Short-acting Insulin

Actrapid^® [human insulin], Apidra^® [insulin glulisine], Fiasp^® [insulin aspart], Humalog^® [insulin lispro], Humulin^® R [human insulin], Humulin^® S [human insulin], Hypurin^® Porcine Neutral [porcine animal insulin], Insuman^® Infusat [human insulin], Insuman^® Rapid [human insulin], Lyumjev^® [insulin lispro], NovoRapid^®[insulin aspart], Trurapi^® [insulin aspart]

  Issues for Surgery

Hypoglycaemia if continued during nil by mouth period / during liver reduction diet (LRD) in patients undergoing Bariatric Surgery.

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

  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 

Omit doses whilst not eating - see figure 1 below for details.

When reducing insulin doses round to the nearest unit.

EXCEPT: -

• Patients undergoing Bariatric Surgery – see below

Figure 1 – Management of SHORT-ACTING insulin in the perioperative period¹

Patients undergoing Bariatric Surgery
Patients with type 1 diabetes mellitus need an individualised management plan formulated with the Diabetes Specialist Team.

Patients with type 2 diabetes mellitus commencing on liver reduction diet (LRD): Stop regular administration of short-acting insulin when LRD commences and monitor CBG closely. If CBG >15mmol/L give 50% of usual dose of short-acting insulin as a rescue / correction dose² (see Further Information). When reducing insulin doses round to the nearest unit.

Patients with type 2 diabetes mellitus not following a LRD: Follow the advice in figure 1 above for Elective Surgery.

Emergency Surgery
Monitor CBG, ketones, renal profile and lactate on admission to exclude diabetic ketoacidosis (DKA) or hyperosmolar hyperglycaemic state (HHS)¹. 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 infusion¹. Continue to monitor ketones if capillary blood glucose (CBG) >13mmol/mol¹.

Perioperative Considerations
Commence variable rate intravenous insulin infusion (VRIII) perioperatively where indicated and omit patient’s SHORT-ACTING insulin during VRIII treatment.  Patients on basal-bolus regimens should continue their long-acting insulin at 80% of the usual dose (see figure 1 above and Further Information). If not usually prescribed long-acting insulin commence at dose of 0.2 units per kilogram¹.

Ensure emergency treatment of hypoglycaemia is prescribed i.e. Glucogel^® and 20% dextrose. Rapid acting insulin should also be prescribed^{1, 3}.

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 regimen¹.  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^{1, 3}.

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 should be reviewed by the Diabetes Specialist Team post-operatively.

Patients with type 2 diabetes should discontinue their short-acting insulin post-operatively. Blood glucose should be monitored until eating habits and food intake stabilises², if long-acting insulin is recommenced post-operatively follow advice in Long-acting Insulin monograph. Patients should have their need for ongoing pharmacological management of their diabetes reviewed by their General Practitioner / Bariatric Surgical Team.

  Interaction(s) with Common Anaesthetic Agents

Reduction of Blood-Glucose Lowering Effect
Substances that may reduce the blood-glucose-lowering effect of insulin include sympathomimetics (e.g. epinephrine / adrenaline)^{4, 5, 6}.

  Interaction(s) 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)^{4, 5, 6}.

Reduction of Blood-Glucose Lowering Effect
Corticosteroids can reduce the blood-glucose-lowering effect of insulin^{4, 5, 6}.  Clinically important hyperglycaemia has been seen⁷. Monitor CBG closely when corticosteroids are given to patients with diabetes⁶.

Somatostatin analogues (octreotide and possibly lanreotide) may increase or decrease insulin requirements^{4, 6, 7}, 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^{6, 7}.  Monitor CBG when somatostatin analogues are given to patients with diabetes⁷.

  Further Information

Safe Prescribing and Administration of Insulin
European Medicines Agency – Guidance on prevention of medication errors with high-strength insulins⁷

A high-strength insulin is a medicine that contains insulin at a concentration of more than the standard 100 units/ml.  There are differences in the way high-strength insulin products are used compared with existing insulin formulations of standard-strength and there is therefore a risk of medication errors and accidental mix-up.

Advice for Healthcare Professionals: -

• A syringe must NEVER be used to withdraw insulin from a pre-filled pen otherwise severe overdose can result
• Insulin must always be prescribed in units (spelled out in full) and include the dose frequency
• The strength of the insulin formulation should always be included in the prescription

Humulin^® R (500 units/ml) is a HIGH strength insulin that is not currently licensed in the UK.  It is imported from the USA².  It is NOT interchangeable with other short-acting insulin preparations.  It is usually prescribed for patients with high insulin resistance and such patients should be referred to the Diabetes Team for a specialist management plan.

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 insulin³.

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 who have not received their long-acting insulin, in patients with type 1 diabetes who are expected to miss more than one meal, if emergency surgery or in people with poorly controlled diabetes (HbA1c >69mmol/mol))¹. 

For patients on basal-bolus regimen, continue long-acting insulin at 80% of usual dose during treatment with VRIII to prevent hyperglycaemia and ketosis on cessation of VRIII, if not usually prescribed long-acting insulin commence at dose of 0.2 units per kilogram¹.  In patients with type 1 diabetes do not discontinue VRIII unless patient has received alternative subcutaneous insulin within the last 30 minutes¹.

Liver Reduction Diet (LRD)
Most people needing bariatric surgery have a large, fatty liver which can cause difficulty for laparoscopic surgery, as the stomach cannot be easily accessed. The LRD typically start 10 – 15 days prior to bariatric 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 short-acting insulin is continued during this period.

  References

1. Centre for Perioperative Care. Guideline for Perioperative Care for People with Diabetes Mellitus Undergoing Elective and Emergency Surgery (March 2021). Available at: https://cpoc.org.uk/guidelines-resources/guidelines [Accessed on 8^th March 2021]
2. 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
3. Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press. http://www.medicinescomplete.com [Accessed on 1^st March 2021]
4. Summary of Product Characteristics – Actrapid^® (human insulin) 100 international units/ml, Solution for Injection in a vial. Novo Nordisk Limited. Accessed via www.medicines.org.uk 01/03/2021 [date of revision of the text October 2020]
5. Summary of Product Characteristics – Apidra^® (insulin glulisine) SoloStar 100 Units/ml solution for injection in a pre-filled pen. SANOFI. Accessed via www.medicines.org.uk 01/03/2021 [date of revision of the text September 2020]
6. Insulin. In: Brayfield A (Ed), Martindale: The Complete Drug Reference. London: The Royal Pharmaceutical Society of Great Britain. http://www.medicinescomplete.com [Accessed 1^st March 2021]
7. Baxter K, Preston CL (eds), Stockley’s Drug Interactions (online) London: Pharmaceutical Press. http://www.medicinescomplete.com [Accessed 1^st March 2021]
8. European Medicines Agency: Guidance on prevention of medication errors with high-strength insulins. 27 November 2015. Available at: www.ema.europa.eu [Accessed 1^st March 2021)