Citrate dose for continuous hemofiltration: effect on calcium and magnesium balance, parathormone and vitamin D status, a randomized controlled trial

Background Regional citrate anticoagulation may cause a negative calcium balance, systemic hypocalcemia and parathormone (PTH) activation but randomzed studies are not available. Aim was to determine the effect of citrate dose on calcium (Ca) and magnesium (Mg) balance, PTH and Vitamin D. Methods Single center prospective randomized study. Patients, requiring continuous venovenous hemofiltration (CVVH) with citrate, randomized to low dose citrate (2.5 mmol/L) vs. high dose (4.5 mmol/L) for 24 h, targeting post-filter ionized calcium (pfiCa) of 0.325–0.4 mmol/L vs. 0.2–0.275 mmol/L, using the Prismaflex® algorithm with 100% postfilter calcium replacement. Extra physician-ordered Ca and Mg supplementation was performed aiming at systemic iCa > 1.0 mmol/L. Arterial blood, effluent and post-filter aliquots were taken for balance calculations (area under the curve), intact (i), oxidized (ox) and non-oxidized (nox) PTH, 25-hydroxy-Vitamin D (25D) and 1,25-dihydroxy-Vitamin D (1,25D). Results 35 patients were analyzed, 17 to high, 18 to low citrate. Mean 24-h Ca balance was - 9.72 mmol/d (standard error 1.70) in the high vs − 1.18 mmol/d (se 1.70)) (p = 0.002) in the low citrate group and 24-h Mg-balance was − 25.99 (se 2.10) mmol/d vs. -17.63 (se 2.10) mmol/d (p = 0.008) respectively. Physician-ordered Ca supplementation, higher in the high citrate group, resulted in a positive Ca-balance in both groups. iPTH, oxPTH or noxPTH were not different between groups. Over 24 h, median PTH decreased from 222 (25th–75th percentile 140–384) to 162 (111–265) pg/ml (p = 0.002); oxPTH from 192 (124–353) to 154 pg/ml (87–231), p = 0.002. NoxPTH did not change significantly. Mean 25 D (standard deviation), decreased from 36.5 (11.8) to 33.3 (11.2) nmol/l (p = 0.003), 1,25D rose from 40.9 pg/ml (30.7) to 43.2 (30.7) pg/ml (p = 0.046), without differences between groups. Conclusions A higher citrate dose caused a more negative CVVH Ca balance than a lower dose, due to a higher effluent Calcium loss. Physician-ordered Ca supplementation, targeting a systemic iCa > 1.0 mmol/L, higher in the high citrate group, resulted in a positive Ca-balance in both groups. iPTH and oxPTH declined, suggesting decreased oxidative stress, while noxPTH did not change. 25D decreased while 1,25-D rose. Mg balance was negative in both groups, more so in the high citrate group. Trial registration ClinicalTrials.gov: NCT02194569. Registered 18 July 2014.

Continuous Renal Replacement Therapy among Patients with COVID-19 and Acute Kidney Injury

<b><i>Background and Objectives:</i></b> Acute kidney injury (AKI) is a common complication among patients with COVID-19 and acute respiratory distress syndrome. Reports suggest that COVID-19 confers a pro-thrombotic state, which presents challenges in maintaining hemofilter patency and delivering continuous renal replacement therapy (CRRT). We present our initial experience with CRRT in critically ill patients with COVID-19, emphasizing circuit patency and the association between fluid balance during CRRT and respiratory parameters. <b><i>Design, Setting, Participants, and Measurements:</i></b> Retrospective chart review of 32 consecutive patients with COVID-19 and AKI managed with continuous venovenous hemodiafiltration with regional citrate anticoagulation (CVVHDF-RCA) according to the University of Michigan protocol. Primary outcome was mean CRRT circuit life per patient during the first 7 days of CRRT. We used simple linear regression to assess the relationship between patient characteristics and filter life. We also explored the relationship between fluid balance on CRRT and respiratory parameters using repeated measures modeling. <b><i>Results:</i></b> Patients’ mean age was 54.8 years and majority were Black (75%). Comorbidities included hypertension (90.6%), obesity (70.9%) diabetes (56.2%), and chronic kidney disease (40.6%). Median CRRT circuit life was 53.5 [interquartile range 39.1–77.6] hours. There was no association between circuit life and inflammatory or pro-thrombotic laboratory values (ferritin <i>p</i> = 0.92, C-reactive protein <i>p</i> = 0.29, D-dimer <i>p</i> = 0.24), or with systemic anticoagulation (<i>p</i> = 0.37). Net daily fluid removal during the first 7 days of CRRT was not associated with daily (closest recorded values to 20:00) PaO₂/FIO₂ ratio (<i>p</i> = 0.21) or positive end-expiratory pressure requirements (<i>p</i> = 0.47). <b><i>Conclusions:</i></b> We achieved adequate CRRT circuit life in COVID-19 patients using an established CVVHDF-RCA protocol. During the first 7 days of CRRT therapy, cumulative fluid balance was not associated with improvements in respiratory parameters, even after accounting for baseline fluid balance.

Ionic homeostasis, acid-base balance and the risk of citrate accumulation in patients after cardiovascular surgery treated with continuous veno-venous haemofiltration with post-dilution regional citrate anticoagulation – An observational case-control stud

Background: Patients after cardiovascular surgery, requiring renal replacement therapy, can benefit from adequate non-heparin circuit anticoagulation. Simplified regional citrate anticoagulation (RCA) protocol proposes the use of citric acid dextrose formula A (ACD-A) during post-dilutional continuous veno-venous hemofiltration (CVVH) with standard bicarbonate buffered calcium containing replacement solution. Citrate accumulation diagnosed upon total to ionized calcium ratio (tCa/iCa) and low ionized calcium (iCa) are considered as the biggest risks related to regional citrate accumulation. Methods: This prospective observational case-control study evaluated electrolyte and acid-base homeostasis in cardiovascular surgery patients treated with post-dilution CVVH with a simplified RCA protocol with ACD-A. In total, 50 consecutive cardiovascular surgery patients were evaluated. Base excess, pH, bicarbonate, lactate, Na+, Cl-, Mg++, and inorganic phosphate concentrations, the total to ionized calcium ratio (tCa/iCa), and high anion gap metabolic acidosis were assessed during haemofiltration treatment in survivors and non-survivors. Results: Thirty-three (66%) patients died. The therapies were very well balanced in sodium and chloride homeostasis. The lactate concentration and anion gap decreased during CVVH sessions lasting longer than 72 hours, but no inter-group difference was observed. The tCa/iCa ratio exceeded 4.5% and was significantly higher in non-survivors (p=0.037). Initial lactate concentration did not correlate with tCa/iCa ratio during haemofiltration. Magnesium and phosphate concentrations decreased and additional supplementation with magnesium was necessary. The magnesium concentration was lower in the non-survivors. Conclusions: The incidence of citrate accumulation exceeded 4% and was significantly higher in non-survivors. Supplementation with magnesium and phosphate ions is needed in CVVH with RCA.

Monitoring of Enoxaparin during Hemodialysis Covered by Regional Citrate Anticoagulation in Acute Kidney Injury: A Prospective Cohort Study

Background: Current guidelines recommend the monitoring of anti-factor Xa (anti-Xa) levels to avoid an accumulation of low-molecular-weight heparins in patients with acute kidney injury, but there is no evidence on how to proceed with such monitoring during continuous renal replacement therapy. Against this background, we investigated the potential accumulation of enoxaparin administered subcutaneously for venous thromboembolism prophylaxis in critically ill patients during continuous renal replacement therapy covered by regional citrate anticoagulation. Methods: Anti-Xa levels were measured at baseline (≤12 h before renal replacement therapy) and on three consecutive days (A to C) when enoxaparin had reached trough levels. Supplementary testing included modified assays of rotational thromboelastometry known to be highly sensitive for low-molecular-weight heparins. Results: The 16 men and 13 women included were adults comparable in age, body mass index, thromboembolism risk assessment, and clinical severity of the disease. Throughout the four examinations, the median trough levels of anti-Xa remained below the detection limit of the test (<0.1 IU mL−1), with interquartile ranges of <0.1 to 0.14 IU mL−1 at baseline and <0.1 to 0.16 IU mL−1 on days A/B/C. All rotational thromboelastometry parameters of clot initiation and clot formation dynamics did not significantly change from baseline to day C. Conclusions: Neither anti-Xa levels nor modified assays of rotational thromboelastometry revealed any accumulation of enoxaparin administered for thromboprophylaxis during continuous renal replacement therapy covered by regional citrate anticoagulation. Although generally recommended in patients with acute kidney injury, monitoring of anti-Xa levels should be questioned in this defined setting.

Effect of Dynamic Circuit Pressures Monitoring on the Lifespan of Extracorporeal Circuit and the Efficiency of Solute Removal During Continuous Renal Replacement Therapy

Objective: To observe the effects of dynamic pressure monitoring on the lifespan of the extracorporeal circuit and the efficiency of solute removal during continuous renal replacement therapy (CRRT).Materials and Methods: A prospective observational study was performed at the West China Hospital of Sichuan University in the ICU. Analyses of the downloaded pressure data recorded by CRRT machines and the solute removal efficiencies, calculated by 2*Ce/(Cpre+Cpost), where Ce, Cpre, and Cpost are the concentrations of the effluent, pre-filter blood, and post-filter blood, respectively, were performed. Samples were collected at 0, 2, 6, 12, and 24 h when continuous veno-venous hemodiafiltration (CVVHDF) was used after the initiation of CRRT. Measurements in concentrations of creatinine, blood urea nitrogen, and β2-microglobulin in the plasma and effluent were recorded.Results: Extracorporeal circuits characterized by moderate-to-severe (M–S) access outflow dysfunction (AOD) events, defined as access outflow pressure less than or equal to −200 mmHg for more than 5 min, had shorter median lifespans with no anticoagulation (32.3 vs. 10.90 h, P = 0.001) compared with the no M–S AOD events group. The significant outcome also existed in regional citrate anticoagulation (RCA) (72 vs. 42.47 h, P = 0.02). Moreover, Cox regression analysis revealed that the lack of M–S AOD events, RCA, or CVVHDF independently prolonged the circuit lifespan. All tested solutes removal efficiencies started to decline at 12 h. Furthermore, efficiencies of all solutes removal dropped obviously at 24 h when TMP ≥ 150 mmHg.Conclusion: RCA and CVVHDF predicted a longer circuit lifespan. M–S AOD events were associated with a shorter circuit lifespan when RCA or no anticoagulant was used. Replacement of extracorporeal circuit could be considered when running time of filter lasted up to 24 h with TMP ≥ 150 mmHg.