ares the patients mean blood glycaemic level with the glycaemic level when Glycaemic Control Therapy was commenced on Intensive Care Unit in both hospitals. The horizontal line on the graph divides the patients into the groups of patients, who commenced Glycaemic Control Therapy when the patient’s blood glycaemic was 10 mmol/L.

Figure 2. Examining the patient’s mean blood glycaemic level with their actual blood glycaemic level when Glycaemic Control Therapy was commenced and the number of hours the patient was on Intensive Care Unit before Glycaemic Control Therapy was initiated.

1 - 114 in Hospital B. The majority of patients were commenced on GCT between 1 - 10 hours, including 46.7% (n = 35) of patients in Hospital A compared to 55.1% (n = 27) in Hospital B (Table 3).


Prior to the discussion of the results, a brief synopsis is provided of the protocols used in each of the respective hospitals because of the different glycaemic control protocols implemented, despite both belonging to the same ICU network. In most incidences, regardless of age, diabetes status or diagnosis, patients were administered the same SSI.

4.1. Hospital Protocols

Hospitals A and B have different Actrapid intravenous sliding scales with separate titrations, whilst Hospital B also administered a subcutaneous SSI infrequently, but on an irregular basis.

Despite both hospitals belonging to the same ICU network, Hospital A had documented glycaemic control ranges of 1) 4 - 8.3 mmol/L; 2) 4 - 6.9 mmol/L and 3) 8 - 11 mmol/L compared to 4 - 6.1 mmol/L in Hospital B.

Additionally, Hospital B’s titration regimen was developed in 2001, whilst Hospital A’s protocol and regimens were last updated in 2008.

Thus, a number of issues have arisen, as a result of investigations in to these ITUs. 1) A variety of insulin protocols are available, which may or may not be implemented; 2) Insulin infusions are irregularly implemented, between and within these hospitals; 3) Protocols/regimens are out of date, which could impact the care provided.

4.2. Discussion

It was hypothesised that there would be no difference in the glycaemic control protocols used between the two hospitals but this audit has raised many questions surrounding the administration of GCT.

Figure 1 illustrates the hyperglycaemic threshold of ≥10 mmol/L [11] recommended by the NICE-SUGAR Investigators, [12] with a horizontal line. It shows that 41.9% (n = 52) across Hospital A & B were commenced on GCT below this threshold of ≤10 mmol/L, despite the recommendations in the literature. On the other hand, the ADA recommends a threshold of 7.8 mmol/L for nondiabetic patients because they suggest this level is hyper-

Table 3. The majority of patients in both hospitals were commenced on Glycaemic Control Therapy between 1 - 10 hours with 46.7% (n = 35) in Hospital A compared to 55.1% (n = 27) in Hospital B.

glycaemic for a non-diabetic [20]. While 8.3 mmol/L (150 mg/dL) is suggested to reduce the probability of sepsis, [15] yet there is little supporting evidence for this. As a result of this contradictory information, many healthcare practitioners are unsure as to which form of treatment is beneficial to the care and QoL for the patient.

This contradictory information could have resulted in many non-diabetics being commenced on insulin, when their glycaemic levels were within the medioglycaemic range. Both hospitals verbally stated, but had not previously documented, that they commenced their insulin therapy at blood glycaemic values of ≥10 mmol/L (hyperglycaemia), although, 41.9% (n = 52) were commenced at values ≤ 9.9 mmol/L. The dichotomy between what is stated and actually delivered could indicate that hyperglycaemia levels may in fact be <10mmol/L, especially as 71.4% (n = 90) of the patients in Hospital A and 60.0% (n = 30) of the patients in Hospital B were non-diabetics requiring GCT. This may indicate that healthcare professionals are inappropriately and ineffectively diagnosing hyperglycaemia.

Thus, the blood glycaemic level where GCT is commenced needs to be re-evaluated.

It has been found that patients who were commenced earlier on GCT were those who had had hyperglycaemic blood glycaemic values early on in their admission (Figure 2). The patients who were commenced on GCT later than these patients seemed to have blood glycaemic levels that were medioglycaemic. It seems that in both hospitals, a decision was made to control their blood glycaemic levels because they remained constantly above normal.

The glycaemic control results have shown that there are now four glycaemic groups: 1) hypoglycaemia; 2) normoglycaemia; 3) medioglycaemia and 4) hyperglycaemia, with the introduction of this nascent medioglycaemic range (5.6 - 9.9 mmol/L). What is important to establish, however, is the distinction between medioglycaemia triggering GCT, and actually having blood glucose maintained in the medioglycaemic range.

We shall now explore each of these points in turn:

1) If medioglycaemia is the trigger for treatment, this means that clinicians perceive a need for treatment, but there is no empirical evidence for doing so;

2) If blood glucose is being maintained within the medioglycaemic range, this reflects the wide variety of recommended maintenance values identified within the literature. However, there is a lack of consistency as to the ideal maintenance range.

The American Association of Clinical Endocrinologists (AACE) & American Diabetes Association (ADA) still fail to provide health professionals with a protocol that addresses the variety of patients admitted to ICU. An established glycaemic control protocol is, nevertheless, still required to accommodate the needs of patients admitted with different diagnoses [17].

Health professionals fear the implications of hyperglycaemia and more so hypoglycaemia [13]. However, if patients are maintained within this medioglycaemic range with the development of a new TGC titration regimen and protocol, healthcare professionals could reduce the glycaemic variance experienced by the patients and minimise still further the risks of hyperglycaemic and hypoglycaemic events [21].

Defining normoglycaemia is also difficult. The normoglycaemic level used for this audit follows the ADA recommendations of between 3.9 - 5.5 mmol/L [22,23] although other published blood glycaemic ranges that are described as normoglycaemic include 4.4 - 6.1 mmol/L [13], 4.4 - 5.6 mmol/L [2] and 3.8 - 7.2 mmol/L [24]. This therefore, indicates inconsistencies surrounding the definition of normoglycaemia and this will affect and determine titration regimens.

This audit confirms clinicians are maintaining glycaemia within recommended ranges that together constitute medioglycaemia. However the ranges are wide and this is reflected in our data. Between one-third and onehalf of all ICU patients on GCT have their treatment instigated below the established threshold of 10 mmol/L. Does this mean this level should be re-evaluated/ amended or are clinicians inadvertently responding to other cues about patients’ conditions, which are not recorded in the audit data?

Neither our data nor the literature can answer this question. Therefore, a qualitative study which addresses this question needs to be undertaken to try to establish why clinicians instigate GCT treatment below 10 mmol/ L.

4.3. Limitations

Only selecting 2 months of data has meant that only a snap-shot of ICU glycaemic control data has been collected and therefore cannot be generalised across the whole year, because the ICU environment is constantly changing with a variety of patients, diagnoses and rotating health professionals.

Some patients’ notes were poorly documented, thus hindering the evaluation of what the patients may have been administered and how they were controlled.

Mean blood glucose levels were calculated for each patient however, mean values can be distorted by extreme values. Other metrics could have reflected different blood glycaemic values [25].


The retrospective audit carried out on patients’ case notes across two ICU’s in the East Midlands, UK has shown that different glycaemic control protocols were implemented in each intensive care setting, despite both belonging to the same ICU network. In most instances, regardless of age, diabetes status or diagnosis, patients were administered the same SSI, medications were not taken into account for protocol titrations and Actrapid was the only insulin used for SSI.

The authors also established that the majority of patients receiving GCT were not controlled in hypoglycaemia, normoglycaemia or hyperglycaemia, but within the nascent medioglycaemic range of 5.6 - 9.9 mmol/L.


Dr. Alan Liddle, Consultant Intensivist, Lincolnshire County Hospital PCT.

Dr. David Sperry, Consultant Intensivist, Nottingham University Hospitals NHS Trust.


  1. Marik, P.E. and Preiser, J.C. (2010) Towards understanding tight glycemic control in the ICU: A systematic review and metaanalysis. Chest, 137, 544-551. doi:10.1378/chest.09-1737
  2. Spuhler, V.J. and Veale, K.V. (2007) Tighten up glycaemic control: Aggressive insulin therapy in critical care settings is the latest method for reducing mortality rates. Critical Care Insider, 37, 10-13.
  3. Sage, D. (2009) Glycaemic control: It’s not just about diabetes. Academy of Medical-Surgical Nurses, 18, 11-15.
  4. Van den Berghe, G., Wouters, P., Weekers, F., et al. (2001) Intensive Insulin Therapy in Critically Ill patients. The New England Journal of Medicine, 345, 1359-1366. doi:10.1056/NEJMoa011300
  5. Parsons, P. and Watkinson, P. (2007) Blood glucose control in critical care patients—A review of the literature. British Association of Critical Care Nurses, 12, 202-210.
  6. Pielmeier, U., Andreassen, S., Juliussen, B., Chase, J.G., Nielsen, B.S. and Haure, P. (2010) The Glucosafe system for tight glycaemic control in critical care: A pilot evaluation study. Journal of Critical Care, 25, 97-104. doi:10.1016/j.jcrc.2009.10.003
  7. Gerstein, H.C. (2010) Prevention of the consequences of diabetes—A commentary. In: Herman, W.H., Kinmonth, A.L., Wareham, N.J. and Williams, R., Eds., The Evidence Base for Diabetes Care, 2nd Edition, Wiley-Blackwell, Oxford, 266-272.
  8. Bellomo, R. (2009) What is a nice-sugar for patients in the intensive care unit? Mayo Clinic Procedures, 84, 400- 402.
  9. Harper, J. (2007) BAPEN Symposium 6 on “Inflammation technology: Putting theory into practice” Glucose control in the intensive care unit: How it is done. Proceedings of the Nutrition Society, 66, 362-366. doi:10.1017/S0029665107005629
  10. Siegelaar, S.E., Holleman, F., Hoekstra, J.B.L. and Hans DeVries, J. (2010) Glucose variability; Does it matter? Endocrine Reviews, 31, 171-182. doi:10.1210/er.2009-0021
  11. Anabtawi, A., Hurst, M., Titi, M., Patel, S., Palacio, C. and Rajamani, K. (2010) Incidence of hypoglycemia with tight glycemic control protocols: A comparative study. Diabetes Technology & Therapeutics, 12, 635-639. doi:10.1089/dia.2010.0009
  12. Investigators, N.-S. (2009) Intensive versus conventional glucose control in critically ill patients. The New England Journal of Medicine, 360, 1283-1297. doi:10.1056/NEJMoa0810625
  13. Van den Berghe, G., Wilmer, A., Hermans, G., et al. (2006) Intensive insulin therapy in the medical ICU. New England Journal of Medicine, 354, 449-461. doi:10.1056/NEJMoa052521
  14. Webater, N.R. and Galley, H.F. (2009) Does strict glucose control improve outcome? British Journal of Anaesthesia, 103, 331-334. doi:10.1093/bja/aep226
  15. Dellinger, R.P., Levy, M.M., Carlet, J.M., et al. (2008) Surviving sepsis campaign: International guidelines for management of severe sepsis and septic shock. Critical Care Medicine, 36, 296-327. doi:10.1097/01.CCM.0000298158.12101.41
  16. Moghissi, E.S., Korytkowski, M.T., DiNardo, M., et al. (2009) American association of clinical Endocrinologists (AACE) and the American diabetes association (ADA) consensus statement on inpatient glycemic control. AACE/ ADA Consensus Statement. Endocrine Practice, 15, 1-11. doi:10.4158/EP09102.RA
  17. Corbin, A.E., Carmical, D., Goetz, J.A., et al. (2010) One institution’s experience in implementing protocols for glycemic management. Dimensions of Critical Care Nursing, 29, 167-170. doi:10.1097/DCC.0b013e3181de98da
  18. Ghosh, R. (2009) Clinical audit for doctors. Developmedica, Nottingham.
  19. Tomlinson, V. (2011) Unpublished Thesis.
  20. American Diabetes Association (2010) Standards of medical care in diabetes. Diabetes Care, 33, S11-S61. doi:10.2337/dc10-S011
  21. Meyfroidt, G., Keenan, D.M., Wang, X., Wouters, P.J., Veldhuis, J.D. and Van den Berghe, G. (2010) Dynamic characteristics of blood glucose time series during the course of critical illness: Effects of intensive insulin therapy and relative association with mortality. Critical Care Medicine, 38, 1021-1029. doi:10.1097/CCM.0b013e3181cf710e
  22. American Diabetes Association (2011) Diagnosis and classification of diabetes mellitus. Diabetes Care, 34, S62-S69.
  23. American Diabetes Association (2011) Standards of medical care in diabetes. Diabetes Care, 34, S11-S61. doi:10.2337/dc11-S011
  24. Shogbon, A.O. and Levy, S.B. (2010) Intensive glucose control in the management of diabetes mellitus and inpatient hyperglycemia. American Journal of Health-System Pharmacy, 67, 798-805. doi:10.2146/ajhp090211
  25. Mackenzie, I.M.J., Whitehouse, T. and Nightingale, P.G. (2011) The metrics of glycaemic control in critical care. Intensive Care Medicine, 37, 435-443. doi:10.1007/s00134-010-2103-2


BG:                              Blood Glucose

DKA:                           Diabetic Ketoacidosis

DM:                             Diabetes Mellitus

Hyperglycaemia:     Glycaemic levels are ≥10mmol/L

Hypoglycaemia:      Glycaemic levels are ≤3.3mmol/L

ICU:                                     Intensive Care Unit

Medioglycaemia:     Glycaemic levels between 5.6 - 9.9 mmol/L

TGC:                           Tight Glycaemic Control

T1DM:                        Type 1 Diabetes Mellitus

T2DM:                        Type 2 Diabetes Mellitus


The research has shown that different glycaemic control protocols were implemented in each intensive care setting, despite both belonging to the same ICU network.

Patients were administered the same SSI, regardless of age, diabetes status or diagnosis. Patient medications were not taken into account for protocol titrations.

Actrapid was the only insulin used for SSI despite the clear need for individualised care. The majority of patients receiving GCT were not controlled in hypoglycaemia, normoglycaemia or hyperglycaemia, but within the posited medioglycaemic range of 5.6 - 9.9 mmol/L.


More information needs to be gathered from other hospitals, so that the development of different titration regimens for specific diagnostic groups can advance. The glycaemic level that GCT should be commenced needs to be re-evaluated as there are inconsistencies surrounding the definition of normoglycaemia.

The authors are now investigating glycaemic therapies and the ranges, therein. In addition, they are also investigating different insulin administrations because the audit found that the only insulin to be used for SSI within each ICU was Actrapid.

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