Population pharmacokinetic modeling of multiple-dose intravenous fosfomycin in critically ill patients during continuous venovenous hemodialysis.

The aim of this study was to investigate the pharmacokinetics of multiple-dose intravenous (i.v.) fosfomycin in critically ill patients during continuous venovenous hemodialysis (CVVHD). Non-compartmental analysis and population pharmacokinetic modeling were used to simulate different dosing regimens. We evaluated 15 critically ill patients with renal insufficiency and CVVHD undergoing anti-infective treatment with fosfomycin in our ICU. Five grams of fosfomycin were administered for 120 min every 6 h. Plasma concentrations were determined with and without CVVHD. Pharmacokinetic analysis and simulations were performed using non-linear mixed effects modelling (NONMEM). A two-compartment model with renal and dialysis clearance was most accurate in describing the pharmacokinetics of i.v. fosfomycin during CVVHD. Population parameter estimates were 18.20 L and 20.80 L for the central and peripheral compartment volumes, and 0.26 L/h and 5.08 L/h for renal and intercompartmental clearance, respectively. Urinary creatinine clearance (CLCR) represented a considerable component of renal clearance. Central compartment volume increased over time after the first dose. For patients with CLCR > 50 (90) mL/min and CVVHD, dosage should be increased to ≥ 15 (16) grams of i.v. fosfomycin across three (four) daily doses. Individual CLCR must be considered when dosing i.v. fosfomycin in critically ill patients during CVVHD.

Use of extracorporeal circulation (ECLS/ECMO) for cardiac and circulatory failure -A clinical practice Guideline Level 3.

Aims Worldwide applications of extracorporeal circulation for mechanical support in cardiac and circulatory failure, which are referred to as extracorporeal life support (ECLS) or veno-arterial extracorporeal membrane oxygenation (va-ECMO), have dramatically increased over the past decade. In spite of the expanding use and the immense medical as well as socio-economic impact of this therapeutic approach, there has been a lack of interdisciplinary recommendations considering the best available evidence for ECLS treatment. Methods and Results In a multiprofessional, interdisciplinary scientific effort of all scientific societies involved in the treatment of patients with acute cardiac and circulatory failure, the first evidence- and expert consensus-based guideline (level S3) on ECLS/ECMO therapy was developed in a structured approach under regulations of the AWMF (Association of the Scientific Medical Societies in Germany) and under use of GRADE (Grading of Recommendations Assessment, Development and Evaluation) criteria. This article presents all recommendations created by the expert panel, addressing a multitude of aspects for ECLS initiation, continuation, weaning and aftercare as well as structural and personnel requirements. Conclusions This first evidence- and expert consensus-based guideline (level S3) on ECLS/ECMO therapy should be used to apply the best available care nationwide. Beyond clinical practice advice, remaining important research aspects for future scientific efforts are formulated.

Sonographic Evaluation of Gastric Residual Volume during Enteral Nutrition in Critically Ill Patients Using a Miniaturized Ultrasound Device.

BACKGROUND: To assess the risk of aspiration, nutrient tolerance, and gastric emptying of patients in ICUs, gastric ultrasound can provide information about the gastric contents. Using established formulas, the gastric residual volume (GRV) can be calculated in a standardized way by measuring the gastric antrum. The purpose of this study was to determine the GRV in a cohort of enterally fed patients using a miniaturized ultrasound device to achieve knowledge about feasibility and the GRV over time during the ICU stay. The findings could contribute to the optimization of enteral nutrition (EN) therapy. METHODS: A total of 217 ultrasound examinations with 3 measurements each (651 measurements in total) were performed twice daily (morning and evening) in a longitudinal observational study on 18 patients with EN in the interdisciplinary surgical ICU of Saarland University Medical Center. The measured values of the GRV were analyzed in relation to the clinical course, the nutrition, and other parameters. RESULTS: Measurements could be performed without interrupting the flow of clinical care and without pausing EN. The GRV was significantly larger with sparsely auscultated bowel sounds than with normal and excited bowel sounds (p < 0.01). Furthermore, a significantly larger GRV was present when using a high-caloric/low-protein nutritional product compared to an isocaloric product (p = 0.02). The GRV at the morning and evening measurements showed no circadian rhythm. When comparing the first and last ultrasound examination of each patient, there was a tendency towards an increased GRV (p = 0.07). CONCLUSION: The GRV measured by miniaturized ultrasound devices can provide important information about ICU patients without restricting treatment procedures in the ICU. Measurements are possible while EN therapy is ongoing. Further studies are needed to establish gastric ultrasound as a management tool in nutrition therapy.

Sex Differences in Clinical Course and Intensive Care Unit Admission in a National Cohort of Hospitalized Patients with COVID-19.

Males have a higher risk for an adverse outcome of COVID-19. The aim of the study was to analyze sex differences in the clinical course with focus on patients who received intensive care. Research was conducted as an observational retrospective cohort study. A group of 23,235 patients from 83 hospitals with PCR-confirmed infection with SARS-CoV-2 between 4 February 2020 and 22 March 2021 were included. Data on symptoms were retrieved from a separate registry, which served as a routine infection control system. Males accounted for 51.4% of all included patients. Males received more intensive care (ratio OR = 1.61, 95% CI = 1.51-1.71) and mechanical ventilation (invasive or noninvasive, OR = 1.87, 95% CI = 1.73-2.01). A model for the prediction of mortality showed that until the age 60 y, mortality increased with age with no substantial difference between sexes. After 60 y, the risk of death increased more in males than in females. At 90 y, females had a predicted mortality risk of 31%, corresponding to males of 84 y. In the intensive care unit (ICU) cohort, females of 90 y had a mortality risk of 46%, equivalent to males of 72 y. Seventy-five percent of males over 90 died, but only 46% of females of the same age. In conclusion, the sex gap was most evident among the oldest in the ICU. Understanding sex-determined differences in COVID-19 can be useful to facilitate individualized treatments.

[Use of extracorporeal circulation (ECLS/ECMO) for cardiac and circulatory failure : Short version of the S3 guideline]. / Einsatz der extrakorporalen Zirkulation (ECLS/ECMO) bei Herz- und Kreislaufversagen : Kurzversion der AWMF-S3-Leitlinie.

In Germany, a remarkable increase regarding the usage of extracorporeal membrane oxygenation (ECMO) and extracorporeal life support (ECLS) systems has been observed in recent years with approximately 3000 ECLS/ECMO implantations annually since 2015. Despite the widespread use of ECLS/ECMO, evidence-based recommendations or guidelines are still lacking regarding indications, contraindications, limitations and management of ECMO/ECLS patients. Therefore in 2015, the German Society of Thoracic and Cardiovascular Surgery (GSTCVS) registered the multidisciplinary S3 guideline "Use of extracorporeal circulation (ECLS/ECMO) for cardiac and circulatory failure" to develop evidence-based recommendations for ECMO/ECLS systems according to the requirements of the Association of the Scientific Medical Societies in Germany (AWMF). Although the clinical application of ECMO/ECLS represents the main focus, the presented guideline also addresses structural and economic issues. Experts from 17 German, Austrian and Swiss scientific societies and a patients' organization, guided by the GSTCVS, completed the project in February 2021. In this report, we present a summary of the methodological concept and tables displaying the recommendations for each chapter of the guideline.

[Use of extracorporeal circulation (ECLS/ECMO) for cardiac and circulatory failure : Short version of the S3 guideline]. / Einsatz der extrakorporalen Zirkulation (ECLS/ECMO) bei Herz- und Kreislaufversagen : Kurzversion der AWMF-S3-Leitlinie.

In Germany, a remarkable increase regarding the usage of extracorporeal membrane oxygenation (ECMO) and extracorporeal life support (ECLS) systems has been observed in recent years with approximately 3000 ECLS/ECMO implantations annually since 2015. Despite the widespread use of ECLS/ECMO, evidence-based recommendations or guidelines are still lacking regarding indications, contraindications, limitations and management of ECMO/ECLS patients. Therefore in 2015, the German Society of Thoracic and Cardiovascular Surgery (GSTCVS) registered the multidisciplinary S3 guideline "Use of extracorporeal circulation (ECLS/ECMO) for cardiac and circulatory failure" to develop evidence-based recommendations for ECMO/ECLS systems according to the requirements of the Association of the Scientific Medical Societies in Germany (AWMF). Although the clinical application of ECMO/ECLS represents the main focus, the presented guideline also addresses structural and economic issues. Experts from 17 German, Austrian and Swiss scientific societies and a patients' organization, guided by the GSTCVS, completed the project in February 2021. In this report, we present a summary of the methodological concept and tables displaying the recommendations for each chapter of the guideline.

High Central Venous Pressure after Cardiac Surgery Might Depict Hemodynamic Deterioration Associated with Increased Morbidity and Mortality.

BACKGROUND: Cardiac surgery patients represent a high-risk cohort in intensive care units (ICUs). Central venous pressure (CVP) measurement seems to remain an integral part in hemodynamic monitoring, especially in cardio-surgical ICUs. However, its value as a prognostic marker for organ failure is still unclear. Therefore, we analyzed postoperative CVP values after adult cardiac surgery in a large cohort with regard to its prognostic value for morbidity and mortality. METHODS: All adult patients admitted to our ICUs between 2006 and 2019 after cardiac surgery were eligible for inclusion in the study (n = 11,198). We calculated the median initial CVP (miCVP) after admission to the ICU, which returned valid values for 9802 patients. An ROC curve analysis for optimal cut-off miCVP to predict ICU mortality was conducted with consecutive patient allocation into a (a) low miCVP (LCVP) group (≤11 mmHg) and (b) high miCVP (HCVP) group (>11 mmHg). We analyzed the impact of high miCVP on morbidity and mortality by propensity score matching (PSM) and logistic regression. RESULTS: ICU mortality was increased in HCVP patients. In addition, patients in the HCVP group required longer mechanical ventilation, had a higher incidence of acute kidney injury, were more frequently treated with renal replacement therapy, and showed a higher risk for postoperative liver dysfunction, parametrized by a postoperative rise of ≥ 10 in MELD Score. Multiple regression analysis confirmed HCVP has an effect on postoperative ICU-mortality and intrahospital mortality, which seems to be independent. CONCLUSIONS: A high initial CVP in the early postoperative ICU course after cardiac surgery is associated with worse patient outcome. Whether or not CVP, as a readily and constantly available hemodynamic parameter, should promote clinical efforts regarding diagnostics and/or treatment, warrants further investigations.

Real-Time Evaluation of Optic Nerve Sheath Diameter (ONSD) in Awake, Spontaneously Breathing Patients.

(1) Background: Reliable ultrasonographic measurements of optic nerve sheath diameter (ONSD) to detect increased intracerebral pressure (ICP) has not been established in awake patients with continuous invasive ICP monitoring. Therefore, in this study, we included fully awake patients with and without raised ICP and correlated ONSD with continuously measured ICP values. (2) Methods: In a prospective study, intracranial pressure (ICP) was continuously measured in 25 patients with an intraparenchymatic P-tel probe. Ultrasonic measurements were carried out three times for each optic nerve in vertical and horizontal directions. ONSD measurements and ICP were correlated. Patients with ICP of 2.0-10.0 mmHg were compared with patients suffering from an ICP of 10.1-24.2 mmHg. (3) Results: In all patients, the ONSD vertical and horizontal measurement for both eyes correlated well with the ICP (Pearson R = 0.68-0.80). Both measurements yielded similar results (Bland-Altman: vertical bias: -0.09 mm, accuracy: ±0.66 mm; horizontal bias: -0.06 mm, accuracy: ±0.48 mm). For patients with an ICP of 2.0-10.0 mmHg compared to an ICP of 10.1-24.2, ROC (receiver operating characteristic) analyses showed that ONSD measurement accurately predicts elevated ICP (optimal cut-off value 5.05 mm, AUC of 0.91, sensitivity 92% and specificity 90%, p < 0.001). (4) Conclusions: Ultrasonographic measurement of ONSD in awake, spontaneously breathing patients provides a valuable method to evaluate patients with suspected increased ICP. Additionally, it provides a potential tool for rapid assessment of ICP at the bedside and to identify patients at risk for a poor neurological outcome.

[Mortality in sepsis and septic shock in Germany. Results of a systematic review and meta-analysis]. / Sterblichkeit bei Sepsis und septischem Schock in Deutschland. Ergebnisse eines systematischen Reviews mit Metaanalyse.

BACKGROUND: The reported mortality for sepsis and septic shock varies between 15% and 59% in international comparison. For Germany, the number of studies is limited. Previous estimations of mortality in Germany are outdated or based on claims data analyses. Various authors discuss whether lacking quality initiatives and treatment standards in Germany could cause higher mortality for sepsis. This contrasts with the internationally well-recognized performance of the German intensive care infrastructure during the COVID-19 pandemic. OBJECTIVES: The objectives of this systematic review and meta-analysis were to estimate 30-day and 90-day mortality of patients with sepsis and patients with septic shock in Germany and to compare the mortality with that of other industrialized regions (Europe, North America). MATERIAL AND METHODS: A systematic literature search included interventional and observational studies published between 2009 and 2020 in PubMed and the Cochrane Library that analyzed adult patients with sepsis, severe sepsis and septic shock in Europe and North America. Studies with less than 20 patients were excluded. The 30-day and 90-day mortality for sepsis and septic shock were pooled separately for studies conducted in Germany, Europe (excluding Germany) and North America in a meta-analysis using a random effects model. Mortality over time was analyzed in a linear regression model. RESULTS: Overall, 134 studies were included. Of these, 15 studies were identified for the estimation of mortality in Germany, covering 10,434 patients, the number of patients per study ranged from 28 to 4183 patients. The 30-day mortality for sepsis was 26.50% (95% confidence interval, CI: 19.86-33.15%) in Germany, 23.85% (95% CI: 20.49-27.21%) in Europe (excluding Germany) and 19.58% (95% CI: 14.03-25.14%) in North America. The 30-day mortality for septic shock was 30.48% (95% CI: 29.30-31.67%) in Germany, 34.57% (95% CI: 33.51-35.64%) in Europe (excluding Germany) and 33.69% (95% CI: 31.51-35.86%) in North America. The 90-day mortality for septic shock was 38.78% (95% CI: 32.70-44.86%) in Germany, 41.90% (95% CI: 38.88-44.91%) in Europe (excluding Germany) and 34.41% (95% CI: 25.66-43.16%) in North America. A comparable decreasing trend in sepsis 30-day mortality was observed in all considered regions since 2009. CONCLUSION: Our analysis does not support the notion that mortality related to sepsis and septic shock in Germany is higher in international comparison. A higher mortality would not be obvious either, since intensive care, for example also during the COVID-19 pandemic, is regarded as exemplary in Germany and the structural quality, such as the number of intensive care beds per 100,000 inhabitants, is high in international comparison. Nevertheless, deficits could also exist outside intensive care medicine. A comparison of international individual studies should take greater account of the structure of healthcare systems, the severity of disease and the limitations resulting from the data sources used.

Washout and Awakening Times after Inhaled Sedation of Critically Ill Patients: Desflurane Versus Isoflurane.

In recent years, inhaled sedation has been increasingly used in the intensive care unit (ICU). The aim of this prospective, controlled trial was to compare washout and awakening times after long term sedation with desflurane and isoflurane both administered with the Mirus™ system (TIM GmbH, Koblenz, Germany). Twenty-one consecutive critically ill patients were alternately allocated to the two study groups, obtaining inhaled sedation with either desflurane or isoflurane. After 24 h study sedation, anesthetic washout curves were recorded, and a standardized wake-up test was performed. The primary outcome measure was the time required to decrease the endtidal concentration to 50% (T50%). Secondary outcome measures were T80% and awakening times (all extremities moved, RASS -2). Decrement times (min) (desflurane versus isoflurane, median (1st quartile-3rd quartile)) (T50%: 0.3 (0.3-0.4) vs. 1.3 (0.4-2.3), log-rank test P = 0.002; P80%: 2.5 (2-5.9) vs. 12.1 (5.1-20.2), P = 0.022) and awakening times (to RASS -2: 7.5 (5.5-8.8) vs. 41.0 (24.5-43.0), P = 0.007; all extremities moved: 5.0 (4.0-8.5) vs. 13.0 (8.0-41.25), P = 0.037) were significantly shorter after desflurane compared to isoflurane. The use of desflurane with the Mirus™ system significantly shortens the washout times and leads to faster awakening after sedation of critically ill patients.

Vasopressor Therapy in Cardiac Surgery-An Experts' Consensus Statement.

Hemodynamic conditions with reduced systemic vascular resistance commonly are observed in patients undergoing cardiac surgery and may range from moderate reductions in vascular tone, as a side effect of general anesthetics, to a profound vasodilatory syndrome, often referred to as vasoplegic shock. Therapy with vasopressors is an important pillar in the treatment of these conditions. There is limited guidance on the appropriate choice of vasopressors to restore and optimize systemic vascular tone in patients undergoing cardiac surgery. A panel of experts in the field convened to develop statements and evidence-based recommendations on clinically relevant questions on the use of vasopressors in cardiac surgical patients, using a critical appraisal of the literature following the GRADE system and a modified Delphi process. The authors unanimously and strongly recommend the use of norepinephrine and/or vasopressin for restoration and maintenance of systemic perfusion pressure in cardiac surgical patients; despite that, the authors cannot recommend either of these drugs with respect to the risk of ischemic complications. The authors unanimously and strongly recommend against using dopamine for treating post-cardiac surgery vasoplegic shock and against using methylene blue for purposes other than a rescue therapy. The authors unanimously and weakly recommend that clinicians consider early addition of a second vasopressor (norepinephrine or vasopressin) if adequate vascular tone cannot be restored by a monotherapy with either norepinephrine or vasopressin and to consider using vasopressin as a first-line vasopressor or to add vasopressin to norepinephrine in cardiac surgical patients with pulmonary hypertension or right-sided heart dysfunction.

Quantitative Determination of Fosfomycin in 10 µL of Plasma and Dialysate by Hydrophilic Interaction Liquid Chromatography Electrospray Ionization Mass Spectrometry.

Fosfomycin is an antibiotic with a broad spectrum of activity against many multidrug-resistant bacterial strains. It is mainly excreted unchanged by the kidneys, and its half-life therefore depends on kidney function which varies considerably among individuals, and within individuals over time. Proper fosfomycin dosing thus depends on assaying blood concentration of the drug. We developed and validated a simple, sensitive and specific chromatography assay, which was coupled to electrospray ionization mass spectrometry for determination of fosfomycin. Separation of fosfomycin was based on the method of the hydrophilic interaction liquid chromatography; specifically, plasma and dialysate samples were acidified and the protein precipitated with acetonitrile. The calibration curves showed excellent coefficients of determination (R2 > 0.999) over the relevant concentration range of 25-700 µg/mL. Intraday precision was 1.1-1.2% and accuracy was -5.9% to 0.9% for quality control samples. Interday precision was 2.9-3.4% and accuracy was -3.7% to 5.5%. Extraction recovery was ≥87% and matrix effects ranged from 2.2% to 4.3%. After laboratory validation, the method was successfully applied to clinical samples.

Evaluating the Use of Circulating MicroRNA Profiles for Lung Cancer Detection in Symptomatic Patients.

Importance: The overall low survival rate of patients with lung cancer calls for improved detection tools to enable better treatment options and improved patient outcomes. Multivariable molecular signatures, such as blood-borne microRNA (miRNA) signatures, may have high rates of sensitivity and specificity but require additional studies with large cohorts and standardized measurements to confirm the generalizability of miRNA signatures. Objective: To investigate the use of blood-borne miRNAs as potential circulating markers for detecting lung cancer in an extended cohort of symptomatic patients and control participants. Design, Setting, and Participants: This multicenter, cohort study included patients from case-control and cohort studies (TREND and COSYCONET) with 3102 patients being enrolled by convenience sampling between March 3, 2009, and March 19, 2018. For the cohort study TREND, population sampling was performed. Clinical diagnoses were obtained for 3046 patients (606 patients with non-small cell and small cell lung cancer, 593 patients with nontumor lung diseases, 883 patients with diseases not affecting the lung, and 964 unaffected control participants). No samples were removed because of experimental issues. The collected data were analyzed between April 2018 and November 2019. Main Outcomes and Measures: Sensitivity and specificity of liquid biopsy using miRNA signatures for detection of lung cancer. Results: A total of 3102 patients with a mean (SD) age of 61.1 (16.2) years were enrolled. Data on the sex of the participants were available for 2856 participants; 1727 (60.5%) were men. Genome-wide miRNA profiles of blood samples from 3046 individuals were evaluated by machine-learning methods. Three classification scenarios were investigated by splitting the samples equally into training and validation sets. First, a 15-miRNA signature from the training set was used to distinguish patients diagnosed with lung cancer from all other individuals in the validation set with an accuracy of 91.4% (95% CI, 91.0%-91.9%), a sensitivity of 82.8% (95% CI, 81.5%-84.1%), and a specificity of 93.5% (95% CI, 93.2%-93.8%). Second, a 14-miRNA signature from the training set was used to distinguish patients with lung cancer from patients with nontumor lung diseases in the validation set with an accuracy of 92.5% (95% CI, 92.1%-92.9%), sensitivity of 96.4% (95% CI, 95.9%-96.9%), and specificity of 88.6% (95% CI, 88.1%-89.2%). Third, a 14-miRNA signature from the training set was used to distinguish patients with early-stage lung cancer from all individuals without lung cancer in the validation set with an accuracy of 95.9% (95% CI, 95.7%-96.2%), sensitivity of 76.3% (95% CI, 74.5%-78.0%), and specificity of 97.5% (95% CI, 97.2%-97.7%). Conclusions and Relevance: The findings of the study suggest that the identified patterns of miRNAs may be used as a component of a minimally invasive lung cancer test, complementing imaging, sputum cytology, and biopsy tests.

Image quality to estimate ventricular ejection fraction by last year medical students improves after short courses of training.

BACKGROUND: Transthoracic echocardiography is the primary imaging modality for diagnosing cardiac conditions but medical education in this field is limited. We tested the hypothesis that a structured theoretical and supervised practical course of training in focused echocardiography in last year medical students results in a more accurate assessment and more precise calculation of left ventricular ejection fraction after ten patient examinations. METHODS: After a theoretical introduction course 25 last year medical students performed ten transthoracic echocardiographic examination blocks in postsurgical patients. Left ventricular function was evaluated both with an eye-balling method and with the calculated ejection fraction using diameter and area of left ventricles. Each examination block was controlled by a certified and blinded tutor. Bias and precision of measurements were assessed with Bland and Altman method. RESULTS: Using the eye-balling method students agreed with the tutor's findings both at the beginning (88%) but more at the end of the course (95.7%). The variation between student and tutor for calculation of area, diameter and ejection fraction, respectively, was significantly lower in examination block 10 than in examination block 1 (each p < 0.001). Students underestimated both the length and the area of the left ventricle at the outset, as complete imaging of the left heart in the ultrasound sector was initially unsuccessful. CONCLUSIONS: A structured theoretical and practical transthoracic echocardiography course of training for last year medical students provides a clear and measurable learning experience in assessing and measuring left ventricular function. At least 14 examination blocks are necessary to achieve 90% agreement of correct determination of the ejection fraction.

Halving the Volume of AnaConDa: Evaluation of a New Small-Volume Anesthetic Reflector in a Test Lung Model.

BACKGROUND: Volatile anesthetics are increasingly used for sedation in intensive care units. The most common administration system is AnaConDa-100 mL (ACD-100; Sedana Medical, Uppsala, Sweden), which reflects volatile anesthetics in open ventilation circuits. AnaConDa-50 mL (ACD-50) is a new device with half the volumetric dead space. Carbon dioxide (CO2) can be retained with both devices. We therefore compared the CO2 elimination and isoflurane reflection efficiency of both devices. METHODS: A test lung constantly insufflated with CO2 was ventilated with a tidal volume of 500 mL at 10 breaths/min. End-tidal CO2 (EtCO2) partial pressure was measured using 3 different devices: a heat-and-moisture exchanger (HME, 35 mL), ACD-100, and ACD-50 under 4 different experimental conditions: ambient temperature pressure (ATP), body temperature pressure saturated (BTPS) conditions, BTPS with 0.4 Vol% isoflurane (ISO-0.4), and BTPS with 1.2 Vol% isoflurane. Fifty breaths were recorded at 3 time points (n = 150) for each device and each condition. To determine device dead space, we adjusted the tidal volume to maintain normocapnia (n = 3), for each device. Thereafter, we determined reflection efficiency by measuring isoflurane concentrations at infusion rates varying from 0.5 to 20 mL/h (n = 3), for each device. RESULTS: EtCO2 was consistently greater with ACD-100 than with ACD-50 and HME (ISO-0.4, mean ± standard deviations: ACD-100, 52.4 ± 0.8; ACD-50, 44.4 ± 0.8; HME, 40.1 ± 0.4 mm Hg; differences of means of EtCO2 [respective 95% confidence intervals]: ACD-100 - ACD-50, 8.0 [7.9-8.1] mm Hg, P < .001; ACD-100 - HME, 12.3 [12.2-12.4] mm Hg, P < .001; ACD-50 - HME, 4.3 [4.2-4.3] mm Hg, P < .001). It was greatest under ATP, less under BTPS, and least with ISO-0.4 and BTPS with 1.2 Vol% isoflurane. In addition to the 100 or 50 mL "volumetric dead space" of each AnaConDa, "reflective dead space" was 40 mL with ACD-100 and 25 mL with ACD-50 when using isoflurane. Isoflurane reflection was highest under ATP. Under BTPS with CO2 insufflation and isoflurane concentrations around 0.4 Vol%, reflection efficiency was 93% with ACD-100 and 80% with ACD-50. CONCLUSIONS: Isoflurane reflection remained sufficient with the ACD-50 at clinical anesthetic concentrations, while CO2 elimination was improved. The ACD-50 should be practical for tidal volumes as low as 200 mL, allowing lung-protective ventilation even in small patients.