Clinical phenotypes of acute kidney injury are associated with unique outcomes in critically ill septic children.

BACKGROUND: Assessment of acute kidney injury (AKI) in septic patients remains imprecise. In adults, the classification of septic patients by clinical AKI phenotypes (severity and timing) demonstrates unique associations with patient outcome vs. broadly defined AKI. METHODS: In a multinational prospective observational study, AKI diagnosis in critically ill septic children was stratified by duration (transient vs. persistent) and severity (mild vs. severe by creatinine change and urine output). The outcomes of interest were mortality and intensive care unit resource complexity at 28 days. RESULTS: Seven hundred and fifty-seven septic children were studied (male 52.7%, age 4.6 years (1.5-11.9)). Mortality (overall 12.1%) was different between severe AKI and mild AKI (18.3 vs. 4.4%, p < 0.001) as well as intensive care unit (ICU) complexity (overall 34.5%, 45 vs. 21.7%, p < 0.001). Patients with Persistent AKI had fewer ICU-free days (17 (7, 21) vs. 24 (17, 26), p < 0.001) and higher ICU complexity (52.8 vs. 22.9%, p = 0.002) than transient AKI, even after exclusion of patients with early mortality. AKI phenotypes incorporating temporal and severity data correlate with unique survival (range 4.4-21.6%) and ICU-free days (range of 15-25 days) CONCLUSIONS: The outcome of septic children with AKI changes by clinical phenotype. Our findings underscore the importance of prognostic enrichment in sepsis and AKI for the purpose of trial design and patient management. IMPACT: Although AKI occurs commonly in patients with sepsis (S-AKI), outcomes for children with S-AKI varies based on the severity and timing of the AKI. Existing S-AKI pediatric data utilize a broad singular definition of kidney injury. Increasing the precision of AKI classification results in a new understanding of how S-AKI associates with patient outcome. A refined classification of S-AKI identifies subgroups of children, making possible a targeted and a personalized medicine approach to S-AKI study and management.

Racial/Ethnic Minority Children With Cancer Experience Higher Mortality on Admission to the ICU in the United States.

OBJECTIVE: We investigated whether differences in survival exist between children of various racial/ethnic groups with cancer admitted to the PICU. DESIGN: A retrospective multicenter analysis was conducted using Virtual Pediatric Systems data from reporting centers. Demographic information, Pediatric Risk for Mortality III score, and outcome variables were analyzed using mixed-effects logistic regression modeling to assess for differences in mortality. SETTING: One hundred thirty-five PICUs in the United States. PATIENTS: Pediatric patients with cancer admitted to PICUs in the United States. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: This study details the analysis of 23,128 PICU admissions of 12,232 unique oncology patients representing 3% of all PICU admissions with 1,610 deaths (7.0% case fatality). African American (8.5%) and Hispanic children (8.1%) had significantly higher mortality (p < 0.05) compared with Caucasian children (6.3%). Regional analysis showed Hispanic patients to have higher mortality in the West in the United States, whereas African American patients in the South in the United States had higher mortality. A pulmonary disease diagnosis in Hispanics increased odds of mortality (odds ratio, 1.39; 95% CI, 1.13-1.70), whereas a diagnosis of shock/sepsis increased risk for mortality in African Americans (odds ratio, 1.56; 95% CI, 1.11-2.20) compared with Caucasians. There were no differences between races/ethnic groups in the rates of limitations of care. After controlling for Pediatric Risk of Mortality III, PICU length of stay, stem cell transplant status, readmissions, cancer type (solid, brain, hematologic), mechanical ventilation days, and sex, Hispanic (odds ratio, 1.24; 95% CI, 1.05-1.47) and African Americans (odds ratio, 1.37; 95% CI, 1.14-1.66) had significantly higher odds of mortality compared with Caucasians. CONCLUSIONS: The results show that after controlling for severity and cancer type, a child's race, ethnicity, and region of presentation influence mortality in the PICU. This suggests that additional investigation is warranted along with a need to rethink our approach to the evaluation and treatment of critically ill African American and Hispanic children with cancer.

Clinical evaluation of the Prismaflex™ HF 20 set and Prismaflex™ system 7.10 for acute continuous kidney replacement therapy (CKRT) in children.

BACKGROUND: Continuous kidney replacement therapy (CKRT) is a common modality for treatment of severe acute kidney injury (AKI) in children. Adult technologies routinely utilized to provide this therapy have a large extracorporeal volume. The Prismaflex™ HF20 filter set has a relatively low extracorporeal blood volume of 60 mL, which provides technological benefit for smaller children compared with current filter sets available in the USA. METHODS: We conducted a multicenter, open-label single group study to evaluate whether the Prismaflex™ HF20 filter set delivers efficacious and safe CKRT to support patients with AKI, fluid overload, or both in pediatric patients weighing ≥ 8 to 20 kg. RESULTS: Twenty-three patients were enrolled between April 24, 2016 and April 8, 2018. The mean reduction in blood urea nitrogen from baseline to 24 h was 58.12 ± 20.08% (95% CI, - 68.45 and - 47.79 (p = 0.0008)). Median cumulative normalized effluent rate at 24 h was 60.8 mL/kg/h (25.9, 83.7). None of the patients participating in the study suffered a serious adverse event; thus, no obvious safety concerns were noted. CONCLUSIONS: We suggest that the Prismaflex HF20™ filter set used in conjunction with the Prismaflex™ System Software Version 7.10 or 7.20 is a suitable alternative to larger filter sets for use in pediatric patients weighing less than 20 kg. Graphical abstract.

A prospective multi-center quality improvement initiative (NINJA) indicates a reduction in nephrotoxic acute kidney injury in hospitalized children.

Nephrotoxic medication (NTMx) exposure is a common cause of acute kidney injury (AKI) in hospitalized children. The Nephrotoxic Injury Negated by Just-in time Action (NINJA) program decreased NTMx associated AKI (NTMx-AKI) by 62% at one center. To further test the program, we incorporated NINJA across nine centers with the goal of reducing NTMx exposure and, consequently, AKI rates across these centers. NINJA screens all non-critically ill hospitalized patients for high NTMx exposure (over three medications on the same day or an intravenous aminoglycoside over three consecutive days), and then recommends obtaining a daily serum creatinine level in exposed patients for the duration of, and two days after, exposure ending. Additionally, substitution of equally efficacious but less nephrotoxic medications for exposed patients starting the day of exposure was recommended when possible. The main outcome was AKI as defined by the Kidney Disease Improving Global Outcomes (KDIGO) serum creatinine criteria (increase of 50% or 0.3 mg/dl over baseline). The primary outcome measure was AKI episodes per 1000 patient-days. Improvement was defined by statistical process control methodology and confirmed by Autoregressive Integrated Moving Average (ARIMA) modeling. Eight consecutive bi-weekly measure rates in the same direction from the established baseline qualified as special cause change for special process control. We observed a significant and sustained 23.8% decrease in NTMx-AKI rates by statistical process control analysis and by ARIMA modeling; similar to those of the pilot single center. Thus, we have successfully applied the NINJA program to multiple pediatric institutions yielding decreased AKI rates.

Evidence-based development of a nephrotoxic medication list to screen for acute kidney injury risk in hospitalized children.

PURPOSE: Medications are commonly associated with acute kidney injury (AKI). However, in both clinical practice and research, consideration of specific medications as nephrotoxic varies widely. The Nephrotoxic Injury Negated by Just-in-time Action quality improvement collaborative was formed to focus on prevention or reduction of nephrotoxic medication-associated AKI in noncritically ill hospitalized children. However, there were discrepancies among institutions as to which medications should be considered nephrotoxic. The collaborative convened a Nephrotoxic Medication (NTMx) Subcommittee to develop a consensus for the classification of nephrotoxic medications. SUMMARY: The NTMx Subcommittee initially included pediatric nephrologists, a pharmacist, and a pediatric intensivist. The committee reviewed NTMx lists from the collaborative and identified changes from the initial NTMx list. The NTMx Subcommittee conducted a literature review of the disputed medications and assigned an evidence grade based on the reported association with nephrotoxicity and the quality of the data. The association between medication exposure and AKI was also determined using administrative data from the Pediatric Health Information Systems database. The NTMx Subcommittee then came to a majority consensus regarding which medications should be included on the list. The subcommittee's recommendations were presented to the larger collaborative for approval, and consensus was achieved. The list continues to be reviewed and updated annually. CONCLUSION: Formation of a multicenter quality-improvement initiative exposed current limitations as to which medications are considered nephrotoxic in clinical and research settings and presented an opportunity to approach this problem using an evidence-based process. A consensus definition of nephrotoxic-medication exposure was achieved.

Comparative Effectiveness of Intranasal Dexmedetomidine-Midazolam versus Oral Chloral Hydrate Targeting Moderate Sedation during Pediatric Transthoracic Echocardiograms.

Objective To compare efficacy and safety of two moderate sedation regimens for transthoracic echocardiography (TTE): intranasal dexmedetomidine-midazolam (DM) versus oral chloral hydrate (CH) syrup. Method This was a retrospective cohort of 93 children under 4 years of age receiving moderate sedation with either DM or CH for TTE from January 2011 through December 2014. Measurements and Main Results Forty-nine patients received oral CH and 44 received the intranasal combination of DM. The demographics between groups were similar except the DM patients were slightly older and heavier (each p < 0.05). Failure rate between groups did not reach statistical significance (CH 14.3% vs. DM 6.8%; p = 0.324). Total sedation to discharge time was similar between groups (CH 89.4 minutes vs. DM 89.6 minute; p = 0.97). Cardiopulmonary data did reveal a significantly lower heart rate (101.9 vs. 91.7; p < 0.001) and respiratory rate (23.4 vs. 21.0, p = 0.03) in the DM group, but no difference in blood pressure measurements or echo determined shortening fraction. Conclusion These data support the use of intranasal DM as a safe and efficacious method of moderate sedation for children undergoing TTE.

Red cell transfusions as an independent risk for mortality in critically ill children.

BACKGROUND: Severity of illness is an important consideration in making the decision to transfuse as it is the sicker patient that often needs a red cell transfusion. Red blood cell (RBC) transfusions could potentially have direct effects and interact with presenting illness by contributing to pathologies such as multi-organ dysfunction and acute lung injury thus exerting a considerable impact on overall morbidity and mortality. In this study, we examine if transfusion is an independent predictor of mortality, or if outcomes are merely a result of the initial severity as predicted by Pediatric Risk of Mortality (PRISM) III, Pediatric Index of Mortality (PIM2), and day 1 Pediatric Logistic Organ Dysfunction (PELOD) scores. METHODS: A single center retrospective study was conducted using data from a prospectively maintained transfusion database and center-specific data at our pediatric ICU between January 2009 and December 2012. Multivariate regression was used to control for the effects of clinical findings, therapy, and severity scores, with mortality as the dependent variable. Likelihood ratios and area under the curve were used to test the fidelity of severity scores by comparing transfused vs. non-transfused patients. RESULTS: There were 4975 admissions that met entry criteria. In multivariate analysis, PRISM III scores and serum hemoglobin were significant predictors of transfusion (p < 0.05). Transfused and non-transfused subjects were distinctly disparate, so multivariate regression was used to control for differences. Severity scores, age, volume transfused, and vasoactive agents were significantly associated with mortality whereas hemoglobin was not. A substantial number of transfusions (45 %) occurred in the first 24 h, and patients transfused later (24-48 h) were more likely to die compared to this earlier time point. Likelihood ratio testing revealed statistically significant differences in severity scoring systems to predict mortality in transfused vs. non-transfused patients. CONCLUSIONS: This study suggests that RBC transfusion is an important risk factor that is statistically independent of severity. The timing of transfusions that related strongest to mortality remained outside the purview of severity scoring, as these happened beyond the timing of data collection for most scoring systems.

The safety of propofol sedation for elective nonintubated esophagogastroduodenoscopy in pediatric patients.

OBJECTIVES: To evaluate the safety of deep sedation provided by pediatric intensivists for elective nonintubated esophagogastroduodenoscopy. DESIGN: Retrospective observational study. SETTING: The sedation program at the Helen DeVos Children's Hospital. PATIENTS: A 4-year retrospective analysis was done on all outpatient elective pediatric esophagogastroduodenoscopy procedures performed in an intensivist run sedation program. Safety was examined by reviewing the occurrence of minor and major adverse effects during esophagogastroduodenoscopy sedation. Interventions were studied and reported. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: During the study period, 12,447 sedations were performed by the pediatric sedation program for various procedures. Two thousand one hundred forty-seven patients received 2,325 sedations (18.6%) for esophagogastroduodenoscopies performed for various indications. During the same time period, 53 (one for every 40 esophagogastroduodenoscopy sedations) were screened, found unsuitable for nonintubated sedation, and referred for general anesthesia. There were 2,254 sedations with propofol, 65 methohexital, five ketamine, and one fentanyl/midazolam sedation. Propofol sedation proved safe with a 2.1% prevalence of minor adverse events and no major events. Methohexital, on the other hand, had higher rate (p < 0.001) of minor events and one patient developed an anaphylactic reaction to its use. Regression analysis showed that other sedative agents were 8.6 times more likely to be associated with complications than propofol (odds ratio, 8.6; 95% CI, 4.1-18.2; p < 0.001). CONCLUSIONS: This study demonstrates that deep sedation for elective esophagogastroduodenoscopies can be provided safely in the appropriately screened patient by nonanesthesiologist physicians in a sedation program. These data suggest that propofol is a safe and effective agent for esophagogastroduodenoscopy sedation.

Continuous renal replacement therapy for children ≤10 kg: a report from the prospective pediatric continuous renal replacement therapy registry.

OBJECTIVE: To report circuit characteristics and survival analysis in children weighing ≤10 kg enrolled in the Prospective Pediatric Continuous Renal Replacement Therapy (ppCRRT) Registry. STUDY DESIGN: We conducted prospective cohort analysis of the ppCRRT Registry to: (1) evaluate survival differences in children ≤10 kg compared with other children; (2) determine demographic and clinical differences between surviving and non-surviving children ≤10 kg; and (3) describe continuous renal replacement therapy (CRRT) circuit characteristics differences in children ≤5 kg versus 5-10 kg. RESULTS: The ppCRRT enrolled 84 children ≤10 kg between January 2001 and August 2005 from 13 US tertiary centers. Children ≤10 kg had lower survival rates than children >10 kg (36/84 [43%] versus 166/260 [64%]; P < .001). In children ≤10 kg, survivors were more likely to have fewer days in intensive care unit prior to CRRT, lower Pediatric Risk of Mortality 2 scores at intensive care unit admission and lower mean airway pressure (P(aw)), higher urine output, and lower percent fluid overload (FO) at CRRT initiation. Adjusted regression analysis revealed that Pediatric Risk of Mortality 2 scores, FO, and decreased urine output were associated with mortality. Compared with circuits from children 5-10 kg at CRRT initiation, circuits from children ≤5 kg more commonly used blood priming for initiation, heparin anticoagulation, and higher blood flows/effluent flows for body weight. CONCLUSION: Mortality is more common in children who are ≤10 kg at the time of CRRT initiation. Like other CRRT populations, urine output and FO at CRRT initiation are independently associated with mortality. CRRT prescription differs in small children.

The Bereaved Parent Needs Assessment: a new instrument to assess the needs of parents whose children died in the pediatric intensive care unit*.

OBJECTIVES: To evaluate the reliability and validity of the Bereaved Parent Needs Assessment, a new instrument to measure parents' needs and need fulfillment around the time of their child's death in the pediatric intensive care unit. We hypothesized that need fulfillment would be negatively related to complicated grief and positively related to quality of life during bereavement. DESIGN: Cross-sectional survey. SETTING: Five U.S. children's hospital pediatric intensive care units. SUBJECTS: Parents (n = 121) bereaved in a pediatric intensive care unit 6 months earlier. INTERVENTIONS: Surveys included the 68-item Bereaved Parent Needs Assessment, the Inventory of Complicated Grief, and the abbreviated version of the World Health Organization Quality of Life questionnaire. Each Bereaved Parent Needs Assessment item described a potential need and was rated on two scales: 1) a 5-point rating of importance (1 = not at all important, 5 = very important) and 2) a 5-point rating of fulfillment (1 = not at all met, 5 = completely met). Three composite scales were computed: 1) total importance (percentage of all needs rated ≥4 for importance), 2) total fulfillment (percentage of all needs rated ≥4 for fulfillment), and 3) percent fulfillment (percentage of important needs that were fulfilled). Internal consistency reliability was assessed by Cronbach's α and Spearman-Brown-corrected split-half reliability. Generalized estimating equations were used to test predictions between composite scales and the Inventory of Complicated Grief and World Health Organization Quality of Life questionnaire. MEASUREMENTS AND MAIN RESULTS: Two items had mean importance ratings <3, and 55 had mean ratings >4. Reliability of composite scores ranged from 0.92 to 0.94. Total fulfillment was negatively correlated with Inventory of Complicated Grief (r = -.29; p < .01) and positively correlated with World Health Organization Quality of Life questionnaire (r = .21; p < .05). Percent fulfillment was also significantly correlated with both outcomes. Adjusting for parent's age, education, and loss of an only child, percent fulfillment remained significantly correlated with Inventory of Complicated Grief but not with World Health Organization Quality of Life questionnaire. CONCLUSIONS: The Bereaved Parent Needs Assessment demonstrated reliability and validity to assess the needs of parents bereaved in the pediatric intensive care unit. Meeting parents' needs around the time of their child's death may promote adjustment to loss.

Nonrenal indications for continuous renal replacement therapy: A report from the Prospective Pediatric Continuous Renal Replacement Therapy Registry Group.

OBJECTIVE: Continuous renal replacement therapy is the most often implemented dialysis modality in the pediatric intensive care unit setting for patients with acute kidney injury. However, it also has a role in the management of patients with nonrenal indications such as clearance of drugs and intermediates of disordered cellular metabolism. MEASUREMENTS AND METHODS: Using data from the multicenter Prospective Pediatric Continuous Renal Replacement Therapy Registry, we report a cohort of pediatric patients receiving continuous renal replacement therapy for nonrenal indications. Nonrenal indications were obtained from the combination of "other" category for continuous renal replacement therapy initiation and patient diagnosis (both primary and secondary). This cohort was further divided into three subgroups: inborn errors of metabolism, drug toxicity, and tumor lysis syndrome. RESULTS: From 2000 to 2005, a total of 50 continuous renal replacement therapy events with nonrenal indications for therapy were included in the Prospective Pediatric Continuous Renal Replacement Therapy Registry. Indication-specific survival of the subgroups was 62% (inborn errors of metabolism), 82% (tumor lysis syndrome), and 95% (drug toxicity). The median small solute dose delivered among the subgroups ranged from 2125 to 8213 mL/1.73 m/hr, with 54%-59% receiving solely diffusion-based clearance as continuous venovenous hemodialysis. No association was established between survival and dose delivered, modality of continuous renal replacement therapy, or use of intermittent hemodialysis prior to continuous renal replacement therapy. CONCLUSIONS: Pediatric patients requiring continuous renal replacement therapy for nonrenal indications are a distinct cohort within the population receiving renal replacement therapy with little published experience of outcomes for this group. Survival within this cohort varies by indication for continuous renal replacement therapy and is not associated with continuous renal replacement therapy modality. Additionally, survival is not associated with small solute doses delivered within a cohort receiving >2000 mL/1.73 m/hr. Our data suggest metabolic control is established rapidly in pediatric patients and that acute detoxification may be provided with continuous renal replacement therapy for both the initial and maintenance phases of treatment using either convection or diffusion at appropriate doses.

Multicenter cohort study of out-of-hospital pediatric cardiac arrest.

OBJECTIVES: To describe a large cohort of children with out-of-hospital cardiac arrest with return of circulation and to identify factors in the early postarrest period associated with survival. These objectives were for planning an interventional trial of therapeutic hypothermia after pediatric cardiac arrest. METHODS: A retrospective cohort study was conducted at 15 Pediatric Emergency Care Applied Research Network clinical sites over an 18-month study period. All children from 1 day (24 hrs) to 18 yrs of age with out-of-hospital cardiac arrest and a history of at least 1 min of chest compressions with return of circulation for at least 20 mins were eligible. MEASUREMENTS AND MAIN RESULTS: One hundred thirty-eight cases met study entry criteria; the overall mortality was 62% (85 of 138 cases). The event characteristics associated with increased survival were as follows: weekend arrests, cardiopulmonary resuscitation not ongoing at hospital arrival, arrest rhythm not asystole, no atropine or NaHCO3, fewer epinephrine doses, shorter duration of cardiopulmonary resuscitation, and drowning or asphyxial arrest event. For the 0- to 12-hr postarrest return-of-circulation period, absence of any vasopressor or inotropic agent (dopamine, epinephrine) use, higher lowest temperature recorded, greater lowest pH, lower lactate, lower maximum glucose, and normal pupillary responses were all associated with survival. A multivariate logistic model of variables available at the time of arrest, which controlled for gender, age, race, and asystole or ventricular fibrillation/ventricular tachycardia anytime during the arrest, found the administration of atropine and epinephrine to be associated with mortality. A second model using additional information available up to 12 hrs after return of circulation found 1) preexisting lung or airway disease; 2) an etiology of arrest drowning or asphyxia; 3) higher pH, and 4) bilateral reactive pupils to be associated with lower mortality. Receiving more than three doses of epinephrine was associated with poor outcome in 96% (44 of 46) of cases. CONCLUSIONS: Multiple factors were identified as associated with survival after out-of-hospital pediatric cardiac arrest with the return of circulation. Additional information available within a few hours after the return of circulation may diminish outcome associations of factors available at earlier times in regression models. These factors should be considered in the design of future interventional trials aimed to improve outcome after pediatric cardiac arrest.

Fluid overload and mortality in children receiving continuous renal replacement therapy: the prospective pediatric continuous renal replacement therapy registry.

BACKGROUND: Critically ill children with hemodynamic instability and acute kidney injury often develop fluid overload. Continuous renal replacement therapy (CRRT) has emerged as a favored modality in the management of such children. This study investigated the association between fluid overload and mortality in children receiving CRRT. STUDY DESIGN: Prospective observational study. SETTING & PARTICIPANTS: 297 children from 13 centers across the United States participating in the Prospective Pediatric CRRT Registry. PREDICTOR: Fluid overload from intensive care unit (ICU) admission to CRRT initiation, defined as a percentage equal to (fluid in [L] - fluid out [L])/(ICU admit weight [kg]) x 100%. OUTCOME & MEASUREMENTS: The primary outcome was survival to pediatric ICU discharge. Data were collected regarding demographics, CRRT parameters, underlying disease process, and severity of illness. RESULTS: 153 patients (51.5%) developed < 10% fluid overload, 51 patients (17.2%) developed 10%-20% fluid overload, and 93 patients (31.3%) developed > or = 20% fluid overload. Patients who developed > or = 20% fluid overload at CRRT initiation had significantly higher mortality (61/93; 65.6%) than those who had 10%-20% fluid overload (22/51; 43.1%) and those with < 10% fluid overload (45/153; 29.4%). The association between degree of fluid overload and mortality remained after adjusting for intergroup differences and severity of illness. The adjusted mortality OR was 1.03 (95% CI, 1.01-1.05), suggesting a 3% increase in mortality for each 1% increase in severity of fluid overload. When fluid overload was dichotomized to > or = 20% and < 20%, patients with > or = 20% fluid overload had an adjusted mortality OR of 8.5 (95% CI, 2.8-25.7). LIMITATIONS: This was an observational study; interventions were not standardized. The relationship between fluid overload and mortality remains an association without definitive evidence of causality. CONCLUSIONS: Critically ill children who develop greater fluid overload before initiation of CRRT experience higher mortality than those with less fluid overload. Further goal-directed research is required to accurately define optimal fluid overload thresholds for initiation of CRRT.

Multicenter cohort study of in-hospital pediatric cardiac arrest.

OBJECTIVES: 1) To describe clinical characteristics, hospital courses, and outcomes of a cohort of children cared for within the Pediatric Emergency Care Applied Research Network who experienced in-hospital cardiac arrest with sustained return of circulation between July 1, 2003 and December 31, 2004, and 2) to identify factors associated with hospital mortality in this population. These data are required to prepare a randomized trial of therapeutic hypothermia on neurobehavioral outcomes in children after in-hospital cardiac arrest. DESIGN: Retrospective cohort study. SETTING: Fifteen children's hospitals associated with Pediatric Emergency Care Applied Research Network. PATIENTS: Patients between 1 day and 18 years of age who had cardiopulmonary resuscitation and received chest compressions for >1 min, and had a return of circulation for >20 mins. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 353 patients met entry criteria; 172 (48.7%) survived to hospital discharge. Among survivors, 132 (76.7%) had good neurologic outcome documented by Pediatric Cerebral Performance Category scores. After adjustment for age, gender, and first documented cardiac arrest rhythm, variables available before and during the arrest that were independently associated with increased mortality included pre-existing hematologic, oncologic, or immunologic disorders, genetic or metabolic disorders, presence of an endotracheal tube before the arrest, and use of sodium bicarbonate during the arrest. Variables associated with decreased mortality included postoperative cardiopulmonary resuscitation. Extending the time frame to include variables available before, during, and within 12 hours following arrest, variables independently associated with increased mortality included the use of calcium during the arrest. Variables associated with decreased mortality included higher minimum blood pH and pupillary responsiveness. CONCLUSIONS: Many factors are associated with hospital mortality among children after in-hospital cardiac arrest and return of circulation. Such factors must be considered when designing a trial of therapeutic hypothermia after cardiac arrest in pediatric patients.

In-hospital versus out-of-hospital pediatric cardiac arrest: a multicenter cohort study.

OBJECTIVES: : To describe a large multicenter cohort of pediatric cardiac arrest (CA) with return of circulation (ROC) from either the in-hospital (IH) or the out-of-hospital (OH) setting and to determine whether significant differences related to pre-event, arrest event, early postarrest event characteristics, and outcomes exist that would be critical in planning a clinical trial of therapeutic hypothermia (TH). DESIGN: : Retrospective cohort study. SETTING: : Fifteen Pediatric Emergency Care Applied Research Network sites. PATIENTS: : Patients aged 24 hours to 18 years with either IH or OH CA who had a history of at least 1 minute of chest compressions and ROC for at least 20 minutes were eligible. INTERVENTIONS: : None. MEASUREMENTS AND MAIN RESULTS: : A total of 491 patients met study entry criteria with 353 IH cases and 138 OH cases. Major differences between the IH and OH cohorts were observed for patient prearrest characteristics, arrest event initial rhythm described, and arrest medication use. Several postarrest interventions were used differently, however, the use of TH was similar (<5%) in both cohorts. During the 0-12-hour interval following ROC, OH cases had lower minimum temperature and pH, and higher maximum serum glucose recorded. Mortality was greater in the OH cohort (62% vs. 51%, p = 0.04) with the cause attributed to a neurologic indication much more frequent in the OH than in the IH cohort (69% vs. 20%; p < 0.01). CONCLUSIONS: : For pediatric CA with ROC, several major differences exist between IH and OH cohorts. The finding that the etiology of death was attributed to neurologic indications much more frequently in OH arrests has important implications for future research. Investigators planning to evaluate the efficacy of new interventions, such as TH, should be aware that the IH and OH populations differ greatly and require independent clinical trials.

Protein and calorie prescription for children and young adults receiving continuous renal replacement therapy: a report from the Prospective Pediatric Continuous Renal Replacement Therapy Registry Group.

OBJECTIVE: Few published reports describe nutrition provision for critically ill children and young adults with acute kidney injury receiving continuous renal replacement therapy. The goals of this study were to describe feeding practices in pediatric continuous renal replacement therapy and to evaluate factors associated with over- and under-prescription of protein and calories. DESIGN: Retrospective database study. SETTING: Multicenter study in pediatric critical care units. PATIENTS: Patients with acute kidney injury (estimated glomerular filtration rate < 75 mL/min/1.73 m at continuous renal replacement therapy initiation) enrolled in the Prospective Pediatric Continuous Renal Replacement Therapy Registry. INTERVENTIONS: None. MEASUREMENTS: Nutrition variables: initial and maximal protein (g/kg/day) and caloric (kcal/kg/day) prescription and predicted resting energy expenditure (kcal/kg/day). We determined factors predicting initial and maximal protein and caloric prescription by multivariate analysis. RESULTS: One hundred ninety-five patients (median [interquartile range] age = 8.1 [12.8] yrs, 56.9% men) were studied. Mean protein and caloric prescriptions at continuous renal replacement therapy initiation were 1.3 +/- 1.5 g/kg/day (median, 1.0; range, 0-10) and 37 +/- 27 kcal/kg/day (median, 32; range, 0-107). Mean maximal protein and caloric prescriptions during continuous renal replacement therapy were 2.0 +/- 1.5 g/kg/day (median, 1.7; range, 0-12) and 48 +/- 32 kcal/kg/day (median, 43; range, 0-117). Thirty-four percent of patients were initially prescribed < 1 g/kg/day protein; 23% never attained > 1 g/kg/day protein prescription. By continuous renal replacement therapy day 5, median protein prescribed was > 2 g/kg/day. Protein prescription practices differed substantially between medical centers with 5 of 10 centers achieving maximal protein prescription of > 2 g/kg/day in > or = 40% of patients. Caloric prescription exceeded predicted resting energy expenditure by 30%-100%. Factors independently associated with maximal protein and caloric prescription while on continuous renal replacement therapy were younger age, initial protein and caloric prescription and number of continuous renal replacement therapy treatment days (p < 0.05). CONCLUSIONS: Protein prescription in pediatric continuous renal replacement therapy may be inadequate. Inter-center variation exists with respect to nutrition prescription. Feeding practice standardization and research in pediatric acute kidney injury nutrition are essential to begin providing evidence-based feeding recommendations.

Continuous renal replacement therapy (CRRT) after stem cell transplantation. A report from the prospective pediatric CRRT Registry Group.

Pediatric stem cell transplant (SCT) recipients commonly develop acute renal failure (ARF). We report the demographic and survival data of pediatric SCT patients enrolled in the Prospective Pediatric Continuous Renal Replacement Therapy (ppCRRT) Registry. Since 1 January 2001, 51/370 (13.8%) patients entered in the ppCRRT Registry had received a SCT. Median age was 13.63 (0.53-23.52) years. The primary reasons for the initiation of continuous renal replacement therapy (CRRT) were treatment of fluid overload (FO) and electrolyte imbalance (49%), FO only (39%), electrolyte imbalance only (8%) and other reasons (4%). The CRRT modalities included continuous veno-veno hemodialysis (CVVHD), 43%, continuous veno-veno hemofiltration (CVVH), 37% and continuous veno-veno hemodiafiltration (CVVHDF), 20%. Seventy-six percent had multi-organ dysfunction syndrome (MODS), 72% received ventilatory support and the mean FO was 12.41 +/- 3.70%. Forty-five percent of patients survived. Patients receiving convective therapies had better survival rates (59% vs 27%, P < 0.05). Patients requiring ventilatory support had worse survival (35% vs 71%, P < 0.05). Mean airway pressure (Paw) at the end of CRRT was lower in survivors (8.7 +/- 2.94 vs 25.76 +/- 2.03 mmH(2)O, P < 0.05). Development of high mean airway pressure in non-survivors is likely related to non-fluid injury, as it was not prevented by early and aggressive fluid management by CRRT therapy.

Demographic characteristics of pediatric continuous renal replacement therapy: a report of the prospective pediatric continuous renal replacement therapy registry.

BACKGROUND: This article reports demographic characteristics and intensive care unit survival for 344 patients from the Prospective Pediatric Continuous Renal Replacement Therapy (ppCRRT) Registry, a voluntary multicenter observational network. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: Ages were newborn to 25 yr, 58% were male, and weights were 1.3 to 160 kg. Patients spent a median of 2 d in the intensive care unit before CRRT (range 0 to 135). At CRRT initiation, 48% received diuretics and 66% received vasoactive drugs. Mean blood flow was 97.9 ml/min (range 10 to 350 ml/min; median 100 ml/min); mean blood flow per body weight was 5 ml/min per kg (range 0.6 to 53.6 ml/min per kg; median 4.1 ml/min per kg). Days on CRRT were <1 to 83 (mean 9.1; median 6). A total of 56% of circuits had citrate anticoagulation, 37% had heparin, and 7% had no anticoagulation. RESULTS: Overall survival was 58%; survival differed across participating centers. Survival was lowest (51%) when CRRT was started for combined fluid overload and electrolyte imbalance. There was better survival in patients with principal diagnoses of drug intoxication (100%), renal disease (84%), tumor lysis syndrome (83%), and inborn errors of metabolism (73%); survival was lowest in liver disease/transplant (31%), pulmonary disease/transplant (45%), and bone marrow transplant (45%). Overall survival was better for children who weighed >10 kg (63 versus 43%; P = 0.001) and for those who were older than 1 yr (62 versus 44%; P = 0.007). CONCLUSIONS: CRRT can be used successfully for a wide range of critically ill children. Survival is best for those who have acute, specific abnormalities and lack multiple organ involvement; sicker patients with selected diagnoses may have lower survival. Center differences might suggest opportunities to define best practices with future study.

Medication errors and patient complications with continuous renal replacement therapy.

Continuous renal replacement therapy (CRRT) is commonly used for renal support in the intensive care unit. While the risk of medication errors in the intensive care unit has been described, errors related specifically to CRRT are unknown. The purpose of this study is to characterize medication errors related to CRRT and compare medication errors that occur with manually compounded solutions versus commercially available solutions. We surveyed three separate internet-based, pediatric list serves that are commonly used for communications for programs utilizing CRRT. Data regarding CRRT practices and medication errors were recorded. Medication errors were graded for degree of severity and compared between programs using manually compounded dialysis solutions versus commercially available dialysis solutions. In a survey with 31 program responses, 18 reported medication errors. Two of the 18 were related to heparin compounding, while 16/18 were due to solution compounding errors. Half of the medication errors were classified as causing harm, two of which were fatal. All medication errors were reported by programs that manually compounded their dialysis solutions. Medication errors related to CRRT are associated with a high degree of severity, including death. Industry-based, commercially available solutions can decrease the occurrence of medication errors due to CRRT.

Zero balance ultrafiltration (Z-BUF) in blood-primed CRRT circuits achieves electrolyte and acid-base homeostasis prior to patient connection.

Infants requiring CRRT present a unique challenge due to the large circuit volume to blood volume ratio. Blood priming is often used, but some patients can become unstable during the initiation of CRRT due to electrolyte and acid-base imbalance. We postulated that using Z-BUF we could normalize electrolytes and improve the acid base status of the prime prior to patient connection. To test this we set up a circuit using the Baxter BM-25 CRRT pump, a polysulfone or AN-69 membrane, and a three-way stopcock. The circuit was primed with a 60/40 mix of expired autologous donor pRBCs and 5% albumin. The modalities of CVVH, CVVHD, and CVVHDF were compared for relative efficacy. Electrolytes, lactate, pH, cytokines (TNF-alpha, IL-1beta, bradykinin, and IL-6) were measured. Plasma hemoglobin levels were also measured before and after the Z-BUF procedure. Bradykinin production and elimination in AN-69 membrane circuits were assessed. All lab values equilibrated by 35 minutes. All CRRT modalities were equally efficacious for Z-BUF. Cytokine production or significant hemolysis was not found. In addition, no bradykinin accumulation occurred in AN-69 membrane-containing circuits. We conclude that Z-BUF is a simple and effective way to normalize electrolyte and acid-base status in the CRRT circuit when blood priming is required.