Hideto Yasuda

Who may not benefit from continuous renal replacement therapy in acute kidney injury

This study aimed to identify factors that may predict early kidney recovery (less than 48 hours) or early death (within 48 hours) after initiating continuous renal replacement therapy (CRRT) in acute kidney injury (AKI) patients. This is a multicenter retrospective observational study of 14 Japanese Intensive care units (ICUs) in 12 tertiary hospitals. Consecutive adult patients with severe AKI requiring CRRT admitted to the participating ICUs in 2010 (n = 343) were included. Patient characteristics, variables at CRRT initiation, settings, and outcomes were collected. Patients were grouped into early kidney recovery group (CRRT discontinuation within 48 hours after initiation, n = 52), early death group (death within 48 hours after CRRT initiation, n = 52), and the rest as the control group (n = 239). The mean duration of CRRT in the early kidney recovery group and early death group was 1.3 and 0.9 days, respectively. In multivariable regression analysis, in comparison with the control group, urine output (mL/h) (odds ratio [OR]: 1.02, 95% confidence interval [CI]: 1.01–1.03), duration between ICU admission to CRRT initiation (days) (OR: 0.65, 95% CI: 0.43–0.87), and the sepsis‐related organ failure assessment score (OR: 0.87, 95% CI; 0.78–0.96) were related to early kidney recovery. Serum lactate (mmol/L) (OR: 1.19, 95% CI: 1.11–1.28), albumin (g/dL) (OR: 0.52, 95% CI: 0.28–0.92), vasopressor use (OR: 3.68, 95% CI: 1.37–12.16), and neurological disease (OR: 9.64, 96% CI: 1.22–92.95) were related to early death. Identifying AKI patients who do not benefit from CRRT and differentiating such patients from the study cohort may allow previous and future studies to effectively evaluate the indication and role of CRRT.

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.

Sepsis may not be a risk factor for mortality in patients with acute kidney injury treated with continuous renal replacement therapy

PURPOSE We aimed to study the clinical characteristics, courses, and outcomes of critically ill patients with septic acute kidney injury (AKI) treated with continuous renal replacement therapy (CRRT) in comparison with nonseptic AKI treated with CRRT. METHODS This is a multicenter retrospective observational study conducted in 14 Japanese intensive care units in 2010. All adult patients with severe AKI treated with CRRT were eligible (n = 343), and information on patient characteristics, variables at CRRT initiation, CRRT settings, and outcomes was collected. Patients were categorized into the septic AKI group and the nonseptic AKI group according to contributing factors to AKI. RESULTS Approximately half of study patients (48.7%) had sepsis/septic shock as a contributing factor to AKI, and patients with septic AKI treated with CRRT had more serious clinical conditions than patients with nonseptic AKI. However, no significant difference was observed in intensive care unit mortality (48.5% vs 43.8%; P = .44) and hospital mortality (61.1% vs 56.3%; P = .42) between patients with septic and nonseptic AKIs treated with CRRT. Furthermore, sepsis was associated with lower hospital mortality (odds ratio, 0.378; P = .012) in multivariable regression analysis. CONCLUSION Sepsis may not be a risk factor for mortality in patients with AKI whose condition has become severe enough to require CRRT.

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

IntroductionThe 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).MethodsThis 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.ResultsTotal 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.ConclusionsThe 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.

External Validation for Acute Kidney Injury Severity Scores: A Multicenter Retrospective Study in 14 Japanese ICUs.

Background/Aims: Acute kidney injury (AKI) is associated with high mortality. Multiple AKI severity scores have been derived to predict patient outcome. We externally validated new AKI severity scores using the Japanese Society for Physicians and Trainees in Intensive Care (JSEPTIC) database. Methods: New AKI severity scores published in the 21st century (Mehta, Stuivenberg Hospital Acute Renal Failure (SHARF) II, Program to Improve Care in Acute Renal Disease (PICARD), Vellore and Demirjian), Liano, Simplified Acute Physiology Score (SAPS) II and lactate were compared using the JSEPTIC database that collected retrospectively 343 patients with AKI who required continuous renal replacement therapy (CRRT) in 14 intensive care units. Accuracy of the severity scores was assessed by the area under the receiver-operator characteristic curve (AUROC, discrimination) and Hosmer-Lemeshow test (H-L test, calibration). Results: The median age was 69 years and 65.8% were male. The median SAPS II score was 53 and the hospital mortality was 58.6%. The AUROC curves revealed low discrimination ability of the new AKI severity scores (Mehta 0.65, SHARF II 0.64, PICARD 0.64, Vellore 0.64, Demirjian 0.69), similar to Liano 0.67, SAPS II 0.67 and lactate 0.64. The H-L test also demonstrated that all assessed scores except for Liano had significantly low calibration ability. Conclusions: Using a multicenter database of AKI patients requiring CRRT, this study externally validated new AKI severity scores. While the Demirjians score and Lianos score showed a better performance, further research will be required to confirm these findings.

The anticoagulant treatment for sepsis induced disseminated intravascular coagulation; network meta-analysis

INTRODUCTION The benefits and harm caused by anticoagulant treatments for sepsis induced disseminated intravascular coagulation (DIC) remain unclear. Therefore, we performed a network meta-analysis to assess the effect of available anticoagulant treatments on patient mortality, DIC resolution and the incidence of bleeding complication in patients with septic DIC. MATERIALS AND METHODS We considered all studies from four recent systematic reviews and searched the PubMed, MEDLINE, and Cochrane databases for other studies that investigated anticoagulant treatment for septic DIC using antithrombin, thrombomodulin, heparin, or protease inhibitors in adult critically ill patients. These four anticoagulants and placebo were compared. The primary outcome in this study was patient mortality, and the secondary outcomes were the DIC resolution rate and incidence of bleeding complications. RESULTS The network meta-analysis included 1340 patients from nine studies. There were no significant differences in the risks of mortality and bleeding complications among all direct comparisons and the network meta-analysis. Using a placebo was associated with a significantly lower rate of DIC resolution, compared to antithrombin in the direct comparison (odds ratio [OR]: 0.20, 95% credible interval [95% CrI]: 0.046-0.81) and in the network meta-analysis (OR: 0.20, 95% CrI: 0.043-0.84). CONCLUSIONS Our study revealed no significant differences in the risks for mortality and bleeding complications when a placebo and all four anticoagulants were compared in septic DIC patients. The results also indicated that antithrombin was associated with a five-fold higher likelihood of DIC resolution, compared to placebo.

Oxygen management in mechanically ventilated patients: A multicenter prospective observational study

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