Hydroxocobalamin Versus Methylene Blue for Vasoplegic Syndrome in Cardiothoracic Surgery: A Retrospective Cohort

J Cardiothorac Vasc Anesth. 2020 Jul;34(7):1763-1770. doi: 10.1053/j.jvca.2020.01.033. Epub 2020 Jan 23.


Objective: To compare methylene blue with hydroxocobalamin as a rescue therapy for vasoplegic syndrome.

Design: Retrospective cohort.

Setting: Academic medical center.

Participants: Patients undergoing cardiothoracic surgery treated for vasoplegic syndrome.

Interventions: Thirty-five patients were treated with methylene blue (n = 16) or hydroxocobalamin (n = 19).

Measurements and main results: Mean arterial pressure, systemic vascular resistance, and vasopressor exposures were recorded before and after medication administration. Change in time-averaged norepinephrine equivalents in the hour after administration was the primary outcome. The average norepinephrine equivalent observed at baseline in this cohort was 0.347 µg/kg/min. Methylene blue patients had greater Acute Physiological Assessment and Chronic Health Evaluation II scores (29.8 v 22.2; p = 0.01) and trended toward greater European System for Cardiac Operative Risk Evaluation II values (26.8% v 15.1%; p = 0.07). Methylene blue and hydroxocobalamin were associated with increased mean arterial pressure and systemic vascular resistance 1 hour after administration (10.6 mmHg and 192 dyn*sec/cm5; p = 0.01 and p = 0.01, respectively; 11.8 mmHg and 254 dyn*sec/cm5; p = 0.002 and p = 0.015, respectively). Hemodynamic changes were not different between the rescue therapy groups (p = 0.79 and p = 0.53, respectively). No significant differences were observed within the 1-hour change in time-averaged norepinephrine equivalents for either agent or when methylene blue and hydroxocobalamin were compared (0.012 ± 0.218 µg/kg/min v -0.037 ± 0.027 µg/kg/min; p = 0.46, respectively). When compared with baseline time-averaged norepinephrine equivalent (0.326 ± 0.106 µg/kg/min), only hydroxocobalamin was associated with decreased vasopressor requirements at the 1-hour (0.255 ± 0.129 µg/kg/min; p = 0.03) and 4-hour time points (0.247 ± 0.180 µg/kg/min; p = 0.04) post-administration.

Conclusion: Methylene blue and hydroxocobalamin increased mean arterial pressures and systemic vascular resistance without significantly decreasing time-averaged norepinephrine exposure in the hour after administration.

Keywords: anesthesia; cardiothoracic surgery; hydroxocobalamin; methylene blue; vasoplegia; vasoplegic syndrome.

MeSH terms

  • Humans
  • Hydroxocobalamin*
  • Methylene Blue
  • Retrospective Studies
  • Vascular Resistance
  • Vasoplegia* / diagnosis
  • Vasoplegia* / drug therapy
  • Vasoplegia* / etiology


  • Hydroxocobalamin
  • Methylene Blue