Nates and Children with Septic Shock. Participants: Society of Critical Care Medicine members with special interest in neonatal and pediatric septic shock were identified from general solicitation at the Society of Critical Care Medicine Educational and Scientific Symposia (2001–2006). Methods: The Pubmed/MEDLINE literature database (1966–2006) was searched using the keywords and phrases: sepsis, septicemia, septic shock, endotoxemia, persistent pulmonary hypertension, nitric oxide, extracorporeal membrane oxygenation (ECMO), and American College of Critical Care Medicine guidelines. Best practice centers that reported best outcomes were identified and their practices examined as models of care. Using a modified Delphi method, 30 experts graded new literature. Over 30 additional experts then reviewed the updated recommendations. The document was subsequently modified until there was greater than 90% expert consensus. Results: The 2002 guidelines were widely disseminated, translated into Spanish and Portuguese, and incorporated into Society of Critical Care Medicine and AHA sanctioned recommendations. Centers that implemented the 2002 guidelines reported best practice outcomes (hospital mortality 1%–3% in previously healthy, and 7%–10% in chronically ill children). Early use of 2002 guidelines was associated with improved outcome in the community hospital emergency department (number needed to treat = 3.3) and tertiary pediatric intensive care setting (number needed to treat = 3.6); every hour that went by without guideline adherence was associated with a 1.4-fold increased mortality risk. The updated 2007 guidelines continue to recognize an increased likelihood that children with septic shock, compared with adults, require 1) proportionally larger quantities of fluid, 2) inotrope and vasodilator therapies, 3) hydrocortisone for absolute adrenal insufficiency, and 4) ECMO for refractory shock. The major new recommendation in the 2007 update is earlier use of inotrope support through peripheral access until central access is attained. Conclusion: The 2007 update continues to emphasize early use of age-specific therapies to attain time-sensitive goals, specifically recommending 1) first hour fluid resuscitation and inotrope therapy directed to goals of threshold heart rates, normal blood pressure, and capillary refill ≤2 secs, and 2) subsequent intensive care unit hemodynamic support directed to goals of central venous oxygen saturation >70% and cardiac index 3.3–6.0 L/min/m2....

Recent studies have underscored questions about the balance of risk and benefit of RBC transfusion. A better understanding of the nature and timing of molecular and functional changes in stored RBCs may provide strategies to improve the balance of benefit and risk of RBC transfusion. We analyzed changes occurring during RBC storage focusing on RBC deformability, RBC-dependent vasoregulatory function, and S -nitrosohemoglobin (SNO-Hb), through which hemoglobin (Hb) O ₂ desaturation is coupled to regional increases in blood flow in vivo (hypoxic vasodilation). Five hundred ml of blood from each of 15 healthy volunteers was processed into leukofiltered, additive solution 3-exposed RBCs and stored at 1–6°C according to AABB standards. Blood was subjected to 26 assays at 0, 3, 8, 24 and 96 h, and at 1, 2, 3, 4, and 6 weeks. RBC SNO-Hb decreased rapidly (1.2 × 10 ⁻⁴ at 3 h vs. 6.5 × 10 ⁻⁴ (fresh) mol S -nitrosothiol (SNO)/mol Hb tetramer ( P = 0.032, mercuric-displaced photolysis-chemiluminescence assay), and remained low over the 42-day period. The decline was corroborated by using the carbon monoxide-saturated copper-cysteine assay [3.0 × 10 ⁻⁵ at 3 h vs. 9.0 × 10 ⁻⁵ (fresh) mol SNO/mol Hb]. In parallel, vasodilation by stored RBCs was significantly depressed. RBC deformability assayed at a physiological shear stress decreased gradually over the 42-day period ( P < 0.001). Time courses vary for several storage-induced defects that might account for recent observations linking blood transfusion with adverse outcomes. Of clinical concern is that SNO levels, and their physiological correlate, RBC-dependent vasodilation, become depressed soon after collection, suggesting that even “fresh” blood may have developed adverse biological characteristics.

Objective: To investigate significant new morbidities associated with pediatric critical care . Design: Randomly selected, prospective cohort. Setting: PICU patients from eight medical and cardiac PICUs. Patients: This was a randomly selected, prospective cohort of PICU patients from eight medical and cardiac PICUs. Measurements and Main Results: The main outcomes measures were hospital discharge functional status measured by Functional Status Scale scores and new morbidity defined as an increase in the Functional Status Scale of more than or equal to 3. Of the 5,017 patients, there were 242 new morbidities (4.8%), 99 PICU deaths (2.0%), and 120 hospital deaths (2.4%). Both morbidity and mortality rates differed (p < 0.001) among the sites. The worst functional status profile was on PICU discharge and improved on hospital discharge. On hospital discharge, the good category decreased from a baseline of 72% to 63%, mild abnormality increased from 10% to 15%, moderate abnormality status increased from 13% to 14%, severe status increased from 4% to 5%, and very severe was unchanged at 1%. The highest new morbidity rates were in the neurological diagnoses (7.3%), acquired cardiovascular disease (5.9%), cancer (5.3%), and congenital cardiovascular disease (4.9%). New morbidities occurred in all ages with more in those under 12 months. New morbidities involved all Functional Status Scale domains with the highest proportions involving respiratory, motor, and feeding dysfunction. Conclusions: The prevalence of new morbidity was 4.8%, twice the mortality rate, and occurred in essentially all types of patients, in relatively equal proportions, and involved all aspects of function. Compared with historical data, it is possible that pediatric critical care has exchanged improved mortality rates for increased morbidity rates.

Morbidity assessments are becoming a more important aspect of pediatric outcomes research, especially in studies with a significant risk for decreased functional status due to neurologic or other processes. Assessing functional status in children is particularly difficult when the method must be suitable for large-scale studies. First, functional status assessments that are reliable at the level of the individual are time-consuming and require considerable training; therefore, they are not practical for large-sample studies.^1-4 Second, methods of pediatric functional status assessment must incorporate the rapidly changing norms of growth and development, making them difficult to design and complex to develop.^5,6

Human septic shock involves multiple genome-level perturbations. We have conducted microarray analyses in children with septic shock within 24 h of intensive care unit admission, using whole blood-derived RNA. Based on sequential statistical and expression filters, there were 2,482 differentially regulated gene probes (1,081 upregulated and 1,401 downregulated) between patients with septic shock (n = 42) and controls (n = 15). Both gene lists encompassed several biologically relevant gene ontologies and canonical pathways. Notably, many of the genes downregulated in the patients with septic shock, relative to the controls, participate in gene ontologies related to metal or zinc homeostasis. Comparison of septic shock survivors (n = 33) and nonsurvivors (n = 9) demonstrated differential regulation of 63 gene probes. Among the 63 gene probes differentially regulated between septic shock survivors and nonsurvivors, two isoforms of metallothionein (MT) demonstrated increased expression in the nonsurvivors. Consistent with the ability of MT to sequester zinc in the intracellular compartment, nonsurvivors had lower serum zinc levels compared with survivors. In a corroborating study of murine sepsis, MT-null mice demonstrated a survival advantage compared with wild-type mice. These data represent the largest reported cohort of pediatric patients with septic shock that has undergone genome-level expression profiling based on microarray. The data are biologically plausible and demonstrate that genome-level alterations of zinc homeostasis may be prevalent in clinical pediatric septic shock.

BACKGROUND: The 2009 pandemic influenza A (H1N1) (pH1N1) virus continues to circulate worldwide. Determining the roles of chronic conditions and bacterial coinfection in mortality is difficult because of the limited data for children with pH1N1-related critical illness. METHODS: We identified children (<21 years old) with confirmed or probable pH1N1 admitted to 35 US PICUs from April 15, 2009, through April 15, 2010. We collected data on demographics, baseline health, laboratory results, treatments, and outcomes. RESULTS: Of 838 children with pH1N1 admitted to a PICU, the median age was 6 years, 58% were male, 70% had ≥1 chronic health condition, and 88.2% received oseltamivir (5.8% started before PICU admission). Most patients had respiratory failure with 564 (67.3%) receiving mechanical ventilation; 162 (19.3%) received vasopressors, and 75 (8.9%) died. Overall, 71 (8.5%) of the patients had a presumed diagnosis of early (within 72 hours after PICU admission) Staphylococcus aureus coinfection of the lung with 48% methicillin-resistant S aureus (MRSA). In multivariable analyses, preexisting neurologic conditions or immunosuppression, encephalitis (1.7% of cases), myocarditis (1.4% of cases), early presumed MRSA lung coinfection, and female gender were mortality risk factors. Among 251 previously healthy children, only early presumed MRSA coinfection of the lung (relative risk: 8 [95% confidence interval: 3.1–20.6]; P < .0001) remained a mortality risk factor. CONCLUSIONS: Children with preexisting neurologic conditions and immune compromise were at increased risk of pH1N1-associated death after PICU admission. Secondary complications of pH1N1, including myocarditis, encephalitis, and clinical diagnosis of early presumed MRSA coinfection of the lung, were mortality risk factors.