Premixed Insulin


Humalog Mix® 25 [insulin lispro], Humalog Mix® 50 [insulin lispro], Humulin® M3 [human insulin], Hypurin Porcine® 30/70 mix [porcine animal insulin], Insuman Comb® 15 [human insulin], Insuman Comb® 25 [human insulin], Insuman Comb® 50 [human insulin], NovoMix® 30 [insulin aspart]

[SANOFI have announced discontinuation of Insuman Comb® 15 and Insuman Comb® 25 with an expected end of supply date of June 2020.  At the current time, this preparation remains in the British National Formulary and has been included in this monograph] 

  Issues for Surgery


Hypoglycaemia if continued during nil by mouth period.

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 

Continue, but at a reduced dose - see figure 1 below for details of dose reduction.

When reducing insulin doses round to the nearest unit.

 

*e.g. Humulin® M3 contains isophane insulin 70units per 1ml and soluble insulin 30units per 1ml therefore give 70% of usual dose as Humulin® I (isophane insulin).  For the insulin analogues the basal component is not available separately as a commercially available product therefore for Novomix® 30 use 70% of usual dose as Insulatard® (isophane insulin) and for Humalog® 25 use 75% of usual dose as Humulin I® (isophane insulin).

Figure 1 – Management of PREMIXED insulin in the Perioperative Period1

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 infusion – see Further Information1. Continue to monitor ketones if CBG>13mmol/mol1.

Perioperative Considerations

Commence variable rate intravenous insulin infusion (VRIII) perioperatively where indicated, omit patient’s usual PREMIXED insulin, and commence a long-acting insulin at a dose of 0.2 units per kilogram1 (see figure 1 above and Further Information).

Ensure emergency treatment of hypoglycaemia is prescribed i.e. Glucogel® and 20% dextrose. Rapid acting insulin should also be prescribed1, 2.

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 necessary1, 2.


  Interaction(s) 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)3, 4, 5, 6, 7.


  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)3, 4, 6, 7, 8.

Reduction of Blood-Glucose Lowering Effect

Corticosteroids can reduce the blood-glucose-lowering effect of insulin3, 4, 5, 6, 7, 8, 9.  Clinically important hyperglycaemia has been seen9.  Monitor CBG closely when corticosteroids are given to patients with diabetes9.

Somatostatin analogues (octreotide and possibly lanreotide) may either increase or decrease the insulin requirements3, 5, 6, 7, 8, 9 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 octreotide8, 9.  Monitor CBG when somatostatin analogues are given to patients with diabetes9.


  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 full1, 2.  

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 insulin2.

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.  Patients with type 2 diabetes who are expected to miss more than one meal should have VRIII if they develop hyperglycaemia (CBG >12mmol/L)1.

Commence a long-acting insulin at 0.2 units per kilogram during treatment with VRIII to prevent hyperglycaemia and ketosis on cessation of VRIII1.  In patients with type 1 diabetes do not discontinue VRIII unless patient has received alternative subcutaneous insulin within the last 30 minutes1.

 

  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 8th March 2021]
  2. Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press. http://www.medicinescomplete.com [Accessed on 1st March 2021]
  3. Summary of Product Characteristics – Humulin® M3 (human insulin) KwikPen (Mixture 3) 100 IU/ml suspension for injection. Eli Lilly and Company Limited. Accessed via www.medicines.org.uk 01/03/2021 [date of revision of the text October 2020]
  4. Summary of Product Characteristics – Insuman Comb® 25 (human insulin) SoloStar 100 IU/ml suspension 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]
  5. Summary of Product Characteristics – Hypurin Porcine 30/70 Mix (porcine insulin) Cartridges – PL 29831/0119. Wockhardt UK Ltd. Accessed via www.medicines.org.uk 01/03/2021 [date of revision of the text September 2020]
  6. Summary of Product Characteristics – Humalog Mix® 50 (insulin lispro) 100 units/ml KwikPen, suspension for injection in pre-filled pen. Eli Lilly and Company Limited. Accessed via www.medicines.org.uk 01/03/2021 [date of revision of the text September 2020]
  7. Summary of Product Characteristics – NovoMix® 30 (insulin aspart) FlexPen 100 units/ml. Novo Nordisk Limited. Accessed via www.medicines.org.uk 01/03/2021 [date of revision of the text October 2020]
  8. Insulin. In: Brayfield A (Ed), Martindale: The Complete Drug Reference. London: The Royal Pharmaceutical Society of Great Britain. http://www.medicinescomplete.com [Accessed 1st March 2021]
  9. Baxter K, Preston CL (eds), Stockley’s Drug Interactions (online) London: Pharmaceutical Press. http://www.medicinescomplete.com [Accessed on 1st March 2021]