Reversible Microvascular Hyporeactivity to Acetylcholine During Diabetic Ketoacidosis

Crit Care Med. 2018 Aug;46(8):e772-e778. doi: 10.1097/CCM.0000000000003224.

Abstract

Objectives: Metabolic acidosis is commonly observed in critically ill patients. Experimental studies suggested that acidosis by itself could impair vascular function, but this has been poorly investigated in human.

Design: Prospective observational study.

Setting: Medical ICU in a tertiary teaching hospital.

Patients: To assess the relationship between metabolic acidosis severity and microvascular reactivity, we included adult diabetic patients admitted in ICU for ketoacidosis. Microvascular response to acetylcholine iontophoresis was measured at admission (baseline) and after correction of metabolic acidosis (24 hr).

Interventions: None.

Measurements and main results: Thirty-nine patients with diabetic ketoacidosis were included (68% male), with a median age of 43 (31-57) years. At admission, microvascular reactivity negatively correlated with acidosis severity (R = -0.53; p < 0.001). Microvascular response was strongly depressed at pH less than 7.20 (area under the curve, 1,779 [740-3,079] vs 12,944 [4,874-21,596] at pH > 7.20; p < 0.0001). In addition, acidosis severity was significantly correlated with capillary refill time (R = 0.50; p = 0.02). At H24, after rehydration and insulin infusion, clinical and biological disorders were fully corrected. After acidosis correction, microvascular reactivity increased more in patients with severe baseline acidosis (pH < 7.20) than in those with mild baseline acidosis (area under the curve, +453% [213%-1,470%] vs +121% [79%-312%]; p < 0.01).

Conclusions: We identified an alteration of microvascular reactivity during metabolic acidosis in critically ill patients with diabetic ketoacidosis. Microvascular hyporeactivity recovered after acidosis correction.

Publication types

  • Observational Study

MeSH terms

  • Acetylcholine / pharmacology*
  • Adult
  • Critical Illness
  • Diabetic Ketoacidosis / drug therapy
  • Diabetic Ketoacidosis / physiopathology*
  • Diabetic Ketoacidosis / therapy*
  • Endothelium, Vascular / drug effects
  • Female
  • Fluid Therapy / methods
  • Humans
  • Insulin / therapeutic use
  • Intensive Care Units
  • Iontophoresis
  • Male
  • Microvessels / drug effects*
  • Middle Aged
  • Prospective Studies
  • Severity of Illness Index
  • Tertiary Care Centers

Substances

  • Insulin
  • Acetylcholine