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 µg/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.

Does Extracorporeal Membrane Oxygenation Improve Survival in Pediatric Acute Respiratory Failure?

RATIONALE: Extracorporeal membrane oxygenation (ECMO) has supported gas exchange in children with severe respiratory failure for more than 40 years, without ECMO efficacy studies. OBJECTIVES: To compare the mortality and functional status of children with severe acute respiratory failure supported with and without ECMO. METHODS: This cohort study compared ECMO-supported children to pair-matched non-ECMO-supported control subjects with severe acute respiratory distress syndrome (ARDS). Both individual case matching and propensity score matching were used. The study sample was selected from children enrolled in the cluster-randomized RESTORE (Randomized Evaluation of Sedation Titration for Respiratory Failure) clinical trial. Detailed demographic and daily physiologic data were used to match patients. The primary endpoint was in-hospital mortality. Secondary outcomes included hospital-free days, ventilator-free days, and change in functional status at hospital discharge. MEASUREMENTS AND MAIN RESULTS: Of 2,449 children in the RESTORE trial, 879 (35.9%) non-ECMO-supported patients with severe ARDS were eligible to match to 61 (2.5%) ECMO-supported children. When individual case matching was used (60 matched pairs), the in-hospital mortality rate at 90 days was 25% (15 of 60) for both the ECMO-supported and non-ECMO-supported children (P > 0.99). With propensity score matching (61 matched pairs), the ECMO-supported in-hospital mortality rate was 15 of 61 (25%), and the non-ECMO-supported hospital mortality rate was 18 of 61 (30%) (P = 0.70). There was no difference between ECMO-supported and non-ECMO-supported patients in any secondary outcomes. CONCLUSIONS: In children with severe ARDS, our results do not demonstrate that ECMO-supported children have superior outcomes compared with non-ECMO-supported children. Definitive answers will require a rigorous multisite randomized controlled trial.

Pediatric Ventilator-Associated Events: Analysis of the Pediatric Ventilator-Associated Infection Data.

OBJECTIVES: To compare the prevalence of infection applying the proposed pediatric ventilator-associated events criteria versus clinician-diagnosed ventilator-associated infection to subjects in the pediatric ventilator-associated infection study. DESIGN: Analysis of prospectively collected data from the pediatric ventilator-associated infection study. SETTING: PICUs of 47 hospitals in the United States, Canada, and Australia. PATIENTS: Two-hundred twenty-nine children ventilated for greater than 48 hours who had respiratory secretion cultures performed to evaluate for suspected ventilator-associated infection. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Applying the proposed pediatric ventilator-associated event criteria, 15 of 229 subjects in the ventilator-associated infection study qualified as "ventilator-associated condition" and five of 229 (2%) met criteria for "infection-related ventilator-associated complication." This was compared with 89 of 229 (39%) diagnosed as clinical ventilator-associated infection (Kappa = 0.068). Ten of 15 subjects identified as ventilator-associated condition did not meet criteria for infection-related ventilator-associated complication primarily because they did not receive 4 days of antibiotics. Ventilator-associated condition subjects were similar demographically to nonventilator-associated condition subjects and had similar mortality (13% vs 10%), PICU-free days (6.9 ± 7.7; interquartile range, 0-14 vs 9.8 ± 9.6; interquartile range, 0-19; p = 0.25), but fewer ventilator-free days (6.6 ± 9.3; interquartile range, 1-15 vs 12.4 ± 10.7; interquartile range, 0-22; p = 0.04). The clinical ventilator-associated infection diagnosis in the ventilator-associated infection study was associated with fewer PICU-free days but no difference in mortality or ventilator-free days. CONCLUSIONS: The ventilator-associated event criteria appear to be insensitive to the clinical diagnosis of ventilator-associated infection. Differentiation between ventilator-associated condition and infection-related ventilator-associated complication was primarily determined by the clinician decision to treat with antibiotics rather than clinical signs and symptoms. The utility of the proposed pediatric ventilator-associated event criteria as a surrogate for ventilator-associated infection criteria is unclear.

Abusive Head Trauma and Mortality-An Analysis From an International Comparative Effectiveness Study of Children With Severe Traumatic Brain Injury.

OBJECTIVES: Small series have suggested that outcomes after abusive head trauma are less favorable than after other injury mechanisms. We sought to determine the impact of abusive head trauma on mortality and identify factors that differentiate children with abusive head trauma from those with traumatic brain injury from other mechanisms. DESIGN: First 200 subjects from the Approaches and Decisions in Acute Pediatric Traumatic Brain Injury Trial-a comparative effectiveness study using an observational, cohort study design. SETTING: PICUs in tertiary children's hospitals in United States and abroad. PATIENTS: Consecutive children (age < 18 yr) with severe traumatic brain injury (Glasgow Coma Scale ≤ 8; intracranial pressure monitoring). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Demographics, injury-related scores, prehospital, and resuscitation events were analyzed. Children were dichotomized based on likelihood of abusive head trauma. A total of 190 children were included (n = 35 with abusive head trauma). Abusive head trauma subjects were younger (1.87 ± 0.32 vs 9.23 ± 0.39 yr; p < 0.001) and a greater proportion were female (54.3% vs 34.8%; p = 0.032). Abusive head trauma were more likely to 1) be transported from home (60.0% vs 33.5%; p < 0.001), 2) have apnea (34.3% vs 12.3%; p = 0.002), and 3) have seizures (28.6% vs 7.7%; p < 0.001) during prehospital care. Abusive head trauma had a higher prevalence of seizures during resuscitation (31.4 vs 9.7%; p = 0.002). After adjusting for covariates, there was no difference in mortality (abusive head trauma, 25.7% vs nonabusive head trauma, 18.7%; hazard ratio, 1.758; p = 0.60). A similar proportion died due to refractory intracranial hypertension in each group (abusive head trauma, 66.7% vs nonabusive head trauma, 69.0%). CONCLUSIONS: In this large, multicenter series, children with abusive head trauma had differences in prehospital and in-hospital secondary injuries which could have therapeutic implications. Unlike other traumatic brain injury populations in children, female predominance was seen in abusive head trauma in our cohort. Similar mortality rates and refractory intracranial pressure deaths suggest that children with severe abusive head trauma may benefit from therapies including invasive monitoring and adherence to evidence-based guidelines.

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.

Staphylococcus aureus α-Toxin Response Distinguishes Respiratory Virus-Methicillin-Resistant S. aureus Coinfection in Children.

BACKGROUND: Development of methicillin-resistant Staphylococcus aureus (MRSA) pneumonia after a respiratory viral infection is frequently fatal in children. In mice, S. aureus α-toxin directly injures pneumocytes and increases mortality, whereas α-toxin blockade mitigates disease. The role of α-toxin in pediatric staphylococcal-viral coinfection is unclear. METHODS: We enrolled children across 34 North American pediatric intensive care units with acute respiratory failure and suspected influenza virus infection. Serial serum anti-α-toxin antibody titers and functional α-toxin neutralization capacity were compared across children coinfected with MRSA or methicillin-susceptible S. aureus (MSSA) and control children infected with influenza virus only. MRSA isolates were tested for α-toxin production and lethality in a murine pneumonia model. RESULTS: Influenza virus was identified in 22 of 25 children with MRSA coinfection (9 died) and 22 patients with MSSA coinfection (all survived). Initial α-toxin-specific antibody titers were similar, compared with those in the 13 controls. In patients with serial samples, only MRSA-coinfected patients showed time-dependent increases in anti-α-toxin titer and functional neutralization capacity. MRSA α-toxin production from patient isolates correlated with initial serologic titers and with mortality in murine pneumonia. CONCLUSIONS: These data implicate α-toxin as a relevant antigen in severe pediatric MRSA pneumonia associated with respiratory viral infection, supporting a potential role for toxin-neutralizing therapy.

Optimizing Virus Identification in Critically Ill Children Suspected of Having an Acute Severe Viral Infection.

OBJECTIVES: Multiplex rapid viral tests and nasopharyngeal flocked swabs are increasingly used for viral testing in PICUs. This study aimed at evaluating how the sampling site and the type of diagnostic test influence test results in children with suspected severe viral infection. DESIGN: Prospective cohort study. SETTING: PICUs at 21 tertiary pediatric referral centers in the United States. PATIENTS: During the 2010-2011 and 2011-2012 influenza seasons, we enrolled children (6 mo to 17 yr old) who were suspected to have severe viral infection. INTERVENTIONS: We collected samples by using a standardized protocol for nasopharyngeal aspirate and nasopharyngeal flocked swabs in nonintubated patients and for endotracheal tube aspirate and nasopharyngeal flocked swabs in intubated patients. MEASUREMENTS AND MAIN RESULTS: Viral testing included a single reverse transcription-polymerase chain reaction influenza test and the GenMark Respiratory Viral Panel (20 viruses). We enrolled 90 endotracheally intubated and 133 nonintubated children. We identified influenza in 45 patients with reverse transcription-polymerase chain reaction testing; the multiplex panel was falsely negative for influenza in two patients (4.4%). Six patients (13.3%) had not been diagnosed with influenza in the PICU. Non-influenza viruses were identified in 172 of 223 children (77.1%). In nonintubated children, the same virus was identified by nasopharyngeal flocked swabs and nasopharyngeal aspirate in 133 of 183 paired samples (72.7%), with +nasopharyngeal aspirate/-nasopharyngeal flocked swabs in 32 of 183 paired samples (17.4%). In intubated children, the same virus was identified by nasopharyngeal flocked swabs and endotracheal tube aspirate in 67 of 94 paired samples (71.3%), with +nasopharyngeal flocked swabs/- endotracheal tube aspirate in 22 of 94 paired samples (23.4%). Most discrepancies were either adenovirus or rhinovirus in both groups. CONCLUSIONS: Standardized specimen collection and sensitive diagnostic testing with a reverse transcription-polymerase chain reaction increased the identification of influenza in critically ill children. For most pathogenic viruses identified, results from nasopharyngeal flocked swabs agreed with those from nasopharyngeal or endotracheal aspirates.

A multinational study of thromboprophylaxis practice in critically ill children.

OBJECTIVES: 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. DESIGN: Prospective multinational cross-sectional study over four study dates in 2012. SETTING: Fifty-nine PICUs in Australia, Canada, New Zealand, Portugal, Singapore, Spain, and the United States. PATIENTS: 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. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: 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. CONCLUSIONS: 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.

Duplication of 20qter and deletion of 20pter due to paternal pericentric inversion: patient report and review of 20qter duplications.

Duplications of the terminal long arm of chromosome 20 are rare chromosomal anomalies. We report a male infant found on array comparative genomic hybridization analysis to have a 19.5 Mb duplication of chromosome 20q13.12-13.33, as well as an 886 kb deletion of 20p13 at 18,580-904,299 bp. This anomaly occurred as the recombinant product of a paternal pericentric inversion. There have been 23 reported clinical cases involving 20qter duplications; however, to our knowledge this is only the second reported patient with a paternal pericentric inversion resulting in 46,XY,rec(20)dup(20q). This patient shares many characteristics with previously described patients with 20qter duplications, including microphthalmia, anteverted nares, long ears, cleft palate, small chin, dimpled chin, cardiac malformations, and normal intrauterine growth. While there is variable morbidity in patients with terminal duplications of 20q, a review of previously reported patients and comparison to our patient's findings shows significant phenotypic similarity.

Transthoracic echocardiography in pediatric intensive care: impact on medical and surgical management.

OBJECTIVES: Although transthoracic echocardiography is commonly performed in the PICU, its utility is not specifically known. The purpose of this investigation was to evaluate the clinical impact of echocardiography in the PICU in terms of frequency of unanticipated findings and the frequency and nature of clinical management changes attributed to the results of echocardiography. DESIGN: Prospective cohort study. SETTING: Nineteen-bed combined medical-surgical-cardiac PICU at a tertiary care children's hospital. PATIENTS: All patients in PICU undergoing transthoracic echocardiography. INTERVENTIONS, MEASUREMENTS, AND MAIN RESULTS: Data collected included echocardiography indications, pre-echocardiography clinical assessment of anticipated echocardiography findings, height, weight, primary diagnosis, age, and urgency (stat vs routine) of echocardiography. Input of the attending care team (intensivist, cardiologist, and/or cardiovascular surgeon) allowed classification of echocardiography results as either confirming the pre-echocardiography impression, altering the pre-echocardiography clinical impression regarding the indication for which the test was performed, or altering the impression by virtue of new findings unrelated to the specific indication. The nature of the new findings were recorded and categorized. The team recorded clinical management changes made in response to the echocardiography results; the nature of these were listed and categorized. Echocardiograms (n = 416) were performed in 132 patients. Of these, 244 echocardiograms (59%) were ordered on male patients, 31% were under 30 days old, median age was 103 days, 379 (91%) had a primary cardiac diagnosis, and 92 (22%) were ordered stat. Sixty-three percent of echocardiograms confirmed and 24% altered the pre-echocardiography impression regarding the indication for the echocardiography; 13% introduced new findings unrelated to the indication. Cardiac surgical revision was the management change required in 26 patients (6.3%). Stat echocardiography was more likely to alter the pre-echocardiography assessment than routine echocardiography (p < 0.001). Management changes were more commonly associated with stat echocardiograms (p = 0.002) and those with new unexpected findings (p < 0.001) but had no demonstrable association with age less than 30 days (p = 0.332). CONCLUSIONS: Unanticipated echocardiography results are common in the PICU, and they often alter the clinical impressions that prompted the echocardiogram or introduce new findings unrelated to the reason for which the echocardiogram was recorded. Clinical management changes attributable to echocardiography findings are frequent in the PICU, including occasional surgical intervention. Echocardiography adds diagnostic value and contributes to the management approach in the PICU, accounting for its frequent use.

Pediatric calfactant in acute respiratory distress syndrome trial.

RATIONALE: Our previous studies in children with acute lung injury/acute respiratory distress syndrome demonstrated improved outcomes with exogenous surfactant (calfactant) administration. Sample sizes in those studies were small, however, and the subject populations heterogeneous, thus making recommendations tenuous. OBJECTIVE: To investigate the efficacy of surfactant administration in a larger, more homogenous population of children with lung injury/acute respiratory distress syndrome due to direct lung injury. DESIGN AND SETTING: Masked, randomized, placebo-controlled trial in 24 children's hospitals in six different countries. PATIENTS AND METHODS: Children 37 weeks postconception to 18 years old with lung injury/acute respiratory distress syndrome due to direct lung injury were randomized to receive up to three doses of 30 mg/cm height of surfactant (calfactant) versus placebo (air) within 48 hours of intubation and initiation of mechanical ventilation. The primary outcome was mortality at 90 days. Ventilator-free days, changes in oxygenation, and adverse events were also assessed. RESULTS: The study was stopped at the sponsor's request after the second interim analysis for presumed futility. A total of 110 subjects were enrolled, with consent withdrawn from one whose data are unavailable. There were no significant differences between groups except in hospital-free days (10.4 ± 7.8 placebo vs 6.4 ± 7.8 surfactant; p = 0.01). Overall 90-day mortality was 11% (seven surfactant, five placebo). No immediate improvement in oxygenation was associated with surfactant administration. CONCLUSIONS: Surfactant did not improve outcomes relative to placebo in this trial of children with direct lung injury/acute respiratory distress syndrome. Differences in concentration of the surfactant, failure to recruit the lung during surfactant administration, or using two rather than four position changes during administration are possible explanations for the difference from previous studies. Exogenous surfactant cannot be recommended at this time for children with direct lung injury/acute respiratory distress syndrome.

The relationship of fluid administration to outcome in the pediatric calfactant in acute respiratory distress syndrome trial.

OBJECTIVES: Adult studies have demonstrated the relationship between fluid overload and poor outcomes in acute lung injury/acute respiratory distress syndrome. The approach of pediatric intensivists to fluid management in acute lung injury/acute respiratory distress syndrome and its effect on outcomes is less clear. In a post hoc analysis of our Calfactant in Acute Respiratory Distress Syndrome trial, we examined the relationship of fluid balance to in-hospital outcomes in subjects with acute lung injury/acute respiratory distress syndrome. DESIGN: Calfactant in Acute Respiratory Distress Syndrome was a masked randomized controlled trial of calfactant surfactant versus placebo in pediatric patients with acute lung injury/acute respiratory distress syndrome due to direct lung injury. Caregivers were encouraged to follow a conservative fluid management guideline based on the adult Fluid and Catheter Treatment Trial. Daily fluid balance was collected for the first 7 days after trial enrollment and correlated with clinical outcomes. PATIENTS AND SETTING: Children admitted to PICUs with acute lung injury/acute respiratory distress syndrome from 24 children's hospitals in six different countries. INTERVENTION: Post hoc analysis of daily fluid balance in subjects from the Pediatric Calfactant in Acute Respiratory Distress Syndrome trial. MEASUREMENTS AND MAIN RESULTS: Despite the conservative fluid guideline, fluid management was more consistent with a "liberal" approach. On average, study subjects accumulated 1.96 ± 4.2 L/m over the first 7 days of the trial. Subjects who died accumulated on average 8.7 ± 9.5 L/m versus 1.2 ± 2.4 L/m in survivors. Increasing fluid accumulation was associated with fewer ventilator-free days and worsening oxygenation. Multivariable regression models that included age, gender, Pediatric Risk of Mortality score, initial oxygen saturation index and PaO2/FIO2 ratio, injury category, and treatment arm failed to account for the differences in fluid management. CONCLUSIONS: Pediatric intensivists generally follow a "liberal" approach to fluid management in children with acute lung injury/acute respiratory distress syndrome. Illness severity or oxygenation disturbance did not explain differences in fluid accumulation but such accumulation was associated with worsening oxygenation, a longer ventilator course, and increased mortality. A more conservative approach to fluid management may improve outcomes in children with acute lung injury/acute respiratory distress syndrome.

Does the use of an assistive device by nurses impact peripheral intravenous catheter insertion success in children?

Peripheral intravenous (PIV) access is a common and essential component for the medical management of the hospitalized child. Delayed or failed PIV insertion can increase the risk for complications from delayed intravenous treatment. Repetitive PIV insertion attempts can cause psychological trauma to the child and decrease family satisfaction. This study examined the success of two vein visualization assistive devices in aiding PIV insertions performed by pediatric medical-surgical nurses. During the 11-month investigation period, PIV insertion success was significantly higher when no assistive device was used compared to assisted methods. Implications for practice and further research are discussed.

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.

Functional Transcranial Doppler Ultrasound for Monitoring Cerebral Blood Flow.

Functional transcranial Doppler ultrasound (fTCD) is the use of transcranial Doppler ultrasound (TCD) to study neural activation occurring during stimuli such as physical movement, activation of tactile sensors in the skin, and viewing images. Neural activation is inferred from an increase in the cerebral blood flow velocity (CBFV) supplying the region of the brain involved in processing sensory input. For example, viewing bright light causes increased neural activity in the occipital lobe of the cerebral cortex, leading to increased blood flow in the posterior cerebral artery, which supplies the occipital lobe. In fTCD, changes in CBFV are used to estimate changes in cerebral blood flow (CBF). With its high temporal resolution measurement of blood flow velocities in the major cerebral arteries, fTCD complements other established functional imaging techniques. The goal of this Methods paper is to give step-by-step instructions for using fTCD to perform a functional imaging experiment. First, the basic steps for identifying the middle cerebral artery (MCA) and optimizing the signal will be described. Next, placement of a fixation device for holding the TCD probe in place during the experiment will be described. Finally, the breath-holding experiment, which is a specific example of a functional imaging experiment using fTCD, will be demonstrated.

Most High-Intensity Transient Signals Are Not Associated With Specific Surgical Maneuvers.

BACKGROUND: Mortality after congenital heart defect surgery has dropped dramatically in the last few decades. Current research on long-term outcomes has focused on preventing secondary neurological sequelae, for which embolic burden is suspected. In children, little is known of the correlation between specific surgical maneuvers and embolic burden. Transcranial Doppler ultrasound is highly useful for detecting emboli but has not been widely used with infants and children. METHODS: Bilateral middle cerebral artery blood flow was continuously monitored from sternal incision to chest closure in 20 infants undergoing congenital heart defect repair or palliative surgery. Embolus counts for specific maneuvers were recorded using widely accepted criteria for identifying emboli via high-intensity transient signals (HITS). RESULTS: An average of only 13% of all HITS detected during an operation were correlated with any of the surgical maneuvers of interest. The highest mean number of HITS associated with a specific maneuver occurred during cross-clamp removal. Cross-clamp placement also had elevated HITS counts that significantly differed from other maneuvers. CONCLUSIONS: In this study of infants undergoing cardiac surgery with cardiopulmonary bypass, the great majority of HITS detected are not definitively associated with a specific subset of surgical maneuvers. Among the measured maneuvers, removal of the aortic cross-clamp was associated with the greatest occurrence of HITS. Future recommended research efforts include identifying and confirming other sources for emboli and longitudinal outcome studies to determine if limiting embolic burden affects long-term neurological outcomes.

Progressive Familial Intrahepatic Cholestasis Presenting With an Intracranial Bleed and Mimicking Abusive Head Trauma.

INTRODUCTION: Abusive head trauma is a serious, often fatal condition; early identification is important to prevent repeat episodes and/or injuries to siblings. This case emphasizes the importance of a thorough workup in cases of suspected abusive head trauma. CASE PRESENTATION: A 4-month-old infant was found to have a severe subdural hematoma requiring surgical evacuation. Initially, abusive head trauma was considered as a diagnosis. Testing revealed vitamin K deficiency bleeding (VKDB) despite prophylactic vitamin K administration at birth. The infant eventually was diagnosed with progressive familial Iintrahepatic cholestasis type 2 (PFIC2). DISCUSSION: Although VKDB is a known cause of infantile intracranial hemorrhage, PFIC has not been previously reported to cause severe VKDB resulting in an intracranial hemorrhage. CONCLUSION: Our case illustrates the importance of a comprehensive systematic approach to investigate causes other than abusive head injury when intracranial bleeding is a significant finding.

The Breath-Hold Acceleration Index: A New Method to Evaluate Cerebrovascular Reactivity using Transcranial Doppler.

BACKGROUND AND PURPOSE: Cerebrovascular reactivity (CR) is an ideal biomarker to detect cerebrovascular damage. CR can be quantified by measuring changes in cerebral blood flow velocity (CBFV) resulting from a CO2  vasodilatory stimulus, often using the breath-holding index (BHI). In this method, transcranial Doppler (TCD) ultrasound is used to measure CBFV changes in the middle cerebral artery (MCA) during a breath-hold maneuver. Despite its convenience, BHI has high variability. Changing body position may contribute to potential variability. It is important to determine if CR differs with body position. The aims of this study were, first, to propose an alternative, more robust index to evaluate CR using a breath-hold maneuver; second, investigate the effect of body position on CR measured with conventional (BHI) and a new proposed index. METHODS: Ten healthy young volunteers held their breath for 30 seconds on a tilt table. CR was calculated at five different angles using two indices: the conventional BHI, and the breath-hold acceleration index (BHAI), a new index obtained by linear regression of the most linear portion of the mean velocity change during the breath-hold maneuver. The regression represents acceleration (change in blood flow velocity per unit of time) sampled at each cardiac cycle. RESULTS: The mean coefficient of variation was 43.7% lower in BHAI in comparison with BHI. Neither index was statistically significant between body positions (P > .05). CONCLUSIONS: BHAI has less variability in comparison with the conventional standard BHI. Additionally, neither index showed statistical significance in CR based on change in body position.