西田 修

Objectives: To investigate implementation of evidence-based and supportive cares in ICUs, such as the ABCDEF, nutrition therapy, and ICU diary, for patients with coronavirus disease 2019 infection in ICUs and their association with ICU clinical practice and setting. Design: A worldwide, 2-day point prevalence study. Setting: The study was carried out on June 3, 2020, and July 1, 2020. A total of 212 ICUs in 38 countries participated. Clinicians in each participating ICU completed web-based online surveys. Patients: The ICU patients with coronavirus disease 2019. Interventions: None. Measurements and Main results: The implementation rate for the elements of the ABCDEF bundle, other supportive ICU care measures, and implementation-associated structures were investigated. Data were collected for 262 patients, of whom 47.3% underwent mechanical ventilation and 4.6% were treated with extracorporeal membrane oxygenation. Each element was implemented for the following percentages of patients: elements A (regular pain assessment), 45%; B (both spontaneous awakening and breathing trials), 28%; C (regular sedation assessment), 52%; D (regular delirium assessment), 35%; E (early mobility and exercise), 47%; and F (family engagement and empowerment), 16%. The implementation of element E was 4% for patients on mechanical ventilation and 8% for patients on extracorporeal membrane oxygenation. Supportive care, such as protein provision throughout the ICU stay (under 1.2 g/kg for more than 50% of the patients) and introduction of ICU diary (25%), was infrequent. Implementation rates of elements A and D were higher in ICUs with specific protocols and fewer ICU beds exclusively for patients with coronavirus disease 2019 infection. Element E was implemented at a higher rate in ICUs that had more ICU beds assigned for them. Conclusions: This point prevalence study showed low implementation of the ABCDEF bundle. Specific protocols and the number of ICU beds reserved for patients with coronavirus disease 2019 infection might be key factors for delivering appropriate supportive care.

日本集中治療医学会と日本救急医学会は,合同の特別委員会を組織し,2016年に発表した日本版敗血症診療ガイドライン(J-SSCG)2016の改訂を行った。本ガイドライン(J-SSCG2020)の目的は,J-SSCG2016と同様に,敗血症・敗血症性ショックの診療において,医療従事者が患者の予後改善のために適切な判断を下す支援を行うことである。改訂に際し,一般臨床家だけでなく多職種医療者にも理解しやすく,かつ質の高いガイドラインとすることによって,広い普及を目指した。J-SSCG2016ではSSCG2016にない新しい領域[ICU-acquircd weakness(ICU-AW)とpost-intensive care syndrome(POCS),体温管理など]を取り上げたが,J-SSCG2020では新たに注目すべき4領域(Patient-and Family-Centered Care, sepsis treatment system,神経集中治療,ストレス潰瘍)を追加し,計22領域とした。重要な118の臨床課題(clinical question:CQ)をエビデンスの有無にかかわらず抽出した。これらのCQには,本邦で特に注目されているCQも含まれる。多領域にわたる大規模ガイドラインであることから,委員25名を中心に,多職種(看護師,理学療法士,臨床工学技士,薬剤師)および患者経験者も含めたワーキンググループメンバー,両学会の公募によるシステマティックレビューメンバーによる総勢226名の参加・協力を得た。また,中立的な立場で横断的に活躍するアカデミックガイドライン推進班をJ-SSCG2016に引き続き組織した。将来への橋渡しとなることを企図して,多くの若手医師をシステマティックレビューチーム・ワーキンググループに登用し,学会や施設の垣根を越えたネットワーク構築も進めた。作成工程においては,質の担保と作業過程の透明化を図るために様々な工夫を行い,パブリックコメント募集は計2回行った。推奨作成にはGRADE方式を取り入れ,修正Delphi法を用いて全委員の投票により推奨を決定した。結果,118CQに対する回答として,79個のGRADEによる推奨,5個のGPS(good practice statement),18個のエキスパートコンセンサス,27個のBQ(background question)の解説,および敗血症の定義と診断を示した。新たな試みとして,CQごとに診療フローなど時間軸に沿った視覚的情報を取り入れた。J-SSCG2020は,多職種が関わる国内外の敗血症診療の現場において,ベッドサイドで役立つガイドラインとして広く活用されることが期待される。なお,本ガイドラインは,日本集中治療医学会と日本救急医学会の両機関誌のガイドライン増刊号として同時掲載するものである。(著者抄録)

日本集中治療医学会と日本救急医学会は,合同の特別委員会を組織し,2016年に発表した日本版敗血症診療ガイドライン(J-SSCG)2016の改訂を行った。本ガイドライン(J-SSCG2020)の目的は,J-SSCG2016と同様に,敗血症・敗血症性ショックの診療において,医療従事者が患者の予後改善のために適切な判断を下す支援を行うことである。改訂に際し,一般臨床家だけでなく多職種医療者にも理解しやすく,かつ質の高いガイドラインとすることによって,広い普及を目指した。J-SSCG2016ではSSCG2016にない新しい領域[ICU-acquircd weakness(ICU-AW)とpost-intensive care syndrome(POCS),体温管理など]を取り上げたが,J-SSCG2020では新たに注目すべき4領域(Patient-and Family-Centered Care, sepsis treatment system,神経集中治療,ストレス潰瘍)を追加し,計22領域とした。重要な118の臨床課題(clinical question:CQ)をエビデンスの有無にかかわらず抽出した。これらのCQには,本邦で特に注目されているCQも含まれる。多領域にわたる大規模ガイドラインであることから,委員25名を中心に,多職種(看護師,理学療法士,臨床工学技士,薬剤師)および患者経験者も含めたワーキンググループメンバー,両学会の公募によるシステマティックレビューメンバーによる総勢226名の参加・協力を得た。また,中立的な立場で横断的に活躍するアカデミックガイドライン推進班をJ-SSCG2016に引き続き組織した。将来への橋渡しとなることを企図して,多くの若手医師をシステマティックレビューチーム・ワーキンググループに登用し,学会や施設の垣根を越えたネットワーク構築も進めた。作成工程においては,質の担保と作業過程の透明化を図るために様々な工夫を行い,パブリックコメント募集は計2回行った。推奨作成にはGRADE方式を取り入れ,修正Delphi法を用いて全委員の投票により推奨を決定した。結果,118CQに対する回答として,79個のGRADEによる推奨,5個のGPS(good practice statement),18個のエキスパートコンセンサス,27個のBQ(background question)の解説,および敗血症の定義と診断を示した。新たな試みとして,CQごとに診療フローなど時間軸に沿った視覚的情報を取り入れた。J-SSCG2020は,多職種が関わる国内外の敗血症診療の現場において,ベッドサイドで役立つガイドラインとして広く活用されることが期待される。なお,本ガイドラインは,日本集中治療医学会と日本救急医学会の両機関誌のガイドライン増刊号として同時掲載するものである。(著者抄録)

AIM: Acute liver failure (ALF) patients with coma need to be revived not only for spontaneous recovery but also as a bridge to liver transplantation. We developed a new high-volume plasma purification system using an on-line continuous hemodiafiltration (CHDF) system, and evaluated its safety and efficacy in a multicenter study. METHODS: A single arm interventional study using the new apparatus was undertaken in the six major liver centers in Japan. The primary end-point was the proportion of patients who regained consciousness within 10 days, which was compared with a historical control (47%). Nine ALF patients were enrolled and treated with the new machine. One patient was excluded because of the need for artificial respiration support according to the established protocol. RESULTS: Seven of eight (87.5%) patients regained consciousness during the on-line CHDF session, with five of those seven waking within 4 days. After waking, one patient spontaneously recovered, three received liver transplantation, two died of liver failure, and one died of another disease. The plasma ammonia levels significantly decreased after the start of on-line CHDF from 182.5 ± 64.8 μg/dL (mean ± SD) on day 0 to 87.0 ± 38.9 μg/dL on the last day of the session (P < 0.001). Similarly, the plasma glutamine level also significantly decreased from 2069 ± 1234 μmol/L to 628 ± 193 μmol/L. Although seven severe adverse events occurred during on-line-CHDF, no causal relationship with liver support was recognized. CONCLUSIONS: The newly developed on-line CHDF system showed high efficacy for regain of consciousness and excellent therapeutic safety for managing ALF.

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.

OBJECTIVE: Early mobilization and rehabilitation has become common and expectations for physical therapists working in intensive care units have increased in Japan. The objective of this study was to establish consensus-based minimum clinical practice standards for physical therapists working in intensive care units in Japan. It also aimed to make an international comparison of minimum clinical practice standards in this area. METHODS: In total, 54 experienced physical therapists gave informed consent and participated in this study. A modified Delphi method with questionnaires was used over three rounds. Participants rated 272 items as "essential/unknown/non-essential". Consensus was considered to be reached on items that over 70% of physical therapists rated as "essential" to clinical practice in the intensive care unit. RESULTS: Of the 272 items in the first round, 188 were deemed essential. In round 2, 11 of the 62 items that failed to reach consensus in round 1 were additionally deemed essential. No item was added to the "essential" consensus in round 3. In total, 199 items were therefore deemed essential as a minimum standard of clinical practice. Participants agreed that 42 items were not essential and failed to reach agreement on 31 others. Identified 199 items were different from those in the UK and Australia due to national laws, cultural and historical backgrounds. CONCLUSIONS: This is the first study to develop a consensus-based minimum clinical practice standard for physical therapists working in intensive care units in Japan.

Background: The J-Land 3S trial demonstrated that landiolol is effective and tolerated for treating sepsis-related tachyarrhythmias. Patient characteristics (e.g. baseline heart rate [HR], type of tachyarrhythmia, and concomitant disorders) may impact the outcomes of landiolol therapy. We performed subanalyses of J-Land 3S to evaluate the impact of patient characteristics on the efficacy and safety of landiolol for treating sepsis-related tachyarrhythmia. Methods: Patients (≥20 years old; N = 151) hospitalised with sepsis at 54 participating hospitals in Japan with HR ≥100 beats/min for ≥10 min accompanied by diagnosis of tachyarrhythmia were randomised 1:1 to conventional sepsis therapy alone (control group) or conventional sepsis therapy plus landiolol (landiolol group). The efficacy and safety of landiolol were assessed in prespecified analyses of patients divided into subgroups by baseline characteristics and in post hoc, multivariate analyses with adjustment for age and HR at baseline. Findings: The percentage of patients with HR of 60-94 beats/min at 24 h after randomisation (primary endpoint) was greater in the landiolol group in most subgroups in univariate unadjusted analyses and in multivariate logistic regression. The incidence of new-onset arrhythmia by 168 h and mortality by 28 days were also lower in the landiolol group in most subgroups in univariate and multivariate Cox proportional hazards models. No subgroups showed a markedly higher incidence of adverse events in univariate or multivariate logistic regression analyses. Interpretation: These results of the J-Land 3S study suggest that the efficacy and safety of landiolol are generally unaffected by key patient characteristics. Funding: Ono Pharmaceutical Co., Ltd.

ABO blood groups have been implicated as potential risk factors for various diseases. However, no study has investigated the association between sepsis mortality and ABO blood types. We aimed to evaluate the impact of these blood types on mortality in patients with sepsis and septic shock. This retrospective observational study was conducted at two general hospitals in Japan. Patients diagnosed with sepsis or septic shock were included and divided into four groups based on blood type (O, A, B, and AB). The association between type O vs. other types and 28- and 90-day mortalities was evaluated using multivariate logistic regression analysis adjusted for age, sex, and Sequential (Sepsis-related) Organ Failure Assessment score. This study included 415 patients, of whom 131 (31.6%), 171 (41.2%), 81 (19.5%), and 32 (7.7%) had type O, A, B, and AB, respectively. Blood type O was not associated with 28-day (odds ratio: 1.7 p = 0.08) or 90-day mortality (odds ratio: 1.53, p = 0.091). However, type O was significantly associated with higher 90-day mortality (odds ratio: 3.26, p = 0.009) in patients with septic shock. The role of ABO blood type in risk stratification for septic shock and the mechanisms that potentially affect the prognosis of sepsis patients need further investigation.

Patients who undergo renal replacement therapy often exhibit a high plasma linezolid concentration. Linezolid is metabolized via oxidation. Nafamostat mesilate has antioxidant effects and is frequently used as an anticoagulant during renal replacement therapy. We aimed to investigate the effect of nafamostat mesilate on plasma linezolid concentration. We examined whether the co-administration of linezolid and nafamostat had any effect on plasma linezolid concentration. Mice were randomly allocated to two groups (n = 18/group): linezolid (100 mg kg-1 , subcutaneous injection) + nafamostat (30 mg kg-1 , intraperitoneal injection) and linezolid + saline. At 5 hours, the linezolid concentration was significantly higher in the linezolid + nafamostat co-administration group than that in the linezolid + saline group (20.6 ± 9.8 vs 3.6 ± 1.2 μg/mL, respectively P < .001). The antioxidant effects of nafamostat may inhibit linezolid metabolism, resulting in the adverse event of high linezolid concentration if both are administered concurrently during renal replacement therapy.

We aimed to evaluate whether cardiac output assessed by transpulmonary thermodilution during blood purification is affected by the difference between the blood return temperature and core temperature. We applied different blood return temperatures using a thermostat bath during blood purification in four pigs. After the blood return temperature stabilized and blood purification process stopped, the cardiac output assessed by transpulmonary thermodilution was measured. The thermostat bath was set at 35°C, 40°C, 45°C, and 50°C, with the order changed at random; four measurements were made at each temperature. Cardiac function was evaluated by echocardiography when ice-cold saline was administered in a pig. A decrease in the blood return temperature resulted in decreased cardiac output assessed by transpulmonary thermodilution, whereas an increase resulted in increased cardiac output assessed by transpulmonary thermodilution. Echocardiography revealed that the change in the blood return temperature did not affect the left ventricular ejection fraction.

Aim: We investigated personal protective equipment (PPE) use and its shortage, training, and adverse events among healthcare workers (HCWs) in the intensive care unit (ICU) during the coronavirus disease (COVID-19) pandemic in Japan and compared the results with an international survey that used the same methodology. Methods: This web-based survey was conducted from April 14 to May 6, 2020, in Japan and included HCWs directly involved in ICU management of COVID-19 patients. A survey invitation was emailed using the Japanese Society of Intensive Care Medicine's mailing list. Results: We analyzed 460 valid responses from among 976 responses. The N95/FFP2 mask (77%) was most frequently used than in the international study, although half of our respondents reported reuse of single-use N95/FFP2 masks. The median duration (1 hour) of uninterrupted PPE use per shift was less than that in the international study. The commonest PPE-related adverse event was experiencing intense heat (75%). Logistic regression analysis revealed that being a nurse was independently associated with experiencing intense heat. Conclusion: PPE shortage and frequent mask reuse were prevalent during the COVID-19 pandemic in Japan. Intense heat is the most significant symptom, especially for nurses, even with short-duration PPE use. Strategies to protect HCWs from dehydration and intense heat stroke are needed.

BACKGROUND: Tachycardia and atrial fibrillation frequently occur in patients being treated for sepsis or septic shock and have a poor prognosis. Treatments for tachyarrhythmias are often ineffective or contraindicated in this setting. We aimed to investigate the efficacy and safety of landiolol, an ultra-short-acting β-blocker, for treating sepsis-related tachyarrhythmias. METHODS: We did a multicentre, open-label, randomised controlled trial at 54 hospitals in Japan. Patients admitted to the intensive care units who received conventional treatment for sepsis, according to clinical guidelines for the management of sepsis, and who subsequently developed a tachyarrhythmia, were enrolled. The main inclusion criteria were 20 years of age or older, diagnosis of sepsis according to Third International Consensus Definitions for Sepsis and Septic Shock criteria, administration of catecholamine necessary to maintain mean arterial pressure at 65 mm Hg or more for at least 1 h, and heart rate of 100 beats per min (bpm) or more maintained for at least 10 min without a change in catecholamine dose with diagnosis of atrial fibrillation, atrial flutter, or sinus tachycardia. Only patients who developed these symptoms and signs within 24 h before randomisation, and within 72 h after entering an intensive care unit, were prospectively assigned to receive conventional sepsis therapy alone (control group) or conventional sepsis therapy plus landiolol (landiolol group) in an open-label manner. Landiolol hydrochloride was intravenously infused at an initial dose of 1 μg/kg per min within 2 h after randomisation and the dose could be increased per study protocol to a maximum of 20 μg/kg per min. Patients in both groups received conventional therapy (Japanese Clinical Practice Guidelines for the Management of Sepsis and Septic Shock 2016), including respiratory and fluid resuscitation, antimicrobials, and catecholamines. The treating physicians were required to stabilise the patient's haemodynamic status before randomisation. Randomisation was done using a central randomisation system and dynamic allocation with the minimisation method by institution, heart rate at randomisation (≥100 to <120 bpm or ≥120 bpm), and age (<70 years or ≥70 years). The primary outcome was the proportion of patients with heart rate of 60-94 bpm at 24 h after randomisation. Patients without heart rate data at 24 h after randomisation were handled as non-responders. The primary outcome was analysed using the full analysis set on an as-assigned basis, while safety was analysed using the safety analysis set according to the treatment received. This study was registered with the Japan Pharmaceutical Information Center Clinical Trials Information database, number JapicCTI-173767. FINDINGS: Between Jan 16, 2018 and Apr 22, 2019, 151 patients were randomly assigned, 76 to the landiolol group and 75 to the control group. A significantly larger proportion of patients in the landiolol group had a heart rate of 60-94 bpm 24 h after randomisation than in the control group (55% [41 of 75] vs 33% [25 of 75]), with a between-group difference of 23·1% (95% CI 7·1-37·5; p=0·0031). Adverse events were observed in 49 (64%) of 77 patients in the landiolol group and in 44 (59%) of 74 in the control group, with serious adverse events (including adverse events leading to death) in nine (12%) of 77 and eight (11%) of 74 patients. Serious adverse events related to landiolol occurred in five (6%) of 77 patients, including blood pressure decreases in three patients (4%) and cardiac arrest, heart rate decrease, and ejection fraction decrease occurred in one patient each (1%). INTERPRETATION: Landiolol resulted in significantly more patients with sepsis-related tachyarrhythmia achieving a heart rate of 60-94 bpm at 24 h and significantly reduced the incidence of new-onset arrhythmia. Landiolol was also well tolerated, but it should be used under appropriate monitoring of blood pressure and heart rate owing to the risk of hypotension in patients with sepsis and septic shock. FUNDING: Ono Pharmaceutical Co.

Sepsis-induced coagulopathy has poor prognosis; however, there is no established tool for predicting it. We aimed to create predictive models for coagulopathy progression using machine-learning techniques to evaluate predictive accuracies of machine-learning and conventional techniques. A post-hoc subgroup analysis was conducted based on the Japan Septic Disseminated Intravascular Coagulation retrospective study. We used the International Society on Thrombosis and Haemostasis disseminated intravascular coagulation (DIC) score to calculate the ΔDIC score as ((DIC score on Day 3) - (DIC score on Day 1)). The primary outcome was to determine whether the predictive accuracy of ΔDIC was more than 0. The secondary outcome was the actual predictive accuracy of ΔDIC (predicted ΔDIC-real ΔDIC). We used the machine-learning methods, such as random forests (RF), support vector machines (SVM), and neural networks (NN); their predictive accuracies were compared with those of conventional methods. In total, 1017 patients were included. Regarding DIC progression, predictive accuracy of the multiple linear regression, RF, SVM, and NN models was 63.7%, 67.0%, 64.4%, and 59.8%, respectively. The difference between predicted ΔDIC and real ΔDIC was 2.05, 1.54, 2.24, and 1.77 for the multiple linear regression, RF, SVM, and NN models, respectively. RF had the highest predictive accuracy.

近年の集中治療期におけるリハビリテーション(以下、リハ)は「集中治療における早期リハビリテーション〜根拠に基づくエキスパートコンセンサス〜」(以下、エキスパートコンセンサス)の公表、「早期離床・リハビリテーション加算」などにより、数年前と比べても大きく変化している。今回、われわれ集中治療早期リハビリテーション委員会では、現在の状況を把握する目的でアンケート調査を行った。また、数年後に訪れるエキスパートコンセンサスの改定を視野に入れ、エキスパートコンセンサスに関しても回答を依頼した。様々な回答から、集中治療期においてリハは治療の一つとして定着してきたことがわかったが、問題点や検討事項も認められた。(著者抄録)