Evolution of Acute Kidney Injury and Its Association With Systemic Hemodynamics in Children With Fluid-Refractory Septic Shock

Objectives: There are no studies in pediatrics evaluating the progression of acute kidney injury in septic shock. We investigated the evolution of sepsis-associated acute kidney injury and its association with systemic hemodynamics in children with fluid-refractory septic shock. Design: Prospective cohort study. Setting: PICU of a tertiary care hospital. Patients: All patients with fluid-refractory septic shock (n = 61) between September 2010 and February 2014. Interventions: Hemodynamic variables using noninvasive ultrasound cardiac output monitor were measured at admission and 6 hourly thereafter till 48 hours. We used the Kidney Disease: Improving Global Outcomes criteria to define and stage acute kidney injury. Associations between various hemodynamic variables and development of acute kidney injury were evaluated. Severe acute kidney injury was defined as stage 2 or 3 acute kidney injury and was compared with no acute kidney injury or stage 1 acute kidney injury. Measurements and Main Results: Severe acute kidney injury developed in 29.5% (n = 18) of the 61 children with fluid-refractory septic shock, whereas 43 patients (70.49%) had either no or stage 1 acute kidney injury. Most patients who developed acute kidney injury did so within the first 48 hours of PICU admission. Severe acute kidney injury conferred a three-fold increased risk of death by day 28 (hazard ratio, 3.23; 95% CI, 1.52–6.67; p = 0.002), longer ICU stay, and increased duration of mechanical ventilation. Central venous pressure at presentation was higher in severe acute kidney injury by 5 cm H2O. Highest lactate in the first 24 hours of PICU admission, low diastolic blood pressure, low systemic vascular resistance index at admission were associated with severe acute kidney injury. This model reliably predicted stage 2/3 acute kidney injury by day 3 with area under the curve equals to 94%; 95% CI, 88.3–99.99. None of the other hemodynamic variables showed any association with severe acute kidney injury. Conclusions: Manifestations of sepsis-associated acute kidney injury often occur early after PICU admission and is associated with increased morbidity and mortality. There is a need to develop a predictive model in septic shock which could facilitate early detection of acute kidney injury. This work was performed at King’s College Hospital, Denmark Hill, London SE5 9RS, United Kingdom. Ethical Statement: This was an observational study of routinely monitored hemodynamic and biochemical variables in the clinical management of children in septic shock in PICU and their outcomes. All children received standard therapies. Therefore, according to local guidelines, Ethics Committee review was not required. However, this study was registered as a service evaluation project at King’s College Hospital (Clinical Audit Support System project no. 2902). Dr. Deep is the supervisor who conceptualized the project and supervised data collection, interpretation and has reviewed and edited the article. He is the corresponding author. Drs. Sagar and Karthikeyan collected the data and contributed to the initial article. Drs. Goonasekera and Brierley helped edit the article. Dr. Douiri is senior lecturer of Biostatistics and Epidemiology in the department of primary care and public health sciences at King’s College London who advised the statistical design and analysis of the data. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (https://ift.tt/29S62lw). Dr. Douiri acknowledges financial support from the National Institute for Health Research (NIHR) Biomedical Research and from the NIHR Collaboration for Leadership in Applied Health Research and Care South London at King’s College Hospital NHS Foundation Trust. The remaining authors have disclosed that they do not have any potential conflicts of interest. Address requests for reprints to: Akash Deep, MD, FRCPCH, PICU, King’s College Hospital, Denmark Hill, London SE5 9RS, United Kingdom. E-mail: akash.deep@nhs.net Copyright © by 2018 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

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