Health Resource Use in Survivors of Pediatric Septic Shock in the United States.

OBJECTIVES: To evaluate postdischarge health resource use in pediatric survivors of septic shock and determine patient and hospitalization factors associated with health resource use. DESIGN: Secondary analyses of a multicenter prospective observational cohort study. SETTING: Twelve academic PICUs. PATIENTS: Children greater than or equal to 1 month and less than 18 years old hospitalized for community-acquired septic shock who survived to 1 year. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: For 308/338 patients (91%) with baseline and greater than or equal to one postdischarge survey, we evaluated readmission, emergency department (ED) visits, new medication class, and new device class use during the year after sepsis. Using negative binomial regression with bidirectional stepwise selection, we identified factors associated with each outcome. Median age was 7 years (interquartile range, 2-13), 157 (51%) had a chronic condition, and nearly all patients had insurance (private [n = 135; 44%] or government [n = 157; 51%]). During the year after sepsis, 128 patients (42%) were readmitted, 145 (47%) had an ED visit, 156 (51%) started a new medication class, and 102 (33%) instituted a new device class. Having a complex chronic condition was independently associated with readmission and ED visit. Documented infection and higher sum of Pediatric Logistic Organ Dysfunction--2 hematologic score were associated with readmission, whereas younger age and having a noncomplex chronic condition were associated with ED visit. Factors associated with new medication class use were private insurance, neurologic insult, and longer PICU stays. Factors associated with new device class use were preadmission chemotherapy or radiotherapy, presepsis Functional Status Scale score, and ventilation duration greater than or equal to 10 days. Of patients who had a new medication or device class, most had a readmission (56% and 61%) or ED visit (62% and 67%). CONCLUSIONS: Children with septic shock represent a high-risk cohort with high-resource needs after discharge. Interventions and targeted outcomes to mitigate postdischarge resource use may differ based on patients' preexisting conditions.

Criteria for Pediatric Sepsis-A Systematic Review and Meta-Analysis by the Pediatric Sepsis Definition Taskforce.

OBJECTIVE: To determine the associations of demographic, clinical, laboratory, organ dysfunction, and illness severity variable values with: 1) sepsis, severe sepsis, or septic shock in children with infection and 2) multiple organ dysfunction or death in children with sepsis, severe sepsis, or septic shock. DATA SOURCES: MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were searched from January 1, 2004, and November 16, 2020. STUDY SELECTION: Case-control studies, cohort studies, and randomized controlled trials in children greater than or equal to 37-week-old postconception to 18 years with suspected or confirmed infection, which included the terms "sepsis," "septicemia," or "septic shock" in the title or abstract. DATA EXTRACTION: Study characteristics, patient demographics, clinical signs or interventions, laboratory values, organ dysfunction measures, and illness severity scores were extracted from eligible articles. Random-effects meta-analysis was performed. DATA SYNTHESIS: One hundred and six studies met eligibility criteria of which 81 were included in the meta-analysis. Sixteen studies (9,629 patients) provided data for the sepsis, severe sepsis, or septic shock outcome and 71 studies (154,674 patients) for the mortality outcome. In children with infection, decreased level of consciousness and higher Pediatric Risk of Mortality scores were associated with sepsis/severe sepsis. In children with sepsis/severe sepsis/septic shock, chronic conditions, oncologic diagnosis, use of vasoactive/inotropic agents, mechanical ventilation, serum lactate, platelet count, fibrinogen, procalcitonin, multi-organ dysfunction syndrome, Pediatric Logistic Organ Dysfunction score, Pediatric Index of Mortality-3, and Pediatric Risk of Mortality score each demonstrated significant and consistent associations with mortality. Pooled mortality rates varied among high-, upper middle-, and lower middle-income countries for patients with sepsis, severe sepsis, and septic shock (p < 0.0001). CONCLUSIONS: Strong associations of several markers of organ dysfunction with the outcomes of interest among infected and septic children support their inclusion in the data validation phase of the Pediatric Sepsis Definition Taskforce.

Severe Acute Kidney Injury Is Associated With Increased Risk of Death and New Morbidity After Pediatric Septic Shock.

OBJECTIVES: Acute kidney injury is common in critically ill children; however, the frequency of septic shock-associated acute kidney injury and impact on functional status are unknown. We evaluated functional outcomes of children with septic shock-associated acute kidney injury. DESIGN: Secondary analysis of patients with septic shock from the prospective Life after Pediatric Sepsis Evaluation study. We defined acute kidney injury using Kidney Disease Improving Global Outcomes criteria, comparing patients with absent/Stage 1 acute kidney injury to those with Stage 2/3 acute kidney injury (severe acute kidney injury). Our primary outcome was a composite of mortality or new functional morbidity at day 28 of hospitalization or discharge. We also assessed poor long-term outcome, defined as mortality or a persistent, serious deterioration in health-related quality of life at 3 months. SETTING: Twelve academic PICUs in the United States. PATIENTS: Critically ill children, 1 month to 18 years, with community-acquired septic shock requiring vasoactive-inotropic support. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: More than 50% of patients (176/348) developed severe acute kidney injury; of those, 21.6% (38/176) required renal replacement therapy. Twice as many patients with severe acute kidney injury died or developed new substantive functional morbidity (38.6 vs 16.3%; p < 0.001). After adjustment for age, malignancy, and initial illness severity, severe acute kidney injury was independently associated with mortality or new substantive morbidity (adjusted odds ratio, 2.78; 95% CI, 1.63-4.81; p < 0.001). Children with severe acute kidney injury had poorer health-related quality of life at 3 months (adjusted effect size 2.46; 95% CI, 1.44-4.20; p = 0.002). Children with severe acute kidney injury required longer duration of mechanical ventilation (11.0 vs 7.0 d; p < 0.001) and PICU stay (11.7 vs 7.1 d; p < 0.001). CONCLUSIONS: Among children with septic shock, severe acute kidney injury was independently associated with increased risk of death or new substantive functional morbidity. Survivors of sepsis with severe acute kidney injury were more likely to have persistent, serious health-related quality of life deterioration at 3 months.

Serum Protein Changes in Pediatric Sepsis Patients Identified With an Aptamer-Based Multiplexed Proteomic Approach.

OBJECTIVES: Sepsis, a life-threatening organ dysfunction caused by a dysregulated host response to infection, is a leading cause of death and disability among children worldwide. Identifying sepsis in pediatric patients is difficult and can lead to treatment delay. Our objective was to assess the host proteomic response to infection utilizing an aptamer-based multiplexed proteomics approach to identify novel serum protein changes that might help distinguish between pediatric sepsis and infection-negative systemic inflammation and hence can potentially improve sensitivity and specificity of the diagnosis of sepsis over current clinical criteria approaches. DESIGN: Retrospective, observational cohort study. SETTING: PICU and cardiac ICU, Seattle Children's Hospital, Seattle, WA. PATIENTS: A cohort of 40 children with clinically overt sepsis and 30 children immediately postcardiopulmonary bypass surgery (infection-negative systemic inflammation control subjects) was recruited. Children with sepsis had a confirmed or suspected infection, two or more systemic inflammatory response syndrome criteria, and at least cardiovascular and/or pulmonary organ dysfunction. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Serum samples from 35 of the sepsis and 28 of the bypass surgery subjects were available for screening with an aptamer-based proteomic platform that measures 1,305 proteins to search for large-scale serum protein expression pattern changes in sepsis. A total of 111 proteins were significantly differentially expressed between the sepsis and control groups, using the linear models for microarray data (linear modeling) and Boruta (decision trees) R packages, with 55 being previously identified in sepsis patients. Weighted gene correlation network analysis helped identify 76 proteins that correlated highly with clinical sepsis traits, 27 of which had not been previously reported in sepsis. CONCLUSIONS: The serum protein changes identified with the aptamer-based multiplexed proteomics approach used in this study can be useful to distinguish between sepsis and noninfectious systemic inflammation.

Diagnostic Accuracy of a Host Gene Expression Signature That Discriminates Clinical Severe Sepsis Syndrome and Infection-Negative Systemic Inflammation Among Critically Ill Children.

OBJECTIVES: SeptiCyte Lab (Immunexpress, Seattle, WA), a molecular signature measuring the relative expression levels of four host messenger RNAs, was developed to discriminate critically ill adults with infection-positive versus infection-negative systemic inflammation. The objective was to assess the performance of Septicyte Lab in critically ill pediatric patients. DESIGN: Prospective observational study. SETTING: Pediatric and Cardiac ICUs, Seattle Children's Hospital, Seattle, WA. PATIENTS: A cohort of 40 children with clinically overt severe sepsis syndrome and 30 children immediately postcardiopulmonary bypass surgery was recruited. The clinically overt severe sepsis syndrome children had confirmed or highly suspected infection (microbial culture orders, antimicrobial prescription), two or more systemic inflammatory response syndrome criteria (including temperature and leukocyte criteria), and at least cardiovascular ± pulmonary organ dysfunction. INTERVENTIONS: None (observational study only). MEASUREMENTS AND MAIN RESULTS: Next-generation RNA sequencing was conducted on PAXgene blood RNA samples, successfully for 35 of 40 (87.5%) of the clinically overt severe sepsis syndrome patients and 29 of 30 (96.7%) of the postcardiopulmonary bypass patients. Forty patient samples (~ 60% of cohort) were reanalyzed by reverse transcription-quantitative polymerase chain reaction, to check for concordance with next-generation sequencing results. Postcardiopulmonary bypass versus clinically overt severe sepsis syndrome descriptors included the following: age, 7.3 ± 5.5 versus 9.0 ± 6.6 years; gender, 41% versus 49% male; Pediatric Risk of Mortality, version III, 7.0 ± 4.6 versus 8.7 ± 6.4; Pediatric Logistic Organ Dysfunction, version II, 5.1 ± 2.2 versus 4.8 ± 2.8. SeptiCyte Lab strongly differentiated postcardiopulmonary bypass and clinically overt severe sepsis syndrome patients by receiver operating characteristic curve analysis, with an area-under-curve value of 0.99 (95% CI, 0.96-1.00). Equivalent performance was found using reverse transcription-quantitative polymerase chain reaction. There was no significant correlation between the score produced by the SeptiCyte Lab test and measures of illness severity, immune compromise, or microbial culture status. CONCLUSIONS: SeptiCyte Lab is able to discriminate clearly between clinically well-defined and homogeneous postcardiopulmonary bypass and clinically overt severe sepsis syndrome groups in children. A broader investigation among children with more heterogeneous inflammation-associated diagnoses and care settings is warranted.

Research as a Standard of Care in the PICU.

OBJECTIVES: Excellence in clinical care coupled with basic and applied research reflects the maturation of a medical subspecialty, advances that field, and provides objective data for identifying best practices. PICUs are uniquely suited for conducting translational and clinical research. In addition, multiple investigations have reported that a majority of parents are interested in their children's participation in clinical research, even when the research offers no direct benefit to their child. However, such activity may generate ethical conflict with bedside care providers trying to acutely identify the best approach for an individual critically ill child. Ultimately, this conflict may diminish enthusiasm for the generation of scientific evidence that supports the application of evidence-based medicine into PICU clinical standard work. Accordingly this review endeavors to provide an overview of current state PICU clinical research strengths, liabilities, opportunities, and barriers and contrast this with an established pediatric hematology-oncology iterative research model that constitutes a learning healthcare system. DATA SOURCES, DATA EXTRACTION, AND DATA SYNTHESIS: Narrative review of medical literature published in English. CONCLUSIONS: Currently, most PICU therapy is not evidence based. Developing a learning healthcare system in the PICU integrates clinical research into usual practice and fosters a culture of evidence-based learning and continual care improvement. As PICU mortality has significantly decreased, identification and validation of patient-centered, clinically relevant research outcome measures other than mortality is essential for future clinical trial design. Because most pediatric critical illness may be classified as rare diseases, participation in research networks will facilitate iterative, collaborative, multiinstitutional investigations that over time identify the best practices to improve PICU outcomes. Despite real ethical challenges, critically ill children and their families should have the opportunity to participate in translational/clinical research whenever feasible.

Increased cerebrospinal fluid cleaved tau protein (C-tau) levels suggest axonal damage in pediatric patients with brain tumors.

OBJECTIVE: This study aims to determine if cerebrospinal fluid/serum cleaved tau protein and CSF 9-hydroxyoctadecadienoic acid levels, reflecting potential biomarkers of overall neuronal injury and lipid peroxidation, respectively, are elevated in brain tumor patients compared with controls. DESIGN: This article is a prospective clinical observational study. SETTING: This study is conducted at a tertiary-care children's hospital. PATIENTS: Our participants are children younger than or equal to 18 years of age undergoing brain tumor surgery. MEASUREMENTS AND MAIN RESULTS: During the study period, 26 consecutive patients newly diagnosed with brain tumors who met the inclusion criteria were prospectively enrolled. Baseline cerebrospinal fluid analysis of cleaved tau and 9-hydroxyoctadecadienoic acid were measured in 15 patients. Cerebrospinal fluid cleaved tau and 9-hydroxyoctadecadienoic acid levels were measured in 22 patients for post-surgery days 1 and 3. Serum cleaved tau levels were measured for 20 and 18 patients for post-surgery days 1 and 3, respectively. The presence of a brain tumor significantly increased the baseline cerebrospinal fluid cleaved tau levels but did not affect cerebrospinal fluid 9-hydroxyoctadecadienoic acid levels. Similarly, there was a significant increase in post-surgery day 1 cerebrospinal fluid cleaved tau levels from baseline (p = 0.01) and a trend toward significant decrease in post-surgery day 3 cerebrospinal fluid cleaved tau from day 1 (p = 0.07). 9-Hydroxyoctadecadienoic acid concentrations remained relatively constant over time with no differences noted between the control and brain tumor patients. There was a trend towards a significant association between cerebrospinal fluid cleaved tau levels and duration of symptoms (p = 0.07). CONCLUSIONS: Cerebrospinal fluid cleaved tau levels in children with newly diagnosed brain tumors exhibit markedly elevated cerebrospinal fluid cleaved tau levels, suggesting axonal damage. This axonal injury does not seem to correlate with lipid peroxidation at least when as assessed by cerebrospinal fluid 9-hydroxyoctadecadienoic acid levels. There was no association found between the biomarkers and multiple independent variables obtained at pre- and post-tumor resection.

A single nucleotide polymorphism in the corticotropin receptor gene is associated with a blunted cortisol response during pediatric critical illness.

OBJECTIVES: The cortisol response during critical illness varies widely among patients. Our objective was to examine single nucleotide polymorphisms in candidate genes regulating cortisol synthesis, metabolism, and activity to determine if genetic differences were associated with variability in the cortisol response among critically ill children. DESIGN: This was a prospective observational study employing tag single nucleotide polymorphism methodology to examine genetic contributions to the variability of the cortisol response in critical illness. Thirty-one candidate genes and 31 ancestry markers were examined. SETTING: Patients were enrolled from seven pediatric critical care units that constitute the Eunice Kennedy Shriver Collaborative Pediatric Critical Care Research Network. SUBJECTS: Critically ill children (n = 92), age 40 weeks gestation to 18 years old, were enrolled. INTERVENTIONS: Blood samples were obtained from all patients for serum cortisol measurements and DNA isolation. Demographic and illness severity data were collected. MEASUREMENTS AND MAIN RESULTS: Single nucleotide polymorphisms were tested for association with serum free cortisol concentrations in context of higher illness severity as quantified by Pediatric Risk of Mortality III score greater than 7. A single nucleotide polymorphism (rs1941088) in the MC2R gene was strongly associated (p = 0.0005) with a low free cortisol response to critical illness. Patients with the AA genotype were over seven times more likely to have a low free cortisol response to critical illness than those with a GG genotype. Patients with the GA genotype exhibited an intermediate free cortisol response to critical illness. CONCLUSIONS: The A allele at rs1941088 in the MC2R gene, which encodes the adrenocorticotropic hormone (corticotropin, ACTH) receptor, is associated with a low cortisol response in critically ill children. These data provide evidence for a genetic basis for a portion of the variability in cortisol production during critical illness. Independent replication of these findings will be important and could facilitate development of personalized treatment for patients with a low cortisol response to severe illness.

Sepsis in the pediatric cardiac intensive care unit.

The survival rate for children with congenital heart disease (CHD) has increased significantly coincident with improved techniques in cardiothoracic surgery, cardiopulmonary bypass and myocardial protection, and perioperative care. Cardiopulmonary bypass, likely in combination with ischemia-reperfusion injury, hypothermia, and surgical trauma, elicits a complex, systemic inflammatory response that is characterized by activation of the complement cascade, release of endotoxin, activation of leukocytes and the vascular endothelium, and release of proinflammatory cytokines. This complex inflammatory state causes a transient immunosuppressed state, which may increase the risk of hospital-acquired infection in these children. Postoperative sepsis occurs in nearly 3% of children undergoing cardiac surgery and has been associated with longer length of stay and mortality risks in the pediatric cardiac intensive care unit. Herein, we review the epidemiology, pathobiology, and management of sepsis in the pediatric cardiac intensive care unit.

Endocrinopathies in the cardiac ICU.

The past several years have seen an increased appreciation of the potential role of the endocrine system in the recovery process following surgery for congenital heart disease. Many of the hormonal changes following cardiac surgery are adaptive and necessary, whereas activation of proinflammatory cytokine and chemokine responses and some of the metabolic changes following surgery are likely mediators leading to detrimental outcomes. Additionally, other hormonal perturbations may contribute to adverse outcomes. This review examines the pain and the stress response, thyroid function and hyperglycemia following cardiopulmonary bypass (CPB), and the potential role of corticosteroids in the pediatric cardiac critical care unit.

Cerebrospinal fluid cleaved-tau protein and 9-hydroxyoctadecadienoic acid concentrations in pediatric patients with hydrocephalus.

OBJECTIVE: To ascertain if cerebrospinal fluid cleaved-tau protein and 9-hydroxyoctadecadienoic acid, reflecting potential biomarkers of overall neuronal injury and lipid peroxidation, respectively, are elevated in hydrocephalus patients compared with controls, and if cleaved-tau and 9-hydroxyoctadecadienoic acid levels correlate with each other. DESIGN: Prospective clinical observational study. SETTING: Tertiary-care children's hospital. PATIENTS: Children younger than or equal to 18 yrs who underwent ventriculoperitoneal shunt placement or revision surgery for intrinsic hydrocephalus. MEASUREMENTS AND MAIN RESULTS: During the study period 12 patients with intrinsic hydrocephalus required ventriculoperitoneal shunt placement or revision. Cerebrospinal fluid cleaved-tau levels were significantly elevated in patients with hydrocephalus (44.7 +/- 9.6 ng/mL, n = 11) compared with control patients (0.0 +/- 0.0 ng/mL, n = 9; p < 0.0001). Cleaved-tau levels correlated with patient age (r = .609, p = 0.047) and duration of symptoms (r = .755, p = 0.007). No significant difference in cerebrospinal fluid 9-hydroxyoctadecadienoic acid levels between patients with hydrocephalus (24.6 +/- 5.7, n = 8) and control patients (24.9 +/- 9.3 ng/mL, n = 7) was detected (p = 0.25). There was also no statistically significant correlation between 9-hydroxyoctadecadienoic acid levels and duration of symptoms (r = .668, p = 0.07), nor was there a significant correlation between 9-hydroxyoctadecadienoic acid levels and patient age (r = -.011, p > 0.10). There was no significant relationship between 9-hydroxyoctadecadienoic acid levels and signs of elevated intracranial pressure, nor was there a correlation between 9-hydroxyoctadecadienoic acid levels and cleaved-tau levels. CONCLUSION: Children with hydrocephalus who have clinical signs of increased intracranial pressure and require ventriculoperitoneal shunt placement or revision exhibit markedly elevated cerebrospinal fluid cleaved-tau levels, suggesting evidence of axonal damage. However, this axonal injury does not seem to be associated with significant lipid peroxidation, at least as assessed by quantifying cerebrospinal fluid 9-hydroxyoctadecadienoic acid at a single, concurrent time point. The significant relationship between age and cerebrospinal fluid cleaved-tau levels suggest that brain injury associated with hydrocephalus may be more pronounced in older children.

Complications associated with arterial catheterization in children.

OBJECTIVES: To examine the prevalence of and risk factors associated with arterial catheterization complications in a large pediatric patient population in an effort to generate hypotheses for future prospective study of arterial catheter placement. DESIGN: Retrospective cohort study. SETTING: Patients discharged between January 1, 2000, and March 31, 2005, from 33 children's hospitals belonging to the Child Health Corporation of America. PATIENTS: Patients were 10,394 children identified from the Pediatric Health Information System database. Inclusion criteria included age 1 month to 18 yrs, admitted to a pediatric intensive care unit, received an arterial catheter for monitoring, and hospitalized for >or=1 day following catheter placement. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We assessed complications as defined by ICD-9 coding associated with arterial catheterization, including thrombosis, embolism, and infection. Complications were reported in 10.3% (1,072) of patients, most frequently infection/inflammation (61.8%), complication of vascular device not otherwise specified (14.9%), mechanical complications (14.1%), and embolic or thrombotic issues (7.5%). Independent predictors of complications associated with arterial catheterization were age (compared with 1-4 months) of 5-11 months (odds ratio [OR] 1.5; 95% confidence interval [CI] 1.25-1.82) or 1-2 yrs (OR 1.39; 95% CI 1.09-1.78), insertion of catheters after the first hospital day and need for cardiac surgery (OR 1.31; 95% CI 1.03-1.68), bone marrow transplantation (OR 1.79; 95% CI 1.19-2.70), and dialysis (OR 1.36; 95% CI 1.05-1.77). There was no association of arterial catheter complications with patient gender, Medicaid status, or presence of coagulopathy or shock. CONCLUSIONS: Complications associated with arterial catheterization are common in critically ill children. Significantly, we were unable to account for the potential confounding effect of central venous catheterization in this study secondary to limitations of ICD-9 coding. This study serves as a hypothesis-generating report of a large pediatric sample and suggests the need to carefully assess arterial catheter-associated complications in a prospective study independent of central venous catheters.

Perfluorochemical (PFC) liquid enhances recombinant adenovirus vector-mediated viral interleukin-10 (AdvIL-10) expression in rodent lung.

Adenovirus and cationic liposome mediated transfer of Interleukin-10 (IL-10), a potent anti-inflammatory cytokine, has been shown to decrease pro-inflammatory cytokine levels and overall lung inflammation in models of lung transplantation and injury. Limitations to current approaches of IL-10 gene therapy include poor vector delivery methods and pro-inflammatory properties of human IL-10 under certain conditions. We hypothesize that using perfluorochemical (PFC) liquid to deliver the highly homologous viral IL-10 (vIL-10), which is predominantly anti-inflammatory with minimal pro-inflammatory activities, can potentially be a more effective strategy to combat inflammatory lung diseases. In this study, we compare the use of PFC liquid versus aerosolized method to deliver adenovirus encoding the vIL-10 gene (AdvIL-10) in C57Bl6 mice. Detectable vIL-10 levels were measured from bronchoalveolar lavage fluid and lung homogenates at one, four, ten and thirty days after AdvIL-10. Furthermore, we determined if use of PFC liquid could allow for the use of a lower dose of AdvIL-10 by comparing the levels of detectable vIL-10 at different doses of AdvIL-10 delivered +/- PFC liquid. Results showed that PFC liquid enhanced detectable vIL-10 by up to ten fold and that PFC liquid allowed the use of ten-fold less vector. PFC liquid increased detectable vIL-10 in lung homogenates at all time points; however, the increase in detectable vIL-10 in BAL fluid peaked at four days and was no longer evident by thirty days after intratracheal instillation. In summary, this is the first report utilizing PFC liquid to enhance the delivery of a potentially therapeutic molecule, vIL-10. We believe this strategy can be used to perform future studies on the use of the predominantly anti-inflammatory vIL-10 to treat inflammatory lung diseases.

Cerebral autoregulation in pediatric traumatic brain injury.

OBJECTIVE: The aims of this study were to document the incidence of impaired cerebral autoregulation in children with traumatic brain injury using transcranial Doppler ultrasonography and to examine the relationship between autoregulatory capacity and outcome in children following traumatic brain injury. DESIGN: Prospective cohort study. SETTING: Harborview Medical Center (level I pediatric trauma center) in Washington state. PATIENTS: Thirty-six children <15 yrs old with traumatic brain injury: Glasgow Coma Scale score <9 (n = 12, group 1), Glasgow Coma Scale score 9-12 (n = 12, group 2), and Glasgow Coma Scale score 13-15 (n = 12, group 3). INTERVENTIONS: Cerebral autoregulation testing was conducted during extracranial surgery. Mean middle cerebral artery flow velocities were measured using transcranial Doppler as mean arterial pressure was increased to whichever variable was greater: 20% above baseline or a set value (80 mm Hg for <9 yrs and 90 mm Hg for 9-14 yrs). Autoregulatory capacity was quantified by the Autoregulatory Index. Autoregulatory Index <0.4 was considered impaired cerebral autoregulation. Discharge outcome using the Glasgow Outcome Scale score was considered good if the Glasgow Outcome Scale score was > or =4. MEASUREMENTS AND MAIN RESULTS: Twenty-four (67%) of 36 children had an Autoregulatory Index > or =0.4. The incidence of impaired cerebral autoregulation was 42% (five of 12) in group 1, 42% (five of 12) in group 2, and 17% (two of 12) in group 3. Ten (42%) of the 24 children with intact cerebral autoregulation had a good outcome compared with only one of 12 (8%) children with impaired cerebral autoregulation (p =.04). Six of 12 (50%) children with impaired cerebral autoregulation had hyperemia compared with one of 24 (4%) children with intact cerebral autoregulation (p <.01). Hyperemia was associated with poor outcome (p =.01). CONCLUSIONS: The incidence of impaired cerebral autoregulation was greatest following moderate to severe traumatic brain injury. Impaired cerebral autoregulation was associated with poor outcome. Hyperemia was associated with impaired cerebral autoregulation and poor outcome.

Inflammation and surfactant.

An intact and well-functioning pulmonary surfactant system is critical for normal respiration and protection from lung infection. Surfactant is comprised of phospholipids that reduce surface tension and greatly reduce the work of breathing. The other major component consists of surfactant-associated proteins, which optimise the biophysical function of phospholipids and/or play an important role in host defence by acting as collectins. Alteration of surfactant composition and function occurs with various inflammatory disorders that affect the airways or the lung parenchyma including asthma, infant respiratory distress syndrome/bronchopulmonary dysplasia, cystic fibrosis, acute respiratory distress syndrome and interstitial lung disease. Although surfactant replacement therapy is indicated for infant respiratory distress syndrome, there is no well-proven role for exogenous surfactant in the treatment of inflammatory lung disorders at the present time.