METHODS: A prospective multicenter observational study was performed on patients admitted for clinically suspected leptospirosis. Three hospitals namely Hospital Serdang, Hospital Tengku Ampuan Rahimah and Hospital Teluk Intan were included in the study. Among a total of 165 clinically suspected leptospirosis patients, 83 confirmed cases were investigated for clinical predictors for severe illness. Qualitative variables were performed using χ2 and the relationship between mild and severe cases was evaluated using logistic regression. Multivariable logistic regression was used to predict the independent variable for severity.
RESULTS: Among the 83 patients, 50 showed mild disease and 33 developed severe illness. The mean age of the patients was 41.92 ± 17.99 and most were males (n = 54, 65.06%). We identified mechanical ventilation, acute kidney injury, septic shock, creatinine level of > 1.13 mg/dL, urea > 7 mmol/L, alanine aminotransferase > 50 IU, aspartate aminotransferase > 50 IU, and platelet 50 IU and platelet
METHODS: We conducted a retrospective observational study in our multi-disciplinary Pediatric Intensive Care Unit (ICU) from January 2015 to December 2018. All patients from birth to 16 years of age who were admitted to the pediatric ICU were included. The Kidney Disease Improving Global Outcomes (KDIGO) definition was considered as the reference standard. We compared the incidence data assessed by KDIGO, pediatric risk, injury, failure, loss of kidney function and end- stage renal disease (pRIFLE) and pediatric reference change value optimised for AKI (pROCK).
RESULTS: Out of 7505 patients, 9.2% developed AKI by KDIGO criteria. The majority (59.8%) presented with stage 1 AKI. Recovery from AKI was observed in 70.4% of patients within 7 days from diagnosis. Both pRIFLE and pROCK were less sensitive compared to KDIGO criteria for the classification of AKI. Patients who met all three-KDIGO, pRIFLE and pROCK criteria had a high mortality rate (35.0%).
CONCLUSION: Close to one in ten patients admitted to the pediatric ICU met AKI criteria according to KDIGO. In about 30% of patients, AKI persisted beyond 7 days. Follow-up of patients with persistent kidney function reduction at hospital discharge is needed to reveal the long-term morbidity due to AKI in the pediatric ICU.
Methods: We evaluated commonly used surrogate and imputed baseline creatinine values against a "reference" creatinine measured during follow-up in an adult clinical trial cohort. Known AKI incidence (Kidney Disease: Improving Global Outcomes [KDIGO] criteria) was compared with AKI incidence classified by (1) back-calculation using the Modification of Diet in Renal Disease (MDRD) equation with and without a Chinese ethnicity correction coefficient; (2) back-calculation using the Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation; (3) assigning glomerular filtration rate (GFR) from age and sex-standardized reference tables; and (4) lowest measured creatinine during admission. Back-calculated distributions were performed using GFRs of 75 and 100 ml/min.
Results: All equations using an assumed GFR of 75 ml/min underestimated AKI incidence by more than 50%. Back-calculation with CKD-EPI and GFR of 100 ml/min most accurately predicted AKI but misclassified all AKI stages and had low levels of agreement with true AKI diagnoses. Back-calculation using MDRD and assumed GFR of 100 ml/min, age and sex-reference GFR values adjusted for good health, and lowest creatinine during admission performed similarly, best predicting AKI incidence (area under the receiver operating characteristic curves [AUC ROCs] of 0.85, 0.87, and 0.85, respectively). MDRD back-calculation using a cohort mean GFR showed low total error (22%) and an AUC ROC of 0.85.
Conclusion: Current methods for estimating baseline creatinine are large sources of potential error in acute infection studies. Preferred alternatives include MDRD equation back-calculation with a population mean GFR, age- and sex-specific GFR values corrected for "good health," or lowest measured creatinine. Studies using surrogate baseline creatinine values should report specific methodology.
STUDY DESIGN: Literature-based meta-analysis and individual-study-data meta-analysis of diagnostic studies following PRISMA-IPD guidelines.
SETTING & STUDY POPULATIONS: Studies of adults investigating AKI, severe AKI, and AKI-D in the setting of cardiac surgery, intensive care, or emergency department care using either urinary or plasma NGAL measured on clinical laboratory platforms.
SELECTION CRITERIA FOR STUDIES: PubMed, Web of Science, Cochrane Library, Scopus, and congress abstracts ever published through February 2020 reporting diagnostic test studies of NGAL measured on clinical laboratory platforms to predict AKI.
DATA EXTRACTION: Individual-study-data meta-analysis was accomplished by giving authors data specifications tailored to their studies and requesting standardized patient-level data analysis.
ANALYTICAL APPROACH: Individual-study-data meta-analysis used a bivariate time-to-event model for interval-censored data from which discriminative ability (AUC) was characterized. NGAL cutoff concentrations at 95% sensitivity, 95% specificity, and optimal sensitivity and specificity were also estimated. Models incorporated as confounders the clinical setting and use versus nonuse of urine output as a criterion for AKI. A literature-based meta-analysis was also performed for all published studies including those for which the authors were unable to provide individual-study data analyses.
RESULTS: We included 52 observational studies involving 13,040 patients. We analyzed 30 data sets for the individual-study-data meta-analysis. For AKI, severe AKI, and AKI-D, numbers of events were 837, 304, and 103 for analyses of urinary NGAL, respectively; these values were 705, 271, and 178 for analyses of plasma NGAL. Discriminative performance was similar in both meta-analyses. Individual-study-data meta-analysis AUCs for urinary NGAL were 0.75 (95% CI, 0.73-0.76) and 0.80 (95% CI, 0.79-0.81) for severe AKI and AKI-D, respectively; for plasma NGAL, the corresponding AUCs were 0.80 (95% CI, 0.79-0.81) and 0.86 (95% CI, 0.84-0.86). Cutoff concentrations at 95% specificity for urinary NGAL were>580ng/mL with 27% sensitivity for severe AKI and>589ng/mL with 24% sensitivity for AKI-D. Corresponding cutoffs for plasma NGAL were>364ng/mL with 44% sensitivity and>546ng/mL with 26% sensitivity, respectively.
LIMITATIONS: Practice variability in initiation of dialysis. Imperfect harmonization of data across studies.
CONCLUSIONS: Urinary and plasma NGAL concentrations may identify patients at high risk for AKI in clinical research and practice. The cutoff concentrations reported in this study require prospective evaluation.
Materials and methods: RaFTA is a prospective, observational study in Asian intensive care unit (ICU) patients focusing on fluid therapy and related outcomes. Logistic regression was performed to identify risk factors for increased 90-day mortality and acute kidney injury (AKI).
Results: Twenty-four study centers joined the RaFTA registry and collected 3,187 patient data sets from November 2011 to September 2012. A follow-up was done 90 days after ICU admission. For 90-day mortality, significant risk factors in the overall population were sepsis at admission (OR 2.185 [1.799; 2.654], p < 0.001), cumulative fluid balance (OR 1.032 [1.018; 1.047], p < 0.001), and the use of vasopressors (OR 3.409 [2.694; 4.312], p < 0.001). The use of colloids was associated with a reduced risk of 90-day mortality (OR 0.655 [0.478; 0.900], p = 0.009). The initial colloid dose was not associated with an increased risk for AKI (OR 1.094 [0.754; 1.588], p = 0.635).
Conclusion: RaFTA adds the important finding that colloid use was not associated with increased 90-day mortality or AKI after adjustment for baseline patient condition.
Clinical significance: Early resuscitation with colloids showed potential mortality benefit in the present analysis. Elucidating these findings may be an approach for future research.
How to cite this article: Jacob M, Sahu S, Singh YP, Mehta Y, Yang K-Y, Kuo S-W, et al. A Prospective Observational Study of Rational Fluid Therapy in Asian Intensive Care Units: Another Puzzle Piece in Fluid Therapy. Indian J Crit Care Med 2020;24(11):1028-1036.
METHODS: Proton Nuclear Magnetic Resonance (1H NMR) and Liquid Chromatography Mass Spectroscopy (LCMS) coupled with multivariate data analysis were employed to characterize the metabolic variations of intracellular metabolites and the compositional changes of the corresponding culture media in rat renal proximal tubular cells (NRK-52E).
RESULTS: NMR and LCMS analysis highlighted choline, creatine, phosphocholine, valine, acetic acid, phenylalanine, leucine, glutamic acid, threonine, uridine and proline as the main metabolites which differentiated the cisplatin-induced group of NRK-52E from control cells extract. The corresponding media exhibited lactic acid, glutamine, glutamic acid and glucose-1-phosphate as the varied metabolites. The altered pathways perturbed by cisplatin nephrotoxic on NRK-52E cells included changes in amino acid metabolism, lipid metabolism and glycolysis.
CONCLUSION: The C. nutans aqueous extract (1000 μg/mL) exhibited the most potential nephroprotective effect against cisplatin toxicity on NRK-52E cell lines at 89% of viability. The protective effect could be seen through the changes of the metabolites such as choline, alanine and valine in the C. nutans pre-treated samples with those of the cisplatin-induced group.
Results: Prior to total hip arthroplasty, 20% of all patients met the chronic renal dysfunction criterion of glomerular filtration rates <60ml/min/1.73m2 (glomerular filtration rate categories G3a-G5). Incidence rates of acute kidney injury and acute deterioration of kidney function after total hip arthroplasty were 0.49% and 6.9%, respectively. Multivariate regression analysis showed that diabetes mellitus and use of nonsteroidal anti-inflammatory drugs before total hip arthroplasty were significant risk factors for acute deterioration of kidney function. Advanced age, preoperative renal dysfunction, antihypertensive, diuretics, or statin use, operation time, total blood loss, type of anesthetic, and body mass index were not significant risk factors.
Conclusion: Diabetes mellitus and use of nonsteroidal anti-inflammatory drugs were controllable risks, and multidisciplinary approaches are a reasonable means of minimising peri-operative acute kidney injury or acute deterioration of kidney function.
METHODS: Kidney IRI was performed with bilateral pediculus clamping in Swiss Background mice (3 months, 30-40g). Mice were euthanised on day one (I/R1, n=6), day eight (I/R8, n=6), and day twelve (I/R12, n=6) to exam acute and chronic episodes. Sham operation procedure was performed in the control. Tubular injury was assessed based on periodic acid- Schift (PAS) staining. Reverse transcriptase PCR (RT-PCR) was done to quantify mRNA expression of Bax, Bcl-2, and p16. Immunohistostaining (IHC) was performed to examine localisation of apoptosis (p53) and proliferation (Bcl-2).
RESULTS: RT-PCR analysis showed upregulation of mRNA expression of Bcl-2, Bax, and p16 (p<0.05). The data showed that ischemia/reperfusion induces upregulation of Bax (p=0.20), Bcl-2 (p=0.45), p16 (p=0.18). Apoptosis and proliferation occurred in the epithelial cells in acute episodes, but occurred in interstitial areas in chronic episodes.
CONCLUSIONS: Ischemia/reperfusion injury induces upregulation proliferation, apoptosis, and cellular senescence in acute kidney injury. Apoptosis reached its peak on day 1, proliferation on day 8, and cellular senescence on day 12.
METHODS: Perioperative data from 3008 adult patients undergoing elective cardiac surgery from 2008 to 2011 at the two main heart centers in Singapore was analyzed prospectively, and confirmatory analysis was conducted with the generalized structural equation model.
RESULTS: Diabetes was significantly associated with postoperative acute kidney injury (AKI) and postoperative hyperglycemia. Postoperative AKI, Malay ethnicity, and blood transfusion were associated with postoperative dialysis. Postoperative AKI and blood transfusion were also associated with postoperative arrhythmias. In turn, postoperative dialysis and arrhythmias increased the odds of 30-day mortality by 7.7- and 18-fold, respectively.
CONCLUSIONS: This study identified that diabetes is directly associated with postoperative hyperglycemia and AKI, and indirectly associated with arrhythmias and 30-day mortality. Further, we showed that ethnicity not only affects the prevalence of diabetes, but also postoperative diabetes-related outcomes.