Association between changes in disease severity and physical function after surviving a critical illness: A multicentre retrospective observational study.

BACKGROUND: Whilst disease severity can significantly impact functional outcomes, the ability to predict the scale of this impact has not been consistent. AIM: We aimed to investigate whether changes in disease severity within the first 48 h of ICU admission are more strongly associated with physical dysfunction than a single-time assessment of disease severity at ICU admission. METHODS: A multicentre retrospective study in seven tertiary ICUs in Japan, including all consecutive adult ICU patients (>48 h ICU stay) between September 2019 and February 2020. The primary outcome was physical function defined as the Barthel Index, which is an ordinal scale (0-100: larger indicates better function) to measure physical independence and performance. The association between Barthel Index score at hospital discharge and the Sequential Organ Failure Assessment (SOFA) scores, measured at ICU admission, the highest recorded score within 48 h of ICU admission, and the level of change between these two timepoints were investigated in multivariable analysis. RESULTS: A total of 199 patients were included. Median SOFA score at ICU admission and the highest recorded score within the first 48 h were 6 (interquartile range: 5-10) and 8 (interquartile range: 6-11), respectively. A quarter of patients had a Barthel Index score of 60 or less at hospital discharge. The highest SOFA score within 48 h of ICU admission and the level of change in SOFA scores between ICU admission and the highest recorded score within 48 h were significantly associated with lower Barthel Index scores at hospital discharge. No significant association was identified with regard to Barthel Index scores and SOFA score at ICU admission. An increase in SOFA score of 1 or more within the first 48 h of ICU admission was the threshold to predict a Barthel Index score of 60 or less at hospital discharge. Larger changes in SOFA scores over the first 48 h of ICU admission were also significantly associated with smaller changes in Barthel Index scores from ICU discharge to hospital discharge. CONCLUSIONS: The level of change in SOFA score between ICU admission and the highest recorded score within the first 48 h of ICU stay can more accurately predict the presence of physical dysfunction at hospital discharge than a single-time assessment of disease severity at ICU admission. The larger worsening in SOFA potentially indicates lower recovery after a critical illness.

Population Pharmacokinetic Model and Dosing Simulation of Meropenem Using Measured Creatinine Clearance for Patients with Sepsis.

PURPOSE: Creatinine clearance (CCr) and pharmacokinetic parameters are markedly affected by pathophysiological changes in patients with sepsis. However, only a few reports have assessed renal function in patients with sepsis using the measured CCr. Furthermore, the administration regimen has not been sufficiently evaluated using a population PK (PPK) model across renal function broad ranges. Therefore, this study was performed to construct a meropenem PPK model for patients with sepsis using the measured CCr and evaluate the optimized meropenem dosing regimen based on the CCr. METHODS: Patients with sepsis who received intravenous meropenem at the Showa University Hospital were enrolled in this prospective observational study. The PPK model was constructed using blood samples and clinical information of patients. The probability of target attainment (PTA) indicates the likelihood of achieving 50% time above the minimum inhibitory concentration (% T > MIC) based on 10,000 virtual patients using Monte Carlo simulations. The PTA for each meropenem regimen was 50% T > MIC based on different renal functions using the Monte Carlo simulation. RESULTS: One hundred samples were collected from 31 patients. The final PPK model incorporating the measured CCr as a covariate in CL displayed the best fit. The recommended dosing regimen to achieve a PTA of 50% T > MIC of 4 mcg/mL was 1 g every 8 hours as a 3-hour prolonged infusion for patients with CCr 85-130 mL/min and 1 g every 8 hours as an 8-hour continuous infusion for patients with CCr ≥ 130 mL/min. CONCLUSIONS: This model precisely predicted meropenem concentrations in patients with sepsis by accurately evaluating renal function using the measured CCr. Extended dosing was demonstrated to be necessary to achieve a PTA of 50% T > MIC for patients with CCr ≥ 85 mL/min. Meropenem effectiveness can be maximized in patients with sepsis by selecting the appropriate dosing regimen based on renal function and the MIC.

A novel definition and treatment of hyperinflammation in COVID-19 based on purinergic signalling.

Hyperinflammation plays an important role in severe and critical COVID-19. Using inconsistent criteria, many researchers define hyperinflammation as a form of very severe inflammation with cytokine storm. Therefore, COVID-19 patients are treated with anti-inflammatory drugs. These drugs appear to be less efficacious than expected and are sometimes accompanied by serious adverse effects. SARS-CoV-2 promotes cellular ATP release. Increased levels of extracellular ATP activate the purinergic receptors of the immune cells initiating the physiologic pro-inflammatory immune response. Persisting viral infection drives the ATP release even further leading to the activation of the P2X7 purinergic receptors (P2X7Rs) and a severe yet physiologic inflammation. Disease progression promotes prolonged vigorous activation of the P2X7R causing cell death and uncontrolled ATP release leading to cytokine storm and desensitisation of all other purinergic receptors of the immune cells. This results in immune paralysis with co-infections or secondary infections. We refer to this pathologic condition as hyperinflammation. The readily available and affordable P2X7R antagonist lidocaine can abrogate hyperinflammation and restore the normal immune function. The issue is that the half-maximal effective concentration for P2X7R inhibition of lidocaine is much higher than the maximal tolerable plasma concentration where adverse effects start to develop. To overcome this, we selectively inhibit the P2X7Rs of the immune cells of the lymphatic system inducing clonal expansion of Tregs in local lymph nodes. Subsequently, these Tregs migrate throughout the body exerting anti-inflammatory activities suppressing systemic and (distant) local hyperinflammation. We illustrate this with six critically ill COVID-19 patients treated with lidocaine.

Extracorporeal Membrane Oxygenation for Secondary Organizing Pneumonia after Severe SARS-CoV-2 Infection: A Case Report.

(Background) COVID-19 is caused by SARS-CoV-2 infection and may result in unfavorable outcomes. A recent large-scale study showed that treatment with dexamethasone leads to favorable outcomes in patients with severe COVID-19, and the use of extracorporeal membrane oxygenation (ECMO) has also been shown to improve outcomes. Recently, secondary organizing pneumonia (SOP) has been reported after SARS-CoV-2 infection, but the diagnostic and treatment strategies are still unclear. (Case presentation) Here, we report a patient with severe COVID-19 who developed SOP even after the use of dexamethasone, for whom the introduction of ECMO on the 19th day after hospitalization led to a favorable outcome. (Conclusions) Life-threatening SOP may evolve even after the use of dexamethasone, and the late-phase introduction of ECMO may save such patients with COVID-19.

Excessive Extracellular ATP Desensitizes P2Y2 and P2X4 ATP Receptors Provoking Surfactant Impairment Ending in Ventilation-Induced Lung Injury.

Stretching the alveolar epithelial type I (AT I) cells controls the intercellular signaling for the exocytosis of surfactant by the AT II cells through the extracellular release of adenosine triphosphate (ATP) (purinergic signaling). Extracellular ATP is cleared by extracellular ATPases, maintaining its homeostasis and enabling the lung to adapt the exocytosis of surfactant to the demand. Vigorous deformation of the AT I cells by high mechanical power ventilation causes a massive release of extracellular ATP beyond the clearance capacity of the extracellular ATPases. When extracellular ATP reaches levels >100 μM, the ATP receptors of the AT II cells become desensitized and surfactant impairment is initiated. The resulting alteration in viscoelastic properties and in alveolar opening and collapse time-constants leads to alveolar collapse and the redistribution of inspired air from the alveoli to the alveolar ducts, which become pathologically dilated. The collapsed alveoli connected to these dilated alveolar ducts are subject to a massive strain, exacerbating the ATP release. After reaching concentrations >300 μM extracellular ATP acts as a danger-associated molecular pattern, causing capillary leakage, alveolar space edema, and further deactivation of surfactant by serum proteins. Decreasing the tidal volume to 6 mL/kg or less at this stage cannot prevent further lung injury.

Effects of extrathoracic mechanical ventilation on pulmonary hypertension secondary to lung disease.

PURPOSE: Biphasic cuirass ventilation (BCV) is a form of non-invasive extrathoracic positive and negative pressure mechanical ventilation. The present study was conducted to quantify our positive experience using BCV to dramatically improve gas exchange and cardiac function in patients with acute exacerbation of chronic respiratory failure and secondary pulmonary hypertension (PH). METHODS: BCV was applied for 2 weeks in 17 patients with PH caused by lung disease. Ventilation sessions were limited to 1 h per day to prevent exhaustion. To assess respiratory and circulatory effects, percutaneous arterial oxygen saturation (SpO2) was measured before and after each daily BCV session, and right heart catheter test [mean pulmonary artery pressure (mPAP), right atrium pressure (RAP), pulmonary artery occlusion pressure (PAOP) and cardiac index (CI)] and serum N-terminal pro-brain natriuretic peptide (NT-proBNP) were measured before and after a series of BCV sessions. RESULTS: SpO2 transiently improved after each BCV session. After a series of BCV, mPAP decreased from 27.2 to 22.4 mmHg (p = 0.0007). PAOP, CI and serum NT-proBNP levels decreased compared with baseline. No patients were treated with epoprostenol, iloprost, bosentan or sildenafil for PH. CONCLUSION: BCV may improve circulatory function in patients with PH caused by lung disease.

Electrical impedance tomography-guided prone positioning in a patient with acute cor pulmonale associated with severe acute respiratory distress syndrome.

Electrical impedance tomography (EIT) is a noninvasive technique used to assess regional gas distribution in the lung. We experienced a patient with acute cor pulmonale during high positive-pressure ventilation for the treatment of severe acute respiratory distress syndrome. Prone positioning was beneficial for unloading the right ventricle for treatment of acute cor pulmonale. EIT played a role in detecting lung derecruitment at the patient's bedside. Impedance distribution in ventral, mid-ventral, mid-dorsal, and dorsal layers before and 20 min after the start of prone positioning was 9, 48, 44, and 0 %, and 10, 25, 48, and 16 %, respectively. Lung recruitment monitored by EIT paralleled the improvement of PaO2/FIO2 from 123 to 239 mmHg. Timing of termination of prone positioning and ventilator settings such as lowering positive end-expiration pressure was determined to maintain dorsal recruitment as seen by EIT. The patient was weaned from mechanical ventilation on day 32 and discharged on day 200. EIT assessed the effects of prone positioning with real-time dynamic imaging and guided less injurious mechanical ventilation in a patient with acute cor pulmonale with dorsal lung derecruitment.

Does vasopressin improve the mortality of septic shock patients treated with high-dose NA.

AIM OF STUDY: In Surviving Sepsis Campaign Guidelines 2012, noradrenalin (NA) is recommended as a first choice vasopressor. Although vasopressin (VP) is recommended for the treatment of NA-resistant septic shock, the optimal parameters for its administration remain unclear. MATERIALS AND METHODS: We conducted a retrospective study to evaluate the clinical outcomes of the administration of VP to adult septic shock patients who were undergoing high-dose NA (≥0.25 µg/kg/min) therapy in our Intensive Care Unit between January 2010 and December 2013. We defined high-dose NA as a dose of >0.25 µg/kg/min, based on the definition of low-dose NA as a dose of 5-14 µg/min because the average body weight of the patients in this study was 53.0 kg. RESULTS: Among 29 patients who required the administration of high-dose NA, 18 patients received VP. Although the patient background physiological conditions and NA dose did not differ between the two groups, the survival rate of the VP-treated patients was significantly lower (33%) than that of the patients who were managed with a high-dose of NA-alone (82%) (P = 0.014). The lactate clearance did not change after the administration of VP, whereas it improved when in NA treatment alone. CONCLUSION: The results suggest that the administration of VP did not improve the mortality among septic shock patients when administered in addition to high-dose NA.

An evaluation of the impact of the implementation of the Tele-ICU: a retrospective observational study.

BACKGROUND: The telemedicine intensive care unit (Tele-ICU) is defined as a system in which intensive care professionals remotely provide care to critically ill patients and support the on-site staff in the intensive care unit (ICU) using secured audio-video and electronic links. Although the Tele-ICU is expected to resolve the shortage of intensivists and reduce the regional disparities in intensive care resources, the efficacy has not yet been evaluated in Japan because of a lack of clinically available system. METHODS: This was a single-center, historical comparison study in which the impact of the Tele-ICU on ICU performance and changes in workload of the on-site staff were evaluated. The Tele-ICU system developed in the United States was used. Data for 893 adult ICU patients before the Tele-ICU implementation and for all adult patients registered in the Tele-ICU system from April 2018 to March 2020 were abstracted and included. We investigated ICU and hospital mortality and length of stay and ventilation duration after the Tele-ICU implementation in each ICU, and compared between pre and post implementation and changes over time. We also assessed physician workload as defined by the frequency and duration of access to the electronic medical record (EMR) of the targeted ICU patients. RESULTS: After the Tele-ICU implementation 5438 patients were included. In unadjusted data pre/post study showed significant decreases in ICU (8.5-3.8%) and hospital (12.4-7.7%) mortality and ICU length of stay (p < 0.001), and those values were maintained for 2 years. In data stratified by predicted hospital mortality, ICU and hospital actual mortality in high and medium risk patients decreased significantly after the implementation. Ventilation duration was shortened (p < 0.007). Access frequency of the on-site physicians decreased by 25%, and the decrease occurred in the daytime shift and in the physicians with 3-15 years of work experience. CONCLUSIONS: Our study showed the Tele-ICU implementation was associated with lower mortality, especially in medium and high risk patients, and decreased EMR-related tasks of on-site physicians. These results suggest that the Tele-ICU could be a solution of the shortage of intensivists and regional disparities for intensive care.

Clinical efficacy and safety of multipotent adult progenitor cells (invimestrocel) for acute respiratory distress syndrome (ARDS) caused by pneumonia: a randomized, open-label, standard therapy-controlled, phase 2 multicenter study (ONE-BRIDGE).

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a life-threatening inflammatory lung injury with high mortality; no approved medication exists. Efficacy and safety of bone marrow-derived, allogeneic, multipotent adult progenitor cells (invimestrocel) plus standard treatment in patients with ARDS caused by pneumonia was evaluated. METHODS: A randomized, open-label, standard therapy-controlled, phase 2 study (January 2019-September 2021) conducted in 29 centers in Japan. Patients with ARDS caused by pneumonia, with extensive early fibroproliferation on high-resolution computed tomography and low risk of systemic organ failure identified by an Acute Physiology and Chronic Health Evaluation (APACHE II) score were included. Patients were randomized 2:1 to receive a single intravenous infusion of 9.0 × 108 cells of invimestrocel (administered at a rate of up to 10 mL/min over 30-60 min by free flow) plus standard treatment (N = 20) or standard treatment (N = 10) consistent with the clinical practice guidelines of the Japanese Respiratory Society for the management of ARDS. Primary endpoint was ventilator-free days (VFDs) through day 28 after study treatment. Analysis of covariance was performed with treatment group, age, partial pressure arterial oxygen/fraction of inspired oxygen ratio, and APACHE II score as covariates. RESULTS: Median (interquartile range) number of VFDs was numerically higher in the invimestrocel group versus standard group (20.0 [0.0-24.0] vs 11.0 [0.0-14.0]) but was not statistically significantly different (least square [LS] means [95% confidence interval (CI)]: invimestrocel group, 11.6 [6.9-16.3]; standard group, 6.2 [- 0.4 to 12.8]; LS mean difference [95% CI], 5.4 [- 1.9 to 12.8]; p = 0.1397). Ventilator weaning rate at day 28 was 65% (13/20) versus 30% (3/10), and mortality rate was 21% (4/19) versus 29% (2/7) at day 28 and 26% (5/19 patients) versus 43% (3/7 patients) at day 180, for the invimestrocel and standard groups, respectively. No allergic or serious adverse reactions were associated with invimestrocel. CONCLUSIONS: In Japanese patients with ARDS caused by pneumonia, invimestrocel plus standard treatment resulted in no significant difference in the number of VFDs but may result in improved survival compared with standard treatment. Invimestrocel was well tolerated. TRIAL REGISTRATION: ClinicalTrials.gov, Identifier: NCT03807804; January 8, 2019; https://clinicaltrials.gov/ct2/show/NCT03807804 .

Current Practice and Barriers to the Implementation of Mobilization in ICUs in Japan: A Multicenter Prospective Cohort Study.

Background: Limited information is currently available on the barriers to implementing mobilization at the bedside for critically ill patients. Therefore, we investigated the current practice of and barriers to the implementation of mobilization in intensive care units (ICU). Methods: A multicenter prospective observational study was conducted at nine hospitals between June 2019 and December 2019. Consecutive patients admitted to the ICU for more than 48 h were enrolled. Quantitative data were analyzed descriptively, and qualitative data were analyzed thematically. Results: The 203 patients enrolled in the present study were divided into 69 elective surgical patients and 134 unplanned admission patients. The mean periods of time until the initiation of rehabilitation programs after ICU admission were 2.9 ± 7.7 and 1.7 ± 2.0 days, respectively. Median ICU mobility scales were five (Interquartile range: three and eight) and six (Interquartile range: three and nine), respectively. The most common barriers to mobilization in the ICU were circulatory instability (29.9%) and a physician's order for postoperative bed rest (23.4%) in the unplanned admission and elective surgery groups, respectively. Conclusions: Rehabilitation programs were initiated later for unplanned admission patients and were less intense than those for elective surgical patients, irrespective of the time after ICU admission.

Relationship between grip strength during hospitalisation and mental disorders after discharge in critically ill patients: a post-hoc analysis of a prospective observational study.

OBJECTIVES: Post-intensive care syndrome (PICS) is a recognised sequela after critical care. The development of an index that predicts PICS mental disorders will be of significance for the selection of subsequent interventions. The purpose of this study was to find factors associated with PICS mental disorders. We hypothesised that grip strength during hospitalisation may be associated with the PICS mental status after discharge. DESIGN: A post-hoc analysis of a multicentre prospective observational study. SETTING: Nine hospitals in Japan. PARTICIPANTS: Patients who were newly admitted to intensive care unit and stayed for at least 48 hours were included. Exclusion criteria were patients younger than 18 years, those who required assistance with ambulation prior to admission, those with concomitant central nervous system disorders and those with terminal conditions. PRIMARY AND SECONDARY OUTCOME MEASURES: Psychiatric symptoms 3 months after discharge were assessed using the Hospital Anxiety and Depression Scale (HADS). The HADS total score (HADS-total) was assigned as the primary outcome. RESULTS: 98 patients were included into this study. Grip strength at discharge negatively correlated with HADS-total 3 months after discharge (r=-0.37, p<0.001, 95% CI -0.53 to -0.18). A multivariate analysis showed that grip strength was associated with anxiety (p=0.025, 95% CI -0.21 to -0.015). Area under the curve for HADS anxiety score with grip strength at discharge was higher than that with Medical Research Council scores and the Barthel Index (0.71, 0.60, 0.61). CONCLUSIONS: Grip strength at discharge correlated with mental disorders 3 months after discharge. Therefore, it may be useful for predicting postdischarge mental disorders. TRIAL REGISTRATION NUMBER: UMIN000036503.

Plasma leukocyte cell-derived chemotaxin 2 is associated with the severity of systemic inflammation in patients with sepsis.

The aim of the present study was to determine the correlations between leukocyte cell-derived chemotaxin 2 (LECT2) and inflammation-related variables in human inflammatory disease. Plasma samples from 23 septic patients who had been admitted to the intensive care unit (ICU) of our institution and 31 volunteers were used. Plasma LECT2 concentrations were examined retrospectively and compared with those of various inflammatory cytokines and routine laboratory data. The LECT2 concentrations of the septic patients at the time of ICU entry (5.3 ± 4.1 ng/mL) were significantly lower than those of the volunteers (19.7 ± 3.4 ng/mL) and these concentrations had significantly increased by the time of ICU discharge. Individual analyses showed that the LECT2 concentrations of all 19 patients had increased by the time of ICU discharge. A combination of LECT2 and C-reactive protein (CRP) concentrations was capable of discriminating the acute and recovery phases of sepsis to a degree similar to those of the combinations of CRP concentration and percentage of neutrophils, CRP concentration and percentage of immature white blood cells, or CRP and interleukin-6 concentrations. Thus, the LECT2 concentration correlates with the severity of systemic inflammation in patients with sepsis. LECT2 may be a reliable diagnostic indicator of human inflammatory diseases.

Extracorporeal membrane oxygenation for 2009 influenza A(H1N1) severe respiratory failure in Japan.

PURPOSE: To evaluate procedures and outcomes of extracorporeal membrane oxygenation (ECMO) therapy applied to 2009 influenza A(H1N1) severe respiratory failure patients in Japan. METHODS: This observational study used database information about adults who received ECMO therapy for H1N1-related severe respiratory failure from April 1, 2010 to March 31, 2011. RESULTS: Fourteen patients from 12 facilities were enrolled. Anti-influenza drugs were used in all cases. Before the start of ECMO, the lowest PaO(2)/FiO(2) was median (interquartile) of 50 (40-55) mmHg, the highest peak inspiratory pressure was 30 (29-35) cmH(2)O, and mechanical ventilation had been applied for at least 7 days in 5 patients. None of the facilities had extensive experience with ECMO for respiratory failure (6 facilities, no previous experience; 5 facilities, one or two cases annually). The blood drainage cannula was smaller than 20 Fr. in 10 patients (71.4 %). The duration of ECMO was 8.5 (4.0-10.8) days. The duration of each circuit was only 4.0 (3.2-5.3) days, and the ECMO circuit had to be renewed 19 times (10 cases). Thirteen patients (92.9 %) developed adverse events associated with ECMO, such as oxygenator failure, massive bleeding, and disseminated intravascular coagulation. The survival rate was 35.7 % (5 patients). CONCLUSION: ECMO therapy for H1N1-related severe respiratory failure in Japan has very poor outcomes, and most patients developed adverse events. However, this result does not refute the effectiveness of ECMO. One possible cause of these poor outcomes is the lack of satisfactory equipment, therapeutic guidelines, and systems for patient transfer to central facilities.

Clinical Implications of Determining Individualized Positive End-Expiratory Pressure Using Electrical Impedance Tomography in Post-Cardiac Surgery Patients: A Prospective, Non-Randomized Interventional Study.

Optimal positive end-expiratory pressure (PEEP) can induce sustained lung function improvement. This prospective, non-randomized interventional study aimed to investigate the effect of individualized PEEP determined using electrical impedance tomography (EIT) in post-cardiac surgery patients (n = 35). Decremental PEEP trials were performed from 20 to 4 cmH2O in steps of 2 cmH2O, guided by EIT. PEEP levels preventing ventilation loss in dependent lung regions (PEEPONLINE) were set. Ventilation distributions and oxygenation before the PEEP trial, and 5 min and 1 h after the PEEPONLINE setting were examined. Furthermore, we analyzed the saved impedance data offline to determine the PEEP levels that provided the best compromise between overdistended and collapsed lung (PEEPODCL). Ventilation distributions of dependent regions increased at 5 min after the PEEPONLINE setting compared with those before the PEEP trial (mean ± standard deviation, 41.3 ± 8.5% vs. 49.1 ± 9.3%; p < 0.001), and were maintained at 1 h thereafter (48.7 ± 9.4%, p < 0.001). Oxygenation also showed sustained improvement. Rescue oxygen therapy (high-flow nasal cannula, noninvasive ventilation) after extubation was less frequent in patients with PEEPONLINE ≥ PEEPODCL than in those with PEEPONLINE < PEEPODCL (1/19 vs. 6/16; p = 0.018). EIT-guided individualized PEEP stabilized the improvement in ventilation distribution and oxygenation. Individual PEEP varies with EIT measures, and may differentially affect oxygenation after cardiac surgery.

Association between Early Mobilization in the ICU and Psychiatric Symptoms after Surviving a Critical Illness: A Multi-Center Prospective Cohort Study.

This is a prospective multicenter cohort study aiming to investigate the association between early mobilization (EM), defined as a rehabilitation level of sitting at the edge of the bed or higher within 72 h of ICU admission, and psychiatric outcome. Consecutive patients, admitted to the ICU for more than 48 h, were enrolled. The primary outcome was the incidence of psychiatric symptoms at 3 months after hospital discharge defined as the presence of any of three symptoms: depression, anxiety, or post-traumatic stress disorder (PTSD). Risk ratio (RR) and multiple logistic regression analysis were used. As a sensitivity analysis, two methods for inverse probability of treatment weighting statistics were performed. Of the 192 discharged patients, 99 (52%) were assessed. The patients who achieved EM had a lower incidence of psychiatric symptoms compared to those who did not (25% vs. 51%, p-value 0.008, odds ratio (OR) 0.27, adjusted p = 0.032). The RR for psychiatric symptoms in the EM group was 0.49 [95% Confidence Interval, 0.29-0.83]. Sensitivity analysis accounting for the influence of death, loss to follow-up (OR 0.28, adjusted p = 0.008), or potential confounders (OR 0.49, adjusted p = 0.046) consistently showed a lower incidence of psychiatric symptoms in the EM group. EM was consistently associated with fewer psychiatric symptoms.

Effects of evidence-based ICU care on long-term outcomes of patients with sepsis or septic shock (ILOSS): protocol for a multicentre prospective observational cohort study in Japan.

INTRODUCTION: Sepsis is not only the leading cause of death in the intensive care unit (ICU) but also a major risk factor for physical and cognitive impairment and mental disorders, known as postintensive care syndrome (PICS), reduced health-related quality of life (HRQoL) and even mental health disorders in patient families (PICS-family; PICS-F). The ABCDEF bundle is strongly recommended to overcome them, while the association between implementing the bundle and the long-term outcomes is also unknown. METHODS AND ANALYSIS: This is a multicentre prospective observational study at 26 ICUs. All consecutive patients between 1 November 2020 and 30 April 2022, who are 18 years old or older and expected to stay in an ICU for more than 48 hours due to sepsis or septic shock, are enrolled. Follow-up to evaluate survival and PICS/ PICS-F will be performed at 3, 6 and 12 months and additionally every 6 months up to 5 years after hospital discharge. Primary outcomes include survival at 12 months, which is the primary outcome, and the incidence of PICS defined as the presence of any physical impairment, cognitive impairment or mental disorders. PICS assessment scores, HRQoL and employment status are evaluated. The association between the implementation rate for the ABCDEF bundle and for each of the individual elements and long-term outcomes will be evaluated. The PICS-F, defined as the presence of mental disorders, and HRQoL of the family is also assessed. Additional analyses with data up to 5 years follow-up are planned. ETHICS AND DISSEMINATION: This study received ethics approvals from Saiseikai Utsunomiya Hospital (2020-42) and all other participating institutions and was registered in the University Hospital Medical Information Network Clinical Trials Registry. Informed consent will be obtained from all patients. The findings will be published in peer-reviewed journals and presented at scientific conferences. TRIAL REGISTRATION NUMBER: UMIN000041433.

Roles of Electrical Impedance Tomography in Determining a Lung Protective Strategy for Acute Respiratory Distress Syndrome in the Era of Coronavirus Disease 2019.

Electrical impedance tomography (EIT) is noninvasive and can be used at the bedside for real-time evaluation to identify ventilation distribution of infected lungs. This review briefly describes the basic principle of EIT and summarizes the latest findings on its potential contribution to lung protective strategies in coronavirus disease 2019 patients. Additionally, experimental approaches for detecting the distribution of pulmonary blood flow in coronavirus disease 2019 patients are presented. The findings underscore the role of EIT in determining lung protective strategies for coronavirus disease 2019-associated acute respiratory distress syndrome.

Infective endocarditis secondary to Klebsiella pneumoniae-associated emphysematous cystitis.

Klebsiella pneumoniae is responsible for about 1.5% of infective endocarditis (IE) cases. IE caused by community-acquired K. pneumoniae infection has rarely been reported. An 80-year-old man presented at our hospital with hypotension and hypoxaemia, and a history of aortic valve stenosis and no history of recent dental treatment. Transthoracic echocardiography at admission showed no signs of heart failure or vegetation. CT revealed typical signs of emphysematous cystitis (EC). The patient was treated for EC-associated septic shock. K. pneumoniae was detected in urine and blood cultures on day 3. Symptoms of heart failure developed on day 6 and clinical examination revealed a heart murmur. An identification of vegetation and perforation of the mitral valve on repeat echocardiography confirmed the diagnosis of IE secondary to K. pneumoniae infection. A surgical valve replacement was performed on day 7. Repeated point-of-care ultrasound played a role in the early diagnosis of IE.

Personalisation of Therapies in COVID-19 Associated Acute Respiratory Distress Syndrome, Using Electrical Impedance Tomography.

INTRODUCTION: Each patient suffering from severe coronavirus COVID-19-associated acute respiratory distress syndrome (ARDS), requiring mechanical ventilation, shows different lung mechanics and disease evolution. Therefore, lung protective strategies should be personalised for the individual patient. CASE PRESENTATION: A 64-year-old male patient was intubated ten days after the symptoms of COVID-19 infection presented. He was placed in the prone position for sixteen hours, resulting in a marked improvement in oxygenation. However, after being returned to the supine position, his SpO2 rapidly dropped from 98% to 91%, and electrical impedance tomography showed less ventilation at the dorsal region and a ventral shift of ventilation distribution. An incremental and decremental PEEP trial under electrical impedance tomography monitoring was carried out, confirming that the dependent lung regions were recruited with increased pressures and homogenous ventilation distribution could be provided with 14 cmH2O of PEEP. The optimal settings were reassessed next day after returning from the second session of the prone position. After four prone position-sessions in five days, oxygenation was stabilised and eventually the patient was discharged. CONCLUSIONS: Patients with COVID-19 associated ARDS require individualised ventilation support depending on the stage of their disease. Daily PEEP trial monitored by electrical impedance tomography can provide important information to tailor the respiratory therapies.