Monitoring Cerebral Hemodynamics with Transcranial Doppler Ultrasound during Cognitive and Exercise Testing in Adults following Unilateral Stroke

An observational study was performed as a preliminary investigation into the use of transcranial Doppler ultrasound (TCD) for recording cerebral hemodynamic changes during multiple tasks. TCD is a method of measuring cerebral blood flow (CBF) using ultrasound transducers in contact with the surface of the head. Using the maximum flow envelope of the Doppler spectrum returning from the middle cerebral artery (MCA), standard clinical flow indices can be calculated and displayed in real time providing information concerning perturbations in CBF and their potential cause. These indices as well as flow velocity measurements have been recognized as useful in measuring changes in responses to various stimulus that can be used to indicate cardiovascular health. For this study, the pulsatility index (PI) and resistivity index (RI) were chosen since they indicate composite changes indicative of vasoconstriction and vasodilatation which are normal hemodynamic responses under appropriate conditions. A total of eleven participants were recruited to take part in this study. Nine of these individuals had no known disability (Controls); two had experienced unilateral cerebrovascular accidents (Strokes) in the ipsilateral MCA distribution. Maximum velocity envelopes of the spectral Doppler data were recorded using a fixation device designed to stabilize two ultrasound probes (2 MHz) to sample the bilateral MCAs CBF. These measures were performed separately while the subject performed four activities: 1) rest, 2) cognitive challenge, 3) cardiovascular exercise, and 4) simultaneous exercise and cognitive challenge. Cardiovascular parameters were calculated from the data by extracting maximum (Vs) and minimum flow velocities (Vd), PI, RI, and time signatures for each cardiac cycle. The data for all participants shows significant changes in cardiovascular parameters between states of rest and exercise, as well as slight trends across time. Although the data are preliminary, they show the capability of using Doppler spectral examination of the bilateral MCAs in individuals with physical limitation performing cardiovascular exercise. The novelty of examining a population using dynamic exercise who before could not perform such exercise offers the opportunity to study the impact of exercise on global cerebral recovery in unilateral stroke with significant physical impairment

Successful Use of Venovenous Extracorporeal Membrane Oxygenation for Complicated H1N1 Pneumonia Refractory to Mechanical Ventilation

In April 2009, novel H1N1 influenza A pneumonia was initially identified in young adults by the Mexican Health Ministry. Previously healthy patients progressing to multisystem organ failure were common. Worldwide, hospitals reported surges in intensive care admissions during the initial phase of the pandemic. In patients with H1N1 pneumonia refractory to mechanical ventilation, centers were initially reporting low survival rates despite the use of extracorporeal membrane oxygenation (ECMO). The initial poor outcomes and protracted ECMO treatment epochs resulted in centers limiting or withholding the use of ECMO in this population. With respect to children with H1N1 infection there was uncertainty concerning optimal incorporation of ECMO as a therapeutic option. In children with rapidly progressive pneumonia and hypoxia refractory to mechanical ventilation, venovenous (VV) ECMO has been successfully used with survival ranging from 40–60% depending on the etiology. We report the successful use of VV ECMO in two children with confirmed novel H1N1 complicated by bacterial pneumonia or morbid obesity. Our Institutional Review Board waived the need for consent. Prompt initiation of VV ECMO resulted in rapid clinical improvement, radiographic resolution of diffuse consolidation, and return of full neurocognitive function. For children with rapidly progressive respiratory distress on conventional ventilation, VV ECMO can be used to improve outcomes when initiated early in the disease process even in children with a significant co-morbidity

A multinational study of thromboprophylaxis practice in critically ill children

Although critically ill children are at increased risk for developing deep venous thrombosis, there are few pediatric studies establishing the prevalence of thrombosis or the efficacy of thromboprophylaxis. We tested the hypothesis that thromboprophylaxis is infrequently used in critically ill children even for those in whom it is indicated.Prospective multinational cross-sectional study over four study dates in 2012.Fifty-nine PICUs in Australia, Canada, New Zealand, Portugal, Singapore, Spain, and the United States.All patients less than 18 years old in the PICU during the study dates and times were included in the study, unless the patients were 1) boarding in the unit waiting for a bed outside the PICU or 2) receiving therapeutic anticoagulation.None.Of 2,484 children in the study, 2,159 (86.9%) had greater than or equal to 1 risk factor for thrombosis. Only 308 children (12.4%) were receiving pharmacologic thromboprophylaxis (e.g., aspirin, low-molecular-weight heparin, or unfractionated heparin). Of 430 children indicated to receive pharmacologic thromboprophylaxis based on consensus recommendations, only 149 (34.7%) were receiving it. Mechanical thromboprophylaxis was used in 156 of 655 children (23.8%) 8 years old or older, the youngest age for that device. Using nonlinear mixed effects model, presence of cyanotic congenital heart disease (odds ratio, 7.35; p < 0.001) and spinal cord injury (odds ratio, 8.85; p = 0.008) strongly predicted the use of pharmacologic and mechanical thromboprophylaxis, respectively.Thromboprophylaxis is infrequently used in critically ill children. This is true even for children at high risk of thrombosis where consensus guidelines recommend pharmacologic thromboprophylaxis

Vancomycin Monotherapy May Be Insufficient to Treat Methicillin-resistant Staphylococcus aureus Coinfection in Children With Influenza-related Critical Illness

Background. Coinfection with influenza virus and methicillin-resistant Staphylococcus aureus (MRSA) causes life-threatening necrotizing pneumonia in children. Sporadic incidence precludes evaluation of antimicrobial efficacy. We assessed the clinical characteristics and outcomes of critically ill children with influenza-MRSA pneumonia and evaluated antibiotic use. Methods. We enrolled children (<18 years) with influenza infection and respiratory failure across 34 pediatric intensive care units 11/2008-5/2016. We compared baseline characteristics, clinical courses, and therapies in children with MRSA coinfection, non-MRSA bacterial coinfection, and no bacterial coinfection. Results. We enrolled 170 children (127 influenza A, 43 influenza B). Children with influenza-MRSA pneumonia (N = 30, 87% previously healthy) were older than those with non-MRSA (N = 61) or no (N = 79) bacterial coinfections. Influenza-MRSA was associated with increased leukopenia, acute lung injury, vasopressor use, extracorporeal life support, and mortality than either group (P <= .0001). Influenza-related mortality was 40% with MRSA compared to 4.3% without (relative risk [RR], 9.3; 95% confidence interval [CI], 3.8-22.9). Of 29/30 children with MRSA who received vancomycin within the first 24 hours of hospitalization, mortality was 12.5% (N = 2/16) if treatment also included a second anti-MRSA antibiotic compared to 69.2% (N = 9/13) with vancomycin monotherapy (RR, 5.5; 95% CI, 1.4, 21.3; P = .003). Vancomycin dosing did not influence initial trough levels; 78% were <10 mu g/mL. Conclusions. Influenza-MRSA coinfection is associated with high fatality in critically ill children. These data support early addition of a second anti-MRSA antibiotic to vancomycin in suspected severe cases

Delirium in critically ill children: an international point prevalence study∗

Objectives: To determine prevalence of delirium in critically ill children and explore associated risk factors. Design: Multi-institutional point prevalence study. Setting: Twenty-five pediatric critical care units in the United States, the Netherlands, New Zealand, Australia, and Saudi Arabia. Patients: All children admitted to the pediatric critical care units on designated study days (n = 994). Intervention: Children were screened for delirium using the Cornell Assessment of Pediatric Delirium by the bedside nurse. Demographic and treatment-related variables were collected. Measurements and Main Results: Primary study outcome measure was prevalence of delirium. In 159 children, a final determination of mental status could not be ascertained. Of the 835 remaining subjects, 25% screened positive for delirium, 13% were classified as comatose, and 62% were delirium-free and coma-free. Delirium prevalence rates varied significantly with reason for ICU admission, with highest delirium rates found in children admitted with an infectious or inflammatory disorder. For children who were in the PICU for 6 or more days, delirium prevalence rate was 38%. In a multivariate model, risk factors independently associated with development of delirium included age less than 2 years, mechanical ventilation, benzodiazepines, narcotics, use of physical restraints, and exposure to vasopressors and antiepileptics. Conclusions: Delirium is a prevalent complication of critical illness in children, with identifiable risk factors. Further multi-institutional, longitudinal studies are required to investigate effect of delirium on long-term outcomes and possible preventive and treatment measures. Universal delirium screening is practical and can be implemented in pediatric critical care units

Surfactant Protein D Is Associated With Severe Pediatric ARDS, Prolonged Ventilation, and Death in Children With Acute Respiratory Failure

Elevated surfactant protein D (SP-D) is a relatively specific indicator of lung injury and is associated with both acute and chronic lung disease in adults and respiratory distress syndrome in premature infants. The relationship between plasma SP-D and lung injury in children with acute respiratory failure is unclear. Is plasma SP-D associated with lung injury or outcome in children with acute respiratory failure? This was a prospective cohort study in children 2 weeks to 17 years of age with acute respiratory failure who participated in the BALI multi-center study. Analyses were done using SP-D levels in plasma from the first sample taken on either the day of intubation or one of the following 2 days. SP-D level was measured by enzyme-linked immunosorbent assay. Plasma samples from 350 patients were used in the analysis; 233 had pediatric ARDS (PARDS). SP-D levels varied across primary diagnoses (P < .001). Elevated SP-D levels were associated with severe PARDS after adjusting for age, pediatric risk of mortality III (PRISM-III), and primary diagnosis (OR = 1.02; CI = 1.01-1.04; P = .011). Multivariable analyses also indicated that elevated SP-D levels were associated with death (OR = 1.02; CI = 1.01-1.04; P = .004), duration of mechanical ventilation (P = .012), PICU length of stay (P = .019), and highest oxygenation index (P = .040). SP-D levels also correlated with age (rs = 0.16, P = .002). Elevated plasma SP-D levels are associated with severe PARDS and poor outcomes in children with acute respiratory failure. Future studies will determine whether SP-D can be used to predict the degree of lung injury or response to treatment and whether SP-D is useful in identifying PARDS endotypes

Identification of phenotypes in paediatric patients with acute respiratory distress syndrome: a latent class analysis

BackgroundPrevious latent class analysis of adults with acute respiratory distress syndrome (ARDS) identified two phenotypes, distinguished by the degree of inflammation. We aimed to identify phenotypes in children with ARDS in whom developmental differences might be important, using a latent class analysis approach similar to that used in adults.MethodsThis study was a secondary analysis of data aggregated from the Randomized Evaluation of Sedation Titration for Respiratory Failure (RESTORE) clinical trial and the Genetic Variation and Biomarkers in Children with Acute Lung Injury (BALI) ancillary study. We used latent class analysis, which included demographic, clinical, and plasma biomarker variables, to identify paediatric ARDS (PARDS) phenotypes within a cohort of children included in the RESTORE and BALI studies. The association of phenotypes with clinically relevant outcomes and the performance of paediatric data in adult ARDS classification algorithms were also assessed.Findings304 children with PARDS were included in this secondary analysis. Using latent class analysis, a two-class model was a better fit for the cohort than a one-class model (p&lt;0·001). Latent class analysis identified two classes: class 1 (181 [60%] of 304 patients with PARDS) and class 2 (123 [40%] of 304 patients with PARDS), referred to as phenotype 1 and 2 hereafter. Phenotype 2 was characterised by higher concentrations of inflammatory biomarkers, a higher incidence of vasopressor use, and more frequent diagnosis of sepsis, consistent with the adult hyperinflammatory phenotype. All levels of severity of PARDS were observed across both phenotypes. Children with the hyperinflammatory phenotype (phenotype 2) had worse clinical outcomes than those with the hypoinflammatory phenotype (phenotype 1), with a longer duration of mechanical ventilation (median 10·0 days [IQR 6·3-21·0] for phenotype 2 vs 6·6 days [4·1-10·8] for phenotype 1, p&lt;0·0001), and higher incidence of mortality (17 [13·8%] of 123 patients vs four [2·2%] of 181 patients, p=0·0001). When using adult phenotype classification algorithms in children, the soluble tumour necrosis factor receptor-1 (sTNFr1), vasopressor use, and interleukin (IL)-6 variables gave an area under the curve (AUC) of 0·956, and the sTNFr1, vasopressor use, and IL-8 variables gave an AUC of 0·954, compared with the gold standard of latent class analysis.InterpretationLatent class analysis identified two phenotypes in children with ARDS with characteristics similar to those in adults, including worse outcomes among patients with the hyperinflammatory phenotype. PARDS phenotypes should be considered in design and analysis of future clinical trials in children.FundingUS National Institutes of Health