Brands of biphasic lispro
Humalog Mix25®, Humalog Mix50®
Biphasic insulin lispro is an intermediate-acting combined with rapid-acting insulin.
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 on 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).
| Regimen | Day before procedure | Day of procedure* |
|---|---|---|
| Twice daily | No dose change | Halve usual morning dose Check capillary blood glucose (CBG) on admission |
Three times a day | No dose change | Halve usual morning dose Check CBG on admission Omit lunchtime dose |
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 biphasic insulin lispro when the LRD commences, with close monitoring of CBG (see Further information).
When reducing insulin doses round to the nearest whole unit. If district nursing staff usually administer the insulin, consider practical implications of adjusting doses (see Further information)
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, omit patient’s usual biphasic insulin lispro, and commence a long-acting insulin at a dose of 0.2 units per kilogram (see 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.
Resume usual evening insulin if eating a normal meal. If eating a small meal give half usual dose. If not eating only give basal component of the usual biphasic insulin lispro - see Further information.
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 biphasic insulin lispro post-operatively.
Blood glucose should be monitored until eating habits and food intake stabilises. 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))1. 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).
Commence a long-acting insulin at 0.2 units per kilogram 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. Patients are at increased risk of hypoglycaemia when biphasic insulin lispro is continued during this period.
Calculating basal insulin dose if not eating post-operatively
If patient is not eating post-operatively the biphasic insulin lispro should be withheld and the patient should receive the basal component of their usual mixed insulin. However, as the basal component is not available separately as a commercially available product the following is suggested:
- For Humalog® Mix25 give Humulin® I (isophane insulin) at 75% of usual dose (i.e. 15 units rather than 20 units)
- For Humalog® Mix50 give Humulin® I (isophane insulin) at 50% of usual dose (i.e. 10 units rather than 20 units)
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 – Humalog® Mix25 (insulin lispro) 100 units/ml KwikPen, suspension for injection in a pre-filled pen. Eli Lilly and Company Limited. Accessed via www.medicines.org.uk 06/02/2024 [date of revision of the text January 2021]