UK Clinical Pharmacy Association

Insulin - isophane

Brands of insulin isophane

Humulin® I, Hypurin® Porcine Isophane, Insulatard®

Issues for surgery

Increased risk of post-operative infection and delayed wound healing due to poor glycaemic control if omitted.

Hypoglycaemia if continued during nil by mouth period / in patients undertaking a liver reduction diet (LRD) pre-operatively.

Advice in the perioperative period

Insulin products are classified according to their duration of action, and it is important to understand the type of insulin the patient is on in relation to the advice to be given perioperatively. Confirm with the patient the exact name, strength, dose, frequency, and preparation of insulin(s) that they are using (see Further information).

Elective surgery 

Adjust doses whilst not eating – see table below.

EXCEPT:

  • patients undertaking a liver reduction diet pre-operatively – see Patients undergoing surgery that requires liver reduction diet (LRD)

When reducing insulin doses round to the nearest whole unit.

If district nursing or care home staff usually administer the insulin, consider practical implications of adjusting doses (see Further information).

NB: Whilst isophane insulin is an intermediate-acting insulin, the advice is the same as for long-acting insulin. The advice is also the same regardless of whether isophane insulin is being used as part of a basal-bolus regimen in type 1 diabetes mellitus or monotherapy / add-on therapy for type 2 diabetes mellitus.

RegimenDay before procedure*Day of procedure*
Once daily (in the morning)No dose changeTake 80% of usual dose
Once daily (at lunchtime)Take 80% of usual doseCheck CBG on admission
ONCE daily (in the evening)Take 80% of usual doseCheck CBG on admission
Twice dailyTake morning dose as usual and taken 80% of usual evening doseTake 80% of morning dose
* Advice is the same for morning and afternoon surgery

Patients undergoing surgery that requires liver reduction diet (LRD)

Patients with type 1 diabetes mellitus

An individualised management plan should be formulated with the diabetes specialist team.

Patients with type 2 diabetes mellitus

Give 50% of usual dose of isophane insulin when the LRD commences, with close monitoring of CBG (see Further information). When reducing insulin doses round to the nearest whole unit.

Emergency surgery 

Monitor CBG, ketones, renal profile, and lactate on admission to exclude diabetic ketoacidosis (DKA) or hyperosmolar hyperglycaemic state (HHS). The advice given above can be applied to patients presenting for emergency surgery; however, it must be remembered that these patients are high risk and are likely to require intravenous insulin infusion; either variable rate intravenous insulin infusion (VRIII), or in the case of DKA or HHS a fixed rate intravenous insulin infusion – see Further information. Continue to monitor ketones if CBG greater than 13mmol/mol.

Perioperative considerations

Commence variable rate intravenous insulin infusion (VRIII) perioperatively where indicated, with the patient’s isophane insulin continued at 80% of their usual pre-operative dose (see above and Further information).

Ensure emergency treatment of hypoglycaemia is prescribed, i.e. Glucogel® and 20% dextrose. Rapid-acting insulin should also be prescribed.

Post-operative advice

Encourage an early return to normal eating and drinking (as deemed appropriate by the surgical team), facilitating return to the patient’s usual diabetic regimen. However, the insulin dose(s) may need adjusting, as insulin requirements can change due to post-operative stress, infection or altered food intake – monitor CBG levels and seek advice from specialist diabetes team if necessary.

Patients undergoing bariatric surgery

Improved glycaemic control is expected because of reduced calorie intake, early satiety and weight loss following bariatric surgery.

Patients with type 1 diabetes mellitus

Review by the specialist diabetes team post-operatively.

Patients with type 2 diabetes mellitus

Discontinue isophane insulin post-operatively. Blood glucose should be monitored until eating habits and food intake stabilises. If there is a need to recommence isophane insulin post-operatively the dose should be tapered on discharge with strict glucose monitoring to avoid hypoglycaemia. Patients should have their need for ongoing pharmacological management of their diabetes reviewed by their general practitioner or bariatric surgical team.

Interactions with common anaesthetic agents

Reduction of blood-glucose lowering effect

Substances that may reduce the blood-glucose-lowering effect include sympathomimetics (e.g. epinephrine / adrenaline).

Interactions with other common medicines used in the perioperative period

Enhancement of blood-glucose lowering effect

Substances that may enhance the blood-glucose lowering effect of insulin and increase susceptibility to hypoglycaemia include sulphonamide antibiotics (e.g. co-trimoxazole).

Reduction of blood-glucose lowering effect

Corticosteroids can reduce the blood-glucose-lowering effect of insulin. Clinically important hyperglycaemia has been seen. Monitor CBG closely when corticosteroids are given to patients with diabetes.

Somatostatin analogues (octreotide and possibly lanreotide) may either increase or decrease the insulin requirements but most patients with type 1 diabetes are likely to require a reduction in insulin dose, with some studies suggesting a potential reduction of 50% in patients taking concomitant octreotide. Monitor CBG when somatostatin analogues are given to patients with diabetes.

Further information

Safe prescribing and administration of insulin

Insulin should be prescribed according to National Patient Safety Agency (NPSA) recommendations for safe use of insulin, with the brand name and units written in full.

Patients and nursing staff should be reminded of the importance of rotating injection sites within the same body region to reduce or prevent the risk of cutaneous amyloidosis and other skin reactions; injecting into an affected ‘lumpy’ area may reduce the effectiveness of insulin.

VRIII

Patients with a planned short starvation period (no more than one missed meal in total) should be managed by modification of their usual diabetes medication, avoiding VRIII wherever possible (although VRIII may be necessary in patients with type 1 diabetes mellitus who have not received their long-acting insulin, in patients with type 1 diabetes mellitus who are expected to miss more than one meal, if emergency surgery or in people with poorly controlled diabetes mellitus (HbA1c >69mmol/mol)). Patients with type 2 diabetes mellitus who are expected to miss more than one meal should have VRIII if they develop hyperglycaemia (CBG >12mmol/L).

Continue isophane insulin at 80% of usual dose during treatment with VRIII to prevent hyperglycaemia and ketosis on cessation of VRIII. In patients with type 1 diabetes mellitus do not discontinue VRIII unless patient has received alternative subcutaneous insulin within the last 30 minutes.

Liver reduction diet (LRD)

Obese patients often have a large, fatty liver which can cause difficulty for laparoscopic surgery, as the stomach cannot be easily accessed. The LRD typically starts 10 – 15 days prior to surgery and is based on low calories, in particular low carbohydrate and fat. This forces stored glycogen to be released from the liver (plus some water), making it softer, more flexible and easier to move. Due to the reduced calorie and carbohydrate intake, CBG levels will most likely be reduced. The isophane insulin dose should be reduced by 50% when the LRD commences to compensate for the reduction in dietary intake.

Administration by district nursing team or nursing home 

Ensure any instructions about temporary dose reductions are directly communicated to the relevant district nursing team or nursing home. In the case of district nurse administration an amended authorisation form is likely to be required to enable a different dose to be administered. If patients are due their dose in the morning but are due to be admitted to hospital early in the morning before the dose can be given, arrangements should be made for it to be given on admission. 

References

Baxter K, Preston CL (eds), Stockley’s Drug Interactions (online) London: Pharmaceutical Press. http://www.medicinescomplete.com [Accessed on 6th February 2024]

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

Centre for Perioperative Care. Guideline for Perioperative Care for People with Diabetes Mellitus Undergoing Elective and Emergency Surgery (October 2023). Available at: https://cpoc.org.uk/guidelines-resources/guidelines [Accessed on 6th February 2024]

Insulin. In: Brayfield A (Ed), Martindale: The Complete Drug Reference. London: The Royal Pharmaceutical Society of Great Britain. http://www.medicinescomplete.com [Accessed 6th February 2024]

Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press. http://www.medicinescomplete.com [Accessed on 6th February 2024]

Summary of Product Characteristics – Humulin® I (Isophane) (human insulin) KwikPen 100IU/ml suspension for injection in cartridge. Eli Lilly and Company Limited. Accessed via www.medicines.org.uk 06/02/2024 [date of revision of the text April 2021]