Ventilatory chemosensitivity in subjects with a history of childhood cyanotic breath-holding spells.

The ability of children with cyanotic breath-holding spells to respond to anger or frustration by voluntary breath-holding for prolonged periods (often to the point of precipitating hypoxic seizure activity) suggested the hypothesis that such children may have a less powerful urge to breathe in the presence of hypoxia and/or hypercapnia than children who do not have breath-holding spells. Because ventilatory chemosensitivity is difficult to measure in infants and young children, this hypothesis was tested indirectly by measuring the ventilatory responses to hyperoxic progressive hypercapnia and to isocapnic progressive hypoxia of seven individuals who had a history of cyanotic breath-holding spells in infancy and 17 control subjects. The mean values for sensitivity to hypoxia and to hypercapnia were not significantly different between the two groups, and the responses of the majority of the subjects with cyanotic breath-holding spells were clearly within the normal range. There were fewer individuals with high-normal ventilatory responses among the subjects with cyanotic breath-holding spells. Although children with cyanotic breath-holding spells may have decreased ventilatory chemosensitivity transiently during infancy or may differ from other children in some other aspect of the control of breathing, the pathogenesis of infantile cyanotic breath-holding spells does not involve a permanently blunted sensitivity to hypercapnia or hypoxia.

Mercury inhalation poisoning and acute lung injury in a child. Use of high-frequency oscillatory ventilation.

Acute mercury inhalation poisoning is a rare cause of acute lung injury. It is commonly fatal in the young child because of progressive pulmonary failure. We describe a 3-month-old infant who survived this insult with the use of high-frequency oscillatory ventilation. This form of support may be an option in the patient with severe adult respiratory distress syndrome (ARDS) or air leak syndromes.

Mechanisms and management of anaphylactic shock not responding to traditional therapy.

Anaphylaxis results from the generation and release of a variety of mediators and their effects on various organs. Involvement of the respiratory and cardiovascular systems is of primary importance to the attending physician. Prompt recognition and initial therapy directed to maintenance of an effective airway and circulatory system is critical. Cardiovascular collapse may involve the parallel operation of several mechanisms including hypovolemia, alterations in pulmonary or systemic vascular resistance, depressed myocardial contractility, dysrhythmias, and exogenous drug administration. Although epinephrine is the mainstay of therapy, improvement in cardiovascular status may require aggressive fluid administration, and additional pharmacologic and non-pharmacologic aids.

Dobutamine pharmacokinetics and pharmacodynamics in pediatric intensive care patients.

OBJECTIVE: To evaluate the pharmacokinetics and pharmacodynamics of dobutamine in critically ill children. DESIGN: A prospective study of pediatric patients receiving continuous infusions of dobutamine in a stepwise format from 2.5 to 10.0 micrograms/kg/min. SETTING: A pediatric critical care unit. PATIENTS: Twelve children ranging in age from 1 month to 17 yrs with primary medical conditions. MEASUREMENTS: Plasma dobutamine concentrations and hemodynamic responses were measured at each infusion rate at steady state. Dose response data were analyzed to determine the threshold or minimum plasma dobutamine concentration necessary for discernible hemodynamic effects. MAIN RESULTS: Dobutamine plasma clearance rates ranged from 40 to 130 mL/kg/min. Each patient presented a linear increase in the plasma dobutamine concentration at each infusion rate (r2 = .97, p less than .001). Plasma clearance rate vs. actual dobutamine concentration did not vary. Cardiac output, BP, and heart rate increased 30%, 17%, and 7%, respectively, at maximal dose. The dobutamine concentration thresholds for changes in cardiac output, BP, and heart rate were 13 +/- 6, 23 +/- 14, and 65 +/- 30 ng/mL, respectively. CONCLUSIONS: There was no effect of plasma dobutamine concentration or infusion rate on plasma clearance rate. For this group of patients, over the range of the intravenous doses studied, dobutamine pharmacokinetics followed a first-order kinetic model. Threshold values for dobutamine usually show increases in cardiac output before changes in heart rate. These data demonstrate that dobutamine is an effective inotropic agent in critically ill pediatric patients and has minimal chronotropic action.

Respiratory syncytial virus-related apnea in infants. Demographics and outcome.

Medical records of 261 hospitalized patients less than 1 year old with documented respiratory syncytial virus (RSV) infection were reviewed to determine the incidence of RSV-associated apnea and the accompanying risk of subsequent apnea or death. Apnea in association with RSV infection occurred in 18% of the infants. Premature birth and a young postnatal age were risk factors for development of apnea with RSV disease. Apnea of prematurity appeared to be a significant risk factor for RSV apnea development in infants with a gestational age of 32 weeks or less at birth, but infants with RSV apnea did not appear to be at risk for subsequent apnea. These results suggested that in hospitalized infants, RSV apnea may be related to immaturity of respiratory drive. Two of the 48 infants with RSV apnea subsequently died during the first year of life.

Pulmonary hypertension in infants with bronchopulmonary dysplasia.

Seventeen children with oxygen-dependent bronchopulmonary dysplasia, right ventricular hypertrophy, and Doppler echocardiographic evidence of pulmonary hypertension were studied by cardiac catheterization. Fifteen of these patients had pulmonary hypertension when placed in room air; six of these 15 patients were shown to have large systemic-to-pulmonary collateral vessels. The hemodynamic responses to oxygen and hydralazine were evaluated. Five patients developed normal pulmonary artery pressure while receiving supplemental oxygen and were not studied further. Of the remaining ten patients, the six patients with large, hemodynamically significant collateral vessels all had deleterious reactions to hydralazine. Two of the four patients without collateral pulmonary circulation responded to hydralazine with further reductions in mean pulmonary artery pressure. Five of the ten patients who had persistent pulmonary hypertension while receiving oxygen have died. Cardiac catheterization and angiography may provide important diagnostic, therapeutic, and prognostic information in patients with pulmonary hypertension complicating bronchopulmonary dysplasia.

Prediction of childhood drowning and near-drowning morbidity and mortality.

OBJECTIVES: (a) Evaluate the presenting hemodynamic status and neurologic function of a series of warm water submersion injuries. (b) To ascertain the importance of the timing of the neurologic examination. (c) To identify risk factors that predict which patients will not return to presubmersion status. DESIGN: Retrospective review of all patients with a diagnosis of drowning/near-drowning responded to by the Children's Hospital pediatric transport service. Data were collected over a 24-month period regarding patient characteristics, submersion medium, rescue efforts, time out of sight, elapsed times to emergency department (ED) and pediatric intensive care unit (PICU) arrival, neurologic and hemodynamic status on arrival at the ED and PICU, reconstructed Conn-Modell category, and neurologic outcome. SETTING: EDs of the referring hospitals and PICU of the Children's Hospital of Orange County (CHOC), California. PATIENTS: Ninety-three submersion victims at an average age of 31 months. All patients were provided intensive care support. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Twenty-three percent (21/ 93) of patients died or survived vegetative. No patient arriving comatose and asystolic in the ED survived neurologically intact (n = 21, three patients expired in the ED). This group of patients had a mean duration of documented asystole = 41 minutes, range of 18 to 107 minutes, and time to ED arrival = 21 minutes. All patients with a detectable pulse and blood pressure (n = 72) on arrival to the ED, regardless of their neurologic status, recovered to their presubmersion status. Patients arriving comatose (decorticate, decerebrate, or flaccid posture) in the PICU (n = 18, mean arrival = 192 minutes) all died or were vegetative. All patients with non-coma (n = 72, Conn-Modell category A or B) on arrival to the PICU recovered normally. CONCLUSIONS: Hemodynamic status in the ED and neurologic status in the PICU are highly predictive of outcome. On arrival to the ED, the cardiovascular status is more predictive of abnormal outcome than neurologic status. Poor neurologic outcome appears inevitable for warm water submersion victims who are asystolic at ED arrival and remain comatose for more than 200 minutes.

Renal clearance of gentamicin in cystic fibrosis.

This study was designed to corroborate previous observations of low serum concentrations of aminoglycosides after usual doses in patients with cystic fibrosis and to investigate possible mechanisms for this change. We studied gentamicin clearance after single and multiple intravenously administered doses in 10 non-acutely ill patients with mild to moderate CF. The data could best be described by a two-compartment model for drug elimination. The mean 1-hour serum concentration, mean volume of distribution, and mean total plasma clearance of gentamicin were not different from those reported for patients without CF. The similarity of the plasma and the renal gentamicin clearances, supported by the observations that greater than 80% of administered drug was excreted in the urine by 4 hours and that negligible amounts were detected in sweat, saliva, or sputum, implies that the kidney is the major route of elimination in patients with mild CF. The correlation of increased plasma gentamicin clearance as NIH score decreases supports the hypothesis that aminoglycoside pharmacokinetics are changed as the severity of disease increases. For patients with mild CF, standard doses of gentamicin (60 mg/m2) will give safe and therapeutic concentrations.

Use of the anterior cricoid split operation in infants with acquired subglottic stenosis.

Ten infants with acquired subglottic stenosis were treated successfully using the anterior cricoid split operation. Eight had been preterm infants who required endotracheal intubation and assisted ventilation for the respiratory distress syndrome. Two had been born at term; 1 required mechanical ventilation for aspiration of meconium and the other intubation for obstructive apnea. All had been extubated successfully in less than 2 wk and were discharged home with no signs of subglottic stenosis. These infants were referred at 2 to 13 months of age for evaluation of upper airway obstruction. By bronchoscopy, we confirmed severe subglottic stenosis in each of the infants. The anterior cricoid split procedure requires a single midline vertical incision through the anterior cartilaginous ring of the cricoid cartilage and the upper 2 tracheal rings. Our postoperative management included 7 to 10 days of endotracheal intubation, mechanical ventilation, neuromuscular blockade, sedation, and total parenteral nutrition. All were extubated at the end of this period without evidence of stridor or obstructive apnea. One patient developed a subglottic granuloma at the level of the cricoid cartilage 4 months after the operation; this was successfully excised with the carbon dioxide laser. The other 9 patients remain asymptomatic 1 month to 1 yr after the surgical repair.

High-frequency oscillatory ventilation in pediatric respiratory failure: a multicenter experience.

OBJECTIVE: The use of high-frequency oscillatory ventilation (HFOV) has increased dramatically in the management of respiratory failure in pediatric patients. We surveyed ten pediatric centers that frequently use high-frequency oscillation to describe current clinical practice and to examine factors related to improved outcomes. DESIGN: Retrospective, observational questionnaire study. SETTING: Ten tertiary care pediatric intensive care units. PATIENTS: Two hundred ninety patients managed with HFOV between January 1997 and June 1998. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients were classified according to presence or absence of preexisting lung disease, symptomatic respiratory syncytial virus infection, or presence of cyanotic heart disease or residual right-to-left intracardiac shunt. In addition, patients for whom HFOV acutely failed were analyzed separately. Those patients with preexisting lung disease were significantly smaller, had a significantly higher incidence of pulmonary infection as the triggering etiology, and had a significantly greater duration of conventional ventilation before institution of HFOV compared with patients without preexisting lung disease. Stepwise logistic regression was used to predict mortality and the occurrence of chronic lung disease in survivors. In patients without preexisting lung disease, the model predicted a 70% probability of death when the oxygenation index (OI) after 24 hrs was 28 in the immunocompromised patients and 64 in the patients without immunocompromise. In the immunocompromised patients, the model predicted a 90% probability of death when the OI after 24 hrs was 58. In survivors without preexisting lung disease, the model predicted a 70% probability of developing chronic lung disease when the OI at 24 hrs was 31 in the patients with sepsis syndrome and 50 in the patients without sepsis syndrome. In the patients with sepsis syndrome, the model predicted a 90% probability of developing chronic lung disease when the OI at 24 hrs was 45. CONCLUSIONS: Given the number of centers involved and the size of the database, we feel that our results broadly reflect current practice in the use of HFOV in pediatric patients. These results may help in deciding which patients are most likely to benefit from aggressive intervention by using extracorporeal techniques and may help identify high-risk populations appropriate for prospective study of innovative modes of supporting gas exchange (e.g., partial liquid breathing or intratracheal pulmonary ventilation).

Multicenter randomized controlled trial of the effects of inhaled nitric oxide therapy on gas exchange in children with acute hypoxemic respiratory failure.

OBJECTIVES AND BACKGROUND: To determine whether inhaled nitric oxide (iNO) therapy can attenuate the progression of lung disease in acute hypoxemic respiratory failure, we performed a multicenter, randomized, masked, controlled study of the effects of prolonged iNO therapy on oxygenation. We hypothesized that iNO therapy would improve oxygenation in an acute manner, slow the rate of decline in gas exchange, and decrease the number of patients who meet pre-established oxygenation failure criteria. STUDY DESIGN: A total of 108 children (median age 2.5 years) with severe acute hypoxemic respiratory failure from 7 centers were enrolled. After consent was obtained, patients were randomized to treatment with iNO (10 ppm) or mechanical ventilation alone for at least 72 hours. Patients with an oxygenation index >/=40 for 3 hours or >/=25 for 6 hours were considered treatment failures and exited the study. RESULTS: Patient age, primary diagnosis, pediatric risk of mortality score, mode of ventilation, and median oxygenation index (35 +/- 22 vs 30 +/- 15; iNO vs control; mean +/- SEM) were not different between groups at study entry. Comparisons of oxygenation indexes during the first 12 hours demonstrated an acute improvement in oxygenation in the iNO group at 4 hours (-10.2 vs -2.7, mean values; P <.014) and at 12 hours (-9.2 vs -2.8; P <.007). At 12 hours 36% of the control group met failure criteria in contrast with 16% in the iNO group (P <.05). During prolonged therapy the failure rate was reduced in the iNO group in patients whose entry oxygenation index was >/=25 (P <.04) and in immunocompromised patients (P <.03). CONCLUSIONS: We conclude that iNO causes an acute improvement in oxygenation in children with severe AHRF. Two subgroups (immunocompromised and an entry oxygen index >/=25) appear to have a more sustained improvement in oxygenation, and we speculate that these subgroups may benefit from prolonged therapy.