Influence of pulmonary factors on pulse oximeter saturation in preterm infants.

AIM: To describe how the stability of oxygen saturation measured by pulse oximetry (SpO2%) varies within and between infants with bronchopulmonary dysplasia (BPD). METHODS: Clinically stable infants with BPD had SpO2 measured at different inspired oxygen concentrations (FIO2 expressed as %). A computer model of gas exchange, that is, ventilation/perfusion ratio (VA/Q) and shunt, plotted the curve of SpO2 versus FIO2 best fitting these data. The slope of this curve is the change in SpO2 per % change in FIO2, hence SpO2 stability, calculated at each SpO2 from 85% to 95%. RESULTS: Data from 16 infants with BPD previously described were analysed. The dominant gas exchange impairment was low VA/Q (median 0.35, IQR, 0.16-0.4, normal 0.86). Median shunt was 1% (IQR, 0-10.5; normal <2%). Slope varied markedly between infants, but above 95% SpO2 was always <1.5. In infants with least severe BPD (VA/Q ≈0.4, shunt ≤2%) median slope at 85% SpO2 was 5.1 (IQR, 3.7-5.5). With more severe BPD (VA/Q ≤0.3) slope was flatter throughout the SpO2 range. The highest FIO2 for 90% SpO2 was in infants with the lowest VA/Q values. CONCLUSIONS: In infants with BPD, there was large variation in the slope of the curve relating SpO2% to inspired oxygen fraction in the SpO2 range 85%-95%. Slopes were considerably steeper at lower than higher SpO2, especially in infants with least severe BPD, meaning that higher SpO2 target values are intrinsically much more stable. Steep slopes below 90% SpO2 may explain why some infants appear dependent on remarkably low oxygen flows.

Assessing efficient patient care: should length of stay be calculated independently of local admission rates?

OBJECTIVE: To compare the length of hospitalisation for infants with bronchiolitis across the Eastern region and to assess the impact of the varying admission rates in each hospital. DESIGN: Data collection through the Hospital Episode Statistics (HES) using the ICD clinical coding for bronchiolitis across all hospitals in east of England for three winter seasons (October to March for the years 2009/10, 2010/11 and 2011/12). MAIN OUTCOME MEASURE: Length of hospital stay, corrected to adjust for local population. RESULTS: Seventeen hospitals across the east of England were included in this study. Overall admission rate (as a percentage of the population) for the region was 3.3% and consistent with national data, but rates within individual hospitals varied between 1.5% and 5.7% over the 3-year period. Bed days per 1000 population ('standardised bed days') per year varied almost fourfold, from 34.5 to 122.3 in different hospitals. Corrected length of stay showed high discordance when compared to average length of stay. CONCLUSIONS: The average length of stay is substantially affected by admission rates, with hospitals who admit a greater proportion of infants appearing to have a shorter uncorrected length of stay. We propose that a single corrected measure for length of stay should be used when assessing the efficiency of care because it is unaffected by variations in local admission rates and is adjusted for local population size.

Paediatrics in Barcelona: highlights from the 2010 ERS Annual Congress.

The aim of this update is to describe the paediatric highlights from the 2010 European Respiratory Society Annual Congress in Barcelona, Spain. Abstracts from the seven groups of the Paediatric Assembly (Respiratory physiology, Asthma and allergy, Cystic fibrosis, Respiratory infection and immunology, Neonatology and paediatric intensive care, Respiratory epidemiology and Bronchology) are presented in the context of the current literature.

Paediatrics in Vienna.

The aim of this article is to describe the paediatric highlights from the 2009 European Respiratory Society Annual Congress in Vienna, Austria. The best abstracts from the seven groups of the Paediatric Assembly (asthma and allergy, respiratory epidemiology, cystic fibrosis, respiratory physiology, respiratory infections and immunology, neonatology and paediatric intensive care, and bronchology) are presented alongside findings from the current literature.

A longitudinal assessment of the effect of inhaled fluticasone propionate therapy on adrenal function and growth in young children with asthma.

OBJECTIVE: Fluticasone proprionate (FP) is increasingly used to treat very young children with asthma. Its safety in terms of effects on the hypothalamic pituitary axis (HPA) and growth in this age group is uncertain. PATIENTS AND METHODS: Eleven children (median (range) age 10 (5.6-24.3) months) presenting with recurrent wheeze and family history of asthma were studied prospectively for a period of 18 months. Children received daily-inhaled FP 250 microg via a spacer device. No other corticosteroid therapy was administered prior to or during the study. A Short Standard Synacthen Test (SST) (125 microg) was performed pretreatment, and after 6 and 18 months. Weight (Wt), height (Ht), and body mass index (BMI) were measured at 3-6 monthly intervals. RESULTS: Fasting early morning and peak cortisol levels remained within the normal reference range with therapy. There were no changes in Ht SDS, whereas both Wt SDS (baseline 0.05 (-2.17 to 0.52) vs. +18 months 0.68 (-0.5 to 1.36) P < 0.02) and BMI SDS (-0.22 (-1.73 to 0.75) vs. 0.86 (0.03 to 1.99) P < 0.005) increased after 18 months of treatment. CONCLUSION: Daily treatment with inhaled FP 250 microg in young children with asthma appears to have no adverse effects on the HPA or on linear growth, however, treatment is associated with increases in body Wt and BMI in young children.

Lymphocyte apoptosis in acute respiratory syncytial virus bronchiolitis.

Respiratory syncytial virus (RSV) infection may have an effect on the development of T cell memory responses. RSV bronchiolitis in infants is associated with a transient decline in circulating lymphocytes. We hypothesized that the mechanism underlying this lymphopenia is apoptosis. Blood was taken from 32 infants during primary RSV bronchiolitis and three months later. Using flow cytometry, we found that absolute numbers of both CD3+/CD4+ T-helper lymphocytes (P = 0.029) and CD3+/CD8+ cytotoxic lymphocytes (CTL) (P = 0.043) were significantly reduced during acute infection. Up-regulated expression both of Fas (P < 0.001) and tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor (P < 0.001) was found during acute illness on both CD3+/CD4+ and CD3+/CD8+ lymphocytes, when compared with convalescent samples. Expression of Fas on CD4+ lymphocytes was inversely related to CD4+ number (P = 0.03). Plasma levels of soluble Fas ligand (P = 0.028) and caspase-1 (P = 0.037), determined by enzyme-linked immunosorbent assay, were increased during bronchiolitis. Plasma interleukin-18, a product of caspase-1 activity, was not raised. Taken together, these data suggest that in acute RSV infection, CD4+ helper lymphocytes and CD8+ cytotoxic lymphocytes are primed to undergo apoptosis. This is a mechanism through which lymphopenia may occur and T cell memory may be altered.

Survey of adrenal crisis associated with inhaled corticosteroids in the United Kingdom.

BACKGROUND: Until recently, only two cases of acute adrenal crisis associated with inhaled corticosteroids (ICS) had been reported worldwide. We identified four additional cases and sought to survey the frequency of this side effect in the United Kingdom. METHODS: Questionnaires were sent to all consultant paediatricians and adult endocrinologists registered in a UK medical directory, asking whether they had encountered asthmatic patients with acute adrenal crisis associated with ICS. Those responding positively completed a more detailed questionnaire. Diagnosis was confirmed by symptoms/signs and abnormal hypothalamic-pituitary-adrenal axis function test results. RESULTS: From an initial 2912 questionnaires, 33 patients met the diagnostic criteria (28 children, five adults). Twenty-three children had acute hypoglycaemia (13 with decreased levels of consciousness or coma; nine with coma and convulsions; one with coma, convulsions and death); five had insidious onset of symptoms. Four adults had insidious onset of symptoms; one had hypoglycaemia and convulsions. Of the 33 patients treated with 500-2000 micro g/day ICS, 30 (91%) had received fluticasone, one (3%) fluticasone and budesonide, and two (6%) beclomethasone. CONCLUSIONS: The frequency of acute adrenal crisis was greater than expected as the majority of these patients were treated with ICS doses supported by British Guidelines on Asthma Management. Despite being the least prescribed and most recently introduced ICS, fluticasone was associated with 94% of the cases. We therefore advise that the licensed dosage of fluticasone for children, 400 micro g/day, should not be exceeded unless the patient is being supervised by a physician with experience in problematic asthma. We would also emphasise that until adrenal function has been assessed patients receiving high dose ICS should not have this therapy abruptly terminated as this could precipitate adrenal crisis.

Acute adrenal crisis in asthmatics treated with high-dose fluticasone propionate.

Four cases of asthma (one adult, three children) developing acute adrenal crisis after introduction of high-dose inhaled fluticasone proprionate are presented. The three children, aged 7-9 yrs, had been prescribed inhaled fluticasone, dosage 500-2,000 microg x day(-1) and duration 5 months-5 yrs. All presented with convulsions due to hypoglycaemia (blood glucose 1.3-1.8 mM). The fourth case was a male of 33 yrs with difficult-to-control asthma and had been taking fluticasone propionate 1,000-2,000 microg x day(-1) for 3 yrs. He presented with fatigue, lethargy, nausea and postural hypotension. Acute adrenal crisis in each case was confirmed by investigations which included measurement of acute phase cortisol levels, short and long Synacthen stimulation tests and glucagon stimulation tests. Other cases of hypthoalamic-pituitary-adrenal axis suppression were excluded.

Bereavement support following sudden and unexpected death: guidelines for care.

Dealing with families who have suffered a sudden and unexpected death is a skill that may be needed by any paediatrician. Offering a bereavement follow up meeting to such families is part of accepted practice and is perceived to be of value in helping the family to come to terms with the loss. Unfortunately, there is very little guidance on the objectives for such a meeting, or the training required to help staff conduct such meetings. The nature of the work on a paediatric intensive care unit (PICU) means that staff have a greater experience of handling families in such a situation. We have reviewed our experience over the past five years following up the families of 51 children who have died suddenly and unexpectedly in our regional PICU. In doing this we have identified five key elements that we suggest are essential to a successful follow up meeting, and have supported this with case studies as illustration.

Association of alpha(1)-antichymotrypsin deficiency with milder lung disease in patients with cystic fibrosis.

BACKGROUND: Cystic fibrosis (CF) is characterised by an excess of free proteinases that destroy lung tissue. Despite this, previous studies have shown that patients with CF with a mild deficiency variant of the proteinase inhibitor alpha(1)-antitrypsin have less, rather than more, severe pulmonary disease. Alpha(1)-antichymotrypsin is another important serine proteinase inhibitor that protects the lung against proteolytic attack, and point mutations in the alpha(1)-antichymotrypsin gene that result in plasma deficiency are associated with chronic obstructive pulmonary disease. METHODS: The effect of alpha(1)-antichymotrypsin deficiency and the -15 alpha(1)-antichymotrypsin signal peptide genotype on lung function was assessed in patients with CF. RESULTS: One hundred and fifty seven patients with CF were screened and 10 were identified with a plasma deficiency of alpha(1)-antichymotrypsin (plasma concentration <0.2 g/l). In a multivariate analysis these individuals had significantly less severe lung disease than those who had normal or raised levels of alpha(1)-antichymotrypsin: forced expiratory volume in one second (FEV(1)) 69.9% predicted versus 53. 2% predicted (p=0.04) and chest radiographic score of 7.2 versus 9.7 (p=0.03) for those with and without alpha(1)-antichymotrypsin deficiency, respectively. The -15 signal peptide genotype did not affect plasma levels, but the -15 Ala/Ala signal peptide genotype was over-represented in individuals with CF compared with healthy blood donor controls. CONCLUSION: These data indicate that deficiency of alpha(1)-antichymotrypsin is associated with less severe pulmonary disease in patients with CF, and support our previous observations that mild genetic deficiency of a proteinase inhibitor is associated with an improved outcome.

Meningococcal septicaemia and plastic surgery--a strategy for management.

Meningococcal septicaemia is a severe life threatening illness that is part of the spectrum of meningococcal disease. It is of particular concern to the plastic and reconstructive surgeon because as the medical and intensive care of these patients improves, more are surviving the acute phase of the septicaemia and suffering from the associated complications such as skin necrosis and extremity loss. Recently there have been several reports in the literature concerning the management of skin infarction with both skin grafting and free flap surgery. This paper will provide an update on the proposed pathophysiological mechanisms involved, summarise the present data on plastic surgical care and suggest a stratagem for future management of these difficult cases.

Anti-neutrophil cytoplasmic antibodies (ANCA) against bactericidal/permeability-increasing protein (BPI) and cystic fibrosis lung disease.

Persistent infection with Pseudomonas aeruginosa and inflammatory mechanisms play an important role in cystic fibrosis (CF) lung disease. ANCA against BPI, a potent host defence protein with anti-bacterial and anti-endotoxin properties, have been described in CF. We have assessed the relationship of anti-BPI antibodies to pulmonary disease severity in 148 CF subjects. IgA and IgG anti-BPI antibodies were found in 55.4% and 70.3% of CF patients, respectively, and higher levels were strongly associated with colonization with P. aeruginosa (P = 0.001 and 0.039 for IgA and IgG antibodies, respectively). IgA and IgG anti-BPI antibodies were independently associated with more severe lung disease as assessed by chest radiograph score (P = 0.023) and a significantly lower forced expiratory volume in 1 s (FEV1)% (P = 0.01). The pathophysiological relevance of the autoantibodies was investigated further by determining their epitope specificity and their effect on bacterial phagocytosis in vitro. Both isotypes of anti-BPI antibodies were specific for the C-terminus of BPI shown recently to be important for BPI-mediated opsonization, and in vitro affinity-purified anti-BPI antibodies significantly reduced BPI-induced phagocytosis of Escherichia coli compared with controls. These data indicate that anti-BPI autoantibodies are associated with colonization with P. aeruginosa and worse lung disease in CF. The inhibition of bacterial phagocytosis suggests that these autoantibodies may contribute to the persistence of P. aeruginosa in the CF lung and so play a role in perpetuating CF lung damage.

Alpha1-antitrypsin deficiency alleles and the Taq-I G-->A allele in cystic fibrosis lung disease.

Cystic fibrosis (CF) is characterized by progressive and ultimately fatal pulmonary disease although there are notable variations in clinical features. This heterogeneity is thought to lie outside the cystic fibrosis transmembrane regulator (CFTR) gene locus and may stem from deficiencies in the antiproteinase screen that protects the lung from proteolytic attack. One hundred and fifty seven patients were recruited from two UK CF centres. The serum concentrations of alpha1-antitrypsin, alpha1-antichymotrypsin and C-reactive protein (CRP) were determined and patients were screened for the common S and Z deficiency alleles of alpha1-antitrypsin and the G-->A mutation in the 3' noncoding region of the alpha1-antitrypsin gene (Taq-I G-->A allele). Alpha1-antitrypsin deficiency phenotypes were detected in 20 (16 MS, 1 S and 3 MZ) out of 147 unrelated tested CF patients and were, surprisingly, associated with significantly better lung function (adjusted mean forced expiratory volume in one second (FEV1) 62.5% of predicted for deficient group and 51.1% pred for normal alleles; p=0.043). The Taq-I G-->A allele was found in 21 out of 150 unrelated patients and had no significant effect on CF lung disease or on levels of alpha1-antitrypsin during the inflammatory response. We show here that, contrary to current thinking, common mutations of alpha1-antitrypsin that are associated with mild to moderate deficiency of the protein predict a subgroup of cystic fibrosis patients with less severe pulmonary disease. Moreover, the Taq-I G-->A allele has no effect on serum levels of alpha1-antitrypsin in the inflammatory response, which suggests that the previously reported association of the Taq-I G-->A allele with chronic obstructive pulmonary disease is not mediated by its effect on the serum level of alpha1-antitrypsin.

Longer term quality of life and outcome in stroke patients: is the Barthel index alone an adequate measure of outcome?

OBJECTIVES: To consider whether the Barthel Index alone provides sufficient information about the long term outcome of stroke. DESIGN: Cross sectional follow up study with a structured interview questionnaire and measures of impairment, disability, handicap, and general health. The scales used were the hospital anxiety and depression scale, mini mental state examination, Barthel index, modified Rankin scale, London handicap scale, Frenchay activities index, SF36, Nottingham health profile, life satisfaction index, and the caregiver strain index. SETTING: South east London. SUBJECTS: People, and their identified carers, resident in south east London in 1989-90 when they had their first in a life-time stroke aged under 75 years. INTERVENTIONS: Observational study. MAIN OUTCOME MEASURES: Comparison and correlation of the individual Barthel index scores with the scores on other outcome measures. RESULTS: One hundred and twenty three (42%) people were known to be alive, of whom 106 (86%) were interviewed. The median age was 71 years (range 34-79). The mean interval between the stroke and follow up was 4.9 years. The rank correlation coefficients between the Barthel and the different dimensions of the SF36 ranged from r = 0.217 (with the role emotional dimension) to r = 0.810 (with the physical functioning dimension); with the Nottingham health profile the range was r = -0.189 (with the sleep dimension, NS) to r = -0.840 (with the physical mobility dimension); with the hospital and anxiety scale depression component the coefficient was r = -0.563, with the life satisfaction index r = 0.361, with the London handicap scale r = 0.726 and with the Frenchay activities index r = 0.826. CONCLUSIONS: The place of the Barthel index as the standard outcome measure for populations of stroke patients is still justified for long term follow up, and may be a proxy for different outcome measures intended for the assessment of other domains.

A long-term follow-up of stroke patients.

BACKGROUND AND PURPOSE: Two hundred ninety-one residents of southeast London, younger than 75 years, suffered their first stroke in 1989/1990. The objectives of this study were to determine the long-term outcome of this cohort of stroke patients in terms of impairment, disability, handicap, and quality of life and their use of services and prevention measures subsequent to their stroke. METHODS: The survivors and their identified caregivers were traced and completed a structured interview questionnaire that included the Barthel Index, modified Rankin Scale, Hospital Anxiety and Depression Scale (HAD), Mini-Mental State Examination, Frenchay Activities Index, and Caregiver Strain Index. RESULTS: One hundred twenty-three people (42%) were alive, of whom 106 were interviewed. The mean interval between the stroke and the long-term follow-up was 4.9 years. Thirty-one of the survivors (29%) were severely or moderately disabled, 39 (37%) were mildly disabled, and 36 (34%) were functionally independent. Of the 96 people who completed the HAD, 35 (36%) had scores suggesting that they were depressed or had borderline depression. The most likely nontherapy services to have been provided were chiropody and district nursing. Five people had received respite care. Of the 104 subjects for whom information about their home was available, 53 (51%) had had an adaptation. Seventy-five people (71%) had an aid or appliance. Sixty-five people (61%) were on aspirin, and an additional 14 (13%) were on warfarin. Fifty subjects (47%) identified a main caregiver. No one with a moderate or more severe disability was living at home without an identified caregiver. CONCLUSIONS: The levels of both health and social service provision are likely to be inadequate for this population. The use of prevention measures is encouraging. There is a clear need for a coordinated policy to guide assessment and management across sectors.

Reversible neurologic dysfunction following isoflurane sedation in pediatric intensive care.

OBJECTIVE: To examine the relationship between prolonged isoflurane sedation and reversible neurologic dysfunction in children requiring intensive care. DESIGN: Retrospective, case note review from January 1987 to August 1993. SETTING: Pediatric intensive care unit. PATIENTS: Twenty-nine children, aged 6 months to 10 yrs, requiring endotracheal intubation and mechanical ventilation for upper airway infection. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Fourteen patients with laryngotracheobronchitis (croup) and 15 patients with epiglottitis required endotracheal intubation and ventilation. These children were treated with different sedative and muscle relaxant drugs, including opiates, benzodiazepines and chloral hydrate. Twelve (41%) of 29 children were sedated with isoflurane (0.25% to 1.5%) for > 24 hrs. All patients subsequently developed reversible ataxia, agitation, hallucinations, and confusion lasting < or = 72 hrs postextubation. Neurologic dysfunction was not observed in 12 patients who did not receive isoflurane nor in five patients who received isoflurane for between 1 and 15 hrs. Neurologic signs resolved in all patients before hospital discharge, and all children had normal neurologic examinations 4 to 6 wks later as outpatients. CONCLUSIONS: A high occurrence rate of reversible neurologic dysfunction occurs when isoflurane is used as a sedative for > 24 hrs in pediatric patients.

Phrenic nerve damage via a right thoracotomy in older children with secundum ASD.

Phrenic nerve damage (PND) in children after cardiac operations is now recognized as being more frequent than previously thought. In a prospective study on 400 children, we previously demonstrated electrophysiologic evidence of postoperative PND in approximately 16% of patients, with one third of cases occurring in children under 18 months. In the past 18 months, 30 children have had atrial septal defect (ASD) repairs as their only operative procedure. Fourteen children had ASD repairs via a midline incision, and 16 ASD repairs were via a right thoracotomy. No PND (assessed by phrenic nerve latency) was found after a midline approach. In the right thoracotomy group, 5 children had evidence of PND (31%; p = 0.05). Four of these 5 patients were female and more than 14 years of age. The incidence of damage in this pubescent group was 80% (p < 0.05). In the older age group the duration of ventilation was not prolonged, but affected patients had symptoms of fatigue and breathlessness postoperatively. These data suggest a strong association between right thoracotomies for ASD repairs and PND, especially in the female pubescent group when a low submammary skin incision (seventh to eighth space) is used with a fifth to sixth space entry into the thoracic cavity. In conclusion, the right thoracotomy approach for ASD repair appears to be a significant risk factor for PND in older children.