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

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.

An analysis of lactate/albumin, procalcitonin/albumin, and blood urea nitrogen/albumin ratios as a predictor of mortality in uroseptic patients.

OBJECTIVE: The aim of this study was to investigate the ratios of lactate/albumin, procalcitonin/albumin, and blood urea nitrogen/albumin to predict 14- and 28-day mortality in uroseptic patients. Urosepsis is a disease with high mortality, and early diagnosis and treatment are important. METHODS: Patients with urosepsis who were admitted to the intensive care unit between January 2021 and September 2022, had a follow-up of at least 28 days, and met the inclusion criteria were evaluated retrospectively. RESULTS: The mean age was 70.23 (15.66) years and 84 (53.85%) were males. The number of non-survivors were 75 (48%) in the 14-day mortality group and 97 (62.1%) in the 28-day mortality group. Based on the 14-day mortality data, the blood urea nitrogen/albumin ratio was higher in non-survivors vs. survivors (median, 15.88 vs. 9.62), and the lactate/albumin ratio was higher (median, 0.96 vs. 0.52, p<0.01, all). Based on the 28-day mortality data, the blood urea nitrogen/albumin ratio was higher in non-survivors vs. survivors (median, 14.78 vs. 8.46), and the lactate/albumin ratio was higher (median, 0.90 vs. 0.50, p<0.01, all). CONCLUSION: It is very difficult to determine the prognosis of patients admitted to the emergency department with the diagnosis of urosepsis. The lactate/albumin ratio and the blood urea nitrogen/albumin ratio can be used as early prognostic markers for both 14-day and 28-day mortality until more reliable markers are identified.

Compliance With the Surviving Sepsis Campaign Bundle: A Multicenter Study From Turkey.

Objectives Sepsis bundle compliance is not clear. We evaluated rates of compliance with sepsis bundle protocols among health care providers in Turkey. Methods Our study was carried out retrospectively. Forty-five intensive care units (ICU) participated in this study between March 2, 2018 and October 1, 2018. Results One hundred thirty-eight ICUs were contacted and 45 ICUs agreed to participate. The time taken for the diagnosis of sepsis was less than six hours in 384 (59.8%) patients, while it was more than six hours in 258 (40.2%) patients. The median [interquartile range (IQR)] times for initial antibiotic administration, culturing, vasopressor initiation, and second lactate measurement were 120.0 (60-300) minutes, 24 (12-240) minutes, 40 (20-60) minutes, and 24 (18-24) hours, respectively. The rate of compliance with tissue and organ perfusion follow-up in the first six hours was 0%. The rates of three- and six-hour sepsis bundle protocol compliance were both 0%. The ICU mortality rates for sepsis and septic shock were 22% and 78%, respectively. The ICU mortality rates for sepsis and septic shock were 22% and 78%, respectively. Conclusions The rate of compliance with sepsis bundle protocols was evaluated in Turkey for the first time and determined to be 0%.

The effects of a small-dose ketamine-propofol combination on tourniquet-induced ischemia-reperfusion injury during arthroscopic knee surgery.

STUDY OBJECTIVE: To determine the effects of a small-dose ketamine-propofol combination used for sedation during spinal anesthesia on tourniquet-induced ischemia-reperfusion injury. STUDY DESIGN: Prospective randomized study. SETTING: Training and research hospital. PATIENTS: 60 adult, ASA physical status 1 and 2 patients, ages 20-60 years, scheduled for elective arthroscopic knee surgery for meniscal and chondral lesions. INTERVENTIONS: The initial hemodynamic parameters were recorded and blood samples were collected at baseline (T1); then spinal anesthesia was performed. In Group I (n=30), a combination of 0.5 mg/kg/hr of ketamine and 2 mg/kg/hr of propofol was administered; Group II (n=30) received an equivalent volume of saline as an infusion. A pneumatic tourniquet was applied. MEASUREMENTS: Malondialdehyde (MDA), superoxide dismutase (SOD), and catalase levels were measured one minute before tournique deflation in the ischemic period (T2), then 5 (T3) and 30 (T4) minutes following tourniquet deflation in the reperfusion period. MAIN RESULTS: No differences were noted between groups in hemodynamic data (P > 0.05) or SOD levels (P > 0.05). In Group I, MDA levels at T2 were lower than in Group II (P < 0.05). In Group I, catalase levels were lower at T2 and T4 than they were in Group II (P < 0.05). CONCLUSION: Small-dose ketamine-propofol combination may be useful in reducing tourniquet-induced ischemia-reperfusion injury in arthroscopic knee surgery.