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

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.

The effect of nebulized epinephrine on respiratory mechanics and gas exchange in bronchiolitis.

Nebulized epinephrine has been advocated as a treatment for airway obstruction in infants with bronchiolitis; however, its effect on respiratory mechanics and gas exchange has been poorly documented to date. We performed a preinterventional and postinterventional study with primary outcome measures of mechanics (measured by single-breath occlusion passive deflation) and oxygenation and ventilation indices in order to measure the effects of nebulized epinephrine in infants requiring mechanical ventilation for RSV-positive bronchiolitis. A two-compartment model was used to describe respiratory mechanics in patients with nonlinear flow-volume curves. Nebulized epinephrine (0.5 mg/kg) was administered to 15 patients (median age, 0.19 yr; weight, 4.4 kg). Resistance decreased significantly in slow and fast compartments in 87 and 70% of patients, respectively. Median resistance in the slow compartment decreased from 0.427 to 0.198 cm H2O/ml/s (p = 0.0015) and in the fast compartment from 0.167 to 0.116 cm H2O/ ml/s (p = 0.018). Compliance, oxygenation index, and ventilation index were not significantly changed after administration of epinephrine. We conclude that nebulized epinephrine substantially improves respiratory system resistance but not oxygenation or ventilation indices. This may be because of the effects of epinephrine on oxygen consumption or ventilation-perfusion matching.

Evaluating the effectiveness of evidence-based guidelines for the use of spacer devices in children with acute asthma.

OBJECTIVE: To change standard practice from using nebulisers to metered dose inhalers and holding chambers (spacers) in children presenting with mild to moderate acute asthma. DESIGN: A before-after comparison of children with acute asthma presenting to the emergency department (ED) between August and October 1999 with those presenting between June and August 1997. SETTING: A tertiary care metropolitan children's hospital. INTERVENTIONS: Evidence-based clinical practice guidelines for using spacers were developed by a local multidisciplinary consensus process. A multifaceted guideline implementation program was used in 1999. MAIN OUTCOME MEASURES: Physician prescribing practices (spacer use); clinical outcomes (need for hospitalisation, admission to intensive care unit, and length of stay [LOS]). RESULTS: 75 of 247 children (30%; 95% CI, 25%-36%) required hospital admission in 1999. This was similar to the 1997 study period, when 95 of 326 (29%; 95% CI, 24%-34%) children were admitted. Of those with mild to moderate asthma, 160 (68%) received bronchodilators in the ED; 151 (94%) were initially treated with a spacer device in 1999. In 1997, no children were initially treated with spacers in the ED. The median (range) LOS in hospital for children with asthma of all severities was 1.7 (0.5-19.8) days in 1999 and 1.7 (0.2-7.6) days in 1997 (P=0.85). CONCLUSIONS: We successfully changed standard practice from using nebulisers to spacers for bronchodilator delivery in children with mild to moderate acute asthma, with no difference in the need for or duration of hospitalisation.

Acute lung injury: outcomes and new therapies.

Mortality rates in ARDS are improving, with several recent studies reporting mortality in the order of 20-40% rather than the early descriptions of this disease in which a mortality of 40-60% or higher was frequently cited. The ability to accurately predict outcomes plays an important role in the assessment of the impact of new therapies. Traditionally clinicians have relied on simple respiratory indices to assess mortality risk; however, the predictive ability of such indices, particularly early in the course of the disease, is somewhat limited. Adult data suggest that improved prediction not only of the outcome of established ARDS but also of the development of ARDS in at-risk patients may be obtained by measuring the concentrations of inflammatory mediators and/or surfactant-associated proteins in plasma or bronchoalveolar lavage samples. A bewildering array of therapies for ARDS is available; in many cases the benefits are uncertain. Treatments of proven value in adults include using PEEP beyond the lower inflection point of the pressure-volume curve and limiting tidal volumes to 6 ml/kg. Nitric oxide appears to offer no benefit to outcomes, although it does improve oxygenation in some patients. Surfactant is still undergoing assessment in randomised controlled trials; however, the use of aerosolised surfactant has been recently shown to be ineffective in adult patients with ARDS. Perfluorocarbon-assisted gas exchange (PAGE) or partial liquid ventilation is similarly still being assessed in randomised controlled trials in adults.

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 gamma-globulin (Respigam; CSL Laboratories, Melbourne, Victoria, Australia) and monoclonal antibody (Synagis; Abbott Australasia, Kurnell, NSW, Australia) in the Australian context. METHODS: Retrospective outcome study using data from an Australian hospital and intensive care databases over a 30 month period encompassing three RSV seasons (1 May 1997-31 October 1999). RESULTS: The mortality for RSV infection was very low, being 0.29% of all patients admitted to hospital and 0% in infants without co-existing disease. Only 11.4% of infants required admission to the intensive care unit (ICU). Respiratory syncytial virus infection was not associated with prolonged hospitalization; patients managed in the general wards had a mean length of stay (LOS) of 4.13 days with a median of 3.0 days, while those requiring intensive care had a mean LOS of 9.8 days (including 5.1 days in the ICU). Use of RSV prophylaxis would be expected to reduce the requirement for hospital admission; however, the cost of prophylaxis is conservatively estimated to be between 7.2- and 65.3-fold the money saved in hospital care, depending on the weight of the patient and choice of drug. CONCLUSIONS: Respiratory syncytial virus is a major cause of morbidity, but not mortality, in infants. In infants requiring hospitalization for this disease, the LOS is relatively short and the mortality extremely low. Use of prophylactic agents, which reduce the probability of hospital admission but have no effect on mortality, cannot be justified in the Australian context on cost-benefit grounds.

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 children's 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 beta2-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 H20/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.

Total lung capacity by N2 washout from high and low lung volumes in ventilated infants and children.

Although there is a strong rationale for the assessment of the subdivisions of lung volume, lung function testing has focused on the measurement of FRC alone in ventilated infants and children. To assess the feasibility, reproducibility, and accuracy of measurements of total lung capacity (TLC), FRC, and their ratio, we determined both lung volumes in 50 critically ill, intubated, and paralyzed infants (mean age [SEM]), 19.9 [4.6] mo) with a variety of lung diseases, by a modified N2 washout technique from end-exhalation and from +40 cm H2O inspiratory pressure, respectively. In the same infants, we also defined TLC by adding inspiratory capacity, measured by pneumotachograph during a passive exhalation from +40 cm H2O to FRC measured by N2 washout. Respiratory mechanics were measured by single-breath occlusion, and the patients were classified according to clinical picture and lung function into groups without lung disease or with restrictive or obstructive disease. The TLC data obtained by both methods showed good agreement for the infants without lung disease or restrictive disease (limits of agreement [LOA]: -3.8/4.6 and -2.9/3.2 ml/kg, respectively). The agreement was less in the infants with airflow obstruction where the N2 washout gave slightly higher values (LOA: -7.1/11.3 ml/kg). Mean FRC/TLC was significantly elevated in the obstructive group, whereas mean FRC alone did not differ from the group without lung disease. Our results suggest that TLC can be measured by both methods in intubated infants, but with limited agreement in obstructive disease. FRC/TLC ratios allow an estimation of the degree of pulmonary hyperinflation.

Effect of prone and supine positions on functional residual capacity, oxygenation, and respiratory mechanics in ventilated infants and children.

Although numerous reports have described the improvement in PAO2 in patients in the prone position, the underlying mechanism has yet to be determined. Some authors have suggested this phenomenon may be related to an increase in functional residual capacity (FRC); however, no previous studies have described positional changes in FRC in children with severe lung disease or in those under neuromuscular blockade. We measured arterial blood gases, FRC, Rrs, and Crs in supine and prone positions in 30 patients under neuromuscular blockade with lung disorders including moderately severe restrictive (n = 10) and obstructive (n = 10) disease and control subjects without significant lung disease (n = 10). Prone positioning was not associated with a significant increase in FRC in the cohort of 30 patients, nor in any of the subgroups. Although individual patients demonstrated large improvements in oxygenation, a statistically significant (but clinically insignificant) increase in AaPO2 ratio was observed only in the subgroup of patients with obstructive disease (0.35+/-0.03 to 0.38+/-0.04, p = 0.027). There was no correlation between changes in FRC and changes in AaPO2 (r = 0.225, p = 0.23). A significant improvement in Rrs occurred in the prone position compared to supine in patients with obstructive lung disease, decreasing from 0.264+/-0.024 to 0.216+/-0.021 cm H2O/ml/s, p = 0.009. No significant changes in Crs were seen in the prone position. We conclude that prone positioning has no effect on FRC and in this series of 30 patients significantly improved oxygenation only in patients with obstructive airway disease. A significant decrease in Rrs in patients with obstructive lung disease was also observed.

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 Fisher's 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.

Anatomic dead space in infants and children.

In adults, anatomic dead space is 2.2 ml/kg. Because of the relatively large head size of infants and children, we hypothesized that extrathoracic and, therefore, total dead space would be relatively larger in pediatric subjects. Extrathoracic dead space was measured by a "water displacement" technique in 40 patients aged 7 days to 14.2 yr who were intubated with cuffed endotracheal tubes. Intrathoracic dead space was measured by continuous analysis of end-tidal and mixed-expired PCO2 and minute ventilation in 10 patients, aged 18 days to 14.7 yr. Extrathoracic dead space per kilogram decreased exponentially with increasing age, ranging from 2.3 ml/kg in early infancy to 0.8 ml/kg in children older than 6 yr. Mean intrathoracic anatomic dead space was 1.03 ml/kg and was not related to age. The following relationship between total anatomic dead space (DStotal; in ml/kg) and age (in yr) is derived: DStotal = 3.28 - 0.56 [ln(1 + Age)], with r = 0.95 and P = 0.0001. Anatomic dead space is age dependent and is > 3 ml/kg in early infancy.

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.

Assessment of lung function in the intensive care unit.

Tests of pulmonary function have become more accurate and less invasive in recent years. Our ability to monitor patients continuously with pulse oximetry, transcutaneous and end-tidal CO2, and intraarterial blood gas monitors has greatly enhanced ICU care. In intubated patients in the PICU detailed lung function studies can be performed, and in general they can be carried out with minimal disruption of routine management. Much work remains to be done to define the changes seen in various disease processes and the effects of therapeutic interventions on functional parameters. Many of the available techniques have already been developed to a point that allows them to be employed in clinical decision making. We expect that assessment of lung volumes, compliance, and resistance will become a routine part of management in children with life-threatening pulmonary diseases in the near future, and that a more intimate knowledge of the pathophysiology of respiratory disorders treated in PICU will lead to improved outcomes.

Long-term corneal endothelial changes after intraocular lens implantation. Anterior vs posterior chamber lenses.

The use of semiflexible anterior chamber intraocular lenses, widespread during the early 1980's, has been abandoned due to the many complications associated with their use. Patients who received these lenses currently represent the majority of patients with pseudophakic bullous keratopathy. We studied the morphologic characteristics of the corneal endothelium in 20 patients who had undergone extracapsular cataract extraction followed by anterior chamber or posterior chamber intraocular lens implantation. Specular microscopy and computer-assisted morphometry were performed preoperatively, 3 months postoperatively, and once a year thereafter. The follow-up period for each subject was 5 years or longer. The endothelial cell density of the central cornea in the anterior chamber lens group decreased from 304 to 196 (x 10 cells/mm2), and in the posterior chamber lens group decreased from 315 to 269 (x 10 cells/mm2). Four patients in the anterior chamber lens group developed pseudophakic bullous keratopathy 6 or 7 years after surgery. Severe endothelial cell loss and morphologic change were seen in patients who received anterior chamber lenses.

Deep venous thrombosis caused by femoral exostosis.

OBJECTIVE: To present the first case of deep venous thrombosis caused by femoral exostosis reported in Australia. CLINICAL FEATURES: An 11-year-old prepubertal Caucasian girl had a two-year history of a posterior femoral exostosis. She then presented with a deep venous thrombosis 24 hours after riding a horse for the first time. The deep venous thrombosis was diagnosed by Doppler ultrasound, which showed an intimate relationship between the femoral exostosis and the femoral vein. Coagulation abnormalities were excluded. INTERVENTION AND OUTCOME: The patient was given anticoagulation therapy with heparin intravenously and warfarin orally. The popliteal vein recanalised within two days. The exostosis was excised 10 weeks after initial presentation, with warfarin being continued for four weeks postoperatively. Two months after excision the patient was symptom free. CONCLUSIONS: It is possible for venous compression by an exostosis to result in thrombosis in a patient with no underlying coagulation abnormality. Palpation and plain radiography of the region will demonstrate the exostosis; ultrasound is the next investigation of choice.

Outcome of infants with birthweight 2000 g or less who undergo major cardiac surgery.

A retrospective study of all neonates with birthweight 2000 g or less undergoing major cardiac surgery at the Royal Children's Hospital, Melbourne over the last 5 years was performed in order to determine outcome and identify subgroups within this population that may have a poor prognosis. The mean length of stay in intensive care following surgery was 32 days, with non-survivors having a significantly longer duration of stay than survivors. Overall mortality was 43%, and for children with congenital heart disease as part of a recognizable syndrome the mortality was 100%. None of the survivors suffered incapacitating cardiac, neurological or respiratory handicap. These children in general have a poor prognosis and utilize significant resources; results of cardiac surgery in this group need to be closely followed in the future.

Can short hospital admissions be avoided? A review of admissions of less than 24 hours' duration in a paediatric teaching hospital.

OBJECTIVE: To review the records of children admitted to hospital for less than 24 hours to assess the appropriateness of the admission and subsequent discharge, and the suitability of these patients for admission to a short stay area rather than the hospital wards. DESIGN: Retrospective study consisting of a one in three sample of all children admitted to the hospital's general medical units over one year. All admissions were listed sequentially, and every third patient was included in the study. SETTING: Royal Children's Hospital, Melbourne; a tertiary paediatric hospital with a major primary care role. PARTICIPANTS: There were a total of 660 patients eligible for inclusion in the study; 220 were selected, and all records were reviewed. RESULTS: It was found that although 87.7% of admissions could be justified on medical grounds alone, the children quickly recovered with at least 65% being fit for discharge within 12 hours of admission. In spite of this the mean duration of admission was 17.0 hours. The majority of patients were suffering from easily diagnosed and treated disorders, with 78.9% falling into four diagnostic groups (asthma, ingestions, infections, and convulsions). Criteria for admission to a short stay observation area were satisfied in 65% of patients (at the time of the study no such area existed in the hospital). No patients were discharged inappropriately early. CONCLUSIONS: A significant number of children require brief hospitalisation for relatively minor illness, but unnecessary delays caused by administrative aspects of hospital admission and relatively infrequent inpatient review by medical staff often lengthen the period of admission. Significant cost savings are possible with the use of a short stay facility, and a large number of patients are suitable for this form of care.

Neuroleptic malignant syndrome in children.

OBJECTIVES: To report a case of neuroleptic malignant syndrome (NMS) in a child, and review reports of 11 other paediatric cases of NMS. CLINICAL FEATURES: A 6-year-old child treated with thioridazine for behavioural disturbance developed NMS following an episode of dehydration. The clinical features of this case are compared to other reports of NMS in childhood, and in adults, where the disease is far more common, usually being precipitated by major tranquillisers. INTERVENTION AND OUTCOME: The patient made a full recovery with supportive management. In adults the disease has a mortality of 15%-40%, and two of the previously reported paediatric cases have also been fatal. Treatment options, including dantrolene and antiparkinsonian agents are reviewed. CONCLUSION: NMS is rare in childhood, but is usually precipitated by commonly prescribed drugs. There is a significant mortality associated with the condition, and early diagnosis and treatment are essential for a good outcome.