Use of furosemide in preterm neonates with acute kidney injury is associated with increased mortality: results from the TINKER registry.

BACKGROUND: Diuretics are commonly used in neonatal AKI with the rationale to decrease positive fluid balance in critically sick neonates. The patterns of furosemide use vary among hospitals, which necessitates the need for a well-designed study. METHODS: The TINKER (The Indian Iconic Neonatal Kidney Educational Registry) study provides a database, spanning 14 centres across India since August 2018. Admitted neonates (≤ 28 days) receiving intravenous fluids for at least 48 h were included. Neonatal KDIGO criteria were used for the AKI diagnosis. Detailed clinical and laboratory parameters were collected, including the indications of furosemide use, detailed dosing, and the duration of furosemide use (in days). RESULTS: A total of 600 neonates with AKI were included. Furosemide was used in 8.8% of the neonates (53/600). Common indications of furosemide use were significant cardiac disease, fluid overload, oliguria, BPD, RDS, hypertension, and hyperkalemia. The odds of mortality was higher in neonates < 37 weeks gestational age with AKI who received furosemide compared to those who did not receive furosemide 3.78 [(1.60-8.94); p = 0.003; univariate analysis] and [3.30 (1.11-9.82); p = 0.03]; multivariate logistic regression]. CONCLUSIONS: In preterm neonates with AKI, mortality was independently associated with furosemide treatment. The furosemide usage rates were higher in neonates with associated co-morbidities, i.e. significant cardiac diseases or surgical interventions. Sicker babies needed more resuscitation at birth, and died early, and hence needed shorter furosemide courses. Thus, survival probability was higher in neonates treated with long furosemide courses vs. short courses.

Validation of the STARZ neonatal acute kidney injury risk stratification score in an independent prospective cohort.

OBJECTIVE: A rapid AKI risk assessment score would allow for improving management and outcomes. STARZ (Sethi, Tibrewal, Agrawal, Raina, waZir) score was developed for acute kidney injury (AKI) risk stratification of critically ill neonates. This is the first independent validation for the novel score outside the original enrolled centres. STUDY DESIGN: 750 neonates were included in the study. The STARZ score was calculated after 12 hours of admission. Neonates admitted in NICU and receiving IV fluids for at least 48 hours were included. RESULTS: A total of 8.8% neonates had AKI in the first 7 days post admission. The duration of hospital stay was significantly higher among neonates with AKI [10.5 (7-19) vs. 7 (5-10) days; p < 0.001]. Mortality risk was 6.4 times higher among those with AKI [8 (12.1%) vs. 13 (1.9%); p < 0.001; RR (95% CI): 6.38 (2.74-14.83)]. In this study, the STARZ neonatal scoring model showed a sensitivity of 89.4% in detecting AKI with a 90.9% specificity and a high negative predictive value of 98.9%. The area under ROC was 0.958 (0.934-0981) - a high discriminative power. CONCLUSIONS: The STARZ score allows for AKI risk stratification, providing opportunity for therapeutic interventions which may improve outcomes in critically ill neonates.

Risk factors and outcomes of neonates with acute kidney injury needing peritoneal dialysis: Results from the prospective TINKER (The Indian PCRRT-ICONIC Neonatal Kidney Educational Registry) study.

BACKGROUND: Acute kidney injury (AKI) is common in neonates admitted to neonatal intensive care units (NICUs). There is a need to have prospective data on the risk factors and outcomes of acute peritoneal dialysis (PD) in neonates. The use of kidney replacement therapy in this population compared to older populations has been associated with worse outcomes (mortality rates 17-24%) along with a longer stay in the NICU and/or hospital. METHODS: The following multicentre, prospective study was derived from the TINKER (The Indian PCRRT-ICONIC Neonatal Kidney Educational Registry) database, assessing all admitted neonates ≤28 days who received intravenous fluids for at least 48 h. The following neonates were excluded: death within 48 h, presence of any lethal chromosomal anomaly, requirement of congenital heart surgery within the first 7 days of life and those receiving only routine care in nursery. Demographic data (maternal and neonatal) and daily clinical and laboratory parameters were recorded. AKI was defined according to the Neonatal Kidney Disease: Improving Global Outcomes criteria. RESULTS: Of the included 1600 neonates, a total of 491 (30.7%) had AKI. Of these 491 neonates with AKI, 44 (9%) required PD. Among neonates with AKI, the odds of needing PD was significantly higher among those with significant cardiac disease (odds ratio (95% confidence interval): 4.95 (2.39-10.27); p < 0.001), inotropes usage (4.77 (1.98-11.51); p < 0.001), severe peripartum event (4.37 (1.31-14.57); p = 0.02), requirement of respiratory support in NICU (4.17 (1.00-17.59); p = 0.04), necrotising enterocolitis (3.96 (1.21-13.02); p = 0.03), any grade of intraventricular haemorrhage (3.71 (1.63-8.45); p = 0.001), evidence of fluid overload during the first 12 h in NICU (3.69 (1.27-10.70); p = 0.02) and requirement of resuscitation in the delivery room (2.72 (1.45-5.12); p = 0.001). AKI neonates with PD as compared to those without PD had a significantly lower median (interquartile range) duration of stay in NICU (7 (4-14) vs. 11 (6-21) days; p = 0.004), but significantly higher mortality (31 (70.5%) vs. 50 (3.2%); p < 0.001). This discrepancy is likely attributable to the critical state of the neonates with AKI. CONCLUSIONS: This is the largest prospective, multicentre study specifically looking at neonatal AKI and need for dialysis in neonates. AKI was seen in 30.7% of neonates (with the need for acute PD in 9% of the AKI group). The odds of needing acute PD were significantly higher among those with significant cardiac disease, inotropes usage, severe peripartum event, requirement of respiratory support in NICU, necrotising enterocolitis, any grade of intraventricular haemorrhage, evidence of fluid overload more than 10% during the first 12 h in NICU and requirement of resuscitation in the delivery room. AKI neonates with PD as compared to AKI neonates without PD had a significantly higher mortality. There is a need to keep a vigilant watch in neonates with risk factors for the development of AKI and need for PD.

Validation of the STARZ neonatal acute kidney injury risk stratification score.

BACKGROUND: Neonatal acute kidney injury (AKI) is common in neonatal intensive care units (NICU) and leads to worse outcomes. Stratifying neonates into an "at risk" category allows health care providers to objectively recognize opportunities for improvements in quality of care. METHODS: The "Neonatal AKI Risk Prediction Scoring" was devised as the "STARZ [Sethi, Tibrewal, Agrawal, Raina, waZir]" Score. The STARZ score was derived from our prior multicentre study analysing risk factors for AKI in neonates admitted to the NICU. This tool includes 10 variables with a total score ranging from 0 to 100 and a cut-off score of 31.5. In the present study, the scoring model has been validated in our multicentre cohort of 744 neonates. RESULTS: In the validation cohort, this scoring model had sensitivity of 82.1%, specificity 91.7%, positive predictive value 81.2%, negative predictive value 92.2% and accuracy 88.8%. Based on the STARZ cut-off score of ≥ 31.5, an area under the receiver operating characteristic (ROC) curve was observed to be 0.932 (95% CI, 0.910-0.954; p < 0.001) signifying that the discriminative power was high. In the validation cohort, the probability of AKI was less than 20% for scores up to 32, 20-40% for scores between 33 and 36, 40-60% for scores between 37 and 43, 60-80% for scores between 44 and 49, and ≥ 80% for scores ≥ 50. CONCLUSIONS: To promote the survival of susceptible neonates, early detection and prompt interventional measures based on highly evidenced research is vital. The risk of AKI in admitted neonates can be quantitatively determined by the rapid STARZ scoring system. A higher resolution version of the Graphical abstract is available as Supplementary information.

Neonatal acute kidney injury risk stratification score: STARZ study.

BACKGROUND: Neonates admitted in the neonatal intensive care unit are vulnerable to acute kidney injury leading to worse outcomes. It is important to identify "at-risk" neonates for early preventive measures. METHODS: The study was a multicenter, national, prospective cohort study done in 11 centers in India. A multivariable logistic regression technique with step-wise backward elimination method was used, and a "Risk Prediction Scoring" was devised [the STARZ score]. RESULTS: The neonates with admission in the NICU within <25.5 h of birth, requirement of positive pressure ventilation in the delivery room, <28 weeks gestational age, sepsis, significant cardiac disease, urine output <1.32 ml/kg/h or serum creatinine ≥0.98 mg/dl during the first 12 h post admission, use of nephrotoxic drugs, use of furosemide, or use of inotrope had a significantly higher risk of AKI at 7 days post admission in the multivariate logistic regression model. This scoring model had a sensitivity of 92.8%, specificity of 87.4% positive predictive value of 80.5%, negative predictive value of 95.6%, and accuracy of 89.4%. CONCLUSIONS: The STARZ neonatal score serves to rapidly and quantitatively determine the risk of AKI in neonates admitted to the neonatal intensive care unit. IMPACT: The STARZ neonatal score serves to rapidly and quantitatively determine the risk of AKI in neonates admitted to the neonatal intensive care unit. These neonates with a higher risk stratification score need intense monitoring and daily kidney function assessment. With this intensification of research in the field of AKI risk stratification prediction, there is hope that we will be able to decrease morbidity and mortality associated with AKI in this population.

Incidence, Risk Factors, and Outcomes of Neonatal Acute Kidney Injury: Protocol of a Multicentric Prospective Cohort Study [The Indian Iconic Neonatal Kidney Educational Registry].

Background: Acute kidney injury (AKI) is a significant problem in neonates, but the evidence is sparse. Neonatal AKI is an independent risk factor for increased mortality and prolonged hospital stay. There are stark differences in the epidemiology of AKI in neonates amongst the developing and the developed world. Increased prevalence of neonatal sepsis, lack of awareness about neonatal AKI and poor access to pediatric nephrologists add to the improper management of neonatal AKI in the developing countries. Methods: This study is a multicentric, national, prospective cohort study [The Indian iconic Neonatal Kidney Educational Registry (TINKER)] conducted in level 2-3 NICUs in 11 centers across India. We have enrolled nearly 2,000 neonates over the study period. Neonates (≤ 28 days) who were admitted in NICU and those who received intravenous (IV) fluids for at least 48 h for hydration and/or nutrition have been included. Data collection included: (1) baseline demographics (2) daily physiologic and laboratory parameters (3) discharge data. KDIGO workgroup AKI definition modified for neonates was used for defining AKI. Data entry was carried out by individual participating centers using a web-based database (akiregistry.org). De-identified data has been maintained and handled by the principal investigator (PI). This collaboration plans to disseminate data through peer-reviewed publications and through presentations at educational conferences. Conclusions: The purpose of this study is to create the first prospective neonatal all-cause AKI data repository and describe the incidence of neonatal AKI in NICUs in the country and determine the risk factors as well as the outcomes of such neonates-both short-term and long-term outcomes. This will eventually spur therapeutic advancements, facilitate decipherment of epidemiological trends, risk factors as well as outcomes and identify disparities in management across the nation.

To Compare the Efficacy of Heated Humidified High-Flow Nasal Cannula and Continuous Positive Airway Pressure in Post-Extubation Period in VLBW Infants.

OBJECTIVE: The objective of this study was to compare efficacy of continuous positive airway pressure (CPAP) and heated humidified high-flow nasal cannula (HHHFNC) as noninvasive respiratory support in post-extubation period in very low birth weight (VLBW) infants. METHOD: This retrospective study enrolled 136 neonates, ≤32 weeks gestation and ≤1500 grams birth weight, requiring noninvasive respiratory support during post-extubation period. RESULTS: There was no significant difference in post-extubation failure in HHHFNC group when compared with CPAP group (p > 0.05) but post-extubation complication was significantly higher in CPAP group (p < 0.05) including nasal septal trauma and pneumothorax. CONCLUSIONS: In neonates ≤32 weeks of gestational age, HHHFNC showed similar efficacy, and better safety profile than nasal-CPAP when used during post-extubation period for respiratory support.

Variability in survival of very low birth weight neonates in hospitals of India.

This prospective cohort study was conducted to evaluate variability in mortality of very low birth weight (VLBW) neonates during their birth hospitalization in different hospitals of India. A liveborn neonate was eligible for inclusion in the study if it was born or admitted in a participating hospital between 1st January and 31st December 2012 and weighed 1500g or less at birth. Neonates were given clinical care as per standard protocols. Standardized neonatal mortality ratio (SNMR) was calculated as the ratio of the observed mortality to the expected mortality. Expected mortality rate for each unit was calculated by adjusting for various prognostic factors at the time of birth or admission in the participating unit. Among 1345 neonates [mean birth weight: 1168 ± 240g, median gestation: 30wk (IQR: 28-32)] enrolled in the study 199 (14.8%) died before hospital discharge. Although variation in inter-hospital SNMR was statistically insignificant (P 0.49), 95% CI of SNMR of most hospitals was broad reaching level of clinical significance on both sides of line of equivalence. This indicates the need to establish an ongoing quality-improvement collaborative network to identify and adopt clinical practices associated with decreased mortality.

Screening coronary angiography prior to surgery in rheumatic valvular heart disease: a study of 2,188 patients.

BACKGROUND AND AIM OF THE STUDY: The role of screening coronary angiography in Asian Indian patients with rheumatic heart disease (RHD) due to undergo valve replacement surgery is unclear. Hence, the study aim was to determine the prevalence of coronary artery disease (CAD), and to monitor its correlation with demographic variables and valvular lesion type, in this patient group. METHODS: A retrospective analysis of 2,188 consecutive patients (1,319 men, 869 women; mean age 48 +/- 7 years) with rheumatic valvular heart disease was conducted. The patients underwent preoperative coronary angiography in a tertiary care hospital between 1991 and 2004. RESULTS: The overall prevalence of CAD was 11% (12% in men, 8% in women). The prevalence of CAD in the age groups of 40-44, 45-49, 50-54, 55-59 and > 60 years was 4%, 5%, 9%, 15% and 20% in men, and 2%, 2%, 3%, 7% and 10% in women, respectively. Both, age and male gender were independently associated with the occurrence of CAD (p < 0.01). The unadjusted odds ratio of having CAD was highest in patients with aortic stenosis (2.08; p < 0.01), and lowest in those with aortic regurgitation (AR) (0.58; p = 0.018). Those patients with AR also showed an independent inverse association with the occurrence of CAD (p = 0.006). CONCLUSION: The overall prevalence of CAD among Asian Indian patients with RHD was lower than that in patients from western countries. The cut-off age to perform coronary angiographic screening should be maintained at 40 years for men, and 55 years for women. The prevalence of CAD may be lower in those patients with AR.

Room air vs. 100 per cent oxygen for neonatal resuscitation: a controlled clinical trial.

The aim of the study was to determine whether neonates resuscitated with room air compared with 100 per cent oxygen in the delivery room were less likely to have hypoxic ischemic encephalopathy and/or death before discharge. A controlled clinical trial was carried out at a tertiary care institute. All newborns weighing 1000 g or more with apnea or gasping respiration and/or heart rate less than 100 beats/min requiring positive pressure ventilation after initial steps of resuscitation were included. All eligible neonates were randomized to receive room air or 100 per cent oxygen for the first 90 s after birth if they required positive pressure ventilation. The composite primary outcome variable was hypoxic ischemic encephalopathy (HIE) and/or death before discharge. A total of 204 neonates fulfilling the inclusion criteria were enrolled. Of these, 107 neonates received room air and 97 neonates received 100 per cent oxygen for resuscitation. The composite primary outcome occurred in 41.1 per cent of the neonates assigned to receive room air and 43.3 per cent of those in the 100 per cent oxygen group (odds ratio in the group assigned to room air, 0.92; 95 per cent confidence interval, 0.52-1.60). Resuscitation of a newborn baby with room air instead of the current practice of 100 per cent oxygen does not confer a benefit in terms of reduced HIE and/or mortality. Significantly, there is no increase in adverse outcome with the use of room air, which can be recommended for resuscitation if oxygen is not available.