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.

The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2020 (J-SSCG 2020).

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.

Examination of the frequency of upward and downward fluctuations in the pressure obtained from the cuff pressure-time curve by continuous measurement of endotracheal tube cuff pressure during thyroid surgery: a case series.

BACKGROUND: Few studies examined time-to-time changes of cuff pressure of an endotracheal tube during surgery. We retrospectively analyzed the changes of cuff pressure during thyroid surgery and examined its relationships with postoperative airway complications. CASE PRESENTATION: Cuff pressure was initially adjusted at 26 cmH2O and continuously measured in 61 patients. The cuff pressure-time curve dynamically fluctuated, and exceeded 30 cmH2O in all patients, whereas decreased to ≤ 20 cmH20 in 42 (69%) patients. Ratio of the period with such an increase and decrease of cuff pressure to the total duration of surgery were 40% (28-66%) and 9% (0-21%), respectively (median, interquartile range). No patients showed symptoms of airway stenosis requiring treatment except one who developed recurrent laryngeal nerve palsy. No patients had lower respiratory tract infection. CONCLUSIONS: Cuff pressure dynamically fluctuated during thyroid surgery. Preventing an increase as well as decrease of cuff pressure is required.

The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2020 (J-SSCG 2020).

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.

Associations between low body mass index and mortality in patients with sepsis: A retrospective analysis of a cohort study in Japan.

BACKGROUND: The distribution of body mass in populations of Western countries differs from that of populations of East Asian countries. In East Asian countries, fewer people have a high body mass index than those in Western countries. In Japan, the country with the highest number of older adults worldwide, many people have a low body mass index. Therefore, this study aimed to determine the association between a low body mass index and mortality in patients with sepsis in Japan. METHODS: We conducted this retrospective analysis of 548 patients with severe sepsis from a multicenter prospective observational study. Multivariate logistic regression analyses determined the association between body mass index and 28-day mortality adjusted for age, sex, pre-existing conditions, the occurrence of septic shock, Acute Physiology and Chronic Health Evaluation II scores, and Sequential Organ Failure Assessment scores. Furthermore, the association between a low body mass index and 28-day mortality was analyzed. RESULTS: The low body mass index group represented 18.8% of the study population (103/548); the normal body mass index group, 57.3% (314/548); and the high body mass index group, 23.9% (131/548), with the 28-day mortality rates being 21.4% (22/103), 11.2% (35/314), and 14.5% (19/131), respectively. In the low body mass index group, the crude and adjusted odds ratios (95% confidence intervals) for 28-day mortality relative to the non-low body mass index (normal and high body mass index groups combined) group were 2.0 (1.1-3.4) and 2.3 (1.2-4.2), respectively. CONCLUSION: A low body mass index was found to be associated with a higher 28-day mortality than the non-low body mass index in patients with sepsis in Japan. Given that older adults often have a low body mass index, these patients should be monitored closely to reduce the occurrence of negative outcomes.

The impact of organ dysfunctions on mortality in patients with severe sepsis: A multicenter prospective observational study.

PURPOSE: Disseminated intravascular coagulations (DIC), acute respiratory distress syndrome (ARDS), and acute kidney injury (AKI) are major organ dysfunctions that occur in patients with sepsis. This study aimed to elucidate the impact of these organ dysfunctions on mortality in patients with severe sepsis. MATERIAL AND METHODS: A prospective observational study was performed in 10 ICUs to obtain data from patients with severe sepsis. Multivariate analyses to examine in-hospital mortality were performed. RESULTS: Data of 573 patients were analyzed. In-hospital mortality rate was 19.4% (111/573). The incidences of DIC, ARDS, and AKI were 58.4%, 18.7%, and 41.7%, while the associated mortality rates were 28.9%, 36.4%, and 31.8%, respectively. In multiple regression model, DIC (odds ratio 2.71, 95% confidence interval [CI] 1.45-5.27) and AKI stage 3 (odds ratio 1.98, 95% CI 1.07-3.63) were significantly associated with higher in-hospital all-cause mortality. DIC (hazard ratio 2.58, 95% CI 1.53-4.55) and AKI stage 3 (hazard ratio 1.73, 95% CI 1.07-2.80) were also significantly associated with longer survival durations. However, severe ARDS was not associated with these outcomes. CONCLUSIONS: DIC and AKI are frequent complications in patients with severe sepsis. In this study, DIC, and AKI stage 3 were independent risk factors of in-hospital mortality.

Comparison of the efficacy of three topical antiseptic solutions for the prevention of catheter colonization: a multicenter randomized controlled study.

BACKGROUND: To compare the efficacy of three antiseptic solutions [0.5%, and 1.0% alcohol/chlorhexidine gluconate (CHG), and 10% aqueous povidone-iodine (PVI)] for the prevention of intravascular catheter colonization, we conducted a randomized controlled trial in patients from 16 intensive care units in Japan. METHODS: Adult patients undergoing central venous or arterial catheter insertions were randomized to have one of three antiseptic solutions applied during catheter insertion and dressing changes. The primary endpoint was the incidence of catheter colonization, and the secondary endpoint was the incidence of catheter-related bloodstream infections (CRBSI). RESULTS: Of 1132 catheters randomized, 796 (70%) were included in the full analysis set. Catheter-tip colonization incidence was 3.7, 3.9, and 10.5 events per 1000 catheter-days in 0.5% CHG, 1% CHG, and PVI groups, respectively (p = 0.03). Pairwise comparisons of catheter colonization between groups showed a significantly higher catheter colonization risk in the PVI group (0.5% CHG vs. PVI: hazard ratio, HR 0.33 [95% confidence interval, CI 0.12-0.95], p = 0.04; 1.0% CHG vs. PVI: HR 0.35 [95% CI 0.13-0.93], p = 0.04). Sensitivity analyses including all patients by multiple imputations showed consistent quantitative conclusions (0.5% CHG vs. PVI: HR 0.34, p = 0.03; 1.0% CHG vs. PVI: HR 0.35, p = 0.04). No significant differences were observed in the incidence of CRBSI between groups. CONCLUSIONS: Both 0.5% and 1.0% alcohol CHG are superior to 10% aqueous PVI for the prevention of intravascular catheter colonization. TRIAL REGISTRATION: Japanese Primary Registries Network; No.: UMIN000008725 Registered on 1 September 2012.

Low-dose immunoglobulin G is not associated with mortality in patients with sepsis and septic shock.

BACKGROUND: The administration of low-dose intravenous immunoglobulin G (IVIgG) (5 g/day for 3 days; approximate total 0.3 g/kg) is widely used as an adjunctive treatment for patients with sepsis in Japan, but its efficacy in the reduction of mortality has not been evaluated. We investigated whether the administration of low-dose IVIgG is associated with clinically important outcomes including intensive care unit (ICU) and in-hospital mortality. METHODS: This is a post-hoc subgroup analysis of data from a retrospective cohort study, the Japan Septic Disseminated Intravascular Coagulation (JSEPTIC DIC) study. The JSEPTIC DIC study was conducted in 42 ICUs in 40 institutions throughout Japan, and it investigated associations between sepsis-related coagulopathy, anticoagulation therapies, and clinical outcomes of 3195 adult patients with sepsis and septic shock admitted to ICUs from January 2011 through December 2013. To investigate associations between low-dose IVIgG administration and mortalities, propensity score-based matching analysis was used. RESULTS: IVIgG was administered to 960 patients (30.8%). Patients who received IVIgG were more severely ill than those who did not (Acute Physiology and Chronic Health Evaluation (APACHE) II score 24.2 ± 8.8 vs 22.6 ± 8.7, p < 0.001). They had higher ICU mortality (22.8% vs 17.4%, p < 0.001), but similar in-hospital mortality (34.4% vs 31.0%, p = 0.066). In propensity score-matched analysis, 653 pairs were created. Both ICU mortality and in-hospital mortality were similar between the two groups (21.0% vs 18.1%, p = 0.185, and 32.9% vs 28.6%, p = 0.093, respectively) using generalized estimating equations fitted with logistic regression models adjusted for other therapeutic interventions. The administration of IVIgG was not associated with ICU or in-hospital mortality (odds ratio (OR) 0.883; 95% confidence interval (CI) 0.655-1.192, p = 0.417, and OR 0.957, 95% CI, 0.724-1.265, p = 0.758, respectively). CONCLUSIONS: In this analysis of a large cohort of patients with sepsis and septic shock, the administration of low-dose IVIgG as an adjunctive therapy was not associated with a decrease in ICU or in-hospital mortality. TRIAL REGISTRATION: University Hospital Medical Information Network Individual Clinical Trials Registry, UMIN-CTR000012543 . Registered on 10 December 2013.

Antithrombin Supplementation and Mortality in Sepsis-Induced Disseminated Intravascular Coagulation: A Multicenter Retrospective Observational Study.

Supplemental doses of antithrombin (AT) are widely used to treat sepsis-induced disseminated intravascular coagulation (DIC) in Japan. However, evidence on the benefits of AT supplementation for DIC is insufficient. This multicenter retrospective observational study aimed to clarify the effect of AT supplementation on sepsis-induced DIC using propensity score analyses. Data from 3,195 consecutive adult patients admitted to 42 intensive care units for severe sepsis treatment were retrospectively analyzed; 1,784 patients were diagnosed with DIC (n = 715, AT group; n = 1,069, control group). Inverse probability of treatment-weighted propensity score analysis indicated a statistically significant association between AT supplementation and lower in-hospital all-cause mortality (n = 1,784, odds ratio [95% confidence intervals]: 0.748 [0.572-0.978], P = 0.034). However, quintile-stratified propensity score analysis (n = 1,784, odds ratio: 0.823 [0.646-1.050], P = 0.117) and propensity score matching analysis (461 matching pairs, odds ratio: 0.855 [0.649-1.125], P = 0.263) did not show this association. In the early days after intensive care unit admission, the survival rate was statistically higher in the propensity score-matched AT group than in the propensity score-matched control group (P = 0.007). In DIC patients without concomitant heparin administration, similar results were observed. In conclusion, AT supplementation may be associated with reduced in-hospital all-cause mortality in patients with sepsis-induced DIC. However, the statistical robustness of this connection was not strong. In addition, although the number of transfusions needed in patients with AT supplementation increased, severe bleeding complications did not.

Characteristics, treatments, and outcomes of severe sepsis of 3195 ICU-treated adult patients throughout Japan during 2011-2013.

Severe sepsis is a major concern in the intensive care unit (ICU), although there is very little epidemiological information regarding severe sepsis in Japan. This study evaluated 3195 patients with severe sepsis in 42 ICUs throughout Japan. The patients with severe sepsis had a mean age of 70 ± 15 years and a mean Acute Physiology and Chronic Health Evaluation II score of 23 ± 9. The estimated survival rates at 28 and 90 days after ICU admission were 73.6 and 56.3 %, respectively.

Sivelestat, a neutrophil elastase inhibitor, reduces mortality rate of critically ill patients.

Many studies have suggested that neutrophil elastase (NE) may contribute to multiple organ failure (MOF) and acute injury of lung endothelial cells. It is therefore conceivable that NE inhibitors may improve the outcome of MOF patients. A synthetic NE inhibitor, sivelestat, which was developed and released in Japan, inhibited inflammatory reactions in various animal models. We examined the medical records of patients requiring more than two days of respiratory care in four intensive care units to investigate whether sivelestat contributed to improvement of their conditions. A total of 110 patients were divided into two groups (sivelestat treated group of 57 patients and untreated group of 53 patients). The conditions and age of the patients were similar in both groups. Sivelestat (0.2 mg/kg/hr) was administered continuously for 14 days beginning on the day of the intensive care unit (ICU) admission or for less than 14 days until discharge from the ICU. Hospital mortality differed significantly between the two groups (treated: 19% and untreated: 40%, p < 0.05). The severity of acute lung injury is defined by the ratio of arterial oxygen partial pressure (PaO2)/fraction concentration of oxygen in the inspired air (FiO2). When the PaO2/FiO(2) ratio is more than 200 mmHg, the morbidity is lower. In patients with PaO2/FiO2 ratio more than 200 mmHg, the hospital mortality was 33.3% (7/21) in the untreated group and 6.0% (1/18) in the treated group (p = 0.0236). We conclude that administration of sivelestat reduces mortality of critically ill patients.