Intravenous or Oral Acetazolamide for Treatment of Diuretic-Induced Alkalosis in Patients With Heart Failure.

BACKGROUND: Acetazolamide has been used for diuretic-induced metabolic alkalosis, but the preferred dose, route, and frequency of administration remain unknown. OBJECTIVE: The purpose of this study was to characterize dosing strategies and determine the effectiveness of intravenous (IV) and oral (PO) acetazolamide for patients with heart failure (HF) with diuretic-induced metabolic alkalosis. METHODS: This was a multicenter, retrospective cohort study comparing the use of IV versus PO acetazolamide in patients with HF receiving at least 120 mg of furosemide for the treatment of metabolic alkalosis (serum bicarbonate CO2 ≥32). The primary outcome was the change in CO2 on the first basic metabolic panel (BMP) within 24 hours of the first dose of acetazolamide. Secondary outcomes included laboratory outcomes, such as change in bicarbonate, chloride, and incidence of hyponatremia and hypokalemia. This study was approved by the local institutional review board. RESULTS: IV acetazolamide was given in 35 patients and PO acetazolamide was given in 35 patients. Patients in both groups were given a median of 500 mg of acetazolamide in the first 24 hours. For the primary outcome, there was a significant decrease in CO2 on the first BMP within 24 hours after patients received the IV acetazolamide (-2 [interquartile range, IQR: -2, 0] vs 0 [IQR: -3, 1], P = 0.047). There were no differences in secondary outcomes. CONCLUSION AND RELEVANCE: IV acetazolamide resulted in significantly decreased bicarbonate within 24 hours of administration. IV acetazolamide may be preferred to treat diuretic-induced metabolic alkalosis in patients with HF.

A Comparison of Midazolam and Propofol for Deep Sedation in Patients with Acute Respiratory Distress Syndrome Requiring Neuromuscular Blocking Agents.

Purpose: The optimal agent for deep sedation in patients undergoing continuous infusion (CI) neuromuscular blocking agent (NMBA) use for acute respiratory distress syndrome (ARDS) is unknown. The purpose of this study is to compare the efficacy and safety of propofol and midazolam in ARDS patients requiring CI NMBA. Methods: A multi-center, retrospective study was performed in mechanically ventilated (MV) adult patients requiring CI NMBA for management of ARDS. The primary outcome was to compare the time to liberation from MV in patients sedated with propofol vs midazolam. Results: In the 109 patients included, there was no difference in time to MV liberation with propofol as compared to midazolam (121 hr [Interquartile range (IQR) 67 195] vs 98 hr [IQR 48, 292], P = .72). Median time to sedation emergence after NMBA discontinuation was shorter in patients receiving propofol (12.9 hr [IQR 19.8, 72.5] vs 31.5 hr [IQR 6.4, 34.6], P < .01). There were no significant differences in time to therapeutic sedation, ICU stay, mortality, and adverse events. Conclusion: Propofol may be an effective and safe alternative to midazolam for patients undergoing CI NMBA for ARDS. Additionally, patients receiving propofol may have a quicker return to light sedation after NMBA discontinuation.

Portability and Structure of the Four-Helix Bundle Docking Domains of trans-Acyltransferase Modular Polyketide Synthases.

The polypeptides of multimodular polyketide synthases self-assemble into biosynthetic factories. While the docking domains that mediate the assembly of cis-acyltransferase polyketide synthase polypeptides are well-studied, those of the more recently discovered trans-acyltransferase polyketide synthases have just started to be described. Located at the C- and N-termini of many polypeptides, these 25-residue, two-helix, pseudosymmetric motifs noncovalently connect domains both between and within modules. Domains expressed with their natural, cognate docking motifs formed complexes stable to size-exclusion chromatography with 1-10 µM dissociation constants as measured by isothermal titration calorimetry. Deletion and swapping experiments demonstrate portability of the docking motifs. A 1.72 Å-resolution structure of the N-terminal portion of the macrolactin synthase polypeptide MlnE shows an uncomplexed N-terminal docking motif to be preorganized in the conformation it assumes within the docking domain complex.