Change in Oxygen Consumption Following Inhalation of Albuterol in Comparison with Levalbuterol in Healthy Adult Volunteers.

BACKGROUND: Albuterol is the most commonly used ß agonist to treat reversible lower airway obstruction. Albuterol contains a racemic mixture of two enantiomers. Levalbuterol contains the single R form enantiomer. Levalbuterol is frequently prescribed to limit cardiovascular toxicity. OBJECTIVE: We examined changes in oxygen consumption (V'O2) and heart rate (HR) following administration of albuterol and levalbuterol. METHODS: This is a prospective, randomized, single-blinded, controlled study of healthy adult volunteers. Subjects separately received albuterol (5 mg) and levalbuterol (2.5 mg) aerosolized over 15 min. V'O2 and vital signs were measured before the medications and 5, 10, 20, 40, and 60 min after. RESULTS: We enrolled 24 volunteers with a median age of 32 years. Compared to baseline, there was a significant maximum increase in V'O2 following administration of both albuterol (median 17% (1, 3 IQR 9, 43%) p < 0.001) and levalbuterol (median 23% (1, 3 IQR 10, 32%) p < 0.001). There was no significant difference between the maximum increase in V'O2 following administration of albuterol compared to levalbuterol (p = 0.57). Compared to baseline, there was a significant maximal increase in HR with both albuterol (median 30% (1, 3 IQR 19, 43%) p < 0.001) and levalbuterol (median 23% (1, 3 IQR 19, 31%) p < 0.001). There was a statistically significant greater increase in maximal HR following administration of albuterol as compared to levalbuterol (p = 0.009). CONCLUSION: Albuterol and levalbuterol both cause a significant increase in V'O2 and HR. There was no significant difference between albuterol and levalbuterol regarding the maximum increase in V'O2. There was a statistically significant but likely clinically insignificant difference in maximum increase in HR in patients with adequate oxygen delivery when comparing albuterol to levalbuterol.

Elevated bile acids are associated with left ventricular structural changes in biliary atresia.

BACKGROUND: In children with biliary atresia (BA), pathologic structural changes within the heart, which define cirrhotic cardiomyopathy, are associated with adverse perioperative outcomes. Despite their clinical relevance, little is known about the pathogenesis and triggers of pathologic remodeling. Bile acid excess causes cardiomyopathy in experimental cirrhosis, but its role in BA is poorly understood. METHODS: Echocardiographic parameters of left ventricular (LV) geometry [LV mass (LVM), LVM indexed to height, left atrial volume indexed to BSA (LAVI), and LV internal diameter (LVID)] were correlated with circulating serum bile acid concentrations in 40 children (52% female) with BA listed for transplantation. A receiver-operating characteristic curve was generated to determine optimal threshold values of bile acids to detect pathologic changes in LV geometry using Youden index. Paraffin-embedded human heart tissue was separately analyzed by immunohistochemistry for the presence of bile acid-sensing Takeda G-protein-coupled membrane receptor type 5. RESULTS: In the cohort, 52% (21/40) of children had abnormal LV geometry; the optimal bile acid concentration to detect this abnormality with 70% sensitivity and 64% specificity was 152 µmol/L (C-statistics=0.68). Children with bile acid concentrations >152 µmol/L had ∼8-fold increased odds of detecting abnormalities in LVM, LVM index, left atrial volume index, and LV internal diameter. Serum bile acids positively correlated with LVM, LVM index, and LV internal diameter. Separately, Takeda G-protein-coupled membrane receptor type 5 protein was detected in myocardial vasculature and cardiomyocytes on immunohistochemistry. CONCLUSION: This association highlights the unique role of bile acids as one of the targetable potential triggers for myocardial structural changes in BA.

Minimal Change in Cardiac Index With Increasing PEEP in Pediatric Acute Respiratory Distress Syndrome.

Objective: To determine if increasing positive end expiratory pressure (PEEP) leads to a change in cardiac index in children with Pediatric Acute Respiratory Distress Syndrome ranging from mild to severe. Design: Prospective interventional study. Setting: Multidisciplinary Pediatric Intensive Care Unit in a University teaching hospital. Patients: Fifteen intubated children (5 females, 10 males) with a median age of 72 months (IQR 11, 132) and a median weight of 19.3 kg (IQR 7.5, 53.6) with a severity of Pediatric Acute Respiratory Distress Syndrome that ranged from mild to severe with a median lung injury score of 2.3 (IQR 2.0, 2.7). Measurements: Cardiac index (CI) and stroke volume (SV) were measured on baseline ventilator settings and subsequently with a PEEP 4 cmH2O higher than baseline. Change in CI and SV from baseline values was evaluated using Wilcoxon signed rank test. Results: A total of 19 paired measurements obtained. The median baseline PEEP was 8 cmH2O (IQR 8, 10) Range 6-14 cmH2O. There was no significant change in cardiac index or stroke volume with change in PEEP. Baseline median CI 4.4 L/min/m2 (IQR 3.4, 4.8) and PEEP 4 higher median CI of 4.3 L/min/m2 (IQR 3.6, 4.8), p = 0.65. Baseline median SV 26 ml (IQR 13, 44) and at PEEP 4 higher median SV 34 ml (IQR 12, 44) p = 0.63. Conclusion: There is no significant change in cardiac index or stroke volume with increasing PEEP by 4 cmH2O in a population of children with mild to severe PARDS. Clinical Trial Registration: The study is registered on Clinical trails.gov under the Identifier: NCT02354365.