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Updated: Feb 10, 2026

Acetylcholine Re-Challenge After Intracoronary Nitroglycerine Administration
Published on: April 4, 2022
Reversible Microvascular Hyporeactivity to Acetylcholine During Diabetic Ketoacidosis
Jérémie Joffre1,2,3, Simon Bourcier1, Geoffroy Hariri1
1Medical Intensive Care Unit, Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris, 75571 Paris Cedex 12, France.
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.
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