Simplified regional citrate anticoagulation protocol for CVVH, CVVHDF and SLED focused on the prevention of KRT-related hypophosphatemia while optimizing acid-base balance.

BACKGROUND: Hypophosphatemia is a common electrolyte disorder in critically ill patients undergoing prolonged kidney replacement therapy (KRT). We evaluated the efficacy and safety of a simplified regional citrate anticoagulation (RCA) protocol for continuous venovenous hemofiltration (CVVH), continuous venovenous hemodiafiltration (CVVHDF) and sustained low-efficiency dialysis filtration (SLED-f). We aimed at preventing KRT-related hypophosphatemia while optimizing acid-base equilibrium. METHODS: KRT was performed by the Prismax system (Baxter) and polyacrylonitrile AN69 filters (ST 150, 1.5 m2, Baxter), combining a 18 mmol/L pre-dilution citrate solution (Regiocit 18/0, Baxter) with a phosphate-containing solution (HPO42- 1.0 mmol/L, HCO3- 22.0 mmol/L; Biphozyl, Baxter). When needed, phosphate loss was replaced with sodium glycerophosphate pentahydrate (Glycophos™ 20 mmol/20 mL, Fresenius Kabi Norge AS, Halden, Norway). Serum citrate measurements were scheduled during each treatment. We analyzed data from three consecutive daily 8-h SLED-f sessions, as well as single 72-h CVVH or 72-h CVVHDF sessions. We used analysis of variance (ANOVA) for repeated measures to evaluate differences in variables means (i.e. serum phosphate, citrate). Because some patients received phosphate supplementation, we performed analysis of covariance (ANCOVA) for repeated measures modelling phosphate supplementation as a covariate. RESULTS: Forty-seven patients with acute kidney injury (AKI) or end stage kidney disease (ESKD) requiring KRT were included [11 CVVH, 11 CVVHDF and 25 SLED-f sessions; mean Acute Physiology and Chronic Health Evaluation II (APACHE II) score 25 ± 7.0]. Interruptions for irreversible filter clotting were negligible. The overall incidence of hypophosphatemia (s-P levels <2.5 mg/dL) was 6.6%, and s-P levels were kept in the normality range irrespective of baseline values and the KRT modality. The acid-base balance was preserved, with no episode of citrate accumulation. CONCLUSIONS: Our data obtained with a new simplified RCA protocol suggest that it is effective and safe for CVVH, CVVHDF and SLED, allowing to prevent KRT-related hypophosphatemia and maintain the acid-base balance without citrate accumulation. TRIAL REGISTRATION: NCT03976440 (registered 6 June 2019).

Hypophosphatemia in critically ill patients undergoing Sustained Low-Efficiency Dialysis with standard dialysis solutions.

BACKGROUND: In patients admitted to the Intensive Care Unit (ICU), Kidney Replacement Therapy (KRT) is an important risk factor for hypophosphataemia. However, studies addressing the development of hypophosphatemia during prolonged intermittent KRT modalities are lacking. Thus, we evaluated the incidence of hypophosphatemia during Sustained Low-Efficiency Dialysis (SLED) in ICU patients; we also examined the determinants of post-SLED serum phosphate level (s-P) and the relation between s-P and phosphate supplementation and ICU mortality. METHODS: We conducted a retrospective analysis on a cohort of critically ill patients with severe renal failure and KRT need, who underwent at least three consecutive SLED sessions at 24-72 h time intervals with daily monitoring of s-P concentration. SLED with Regional Citrate Anticoagulation (RCA) was performed with either conventional dialysis machines or continuous-KRT monitors and standard dialysis solutions. When deemed necessary by the attending physician, intravenous phosphate supplementation was provided by sodium glycerophosphate pentahydrate. We used mixed-effect models to examine the determinants of s-P and Cox proportional hazards regression models with time-varying covariates to examine the adjusted relation between s-P, intravenous phosphate supplementation and ICU mortality. RESULTS: We included 65 patients [mean age 68 years (SD 10.0); mean Acute Physiology and Chronic Health Evaluation II score 25 (range 9-40)] who underwent 195 SLED sessions. The mean s-P before the start of the first SLED session (baseline s-P) was 5.6 ± 2.1 mg/dL (range 1.5-12.3). Serum phosphate levels at the end of each SLED decreased with increasing age, SLED duration and number of SLED sessions (P < .05 for all). The frequency of hypophosphatemia increased after the first through the third SLED session (P = .012). Intravenous phosphate supplementation was scheduled after 12/45 (26.7%) SLED sessions complicated by hypophosphataemia. The overall ICU mortality was 23.1% (15/65). In Cox regression models, after adjusting for potential confounders and for current s-P, intravenous phosphate supplementation was associated with a decrease in ICU mortality [adjusted hazard ratio: 0.24 (95% confidence interval: 0.06 to 0.89; P = 0.033)]. CONCLUSIONS: Hypophosphatemia is a frequent complication in critically ill patients undergoing SLED with standard dialysis solutions, that worsens with increasing SLED treatment intensity. In patients undergoing daily SLED, phosphate supplementation is strongly associated with reduced ICU mortality.

Acute kidney injury referred to the nephrologist: A single centre experience in a tertiary care hospital.

AIM: Acute kidney injury (AKI) shows an increasing incidence, accounting for a remarkable proportion of nephrology team in-hospital activity. The aim was to describe main features and outcomes of AKI observed in patients admitted to a tertiary care hospital. METHODS: We conducted a retrospective analysis in all consecutive AKI patients referred for nephrology consultation (November 2018-February 2020) focusing on the factors associated with in-hospital mortality within 90 days and kidney function recovery (KFR) upon discharge. Demographic, clinical and laboratory data, as well as main features of AKI episodes, were collected from medical records of the entire hospital stay. AKI was defined according to KDIGO Clinical Practice Guideline. RESULTS: Among 1145 patients referred for nephrology consultation, 559 were evaluated for AKI (598 episodes). Pre-existing CKD was present in 54.7% of patients. In 69.2% of cases AKI was evaluated within 48 h from its onset. Most of the episodes (66.6%) were classified as KDIGO Stage 3. In-hospital mortality within 90 days since admission was 43.3%. Multivariate Cox regression analysis showed a higher mortality risk for advancing age (HR 1.02/unit, 95% CI 1.01-1.03) and oliguria (HR 1.91, 95% CI 1.45-2.52), while a higher eGFR (HR 0.72/unit, 95% CI 0.54-0.95) and KFR within 7 days (HR 0.62, 95% CI 0.41-0.94) were associated to a lower mortality. KFR was observed in 96.4% of survivors. In patients with partial KFR, the loss of eGFR was -29.2 ± 17.9 ml/min. KFR incidence rate was 6.79 per 100-person days (95% CI 6.72-6.87) in survivors and 2.30 (95% CI 2.25-2.35) in non-survivors. CONCLUSION: AKI-related nephrology activity accounts for most of the nephrologist workload as consultant. Referred AKI episodes are frequently severe and superimposed on CKD, carrying a relatively high mortality in a patient population developing AKI outside ICU. Early KFR appears strongly associated with a favourable impact upon in-hospital survival.

Acute Kidney Injury and COVID-19: A Picture from an Intensive Care Unit.

INTRODUCTION: Acute kidney injury (AKI) is a frequent complication in coronavirus disease 2019 (COVID-19) patients admitted to intensive care unit (ICU) for severe respiratory failure. The aim is to evaluate the rate of AKI, defined according to Kidney Disease: Improving Global Outcome guidelines, in a series of critical COVID-19 patients admitted to the ICU of a single tertiary teaching hospital. METHODS: From April to May 2020, all consecutive critically ill COVID-19 patients admitted to the ICU who did not meet exclusion criteria (length of ICU stay <48 h, ESRD requiring dialysis, and patients still hospitalized in ICU at the time of data analysis) were enrolled in this study. Patients were stratified according to the highest AKI stage attained during ICU stay. RESULTS: Sixty-one patients were included in the analysis. AKI was observed in 35/61 patients (57.4%): 25/35 episodes (71.4%) were observed within the first 7 days. AKI was classified as follows: 17.1% stage 1, 25.7% stage 2, and 57.2% stage 3. Fourteen out of 20 stage-3 patients required continuous renal replacement therapy (CRRT), mostly related to persistent oliguria. The overall ICU mortality was 68.9%, and it was higher in patients developing AKI if compared to no-AKI patients (p = 0.006). Renal function recovery of any grade was observed in 14 out of 35 AKI patients (40%). Among patients undergoing CRRT, 13 patients were still dialysis dependent at the time of death. CONCLUSION: In critical COVID-19 patients, ICU mortality is particularly high, especially in patients developing AKI. An accurate monitoring of renal function in early phases of respiratory failure should be ensured in order to timely apply any strategy aimed at limiting renal complications during ICU stay.

A Guide to Understanding Antimicrobial Drug Dosing in Critically Ill Patients on Renal Replacement Therapy.

A careful management of antimicrobials is essential in the critically ill with acute kidney injury, especially if renal replacement therapy is required. Acute kidney injury may lead per se to clinically significant modifications of drugs' pharmacokinetic parameters, and the need for renal replacement therapy represents a further variable that should be considered to avoid inappropriate antimicrobial therapy. The most important pharmacokinetic parameters, useful to determine the significance of extracorporeal removal of a given drug, are molecular weight, protein binding, and distribution volume. In many cases, the extracorporeal removal of antimicrobials can be relevant, with a consistent risk of underdosing-related treatment failure and/or potential onset of bacterial resistance. It should also be taken into account that renal replacement therapies are often not standardized in critically ill patients, and their impact on plasma drug concentrations may substantially vary in relation to membrane characteristics, treatment modality, and delivered dialysis dose. Thus, in this clinical scenario, the knowledge of the pharmacokinetic and pharmacodynamic properties of different antimicrobial classes is crucial to tailor maintenance dose and/or time interval according to clinical needs. Finally, especially for antimicrobials known for a tight therapeutic range, therapeutic drug monitoring is strongly suggested to guide dosing adjustment in complex clinical settings, such as septic patients with acute kidney injury undergoing renal replacement therapy.

Preventing Continuous Renal Replacement Therapy-Induced Hypophosphatemia: An Extended Clinical Experience with a Phosphate-Containing Solution in the Setting of Regional Citrate Anticoagulation.

AIMS: To evaluate the efficacy and safety of a commercially available phosphate-containing solution for continuous renal replacement therapy (CRRT) in preventing CRRT-related hypophosphatemia. METHODS: In heart surgery patients undergoing continuous veno-venous haemodiafiltration (CVVHDF) with regional citrate anticoagulation (RCA), we combined an 18 mmol/l citrate solution with a phosphate-containing (1.2 mmol/l) dialysate/replacement fluid evaluating the incidence of hypophosphatemia and the need for parenteral phosphorus supplementation. RESULTS: In 75 patients on RCA-CVVHDF, the mean filter life was 53.9 ± 33.6 h. Regardless of baseline levels, phosphoremia was progressively corrected and maintained in a narrow normality range throughout RCA-CRRT days (after 72 h: 1.14 ± 0.25 mmol/l). Considering the whole CRRT period, 45 out of 975 (4.6%) serum phosphorus determinations met the criteria for mild (<0.81 mmol/l) or moderate (<0.61 mmol/l) hypophosphatemia; severe hypophosphatemia (<0.32 mmol/l) never occurred. After 72 h 88% of the patients were normophosphatemic, 9% hyperphosphatemic and 3% hypophosphatemic. CONCLUSIONS: RCA-CVVHDF with a phosphate-containing solution enabled the maintenance of phosphorus levels within normophosphatemic range in most of the patients, minimizing the occurrence of CRRT-related hypophosphatemia.

Colistin Use in Patients With Reduced Kidney Function.

Colistin (polymyxin E) is a mainly concentration-dependent bactericidal antimicrobial active against multidrug-resistant Gram-negative bacteria. After being abandoned over the past 30 years due to its neuro- and nephrotoxicity, colistin has been reintroduced recently as a last-resort drug for the treatment of multidrug-resistant Gram-negative bacteria infections in combination with other antimicrobials. Unfortunately, although renal toxicity is a well-known dose-related adverse effect of colistin, relatively few studies are currently available on its peculiar pharmacodynamic/pharmacokinetic properties in clinical settings at high risk for drug accumulation, such as acute or chronic kidney disease. In these specific contexts, the risk for underdosing is also substantial because colistin can be easily removed by dialysis/hemofiltration, especially when the most efficient modalities of renal replacement therapy (RRT) are used in critically ill patients. For this reason, recent recommendations in patients undergoing RRT have shifted toward higher dosing regimens, and therapeutic drug monitoring is advised. This review aims to summarize the main issues related to chemical structure, pharmacodynamics/pharmacokinetics, and renal toxicity of colistin. Moreover, recent data and current recommendations concerning colistin dosing in patients with reduced kidney function, with special regard to those receiving RRT such as dialysis or hemofiltration, are also discussed.

Alterations of intestinal barrier and microbiota in chronic kidney disease.

Recent studies have highlighted the close relationship between the kidney and the gastrointestinal (GI) tract--frequently referred to as the kidney--gut axis--in patients with chronic kidney disease (CKD). In this regard, two important pathophysiological concepts have evolved: (i) production and accumulation of toxic end-products derived from increased bacterial fermentation of protein and other nitrogen-containing substances in the GI tract, (ii) translocation of endotoxins and live bacteria from gut lumen into the bloodstream, due to damage of the intestinal epithelial barrier and quantitative/qualitative alterations of the intestinal microbiota associated with the uraemic milieu. In both cases, these gut-centred alterations may have relevant systemic consequences in CKD patients, since they are able to trigger chronic inflammation, increase cardiovascular risk and worsen uraemic toxicity. The present review is thus focused on the kidney-gut axis in CKD, with special attention to the alterations of the intestinal barrier and the local microbiota (i.e. the collection of microorganisms living in a symbiotic coexistence with their host in the intestinal lumen) and their relationships to inflammation and uraemic toxicity in CKD. Moreover, we will summarize the most important clinical data suggesting the potential for nutritional modulation of gut-related inflammation and intestinal production of noxious by-products contributing to uraemic toxicity in CKD patients.

Body cell mass evaluation in critically ill patients: killing two birds with one stone.

Body cell mass (BCM) is the metabolically active cell mass involved in O2 consumption, CO2 production and energy expenditure. BCM measurement has been suggested as a tool for the evaluation of nutritional status. Since BCM is closely related to energy expenditure, it could also represent a good reference value for the calculation of nutrient needs. In a recent issue of Critical Care, Ismael and colleagues used bioelectrical impedance analysis parameters and anthropometric variables to evaluate BCM in patients with acute kidney injury, before and after a hemodialysis session. The results of this study suggest that BCM is relatively insensitive to major body fluid shifts, a well known factor interfering with nutritional evaluation/monitoring and energy need calculations in the ICU. Thus, BCM seems to be a more 'stable' nutritional variable, as it is apparently less influenced by non-nutritional factors. The results of this paper emphasize the need to identify biologically sound parameters for nutritional status evaluation and energy need calculation in critically ill patients; in this regard, BCM could fulfill these expectations.

Continuous venovenous hemodiafiltration with a low citrate dose regional anticoagulation protocol and a phosphate-containing solution: effects on acid-base status and phosphate supplementation needs.

BACKGROUND: Recent guidelines suggest the adoption of regional citrate anticoagulation (RCA) as first choice CRRT anticoagulation modality in patients without contraindications for citrate. Regardless of the anticoagulation protocol, hypophosphatemia represents a potential drawback of CRRT which could be prevented by the adoption of phosphate-containing CRRT solutions. The aim was to evaluate the effects on acid-base status and phosphate supplementation needs of a new RCA protocol for Continuous Venovenous Hemodiafiltration (CVVHDF) combining the use of citrate with a phosphate-containing CRRT solution. METHODS: To refine our routine RCA-CVVH protocol (12 mmol/l citrate, HCO3- 32 mmol/l replacement fluid) (protocol A) and to prevent CRRT-related hypophosphatemia, we introduced a new RCA-CVVHDF protocol (protocol B) combining an 18 mmol/l citrate solution with a phosphate-containing dialysate/replacement fluid (HCO3- 30 mmol/l, Phosphate 1.2). A low citrate dose (2.5-3 mmol/l) and a higher than usual target circuit-Ca(2+) (≤ 0.5 mmol/l) have been adopted. RESULTS: Two historical groups of heart surgery patients (n = 40) underwent RCA-CRRT with protocol A (n = 20, 102 circuits, total running time 5283 hours) or protocol B (n = 20, 138 circuits, total running time 7308 hours). Despite higher circuit-Ca(2+) in protocol B (0.37 vs 0.42 mmol/l, p < 0.001), circuit life was comparable (51.8 ± 36.5 vs 53 ± 32.6 hours). Protocol A required additional bicarbonate supplementation (6 ± 6.4 mmol/h) in 90% of patients while protocol B ensured appropriate acid-base balance without additional interventions: pH 7.43 (7.40-7.46), Bicarbonate 25.3 (23.8-26.6) mmol/l, BE 0.9 (-0.8 to +2.4); median (IQR). No episodes of clinically relevant metabolic alkalosis, requiring modifications of RCA-CRRT settings, were observed. Phosphate supplementation was needed in all group A patients (3.4 ± 2.4 g/day) and in only 30% of group B patients (0.5 ± 1.5 g/day). Hypophosphatemia developed in 75% and 30% of group A and group B patients, respectively. Serum phosphate was significantly higher in protocol B patients (P < 0.001) and, differently to protocol A, appeared to be steadily maintained in near normal range (0.97-1.45 mmol/l, IQR). CONCLUSIONS: The proposed RCA-CVVHDF protocol ensured appropriate acid-base balance without additional interventions, providing prolonged filter life despite adoption of a higher target circuit-Ca(2+). The introduction of a phosphate-containing solution, in the setting of RCA, significantly reduced CRRT-related phosphate depletion.

Nutritional evaluation and management of AKI patients.

Protein-energy wasting is common in patients with acute kidney injury (AKI) and represents a major negative prognostic factor. Nutritional support as parenteral and/or enteral nutrition is frequently needed because the early phases of this are often a highly catabolic state, although the optimal nutritional requirements and nutrient intake composition remain a partially unresolved issue. Nutrient needs of patients with AKI are highly heterogeneous, depending on different pathogenetic mechanisms, catabolic rate, acute and chronic comorbidities, and renal replacement therapy (RRT) modalities. Thus, quantitative and qualitative aspects of nutrient intake should be frequently evaluated in this clinical setting to achieve better individualization of nutritional support, to integrate nutritional support with RRT, and to avoid under- and overfeeding. Moreover, AKI is now considered a kidney-centered inflammatory syndrome; indeed, recent experimental data indicate that specific nutrients with anti-inflammatory effects could play an important role in the prevention of renal function loss after an episode of AKI.

Extracorporeal blood purification therapies for sepsis-associated acute kidney injury in critically ill patients: expert opinion from the SIAARTI-SIN joint commission.

Sepsis-Associated Acute Kidney Injury is a life-threatening condition leading to high morbidity and mortality in critically ill patients admitted to the intensive care unit. Over the past decades, several extracorporeal blood purification therapies have been developed for both sepsis and sepsis-associated acute kidney injury management. Despite the widespread use of extracorporeal blood purification therapies in clinical practice, it is still unclear when to start this kind of treatment and how to define its efficacy. Indeed, several questions on sepsis-associated acute kidney injury and extracorporeal blood purification therapy still remain unresolved, including the indications and timing of renal replacement therapy in patients with septic vs. non-septic acute kidney injury, the optimal dialysis dose for renal replacement therapy modalities in sepsis-associated acute kidney injury patients, and the rationale for using extracorporeal blood purification therapies in septic patients without acute kidney injury. Moreover, the development of novel extracorporeal blood purification therapies, including those based on the use of adsorption devices, raised the attention of the scientific community both on the clearance of specific mediators released by microorganisms and by injured cells and potentially involved in the pathogenic mechanisms of organ dysfunction including sepsis-associated acute kidney injury, and on antibiotic removal. Based on these considerations, the joint commission of the Italian Society of Anesthesiology and Critical Care (SIAARTI) and the Italian Society of Nephrology (SIN) herein addressed some of these issues, proposed some recommendations for clinical practice and developed a common framework for future clinical research in this field.

Regional citrate anticoagulation (RCA) in critically ill patients undergoing renal replacement therapy (RRT): expert opinion from the SIAARTI-SIN joint commission.

Renal replacement therapies (RRT) are essential to support critically ill patients with severe acute kidney injury (AKI), providing control of solutes, fluid balance and acid-base status. To maintain the patency of the extracorporeal circuit, minimizing downtime periods and blood losses due to filter clotting, an effective anticoagulation strategy is required.Regional citrate anticoagulation (RCA) has been introduced in clinical practice for continuous RRT (CRRT) in the early 1990s and has had a progressively wider acceptance in parallel to the development of simplified systems and safe protocols. Main guidelines on AKI support the use of RCA as the first line anticoagulation strategy during CRRT in patients without contraindications to citrate and regardless of the patient's bleeding risk.Experts from the SIAARTI-SIN joint commission have prepared this position statement which discusses the use of RCA in different RRT modalities also in combination with other extracorporeal organ support systems. Furthermore, advise is provided on potential limitations to the use of RCA in high-risk patients with particular attention to the need for a rigorous monitoring in complex clinical settings. Finally, the main findings about the prospective of optimization of RRT solutions aimed at preventing electrolyte derangements during RCA are discussed in detail.

Impact of Continuous Kidney Replacement Therapy and Hemoadsorption with CytoSorb on Antimicrobial Drug Removal in Critically Ill Children with Septic Shock: A Single-Center Prospective Study on a Pediatric Cohort.

Background: Extracorporeal therapies (ET) are increasingly used in pediatric settings as adjuvant therapeutic strategies for overwhelming inflammatory conditions. Although these treatments seem to be effective for removing inflammatory mediators, their influence on antimicrobials pharmacokinetic should not be neglected. Methods: A prospective observational study of children admitted to the pediatric intensive care unit (PICU) with a diagnosis of sepsis/septic shock. All critically ill children received hemoadsorption treatment with CytoSorb (CS) in combination with CKRT. Therapeutic drug monitoring has been performed on 10 critically ill children, testing four antimicrobial molecules: meropenem, ceftazidime, amikacin and levofloxacin. In order to evaluate the total and isolated CKRT and CS contributions to antibiotic removal, blood samples at each circuit point (post-hemofilter, post-CS and in the effluent line) were performed. Therefore, the clearance and mass Removal (MR) of the hemofilter and CS were calculated. Results: Our preliminary report describes a different impact of CS on these target drugs removal: CS clearance was low for amikacine (6-12%), moderate for ceftazidime (43%) and moderate to high for levofloxacine (52-72%). Higher MR and clearance were observed with CKRT compared to CS. To the best of our knowledge, this is the first report regarding pharmacokinetic dynamics in critically ill children treated with CKRT and CS for septic shock.

Regional citrate anticoagulation in cardiac surgery patients at high risk of bleeding: a continuous veno-venous hemofiltration protocol with a low concentration citrate solution.

INTRODUCTION: Regional citrate anticoagulation (RCA) is a valid option in patients at high risk of bleeding who are undergoing continuous renal replacement therapy (CRRT). The aim of this study was to evaluate, in critically ill patients with severe acute kidney injury following cardiac surgery, the efficacy and safety of RCA-continuous veno-venous hemofiltration (CVVH) using a low concentration citrate solution. METHODS: In high bleeding-risk cardiac surgery patients, we adopted, as an alternative to heparin or no anticoagulation, RCA-CVVH using a 12 mmol/l citrate solution. For RCA-CVVH settings, we developed a mathematical model to roughly estimate citrate load and calcium loss. In order to minimize calcium chloride supplementation, a calcium-containing solution was used as post-dilution replacement fluid. RESULTS: Thirty-three patients (age 70.8 ± 9.5, Sequential Organ Failure Assessment (SOFA) score 13.9 ± 2.5) were switched to RCA-CVVH from no anticoagulation CRRT. Among them, 16 patients had been previously switched from heparin to no anticoagulation because of bleeding or heparin-related complications. RCA-CVVH filter life (49.8 ± 35.4 hours, median 41, 152 circuits) was significantly longer (P < 0.0001) when compared with heparin (30.6 ± 24.3 hours, median 22, 73 circuits) or no anticoagulation (25.7 ± 21.2 hours, median 20, 77 circuits). Target circuit and systemic Ca(++) were easily maintained (0.37 ± 0.09 and 1.18 ± 0.13 mmol/l), while the persistence of a mild metabolic acidosis required bicarbonate supplementation (5.8 ± 5.9 mmol/hours) in 27 patients. The probability of circuit running at 24, 48, 72 hours was higher during RCA-CVVH (P < 0.0001), with a lower discrepancy between delivered and prescribed CRRT dose (P < 0.0001). RCA was associated with a lower transfusion rate (P < 0.02). Platelet count (P = 0.012) and antithrombin III activity (P = 0.004) increased throughout RCA-CVVH, reducing the need for supplementation. CONCLUSIONS: RCA safely prolonged filter life while decreasing CRRT downtime, transfusion rates and supplementation needs for antithrombin III and platelets. In cardiac surgery patients with severe multiple organ dysfunction syndrome, the adoption of a 12 mmol/l citrate solution may provide a suboptimal buffers supply, easily overwhelmed by bicarbonate supplementation.

[Regional citrate anticoagulation: towards a first-choice treatment]. / Anticoagulazione regionale con citrato: verso un trattamento di prima scelta.

Continuous renal replacement therapy (CRRT) is the most widely used technique for the treatment of severe acute kidney injury in the critically ill. The need for prolonged anticoagulation is the most important drawback of CRRT and clinically important bleeding significantly increases the risk of death. Therefore, alternative anticoagulation methods should be more widely adopted. Among the potential alternatives to systemic heparin anticoagulation, regional citrate anticoagulation (RCA) is the most promising. By reducing ionized calcium inside the extracorporeal circuit, citrate is able to block the coagulation cascade at different levels. Compared with unfractionated heparin, several studies reported better filter survival times and a marked reduction of transfusion rates with RCA. Despite the positive reports about the efficacy and safety of RCA, the use of this alternative method of anticoagulation appears to be relatively limited. Desirable future improvements in RCA should be focused on simplifying protocols, minimizing the need for calcium and magnesium supplementation, increasing the flexibility of buffer balance, and introducing customized dialysis systems able to deliver automated RCA. In particular, safe protocols with automated delivery of citrate and calcium can allow easy parameter settings that can be adapted to a wide range of clinical situations, facilitating the wider use of RCA in the coming years.

[Pharmacokinetics of antibiotics in continuous renal replacement therapies (CRRT)]. / Farmacocinetica degli antibiotici nelle terapie sostitutive renali continue (CRRT).

In the critically ill patient, acute kidney injury (AKI) is frequently associated with infective complications requiring appropriate antimicrobial treatment. AKI and multiple organ dysfunction syndrome can affect the pharmacokinetic parameters of many drugs. Furthermore, the start of renal replacement therapy (RRT) is an additional variable to be taken into consideration to avoid inappropriate antimicrobial therapy. Continuous renal replacement therapies (CRRT) are widely adopted in the intensive care unit (ICU) and antibiotics that are significantly eliminated by the kidney are likely to be removed during RRT. Generally, drug-dosing adjustments are required if the extracorporeal clearance accounts for more than 25-30% of the total body clearance. The molecular weight cutoffs of the more widely used membranes are much higher than the molecular weight of most drugs. Therefore, molecular size will not be a limitation for the removal of the unbound fraction of the antibiotics most commonly used in ICU patients. However, CRRTs are still not standardized and the impact of RRT on plasma drug concentrations can be substantially different depending on the CRRT modality (diffusive, convective or both), membrane characteristics and delivered dialysis dose. In any case, drug-dosing adjustments should be based on the knowledge of the pharmacokinetic and pharmacodynamic properties of the different classes of antimicrobials, taking into account that high extracorporeal clearances could lead to drug underexposure in clinical conditions where appropriate antibiotic treatment is essential.

Management of Acute Kidney Injury and Extracorporeal Blood Purification Therapies During the COVID-19 Pandemic: The Italian SIN-SIAARTI Joint Survey (and Recommendations for Clinical Practice).

Background and Aim: The novel coronavirus disease 2019 remains challenging. A large number of hospitalized patients are at a high risk of developing AKI. For this reason, we conducted a nationwide survey to assess the incidence and management of AKI in critically ill patients affected by the SARS-CoV-2 infection. Methods: This is a multicenter, observational, nationwide online survey, involving the Italian Society of Nephrology and the critical care units in Italy, developed in partnership between the scientific societies such as SIN and SIAARTI. Invitations to participate were distributed through emails and social networks. Data were collected for a period of 1 week during the COVID-19 pandemic. Results: A total of 141 responses were collected in the SIN-SIAARTI survey: 54.6% from intensivists and 44.6% from nephrologists. About 19,000 cases of COVID-19 infection have been recorded in hospitalized patients; among these cases, 7.3% had a confirmed acute kidney injury (AKI), of which 82.2% were managed in ICUs. Only 43% of clinicians routinely used the international KDIGO criteria. Renal replacement therapy (RRT) was performed in 628 patients with continuous techniques used most frequently, and oliguria was the most common indication (74.05%). Early initiation was preferred, and RRT was contraindicated in the case of therapeutic withdrawal or in the presence of severe comorbidities or hemodynamic instability. Regional anticoagulation with citrate was the most common choice. About 41.04% of the interviewed physicians never used extracorporeal blood purification therapies (EBPTs) for inflammatory cytokine or endotoxin removal. Moreover, 4.33% of interviewed clinicians used these techniques only in the presence of AKI, whereas 24.63% adopted them even in the absence of AKI. Nephrologists made more use of EBPT, especially in the presence of AKI. HVHF was never used in 58.54% of respondents, but HCO membranes and adsorbents were used in more than 50% of cases. Conclusion: This joint SIN-SIAARTI survey at the Italian Society of Nephrology and the critical care units in Italy showed that, during the COVID-19 pandemic, there was an underestimation of AKI based on the "non-use" of common diagnostic criteria, especially by intensivists. Similarly, the use of specific types of RRT and, in particular, blood purification therapies for immune modulation and organ support strongly differed between centers, suggesting the need for the development of standardized clinical guidelines.