancing collapse and overdistension in Trendelenburg position with capnoperitoneum were significantly higher than those required for achieving the same goals in supine position without capnoperitoneum. Even with high PEEP levels, alveolar overdistension was negligible during MV in Trendelenburg position with capnoperitoneum. TRIAL REGISTRATION: This study was prospectively registered at German Clinical Trials registry (DRKS00016974).

(1 → 3)-ß-D-Glucan-guided antifungal therapy in adults with sepsis: the CandiSep randomized clinical trial.

PURPOSE: To investigate whether (1 → 3)-ß-d-Glucan (BDG)-guidance shortens time to antifungal therapy and thereby reduces mortality of sepsis patients with high risk of invasive Candida infection (ICI). METHODS: Multicenter, randomized, controlled trial carried out between September 2016 and September 2019 in 18 intensive care units enrolling adult sepsis patients at high risk for ICI. Patients in the control group received targeted antifungal therapy driven by culture results. In addition to targeted therapy, patients in the BDG group received antifungals if at least one of two consecutive BDG samples taken during the first two study days was ≥ 80 pg/mL. Empirical antifungal therapy was discouraged in both groups. The primary endpoint was 28-day-mortality. RESULTS: 339 patients were enrolled. ICI was diagnosed in 48 patients (14.2%) within the first 96 h after enrollment. In the BDG-group, 48.8% (84/172) patients received antifungals during the first 96 h after enrollment and 6% (10/167) patients in the control group. Death until day 28 occurred in 58 of 172 patients (33.7%) in the BDG group and 51 of 167 patients (30.5%) in the control group (relative risk 1.10; 95% confidence interval, 0.80-1.51; p = 0.53). Median time to antifungal therapy was 1.1 [interquartile range (IQR) 1.0-2.2] days in the BDG group and 4.4 (IQR 2.0-9.1, p < 0.01) days in the control group. CONCLUSIONS: Serum BDG guided antifungal treatment did not improve 28-day mortality among sepsis patients with risk factors for but unexpected low rate of IC. This study cannot comment on the potential benefit of BDG-guidance in a more selected at-risk population.

Individualization of PEEP and tidal volume in ARDS patients with electrical impedance tomography: a pilot feasibility study.

BACKGROUND: In mechanically ventilated patients with acute respiratory distress syndrome (ARDS), electrical impedance tomography (EIT) provides information on alveolar cycling and overdistension as well as assessment of recruitability at the bedside. We developed a protocol for individualization of positive end-expiratory pressure (PEEP) and tidal volume (VT) utilizing EIT-derived information on recruitability, overdistension and alveolar cycling. The aim of this study was to assess whether the EIT-based protocol allows individualization of ventilator settings without causing lung overdistension, and to evaluate its effects on respiratory system compliance, oxygenation and alveolar cycling. METHODS: 20 patients with ARDS were included. Initially, patients were ventilated according to the recommendations of the ARDS Network with a VT of 6 ml per kg predicted body weight and PEEP adjusted according to the lower PEEP/FiO2 table. Subsequently, ventilator settings were adjusted according to the EIT-based protocol once every 30 min for a duration of 4 h. To assess global overdistension, we determined whether lung stress and strain remained below 27 mbar and 2.0, respectively. RESULTS: Prospective optimization of mechanical ventilation with EIT led to higher PEEP levels (16.5 [14-18] mbar vs. 10 [8-10] mbar before optimization; p = 0.0001) and similar VT (5.7 ± 0.92 ml/kg vs. 5.8 ± 0.47 ml/kg before optimization; p = 0.96). Global lung stress remained below 27 mbar in all patients and global strain below 2.0 in 19 out of 20 patients. Compliance remained similar, while oxygenation was significantly improved and alveolar cycling was reduced after EIT-based optimization. CONCLUSIONS: Adjustment of PEEP and VT using the EIT-based protocol led to individualization of ventilator settings with improved oxygenation and reduced alveolar cycling without promoting global overdistension. Trial registrationThis study was registered at clinicaltrials.gov (NCT02703012) on March 9, 2016 before including the first patient.

Adaptive mechanical ventilation with automated minimization of mechanical power-a pilot randomized cross-over study.

BACKGROUND: Adaptive mechanical ventilation automatically adjusts respiratory rate (RR) and tidal volume (VT) to deliver the clinically desired minute ventilation, selecting RR and VT based on Otis' equation on least work of breathing. However, the resulting VT may be relatively high, especially in patients with more compliant lungs. Therefore, a new mode of adaptive ventilation (adaptive ventilation mode 2, AVM2) was developed which automatically minimizes inspiratory power with the aim of ensuring lung-protective combinations of VT and RR. The aim of this study was to investigate whether AVM2 reduces VT, mechanical power, and driving pressure (ΔPstat) and provides similar gas exchange when compared to adaptive mechanical ventilation based on Otis' equation. METHODS: A prospective randomized cross-over study was performed in 20 critically ill patients on controlled mechanical ventilation, including 10 patients with acute respiratory distress syndrome (ARDS). Each patient underwent 1 h of mechanical ventilation with AVM2 and 1 h of adaptive mechanical ventilation according to Otis' equation (adaptive ventilation mode, AVM). At the end of each phase, we collected data on VT, mechanical power, ΔP, PaO2/FiO2 ratio, PaCO2, pH, and hemodynamics. RESULTS: Comparing adaptive mechanical ventilation with AVM2 to the approach based on Otis' equation (AVM), we found a significant reduction in VT both in the whole study population (7.2 ± 0.9 vs. 8.2 ± 0.6 ml/kg, p <  0.0001) and in the subgroup of patients with ARDS (6.6 ± 0.8 ml/kg with AVM2 vs. 7.9 ± 0.5 ml/kg with AVM, p <  0.0001). Similar reductions were observed for ΔPstat (whole study population: 11.5 ± 1.6 cmH2O with AVM2 vs. 12.6 ± 2.5 cmH2O with AVM, p <  0.0001; patients with ARDS: 11.8 ± 1.7 cmH2O with AVM2 and 13.3 ± 2.7 cmH2O with AVM, p = 0.0044) and total mechanical power (16.8 ± 3.9 J/min with AVM2 vs. 18.6 ± 4.6 J/min with AVM, p = 0.0024; ARDS: 15.6 ± 3.2 J/min with AVM2 vs. 17.5 ± 4.1 J/min with AVM, p = 0.0023). There was a small decrease in PaO2/FiO2 (270 ± 98 vs. 291 ± 102 mmHg with AVM, p = 0.03; ARDS: 194 ± 55 vs. 218 ± 61 with AVM, p = 0.008) and no differences in PaCO2, pH, and hemodynamics. CONCLUSIONS: Adaptive mechanical ventilation with automated minimization of inspiratory power may lead to more lung-protective ventilator settings when compared with adaptive mechanical ventilation according to Otis' equation. TRIAL REGISTRATION: The study was registered at the German Clinical Trials Register ( DRKS00013540 ) on December 1, 2017, before including the first patient.

Determination of respiratory system compliance during pressure support ventilation by small variations of pressure support.

In mechanically ventilated patients, measurement of respiratory system compliance (Crs) is of high clinical interest. Spontaneous breathing activity during pressure support ventilation (PSV) can impede the correct assessment of Crs and also alter the true Crs by inducing lung recruitment. We describe a method for determination of Crs during PSV and assess its accuracy in a study on 20 mechanically ventilated patients. To assess Crs during pressure support ventilation (Crs,PSV), we performed repeated changes in pressure support level by ± 2 cmH2O. Crs,PSV was calculated from the volume change induced by these changes in pressure support level, taking into account the inspiration time and the expiratory time constant. As reference methods, we used Crs, measured during volume controlled ventilation (Crs,VCV). In a post-hoc analysis, we assessed Crs during the last 20% of the volume-controlled inflation (Crs,VCV20). Values were compared by linear regression and Bland-Altman methods comparison. Comparing Crs,PSV to the reference value Crs,VCV, we found a coefficient of determination (r2) of 0.90, but a relatively high bias of - 7 ml/cm H2O (95% limits of agreement - 16.7 to + 2.7 ml/cmH2O). Comparison with Crs,VCV20 resulted in a negligible bias (- 1.3 ml/cmH2O, 95% limits of agreement - 13.9 to + 11.3) and r2 of 0.81. We conclude that the novel method provides an estimate of end-inspiratory Crs during PSV. Despite its limited accuracy, it might be useful for non-invasive monitoring of Crs in patients undergoing pressure support ventilation.

The effect of a novel extracorporeal cytokine hemoadsorption device on IL-6 elimination in septic patients: A randomized controlled trial.

OBJECTIVE: We report on the effect of hemoadsorption therapy to reduce cytokines in septic patients with respiratory failure. METHODS: This was a randomized, controlled, open-label, multicenter trial. Mechanically ventilated patients with severe sepsis or septic shock and acute lung injury or acute respiratory distress syndrome were eligible for study inclusion. Patients were randomly assigned to either therapy with CytoSorb hemoperfusion for 6 hours per day for up to 7 consecutive days (treatment), or no hemoperfusion (control). Primary outcome was change in normalized IL-6-serum concentrations during study day 1 and 7. RESULTS: 97 of the 100 randomized patients were analyzed. We were not able to detect differences in systemic plasma IL-6 levels between the two groups (n = 75; p = 0.15). Significant IL-6 elimination, averaging between 5 and 18% per blood pass throughout the entire treatment period was recorded. In the unadjusted analysis, 60-day-mortality was significantly higher in the treatment group (44.7%) compared to the control group (26.0%; p = 0.039). The proportion of patients receiving renal replacement therapy at the time of enrollment was higher in the treatment group (31.9%) when compared to the control group (16.3%). After adjustment for patient morbidity and baseline imbalances, no association of hemoperfusion with mortality was found (p = 0.19). CONCLUSIONS: In this patient population with predominantly septic shock and multiple organ failure, hemoadsorption removed IL-6 but this did not lead to lower plasma IL-6-levels. We did not detect statistically significant differences in the secondary outcomes multiple organ dysfunction score, ventilation time and time course of oxygenation.

Automated control of mechanical ventilation during general anaesthesia: study protocol of a bicentric observational study (AVAS).

INTRODUCTION: Automated control of mechanical ventilation during general anaesthesia is not common. A novel system for automated control of most of the ventilator settings was designed and is available on an anaesthesia machine. METHODS AND ANALYSIS: The 'Automated control of mechanical ventilation during general anesthesia study' (AVAS) is an international investigator-initiated bicentric observational study designed to examine safety and efficacy of the system during general anaesthesia. The system controls mechanical breathing frequency, inspiratory pressure, pressure support, inspiratory time and trigger sensitivity with the aim to keep a patient stable in user adoptable target zones. Adult patients, who are classified as American Society of Anesthesiologists physical status I, II or III, scheduled for elective surgery of the upper or lower limb or for peripheral vascular surgery in general anaesthesia without any additional regional anaesthesia technique and who gave written consent for study participation are eligible for study inclusion. Primary endpoint of the study is the frequency of specifically defined adverse events. Secondary endpoints are frequency of normoventilation, hypoventilation and hyperventilation, the time period between switch from controlled ventilation to assisted ventilation, achievement of stable assisted ventilation of the patient, proportion of time within the target zone for tidal volume, end-tidal partial pressure of carbon dioxide as individually set up for each patient by the user, frequency of alarms, frequency distribution of tidal volume, inspiratory pressure, inspiration time, expiration time, end-tidal partial pressure of carbon dioxide and the number of re-intubations. ETHICS AND DISSEMINATION: AVAS will be the first clinical study investigating a novel automated system for the control of mechanical ventilation on an anaesthesia machine. The study was approved by the ethics committees of both participating study sites. In case that safety and efficacy are acceptable, a randomised controlled trial comparing the novel system with the usual practice may be warranted. TRIAL REGISTRATION: DRKS DRKS00011025, registered 12 October 2016; clinicaltrials.gov ID. NCT02644005, registered 30 December 2015.

Effect of Hydrocortisone on Development of Shock Among Patients With Severe Sepsis: The HYPRESS Randomized Clinical Trial.

Importance: Adjunctive hydrocortisone therapy is suggested by the Surviving Sepsis Campaign in refractory septic shock only. The efficacy of hydrocortisone in patients with severe sepsis without shock remains controversial. Objective: To determine whether hydrocortisone therapy in patients with severe sepsis prevents the development of septic shock. Design, Setting, and Participants: Double-blind, randomized clinical trial conducted from January 13, 2009, to August 27, 2013, with a follow-up of 180 days until February 23, 2014. The trial was performed in 34 intermediate or intensive care units of university and community hospitals in Germany, and it included 380 adult patients with severe sepsis who were not in septic shock. Interventions: Patients were randomly allocated 1:1 either to receive a continuous infusion of 200 mg of hydrocortisone for 5 days followed by dose tapering until day 11 (n = 190) or to receive placebo (n = 190). Main Outcomes and Measures: The primary outcome was development of septic shock within 14 days. Secondary outcomes were time until septic shock, mortality in the intensive care unit or hospital, survival up to 180 days, and assessment of secondary infections, weaning failure, muscle weakness, and hyperglycemia (blood glucose level >150 mg/dL [to convert to millimoles per liter, multiply by 0.0555]). Results: The intention-to-treat population consisted of 353 patients (64.9% male; mean [SD] age, 65.0 [14.4] years). Septic shock occurred in 36 of 170 patients (21.2%) in the hydrocortisone group and 39 of 170 patients (22.9%) in the placebo group (difference, -1.8%; 95% CI, -10.7% to 7.2%; P = .70). No significant differences were observed between the hydrocortisone and placebo groups for time until septic shock; mortality in the intensive care unit or in the hospital; or mortality at 28 days (15 of 171 patients [8.8%] vs 14 of 170 patients [8.2%], respectively; difference, 0.5%; 95% CI, -5.6% to 6.7%; P = .86), 90 days (34 of 171 patients [19.9%] vs 28 of 168 patients [16.7%]; difference, 3.2%; 95% CI, -5.1% to 11.4%; P = .44), and 180 days (45 of 168 patients [26.8%] vs 37 of 167 patients [22.2%], respectively; difference, 4.6%; 95% CI, -4.6% to 13.7%; P = .32). In the hydrocortisone vs placebo groups, 21.5% vs 16.9% had secondary infections, 8.6% vs 8.5% had weaning failure, 30.7% vs 23.8% had muscle weakness, and 90.9% vs 81.5% had hyperglycemia. Conclusions and Relevance: Among adults with severe sepsis not in septic shock, use of hydrocortisone compared with placebo did not reduce the risk of septic shock within 14 days. These findings do not support the use of hydrocortisone in these patients. Trial Registration: clinicaltrials.gov Identifier: NCT00670254.

Functional Regions of Interest in Electrical Impedance Tomography: A Secondary Analysis of Two Clinical Studies.

INTRODUCTION: Patients with acute respiratory distress syndrome (ARDS) typically show a high degree of ventilation inhomogeneity, which is associated with morbidity and unfavorable outcomes. Electrical impedance tomography (EIT) is able to detect ventilation inhomogeneity, but it is unclear which method for defining the region of interest (ROI) should be used for this purpose. The aim of our study was to compare the functional region of interest (fROI) method to both the lung area estimation method (LAEM) and no ROI when analysing global parameters of ventilation inhomogeneity. We assumed that a good method for ROI determination would lead to a high discriminatory power for ventilation inhomogeneity, as defined by the area under the receiver operating characteristics curve (AUC), comparing patients suffering from ARDS and control patients without pulmonary pathologies. METHODS: We retrospectively analysed EIT data from 24 ARDS patients and 12 control patients without pulmonary pathology. In all patients, a standardized low-flow-pressure volume maneuver had been performed and was used for EIT image generation. We compared the AUC for global inhomogeneity (GI) index and coefficient of variation (CV) between ARDS and control patients using all EIT image pixels, the fROI method and the LAEM for ROI determination. RESULTS: When analysing all EIT image pixels, we found an acceptable AUC both for the GI index (AUC = 0.76; 95% confidence interval (CI) 0.58-0.94) and the CV (AUC = 0.74; 95% CI 0.55-0.92). With the fROI method, we found a deteriorating AUC with increasing threshold criteria. With the LAEM, we found the best AUC both for the GI index (AUC = 0.89; 95% CI 0.78-1.0) and the CV (AUC = 0.89; 95% CI 0.78-1.0) using a threshold criterion of 50% of the maximum tidal impedance change. CONCLUSION: In the assessment of ventilation inhomogeneity with EIT, functional regions of interest obscure the difference between patients with ARDS and control patients without pulmonary pathologies. The LAEM is preferable to the fROI method when assessing ventilation inhomogeneity.

Hyperlactatemia is an independent predictor of mortality and denotes distinct subtypes of severe sepsis and septic shock.

PURPOSE: Current guidelines and most trials do not consider elevated lactate (Lac) serum concentrations when grading sepsis severity. We therefore assessed the association of different types of circulatory dysfunction regarding presence of hyperlactatemia and need for vasopressor support with clinical presentation and outcome of sepsis. METHODS: In a secondary analysis of a prospective observational multicenter cohort study, 988 patients with severe sepsis were investigated regarding vasopressor support, Lac levels, and outcome. RESULTS: Twenty-eight-day mortality regarding shock or hyperlactatemia was as follows: hyperlactatemia more than 2.5 mmol/L and septic shock (tissue dysoxic shock): 451 patients with a mortality of 44.8%; hyperlactatemia without vasopressor need (cryptic shock): 72 patients, mortality 35.3%; no hyperlactatemia with vasopressor need (vasoplegic shock): 331 patients, mortality 27.7%; and absence of hyperlactemia or overt shock (severe sepsis): 134 patients, mortality 14.2% (P < .001). These groups showed differences in source and origin of infection. The influence of hyperlactatemia on 28-day mortality (P < .001) (odds ratio 3.0, 95% confidence interval 2.1-4.1 for Lac >4 mmol/L) was independent of vasopressor support (P < .001) (odds ratio 2.0, 95% confidence interval 1.3-3.0 for norepinephrine >0.1 µg/kg per minute) in logistic regression. CONCLUSIONS: Hyperlactatemia increases risk of death independent of vasopressor need resulting in different phenotypes within the classic categories of severe sepsis and septic shock.

Assessment of respiratory system compliance with electrical impedance tomography using a positive end-expiratory pressure wave maneuver during pressure support ventilation: a pilot clinical study.

INTRODUCTION: Assessment of respiratory system compliance (Crs) can be used for individual optimization of positive end-expiratory pressure (PEEP). However, in patients with spontaneous breathing activity, the conventional methods for Crs measurement are inaccurate because of the variable muscular pressure of the patient. We hypothesized that a PEEP wave maneuver, analyzed with electrical impedance tomography (EIT), might be suitable for global and regional assessment of Crs during assisted spontaneous breathing. METHODS: After approval of the local ethics committee, we performed a pilot clinical study in 18 mechanically ventilated patients (61 ± 16 years (mean ± standard deviation)) who were suitable for weaning with pressure support ventilation (PSV). For the PEEP wave, PEEP was elevated by 1 cmH2O after every fifth breath during PSV. This was repeated five times, until a total PEEP increase of 5 cmH2O was reached. Subsequently, PEEP was reduced in steps of 1 cmH2O in the same manner until the original PEEP level was reached. Crs was calculated using EIT from the global, ventral and dorsal lung regions of interest. For reference measurements, all patients were also examined during controlled mechanical ventilation (CMV) with a low-flow pressure-volume maneuver. Global and regional Crs(low-flow) was calculated as the slope of the pressure-volume loop between the pressure that corresponded to the selected PEEP and PEEP +5 cmH2O. For additional reference, Crs during CMV (Crs(CMV)) was calculated as expired tidal volume divided by the difference between airway plateau pressure and PEEP. RESULTS: Respiratory system compliance calculated from the PEEP wave (Crs(PEEP wave)) correlated closely with both reference measurements (r = 0.79 for Crs(low-flow) and r = 0.71 for Crs(CMV)). No significant difference was observed between the mean Crs(PEEP wave) and the mean Crs(low-flow). However, a significant bias of +17.1 ml/cmH2O was observed between Crs(PEEP wave) and Crs(CMV). CONCLUSION: Analyzing a PEEP wave maneuver with EIT allows calculation of global and regional Crs during assisted spontaneous breathing. In mechanically ventilated patients with spontaneous breathing activity, this method might be used for assessment of the global and regional mechanical properties of the respiratory system.

Acid sphingomyelinase serum activity predicts mortality in intensive care unit patients after systemic inflammation: a prospective cohort study.

INTRODUCTION: Acid sphingomyelinase is involved in lipid signalling pathways and regulation of apoptosis by the generation of ceramide and plays an important role during the host response to infectious stimuli. It thus has the potential to be used as a novel diagnostic marker in the management of critically ill patients. The objective of our study was to evaluate acid sphingomyelinase serum activity (ASM) as a diagnostic and prognostic marker in a mixed intensive care unit population before, during, and after systemic inflammation. METHODS: 40 patients admitted to the intensive care unit at risk for developing systemic inflammation (defined as systemic inflammatory response syndrome plus a significant procalcitonin [PCT] increase) were included. ASM was analysed on ICU admission, before (PCT before), during (PCT peak) and after (PCT low) onset of SIRS. Patients undergoing elective surgery served as control (N = 8). Receiver-operating characteristics curves were computed. RESULTS: ASM significantly increased after surgery in the eight control patients. Patients from the intensive care unit had significantly higher ASM on admission than control patients after surgery. 19 out of 40 patients admitted to the intensive care unit developed systemic inflammation and 21 did not, with no differences in ASM between these two groups on admission. In patients with SIRS and PCT peak, ASM between admission and PCT before was not different, but further increased at PCT peak in non-survivors and was significantly higher at PCT low compared to survivors. Survivors exhibited decreased ASM at PCT peak and PCT low. Receiver operating curve analysis on discrimination of ICU mortality showed an area under the curve of 0.79 for ASM at PCT low. CONCLUSIONS: In summary, ASM was generally higher in patients admitted to the intensive care unit compared to patients undergoing uncomplicated surgery. ASM did not indicate onset of systemic inflammation. In contrast to PCT however, it remained high in non-surviving ICU patients after systemic inflammation.

Impact of compliance with infection management guidelines on outcome in patients with severe sepsis: a prospective observational multi-center study.

INTRODUCTION: Current sepsis guidelines recommend antimicrobial treatment (AT) within one hour after onset of sepsis-related organ dysfunction (OD) and surgical source control within 12 hours. The objective of this study was to explore the association between initial infection management according to sepsis treatment recommendations and patient outcome. METHODS: In a prospective observational multi-center cohort study in 44 German ICUs, we studied 1,011 patients with severe sepsis or septic shock regarding times to AT, source control, and adequacy of AT. Primary outcome was 28-day mortality. RESULTS: Median time to AT was 2.1 (IQR 0.8 - 6.0) hours and 3 hours (-0.1 - 13.7) to surgical source control. Only 370 (36.6%) patients received AT within one hour after OD in compliance with recommendation. Among 422 patients receiving surgical or interventional source control, those who received source control later than 6 hours after onset of OD had a significantly higher 28-day mortality than patients with earlier source control (42.9% versus 26.7%, P <0.001). Time to AT was significantly longer in ICU and hospital non-survivors; no linear relationship was found between time to AT and 28-day mortality. Regardless of timing, 28-day mortality rate was lower in patients with adequate than non-adequate AT (30.3% versus 40.9%, P < 0.001). CONCLUSIONS: A delay in source control beyond 6 hours may have a major impact on patient mortality. Adequate AT is associated with improved patient outcome but compliance with guideline recommendation requires improvement. There was only indirect evidence about the impact of timing of AT on sepsis mortality.

A knowledge- and model-based system for automated weaning from mechanical ventilation: technical description and first clinical application.

To describe the principles and the first clinical application of a novel prototype automated weaning system called Evita Weaning System (EWS). EWS allows an automated control of all ventilator settings in pressure controlled and pressure support mode with the aim of decreasing the respiratory load of mechanical ventilation. Respiratory load takes inspired fraction of oxygen, positive end-expiratory pressure, pressure amplitude and spontaneous breathing activity into account. Spontaneous breathing activity is assessed by the number of controlled breaths needed to maintain a predefined respiratory rate. EWS was implemented as a knowledge- and model-based system that autonomously and remotely controlled a mechanical ventilator (Evita 4, Dräger Medical, Lübeck, Germany). In a selected case study (n = 19 patients), ventilator settings chosen by the responsible physician were compared with the settings 10 min after the start of EWS and at the end of the study session. Neither unsafe ventilator settings nor failure of the system occurred. All patients were successfully transferred from controlled ventilation to assisted spontaneous breathing in a mean time of 37 ± 17 min (± SD). Early settings applied by the EWS did not significantly differ from the initial settings, except for the fraction of oxygen in inspired gas. During the later course, EWS significantly modified most of the ventilator settings and reduced the imposed respiratory load. A novel prototype automated weaning system was successfully developed. The first clinical application of EWS revealed that its operation was stable, safe ventilator settings were defined and the respiratory load of mechanical ventilation was decreased.