Andrew Numa

Acute lung injury in pediatric intensive care in Australia and New Zealand: a prospective, multicenter, observational study

Objective: Acute lung injury (ALI) is poorly defined in children. The objective of this prospective study was to clarify the incidence, demographics, management strategies, outcome, and mortality predictors of ALI in children in Australia and New Zealand. Design: Multicenter prospective study during a 12-month period. Setting: Intensive care unit. Patients: All children admitted to intensive care and requiring mechanical ventilation were screened daily for development of ALI based on American-European Consensus Conference guidelines. Identified patients were followed for 28 days or until death or discharge. Interventions: None. Measurements and Main Results: There were 117 cases of ALI during the study period, giving a population incidence of 2.95/100,000 <16 yrs. ALI accounted for 2.2% of pediatric intensive care unit admissions. Mortality was 35% for ALI, and this accounted for 30% of all pediatric intensive care unit deaths during the study period. Significant preadmission risk factors for mortality were chronic disease, older age, and immunosuppression. Predictors of mortality during admission were ventilatory requirements (peak inspiratory pressures, mean airway pressure, positive end-expiratory pressure) and indexes of respiratory severity on day 1 (Pao2/Fio2 ratio and oxygenation index). Higher maximum and median tidal volumes were associated with reduced mortality, even when corrected for severity of lung disease. Development of single and multiple organ failure was significantly associated with mortality. Conclusions: ALI in children is uncommon but has a high mortality rate. Risk factors for mortality are easily identified. Ventilatory variables and indexes of lung severity were significantly associated with mortality.

Acute respiratory distress syndrome caused by respiratory syncytial virus

Acute respiratory distress syndrome (ARDS) complicating severe respiratory syncytial virus (RSV) infection has been described in only a few infants. In contrast to the low mortality rates usually associated with RSV infections (<5%), mortality rates in the range of 40–70% have been reported in pediatric patients with ARDS. However, studies on patients with ARDS are usually lumped with respect to causation, and the disease course of RSV‐induced ARDS has not been previously studied. We examined the pulmonary function abnormalities of 37 infants with RSV‐induced respiratory failure who were admitted to our pediatric intensive care unit for assisted ventilation. Measurements included respiratory mechanics, maximum expiratory flow‐volume curves, and lung volumes. These allowed the calculation of a Murray lung injury score (modified for pediatric use) in which radiographic findings, ventilator settings, lung compliance, and blood gas results were considered. We identified ten infants with severe restrictive lung disease who fulfilled the clinical criteria for classification as ARDS. All had lung injury scores above 2.5, compatible with a diagnosis of ARDS. Twenty‐seven infants had obstructive patterns of lung function consistent with a clinical diagnosis of RSV bronchiolitis. The patients with RSV‐induced ARDS were significantly younger, and had a longer time on assisted ventilation (P < 0.05) and a higher proportion of predisposing illnesses (P < 0.05, odds ratio = 6.67, two‐tailed Fishers exact test) when compared with the patients who had obstructive disease. Only one patient (who had immunodeficiency) died, and all others were successfully managed on conventional mechanical ventilation. We conclude that RSV‐induced respiratory failure represents a relatively benign cause of ARDS in pediatric patients. Our observations support the notion of differentiating ARDS with respect to causation, especially when novel and experimental therapy is considered and mortality rates are analyzed. Pediatr. Pulmonol. 1997; 23:176–183

Early Cystic Fibrosis Lung Disease Detected by Bronchoalveolar Lavage and Lung Clearance Index

RATIONALE Unrecognized airway infection and inflammation in young children with cystic fibrosis (CF) may lead to irreversible lung disease; therefore early detection and treatment is highly desirable. OBJECTIVES To determine whether the lung clearance index (LCI) is a sensitive and repeatable noninvasive measure of airway infection and inflammation in newborn-screened children with CF. METHODS Forty-seven well children with CF (mean age, 1.55 yr) and 25 healthy children (mean age, 1.26 yr) underwent multiple-breath washout testing. LCI within and between-test variability was assessed. Children with CF also had surveillance bronchoalveolar lavage performed. MEASUREMENTS AND MAIN RESULTS The mean (SD) LCI in healthy children was 6.45 (0.49). The LCI was higher in children with CF (7.21 [0.81]; P < 0.001). The upper limit of normal for the LCI was 7.41. Fifteen (32%) children with CF had an elevated LCI. LCI measurements were repeatable and reproducible. Airway infection was present in 17 (36%) children with CF, including 7 (15%) with Pseudomonas aeruginosa. Polymicrobial growth was associated with worse inflammation. The LCI was higher in children with Pseudomonas (7.92 [1.16]) than in children without Pseudomonas (7.02 [0.56]) (P = 0.038). The LCI correlated with bronchoalveolar lavage IL-8 (R(2) = 0.20, P = 0.004) and neutrophil count (R(2) = 0.21, P = 0.001). An LCI below the upper limit of normality had a high negative predictive value (93%) in excluding Pseudomonas. CONCLUSIONS The LCI is elevated early in CF, especially in the presence of Pseudomonas and airway inflammation. The LCI is a feasible, repeatable, and sensitive noninvasive marker of lung disease in young children with CF.

Albuterol responsiveness in infants with respiratory failure caused by respiratory syncytial virus infection

OBJECTIVE To assess the bronchodilator effect of inhaled albuterol in the acute stage of severe respiratory syncytial virus (RSV) infection. DESIGN Prospective, nonrandomized study of previously healthy infants who underwent intubation and whose lungs were ventilated because of respiratory failure caused by RSV infection. Ten infants with an endotracheal tube in place and without lung disease were matched for age and weight and served as normal control subjects. METHODS Lung function tests, including respiratory mechanics by single-breath occlusion, small airway function by forced deflation, and lung volumes by nitrogen washout, were performed before and after inhalation of 900 micrograms albuterol by metered dose inhaler. Bronchodilator response was defined as a change of more than twice the coefficient of variation of repeated baseline measurements. RESULTS Twenty-three infants (mean +/- SE age = 4.2 +/- 1.1 months) were studied, of whom 20 (87%) had obstructive small airway disease, and 3 (13%) had exclusively restrictive lung function profiles. Ten of the infants with obstructive disease (50%) did not benefit from albuterol, and 9 (45%) had small but significant improvements in lung function. Deterioration of lung function was documented in 1 patient after albuterol inhalation. CONCLUSION Inhaled albuterol is of limited value as a bronchodilator in infants with RSV-induced respiratory failure and should be discontinued if a beneficial response cannot be observed.

Outcome of respiratory syncytial virus infection and a cost-benefit analysis of prophylaxis

Objectives: To determine outcome and length of stay (LOS) for infants younger than 2 years of age admitted to hospital for respiratory syncytial virus (RSV) infection and to perform a cost–benefit analysis of prophylaxis with RSV γ‐globulin (Respigam; CSL Laboratories, Melbourne, Victoria, Australia) and monoclonal antibody (Synagis; Abbott Australasia, Kurnell, NSW, Australia) in the Australian context.

Late-onset and Recurrent Neonatal Group B Streptococcal Disease Associated with Breast-milk Transmission

The purpose of the study was to determine the epidemiological relationships in three unrelated cases of neonatal late-onset Group B streptococcal (GBS) disease and maternal breast-milk infection with GBS. All deliveries were by cesarean section; case 1 was at term, and cases 2 and 3 were at 32- and 33-wk gestation, respectively. Case 1 relates to a mother with clinical mastitis and recurrent GBS infection in a 20-day-old male infant. Following antibiotic therapy and cessation of breastfeeding, the infant recovered without sequelae. Case 2 refers to a mother with clinical mastitis and the occurrence of late-onset GBS disease in 5-wk-old male twins. Despite intervention, one infant died and the second became ill. Following antibiotic therapy and cessation of breast-feeding, the surviving infant recovered without sequelae. Case 3 refers to a mother with sub-clinical mastitis and late-onset GBS infection occurring in a 6-day-old female twin. Following intervention, the infant recovered but suffered a bilateral thalamic infarction resulting in developmental delay and a severe seizure disorder. Following recovery of GBS from an inapparent mastitis and cessation of breast-feeding, the second infant remained well. Blood cultures from all affected infants and maternal breast milk were positive for GBS. Epidemiological relationships between neonatal- and maternal-derived GBS isolates were confirmed by a random amplified polymorphic DNA polymerase chain reaction assay (RAPD-PCR). This study is significant in that it has demonstrated that maternal milk (in cases of either clinical or sub-clinical mastitis) can be a potential source of infection resulting in either late-onset or recurrent neonatal GBS disease.

Effect of inhaled nitric oxide on respiratory mechanics in ventilated infants with RSV bronchiolitis

Objective: To evaluate the bronchodilator effect of inhaled nitric oxide (NO) in infants with respiratory failure caused by respiratory syncytial virus (RSV) bronchiolitis and to compare the effect with the one obtained by salbutamol. Design: Prospective study. Setting: Pediatric intensive care unit of a university childrens hospital. Patients: Twelve acutely ill, intubated infants (mean age 4.5 months, mean weight 4.9 kg) with respiratory failure due to documented RSV bronchiolitis. Interventions: Total respiratory system resistance (Rrs) was measured by single breath occlusion at the baseline and after inhaling NO at 20, 40 and 60 ppm for 1 h, and after inhalation of a standard β2-agonist, salbutamol. Arterial blood gas analysis was performed at each study level on 6 of the 12 patients. Results: The baseline mean Rrs (SE) was 0.29 (0.04) cm H2O/ml per s. At each dose of NO, the mean Rrs (SE) was 0.28 (0.04) cm H2O/ml per s. With salbutamol, the mean Rrs (SE) was 0.21 (0.03) cm H2O/ml per s. These values were not significantly different from each other (by ANOVA). Inhaled NO produced a significant decrease in Rrs of greater than 4 times the coefficient of variation of the baseline measurement in 3 of 12 patients. Seven of 12 patients had no significant change while two patients had a significant increase in Rrs. Inhaled salbutamol produced a significant decrease in Rrs in 5 of 11 patients, while 6 showed no change in Rrs. Conclusion: Inhaled NO has no apparent bronchodilator effect in the majority of acutely ill infants with RSV bronchiolitis and does not appear to provide any additional benefit over the use of salbutamol. The clinical benefit of inhaled NO as a bronchodilator is questionable under these conditions.

ECLS in pertussis: does it have a role?

Objectives: To investigate the value of extracorporeal circulatory life support (ECLS) in paediatric patients with severe Bordetella pertussis infection. Design: Single case report and a review of the ECLS database. Setting: Tertiary referral hospital paediatric intensive care unit. Patients and participants: A single case report of an infant with B. pertussis infection is described. Despite receiving ECLS, this infant died from overwhelming cardiac and cerebral insults. Outcome for children receiving ECLS registered on the Extracorporeal Life Support Organization database is reviewed. Measurements and results: The mortality of infants receiving ECLS for B. pertussis infection is high, with only 5 survivors reported among 22 registered cases. The majority of nonsurvivors had evidence of circulatory collapse in addition to severe respiratory failure, and these patients commonly died of hypoxic-ischaemic cerebral insult. These data suggest the existence of a subgroup of patients with respiratory failure only, who may benefit from ECLS, and a larger subgroup who suffer ischaemic cardiac and cerebral insults which are unlikely to be improved by ECLS. Conclusions: The value of ECLS in patients with B. pertussis infection who present with major cardiac dysfunction is questionable. Such patients almost invariably have a poor outcome despite maximal therapy.

The importance of metabolic rate and the folly of body surface area calculations

Summary Mathematical formulae to calculate body surface area from measurements of height, weight and other parameters date from the late 19th century. Drug doses, fluid therapy, caloric requirements and physiological parameters such as cardiac output, glomerular filtration rate and a variety of respiratory function parameters are all frequently expressed in terms of a body surface area. Body surface area is often used in preference to body mass (weight). However, the original rationale for using body surface area as an estimate for metabolic rate has never been tested and the algorithms used to approximate body surface area have little evidence to support their use in this role. Recent developments in technology using indirect calorimetry allow easy measurement of metabolic rate in the clinical setting. Such measurements should be used for standardisation when weight alone is considered inadequate.

Neurodevelopmental Outcomes of Premature Infants Treated for Patent Ductus Arteriosus: A Population-Based Cohort Study.

OBJECTIVE To compare neurodevelopmental outcomes of extremely preterm infants diagnosed with patent ductus arteriosus (PDA) who were treated medically or surgically and those who were not diagnosed with PDA or who did not undergo treatment for PDA. STUDY DESIGN This retrospective population-based cohort study used data from a geographically defined area in New South Wales and the Australian Capital Territory served by a network of 10 neonatal intensive care units. Patients included all preterm infants born at <29 completed weeks of gestation between 1998 and 2004. Moderate/severe functional disability at 2-3 years corrected age was defined as developmental delay, cerebral palsy requiring aids, sensorineural or conductive deafness (requiring bilateral hearing aids or cochlear implant), or bilateral blindness (best visual acuity of <6/60). RESULTS Follow-up information at age 2-3 years was available for 1473 infants (74.8%). Compared with infants not diagnosed with a PDA or who did not receive PDA treatment for PDA, those with medically treated PDA (aOR, 1.622; 95% CI, 1.199-2.196) and those with surgically treated PDA (aOR, 2.001; 95% CI, 1.126-3.556) were at significantly greater risk for adverse neurodevelopmental outcomes at age 2-3 years. CONCLUSION Our results demonstrate that treatment for PDA may be associated with a greater risk of adverse neurodevelopmental outcome at age 2-3 years. This was particularly so among infants born at <25 weeks gestation. These results may support permissive tolerance of PDAs; however, reasons for this association remain to be elucidated through carefully designed prospective trials.