Michael Seear

Effect of hyperventilation on regional cerebral blood flow in head-injured children.

OBJECTIVES To study cerebral blood flow and cerebral oxygen consumption in severe head-injured children and also to assess the effect of hyperventilation on regional cerebral blood flow. DESIGN Prospective cohort study. SETTING Pediatric intensive care unit at a tertiary-level university childrens hospital. PATIENTS Twenty-three children with isolated severe brain injury, whose admission Glasgow Coma Scores were <8. INTERVENTIONS PaCO2 was adjusted by altering minute ventilation. Cerebral metabolic measurements were made at three levels of PaCO2 (>35, 25 to 35, and <25 torr [>4.7, 3.3 to 4.7, and <3.3 kPa]) after allowing 15 mins for equilibrium. MEASUREMENTS AND MAIN RESULTS Thirty-eight studies (each study consisting of three sets of measurements at different levels of PaCO2) were performed on 23 patients. At each level of PaCO2, the following measurements were made: xenon-enhanced computed tomography scans; cerebral blood flow; intracranial pressure; jugular venous bulb oxygen saturation; mean arterial pressure; and arterial oxygen saturation. Derived variables included: cerebral oxygen consumption; cerebral perfusion pressure; and oxygen extraction ratio. Cerebral blood flow decreased below normal after head injury (mean 49.6 +/- 14.6 mL/min/100 g). Cerebral oxygen consumption decreased out of proportion to the decrease in cerebral blood flow; cerebral oxygen consumption was only a third of the normal range (mean 1.02 +/- 0.59 mL/min/100 g). Neither cerebral blood flow nor cerebral oxygen consumption showed any relationship to time after injury, Glasgow Coma Score at the time of presentation, or intracranial pressure. The frequency of one or more regions of ischemia (defined as cerebral blood flow of <18 mL/min/100 g) was 28.9% during normocapnia. This value increased to 73.1% for PaCO2 at <25 torr. CONCLUSIONS Severe head injury in children produced a modest decrease in cerebral blood flow but a much larger decrease in cerebral oxygen consumption. Absolute hyperemia was uncommon at any time, but measured cerebral blood flow rates were still above the metabolic requirements of most children. The clear relationship between the frequency of cerebral ischemia and hypocarbia, combined with the rarity of hyperemia, suggests that hyperventilation should be used with caution and monitored carefully in children with severe head injuries.

How accurate is the diagnosis of exercise induced asthma among Vancouver schoolchildren

Background: Limited access to exercise testing facilities means that the diagnosis of exercise induced asthma (EIA) is mainly based on self-reported respiratory symptoms. This is open to error since the correlation between exercise related symptoms and subsequent exercise testing has been shown to be poor. Aim: To study the accuracy of clinically diagnosed EIA among Vancouver schoolchildren. Methods: Fifty two children referred for investigation of poorly controlled EIA were studied. Following a careful history and physical examination, children performed pulmonary function tests before, then 5 and 15 minutes after a standardised treadmill exercise test. Based on overall assessment, a diagnostic explanation for each child’s respiratory complaints was provided as far as possible. Results: Only eight children (15.4%) fulfilled diagnostic criteria for EIA (fall in FEV1 ⩾10%). Of the remainder: 12 (23.1%) were unfit, 14 (26.9%) had vocal cord dysfunction/sigh dyspnoea, 7 (13.5%) had a habit cough, and 11 (21.1%) had no abnormalities on clinical or laboratory testing, so were given no diagnosis. Initial reported symptoms of wheeze or cough often changed significantly following a careful history, particularly among the eight elite athletes. The final complaint was sometimes not respiratory, and, in a few cases, was not even associated with exercise. Conclusions: The clinical diagnosis of EIA is inaccurate among Vancouver schoolchildren, principally due to the unreliability of their initial exercise related complaints. Symptom exaggeration, familiarity with medical jargon, and psychogenic complaints are all common. A careful history is essential in this population before basing any diagnosis on self-reported respiratory symptoms.

A controlled study of postpartum depression among Nepalese women: validation of the Edinburgh Postpartum Depression Scale in Kathmandu

OBJECTIVES To measure the prevalence of depression amongst postpartum and non‐postpartum Nepalese women in Kathmandu using the Edinburgh Postpartum Depression Scale (EPDS) and to assess the ease of use and validity of the scale compared with Diagnostic and Statistical Manual of Mental Disorders (DSM‐IV) criteria for major depression.

Thiamine, riboflavin, and pyridoxine deficiencies in a population of critically ill children

The unexpected autopsy finding of Wernicke encephalopathy in three children who died after prolonged enteral feeding prompted us to examine the incidence of thiamine deficiency in three high-risk pediatric populations. We also measured riboflavin and pyridoxine activity in the same groups. We used activated enzyme assays (erythrocyte transketolase, glutathione reductase, aspartate aminotransferase) to assess tissue stores of the dependent vitamin cofactors (thiamine (vitamin B1), riboflavin (vitamin B2), and pyridoxine (vitamin B6), respectively). Using our own reference ranges based on data from 80 healthy adults and children, we prospectively investigated the B vitamin status of three groups of children: (1) 27 patients who were fed solely by nasogastric tube for more than 6 months, (2) 80 children admitted to a pediatric intensive care unit for more than 2 weeks, and (3) 6 children receiving intensive chemotherapy. The upper limits for stimulated enzyme activity in control subjects were unaffected by age or gender (16% for transketolase, 63% for glutathione reductase, 123% for aspartate aminotransferase). Using these limits, 10 (12.5%) of 80 patients receiving intensive care and 4 of 6 patients receiving chemotherapy were thiamine deficient. Elevated levels returned to normal after thiamine supplementation. No patients were pyridoxine deficient, but 3 (3.8%) of the 80 patients receiving intensive care and 1 of the 6 patients receiving chemotherapy were also riboflavin deficient. We conclude that unrecognized thiamine deficiency is common in our pediatric intensive care and oncology groups. This potentially fatal but treatable disease can occur in malnourished patients of any age and is probably underdiagnosed among chronically ill children. Our findings may be applicable to other high-risk pediatric groups.

Long-term ventilation in children: longitudinal trends and outcomes

Background Cross-sectional studies have suggested a rapid expansion in paediatric long-term ventilation (LTV) over the last 20 years but information on longitudinal trends is limited. Methods Data were collected prospectively on all patients receiving LTV over a 15-year period (1.1.95–31.12.09) in a single regional referral centre. Results 144 children commenced LTV during the 15-year period. The incidence of LTV increased significantly over time, with an accompanying 10-fold increase in prevalence due to a significant increase in institution of non-invasive ventilation (NIV). There was no significant increase in invasive ventilation. 5-year survival was 94% overall and was significantly higher for patients on NIV (97%) than invasively ventilated patients (84%). 10-year survival was 91% overall. Although some children were able to discontinue respiratory support (21% at 5 years and 42% at 10 years), the number of patients transitioned to adult services increased significantly over time (26% of total cohort). Patients with neuromuscular disease were less likely to discontinue support than other patients. Conclusions The paediatric LTV population has expanded significantly over 15 years. Future planning of paediatric hospital and community services, as well as adult services, must take into account the needs of this growing population.

Life-Threatening Human Metapneumovirus Pneumonia Requiring Extracorporeal Membrane Oxygenation in a Preterm Infant

We present the first report in the literature of a child with human metapneumovirus pneumonia who required extracorporeal membrane oxygenation for survival. This was a 3-month-old premature boy from British Columbia, Canada, who developed severe respiratory failure, experienced failure of high-frequency oscillatory mechanical ventilation, and required extracorporeal membrane oxygenation support for 10 days. This case illustrates the importance of including this newly discovered pathogen among the causes of childhood pneumonia.

Functional characteristics of pediatric veno-venous hemofiltration

ObjectiveTo evaluate the functional characteristics of continuous veno-venous hemofiltration in a pediatric size animal model. DesignProspective trial. SettingAnimal laboratory at a large university-affiliated medical center. SubjectsFour-week old lambs (weight 12.2 ± 1.3 kg). InterventionsVeno-venous hemofiltration was performed in anesthetized lambs (n = 5, 12.2 ± 1.3 kg) using a standard pediatric hemofilter and pumped blood and ultrafiltrate. We compared postdilution, predilution, and hemofiltration with counterflow dialysis. Measurements and Main ResultsAt net ultrafiltrate flows of 200, 400, and 600 mL/hr, we measured system pressures and urea clearance. Stable blood flow could reproducibly be achieved up to 140 mL/min (10 mL/kg/min); at higher flow demand, tubing collapse occurred. At blood flow rates of 5 to 10 mL/kg/min, ultrafiltrate flow of 1 mL/kg/min would create negative filter compartment pressure but consistently less negative than −500 mm Hg. During postdilution, predilution, and counterflow dialysis, urea clearance was virtually equal to ultrafiltrate flow. There was no increase in urea clearance when adding predilution or dialysis to basic postdilution. ConclusionsVeno-venous hemofiltration, using small filters and circuits in a pediatric size animal, can achieve stable blood flow up to 10 mL/kg/min. At this flow, ultrafiltrate flow of 1 mL/kg/min can produce a urea clearance of 1 mL/kg/min while keeping filter compartment pressure above maximal recommended negative pressures. Addition of dialysis in this nonuremic model did not increase urea clearance. (Crit Care Med 1994; 22:320–325)

Doppler-derived mean aortic flow velocity in children: An alternative to cardiac index

SummaryThis study tested the hypothesis that mean aortic velocity is relatively constant in children. Eighty-eight normal children (aged 1 month to 15 years) were studied prospectively. Ascending aortic flow velocities were obtained by pulse Doppler and mean aortic velocities calculated. Mean aortic flow velocity was relatively constant for all ages at 28.4±4.8 cm/s. As Doppler is easy to perform, mean aortic flow velocity may be an alternative approach to the assessment of cardiac output.

Fifty years of pediatric asthma in developed countries: How reliable are the basic data sources?†‡§¶

Given the difficulties in diagnosing, or even defining, asthma in children, claims of a pediatric asthma epidemic in Canada and other developed countries are accepted with surprisingly little critical examination. We reviewed a broad range of data sources to understand how the epidemic evolved during the last 50 years and also to assess the reliability of the conclusions drawn from that data. We obtained Canadian National and Provincial data from Statistics Canada National Population Health Survey, and the British Columbia Ministry of Health respiratory database. International data were obtained by extensive review of pediatric asthma epidemiological surveys published during the last 50 years. In many developed countries, there have been three separate epidemics involving different aspects of pediatric asthma during the last 50 years: a double peaked mortality epidemic (1960s and 1980s), a hospital admission epidemic (peaked around 1990) and a steadily growing epidemic of children who report asthmatic symptoms on questionnaires. Canadian pediatric rates for asthma mortality (1–2/million/year) and hospital admission (1–2/thousand/year) are low and have fallen for the last 20 years. Rates based on questionnaire studies are high (10–15/hundred) and rose steadily over the same period. Objective reductions in asthma deaths and hospital admission likely reflect improved education and treatment programmes. Current claims of an epidemic based largely on subjective self‐reported symptoms require more careful analysis. The possibility that symptom misperception, disease fashions, and poor recall, may be part of the explanation for the current high levels of self‐reported symptoms deserves more attention. Pediatr Pulmonol. 2012; 47:211–219.

JAK1 gain-of-function causes an autosomal dominant immune dysregulatory and hypereosinophilic syndrome

Kate L. Del Bel, MSc, Robert J. Ragotte, BSc, Aabida Saferali, MSc, Susan Lee, RN, Suzanne M. Vercauteren, MD PhD, Sara A. Mostafavi, PhD, Richard A. Schreiber, MD, Julie S. Prendiville, MD, Min S. Phang, MD, Jess Halperin, MD, Nicholas Au, MD, John M. Dean, MD BS, Emily Jewels, RN, Anne K. Junker, MD, Paul C. Rogers, MB ChB MBA, Michael Seear, MB ChB, Margaret L. McKinnon, MD, Stuart E. Turvey, MB BS, DPhil