title: Hyperlactatemia Predicts Citrate Intolerance With Regional Citrate Anticoagulation During Continuous Renal Replacement Therapy.
abstract: We aim to determine whether hyperlactatemia, which suggests multi-organ dysfunction and impaired organic substrate metabolism, may predict intolerance to regional citrate anticoagulation (RCA) during continuous venovenous hemofiltration (CVVH).
  We performed a single-center, retrospective observational study in critically ill patients with acute kidney injury or end-stage renal disease and evaluated the association of peak serum lactate levels with citrate intolerance (CI) during the initial 72 hours of RCA-CVVH, defined by serum total-to-ionized calcium >2.5 plus systemic hypocalcemia.
  Eighty-eight patients were studied (aged 59 ± 14 years, 66% males, Acute Physiology and Chronic Health Evaluation II: 31 ± 8). Citrate was dosed at median 2.1 mmol/L of blood flow, with citrate load of 30 mmol/h, and CVVH effluent of 43 mL/kg/h. Twenty patients developed CI. Comparing patients with CI versus none, peak lactate levels were 8 (5-11) versus 3 (2-6) mmol/L, calcium replacement was 13 (10-17) versus 11 (8-12) mmol/h, and standard base excess was -4 (-12 to 1) versus 2(-4 to 7) mmol/L, respectively ( P < .05). Citrate intolerance developed in 38%, 44%, and 55%, in patients with peak lactate >4, >6, >7 mmol/L, respectively, versus 7% in those with peak lactate ≤4 mmol/L ( P ≤ .001), despite comparable citrate load and effluent rates across all categories. On multivariate analysis, hyperlactatemia and hyperbilirubinemia predicted CI ( P ≤ .01), which was associated with increasing calcium infusion requirement. Higher peak lactate from >4 to >7 mmol/L predicted CI with graded increase in odds ratio and specificity from 59% to 87%, but the corresponding negative predictive value from 93% to 87%. Area under nonparametric receiver operating characteristic curve for peak lactate and CI was 0.78.
  Hyperlactatemia predicts CI during RCA-CVVH with reasonable discriminatory performance in critically ill patients. Serum lactate surveillance may help preempt issues with citrate toxicity.
authors.affiliation: 1 Division of Nephrology, University Medicine Cluster, National University Hospital, Republic of Singapore.|2 Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Republic of Singapore.
authors.forename: Jia-Neng
authors.initials: JN
authors.lastname: Tan
authors.affiliation: 1 Division of Nephrology, University Medicine Cluster, National University Hospital, Republic of Singapore.|2 Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Republic of Singapore.
authors.forename: Sabrina Wong Peixin
authors.initials: SWP
authors.lastname: Haroon
authors.affiliation: 2 Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Republic of Singapore.|3 Division of Respiratory and Critical Care Medicine, University Medicine Cluster, National University Hospital, Republic of Singapore.
authors.forename: Amartya
authors.initials: A
authors.lastname: Mukhopadhyay
authors.affiliation: 1 Division of Nephrology, University Medicine Cluster, National University Hospital, Republic of Singapore.|2 Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Republic of Singapore.
authors.forename: Titus
authors.initials: T
authors.lastname: Lau
authors.affiliation: 1 Division of Nephrology, University Medicine Cluster, National University Hospital, Republic of Singapore.|2 Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Republic of Singapore.
authors.forename: Tanusya M
authors.initials: TM
authors.lastname: Murali
authors.affiliation: 2 Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Republic of Singapore.|3 Division of Respiratory and Critical Care Medicine, University Medicine Cluster, National University Hospital, Republic of Singapore.
authors.forename: Jason
authors.initials: J
authors.lastname: Phua
authors.affiliation: 4 National University of Singapore High School of Mathematics and Science, Republic of Singapore.
authors.forename: Zong-Yao
authors.initials: ZY
authors.lastname: Tan
authors.affiliation: 4 National University of Singapore High School of Mathematics and Science, Republic of Singapore.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Lee
authors.affiliation: 1 Division of Nephrology, University Medicine Cluster, National University Hospital, Republic of Singapore.|2 Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Republic of Singapore.
authors.forename: Horng-Ruey
authors.initials: HR
authors.lastname: Chua
mesh_terms: D018806:APACHE; D058186:Acute Kidney Injury / Q000097:blood / Q000150:complications / Q000628:therapy; D000368:Aged; D000925:Anticoagulants / Q000494:pharmacology*; D019343:Citric Acid / Q000494:pharmacology*; D004361:Drug Tolerance / Q000502:physiology*; D005260:Female; D006801:Humans; D065906:Hyperlactatemia / Q000209:etiology / Q000378:metabolism*; D007676:Kidney Failure, Chronic / Q000097:blood / Q000150:complications / Q000628:therapy; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis / Q000009:adverse effects* / Q000379:methods; D012189:Retrospective Studies
chemical_list: D000925:Anticoagulants; D019343:Citric Acid
keywords: acute kidney injury; citrate toxicity and intolerance; continuous renal replacement therapy; critical care; hemodialysis; hyperlactatemia; intensive care unit; lactate and shock; regional citrate anticoagulation