ABSTRACT
Background: Glycine is an endogenous, non-essential, simple amino acid produced in the human body. A 1.5% solution is commonly used for irrigation in gynecologic and urologic procedures as it is a sterile, clear, non-irritating liquid. It is neutral, mildly acidic and nonpyrogenic, and as it is produced by the human body it does not cause allergic reactions. If an excessive amount is absorbed during a procedure it can result in electrolyte abnormalities, such as hyponatremia or hypocalcemia. It can also result in transient vision disturbances, changes in heart rate, hypotension, hyperammonemia, or encephalopathy. Glycine has been used as a diluent in certain inhaled therapies for COVID-19 infections, such as epoprostenol. We describe a case where a 1.5% glycine solution was inadvertently used for humidified oxygen via high flow nasal cannula as opposed to distilled water. Case report: The patient was a 70-year-old male who was admitted to the hospital for hypoxia related to a COVID-19 infection with O2 saturations in the 70-80% range. He was placed on high flow nasal cannula to improve his oxygen levels. During his inpatient stay it was discovered that a 3-L bag of 1.5% glycine solution had been connected to the high flow nasal cannula instead of distilled water. This ran from Friday evening to the following Monday morning before the error was discovered. There was only 100mL of the glycine solution remaining in the bag when it was found. The patient continued to do well and had no new complaints during his stay. The case was called to the regional poison center which recommended monitoring electrolytes, watching for any possible respiratory symptoms and continuing supportive care. Initial lab work on admission showed a chemistry panel of Na 146, K 3.6, Cl 102, CO2 25.3, BUN 9, Cr 0.70, Glucose 106, Ca 9.3. Repeat lab work immediately after the mistake was found showed: Na 137, K 4.8 Cl 100, CO2 28, BUN 15, Cr 0.70, Glucose 129, Ca 9.0. On recommendations from poison control, electrolytes were monitored with repeat lab work 10 h after discontinuation of the glycine solution, showing: Na 135, K 4.3, Cl 97, CO2 26.8, Glucose 175, Ca 9.2. The patient did not develop any new complaints, had no reported altered mental status, epistaxis, nasal irritation or other symptoms related to the inhalation. He was eventually discharged home on oxygen for his persistent hypoxia related to his COVID-19 lung infection. Discussion(s): This case demonstrates that prolonged continuous inhalational exposure to a 1.5% glycine irrigation solution does not result in any mucosal irritation, metabolic or systemic toxic reactions, even though its pH is reportedly between 4.5 and 6.5. Thus, glycine solutions up to this concentration appear to be safely tolerated for its increasing use as an excipient for aerosolized medications. Conclusion(s): We describe a case where 1.5% glycine solution was inadvertently used in place of distilled water for humidified oxygen via high flow nasal cannula for approximately 3 days in a patient being treated for COVID-19 related pneumonia with no notable adverse effects.
ABSTRACT
Oseltamivir phosphate (OP) is an antiviral drug available only as oral therapy for the treatment of influenza and as a potential treatment option when in combination with other medication in the fight against the corona virus disease (COVID-19) pneumonia. In this study, OP was formulated as a dry powder for inhalation, which allows drug targeting to the site of action and potentially reduces the dose, aiming a more efficient therapy. Binary formulations were based on micronized excipient particles acting like diluents, which were blended with the drug OP. Different excipient types, excipient ratios, and excipient size distributions were prepared and examined. To investigate the feasibility of delivering high doses of OP in a single dose, 1:1, 1:3, and 3:1 drug/diluent blending ratios have been prepared. Subsequently, the aerosolization performance was evaluated for all prepared formulations by cascade impaction using a novel medium-resistance capsule-based inhaler (UNI-Haler). Formulations with micronized trehalose showed relatively excellent aerosolization performance with highest fine-particle doses in comparison to examined lactose, mannitol, and glucose under similar conditions. Focusing on the trehalose-based dry-powder inhalers' (DPIs) formulations, a physicochemical characterization of extra micronized grade trehalose in relation to the achieved performance in dispersing OP was performed. Additionally, an early indication of inhaled OP safety on lung cells was noted by the viability MTT assay utilizing Calu-3 cells.