岸原 悠貴

Early and accurate identification of high-risk patients with peripheral intravascular catheter (PIVC)-related phlebitis is vital to prevent medical device-related complications. This study aimed to develop and validate a machine learning-based model for predicting the incidence of PIVC-related phlebitis in critically ill patients. Four machine learning models were created using data from patients ≥ 18 years with a newly inserted PIVC during intensive care unit admission. Models were developed and validated using a 7:3 split. Random survival forest (RSF) was used to create predictive models for time-to-event outcomes. Logistic regression with least absolute reduction and selection operator (LASSO), random forest (RF), and gradient boosting decision tree were used to develop predictive models that treat outcome as a binary variable. Cox proportional hazards (COX) and logistic regression (LR) were used as comparators for time-to-event and binary outcomes, respectively. The final cohort had 3429 PIVCs, which were divided into the development cohort (2400 PIVCs) and validation cohort (1029 PIVCs). The c-statistic (95% confidence interval) of the models in the validation cohort for discrimination were as follows: RSF, 0.689 (0.627-0.750); LASSO, 0.664 (0.610-0.717); RF, 0.699 (0.645-0.753); gradient boosting tree, 0.699 (0.647-0.750); COX, 0.516 (0.454-0.578); and LR, 0.633 (0.575-0.691). No significant difference was observed among the c-statistic of the four models for binary outcome. However, RSF had a higher c-statistic than COX. The important predictive factors in RSF included inserted site, catheter material, age, and nicardipine, whereas those in RF included catheter dwell duration, nicardipine, and age. The RSF model for the survival time analysis of phlebitis occurrence showed relatively high prediction performance compared with the COX model. No significant differences in prediction performance were observed among the models with phlebitis occurrence as the binary outcome.

Peripheral intravascular catheter (PIVC) insertion is frequently performed in the emergency room (ER) and many failures of initial PIVC insertion occur. To reduce the failures, new needles were developed. This study aimed to investigate whether the use of the newly developed needle reduced the failure of initial PIVC insertion in the ER compared with the use of the existing needle. This single-centre, prospective observational study was conducted in Japan between April 1, 2022, and February 2, 2023. We included consecutive patients who visited our hospital by ambulance as a secondary emergency on a weekday during the day shift (from 8:00 AM to 5:00 PM). The practitioners for PIVC insertion and assessors were independent. The primary and secondary outcomes were the failure of initial PIVC insertion and number of procedures, respectively. We defined the difficulty of titrating, leakage, and hematoma within 30 s after insertion as failures. To evaluate the association between the outcomes and the use of newly developed needles, we performed multivariate logistic regression and multiple regression analyses by adjusting for covariates. In total, 522 patients without missing data were analysed, and 81 (15.5%) patients showed failure of initial PIVC insertion. The median number of procedures (interquartile range) was 1 (1-1). Multivariate logistic regression analysis revealed no significant association between the use of newly developed PIVCs and the failure of initial PIVC insertion (odds ratio, 0.79; 95% confidence interval, [0.48-1.31]; p = 0.36). Moreover, multiple regression analysis revealed no significant association between the use of newly developed PIVCs and the number of procedures (regression coefficient, -0.0042; 95% confidence interval, [-0.065-0.056]; p = 0.89). Our study did not show a difference between the two types of needles with respect to the failure of initial PIVC insertion and the number of procedures.

<h4>Introduction</h4>Hybrid emergency room systems (HERSs) have shown promise for the management of severe trauma by reducing mortality. However, the effectiveness of HERSs in the treatment of acute ischemic stroke (AIS) remains unclear. This study aimed to evaluate the impact of HERSs on treatment duration and neurological outcomes in patients with AIS undergoing endovascular therapy.<h4>Materials and methods</h4>This single-center retrospective study included 83 patients with AIS who were directly transported to our emergency department and underwent endovascular treatment between June 2017 and December 2023. Patients were divided into the HERS and conventional groups based on the utilization of HERSs. The primary outcome was the proportion of patients achieving a favorable neurological outcome (modified Rankin Scale score 0-2) at 30 days. The secondary outcomes included door-to-puncture and door-to-recanalization times. Univariate analysis was performed using the Mann-Whitney U test for continuous variables and the chi-squared test or Fisher's exact test for categorical variables, as appropriate.<h4>Results</h4>Of the 83 eligible patients, 50 (60.2%) were assigned to the HERS group and 33 (39.8%) to the conventional group. The median door-to-puncture time was significantly shorter in the HERS group than in the conventional group (99.5 vs. 131 min; p = 0.001). Similarly, the median door-to-recanalization time was significantly shorter in the HERS group (162.5 vs. 201.5 min, p = 0.018). Favorable neurological outcomes were achieved in 16/50 (32.0%) patients in the HERS group and 6/33 (18.2%) in the conventional group. The HERS and conventional groups showed no significant difference in the proportion of patients achieving favorable neurological outcomes (p = 0.21).<h4>Conclusion</h4>Implementation of the HERS significantly reduced the door-to-puncture and door-to-recanalization times in patients with AIS undergoing endovascular therapy. Despite these reductions in treatment duration, no significant improvement in neurological outcomes was observed. Further research is required to optimize patient selection and treatment strategies to maximize the benefits of the HERS in AIS management.

Status epilepticus (SE) is potentially life-threatening, however, it is unclear which antiepileptic drugs (AEDs) should be used as second-line AEDs. We conducted a network meta-analysis (NMA) of randomized controlled trials (RCTs) comparing multiple second-line AEDs for SE to investigate the efficacy of AEDs. We searched MEDLINE, CENTRAL, ClinicalTrials.gov, and World Health Organization International Clinical Trials Platform Search Portal and included RCTs for patients aged ≥15 years with SE on December 31, 2023. We compared multiple second-line AEDs for SE including fosphenytoin (fPHT), lacosamide (LCM), levetiracetam (LEV), phenytoin (PHT), phenobarbital (PHB), and valproate (VPA). The primary and secondly outcomes were termination of seizures integrating the absence of seizure recurrence at 30 min and 60 min, and adverse events associated with AEDs, respectively, with expressing as relative risk (RR) with a 95% confidence interval (CI). We conducted a NMA using frequentist-based approach with multivariate random effects, and assessed the certainty based on the Grading of Recommendations, Assessment, Development, and Evaluations framework. Seven RCTs (n = 780) were included, and statistically significant difference was detected between VPA vs. PHB (RR, 0.67; 95% CI, 0.53-0.85; very low certainty), fPHT vs. PHB (RR, 0.66; 95% CI, 0.48-0.90; very low certainty), LCM vs. PHB (RR, 0.62; 95% CI, 0.41-0.93; very low certainty), and LEV vs. PHB (RR, 0.69; 95% CI, 0.51-0.94; very low certainty). Moreover, PHB was the highest in the ranking for termination of seizures. For adverse events, no significant reduction was observed owing to the selection of AEDs, although the ranking of PHB was the lowest. PHB may have been the most effective for seizure termination as second-line AEDs in adult patients with SE. However, the certainty of almost all comparisons was "very low", and careful interpretation is essential.

<h4>Objective</h4>The objective was to investigate whether early advanced airway management during the entire resuscitation period is associated with favorable neurological outcomes and survival in patients with out-of-hospital cardiac arrest (OHCA).<h4>Methods</h4>We performed a retrospective cohort study of patients with OHCA aged ≥18 years enrolled in OHCA registry in Japan who received advanced airway management during cardiac arrest between June 2014 and December 2020. To address resuscitation time bias, we performed risk set matching analyses in which patients who did and did not receive advanced airway management were matched at the same time point (min) using the time-dependent propensity score; further, we compared early (≤10 min) and late (>10 min) advanced airway management. The primary and secondary outcome measures were favorable neurological outcomes using Cerebral Performance Category scores and survival at 1 month after cardiac arrest.<h4>Results</h4>Of the 41,101 eligible patients, 21,446 patients received early advanced airway management. Thus, risk set matching was performed with a total of 42,866 patients. In the main analysis, early advanced airway management was significantly associated with favorable neurological outcomes (risk ratio [RR] 0.997, 95% confidence interval [CI] 0.995-0.999) and survival (RR 0.990, 95% CI 0.986-0.994) at 1 month after cardiac arrest. In the sensitivity analysis with early advanced airway management defined as ≤5 min and ≤20 min, the results were comparable.<h4>Conclusions</h4>Although early advanced airway management was statistically significant for improved neurological outcomes and survival at 1 month after cardiac arrest, the RR was very close to 1, indicating that the timing of advanced airway management has minimal impact on clinical outcomes, and decisions should be made based on the individual needs of the patient.

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.

<h4>Study objective</h4>To determine the association between early versus late advanced airway management and improved outcomes in pediatric out-of-hospital cardiac arrest.<h4>Methods</h4>We performed a retrospective cohort study using data from the out-of-hospital cardiac arrest registry in Japan. We included pediatric patients (<18 years) with out-of-hospital cardiac arrest who had received advanced airway management (tracheal intubation, supraglottic airway, and esophageal obturator). The main exposure was early (≤20 minutes) versus late (>20 minutes) advanced airway management. The primary and secondary outcome measurements were survival and favorable neurologic outcomes at 1 month, respectively. To address resuscitation time bias, we performed risk-set matching analyses using time-dependent propensity scores.<h4>Results</h4>Out of the 864 pediatric patients with both out-of-hospital cardiac arrest and advanced airway management over 67 months (2014 to 2019), we included 667 patients with adequate data (77%). Of these 667 patients, advanced airway management was early for 354 (53%) and late for 313 (47%) patients. In the risk-set matching analysis, the risk of both survival (risk ratio 0.98 for early versus late [95% confidence interval 0.95 to 1.02]) and favorable 1-month neurologic outcomes (risk ratio 0.99 [95% confidence interval 0.97 to 1.00]) was similar between early and late advanced airway management groups. In sensitivity analyses, with time to early advanced airway management defined as ≤10 minutes and ≤30 minutes, both outcomes were again similar.<h4>Conclusion</h4>In pediatric out-of-hospital cardiac arrest, the timing of advanced airway management may not affect patient outcomes, but randomized controlled trials are needed to address this question further.

<h4>Background</h4>Out-of-hospital cardiac arrest (OHCA) is a serious condition. The volume-outcome relationship and various post-cardiac arrest care elements are believed to be associated with improved neurological outcomes. Although previous studies have investigated the volume-outcome relationship, adjusting for post-cardiac arrest care, intra-class correlation for each institution, and other covariates may have been insufficient.<h4>Objective</h4>To investigate the volume-outcome relationships and favorable neurological outcomes among OHCA cases in each institution.<h4>Methods</h4>We conducted a prospective observational study of adult patients with non-traumatic OHCA using the OHCA registry in Japan. The primary outcome was 30-day favorable neurological outcomes, and the secondary outcome was 30-day survival. We set the cutoff values to trisect the number of patients as equally as possible and classified institutions into high-, middle-, and low-volume. Generalized estimating equations (GEE) were performed to adjust for covariates and within-hospital clustering.<h4>Results</h4>Among the 9909 registry patients, 7857 were included. These patients were transported to either low- (2679), middle- (2657), or high- (2521) volume institutions. The median number of eligible patients per institution in 19 months of study periods was 82 (range, 1-207), 252 (range, 210-353), and 463 (range, 390-701), respectively. After multivariable GEE using the low-volume institution as a reference, no significant difference in odds ratios and 95% confidence intervals were noted for 30-day favorable neurological outcomes for middle volume [1.22 (0.69-2.17)] and high volume [0.80 (0.47-1.37)] institutions. Moreover, there was no significant difference for 30-day survival for middle volume [1.02 (0.51-2.02)] and high volume [1.09 (0.53-2.23)] institutions.<h4>Conclusion</h4>The patient volume of each institution was not associated with 30-day favorable neurological outcomes. Although this result needs to be evaluated more comprehensively, there may be no need to set strict requirements for the type of institution when selecting a destination for OHCA cases.

<h4>Purpose</h4>We performed a network meta-analysis (NMA) of multiple tracheostomy timings using data from randomized control trials (RCTs) to investigate the impact on patient prognosis.<h4>Materials and methods</h4>We searched MEDLINE, CENTRAL, ClinicalTrials.gov, and World Health Organization International Clinical Trials Platform Search Portal for RCTs on mechanically ventilated patients aged ≥18 years on February 2, 2023. We classified the timing of tracheostomy into three groups based on the clinical importance and previous studies: ≤ 4 days, 5-12 days, and ≥ 13 days. The primary outcome was short-term mortality, defined as mortality at any reported time point up to hospital discharge.<h4>Results</h4>Eight RCTs were included. The results revealed no effect between ≤4 days vs. 5-12 days and 5-12 days vs. ≥ 13 days and a significant effect in ≤4 days vs. ≥ 13 days as follows: in ≤4 days vs. 5-12 days (RR, 0.79 [95% CI, 0.56-1.11]; very low certainty), ≤ 4 days vs. ≥ 13 days (RR, 0.67 [95% CI, 0.49-0.92]; very low certainty), and 5-12 days vs. ≥ 13 days (RR, 0.85 [95% CI, 0.59-1.24]; very low certainty).<h4>Conclusions</h4>Tracheostomy ≤4 days may result in lower short-term mortality than tracheostomy ≥13 days.

<h4>Aim</h4>The study aimed to determine the current status of face mask use, deep body temperature measurement, and active cooling in patients suffering from heat stroke and heat exhaustion in Japan.<h4>Methods</h4>This was a prospective, observational, multicenter study using data from the Heatstroke STUDY 2020-2021, a nationwide periodical registry of heat stroke and heat exhaustion patients. Based on the Bouchama heatstroke criteria, we classified the patients into two groups: severe and mild-to-moderate. We compared the outcomes between the two groups and reclassified them into two subgroups according to the severity of the illness, deep body temperature measurements, and face mask use. Cramer's V was used to determine the effect sizes for a comparison between groups.<h4>Results</h4>Almost all patients in this study were categorized as having degree III based on the Japanese Association for Acute Medicine heatstroke criteria (JAAM-HS). However, the severe group was significantly worse than the mild-to-moderate group in outcomes like in-hospital death and modified Rankin Scale scores, when discharged. Heat strokes had significantly higher rates of active cooling and lower mortality rates than heat stroke-like illnesses. Patients using face masks often use them during labor, sports, and other exertions, had less severe conditions, and were less likely to be young male individuals.<h4>Conclusions</h4>It is suggested that severe cases require a more detailed classification of degree III in the JAAM-HS criteria, and not measuring deep body temperature could have been a factor in the nonperformance of active cooling and worse outcomes.

Both coronavirus disease 2019 (COVID-19) and heat stroke have symptoms of fever or hyperthermia and the difficulty in distinguishing them could lead to a strain on emergency medical care. To mitigate the potential confusion that could arise from actions for preventing both COVID-19 spread and heat stroke, particularly in the context of record-breaking summer season temperatures, this work offers new knowledge and evidence that address concerns regarding indoor ventilation and indoor temperatures, mask wearing and heat stroke risk, and the isolation of older adults. Specifically, the current work is the second edition to the previously published guidance for handling heat stroke during the COVID-19 pandemic, prepared by the "Working group on heat stroke medical care during the COVID-19 epidemic," composed of members from four organizations in different medical and related fields. The group was established by the Japanese Association for Acute Medicine Heatstroke and Hypothermia Surveillance Committee. This second edition includes new knowledge, and conventional evidence gleaned from a primary selection of 60 articles from MEDLINE, one article from Cochrane, 13 articles from Ichushi, and a secondary/final selection of 56 articles. This work summarizes the contents that have been clarified in the prevention and treatment of infectious diseases and heat stroke to provide guidance for the prevention, diagnosis, and treatment of heat stroke during the COVID-19 pandemic.

<h4>Aim</h4>To investigate the effect of intra-aortic balloon pump (IABP) use after extracorporeal membrane oxygenation-assisted cardiopulmonary resuscitation (ECPR) on short-term neurological outcomes and survival in patients with out-of-hospital cardiac arrest (OHCA).<h4>Methods</h4>We retrospectively analysed data collected between June 2014 and December 2019 from the Japanese OHCA registry. Adult patients (aged ≥18 years) who underwent ECPR were included. We divided the patients into those who received IABP and those who did not receive IABP. The primary outcome was the 30-day favourable neurological outcomes in survived patients. The secondary outcome was the 30-day survival. We performed propensity score matching (PSM) to adjust for confounding factors after multiple imputations of missing data. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were estimated using logistic regression analysis after PSM to adjust for confounding factors after IABP initiation.<h4>Results</h4>Among 2,135 adult patients who underwent ECPR, 1,173 received IABP. In 842 matched patients, IABP use was associated with survival (aOR, 1.98; 95% CI, 1.39-2.83; p < 0.001). However, IABP use was not significantly associated with the 30-day neurologically favourable outcome in 190 survived patients (aOR, 1.22; 95% CI, 0.79-1.89; p = 0.36).<h4>Conclusion</h4>The use of IABP in patients with OHCA who underwent ECPR was associated with 30-day survival. Among survived patients, there was no significant association between IABP use and 30-day neurological outcome. A further well-designed prospective study is needed.

Peripheral intravascular catheters (PIVCs) are inserted in most patients admitted to the intensive care unit (ICU). Previous research has discussed various risk factors for phlebitis, which is one of the complications of PIVCs. However, previous studies have not investigated the risk factors based on the patient's severity of illness, such as the Acute Physiology and Chronic Health Evaluation (APACHE) II score. Different treatments can be used based on the relationship of risk factors to the illness severity to avoid phlebitis. Therefore, in this study, we investigate whether the risk factors for phlebitis vary depending on the APACHE II score. This study was a post hoc analysis of the AMOR-VENUS study involving 23 ICUs in Japan. We included patients with age ≥ 18 years and consecutive admissions to the ICU with PIVCs inserted during ICU admission. The primary outcome was phlebitis, and the objective was the identification of the risk factors evaluated by hazard ratio (HR) and 95% confidence interval (CI). The cut-off value of the APACHE II score was set as ≤15 (group 1), 16-25 (group 2), and ≥26 (group 3). Multivariable marginal Cox regression analysis was performed for each group using the presumed risk factors. A total of 1,251 patients and 3,267 PIVCs were analyzed. Multivariable marginal Cox regression analysis reveals that there were statistically significant differences among the following variables evaluated HR (95%CI): (i) in group 1, standardized drug administration measures (HR, 0.4 [0.17-0.9]; p = 0.03) and nicardipine administration (HR, 2.25 [1.35-3.75]; p < 0.01); (ii) in group 2, insertion in the upper arm using the forearm as a reference (HR, 0.41 [0.2-0.83]; p = 0.01), specified polyurethane catheter using polyurethane as a reference (HR, 0.56 [0.34-0.92]; p = 0.02), nicardipine (HR, 1.9 [1.16-3.12]; p = 0.01), and noradrenaline administration (HR, 3.0 [1.52-5.88]; p < 0.01); (iii) in group 3, noradrenaline administration (HR, 3.39 [1.14-10.1]; p = 0.03). We found that phlebitis risk factors varied according to illness severity. By considering these different risk factors, different treatments may be provided to avoid phlebitis based on the patient's severity of illness.

<h4>Introduction</h4>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).<h4>Materials and methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>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.

<h4>Background</h4>Out-of-hospital cardiac arrest (OHCA) with shockable rhythms, including ventricular fibrillation and pulseless ventricular tachycardia, is associated with better prognosis and neurological outcome than OHCA due to other rhythms. Antiarrhythmic drugs, including lidocaine and amiodarone, are often used for defibrillation. This study aimed to compare the effects of lidocaine and amiodarone on the prognosis and neurological outcome of patients with OHCA due to shockable rhythms in a real-world setting.<h4>Methods</h4>We conducted a retrospective observational study using a multicenter OHCA registry of 91 participating hospitals in Japan. We included adult patients with shockable rhythms, such as ventricular fibrillation and pulseless ventricular tachycardia, who were administered either lidocaine or amiodarone. The primary outcome was 30-day survival, and the secondary outcome was a good neurological outcome at 30 days. We compared the effects of lidocaine and amiodarone for patients with OHCA due to shockable rhythms for these outcomes using logistic regression analysis after propensity score matching (PSM).<h4>Results</h4>Of the 51,199 patients registered in the OHCA registry, 1970 patients were analyzed. In total, 105 patients (5.3%) were administered lidocaine, and 1865 (94.7%) were administered amiodarone. After performing PSM with amiodarone used as the reference, the odds ratios and 95% confidence intervals of lidocaine use for 30-day survival and 30-day good neurological outcome were 1.44 (0.58-3.61) and 1.77 (0.59-5.29), respectively.<h4>Conclusion</h4>The use of lidocaine and amiodarone for patients with OHCA due to shockable rhythms within a real-world setting showed no significant differences in short-term mortality or neurological outcome. There is no evidence that either amiodarone or lidocaine is superior in treatment; thus, either or both drugs could be administered.

<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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).

<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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).<h4>Conclusions</h4>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.

<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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).<h4>Conclusions</h4>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.

<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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).<h4>Conclusions</h4>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.

<h4>Background</h4>To investigate the impact of hyperoxia that developed immediately after extracorporeal membrane oxygenation (ECMO)-assisted cardiopulmonary resuscitation (ECPR) on patients' short-term neurological outcomes after out-of-hospital cardiac arrest (OHCA).<h4>Methods</h4>This study retrospectively analyzed data from the Japanese OHCA registry from June 2014 to December 2017. We analyzed adult patients (≥ 18 years) who had undergone ECPR. Eligible patients were divided into the following three groups based on their initial partial pressure of oxygen in arterial blood (PaO₂) levels after ECMO pump-on: normoxia group, PaO₂ ≤ 200 mm Hg; moderate hyperoxia group, 200 mm Hg < PaO₂ ≤ 400 mm Hg; and extreme hyperoxia group, PaO₂ > 400 mm Hg. The primary and secondary outcomes were 30-day favorable neurological outcomes. Logistic regression statistical analysis model of 30-day favorable neurological outcomes was performed after adjusting for multiple propensity scores calculated using pre-ECPR covariates and for confounding factors post-ECPR.<h4>Results</h4>Of the 34,754 patients with OHCA enrolled in the registry, 847 were included. The median PaO₂ level was 300 mm Hg (interquartile range: 148-427 mm Hg). Among the eligible patients, 277, 313, and 257 were categorized as normoxic, moderately hyperoxic, and extremely hyperoxic, respectively. Moderate hyperoxia was not significantly associated with 30-day neurologically favorable outcomes compared with normoxia as a reference (adjusted odds ratio, 0.86; 95% confidence interval: 0.55-1.35; p = 0.51). However, extreme hyperoxia was associated with less 30-day neurologically favorable outcomes when compared with normoxia (adjusted odds ratio, 0.48; 95% confidence interval: 0.29-0.82; p = 0.007).<h4>Conclusions</h4>For patients with OHCA who received ECPR, extreme hyperoxia (PaO₂ > 400 mm Hg) was associated with 30-day poor neurological outcomes. Avoidance of extreme hyperoxia may improve neurological outcomes in patients with OHCA treated with ECPR.

<h4>Background</h4>Phlebitis is an important complication occurring in patients with peripheral intravascular catheters (PIVCs). The risk factors for phlebitis in the intensive care unit (ICU) was examined.<h4>Methods</h4>A secondary analysis of a prospective multicenter cohort study was conducted, involving 23 ICUs in Japan-the AMOR-VENUS study. Consecutive patients aged ≥ 18 years admitted to the ICU with newly inserted PIVCs after ICU admission were enrolled. Characteristics of the ICU, patients, PIVCs, and the drugs administered via PIVCs were recorded. A marginal Cox regression model was used to identify the risk factors associated with phlebitis.<h4>Results</h4>A total of 2741 consecutive patients from 23 ICUs were reviewed for eligibility, resulting in 1359 patients and 3429 PIVCs being included in the analysis population. The median dwell time was 46.2 h (95% confidence interval [CI], 21.3-82.9). Phlebitis occurred in 9.1% (95% CI, 8.2-10.1%) of catheters (3.5 cases/100 catheter days). The multivariate analysis revealed that the only factors that increased the risk of developing phlebitis were drugs administered intravenously. This study included 26 drugs, and 4 were associated with increased phlebitis: nicardipine (HR, 1.85; 95% CI, 1.29-2.66), noradrenaline (HR, 2.42; 95% CI, 1.40-4.20), amiodarone (HR, 3.67; 95% CI, 1.75-7.71) and levetiracetam (HR, 5.65; 95% CI, 2.80-11.4). Alternatively, factors significantly associated with a reduced risk of phlebitis were: standardized drug administration measures in the ICU (HR, 0.35; 95% CI, 0.17-0.76), 30≤ BMI (HR, 0.43; 95% CI, 0.20-0.95), catheter inserted by a doctor as nurse reference (HR, 0.55; 95% CI, 0.32-0.94), and upper arm insertion site as forearm reference (HR, 0.52; 95% CI, 0.32-0.85). The nitroglycerin was associated with a reduced phlebitis risk (HR, 0.22; 95% CI, 0.05-0.92).<h4>Conclusion</h4>Various factors are involved in the development of phlebitis caused by PIVCs in critically ill patients, including institutional, patient, catheter, and drug-induced factors, indicating the need for appropriate device selection or models of care in the ICU.<h4>Trial registration</h4>UMIN-CTR, the Japanese clinical trial registry (registration number: UMIN000028019, July 1, 2017).

<h4>Introduction</h4>Sudden cardiac arrest causes numerous deaths worldwide. High-quality chest compressions are important for good neurological recovery. Arterial pressure is considered useful to monitor the quality of chest compressions by the American Heart Association. However, arterial pressure catheter might be inconvenient during resuscitation. Conversely, cerebral regional oxygen saturation (rSO₂) during resuscitation may be associated with a good neurological prognosis. Therefore, we aimed to evaluate the correlation between mean arterial pressure and rSO₂ during resuscitation to evaluate rSO₂ as an indicator of the quality of chest compressions.<h4>Materials and methods</h4>This study was a single-center, prospective, observational study. Patients with out-of-hospital cardiac arrest who were transported to a tertiary care emergency center in Japan between October 2014 and March 2015 were included. The primary outcome was the regression coefficient between mean arterial pressure (MAP) and rSO₂. MAP and rSO₂ were measured during resuscitation (at hospital arrival [0 min], 3, 6, 9, 12, and 15 min), and MAP was measured by using an arterial catheter inserted into the femoral artery. For analysis, we used the higher value of rSO₂ obtained from the left and right forehead of the patient measured using a near-infrared spectrometer. Regression coefficients were calculated using the generalized estimating equation with MAP and systolic arterial pressure as response variables and rSO₂ as an explanatory variable since MAP and rSO₂ were repeatedly measured in the same patient. Since the confounding factors between MAP or systolic arterial pressure and rSO₂ were not clear clinically or from previous studies, the generalized estimating equation was analyzed using a univariate analysis.<h4>Results</h4>In this study, 37 patients were analyzed. The rSO₂ and MAP during resuscitation from hospital arrival to 15 min later were expressed as follows: (median [interquartile range, IQR]): rSO₂, 29.5 (24.3-38.8)%, and MAP, 36.5 (26-46) mmHg. The regression coefficient (95% CI) of log-rSO₂ and log-MAP was 0.42 (0.03-0.81) (p = 0.035).<h4>Conclusion</h4>The values of rSO₂ and MAP showed a mild but statistically significant association. rSO₂ could be used to assess the quality of chest compressions during resuscitation as a non-invasive and simple method.

<h4>Background</h4>The 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).<h4>Methods</h4>This 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.<h4>Results</h4>We 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.<h4>Conclusion</h4>PIVC-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.<h4>Trial registration</h4>UMIN-CTR, the Japanese clinical trial registry (registration number: UMIN000028019 , July 1, 2017).