Toshifumi Asada

Association of Heart Rate with N-terminal Pro-b-type Natriuretic Peptide in Septic Patients: A Prospective Observational Cohort Study

ABSTRACT Background: Excessive sympathetic stress has multiple adverse effects during critical illness including sepsis. Recent studies showed that heart rate control had a significant effect on reducing mortality in septic shock patients. Furthermore, elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels in septic patients were reportedly associated with adverse outcome. However, no study has evaluated the relationship between hemodynamic profiles of septic patients and the circulating cardiac biomarker. Our objective was to determine whether hemodynamic profiles, specifically tachycardia and new-onset atrial fibrillation (AF), were associated with NT-proBNP elevation in septic patients. Methods: We consecutively enrolled patients admitted to our intensive care unit (ICU). NT-proBNP levels, heart rate, and rhythm at ICU admission were measured, and all clinical and laboratory data were prospectively collected. Tachycardia was defined as a heart rate of above 100 bpm. Results: Ninety-five patients out of 267 patients (35.6%) were diagnosed as sepsis. Of these septic patients, 47 presented with tachycardia and 6 developed new-onset AF. Multivariate Cox regression analysis revealed that tachycardia was an independent predictor of 28-day overall survival in septic patients (hazard ratio, 4.22; 95% confidence interval, 1.10–27.72; P < 0.05), but not in nonseptic patients. Multivariate linear regression analysis demonstrated that the presence of tachycardia was an independent determinant of NT-proBNP elevation (P < 0.05) in septic patients, but not in nonseptic patients. Conclusions: Tachycardia was significantly and independently associated with NT-proBNP elevation and lower survival rate in septic patients, although no association was observed in nonseptic patients. Increased NT-proBNP in sepsis with tachycardia might predict poor outcomes in ICU.

Association of Urinary Neutrophil Gelatinase-Associated Lipocalin With Long-Term Renal Outcomes in ICU Survivors: A Retrospective Observational Cohort Study.

Background: Epidemiological studies recently suggested that acute kidney injury (AKI) in intensive care units (ICUs) increases the risk of chronic kidney disease development and progression. However, whether any AKI biomarker can predict long-term renal outcomes in ICU survivors remains unclear. This study was undertaken to elucidate the role of urinary biomarkers for long-term renal outcome prediction after ICU discharge. Methods: This retrospective observational study examined 495 adult patients who had been admitted to the ICU of the University of Tokyo Hospital. Major adverse kidney events (MAKE): death, incident end-stage renal disease (ESRD), and halving of estimated glomerular filtration rate (eGFR), at hospital discharge and long-term renal outcomes of 30% reduction of eGFR or incident ESRD were evaluated. Results: Among all the enrolled 495 patients, 393 patients were discharged from the hospital without MAKE. Data of eGFR up to two years after ICU discharge were available for 173 patients; 63 patients (36.4%) were positive for long-term renal outcomes. Step-wise logistic regression analysis demonstrated that male sex and urinary neutrophil gelatinase-associated lipocalin (NGAL) measured at ICU admission showed significant associations with long-term renal outcomes. Receiver operating characteristic curve analysis showed the area under the curve of 0.66 (95% confidence interval 0.57–0.74) for prediction of long-term renal outcome by urinary NGAL. Conclusion: Urinary NGAL measured at ICU admission was significantly associated with long-term renal outcomes after hospital discharge in MAKE-free ICU survivors. Urinary NGAL measurements at ICU might be useful to identify a high risk population of kidney disease progression after intensive care.

Organ System Network Disruption in Nonsurvivors of Critically Ill Patients

Objectives:As interactions of each organ system have been conceptually known to play an important role during life-threatening conditions, we quantitatively evaluated the organ system interactions in critically ill patients and examined the difference in the organ system network structure between the survivors and the nonsurvivors. Design:Prospective observational study. Settings:An ICU of a university hospital. Patients:Two hundred and eighty-two patients who were admitted to the ICU. Interventions:Blood samples were obtained at ICU admission. Measurements and Main Results:We analyzed the associations among nine representative laboratory variables of each organ system using network analysis. We compared the network structure of the variables in the 40 nonsurvivors with that in the 40 survivors. Their baseline characteristics, including the degree of organ dysfunction, were matched using propensity score matching method. Network structure was quantitatively evaluated using edge (significant correlation among variables evaluated by the p value), weight (connective strength of edge evaluated by coefficient), and cluster (group with tight connection evaluated by edge betweenness). The number of edges among the nine variables was significantly fewer for the nonsurvivors than for the severity-matched survivors (3 vs 12; p = 0.035). The mean weight of edges was significantly smaller for the nonsurvivors (0.055 vs 0.119; p = 0.007). The nine laboratory variables for the nonsurvivors were divided into a significantly larger number of clusters (7 vs 2; p = 0.001). Statistical conclusions were preserved with Bonferroni multiple comparison procedure. These findings were consistently observed in comparison of the 40 nonsurvivors with all the survivors. Conclusions:This study, as a preliminary proof-of-concept, quantitatively demonstrated a more disrupted network structure of organ systems in the nonsurvivors compared with that in the survivors. These observations suggest the necessity of assessment for organ system interactions to evaluate critically ill patients.

Mortality prediction by acute kidney injury biomarkers in comparison with serum creatinine

Abstract Objectives: To investigate the performance of acute kidney injury (AKI) biomarkers for mortality prediction. Materials and methods: Cutoff values of urinary L-type fatty acid-binding protein (L-FABP) and N-acetyl-β-d-glucosaminidase (NAG) for AKI diagnosis in ICU were determined in the derivation cohort. The performance of these AKI biomarkers for mortality prediction was evaluated in the validation cohort with stratification of serum-creatinine based AKI diagnosis. Results: Mortality in the AKI patients diagnosed by serum creatinine was increased remarkably when urinary L-FABP and NAG were positive. Conclusions: These AKI biomarkers can specifically detect high-risk patients among creatinine-base diagnosed AKI.

Impact of clinical context on acute kidney injury biomarker performances: differences between neutrophil gelatinase-associated lipocalin and L-type fatty acid-binding protein

Application of acute kidney injury (AKI) biomarkers with consideration of nonrenal conditions and systemic severity has not been sufficiently determined. Herein, urinary neutrophil gelatinase-associated lipocalin (NGAL), L-type fatty acid-binding protein (L-FABP) and nonrenal disorders, including inflammation, hypoperfusion and liver dysfunction, were evaluated in 249 critically ill patients treated at our intensive care unit. Distinct characteristics of NGAL and L-FABP were revealed using principal component analysis: NGAL showed linear correlations with inflammatory markers (white blood cell count and C-reactive protein), whereas L-FABP showed linear correlations with hypoperfusion and hepatic injury markers (lactate, liver transaminases and bilirubin). We thus developed a new algorithm by combining urinary NGAL and L-FABP with stratification by the Acute Physiology and Chronic Health Evaluation score, presence of sepsis and blood lactate levels to improve their AKI predictive performance, which showed a significantly better area under the receiver operating characteristic curve [AUC-ROC 0.940; 95% confidential interval (CI) 0.793–0.985] than that under NGAL alone (AUC-ROC 0.858, 95% CI 0.741–0.927, P = 0.03) or L-FABP alone (AUC-ROC 0.837, 95% CI 0.697–0.920, P = 0.007) and indicated that nonrenal conditions and systemic severity should be considered for improved AKI prediction by NGAL and L-FABP as biomarkers.

Modest Impact of Serial Measurements of Acute Kidney Injury Biomarkers in an Adult Intensive Care Unit

Background/Aims: Acute kidney injury (AKI) biomarkers have been developed with the aim of being able to detect kidney damage earlier than the detection process based on serum creatinine levels. However, single time-point measurements appear to furnish insufficient information for detecting and predicting AKI in intensive care unit patients who are frequently affected by multiple and transient/persistent renal insults. We evaluated whether serial measurements enable the prediction of AKI outcomes in such patients. Methods: Serial measurements of AKI biomarkers, including plasma and urinary neutrophil gelatinase-associated lipocalin, urinary L-type fatty acid-binding protein, and urinary N-acethyl-β-D-glucosaminidase, at intensive care unit (ICU) admission (d1) and 24 h later (d2) were performed for critically ill adult patients in a mixed ICU. We assessed whether each biomarker could predict newly developed AKI, recovery from AKI, worsening of AKI, and hospital mortality. Results: Among the enrolled 272 patients, 33 were determined to show newly developed AKI after ICU admission, 58 showed worsening of AKI, 57 recovered from AKI, and 38 died in the hospital. ROC analysis showed that biomarkers at day 2 provided no significant additional benefit in predicting the above-mentioned AKI outcomes compared with those at day 1. However, net reclassification improvement analysis demonstrated that adding day 2 biomarkers to the clinical model comprising clinical variables along with day 1 biomarkers significantly improved the prediction of these AKI outcomes. Conclusion: Serial measurement of AKI biomarkers used in clinical models could contribute to the prediction of AKI outcomes in a heterogeneous cohort of adult mixed ICU patients, although its reliability seemed to be modest.

Interface design dividing physical findings into medical and trauma findings facilitates clinical document entry in the emergency department: A prospective observational study

PURPOSE The interface design and its effect on workflow are key determinants of the usability of electronic medical records (EMRs) in the emergency department (ED). However, whether the overall clinical care can be improved by dividing the interface design of physical findings into medical and trauma findings is unknown. We previously developed an EMR system in which the checkpoints were separated into different sections according to the body part. Herein, we modified this EMR system by remaking the interface design specifically for trauma patients, and evaluated its performance. METHODS This study was undertaken in a single-center ED between October 2014 and September 2015. In the modified EMR system, all trauma findings are displayed together on the screen, according to the Japan Advanced Trauma Evaluation and Care. We compared the time to final documentation entry and the length of ED stay between the previous (used in the first 6 months) and current systems (used in the latter 6 months). Furthermore, we stratified the patients by triage levels. RESULTS The study involved 2141 patients (934 and 1207 assessed using the previous and modified EMR systems, respectively). The modified EMR in trauma patients significantly decreased the time to final documentation entry from 131.5 [interquartile range, 86.8-207.3] to 115 [78.8-161] min (p = 0.049). When stratifying trauma patients by triage level, significantly shorter clinical documentation times were observed with the modified EMR system in levels 2 (emergency) and 3 (urgent). CONCLUSIONS Using different interfaces for trauma findings shortened the time for clinical documentation for trauma patients.