Rita Jacobs

Regional citrate anticoagulation (RCA) is recommended by guidelines over systemic heparinization for continuous renal replacement therapy (CRRT). However,

(1) Background: Citrate is preferred in continuous renal replacement therapy (CRRT) for critically ill patients because it prolongs filter life and reduces bleeding risks compared to unfractionated heparin (UFH). However, regional citrate anticoagulation (RCA) can lead to acid–base disturbances, citrate accumulation, and overload. This study compares the safety and efficacy of citrate-based CRRT with UFH and no anticoagulation (NA) in acute kidney injury (AKI) patients. (2) Methods: A retrospective analysis was conducted on adult patients (≥18 years) who underwent CRRT from July 2010 to June 2021 in an intensive care unit. (3) Results: Among 829 AKI patients on CRRT: 552 received RCA, 232 UFH, and 45 NA. The RCA group had a longer filter lifespan compared to UFH and NA (56 h [IQR, 24–110] vs. 36.0 h [IQR, 17–63.5] vs. 22 h [IQR, 12–48]; all P_adj < 0.001). Bleeding complications were fewer in the RCA group than in the UFH group (median 3 units [IQR, 2–7 units] vs. median 5 units [IQR, 2–12 units]; P_adj < 0.001) and fewer in the NA group than in the UFH group (median 3 units [IQR, 1–5 units] vs. 5 units [IQR, 2–12 units]; P_adj = 0.03). Metabolic alkalosis was more common in the RCA group (32.5%) compared to the UFH (16.2%) and NA (13.5%) groups, while metabolic acidosis persisted more in the UFH group and NA group (29.1% and 34.6%) by the end of therapy vs. the citrate group (16.8%). ICU mortality was lower in the RCA group (52.7%) compared to the UFH group (63.4%; P_adj = 0.02) and NA group (77.8%; P_adj = 0.003). (4) Conclusions: Citrate anticoagulation outperforms heparin-based and no anticoagulation in filter patency, potentially leading to better outcomes through improved therapy effectiveness and reduced transfusion needs. However, careful monitoring is crucial to limit potential complications attributable to its use.

Intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) have significant pathophysiological consequences that can affect multiple organ systems. Fluid resuscitation is often used to restore hemodynamic stability in patients with elevated IAP; however, excessive intravenous fluid administration can paradoxically lead to ACS. This chapter explores the impact of fluid management in patients with IAH and ACS, including the effects of fluid on IAP in different patient populations and conditions. The importance of appropriate management of patients with elevated pressures in adjacent compartments, such as the abdomen, thorax, and skull, is also highlighted. The Abdominal Compartment Society's clear definitions for IAH and ACS, as well as concepts such as abdominal perfusion pressure, are discussed. Additionally, this chapter delves into the effects of elevated pressure on different organ systems, including the cardiovascular, respiratory, central nervous, renal, and gastrointestinal systems. The authors emphasize the need for careful fluid management in these patients to avoid exacerbating the pathophysiological consequences of elevated IAP.

Background: Anticoagulation is recommended to maintain the patency of the circuit in continuous renal replacement therapy (CRRT). However, anticoagulation-associated complications can occur. We performed a systematic review and meta-analysis to compare the efficacy and safety of citrate anticoagulation to heparin anticoagulation in critically ill patients treated with CRRT. Methods: Randomised controlled trials (RCTs) evaluating the safety and efficacy of citrate anticoagulation and heparin in CRRT were included. Articles not describing the incidence of metabolic and/or electrolyte disturbances induced by the anticoagulation strategy were excluded. The PubMed, Embase, and MEDLINE electronic databases were searched. The last search was performed on 18 February 2022. Results: Twelve articles comprising 1592 patients met the inclusion criteria. There was no significant difference between the groups in the development of metabolic alkalosis (RR = 1.46; (95% CI (0.52–4.11); p = 0.470)) or metabolic acidosis (RR = 1.71, (95% CI (0.99–2.93); p = 0.054)). Patients in the citrate group developed hypocalcaemia more frequently (RR = 3.81; 95% CI (1.67–8.66); p = 0.001). Bleeding complications in patients randomised to the citrate group were significantly lower than those in the heparin group (RR 0.32 (95% CI (0.22–0.47); p < 0.0001)). Citrate showed a significantly longer filter lifespan of 14.52 h (95% CI (7.22–21.83); p < 0.0001), compared to heparin. There was no significant difference between the groups for 28-day mortality (RR = 1.08 (95% CI (0.89–1.31); p = 0.424) or 90-day mortality (RR 0.9 (95% CI (0.8–1.02); p = 0.110). Conclusion: regional citrate anticoagulation is a safe anticoagulant for critically ill patients who require CRRT, as no significant differences were found in metabolic complications between the groups. Additionally, citrate has a lower risk of bleeding and circuit loss than heparin.

Background: General pathophysiological mechanisms regarding associations between fluid administration and intra-abdominal hypertension (IAH) are evident, but specific effects of type, amount, and timing of fluids are less clear. Objectives: This review aims to summarize current knowledge on associations between fluid administration and intra-abdominal pressure (IAP) and fluid management in patients at risk of intra-abdominal hypertension and abdominal compartment syndrome (ACS). Methods: We performed a structured literature search from 1950 until May 2021 to identify evidence of associations between fluid management and intra-abdominal pressure not limited to any specific study or patient population. Findings were summarized based on the following information: general concepts of fluid management, physiology of fluid movement in patients with intra-abdominal hypertension, and data on associations between fluid administration and IAH. Results: We identified three randomized controlled trials (RCTs), 38 prospective observational studies, 29 retrospective studies, 18 case reports in adults, two observational studies and 10 case reports in children, and three animal studies that addressed associations between fluid administration and IAH. Associations between fluid resuscitation and IAH were confirmed in most studies. Fluid resuscitation contributes to the development of IAH. However, patients with IAH receive more fluids to manage the effect of IAH on other organ systems, thereby causing a vicious cycle. Timing and approach to de-resuscitation are of utmost importance, but clear indicators to guide this decision-making process are lacking. In selected cases, only surgical decompression of the abdomen can stop deterioration and prevent further morbidity and mortality. Conclusions: Current evidence confirms an association between fluid resuscitation and secondary IAH, but optimal fluid management strategies for patients with IAH remain controversial.

BACKGROUND: SARS-CoV-2 infection induces mucin overexpression, further promoting disease. Given that mucins are critical components of innate immunity, unraveling their expression profiles that dictate the course of disease could greatly enhance our understanding and management of COVID-19. METHODS: Using validated RT-PCR assays, we assessed mucin mRNA expression in the blood of patients with symptomatic COVID-19 compared with symptomatic patients without COVID-19 and healthy controls and correlated the data with clinical outcome parameters. Additionally, we analyzed mucin expression in mucus and lung tissue from patients with COVID-19 and investigated the effect of drugs for COVID-19 treatment on SARS-CoV-2–induced mucin expression in pulmonary epithelial cells. RESULTS: We identified a dynamic blood mucin mRNA signature that clearly distinguished patients with symptomatic COVID-19 from patients without COVID-19 based on expression of MUC1 , MUC2 , MUC4 , MUC6 , MUC13 , MUC16 , and MUC20 (AUC _ROC of 91.8%; sensitivity and specificity of 90.6% and 93.3%, respectively) and that discriminated between mild and critical COVID-19 based on the expression of MUC16, MUC20, and MUC21 (AUC _ROC of 89.1%; sensitivity and specificity of 90.0% and 85.7%, respectively). Differences in the transcriptional landscape of mucins in critical cases compared with mild cases identified associations with COVID-19 symptoms, respiratory support, organ failure, secondary infections, and mortality. Furthermore, we identified different mucins in the mucus and lung tissue of critically ill COVID-19 patients and showed the ability of baricitinib, tocilizumab, favipiravir, and remdesivir to suppress expression of SARS-CoV-2–induced mucins. CONCLUSION: This multifaceted blood mucin mRNA signature showed the potential role of mucin profiling in diagnosing, estimating severity, and guiding treatment options in patients with COVID-19. FUNDING: The Antwerp University Research and the Research Foundation Flanders COVID-19 funds.

For almost three decades, researchers have invested in strategies that involved removal of excess inflammatory mediators from the circulation (that is, the "cytotoxic" approach). Blood purification techniques using an extracorporeal device can indeed non-specifically remove a wide array of inflammatory mediators from the circulation. In animal models, this multimediator targeting or pleiotropic approach was shown to downregulate systemic inflammation and to restore immune homeostasis. In this issue, Namas et al. seriously challenge this cytotoxic hypothesis and propose to replace it by a cytokinic approach. In a rodent model of sepsis, these authors elegantly demonstrate that hemoadsorption using a large surface-area polymer could reduce and, more importantly, relocalize and reprogram sepsis-induced acute inflammation, while simultaneously lowering infectious burden and liver damage. Although challenging, this new theory can be considered complementary to the existing cytotoxic hypotheses by coupling reduced endothelial damage at the interstitial level (cytotoxic approach) with the concept of reprogramming leucocytes and mediators toward infected tissue, thus emptying the bloodstream of important promoters of remote organ damages (cytokinic approach).