Pharmacokinetics and pharmacodynamics studies of a loading dose of cisatracurium in critically ill patients with respiratory failure.

BACKGROUND: Previous studies reported a slow neuromuscular response with the currently recommended dose of cisatracurium in critically ill patients. Pharmacokinetic and pharmacodynamic studies of cisatracurium in critically ill patients are still limited. To our knowledge, this is the first study performed to better understand the pharmacokinetics (PKs) and pharmacodynamics (PDs) of a loading dose of cisatracurium and to identify factors that affect PK and PD changes in critically ill patients. METHODS: A prospective PKs and PDs study was designed. Arterial blood samples of 10 critically ill patients with respiratory failure were collected after administering a loading dose of 0.2 mg/kg of cisatracurium. Plasma cisatracurium and laudanosine concentrations were determined using liquid chromatography-tandem mass spectrometry. The achievement of the desired pharmacodynamic response was evaluated by both 1) clinical assessment and 2) train-of-four monitoring. The PK/PD indices were analyzed for their correlation with patient'characteristics and other factors. RESULTS: The one-compartment model best described the plasma pharmacokinetic parameters of cisatracurium. The volume of distribution at steady state and total clearance were 0.11 ± 0.04 L/kg and 2.74 ± 0.87 ml/minute/kg, respectively. The mean time to train-of-four 0/4 was 6 ± 3.86 minutes. A time to the desired pharmacodynamic response of less than 5 minutes was found in 10% of the patients. A positive correlation was found between cisatracurium concentration and albumin levels and between pharmacokinetics data and patient factors [partial pressure of carbon dioxide and respiratory alkalosis]. CONCLUSION: The currently recommended loading dose of cisatracurium might not lead to the desired pharmacodynamic response in critically ill patients with respiratory failure. TRIAL REGISTRATION: ClinicalTrials.gov , NCT03337373. Registered on 9 November 2017.

A case report of intravenous posaconazole in hepatic and renal impairment patient with invasive Aspergillus terreus infection: safety and role of therapeutic drug monitoring.

BACKGROUND: Invasive aspergillosis (IA) is a fatal infectious complication among immunocompromised patients. Aspergillus terreus, the fourth common species can be difficult to treat due to a unique resistance pattern. To date, there has been no report on safety and dose adjustment when intravenous posaconazole is selected in hepatic and renal impairment patient. We present a rare case of intravenous posaconazole use in a hepatic and renal impairment patient with invasive A. terreus pulmonary infection. To our knowledge, this is the first report of intravenous posaconazole use in IA due to A. terreus with hepatic and renal impairment focusing on drug safety and role of therapeutic drug monitoring (TDM). CASE PRESENTATION: A 37-year-old previously healthy man with diagnosis of dengue hemorrhagic fever and shock complicated with hepatic and renal impairment proposed to have proven invasive A. terreus pulmonary infection is described. Due to lack of good clinical response and concern of potential adverse effects whilst on intravenous voriconazole, intravenous posaconazole 300 mg every 48 h was chosen with confirmed therapeutic plasma concentrations. Despite the death of the patient and IA deemed uncontrollable, there were no significant side effects attributable to intravenous posaconazole use demonstrated over a period of 34 days. CONCLUSIONS: Intravenous posaconazole use with TDM implementation maybe a safe alternative option to standard therapy. Therapeutic plasma posaconazole level may be reached at lower dosing regimen in renal and hepatic impairment patient. However, explanations of clinical failure on this patient with immunodeficiency state were multifactorial.