Making best practice, everyday practice

Login Register

Read below to complete the CPD questions
This content is not optimized for small mobile sites and is best experienced on a 7 inch tablet or larger screen size.
Insulin therapy: Where are we now in 2018
1
2

 

Hyperglycaemia in-hospital results in increased morbidity and mortality.

This review provides practical insights and case studies of typical patients commonly encountered in this situation.1

The patient identified with hyperglycaemia in-hospital may have been previously diagnosed with diabetes or the diabetic condition was unrecognised and not diagnosed. Hospital-related hyperglycaemia which reverts to normal after discharge is encountered in the ICU due to critical illness following treatment with steroids or TPN.

Remember that, as the attending clinician, you may be the first to identify the patient as diabetic and will need to counsel and treat appropriately.

3

 

Insulin therapy and its benefits are based on countering the harm caused by hyperglycaemic effects on the immune system and on the mediators of inflammation, vascular responses and brain cell responses.1

4

 

Hyperglycaemia produces oxidative stress which causes cell and tissue injury.

5

 

The increased levels of reactive O2 species (ROS) cause activation of transcription factors, growth factors and secondary mediators. This oxidative stress causes both direct tissue injury and injury via activation of inflammation, causing tissue damage. Immune dysfunction prolongs hospitalisation with increased morbidity or death.1

6

 

The most important decision concerning the introduction of a suitable IV insulin protocol is how easily it can be standardised in your hospital. The protocol must importantly be designed to limit hypoglycaemic risk to a minimum, particularly in cardiac patients. The three variables to be considered are the tested current blood glucose, how does it change over time (“dynamic scale”) and then determine/adjust the insulin infusion rate.2

 The Ideal IV Insulin Protocol

In addition to specifying insulin dose, protocols should include specific guidelines for identifying patients at risk for hypoglycaemia and actions to be taken to prevent and treat hypoglycaemia.

7

 

If you are providing insulin IV, the insulin type (whether human or analogue) does not matter.

However, when administration is subcutaneous, then the analogue aspart, lispro or glulisine format is safer, works faster and is removed speedily from the system. This is important as meal-times in hospital are often unpredictable.3

8

 

This is an example of infusion dilutions. Dr Kok noted a practical tip: “In our hospital, we use 1 unit/ml in cardiac patients to reduce the administered volume”.

9

 

It is essential to understand insulin compatibility with IV fluids; noting particularly that insulin glulisine can only be used with normal saline.

10

 

The clinician needs to take insulin adsorption onto the plastic drip sets into account; this is a non-specific phenomenon and can alter the rate of insulin delivery to the patient.4

11

 

As insulin is being delivered and occupies all the receptors, a steady-state is reached.

“It is important to monitor the patient response to the insulin dose you have selected; thereafter ongoing monitoring can be done easily by trained nursing staff.”

12

 

The clinician needs to adjust and develop insulin delivery to suit the individual patient.

Do NOT use a sliding scale.

13

 

The most important risk to tight glucose control in hospital is hypoglycaemia. Other aspects to consider are stimulation of the sympathetic nervous system, increased myocardial O2 demand, influence on potassium and phosphate, and that different nutritional support will influence the insulin dosage for the particular patient.

14

 

Clinical trials guide our selection of patients and help to provide suitable glucose targets for different classes of patients in order to optimise the benefits of insulin therapy and control of hyperglycaemia.

15

 

The first study to focus clinicians’ attention on the importance of in-hospital hyperglycaemia was the Leuven Study.5

16

 

In this study, nursing staff were well educated and informed about the dangers of hypoglycaemia. In the surgical unit, the benefits of tight glucose control was evident as shown in the accompanying slide.5

17

 

The second study in this series, Leuven 2,6 looked at benefits in the medical intensive care unit and compared intensive treatment (4.4-6.1mmol/l) as compared to conventional therapy targeting 10-11.1mmol/l.

18

 

The benefits of intensive treatments over 3 days is shown in terms of weaning from mechanical ventilation (fewer ventilation days).6

19

 

The benefits of intensive treatments over 3 days is shown in terms of earlier discharge from ICU.6

20

 

The benefits of intensive treatments over 3 days is shown in terms of earlier discharge from hospital.

21

 

A larger trial (NICE-SUGAR) conducted in Australia, New Zealand and Canada (6104 patients recruited) and controlled to an intensive target (4.5-6mmol/l) versus a less intensive approach (<10mmol/l) using a computer-generated algorithm failed to show benefit mainly because of hypoglycaemia. Additionally, it should be pointed out that the patients in the intensive arm were sicker than the conventional therapy arm.

22

 

Subsequent to this study, its influence on clinical practice was assessed by comparing results before and after the published study. This showed that the lesson concerning adverse effects of hypoglycaemia had been learned and that most units achieved improved mortality rate and morbidity benefit by introducing glucose control but to less strict levels than that used in the intensive insulin therapy arm (4.4-6.1mmol/l).

23

 

While recommendations from ACP/ADA/AACE differ with regard to in-hospital levels, it is clear that:

  • To not control in-hospital hyperglycaemia (defined by SEMDSA as glucose levels >7.8mmol/l) is not acceptable
  • The better approach is to achieve benefit at a lower glucose range as long as there is no undue hypoglycaemia.

“It is very, very important to decide on levels in your individual unit, taking into account whether staff are permanent/agency and their capacity to implement the protocol without hypoglycaemia,” Dr Adri Kok stressed.

24

 

Special situations do demand more intensive therapy. These are:

  • In burn units
  • In patients with acute myocardial infarction
  • In brain injury patients.
25

 

In patients with severe burns, the tighter the control, ideally around 6mmol/l, results in improved mortality and mobidity.8

26

 

In the patient with severe burns, the particular circumstances of high risk of bacteraemia, increased catabolism and metabolic rate set the stage for the benefits of insulin.

27

 

The benefits of insulin in severely burned patients are summarised in the accompanying slide.9

28

 

The clinician should note these special aspects in Burn Units that relate to worse clinical outcomes.

29

 

DIGAMI (Diabetes and Insulin-Glucose Infusion in Acute Myocardial Infarction) was the first trial to show benefit of glucose control using initial intensive metabolic control by insulin-glucose infusion for at least 24 hours after AMI in diabetic patients (followed by long-term insulin treatment). This benefit persisted for many years and was shown in the 5 years of follow-up. “It is important to remember that some 30% of patients will only be diagnosed as diabetic after their first MI.”11

30

 

This study did not show a mortality benefit but did show a decreased incidence of congestive cardiac failure (CCF) and a decreased rate of re-infarction.12

31

 

There is significant benefit in tighter glucose control in patients with traumatic brain injury.

Studies have shown that mortality rate is much higher (2 fold) if hyperglycaemia at admission was >11.1mmol/l versus <11.1mmol/l.

The most important period to control hyperglycaemia for maximum benefit is therefore in the first 24 hours following admission.13

32

 

Nurses are our allies in implementing an insulin protocol.

33

 

The most recent South African guidelines for In-hospital hyperglycaemia provide useful overall guidance to clinicians, they support the approach and discussion outlined earlier.

34
35
Slide01
Insulin-in-Hospital-Presentation-1
Insulin-in-Hospital-Presentation-2
Insulin-in-Hospital-Presentation-3
Insulin-in-Hospital-Presentation-4
Insulin-in-Hospital-Presentation-5
Insulin-in-Hospital-Presentation-6
Insulin-in-Hospital-Presentation-7
Insulin-in-Hospital-Presentation-8
Insulin-in-Hospital-Presentation-9
Insulin-in-Hospital-Presentation-10
Insulin-in-Hospital-Presentation-11
Insulin-in-Hospital-Presentation-12
Insulin-in-Hospital-Presentation-13
Insulin-in-Hospital-Presentation-14
Insulin-in-Hospital-Presentation-15
Insulin-in-Hospital-Presentation-16
Insulin-in-Hospital-Presentation-17
Insulin-in-Hospital-Presentation-18
Insulin-in-Hospital-Presentation-19
Insulin-in-Hospital-Presentation-20
Insulin-in-Hospital-Presentation-21
Insulin-in-Hospital-Presentation-22
Insulin-in-Hospital-Presentation-23
Insulin-in-Hospital-Presentation-24
Insulin-in-Hospital-Presentation-25
Insulin-in-Hospital-Presentation-26
Insulin-in-Hospital-Presentation-27
Insulin-in-Hospital-Presentation-28
Insulin-in-Hospital-Presentation-29
Insulin-in-Hospital-Presentation-30
Insulin-in-Hospital-Presentation-31
Insulin-in-Hospital-Presentation-32
Insulin-in-Hospital-Presentation-33
Insulin-in-Hospital-Presentation-34
Slide011
Insulin-in-Hospital-Presentation-12
Insulin-in-Hospital-Presentation-23
Insulin-in-Hospital-Presentation-34
Insulin-in-Hospital-Presentation-45
Insulin-in-Hospital-Presentation-56
Insulin-in-Hospital-Presentation-67
Insulin-in-Hospital-Presentation-78
Insulin-in-Hospital-Presentation-89
Insulin-in-Hospital-Presentation-910
Insulin-in-Hospital-Presentation-1011
Insulin-in-Hospital-Presentation-1112
Insulin-in-Hospital-Presentation-1213
Insulin-in-Hospital-Presentation-1314
Insulin-in-Hospital-Presentation-1415
Insulin-in-Hospital-Presentation-1516
Insulin-in-Hospital-Presentation-1617
Insulin-in-Hospital-Presentation-1718
Insulin-in-Hospital-Presentation-1819
Insulin-in-Hospital-Presentation-1920
Insulin-in-Hospital-Presentation-2021
Insulin-in-Hospital-Presentation-2122
Insulin-in-Hospital-Presentation-2223
Insulin-in-Hospital-Presentation-2324
Insulin-in-Hospital-Presentation-2425
Insulin-in-Hospital-Presentation-2526
Insulin-in-Hospital-Presentation-2627
Insulin-in-Hospital-Presentation-2728
Insulin-in-Hospital-Presentation-2829
Insulin-in-Hospital-Presentation-29
Insulin-in-Hospital-Presentation-30
Insulin-in-Hospital-Presentation-31
Insulin-in-Hospital-Presentation-32
Insulin-in-Hospital-Presentation-33
Insulin-in-Hospital-Presentation-34

NOTE: This article was made possible by an unrestricted educational grant from Sanofi, which had no control over content.

References

  1. Clement S, Braithwaite SS, Magee MF, et al. Management of diabetes and hyperglycaemia in hospital. Diabetes Care 2004; 27: 553-591.
  2. Meijering S, Corstjens AM, Tulleken JE, et al. Towards a feasible algorithm for tight glycaemic control in critically ill patients: a systematic review of the literature. Crit Care 2006; 10(1): R19. Doi: 10.1186/cc3981.
  3. Brange J, Ribel U, Hansen JF, et al. Monomeric insulins obtained by protein engineering and their medical implications. Nature 1988; 333(61754): 679-682.
  4. Kaira S and Bajwa SJ. Intravenous insulin use; technical aspects and caveats. J Pak Med Assoc 2013; 63(5): 650-653.
  5. Van Den Berghe G, Wouters P, Weekers F, et al. Intensive insulin therapy in critically ill patients. N Engl J Med. 2001; 345(19):1359-1367.
  6. Van den Berghe G, Wilmer A, Hermans G, et al. Intensive insulin therapy in the medical ICU. N Engl J Med. 2006; 354(5): 449-461.
  7. NICE-SUGAR Study Investigators. Intensive versus conventional glucose control in critically ill patients. N Engl J Med 2009; 360(13): 1283-1297.
  8. Kamolz LP, Pieber R, Smolle-Juttner FM, et al. Optimal blood glucose control in severely burned patients. Crit Care 2013; 17(5): 1005.
  9. Jeschke MG. Clinical review: Glucose control in severely burned patients – current best practice. Crit Care 2013; 17(4): 232. Doi: 10/1186/cc12678.
  10. Wilkinson D, Chapman IM and Heilbronn LK. Hyperbaric oxygen therapy improves peripheral insulin sensitivity in human. Diabet Med 2012; 29(8): 986-989.
  11. Malmberg K. Prospective randomised study of intensive insulin treatment on long term survival after acute myocardial infarction in patients with diabetes. GMJ 1997; 314(7093): 1512-1515.
  12. Cheung NW. The hyperglycaemia intensive insulin infusion in infarction (HI-5) study. Diab Care 2006; 29(4): 765-770.
  13. Liu-De Ryke. Clinical impact of early hyperglycaemia during acute phase of traumatic brain injury. Neurcrit Care 2009; 11(2): 151-157.

 

Do you like this? Share with a colleague