Emerging Agents for Vasoplegia: Don’t Forget to Take Your Vitamins: B12

To the Editor In a recent issue of Anesthesia & Analgesia, Chow et al1 present a sophisticated narrative review of the pharmacology and clinical evidence for the use of vasopressors, both well-established and “emerging,” in the treatment of vasodilatory shock. The article evaluates medications that target widely known pathways (sympathetic nervous system, vasopressin system, corticosteroids, renin-angiotensin-aldosterone) as well as lesser elucidated ones (nitric oxide synthetase [NOS], guanylate cyclase, Krebs cycle). The authors emphasize the importance of targeting multiple receptors and biochemical pathways due to the occurrence of tachyphylaxis and the numerous potential causes of vasodilation. One possible mechanism implicated in vasodilatory shock is an exaggerated inflammatory response with over production of endogenous vasodilators (eg, nitric oxide). Among the “emerging” agents, the authors review methylene blue (MB), which targets dysregulated vasodilation via inhibition of NOS and guanylyl cyclase. However, its use may be limited in the setting of glucose-6-phosphate dehydrogenase deficiency and in patients at risk for serotonin syndrome.1 An alternative vasopressor to MB not mentioned by Chow et al,1 and one that is increasingly being used as rescue therapy in refractory vasodilatory shock, is high-dose vitamin B12 (hydroxocobalamin).2 Hydroxocobalamin was first approved for use in cyanide toxicity associated with smoke inhalation where its common side-effect of hypertension was initially described.3 This side-effect is now being exploited “off-label” to treat refractory vasoplegia via nitric oxide inhibition and scavenging, as well as through a direct inhibitory effect on NOS. An additional proposed mechanism is its inhibitory effect on hydrogen sulfide, a “gasotransmitter” that modifies potassium channels and acts as an endogenous vasodilator.2 Although it is not without potential side-effects (eg, laboratory abnormalities, chromaturia, erythema, headache, and photophobia), and its use has been limited to mostly case reports/series,2–4 hydroxocobalamin is another emerging agent for vasodilatory shock. Though the current evidence base lacks high-quality trials, we believe it is important for the reader to be aware of its potential application as a reasonable alternative to MB in refractory vasoplegia, particularly in patients with a contraindication to MB. Duncan Maguire, MDDouglas Maguire, MD, FRCPCDepartment of Anesthesiology, Perioperative and Pain MedicineUniversity of ManitobaWinnipeg, Manitoba[email protected]

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