Favipiravir pharmacokinetics in COVID-19 patients with moderate to severe kidney dysfunction: Lessons learned.

OBJECTIVE: There is limited information on favipiravir pharmacokinetics in critically ill patients and no studies on pharmacokinetics in patients with moderate and severe kidney dysfunction. The aim was to determine favipiravir pharmacokinetics (oral, 1,600 mg, q12h on day 1, then 600 mg, q12h for 4 days) in critically ill COVID-19 patients with kidney dysfunction and to compare those with observations reported in healthy adults. MATERIALS AND METHODS: In a descriptive study, blood samples taken from patients meeting the relevant criteria (estimated glomerular filtration rate < 60 mL/min) were collected and analyzed. Analysis of blood samples was done by high performance liquid chromatography (HPLC), and the maximal concentration (Cmax), the time of maximal concentration (tmax), half-life (T1/2) and area under the curve (AUC0-12h) of favipiravir were calculated (WinNonlin) and compared to reported data in healthy subjects after first administration. RESULTS: Based on analysis of samples collected in 7 patients, the Cmax (29.99 vs. 64.5 µg/mL) of favipiravir was decreased, T1/2 (5.8 vs. 4.8 hours) longer, tmax delayed, while total exposure was lower (AUC0-12: 192.53 vs. 446.09 µg/mL) compared to reported data in healthy subjects after first administration. Exposure remained lower up to day 5. CONCLUSION: In patients with kidney dysfunction related to COVID-19, favipiravir did not reach the expected exposure. This may be due to poorer and delayed absorption, and subsequent altered disposition. Population pharmacokinetic and mechanistic studies are needed to better explore the relevant covariates and to determine the optimal dose in these patients, as this drug is likely of relevance for other indications.

Earthquake victims in focus: a cross-sectional examination of trauma and management in intensive care unit.

BACKGROUND: After the Kahramanmaras earthquake of February 6, 2023, the disaster of the century, a significant number of victims were admitted to intensive care units (ICUs). In this study, we aimed to share the characteristics and management of critical earthquake victims and shed light on our experiences as intensivists in future earthquakes. METHODS: The study included 62 earthquake victims in two tertiary ICUs. Demographic characteristics, laboratory findings, clinical characteristics, trauma and disease severity scores, treatments administered to patients, and the clinical course of the patients were recorded retrospectively. The patients were divided into two groups, survivors and nonsurvivors, according to 7-day mortality and into two groups according to the duration of their stay under the rubble: those who remained under the rubble for 72 hours or less and those who remained under the rubble for more than 72 hours. A receiver operating characteristic (ROC) curve analysis was used to determine the best cutoff value for the 'Circulation, Respiration, Abdomen, Motor, and Speech' (CRAMS) score. RESULTS: The median age of the 62 patients included in the study was 35.5 (23-53) years. The median length of stay under the rubble for the patients was 30.5 (12-64.5) hours. The patient was transferred to the ward with a maximum duration of 222 hours under the rubble. The limb (75.8%) was the most common location of trauma in patients admitted to the ICU. Crush syndrome developed in 96.8% of the patients. There was a positive correlation between the development of acute kidney injury (AKI) and myoglobin, serum lactate, and uric acid levels (r = 0.372, p = 0.003; r = 0.307, p = 0.016; r = 0.428, p = 0.001, respectively). The best cutoff of the CRAMS score to predict in-7-day mortality was < 4.5 with 0.94 area under the curve (AUC); application of this threshold resulted in 75% sensitivity and 96.3% specificity. CONCLUSION: Search and rescue operations should continue for at least ten days after an earthquake. The CRAMS score can be used to assess trauma severity and predict mortality in critically ill earthquake victims.

Vaccination status of COVID-19 patients followed up in the ICU in a country with heterologous vaccination policy: A multicenter national study in Turkey.

OBJECTIVE: Vaccination against severe acute respiratory syndrome coronavirus-2 (SARS-2) prevents the development of serious diseases has been shown in many studies. However, the effect of vaccination on outcomes in COVID-19 patients requiring intensive care is not clear. METHODS: This is a retrospective multicenter study conducted in 17 intensive care unit (ICU) in Turkey between January 1, 2021, and December 31, 2021. Patients aged 18 years and older who were diagnosed with COVID-19 and followed in ICU were included in the study. Patients who have never been vaccinated and patients who have been vaccinated with a single dose were considered unvaccinated. Logistic regression models were fit for the two outcomes (28-day mortality and in-hospital mortality). RESULTS: A total of 2968 patients were included final analysis. The most of patients followed in the ICU during the study period were unvaccinated (58.5%). Vaccinated patients were older, had higher Charlson comorbidity index (CCI), and had higher APACHE-2 scores than unvaccinated patients. Risk for 28-day mortality and in-hospital mortality was similar in across the year both vaccinated and unvaccinated patients. However, risk for in-hospital mortality and 28-day mortality was higher in the unvaccinated patients in quarter 4 adjusted for gender and CCI (OR: 1.45, 95% CI: 1.06-1.99 and OR: 1.42, 95% CI: 1.03-1.96, respectively) compared to the vaccinated group. CONCLUSION: Despite effective vaccination, fully vaccinated patients may be admitted to ICU because of disease severity. Unvaccinated patients were younger and had fewer comorbid conditions. Unvaccinated patients have an increased risk of 28-day mortality when adjusted for gender and CCI.