Brady S. Moffett

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 Childrens 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.

Acute kidney injury in non-critically ill children treated with aminoglycoside antibiotics in a tertiary healthcare centre: a retrospective cohort study

BACKGROUND Aminoglycosides (AG) cause acute kidney injury (AKI), but the incidence and severity distribution are unclear, particularly in non-critically ill children. We determined the incidence, severity and risk factors of AG-associated AKI and assessed for associations with longer hospitalization and higher costs. METHODS At Texas Childrens Hospital, we conducted a retrospective cohort study of children treated with AG for ≥ 5 days in 2005, excluding children with admission primary renal diagnoses. AKI was defined by the paediatric Risk, Injury, Failure, Loss, End Stage Kidney Disease (pRIFLE) and Acute Kidney Injury Network (AKIN) definitions. Multiple logistic and linear regression analyses were used to assess independence of associations with outcomes. RESULTS Five hundred and fifty-seven children [mean ± SD age = 8.0 ± 5.9 years, 286 (51%) male, 489 (88%) gentamicin] were studied. The AKI rate was 33% and 20% by pRIFLE and AKIN definitions, respectively. Longer treatment, higher baseline estimated glomerular filtration rate, being on a medicine (versus surgical) treatment service and prior AG treatment were independent risk factors for AKI development. AKI by pRIFLE or AKIN was independently associated with longer hospital stay and higher total hospital costs. The pRIFLE definition was more sensitive for AKI detection, but the AKIN definition was more strongly related to outcomes. CONCLUSIONS AKI is common and associated with poorer outcomes in non-critically ill children treated with AG. Future research should attempt to understand how to best define AKI in the non-critical illness paediatric setting.

Safety of ketorolac in neonates and infants after cardiac surgery

Background:  Ketorolac is an injectable nonsteroidal anti‐inflammatory drug that is often used as a transitional short‐term analgesic to treat moderate pain and to decrease opioid use. There is a paucity of literature documenting the safety of using ketorolac in neonates and infants after cardiac surgery.

Incidence and treatment of chylothorax after cardiac surgery in children: analysis of a large multi-institution database.

OBJECTIVE There is limited information regarding the true incidence of and risk factors for chylothorax after pediatric cardiac surgery. The objective of this study was to determine, from a large multi-institution database, incidence, associated factors, and treatment strategy in patients undergoing pediatric cardiac surgery. METHODS All patients younger than 18 years in the Pediatric Health Information System (PHIS) database who underwent congenital heart surgery or heart transplant from 2004 to 2011 were included. Procedure complexity was assessed by Risk Adjustment for Congenital Heart Surgery-1. RESULTS In all, 77,777 patients (55% male) of median age 6.7 months were included. Overall incidence of chylothorax was 2.8% (n = 2205), significantly associated with increased procedure complexity, younger age, genetic syndromes, vein thrombosis, and higher annual hospital volume. Patients with multiple congenital procedures had the highest incidence. Incidence increased with time, from 2% in 2004 to 3.7% in 2011 (P < .0001). Chylothorax was associated with longer stay (P < .0001), increased adjusted risk for in-hospital mortality (odds ratio, 2.13; 95% confidence interval, 1.75-2.61), and higher cost (P < .0001), regardless of procedure complexity. Of all patients with chylothorax, 196 (8.9%) underwent thoracic duct ligation or pleurodesis a median of 18 days after surgery. Total parenteral nutrition, medium-chain fatty acid supplementation, and octreotide were used in 56%, 1.7%, and 16% of patients, respectively. CONCLUSIONS Chylothorax is a significant problem in pediatric cardiac surgery and is associated with increased mortality, cost, and length of stay. Strategies should be developed to improve prevention and treatment.

Renal effects of fenoldopam in critically ill pediatric patients: A retrospective review.

Objective: Published data describe the use of fenoldopam in adults for treatment of oliguria/anuria and for renal perfusion and protection, but pediatric data are scant. We assessed the effects of fenoldopam on urine output and potential deleterious changes in hemodynamics or serum creatinine in children. Design: Retrospective analysis. Setting: Academic institution. Patients: All patients ≤18 yrs old at our institution who received ≥24 hrs of fenoldopam therapy. Exclusion criteria included mechanical circulatory support, initiation of fenoldopam in the operating room, and age >18 yrs. Interventions: None. Measurements and Main Results: Demographics, renal function, fenoldopam dosing, concomitant inotropes, and inotrope score data were collected and analyzed. Thirteen patients (age 0.3–18.7 yrs, median 5.5 yrs) received a mean infusion dose of 0.07 ± 0.08 &mgr;g/kg/min (range 0.01–0.26 &mgr;g/kg/min) over the first 24 hrs of therapy. Eight patients received fenoldopam to augment urine output, and five patients received fenoldopam to increase renal perfusion. Nine (69%) patients received dopamine concurrently. Mean inotrope score at the beginning of therapy was 11.3 ± 7.6 and did not change during therapy. Mean urine output increased from 1.82 ± 1.5 mL/kg/hr to 2.74 ± 1.4 mL/kg/hr (p = .009) in the first 24 hrs of fenoldopam therapy. No change in serum creatinine occurred (p not significant). Blood urea nitrogen was significantly different from baseline (41.7 ± 18.7 vs. 49.0 ± 19.8 mg/dL, p = .02). Patients with lower baseline urine output had a greater increase in urine output with fenoldopam. One patient experienced clinically significant hypotension while receiving fenoldopam, which was thought to be due to a concurrent nitroprusside infusion. Conclusions: Fenoldopam increases urine output in select critically ill pediatric patients without requiring escalation of inotropic support. There were no adverse hemodynamic effects or alterations in serum creatinine. Further prospective pediatric studies to define the role of fenoldopam in children are warranted.

Safety and efficacy of intravenous labetalol for hypertensive crisis in infants and small children.

Objective: To determine the efficacy and safety of labetalol for hypertensive crisis in children ≤24 months of age. Design: Retrospective chart review. Statistical analysis utilized analysis of variance for continuous data, chi-square tests for nominal data, and linear regression. Setting: A 737-bed pediatric teaching institution. Patients: Twenty-seven patients ≤24 months of age were treated with 37 intravenous infusions of labetalol, nicardipine, or nitroprusside for hypertensive crisis or hypertensive urgency. Interventions: None. Measurements and Main Results: The primary end point consisted of time to 20% reduction in systolic blood pressure. Primary safety end points measured the prevalence of deleterious effects of labetalol. Continuous infusion of labetalol reduced mean systolic blood pressure by at least 20% in <8 hrs. This effect was similar to nicardipine and nitroprusside infusions. The reported side effects were similar in each group. Patients receiving labetalol and presenting with ischemic or traumatic brain injury were likely to develop hypotension requiring infusion discontinuation. Conclusions: Continuous intravenous labetalol infusion is efficacious for treatment of hypertensive crisis in children ≤24 months of age. Aside from patients presenting with ischemic or traumatic brain injury, labetalol was safe to use in this population for hypertensive emergencies and had a satisfactory adverse effect profile. Labetalol may reach dose saturation at a much lower dose in young children in comparison to adults. Clinicians should use caution when initiating labetalol infusions in young patients with brain injury.

Evaluation of Sodium Nitroprusside Toxicity in Pediatric Cardiac Surgical Patients

Background: Sodium nitroprusside (SNP) is often used in postoperative pediatric cardiac surgical patients. Cyanide toxicity may occur with the use of SNP. There is a paucity of literature describing dosing parameters or physical signs and symptoms of toxicity with SNP. Objective: To determine the incidence of cyanide toxicity in postoperative pediatric cardiac surgical patients treated with SNP and identify dosing parameters and physical signs and symptoms that may predict elevated cyanide concentrations. Methods: Medical records of patients who received SNP in the pediatric cardiac intensive care unit from January 2002 through December 2002 were identified and evaluated for cyanide and thiocyanate levels, dosing, and signs and symptoms of toxicity. Patients were included if they had received SNP after cardiac surgery, were 18 years of age or less, and had at least one cyanide or thiocyanate level determined while receiving therapy. Patients were excluded if they had received sodium thiosulfate. The Mann-Whitney U test was used to determine significant differences in mean dose, duration of infusion, renal function, serum lactate, and acid-base status between groups with elevated or nonelevated levels. Logistic regression and receiver operator curve were used to determine variables associated with elevated levels. Relationships between signs and symptoms of toxicity and elevated levels were evaluated with Fishers exact test. Results: Cyanide concentrations were in the toxic range in 7 of 63 (11%) patients. Patients with elevated concentrations had significantly higher mean dose, cumulative dose, and acid-base excess values. Elevated cyanide levels were independently predicted by mean dose, cumulative dose, and acid-base excess values, and a dose of 1.8 μg/kg/min predicted an elevated cyanide concentration with 89% sensitivity and 88% specificity. Adverse events were not reliable predictors of elevated cyanide levels. Conclusions: Mean dose of SNP is the best predictor of elevated cyanide levels. Adverse events commonly associated with cyanide toxicity may not be reliable indicators of elevated cyanide concentrations.

Vancomycin-associated acute kidney injury in pediatric cardiac intensive care patients.

OBJECTIVE Acute kidney injury (AKI) is a significant source of morbidity among critically ill pediatric patients, including those that have undergone cardiac surgery. Vancomycin may contribute to AKI in pediatric patients admitted to a cardiac intensive care unit. DESIGN AND SETTING Patients admitted to the cardiac intensive care unit at Texas Childrens Hospital and received vancomycin over a 4-year period were included in a case-control study. Patients were excluded if they underwent renal replacement therapy during vancomycin therapy. Patient demographic and disease state variables, vancomycin therapy variables, and use of other nephrotoxic medications were collected. The overall incidence of AKI was calculated based on doubling of serum creatinine during or within 72 hours of vancomycin therapy (vancomycin-associated AKI [vAKI]). Patients who developed vAKI were matched with three patients who did not develop vAKI, and conditional logistic regression was used to determine independent risk factors for vAKI. RESULTS A total of 418 patients met study criteria (males 57.8%) and infants (31 days to 2 years) were the most populous age group (48.6%). Vancomycin-associated AKI occurred in 30 patients (7.2%), which resulted in a total of 120 patients (30 cases; 90 controls). No significant differences were noted in vancomycin dosing between groups. Vancomycin-associated AKI patients were less likely to have undergone cardiac surgery (P < .05), more likely to have undergone extracorporeal membrane oxygenation (P < .05), and had greater exposure to nephrotoxic medications (P < .05). A conditional logistic regression model identified extracorporeal membrane oxygenation as associated with vAKI (odds ratio 14.4, 95% confidence interval 1.02-203, P = .048) and patients with prior cardiovascular surgery (odds ratio 0.10, 95% confidence interval 0.02-0.51, P < .01) or an elevated baseline serum creatinine (odds ratio 0.009, 95% confidence interval 0.0002-0.29, P < .01) as less likely to develop vAKI. CONCLUSIONS Vancomycin-associated AKI occurs infrequently in the pediatric cardiac intensive care population and is strongly associated with patient critical illness.

Infectious Complications and Outcomes in Children Supported with Left Ventricular Assist Devices

BACKGROUND Infectious complications constitute a major cause of morbidity and death in adult patients supported with left ventricular assist devices (VADs). The incidence and patient outcomes related to infectious complications in pediatric patients on VAD support remain largely unknown. The aim of this study was to determine the incidence of infection among pediatric VAD recipients and to characterize the microbiology, associated risk factors, and clinical outcome. METHODS We conducted a retrospective record review of all patients undergoing VAD support for ≥2 weeks at Texas Childrens Hospital from June 1999 to December 2011. Infections were categorized as VAD-specific, VAD-related, or non-VAD-related using the International Society for Heart and Lung Transplantation (ISHLT) definitions for VAD infections. RESULTS Fifty-two VADs were implanted in 51 patients; of these, 35 patients (69%) had 92 infections while receiving VAD support. These included 10 VAD-specific infections, 23 VAD-related infections, and 59 non-VAD infections. The overall rate of VAD infections (specific + related) was 8/1,000 days of VAD support. The most common pathogens were Staphylococcus aureus, coagulase-negative staphylococci, Pseudomonas aeruginosa, and Candida spp. Of 8 deaths that occurred during VAD support, 3 (37.5%) were directly related to infections. Continuous-flow VAD (p = 0.0427) and prior cardiac transplantation with rejection (p = 0.0191) were significantly associated with development of VAD infections. CONCLUSIONS Infectious complications are common in pediatric patients undergoing VAD support. VAD infections do not prevent successful cardiac transplantation in children.

Sodium nitroprusside induced cyanide toxicity in pediatric patients

Background: Sodium nitroprusside (SNP) is often used as a continuous infusion intravenous vasodilator in pediatric patients. However, cyanide toxicity can occur with SNP therapy. Scant literature is available determining the safety of SNP therapy, the incidence of cyanide toxicity or the risk factors for cyanide toxicity in pediatric patients. Objective: To review the literature concerning the safety of intravenous SNP with regard to cyanide toxicity in the pediatric patient population. Methods: A MedLine search was used to identify articles pertaining to SNP therapy and cyanide toxicity in pediatric patients. Conclusions: Sodium nitroprusside seems to be safe when used in critically ill pediatric patients. Cyanide toxicity may occur in patients with specific risk factors. Routine monitoring of cyanide levels may not be warranted.