Association of Contrast Extravasation Grade With Massive Transfusion in Pediatric Blunt Liver and Spleen Injuries: A Multicenter Retrospective Cohort Study.

BACKGROUND: This study aimed to assess whether the grade of contrast extravasation (CE) on CT scans was associated with massive transfusion (MT) requirements in pediatric blunt liver and/or spleen injuries (BLSI). METHODS: This multicenter retrospective cohort study included pediatric patients (≤16 years old) who sustained BLSI between 2008 and 2019. MT was defined as transfusion of all blood products ≥40 mL/kg within the first 24 h of admission. Associations between CE and MT requirements were assessed using multivariate logistic regression analysis with cluster-adjusted robust standard errors to calculate the adjusted odds ratio (AOR). RESULTS: A total of 1407 children (median age: 9 years) from 83 institutions were included in the analysis. Overall, 199 patients (14 %) received MT. CT on admission revealed that 54 patients (3.8 %) had CE within the subcapsular hematoma, 100 patients (7.1 %) had intraparenchymal CE, and 86 patients (6.1 %) had CE into the peritoneal cavity among the overall cohort. Multivariate analysis, adjusted for age, sex, age-adjusted shock index, injury severity, and laboratory and imaging factors, showed that intraparenchymal CE and CE into the peritoneal cavity were significantly associated with the need for MT (AOR: 2.50; 95 % CI, 1.50-4.16 and AOR: 4.98; 95 % CI, 2.75-9.02, respectively both p < 0.001). The latter significant association persisted in the subgroup of patients with spleen and liver injuries. CONCLUSION: Active CE into the free peritoneal cavity on admission CT was independently associated with a greater probability of receiving MT in pediatric BLSI. The CE grade may help clinicians plan blood transfusion strategies. LEVEL OF EVIDENCE: Level 4; Therapeutic/Care management.

Naphazoline intoxication managed with minimally invasive cardiac output monitoring.

Naphazoline, a nonspecific alpha-adrenoceptor stimulant, is a potent vasoconstrictor used in nasal sprays, eye drops, and over-the-counter antiseptics. Naphazoline intoxication increases afterload by constricting the peripheral arteries, which can lead to complications including multiple organ failure. Although phentolamine, a nonselective alpha-adrenoceptor antagonist, and nicardipine, a calcium channel blocker, are used for the treatment of naphazoline intoxication, no established administration protocols currently exist. We present the case of a 32-year-old male with depression who ingested 150 mL of an antiseptic containing 0.1% naphazoline (equivalent to 150 mg of naphazoline). Five hours after ingestion, the patient was admitted to hospital exhibiting signs of naphazoline intoxication, such as bradycardia (46 beats/min), blood pressure of 166/122 mmHg, and peripheral cyanosis. We used the FloTrac™/EV1000™ system (Edwards Lifesciences, Irvine, CA, USA), a minimally invasive cardiac output monitoring system, to monitor systemic vascular resistance. The systemic vascular resistance index (SVRI) was elevated (4457 dyne.s/cm5/m2; nomal range: 1970-2390 dyne.s/cm5/m2) upon admission and initial treatment with continuous intravenous infusion of phentolamine led to SVRI normalization within 2 h. With the goal of maintaining SVRI normalization, continuous infusion with nicardipine was then started. At 10 h after treatment initiation, the nicardipine dose peaked at 9 mg/h (1.9 µg/kg/min). Treatment was discontinued 8 h later, and the patient was discharged on the fourth day without sequelae. In conclusion, the use of a minimally invasive cardiac output monitoring system to track vascular resistance can effectively guide the dosing of phentolamine or nicardipine in the treatment of naphazoline intoxication.

Impact of the failure of initial insertion of a peripheral intravascular catheter on the development of adverse events in patients admitted to the intensive care unit from the emergency room: A post hoc analysis of the AMOR-VENUS study.

Aim: To investigate an association between failure of initial peripheral intravascular catheter (PIVC) insertion and adverse events in patients admitted to the intensive care unit (ICU) from the emergency room (ER). Methods: This study was a post hoc analysis of the AMOR-VENUS study, a multicenter cohort study that included 22 institutions and 23 ICUs in Japan between January and March of 2018. Study participants included consecutive adult patients admitted to the ICU with PIVCs inserted in ICU during the study period exclusively from the ER. The primary outcome was adverse events. Adverse events were composite of arterial puncture, hematoma, extravasation, nerve injury, tendon injury, compartment syndrome, pain, redness, bad location, and effusion. Multivariate logistic regression analyses were performed to assess the association between adverse events and the failure of initial PIVC insertion. Results: In total, 363 patients and 1121 PIVCs were analyzed. Moreover, 199 catheters failed to insert properly, and 36 patients and 107 catheters experienced adverse events. After performing multivariate logistic regression analysis, there were statistically significant associations in the odds ratio (OR) and 95% confidence interval (CI) for the failure of initial insertion (OR, 1.66 [1.02-2.71]; p = 0.04). Conclusion: Failure of initial insertion may be a risk factor for adverse events. We could potentially provide various interventions to avoid failure of initial PIVC insertion. For example, PIVC insertion could be performed by experienced practitioners.

Therapeutic strategies for pseudoaneurysm following blunt liver and spleen injuries: A multicenter cohort study in the pediatric population.

BACKGROUND: Little guidance exists for the treatment of pseudoaneurysm (PA) following pediatric blunt liver and/or spleen injuries (BLSIs). We aimed to describe the incidence of delayed PA development and the subsequent clinical course of PA in pediatric BLSIs. METHODS: This multicenter retrospective cohort study from Japan included pediatric patients (16 years and younger) who sustained BLSIs from 2008 to 2019. The cohort was divided into four groups based on hemostatic intervention within 48 hours of admission, namely, nonoperative management (NOM), NOM with interventional radiology (IR), operative management (OM), and combined IR/OM. Descriptive statistics were used to describe the incidence of delayed PA among the groups and to characterize the clinical course of any PAs. RESULTS: A total of 1,407 children (median age, 9 years) from 83 institutions were included. The overall number (incidence) of cases of delayed PA formation was 80 (5.7%), and the number with delayed PA rupture was 16 cases (1.1%) in the entire cohort. Patients treated with NOM (1,056), NOM with IR (276), OM (53), and combined IR/OM (22) developed 43 (4.1%), 32 (12%), 2 (3.8%), and 3 (14%) delayed PAs, respectively. Among patients who developed any PAs, 39% of patients underwent prophylactic IR for unruptured PA, while 13% required emergency angioembolization for delayed PA rupture, with one ruptured case requiring total splenectomy. At least 45% of patients experienced spontaneous resolution of PA without any interventions. CONCLUSION: Our results suggest that the risk of delayed PA still exists even after acute phase IR as an adjunct to NOM for BLSIs in children, indicating the necessity of a period of further observation. While endovascular interventions are usually successful for PA management, including rupture cases, given the high incidence of spontaneous resolution, the ideal management of PA remains to be investigated in future studies. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level IV.

Risk factors for peripheral venous catheter-related phlebitis stratified by body mass index in critically ill patients: A post-hoc analysis of the AMOR-VENUS study.

Introduction: Phlebitis is an important complication in patients with peripheral intravascular catheters (PIVCs). Although an association between body mass index (BMI) and phlebitis has been suggested, the risk of phlebitis according to BMI has not been well elucidated. Therefore, in this study, we analyzed the risk of phlebitis according to BMI in patients in the intensive care unit (ICU). Materials and methods: This study undertook a secondary analysis of the data from a prospective multicenter observational study assessing the epidemiology of phlebitis at 23 ICUs in Japan. Patients admitted into the ICU aged ≥18 years with a new PIVC inserted after ICU admission were consecutively enrolled and stratified into the following groups based on BMI: Underweight (BMI < 18.5 kg/m2), normal weight (18.5 ≤ BMI < 25.0 kg/m2), and overweight/obese (BMI ≥ 25.0 kg/m2). The primary outcome was phlebitis. The risk factors for phlebitis in each BMI-based group were investigated using a marginal Cox regression model. In addition, hazard ratios and 95% confidence intervals were calculated. Results: A total of 1,357 patients and 3,425 PIVCs were included in the analysis. The mean BMI for all included patients was 22.8 (standard deviation 4.3) kg/m2. Among the eligible PIVCs, 455; 2,041; and 929 were categorized as underweight, normal weight, and overweight/obese, respectively. In the underweight group, catheter size ≥ 18 G and amiodarone administration were independently associated with the incidence of phlebitis. Drug administration standardization was associated with the reduction of phlebitis. In the normal weight group, elective surgery as a reason for ICU admission, and nicardipine, noradrenaline, and levetiracetam administration were independently associated with the incidence of phlebitis. Heparin administration was associated with the reduction of phlebitis. In the overweight/obese group, the Charlson comorbidity index, catheter size ≥ 18 G, and levetiracetam administration were independently associated with the incidence of phlebitis. Catheters made from PEU-Vialon (polyetherurethane without leachable additives) and tetrafluoroethylene were associated with the reduction of phlebitis. Conclusion: We investigated the risk factors for peripheral phlebitis according to BMI in ICU and observed different risk factors in groups stratified by BMI. For example, in underweight or overweight patients, large size PIVCs could be avoided. Focusing on the various risk factors for phlebitis according to patients' BMIs may aid the prevention of phlebitis.

Japanese rapid/living recommendations on drug management for COVID-19: updated guidelines (July 2022).

Background: Coronavirus disease (COVID-19), an infectious disease caused by the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread worldwide since early 2020, and there are still no signs of resolution. The Japanese Clinical Practice Guidelines for the Management of Sepsis and Septic Shock (J-SSCG) 2020 Special Committee created the Japanese Rapid/Living recommendations on drug management for COVID-19 using the experience of creating the J-SSCG. Methods: The Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) approach was used to determine the certainty of the evidence and strength of recommendations. The first edition of this guideline was released on September 9, 2020, and this is the revised edition (version 5.0; released on July 15, 2022). Clinical questions (CQs) were set for the following 10 drugs: favipiravir (CQ1), remdesivir (CQ2), corticosteroids (CQ4), tocilizumab (CQ5), anticoagulants (CQ7), baricitinib (CQ8), casirivimab/imdevimab (CQ9-1), sotrovimab (CQ9-2), molnupiravir (CQ10), and nirmatrelvir/ritonavir (CQ11). Recommendations: Favipiravir is not suggested for all patients with COVID-19 (GRADE 2C). Remdesivir is suggested for patients with mild COVID-19 who do not require oxygen, and patients with moderate COVID-19 requiring supplemental oxygen/hospitalization (both GRADE 2B). Corticosteroids are recommended for moderate and severe COVID-19 (GRADE 1B, 1A). However, their administration is not recommended for mild COVID-19 (GRADE 1B). Tocilizumab is suggested for moderate and severe COVID-19 (GRADE 2B, 2C). Anticoagulant administration is recommended for moderate and severe COVID-19 (Good Practice Statement). Baricitinib is suggested for moderate and severe COVID-19 (both GRADE 2C). Casirivimab/imdevimab and sotrovimab are recommended for mild COVID-19 (both GRADE 2C). Molnupiravir and nirmatrelvir/ritonavir are recommended for mild COVID-19 (both GRADE 2C). SARS-CoV-2 mutant strains emerge occasionally, and each time, the treatment policy at clinics is forced to change drastically. We ask health-care professionals in the field to refer to the recommendations in these guidelines and use these to keep up to date with COVID-19 epidemiological information.

A burden of fluid, sodium, and chloride due to intravenous fluid therapy in patients with respiratory support: a post-hoc analysis of a multicenter cohort study.

BACKGROUND: Fluid creep, including fluids administered as drug diluents and for the maintenance of catheter patency, is the major source of fluid intake in critically ill patients. Although hypoxemia may lead to fluid restriction, the epidemiology of fluid creep in patients with hypoxemia is unclear. This study aimed to address the burden due to fluid creep among patients with respiratory support according to oxygenation status. METHODS: We conducted a post-hoc analysis of a prospective multicenter cohort study conducted in 23 intensive care units (ICUs) in Japan from January to March 2018. Consecutive adult patients who underwent invasive or noninvasive ventilation upon ICU admission and stayed in the ICU for more than 24 h were included. We excluded the following patients when no fluids were administered within 24 h of ICU admission and no records of the ratio of arterial oxygen partial pressure to fractional inspired oxygen. We investigated fluid therapy until 7 days after ICU admission according to oxygenation status. Fluid creep was defined as the fluids administered as drug diluents and for the maintenance of catheter patency when administered at ≤ 20 mL/h. RESULTS: Among the 588 included patients, the median fluid creep within 24 h of ICU admission was 661 mL (25.2% of the total intravenous-fluid volume), and the proportion of fluid creep gradually increased throughout the ICU stay. Fluid creep tended to decrease throughout ICU days in patients without hypoxemia and in those with mild hypoxemia (p < 0.001 in both patients), but no significant trend was observed in those with severe hypoxemia (p = 0.159). Similar trends have been observed in the proportions of sodium and chloride caused by fluid creep. CONCLUSIONS: Fluid creep was the major source of fluid intake among patients with respiratory support, and the burden due to fluid creep was prolonged in those with severe hypoxemia. However, these findings may not be conclusive as this was an observational study. Interventional studies are, therefore, warranted to assess the feasibility of fluid creep restriction. Trial registration UMIN-CTR, the Japanese clinical trial registry (registration number: UMIN 000028019, July 1, 2017).

ARDS Clinical Practice Guideline 2021.

BACKGROUND: The joint committee of the Japanese Society of Intensive Care Medicine/Japanese Respiratory Society/Japanese Society of Respiratory Care Medicine on ARDS Clinical Practice Guideline has created and released the ARDS Clinical Practice Guideline 2021. METHODS: The 2016 edition of the Clinical Practice Guideline covered clinical questions (CQs) that targeted only adults, but the present guideline includes 15 CQs for children in addition to 46 CQs for adults. As with the previous edition, we used a systematic review method with the Grading of Recommendations Assessment Development and Evaluation (GRADE) system as well as a degree of recommendation determination method. We also conducted systematic reviews that used meta-analyses of diagnostic accuracy and network meta-analyses as a new method. RESULTS: Recommendations for adult patients with ARDS are described: we suggest against using serum C-reactive protein and procalcitonin levels to identify bacterial pneumonia as the underlying disease (GRADE 2D); we recommend limiting tidal volume to 4-8 mL/kg for mechanical ventilation (GRADE 1D); we recommend against managements targeting an excessively low SpO2 (PaO2) (GRADE 2D); we suggest against using transpulmonary pressure as a routine basis in positive end-expiratory pressure settings (GRADE 2B); we suggest implementing extracorporeal membrane oxygenation for those with severe ARDS (GRADE 2B); we suggest against using high-dose steroids (GRADE 2C); and we recommend using low-dose steroids (GRADE 1B). The recommendations for pediatric patients with ARDS are as follows: we suggest against using non-invasive respiratory support (non-invasive positive pressure ventilation/high-flow nasal cannula oxygen therapy) (GRADE 2D), we suggest placing pediatric patients with moderate ARDS in the prone position (GRADE 2D), we suggest against routinely implementing NO inhalation therapy (GRADE 2C), and we suggest against implementing daily sedation interruption for pediatric patients with respiratory failure (GRADE 2D). CONCLUSIONS: This article is a translated summary of the full version of the ARDS Clinical Practice Guideline 2021 published in Japanese (URL: https://www.jsicm.org/publication/guideline.html ). The original text, which was written for Japanese healthcare professionals, may include different perspectives from healthcare professionals of other countries.

ARDS clinical practice guideline 2021.

BACKGROUND: The joint committee of the Japanese Society of Intensive Care Medicine/Japanese Respiratory Society/Japanese Society of Respiratory Care Medicine on ARDS Clinical Practice Guideline has created and released the ARDS Clinical Practice Guideline 2021. METHODS: The 2016 edition of the Clinical Practice Guideline covered clinical questions (CQs) that targeted only adults, but the present guideline includes 15 CQs for children in addition to 46 CQs for adults. As with the previous edition, we used a systematic review method with the Grading of Recommendations Assessment Development and Evaluation (GRADE) system as well as a degree of recommendation determination method. We also conducted systematic reviews that used meta-analyses of diagnostic accuracy and network meta-analyses as a new method. RESULTS: Recommendations for adult patients with ARDS are described: we suggest against using serum C-reactive protein and procalcitonin levels to identify bacterial pneumonia as the underlying disease (GRADE 2D); we recommend limiting tidal volume to 4-8 mL/kg for mechanical ventilation (GRADE 1D); we recommend against managements targeting an excessively low SpO2 (PaO2) (GRADE 2D); we suggest against using transpulmonary pressure as a routine basis in positive end-expiratory pressure settings (GRADE 2B); we suggest implementing extracorporeal membrane oxygenation for those with severe ARDS (GRADE 2B); we suggest against using high-dose steroids (GRADE 2C); and we recommend using low-dose steroids (GRADE 1B). The recommendations for pediatric patients with ARDS are as follows: we suggest against using non-invasive respiratory support (non-invasive positive pressure ventilation/high-flow nasal cannula oxygen therapy) (GRADE 2D); we suggest placing pediatric patients with moderate ARDS in the prone position (GRADE 2D); we suggest against routinely implementing NO inhalation therapy (GRADE 2C); and we suggest against implementing daily sedation interruption for pediatric patients with respiratory failure (GRADE 2D). CONCLUSIONS: This article is a translated summary of the full version of the ARDS Clinical Practice Guideline 2021 published in Japanese (URL: https://www.jrs.or.jp/publication/jrs_guidelines/). The original text, which was written for Japanese healthcare professionals, may include different perspectives from healthcare professionals of other countries.

Clinical application of skin antisepsis using aqueous olanexidine: a scoping review.

Surgical site infections (SSIs) and catheter-related bloodstream infections (CRBSIs) caused by bacteria from surfaces poorly disinfected with chlorhexidine gluconate (CHG) and povidone-iodine (PVP-I) are increasing. Olanexidine gluconate (OLG) was developed in 2015 in Japan to prevent SSI and CRBSI caused by bacteria resistant to CHG and PVP-I. This scoping review aimed to identify the knowledge gap between what is known and what is not known about the disinfection efficacy of OLG. We searched MEDLINE through PubMed, the Cochrane Central Register of Controlled Trials, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), the International Clinical Trials Registry Platform search database, ClinicalTrials.gov, and the Web-based database of Japanese medical articles for works published to July 18, 2021. Manual reference searches were also carried out. A total of 131 studies were screened. Forty-seven studies were included in this review and classified into two major categories: studies on pharmacological effects and spectrum (n = 29) and studies on clinical and adverse effects (n = 18). Olanexidine gluconate showed bactericidal activity against methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci, in addition to common Gram-positive and Gram-negative bacteria. In clinical settings, although there is limited evidence on SSI prevention, 1.5% OLG might be more effective than 10% PVP-I and 1% CHG in preventing SSI. However, the clinical usefulness of OLG is unclear due to the limited number of clinical studies. Also, clinical research is limited to studies targeting SSI prevention, and there are no clinical studies on CRBSI. Further clinical studies are needed on SSI and CRBSI prevention.

Japanese rapid/living recommendations on drug management for COVID-19: updated guidelines (September 2021).

BACKGROUND: The coronavirus disease 2019 (COVID-19) has spread worldwide since early 2020, and there are still no signs of resolution. The Japanese Clinical Practice Guidelines for the Management of Sepsis and Septic Shock (J-SSCG) 2020 Special Committee created the Japanese rapid/living recommendations on drug management for COVID-19 using the experience of creating the J-SSCG. METHODS: The Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) approach was used to determine the certainty of the evidence and strength of the recommendations. The first edition of this guideline was released on September 9, 2020, and this document is the revised edition (version 4.0; released on September 9, 2021). Clinical questions (CQs) were set for the following seven drugs: favipiravir (CQ1), remdesivir (CQ2), corticosteroids (CQ4), tocilizumab (CQ5), anticoagulants (CQ7), baricitinib (CQ8), and casirivimab/imdevimab (CQ9). Two CQs (hydroxychloroquine [CQ3] and ciclesonide [CQ6]) were retrieved in this updated version. RECOMMENDATIONS: Favipiravir is not suggested for all patients with COVID-19 (GRADE 2C). Remdesivir is suggested for patients with moderate COVID-19 requiring supplemental oxygen/hospitalization (GRADE 2B). Corticosteroids are recommended for patients with moderate COVID-19 requiring supplemental oxygen/hospitalization (GRADE 1B) and for patients with severe COVID-19 requiring mechanical ventilation/intensive care (GRADE 1A); however, their administration is not recommended for patients with mild COVID-19 not requiring supplemental oxygen (GRADE 1B). Tocilizumab is suggested for patients with moderate COVID-19 requiring supplemental oxygen/hospitalization (GRADE 2B). Anticoagulant administration is recommended for patients with moderate COVID-19 requiring supplemental oxygen/hospitalization and patients with severe COVID-19 requiring mechanical ventilation/intensive care (good practice statement). Baricitinib is suggested for patients with moderate COVID-19 requiring supplemental oxygen/hospitalization (GRADE 2C). Casirivimab/imdevimab is recommended for patients with mild COVID-19 not requiring supplemental oxygen (GRADE 1B). We hope that these updated clinical practice guidelines will help medical professionals involved in the care of patients with COVID-19.

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.

Japanese rapid/living recommendations on drug management for COVID-19.

The coronavirus disease (COVID-19) has spread worldwide since early 2020, and there are still no signs of resolution. The Japanese Clinical Practice Guidelines for the Management of Sepsis and Septic Shock (J-SSCG) 2020 Special Committee created the Japanese rapid/living recommendations on drug management for COVID-19 using the experience of creating the J-SSCGs. The Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) approach was used to determine the certainty of the evidence and strength of the recommendations. The first edition of this guideline was released on 9 September, 2020, and this document is the revised edition (version 3.1) (released 30 March, 2021). Clinical questions (CQs) were set for the following seven drugs: favipiravir (CQ1), remdesivir (CQ2), hydroxychloroquine (CQ3), corticosteroids (CQ4), tocilizumab (CQ5), ciclesonide (CQ6), and anticoagulants (CQ7). Favipiravir is recommended for patients with mild COVID-19 not requiring supplemental oxygen (GRADE 2C); remdesivir for moderate COVID-19 patients requiring supplemental oxygen/hospitalization (GRADE 2B). Hydroxychloroquine is not recommended for all COVID-19 patients (GRADE 1B). Corticosteroids are recommended for moderate COVID-19 patients requiring supplemental oxygen/hospitalization (GRADE 1B) and severe COVID-19 patients requiring ventilator management/intensive care (GRADE 1A); however, their use is not recommended for mild COVID-19 patients not requiring supplemental oxygen (GRADE 1B). Tocilizumab is recommended for moderate COVID-19 patients requiring supplemental oxygen/hospitalization (GRADE 2B). Anticoagulant therapy is recommended for moderate COVID-19 patients requiring supplemental oxygen/hospitalization and severe COVID-19 patients requiring ventilator management/intensive care (GRADE 2C). We hope that these clinical practice guidelines will aid medical professionals involved in the care of COVID-19 patients.

Galápagosization of sepsis management in Japan: a nationwide survey of current practices.

AIM: Sepsis treatment has been standardized in many countries worldwide. However, treatment of sepsis in Japan has developed independently, and how Japanese physicians actually treat sepsis patients nationwide remains uninvestigated. The aim of this study was to clarify the current practice for septic patients in Japan and how it differs from standard care throughout the world. METHODS: This study was designed as a prospective, cross-sectional, self-reported questionnaire- and Web-based electronic survey in Japan. The survey was undertaken to assess respondents' clinical practices and preferences regarding treatment strategies, sepsis assessment, and management in the setting of critical illness. An exploratory factor analysis and a hierarchical cluster analysis were carried out to identify the treatments distinctive to Japan, called "Galápagos therapies". RESULTS: The final analysis included 295 respondents. According to the factor analysis, we defined anticoagulant therapy for disseminated intravascular coagulation, antimediator renal replacement therapy, and others as Galápagos therapies. These Galápagos therapies were undertaken by approximately two-thirds of the Japanese physicians who responded. We classified Japanese physicians according to three patterns of clinical practice carried out for sepsis: (i) those who do not perform Galápagos therapies but do perform worldwide standardized care, (ii) those who perform Galápagos therapies on top of worldwide standardized care, (iii) those who do not perform worldwide standardized care. CONCLUSION: On the basis of a nationwide questionnaire-based survey in Japan, we clarified distinctive sepsis treatments performed in Japan, such as antimediator renal replacement therapy and treatment for sepsis-induced disseminated intravascular coagulation.

Can the global end-diastolic volume index guide fluid management in septic patients? A multicenter randomized controlled trial.

AIM: An index that accurately measures intravascular volume is paramount for the optimal resuscitation of sepsis. Selecting an adequate indicator to substitute for central venous pressure (CVP) has remained an issue. The objective of our study was to compare the usefulness of standard early goal-directed therapy (EGDT) with CVP (EGDT-CVP) and modified EGDT with global end-diastolic volume index (GEDI; EGDT-GEDI) for sepsis. METHODS: This was a multicenter prospective randomized controlled study. All patients with sepsis who were expected to require mechanical ventilator support for a minimum of 48 h were included. The patients were classified into an EGDT-CVP group and an EGDT-GEDI group. All participants underwent the extubation protocol. The primary outcome was the ventilator-free days over a 28-day period. RESULTS: The ventilator-free days was not significantly different between the two groups (P = 0.59). However, the EGDT-GEDI group showed a trend of shorter ventilator support duration (5.1 days [2.0-8.7 days] versus 3.9 days [2.4-5.7 days], P = 0.27) and length of stay in the intensive care unit (7.2 days [3.8-10.7 days] versus 5.1 days [3.7-8.8 days], P = 0.05) and a smaller 3-day infusion balance than the EGDT-CVP group (4,405 mL [1,092-8,163 mL] versus 3,046 mL [830-6,806 mL], P = 0.34), but the differences were not statistically significant. CONCLUSION: Although there was no significant efficacy, EGDT guided by GEDI showed a trend of shorter length of stay in the intensive care unit and lower 3-day infusion balance than the EGDT-CVP group in sepsis. The GEDI monitoring did not appear to improve the ventilator-free days over a 28-day period.

The Effect of an Invasive Strategy for Treating Pancreatic Necrosis on Mortality: a Retrospective Multicenter Cohort Study.

BACKGROUND: Infected acute necrotic collections (ANC) and walled-off necrosis (WON) of the pancreas are associated with high mortality. The difference in mortality between open necrosectomy and minimally invasive therapies in these patients remains unclear. METHODS: This retrospective multicenter cohort study was conducted among 44 institutions in Japan from 2009 to 2013. Patients who had undergone invasive treatment for suspected infected ANC/WON were enrolled and classified into open necrosectomy and minimally invasive treatment (laparoscopic, percutaneous, and endoscopic) groups. The association of each treatment with mortality was evaluated and compared. RESULTS: Of 1159 patients with severe acute pancreatitis, 122 with suspected infected ANC or WON underwent the following treatments: open necrosectomy (33) and minimally invasive treatment (89), (laparoscopic three, percutaneous 49, endoscopic 37). Although the open necrosectomy group had a significantly higher mortality on univariate analysis (p = 0.047), multivariate analysis showed no significant associations between open necrosectomy or Charlson index and mortality (p = 0.29, p = 0.19, respectively). However, age (for each additional 10 years, p = 0.012, odds ratio [OR] 1.50, 95% confidence interval [CI] 1.09-2.06) and revised Atlanta criteria-severe (p = 0.001, OR 7.84, 95% CI 2.40-25.6) were significantly associated with mortality. CONCLUSIONS: In patients with acute pancreatitis and infected ANC/WON, age and revised Atlanta criteria-severe classification are significantly associated with mortality whereas open necrosectomy is not. The mortality risk for patients undergoing open necrosectomy and minimally invasive treatment does not differ significantly. Although minimally invasive surgery is generally preferred for patients with infected ANC/WON, open necrosectomy may be considered if clinically indicated.

The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2016 (J-SSCG 2016).

Background and Purpose: The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2016 (J-SSCG 2016), a Japanese-specific set of clinical practice guidelines for sepsis and septic shock created jointly by the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine, was first released in February 2017 in Japanese. An English-language version of these guidelines was created based on the contents of the original Japanese-language version. Methods: Members of the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine were selected and organized into 19 committee members and 52 working group members. The guidelines were prepared in accordance with the Medical Information Network Distribution Service (Minds) creation procedures. The Academic Guidelines Promotion Team was organized to oversee and provide academic support to the respective activities allocated to each Guideline Creation Team. To improve quality assurance and workflow transparency, a mutual peer review system was established, and discussions within each team were open to the public. Public comments were collected once after the initial formulation of a clinical question (CQ), and twice during the review of the final draft. Recommendations were determined to have been adopted after obtaining support from a two-thirds (>66.6%) majority vote of each of the 19 committee members. Results: A total of 87 CQs were selected among 19 clinical areas, including pediatric topics and several other important areas not covered in the first edition of the Japanese guidelines (J-SSCG 2012). The approval rate obtained through committee voting, in addition to ratings of the strengths of the recommendation and its supporting evidence were also added to each recommendation statement. We conducted meta-analyses for 29 CQs. Thirty seven CQs contained recommendations in the form of an expert consensus due to insufficient evidence. No recommendations were provided for 5 CQs. Conclusions: Based on the evidence gathered, we were able to formulate Japanese-specific clinical practice guidelines that are tailored to the Japanese context in a highly transparent manner. These guidelines can easily be used not only by specialists, but also by non-specialists, general clinicians, nurses, pharmacists, clinical engineers, and other healthcare professionals.