方山 真朱

BACKGROUND: Reduced or delayed access to medical resources on weekends could lead to worsening outcomes, in critically ill infected patients requiring intensive care unit (ICU) admission. OBJECTIVE: To investigate the "weekend effect," on critically ill infected patients in Japanese ICUs for the first time. DESIGN: Multicenter retrospective cohort study. METHODS: We examined data from Japanese ICU patients participating in the DIANA study, a multicenter international observational cohort study. This prospective investigation enrolled critically ill patients with infections admitted to the ICU. The primary endpoint was successful discharge from the ICU within 28 days of admission. Outcome measures were evaluated through both univariate and covariate Cox regression analyses, providing hazard ratios (HRs) along with estimated 95% confidence intervals (CIs). RESULTS: Out of the 276 patients enrolled in the DIANA study across 31 facilities, 208 patients (75.4%) meeting the inclusion criteria were included in the analysis. The weekday ICU admission group comprised 156 patients (75.0%), while the weekend ICU admission group comprised 52 patients (25.0%). In the multivariate Cox regression analysis, there were no statistically significant differences observed in the rates of ICU discharge alive within 28 days and 14 days (28 days, HR: 0.94, 95% CI: 0.63-1.40; 14 days, HR: 0.97, 95% CI: 0.64-1.48). Furthermore, the overall ICU mortality rates at 28 days and 14 days after ICU admission did not show statistical significance between patients admitted on weekends and those admitted on weekdays (ICU mortality, 28 days: 13.5% vs 11.5%, p = 0.806; 14 days: 7.7% vs 10.9%, p = 0.604). CONCLUSION: The rates of ICU discharge alive within 28 days after ICU admission did not differ significantly between weekday and weekend admissions, both in the unadjusted and adjusted analyses. Moreover, further well-designed studies are warranted to thoroughly assess this effect.

BACKGROUND: The dynamic regional accuracy of electrical impedance tomography has not yet been validated. We aimed to compare the regional accuracy of electrical impedance tomography with that of four-dimensional computed tomography during dynamic ventilation. METHODS: This single-center, prospective, observational study conducted in a general intensive care unit included adult patients receiving mechanical ventilation from July 2021 to February 2024. The patients were mechanically ventilated passively and underwent electrical impedance tomography and four-dimensional computed tomography on the same day. RESULTS: Overall, 45 patients were analyzed. The correlation coefficients in regional dynamic ventilation between four-dimensional computed tomography and electrical impedance tomography in each region were 0.963, 0.963, 0.835 (ventral, central, and dorsal, respectively) in the right lung and 0.947, 0.927, 0.823 (ventral, central, and dorsal, respectively) in the left lung. The correlation coefficient was low when the regional ventilation distribution detected by the electrical impedance tomography was < 2%. After excluding nine patients with a regional ventilation distribution of < 2%, the ventral, central, and dorsal correlation coefficients were 0.963, 0.963, and 0.946 in the right lung and 0.942, 0.924, and 0.951, respectively, in the left lung. CONCLUSIONS: Regional ventilation using electrical impedance tomography during dynamic ventilation was highly accurate and consistent with the time phase compared to four-dimensional computed tomography. Given the high correlation between these modalities, they can contribute significantly to further studies on regional ventilation dynamics. Trial registration number ClinicalTrials.gov (No. UMIN00044386).

Normally aerated lung tissue on computed tomography (CT) is correlated with static respiratory system compliance (Crs) at zero end-expiratory pressure. In clinical practice, however, patients with acute respiratory failure are often managed using elevated PEEP levels. No study has validated the relationship between lung volume and tissue and Crs at the applied positive end-expiratory pressure (PEEP). Therefore, this study aimed to demonstrate the relationship between lung volume and tissue on CT and Crs during the application of PEEP for the clinical management of patients with acute respiratory distress syndrome due to COVID-19. Additionally, as a secondary outcome, the study aimed to evaluate the relationship between CT characteristics and Crs, considering recruitability using the recruitment-to-inflation ratio (R/I ratio). We analyzed the CT and respiratory mechanics data of 30 patients with COVID-19 who were mechanically ventilated. The CT images were acquired during mechanical ventilation at PEEP level of 15 cmH2O and were quantitatively analyzed using Synapse Vincent system version 6.4 (Fujifilm Corporation, Tokyo, Japan). Recruitability was stratified into two groups, high and low recruitability, based on the median R/I ratio of our study population. Thirty patients were included in the analysis with the median R/I ratio of 0.71. A significant correlation was observed between Crs at the applied PEEP (median 15 [interquartile range (IQR) 12.2, 15.8]) and the normally aerated lung volume (r = 0.70 [95% CI 0.46-0.85], P < 0.001) and tissue (r = 0.70 [95% CI 0.46-0.85], P < 0.001). Multivariable linear regression revealed that recruitability (Coefficient = - 390.9 [95% CI - 725.0 to - 56.8], P = 0.024) and Crs (Coefficient = 48.9 [95% CI 32.6-65.2], P < 0.001) were significantly associated with normally aerated lung volume (R-squared: 0.58). In this study, Crs at the applied PEEP was significantly correlated with normally aerated lung volume and tissue on CT. Moreover, recruitability indicated by the R/I ratio and Crs were significantly associated with the normally aerated lung volume. This research underscores the significance of Crs at the applied PEEP as a bedside-measurable parameter and sheds new light on the link between recruitability and normally aerated lung.

Whether empirical therapy with carbapenems positively affects the outcomes of critically ill patients with bacterial infections remains unclear. This study aimed to investigate whether the use of carbapenems as the initial antimicrobial administration reduces mortality and whether the duration of carbapenem use affects the detection of multidrug-resistant (MDR) pathogens. This was a post hoc analysis of data acquired from Japanese participating sites from a multicenter, prospective observational study [Determinants of Antimicrobial Use and De-escalation in Critical Care (DIANA study)]. A total of 268 adult patients with clinically suspected or confirmed bacterial infections from 31 Japanese intensive care units (ICUs) were analyzed. The patients were divided into two groups: patients who were administered carbapenems as initial antimicrobials (initial carbapenem group, n = 99) and those who were not administered carbapenems (initial non-carbapenem group, n = 169). The primary outcomes were mortality at day 28 and detection of MDR pathogens. Multivariate logistic regression analysis revealed that mortality at day 28 did not differ between the two groups [18 (18%) vs 27 (16%), respectively; odds ratio: 1.25 (95% confidence interval (CI): 0.59-2.65), P = 0.564]. The subdistribution hazard ratio for detecting MDR pathogens on day 28 per additional day of carbapenem use is 1.08 (95% CI: 1.05-1.13, P < 0.001 using the Fine-Gray model with death regarded as a competing event). In conclusion, in-hospital mortality was similar between the groups, and a longer duration of carbapenem use as the initial antimicrobial therapy resulted in a higher risk of detection of new MDR pathogens.IMPORTANCEWe found no statistical difference in mortality with the empirical use of carbapenems as initial antimicrobial therapy among critically ill patients with bacterial infections. Our study revealed a lower proportion of inappropriate initial antimicrobial administrations than those reported in previous studies. This result suggests the importance of appropriate risk assessment for the involvement of multidrug-resistant (MDR) pathogens and the selection of suitable antibiotics based on risk. To the best of our knowledge, this study is the first to demonstrate that a longer duration of carbapenem use as initial therapy is associated with a higher risk of subsequent detection of MDR pathogens. This finding underscores the importance of efforts to minimize the duration of carbapenem use as initial antimicrobial therapy when it is necessary.

BACKGROUND: Sepsis-3 emphasizes the recognition of sepsis-induced cellular metabolic abnormalities, and utilizes serum lactate level as a biomarker of cellular metabolic abnormalities. Magnesium plays an important role as a cofactor in glucose metabolism, although it is not well known that magnesium deficiency causes elevated serum lactate levels. Additionally, it remains unclear how magnesium status affects the role of serum lactate levels as a marker of metabolic abnormalities in sepsis. Thus, this study aimed to investigate the association between serum magnesium and lactate levels in patients with sepsis and explore this relationship from the perspectives of time course and circulatory abnormalities. METHODS: This retrospective observational study of adult patients with sepsis was performed at the 16-bed intensive care unit of Jichi Medical University Hospital between June 2011 and December 2017. The relationship between serum magnesium and lactate levels for 5 days from intensive care unit admission was investigated along the time course. Multivariate logistic regression analysis was performed to evaluate the association between serum magnesium and lactate levels during intensive care unit admission. RESULTS: Among 759 patients included, 105 had hypomagnesemia (magnesium level < 1.6 mg/dL), 558 had normal serum magnesium levels (1.6-2.4 mg/dL), and 96 had hypermagnesemia (magnesium level > 2.4 mg/dL) at intensive care unit admission. From intensive care unit admission to day 5, the hypomagnesemia group had higher serum lactate levels and a higher frequency of lactic acidosis than the normal magnesium level and hypermagnesemia groups (70% vs. 51.6% vs. 50%; P < 0.001). Hypomagnesemia at intensive care unit admission was independently associated with lactic acidosis, i.e., lactic acid level > 2 mmol/L (odds ratio, 2.76; 95% confidence interval, 1.60-4.76; P < 0.001). CONCLUSIONS: Hypomagnesemia was associated with serum lactate levels in the early and post-resuscitation phases of sepsis. Further studies are needed to elucidate whether the magnesium status is associated with sepsis-induced cellular and metabolic abnormalities.

A 45-year-old woman was hospitalized with severe coronavirus disease 2019 pneumonia. Following cytokine storm-induced multiorgan failure and lethal arrhythmia, the patient developed a sustained coma with flaccid quadriplegia. A cerebrospinal fluid examination excluded infectious and immunogenic encephalopathies, and diffusion-weighted magnetic resonance imaging demonstrated high-intensity areas in the white matter with a cortex-sparing distribution, suggesting delayed post-hypoxic leukoencephalopathy. As a result of intensive cardiopulmonary support for a month, the neurological function gradually recovered. Based on the reversible clinical course noted in this patient, accurate diagnosis and persistent medical approaches are important for the management of coronavirus disease 2019-related delayed post-hypoxic leukoencephalopathy.

BACKGROUND: Most ventilators measure airway occlusion pressure (occlusion P0.1) by occluding the breathing circuit; however, some ventilators can predict P0.1 for each breath without occlusion. Nevertheless, few studies have verified the accuracy of continuous P0.1 measurement. The aim of this study was to evaluate the accuracy of continuous P0.1 measurement compared with that of occlusion methods for various ventilators using a lung simulator. METHODS: A total of 42 breathing patterns were validated using a lung simulator in combination with 7 different inspiratory muscular pressures and 3 different rise rates to simulate normal and obstructed lungs. PB980 and Dräger V500 ventilators were used to obtain occlusion P0.1 measurements. The occlusion maneuver was performed on the ventilator, and a corresponding reference P0.1 was recorded from the ASL5000 breathing simulator simultaneously. Hamilton-C6, Hamilton-G5, and Servo-U ventilators were used to obtain sustained P0.1 measurements (continuous P0.1). The reference P0.1 measured with the simulator was analyzed by using a Bland-Altman plot. RESULTS: The 2 lung mechanical models capable of measuring occlusion P0.1 yielded values equivalent to reference P0.1 (bias and precision values were 0.51 and 1.06, respectively, for the Dräger V500, and were 0.54 and 0.91, respectively, for the PB980). Continuous P0.1 for the Hamilton-C6 was underestimated in both the normal and obstructive models (bias and precision values were -2.13 and 1.91, respectively), whereas continuous P0.1 for the Servo-U was underestimated only in the obstructive model (bias and precision values were -0.86 and 1.76, respectively). Continuous P0.1 for the Hamilton-G5 was mostly similar to but less accurate than occlusion P0.1 (bias and precision values were 1.62 and 2.06, respectively). CONCLUSIONS: The accuracy of continuous P0.1 measurements varies based on the characteristics of the ventilator and should be interpreted by considering the characteristics of each system. Moreover, measurements obtained with an occluded circuit could be desirable for determining the true P0.1.

PURPOSE OF REVIEW: The last 25 years have seen considerable development in modes of closed-loop ventilation and there are now several of them commercially available. They not only offer potential benefits for the individual patient, but may also improve the organization within the intensive care unit (ICU). Clinicians are showing both greater interest and willingness to address the issues of a caregiver shortage and overload of bedside work in the ICU. This article reviews the clinical benefits of using closed-loop ventilation modes, with a focus on control of oxygenation, lung protection, and weaning. RECENT FINDINGS: Closed-loop ventilation modes are able to maintain important physiological variables, such as oxygen saturation measured by pulse oximetry, tidal volume (VT), driving pressure (ΔP), and mechanical power (MP), within target ranges aimed at ensuring continuous lung protection. In addition, these modes adapt the ventilator support to the patient's needs, promoting diaphragm activity and preventing over-assistance. Some studies have shown the potential of these modes to reduce the duration of both weaning and mechanical ventilation. SUMMARY: Recent studies have primarily demonstrated the safety, efficacy, and feasibility of using closed-loop ventilation modes in the ICU and postsurgery patients. Large, multicenter randomized controlled trials are needed to assess their impact on important short- and long-term clinical outcomes, the organization of the ICU, and cost-effectiveness.

BACKGROUND: Hypomagnesemia reportedly has significant associations with poor clinical outcomes such as increased mortality and septic shock in patients with sepsis. Although the mechanism underlying these outcomes mostly remains unclear, some experimental data suggest that magnesium deficiency could potentiate coagulation activation in sepsis. However, in sepsis, the association between serum magnesium levels and coagulopathy, including disseminated intravascular coagulation (DIC), remains unknown. Thus, we aimed to investigate the relationship between serum magnesium levels and coagulation status and the association between hypomagnesemia and DIC in patients with sepsis. METHODS: This retrospective observational study was conducted at the intensive care unit (ICU) of a university hospital from June 2011 to December 2017. Patients older than 19 years who met the Sepsis-3 definition were included. We categorized patients into three groups according to their serum magnesium levels: hypomagnesemia (< 1.6 mg/dL), normal serum magnesium level (1.6-2.4 mg/dL), and hypermagnesemia (> 2.4 mg/dL). We investigated the association between serum magnesium levels and overt DIC at the time of ICU admission according to the criteria of the International Society on Thrombosis and Haemostasis. RESULTS: Among 753 patients included in this study, 181 had DIC, 105 had hypomagnesemia, 552 had normal serum magnesium levels, and 96 had hypermagnesemia. Patients with hypomagnesemia had a more activated coagulation status indicated by lower platelet counts, lower fibrinogen levels, higher prothrombin time-international normalized ratios, higher thrombin-antithrombin complex, and more frequent DIC than those with normal serum magnesium levels and hypermagnesemia (DIC: 41.9% vs. 20.6% vs. 24.0%, P < 0.001). The coagulation status in patients with hypomagnesemia was more augmented toward suppressed fibrinolysis than that in patients with normal serum magnesium levels and hypermagnesemia. Multivariate logistic regression revealed that hypomagnesemia was independently associated with DIC (odds ratio, 1.69; 95% confidence interval, 1.00-2.84; P = 0.048) after adjusting for several confounding variables. CONCLUSIONS: Patients with hypomagnesemia had a significantly activated coagulation status and suppressed fibrinolysis. Hypomagnesemia was independently associated with DIC in patients with sepsis. Therefore, the treatment of hypomagnesemia may be a potential therapeutic strategy for the treatment of coagulopathy in sepsis.

BACKGROUND: Since the response to lung recruitment varies greatly among patients receiving mechanical ventilation, lung recruitability should be assessed before recruitment maneuvers. The pressure-volume curve (PV curve) and recruitment-to-inflation ratio (R/I ratio) can be used bedside for evaluating lung recruitability and individualing positive end-expiratory pressure (PEEP). Lung tissue recruitment on computed tomography has been correlated with normalized maximal distance (NMD) of the quasi-static PV curve. NMD is the maximal distance between the inspiratory and expiratory limb of the PV curve normalized to the maximal volume. However, the relationship between the different parameters of hysteresis of the quasi-static PV curve and R/I ratio for recruitability is unknown. METHODS: We analyzed the data of 33 patients with severe coronavirus disease 2019 (COVID-19) who received invasive mechanical ventilation. Respiratory waveform data were collected from the ventilator using proprietary acquisition software. We examined the relationship of the R/I ratio, quasi-static PV curve items such as NMD, and respiratory system compliance (Crs). RESULTS: The median R/I ratio was 0.90 [interquartile range (IQR), 0.70-1.15] and median NMD was 41.0 [IQR, 37.1-44.1]. The NMD correlated significantly with the R/I ratio (rho = 0.74, P < 0.001). Sub-analysis showed that the NMD and R/I ratio did not correlate with Crs at lower PEEP (- 0.057, P = 0.75; and rho = 0.15, P = 0.41, respectively). On the contrary, the ratio of Crs at higher PEEP to Crs at lower PEEP (Crs ratio (higher/lower)) moderately correlated with NMD and R/I ratio (rho = 0.64, P < 0.001; and rho = 0.67, P < 0.001, respectively). CONCLUSIONS: NMD of the quasi-static PV curve and R/I ratio for recruitability assessment are highly correlated. In addition, NMD and R/I ratio correlated with the Crs ratio (higher/lower). Therefore, NMD and R/I ratio could be potential indicators of recruitability that can be performed at the bedside.

BACKGROUND: Large multicenter studies reporting on the association between the duration of broad-spectrum antimicrobial administration and the detection of multidrug-resistant (MDR) bacteria in the intensive care unit (ICU) are scarce. We evaluated the impact of broad-spectrum antimicrobial therapy for more than 72 h on the detection of MDR bacteria using the data from Japanese patients enrolled in the DIANA study. METHODS: We analyzed the data of ICU patients in the DIANA study (a multicenter international observational cohort study from Japan). Patients who received empirical antimicrobials were divided into a broad-spectrum antimicrobial group and a narrow-spectrum antimicrobial group, based on whether they received broad-spectrum antimicrobials for more or less than 72 h, respectively. Differences in patient characteristics, background of infectious diseases and empirical antimicrobial administration, and outcomes between the two groups were compared using the chi-square tests (Monte Carlo method) for categorical variables and the Mann-Whitney U-test for continuous variables. We also conducted a logistic regression analysis to investigate the factors associated with the detection of new MDR bacteria. RESULTS: A total of 254 patients from 31 Japanese ICUs were included in the analysis, of whom 159 (62.6%) were included in the broad-spectrum antimicrobial group and 95 (37.4%) were included in the narrow-spectrum antimicrobial group. The detection of new MDR bacteria was significantly higher in the broad-spectrum antimicrobial group (11.9% vs. 4.2%, p = 0.042). Logistic regression showed that broad-spectrum antimicrobial continuation for more than 72 h (OR [odds ratio] 3.09, p = 0.047) and cerebrovascular comorbidity on ICU admission (OR 2.91, p = 0.041) were associated with the detection of new MDR bacteria. CONCLUSIONS: Among Japanese ICU patients treated with empirical antimicrobials, broad-spectrum antimicrobial usage for more than 72 h was associated with the increased detection of new MDR bacteria. Antimicrobial stewardship programs in ICUs should discourage the prolonged use of empirical broad-spectrum antimicrobial therapy. Trial registration ClinicalTrials.gov, NCT02920463, Registered 30 September 2016, https://clinicaltrials.gov/ct2/show/NCT02920463.

Objectives: This retrospective observational study investigated whether the degree of muscular echogenicity in patients admitted to the intensive care unit (ICU) could help with the early detection of ICU-acquired weakness (ICU-AW) and predict physical function at hospital discharge. Methods: Twenty-five patients who were mechanically ventilated for more than 48 h in the ICU were enrolled. We also enrolled 23 outpatients with nonmuscular diseases as the control group. The target sites for measuring muscular echogenicity were the upper arm and lower leg. First, the muscular echogenicity was compared between surviving nonsurgical patients admitted to the ICU and stable outpatients with nonmuscular diseases. Second, we investigated the relationship between muscular echogenicity and clinical features, e.g., the manual muscle test (MMT), Medical Research Council (MRC) sum score, and Functional Independence Measure (FIM). Results: Muscular echogenicity in the upper arm in the ICU group was significantly higher than that in the control group. In the ICU group, the degree of muscular echogenicity of the upper arm was inversely correlated with the MMT of elbow flexion (P=0.006; r=-0.532) and the MRC sum score (P=0.002; r=-0.591). However, muscular echogenicity of the upper arm did not correlate with functional FIM (P=0.100; r=-0.344) at hospital discharge. Conclusions: Critically ill patients can experience pathological muscle weakness associated with increased muscular echogenicity in the upper arm. Additionally, the degree of muscular echogenicity in the upper arm correlated with the MRC sum score and can facilitate early detection of ICU-AW. The relationship between echogenicity and functional outcome at discharge requires elucidation.

<title>Abstract</title><sec> <title>Background</title> Electrical cardioversion (ECV) is widely used to restore sinus rhythm in critically ill adult patients with atrial fibrillation, although its prognostic value is uncertain. This study aims to elucidate the clinical meaning of successful ECV. </sec><sec> <title>Methods</title> This is a sub-analysis of the AFTER-ICU study, a multicenter prospective study with a cohort of 423 adult non-cardiac patients with new-onset atrial fibrillation (AF). Patients that underwent ECV within 7 days after initial onset of AF were included in the sub-analysis. We compared intensive care unit (ICU) and overall hospital mortality, survival time within 30 days, cardiac rhythm at ICU discharge, and the length of ICU and overall hospital stay between patients whose sinus rhythm was restored immediately after the first ECV session (primary success group) and those in whom it was not restored (unsuccessful group). To find the factors related to the primary success of ECV, we also compared patient characteristics, the delivered energy, and pretreatment. </sec><sec> <title>Results</title> Sixty-five patients received ECV and were included in this study. Although 35 patients (54%) had primary success, recurrence of AF occurred in 24 of these patients (69%). At ICU discharge, three patients still had AF in the unsuccessful group, but no patients in the primary success group still had AF. ICU mortality was 34% in the primary success group and 17% in the unsuccessful group (<italic>P</italic> = 0.10). Survival time within 30 days did not differ between the groups. Delivered energy and pretreatment were not associated with primary success of ECV. </sec><sec> <title>Conclusions</title> The primary success rate of ECV for new-onset AF in adult non-cardiac ICU population was low, and even if it succeeded, the subsequent recurrence rate was high. Primary success of ECV did not affect the rate of mortality. Pretreatment and delivered energy were not associated with the primary success of ECV. </sec><sec> <title>Trial registration</title> UMIN clinical trial registry, the Japanese clinical trial registry (registration number: <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000030333">UMIN000026401</ext-link>, March 31, 2017). </sec>

Recently, maintaining a certain oxygen saturation measured by pulse oximetry (SpO2) range in mechanically ventilated patients was recommended; attaching the INTELLiVENT-ASV to ventilators might be beneficial. We evaluated the SpO2 measurement accuracy of a Nihon Kohden and a Masimo monitor compared to actual arterial oxygen saturation (SaO2). SpO2 was simultaneously measured by a Nihon Kohden and Masimo monitor in patients consecutively admitted to a general intensive care unit and mechanically ventilated. Bland-Altman plots were used to compare measured SpO2 with actual SaO2. One hundred mechanically ventilated patients and 1497 arterial blood gas results were reviewed. Mean SaO2 values, Nihon Kohden SpO2 measurements, and Masimo SpO2 measurements were 95.7%, 96.4%, and 96.9%, respectively. The Nihon Kohden SpO2 measurements were less biased than Masimo measurements; their precision was not significantly different. Nihon Kohden and Masimo SpO2 measurements were not significantly different in the "SaO2 < 94%" group (P = 0.083). In the "94% ≤ SaO2 < 98%" and "SaO2 ≥ 98%" groups, there were significant differences between the Nihon Kohden and Masimo SpO2 measurements (P < 0.0001; P = 0.006; respectively). Therefore, when using automatically controlling oxygenation with INTELLiVENT-ASV in mechanically ventilated patients, the Nihon Kohden SpO2 sensor is preferable.Trial registration UMIN000027671. Registered 7 June 2017.

OBJECTIVES: Moral distress occurs when professionals cannot carry out what they believe to be ethically appropriate actions because of constraints or barriers. We aimed to assess the validity and reliability of the Japanese translation of the Measure of Moral Distress for Healthcare Professionals (MMD-HP). METHODS: We translated the questionnaire into Japanese according to the instructions of EORTC Quality of Life group translation manual. All physicians and nurses who were directly involved in patient care at nine departments of four tertiary hospitals in Japan were invited to a survey to assess the construct validity, reliability and factor structure. Construct validity was assessed with the relation to the intention to leave the clinical position, and internal consistency was assessed with Cronbach's alpha. Confirmatory factor analysis was conducted. RESULTS: 308 responses were eligible for the analysis. The mean total score of MMD-HP (range, 0-432) was 98.2 (SD, 59.9). The score was higher in those who have or had the intention to leave their clinical role due to moral distress than in those who do not or did not have the intention of leaving (mean 113.7 [SD, 61.3] vs. 86.1 [56.6], t-test p < 0.001). The confirmatory factor analysis and Cronbach's alpha confirmed the validity (chi-square, 661.9; CMIN/df, 2.14; GFI, 0.86; CFI, 0.88; CFI/TLI, 1.02; RMSEA, 0.061 [90%CI, 0.055-0.067]) and reliability (0.91 [95%CI, 0.89-0.92]) of the instrument. CONCLUSIONS: The translated Japanese version of the MMD-HP is a reliable and valid instrument to assess moral distress among physicians and nurses.

BACKGROUND: Metabolic acidosis is a major complication of critical illness. However, its current epidemiology and its treatment with sodium bicarbonate given to correct metabolic acidosis in the ICU are poorly understood. METHOD: This was an international retrospective observational study in 18 ICUs in Australia, Japan, and Taiwan. Adult patients were consecutively screened, and those with early metabolic acidosis (pH < 7.3 and a Base Excess < -4 mEq/L, within 24-h of ICU admission) were included. Screening continued until 10 patients who received and 10 patients who did not receive sodium bicarbonate in the first 24 h (early bicarbonate therapy) were included at each site. The primary outcome was ICU mortality, and the association between sodium bicarbonate and the clinical outcomes were assessed using regression analysis with generalized linear mixed model. RESULTS: We screened 9437 patients. Of these, 1292 had early metabolic acidosis (14.0%). Early sodium bicarbonate was given to 18.0% (233/1292) of these patients. Dosing, physiological, and clinical outcome data were assessed in 360 patients. The median dose of sodium bicarbonate in the first 24 h was 110 mmol, which was not correlated with bodyweight or the severity of metabolic acidosis. Patients who received early sodium bicarbonate had higher APACHE III scores, lower pH, lower base excess, lower PaCO2, and a higher lactate and received higher doses of vasopressors. After adjusting for confounders, the early administration of sodium bicarbonate was associated with an adjusted odds ratio (aOR) of 0.85 (95% CI, 0.44 to 1.62) for ICU mortality. In patients with vasopressor dependency, early sodium bicarbonate was associated with higher mean arterial pressure at 6 h and an aOR of 0.52 (95% CI, 0.22 to 1.19) for ICU mortality. CONCLUSIONS: Early metabolic acidosis is common in critically ill patients. Early sodium bicarbonate is administered by clinicians to more severely ill patients but without correction for weight or acidosis severity. Bicarbonate therapy in acidotic vasopressor-dependent patients may be beneficial and warrants further investigation.

BACKGROUND: INTELLiVENT-ASV® (I-ASV) is a closed-loop ventilation mode that automatically controls the ventilation settings. Although a number of studies have reported the usefulness of I-ASV, the clinical situations in which it may be useful have not yet been clarified. We aimed to report our initial 3 years of experience using I-ASV, particularly the clinical conditions and the technical and organizational factors associated with its use. Furthermore, we evaluated the usefulness of I-ASV and determined the predictive factors for successful management with I-ASV. METHODS: This single-center, retrospective observational study included patients who were ventilated using the Hamilton G5® ventilator (Hamilton Medical AG, Rhäzüns, Switzerland) from January 2016 to December 2018. The patients were categorized into the "I-ASV success" group and "I-ASV failure" group (those receiving mechanical ventilation with I-ASV along with any other mode). Multivariate analysis was performed to identify factors associated with successful I-ASV management. RESULTS: Of the 189 patients, 135 (71.4%) were categorized into the I-ASV success group. In the I-ASV success group, the reasons for ICU admission included post-elective surgery (94.1%), post-emergent surgery (81.5%), and other medical reasons (55.6%). I-ASV failure was associated with a low P/F ratio (278 vs. 167, P = 0.0003) and high Acute Physiology and Chronic Health Evaluation (APACHE) II score (21 vs. 26, P < 0.0001). The main reasons for not using I-ASV included strong inspiratory effort and asynchrony. The APACHE II score was an independent predictive factor for successful management with I-ASV, with an odds ratio of 0.92 (95% confidential interval 0.87-0.96, P = 0.0006). The area under the receiver operating curve for the APACHE II score was 0.722 (cut-off: 24). CONCLUSIONS: In this study, we found that 71.4% of the fully mechanically ventilated patients could be managed successfully with I-ASV. The APACHE II score was an independent factor that could help predict the successful management of I-ASV. To improve I-ASV management, it is necessary to focus on patient-ventilator interactions.

BACKGROUND: Altered coagulation and alveolar injury are the hallmarks of acute respiratory distress syndrome (ARDS). However, whether the biomarkers that reflect pathophysiology differ depending on the etiology of ARDS has not been examined. This study aimed to investigate the biomarker profiles of coagulopathy and alveolar epithelial injury in two subtypes of ARDS: patients with direct common risk factors (dARDS) and those with idiopathic or immune-related diseases (iARDS), which are classified as "ARDS without common risk factors" based on the Berlin definition. METHODS: This retrospective, observational study included adult patients who were admitted to the intensive care unit (ICU) at a university hospital with a diagnosis of ARDS with no indirect risk factors. Plasma biomarkers (thrombin-antithrombin complex [TAT], plasminogen activator inhibitor [PAI]-1, protein C [PC] activity, procalcitonin [PCT], surfactant protein [SP]-D, and KL-6) were routinely measured during the first 5 days of the patient's ICU stay. RESULTS: Among 138 eligible patients with ARDS, 51 were excluded based on the exclusion criteria (n = 41) or other causes of ARDS (n = 10). Of the remaining 87 patients, 56 were identified as having dARDS and 31 as having iARDS. Among the iARDS patients, TAT (marker of thrombin generation) and PAI-1 (marker of inhibited fibrinolysis) were increased, and PC activity was above normal. In contrast, PC activity was significantly decreased, and TAT or PAI-1 was present at much higher levels in dARDS compared with iARDS patients. Significant differences were also observed in PCT, SP-D, and KL-6 between patients with dARDS and iARDS. The receiver operating characteristic (ROC) analysis showed that areas under the ROC curve for PC activity, PAI-1, PCT, SP-D, and KL-6 were similarly high for distinguishing between dARDS and iARDS (PC 0.86, P = 0.33; PAI-1 0.89, P = 0.95; PCT 0.89, P = 0.66; and SP-D 0.88, P = 0.16 vs. KL-6 0.90, respectively). CONCLUSIONS: Coagulopathy and alveolar epithelial injury were observed in both patients with dARDS and with iARDS. However, their biomarker profiles were significantly different between the two groups. The different patterns of PAI-1, PC activity, SP-D, and KL-6 may help in differentiating between these ARDS subtypes.

BACKGROUND: Recent studies have suggested a low potential risk for contrast medium-induced kidney injury in patients with relatively normal renal function. However, whether contrast media cause additional deterioration of renal function in patients with acute kidney injury (AKI), including those with sepsis-associated AKI, remains unclear. This study aimed to evaluate the effect of contrast media on renal function and mortality in patients with sepsis who already had AKI. METHODS: We performed a propensity score-matched historical cohort study in the medico-surgical intensive care unit of Jichi Medical University Hospital. Adult patients who were diagnosed with sepsis and AKI were enrolled. Records from our sepsis database from 2011 to 2017 were examined. Septic patients with AKI who received contrast media within 24 h of admission (C group) were matched 1:1 with septic patients who did not receive contrast media (NC group). The primary outcome was deterioration of kidney function (DRF), which was defined as an elevation of serum creatinine levels (> 0.3 mg/dL or 1.5-fold from baseline) or induction of renal replacement therapy. RESULTS: A total of 339 septic patients with AKI were included. After propensity score adjustment, the DRF rate was similar between the C and NC groups (34.0% versus 35.0%; P = 1.00). The 7-day mortality (3.0% versus 6.0%; P = 0.50), 28-day mortality (9.2% versus 15.0%; P = 0.25), and 90-day mortality (25.8% versus 32.1%; P = 0.45) rates were comparable between the two groups. In propensity-adjusted subsets of a high-risk subset (AKI stages 2 and 3 on admission), the rate of DRF was also similar between the two groups. CONCLUSIONS: A single administration of contrast media was not associated with exacerbation of AKI or increased short/long-term mortality in patients with sepsis.

Since endothelial function is closely related to organ dysfunction in sepsis and the relationship among endothelial injury, organ dysfunction, and other biomarkers remains unclear, we aimed to evaluate the correlation among endothelial injury, organ dysfunction, and several biomarkers in patients with sepsis. Design: This was a retrospective observational study. Setting: The study was conducted in a university hospital with 14 mixed ICU beds. Patients: ICU patients with sepsis from June 2011 to December 2017 were enrolled in this study. Interventions: Endothelial biomarkers (soluble thrombomodulin, plasminogen activator inhibitor-1, and protein C) and markers of inflammation and coagulation were evaluated during the ICU stay. Sequential Organ Failure Assessment scores were assessed for 7 days after ICU admission to determine organ dysfunction. Variables were compared among five stratified groups according to the Sequential Organ Failure Assessment score (0-2, 3-5, 6-8, 9-12, and 13-24). Regression analysis and 95% CIs were used to evaluate trends in biomarkers. Measurements and Main Results: The patients were divided into five stratified groups (Sequential Organ Failure Assessment 0-2, n = 159 [20.5%]; Sequential Organ Failure Assessment 3-5, n = 296 [38.2%]; Sequential Organ Failure Assessment 6-8, n = 182 [23.5%]; Sequential Organ Failure Assessment 9-12, n = 75 [9.7%]; Sequential Organ Failure Assessment 13-24, n = 31 [4.0%]). Protein C activity was significantly correlated with the severity of organ dysfunction. It was lower on day 1, increased upon successful treatment, and was significantly higher in groups with lower Sequential Organ Failure Assessment scores. Conclusions: Trends and activity of protein C were superior in predicting organ dysfunction compared with other endothelial biomarkers. Monitoring the level of protein C activity is an ideal tool to monitor organ dysfunctions in patients with sepsis.

Background: Intravenous glycerol treatment, usually administered in the form of a 5% fructose solution, can be used to reduce intracranial pressure. The administered fructose theoretically influences blood lactate levels, although little is known regarding whether intravenous glycerol treatment causes transient hyperlactatemia. This study aimed to evaluate blood lactate levels in patients who received intravenous glycerol or mannitol. Methods: This single-center prospective observational study was performed at a 14-bed general intensive care unit between August 2016 and January 2018. Patients were excluded if they were < 20 years old or had pre-existing hyperlactatemia (blood lactate > 2.0 mmol/L). The included patients received intravenous glycerol or mannitol to reduce intracranial pressure and provided blood samples for lactate testing before and after the drug infusion (before the infusion and after 15 min, 30 min, 45 min, 60 min, 90 min, 120 min, and 150 min). Results: Among the 33 included patients, 13 patients received 200 mL of glycerol over 30 min, 13 patients received 200 mL of glycerol over 60 min, and 7 patients received 300 mL of mannitol over 60 min. Both groups of patients who received glycerol had significantly higher lactate levels than the mannitol group (2.8 mmol/L vs. 2.2 mmol/L vs. 1.6 mmol/L, P < 0.0001), with the magnitude of the increase in lactate levels corresponding to the glycerol infusion time. There were no significant inter-group differences in cardiac index, stroke volume, or stroke volume variation. In the group that received the 30-min glycerol infusion, blood lactate levels did not return to the normal range until after 120 min. Conclusions: Intravenous administration of glycerol leads to higher blood lactate levels that persist for up to 120 min. Although hyperlactatemia is an essential indicator of sepsis and/or impaired tissue perfusion, physicians should be aware of this phenomenon when assessing the blood lactate levels.