Time in Therapeutic Range of Unfractionated Heparin-Based Therapy in Critically Ill Patients with COVID-19 Pneumonia.

Purpose: Anticoagulation therapy aims to improve the outcome of critically ill patients with severe COVID-19-associated pneumonia. Activated partial thromboplastin time (aPTT) is commonly used to maintain the target therapeutic range of continuous infusion of unfractionated heparin (UFH). The UFH infusion efficacy can be evaluated by determining the time in therapeutic range (TTR) using a modified Rosendaal method. The present study's primary aim was to evaluate TTR based on the aPTT in critically ill patients with severe forms of COVID-19 pneumonia and its influence on survival. The secondary aim was to evaluate the time spent above (TATR) and below the therapeutic range (TBTR). Patients and Methods: We performed a retrospective analysis of critically ill patients with COVID-19-associated pneumonia. All patients received a continuous infusion of UFH from the 2nd to 8th day since admission to the ICU. TTR, TATR, and TBTR were calculated using the modified Rosendaal method, and survival days were analyzed by regression (censored after 60 days). Results: Of 103 patients, the median TTR was 49% (IQR 38-63%), TATR 11% (IQR 5-20%), and TBTR 33% (IQR 22-51%). The regression analysis indicated a positive impact of higher TTR and TATR on the number of survival days [ß=0.598 (p=0.0367) and ß=1.032 (p=0.0208), respectively] and a negative impact of higher TBTR [ß=-0.681 (p=0.0033)] on the number of survival days. Conclusion: Higher TTR and TATR were associated with better survival of critically ill patients with a severe course of COVID-19-associated pneumonia. Higher TBTR was associated with worse survival in these patients.

Role of Alveolar-Arterial Difference in Estimation of Extravascular Lung Water in COVID-19-Related ARDS.

BACKGROUND: The dominant feature of COVID-19-associated ARDS is gas exchange impairment. Extravascular lung water index is a surrogate for lung edema and reflects the level of alveolocapillary disruption. The primary aim was the prediction of extravascular lung water index by the alveolar-arterial oxygen difference. The secondary aims were in determining the relationship between the extravascular lung water index and other oxygenation parameters, the FIO2 , end-tidal oxygen concentration, pulmonary oxygen gradient (FIO2 minus end-tidal oxygen concentration), and PaO2 . METHODS: This observational prospective single-center study was performed at the Department of Anaesthesiology and Intensive Care, The University Hospital in Ostrava, The Czech Republic, during the COVID-19 pandemic, from March 20, 2020, until May 24, 2021. RESULTS: The relationship between the extravascular lung water index and alveolar-arterial oxygen difference showed only a mild-to-moderate correlation (r = 0.33, P < .001). Other extravascular lung water index correlations were as follows: FIO2 (r = 0.33, P < .001), end-tidal oxygen concentration (r = 0.26, P = .0032), FIO2 minus end-tidal oxygen concentration (r = 0.15, P = .0624), and PaO2 (r = -0.15, P = .01). CONCLUSIONS: The alveolar-arterial oxygen difference does not reliably correlate with the extravascular lung water index and the degree of lung edema in COVID-19-associated ARDS.

Therapeutic monitoring of serum concentrations of acyclovir and its metabolite 9-(carboxymethoxymethyl) guanine in routine clinical practice.

OBJECTIVE: To obtain information on the serum concentrations of acyclovir and its metabolite in routine health care with respect to the renal function. METHODS: This prospective study analyzed data from 27 patients receiving acyclovir intravenously between June 2019 and October 2021. Patients were divided into two subgroups according to the estimated glomerular filtration rate. Serum concentrations of acyclovir and its metabolite 9-(carboxymethoxymethyl) guanine were mainly analyzed on day 5 after the initiation of treatment before the morning dose (trough concentration) and 30 min after the end of the infusion (peak concentration). RESULTS: Trough acyclovir concentrations ranged from 0.8 to 7.6 mg/L and peak concentrations from 6.3 to 25.7 mg/L, and trough metabolite concentrations ranged from 0.12 to 2.30 mg/L and peak concentrations from 0.47 to 2.70 mg/L, respectively. The ratio of trough metabolite and acyclovir concentrations ranged from 0.07 to 0.63 and the ratio of peak concentrations from 0.03 to 0.24. Patients in the subgroup with reduced renal function were significantly older, smaller, and of lower body weight and received significantly lower doses of acyclovir. CONCLUSIONS: A 10-fold difference in the weight-adjusted apparent clearance of acyclovir was observed between patients. This wide interindividual variability in acyclovir pharmacokinetics can lead not only to toxicity but also to suboptimal acyclovir concentrations in severe infections. Therefore, therapeutic monitoring of serum concentrations of acyclovir and its metabolite may be important for optimizing pharmacotherapy, especially in patients with severe clinical conditions.

[Neuroleptic malignant syndrome - unexpected complication in a COVID-19 patient].

Neuroleptic malignant syndrome is a life-threatening condition that can be fatal if unrecognized and inadequately treated. This disease is rarely seen in infectious diseases wards. As infectiologists, however, we are confronted with an increasingly broader spectrum of diagnoses and this disease should therefore be considered in any patient taking psychiatric medication who develops the typical symptoms of hyperthermia, rigidity and muscle tremors, autonomic lability and impaired consciousness. A case report is presented of a young man with schizophrenia admitted to the intensive care unit with COVID-19, who was treated with antipsychotics (formerly known as neuroleptics) for restlessness and who developed neuroleptic malignant syndrome. In cooperation with psychiatrists, a targeted therapy was initiated, after which the symptoms subsided and the patient's clinical condition resolved.

Determination of acyclovir and its metabolite 9-carboxymethoxymethylguanide in human serum by ultra-high-performance liquid chromatography-tandem mass spectrometry.

A simple and rapid ultra-high-performance liquid chromatography coupled with mass spectrometry method was developed for acyclovir and its metabolite 9-carboxymethoxymethylguanine in human serum. After precipitation of serum samples with 0.1% formic acid in acetonitrile/methanol (40:60, v/v), components were separated on a Luna Omega C18 column (1.6 µm; 2.1 × 150 mm) at 40°C. Mobile phase A (2 mmol/L ammonium acetate, 0.1% formic acid in 5% acetonitrile, v/v/v) and mobile phase B (2 mmol/L ammonium acetate, 0.1% formic acid in 95% acetonitrile, v/v/v) were used for gradient elution. A linear calibration curve was obtained over the range of 0.05-50 mg/L, and the correlation coefficients were better than 0.999. The limit of quantitation was 0.05 mg/L for both analytes. The intra- and interday accuracy and precision at three concentration levels ranged between 1.6 and 13.3%, and recoveries were achieved with a range between 92.2 and 114.2%. This method was developed and validated for the therapeutic monitoring of acyclovir in patients.

[Drug repositioning - antibiotics as cytostatics].

Antibiotics are considered to be one of the most important discoveries of medicine, which has significantly affected the mortality due to infectious diseases. Given their increasing use, certain problems arise over time, resulting from non-indicated and inadequate - administration of antibiotics. This results in increasing antibiotic resistance as well as a higher risk of side/adverse effects. Recently, these side effects of drugs have been used for indications other than those originally intended and approved. Such a process is called drug repositioning. Due to the recent increase in the cost of developing novel drugs and the high risk of failure in clinical trials, the pharmaceutical industry is trying to find new indications for existing drugs.

[Severe course of influenza B complicated by rhabdomyolysis and acute respiratory failure resulting in death].

Influenza is an acute viral disease that causes influenza A, B, C. Clinically, flu is typically characterized by fever and respiratory symptoms, sometimes with the need for mechanical ventilation, less frequently by gastrointestinal symptoms and muscle problems; severe are cases with central nervous system involvement. The most common complication of influenza is secondary bacterial infection, typically pneumonia, which is most frequently caused by pneumococci and staphylococci. Every year, thousands of patients die of influenza or its complications. In the Czech Republic, namely the Moravian-Silesian Region, influenza B virus dominated the 2017/2018 flu season. Presented is a case of a 51-year-old male with influenza B as an etiologic agent of rapidly progressing muscle weakness and laboratory tests showing rhabdomyolysis and significantly elevated muscle enzyme and aminotransferase, resulting in acute respiratory failure and death.