Thomas P. Green

Controlled trial of dexamethasone therapy in infants with bronchopulmonary dysplasia.

Dexamethasone was compared with placebo in a double-blind, crossover, randomised study of infants with severe bronchopulmonary dysplasia who had required mechanical ventilation for at least four weeks, despite treatment with diuretics, methylxanthines, bronchodilators, fluid restriction, nutritional supplementation, and ligation of the patent ductus arteriosus when indicated. Gestational age ranged from 27 to 33 weeks and birth weight from 800 to 1730 g. Patients received dexamethasone (0 . 5 mg/kg/day) or normal saline for the first 3 days, then treatment was crossed over for the next 3 days. The study was terminated when sequential analysis showed that all six patients had improved during dexamethasone therapy. Significant improvements were seen in ventilator-determined respiratory rate, peak inspiratory pressure, fractional inspired oxygen concentration, and alveolar arterial oxygen gradients (p less than 0 . 05). Although dexamethasone hastened weaning from mechanical ventilation, infection occurred in a substantial proportion of patients.

Dexamethasone reduces the inflammatory response to cardiopulmonary bypass in children

BACKGROUND A randomized, prospective, double-blind study of 29 children was performed to evaluate the hypothesis that dexamethasone administration prior to cardiopulmonary bypass would decrease the inflammatory mediator release and improve the postoperative clinical course. METHODS Fifteen children received dexamethasone (1 mg/kg intravenously) and 14 (controls) received saline solution 1 hour prior to CPB. Serial blood analyses for interleukin-6, tumor necrosis factor-alpha, complement component C3a, and absolute neutrophil count were performed. Postoperative variables evaluated included temperature, supplemental fluids, alveolar-arterial oxygen gradient, and days of mechanical ventilation. RESULTS Dexamethasone caused an eightfold decrease in interleukin-6 levels and a greater than threefold decrease in tumor necrosis factor-alpha levels after CPB (p < 0.05). Complement component C3a and absolute neutrophil count were not affected by dexamethasone. The mean rectal temperature for the first 24 hours postoperatively was significantly lower in the group given dexamethasone than in the controls (37.2 degrees +/- 0.4 degrees C versus 37.7 degrees +/- 4 degrees C; p = 0.007). Dexamethasone-treated patients required less supplemental fluid during the first 48 hours (22 +/- 28 mL/kg versus 47 +/- 34 mL/kg; p = 0.04). Compared with controls, dexamethasone-treated children had significantly lower alveolar-arterial oxygen gradients during the first 24 hours (144 +/- 108 mm Hg versus 214 +/- 118 mm Hg; p = 0.02) and required less mechanical ventilation (median duration, 3 days versus 5 days; p = 0.02). CONCLUSIONS Dexamethasone administration prior to CPB in children leads to a reduction in the postbypass inflammatory response as assessed by cytokine levels and clinical course.

The impact of extracorporeal membrane oxygenation on survival in pediatric patients with acute respiratory failure

OBJECTIVE Extracorporeal membrane oxygenation (ECMO) has been used with increasing frequency in the treatment of acute respiratory failure in pediatric patients. Our objective in this study was to test the hypothesis that ECMO improves outcome in pediatric patients with acute respiratory failure. DESIGN Multicenter, retrospective cohort analysis. SETTING Forty one pediatric intensive care units participated in the study under the auspices of the Pediatric Critical Care Study Group. PATIENTS All pediatric patients admitted to the participating institutions with acute respiratory failure during 1991 were included. Patients with congenital heart disease, contraindications to ECMO, or incomplete data were excluded, yielding a data set of 331 patients from 32 hospitals. INTERVENTIONS Conventional mechanical ventilation, high-frequency ventilation, and extracorporeal membrane oxygenation. MEASUREMENTS AND MAIN RESULTS Multivariate logistic regression analysis was used to identify factors associated with survival. In a second analysis, pairs of ECMO and non-ECMO patients, matched by severity of disease and respiratory diagnosis, were compared. The use of ECMO (p = .0082), but not the use of high-frequency ventilation, was associated with a reduction in mortality. Other factors independently associated with mortality included oxygenation index (p < .0001), Pediatric Risk of Mortality score (PRISM) (p < .0001) and the Paco2 (p = .045). In 53 diagnosis- and risk-matched pairs, there was a significantly lower mortality rate (26.4% vs. 47.2%; p < .01) in the ECMO-treated patients. When all patients were stratified into mortality risk quartiles on the basis of oxygenation index and PRISM score, the proportion of deaths among ECMO-treated patients in the 50% to 75% mortality risk quartile was less than half the proportion in the non-ECMO treated patients (28.6% vs. 71.4% p < .05)> No effect was seen in the other quartiles. CONCLUSIONS The use of ECMO was associated with an improved survival in pediatric patients with respiratory failure. The lack of association of outcome with treatment in the ECMO-capable hospital or with another tertiary technology (i.e. high-frequency ventilation) suggests that ECMO itself was responsible for the improved outcome. Further studies of this procedure are warranted but require broad-based multi-institutional participation to provide sufficient statistical power and sensitivity to demonstrate efficacy.

Noninvasive positive-pressure ventilation in children with lower airway obstruction

Study Objectives: Mechanical ventilation of patients with severe lower airway obstruction presents significant risks; therefore, avoiding the intubation in these patients has been a principal goal of clinical management. Noninvasive positive-pressure ventilation has been shown to be effective in treating adults with chronic obstructive pulmonary disease, but its use has not been studied prospectively in children with acute obstructive lower airways disease. The objective of this study was to determine whether noninvasive mask ventilation improved respiratory function in children with asthma and other obstructive lower airways diseases. Study Design: A prospective, randomized, crossover study. Patients: A total of 20 children admitted to the pediatric intensive care unit with acute lower airway obstruction. Methods: Children were randomized to receive either 2 hrs of non-invasive ventilation followed by crossover to 2 hrs of standard therapy or 2 hrs of standard therapy followed by 2 hrs of noninvasive ventilation. Results: Using a Clinical Asthma Score, we found that noninvasive ventilation decreased signs of work of breathing such as respiratory rate, accessory muscle use, and dyspnea as compared with standard therapy. There was no serious morbidity associated with noninvasive ventilation. Conclusions: We conclude that noninvasive ventilation can be an effective treatment for children with acute lower airway obstruction.

Percutaneous femoral venous catheterizations: A prospective study of complications

In a prospective, 45-month study, we compared the complication rates of percutaneously placed femoral and nonfemoral central venous catheters in critically ill pediatric patients. Forty-one percent of the 395 central venous catheters placed during this interval were femoral. Noninfectious complications were recognized for 2.5% of femoral catheters and 2.1% of nonfemoral catheters. Only three complications occurred with catheter insertion, all during nonfemoral attempts. Systemic infections that were possibly attributable to the central venous catheter were found in 3.7% of patients with femoral catheters and 7.3% of those with nonfemoral catheters. Femoral venous catheterization offers several practical advantages for central access over other sites. The low incidence of complications documented in this study suggests that the femoral vein is the preferred site in most critically ill children when central venous catheterization is indicated.

Furosemide Promotes Patent Ductus Arteriosus in Premature Infants with the Respiratory-Distress Syndrome

Furosemide stimulates the renal synthesis of prostaglandin E2, a potent dilator of the ductus arteriosus. We administered this drug to 33 premature infants with the respiratory-distress syndrome, to determine whether it increased the incidence of patent ductus arteriosus. Chlorothiazide, a diuretic that does not stimulate prostaglandin E synthesis, was used as the control drug in 33 other infants. During the study, the incidence of patent ductus arteriosus was significantly higher (P less than 0.02) in the furosemide group (18 of 33 infants) than in the chlorothiazide group (8 of 33). Eleven infants in the furosemide group and seven in the chlorothiazide group required ductal ligation (P greater than 0.2). An additional six infants (all from the furosemide group) who did not have evidence of a patent ductus during the study were later found to have one. Overall survival was 76 and 61 per cent in the furosemide and chlorothiazide groups, respectively (P greater than 0.2). Small (less than twofold) increases in the urinary excretion of prostaglandin E were seen after the initial dose of both drugs. When the analysis was repeated after the fifth day of life, prostaglandin E excretion tripled after furosemide administration, whereas no increase occurred with chlorothiazide. We conclude that furosemide increases the incidence of patent ductus arteriosus in premature infants with the respiratory-distress syndrome, probably through a prostaglandin-mediated process.

Percutaneous central venous catheterization in a pediatric intensive care unit: a survival analysis of complications

We investigated the relationship between the duration of percutaneous central venous catheterization and the occurrence of catheter-related complications in critically ill children by survival analysis techniques. Data were collected prospectively and analyzed for infectious and noninfectious complications from 379 pediatric patients in whom central venous catheters had been placed in the pediatric ICU over a 45-month period. Cumulative survival rate analysis revealed a linear decrease in the number of complication-free catheters with time. The median duration of complication-free catheter survival was projected to be 23.3 days. The risk of catheter complication did not increase with increasing daily duration of catheter use as demonstrated by probability density function: catheter complication rates were similar on the first day after insertion (1.06 +/- 0.5%), the seventh day (4.27 +/- 1.6%), and the 24th day (2.48 +/- 2.4%). Therefore, in this population, routine catheter replacement would not be expected to lower the incidence of catheter-related complications, but may unnecessarily increase the number of insertion-related complications.

Hemolysis during long-term extracorporeal membrane oxygenation

We studied the cause of hemolysis during extracorporeal membrane oxygenation (ECMO) by monitoring hematologic and coagulation profiles in seven consecutive infants treated with this procedure. A constrained vortex pump was used in all patients, and the average duration of ECMO was 224 +/- 111 (SD) hours. In all patients, plasma free hemoglobin was low during the first 48 hours after the initiation of ECMO. Later, when visible clots appeared in the ECMO circuit, plasma hemoglobin progressively rose. A rise in the level of fibrin degradation products and a fall in the fibrinogen level were observed concurrently with a rise in the plasma hemoglobin level. After complete circuit changes in six patients, plasma free hemoglobin, fibrin split products, and fibrinogen all returned to baseline values. Neither circuit component changes nor exchange transfusion was effective in normalizing the levels of plasma free hemoglobin, fibrin split products, and fibrinogen. We conclude that when ECMO is administered for prolonged periods, circuit thrombosis occurs and hemolysis ensues. Additional studies are needed to assess the contribution of the constrained vortex pump to this process.

Dexamethasone reduces postoperative troponin levels in children undergoing cardiopulmonary bypass.

OBJECTIVE We previously demonstrated that dexamethasone treatment before cardiopulmonary bypass in children reduces the postoperative systemic inflammatory response. The purpose of this study was to test the hypothesis that dexamethasone administration before cardiopulmonary bypass in children correlates with a lesser degree of myocardial injury as measured by a decrease in cardiac troponin I release. DESIGN A prospective, randomized, double-blind study. SETTING The cardiac surgery operating room and intensive care unit of a pediatric referral hospital. SUBJECTS Twenty-eight patients who underwent open-heart surgery for congenital heart defects. INTERVENTIONS Patients received either placebo (group I, n = 13) or dexamethasone, 1 mg/kg iv (group II, n = 15), 1 hr before initiation of cardiopulmonary bypass. Plasma cardiac troponin I samples were obtained at three time points: immediately before study agent (sample 1), 10 mins after protamine sulfate administration after cardiopulmonary bypass (sample 2), and 24 hrs postoperatively (sample 3). MEASUREMENTS AND MAIN RESULTS Mean cardiac troponin I levels (+/-sd) were significantly lower at sample time 3 in group II (dexamethasone; 33.4 +/- 20.0 ng/mL) vs. group I (control; 86.9 +/- 81.1) (p =.04). CONCLUSION Dexamethasone administration before cardiopulmonary bypass in children resulted in a significant decrease in cardiac troponin I levels at 24 hrs postoperatively. We postulate that this may represent a decrease in myocardial injury, and, thus, a possible cardioprotective effect produced by dexamethasone.

Antihypertensive effect and elimination kinetics of captopril in hypertensive children with renal disease

The efficacy and safety of captopril were studied in 10 patients with secondary hypertension (renal parenchymal disease, four patients; renal artery stenosis, two; and renal transplant rejection, four). Captopril was administered according to a dose titration protocol that randomized the initial three doses (0.5, 1.0, and 2.0 mg/kg) of drug to one of six possible sequences. All patients received diuretics prior to and during captopril therapy. A significant reduction in mean blood pressure was observed in all 10 patients during the initial dose titration. No correlation was observed between captopril dose and magnitude of the blood pressure reduction. The onset of antihypertensive action began approximately 15 minutes after each orally administered dose and reached the nadir approximately 1 1/2 hours later. Blood pressure returned to predrug levels between 6 and 10 hours after the dose. A significant reduction in systolic and diastolic blood pressure was noted in all subjects after 1 week of captopril treatment and was maintained during the course of continuous therapy in nine of 10 patients. Captopril combined with hydrochlorothiazide produced a satisfactory therapeutic response in five patients; in four others, additional antihypertensive drugs were required. No significant adverse effects were observed. Plasma renin activity determined prior to initiation of captopril was not predictive of blood pressure response to the drug. The clearance of captopril from patients with kidney failure ranged from 14.1 to 18.8 ml/min/kg in five subjects with creatine clearance between 10 and 21 ml/min/1.73 m2.