Peter L. Havens

Unmeasured anions identified by the Fencl-stewart method predict mortality better than base excess, anion gap, and lactate in patients in the pediatric intensive care unit

OBJECTIVES This study was undertaken to compare three methods for the identification of unmeasured anions in pediatric patients with critical illness. We compared the base excess (BE) and anion gap (AG) methods with the less commonly used Fencl-Stewart strong ion method of calculating BE caused by unmeasured anions (BEua). We measured the relationship of unmeasured anions identified by the three methods to serum lactate concentrations and to mortality. DESIGN Retrospective cohort study. SETTING Tertiary care pediatric intensive care unit in an academic pediatric hospital. PATIENTS The study population included 255 patients in the pediatric intensive care unit who had simultaneous measurements of arterial blood gases, electrolytes, and albumin during the period of July 1995 to December 1996. Sixty-six of the 255 patients had a simultaneous measurement of serum lactate. MEASUREMENTS AND MAIN RESULTS The BEua was calculated using the Fencl-Stewart method. The AG was defined as (sodium plus potassium) - (chloride plus total carbon dioxide). BE was calculated from the standard bicarbonate, which is derived from the Henderson-Hasselbalch equation and reported on the blood gas analysis. A BE or BEua value of < or =-5 mEq/L or an AG > or =17 mEq/L was defined as a clinically significant presence of unmeasured anions. A lactate level of > or =45 mg/dL was defined as being abnormally elevated for this study. The presence of unmeasured anions identified by significantly abnormal BEua was poorly identified by BE or AG. Of the 255 patients included in the study, 67 (26%) had a different interpretation of acid base balance when the Fencl method was used compared with when BE and AG were used. Plasma lactate concentration correlated better with BEua (r2 = .55; p = .0001) than with AG (r2 = .41; p = .0005) or BE (r2 = .27; p = .025). Mortality was more strongly related to BEua < or =-5 mEq/L (relative risk of death = 10.25; p = .002) than to lactate > or =45 mg/dL (relative risk of death = 2.35; p = .04). In logistic regression analysis, mortality was more strongly associated with BEua (area under the receiver operating characteristic curve = 0.79; p = .0002) than lactate (receiver operating characteristic curve area = 0.63; p = .05), BE (receiver operating characteristic curve area = 0.53; p = .32), or AG (receiver operating characteristic curve area = 0.64; p = .08) in this patient sample. CONCLUSIONS Critically ill patients with normal BE and normal AG frequently have elevated unmeasured anions detectable by BEua. The Fencl-Stewart method is better than BE and similar to AG in identifying patients with high lactate levels. Elevated unmeasured anions identified by the Fencl-Stewart method were more strongly associated with mortality than with BE, AG, or lactate in this patient sample.

A cluster of anaphylactic reactions in children with spina bifida during general anesthesia: Epidemiologic features, risk factors, and latex hypersensitivity

BACKGROUND Anaphylactic reactions (ARs) in high-risk pediatric patients undergoing general anesthesia, especially those with spina bifida, have been attributed to anesthetics, muscle relaxants, antimicrobials, ethylene oxide, and latex. METHODS To identify risk factors for AR during general anesthesia and to investigate the role of latex allergy, we studied epidemiologic and immunologic characteristics of patients with ARs during general anesthesia during a 13-month cluster of such reactions at Childrens Hospital of Wisconsin (case patients). Patients with AR were compared with patients with spina bifida undergoing uneventful general anesthesia during the same period (control patients). For each case patient and control patient, we conducted a chart review; a parental interview; skin prick testing with latex, anesthetics, aeroallergens, and banana extract; ELISA and RAST for latex-specific IgE; a total serum IgE; and an ELISA for IgE antibody to ethylene oxide. RESULTS Anaphylactic reactions occurred exclusively in patients with spina bifida (n = 10) or patients with a congenital urinary tract anomaly (n = 1). Case-patients were more likely than control patients to have a history of asthma (p = 0.002), rubber contact allergy (p = 0.001), food allergy (p = 0.001), rash caused by adhesive tape (p = 0.05), daily rectal disimpaction (p < 0.001), nine or more prior surgical procedures (p < 0.002), latex-specific IgE (p = 0.027), or elevated total serum IgE levels (p = 0.002). Multivariate analysis identified non-white race, rubber contact allergy, history of food allergy, and nine or more surgical procedures as significant independent risk factors. Logistic model equation identified the predicted probability of AR with a sensitivity, specificity, and positive predictive value of 82%, 97%, and 82%, respectively. CONCLUSIONS These findings demonstrate that atopy, especially symptomatic latex allergy, is associated with AR during anesthesia in patients with spina bifida. Until a standardized latex test is available, a medical history of immediate rubber contact allergy, non-white race, food allergy, or nine or more prior surgical procedures can identify patients with spina bifida at highest risk for ARs. A complete history, including rubber contact and food allergy, should be compiled on all patients with spina bifida before surgery.

LYTIC ANTI-ENDOTHELIAL CELL ANTIBODIES IN HAEMOLYTIC-URAEMIC SYNDROME

Sera from 13 of 14 children with acute haemolytic uraemic syndrome (HUS) contained complement-fixing IgG and IgM antibodies that lysed cultured human umbilical vein endothelial cells. In 3 of 3 sera tested, no lysis of dermal fibroblasts was observed. The endothelial cell antigen was lost after treatment of the cells with gamma interferon. In contrast, only 3 of 5 adult patients with acute, non-relapsing, thrombotic thrombocytopenic purpura (TTP) had lytic anti-endothelial antibodies and only 1 of these recognised an antigen lost upon gamma interferon treatment. None of 32 control sera contained lytic anti-endothelial cell antibodies. These data suggest that HUS involves a disorder of immunoregulation and that a unique class of anti-endothelial cell antibodies is produced that may take part in the pathogenesis of vascular injury in HUS.

Trends in mortality in children hospitalized with meningococcal infections, 1957 to 1987

We reviewed charts of 261 children seen at Childrens Hospital of Wisconsin from 1957 to 1987 with culture-proven meningococcemia or meningococcal meningitis, and we analyzed trends in mortality and disease severity for that interval. Overall case fatality was 10%, ranging from 9% in the period 1957 to 1963, to 16% in the period 1980 to 1987 (P = 0.15). The percent of patients admitted with severe disease increased from 14% to 38% (P = 0.001). When stratified by disease severity, case-fatality rates did not change with time. We conclude that technologic advances of the past 30 years had no measurable impact on mortality from meningococcal infection in our hospital and that crude case-fatality rates can be misleading if disease severity is not considered.

Neonatal hemodialysis: effective therapy for the encephalopathy of inborn errors of metabolism.

Maple syrup urine disease and argininosuccinate synthetase deficiency are two of many inborn errors of metabolism that may result in neonatal encephalopathy. Early treatment is designed to suppress endogenous proteolysis and amino acid catabolism with the infusion of glucose, and to remove presumed toxic metabolites. The latter goal has been accomplished with exchange transfusion, 13 peritoneal dialysis, 24 and hemodialysis. 2, 3 We present the cases of two neonates, one with M S U D and the other with argininosuccinate synthetase deficiency. The infants were treated with hemodialysis, during which the clearances of amino acids and ammonium were measured. We examined the hypothesis that hemodialysis is more effective then peritoneal dialysis or exchange transfusion in removing putative toxic metabolites,

Early Volume Expansion During Diarrhea and Relative Nephroprotection During Subsequent Hemolytic Uremic Syndrome

OBJECTIVES To determine if interventions during the pre-hemolytic uremic syndrome (HUS) diarrhea phase are associated with maintenance of urine output during HUS. DESIGN Prospective observational cohort study. SETTINGS Eleven pediatric hospitals in the United States and Scotland. PARTICIPANTS Children younger than 18 years with diarrhea-associated HUS (hematocrit level <30% with smear evidence of intravascular erythrocyte destruction), thrombocytopenia (platelet count <150 × 10³/mm³), and impaired renal function (serum creatinine concentration > upper limit of reference range for age). INTERVENTIONS Intravenous fluid was given within the first 4 days of the onset of diarrhea. OUTCOME MEASURE Presence or absence of oligoanuria (urine output ≤ 0.5 mL/kg/h for >1 day). RESULTS The overall oligoanuric rate of the 50 participants was 68%, but was 84% among those who received no intravenous fluids in the first 4 days of illness. The relative risk of oligoanuria when fluids were not given in this interval was 1.6 (95% confidence interval, 1.1-2.4; P = .02). Children with oligoanuric HUS were given less total intravenous fluid (r = -0.32; P = .02) and sodium (r = -0.27; P = .05) in the first 4 days of illness than those without oligoanuria. In multivariable analysis, the most significant covariate was volume infused, but volume and sodium strongly covaried. CONCLUSIONS Intravenous volume expansion is an underused intervention that could decrease the frequency of oligoanuric renal failure in patients at risk of HUS.

Clinical and epidemiologic characteristics of children hospitalized with 2009 pandemic H1N1 influenza A infection.

Background: In 2009, pandemic H1N1 influenza caused significant morbidity and mortality worldwide. We describe the clinical and epidemiologic characteristics of children and adolescents hospitalized for 2009 H1N1 infections in Milwaukee, Wisconsin from April 2009 to August 2009. Methods: We conducted retrospective chart reviews of hospitalized patients with laboratory-confirmed 2009 H1N1 infections. Data on financial burden associated with these infections were obtained and analyzed. Results: A total of 75 children hospitalized for 2009 pandemic H1N1 infections were identified; the median age was 5 years (range, 2 months–19.2 years); 56% were males; 56% were Non-Hispanic Blacks; and 75% had at least one underlying medical condition. Twenty-four percent had only upper respiratory symptoms. Bacterial coinfections occurred in 1.3%. All but one patient received antivirals, 80% of patients received antibacterials, 18.6% were admitted to the intensive care unit, 6% required mechanical ventilation, 2.6% required extracorporeal membrane oxygenation, and 2.6% died. The total charges incurred for H1N1 influenza hospitalizations were

Incidence and risk factors for venous thromboembolism in critically ill children after trauma.

4,454,191, with individual charges being highest for children >12 years of age. Conclusions: The majority of children with pandemic H1N1 influenza-associated hospitalizations had uncomplicated illness despite the frequent presence of high-risk conditions in our patient population. Laboratory-confirmed 2009 pandemic H1N1 influenza hospitalizations resulted in substantial health care and economic burden during the first wave of the pandemic in spring 2009.

Early Archiving and Predominance of Nonnucleoside Reverse Transcriptase Inhibitor—Resistant HIV-1 among Recently Infected Infants Born in the United States

BACKGROUND Venous thromboembolism (VTE) causes major morbidity in adults after trauma, occurring in up to 50% of patients without prophylaxis. The incidence of VTE after trauma is lower in children. No study has measured the incidence of and risk factors for VTE in critically ill children after trauma. METHODS Nested case-control study of children, younger than 18 years, admitted to the pediatric intensive care unit at a level I trauma center. Three controls were selected for each identified VTE case. RESULTS Nine of 144 children admitted to the pediatric intensive care unit after trauma developed VTE (incidence 6.2%, 95% confidence interval [CI] 2.3-10.2), with a median age of 8.6 years (range, 2.3-17.9). VTE was diagnosed at a median of 9 days after admission, with 67% of VTE located at the site of previous or existing central venous line (CVL). Significant risk factors for thrombosis included parenteral nutrition (odds ratio [OR] 20, 95% CI 1.9-227), CVL (OR 19, 95% CI 2-178), deep sedation (OR 13, 95% CI 1.6-48), neuromuscular blockade (OR 10, 95% CI 1.4-70), inotropic support (OR 10, 95% CI 1.7-59), and recombinant factor VIIa administration (p = 0.012, OR not calculable). Logistic analysis found a 7.9-fold increase in the odds of developing VTE for each additional CVL (p = 0.005), a threefold increase with each additional risk factor present (p = 0.009), and a 1.3-fold increase for an increase in injury severity (p = 0.03). VTE was not associated with sepsis, spinal cord injury, fracture, or elevated D-dimer level. CONCLUSIONS VTE is not a rare event in critically ill children after trauma. Most patients developing thrombosis have multiple risk factors, including poor perfusion, immobility, and presence of a CVL.

Increasing antiretroviral drug access for children with HIV infection.

BACKGROUND The extent to which drug-resistant human immunodeficiency virus type 1 (HIV-1) acquired through mother-to-child transmission (MTCT) or failed chemoprophylaxis populates viral reservoirs and limits responses to antiretroviral treatment in infants is unknown. METHODS We evaluated the presence, type, and persistence of drug-resistant HIV-1 in pretreatment plasma and resting CD4(+) T cells from US infants enrolled in a multicenter, open-label, phase 1/2 treatment trial of lopinavir/ritonavir (Pediatric AIDS Clinical Trials Group Protocol 1030) in young infants. RESULTS Twenty-two consecutively enrolled infants initiating highly active antiretroviral therapy at a median age of 9.7 weeks and treated for up to 96 weeks were studied. Drug-resistant HIV-1 was present in 5 (23.8%) of 21 infants analyzed; 4 (80.0%) had nonnucleoside reverse transcriptase inhibitor (NNRTI)-resistant HIV-1, only 1 of whom had a history of receiving nevirapine chemoprophylaxis. All 4 infants had NNRTI-resistant variants other than the K103N mutation. The fifth infant had the M184V mutation. Drug-resistant virus was archived in the resting CD4(+) T cell latent reservoir in all 5 infants. CONCLUSIONS The high rate, types, and early archiving of drug-resistant HIV-1 suggests that resistance testing be considered for infants, especially when an NNRTI-based regimen is planned. Furthermore, drug-resistance outcomes in infants should be an important secondary end point in MTCT trials.