Hydroxocobalamin

We hypothesized that the prophylactic use of hydroxocobalamin in patients at high-risk patients to develop vasoplegia after cardiopulmonary bypass (CPB) may decrease its incidence.

This randomized placebo-controlled prospective single-center study was conducted on high-risk patients for vasoplegia who underwent coronary artery bypass grafting (CABG).

This study was conducted in Ain Shams University Hospitals from August 2019 to October 2023 in cardiothoracic operative rooms and its intensive care unit.

Patients included in the study were 18 to 60 years old and undergoing CABG and/or valve surgery on CPB and had 2 or more preoperative risk factors for vasoplegia. They were receiving using preoperative β-blocker or angiotensin-converting enzyme inhibitor with a preoperative ejection fraction of less than 35% and a history of thyroid disease and preoperative diuretics.

At the end of CPB, the patients were assigned randomly into two groups: group I consisted of 30 patients who received hydroxocobalamin 5 g intravenously via the central venous catheter as a bolus over 15 minutes reconstituted in 200 mL of normal saline, and group II (control) consisted of 30 patients who received 200 mL of normal saline intravenously over 15 minutes.

The primary outcome was the change in mean arterial pressure between baseline and all time points (30 and 60 minutes after CPB initiation and 30 and 60 minutes after CPB separation) between the two groups and within the same group. The comparison regarding the change in systemic venous resistance between baseline and all time points (30 and 60 minutes before CPB initiation and 30 and 60 minutes after CPB separation) between the two groups and within the same group is calculated. Cardiac index was calculated 30 min before CPB initiation and 30 min after CPB separation. Doses of norepinephrine and its equivalent, incidence of vasoplegic shock syndrome, serum lactate, number of ventilator days, intensive care unit length of stay, hospital length of stay, incidence of norepinephrine-resistant refractory vasoplegia, acute kidney injury, shock liver and mortality in 1 week were calculated. Results showed that mean arterial pressure and systemic venous resistance at minutes 30 and 60 after CPB separation was significantly higher in group I compared to group II. Cardiac index was significantly lower in group I compared to group II. Norepinephrine requirements (µg/kg/min) at minutes 30 and 60 after CPB separation as well as average total dose norepinephrine equivalent were significantly lower in group I. Serum lactate was also found to be significantly lower in group I. Incidence of vasoplegic shock syndrome, norepinephrine-resistant refractory vasoplegia, number of ventilator days, intensive care unit length of stay, hospital length of stay, acute kidney injury, shock liver, and mortality was less frequent in group I, but the differences were statistically significant only for vasoplegia and refractory vasoplegia.

This study showed that prophylactic hydroxocobalamin can be used effectively to decrease the incidence of vasoplegic syndrome, and total vasopressor dose, as well as improve tissue perfusion in high-risk patients in cardiac surgeries.

In this report, we present the case of a 16‐month‐old patient who was diagnosed with cobalamin G deficiency at 4 months of age via whole exome sequencing by detecting compound heterozygous variants of uncertain significance (VUS) in the MTR gene: (1) c.1283T>A, p.Met428Lys; (2) c.2411T>C, p.Ile804Thr. Before the diagnosis, the initial clinical presentation included failure to thrive, skin hyperpigmentation, hypotonia, seizures, and developmental delay. We initiated the treatment with high‐dose parenteral hydroxocobalamin, oral betaine, and folinic acid at 5 months of age (right after receiving WES report). His symptoms, such as skin hyperpigmentation, seizure resolution, developmental delay, and anemia, improved rapidly after the treatment initiation. With treatment, his homocysteine levels declined rapidly and significantly from 117.08 μmol/L at 5 months to 20.23 μmol/L at 5 months and 2 weeks of age. Further, methionine levels increased with treatment from 9.26 μM at 5 months to 14.05 μM at 5 months and 2 weeks of age. The patient is currently receiving intramuscular hydroxocobalamin (2 mg/kg), oral betaine (200 mg/kg), and oral folinic acid (7.5 mg) daily without adverse effects. This case demonstrates the safety and efficacy of early high‐dose parenteral hydroxocobalamin, and oral betaine and folinic acid treatment for cobalamin G deficiency. Moreover, given the patient's clinical manifestations, serologic data, and rapid response to therapy, the MTR gene variant previously classified as a VUS should be reclassified as pathogenic and necessitating early diagnosis and treatment.