Efficacy of IV theophylline in children with severe status asthmaticus.

STUDY OBJECTIVE: To determine whether adding IV theophylline to an aggressive regimen of inhaled and IV beta-agonists, inhaled ipratropium, and IV methylprednisolone would enhance the recovery of children with severe status asthmaticus admitted to the pediatric ICU (PICU). DESIGN: A prospective, randomized, controlled trial. Asthma scoring was performed by investigators not involved in treatment decisions and blinded to group assignment. SETTING: The PICU of an urban, university-affiliated, tertiary-care children's hospital. PATIENTS: Children with a diagnosis of status asthmaticus who were admitted to the PICU for < or = 2 h and who were in severe distress, as indicated by a modified Wood-Downes clinical asthma score (CAS) of > or = 5. INTERVENTIONS: All subjects initially received continuous albuterol nebulizations; intermittent, inhaled ipratropium; and IV methylprednisolone. The theophylline group was also administered infusions of IV theophylline to achieve serum concentrations of 12 to 17 microg/mL. A CAS was tabulated twice daily. MEASUREMENTS AND RESULTS: Forty-seven children (median age, 8.3 years; range, 13 months to 17 years) completed the study. Twenty-three children received theophylline. The baseline CASs of both groups were similar and included three subjects receiving mechanical ventilation in each group. All subjects receiving mechanical ventilation and theophylline were intubated before drug infusion. Among the 41 subjects who were not receiving mechanical ventilation, those receiving theophylline achieved a CAS of < or = 3 sooner than control subjects (18.6 +/- 2.7 h vs 31.1 +/- 4.5 h; p < 0.05). Theophylline had no effect on the length of PICU stay or the total incidence of side effects. Subjects receiving theophylline had more emesis (p < 0.05), and control patients had more tremor (p < 0.05). CONCLUSIONS: Theophylline safely hastened the recovery of children in severe status asthmaticus who were also receiving albuterol, ipratropium, and methylprednisolone. The role of theophylline in the management of asthmatic children in impending respiratory failure should be reexamined.

Low-dose inhaled nitric oxide improves the oxygenation and ventilation of infants and children with acute, hypoxemic respiratory failure.

OBJECTIVE: To describe the effects of inhaled nitric oxide on oxygenation and ventilation in patients with acute, hypoxic respiratory failure and to characterize those who respond to low doses with a significant improvement in PaO2. DESIGN: Prospective dose response trial of inhaled nitric oxide. Patients who demonstrated a > or =15% improvement in PaO2 were randomized to receive conventional mechanical ventilation with or without prolonged inhaled nitric oxide. SETTING: Pediatric intensive care unit of a tertiary care children's hospital serving as a regional referral center for respiratory failure. PATIENTS: Pediatric patients with an acute parenchymal lung disease requiring mechanical ventilation, an F(IO2) of > or =0.5, a positive end-expiratory pressure of > or =7 cm H2O, and whose PaO2/FIO2 ratio was < or =160. INTERVENTIONS: PaO2, PaCO2, pH, heart rate, blood pressure, and methemoglobin were recorded at baseline and after inhaling 1, 5, 10, and 20 ppm of nitric oxide. Peak expiratory flow rate and mean airway resistance were measured while subjects received 0 and 20 ppm of inhaled nitric oxide. Patients were followed up until extubation or death. MEASUREMENTS AND MAIN RESULTS: Twenty-six patients (median age, 2.6 yrs [range, 1 mo-18.2 yrs]) were enrolled in the study. PaO2 increased (p< .001) and Pa(CO2) fell (p< .0001) from baseline with the administration of inhaled nitric oxide. There was no statistical difference among 1, 5, 10, and 20 ppm with regard to effects on oxygenation. Sixteen patients (62%) responded to inhaled nitric oxide with a > or =15% improvement in PaO2; 14 of these responses occurred at a dose of 1 or 5 ppm. Response to inhaled nitric oxide was not associated with age, length of intubation, presence of primary lung disease, chest radiograph, or illness severity. Among patients weighing < or =20 kg, responders showed a greater fall in mean airway resistance (p < .05) than nonresponders. Mortality was not influenced by prolonged inhaled nitric oxide when analyzed by intention to treat. Patients receiving prolonged inhaled nitric oxide at doses of < or =20 ppm maintained methemoglobin levels of <3.0% and circuit concentrations of NO2 of <1 ppm. CONCLUSIONS: Inhaled nitric oxide at doses of < or =5 ppm improves the oxygenation and (to a lesser extent) ventilation of most children with acute, hypoxic respiratory failure. The unpredictable response of patients necessitates individualized dosing of inhaled nitric oxide, starting at concentrations of < or =1 ppm. Inhaled nitric oxide at < or =20 ppm may exert a small salutary effect on bronchial tone. The benefits of prolonged inhaled nitric oxide remain unknown.

Volumetric capnography in children. Influence of growth on the alveolar plateau slope.

BACKGROUND: Lung growth in children is associated with dramatic increases in the number and surface area of alveolated airways. Modelling studies have shown the slope of the alveolar plateau (phase III) is sensitive to the total cross-sectional area of these airways. Therefore, the influence of age and body size on the phase III slope of the volumetric capnogram was investigated. METHODS: Phase III slope (alveolar dcCO2/dv) and airway deadspace (VDaw) were derived from repeated single-breath carbon dioxide expirograms collected on 44 healthy mechanically ventilated children (aged 5 months-18 yr) undergoing minor surgery. Ventilatory support was standardized (VT = 8.5 and 12.5 ml/kg, f = 8-15 breaths/min, inspiratory time = 1 s, end-tidal partial pressure of carbon dioxide = 30-45 mmHg), and measurements were recorded by computerized integration of output from a heated pneumotachometer and mainstream infrared carbon dioxide analyzer inserted between the endotracheal tube and anesthesia circuit. Experimental data were compared to simulated breath data generated from a numeric pediatric lung model. RESULTS: An increased VDaw, a smaller VDaw/VT, and flatter phase III slope were found at the larger tidal volume (P < 0.01). Strong relationships were seen at VT = 12.5 ml/kg between airway deadspace and age (R2 = 0.77), weight (R2 = 0.93), height (R2 = 0.78), and body surface area (R2 = 0.89). The normalized phase III slopes of infants were markedly steeper than that of adolescents and were reduced at both tidal volumes with increasing age, weight, height, and body surface area. Phase III slopes and VDaw generated from modelled carbon dioxide washout simulations closely matched the experimental data collected in children. CONCLUSIONS: Morphometric increases in the alveolated airway cross-section with lung growth is associated with a decrease of the phase III slope. During adolescence, normalized phase III slopes approximate those of healthy adults. The change in slope with lung growth may reflect a decrease in diffusional resistance for carbon dioxide transport within the alveolated airway resulting in diminished acinar carbon dioxide gradients.