Background Endotoxin removal therapy using a polymyxin B-immobilized fiber column (PMX) has been reported to improve hemodynamics in patients with septic shock. However, the mechanisms underlying the blood pressure‒increasing effects of PMX treatment remain unclear, and factors other than endotoxin adsorption may be involved. This study focused on vasoconstrictive lipid mediators in the blood and comprehensively analyzed these mediators in patients with septic shock. Methods This prospective observational study included 10 patients with septic shock who underwent PMX treatment. Blood samples were collected at multiple time points up to 120 minutes after PMX initiation, and 23 lipid mediators were measured by mass spectrometry. Hemodynamic changes were evaluated using the vasopressor dependency index (VDI). Furthermore, platelet-rich plasma from healthy subjects was incubated with PMX fibers in vitro to assess platelet adhesion by electron microscopy and thromboxane production. Results Among the 10 patients included, the plasma concentration of thromboxane B2 (TXB2), a stable derivative of thromboxane A2 (TXA2), was significantly higher at the PMX column outlet than at the inlet. This difference in TXB2 concentration showed a significant positive correlation with the platelet count. Patients with higher platelet counts tended to exhibit a greater decrease in VDI, although the difference was not statistically significant. In vitro experiments demonstrated that platelets adhered to PMX fibers, accompanied by morphological changes, and that the fibers stimulated TXB2 production. Importantly, this production was suppressed by an antibody against the platelet surface antigen αIIbβ3. Conclusion TXA2, produced by platelets upon contact with PMX fibers during treatment, may contribute to the rapid increase in blood pressure observed after initiation of therapy.

Introduction Sleep disturbances among nurses engaged in night duty and their spouses need to be improved to ensure their ability to provide care and perform daily tasks. Therefore, an objective investigation is needed to establish a sleep improvement strategy. Objective To investigate the utility of a sleep tracker to assess sleep quality in nurses and spouses. Method Nurses ( n = 30) and spouses ( n = 30) wore a sleep tracker for 14 days to investigate sleep scores. Sleep quality and number of steps were evaluated by Fitbit. They responded to the Richards-Campbell Sleep Questionnaire and Pittsburgh Sleep Quality Index. A multiple regression analysis was performed to identify the factors affecting sleep quality. Results Factors affecting sleep scores in nurses were hypnotic medication, night duty, and steps, while those in spouses were mental instability, hypnotic medication, alcohol, night duty, and steps. Factors affecting the Richards-Campbell Sleep Questionnaire in nurses were household chores, night duty, and steps, while those in spouses were hypnotic medication and steps. Conclusion The sleep quality of nurses was affected by household chores, hypnotic medication, night duty, and steps. Besides the factors of nurses, spouses were affected by mental instability and alcohol. Night duty affected negativity in both nurses and spouses. Steps exerted positive effects in both the sleep tracker and the Richards-Campbell Sleep Questionnaire. The sleep tracker may be useful for identifying factors that improve sleep quality.

BackgroundAmong damage-associated molecular patterns (DAMPs), the specific contributions of histone and high mobility group box 1 (HMGB1) levels to disseminated intravascular coagulation (DIC) and multiple organ dysfunction (MOD) remain unclear. In this study, we aimed to investigate the association between two DAMP markers, plasma histone H3 and HMGB1 levels, and concurrent DIC and Sequential Organ Failure Assessment (SOFA) score in critically ill patients.MethodsPlasma levels of histone H3 and HMGB1 were prospectively quantified in 46 critically ill patients who demonstrated systemic inflammatory response syndrome, possible sepsis, and required intensive care unit (ICU) treatment. We analyzed two DAMP marker values, various plasma-inflammatory and non-inflammatory cytokine levels, acute DIC on ICU day 3, and the maximum SOFA score at 48 h after ICU admission.ResultsOn ICU day 3, 25 patients had DIC while 21 did not. In multivariate logistic regression analysis, plasma histone H3 levels (odds ratio [95% confidence interval]: 1.17 [1.02- 1.49], p = 0.008) and TNF-α (1.006 [1.001- 1.014], p = 0.007) were significant independent factors of DIC pathogenesis. The Spearman's rank correlation coefficients for the maximum SOFA score were 0.664, 0.602, 0.348, and 0.221 for IL-8, IL-6, histone H3, and HMGB1, respectively.ConclusionIn the early phase requiring intensive care, histone H3 levels exhibited a more positive association with the onset of DIC than HMGB1. Conversely, inflammatory cytokines may exert a more substantial influence on the pathogenesis of multiple organ failure in comparison to DAMPs.

OBJECTIVE:Amino acid and protein loss during continuous renal replacement therapy has been proposed to contribute to protein-energy wasting in patients with acute kidney injury (AKI); however, the actual amount removed remains unclear. We investigated the loss of amino acids and proteins in the filtrate during continuous renal replacement therapy in patients who did not receive nutritional supplementation. METHODS:A total of 19 patients with AKI who received low-dose continuous venovenous hemofiltration (CVVH) were included. Blood samples were collected before CVVH initiation and at 30, 60, 120, and 240 minutes thereafter, and a filtrate sample was collected at 240 minutes. Changes in blood amino acid concentrations during 240-minute CVVH sessions were measured. The amino acid and protein concentrations in the filtrate were determined at the end of the 240-minute CVVH session, and the amounts of amino acids and proteins lost during 240-minute CVVH were calculated. RESULTS:The median total amino acid blood concentrations did not decrease and were near the lower limits of the reference ranges. The median concentrations of 3-methyl histidine, a marker of skeletal muscle catabolism, were above the upper limits of the reference ranges throughout the CVVH session. The median total amino acidloss during the 240-minute CVVH session was 0.95 g. In 10 patients with detectable proteins in the filtrate, the median protein loss was 2.52 g. CONCLUSION:These results suggest that optimal nutritional management in patients with AKI who receive CVVH should take into account amino acid and protein loss and hypercatabolism.

BACKGROUND & AIMS:Protein intake guidelines for critically ill patients during the acute phase vary significantly. In Japan, where many patients are older, underweight, and thinner compared to other countries, it is unclear whether international recommendations are applicable. This study aimed to evaluate the impact of protein administration on the survival of critically ill patients on ICU days 4 and 7. METHODS:This retrospective study included adult patients admitted to the intensive care unit (ICU) of Sapporo Medical University Hospital between February 2018 and November 2023. Eligible patients received artificial nutrition (enteral and/or parenteral) and remained in the ICU for >8 days. Patients were categorized into three groups based on protein intake quartiles on ICU days 4 and 7: Low Protein (<0.8 g/kg/day), Middle Protein (0.8-1.4 g/kg/day), and High Protein (≥1.4 g/kg/day). The association between protein dose and survival was analyzed. RESULTS:A total of 262 patients met the inclusion criteria. On ICU day 4, the HP group demonstrated significantly lower day 28 survival (adjusted HR: 1.941, 95 % CI: 1.018-3.701) and day 90 survival (adjusted HR: 1.683, 95 % CI: 1.007-2.815) compared to the MP group. High protein dose on day 4 was identified as an independent risk factor for poorer clinical outcomes. However, protein dose on ICU day 7 was not associated with survival outcomes. CONCLUSIONS:In critically ill patients in Japan, high-dose protein administration (≥1.4 g/kg/day) on ICU day 4 may adversely affect clinical outcomes. Careful consideration of protein dosing during the early acute phase is recommended.

Polymyxin B haemoperfusion is commonly used to adsorb endotoxins in septic shock caused by Gram-negative bacterial infections. Polymyxin B haemoperfusion has been reported to improve hypotension in Gram-positive bacterial infections; however, its efficacy and mechanism in treating such cases are unclear. We hypothesised that polymyxin B haemoperfusion would be equally effective in improving haemodynamics during Gram-positive bacterial infections as in Gram-negative bacterial infections. We conducted a retrospective study that included patients with septic shock admitted to the intensive care unit. The patients were divided into two groups according to bacterial culture results: Gram-negative rod (GNR) and Gram-positive coccus (GPC). We calculated the vasoactive inotropic score (VIS) before (0 h) and 2, 6, 12 and 24 h after polymyxin B haemoperfusion therapy. Data were analysed using two-way analysis of variance and post hoc tests for the associations between infection type and treatment time. Overall, 157 patients with septic shock were enrolled in the study: 81 and 76 patients were treated or not treated with extracorporeal haemoperfusion therapy, respectively. Although there was no significant difference in the VIS in polymyxin B haemoperfusion between patients with GNR and GPC infections, there was a significant decrease in the VIS over time, even when GPC was the causative organism. In addition, the degree of reduction in the VIS was significantly different in both the GNR and GPC groups compared with that in the non-extracorporeally treated group. Thus, polymyxin B haemoperfusion for septic shock caused by GNR reduced the VIS and could be effective even in cases of GPC infection.

BackgroundIn recent years, continuous kidney replacement therapy (CKRT) with a cytokine adsorbing hemofilter (CAH) has been used in clinical practice to treat acute kidney injury associated with hypercytokinemia. Two types of CAH are available, including polymethyl methacrylate (PMMA) and polyethylenimine-coated polyacrylonitrile (AN69ST), each having distinct adsorption mechanisms. PMMA adsorbs substances with hydrophobic bases through hydrophobic interactions, resulting in occlusion of the membrane pores. AN69ST adsorbs positively charged substances through electrostatic bonds because its bulk layer is negatively charged. In both CAH, the adsorption efficiency of cytokines with large molecular weights is likely affected by filtration rather than by diffusion transfer. These adsorbing-type membranes have limitations in terms of filtration flow rate because of their low water permeability. The relationship between the adsorption effect and the filtration flow rate in CAH-CKRT has not been fully investigated.PurposeThe effect of low-convection volume settings below 600 mL/h on cytokine adsorption characteristics was experimentally investigated in CKRT.Materials and methodsTest solutions, including albumin (4.5%), creatinine (10 mg/dL), interleukin (IL)-6 (1000 pg/mL), and IL-8 (1000 pg/mL), were prepared. The test solution was circulated through the experimental circuit of continuous hemodiafiltration (CHDF) with a total convection volume ranging from 0 to 600 mL/h. The test solution was circulated through the experimental circuit of hemodiafiltration (CHDF) with various dialysate flow rates (QD; 0, 200, 400, and 600 ml/h) and filtration flow rates (QF; 0, 200, 400, and 600 ml/h). Samples immediately before and after CAH from the sampling port of the circuit were collected seven times at 1-min intervals. Clearances of creatinine, IL-6, and IL-8 were calculated for each setting of the proportions of QD and QF during CKRT using PMMA and AN69ST.ResultsCreatinine clearance increased with increasing QD and QF, regardless of the membrane type. There were no significant differences in the adsorption clearance of IL-6 and IL-8 among the different settings, regardless of the membrane type.ConclusionThe results of this study indicate that the cytokine clearance at a low convection volume in CAH-CKRT was not affected by the filtration flow rate.

In Japan, the post-dilution method is preferred to maintain the dialysis efficiency of low molecular weight substances in continuous hemodiafiltration (CHDF). In contrast, the pre-dilution method is preferable to ensure a stable filter lifetime, especially for membranes with cytokine absorptive characteristics that are at high risk of membrane coagulation. However, the impact of the dilution method on the removal performance of adsorptive membranes for cytokines remains unclear. This study aimed to investigate the effect of different dilution methods on the adsorption clearance of cytokine on polymethylmethacrylate (PMMA) membranes by in vitro experiments. Bovine albumin, interleukin (IL)-6, and creatinine were added to phosphate-buffered saline to achieve final concentrations of 3.5 g/dL, 1000 pg/mL, and 10 mg/dL, respectively. The test solution was passed through the 1.8 m2 PMMA membrane hemofilter at a flow rate of 100 mL/min in a single-pass system. The dialysate/filtration flow rates used were 2.5/2.5, 5.0/5.0, and 7.5/7.5 mL/min for each pre- and post-dilution method. Samples were collected seven times from pre- and post-hemofilter every minute, 10 min after the start of CHDF. Samples were frozen and stored, and the concentration of IL-6 was measured by enzyme-linked immunosorbent assay (ELISA), and clearance was calculated. Creatinine clearance increased with an increasing flow rate in pre- and post-dilution, while IL-6 clearance was less affected by flow rate. IL-6 clearance was 35.5 mL/min (32.1-39.6) for pre-dilution and 37.1 mL/min (33.8-41.1) for post-dilution in the 2.5/2.5 setting, and 34.2 mL/min (28.8-36.2) for pre-dilution and 32.4 mL/min (32.4-37.4) for post-dilution in the 5.0/5.0 setting. The dilution methods showed no significant differences. Moreover, in the 7.5/7.5 setting, clearance was 29.5 mL/min (27.7-37.2) for pre-dilution and 39.9 mL/min (37.8-41.5) for post-dilution (P<0.001); however, all clearance values were higher than theoretical values expected from filtration removal. In conclusion, the cytokine removal characteristics of the PMMA membrane hemofilter were not largely affected by the dilution method, and IL-6 clearance could be fully demonstrated even in the pre-dilution method.

Background Fatigue presents an important challenge for patients discharged from intensive care units (ICUs). Despite its importance, data on the prevalence and clinical impact of post-ICU fatigue remain limited. In particular, the proportion of patients in clinical settings in Japan who find fatigue distressing, as well as the associations between fatigue, risk factors, and self-rated health, have not been fully explored using validated fatigue measures. Therefore, this study aimed to assess the prevalence of fatigue, identify its associated risk factors, and examine the relationship between fatigue and self-rated health status six months after ICU discharge in Japan. Methods This single-center, ambidirectional cohort study administered a survey to patients aged ≥18 years, six months after ICU discharge, to assess fatigue and self-rated health. Retrospective data were also collected from patients' medical records during hospitalization. Fatigue prevalence was the primary endpoint, measured using the cutoff value of the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) scale. Logistic regression analysis was performed to identify risk factors for fatigue. Locally weighted scatterplot smoothing (LOWESS) plots were generated with FACIT-F scale scores, and the association between fatigue and EuroQol 5 Dimensions 5-Level Visual Analog Scale (EQ-VAS) was analyzed. Results Questionnaires were sent to 87 patients, of whom 81 (93.1%) responded. Eight patients (9.9%) with missing FACIT-F scores were excluded, leaving 73 patients for analysis. The median (interquartile range) age of eligible patients was 74 (63-81) years, and 33 patients (45%) were male. Forty-six patients (63%) reported fatigue. Multivariate analysis identified a higher body mass index (BMI) at ICU admission as an independent risk factor for fatigue (odds ratio (OR) = 1.195; 95% confidence interval (CI) 1.018-1.447; p < 0.05). EQ-VAS scores were significantly lower in the fatigue group (OR 72.5, 95% CI 60-83.8 vs. OR 90, 95% CI 80-90; p < 0.01). Conclusion This study found that many patients in Japanese ICUs experience fatigue, even when disease severity is low. Additionally, BMI at ICU admission was identified as an independent risk factor for fatigue six months after ICU discharge. Regular follow-up on fatigue after ICU discharge is essential for improving long-term outcomes.

INTRODUCTION:Continuous renal replacement therapy (CRRT) is often performed for critically ill patients in intensive care units (ICUs), but its optimal indication and settings have yet to be determined. Thus, we aimed to describe the current status of CRRT in Japan through a multicenter retrospective observational study. METHODS:Adult ICU patients receiving CRRT at 18 tertiary hospitals in Japan (up to 100 patients from each hospital over the past year) were retrospectively enrolled. Patients receiving CRRT for <24 h or intermittent renal replacement therapy together with CRRT were excluded. The primary outcomes were the temporal changes in the electrolyte levels, acid-base balance, and uremia-related small solute concentrations. The secondary outcomes included potassium (K) and phosphate (P) supplementations during CRRT. RESULTS:Altogether, 1,045 patients were enrolled. The median CRRT duration and dose were 4.4 days and 17.3 mL/kg/h, respectively. The electrolyte levels, acid-base balance, and uremia-related small solute concentrations returned to normal by day 4 of treatment. A total of 732 (70.0%) patients received K supplementation, and only a few patients had hypokalemia until day 5. Moreover, 414 (39.6%) patients received P supplementation, and approximately 30%-50% of the patients had hypophosphatemia until day 5. CONCLUSION:The CRRT dose in Japan was lower than that was recommended by the Kidney Disease: Improving Global Outcomes guideline. The electrolyte level abnormalities and acid-base imbalances of the studied patients were improved within 72-96 h of CRRT. Contrarily, K and P supplementations were common, indicating that the current CRRT solutions need to be modified.

BACKGROUND:The pathogenesis of sepsis is thought to be linked to a dysregulated immune response, particularly that involving neutrophils. We have developed a granulocyte adsorption column as a "decoy organ," which relocates the massive inflammation in organs in the body to a blood purification column. This study was conducted to assess the safety and experimental effectiveness of granulocyte monocyte adsorption apheresis-direct hemoperfusion (G1-DHP) in the treatment of patients with sepsis, using a prospective, multicenter design. METHODS:The study included patients diagnosed with sepsis and with an APACHE II score ranging from 17 to 34. A total of five G1-DHP were performed within 3 days of patient enrollment. The primary endpoint was the change in sequential organ failure assessment (SOFA) score from enrollment to 7 days, and the safety endpoints were adverse events and mortality at 28 days. RESULTS:G1-DHP was performed on 82 patients. The median (interquartile range) SOFA score decreased from 10 (8-11) to 4 (3-7) after 7 days (n = 70; p < 0.01). Granulocytes, mainly neutrophils, were adsorbed, and the neutrophil-to-lymphocyte ratio significantly improved (p < 0.01). Notable improvements were observed in the SOFA scores for circulation and renal function. The acute physiology and chronic health evaluation II score of the 77 patients evaluated for mortality was 27, and the 28-day mortality rate was 7.8%. CONCLUSIONS:This study confirmed that G1-DHP can be safely used as an adjunct to standard sepsis treatment regimens. Although further investigations are required, G1-DHP is a promising supplemental therapy for sepsis. TRIAL REGISTRATION:jRCT1080225183 (Japan Registry of Clinical Trials identifier).

Recently, the Nellcor PM1000N was developed for the concurrent assessment of respiratory rate and percutaneous oxygen saturation. However, the validation of respiratory rate measurements in patients receiving a high-flow nasal cannula (HFNC) using the PM1000N remains unestablished. Therefore, this study aimed to assess the validity of respiratory rate measurements obtained using PM1000N in patients receiving HFNC. A retrospective assessment was conducted on the respiratory rate measurements obtained using the PM1000N and electrocardiogram (ECG) impedance methods in comparison to those visually assessed by nurses. This evaluation included patients admitted to the Intensive Care Unit (ICU) of Sapporo Medical University Hospital who received HFNC between June 2022 and December 2022. Correlation coefficients, intraclass correlation coefficients (ICCs), Bland–Altman plots, and t-tests were employed to assess the concordance between the visually observed respiratory rates by nurses and those recorded by the PM1000N and ECG impedance. Twenty patients were enrolled in this study. Among them, 119 instances of respiratory rate were recorded. The ICCs for the PM1000N and impedance methods were 0.918 and 0.846, respectively, compared with the rates visually assessed by nurses. The mean differences were p = 0.947 (95

Introduction:Continuous renal replacement therapy(CRRT) eliminates these small solutes with equal efficacyunder the same conditions. However, variations in thereduction rates of these solutes observed in patients withCRRT are likely influenced by factors other than removalthrough CRRT. This study evaluated the reduction ratesof these small solutes during CRRT and their possibleassociation with mortality.Methods:This study used thedata of limited patients registered in the CHANGE study,which is a large retrospective observational study onCRRT management across 18 Japanese ICUs. Reductionrates of three solutes in blood, calculated on the 1st and2nd days, were compared in patients with acute kidneyinjury (AKI) treated by CRRT. The potential associationbetween solute reduction rates and mortality duringCRRT or within 7 days after the termination of CRRT wasevaluated.Results:In total, 163 patients with AKI wereincluded in the analysis. The reduction rates of uric acid(UA) were significantly higher than those of urea andcreatinine for the 1st and 2nd tests in the entire cohort.Receiver operating characteristic (ROC) curve analysisrevealed that lower UA reduction rates were significantlyassociated with mortality during CRRT or within 7 daysafter CRRT termination {area under the ROC curve: 0.62[95% confidence interval (CI): 0.52-0.71] for the 1st testand 0.63 [95% CI: 0.54-0.72] for the 2nd test}. Afteradjusting for age and SOFA score, a significant associ-ation was observed between lower UA reduction ratesand hospital mortality for both tests.Conclusion:Amongthe small solutes, UA reduction rates in patients with AKItreated with CRRT were notably higher than those ofcreatinine and urea. Furthermore, the significant asso-ciation between lower UA reduction rates and mortalitysuggests that UA reduction rate may serve as a valuableindicator of insufficient removal of uremic solutes byCRRT, although the decline in UA production must betaken into account.(c) 2024 The Author(s).Published by S. Karger AG, Basel

BACKGROUND:The COVID-19 pandemic has led to an unprecedented increase in cases of acute respiratory distress syndrome (ARDS). In such cases, deep sedation using sedatives and muscle relaxants is commonly used to prevent patient self-inflicted lung injury during the early phase. However, such sedation limits the ability to perform early rehabilitation, leading to ICU-acquired muscle weakness (ICU-AW) and a worse prognosis. SUBJECTS:This study aimed to clarify the preventive effect of neuromuscular electrical stimulation (NMES) during deep sedation on ICU-AW and physical function at discharge in critically ill patients with COVID-19 with ARDS. METHODS:A retrospective, single-center study was conducted on patients admitted to the ICU or advanced critical care center with severe COVID-19 with ARDS between March 1, 2020, and March 31, 2022. Patients who were managed with the Richmond Agitation-Sedation Scale between -4 and -5 for at least three days were included. Patients in the NMES group received NMES within two days of deep sedation, whereas those in the non-NMES group did not. The primary endpoint was the incidence of ICU-AW at discharge from the ICU, and the secondary endpoints included physical activity levels, skeletal muscle mass index, time to active mobilization, and Barthel index (BI) at discharge. Statistical analyses included Pearson's chi-squared test, Fisher's exact test, and multiple logistic and linear regression analyses. RESULTS:Of the 129 patients, 68 (54 males and 14 females) were included after applying the exclusion criteria, with 38 in the NMES group and 30 in the non-NMES group. The incidence of ICU-AW was significantly lower in the NMES group (28.95% vs. 56.67%, p = 0.0211). NMES implementation (OR: 0.20, p = 0.03), ventilator weaning (OR: 0.10, p = 0.01), and duration of deep sedation (OR: 0.81, p < 0.01) were significant predictors of ICU-AW. Higher ICU Mobility Scale scores and shorter time to active mobilization were associated with a higher BI at discharge. CONCLUSIONS:Early rehabilitation using NMES during deep sedation may prevent ICU-AW in critically ill patients with COVID-19 with ARDS. NMES is associated with a reduced risk of ICU-AW and improved functional independence at discharge. This procedure can be safely performed in sedated patients and may help prevent ICU-AW, supporting early mobilization strategies in ARDS rehabilitation.

Aggressive pharmacokinetic (PK)/pharmacodynamic (PD) targets have shown better microbiological eradication rates and a lower propensity to develop resistant strains than conservative targets. We investigated whether meropenem blood levels, including aggressive PK/PD, were acceptable in terms of efficacy and safety using a meropenem regimen of 1 g infusion every 8 h over 3 h in patients undergoing continuous renal replacement therapy (CRRT) for septic acute kidney injury (AKI). Aggressive PK/PD targets were defined as the percentage of time that the free concentration (%fT) > 4 × minimal inhibitory concentration (MIC), the toxicity threshold was defined as a trough concentration >45 mg/L, and the percentage of achievement at each MIC was evaluated. The 100% fT > 4 × MIC for a pathogen with an MIC of 0.5 mg/L was 89%, and that for a pathogen with an MIC of 2 mg/L was 56%. The mean steady-state trough concentration of meropenem was 11.9 ± 9.0 mg/L and the maximum steady-state trough concentration was 29.2 mg/L. Simulations using Bayesian estimation showed the probability of achieving 100% fT > 4 × MIC for up to an MIC of 2 mg/L for the administered administration via continuous infusion at 3 g/24 h. We found that an aggressive PK/PD could be achieved up to an MIC of 0.5 mg/L with a meropenem regimen of 1 g infused every 8 h over 3 h for patients receiving CRRT for septic AKI. In addition, the risk of reaching the toxicity range with this regimen is low. In addition, if the MIC was 1-2 mg/L, the simulation results indicated that aggressive PK/PD can be achieved by continuous infusion at 3 g/24 h without increasing the daily dose.

Background/Objectives: Hyperlactatemia is a common predictive factor for poor post-cardiovascular surgery outcomes. However, it is not well understood whether the rapid postoperative lactate level elevation in a short period of time is associated with patient outcomes. Herein, we investigated the relationship between the degree of change in serum lactate levels and postoperative serious adverse events (PSAEs), including mortality, within 24 h of cardiovascular surgery. Methods: In this retrospective study, we evaluated the relationship between a rapid serum lactate level increase and PSAEs after open-heart and major vascular surgery. We divided the patients into those with and without PSAEs. Univariate and multivariate analyses were performed to evaluate the association between PSAEs and rapid lactate level increases. Results: We enrolled 445 patients; 16% (n = 71) had PSAEs. The peak lactate levels during the first 24 h of intensive care unit (ICU) stay were higher in patients with PSAEs than in those without. The maximum change in lactate levels between two consecutive lactate measurements during the first 24 h after ICU admission was higher in patients with PSAEs than in those without. A multivariate logistic regression analysis revealed that changes in lactate levels of 2 mmol/L or more between two consecutive lactate measurements were associated with PSAEs. ICU peak lactate levels of 3 mmol/L or more were not associated with PSAEs. Conclusions: Rapid serum lactate level increases of 2 mmol/L or more during the first 24 h of ICU admission post-cardiovascular surgery are associated with PSAEs.

BACKGROUND:Although mortality due to sepsis has decreased in recent decades, there are few studies on the timing of death during ICU stay. Characteristics of patients related to changes over the years of ICU death and changes in the timing of ICU death will provide new insights for future sepsis management.METHODS:This was a single-center, retrospective study. Patients admitted to the ICU for sepsis between 2005 and 2019 were included in the study. The study period was divided into three five-year intervals, and the timing of death in the ICU was divided into early-stage (1-3 ICU days), mid-stage (4-14 ICU days), and late-stage (15 or more ICU days). Patient characteristics related to ICU death at three five-year intervals and the timing of death were evaluated.RESULTS:ICU mortality for sepsis has decreased over time (2005-2009, 30.2%; 2010-2014, 21.0%; 2015-2019, 12.1%; p<0.01). In the timing of death, only mid-stage mortality decreased. Multiple-organ failure (OR, 4.53; 95% CI, 2.79-7.48) and hematological malignancies (OR, 2.48; 95% CI, 1.19-5.07) were associated with ICU mortality over entire study periods. Only multiple-organ failure was associated with ICU mortality at the five-year intervals (OR, 5.94; 95% CI, 2.73-13.7 for 2005-2009; OR, 4.01; 95% CI, 1.82-9.31 for 2010-2014; OR, 2.58; 95% CI, 1.05-6.59 for 2015-2019). Mid-stage mortality of multiple-organ failure decreased (2005-2009, 12.8%; 2010-2014, 7.6%; 2015-2019, 1.6%; p=0.02). However, early- and late-stage mortality of multiple-organ failure did not change.CONCLUSIONS:Improvement in mid-stage mortality in septic patients with multiple-organ failure can contribute to the improvement of overall ICU mortality in patients with sepsis.

The effectiveness of rehabilitation programs (RP) for chronic obstructive pulmonary disease (COPD) exacerbation remains controversial. However, few studies have investigated the combined effects of exercise and nutritional therapy. This study aimed to determine the effects of combined nutritional therapy on the physical function and nutritional status of patients with COPD exacerbation who underwent early RP. A randomized controlled trial was conducted in patients hospitalized for COPD exacerbations. Patients were assigned to receive a regular diet in addition to RP (control group) or RP and nutrition therapy (intervention group). Physical function, including quadricep strength and body composition, was assessed. The intervention group was administered protein-rich oral nutritional supplements. A total of 38 patients with negligible baseline differences were included in the analysis. The intervention group showed a notably greater change in quadriceps strength. Lean body mass and skeletal muscle indices markedly decreased in the control group but were maintained in the intervention group. Logistic regression analysis identified nutritional therapy as a significant factor associated with increased muscle strength. No serious adverse events were observed in either group. Therefore, nutritional therapy combined with RP is safe and effective for improving exercise function while maintaining body composition in patients with COPD exacerbation.

Background: Since severe acute pancreatitis (SAP) involves inflammatory mediators produced by local inflammation of the pancreas that trigger a systemic inflammatory response, intensive fluid management is required to maintain hemodynamics in the early stages of the onset of SAP. Goreisan is considered to have a diuretic effect in a state of excess water and an antidiuretic effect in a state of dehydration, regulating water balance in both directions. We investigated the clinical effects of Goreisan on water balance in SAP patients. Patients and methods : SAP patients admitted to our ICU within 72 hours of being diagnosed with SAP were divided into two groups: the Rikkunshito group (before October 2015) and the Goreisan group (after November 2015). Cumulative volume of fluid infusion, urine, fluid removal by CHF, nasogastric tube drainage, and water balance from day 1 to day 5 of ICU admission. Results: Thirty patients were included. The median age was 57 (40-69) years, and 21/30 (70%) were male. The prognostic factor score in Japanese criteria for acute pancreatitis was 5.5 (3.3-7). Of the thirty patients, 14 were in the Rikkunshito group, and 16 were in the Goreisan group. There were no differences in the cumulative volume of fluid infusion, urine, fluid removal by CHF, or nasogastric tube drainage from day 1 to day 5 of ICU admission between the two groups. However, the cumulative water balance from day 1 to day 5 of admission was 4,957 +/- 6,091 mL in the Rikkunshito group, whereas it was lower in the Goreisan group at 498 +/- 3,918 mL (P = 0.023). Conclusion: Our study showed that Goreisan administration in patients with severe acute pancreatitis might improve water balance in the early phase of onset. Early administration of Goreisan at the onset of severe acute pancreatitis may regulate fluid movement between capillaries and interstitium and alleviate fluid overload due to water refill.

Introduction Linezolid (LZD) is one of the antibiotics used to treat methicillin-resistant Staphylococcus aureus. In Japan, the dose of LZD is not generally adjusted by renal function or therapeutic drug monitoring and is readily available for critically ill patients. The adverse effects of LZD include pancytopenia, especially thrombocytopenia. We investigated the effect of LZD on platelet counts in critically ill patients with thrombocytopenia during admission to the intensive care unit (ICU). Methods Fifty-five critically ill patients with existing thrombocytopenia (platelet count < 100 ×103 /μL) who received LZD for five days or more during the period from January 2011 to October 2018 were included. Changes in platelet count and frequency of platelet concentrate (PC) transfusion were evaluated retrospectively. Results Mean (± standard error) platelet count prior to initiation of LZD was 47 ± 4 ×103 /uL, which increased significantly to 86 ± 13 ×103 /uL on day 15 (p<0.01). Median [interquartile range] duration of LZD therapy was 9 [8–12] days. Thirty-two patients (58.2%) required PC transfusion in the 15-day study period. The daily rate of PC transfusion decreased from 30.2% on days 1–5 to 18.2% on days 11–15. Similar tendencies were observed in patients with non-hematological and hematological disease. Conclusion Thrombocytopenia in critically ill patients in the ICU did not worsen after initiation of LZD therapy, and may be considered for the treatment of MRSA in this setting.