Patterns of Multiple Organ Dysfunction and Renal Recovery in Critically Ill Children and Young Adults Receiving Continuous Renal Replacement Therapy.

OBJECTIVES: Acute kidney injury requiring dialysis (AKI-D) commonly occurs in the setting of multiple organ dysfunction syndrome (MODS). Continuous renal replacement therapy (CRRT) is the modality of choice for AKI-D. Mid-term outcomes of pediatric AKI-D supported with CRRT are unknown. We aimed to describe the pattern and impact of organ dysfunction on renal outcomes in critically ill children and young adults with AKI-D. DESIGN: Retrospective cohort. SETTING: Two large quarternary care pediatric hospitals. PATIENTS: Patients 26 y old or younger who received CRRT from 2014 to 2020, excluding patients with chronic kidney disease. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Organ dysfunction was assessed using the Pediatric Logistic Organ Dysfunction-2 (PELOD-2) score. MODS was defined as greater than or equal to two organ dysfunctions. The primary outcome was major adverse kidney events at 30 days (MAKE30) (decrease in estimated glomerular filtration rate greater than or equal to 25% from baseline, need for renal replacement therapy, and death). Three hundred seventy-three patients, 50% female, with a median age of 84 mo (interquartile range [IQR] 16-172) were analyzed. PELOD-2 increased from 6 (IQR 3-9) to 9 (IQR 7-12) between ICU admission and CRRT initiation. Ninety-seven percent of patients developed MODS at CRRT start and 266 patients (71%) had MAKE30. Acute kidney injury (adjusted odds ratio [aOR] 3.55 [IQR 2.13-5.90]), neurologic (aOR 2.07 [IQR 1.15-3.74]), hematologic/oncologic dysfunction (aOR 2.27 [IQR 1.32-3.91]) at CRRT start, and progressive MODS (aOR 1.11 [IQR 1.03-1.19]) were independently associated with MAKE30. CONCLUSIONS: Ninety percent of critically ill children and young adults with AKI-D develop MODS by the start of CRRT. Lack of renal recovery is associated with specific extrarenal organ dysfunction and progressive multiple organ dysfunction. Currently available extrarenal organ support strategies, such as therapeutic plasma exchange lung-protective ventilation, and other modifiable risk factors, should be incorporated into clinical trial design when investigating renal recovery.

Post-operative dysnatremia is associated with adverse early outcomes after surgery for congenital heart disease.

BACKGROUND: Dysnatremia is a common disorder in critically ill surgical children. The study's aim is to determine the prevalence of dysnatremia and its association with outcomes after surgery for congenital heart disease (CHD). METHODS: This is a single-center retrospective cohort study of children <18 years of age undergoing surgery for CHD between January 2012 and December 2014. Multivariable logistic regression analysis was used to evaluate the relationship between dysnatremia and outcomes during the perioperative period. A total of 1345 encounters met the inclusion criteria. RESULTS: The prevalence of pre- and post-operative dysnatremia were 10.2% and 47.1%, respectively. Hyponatremia occurred in 19.1%, hypernatremia in 25.6%. Hypernatremia at 24, 48, and 72 h post-operative was associated with increased hospital mortality (odds ratios (OR) [95% confidence intervals (CI)] 3.08 [1.16-8.17], p = 0.024; 4.35 [1.58-12], p = 0.0045; 4.14 [1.32-12.97], p = 0.0148, respectively. Hypernatremia was associated with adverse neurological events 3.39 [1.12-10.23], p = 0.0302 at 48 h post-operative. Hyponatremia was not associated with any adverse outcome in our secondary analysis. CONCLUSIONS: Post-operative dysnatremia is a common finding in this heterogeneous cohort of pediatric cardiac-surgical patients. Hypernatremia was more prevalent than hyponatremia and was associated with adverse early post-operative outcomes. IMPACT: Our study has shown that dysnatremia was highly prevalent in children after congenital heart surgery with hypernatremia associated with adverse outcomes including mortality. It is important to understand fluid and sodium regulation in the post-operative period in children with congenital heart disease to better address fluid overload and associated electrolyte imbalances and acute kidney injury. While clinicians are generally very aware of the importance of hyponatremia in critically ill children, similar attention should be given to hypernatremia in this population.

Comparison of Cystatin C and Creatinine-Based Equations with Measured Glomerular Filtration Rate in a Diverse Pediatric Population.

BACKGROUND: Accurate assessment of kidney function is essential for early detection of kidney damage. While measured glomerular filtration rate (mGFR) is occasionally used as a reference, estimated GFR (eGFR) from serum creatinine- and cystatin C (CysC)-based equations are routinely used in clinical practice as a reliable and less invasive approach. In pediatric populations, CysC-based equations provide a closer approximation as they are independent of body composition. Limited information is available on the performance of CysC-based equations in comparison with mGFR with tracers other than iohexol. Therefore, the goal of our study was to evaluate how eGFR, based on several CysC- and creatinine-based equations, with and without race correction, relates to mGFR in a diverse pediatric population. METHODS: A total of 43 patients (7 months to 21 years) from diverse race/ethnicity were retrospectively studied to compare the mGFR from multiple blood sample collections after intravenous tracer injection (Tc-99mDTPA) with eGFR using 9 equations. Deming regression analyses were performed to assess correlation between the mGFR and eGFRs. RESULTS: The average mGFR for this cohort was 95.0 mL/min/1.73 m2. Race-corrected (RC) equations gave overestimated eGFR across all ethnic groups, with the lowest bias for Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) CysC-creatinine (34.14 mL/min/1.73 m2). The best correlations to mGFR, percentage of eGFR within 30% of mGFR (P30), and lowest biases were from non-race-corrected (NRC) equations Chronic Kidney Disease in Children (CKiD) (0.6460, 65.1%, 2.86 mL/min/1.73 m2), CKD-EPI CysC (0.6858, 69.8%, 11.01 mL/min/1.73 m2), and Schwartz CysC (0.6876, 79.1%, -14.00 mL/min/1.73 m2). CONCLUSION: Overall, CysC-based equations without race correction provide a good approximation of mGFR and a less invasive alternative to monitoring kidney function in pediatric population, irrespective of race/ethnicity.

Neurodevelopmental Outcomes in Infants With Cardiac Surgery Associated Acute Kidney Injury.

BACKGROUND: Infants who undergo surgery for congenital heart disease are at risk of neurodevelopmental delay. Cardiac surgery-associated acute kidney injury (CS-AKI) is common but its association with neurodevelopment has not been explored. METHODS: This was a single-center retrospective observational study of infants who underwent cardiac surgery in the first year of life who had neurodevelopmental testing using the Bayley Scale for Infant Development, third edition. Single and recurrent episodes of stages 2 and 3 CS-AKI were determined. RESULTS: Of 203 children with median age at first surgery of 12 days, 31% had one or more episodes of severe CS-AKI; of those, 16% had recurrent CS-AKI. Median age at neurodevelopmental assessment was 20 months. The incidence of delay was similar for patients with and patients without CS-AKI but all children with recurrent CS-AKI had a delay in one or more domains and had significantly lower scores in all three domains, namely, cognitive, language, and motor. CONCLUSIONS: This study has assessed the association of CS-AKI with neurodevelopmental delay after surgery for congenital heart disease in infancy. Infants who have recurrent CS-AKI in the first year of life are more likely to be delayed and have lower neurodevelopmental scores.

Correlation of Venous Oxygen Saturations from Noninvasive Hematocrit Monitoring Using Blood Gas Measured Oximetry in Chronic Pediatric Hemodialysis Patients.

INTRODUCTION: Noninvasive hematocrit monitoring (NIVHM) during pediatric hemodialysis (pedHD) provides data in real time regarding changes in hematocrit and blood volume and also provides venous oxygen saturations. The latter has been proposed to indicate changes in tissue oxygen consumption. It is not known how well NIVHM oxygen saturations (O2sat) approximate blood gas measured oximetry saturation (mO2sat) in the course of pedHD. We aimed to assess the validity and reliability of NIVHM O2sat compared to mO2sat. METHODS: This is a prospective study in 15 patients <21 years old with >90 days on hemodialysis (HD) without congenital heart disease. HD access was fistula (AVF) in 4 patients and tunneled catheters in the remainder. Pulse oximetry (spO2) was continuously monitored; mO2sat was measured via oximetry in a blood gas analyzer and NIVHM O2sat values collected at the start, middle, and end of HD treatment. RESULTS: A total of 45 dyad measurements were obtained. NIVHM O2sat correlated well with mO2sat (R = 0.89, p < 0.0001); the same was seen at pre, mid, and post HD time points (R = 0.86-0.95, p < 0.001). NIVHM O2sat was lower than mO2sat; with catheter as access, the difference was 9.3 ± 8.6 (CI: 12.3-6.22, p < 0.0001) and with AVF was 2.1 ± 0.78 (CI: 2.6-1.7, p < 0.0001). Bland-Altman analysis demonstrated the difference but did not show any systematic bias. Continuous monitor of spO2 showed no hypoxia. DISCUSSION/CONCLUSION: Intradialytic NIVHM O2sat correlates well with mO2sat but yield lower values. Future studies can include NIVHM O2sat changes as a surrogate for central venous O2 saturation changes and potentially yield useful information regarding tissue oxygen consumption in pedHD patients.

Population Pharmacokinetics of Vancomycin in the Pediatric Cardiac Surgical Population.

OBJECTIVE: Vancomycin is often used in the pediatric cardiac surgical population, but few pharmacokinetic data are available to guide dosing. METHODS: A retrospective, population pharmacokinetic study was performed for patients <19 years of age initiated on vancomycin after cardiac surgery in the cardiac intensive care unit from 2011-2016 in our institution. Patient data were summarized by using descriptive statistical methods, and population pharmacokinetic analysis was performed by using NONMEM. Simulation was performed to determine a dosing strategy that most frequently obtained an AUC0-24:MIC (minimum inhibitory concentration) ratio of >400. RESULTS: A total of 261 patients (281 cardiac surgical procedures, cardiopulmonary bypass 82.3%) met inclusion criteria (60.1% male, median age 0.31 [IQR, 0.07-0.77] years). Vancomycin (14.5 ± 1.7 mg/kg/dose) was administered at median postoperative day 9 (IQR, 4-14), with a mean serum concentration of 11.5 ± 5.5 mg/L at 8.9 ± 3.8 hours after a dose. Population pharmacokinetic analysis demonstrated that a 1-compartment proportional error model with allometrically scaled weight best fit the data, with creatinine clearance and postmenstrual age as significant covariates. Simulation identified that a dosing regimen of 20 mg/kg/dose every 8 hours was most likely to achieve an AUC0-24:MIC ratio > 400 at a mean trough serum concentration of 12.9 ± 3.2 mg/L. CONCLUSIONS: Vancomycin dosing in the postoperative pediatric cardiac surgical population should incorporate postmenstrual age and creatinine clearance. A vancomycin dose of 20 mg/kg every 8 hours is a reasonable empiric strategy.

Enhancement of diuresis with metolazone in infant paediatric cardiac intensive care patients.

BACKGROUND: Few data are available regarding the use of metolazone in infants in cardiac intensive care. Researchers need to carry out further evaluation to characterise the effects of this treatment in this population. METHODS: This is a descriptive, retrospective study carried out in patients less than a year old. These infants had received metolazone over a 2-year period in the paediatric cardiac intensive care unit at our institution. The primary goal was to measure the change in urine output from 24 hours before the start of metolazone therapy to 24 hours after. Patient demographic variables, laboratory data, and fluid-balance data were analysed. RESULTS: The study identified 97 infants with a mean age of 0.32±0.25 years. Their mean weight was 4.9±1.5 kg, and 58% of the participants were male. An overall 63% of them had undergone cardiovascular surgery. The baseline estimated creatinine clearance was 93±37 ml/minute/1.73 m2. Initially, the participants had received a metolazone dose of 0.27±0.10 mg/kg/day, the maximum dose being 0.43 mg/kg/day. They had also received other diuretics during metolazone initiation, such as furosemide (87.6%), spironolactone (58.8%), acetazolamide (11.3%), bumetanide (7.2%), and ethacrynic acid (1%). The median change in urine output after metolazone was 0.9 ml/kg/hour (interquartile range 0.15-1.9). The study categorised a total of 66 patients (68.0%) as responders. Multivariable analysis identified acetazolamide use (p=0.002) and increased fluid input in the 24 hours after metolazone initiation (p0.05). CONCLUSIONS: Metolazone increased urine output in a select group of patients. Efficacy can be maximised by strategic selection of patients.

Efficacy of sequential nephron blockade with intravenous chlorothiazide to promote diuresis in cardiac intensive care infants.

BACKGROUND: Sequential nephron blockade using intravenous chlorothiazide is often used to enhance urine output in patients with inadequate response to loop diuretics. A few data exist to support this practice in critically ill infants. METHODS: We included 100 consecutive patients <1 year of age who were administered intravenous chlorothiazide while receiving furosemide therapy in the cardiac ICU in our study. The primary end point was change in urine output 24 hours after chlorothiazide administration, and patients were considered to be responders if an increase in urine output of 0.5 ml/kg/hour was documented. Data on demographic, clinical, fluid intake/output, and furosemide and chlorothiazide dosing were collected. Multivariable regression analyses were performed to determine variables significant for increase in urine output after chlorothiazide administration. RESULTS: The study population was 48% male, with a mean weight of 4.9±1.8 kg, and 69% had undergone previous cardiovascular surgery. Intravenous chlorothiazide was initiated at 89 days (interquartile range 20-127 days) of life at a dose of 4.6±2.7 mg/kg/day (maximum 12 mg/kg/day). Baseline estimated creatinine clearance was 83±42 ml/minute/1.73 m2. Furosemide dose before chlorothiazide administration was 2.8±1.4 mg/kg/day and 3.3±1.5 mg/kg/day after administration. A total of 43% of patients were categorised as responders, and increase in furosemide dose was the only variable significant for increase in urine output on multivariable analysis (p<0.05). No graphical trends were noted for change in urine output and dose of chlorothiazide. CONCLUSIONS: Sequential nephron blockade with intravenous chlorothiazide was not consistently associated with improved urine output in critically ill infants.

Acute Kidney Injury in Pediatric Severe Sepsis: An Independent Risk Factor for Death and New Disability.

OBJECTIVES: The prevalence of septic acute kidney injury and impact on functional status of PICU survivors are unknown. We used data from an international prospective severe sepsis study to elucidate functional outcomes of children suffering septic acute kidney injury. DESIGN: Secondary analysis of patients in the Sepsis PRevalence, OUtcomes, and Therapies point prevalence study: acute kidney injury was defined on the study day using Kidney Disease Improving Global Outcomes definitions. Patients with no acute kidney injury or stage 1 acute kidney injury ("no/mild acute kidney injury") were compared with those with stage 2 or 3 acute kidney injury ("severe acute kidney injury"). The primary outcome was a composite of death or new moderate disability at discharge defined as a Pediatric Overall Performance Category score of 3 or higher and increased by 1 from baseline. SETTING: One hundred twenty-eight PICUs in 26 countries. PATIENTS: Children with severe sepsis in the Sepsis PRevalence, OUtcomes, and Therapies study. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One hundred two (21%) of 493 patients had severe acute kidney injury. More than twice as many patients with severe acute kidney injury died or developed new moderate disability compared with those with no/mild acute kidney injury (64% vs 30%; p < 0.001). Severe acute kidney injury was independently associated with death or new moderate disability (adjusted odds ratio, 2.5; 95% CI, 1.5-4.2; p = 0.001) after adjustment for age, region, baseline disability, malignancy, invasive mechanical ventilation, albumin administration, and the pediatric logistic organ dysfunction score. CONCLUSIONS: In a multinational cohort of critically ill children with severe sepsis and high mortality rates, septic acute kidney injury is independently associated with further increased death or new disability.

Neonatal extracorporeal renal replacement therapy-a routine renal support modality?

Peritoneal dialysis (PD) is generally considered the preferred extracorporeal therapy for neonates with acute kidney injury (AKI). However, there are situations when PD is not suitable, such as in patients with previous abdominal surgery, hyperammonemia and significant ascites or anasarca. Additionally, with a need to start PD soon after catheter placement, there is increased risk of PD catheter leak and infection. Extracorporeal continuous renal replacement therapy (CRRT) is challenging in severely ill neonates as it requires obtaining adequately sized central venous access to accommodate adequate blood flow rates and also adaptation of a CRRT machine meant for older children and adults. In addition, ultrafiltration often cannot be set in sufficiently small increments to be suitable for neonates. Although CRRT practices can be modified to fit the needs of infants and neonates, there is a need for a device designed specifically for this population. Until that becomes available, providing the highest level of care for neonates with AKI is dependent on the shared experiences of members of the pediatric nephrology community.

Acute Kidney Injury in Pediatric Heart Failure.

Acute kidney injury (AKI) is very common in pediatric medical and surgical cardiac patients. Not only is it an independent risk factor for increased morbidity and mortality in the short run, but repeated episodes of AKI lead to chronic kidney disease (CKD) especially in the most vulnerable hosts with multiple risk factors, such as heart transplant recipients. The cardiorenal syndrome, a term coined to emphasize the bidirectional nature of simultaneous or sequential cardiac-renal dysfunction both in acute and chronic settings, has been recently described in adults but scarcely reported in children. Despite the common occurrence and clinical and financial impact, AKI in pediatric heart failure outside of cardiac surgery populations remains poorly studied and there are no large-scale pediatric specific preventive or therapeutic studies to date. This article will review pediatric aspects of the cardiorenal syndrome in terms of pathophysiology, clinical impact and treatment options.

Nature of the underlying heart disease affects survival in pediatric patients undergoing extracorporeal cardiopulmonary resuscitation.

OBJECTIVE: To describe the use of extracorporeal membrane oxygenation (ECMO) in acute resuscitation after cardiac arrest in pediatric patients with heart disease, with reference to patient selection and predictors of outcome. METHODS: A retrospective medical record review was performed of all patients aged ≤21 years with heart disease who had undergone ECMO for cardiopulmonary resuscitation (ECPR) at Texas Children's Hospital from January 2005 to December 2012. The most recent Pediatric Overall Performance Category score was determined from the patients' medical records. RESULTS: During the study period, 62 episodes of ECPR occurred in 59 patients, with 27 (46%) surviving to hospital discharge and 25 (43%) alive at the most recent follow-up visit. The overall survival to discharge for patients with myocardial failure (myocarditis, cardiomyopathy, or after transplantation) and structural heart disease was similar (40% vs 50%, P=.6). No patient with restrictive cardiomyopathy survived; 1 patient (13%) in ECPR group after late cardiac graft failure survived to discharge. Survival to discharge was greater for patients who were intubated (70%) at cardiac arrest (P=.001). The presence of pre-existing acute kidney injury at cardiac arrest (62%) was associated with greater mortality (P=.059). A Pediatric Overall Performance Category score of ≤2 (indicating good neurologic performance) was present in 68% of the survivors; 7 patients (87%) with a score>2 had abnormal imaging findings (P=.01). CONCLUSIONS: ECPR was associated with modest survival in pediatric patients with heart disease; however, this was associated in part with the underlying disease and pre-existing comorbidities, including the presence of acute kidney injury.

Ascertainment and epidemiology of acute kidney injury varies with definition interpretation.

BACKGROUND AND OBJECTIVES: Differences in defining acute kidney injury (AKI) may impact incidence ascertainment. We assessed the effects of different AKI definition interpretation methods on epidemiology ascertainment. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Two groups were studied at Texas Children's Hospital, Houston, Texas: 150 critically ill children (prospective) and 254 noncritically ill, hospitalized children receiving aminoglycosides (retrospective). SCr was collected for 14 d in the prospective study and 21 d in the retrospective study. Children with known baseline serum creatinine (bSCr) were classified by the pediatric Risk, Injury, Failure, Loss, End-Stage Kidney Disease (pRIFLE) AKI definition using SCr change (pRIFLE(DeltaSCr)), estimated creatinine clearance (eCCl) change (pRIFLE(DeltaCCl)), and the Acute Kidney Injury Network (AKIN) definition. In subjects without known bSCr, bSCR was estimated as eCCl = 100 (eCCl(100)) and 120 ml/min per 1.73 m(2) (eCCl(120)), admission SCr (AdmSCr) and lower/upper normative values (NormsMin, NormsMax). The differential impact of each AKI definition interpretation on incidence estimation and severity distribution was evaluated. RESULTS: pRIFLE(DeltaSCr) and AKIN led to identical AKI distributions. pRIFLE(DeltaCCl) resulted in 14.5% (critically ill) and 11% (noncritical) more patients diagnosed with AKI compared to other methods (P 0.05). Different bSCr estimates led to differences in AKI incidence, from 12% (AdmSCr) to 87.8% (NormsMin) (P 0.05) in the critically ill group and from 4.6% (eCCl(100)) to 43.1% (NormsMin) (P 0.05) in the noncritical group. CONCLUSIONS: AKI definition variation causes interstudy heterogeneity. AKI definition should be standardized so that results can be compared across studies.