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Enteral nutrition (EN) can maintain the structure and function of the gastrointestinal mucosa better than parenteral nutrition. In critically ill patients, EN must be discontinued or interrupted, if gastrointestinal complications, particularly vomiting and bowel movement disorders, do not resolve with appropriate management. To avoid such gastrointestinal complications, EN should be started as soon as possible with a small amount of EN first and gradually increased. EN itself may also promote intestinal peristalsis. The measures to decrease the risk of reflux and aspiration include elevation the head of the bed (30° to 45°), switch to continuous administration, administration of prokinetic drugs or narcotic antagonists to promote gastrointestinal motility, and switch to jejunal access (postpyloric route). Moreover, the control of bowel movement is also important for intensive care and management. In particular, prolonged diarrhea can cause deficiency in nutrient absorption, malnutrition, and increase in mortality. In addition, diarrhea may cause a decrease the circulating blood volume, metabolic acidosis, electrolyte abnormalities, and contamination of surgical wounds and pressure ulcers. If diarrhea occurs in critically ill patients on EN management, it is important to determine whether diarrhea is EN-related or not. After ruling out the other causes of diarrhea, the measures to prevent EN-related diarrhea include switch to continuous infusion, switch to gastric feeding, adjustment of agents that improve gastrointestinal peristalsis or laxative, administration of antidiarrheal drugs, changing the type of EN formula, and semisolidification of EN formula. One of the best ways to success for EN management is to continue as long as possible without interruption and discontinuation of EN easily by appropriate measures, even if gastrointestinal complications occur.

Purpose This study evaluated the usefulness of SUV analysis of 99mTc-galactosyl human serum albumin (99mTc-GSA) scintigraphy including SUV analysis of the cardiac blood pool normalized by blood volume as a predictor of short-term survival in severe liver failure. Patients and methods We enrolled 24 patients with severe liver failure who underwent 99mTc-GSA scintigraphy and were admitted to the intensive care unit. Patients were divided into survival and non-survival groups at 7, 14, and 28 days from the performance of 99mTc-GSA scintigraphy. From SPECT images we calculated SUVs of the cardiac blood pool, performing normalization for body weight, lean body weight, Japanese lean body weight, and blood volume and we calculated SUVs of the liver, normalizing by body weight, lean body weight, and Japanese lean body weight. We also calculated the uptake ratio of the heart at 15 min to that at 3 min (HH15) and the uptake ratio of the liver at 15 min to the liver plus the heart at 15 min (LHL15) from planar images of 99mTc-GSA scintigraphy. Results There were significant differences between the 7 day survival and non-survival groups for all SUVs of the heart and the liver and HH15, for 14 day survival groups in SUVs of the heart normalized by Japanese lean body weight and blood volume, and no significant differences between 28 day survival groups for any SUVs, HH15, or LHL15. Although the difference was not significant, SUV analysis of the heart normalized by blood volume showed the highest value for the area under the receiver-operating-characteristics curve for both 7 day and 14 day survival. Conclusion SUV analysis of 99mTc-GSA including SUV analysis of cardiac blood pool normalized by blood volume is of value for prediction of short-term survival in cases with severe liver failure.

Multiple organ dysfunction induced by sepsis often involves kidney injury. Extracellular histones released in response to damage-associated molecular patterns are known to facilitate sepsis-induced organ dysfunction. Recombinant human soluble thrombomodulin (rhTM) and its lectin-like domain (D1) exert anti-inflammatory effects and neutralize damage-associated molecular patterns. However, the effects of rhTM and D1 on extracellular histone H3 levels and kidney injury remain poorly understood. Our purpose was to investigate the association between extracellular histone H3 levels and kidney injury, and to clarify the effects of rhTM and D1 on extracellular histone H3 levels, kidney injury, and survival in sepsis-induced rats. Rats in whom sepsis was induced via cecal ligation and puncture were used in this study. Histone H3 levels, histopathology of the kidneys, and the survival rate of rats at 24 h after cecal ligation and puncture were investigated. Histone H3 levels increased over time following cecal ligation and puncture. Histopathological analyses indicated that the distribution of degeneration foci among tubular epithelial cells of the kidney and levels of histone H3 increased simultaneously. Administration of rhTM and D1 significantly reduced histone H3 levels compared with that in the vehicle-treated group and improved kidney injury. The survival rates of rats in rhTM- and D1-treated groups were significantly higher than that in the vehicle-treated group. The results of this study indicated that rhTM and its D1 similarly reduce elevated histone H3 levels, thereby reducing acute kidney injury. Our findings also proposed that rhTM and D1 show potential as new treatment strategies for sepsis combined with acute kidney injury.

Background In 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. Purpose The effect of low-convection volume settings below 600 mL/h on cytokine adsorption characteristics was experimentally investigated in CKRT. Materials and methods Test 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. Results Creatinine 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. Conclusion The 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.

Background Among 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. Methods Plasma 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. Results On 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. Conclusion In 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.

Background Extubation failure, i.e., reintubation in ventilated patients, is a well-known risk factor for mortality and prolonged stay in the intensive care unit (ICU). Although sputum volume is a risk factor, the frequency of tracheal suctioning has not been validated as a predictor of reintubation. We conducted this study to examine whether frequent tracheal suctioning is a risk factor for reintubation. Patients and methods We included adult patients who were intubated for > 72 h in the ICU and extubated after completion of spontaneous breathing trial (SBT). We compared the characteristics and weaning-related variables, including the frequency of tracheal suctioning between patients who required reintubation within 24 h after extubation and those who did not, and examined the factors responsible for reintubation. Results Of the 400 patients enrolled, reintubation was required in 51 (12.8%). The most common cause of reintubation was difficulty in sputum excretion (66.7%). There were significant differences in sex, proportion of patients with chronic kidney disease, pneumonia, ICU admission type, the length of mechanical ventilation, and ICU stay between patients requiring reintubation and those who did not. Multivariate analysis showed frequent tracheal suction (> once every 2 h) and the length of mechanical ventilation were independent factors for predicting reintubation. Conclusion We should examine the frequency of tracheal suctioning > once every 2 h in addition to the length of mechanical ventilation before deciding to extubate after completion of SBT in patients intubated for > 72 h in the ICU.

The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2020 (J-SSCG 2020), a Japanese-specific set of clinical practice guidelines for sepsis and septic shock created as revised from J-SSCG 2016 jointly by the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine, was first released in September 2020 and published in February 2021. An English-language version of these guidelines was created based on the contents of the original Japanese-language version. The purpose of this guideline is to assist medical staff in making appropriate decisions to improve the prognosis of patients undergoing treatment for sepsis and septic shock. We aimed to provide high-quality guidelines that are easy to use and understand for specialists, general clinicians, and multidisciplinary medical professionals. J-SSCG 2016 took up new subjects that were not present in SSCG 2016 (e.g., ICU-acquired weakness [ICU-AW], post-intensive care syndrome [PICS], and body temperature management). The J-SSCG 2020 covered a total of 22 areas with four additional new areas (patient- and family-centered care, sepsis treatment system, neuro-intensive treatment, and stress ulcers). A total of 118 important clinical issues (clinical questions, CQs) were extracted regardless of the presence or absence of evidence. These CQs also include those that have been given particular focus within Japan. This is a large-scale guideline covering multiple fields; thus, in addition to the 25 committee members, we had the participation and support of a total of 226 members who are professionals (physicians, nurses, physiotherapists, clinical engineers, and pharmacists) and medical workers with a history of sepsis or critical illness. The GRADE method was adopted for making recommendations, and the modified Delphi method was used to determine recommendations by voting from all committee members. As a result, 79 GRADE-based recommendations, 5 Good Practice Statements (GPS), 18 expert consensuses, 27 answers to background questions (BQs), and summaries of definitions and diagnosis of sepsis were created as responses to 118 CQs. We also incorporated visual information for each CQ according to the time course of treatment, and we will also distribute this as an app. The J-SSCG 2020 is expected to be widely used as a useful bedside guideline in the field of sepsis treatment both in Japan and overseas involving multiple disciplines.

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). 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. 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. 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.

The efficacy of intravenous immunoglobulin (IVIG) administration in patients with sepsis or septic shock remains unclear. A single-center retrospective study was conducted to evaluate the association between IVIG supplementation and favorable outcomes in patients with sepsis and low serum immunoglobulin G (IgG) levels. A total of 239 patients with sepsis were identified whose serum IgG levels were determined upon admission to the intensive care unit between January 2014 and March 2021. Patients with low IgG levels (<670 mg/dL) were divided into the IVIG and non-IVIG groups. Patient data were collected from electronic medical records to evaluate the patients’ characteristics, sepsis severity, and prognosis. The primary outcome was 28-day mortality. The propensity score was calculated by using the following variables: age, Sequential Organ Failure Assessment score, immunocompromised status, and serum IgG levels. Logistic regression analysis using propensity score as the adjusted variable was performed to evaluate the outcome. Of 239 patients, 87 had low IgG levels. Of these patients, 47 received IVIG therapy. The 28-day (odds ratio [OR], 0.15; 95% CI, 0.04–0.54; P = 0.004) and 90-day (OR, 0.31; 95% CI, 0.11–0.83; P = 0.020) mortality rates were significantly lower in the IVIG group than in the non-IVIG group. Moreover, the number of days free from renal replacement therapy was significantly higher in the IVIG group than in the non-IVIG group (OR, 1.06; 95% CI, 1.01–1.11; P = 0.025). Serum IgG levels in the IVIG group showed no significant difference compared with those in the non-IVIG group. No significant differences in the patients’ characteristics were observed between the groups. This study found that IVIG administration in patients with sepsis and low serum IgG levels was associated with improved prognosis. Further studies are warranted to evaluate the validity of IVIG therapy for patients with sepsis and low serum IgG levels.

Background: The utility of using indirect calorimetry (IC) to estimate energy needs and methods for its application to this purpose remain unclear. This systematic review investigated whether using IC to estimate energy expenditure in critically ill patients is more meaningful for improving survival than other estimation methods. Methods: Comprehensive searches were conducted in MEDLINE using PubMed, Cochrane Central Register of Controlled Trials, and Igaku-Chuo-Zasshi up to March 2023. Results: Nine RCTs involving 1178 patients were included in the meta-analysis. The evidence obtained suggested that energy delivery by IC improved short-term mortality (risk ratio, 0.86; 95% confidence interval [CI], 0.70 to 1.06). However, the use of IC did not appear to affect the length of ICU stay (mean difference [MD], 0.86; 95% CI, −0.98 to 2.70) or the duration of mechanical ventilation (MD, 0.66; 95% CI, −0.39 to 1.72). Post hoc analyses using short-term mortality as the outcome found no significant difference by target calories in resting energy expenditure, whereas more frequent IC estimates were associated with lower short-term mortality and were more effective in mechanically ventilated patients. Conclusions: This updated meta-analysis revealed that the use of IC may improve short-term mortality in patients with critical illness and did not increase adverse events.