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Richard J Brilli

Publications and source records attributed to Richard J Brilli.

11 recordsLinked to original sources

Theophylline versus terbutaline in treating critically ill children with status asthmaticus: a prospective, randomized, controlled trial.

OBJECTIVE: To compare the efficacy of theophylline, terbutaline, or theophylline combined with terbutaline treatment in critically ill children with status asthmaticus who are already receiving continuous nebulized albuterol and intravenous corticosteroids. DESIGN: Randomized, prospective, controlled, double-blind trial. SETTING: Pediatric intensive care unit of a tertiary-care children's medical center. PATIENTS: Forty critically ill children between the ages of 3 and 15 yrs with impending respiratory failure secondary to status asthmaticus. INTERVENTIONS: All patients received intravenous methylprednisolone and continuous nebulized albuterol. The three study groups received theophylline plus placebo (group 1), terbutaline plus placebo (group 2), or theophylline and terbutaline together (group 3). MEASUREMENTS AND MAIN RESULTS: Differences in baseline characteristics, change in clinical asthma score over time, length of pediatric intensive care unit stay, and incidence of adverse events were determined. The three study groups were similar in age, gender, race, asthma severity, and treatment. There were no differences in clinical asthma score over time, length of pediatric intensive care unit stay, or incidence of adverse events between the three groups, with the exception of a higher incidence of nausea in children in group 3. The median hospital cost of medication and theophylline blood levels was significantly lower in group 1 compared with groups 2 and 3 (280 US dollars vs. 3,908 US dollars vs. 4,045 US dollars, respectively, p < .0001). CONCLUSIONS: Theophylline, when added to continuous nebulized albuterol therapy and intravenous corticosteroids, is as effective as terbutaline in treating critically ill children with status asthmaticus. The addition of theophylline to baseline therapy is more cost-effective when compared with terbutaline alone or terbutaline and theophylline together. Theophylline should be considered for use early in the management of critically ill asthmatic children.

Adolescent↗

Pediatric sepsis definitions: past, present, and future.

OBJECTIVE: To review the past, present, and future definitions of sepsis and the systemic inflammatory response syndrome in children. METHODS: Review of the literature. RESULTS: The history and development of the adult-derived sepsis syndrome and its application to pediatric-specific sepsis definitions is provided. Initially, only adult definitions were applied to pediatric studies. Recently, pediatric-specific definitions have been published. The pediatric consensus conference-derived definitions for systemic inflammatory response syndrome, sepsis, severe sepsis, and septic shock are summarized, and their limitations are discussed. CONCLUSIONS: The potential value and inconsistencies of the current pediatric-specific sepsis definitions are discussed. Future direction of the definitions and their applications are presented.

Child↗

Safety, pharmacokinetics, and pharmacodynamics of drotrecogin alfa (activated) in children with severe sepsis.

OBJECTIVE: In a phase 3 trial, recombinant human activated protein C (drotrecogin alfa [activated]) significantly reduced mortality in adult patients with severe sepsis. We have now performed a preliminary analysis of the safety, pharmacokinetics, and pharmacodynamics of drotrecogin alfa (activated) in pediatric patients with severe sepsis. DESIGN AND SETTING: Open-label, nonrandomized, sequential, 2-part study conducted in 11 medical centers in the United States and United Kingdom. PATIENTS: Eighty-three pediatric patients with severe sepsis aged term newborn (>or=38 weeks' gestation) to <18 years old. INTERVENTION: In part 1, drotrecogin alfa (activated) was administered as escalating doses of 6, 12, 24, and 36 micro g/kg per hour for 6 hours for each patient (n = 21). In part 2, drotrecogin alfa (activated) was infused at a rate of 24 micro g/kg per hour for 96 hours in 62 patients. MAIN OUTCOME MEASURES: Plasma clearance, plasma concentration, D-dimer, protein C, and antithrombin levels were measured, and adverse events were monitored. RESULTS: The trial enrolled 83 pediatric patients with severe sepsis, aged term newborn (>or=38 weeks' gestation) to <18 years. In part 1, a dose of 24 micro g/kg per hour produced steady-state plasma concentrations of activated protein C similar to those attained in equivalently dosed adult severe sepsis patients. For all pediatric patients dosed at 24 micro g/kg per hour, the median weight-normalized clearance was 0.45 L/hour/kg and the median steady-state concentration was 51.3 ng/mL. The mean plasma half-life was 30 minutes. Weight-normalized clearance in pediatric and adult patients did not differ significantly with age or weight. D-dimer levels decreased 26% from baseline to end of infusion. Baseline levels of protein C and antithrombin increased 79% and 24%, respectively, over the 96-hour treatment period in part 2. The incidence of serious bleeding during infusion and during the entire study period was 2.4% and 4.8%, respectively. CONCLUSIONS: Pediatric patients with severe sepsis manifest sepsis-induced coagulopathy including protein C deficiency comparable to that seen in adults with severe sepsis. The pharmacokinetics, pharmacodynamic effects, and safety profile of drotrecogin alfa (activated) in pediatric patients are similar to those previously published for adult patients. A large, phase 3, randomized, placebo-controlled study is ongoing to confirm these results and formally assess the safety and efficacy of drotrecogin alfa (activated) in children.

Adolescent↗

Coagulation dysfunction in sepsis and multiple organ system failure.

In patients diagnosed with sepsis, severe sepsis or septic shock, cytokine-mediated endothelial injury, and TF activation initiate a cascade of events that culminate in the development of coagulation dysfunction characterized as procoagulant and antifibrinolytic. This abnormal state predisposes the patient to develop microvascular thrombosis, tissue ischemia, and organ hypoperfusion. Multiple organ dysfunction syndrome may be a product of this pertubation in coagulation regulation. Treatments aimed at correcting this coagulation dysfunction have met with mixed success. Current data suggest that AT III replacement therapy has limited efficacy in adults with severe sepsis. In contrast, adult patients diagnosed with severe sepsis and organ failure and treated with aPC (drotrecogin alfa activate) have a significantly reduced risk of death when compared with placebo-treated patients. A phase III trial examining the efficacy of protein C replacement therapy in pediatric patients with severe sepsis and organ failure is underway.

Antithrombin III↗

Cardiopulmonary compromise associated with milk and molasses enema use in children.

OBJECTIVE: Constipation is a common childhood problem that frequently confronts pediatric practitioners. When enema treatment is indicated to treat constipation, milk and molasses enemas are sometimes used. Side effects and adverse outcomes have been described with many types of enemas, but not with milk and molasses. The purpose of this study is to describe five children who acutely decompensated after receiving milk and molasses enemas. METHODS: Retrospective review of the medical records of children with constipation who received milk and molasses enema with subsequent PICU admission at Cincinnati Children's Hospital Medical Center between 1994 and 2000. RESULTS: Five children developed significant hemodynamic deterioration after receiving milk and molasses enemas. One of these children died and the others recovered after aggressive resuscitation. CONCLUSIONS: Milk and molasses enema administration can be associated with significant hemodynamic compromise. These risks appear similar to those risk observed with the use of other enema preparations.

Animals↗

Erythropoietin therapy in children with bronchiolitis and anemia.

OBJECTIVE: Critically ill children with bronchiolitis often require red blood cell transfusions. Anemia normally results in increased circulating erythropoietin concentrations; however, critical illness has been associated with a blunted erythropoietin response. Treatment with erythropoietin decreases the need for red blood cell transfusion in several disease states. We hypothesized that critically ill children with bronchiolitis and anemia would have a circulating erythropoietin deficiency and that treatment with exogenous erythropoietin would increase reticulocyte count and hematocrit and reduce red blood cell transfusion requirements. DESIGN: Randomized, blinded, placebo-controlled trial. SETTING: Children's hospital. PATIENTS: Critically ill children with bronchiolitis, anemia, and respiratory failure. Anemia was defined as a hematocrit >2 SD below normal for age. INTERVENTION: Patients were randomized to one of two groups. In the erythropoietin group, patients received daily intravenous erythropoietin. In the control group, patients received daily intravenous placebo. Both groups were treated with elemental iron. MEASUREMENTS AND MAIN RESULTS: Blood for complete blood count, reticulocyte count, and ferritin and erythropoietin concentration was obtained at admission and discharge. Red blood cell transfusions were administered to patients with a persistent oxygen requirement and a hematocrit of <25%. Outcome variables included number of red blood cell transfusions, change in reticulocyte count, ferritin values, and circulating erythropoietin values between groups. Forty-four patients completed the study (mean 3.1 +/- 0.6 months), with a baseline hematocrit of 27.6 +/- 0.5%, ventilator days of 8.2 +/- 0.6, and pediatric intensive care unit length of stay of 9.8 +/- 0.6 days. There were no significant baseline demographic differences between the control and erythropoietin groups. Ten of 22 (45%) children in the erythropoietin group required red blood cell transfusion compared with 11 of 22 (50%) in the control group (p = nonsignificant). The increase in reticulocyte count was greater in the erythropoietin group compared with the control group (2.1 +/- 0.3% to 4.7 +/- 0.7%, p = .003 vs. 2.1 +/- 0.3% to 2.7 +/- 0.5%, p = nonsignificant). CONCLUSIONS: Despite a favorable reticulocyte and circulating erythropoietin response, red blood cell transfusion requirements were not significantly diminished by erythropoietin treatment in children with bronchiolitis and respiratory failure. Erythropoietin cannot be routinely recommended for this patient population.

Anemia↗

Guidelines on critical care services and personnel: Recommendations based on a system of categorization of three levels of care.

OBJECTIVES: To describe three levels of hospital-based critical care centers to optimally match services and personnel with community needs, and to recommend essential intensive care unit services and personnel for each critical care level. PARTICIPANTS: A multidisciplinary writing panel of professionals with expertise in the clinical practice of critical care medicine working under the direction of the American College of Critical Care Medicine (ACCM). DATA SOURCES AND SYNTHESIS: Relevant medical literature was accessed through a systematic Medline search and synthesized by the ACCM writing panel, a multidisciplinary group of critical care experts. Consensus for the final written document was reached through collaboration in meetings and through electronic communication modalities. Literature cited included previously written guidelines from the ACCM, published expert opinion and statements from official organizations, published review articles, and nonrandomized, historical cohort investigations. With this background, the ACCM writing panel described a three-tiered system of intensive care units determined by service-based criteria. CONCLUSIONS: Guidelines for optimal intensive care unit services and personnel for hospitals with varying resources will facilitate both local and regional delivery of consistent and excellent care to critically ill patients.

Adult↗

Extubation failure in pediatric intensive care: a multiple-center study of risk factors and outcomes.

OBJECTIVE: To determine a contemporary failed extubation rate, risk factors, and consequences of extubation failure in pediatric intensive care units (PICUs). Three hypotheses were investigated: a) Extubation failure is in part disease specific; b) preexisting respiratory conditions predispose to extubation failure; and c) admission acuity scoring does not affect extubation failure. DESIGN: Twelve-month prospective, observational, clinical study. SETTING: Sixteen diverse PICUs in the United States. PATIENTS: Patients were 2,794 patients from the newborn period to 18 yrs of age experiencing a planned extubation trial. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A descriptive statistical analysis was performed, and outcome differences of the failed extubation population were determined. The extubation failure rate was 6.2% (174 of 2,794; 95% confidence interval, 5.3-7.1). Patient features associated with extubation failure (p <.05) included age < or =24 months; dysgenetic condition; syndromic condition; chronic respiratory disorder; chronic neurologic condition; medical or surgical airway condition; chronic noninvasive positive pressure ventilation; the need to replace the endotracheal tube on admission to the PICU; and the use of racemic epinephrine, steroids, helium-oxygen therapy (heliox), or noninvasive positive pressure ventilation within 24 hrs of extubation. Patients failing extubation had longer pre-extubation intubation time (failed, 148.7 hrs, SD +/- 207.8 vs. success, 107.9 hrs, SD +/- 171.3; p <.001), longer PICU length of stay (17.5 days, SD +/- 15.6 vs. 7.6 days, SD +/- 11.1; p <.001), and a higher mortality rate than patients not failing extubation (4.0% vs. 0.8%; p <.001). Failure was found to be in part disease specific, and preexisting respiratory conditions were found to predispose to failure whereas admission acuity did not. CONCLUSION: A variety of patient features are associated with an increase in extubation failure rate, and serious outcome consequences characterize the extubation failure population in PICUs.

Adolescent↗

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Critical Care↗

Continuation of transpyloric feeding during weaning of mechanical ventilation and tracheal extubation in children: a randomized controlled trial.

BACKGROUND: Nutrition support is essential in the management of critically ill children. There is no current literature to support the common practice of discontinuing enteral nutrition delivered through a transpyloric feeding tube during the tracheal extubation process. We conducted a prospective, randomized controlled trial in mechanically ventilated children to examine the safety and efficacy of continuous transpyloric feeding compared with interrupted transpyloric feeding at the time of tracheal extubation. METHODS: Subjects were randomly assigned to receive transpyloric feeding throughout the tracheal extubation process (Continuous Group) or to have transpyloric feeding discontinued 4 hours before tracheal extubation and restarted 4 hours after tracheal extubation (Interrupted Group). Data consisting of patient demographics, admission pediatric risk of mortality (PRISM) score, diagnoses, adverse events (feeding intolerance, gastroesophageal reflux, and pulmonary aspiration), daily feeding volume, and caloric intake were recorded for the 3 days surrounding tracheal extubation. RESULTS: Fifty-nine patients completed the study (29 in Continuous Group, 30 in Interrupted Group). There was no episode of pulmonary aspiration in either group. The Continuous Group experienced 4 adverse events, whereas the Interrupted Group experienced 3 adverse events (p = not significant). The Continuous Group received 92 +/- 2.5% of their caloric goal on the day of weaning from the ventilator (day 1) and 93 +/- 3.2% on the day of tracheal extubation (day 2) compared with 76 +/- 4.2% and 43 +/- 4.3%, respectively, in the Interrupted Group (p < .004 and p < .0001, respectively). CONCLUSIONS: Continuous transpyloric feeding during weaning from the ventilator and tracheal extubation is safe and results in the delivery of more optimal nutrition.

Critical Illness↗