Thanks for listening to our pilot episode
Here is a handout made by the SRNA who presented the case
Vasoplegic syndrome: severe, persistent hypotension refractory to fluids and pressors, characterized by arterial hypotension in the setting of a normal/high CO and low SVR.
Vasoplegic syndrome is ultimately caused by overproduction of nitric oxide and/or guanylate cyclase and cGMP.
Substrate: L-arginine
Nitric oxide synthase converts L-arginine to nitric oxide
Nitric oxide causes the activation of guanylyl cyclase
Cyclic GMP activates cGMP-dependent protein kinase
This leads to inhibition of calcium release, inhibition of calcium-sensitive potassium channels, decreased sensitivity to myosin
Through these mechanisms, relaxation of vascular smooth muscle occurs
Ultimately: decreased SVR, hypotension
Associated pathophysiologies and interventions
Anaphylaxis
Burns
Sepsis
Iatrogenic/pharmaceutical
Bypass for cardiac surgery/ICU care
Blood transfusion
ACE-I and ARBs
Amiodarone Calcium channel blockers
Metformin-induced lactic acidosis
Evidence for methylene blue as a treatment for vasoplegia is within Category B (moderate-quality evidence), with a Class IIb recommendation (weak, but benefits > risks) for its clinical use in patient care.
Dose: 1-3mg/kg over 10-60 minutes
Splanchnic perfusion may be decreased at 7mg/kg
Lethal dose is 40mg/kg
Benefits
Significant increase in mean arterial pressure
Reduction of vasopressor and inotropic requirements
Reverses myocardial depression
Reduced mortality and morbidity
Contraindications
MAOI therapy (serotonin syndrome)
G6PD deficiency (hemolytic anemia)
Severe renal failure (impairment in excretion of methylene blue & metabolites)
Hypersensitivity (anaphylaxis)
Pregnancy (reports of teratogenicity w/ intra-amniotic use, fetal hypoxia 2/2 increased placental NO leading to decreased placental perfusion)
Risks
Hepatic
Altered medication metabolism due to inhibition of cytochrome P450 isoenzymes
Induced hyperbilirubinemia
Pulmonary
Increased pulmonary vascular resistance
Inhibition of hypoxic pulmonary vasoconstriction
Blue/greenish discoloration of skin and urine
Interference with pulse oximetry
References
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Gachot B, Bedos J, Veber B, Wolff M, Reginer B. Short-term effects of methylene blue on hemodynamics and gas exchange in humans with septic shock. Intensive Care Medicine 1995; 21:1027-1031.
Grahm R, Cartner M, Winearls J. A severe case of vasoplegic shock following metformin overdose successfully treated with methylene blue as a last line therapy. BMJ Case Reports, 2015; doi:10.1136/bcr-2015-210229
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Methylene Blue. In: IBM Micromedex® DRUGDEX® (electronic version). Truven Health Analytics, Greenwood Village, Colorado, USA. Available at: http://www.micromedexsolutions.com.liboff.ohsu.edu/ (cited: 06/08/2018).
Pasin LU, M.; Greco, T.; Zambon, M.; Pappalardo, F.; Crivellari, M.; Borghi, G.; Morelli, A.; Zangrillo, A.; Landoni, G.;. Methylene blue as a vasopressor: A meta-analysis of randomised trials. Journal of the Australasian Academy of Critical Care Medicine. 2013.
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Perrinez P, Cox J, Harrell T, Nayak KR. Vasoplegic Syndrome during Left Atrial Appendage Occlusion: Early Recognition and Therapeutic Options for Catecholamine Refractory Hypotension in the Perioperative Setting. J Am Coll Cardiol. 2018;71(11).
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