Association between intrarenal venous flow from Doppler ultrasonography and acute kidney injury in patients with sepsis in critical care: a prospective, exploratory observational study.

BACKGROUND: Intrarenal venous flow (IRVF) patterns assessed using Doppler renal ultrasonography are real-time bedside visualizations of renal vein hemodynamics. Although this technique has the potential to detect renal congestion during sepsis resuscitation, there have been few studies on this method. We aimed to examine the relationship between IRVF patterns, clinical parameters, and outcomes in critically ill adult patients with sepsis. We hypothesized that discontinuous IRVF was associated with elevated central venous pressure (CVP) and subsequent acute kidney injury (AKI) or death. METHODS: We conducted a prospective observational study in two tertiary-care hospitals, enrolling adult patients with sepsis who stayed in the intensive care unit for at least 24 h, had central venous catheters placed, and received invasive mechanical ventilation. Renal ultrasonography was performed at a single time point at the bedside after sepsis resuscitation, and IRVF patterns (discontinuous vs. continuous) were confirmed by a blinded assessor. The primary outcome was CVP obtained at the time of renal ultrasonography. We also repeatedly assessed a composite of Kidney Disease Improving Global Outcomes of Stage 3 AKI or death over the course of a week as a secondary outcome. The association of IRVF patterns with CVP was examined using Student's t-test (primary analysis) and that with composite outcomes was assessed using a generalized estimating equation analysis, to account for intra-individual correlations. A sample size of 32 was set in order to detect a 5-mmHg difference in CVP between IRVF patterns. RESULTS: Of the 38 patients who met the eligibility criteria, 22 (57.9%) showed discontinuous IRVF patterns that suggested blunted renal venous flow. IRVF patterns were not associated with CVP (discontinuous flow group: mean 9.24 cm H2O [standard deviation: 3.19], continuous flow group: 10.65 cm H2O [standard deviation: 2.53], p = 0.154). By contrast, the composite outcome incidence was significantly higher in the discontinuous IRVF pattern group (odds ratio: 9.67; 95% confidence interval: 2.13-44.03, p = 0.003). CONCLUSIONS: IRVF patterns were not associated with CVP but were associated with subsequent AKI in critically ill adult patients with sepsis. IRVF may be useful for capturing renal congestion at the bedside that is related to clinical patient outcomes.

Comparison of mainstream end tidal carbon dioxide on Y-piece side versus patient side of heat and moisture exchanger filters in critically ill adult patients: a prospective observational study.

The purpose of the study was to investigate the accuracy of mainstream EtCO2 measurements on the Y-piece (filtered) side of the heat and moisture exchanger filter (HMEF) in adult critically ill patients, compared to that on the patient (unfiltered) side of HMEF. We conducted a prospective observational method comparison study between July 2019 and December 2019. Critically ill adult patients receiving mechanical ventilation with HMEF were included. We performed a noninferiority comparison of the accuracy of EtCO2 measurements on the two sides of HMEF. The accuracy was measured by the absolute difference between PaCO2 and EtCO2. We set the non-inferiority margin at + 1 mmHg in accuracy difference between the two sides of HMEF. We also assessed the agreement between PaCO2 and EtCO2 using Bland-Altman analysis. Among thirty-seven patients, the accuracy difference was - 0.14 mmHg (two-sided 90% CI - 0.58 to 0.29), and the upper limit of the CI did not exceed the predefined margin of + 1 mmHg, establishing non-inferiority of EtCO2 on the Y-piece side of HMEF (P for non-inferiority < 0.001). In the Bland-Altman analyses, 95% limits of agreement between PaCO2 and EtCO2 were similar on both sides of HMEF (Y-piece side, - 8.67 to + 10.65 mmHg; patient side, - 8.93 to + 10.67 mmHg). The accuracy of mainstream EtCO2 measurements on the Y-piece side of HMEF was noninferior to that on the patient side in critically ill adults. Mechanically ventilated adult patients could be accurately monitored with mainstream EtCO2 on the Y-piece side of the HMEF unless their tidal volume was extremely low.

Association of Advanced Airway Insertion Timing and Outcomes After Out-of-Hospital Cardiac Arrest.

STUDY OBJECTIVE: While often prioritized in the resuscitation of patients with out-of-hospital cardiac arrest, the optimal timing of advanced airway insertion is unknown. We evaluated the association between the timing of advanced airway (laryngeal tube and endotracheal intubation) insertion attempt and survival to hospital discharge in adult out-of-hospital cardiac arrest. METHODS: We performed a secondary analysis of the Pragmatic Airway Resuscitation Trial (PART), a clinical trial comparing the effects of laryngeal tube and endotracheal intubation on outcomes after adult out-of-hospital cardiac arrest. We stratified the cohort by randomized airway strategy (laryngeal tube or endotracheal intubation). Within each subset, we defined a time-dependent propensity score using patients, arrest, and emergency medical services systems characteristics. Using the propensity score, we matched each patient receiving an initial attempt of laryngeal tube or endotracheal intubation with a patient at risk of receiving laryngeal tube or endotracheal intubation attempt within the same minute. RESULTS: Of 2,146 eligible patients, 1,091 (50.8%) and 1,055 (49.2%) were assigned to initial laryngeal tube and endotracheal intubation strategies, respectively. In the propensity score-matched cohort, timing of laryngeal tube insertion attempt was not associated with survival to hospital discharge: 0 to lesser than 5 minutes (risk ratio [RR]=1.35, 95% confidence interval [CI] 0.53 to 3.44); 5 to lesser than10 minutes (RR=1.07, 95% CI 0.66 to 1.73); 10 to lesser than 15 minutes (RR=1.17, 95% CI 0.60 to 2.31); or 15 to lesser than 20 minutes (RR=2.09, 95% CI 0.35 to 12.47) after advanced life support arrival. Timing of endotracheal intubation attempt was also not associated with survival: 0 to lesser than 5 minutes (RR=0.50, 95% CI 0.05 to 4.87); 5 to lesser than10 minutes (RR=1.20, 95% CI 0.51 to 2.81); 10 to lesser than15 minutes (RR=1.03, 95% CI 0.49 to 2.14); 15 to lesser than 20 minutes (RR=0.85, 95% CI 0.30 to 2.42); or more than/equal to 20 minutes (RR=0.71, 95% CI 0.07 to 7.14). CONCLUSION: In the PART, timing of advanced airway insertion attempt was not associated with survival to hospital discharge.

High versus low blood pressure targets for cardiac surgery while on cardiopulmonary bypass.

BACKGROUND: Cardiac surgery is performed worldwide. Most types of cardiac surgery are performed using cardiopulmonary bypass (CPB). Cardiac surgery performed with CPB is associated with morbidities. CPB needs an extracorporeal circulation that replaces the heart and lungs, and performs circulation, ventilation, and oxygenation of the blood. The lower limit of mean blood pressure to maintain blood flow to vital organs increases in people with chronic hypertension. Because people undergoing cardiac surgery commonly have chronic hypertension, we hypothesised that maintaining a relatively high blood pressure improves desirable outcomes among the people undergoing cardiac surgery with CPB. OBJECTIVES: To evaluate the benefits and harms of higher versus lower blood pressure targets during cardiac surgery with CPB. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search of databases was November 2021 and trials registries in January 2020. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing a higher blood pressure target (mean arterial pressure 65 mmHg or greater) with a lower blood pressure target (mean arterial pressure less than 65 mmHg) in adults undergoing cardiac surgery with CPB. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Primary outcomes were 1. acute kidney injury, 2. cognitive deterioration, and 3. all-cause mortality. Secondary outcomes were 4. quality of life, 5. acute ischaemic stroke, 6. haemorrhagic stroke, 7. length of hospital stay, 8. renal replacement therapy, 9. delirium, 10. perioperative transfusion of blood products, and 11. perioperative myocardial infarction. We used GRADE to assess certainty of evidence. MAIN RESULTS: We included three RCTs with 737 people compared a higher blood pressure target with a lower blood pressure target during cardiac surgery with CPB. A high blood pressure target may result in little to no difference in acute kidney injury (risk ratio (RR) 1.30, 95% confidence interval (CI) 0.81 to 2.08; I² = 72%; 2 studies, 487 participants; low-certainty evidence), cognitive deterioration (RR 0.82, 95% CI 0.45 to 1.50; I² = 0%; 2 studies, 389 participants; low-certainty evidence), and all-cause mortality (RR 1.33, 95% CI 0.30 to 5.90; I² = 49%; 3 studies, 737 participants; low-certainty evidence). No study reported haemorrhagic stroke. Although a high blood pressure target may increase the length of hospital stay slightly, we found no differences between a higher and a lower blood pressure target for the other secondary outcomes. We also identified one ongoing RCT which is comparing a higher versus a lower blood pressure target among the people who undergo cardiac surgery with CPB. AUTHORS' CONCLUSIONS: A high blood pressure target may result in little to no difference in patient outcomes including acute kidney injury and mortality. Given the wide CIs, further studies are needed to confirm the efficacy of a higher blood pressure target among those who undergo cardiac surgery with CPB.

Public-Access Defibrillation and Out-of-Hospital Cardiac Arrest in Japan.

BACKGROUND: Early defibrillation plays a key role in improving survival in patients with out-of-hospital cardiac arrests due to ventricular fibrillation (ventricular-fibrillation cardiac arrests), and the use of publicly accessible automated external defibrillators (AEDs) can help to reduce the time to defibrillation for such patients. However, the effect of dissemination of public-access AEDs for ventricular-fibrillation cardiac arrest at the population level has not been extensively investigated. METHODS: From a nationwide, prospective, population-based registry of patients with out-of-hospital cardiac arrest in Japan, we identified patients from 2005 through 2013 with bystander-witnessed ventricular-fibrillation arrests of presumed cardiac origin in whom resuscitation was attempted. The primary outcome measure was survival at 1 month with a favorable neurologic outcome (Cerebral Performance Category of 1 or 2, on a scale from 1 [good cerebral performance] to 5 [death or brain death]). The number of patients in whom survival with a favorable neurologic outcome was attributable to public-access defibrillation was estimated. RESULTS: Of 43,762 patients with bystander-witnessed ventricular-fibrillation arrests of cardiac origin, 4499 (10.3%) received public-access defibrillation. The percentage of patients receiving public-access defibrillation increased from 1.1% in 2005 to 16.5% in 2013 (P<0.001 for trend). The percentage of patients who were alive at 1 month with a favorable neurologic outcome was significantly higher with public-access defibrillation than without public-access defibrillation (38.5% vs. 18.2%; adjusted odds ratio after propensity-score matching, 1.99; 95% confidence interval, 1.80 to 2.19). The estimated number of survivors in whom survival with a favorable neurologic outcome was attributed to public-access defibrillation increased from 6 in 2005 to 201 in 2013 (P<0.001 for trend). CONCLUSIONS: In Japan, increased use of public-access defibrillation by bystanders was associated with an increase in the number of survivors with a favorable neurologic outcome after out-of-hospital ventricular-fibrillation cardiac arrest.

Characteristics and Outcomes of Bath-Related Out-of-Hospital Cardiac Arrest in Japan.

BACKGROUND: Characteristics and outcomes of emergency patients with bath-related sudden cardiac arrest in prehospital settings have not been sufficiently investigated. METHODS AND RESULTS: From a prospective population-based registry, which covers all out-of-hospital cardiac arrests (OHCAs) in Osaka City, a total of 642 patients who had a bath-related OHCA from 2012 to 2014 were enrolled in the analyses. The characteristics and outcomes of OHCA were compared by three locations of arrest: home baths (n=512), public baths (n=102), and baths in other public institutions (n=28). Overall, bath-related OHCAs mainly occurred in winter (December-February, 48.9%, 314/642). The proportion of OHCAs that were witnessed by bystanders was 6.4% (33/512) in home baths, 17.6% (18/102) in public baths, and 25.0% (7/28) in baths in other public institutions. The proportion of public-access automated external defibrillator pad application was 0.8% (4/512) in home baths, 6.9% (7/102) in public baths, and 50.0% (14/28) in baths in other public institutions. Only 1 survivor with a favorable neurologic outcome was observed in a home bath, whereas there were no patients who survived with favorable neurologic outcomes in public baths and baths in other public institutions. CONCLUSIONS: Bath-related OHCAs mainly occurred in winter, and the outcome of victims was exceedingly poor, irrespective of location of arrest. The establishment of preventive measures as well as earlier recognition of cardiac arrest by bystanders are needed. (Circ J 2016; 80: 1564-1570).

Early-phase cumulative hypotension duration and severe-stage progression in oliguric acute kidney injury with and without sepsis: an observational study.

BACKGROUND: Managing blood pressure in patients with acute kidney injury (AKI) could effectively prevent severe-stage progression. However, the effect of hypotension duration in the early phase of AKI remains poorly understood. This study investigated the association between early-phase cumulative duration of hypotension below threshold mean arterial pressure (MAP) and severe-stage progression of oliguric AKI in critically ill patients, and assessed the difference in association with presence of sepsis. METHODS: This was a single-center, observational study conducted in the ICU of a university hospital in Japan. We examined data from adults with oliguric AKI who were admitted to the ICU during 2010-2014 and stayed in the ICU for ≥24 h after diagnosis of stage-1 oliguric AKI defined in the Kidney Disease Improving Global Outcomes (KDIGO) guidelines. The primary outcome was the progression from stage-1 oliguric AKI to stage-3 oliguric AKI (progression to oligoanuria and use of renal replacement therapy) according to the KDIGO criteria. During the first 6 h after oliguric AKI, we analyzed the association between cumulative time the patient had below threshold MAP (65, 70, and 75 mm Hg) and progression to stage-3. RESULTS: Among 538 patients with oliguric AKI, progression to stage-3 increased as the time spent below any threshold MAP was elongated. In the multivariable analysis of all patients, longer hypotension time (3-6 h) showed significant association with stage-3 progression for the time spent below MAP of 65 mm Hg (adjusted odds ratio (OR) 3.73, 95% confidence interval (CI) 1.53-9.09, p = 0.004), but the association was attenuated for the threshold MAP of 70 mm Hg (adjusted OR 2.35, 95% CI 0.96-5.78, p = 0.063) and 75 mm Hg (adjusted OR 1.92, 95% CI 0.72-5.15, p = 0.200). Longer hypotension time with the thresholds of 65 and 70 mm Hg was significantly associated with the risk of stage-3 progression in patients without sepsis, whereas the association was weak and not significant in patients with sepsis. CONCLUSIONS: Even in a short time frame (6 h) after oliguric AKI diagnosis, early-phase cumulative hypotension duration was associated with progression to stage-3 oliguric AKI, especially in patients without sepsis.

Is Survival After Out-of-Hospital Cardiac Arrests Worse During Days of National Academic Meetings in Japan? A Population-Based Study.

BACKGROUND: Outcomes after out-of-hospital cardiac arrests (OHCAs) might be worse during academic meetings because many medical professionals attend them. METHODS: This nationwide population-based observation of all consecutively enrolled Japanese adult OHCA patients with resuscitation attempts from 2005 to 2012. The primary outcome was 1-month survival with a neurologically favorable outcome. Calendar days at three national meetings (Japanese Society of Intensive Care Medicine, Japanese Association for Acute Medicine, and Japanese Circulation Society) were obtained for each year during the study period, because medical professionals who belong to these academic societies play an important role in treating OHCA patients after hospital admission, and we identified two groups: the exposure group included OHCAs that occurred on meeting days, and the control group included OHCAs that occurred on the same days of the week 1 week before and after meetings. Multiple logistic regression analysis was used to adjust for confounding variables. RESULTS: A total of 20 143 OHCAs that occurred during meeting days and 38 860 OHCAs that occurred during non-meeting days were eligible for our analyses. The proportion of patients with favorable neurologic outcomes after whole arrests did not differ during meeting and non-meeting days (1.6% [324/20 143] vs 1.5% [596/38 855]; adjusted odds ratio 1.02; 95% confidence interval, 0.88-1.19). Regarding bystander-witnessed ventricular fibrillation arrests of cardiac origin, the proportion of patients with favorable neurologic outcomes also did not differ between the groups. CONCLUSIONS: In this population, there were no significant differences in outcomes after OHCAs that occurred during national meetings of professional organizations related to OHCA care and those that occurred during non-meeting days.

A detailed evaluation of the new acute kidney injury criteria by KDIGO in critically ill patients.

PURPOSE: Two previous classifications of acute kidney injury (AKI) have shown that AKI is associated with increased mortality. In 2012, Kidney Disease Improving Global Outcomes (KDIGO) created new AKI criteria by combining the two previous classifications. However, such combination might cause inconsistency among each definition in the criteria. We have investigated all the definitions in the new KDIGO criteria. METHODS: We retrospectively studied 767 adult patients whose stay in the ICU exceeded 24 h. The KDIGO criteria were applied to all patients to diagnose AKI. Hospital mortality of patients with AKI diagnosed by the ten definitions in the criteria was compared. RESULTS: AKI occurred in 51.9 % with the standard definition of KDIGO. By multivariable analysis, odds ratios were increased with AKI stage progression and AKI stage 3 was significantly associated with hospital mortality. Crude hospital mortality stratified by the ten definitions showed increasing trends with stage progression. Mortality of the three definitions in stage 1 was from 4.0 to 10.8 %. Stage 2 had two definitions and their mortality was 13.6 and 17.6 %. Stage 3 had five definitions and their mortality ranged from 27.6 to 55.6 %. CONCLUSION: AKI defined by the new KDIGO criteria was associated with increased hospital mortality. Although definitions in the KDIGO criteria seem to be appropriate because of the clear relationship between mortality and stage progression on the whole, several limitations may exist, especially in stage 3. Further research should be needed to clarify the validity of the KDIGO criteria and the detailed categories.

The lower limit of intensity to control uremia during continuous renal replacement therapy.

INTRODUCTION: The recommended lower limit of intensity during continuous renal replacement therapy (CRRT) is 20 or 25 mL/kg/h. However, limited information is available to support this threshold. We aimed to evaluate the impact of different intensities of CRRT on the clearance of creatinine and urea in critically ill patients with severe acute kidney injury (AKI). METHODS: This is a multicenter retrospective study conducted in 14 Japanese ICUs in 12 centers. All patients older than 18 years and treated with CRRT due to AKI were eligible. We evaluated the effect of CRRT intensity by two different definitions: daily intensity (the mean intensity over each 24-h period) and average intensity (the mean of daily intensity during the period while CRRT was performed). To study the effect of different CRRT intensity on clearance of urea and creatinine, all patients/daily observations were arbitrarily allocated to one of 4 groups based on the average intensity and daily intensity: <10, 10-15, 15-20, and >20 mL/kg/h. RESULTS: Total 316 patients were included and divided into the four groups according to average CRRT intensity. The groups comprised 64 (20.3%), 138 (43.7%), 68 (21.5%), and 46 patients (14.6%), respectively. Decreases in creatinine and urea increased as the average intensity increased over the first 7 days of CRRT. The relative changes of serum creatinine and urea levels remained close to 1 over the 7 days in the "<10" group. Total 1,101 daily observations were included and divided into the four groups according to daily CRRT intensity. The groups comprised 254 (23.1%), 470 (42.7%), 239 (21.7%), and 138 observations (12.5%), respectively. Creatinine and urea increased (negative daily change) only in the "<10" group and decreased with the increasing daily intensity in the other groups. CONCLUSIONS: The lower limit of delivered intensity to control uremia during CRRT was approximately between 10 and 15 mL/kg/h in our cohort. A prescribed intensity of approximately 15 mL/kg/h might be adequate to control uremia for patients with severe AKI in the ICU. However, considering the limitations due to the retrospective nature of this study, prospective studies are required to confirm our findings.

Sequence of Epinephrine and Advanced Airway Placement After Out-of-Hospital Cardiac Arrest.

Importance: While epinephrine and advanced airway management (AAM) (supraglottic airway insertion and endotracheal intubation) are commonly used for out-of-hospital cardiac arrest (OHCA), the optimal sequence of these interventions remains unclear. Objective: To evaluate the association of the sequence of epinephrine administration and AAM with patient outcomes after OHCA. Design, Setting, and Participants: This cohort study analyzed the nationwide, population-based OHCA registry in Japan and included adults (aged ≥18 years) with OHCA for whom emergency medical services personnel administered epinephrine and/or placed an advanced airway between January 1, 2014, and December 31, 2019. The data analysis was performed between October 1, 2022, and May 12, 2023. Exposure: The sequence of intravenous epinephrine administration and AAM. Main Outcomes and Measures: The primary outcome was 1-month survival. Secondary outcomes were 1-month survival with favorable functional status and prehospital return of spontaneous circulation. To control imbalances in measured patient demographics, cardiac arrest characteristics, and bystander and prehospital interventions, propensity scores and inverse probability of treatment weighting (IPTW) were performed for shockable and nonshockable initial rhythm subcohorts. Results: Of 259 237 eligible patients (median [IQR] age, 79 [69-86] years), 152 289 (58.7%) were male. A total of 21 592 patients (8.3%) had an initial shockable rhythm, and 237 645 (91.7%) had an initial nonshockable rhythm. Using IPTW, all covariates between the epinephrine-first and AAM-first groups were well balanced, with all standardized mean differences less than 0.100. After IPTW, the epinephrine-first group had a higher likelihood of 1-month survival for both shockable (odds ratio [OR], 1.19; 95% CI, 1.09-1.30) and nonshockable (OR, 1.28; 95% CI, 1.19-1.37) rhythms compared with the AAM-first group. For the secondary outcomes, the epinephrine-first group experienced an increased likelihood of favorable functional status and prehospital return of spontaneous circulation for both shockable and nonshockable rhythms compared with the AAM-first group. Conclusions and Relevance: These findings suggest that for patients with OHCA, administration of epinephrine before placement of an advanced airway may be the optimal treatment sequence for improved patient outcomes.

Survival After Intra-Arrest Transport vs On-Scene Cardiopulmonary Resuscitation in Children.

Importance: For pediatric out-of-hospital cardiac arrest (OHCA), emergency medical services (EMS) may elect to transport to the hospital during active cardiopulmonary resuscitation (CPR) (ie, intra-arrest transport) or to continue on-scene CPR for the entirety of the resuscitative effort. The comparative effectiveness of these strategies is unclear. Objective: To evaluate the association between intra-arrest transport compared with continued on-scene CPR and survival after pediatric OHCA, and to determine whether this association differs based on the timing of intra-arrest transport. Design, Setting, and Participants: This cohort study included pediatric patients aged younger than 18 years with EMS-treated OHCA between December 1, 2005 and June 30, 2015. Data were collected from the Resuscitation Outcomes Consortium Epidemiologic Registry, a prospective 10-site OHCA registry in the US and Canada. Data analysis was performed from May 2022 to February 2024. Exposures: Intra-arrest transport, defined as an initiation of transport prior to the return of spontaneous circulation, and the interval between EMS arrival and intra-arrest transport. Main Outcomes and Measures: The primary outcome was survival to hospital discharge. Patients who underwent intra-arrest transport at any given minute after EMS arrival were compared with patients who were at risk of undergoing intra-arrest transport within the same minute using time-dependent propensity scores calculated from patient demographics, arrest characteristics, and EMS interventions. We examined subgroups based on age (<1 year vs ≥1 year). Results: Of 2854 eligible pediatric patients (median [IQR] age, 1 [0-9] years); 1691 males [59.3%]) who experienced OHCA between December 2005 and June 2015, 1892 children (66.3%) were treated with intra-arrest transport and 962 children (33.7%) received continued on-scene CPR. The median (IQR) time between EMS arrival and intra-arrest transport was 15 (9-22) minutes. In the propensity score-matched cohort (3680 matched cases), there was no significant difference in survival to hospital discharge between the intra-arrest transport group and the continued on-scene CPR group (87 of 1840 patients [4.7%] vs 95 of 1840 patients [5.2%]; risk ratio [RR], 0.81 [95% CI, 0.59-1.10]). Survival to hospital discharge was not modified by the timing of intra-arrest transport (P value for the interaction between intra-arrest transport and time to matching = .10). Among patients aged younger than 1 year, intra-arrest transport was associated with lower survival to hospital discharge (RR, 0.52; 95% CI, 0.33-0.83) but there was no association for children aged 1 year or older (RR, 1.22; 95% CI, 0.77-1.93). Conclusions and Relevance: In this cohort study of a North American OHCA registry, intra-arrest transport compared with continued on-scene CPR was not associated with survival to hospital discharge among children with OHCA. However, intra-arrest transport was associated with a lower likelihood of survival to hospital discharge among children aged younger than 1 year.

Validity of low-intensity continuous renal replacement therapy*.

OBJECTIVE: To study the hospital mortality of patients with severe acute kidney injury treated with low-intensity continuous renal replacement therapy. DESIGN: Multicenter retrospective observational study (Japanese Society for Physicians and Trainees in Intensive Care), combined with previously conducted multinational prospective observational study (Beginning and Ending Supportive Therapy). SETTING: Fourteen Japanese ICUs in 12 tertiary hospitals (Japanese Society for Physicians and Trainees in Intensive Care) and 54 ICUs in 23 countries (Beginning and Ending Supportive Therapy). PATIENTS: Consecutive adult patients with severe acute kidney injury requiring continuous renal replacement therapy admitted to the participating ICUs in 2010 (Japanese Society for Physicians and Trainees in Intensive Care, n = 343) and 2001 (Beginning and Ending Supportive Therapy Beginning and Ending Supportive Therapy, n = 1,006). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patient characteristics, variables at continuous renal replacement therapy initiation, continuous renal replacement therapy settings, and outcomes (ICU and hospital mortality and renal replacement therapy requirement at hospital discharge) were collected. Continuous renal replacement therapy intensity was arbitrarily classified into seven subclasses: less than 10, 10-15, 15-20, 20-25, 25-30, 30-35, and more than 35 mL/kg/hr. Multivariable logistic regression analysis was conducted to investigate risk factors for hospital mortality. The continuous renal replacement therapy dose in the Japanese Society for Physicians and Trainees in Intensive Care database was less than half of the Beginning and Ending Supportive Therapy database (800 mL/hr vs 2,000 mL/hr, p < 0.001). Even after adjusting for the body weight and dilution factor, continuous renal replacement therapy intensity was statistically different (14.3 mL/kg/hr vs 20.4 mL/kg/hr, p < 0.001). Patients in the Japanese Society for Physicians and Trainees in Intensive Care database had a lower ICU mortality (46.1% vs 55.3%, p = 0.003) and hospital mortality (58.6% vs 64.2%, p = 0.070) compared with patients in the Beginning and Ending Supportive Therapy database. In multivariable regression analysis after combining the two databases, no continuous renal replacement therapy intensity subclasses were found to be statistically different from the reference intensity (20-25 mL/kg/hr). Several sensitivity analyses (patients with sepsis, patients from Western countries in the Beginning and Ending Supportive Therapy database) confirmed no intensity-outcome relationship. CONCLUSIONS: Continuous renal replacement therapy at a mean intensity of 14.3 mL/kg/hr did not have worse outcome compared with 20-25 mL/kg/hr of continuous renal replacement therapy, currently considered the standard intensity. However, our study is insufficient to support the use of low-intensity continuous renal replacement therapy, and more studies are needed to confirm our findings.

Evaluation of Use of Epinephrine and Time to First Dose and Outcomes in Pediatric Patients With Out-of-Hospital Cardiac Arrest.

Importance: While epinephrine has been widely used in prehospital resuscitation for pediatric patients with out-of-hospital cardiac arrest (OHCA), the benefit and optimal timing of epinephrine administration have not been fully investigated. Objectives: To evaluate the association between epinephrine administration and patient outcomes and to ascertain whether the timing of epinephrine administration was associated with patient outcomes after pediatric OHCA. Design, Setting, and Participants: This cohort study included pediatric patients (<18 years) with OHCA treated by emergency medical services (EMS) from April 2011 to June 2015. Eligible patients were identified from the Resuscitation Outcomes Consortium Epidemiologic Registry, a prospective OHCA registry at 10 sites in the US and Canada. Data analysis was performed from May 2021 to January 2023. Exposures: The main exposures were prehospital intravenous or intraosseous epinephrine administration and the interval between arrival of an advanced life support (ALS)-capable EMS clinician (ALS arrival) and the first administration of epinephrine. Main Outcomes and Measures: The primary outcome was survival to hospital discharge. Patients who received epinephrine at any given minute after ALS arrival were matched with patients who were at risk of receiving epinephrine within the same minute using time-dependent propensity scores calculated from patient demographics, arrest characteristics, and EMS interventions. Results: Of 1032 eligible individuals (median [IQR] age, 1 [0-10] years), 625 (60.6%) were male. 765 patients (74.1%) received epinephrine and 267 (25.9%) did not. The median (IQR) time interval between ALS arrival and epinephrine administration was 9 (6.2-12.1) minutes. In the propensity score-matched cohort (1432 patients), survival to hospital discharge was higher in the epinephrine group compared with the at-risk group (epinephrine: 45 of 716 [6.3%] vs at-risk: 29 of 716 [4.1%]; risk ratio, 2.09; 95% CI, 1.29-3.40). The timing of epinephrine administration was also not associated with survival to hospital discharge after ALS arrival (P for the interaction between epinephrine administration and time to matching = .34). Conclusions and Relevance: In this study of pediatric patients with OHCA in the US and Canada, epinephrine administration was associated with survival to hospital discharge, while timing of the administration was not associated with survival.

Intravenous Tranexamic Acid in Percutaneous Kidney Biopsy: A Randomized Controlled Trial.

BACKGROUND: Tranexamic acid is frequently reported to reduce bleeding-related complications in major surgery and trauma. We aimed to investigate whether tranexamic acid reduced hematoma size after percutaneous kidney biopsy. METHODS: We conducted a double-blind, parallel three-group, randomized placebo-controlled trial at a teaching hospital in Japan between January 2016 and July 2018. Adult patients with clinical indication for ultrasound-guided percutaneous biopsy of a native kidney were included. Participants were randomly assigned into three groups: high-dose tranexamic acid (1,000 mg in total), low-dose tranexamic acid (500 mg in total), or placebo (counterpart saline). Intervention drugs were intravenously administered twice, as a bolus just before the biopsy and as a continuous infusion initiated just after the biopsy. Primary outcome was post-biopsy perirenal hematoma size as measured by ultrasound on the morning after the biopsy. RESULTS: We assessed 90 adult patients for study eligibility, of whom 56 were randomly allocated into the three groups: 20 for high-dose tranexamic acid, 19 for low-dose tranexamic acid, and 17 for placebo. The median size of perirenal hematoma was 200 mm2 (interquartile range, 21-650) in the high-dose tranexamic acid group, 52 mm2 (0-139) in the low-dose tranexamic acid group, and 0 mm2 (0-339) in the placebo group (p = 0.048 for high-dose tranexamic acid vs. placebo). CONCLUSION: In this trial, the median size of post-kidney biopsy hematoma was unexpectedly larger in the high-dose tranexamic acid group than in the placebo group. Although our results do not support the routine use of tranexamic acid in percutaneous kidney biopsy at present, further studies are needed to confirm the results.

Contamination of Blood Cultures From Arterial Catheters and Peripheral Venipuncture in Critically Ill Patients: A Prospective Multicenter Diagnostic Study.

BACKGROUND: Collecting blood cultures from indwelling arterial catheters is an attractive option in critically ill adult patients when peripheral venipuncture is difficult. However, whether the contamination proportion of blood cultures from arterial catheters is acceptable compared with that from venipuncture is inconclusive. RESEARCH QUESTION: Is contamination of blood cultures from arterial catheters noninferior to that from venipuncture in critically ill adult patients with suspected bloodstream infection? STUDY DESIGN AND METHODS: In this multicenter prospective diagnostic study conducted at five hospitals, we enrolled episodes of paired blood culture collection, each set consisting of blood drawn from an arterial catheter and another by venipuncture, were obtained from critically ill adult patients with cilinical indication. The primary measure was the proportion of contamination, defined as the number of false-positive results relative to the total number of procedures done. The reference standard for true bloodstream infection was blinded assessment by infectious disease specialists. We examined the noninferiority hypothesis that the contamination proportion of blood cultures from arterial catheters did not exceed that from venipuncture by 2.0%. RESULTS: Of 1,655 episodes of blood culture from December 2018 to July 2021, 590 paired blood culture episodes were enrolled, and 41 of the 590 episodes (6.9%) produced a true bloodstream infection. In blood cultures from arterial catheters, 33 of 590 (6.0%) were positive, and two of 590 (0.3%) were contaminated; in venipuncture, 36 of 590 (6.1%) were positive, and four of 590 (0.7%) were contaminated. The estimated difference in contamination proportion (arterial catheter - venipuncture) was -0.3% (upper limit of one-sided 95% CI, +0.3%). The upper limit of the 95% CI did not exceed the predefined margin of +2.0%, establishing noninferiority (P for noninferiority < .001). INTERPRETATION: Obtaining blood cultures from arterial catheters is an acceptable alternative to venipuncture in critically ill patients. CLINICAL TRIAL REGISTRATION: University Hospital Medical Information Network Center (UMIN-CTR); No.: UMIN000035392; URL: https://center6.umin.ac.jp/.

Association between blood urea nitrogen to creatinine ratio and neurologically favourable outcomes in out-of-hospital cardiac arrest in adults: A multicentre cohort study.

BACKGROUND: We aimed to investigate the association between blood urea nitrogen to creatinine ratio (BCR) and survival with favourable neurological outcomes in patients with out-of-hospital cardiac arrest (OHCA). METHODS: This prospective, multicentre, observational study conducted in Osaka, Japan enrolled consecutive OHCA patients transported to 16 participating institutions from 2012 through 2019. We included adult patients with non-traumatic OHCA who achieved a return of spontaneous circulation and whose blood urea nitrogen and creatinine levels on hospital arrival were available. Based on BCR values, they were divided into: 'low BCR' (BCR <10), 'normal BCR' (10 ≤ BCR < 20), 'high BCR' (20 ≤ BCR < 30), and 'very high BCR' (BCR ≥ 30). We evaluated the association between BCR values and neurologically favourable outcomes, defined as cerebral performance category score of 1 or 2 at one month after OHCA. RESULTS: Among 4415 eligible patients, the 'normal BCR' group had the highest favourable neurological outcome [19.4 % (461/2372)], followed by 'high BCR' [12.5 % (141/1127)], 'low BCR' [11.2 % (50/445)], and 'very high BCR' groups [6.6 % (31/471)]. In the multivariable analysis, adjusted odds ratios for 'low BCR', 'high BCR', and 'very high BCR' compared with 'normal BCR' for favourable neurological outcomes were 0.58 [95 % confidence interval (CI 0.37-0.91)], 0.70 (95 % CI 0.49-0.99), and 0.40 (95 % CI 0.21-0.76), respectively. Cubic spline analysis indicated that the association between BCR and favourable neurological outcomes was non-linear (p for non-linearity = 0.003). In subgroup analysis, there was an interaction between the aetiology of arrest and BCR in neurological outcome (p for interaction <0.001); favourable neurological outcome of cardiogenic OHCA patients was lower when the BCR was higher or lower, but not in non-cardiogenic OHCA patients. CONCLUSIONS: Both higher and lower BCR were associated with poor neurological outcomes compared to normal BCR, especially in cardiogenic OHCA patients.

Outcomes associated with intra-arrest hyperoxaemia in out-of-hospital cardiac arrest: A registry-based cohort study.

BACKGROUND: An association between post-arrest hyperoxaemia and worse outcomes has been reported for out-of-hospital cardiac arrest (OHCA) patients, but little is known about the relationship between intra-arrest hyperoxaemia and clinically relevant outcomes. This study aimed to investigate the association between intra-arrest hyperoxaemia and outcomes for OHCA patients. METHODS: This was an observational study using a registry database of OHCA cases that occurred between 2014 and 2017 in Japan. We included adult, non-traumatic OHCA patients who were in cardiac arrest at the time of hospital arrival and for whom partial pressure of arterial oxygen (PaO2) levels was measured during resuscitation. Main exposure was intra-arrest PaO2 level, which was divided into three categories: hypoxaemia, PaO2 < 60 mmHg; normoxaemia, 60-300; or hyperoxaemia, ≥300. Primary outcome was favourable functional survival at one month or at hospital discharge. Multivariable logistic regression was performed to adjust for clinically relevant variables. RESULTS: Among 16,013 patients who met the eligibility criteria, the proportion of favourable functional survival increased as the PaO2 categories became higher: 0.5 % (57/11,484) in hypoxaemia, 1.1 % (48/4243) in normoxaemia, and 5.2 % (15/286) in hyperoxaemia (p-value for trend < 0.001). Higher PaO2 categories were associated with favourable functional survival and the adjusted odds ratios increased as the PaO2 categories became higher: 2.09 (95 % CI: 1.39-3.14) in normoxaemia and 5.04 (95 % CI: 2.62-9.70) in hyperoxaemia when compared to hypoxaemia as a reference. CONCLUSION: In this observational study of adult OHCA patients, intra-arrest normoxaemia and hyperoxaemia were associated with better functional survival, compared to hypoxaemia.

Epinephrine administration for adult out-of-hospital cardiac arrest patients with refractory shockable rhythm: time-dependent propensity score-sequential matching analysis from a nationwide population-based registry.

AIMS: Little is known about the effect of prehospital epinephrine administration in out-of-hospital cardiac arrest (OHCA) patients with refractory shockable rhythm, for whom initial defibrillation was unsuccessful. METHODS AND RESULTS: This study using Japanese nationwide population-based registry included all adult OHCA patients aged ≥18 years with refractory shockable rhythm between January 2014 and December 2017. Patients with or without epinephrine during cardiac arrest were sequentially matched using a risk set matching based on the time-dependent propensity scores within the same minute. The primary outcome was 1-month survival. The secondary outcomes included 1-month survival with favourable neurological outcome (cerebral performance category scale: 1 or 2) and prehospital return of spontaneous circulation (ROSC). Of the 499 944 patients registered in the database during the study period, 22 877 were included. Among them, 8467 (37.0%) received epinephrine. After time-dependent propensity score-sequential matching, 16 798 patients were included in the matched cohort. In the matched cohort, positive associations were observed between epinephrine and 1-month survival [epinephrine: 17.3% (1454/8399) vs. no epinephrine: 14.6% (1224/8399); RR 1.22 (95% confidence interval, CI: 1.13-1.32)] and prehospital ROSC [epinephrine: 22.2% (1868/8399) vs. no epinephrine: 10.7% (900/8399); RR 2.07 (95% CI: 1.91-2.25)]. No significant positive association was observed between epinephrine and favourable neurological outcome [epinephrine: 7.8% (654/8399) vs. no epinephrine: 7.1% (611/8399); RR 1.13 (95% CI 0.998-1.27)]. CONCLUSION: Using the nationwide population-based registry with time-dependent propensity score-sequential matching analysis, prehospital epinephrine administration in adult OHCA patients with refractory shockable rhythm was positively associated with 1-month survival and prehospital ROSC.

No Association of Early Postoperative Heart Rate With Outcomes After Coronary Artery Bypass Grafting.

BACKGROUND: Elevated perioperative heart rate potentially causes perioperative myocardial injury because of imbalance in oxygen supply and demand. However, large multicenter studies evaluating early postoperative heart rate and major adverse cardiac and cerebrovascular events (MACCEs) are lacking. OBJECTIVE: To assess the associations of 4 postoperative heart rate assessment methods with in-hospital MACCEs after elective coronary artery bypass grafting (CABG). METHODS: Using data from the eICU Collaborative Research Database in the United States from 2014 to 2015, the study evaluated postoperative heart rate measured during hospitalization within 24 hours after intensive care unit admission. Four heart rate assessment methods were evaluated: maximum heart rate, duration above heart rate 100/min, area above heart rate 100/min, and time-weighted average heart rate. The outcome was in-hospital MACCEs, defined as a composite of in-hospital death, myocardial infarction, angina, arrhythmia, heart failure, stroke, cardiac arrest, or repeat revascularization. RESULTS: Among 2585 patients, the crude rate of in-hospital MACCEs was 6.2%. In multivariable logistic regression analysis, the adjusted odds ratios (95% CI) for in-hospital MAC-CEs assessed by maximum heart rate in each heart rate category (beats per minute: >100-110, >110-120, >120-130, and >130) were 1.43 (0.95-2.15), 0.98 (0.56-1.64), 1.47 (0.76-2.69), and 1.71 (0.80-3.35), respectively. Similarly, none of the other 3 methods were associated with MACCEs. CONCLUSIONS: More research is needed to assess the usefulness of heart rate measurement in patients after CABG.