Timing of Kidney Replacement Therapy Initiation and Survival during Pediatric Extracorporeal Membrane Oxygenation: An Extracorporeal Life Support Organization Registry Study.

To characterize kidney replacement therapy (KRT) and pediatric extracorporeal membrane oxygenation (ECMO) outcomes and to identify the optimal timing of KRT initiation during ECMO associated with increased survival. Observational retrospective cohort study using the Extracorporeal Life Support Organization Registry database in children (0-18 yo) on ECMO from January 1, 2016, to December 31, 2020. Of the 14,318 ECMO runs analyzed, 26% of patients received KRT during ECMO. Patients requiring KRT before ECMO had increased mortality to ECMO decannulation (29% vs. 17%, OR 1.97, P < 0.001) and to hospital discharge (58% vs. 39%, OR 2.16, P < 0.001). Patients requiring KRT during ECMO had an increased mortality to ECMO decannulation (25% vs. 15%, OR 1.85, P < 0.001) and to hospital discharge (56% vs. 34%, OR 2.47, P < 0.001). Multivariable logistic regression demonstrated that the need for KRT during ECMO was an independent predictor for mortality to ECMO decannulation (OR 1.49, P < 0.001) and to hospital discharge (OR 2.02, P < 0.001). Patients initiated on KRT between 24 and 72 hours after cannulation were more likely to survive to ECMO decannulation and showed a trend towards survival to hospital discharge as compared to those initiated before 24 hours and after 72 hours.

Augmented Renal Clearance of Vancomycin in Suspected Sepsis: Single-Center, Retrospective Pediatric Cohort.

OBJECTIVES: To identify associations between augmented renal clearance (ARC) in pediatric patients treated for suspected sepsis and vancomycin pharmacokinetics. ARC has been associated with lower serum drug levels in both adult and pediatric cohorts for multiple drugs. We hypothesize that presence of ARC is associated with subtherapeutic initial vancomycin trough level (VTL). DESIGN: Retrospective study, with patients divided into two groups based on the presence of ARC (estimated glomerular filtration rate [eGFR] above 130 mL/min/1.73 m2) in comparison with VTL. Multivariable logistic regression analysis was performed to evaluate the association between eGFR and subtherapeutic VTL. SETTING: Tertiary children's hospital. PATIENTS: Hospitalized children (0-18 yr) initiated on empiric vancomycin therapy for suspected sepsis. INTERVENTIONS: Retrospective measurement of VTL, eGFR, and clinical variables. MEASUREMENTS AND MAIN RESULTS: Seventy-three patients were treated with empiric vancomycin for sepsis. ARC was present in 32 patients (44%). Subtherapeutic first VTL was present in 40 patients (55%). Higher eGFR was independently associated with subtherapeutic VTL in the multivariable logistic regression analysis. CONCLUSIONS: Subtherapeutic VTL is associated with ARC in our single-center retrospective cohort of children with suspected sepsis. This problem may present a potential risk of treatment failure in Gram-positive sepsis or longer time to clinical response. Prospective studies to investigate the clinical significance and effect of optimizing vancomycin dose in patients with ARC are recommended.

Fluid balance assessment in pediatric hemodialysis patients by using whole-body bioimpedance spectroscopy (WB-BIS).

BACKGROUND: Fluid overload is a major factor in morbidity and mortality in dialysis patients. Whole-body bioimpedance spectroscopy (WB-BIS) is a noninvasive method for assessing fluid status. We hypothesized that fluid status measurement of changes in total body water (TBW), extracellular fluid (ECF), and intracellular fluid (ICF) by WB-BIS would correlate with the weight (Wt) changes before and after hemodialysis (HD) and the amount of ultrafiltration (UF) in pediatric HD patients. We also examined the relationship between the ECF percent of total body water (ECF%) and ECF/ICF ratio with the pre-HD systolic blood pressure percentile (SBP%ile). METHODS: WB-BIS measurements were made both before and after HD on three separate occasions in each patient. Pre- and post-HD Wt, BP, and UF volumes were collected on the day of BIS measurement. RESULTS: At total of 96 measurements were obtained from 16 HD patients. There were 6 females (mean age: 13.2 ± 4.5 yrs). UF correlated with changes in weight, TBW and ECF (p < 0.001) but not with ICF changes (p = 0.345). Pre-HD SBP%ile correlated with ECF%. CONCLUSIONS: Our findings suggest that WB-BIS can be used to monitor the fluid status in pediatric HD patients. The fluid that is removed from the patient during the HD treatment primarily comes from the ECF and not the ICF. Mobilization of fluid from the ICF appears to be delayed. Patients with significantly higher pre-HD ECF% and ECF/ICF ratio had higher pre-HD systolic BP. A higher resolution version of the Graphical abstract is available as Supplementary information.

Clonidine for the Treatment of Agitation After Dexmedetomidine Discontinuation in Pediatric Patients: A Retrospective Cohort Study.

OBJECTIVE: Dexmedetomidine has become a widely used drug in PICUs for sedation. We aim to determine the effects of clonidine on pediatric patients after dexmedetomidine use. METHODS: This was a retrospective cohort study that evaluated all pediatric patients admitted to a tertiary PICU who received dexmedetomidine infusion for >48 hours. Outcomes in patients exposed to clonidine (CLON) were compared with those of patients who were not exposed (NoCLON). RESULTS: A total of 216 patients were included in this study (43 CLON and 173 NoCLON). The primary outcome, agitation, was less in the CLON cohort (9.3%) than in the NoCLON cohort (9.3% versus 29.5%, respectively; p < 0.01). Hospital LOS was longer in the CLON group (59 versus 20 days, p < 0.01), as was PICU LOS (37.4 versus 11.1 days, p < 0.01). There was no significant difference in the occurrence of increased heart rate or blood pressure between the 2 cohorts. Patients exposed to concurrent midazolam and opioid infusions had higher incidence of agitation when they did not receive clonidine (CLON 8% versus NoCLON 37%, OR 0.15; 95% CI, 0.05-0.51; p < 0.01). In contrast, there was no difference in the incidence of agitation for the CLON group versus the NoCLON group when dexmedetomidine was administered alone (25% versus 19%, OR 1.4; p = 0.99). CONCLUSIONS: Our study confirms the importance and effectiveness of clonidine to treat agitation after dexmedetomidine discontinuation. A validated withdrawal scoring tool can help better define dexmedetomidine withdrawal in pediatric patients.

Early Fluid Accumulation and Intensive Care Unit Mortality in Children Receiving Extracorporeal Membrane Oxygenation.

Purpose of this study was to evaluate the impact of early fluid accumulation and renal dysfunction on mortality in children receiving extracorporeal membrane oxygenation (ECMO). Retrospective cohort study of neonatal and pediatric patients who received ECMO between January 2010 and December 2012 in a tertiary level multidisciplinary pediatric intensive care unit (ICU). Ninety-six patients were included, and forty-six (48%) of them received continuous renal replacement therapy (CRRT) during ECMO. Overall mortality was 38.5%. Proportion of patients with acute kidney injury (AKI) at ICU admission was 33% and increased to 47% at ECMO initiation. High-risk diagnoses, extracorporeal cardiopulmonary resuscitation (ECPR), and venoarterial (VA)-ECMO were more common among nonsurvivors. Nonsurvivors had significantly higher proportion of AKI at ICU admission (OR: 2.59, p = 0.04) and fluid accumulation on ECMO day 1 (9% vs. 1%, p = 0.05) compared with survivors. Multivariable logistic regression analysis (adjusted for a propensity score based on nonrenal factors associated with increased mortality) demonstrated that fluid accumulation on ECMO day 1 is significantly associated with increased ICU mortality (OR: 1.07, p = 0.04). Fluid accumulation within the first 24 hours after ECMO cannulation is significantly associated with increased ICU mortality in neonatal and pediatric patients. Prospective studies evaluating the impact of conservative fluid management and CRRT during the initial phase of ECMO may help further define this relationship.

Neurodevelopmental Outcomes in Extracorporeal Membrane Oxygenation Patients: A Pilot Study.

In this pilot study, we evaluated the long-term neurodevelopmental outcomes in neonatal and pediatric patients supported by extracorporeal membrane oxygenation (ECMO) and aimed to identify the role of post-ECMO magnetic resonance imaging (MRI) in predicting neurodevelopmental outcomes. Twenty-nine patients were evaluated using the Ages and Stages Questionnaire, Third Edition (ASQ-3) screening tool. Thirteen were evaluated during their visit at the neurodevelopmental clinic and 16 were interviewed via phone. We also reviewed the post-ECMO MRI brain of these patients and scored the severity of their injury based on the neuroimaging findings. In our cohort of 29 patients, 10 patients (34%) had developmental delay. Of those with developmental delay, 80% were newborns. Sixty-seven percent of patients with developmental delay had moderate to severe MRI abnormalities as compared with only 18% with no developmental deficits (p = 0.03). The younger the age at the time of placement on ECMO, the higher the chances of impaired neurodevelopmental outcome. Long-term follow-up of patients who have survived ECMO, with standardized neuropsychologic testing and post-ECMO imaging, should become the standard of care to improve long-term outcomes. Significant abnormalities on brain MRIs done before discharge correlated with developmental delay on follow-up.

Hypertriglyceridemia with Acute Pancreatitis in Pediatric Diabetic Ketoacidosis: A Case Report.

A 16-year-old female with new-onset diabetic ketoacidosis (DKA) developed acute pancreatitis and hypertriglyceridemia within 24 hours after admission. Her insulin regimen was continued after resolution of DKA, and her pancreatitis with hypertriglyceridemia showed resolution. We are presenting a case of pediatric DKA with hypertriglyceridemia and pancreatitis treated with extended insulin.

Coagulation Profile Is Not a Predictor of Acute Cerebrovascular Events in Pediatric Extracorporeal Membrane Oxygenation Patients.

We performed a retrospective matched case-control study evaluating whether the traditional coagulation profile predicts cerebrovascular events in children on extracorporeal membrane oxygenation (ECMO) in a 71 bed intensive care unit at a tertiary children's hospital. Between 2009 and 2014, 241 neonates and children were initiated on ECMO. The cumulative 5 year incidence of intracranial hemorrhage and infarct was 9.2% and 7.9%, respectively. Thirty-six cases were individually matched 1:1 with control subjects based on age, primary diagnosis, ECMO type, cannulation site, and the presence of pre-ECMO coagulopathy. In-hospital mortality was higher among the cases compared with control subjects (78 vs. 22%, p < 0.01). The median laboratory values that assisted with heparin anticoagulation monitoring (activated clotting time, partial thromboplastin time, and antifactor Xa) and the laboratory data that assisted with blood product administration (platelet count, prothrombin time, fibrinogen, and d-dimer) during the 24 and 72 hour periods before the cerebrovascular event did not show any significant difference between the hemorrhage group and their controls or between the infarct group and their controls. The traditional coagulation profile did not predict acute cerebrovascular events in our cohort. Other markers of neurologic injury on ECMO are yet to be elucidated. Prospective studies to determine better predictors of cerebrovascular complications in pediatric ECMO patients are required.

Pre-ECMO coagulopathy does not increase the occurrence of hemorrhage during extracorporeal support.

INTRODUCTION AND METHODS: Observational retrospective cohort study to evaluate the association between precannulation coagulopathy and the occurrence of hemorrhage during extracorporeal membrane oxygenation (ECMO) in neonatal and pediatric patients at a tertiary children's hospital. RESULTS: Of 241 patients supported with ECMO between January 2009 and December 2014, 175 (72.6%) had precannulation coagulation laboratory data and were included in the study. Of the eligible patients, 84 (48%) were identified as coagulopathic and 91 (52%) were noncoagulopathic. In the coagulopathic group, sepsis (27.3%) was the most common diagnosis leading to ECMO. Over half of the patients in both groups (55.9% of the coagulopathic and 52.7% of the noncoagulopathic group) developed hemorrhagic complications during ECMO support. The most frequent bleeding sites for both groups were the cannulation site (24%), the chest tube site (17%), and intracranial (10%). Pre-ECMO coagulopathy was not associated with higher incidence of hemorrhage during extracorporeal support (p = 0.76). CONCLUSIONS: Pre-ECMO coagulopathy was frequent in our cohort but did not increase the occurrence of hemorrhage during extracorporeal support. Although the identification of factors associated with hemorrhage is key to safely managing ECMO anticoagulation, the implication of precannulation coagulopathy seems to be minimal.

A retrospective study of sedation and analgesic requirements of pediatric patients on extracorporeal membrane oxygenation (ECMO) from a single-center experience.

INTRODUCTION: The purpose of this study is to describe the sedative and analgesic requirements identifying factors associated with medication escalation in neonates and children supported on ECMO. METHOD: Observational retrospective cohort study in a tertiary pediatric intensive care unit from June 2009 to June 2013. RESULTS: One hundred and sixty patients were included in the study. Fentanyl and midazolam were the first line agents used while on ECMO. Higher opiate requirements were associated with younger age (p=0.01), thoracic cannulation (p=0.002), the use of dexmedetomidine (p=0.007) and prolonged use of muscle relaxants (p=0.03). Higher benzodiazepine requirements were associated with younger age (p=0.01), respiratory failure (p=0.02) and the use of second line agents (p=0.002). One third of the patients required second line agents as adjuvants for comfort without a decrease in opiate and/or benzodiazepine requirements. CONCLUSIONS: Providing comfort to subpopulations of pediatric ECMO patients seems to be more challenging. The use of second line agents did not improve comfort in our cohort. Prospective studies are required to optimize analgesia and sedation management in children on ECMO.

Early fluid accumulation in children with shock and ICU mortality: a matched case-control study.

PURPOSE: The purpose of this study was to evaluate the association between early fluid accumulation and mortality in children with shock states. METHODS: We retrospectively reviewed children admitted in shock states to the pediatric intensive care unit (ICU) at a tertiary level children's hospital over a 7-month period. The study was designed as a matched case-control study. Children with early fluid overload, defined as fluid accumulation of ≥10% of admission body weight during the initial 3 days, were designated as the cases. They were compared with matched controls without early fluid accumulation. Cases and controls were matched for age, severity of illness at ICU admission and need for organ support. They were compared with respect to all-cause ICU mortality and other secondary outcomes. RESULTS: A total of 114 children (age range 0-17.4 years; N = 42 cases and 72 matched controls) met the study criteria. Mortality rate was 13% (15/114) in this cohort. Multivariable logistic regression analysis identified the presence of early fluid overload [adjusted odds ratio (OR) 9.17, 95% confidence interval (CI) 2.22-55.57], its severity (adjusted OR 1.11, 95% CI 1.05-1.19) and its duration (adjusted OR 1.61, 95% CI 1.21-2.28) as independent predictors of mortality. Cases had higher mortality than the controls (26 vs. 6 %; p 0.003), and this difference remained significant in the matched analysis (37 vs. 3%; p 0.002). CONCLUSION: The presence, severity and duration of early fluid are associated with increased ICU mortality in children admitted to the pediatric ICU in shock states.

Serum Cystatin C as an Early Marker of Neutrophil Gelatinase-associated Lipocalin-positive Acute Kidney Injury Resulting from Cardiopulmonary Bypass in Infants with Congenital Heart Disease.

OBJECTIVE: Acute kidney injury (AKI) is a common complication resulting from cardiopulmonary bypass in infants. Urinary neutrophil gelatinase-associated lipocalin (NGAL) is a sensitive and specific marker of such injury. In this study, we compared the performance of serum cystatin C (Cys C) and serum creatinine (Cr) as early markers of renal dysfunction in infants undergoing cardiac surgery under bypass. STUDY DESIGN, SETTING, AND PATIENTS: The study was designed as a prospective observational study. The study was conducted in the cardiac intensive care unit (ICU) of a tertiary, academic children's hospital in the United States. Infants (age <1 year) undergoing cardiac surgery under cardiopulmonary bypass were included in the study. OUTCOME MEASURE: Acute kidney injury was defined based on postoperative urinary NGAL. RESULTS: A total of 17 infants were included in the study, and five of them developed AKI. Serum Cys C and Cr levels were measured postoperatively on days 1, 2, and 3, and compared with baseline levels. On postoperative day 2, infants with AKI showed significant change from baseline in serum Cys C levels compared with non-AKI infants (28% vs. -9%, P = .03). The two groups did not show significant differences with respect to rise in serum Cr on any of the 3 postoperative days. Serum Cr on days 1 and 2 showed nonspecific increases in both AKI and non-AKI groups. The area under the receiver operating characteristic curve for day 2 Cys C was 0.87 (95% CI 0.67-1.00) in recognizing NGAL-positive AKI. CONCLUSIONS: Postoperative serum Cys C appears to be a more specific and sensitive biomarker for NGAL-positive AKI resulting from cardiopulmonary bypass surgery in infants undergoing cardiac surgery.

Incidence of acute kidney injury following cardiac catheterization prior to cardiopulmonary bypass in children.

OBJECTIVES: To determine whether contrast administration was a risk factor for development of acute kidney injury (AKI) in cyanotic congenital heart disease (CHD) patients undergoing cardiopulmonary bypass (CPB). BACKGROUND: AKI following CPB or contrast administration is well described. In previous studies, administration of contrast prior to CPB has been shown to increase the risk of AKI. Chronic cyanosis leads to glomerular damage and dysfunction, thus potentially placing this population at increased risk of developing AKI following contrast administration prior to CPB. METHODS: One hundred twenty-two patients with cyanotic CHD undergoing preoperative cardiac catheterization (PCC) and subsequent CPB at Children's Medical Center of Dallas from January 1, 2007 until November 30, 2010 were identified, looking specifically at bi-directional Glenn (BDG) anastomoses and Fontan procedures. One hundred thirteen patients undergoing PCC ≤ 48 hr prior to and > 5 days prior to CPB were included. Occurrence of AKI following CPB was the primary outcome variable. RESULTS: Logistic regression analysis revealed pre-catheterization serum creatinine was a risk factor for post-CPB AKI (P < 0.001) in both Fontan and BDG patients. All other variables were not significantly associated with the development of AKI in either BDG or Fontan patients. Length of stay (hospital or ICU) was not different among the groups regardless of the occurrence of AKI. CONCLUSIONS: In this study of cyanotic CHD patients, contrast administration within 48 hr prior to CPB was not an additional risk factor for the development of AKI.

Timing of continuous renal replacement therapy and mortality in critically ill children*.

OBJECTIVES: Acute kidney injury and fluid overload frequently necessitate initiation of continuous renal replacement therapy in critically ill patients admitted to the ICU. In this study, our primary objective was to determine the effect of timing of initiation of continuous renal replacement therapy on ICU mortality in children requiring renal support for management of acute kidney injury and/or fluid overload. DESIGN: Retrospective cohort study. SETTING: Tertiary level, multidisciplinary PICU. PATIENTS: Children who received continuous renal replacement therapy for management of acute kidney injury and/or fluid overload from January 2000 through July 2009 were included in the study. Patients requiring extracorporeal life support and patients initiated on continuous renal replacement therapy for indications other than acute kidney injury and/or fluid overload were excluded. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Timing of initiation was defined chronologically as time from ICU admission to continuous renal replacement therapy initiation. Three hundred eighty treatments were performed during the study period, of which 190 were eligible and included in the study. Overall ICU mortality was 47% among the study population. Median timing of initiation was higher among nonsurvivors compared with survivors (3.4 vs 2.0 d, p = 0.001). Multivariable logistic regression analysis identified timing of initiation as an independent predictor of mortality with an adjusted odds ratio of 1.05 (95% CI, 1.01, 1.11). Fluid overload, indication for continuous renal replacement therapy initiation, severity of illness at ICU admission, and active oncologic diagnosis were the other independent predictors of mortality that were identified in the final regression model. In the survival analysis, late initiators (> 5 d) had higher mortality than early initiators (≤ 5 d) with a hazard ratio of 1.56 (95% CI, 1.02, 2.37). CONCLUSIONS: Earlier initiation of continuous renal replacement therapy was associated with lower mortality in this cohort of critically ill children. Future studies should focus on early identification of such children who may benefit from early continuous renal replacement therapy initiation.

Using noninvasive hemoglobin measurements to estimate measured hemoglobin in a pediatric hemodialysis unit.

Maintaining a dialysis patient's hemoglobin (Hgb) within a very narrow range can be challenging. Relying on Hgb measurements only once or twice a month can cause large fluctuations in their measurements. Utilizing the Hgb measurement from noninvasive modalities has been studied in adult populations. Our study focused on a pediatric hemodialysis population where blood volumes are much smaller to see if these measurements would adequately work for adjusting erythropoietin dosages. We reviewed our patients' data over a 6-month time period and collected simultaneous measurements of Hgb performed in the laboratory, as well as the initial Crit-Line measurement. We then analyzed the correlation of the two estimates of the patient's Hgb using linear regression as well as Bland-Altman plot and ROCs. There were 407 simultaneous measurements of Hgb in our 32 pediatric hemodialysis patients during this time. Linear regression showed good correlation with an R value of 0.85 (P value < 0.0001). The Bland-Altman plot showed excellent agreement between the two methods. The ROC analysis showed that the performance of the noninvasive Hgb measurement was very good at predicting low measurements. Predicting Hgb less than 10 g/dL had an area under the curve of 0.94. Predicting Hgb greater than 12 g/dL had an area under the curve of 0.91. There were 100 simultaneous measurements of hematocrit. The analysis revealed similar results as the hemoglobin. Noninvasive in-line monitoring of Hgb can be a very useful way of assessing the patient's response to erythropoietin on a day-to-day time frame. Utilizing this methodology should help reduce the variability in the pediatric patients' Hgb measurements.