Joseph V. DiCarlo

Frequency of sub‐clinical cerebral edema in children with diabetic ketoacidosis

Abstract:  Symptomatic cerebral edema occurs in approximately 1% of children with diabetic ketoacidosis (DKA). However, asymptomatic or subclinical cerebral edema is thought to occur more frequently. Some small studies have found narrowing of the cerebral ventricles indicating cerebral edema in most or all children with DKA, but other studies have not detected narrowing in ventricle size. In this study, we measured the intercaudate width of the frontal horns of the lateral ventricles using magnetic resonance imaging (MRI) in children with DKA during treatment and after recovery from the DKA episode. We determined the frequency of ventricular narrowing and compared clinical and biochemical data for children with and without ventricular narrowing. Forty‐one children completed the study protocol. The lateral ventricles were significantly smaller during DKA treatment (mean width, 9.3 ± 0.3 vs. 10.2 ± 0.3 mm after recovery from DKA, p < 0.001). Children with ventricular narrowing during DKA treatment (22 children, 54%) were more likely to have mental status abnormalities than those without narrowing [12/22 vs. 4/19 with Glasgow Coma Scale (GCS) scores below 15 during therapy, p = 0.03]. Multiple logistic regression analysis revealed that a lower initial PCO2 level was significantly associated with ventricular narrowing [odds ratio (OR) = 0.88, 95% confidence interval (95% CI) = 0.78–0.99, p = 0.047). No other variables analyzed were associated with ventricular narrowing in the multivariate analysis. We conclude that narrowing of the lateral ventricles is evident in just over half of children being treated for DKA. Although children with ventricular narrowing did not exhibit neurological abnormalities sufficient for a diagnosis of ‘symptomatic cerebral edema’, mild mental status abnormalities occurred frequently, suggesting that clinical evidence of cerebral edema in children with DKA may be more common than previously reported.

Continuous veno-venous hemofiltration may improve survival from acute respiratory distress syndrome after bone marrow transplantation or chemotherapy.

Purpose Acute respiratory distress syndrome (ARDS) may result from immunologic activity triggered by irradiation and/or chemotherapy. Hemofiltration removes plasma water and soluble components below 25 kilodaltons. The authors hypothesized that early hemofiltration might attenuate the inflammatory component of ARDS, resulting in increased survival in immunocompromised children and young adults. Methods Ten children (6 bone marrow transplantation, 3 chemotherapy, 1 lymphoma/hemophagocytosis) with ARDS (Pao2/Fio2 94 ± 37 torr) received early continuous veno-venous hemodiafiltration as adjunctive therapy for respiratory failure, regardless of renal function. Six children had normal urine output and initial serum creatinine (range 0.1–1.2 mg/dL); four had renal insufficiency (initial creatinine 1.7–2.4 mg/dL). Hemofiltration was instituted coincident with intubation. Respiratory failure was precipitated by Enterobacter sepsis in two patients and by Aspergillus in one. Results Hemodiafiltration was performed for 13 ± 9 days. A high rate of clearance was achieved (52 ± 17 mL/min/1.73 m2). Duration of mechanical ventilation was 14 ± 9 days. Nine of the 10 children were successfully extubated; 8 survived. Conclusions Early hemofiltration may improve survival from ARDS following bone marrow transplantation or chemotherapy. Possible mechanisms include strict fluid balance, immunomodulation through filtration of inflammatory constituents, and immunomodulation through intensive extracellular water exchange that delivers biochemicals to organs of metabolism as well as the hemofilter.

Correlation of Clinical and Biochemical Findings with Diabetic Ketoacidosis-Related Cerebral Edema in Children Using Magnetic Resonance Diffusion-Weighted Imaging

OBJECTIVE To determine clinical and biochemical factors influencing cerebral edema formation during diabetic ketoacidosis (DKA) in children. STUDY DESIGN We used magnetic resonance diffusion-weighted imaging to quantify edema formation. We measured the apparent diffusion coefficient (ADC) of brain water during and after DKA treatment in 26 children and correlated ADC changes with clinical and biochemical variables. RESULTS Mean ADC values were elevated during DKA treatment compared with baseline (8.13 +/- 0.47 vs 7.74 +/- 0.49 x 10(-4) mm(2)/sec, difference in means 0.40, 95% CI: 0.25 to 0.55, P < .001). Children with altered mental status during DKA had greater elevation in ADC. ADC elevation during DKA was positively correlated with initial serum urea nitrogen concentration (correlation coefficient 0.41, P = .03) and initial respiratory rate (correlation coefficient 0.61, P < .001). ADC elevation was not significantly correlated with initial serum glucose, sodium or effective osmolality, nor with changes in glucose, sodium or osmolality during treatment. Multivariable analyses identified the initial urea nitrogen concentration and respiratory rate as independently associated with ADC elevation. CONCLUSIONS The degree of edema formation during DKA in children is correlated with the degree of dehydration and hyperventilation at presentation, but not with factors related to initial osmolality or osmotic changes during treatment. These data support the hypothesis that CE is related to cerebral hypoperfusion during DKA, and that osmotic fluctuations during DKA treatment do not play a primary causal role.

Continuous arteriovenous hemofiltration/dialysis improves pulmonary gas exchange in children with multiple organ system failure

Continuous arteriovenous hemofiltration with or without countercurrent dialysis (CAVH[D]) improved pulmonary gas exchange in eight children with concomitant renal and respiratory failure. Fluid accumulation had increased patient weight to 65.2 +/- 18.4 (SD) kg before therapy. After 48 h of CAVH(D), weight was reduced to 60.3 +/- 15.5 kg (p less than .02). Similarly, PaO2/FIO2 improved from 137 +/- 99 to 207 +/- 83 (p = .009) with PEEP unchanged or decreased. In patients with net negative fluid balance, pulmonary artery wedge pressure decreased (from 21.3 +/- 3.8 to 14.8 +/- 5.4 mm Hg; p less than .05). Colloid osmotic pressure increased (15.2 +/- 4.6 vs. 21.4 +/- 4.7 mm Hg; p less than .001). BUN and serum creatinine were unchanged. Parenteral nutrition infused was 212 +/- 427 ml/day before CAVH(D), and 1928 +/- 567 ml/day during its use (p less than .0001). CAVH(D) in children with multiple organ failure allowed better caloric intake, and led to improvement in pulmonary gas exchange. We speculate that CAVH(D) improves pulmonary gas exchange by removal of body and lung water, or by enhancing clearance of mediators associated with pulmonary dysfunction.

Pulmonary mechanics in infants after cardiac surgery.

ObjectiveTo determine pulmonary mechanical characteristics in neonates after cardiac surgery. DesignA prospective study. SettingA 23-bed, pediatric ICU in a 280-bed childrens hospital. PatientsTwenty-six infants on the first post-operative day after cardiac surgery. MethodsPulmonary mechanics measurements were made during spontaneous breathing, using the esophageal balloon technique and a pneumotachometer. The least mean square method of analysis was used to calculate mechanics. Infants who tolerated withdrawal of mechanical ventilation (group 1) were compared with those infants with respiratory failure (group 2). ResultsSpontaneous respiratory rate, tidal volume, and minute ventilation were similar in groups 1 and 2. Lung compliance was decreased, with no difference between groups. Total lung resistance (34.3 ± 21.6 cm H2O/L·sec in group 1 vs. 136.8 ± 105.8 cm H2O/L·sec in group 2, p = .002) and resistive work of breathing (33.4 ± 29.9 g·cm/kg in group 1 vs. 212.9 ± 173.8 g·cm/kg in group 2, p = .001) were significantly higher in group 2. All infants with a total lung resistance >75 cm H2O/L·sec exhibited respiratory failure (resistance >75 cm H2O/L·sec correlated with respiratory failure, r2 = .73, odds ratio of 70 [confidence interval, 4.4 to 3240], p < .001). ConclusionsIncreased lung resistance identifies neonates with respiratory failure after cardiac surgery. Pulmonary mechanics testing may be useful in timing withdrawal of mechanical ventilation. (Crit Care Med 1992; 20:22)

Post hoc analysis of calfactant use in immunocompromised children with acute lung injury: Impact and feasibility of further clinical trials.

Objective: To assess the impact of calfactant (a modified natural bovine lung surfactant) in immunocompromised children with acute lung injury and to determine the number of patients required for a definitive clinical trial of calfactant in this population. Design: Post hoc analysis of data from a previous randomized, control trial. Setting: Tertiary care pediatric intensive care units. Patients: All children, defined as immunocompromised, enrolled in a multicenter, masked, randomized, control trial of calfactant for acute lung injury conducted between July 2000 and July 2003. Interventions: Patients received either an intratracheal instillation of calfactant or an equal volume of air placebo in a protocolized manner. Measurements and Main Results: Eleven of 22 (50%) calfactant-treated patients died when compared with 18 of 30 (60%) placebo patients (absolute risk reduction 10.0%, 95% confidence interval [CI] −17.3, 37.3). Among the 23 patients with an initial oxygen index (OI) ≥13 and ≤37, 44% (4 of 9) of calfactant-treated patients died in comparison with 71% (10 of 14) of placebo (absolute risk reduction 27.0%, 95% CI −13.2, 67.2). Only 33% (3 of 9) of calfactant patients died before intensive care discharge in comparison with 71% (10 of 14) of placebo (absolute risk reduction 38.1%, 95% CI −0.7, 76.9). Calfactant therapy was associated with improved oxygenation in these 23 patients. Using an OI entry criterion of (13 ≤ OI ≤ 37), stratifying on the presence of hematopoietic stem cell transplantation, and accepting the 27% difference in mortality observed in this analysis, 63 patients would be required in each arm of a randomized, control trial to demonstrate a significant effect of calfactant on mortality in this patient population assuming a two-sided alpha of 0.05 and a power of 0.85. Conclusions: These preliminary data suggest a potential benefit of calfactant in this high-risk population. A clinical trial powered to appropriately assess these findings seems warranted and feasible.

Elevated serum amylase and lipase in pediatric diabetic ketoacidosis

Objectives: Pancreatic enzyme concentrations are frequently elevated in children with diabetic ketoacidosis (DKA). We sought to determine the clinical and biochemical characteristics associated with patients with these elevations. Our hypothesis was that pancreatic enzyme elevations would be associated with biochemical markers of hypoperfusion. Design: Prospective cohort study. Setting: Three university-affiliated children’s hospitals. Patients: We collected data on consecutive children <18 yrs of age hospitalized with the diagnosis of DKA. Interventions: Serum electrolyte and lactate concentrations and venous pH and Pco2 were measured every 3 hrs from hours 0 to 12 and then every 6 hrs until hour 24. Serum calcium, phosphate, and magnesium concentrations were measured every 6 hrs from hours 0 to 24. Serum amylase, lipase, and triglyceride concentrations were measured at hour 0 and then 12, 24, and 48 hrs after the initiation of therapy. Measurements and Main Results: We performed multivariable analyses to test for associations between clinical variables and pancreatic enzyme elevation in 67 children with DKA. Lipase was elevated in 21 (31%) and amylase in 16 (24%) of the children. Pancreatic enzyme values peaked 12–24 hrs after admission. There was no significant correlation between pancreatic enzyme elevation and abdominal pain. In multivariable analyses, an elevated blood urea nitrogen (BUN) concentration was associated with elevated serum amylase (odds ratio 1.04 per unit increase; 95% confidence interval, 1.01–1.09; p = .02), and elevated BUN concentrations and hypophosphatemia were associated with elevated serum lipase (odds ratio 1.04 per unit increase; 95% confidence interval, 1.00–1.08; p = .04; and odds ratio 0.35 per unit increase; 95% confidence interval, 0.15–0.81; p = .01, respectively). Conclusions: Elevation of pancreatic enzymes is common in children with DKA, but clinical pancreatitis is rare. Pancreatic enzyme levels reach a peak 12–24 hrs after initiation of treatment for DKA. Pancreatic enzyme elevation is associated with increased BUN concentrations at presentation but is not associated with abdominal pain.

The hemophagocytic syndrome: titrating continuous hemofiltration to the degree of lactic acidosis.

In 3 cases of severe multiple organ failure due to hemophagocytic lymphohistiocytosis (HLH) in children, the authors demonstrate the utility of continuous hemofiltration in attenuating the consequences of excess cytokine activity, with therapy titrated to the degree of lactic acidosis. HLH was diagnosed in 3 encephalopathic children with multiple organ failure, elevated ferritin (49,396–237,582 pmol/L; or 21,983–105,733 ng/mL), elevated serum triglyceride, and depressed cell lines. One had a known malignancy, one had EBV-associated lymphoproliferative disease, and one was previously healthy. Continuous hemofiltration was initiated, with the ultrafiltrate production rate and countercurrent dialysate flow titrated to metabolic acidosis as reflected by the serum lactate (maximum 3.5 mmol/L or 31.6 mg/dL). Hemofiltration was titrated upward until lactic acidosis resolved, through clearance of lactate or interruption of excess cytokine-driven activity; maximum prescription was 2000 mL/h ultrafiltrate production plus 2500 mL/h dialysate flow. Stability was achieved with hemofiltration, then substantial resolution occurred with treatment according to the HLH-94 protocol (dexamethasone, cyclosporin, VP-16, intrathecal methotrexate). One child succumbed to candidiasis. Another made a full recovery. A third succumbed to his primary malignancy. HLH should be suspected in unexplained or unresolving multiple organ failure. Titration of hemofiltration based on measurable parameters of cellular metabolism (e.g., lactate, base deficit) may stabilize the child with metabolic acidosis long enough to allow proper diagnosis and institution of definitive therapy. Hemofiltration is not a panacea but rather a stabilizing mechanism, with poorly understood effects on interstitial water and solute flux, that facilitates recovery over weeks, not days.

Toxic Shock Syndrome With Staphylococcus aureus Exit-Site Infection in a Patient on Peritoneal Dialysis

Toxic shock syndrome (TSS) associated with exit-site infection but without peritonitis has not been described. We report a case of TSS with an isolated Staphylococcus aureus exit-site infection in a boy on chronic peritoneal dialysis. The exit site had minimal erythema and no purulence. This report re-emphasizes the fact that mildly appearing cutaneous infections in patients with chronic renal failure may have significant consequences. Particular attention should be given to patients who present with constitutional symptoms that may be of short duration. The importance of culturing all sites in such cases is highlighted. The prevalence of TSS with exit-site infections is unknown, but TSS should be considered in patients presenting with similar features.