Standard versus no post-filter ionized calcium monitoring in regional citrate anticoagulation for continuous renal replacement therapy (NPC trial).

Background: Current guidelines recommend monitoring of post-filter ionized calcium (pfCa) when using regional citrate anticoagulation during continuous renal replacement therapy (RCA-CRRT) to determine citrate efficiency for the prevention of filter clotting. However, the reliability of pfCa raises the question of whether routine monitoring is required. Reducing the frequency of pfCa monitoring could potentially reduce costs and workload. Our objective was to test the efficacy and safety of no pfCa monitoring among critically ill patients receiving RCA-CRRT. Methods: This study was a non-inferiority randomized controlled trial conducted between January 2021 and October 2021 at King Chulalongkorn Memorial Hospital, Thailand. Critically ill patients who were treated with RCA-CRRT were randomized to receive either standard pfCa monitoring (aiming pfCa level of 0.25-0.35 mmol/L), or no pfCa monitoring, in which a constant rate of citrate infusion was maintained at pre-determined citrate concentrations of 4 mmol/L with blinding of pfCa levels to treating clinicians. The primary outcome was the filter lifespan. Non-inferiority would be demonstrated if the upper limit of the 95% confidence interval (CI) for the difference in filter lifespan between the groups was less than 20 h. Results: Fifty patients were randomized to the standard pfCa monitoring group (n = 25) or no pfCa monitoring group (n = 25). The mean filter lifespan was 54 ± 20 h in the standard pfCa monitoring group and 47 ± 23 h in the no pfCa monitoring group (absolute difference 7.1 h; 95% CI -5.3, 19.5, P = .25). When restricting the analysis to circuits reaching the maximum duration of circuit lifespan at 72 h and clotted filters, the filter lifespan was 61 ± 17 h in the standard pfCa group vs 60 ± 19 h in the no pfCa monitoring group (absolute difference 0.9 h; 95% CI -11.5, 13.4, P = .88). Compared with the no pfCa monitoring group, the standard pfCa monitoring group had a significantly higher mean citrate concentrations (4.43 ± 0.32 vs 4 mmol/L, P < .001) and a higher rate of severe hypocalcemia (44% vs 20%, P = .13). No statistical differences were found in filter clotting, citrate accumulation, citrate overload and mortality between the two groups. Conclusions: Among critically ill patients receiving RCA-CRRT, no pfCa monitoring by maintaining the citrate concentrations of 4 mmol/L is feasible. Larger randomized controlled trials should be conducted to ensure the efficacy, safety and cost-effectiveness of this strategy. Trial registration: ClinicalTrials.gov: NCT04792424 (registered 11 March 2021).

Immunomodulation Effect of Regional Citrate Anticoagulation in Acute Kidney Injury Requiring Renal Replacement Therapy.

INTRODUCTION: Acute kidney injury (AKI) is a common syndrome in critically ill patients. Continuous renal replacement therapy (CRRT) is the standard treatment for patients with AKI. Research on the immunomodulating effects of regional citrate anticoagulation (RCA) remains limited in patients with AKI receiving CRRT. We aimed to evaluate the immunomodulating effects of RCA in patients with AKI receiving CRRT. METHODS: A randomized controlled trial study on critically ill adult patients with AKI undergoing CRRT was undertaken. Participants were randomized into either a regional citrate group or control group (either heparin anticoagulant or normal saline). Measurements were taken at baseline, 6 and 24 h after commencing CRRT for CD11b expression, C3a, C5a, and plasminogen activator inhibitor-1 (PAI-1) levels. Clinical outcomes assessed were 28-day survival rate, length of ICU stay, renal support duration, and renal function at discharge. RESULTS: Thirty patients were recruited and randomized into 2 groups of 15 subjects. Baseline demographic and clinical data were comparable between groups. In the citrate group, CD11b expression was significantly decreased at 24 h compared to the control group (1.84% [1.18-3.32] versus 4.92% [2.63-6.93], p < 0.01). The complement level, including c3b and c5a, was stable during CRRT. Additionally, the PAI-1 levels were significantly decreased at 24 h compared to the control group (114 ng/mL [19-193] versus 359 ng/mL [264-491], p < 0.01). No significant difference in survival rate was observed. CONCLUSIONS: RCA may have the potential to mitigate the inflammatory response by decreasing CD11b expression of neutrophil and improve fibrinolysis activity through a reduction of PAI-1 levels. Larger clinical trials are warranted to test this immunomodulation effect of RCA.

Higher blood pressure versus normotension targets to prevent acute kidney injury: a systematic review and meta-regression of randomized controlled trials.

BACKGROUND: Renal hypoperfusion is one of the most common causes of acute kidney injury (AKI), especially in shock and perioperative patients. An optimal blood pressure (BP) target to prevent AKI remains undetermined. We conducted a systematic review and meta-analysis of available randomized clinical trial (RCT) results to address this knowledge gap. METHODS: From inception to May 13, 2022, we searched Ovid Medline, EMBASE, Cochrane Library, SCOPUS, clinicaltrials.gov, and WHO ICTRP for RCTs comparing higher BP target versus normotension in hemodynamically unstable patients (shock, post-cardiac arrest, or surgery patients). The outcomes of interest were post-intervention AKI rate and renal replacement therapy (RRT) rate. Two investigators independently screened the citations and reviewed the full texts for eligible studies according to a predefined form. RESULTS: Twelve trials were included, enrolling a total of 5759 participants, with shock, non-cardiac, and cardiac surgery patients accounting for 3282 (57.0%), 1687 (29.3%) and 790 (13.7%) patients, respectively. Compared to lower mean arterial blood pressure (MAP) targets that served as normotension, targeting higher MAP had no significant effect on AKI rates in shock (RR [95% CI] = 1.10 [0.93, 1.29]), in cardiac-surgery (RR [95% CI] = 0.87 [0.73, 1.03]) and non-cardiac surgery patients (RR [95% CI] = 1.25 [0.98, 1.60]) using random-effects meta-analyses. In shock patients with premorbid hypertension, however, targeting MAP above 70 mmHg resulted in significantly lower RRT risks, RR [95%CI] = 1.20 [1.03, 1.41], p < 0.05. CONCLUSIONS: Targeting a higher MAP in shock or perioperative patients may not be superior to normotension, except in shock patients with premorbid hypertension. Further studies are needed to assess the effects of a high MAP target to preventing AKI in hypertensive patients across common settings of hemodynamic instability. Trial registration This systematic review has been registered on PROSPERO ( CRD42021286203 ) on November 19, 2021, prior to data extraction and analysis.