Véronique Phan

Risk factors of acute renal failure in critically ill children: A prospective descriptive epidemiological study*

Objective: Acute renal failure is a serious condition in critically ill patients, but little literature is available on acute renal failure in critically ill children. The aim of the study was to determine incidence rate, identify risk factors, and describe the clinical outcome of acute renal failure in the pediatric intensive care unit (PICU). Design: Prospective, descriptive study. Setting: A tertiary PICU. Patients: Patients were 1,047 consecutively admitted children over a 1-yr period. Interventions: None. Measurements and Main Results: Acute renal failure was defined as doubling of baseline serum creatinine. A comparison between patients with acute renal failure and without acute renal failure was carried out, and the risk factors playing a significant role in the manifestation of acute renal failure were analyzed. There were 985 cases included in the study, with the incidence rate of acute renal failure in PICU being 4.5%. The most common PICU admission diagnoses in acute renal failure cases were hemolytic uremic syndrome (18.2%), oncologic pathologies (18.2%), and cardiac surgery (11.4%). Significant risk factors for acute renal failure following multivariate analysis were thrombocytopenia (odds ratio, 6.3; 95% confidence interval, 2.5, 16.2), age >12 yrs (odds ratio, 4.9; 95% confidence interval, 1.9, 13), hypoxemia (odds ratio, 3.2; 95% confidence interval, 1.3, 8.0), hypotension (odds ratio, 3.0; 95% confidence interval, 1.2, 7.5), and coagulopathy (odds ratio, 2.7; 95% confidence interval, 1.3, 5.6). The mortality rate was estimated to be higher in patients with acute renal failure compared with patients without acute renal failure (29.6% vs. 2.3%, p < .001). Conclusions: Although not frequent in the PICU, acute renal failure is associated with a significant increase in mortality. The risk factors of acute renal failure are multiple and are often present before PICU admission. A multiple-center study is planned with the intention to confirm these results.

Acute kidney injury is an independent risk factor for pediatric intensive care unit mortality, longer length of stay and prolonged mechanical ventilation in critically ill children: a two-center retrospective cohort study

IntroductionIn adults, small (< 50%) serum creatinine (SCr) increases predict mortality. It is unclear whether different baseline serum creatinine (bSCr) estimation methods affect findings of acute kidney injury (AKI)-outcome associations. We characterized pediatric AKI, evaluated the effect of bSCr estimation approaches on AKI-outcome associations and evaluated the use of small SCr increases to predict AKI development.MethodsWe conducted a retrospective cohort database study of children (excluding postoperative cardiac or renal transplant patients) admitted to two pediatric intensive care units (PICUs) for at least one night in Montreal, QC, Canada. The AKI definition was based on the Acute Kidney Injury Network staging system, excluding the requirement of SCr increase within 48 hours, which was impossible to evaluate on the basis of our data set. We estimated bSCr two ways: (1) the lowest SCr level in the three months before admission or the average age- and gender-based norms (the standard method) or (2) by using average norms in all patients. Outcomes were PICU mortality and length of stay as well as required mechanical ventilation. We used multiple logistic regression analysis to evaluate AKI risk factors and the association between AKI and mortality. We used multiple linear regression analysis to evaluate the effect of AKI on other outcomes. We calculated diagnostic characteristics for early SCr increase (< 50%) to predict AKI development.ResultsOf 2,106 admissions (mean age ± SD = 5.0 ± 5.5 years; 47% female), 377 patients (17.9%) developed AKI (using the standard bSCr method) during PICU admission. Higher Pediatric Risk of Mortality score, required mechanical ventilation, documented infection and having a bSCr measurement were independent predictors of AKI development. AKI was associated with increased mortality (adjusted odds ratio (OR) = 3.7, 95% confidence interval (95% CI) = 2.1 to 6.4, using the standard bSCr method; OR = 4.5, 95% CI = 2.6 to 7.9, using normative bSCr values in all patients). AKI was independently associated with longer PICU stay and required mechanical ventilation. In children with no admission AKI, the initial percentage SCr increase predicted AKI development (area under the curve = 0.67, 95% CI = 0.60 to 0.74).ConclusionsAKI is associated with increased mortality and morbidity in critically ill children, regardless of the bSCr used. Paying attention to small early SCr increases may contribute to early AKI diagnosis in conjunction with other new AKI biomarkers.

Effect of nitisinone (NTBC) treatment on the clinical course of hepatorenal tyrosinemia in Québec.

BACKGROUND Hepatorenal tyrosinemia (HT1, fumarylacetoacetate hydrolase deficiency, MIM 276700) can cause severe hepatic, renal and peripheral nerve damage. In Québec, HT1 is frequent and neonatal HT1 screening is practiced. Nitisinone (NTBC, Orfadin ®) inhibits tyrosine degradation prior to the formation of toxic metabolites like succinylacetone and has been offered to HT1 patients in Québec since 1994. METHODS We recorded the clinical course of 78 Québec HT1 patients born between 1984 and 2004. There were three groups: those who never received nitisinone (28 patients), those who were first treated after 1 month of age (26 patients) and those treated before 1 month (24 patients). Retrospective chart review was performed for events before 1994, when nitisinone treatment began, and prospective data collection thereafter. FINDINGS No hospitalizations for acute complications of HT1 occurred during 5731 months of nitisinone treatment, versus 184 during 1312 months without treatment (p<0.001). Liver transplantation was performed in 20 non-nitisinone-treated patients (71%) at a median age of 26 months, versus 7 late-treated patients (26%, p<0.001), and no early-treated patient (p<0.001). No early-treated patient has developed detectable liver disease after more than 5 years. Ten deaths occurred in non-nitisinone treated patients versus two in treated patients (p<0.01). Both of the latter deaths were from complications of transplantation unrelated to HT1. One probable nitisinone-related event occurred, transient corneal crystals with photophobia. INTERPRETATION Nitisinone treatment abolishes the acute complications of HT1. Some patients with established liver disease before nitisinone treatment eventually require hepatic transplantation. Patients who receive nitisinone treatment before 1 month had no detectable liver disease after more than 5 years.

Circulating Granulocyte Colony-Stimulating Factor, C-X-C, and C-C Chemokines in Children with Escherichia Coli O157:H7 Associated Hemolytic Uremic Syndrome

Leukocytes are implicated in the pathogenesis of diarrhea-associated hemolytic uremic syndrome (D+ HUS). We hypothesized that increased circulating levels of granulocyte colony-stimulating factor (G-CSF), and the chemokines epithelial cell–derived neutrophil-activating protein-78 (ENA-78), growth related oncogen-α (GRO-α), macrophage inflammatory protein-1β (MIP-1β), and monocyte chemotactic protein-1 (MCP-1) are related to the severity of illness in Escherichia coli O157:H7 infections. We compared the circulating concentrations of these mediators in the course of E. coli O157:H7 enteritis, hemorrhagic colitis, and HUS. Our data show that, on admission, children with HUS presented 10-fold abnormally increased levels of G-CSF (p < 0.007), 3-fold increased MIP-1β concentrations (p < 0.001), and 2-fold lower values of ENA-78 (p < 0.0001). One week later, a further 4-fold decrease in ENA-78 concentration was noted (p < 0.0001) whereas MIP-1β levels returned to normal. HUS patients requiring peritoneal dialysis showed 6-fold increased G-CSF (p < 0.001) and 5-fold decreased ENA-78 (p < 0.001) levels. On admission, children with uncomplicated O157:H7 hemorrhagic colitis (HC) presented 3-fold abnormally increased concentrations of G-CSF (p < 0.001) and MIP-1β (p < 0.0001). Those with O157:H7 enteritis but no bloody stools showed higher rates of abnormal GRO-α, MIP-1β, and MCP-1 measurements than children with O157:H7 HC or HUS: GRO-α (50% enteritis, 36% HC, 17% HUS;p < 0.06), MIP-1β (40% enteritis, 22% HC, 11% HUS;p < 0.02), MCP-1 (77% enteritis, 20% HC, 18% HUS;p < 0.0001). The data indicates that GRO-α, MIP-1β, and MCP-1 are produced during E. coli O157:H7 enteritis, whether or not HC or HUS develops. Our data suggest that children with O157:H7 associated HUS may present abnormally increased circulating levels of G-CSF and decreased ENA-78 concentrations. The mechanisms responsible for leukocytes recruitment in O157:H7 infections are unclear and await further studies.

Renal Complications Following Heajt Transplantation in Children: A Single‐Center Study

Renal dysfunction is common following heajt transplantation (Tx) in adults, but little is known in children. Thus, a retrospective chajt review was performed in children who underwent heajt Tx at the Hospital for Sick Children between April 1994 and April 1999. The inclusion criteria were: age <18 years, survival >1 year post‐Tx. The Schwajtz formula was used to calculate glomerular filtration rate (GFR). Decreased GFR was defined as <80 mL/min/1.73 m2. Changes in GFR were analyzed using Repeated Measures Analysis of Variance. Forty‐one eligible children were included. The mean age at Tx was 7 years (range: 1 month to 16.7 years). The mean F/UP was 33 ± 17 months, with 32/41 patients followed for at least 24 months. The GFR was decreased in 42% pre‐Tx, and in 7.3% at the last F/UP (p = 0.0001). GFR did not decline significantly with time after Tx; in fact, GFR increased in the first year and remained stable afterwards (p = 0.0002). Acute renal dysfunction (ARD) episodes were common (12/41 children). Hypertension was diagnosed in 76% of children during the first year post‐Tx, but persisted in only 11 (27%). GFR improves in the majority of children following heajt Tx. ARD episodes are frequent in the post‐Tx period. Hypertension is common but does not persist.

Association of Malodorous Urine With Urinary Tract Infection in Children Aged 1 to 36 Months

OBJECTIVE: To determine whether parental reporting of malodorous urine is associated with urinary tract infection (UTI) in children. METHODS: We conducted a prospective consecutive cohort study in the emergency department of a pediatric hospital from July 31, 2009 to April 30, 2011. All children aged between 1 and 36 months for whom a urine culture was prescribed for suspected UTI (ie, unexplained fever, irritability, or vomiting) were assessed for eligibility. A standardized questionnaire was administered to the parents by a research assistant. The primary outcome measure was a UTI. RESULTS: Three hundred ninety-six children were initially enrolled, but 65 were excluded a posteriori either because a urine culture, although prescribed, was not done (11), was collected by bag (39), and/or showed gross contamination (25). Therefore, 331 children were included in the final analysis. Their median age was 12 months (range, 1–36). Criteria for UTI were fulfilled in 51 (15%). A malodorous urine was reported by parents in 57% of children with UTI and in 32% of children without UTI. On logistic regression, malodorous urine was associated with UTI (odds ratio 2.83, 95% confidence interval: 1.54–5.20). This association remained statistically significant when adjusted for gender and the presence of vesicoureteral reflux (odds ratio 2.73, 95% confidence interval: 1.46–5.08). CONCLUSIONS: Parental reporting of malodorous urine increases the probability of UTI among young children being evaluated for suspected UTI. However, this association is not strong enough to definitely rule in or out a diagnosis of UTI.

Prevention of CMV disease in pediatric kidney transplant recipients: Evaluation of pp67 NASBA-based pre-emptive ganciclovir therapy combined with CMV hyperimmune globulin prophylaxis in high-risk patients

Abstract:  A new prevention strategy for CMV infection was evaluated in our pediatric kidney transplant unit. This approach comprises a pre‐emptive therapy, based upon the monitoring of CMV pp67 mRNA in whole blood by the qualitative NASBA, combined with prophylactic CMV‐IG in high risk (R−/D+) children. Thirty‐one kidney transplant children were followed for six months with serial measurements of CMV pp67 mRNA in the blood. The R−/D+ patients were given prophylactic CMV‐IG for the first 16 wk after transplantation. I.v. ganciclovir was administered upon CMV detection by NASBA and was discontinued after two consecutive negative results. CMV infection, detected by NASBA, developed in 11 (35%) recipients: one (33%) of the R+/D− patients and 10 (72%) of the R−/D+ patients. CMV disease developed in 9.6% of the patients (3/31), exclusively in the R−/D+ group. These three patients presented concurrently with CMV viremia and disease. It is noteworthy that two of the three patients could not receive a complete course of CMV‐IG, and one of the latter two subjects had been treated for acute rejection 15 days before CMV infection. Ganciclovir was given for the 11 cases of primary infection, and for three cases of relapsed CMV infection. pp67 NASBA‐based pre‐emptive ganciclovir therapy, combined with prophylactic CMV‐IG in high‐risk patients leads to a lower rate of CMV disease, as long as a complete course of CMV‐IG has been administered and ganciclovir is given during the period of treatment for acute rejection in high‐risk populations.

Threshold for toxicity from hyperammonemia in critically ill children.

BACKGROUND & AIMS Hyperammonemia results from reduction of hepatocyte function or enzyme of urea cycle deficiency. Hyperammonemia contributes to cerebral edema that may lead to cerebral herniation. The threshold of toxicity of ammonemia is unknown. METHODS We conducted a retrospective observational study in our pediatric intensive care unit. All children who developed hyperammonemia from January 2000 to April 2009 were included. Clinical and laboratory data at admission, specific treatments implemented, and ammonemias the first 7 days after inclusion were collected. The outcome assessed was 28 day mortality. Risk of mortality was estimated by a logistic regression model. RESULTS Ninety patients with liver failure (63.3%) and primary or secondary urea cycle defect (23.3%) were included. Patients with urea cycle defects were more likely to receive ammonia scavengers than patients with liver failure (47.6% versus 3.5%). The 28 day mortality rate was 31.1%. Risk of mortality increased according to the ammonemia within 48 h: odds ratio 1.5, 1.9, 3.3, 2.4 for ammonemia above 100, 150, 200, and 300 μmol/L, respectively. Peak ammonemia ≥200 μmol/L within the first 48 h was an independent risk factor for mortality, with greater risk found in liver failure than in urea cycle defect. CONCLUSIONS Our study identifies a threshold of exposure to ammonia (≥200 μmol/L) above which mortality increases significantly, especially in liver failure. Specific treatments of hyperammonemia are rarely used in liver failure when compared with urea cycle defect even though use of ammonia scavengers may help to decrease ammonemia.

The AMÉLIE project: failure mode, effects and criticality analysis: a model to evaluate the nurse medication administration process on the floor

OBJECTIVE The objective of this article was to critically evaluate the causes of adverse drug events during the nurse medication administration process in paediatric care units in order to identify and prioritize interventions that need to be implemented. METHODOLOGY This is a failure mode, effects and criticality analysis (FMECA) study. A multidisciplinary committee composed of nurses, pharmacists, physicians and risk managers evaluated through consensus the process of administering medications at the Centre hospitalier universitaire de Sainte-Justine. By mapping the process, all the failure modes were identified and associated with at least one cause each. Using a summary grid, each failure mode was evaluated by rating frequency (from 1 to 9), likelihood of failure detection (from 0 to 100%) and severity (from 1 to 9) using adapted versions of already published scales. RESULTS A 10-member committee was set up, and it met eight times between January and April 2010. In the two specialized paediatric units selected (n = 38 beds), an average number of approximately 20 000 drug doses was administered monthly from about 400 non-proprietary names. Through consensus, the committee identified 16 processes and 53 failure modes. While frequency and severity were based on perceptions that could be objectivized with local data and scientific documentation, the likelihood of detection was mainly based on individual perception. CONCLUSION FMECA is a useful approach to improve the medication process.

Molecular Absorbent Recirculating System therapy (MARS®) in pediatric acute liver failure: a single center experience

BackgroundSupportive care as a bridge to transplant or recovery remains challenging in children suffering from acute liver failure (ALF). We report our experience in children using the Molecular Absorbent Recirculating System (MARS®).MethodsRetrospective data from children receiving therapy using MARS® from October 2009 to October 2012 were included in this single-center retrospective study. Patient characteristics, clinical presentation and complications of ALF, clinical and biological data before and after each MARS® session, technical modalities and adverse events were recorded.ResultsA total of six children underwent 17 MARS® sessions during the study period. Two adolescents were treated with the adult filter MARSFLUX® and four infants were treated with the MiniMARS® filter. The mean PEdiatric Logistic Dysfunction (PELOD) score at admission was 19 (range 11–33). All patients were mechanically ventilated, and four had acute kidney injury. The neurological course improved in one case, judged as stable in two cases and worsened in one case; data were unavailable in two cases. Mean serum ammonia levels decreased significantly following treatment with MARS® from an initial 89 ± 29 to 58 ± 35 mcmol/L (p = 0.02). No other significant biological improvement was observed. Hemodynamic status improved/remained unchanged in the adolescent group, but in the infants four of the seven sessions were poorly tolerated and two sessions were aborted. Three patients died, two were successfully transplanted and one recovered without transplantation.ConclusionIn our experience, treatment with MARS® is associated with encouraging results in adolescents, but it needs modification for very sick infants to improve tolerance.