Abstract The development and use of concentrated insulins have increased in recent years. This can pose unique challenges when transitioning to a non‐concentrated insulin during an inpatient admission. There is no clear consensus on the recommended interchange of the various concentrated insulins in the inpatient setting, with suggestions ranging from implementing a 1:1 unit dose conversion, a minimum 20% dose reduction or selecting an approach based on the total daily dose of the concentrated insulin. In a retrospective cohort analysis at a single health system, a greater number of hypoglycemic events occurred when implementing a 1:1 unit conversion of insulin glargine 300 units/mL (iGlar300) to insulin detemir 100 units/mL (iDet100) compared to the same conversion from insulin glargine 100 units/mL (iGlar100) to iDet100. This prompted identification of a standardized approach that would improve patient safety while also being operationally feasible at a multi‐hospital network. The solution of implementing a minimum 20% dose reduction successfully improved hypoglycemia rates upon transitioning from iGlar300 to iDet100, though many logistical challenges were faced. Although iDet100 is being phased off the market, adhering to this minimum 20% dose reduction is the recommended approach when transitioning from iGlar300 to iGlar100, and this challenge persists as a relevant issue. Ensuring health systems are equipped to implement dose reductions when transitioning from concentrated basal insulins to non‐concentrated basal insulin counterparts is paramount for maintaining patient safety. This paper will discuss the limited evidence available supporting optimal dosing when transitioning iGlar300 and insulin degludec 200 units/mL (iDeg200) to non‐concentrated basal insulins and serve as a “how to” implementation guide for other health systems, based on one health system's approach in navigating this emerging patient safety issue.
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.
Insulin remains a mainstay of treating hyperglycemia in an acute setting. Insulin glargine 300 units/mL (Toujeo, iGlar300) has a different pharmacokinetic profile than 100 units/mL basal insulins, such as insulin detemir (iDet100) and iGlar100. While conversion from iGlar300 to iGlar100 requires a 20% dose decrease, there is currently no recommended interchange from iGlar300 to iDet100.Compare the incidence of hypoglycemia in patients who received a 1:1 unit interchange from home iGlar300 or iGlar100 to iDet100 while admitted.A retrospective study was conducted to evaluate adults within a multi-site network admitted between May and December 2019. Patients were included if they received at least one dose of iDet100 following interchange from home iGlar300 or iGlar100. The primary endpoint was the incidence of hypoglycemic events following a 1:1 interchange of iGlar300 vs. iGlar100 to inpatient iDet100. Secondary outcomes include overall hypoglycemic events, time to hypoglycemia, and doses given before hypoglycemia.Of 615 patients, 394 received a 1:1 unit interchange to iDet100 (52 from iGlar300 and 342 from iGlar100). Incidence of hypoglycemic events was significantly higher in those with a 1:1 interchange from iGlar300 versus iGlar100 (36.5% vs. 18.7%, p = 0.007). Significant differences were observed in overall hypoglycemic events, time to hypoglycemia, and number of doses given before hypoglycemic event.A 1:1 unit interchange from iGlar300 to iDet100 led to a higher incidence of hypoglycemic events compared to those interchanged from iGlar100. Dose reduction should be considered when transitioning from home iGlar300 to iDet100 in the inpatient setting.
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 CO 2 ≥32). The primary outcome was the change in CO 2 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 CO 2 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.
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.
Abstract Purpose A previous study at Ascension Seton Hospital Network (ASHN) found a 1:1 dose conversion to insulin detemir 100 units/mL (iDet100) from insulin glargine 300 units/mL (iGlar300) increased the incidence of hypoglycemia as compared to a 1:1 conversion from insulin glargine 100 units/mL. No studies have evaluated an automatic 20% dose reduction for this specific therapeutic interchange. The purpose of this study was to compare hypoglycemia rates following implementation of a protocol specifying a minimum 20% dose reduction when converting from iGlar300 to inpatient iDet100. Methods This multicenter, retrospective chart review–based study was a before/after study evaluating the impact of an ASHN protocol implemented in April 2021 requiring a minimum 20% reduction when converting from home iGlar300 to inpatient iDet100. Previously, a 1:1 interchange was standard. Patients admitted between May 2019 and December 2022 were included if at least 1 dose of iDet100 was received following interchange from iGlar300. The primary endpoint was hypoglycemia incidence before and after protocol implementation. Secondary endpoints included time to first hypoglycemia and number of doses given before hypoglycemia. Logistic regression was performed to analyze the relationship between percent interchange from home dose and hypoglycemia rate. Results A total of 284 patients were included: 128 in the preprotocol arm and 156 in the postprotocol arm. The incidence of hypoglycemia was significantly lower in the postprotocol arm than in the preprotocol arm (11.9% vs 24.7%; P = 0.018). The median time to first hypoglycemia was longer in the postprotocol versus the preprotocol arm, though the difference was not statistically significant (13 vs 18.5 hours, P = 0.082). For each percent reduction from iGlar300 to iDet100, the likelihood of hypoglycemia was reduced by 5.3%. Conclusion A protocol requiring a minimum 20% dose reduction from iGlar300 to inpatient iDet100 reduced the incidence of hypoglycemia. Health systems should consider adopting a similar approach to reduce the occurrence of hypoglycemia upon interchange.
