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The systemic immune-inflammation index (SII, platelet count × neutrophil-lymphocyte ratio) is a novel parameter for systemic inflammation. Cardiopulmonary bypass (CPB) is associated with systemic inflammatory responses. This retrospective study aimed to determine whether SII could predict postoperative atrial fibrillation (POAF) after cardiac surgery using CPB. Patients who underwent cardiac surgery using CPB between January 2020 and July 2021 were included. The primary outcome was POAF incidence within 7 days. Receiver-operating characteristic (ROC) curve analysis was used to evaluate SII ability in predicting POAF. Multivariable analysis was used to estimate the independent association between SII and POAF development. The study included 212 patients, and 90 (43%) developed POAF. The preoperative SII cutoff of 545 × 10

Purpose Although the most recent systematic review and meta-analyses on acute respiratory distress syndrome (ARDS) have shown that the use of steroids decreases mortality in adult patients, its benefits and risks may differ depending on the type and dosage of the steroid. Therefore, we conducted a network meta-analysis (NMA) to compare the differences in the efficacy among different doses and types of steroids. Methods We searched MEDLINE, CENTRAL, ICHUSHI, ClinicalTrials.gov, and WHO ICTRP databases from the earliest records to March 2021 for randomized control trials, which compared steroids with placebo or conventional therapy for ARDS. Using the random-effects model, we compared various categories of steroids (high-dose methylprednisolone, low-dose methylprednisolone, hydrocortisone, dexamethasone, and no steroid) concerning hospital mortality, incidence of infection, and ventilator-free days (VFD). Results We analyzed nine studies involving adult patients (n = 1212). Although there were no significant differences between the groups in terms of the mortality and incidence of infection, the number of VFD were greater when using low-dose methylprednisolone than when not using any steroids (Mean difference: 6.06; 95% confidence intervals: [2.5, 10.5]). Moreover, the rank probability showed that low-dose methylprednisolone might be the optimal treatment, whereas using no steroid or high-dose methylprednisolone may be inferior to other treatments in terms of mortality, infection, and VFD. Conclusion This NMA suggested that the effect of steroids on the outcome in patients with ARDS might depend on the type of the steroid drug administered. Moreover, further studies are needed to identify the optimal type and dosage. Supplementary Information The online version contains supplementary material available at 10.1007/s00540-021-03016-5.

Infection during extracorporeal membrane oxygenation (ECMO) is a common complication that leads to increased mortality. Thus, antimicrobial prophylaxis during ECMO is often performed to prevent of nosocomial infections. However, the current status of antimicrobial prophylaxis during ECMO in Japan is unclear. Therefore, we conducted a national survey of members of the Japanese Society of Intensive Care Medicine (JSICM) to clarify the current status of antimicrobial prophylaxis during ECMO in intensive care units. An 11-question survey was devised to assess antimicrobial prophylaxis and surveillance practices during ECMO. A total of 253 hospitals responded. Of these, 235 hospitals were the JSICM-certified hospitals, and the response rate was 64%. A total of 96 hospitals (39%) administered antimicrobial prophylaxis during ECMO, and 17% of hospitals had a standardized protocol for antimicrobial prophylaxis during ECMO. Of these 96 hospitals, 79% used single agents. First-generation cephalosporins were the most commonly used (54%), followed by penicillins or penicillin-derived combinations (24%), second-generation cephalosporins (7%), and anti-methicillin-resistant Staphylococcus aureus agents (6%). In conclusion, our survey revealed 39% of hospitals administered antimicrobial prophylaxis during ECMO in Japan. First-generation cephalosporins were the agents most commonly used. Supplementary Information The online version contains supplementary material available at 10.1007/s10047-021-01291-3.

Background Historically, β-blockers have been considered to be relatively contraindicated for septic shock because they may cause cardiac suppression. On the other hand, there is an increasing interest in the use of β-blockers for treating patients with sepsis with persistent tachycardia despite initial resuscitation. Research Question Do ultrashort-acting β-blockers such as esmolol and landiolol improve mortality in patients with sepsis with persistent tachycardia despite initial resuscitation? Study Design and Methods This was a systematic review and meta-analysis. We searched MEDLINE, Cochrane Central Register of Controlled Trials, and Embase for randomized controlled trials (RCTs) that compared the mortality of patients with sepsis and septic shock treated with esmolol or landiolol. We updated our search on April 20, 2020. Two independent reviewers assessed whether titles and abstracts met the following eligibility criteria: (1) RCT, (2) patients with sepsis and septic shock ≥ 18 years of age, and (3) treatment with either esmolol/landiolol or placebo/no interventions. Two authors independently extracted selected patient and study characteristics and outcomes. The results of all analyses are presented using random effect models. Results Seven RCTs with a pooled sample size of 613 patients were included. Of these, six RCTs with 572 patients reported 28-day mortality. Esmolol or landiolol use in patients with sepsis and septic shock was significantly associated with lower 28-day mortality (risk ratio, 0.68; 95% CI, 0.54-0.85; P Interpretation The use of ultrashort-acting β-blockers such as esmolol and landiolol in patients with sepsis with persistent tachycardia despite initial resuscitation was associated with significantly lower 28-day mortality. Trial Registry UMIN Clinical Trials Registry; No.: UMIN000040174; URL: https://www.umin.ac.jp/ctr/index.htm

BackgroundThe lack of precise information on the epidemiology of peripheral intravascular catheter (PIVC)-related phlebitis and complications in critically ill patients results in the absence of appropriate preventive measures. Therefore, we aimed to describe the epidemiology of the use of PIVCs and the incidence/occurrence of phlebitis and complications in the intensive care unit (ICU).MethodsThis prospective multicenter cohort study was conducted in 23 ICUs in Japan. All consecutive patients aged ≥ 18 years admitted to the ICU were enrolled. PIVCs inserted prior to ICU admission and those newly inserted after ICU admission were included in the analysis. Characteristics of the ICU, patients, and PIVCs were recorded. The primary and secondary outcomes were the occurrence and incidence rate of PIVC-related phlebitis and complications (catheter-related blood stream infection [CRBSI] and catheter failure) during the ICU stay.ResultsWe included 2741 patients and 7118 PIVCs, of which 48.2% were inserted in the ICU. PIVC-related phlebitis occurred in 7.5% (95% confidence interval [CI] 6.9–8.2%) of catheters (3.3 cases / 100 catheter-days) and 12.9% (95% CI 11.7–14.2%) of patients (6.3 cases / 100 catheter-days). Most PIVCs were removed immediately after diagnosis of phlebitis (71.9%). Grade 1 was the most common phlebitis (72.6%), while grade 4 was the least common (1.5%). The incidence rate of CRBSI was 0.8% (95% CI 0.4–1.2%). In cases of catheter failure, the proportion and incidence rate per 100 intravenous catheter-days of catheter failure were 21% (95% CI 20.0-21.9%) and 9.1 (95% CI 8.7–10.0), respectively.ConclusionPIVC-related phlebitis and complications were common in critically ill patients. The results suggest the importance of preventing PIVC-related complications, even in critically ill patients.Trial registrationUMIN-CTR, the Japanese clinical trial registry (registration number:UMIN000028019, July 1, 2017).

Prolonged neurological symptoms such as "brain fog" and cognitive impairment have occurred after coronavirus disease 2019 (COVID-19) infection. In this report, we describe impaired consciousness caused by cefepime hydrochloride (CFPM) in a patient with cognitive sequalae of COVID-19. A 56-year-old male patient was diagnosed with penile abscess after COVID-19 infection, and a blood culture detected two drug-resistant Pseudomonas aeruginosa strains. Therefore, CFPM 2 g × twice/day was administered on day 71 after intensive care unit admission. Approximately 48 h after CFPM administration, the patient showed disturbances in consciousness. Contrast-enhanced computed tomography, magnetic resonance imaging, and spinal fluid examination revealed no obvious abnormalities. Therefore, CFPM-induced neurotoxicity was suspected. CFPM was discontinued and ceftazidime 2 g × three times/day was initiated. The patient's consciousness improved 30 h after the final administration of CFPM. Serum CFPM concentrations were 14.2, 21.7, 21.7, and 11.9 μg/mL on days 1, 2, and 3 after the initiation of CFPM and on the day after CFPM was discontinued, respectively. In conclusion, intensivists should pay attention to new neurological symptoms such as CFPM-induced encephalopathy in patients with prolonged neurological symptoms after COVID-19 infection.

Spontaneous abdominal wall hematomas are relatively rare and mainly attributed to anticoagulation and severe cough. Despite the high incidence of anticoagulation-related bleeding complications, there are no reports of spontaneous abdominal wall hematomas during extracorporeal membrane oxygenation (ECMO). We report a case of a spontaneous rectus sheath hematoma caused by alternation of the lateral semi-prone position during ECMO in a 76-year-old female patient with severe acute respiratory distress syndrome. Unfractionated heparin 12,000-14,000 units/day was administered for anticoagulation during ECMO. From Day 6 of ECMO, the patient who was under deep sedation was alternately placed in the left and right lateral semi-prone positions every 4 h, for approximately 20 h per day. On Day 12 of ECMO, the patient developed hypotension with anemia and a palpable mass in the right lower abdomen. Abdominal ultrasonographic imaging revealed a huge echo-free space centered in the right lower abdomen. Emergency contrast-enhanced computed tomography (CT) scanning showed extravasation from the superior and inferior epigastric arteries as well as a rectus sheath hematoma. Despite no apparent contrast leakage, an inferior epigastric artery embolization was undertaken because the patient was on ECMO. On Day 13 after ECMO initiation, ECMO and anticoagulation were discontinued. On CT scanning a week later, the hematoma had reduced. In conclusion, spontaneous abdominal wall hematoma is a rare and important complication that might occur during ECMO. Thus, careful physical examination should be routinely conducted when the patient is semi-prone during ECMO.

The effect of nutrition support therapy on prevention of readmission among patients with acute heart failure (HF) in an intensive care unit (ICU) setting remains unclear. We hypothesized that nutrition support therapy might decrease the readmission rate among these patients. Thus, we conducted a single-center prospective observational study to verify this hypothesis.Patients diagnosed with acute HF admitted to the ICU for more than 14 days between April 2016 and March 2017 were included in the analysis. The primary outcome was the relationship between nutritional intake and HF-related hospital readmission due to HF at 180 days after discharge. We divided the participants into 2 groups: patients who were not readmitted to hospital within 180 days after discharge (non-readmission group) and patients who were readmitted within this timeframe (HF-related readmission group). Data were expressed as median (interquartile range).Sixty patients required readmission due to HF-related events (HF-related readmission group). On the other hand, 127 patients did not require readmission (non-readmission group). The calorie and protein intake on day 3 after ICU admission in the HF-related readmission group was significantly higher than that in the non-readmission group [20.5 (14.2, 27.8) vs. 27.7 (22.5, 31.2) kcal/kg/day, p 0.001; 0.7 (0.5, 0.9) vs. 0.9 (0.7, 1.2) g/kg/day, p 0.001, respectively]. Similarly, the protein intake values on day 7 were also significantly higher in the HF-related readmission group [0.8 (0.6, 1.0) vs. 0.9 (0.7, 1.2) g/kg/day, p = 0.04]. Multivariate analysis indicated that total caloric intake on day 3 was an independent factor affecting readmission (odds ratio = 1.05, 95% confidence interval = 1.01-1.09, p = 0.006). In addition, when the cut off value of calorie intake was set to 18 kcal/kg/day, the group ingesting ≥18 kcal/kg/day on day 3 had a significantly higher readmission rate within 180 days after discharge.Our data showed that total calorie intake ≥18 kcal/kg/day on day 3 might increase the readmission rate among patients with acute HF.

Our aims were to clarify the actual situation regarding preoperative fasting and determine whether multidisciplinary interventions in a perioperative management center shorten the duration of preoperative fasting.The cohort of this before-and-after study comprised patients undergoing elective surgery aged 18 years or older who underwent general anesthesia at one of three stages: after starting a short preoperative fasting protocol (Group A), after the anesthesiologist started explaining the protocol (Group B), and after the start of the perioperative management center (Group C). Instructions on drinking clear fluids were given up to 2 h and 4 h before the start of elective surgery to the first patient on the list (on-time) and to the second and subsequent patients (on-call), respectively. Data were collected retrospectively in Groups A and B and prospectively in Group C.The study cohort comprised 89 patients in Group A (50 on-time, 39 on-call), 108 in Group B (65 on-time, 43 on-call), and 284 in Group C (182 on-time, 102 on-call). The difference between the instructed and last drinking time was significantly shorter in Group C than Group A (30 [10, 140] vs. 30 [10, 60] vs. 20 [0, 50] min, p=0.003). The duration of fasting was significantly shorter in Group C than Group B (243 [150, 395] vs. 213 [151, 323] vs. 180 [146, 280] min, p=0.01).Multidisciplinary interventions at the perioperative management center tended to reduce the duration of fasting, suggesting that this approach may contribute to improved compliance.

The usefulness and safety of continuous glucose monitoring (CGM) systems in adult patients with severe coronavirus disease (COVID-19) have been reported. Using CGM might reduce the exposure patients and healthcare workers to COVID-19 and limit the use of personal protective equipment during the pandemic. CGM devices measure glucose in the subcutaneous interstitial fluid, but the accuracy of this technique has not been established in critically ill patients. The artificial pancreas, STG-55 (Nikkiso, Tokyo), is a closed-loop device that conducts continuous blood glucose monitoring using a peripheral vein. We used the STG-55 for glucose control in a 60-year-old woman with severe COVID-19 admitted to the intensive care unit. Due to severe respiratory failure, the patient was intubated, and extracorporeal membrane oxygenation was introduced. Because she had hyperglycemia despite high-dose intravenous insulin therapy, we decided to use STG-55 for glucose control. The STG-55 safely titrated the insulin infusion and monitored glucose levels. Fifty-six hours after adopting the STG-55, it was removed because the blood sampling failed. No episodes of hypoglycemia were observed despite deep sedation during this period. In conclusion, this case demonstrates the potential utility of an artificial pancreas in patients with severe COVID-19.

Objectives Hyperchloremia is a potential risk factor for acute kidney injury (AKI) in critically ill patients. However, the relationship between hyperchloremia and postoperative AKI in adult patients undergoing cardiovascular surgery with cardiopulmonary bypass (CPB) remains unclear. The authors aimed to determine whether postoperative hyperchloremia was associated with postoperative AKI in these populations. Objectives Retrospective, single-center study. Setting Tertiary care hospital. Participants Adult patients who underwent cardiovascular surgery with CPB. Interventions None. Measurements and Main Results Patients with and without postoperative hyperchloremia were matched (1:1). The primary outcome was the rate of postoperative AKI diagnosed using the Kidney Disease: Improving Global Outcomes consensus criteria. Postoperative hyperchloremia was defined as postoperative serum chloride levels of >110 mmol/L during the first 48 hours. An increase in serum chloride levels (Δ[Cl–]) was defined as the difference between the preoperative and maximum postoperative serum chloride levels during the first 48 hours ([Cl–]max). Propensity-score matching and univariate and multivariate logistic regression analyses were employed. A total of 323 patients were included. Propensity-score matching selected 55 pairs for the final comparison. The incidence of postoperative AKI did not differ between the two groups (47% v 46%, p = 1.0). In the multivariate logistic regression analysis, Δ[Cl–] was associated independently with the development of postoperative AKI (odds ratio, 1.13; 95% confidence interval, 1.06-1.21; p Conclusions Exposure to postoperative hyperchloremia was not associated with postoperative AKI in adult patients undergoing cardiovascular surgery with CPB. However, an increase in the serum chloride level might be associated with postoperative AKI.

Objective Although several studies have demonstrated that noncardiac surgery in patients with hypertrophic cardiomyopathy (HCM) is safe, the long-term outcomes remain unclear. Therefore, the authors investigated the postoperative long-term outcomes of patients with HCM who underwent noncardiac surgery at their hospital. Design Retrospective review. Setting Single university hospital. Participants Seventy-two consecutive patients with HCM who underwent noncardiac surgery. Intervention No intervention. Measurements and Main Results The incidence of HCM-related events during the patient’s hospital stay were evaluated as the short-term outcomes, and HCM-related events after discharge were evaluated as the long-term outcomes. HCM-related events were defined as sudden death, implantable cardioverter-defibrillator discharge with successful recovery from cardiopulmonary arrest, death due to heart failure, hospitalization for heart failure, myocardial infarction, and thrombosis caused by atrial fibrillation. The median postoperative follow-up was 1,382 days (3.8 years). Short-term mortality and morbidity rates were both 1.3%, whereas long-term mortality and morbidity rates were 4.2% and 15%, respectively. The 5-year event-free rate was 76%, whereas the postoperative HCM-related mortality rate was 4.2%. Conclusions This study suggests that noncardiac surgery in patients with HCM is safe in terms of both short- and long-term outcomes. To confirm the findings, additional studies, such as prospective, multicenter, observational studies, should be conducted.

Although tight glucose control might reduce inflammation after cardiac surgery, it remains unclear whether inflammation can be controlled by maintaining glucose levels within 110–180 mg/dL. We hypothesized that a glucose target range of 110–180 mg/dL decreases inflammation after cardiovascular surgery. This retrospective study included 72 cardiovascular surgery patients divided into two groups according to the glucose control approach. Patients allocated to the closed-loop group received closed-loop glucose control (target glucose levels at 110–180 mg/dL) from admission to the intensive care unit until 9 a.m. on postoperative day (POD) 1. Patients allocated to the conventional group received conventional glucose control using a sliding scale method to maintain blood glucose levels

This study evaluated the prognostic value of alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) together with host-related factors in patients with unresectable advanced gastric cancer. The study enrolled 262 patients who received chemotherapy for unresectable advanced gastric cancer at Kochi Medical School from 2007 to 2015. Clinicopathological information and systemic inflammatory response data were analyzed for associations between baseline cancer-related prognostic variables and survival outcomes. The median survival time was significantly lower for patients with high ALP, high LDH, high total bilirubin, high aspartate aminotransferase, high alanine transaminase, high gamma-glutamyltransferase, high creatinine, a Glasgow prognostic score (GPS) of 1 or 2 score compared to GPS 0, higher compared to lower neutrophil to lymphocyte ratio (NLR) 3.9, lower compared to higher prognostic nutrition index 36.1, T3–4 compared to T1–2 tumor and diffuse-type compared to intestinal-type histology. Multivariate survival analysis identified high ALP 322 (HR 1.808; 95% CI 1.015–3.220; P = 0.044), T2–3 (HR 2.622; 95% CI 1.224–5.618; P = 0.013), and diffuse-type gastric cancer (HR 2.325; 95% CI 1.341–4.032; P = 0.003) as significant independent predictors of worse prognosis in the studied group of cancer patients. High level of ALP is an independent, worse prognosis factor for patients receiving chemotherapy for unresectable and recurrent gastric cancer.

Blood purification has been widely performed for critically ill patients, even in cases without renal failure. Effective anticoagulation of the extracorporeal circuit is necessary to prevent circuit clotting. We hypothesized that administration of recombinant human-soluble thrombomodulin (rhsTM) to septic patients undergoing blood purification may prevent circuit clotting, because this agent regulates coagulation. We performed a retrospective, single-center, propensity-matched cohort study in the intensive care unit of Nishichita General Hospital. We included septic patients admitted to the intensive care unit from May 2015 to August 2020 who underwent blood purification. Patients who received rhsTM during intensive care unit admission to the end of the first blood purification (rhsTM group) were matched 1:1 with other patients (control group). The primary outcome was the occurrence of circuit clotting during the first blood purification. A total of 138 patients were included in the study [43 patients (31%) in the rhsTM group and 95 patients (69%) in the control group]. After propensity score matching, 42 pairs of patients were selected, and patients in the rhsTM group had a lower incidence of circuit clotting (21 vs. 55%, P = 0.003). One case of major bleeding occurred in the rhsTM group, but there was no difference in the incidence of major bleeding between groups (2 vs. 0%, P = 1.0). In conclusion, this propensity-matched cohort study indicated that the administration of rhsTM to septic patients undergoing blood purification may prevent extracorporeal circuit clotting.

Historically, β-blockers have been considered to be relatively contraindicated for septic shock because they may cause cardiac suppression. On the other hand, there is an increasing interest in the use of β-blockers for treating patients with sepsis with persistent tachycardia despite initial resuscitation.Do ultrashort-acting β-blockers such as esmolol and landiolol improve mortality in patients with sepsis with persistent tachycardia despite initial resuscitation?This was a systematic review and meta-analysis. We searched MEDLINE, Cochrane Central Register of Controlled Trials, and Embase for randomized controlled trials (RCTs) that compared the mortality of patients with sepsis and septic shock treated with esmolol or landiolol. We updated our search on April 20, 2020. Two independent reviewers assessed whether titles and abstracts met the following eligibility criteria: (1) RCT, (2) patients with sepsis and septic shock ≥ 18 years of age, and (3) treatment with either esmolol/landiolol or placebo/no interventions. Two authors independently extracted selected patient and study characteristics and outcomes. The results of all analyses are presented using random effect models.Seven RCTs with a pooled sample size of 613 patients were included. Of these, six RCTs with 572 patients reported 28-day mortality. Esmolol or landiolol use in patients with sepsis and septic shock was significantly associated with lower 28-day mortality (risk ratio, 0.68; 95% CI, 0.54-0.85; P .001). Unimportant heterogeneity was observed (IThe use of ultrashort-acting β-blockers such as esmolol and landiolol in patients with sepsis with persistent tachycardia despite initial resuscitation was associated with significantly lower 28-day mortality.UMIN Clinical Trials Registry; No.: UMIN000040174; URL: https://www.umin.ac.jp/ctr/index.htm.

The use of standardized internal hospital phone numbers for cardiac arrest is advocated in Europe. We evaluated the current status of variations in medical emergency call numbers for in-hospital patients in Japan and whether anesthesiologists would approve a standardized number. From June 2018 to August 2018, a questionnaire survey was mailed to anesthesiologists in 1373 Japanese Society of Anesthesiologists (JSA)-accredited hospitals. The basis for opinions on using a standardized cardiac arrest call number in all Japanese hospitals was evaluated. Of 1373 facilities (response rate, 58%, n = 800), 741/776 (96%) reported a response system for in-hospital cardiac arrest; 638/710 (90%) responded to cardiac arrest through loudspeaker broadcast, audible to both patients and staff; 346/777 (48%) used a number between one and five digits long, four-digit numbers being the most common. Across Japan, 370 different numbers were reported. Only 385/688 (56%) of respondents had the emergency number memorized. Finally, 423/776 (55%) respondents approved standardizing a hospital telephone number for summoning help. Multivariate analysis showed that facilities where the anesthesiologists already memorized the call number were the only reason identified for opposition to the standardization. Although 96% of JSA-accredited hospitals had a response system for in-hospital cardiac arrests, discussions for standardization of a unified number need to be encouraged for improved emergency response.

Background 5-Aminolevulinic acid (5-ALA) is useful as a photodynamic agent, but its use commonly leads to hypotension. Although avoiding a mean arterial pressure (MAP) < 60 mmHg is important, the incidence of MAP < 60 mmHg when using 5-ALA is unclear. Therefore, we conducted a retrospective study to assess the incidence of post-induction hypotension and identified risk factors of this phenomenon. Methods One-hundred and seventy-two consecutive patients who underwent transurethral resection of the bladder tumor or craniotomy with the use of 5-ALA were enrolled. The primary outcome was the incidence of post-induction hypotension, defined as MAP < 60 mmHg during the first 1 h after anesthesia induction. We divided participants into the normal blood pressure group (group N) and the hypotension group (group L). Results The incidence of post-induction hypotension was 70% (group L = 121, group N = 51). Multivariate analysis revealed that female sex was an independent factor of post-induction hypotension (odds ratio [OR] 3.95; 95% confidence interval [CI] 1.21–12.97; p = 0.02). Systolic blood pressure < 100 mmHg before anesthesia induction and general anesthesia were also identified as significant independent factors (OR 13.30; 95% CI 1.17–151.0; p = 0.04 and OR 25.84; 95% CI 9.80–68.49; p < 0.001, respectively). Conclusions The incidence of post-induction hypotension was 70% in patients using 5-ALA. Female sex, systolic blood pressure < 100 mmHg before anesthesia induction, and general anesthesia might be independent factors of post-induction hypotension when using 5-ALA.

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., 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 sepsis‐induced disseminated intravascular coagulation treatment. In this article, we defined them as Galápagos therapies and advocate their unique clinical concept; however, evaluation of the effectiveness of the Galápagos therapies will require a detailed analysis of the data on a patient level.

Purpose To observe arterial oxygen in relation to fraction of inspired oxygen (FIO2) during mechanical ventilation (MV). Materials and methods In this multicenter prospective observational study, we included adult patients required MV for >48 h during the period from March to May 2015. We obtained FIO2, PaO2 and SaO2 from commencement of MV until the 7th day of MV in the ICU. Results We included 454 patients from 28 ICUs in this study. The median APACHE II score was 22. Median values of FIO2, PaO2 and SaO2 were 0.40, 96 mm Hg and 98%. After day two, patients spent most of their time with a FIO2 between 0.3 and 0.49 with median PaO2 of approximately 90 mm Hg and SaO2 of 97%. PaO2 was ≥100 mm Hg during 47.2% of the study period and was ≥130 mm Hg during 18.4% of the study period. FIO2 was more likely decreased when PaO2 was ≥130 mm Hg or SaO2 was ≥99% with a FIO2 of 0.5 or greater. When FIO2 was Conclusions In our multicenter prospective study, we found that hyperoxemia was common and that hyperoxemia was not corrected.

Surgical stress induces hyperglycemia and gives rise to glucose toxicity, which causes infectious diseases, resulting in unfavorable surgical outcomes. Intensive insulin treatment can control short- and long-term complications in patients with not only diabetes mellitus, but also surgical diabetes; however, it is associated with an increased risk of hypoglycemia. The wearable artificial pancreas was originally developed to control glucose levels in patients with type 1 diabetes, progressing to a device with enhanced stability and safety for these patients. Its usability has further progressed to include patients with type 2 diabetes. The bedside artificial pancreas is the only closed-loop-type artificial pancreas which can maintain stable glycemic control in accordance with a target blood glucose range, based on the patient's actual blood glucose levels. Moreover, this stable glycemic control with a low variation in blood glucose concentration within the target range is produced without any hypoglycemia. Significant advances of this device will now occur due to the approval of treatment for perioperative glycemic control by the Japanese Health Care Insurance System in 2016. Along with an increase in the number of mainly elderly patients with low glucose tolerance, it is expected that the role of the artificial pancreas will increase in the future. Considering the current state and expense of regenerative and transplant medicine, along with donor shortages, further development of the artificial pancreas and associated glycemic control can be expected.

The aim of this pilot study was to investigate the effects of a preoperative immune-modulating diet (IMD) before thoracoscopic esophagectomy for patients with esophageal cancer. Thirty patients who were diagnosed with resectable esophageal cancer were assigned to two groups: the IMD (n = 15) and the standard liquid diet (SLD; n = 15) groups. We evaluated postoperative parameters, such as the incidence of complications and the postoperative levels of cytokines as the primary endpoints. The secondary endpoint was the length of hospital stay. The peak levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-α appeared on postoperative day (POD) 1 and POD 2 in the IMD and SLD group, respectively. The peak level of C-reactive protein (CRP) appeared on POD 3 in both groups (IMD 9.9 mg/dL, SLD 15.2 mg/dL). Overall, TNF-α levels in the IMD group were lower than those in the SLD group (P = 0.033). Furthermore, IL-6 (P = 0.182) and CRP (P = 0.191) levels, and the incidence of postoperative pneumonia (7.1 vs. 26.7%; P = 0.330) tended to be lower in the IMD group than in the SLD group. Preoperative IMD suppressed the elevation of the TNF-α levels after thoracoscopic esophagectomy in patients with esophageal cancer, although no different tendency was detected in terms of IL-6, CRP or postoperative complications.

SummaryRecombinant human soluble thrombomodulin (ART-123) is a novel anticoagulant for patients with disseminated intravascular coagulation (DIC). It is widely used in clinical settings throughout Japan. Furthermore, a global Phase 3 study is currently being conducted. In healthy subjects, ART-123 is excreted mainly via the kidneys. Therefore, ART-123 dose decrease was recommended in DIC patients with severe renal dysfunction. However, the pharmacokinetics of ART-123 in DIC patients with severe acute renal dysfunction has not been elucidated. In an open-label, multicentre, prospective, clinical pharmacological study, we investigated the pharmacokinetics and safety of ART-123 upon repeated administration to DIC patients. ART-123 was administered to patients at a dose of 130 or 380 U/kg/day for six consecutive days. Plasma concentrations of ART-123 were measured at 21 time points until eight days after the final administration. Urinary excretion rates during the first 24 hours (h) were calculated. Patient renal functions were evaluated by measuring 24-h creatinine clearance (Ccr). Forty-three patients were enrolled in the present study. The urinary excretion rates of ART-123 correlated closely with 24-h Ccr. Total body clearance of ART-123 was also weakly related with 24-h Ccr. However, the plasma concentrations of ART-123 were not considerably different among patients with different renal function. Two patients had subcutaneous haemorrhage as an adverse event related to ART-123. In conclusion, plasma concentrations of ART-123 may not be different among patients with different renal functions. ART-123 was well tolerated in these patients.

Unruptured posterior communicating artery aneurysms with oculomotor nerve palsy are at high risk of rupture, and early intervention is recommended to prevent aneurysm bleeding and to improve oculomotor function. Both surgical clipping and endovascular coiling are available, and either of them is applied according to the anatomical condition and patient's comorbidity. In this article, we describe a case of an unruptured posterior communicating artery aneurysm with oculomotor nerve palsy, which was initially treated with surgical clipping. Owing to ventricular tachycardia during surgery, the craniotomy was discontinued and switched to endovascular coiling. In this operation, use of a hybrid operating room for coiling enabled adequate heparinization and immediate recraniotomy to prevent ischemic and hemorrhagic complications, respectively.

Background Although 5-aminolevulinic acid (5-ALA) is used for the photodynamic diagnosis of bladder tumors, hypotension is the most commonly observed adverse effect. We present a case of 5-ALA-induced severe hypotension during transurethral resection of a bladder tumor. Case presentation A 68-year-old man underwent transurethral resection of a bladder tumor using 5-ALA under general anesthesia. Three hours before anesthesia induction, ALA 20 mg/kg was administered orally. After anesthesia induction, his blood pressure decreased to 47/32 mmHg. Although we used phenylephrine and ephedrine, hypotension persisted at 50/33 mmHg. Bolus administration of noradrenaline slightly increased his blood pressure to 65/39 mmHg. Following this, bolus administration of adrenaline elevated his blood pressure. We decided to perform surgery under continuous administration of adrenaline. Conclusions Our case report suggests that anesthesiologists should consider 5-ALA-induced hypotension as a differential diagnosis for hypotension occurring after anesthesia induction. Moreover, ephedrine and phenylephrine might be less effective in treating this condition.

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., other authors: Satoru Hashimoto,Daisuke Hasegawa,Junji Hatakeyama,Naoki Hara,Naoki Higashibeppu,Nana Furushima,Hirotaka Furusono,Yujiro Matsuishi,Tasuku Matsuyama,Yusuke Minematsu,Ryoichi Miyashita,Yuji Miyatake,Megumi Moriyasu,Toru Yamada,Hiroyuki Yamada,Ryo Yamamoto,Takeshi Yoshida,Yuhei Yoshida,Jumpei Yoshimura,Ryuichi Yotsumoto,Hiroshi Yonekura,Takeshi Wada,Eizo Watanabe,Makoto Aoki,Hideki Asai,Takakuni Abe,Yutaka Igarashi,Naoya Iguchi,Masami Ishikawa,Go Ishimaru,Shutaro Isokawa,Ryuta Itakura,Hisashi Imahase,Haruki Imura,Takashi Irinoda,Kenji Uehara,Noritaka Ushio,Takeshi Umegaki,Yuko Egawa,Yuki Enomoto,Kohei Ota,Yoshifumi Ohchi,Takanori Ohno,Hiroyuki Ohbe,Kazuyuki Oka,Nobunaga Okada,Yohei Okada,Hiromu Okano,Jun Okamoto,Hiroshi Okuda,Takayuki Ogura,Yu Onodera,Yuhta Oyama,Motoshi Kainuma,Eisuke Kako,Masahiro Kashiura,Hiromi Kato,Akihiro Kanaya,Tadashi Kaneko,Keita Kanehata,Ken-ichi Kano,Hiroyuki Kawano,Kazuya Kikutani,Hitoshi Kikuchi,Takahiro Kido,Sho Kimura,Hiroyuki Koami,Daisuke Kobashi,Iwao Saiki,Masahito Sakai,Ayaka Sakamoto,Tetsuya Sato,Yasuhiro Shiga,Manabu Shimoto,Shinya Shimoyama,Tomohisa Shoko,Yoh Sugawara,Atsunori Sugita,Satoshi Suzuki,Yuji Suzuki,Tomohiro Suhara,Kenji Sonota,Shuhei Takauji,Kohei Takashima,Sho Takahashi,Yoko Takahashi,Jun Takeshita,Yuuki Tanaka,Akihito Tampo,Taichiro Tsunoyama,Kenichi Tetsuhara,Kentaro Tokunaga,Yoshihiro Tomioka,Kentaro Tomita,Naoki Tominaga,Mitsunobu Toyosaki,Yukitoshi Toyoda,Hiromichi Naito,Isao Nagata,Tadashi Nagato,Yoshimi Nakamura,Yuki Nakamori,Isao Nahara,Hiromu Naraba,Chihiro Narita,Norihiro Nishioka,Tomoya Nishimura,Kei Nishiyama,Tomohisa Nomura,Taiki Haga,Yoshihiro Hagiwara,Katsuhiko Hashimoto,Takeshi Hatachi,Toshiaki Hamasaki,Takuya Hayashi,Minoru Hayashi,Atsuki Hayamizu,Go Haraguchi,Yohei Hirano,Ryo Fujii,Motoki Fujita,Naoyuki Fujimura,Hiraku Funakoshi,Masahito Horiguchi,Jun Maki,Naohisa Masunaga,Yosuke Matsumura,Takuya Mayumi,Keisuke Minami,Yuya Miyazaki,Kazuyuki Miyamoto,Teppei Murata,Machi Yanai,Takao Yano,Kohei Yamada,Naoki Yamada,Tomonori Yamamoto,Shodai Yoshihiro,Hiroshi Tanaka,Osamu Nishida, Guidelines