B12 -as a medication- has also been used by intensive care doctors in severely ill people. There are several interesting papers on the use of hydroxocobalamin for people who suffer from (refractory) vasoplegia after cardiopulmonary bypass surgery, heart surgery. Vasoplegia (vascular shock) is a clinical syndrome characterised by severe vasodilatation (widening of the blood vessels) of the smaller arteries and arterioles, hypotension (very low blood pressure), and low systemic vascular resistance that does not respond to treatments with multiple vasopressor medications, medications that should promote the vessels to get narrower and blood pressure to increase. We have selected three papers in this area:

The 2018 Shah paper:
Shah PR, Reynolds PS, Pal N, Tang D, McCarthy H, Spiess BD. Hydroxocobalamin for the treatment of cardiac surgery-associated vasoplegia: a case series. Can J Anaesth. 2018 May;65(5):560-568. English. doi: 10.1007/s12630-017-1029-3. Epub 2017 Dec 5. PMID: 29209927.
Link: https://link.springer.com/article/10.1007/s12630-017-1029-3

In this paper, the authors from Richmond, Virginia, report their experience with hydroxocobalamin (B12) infusion as a potential rescue adjunct for refractory vasoplegia during cardiopulmonary bypass (CPB), in a retrospective cohort of 33 patients, undergoing cardiac surgery between 1 January 2013 and 31 December 2015, who were given intravenous B12 for refractory hypotension during, or immediately following, CPB. Patients received methylene blue and/or reconstituted hydroxocobalamin (5 g, Cyanokit), administered as an intravenous bolus over 15 min.
The overall finding and conclusion of the paper is that there was considerable diversity in the response of an individual to B12; the authors suggested that this may have depended on both the patient’s preoperative condition and the fact that the timing of the administration was not standardized. Nevertheless, in their opinion, vitamin B12 may provide a useful alternative or additional therapy to treat refractory hypotension and vasoplegia, but -as they were looking back- they state that prospective controlled clinical trials to assess the true efficacy of the therapy are needed.

A second paper on this topic (figure 3) was published in 2025 by a group of doctors in Cairo, Egypt, and it describes the prophylactic use of hydroxocobalamin in patients at high risk of developing vasoplegia after cardiopulmonary bypass. So, a high dose of B12 is administered to assess whether this can prevent severe illness.

Salah D, Ahmed S, Ibrahim DA. Use of Hydroxycobolamin in the Prevention of Vasoplegic Syndrome in Adult Patients Undergoing Cardiopulmonary Bypass: A Controlled Prospective Trial. J Cardiothorac Vasc Anesth. 2025 May;39(5):1180-1187. doi: 10.1053/j.jvca.2025.02.001. Epub 2025 Feb 5. PMID: 40055025.
Link: https://www.jcvaonline.com/article/S1053-0770(25)00114-4/abstract

How did they treat the participants? At the end of cardiopulmonary bypass (CPB), the participants were assigned by chance into two groups: 30 individuals in group I received hydroxocobalamin 5 g intravenously via the central venous catheter as a bolus over 15 minutes reconstituted in 200 ml of normal saline, and 30 individuals in group II (the so-called ‘control group’) received 200 mL of normal saline intravenously over 15 minutes. When they collected all information, it turned out that the B12 prevention group showed higher arterial blood pressure 30 and 60 minutes after CPB separation, they required lower amounts of vasopressor treatment (norepinephrine) at minutes 30 and 60 after CPB separation, as well as total dose norepinephrine equivalent. Also, lower serum lactate concentrations (a sign of poor blood perfusion of the body’s tissues), and lower incidence of vasoplegic shock syndrome and norepinephrine-resistant refractory vasoplegia were noted. The number of days that a patient neededa rtifical ventilation (3.8 vs 4.1 days), the length of stay in the intensive care unit (6.2 vs 7.0 days), the length of the stay in the hospital, and the number of participants who did not survive this severe illness (1 of 30 vs 3 of 30) were lower or less frequent in the B12 group, but the authors note that these differences were not statistically significant.


The third paper which we discuss briefly, is a recent article from a group of doctors in Pittsburgh, PA, USA.

Teletnick A, Suh K, Boisen M, Brown JA, Cabral B, Murray H, Paley C, Sullinger D, Sultan I, Thoma F, Williams J, Subramaniam K, Rivosecchi RM. Evaluating the Impact of a Standardized Protocol for Managing Refractory Vasoplegia After Cardiopulmonary Bypass. J Cardiothorac Vasc Anesth. 2026 Feb 6:S1053-0770(26)00110-2. doi: 10.1053/j.jvca.2026.02.003. Epub ahead of print. PMID: 41765732.
Link: https://www.jcvaonline.com/article/S1053-0770(26)00110-2/fulltext

This article describes a prospective evaluation of the haemodynamic impact and cost-effectiveness of a standardized protocol for treating people who develop refractory vasoplegia after cardiopulmonary bypass. In this paper, refractory vasoplegia was defined as at least 0.25 μg/kg/min norepinephrine equivalents (NEeq), and a stepwise rescue treatment protocol was developed, starting with methylene blue, then giving angiotensin II and subsequently hydroxocobalamin (see figure 4).

The authors assessed the effects of the rescue intervention by looking back in time and comparing patients undergoing CPB after the implementation of this new protocol with those undergoing CPB before protocol implementation, the latter group receiving rescue agents at the discretion of the managing ICU doctor. Again, the hydroxocobalamin dose was 5 g, the so-called Cyanokit.

Their findings in short: they observed a faster reduction in vasopressor therapy and lower associated costs of the treatment with the rescue intervention. They did, however, not find any differences in short-term clinical outcomes between groups.
It appears that hydroxocobalamin has an important role in these critically ill patients. However, several additional questions arise. For example, is there an optimal dose of hydroxocobalamin, and, also, can repeated administrations of B12 add to a prolonged or sustained effect?

Another interesting aspect is that of pre-operative B12 status. Are individuals undergoing surgery while having B12 insufficiency or deficiency at higher risk of developing vasoplegia? We hope that the results described in these papers will encourage more researchers and clinicians to explore the intriguing effects of B12.