UK Clinical Pharmacy Association


Issues for surgery

Risk of anaemia related post-operative complications if discontinued for a prolonged period pre-operatively.

Risk of demyelination and neurological symptoms, which could be exacerbated by use of nitrous oxide anaesthesia, if vitamin B12 deficiency not diagnosed and treated – see Further Information.

Advice in the perioperative period

Elective and emergency surgery 

For intramuscular preparations confirm frequency and date of next dose with patient.

Pre-operative initiation

Screen for anaemia pre-operatively as early as possible in the patient’s pathway if surgery is anticipated to result in more than 500ml blood loss. Follow diagnostic algorithm in Centre of Perioperative Care Guidelines to determine type of anaemia. It is recommended that diagnosis is confirmed before treatment is commenced to avoid masking a folate deficiency.

Post-operative advice

For oral preparations

Restart post-operatively when enteral intake resumes.

For intramuscular preparations

Restart post-operatively when next dose due.

Patients undergoing gastrectomy/bariatric surgery

Review the need to start hydroxocobalamin supplementation post-operatively in patients who have undergone total, or possibly partial, gastrectomy and patients who have undergone bariatric surgery (see Further Information).

Interactions with common anaesthetic agents


Interactions with other common medicines used in the perioperative period


Further information

Nitrous oxide

Nitrous oxide irreversibly chelates cobalamin (vitamin B12) preventing it acting as a coenzyme in the production of components needed for myelin formation. There have been several reports of myelopathy developing 2-6 weeks after nitrous oxide anaesthesia in patients with an underlying, untreated vitamin B12 deficiency. The Medicines and Healthcare products Regulatory Agency advise assessing vitamin B12 levels before nitrous oxide anaesthesia in patients with risk factors for deficiency, e.g., elderly, poor or vegetarian diet and history of anaemia.

Recreational use of nitrous oxide is increasingly common; chronic abuse of nitrous oxide has also been linked to vitamin B12 deficiency and associated neurological sequalae.

Patients undergoing gastrectomy/bariatric surgery

Vitamin B12 deficiency can develop following surgical procedures which result in decreased acid production and reduced availability of intrinsic factor, which is produced by parietal cells (e.g., gastrectomy, sleeve gastrectomy, gastric bypass, biliopancreatic diversion (BPD) and duodenal switch (DS) surgeries) as absorption is adversely affected and stores are depleted over time. Despite the absence of evidence-based recommendations, vitamin B12 supplementation is usually recommended after gastric bypass, sleeve gastrectomy, BPD and DS surgeries and considered after total/partial gastrectomy. 


Safari A, Emadi F, Jamali E et al. Clinical and MRI manifestations of nitrous oxide induced vitamin B12 deficiency: A case report. Iranian Journal of Neurology 2013; 12(3): 111-113

Centre for Perioperative Care. Guideline for the Management of Anaemia in the Perioperative Pathway (September 2022). Available at: [Accessed on 7th September 2022]

Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press. [Accessed on 27th August 2022]

Summary of Product Characteristics – Cobalin-H® (hydroxocobalamin) Injection. ADVANZ Pharma. Accessed via 27/08/2022 [date of revision of the text January 2018]

Baxter K, Preston CL (eds), Stockley’s Drug Interactions (online) London: Pharmaceutical Press. [Accessed on 27th August 2022]

Medicines and Healthcare products Regulatory Agency. Drug Safety Update. Nitrous oxide: neurological and haematological toxic effects. Published 11th December 2014. Available at [Accessed 27th August 2022]

Shoults K. Case report: Neurological complications of nitrous oxide abuse. BC Medical Journal 2016; 58(4): 192-194

O’Kane M, Paretti H.M, Pinkney J et al. British Obesity and Metabolic Surgery Society Guidelines on perioperative and postoperative biochemical monitoring and micronutrient replacement for patients undergoing bariatric surgery – 2020 update. Obesity Reviews. 2020;21:e1307. DOI: 10.1111/obr.13087

Busetto L, Dicker D, Azran C et al. Practical Recommendations of the Obesity Management Task Force of the European Association for the Study of Obesity for the Post-Bariatric Surgery Medical Management. Obesity Facts 2017;10:597 – 632. DOI: 10.1159/000481825