Hyperlactatemia Predicts Citrate Intolerance With Regional Citrate Anticoagulation During Continuous Renal Replacement Therapy

J Intensive Care Med. 2019 May;34(5):418-425. doi: 10.1177/0885066617701068. Epub 2017 Apr 4.

Abstract

Purpose:: 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).

Methods:: 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.

Results:: 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.

Conclusion:: Hyperlactatemia predicts CI during RCA-CVVH with reasonable discriminatory performance in critically ill patients. Serum lactate surveillance may help preempt issues with citrate toxicity.

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.

Publication types

  • Observational Study

MeSH terms

  • APACHE
  • Acute Kidney Injury / blood
  • Acute Kidney Injury / complications
  • Acute Kidney Injury / therapy
  • Aged
  • Anticoagulants / pharmacology*
  • Citric Acid / pharmacology*
  • Drug Tolerance / physiology*
  • Female
  • Humans
  • Hyperlactatemia / etiology
  • Hyperlactatemia / metabolism*
  • Kidney Failure, Chronic / blood
  • Kidney Failure, Chronic / complications
  • Kidney Failure, Chronic / therapy
  • Male
  • Middle Aged
  • Renal Dialysis / adverse effects*
  • Renal Dialysis / methods
  • Retrospective Studies

Substances

  • Anticoagulants
  • Citric Acid