Albuterol in acute bronchiolitis--continued therapy despite poor response?

To determine whether clinicians continue to treat acute bronchiolitis with nebulized albuterol despite lack of clinical improvement after such treatment, we reviewed the medical records of 90 randomly selected infants and children with the primary diagnosis of that disorder who were treated in this 232-bed tertiary care children's hospital. Clinical improvement and no clinical improvement were defined as improvement and lack of improvement, respectively, in air movement, wheezing, retractions, oxygen saturation, work of breathing, and respiratory rate after administration of nebulized albuterol. Response to nebulized albuterol was determined from explicit written documentation in the medical records. Of 68 children who received nebulized albuterol in the emergency department, 52% had written documentation indicating no clinical improvement; however, 94% had admission orders to continue the therapy. Within 12 hours after admission, 61% were again noted to have no clinical improvement with nebulized albuterol. Eighty-seven percent of nonresponders continued to receive albuterol throughout hospitalization, and 54% continued to receive it after discharge. Continuing therapy despite lack of response resulted in unnecessary medical expenses.

Enteral methadone to expedite fentanyl discontinuation and prevent opioid abstinence syndrome in the PICU.

STUDY OBJECTIVE: To determine if enterally administered methadone can facilitate fentanyl discontinuation and prevent withdrawal in children at high risk for opioid abstinence syndrome. DESIGN: Retrospective analysis. SETTING: Pediatric intensive care unit (PICU) in a tertiary care children's hospital. PATIENTS: Twenty-two children (aged 6.1 +/- 5.4 yrs) who received continuous fentanyl infusion for 9 days or longer. INTERVENTION: Guidelines for initiating enteral methadone, rapidly tapering and discontinuing fentanyl infusions, and tapering methadone were implemented in the PICU. Development of opioid abstinence syndrome was evaluated during fentanyl and methadone dosage reductions and for 72 hours thereafter. MEASUREMENTS AND MAIN RESULTS: Children received fentanyl by continuous infusion for 17.8 +/- 8.4 days. Peak fentanyl infusion rate was 5.9 +/- 3.8 microg/kg/hour, and the median cumulative dose was 1302 microg/kg (range 354-7535 microg/kg). Methadone 0.50 +/- 0.22 mg/kg/day was begun 1.6 +/- 1.9 days before tapering fentanyl. The fentanyl infusion rate on starting the taper was 5.0 +/- 3.6 microg/kg/hour. Fentanyl was tapered and discontinued in a median of 2.6 days (range 0-11.9 days). Twenty-one patients had no opioid abstinence syndrome during or after fentanyl taper. One patient experienced significant opioid withdrawal after fentanyl discontinuation, which resolved after reinstitution of fentanyl and increasing the dosage of methadone to 0.3 mg/kg every 6 hours. Overall, methadone was tapered and discontinued in 18.2 +/- 11.9 days without precipitating opioid abstinence syndrome. CONCLUSION: Enteral administration of methadone may expedite fentanyl discontinuation and reduce the risk of withdrawal in critically ill children at high risk for opioid abstinence syndrome.

Accumulation of CO(2) in reservoir devices during simulated neonatal mechanical ventilation.

Aerosolized albuterol is frequently administered to mechanically ventilated neonates by metered dose inhaler (MDI) and a reservoir device. These reservoirs are often placed between the Y-piece and endotracheal tube, thereby creating mechanical dead space and increasing the risk of rebreathing carbon dioxide (CO(2)). The objectives of this study were: 1) to quantify CO(2) accumulation in two commonly used reservoirs (ACE(R), Aerochamber(R)-MV) and a bidirectional nonreservoir actuator (Airlife(R) Minispacer) during mechanical ventilation of a neonatal lung model; and 2) to determine the effect of tidal volume (V(T)) on CO(2) accumulation. We hypothesized that the accumulation of CO(2) in these devices is clinically insignificant at the small tidal volumes used in mechanically ventilated premature neonates. The model was constructed to simulate CO(2) exhalation by a ventilated neonate and consisted of a neonatal ventilator circuit (rate = 40/min; peak inspiratory pressure (PIP) = 20 cm H(2)0) attached to a reservoir/actuator and neonatal test lung. The ventilator delivered inspiratory gas (room air) to the test lung, which was vented into the atmosphere by a small adjustable leak. Expiration was simulated by manually ventilating 7.1% CO(2) (partial pressure of CO(2) (PCO(2)) = 48 mm Hg) back through the model. Accumulation of CO(2) within the reservoir/actuator was measured using an end-tidal CO(2) monitor. Each 4-min experiment was conducted at three V(T) (7.5 mL, 15 mL, and 25 mL), and the median PCO(2) was calculated in 0.5-min increments. For V(T) = 7.5 mL, CO(2) accumulated slowly in the ACE(R) and Minispacer(R) and reached a maximum at 4.0 min (PCO(2) = 2.3 mm Hg and 7.3 mm Hg, respectively). In contrast, the Aerochamber(R)-MV rapidly reached a PCO(2) of 9.5-10.0 mm Hg by 1-1. 5 min. A similar trend occurred with V(T) = 15 mL; however, higher partial pressures (approximately 10-12 mm Hg) were achieved with all devices. At V(T) = 25 mL, PCO(2) rose rapidly with the ACE(R), Aerochamber(R)-MV, and Minispacer(R), reaching peaks of 17.2, 12.3, and 20.3 mm Hg, respectively (P < 0.05). In conclusion, accumulation of CO(2) in reservoir/actuator depends on V(T) as well as the chamber design and internal volume. Due to the short duration of use when administering drugs via MDI, accumulation of CO(2) in these devices is not likely to be clinically relevant for the majority of ventilated newborns.

Albuterol delivery in a neonatal ventilated lung model: Nebulization versus chlorofluorocarbon- and hydrofluoroalkane-pressurized metered dose inhalers.

The aim of this study was to compare albuterol delivery in a neonatal ventilated lung model, using three delivery methods: 1) jet nebulizer; 2) chlorofluorocarbon-pressurized metered dose inhaler (CFC-MDI) actuated into an ACE(R) spacer; and 3) hydrofluoroalkane-pressurized MDI (HFA-MDI) actuated into an ACE(R) spacer. The bench model consisted of a mechanically ventilated infant test lung with ventilator settings to simulate a very low birth weight neonate with moderate lung disease. Albuterol solution (0.5%) was nebulized at the humidifier and temperature port, 125 cm and 30 cm from the Y-piece, respectively. Albuterol metered dose inhalers (MDIs) were actuated into an ACE(R) spacer that was tested in two positions: 1) inline between the endotracheal (ET) tube and the Y-piece; and 2) attached to the ET tube and administered by manual ventilation. Albuterol was collected on a filter at the distal end of the ET tube and was quantitatively analyzed by high performance liquid chromatography. Albuterol delivery by CFC-MDI (position 1, 4.8 +/- 1.0%, vs. position 2, 3.8 +/- 1.6%, P > 0.05) and HFA-MDI (position 1, 5.7 +/- 1.6%, vs. position 2, 5.5 +/- 2.4%, P > 0.05) were significantly greater than delivery by nebulization at 30 cm (0.16 +/- 0.07%) and 125 cm (0.15 +/- 0.03%) from the Y-piece (P < 0.001). A single actuation of albuterol MDI delivered the equivalent of nebulizing 2.5-3.7 mg of albuterol solution. We conclude that albuterol administered by MDI and ACE(R) spacer resulted in more efficient delivery than by nebulization in this mechanically ventilated neonatal lung model. There was no significant difference in drug delivery between CFC-MDI and HFA-MDI; nor did the placement of the spacer significantly affect drug delivery.

Analysis of fentanyl and norfentanyl in human plasma by liquid chromatography-tandem mass spectrometry using electrospray ionization.

This report describes a sensitive and specific high-performance liquid chromatography (HPLC)-electrospray ionization-tandem mass spectrometry (MS-MS) method for the detection of subnanogram concentrations of fentanyl and its metabolite norfentanyl in human plasma. The assay was based on a liquid-liquid extraction of 0.5 mL of human plasma, with a lower limit of quantitation (LLOQ) of 0.05 ng/mL. Sample extracts were analyzed using a ThermoQuest TSQ MS-MS interfaced with a Hewlett-Packard series 1100 HPLC and a Phenomenex (30 x 2.00-mm, 5 microLuna C18(2)) column. The intra-assay precision and accuracy ranged from 2.1 to 12.5% for both analytes at concentrations of 0.1, 0.5, 1.0, and 10 ng/mL. The interassay accuracy and precision ranged from 7.34 to 10.95%.

The effect of midazolam premedication on discharge time in pediatric patients undergoing general anesthesia for dental restorations.

PURPOSE: The purpose of this study was to evaluate the effect of oral premedication with midazolam on recovery times of children undergoing dental restorations under general anesthesia. METHODS: The records of 106 children (1.2-11.3 years, ASA I or II) undergoing ambulatory dental restorations were randomly selected and retrospectively reviewed: 50 subjects received midazolam (M) 0.5 mg/kg orally approximately 30 minutes prior to their procedure and 56 control subjects received no premedication (C). General anesthesia consisted primarily of inhalational anesthesia. Time in the operating room (OR), post-anesthesia care unit (PACU) and same day surgery (SDS) were determined and compared between groups. RESULTS: Both groups were similar with respect to age and weight. There were no significant differences between groups in time spent in the OR, PACU or SDS (p>0.05). In a subset of children having shorter dental procedures (OR time < or =75 minutes, n=29), there remained no significant difference in discharge times between groups. CONCLUSIONS: Preoperative administration of oral midazolam does not delay discharge of children undergoing general anesthesia for dental rehabilitation.

The effect of confirmation calls on appointment-keeping behavior of patients in a children's hospital dental clinic.

PURPOSE: The objective of this prospective, randomized, controlled study was to evaluate whether confirmation calls made one or two working days before scheduled appointments reduce the percentage of broken appointments in a children's hospital dental clinic. METHODS: Patients were randomly assigned to three groups: 1) confirmation call made one working day before appointment, 2) confirmation call made two working days before appointment; and 3) control group (no confirmation call). Clinic staff made confirmation calls during normal office hours. Patient arrival was classified as 1) < or =15 minutes late; 2) > 15 minutes late; or 3) broken appointment. RESULTS: Three hundred and thirteen subjects were enrolled in the study: 77 subjects in group 1; 71 subjects in group 2; and 84 subjects in the control group. Eighty-one subjects (26%) could not be contacted by telephone. Overall, there was a 62% reduction in broken appointments among patients who received a confirmation call as compared to the control group. There was no significant difference between confirmation calls placed one or two working days prior to the appointment (P=0.51). Confirmation calls had no effect on punctuality. In comparing indigent care and private insurance, there was no significant difference in broken appointments. However, within the private insurance group, a confirmation call resulted in 93% of patients keeping their appointment as compared to 63% in the control group (P<0.001). No significant difference was noted in the indigent care group, with 79% of patients in the confirmation call group keeping their appointments as compared to 66% in the control group (P=. 093). CONCLUSIONS: Confirmation calls reduced the percentage of broken appointments in a pediatric dental clinic. There was no difference between calls placed one or two working days prior to the appointment. The greatest reduction in broken appointments was shown in the private insurance group.

Angiotensin-II type 1 receptor (AT1R) and alpha-1D adrenoceptor form a heterodimer during pregnancy-induced hypertension.

Pregnancy courses with low response to angiotensin II and adrenergic agonists. In preeclampsia, both effects are reverted. It is known that angiotensin II regulates adrenergic system. It is not known, however, the interaction between both systems receptors. Our aim was to study if AT(1)R and alpha1D adrenoceptor heterodimerize in preeclampsia. We used subrenal aorctic coarctation in pregnant rats. Aortic tissues were prepared for confocal imaging and coimmunoprecipitated for alpha1D and AT(1) receptors. We found that AT(1)R and alpha1D adrenoceptor heterodimerize in both, healthy and preeclamptic groups. In healthy pregnant rats, heterodimer is barely detected. In preeclamptic rats however, we found higher heterodimerization. These results suggest that AT(1)R and alpha1D -adrenoceptor may form heterodimers, and may play a role in preeclampsia.

Pathogenesis and treatment of bronchiolitis.

The pathogenesis, epidemiology, clinical features, sequelae, and treatment of bronchiolitis are reviewed. Acute bronchiolitis is the most common severe lower-respiratory-tract infection of infancy. During epidemics, more than 80% of cases may be caused by respiratory syncytial virus (RSV). Although signs and symptoms may become severe, most infections are self-limited and improvement occurs within several days. Approximately 1-2% of infants less than one year of age require hospitalization. Generally, patients who develop severe, life-threatening RSV bronchiolitis are those with underlying cardiopulmonary disease, immunosuppression, bronchopulmonary dysplasia, or a history of premature birth. In severe bronchiolitis, necrosis of the respiratory epithelium, excessive mucus production, and lymphocytic infiltration result in edema, dense plugs of debris, and subsequent bronchiolar obstruction. IgE-mediated reactions and release of inflammatory mediators may result in exacerbation of acute obstruction and may contribute to chronic obstructive pulmonary dysfunction, a common sequela of bronchiolitis. Patients hospitalized with bronchiolitis usually require supportive therapy and may require mechanical ventilation. Based on recent data, a trial of aerosolized beta 2 agonists is warranted in all patients. Systemic corticosteroids have not proved efficacious and have a limited role in the treatment of acute bronchiolitis. Inhaled corticosteroids may be useful in reducing the severity of chronic wheezing that may follow acute bronchiolitis. Ribavirin may be considered in patients with severe illness or in those at high risk for severe RSV disease. Intravenous immune globulin may have a role in the treatment of lower-respiratory-tract infections involving RSV; however, since few studies have been performed in humans, it is not possible to determine its place in the treatment of bronchiolitis. A trial of aerosolized beta 2 agonists is warranted in patients with bronchiolitis. Ribavirin may be considered in patients with severe disease or those at high risk for severe disease.