scholarly journals Voriconazole Pharmacokinetics Are Not Altered in Critically Ill Patients with Acute-on-Chronic Liver Failure and Continuous Renal Replacement Therapy: An Observational Study

2021 ◽  
Vol 9 (10) ◽  
pp. 2087
Author(s):  
Jörn Grensemann ◽  
Christoph Pfaffendorf ◽  
Sebastian G. Wicha ◽  
Christina König ◽  
Kevin Roedl ◽  
...  
Keyword(s):  
Steady State ◽  
Renal Replacement Therapy ◽  
Liver Failure ◽  
Continuous Renal Replacement Therapy ◽  
Replacement Therapy ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Chronic Liver ◽  
Therapeutic Drug ◽  
Chronic Liver Failure

Infection and sepsis are a main cause of acute-on-chronic liver failure (ACLF). Besides bacteria, molds play a role. Voriconazole (VRC) is recommended but its pharmacokinetics (PK) may be altered by ACLF. Because ACLF patients often suffer from concomitant acute renal failure, we studied the PK of VRC in patients receiving continuous renal replacement therapy (RRT) with ACLF and compared it to PK of VRC in critically ill patients with RRT without concomitant liver failure (NLF). In this prospective cohort study, patients received weight-based VRC. Pre- and post-dialysis membrane, and dialysate samples obtained at different time points were analyzed by high-performance liquid chromatography. An integrated dialysis pharmacometric model was used to model the available PK data. The recommended, 50% lower, and 50% higher doses were analyzed by Monte-Carlo simulation (MCS) for day 1 and at steady-state with a target trough concentration (TC) of 0.5–3mg/L. Fifteen patients were included in this study. Of these, 6 patients suffered from ACLF. A two-compartment model with linear clearance described VRC PK. No difference for central (V1) or peripheral (V2) volumes of distribution or clearance could be demonstrated between the groups. V1 was 80.6L (95% confidence interval: 62.6–104) and V2 106L (65–166) with a body clearance of 4.7L/h (2.87–7.81) and RRT clearance of 1.46L/h (1.29–1.64). MCS showed TC below/within/above target of 10/74/16% on day 1 and 9/39/52% at steady-state for the recommended dose. A 50% lower dose resulted in 26/72/1% (day 1) and 17/64/19% at steady-state and 7/57/37% and 7/27/67% for a 50% higher dose. VRC pharmacokinetics are not significantly influenced by ACLF in critically ill patients who receive RRT. Maintenance dose should be adjusted in both groups. Due to the high interindividual variability, therapeutic drug monitoring seems inevitable.

scholarly journals Septic shock after liver transplantation successfully treated with endotoxin and cytokine adsorption continuous renal replacement therapy: a case report and literature review

2020 ◽  
Vol 48 (7) ◽  
pp. 030006052094043
Author(s):  
Yining Li ◽  
Linshan Zhou ◽  
Lingzhi Yang ◽  
Fang Yuan
Keyword(s):  
Septic Shock ◽  
Liver Transplantation ◽  
Renal Replacement Therapy ◽  
Liver Failure ◽  
Continuous Renal Replacement Therapy ◽  
Replacement Therapy ◽  
Chronic Liver ◽  
Inflammatory Factors ◽  
Decompensated Cirrhosis ◽  
Chronic Liver Failure

Endotoxins and cytokines play an important role in multiple organ failure pathogenesis in patients with severe Gram-negative bacterial infection. We present a clinical case where an oXiris hemofilter was used for continuous renal replacement therapy (CRRT) treatment in a patient with septic shock after liver transplantation. A 35-year-old man with a 20-year history of hepatitis B presented with jaundice, loss of appetite, and decreased urine output. He was diagnosed with decompensated cirrhosis with acute-on-chronic liver failure, and liver transplantation was indicated. The day after surgery, he developed hyperthermia, hypotension, anuria, and a progressive increase in blood inflammatory markers and creatinine. Combined with the donor source and blood culture results, septic shock after transplantation was considered. The patient was immediately treated with endotoxin and cytokine adsorption CRRT (oXiris hemofilter) with tigecycline, caspofungin, and ganciclovir as anti-infectives. After 48 hours on CRRT, his blood pressure gradually stabilized, the CLIF Consortium Acute-on-Chronic Liver Failure score decreased from 63 to 43. Procalcitonin, endotoxin, and the inflammatory factors interleukin (IL)-6 and IL-10 also decreased gradually. The patient’s liver and kidney functions were completely restored. Our experience suggests that oXiris CRRT combined with antibacterial therapy is an effective treatment for septic shock after liver transplantation.

scholarly journals Drug Dosing Considerations in Critically Ill Patients Receiving Continuous Renal Replacement Therapy

Pharmacy ◽  
2020 ◽  
Vol 8 (1) ◽  
pp. 18 ◽  
Author(s):  
Soo Min Jang ◽  
Sergio Infante ◽  
Amir Abdi Pour
Keyword(s):  
Renal Replacement Therapy ◽  
Continuous Renal Replacement Therapy ◽  
Replacement Therapy ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Patient Specific ◽  
Therapeutic Drug ◽  
Intermittent Hemodialysis ◽  
Drug Dosing ◽  
Low Efficiency

Acute kidney injury is very common in critically ill patients requiring renal replacement therapy. Despite the advancement in medicine, the mortality rate from septic shock can be as high as 60%. This manuscript describes drug-dosing considerations and challenges for clinicians. For instance, drugs’ pharmacokinetic changes (e.g., decreased protein binding and increased volume of distribution) and drug property changes in critical illness affecting solute or drug clearance during renal replacement therapy. Moreover, different types of renal replacement therapy (intermittent hemodialysis, prolonged intermittent renal replacement therapy or sustained low-efficiency dialysis, and continuous renal replacement therapy) are discussed to describe how to optimize the drug administration strategies. With updated literature, pharmacodynamic targets and empirical dosing recommendations for commonly used antibiotics in critically ill patients receiving continuous renal replacement therapy are outlined. It is vital to utilize local epidemiology and resistance patterns to select appropriate antibiotics to optimize clinical outcomes. Therapeutic drug monitoring should be used, when possible. This review should be used as a guide to develop a patient-specific antibiotic therapy plan.

scholarly journals Cefiderocol in Critically Ill Patients with Multi-Drug Resistant Pathogens: Real-Life Data on Pharmacokinetics and Microbiological Surveillance

Antibiotics ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 649
Author(s):  
Christina König ◽  
Anna Both ◽  
Holger Rohde ◽  
Stefan Kluge ◽  
Otto R. Frey ◽  
...  
Keyword(s):  
Renal Replacement Therapy ◽  
Therapeutic Drug Monitoring ◽  
Continuous Renal Replacement Therapy ◽  
Replacement Therapy ◽  
Critically Ill ◽  
Drug Monitoring ◽  
Critically Ill Patients ◽  
Therapeutic Drug ◽  
Renal Elimination ◽  
Drug Resistant

Cefiderocol is a new siderophore-cephalosporin for the treatment of multi-drug resistant Gram-negative pathogens. As a reserve agent, it will and should be used primarily in critically ill patients in the upcoming years. Due to the novelty of the substance little data on the pharmacokinetics in critically ill patients with septic shock and renal failure (including continuous renal replacement therapy and cytokine adsorber therapy) is available. We performed therapeutic drug monitoring in a cohort of five patients treated with cefiderocol, to improve the knowledge on pharmacokinetics in this vulnerable patient population. As expected for a cephalosporin with predominantly renal elimination the maintenance dose could be reduced in patients with renal impairment or on continuous renal replacement therapy. The manufacturer’s dosing instructions were sufficient to achieve a drug level well above the MIC. However, the addition of a cytokine adsorber might reduce serum levels substantially, so that in this context therapeutic drug monitoring and dose adjustment are recommended.

Point-of-Care Echocardiography and Hemodynamic Monitoring in Cirrhosis and Acute-on-Chronic Liver Failure in the COVID-19 Era

2021 ◽  
pp. 088506662098828
Author(s):  
Madhumita Premkumar ◽  
Kamal Kajal ◽  
Anand V. Kulkarni ◽  
Ankur Gupta ◽  
Smita Divyaveer
Keyword(s):  
Intensive Care ◽  
Liver Failure ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Point Of Care ◽  
Kidney Injury ◽  
Regional Wall Motion ◽  
Chronic Liver ◽  
Chronic Liver Failure ◽  
Evidenced Based

Point-of-Care (POC) transthoracic echocardiography (TTE) is transforming the management of patients with cirrhosis presenting with septic shock, acute kidney injury, hepatorenal syndrome and acute-on-chronic liver failure (ACLF) by correctly assessing the hemodynamic and volume status at the bedside using combined echocardiography and POC ultrasound (POCUS). When POC TTE is performed by the hepatologist or intensivist in the intensive care unit (ICU), and interpreted remotely by a cardiologist, it can rule out cardiovascular conditions that may be contributing to undifferentiated shock, such as diastolic dysfunction, myocardial infarction, myocarditis, regional wall motion abnormalities and pulmonary embolism. The COVID-19 pandemic has led to a delay in seeking medical treatment, reduced invasive interventions and deferment in referrals leading to “collateral damage” in critically ill patients with liver disease. Thus, the use of telemedicine in the ICU (Tele-ICU) has integrated cardiology, intensive care, and hepatology practices across the spectrum of ICU, operating room, and transplant healthcare. Telecardiology tools have improved bedside diagnosis when introduced as part of COVID-19 care by remote supervision and interpretation of POCUS and echocardiographic data. In this review, we present the contemporary approach of using POC echocardiography and offer a practical guide for primary care hepatologists and gastroenterologists for cardiac assessment in critically ill patients with cirrhosis and ACLF. Evidenced based use of Tele-ICU can prevent delay in cardiac diagnosis, optimize safe use of expert resources and ensure timely care in the setting of critically ill cirrhosis, ACLF and liver transplantation in the COVID-19 era.

The ten tips to manage critically ill patients with acute-on-chronic liver failure

2018 ◽  
Vol 44 (11) ◽  
pp. 1932-1935 ◽  
Author(s):  
Valentin Fuhrmann ◽  
Tony Whitehouse ◽  
Julia Wendon
Keyword(s):  
Liver Failure ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Chronic Liver ◽  
Chronic Liver Failure
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