CUTE RESPIRATORY DISTRESS syndrome (ARDS) was originally termed the adult respiratory distress syndrome because it resembled the clinical picture of infant respiratory distress syndrome (IRDS), and both exhibited hyaline membranes at autopsy. 1,2 Avery and Mead 3 first reported that lung surfactant quantity and activity were abnormal in infants with IRDS and surfactant replacement has subsequently become standard therapy for premature infants at risk for or having IRDS. Petty and Ashbaugh 2 described qualitative and quantitative surfactant deficiencies in their initial description of ARDS and the subsequent scientific literature (recently reviewed by Notter 4) has supported the role of surfactant dysfunction in both ARDS and less severe acute lung injury (ALI). 5 Surfactant replacement in ARDS and ALI has been Author Affiliations and Participating Hospitals and Collaborating Investigators are listed at the end of this article. Financial Disclosures: Dr Willson has received research grants from ONY Inc (Amherst, NY). Dr Egan is president and equity owner of ONY Inc.
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.
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.
We mapped the cytokine response to hematopoietic stem cell transplantation (HSCT) by assaying 51 cytokines and chemokines each week for 100 days in 51 children receiving allogeneic (n = 44) or autologous HSCT (n = 7). Assay values were reported as mean fluorescence intensity (MFI). Log transformation converted MFI to clinically relevant measures (ie, pg/mL). We searched for potential markers of transplant complications by using mixed treatment by subject analysis of variance. Global cytokine secretion in HSCT recipients was significantly lower than in concurrent control patients (n = 11). Coincident with the nadir in WBC count, the concentration of many cytokines declined further by the second and third week. All analytes (except monokine induced by gamma interferon [MIG]) subsequently rebounded by week 4 (coincident with engraftment and recovery of WBC count) but often still remained well below control levels. Concurrent with the collective nadir of multiple cytokines, monocyte chemoattractant protein 1 (MCP-1), growth-regulated oncogene alpha (GRO-a), and leptin surged during weeks 2 to 4. High levels of leptin persisted throughout the 100 post-transplant days. Also during weeks 2 to 4, hepatocyte growth factor (HGF) and IL-6 surged in children with complications but not in those without complications. The peak in HGF was more pronounced in veno-occlusive disease (VOD). HGF and IL-6 secretion rose at least 2 weeks before the clinical diagnosis of VOD or graft-versus-host disease (GVHD). From week 4 onward in all groups, the MFI of the cytokine resistin increased to 5 to 15 times above concurrent control. HGF has now emerged in 3 or more biomarker discovery efforts for GVHD (and in our population for VOD as well). HGF (with or without IL-6) should be investigated as a potential predictive biomarker of VOD or GVHD. Alternatively, the hyperinflammatory “signature” provided by a multicytokine assay may be predictive.
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.
Objectives: The objective of this study is to describe the relative frequency of use of continuous renal replacement therapy, intermittent hemodialysis, and peritoneal dialysis and to analyze characteristics and outcomes of critically ill children receiving renal replacement therapies admitted to PICUs that participate in the Virtual PICU (VPS LLC, Los Angeles, CA) registry. Design: Retrospective, database analysis. Setting: PICUs that participate in the Virtual PICU (VPS LLC) registry. Patients: Critically ill children admitted to PICUs that participate in the Virtual PICU (VPS LLC) registry and received renal replacement therapy from January 1, 2009, to December 31, 2015. Interventions: None. Measurements and Main Results: A total of 7,109 cases (53% males) received renal replacement therapy during the study period. The median age was 72.3 months (interquartile range, 8.4–170 mo) and median length of stay was 8.7 days (interquartile range, 3.3–21.2 d). Caucasians comprised 42% of the cohort and blacks and Hispanics were 16% each. Continuous renal replacement therapy was used in 46.5%, hemodialysis in 35.5% and peritoneal dialysis in 18%. Of the 7,109 cases, 1,852 (26%) were postoperative cases (68% cardiac surgical) and 981 (14%) had a diagnosis of cancer. Conventional mechanical ventilation was used in 64%, high-frequency oscillatory ventilation in 12%, noninvasive ventilation in 24%, and extracorporeal membrane oxygenation in 5.8%. The overall mortality was 22.3%. Patients who died were younger 40.8 months (interquartile range, 1.5–159.4 mo) versus 79.9 months (interquartile range, 12.6–171.7 mo), had a longer length of stay 15 days (interquartile range, 7–33 d) versus 7 days (interquartile range, 3–18 d) and higher Pediatric Index of Mortality 2 score –2.84 (interquartile range, –3.5 to –1.7) versus –4.2 (interquartile range, –4.7 to –3.0) (p < 0.05). On multivariate logistic regression analysis, higher mortality was associated with the presence of cancer (32.7%), previous ICU admission (32%), requiring mechanical ventilation (33.7%), receiving high-frequency oscillatory ventilation (67%), or extracorporeal membrane oxygenation (58.4%), admission following cardiac surgical procedure (29.4%), and receiving continuous renal replacement therapy (38.8%), and lower mortality was associated with hemodialysis (9.8%), and peritoneal dialysis (12.3%) (p < 0.0001). Conclusions: Continuous renal replacement therapy is an increasingly prevalent renal replacement therapy modality used in critically ill children admitted to an ICU. Higher mortality rate with the use of continuous renal replacement therapy should be interpreted with caution.
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