Gary M. Albers

Safety and efficacy of flumazenil in the reversal of benzodiazepine-induced conscious sedation

Abstract Objective: To determine the safety and efficacy of flumazenil when given for reversal of benzodiazepine-induced conscious sedation in children. Design: Multicenter study conducted in emergency departments and pediatric endoscopy, bronchoscopy, or oncology suites. Patients: One hundred seven children (median age, 6 years; range, 1 to 17 years) who received intravenous benzodiazepine for an invasive procedure. Interventions: Flumazenil was given in increments of 0.01 mg/kg (0.2 mg maximum) at 1-minute intervals to a maximum total dose of 0.05 mg/kg (1.0 mg maximum). Measurements: Clinical efficacy was assessed by the Clinical Global Impression Scale and Observer’s Assessment of Alertness/Sedation Scale. The OAA/S, vital signs, lead II electrocardiogram, and clinical assessments were recorded at 0, 10, 30, 60, 90, and 120 minutes after flumazenil was given. Results: All children received midazolam (mean total dose, 0.18 mg/kg) for sedation. One hundred (96%) patients achieved a complete or partial response to flumazenil by 10 minutes after its administration, on the basis of their CGIS scores (the mean dose of flumazenil administered at the time of the first complete response was 0.017 ± 0.010 mg/kg). Seventy-one of 93 (76%) patients with a baseline OAA/S score ≤ 3 (1 = deep sleep, 5 = alert) experienced an increase of ≥ 2 points at 10 minutes after flumazenil administration, and 81 of 93 (87%) had a score of 4 or 5 after flumazenil administration. Seven patients, all within the 1- to 5-year age range, experienced resedation after initially responding to flumazenil. Thirty-seven of 107 patients (35%) experienced a total of 56 adverse events, most of which were considered to be unrelated to flumazenil administration. The most frequently occurring adverse events were abnormal crying, dizziness, nausea, fever, and headache. There were no clinically significant changes in vital signs or ECG tracings. No adverse events resulted in premature termination of drug administration. Conclusions: Flumazenil promptly and effectively reverses the central nervous system depressant effects of midazolam in children undergoing conscious sedation, with no significant adverse effects. Because of the potential for resedation, children who receive flumazenil should be monitored for 1 to 2 hours after its administration. (J Pediatr 1997;131:582-6)

Intravenous midazolam for sedation of children undergoing procedures: an analysis of age- and procedure-related factors.

OBJECTIVE This study was performed to determine the doses of midazolam used for sedation during procedures in children, and the frequency of adverse events. METHODS We performed a retrospective analysis of data collected for a prospective study of flumazenil in children who had received midazolam for a procedure (n = 91, 1-17 years). RESULTS Practitioners used a wide range of total midazolam doses (0.03-0.6 mg/kg); mean doses ranged from 0.09 +/- 0.06 mg/kg in adolescents to 0.26 +/- 0.13 mg/kg in toddlers (P < 0.001). Opioids were also used in 84% of patients. Twenty-six percent of children with normal lungs, most of whom had received relatively high opioid doses, developed decreased oxygen saturation (as low as 65%) after sedation. Other adverse events included airway obstruction (n = 3) and vomiting (n = 1). CONCLUSIONS The frequent choice of midazolam, usually combined with an opioid, indicates its wide acceptance. Midazolam doses were inversely related to age. The presence of vomiting, airway obstruction, and decreased oxygen saturation underlines the importance of appropriate personnel, equipment, and monitors during sedation.

Severe bilateral panlobular emphysema and pulmonary arterial hypoplasia: Unusual manifestations of Menkes disease

Menkes disease is an X‐linked recessive disorder of copper transport characterized by neurological deterioration, connective tissue, and vascular defects, abnormal hair, and death in early childhood. We report on a patient with Menkes disease in whom severe diffuse emphysema caused respiratory failure and death at 14 months of age. He had severe growth and developmental delays and other typical clinical manifestations of Menkes disease. He developed respiratory problems requiring continuous supplemental oxygen and a progressively enlarging soft tissue mass appeared on the neck. Imaging studies revealed cystic spaces in multiple lobes of the lung consistent with bullous emphysema. The neck mass was determined to be an internal jugular venous aneurysm. At autopsy, extensive emphysematous change was evident. Post‐mortem barium injections of the pulmonary arterial system revealed marked dilatation and tortuosity of the preacinar pulmonary arteries and reduced numbers of intra‐acinar arteries. Severe emphysema, presumably caused by abnormal elastin due to deficiency of the copper‐dependent enzyme lysyl oxidase, may represent an underestimated clinical complication of Menkes disease and should be considered in the differential diagnosis of chronic respiratory disease in these patients.

B-Lymphocyte aggregates in alveoli from a child with hypersensitivity pneumonitis (bird breeders lung)

BACKGROUND Hypersensitivity pneumonitis is an interstitial lung disease mediated through a patients immunologic response to a variety of inhaled organic dusts. Studies of the cellular components of lavage fluid from patients with this disease show marked increases of CD8+ suppressor/cytotoxic T-lymphocytes. OBJECTIVE In this study, we identified, in addition to the expected suppressor T-cells and natural killer cells, follicle-like aggregates of B-cells in the lung interstitium of an affected patient. METHODS The patient was an 11-year-old non-asthmatic, Caucasian male who presented with a 4-month history of progressive dyspnea, cough, and fever. The home contained nine cockatiel and two doves. Admission pulmonary functions revealed a restrictive pattern with diminished diffusion capacity. Prior to a diagnosis, the patient underwent bronchoalveolar lavage and transbronchial biopsy. Serum precipitins were eventually positive to pigeon (which cross-reacts with dove) droppings. The symptoms resolved after a prolonged course of prednisone. RESULTS Analysis of bronchoalveolar lavage lymphocyte population revealed a predominance of CD8+ cells (50%) with 85% expressing the activation marker HLA-DR. The percentage of CD4+ and CD56+ were 32% and 16%, respectively. The transbronchial biopsy revealed CD20+ follicle-like aggregates within the lung interstitium. CONCLUSIONS The histopathologic findings confirm that in hypersensitivity pneumonitis, the predominant immune response is an infiltrate of CD8+ T cells. The presence of B cell aggregates, however, may indicate that the local synthesis of antibody may be involved in an antibody-dependent cellular cytotoxic mechanism.

Improvements in Cystic Fibrosis Quarterly Visits, Lung Function Tests, and Respiratory Cultures

BACKGROUND: The Cystic Fibrosis (CF) Foundation recommends patients attend clinic ≥4 times per year with 4 respiratory cultures and 2 pulmonary function tests (PFTs). However, nationally only 57.4% of patients met these guidelines in 2012. We used a quality improvement program with a goal of 75% of our patients meeting this care guideline by 2012. METHODS: A 2-stage program was started in 2011. Stage 1: education of patients/caregivers on importance of quarterly visits. Stage 2: quarterly tracking system of patient appointments. Data on clinic visits, respiratory cultures, and PFTs were collected from the CF registry from January 2009 through December 2013. Statistical process control charts were used to track improvements. RESULTS: The average number of clinic visits increased significantly from 4.6 ± 2.3 in 2009 to 6.3 ± 4.6 in 2013 (P < .0001). The percentage of patients ages 6 through 18 completing a clinic visit, PFT, and respiratory culture per quarter increased significantly from 76.2% during 2009 to 86.4% in 2013. The percentage of patients completing ≥4 clinic visits with 4 respiratory cultures and 2 PFTs improved significantly from 47.5% in 2009 to 71.0% in 2013 (P < .0001). CONCLUSIONS: A tracking system of patient appointments significantly improved adherence to the care guidelines better than education alone. The multiple-stage quality improvement program we implemented may be modifiable and able to be integrated in other CF centers or other multiple disciplinary chronic illness care centers.

Hypersensitivity Pneumonitis in Children

Hypersensitivity pneumonitis (extrinsic allergic alveolitis) is an immunologic medicated hypersensitivity reaction to a variety of inhaled allergens that may cause an acute and subacute intersititial pneumonitis and may lead to a chronic end-stage lung disease. Although more common in adults, hypersensitivity pneumonitis needs to be considered in the differential diagnosis of interstitial pneumonitis in children. In children, the most common antigens are from residential exposure to birds, humidifiers, and indoor molds. Serum immunoglobulin G (IgG) antibodies are elevated to the inhaled antigen(s) in hypersensitivity pneumonitis, but they may be present in asymptomatic exposed individuals. The immunopathogenesis involves cellular immunity to inhaled allergens, especially CD+ cytotoxic T cells, multinucleated giant cells, and ultimately granulomas. Pulmonary function studies demonstrate a restrictive pattern with a diffusion defect resulting in hypoxemia. Radiographic changes vary according to the stage of...