Hemofiltration in sepsis and systemic inflammatory response syndrome: The role of dosing and timing

Introduction: The benefit of hemofiltration (HF) as an adjunctive treatment of sepsis or the systemic inflammatory response syndrome (SIRS) in critically ill patients is a subject of severe debate. Firm conclusions on this subject are hampered by the heterogeneity in study populations and HF treatments, and the lack of adequately sized randomized controlled clinical trials. The aim of this review was to determine the importance of ultrafiltration dose and timing on the physiologic and clinical effects of HF in sepsis and SIRS. In addition, we discuss the issue of filter pore size. Methods: Literature search was done in Embase and PubMed database for animal and human studies. Results: Animal studies suggest beneficial effects of HF on hemodynamics; gas exchange; sepsis-induced immunoparalysis; histology of gut, lung, and kidney; and (short-term) survival. These effects were more prominent with "very high" ultrafiltrate rates (≥100 mL/kg per hour) and early initiation of HF (ie, before or very early after the septic challenge). Three small randomized studies and 3 observational studies in patients with sepsis or SIRS show beneficial effects of short-term or pulse HF using very high ultrafiltrate rates and/or early initiation of HF on physiologic endpoints and survival. However, the studies were underpowered for survival. The first observations of high permeability HF (pore size, about 10 nm; in vitro cutoff, 100 kd) are promising, but so far, it has not been sufficiently examined to allow strong conclusions. Conclusion: Human and animal studies suggest that early initiation and high ultrafiltrate volumes are determinants of the beneficial physiologic and clinical effect of HF in sepsis and SIRS. As yet, the evidence in humans is too low to recommend HF as an adjunctive therapy for critically ill patients with sepsis or SIRS. Regarding the many uncertainties about optimal volume (high or very high) and type of membrane, clinical studies should first focus on endpoints as recovery from organ failure and length of treatment before survival studies are started

Effects of early high-volume continuous venovenous hemofiltration on survival and recovery of renal function in intensive care patients with acute renal failure: A prospective, randomized trial

Objective: To study the effects of the initiation time of continuous venovenous hemofiltration and of the ultrafiltrate rate in patients with circulatory and respiratory insufficiency developing early oliguric acute renal failure. The primary end points were mortality at 28 days and recovery of renal function. Design: A randomized, controlled, two-center study. Setting: The closed-format multidisciplinary intensive care units of a university hospital (30 beds) and a teaching hospital (18 beds). Patients and Interventions: A total of 106 ventilated severely ill patients who were oliguric despite massive fluid resuscitation, inotropic support, and high-dose intravenous diuretics were randomized into three groups. Thirty-five patients were treated with early high-volume hemofiltration (72-96 L per 24 hrs), 35 patients with early low-volume hemofiltration (24-36 L per 24 hrs), and 36 patients with late low-volume hemofiltration (24-36 L per 24 hrs). Results: Median ultrafiltrate rate was 48.2 (42.3-58.7) mL·kg-1·hr-1 in early high-volume hemofiltration, 20.1 (17.5-22.0) mL·kg-1·hr-1 in early low-volume hemofiltration, and 19.0 (16.6-21.1) mL·kg-1·hr-1 in late low-volume hemofiltration. Survival at day 28 was 74.3% in early high-volume hemofiltration, 68.8% in early low-volume hemofiltration, and 75.0% in late low-volume hemofiltration (p = .80). On average, hemofiltration started 7 hrs after inclusion in the early groups and 42 hrs after inclusion in the late group. All hospital survivors had recovery of renal function at hospital discharge, except for one patient in the early low-volume hemofiltration group. Median duration of renal failure in hospital survivors was 4.3 (1.4-7.8) days in early high-volume hemofiltration, 3.2 (2.4-5.4) days in early low-volume hemofiltration, and 5.6 (3.1-8.5) days in late low-volume hemofiltration (p = .25). Conclusions: In the present study of critically ill patients with oliguric acute renal failure, survival at 28 days and recovery of renal function were not improved using high ultrafiltrate volumes or early initiation of hemofiltration

Incidence, risk factors and pre-emptive screening for COVID-19 associated pulmonary aspergillosis in an era of immunomodulant therapy

Purpose: COVID-19 associated pulmonary aspergillosis (CAPA) is associated with increased morbidity and mortality in ICU patients. We investigated the incidence of, risk factors for and potential benefit of a pre-emptive screening strategy for CAPA in ICUs in the Netherlands/Belgium during immunosuppressive COVID-19 treatment. Materials and methods: A retrospective, observational, multicentre study was performed from September 2020–April 2021 including patients admitted to the ICU who had undergone diagnostics for CAPA. Patients were classified based on 2020 ECMM/ISHAM consensus criteria. Results: CAPA was diagnosed in 295/1977 (14.9%) patients. Corticosteroids were administered to 97.1% of patients and interleukin-6 inhibitors (anti-IL-6) to 23.5%. EORTC/MSGERC host factors or treatment with anti-IL-6 with or without corticosteroids were not risk factors for CAPA. Ninety-day mortality was 65.3% (145/222) in patients with CAPA compared to 53.7% (176/328) without CAPA (p = 0.008). Median time from ICU admission to CAPA diagnosis was 12 days. Pre-emptive screening for CAPA was not associated with earlier diagnosis or reduced mortality compared to a reactive diagnostic strategy. Conclusions: CAPA is an indicator of a protracted course of a COVID-19 infection. No benefit of pre-emptive screening was observed, but prospective studies comparing pre-defined strategies would be required to confirm this observation