A quality initiative to improve recognition of fluid overload among pediatric ICU patients requiring continuous kidney replacement therapy: preliminary results.

BACKGROUND: Initiation of continuous kidney replacement therapy (CKRT) greater than 20% fluid overload is associated with increased morbidity and mortality. We aimed to reduce the number of patients initiated on CKRT greater than 20% fluid overload by 50% in one year by implementation of a quality improvement initiative. METHODS: This is a prospective quality improvement study set in a pediatric ICU of an urban children's hospital of patients initiated on CKRT over 2 years. The intervention included creation of an electronic health record order for daily calculation of net percent fluid overload, incorporation into daily rounds, and education programs tailored to physicians and bedside nursing. We measured adherence with the new order set, percent fluid overload at CKRT initiation, days on CKRT, timing of first nephrology consultation, and death prior to discharge. RESULTS: A total of 32% of patients were initiated on CKRT greater than 20% fluid overload pre-initiative and 9% post-initiative, a 72% reduction over 13 months. Patients initiated on CKRT greater than 20% fluid overload had median CKRT course of 8 (IQR 4-14) vs. 22 days (IQR 13.5-62). CONCLUSION: Creating a system using EHR with education may reduce initiation of CKRT after development of severe fluid overload. A higher resolution version of the Graphical abstract is available as Supplementary information.

Long-term kidney outcomes in children following continuous kidney replacement therapy.

BACKGROUND: Continuous kidney replacement therapy (CKRT) is a mainstay of therapy for management of severe acute kidney injury (AKI) in critically ill pediatric patients. There is limited data on the risk of chronic kidney disease (CKD) after discharge in this population. METHODS: This is a single-center, retrospective cohort study of all pediatric patients ages 0-17 years who received CKRT from 2013 to 2017. The study excluded patients with pre-existing CKD, those who died prior to discharge, and those who had insufficient follow-up data. Patients were followed after hospital discharge and electronic health record data was collected and analyzed to assess for incidence of and risk factors for kidney sequelae. RESULTS: A total of 42 patients were followed at a median time of 27 months (IQR 17.2, 39.8). Of these, 26.2% had evidence of CKD and 19% were at risk for CKD. Lower eGFR at hospital discharge was associated with increased odds of kidney sequelae (aOR 0.985; 95% CI 0.972, 0.996). Ages 0- < 1 and 12-17 were not significantly different (aOR 0.235, 95% CI 0.024, 1.718) and had the highest incidence of kidney sequelae (50% and 77%, respectively). Ages 1-5 and 6-11 had a decreased odds of kidney sequelae compared to the 12-17 year age group (aOR 0.098; 95% CI 0.009, 0.703 and aOR 0.035; 95% CI 0.001, 0.39, respectively). Only 54.8% of patients (n = 23) were seen in the nephrology clinic after discharge. CONCLUSIONS: Patients who receive CKRT for AKI have a significant risk of CKD, while follow-up with a pediatric nephrologist in these high-risk patients is sub-optimal. A higher resolution version of the Graphical abstract is available as Supplementary information.

Non-resuscitation fluid in excess of hydration requirements is associated with higher mortality in critically ill children.

BACKGROUND: Large volumes of non-resuscitation fluids are often administered to critically ill children. We hypothesize that excess maintenance fluid is a significant contributor to non-resuscitation fluid and that non-resuscitation fluid administered beyond hydration requirements is associated with worse clinical outcomes in critically ill children. METHODS: We evaluated all patients admitted to two large urban pediatric intensive care units (PICU) between January 2010-August 2016 and January 2010-August 2018, respectively, who survived and remained in the hospital for at least 3 days following PICU admission. The primary outcome was in-hospital mortality. Association of excess fluid with outcomes was adjusted for confounders (age, Pediatric Risk of Mortality III score, study site, day 3 acute kidney injury, PICU era, resuscitation volume, and volume output) using multivariable regression. RESULTS: We evaluated 14,483 patients; 52% received non-resuscitation fluid in excess of hydration requirements. Non-resuscitation fluid in excess of hydration requirements was associated with higher in-hospital mortality after adjustment for confounders (adjusted odds ratio 1.01 per 10 mL/kg in excess fluid, 95% confidence interval: 1.002-1.02). CONCLUSIONS: Non-resuscitation fluid in excess of hydration requirements is associated with increased mortality in critically ill children. Excess maintenance fluid is a modifiable contributor to this fluid volume. Strategies to reduce excess maintenance fluids warrant further study. IMPACT: Critically ill children frequently receive non-resuscitation fluid in excess of their estimated hydration requirements. Non-resuscitation fluid volume in excess of estimated hydration requirements is associated with higher morbidity and mortality in critically ill children. Critically ill children receive a large volume burden from maintenance fluid. Maintenance fluid represents a modifiable contributor of non-resuscitation fluid in excess of hydration requirements. Strategies focused on limitation of maintenance fluid warrant further study.

Association between the use of balanced fluids and outcomes in critically ill children: a before and after study.

BACKGROUND: Hyperchloremia and chloride load have been associated with worse clinical outcomes in critically ill patients. We sought to evaluate the electrolyte profile and clinical outcomes associated with a unit-wide transition from saline to balanced fluids for resuscitation and maintenance fluids in a pediatric intensive care unit (PICU). METHODS: A before and after analysis of all patients admitted to the PICU in a large, urban, academic hospital between August 2018 and March 2020. The transition from the use of saline to the use of balanced fluids for both resuscitation and maintenance fluid as standard care occurred in June 2019. The primary outcome was day 3 acute kidney injury (AKI). The secondary outcomes included mortality, ventilator-free days (VFDs), need for renal replacement therapy (RRT), hospital length of stay (LOS), and electrolyte abnormalities. RESULTS: Overall, 2863 patients (47% female) with a day 3 AKI rate of 12.9% (n = 130) and a mortality rate of 2.8% (n = 79) were included. After adjusting for confounders (age, PRISM III, mechanical ventilation, and immunocompromised state, septic shock), there were no significant differences in the odds of day 3 AKI (pre 13%, post 12.5%; adjusted odds ratio [aOR] 0.96, 95%CI 0.65-1.42). There were no differences in the secondary outcomes. The post-intervention period had fewer patients with hyperchloremia (pre 15.5% vs. post 10.4%, p = < 0.0001) and hyperkalemia (pre 3.2% vs. post 1.4%, p = 0.02) and more patients with hypochloremia (pre 9.5% vs. post 14.4%, p = < 0.0001) and hypokalemia (pre 38.2% vs. post 47.2%, p = < 0.0001). In reference to the normochloremic cohort, the hypochloremic cohort had an increase in day 3 AKI, need for RRT, hyperchloremia, and hyperkalemia, and a decrease in hypokalemia; and the hyperchloremic cohort had an increase in VFD and a decrease in hospital LOS. CONCLUSIONS: Following a unit-wide implementation of balanced fluids as standard care, there were no differences in rates of day 3 AKI or other clinical outcomes. However, there were lower rates of hyperkalemia and hyperchloremia and higher rates of hypokalemia and hypochloremia. Further evaluation of the effect of balanced fluids and the clinical significance of electrolyte abnormalities in critically ill children is needed.

Immunogenicity of the meningococcal polysaccharide conjugate vaccine in pediatric kidney transplant patients.

BACKGROUND: Immunosuppressed kidney transplant patients may have suboptimal response to vaccinations. The aim of this study was to determine antibody response to a quadrivalent meningococcal conjugate vaccine (MenACWY-D) in adolescents with a kidney transplant. METHODS: This was a prospective, single-center, cohort study. Adolescent patients (11-22 years old) with a functioning kidney transplant for at least 3 months and no previous meningococcal vaccination were eligible for enrollment. Antibody levels to all serogroups were measured before vaccination (baseline) and at 4 weeks and 1, 2 and 3 years after vaccination. Seropositivity was defined as a titer ≥ 1:8 at baseline, and seroconversion as a fourfold or greater increase in antibody titer from baseline at 4 weeks post-vaccination. Geometric mean titers (GMTs) were calculated at each time point and compared to published GMTs from vaccinated healthy adolescents. RESULTS: Nineteen patients were enrolled. No patient had seroprotective titers against all four serogroups at baseline. At 4 weeks post-vaccination 41% of patients seroconverted to all four serogroups, with seroconversion rates of 88, 53, 71 and 94% for serogroups A, C, W and Y, respectively. GMTs were significantly lower in adolescents with a kidney transplant than in healthy adolescents at 1 month (p = 0.02) and 3 years (p = 0.04) post-vaccination. There were no significant adverse events, episodes of rejection or death in any patient. CONCLUSIONS: Adolescents with a kidney transplant may not respond adequately to MenACWY-D and may experience more rapid declines in antibody titers than healthy adolescents. Further study is needed to determine if alternative dosing schedules can improve antibody response in this population.

Immunogenicity of Human Papillomavirus Recombinant Vaccine in Children with CKD.

BACKGROUND AND OBJECTIVES: There is a disproportionate burden of human papillomavirus (HPV) -related genital tract disease in patients with CKD and kidney transplantation; therefore, the potential effect of the quadrivalent HPV vaccine (Gardasil; Merck GmbH, Darmstadt, Germany) is profound. Immune abnormalities associated with CKD and immunosuppression may prevent optimal vaccine response. Our objective was to determine antibody response to the HPV vaccine in adolescent girls with CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This cohort study conducted from 2008 to 2012 included 57 girls aged 9-21 years old with CKD (n=25), on dialysis (n=9), or with status postkidney transplantation (n=23) who received the standard three-dose vaccine series of the HPV vaccine recruited from two pediatric nephrology clinics. Antibody levels to HPV genotypes 6, 11, 16, and 18 were measured before vaccine dose 1 (baseline), <12 months after vaccine dose 3 (blood draw 2), and ≥12 months after vaccine dose 3 (blood draw 3). Seropositivity was defined as antibody level above an established threshold for each HPV genotype. Not all participants completed three blood draws. RESULTS: Antibody response to all four HPV genotypes was 100% in the CKD and dialysis groups with samples drawn at <12 and ≥12 months after dose 3 of the HPV vaccine. Among patients with transplants, the percentages of patients achieving seropositivity were significantly lower at blood draw 2 for HPV genotypes 6 (63.6%; P=0.003), 11 (63.6%; P=0.003), and 18 (72.7%; P=0.02) and blood draw 3 for HPV genotypes 6 (62.5%; P=0.02), 11 (50%; P=0.001), 16 (75%; P=0.04), and 18 (50%; P=0.001). CONCLUSIONS: Antibody response to the quadrivalent recombinant HPV vaccine was robust and sustained in girls and young women with CKD and on dialysis. A less robust response to the vaccine was observed among those with a kidney transplant. Additional study is needed to determine if vaccination before kidney transplantation or an alternative vaccination regimen would benefit transplant recipients.