Kevin D. McBryde

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.

Pediatric acute renal failure: outcome by modality and disease

Abstract. Two hundred and twenty-six children who underwent renal replacement therapy (RRT) from 1992 to 1998 were retrospectively reviewed. The mean age, at the onset of RRT, was 74±11.7 months and weight was 25.3±9.7 kg. RRT therapies included hemofiltration (HF; n=106 children for an average of 8.7±2.3 days), hemodialysis (HD; n=61 children for an average of 9.5±1.7 days), and peritoneal dialysis (PD; n=59 children for an average of 9.6±2.1 days). Factors influencing patient survival included: (1) low blood pressure (BP) at onset of RRT (33% survival with low BP, vs 61% with normal BP, vs 100% with high BP; P<0.05), (2) use of pressors anytime during RRT (35% survival in those on pressors vs 89% survival in those not requiring pressors; P<0.01), (3) diagnosis (primary renal failure with a high likelihood of survival vs secondary renal failure; P<0.05), (4) RRT modality (40% survival with HF, vs 49% survival with PD, vs 81% survival with HD; P<0.01 HD vs PD or HF), and (5) pressor use was significantly higher in children on HF (74%) vs HD (33%) or PD (81%; P<0.05 HD vs HF or PD). In conclusion, pressor use has the greatest prediction of survival, rather than RRT modality. Patient survival in children with the need for RRT for ARF is similar to in adults and, as in adults, is best predicted by the underlying diagnosis and hemodynamic stability.

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.

The effect of vascular access location and size on circuit survival in pediatric continuous renal replacement therapy: a report from the PPCRRT registry.

Purpose Well-functioning vascular access is essential for the provision of adequate CRRT However, few data exist to describe the effect of catheter size or location on CRRT performance in the pediatric population. Methods Data for vascular access site, size, and location, as well as type of anticoagulant used and patient demographic data were gathered from the ppCRRT registry. Kaplan-Meier curves were generated and then analyzed by log-rank test or Cox Proportional Hazards model. Results Access diameter was found to significantly affect circuit survival. None of the 5 French catheters lasted longer than 20 hours. Seven and 9 French, but not 8 French, catheters fared worse than larger diameter catheters (p=0.002). Circuits associated with internal jugular access survived longer than subclavian or femoral access associated circuits (p<0.05). Circuit survival was also found to be favorably associated with the CVVHD modality (p<0.001). Conclusions Functional CRRT circuit survival in children is favored by larger catheter diameter, internal jugular vein insertion site and CVVHD. For patients requiring catheter diameters less than 10 French, CRRT circuit survival might be optimized if internal jugular vein insertion is feasible. Conversely, when a vascular access site other than the internal jugular vein is most prudent, consideration should be given to using the largest diameter catheter appropriate for the size of the child. The CVVHD modality was associated with longer circuit survival, but the mechanism by which this occurs is unclear.

Phenylacetate and benzoate clearance in a hyperammonemic infant on sequential hemodialysis and hemofiltration

An infant with a suspected inborn metabolism error was treated with a metabolic cocktail of intravenous sodium phenylacetate (NaPh) and sodium benzoate (NaBz) for hyperammonemia. Sequential hemodialysis (HD) then hemofiltration (HF) was performed due to hyperammonemia. Dialytic and convective clearance (K; ml/min) of ammonia, NaPh, and NaBz was measured. The K of ammonia was 57 and 37 for HD and HF, respectively. The K of NaBz was 37 and 12 for HD and HF, respectively. The K of NaPh was 38 and 14 ml/min for HD and HF, respectively. Despite high clearance of both NaPh and NaBz by HD and HF, the hyperammonemia was corrected.

Comparison of polyclonal induction agents in pediatric renal transplantation.

Abstract: Collective pediatric data suggest that anti‐T‐cell induction therapy with polyclonal antibodies improves the outcome of both short‐ and long‐term renal allograft survival. Polyclonal agents, including thymoglobulin (Thy), a rabbit anti‐thymocyte globulin; Minnesota (horse) anti‐lymphoblast globulin (ALG); and ATGAM, a horse anti‐thymocyte globulin (ATG), all suppress B and T cells. While no specific T‐cell subset marker exists to measure the adequacy of immunosuppression with polyclonal induction, flow cytometric analysis has been used to evaluate the suppression of CD3, CD4, and CD8 cells. Thy is currently undergoing pediatric trials at our center, and we have utilized ATG and ALG in previous pediatric induction protocols. ALG (20 mg/kg/day) and ATG (15 mg/kg/day) were administered over 10 days, whereas Thy (2 mg/kg/day) was given over 5 days. All inductions were accompanied by preoperative intravenous solumedrol (10 mg/kg) followed by oral prednisone (2 mg/kg/day) with taper. Preoperative (1.5 mg/kg/day) and post‐operative (2 mg/kg/day) azathioprine was administered to patients receiving ALG or ATG. Mycophenolate mofetil (MMF) (1200 mg/m2/day) was given to the patients receiving Thy. Post‐operative cyclosporin A (CsA) (14 mg/kg/day) was started (for all groups) once renal function permitted (creatinine < 50% of baseline with brisk urine output) (trough goal 150–250 ng/mL via HPLC). Values for CD3, CD4, and CD8 T cells were determined by flow cytometry in 2–18‐yr‐old renal transplant recipients, comparing the polyclonal induction agent utilized [Thy (n = 8), mean age 9.7 ± 2.3 yr; ATG (n = 13), mean age 10.1 ± 4.1 yr; and ALG (n = 9), mean age 9.3 ± 3.7 yr] over days 2–10 post‐induction. Data were expressed as the average percentage of cells remaining relative to the baseline T‐cell subsets (day 1 = 100%), because of the large age variation present in basal T‐cell subset values. The flow cytometric data suggest that 5 days of Thy appears to give an equal or greater peripheral blood T‐cell suppression by day 10 than a 10‐day course of either ATG or ALG.

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 m2/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 m2/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.

Dialysis Therapies: A National Dialogue

The National Institute of Diabetes, Digestive, and Kidney Diseases-supported Kidney Research National Dialogue asked the scientific community to formulate and prioritize research objectives that would improve our understanding of kidney function and disease. Kidney Research National Dialogue participants identified the need to improve outcomes in ESRD by decreasing mortality and morbidity and enhancing quality of life as high priority areas in kidney research. To reach these goals, we must identify retained toxins in kidney disease, accelerate technologic advances in dialysate composition and devices to remove these toxins, advance vascular access, and identify measures that decrease the burden of disease in maintenance dialysis patients. Together, these research objectives provide a path forward for improving patient-centered outcomes in ESRD.

Hyperosmolar solutions in continuous renal replacement therapy for hyperosmolar acute renal failure: a preliminary report.

Objective: To demonstrate the efficacy of hyperosmolar dialysis and prefilter replacement fluid solutions for continuous renal replacement therapies in the correction of hyperosmolar disorders in acute renal failure. Data Source: An Institutional Review Board-approved pediatric acute renal failure database at the University of Michigan C. S. Mott Children’s Hospital. Study Selection: Three patients were identified meeting the inclusion criteria. The mean serum sodium concentration and plasma osmolality were 158 mmol/L and 357 mOsm/kg, respectively, at the time of initiation of renal replacement therapy. The sodium and/or dextrose concentrations of the dialysate or replacement fluids initially were increased and subsequently decreased to affect the solutions’ calculated osmolalities in an effort to control the rate of decline of the patients’ measured plasma osmolalities. Data Extraction: The case patients’ serum sodium concentrations and plasma osmolalities were measured. Additionally, the sodium and dextrose concentrations of the dialysate or replacement fluid were recorded and the solutions’ osmolalities calculated. Data Synthesis: The three patients experienced a mean rate of reduction of their serum sodium concentration and plasma osmolality of 0.5 mmol/L/hr and 1.6 mOsm/kg/hr, respectively. Conclusions: Hyperosmolar dialysis or prefilter replacement fluid solutions can affect a slow decline in both the serum sodium and plasma osmolality in cases of hyperosmolar acute renal failure.