Neobook — clinical reference

SEMDSA 2017 Recommendations
Inpatient hyperglycaemia is defined as a blood glucose level > 7.8 mmol/l	B
Efforts should be made to monitor and avoid hypoglycaemia as it has unequivocally been associated with an increased mortality	A
HbA_1c should be performed in all patients with IHH at the time of first detection, unless performed in the prior 2-3 months	C
Bedside blood-glucose (BG) monitoring is a useful tool to monitor response to therapy and helps to guide titration of antihyperglycaemic therapy, especially insulin	C
Fasting and preprandial blood glucose targets generally should be < 8 mmol/l, and random glucose values < 10 mmol/l.	C
Insulin therapy is the preferred form of treatment of in-hospital hyperglycaemia (IHH)	B
The use of “sliding-scale insulin” regimen is not recommended	A
In patients who are maintained as nil per os; prandial insulin dose should be suspended. Patients previously on basal insulin should be maintained on this therapy	B
More frequent blood glucose monitoring should be done in patients who are receiving glucocorticoid therapy	C
Among non-critically ill patients, scheduled subcutaneous insulin consisting of three separate components, basal, nutritional, and correctional doses, is the preferred method for achieving and maintaining glucose control	A
Critically-ill patients in ICU and high-care settings are best managed with intravenous insulin therapy using a validated insulin infusion protocol	C
With regards to enteral feeds, in patients with diabetes the use of diabetes-specific formulas is recommended	B
In patients receiving total parenteral nutrition (TPN) insulin can be added to the TPN solution to maintain euglycaemia	B
Following discharge, patients should be screened for diabetes after 6 weeks	C

INTRODUCTION

Hyperglycaemia is commonly encountered among hospitalised patients with some studies reporting a prevalence of 39.3%.¹ It is the fourth most common condition listed on all hospital discharge forms and can occur in patients with or without diabetes mellitus(DM).^2,3Traditionally in-hospital hyperglycaemia (IHH) has been referred to as “stress hyperglycaemia” and despite being common, many patients remain undiagnosed. Even when recognised, it is often overlooked and treatment is sub-optimal.⁴ Putative mechanisms for “stress hyperglycaemia” include increased circulating levels of pro-inflammatory cytokines and counter-regulatory hormones caused by acute illness.

Initially this was thought to be an adaptive mechanism with possible benefits, however this myth has been dispelled by overwhelming evidence indicating that IHH is associated with adverse clinical outcomes and increased mortality.^2,5,6

IHH correlates with the length of hospitalisation, number of rehospitalisations, morbidity and mortality.⁴ Hyperglycaemia per se may be associated with an enhanced risk for infection as a result of impairment of the innate immune system. It has also been demonstrated to potentiate coagulation and increase the risk of thrombosis.

These effects are further exacerbated in the presence of systemic inflammation.^7,8,9 The management of hyperglycaemia in hospitals can be challenging due to variations in nutrient composition, changes in the frequency and timing of food intake, usage of diabetogenic drugs and the development of renal or other organ dysfunction.

DEFINITION AND AETIOLOGY OF HYPERGLYCAEMIA IN HOSPITAL

The American Association of Clinical Endocrinologists (AACE) and the American Diabetes Association (ADA) consensus statement on inpatient glycaemic control defines hyperglycaemia as a blood glucose level > 7.8 mmol/l.²Three categories of hyperglycaemia can be identified:

Known diabetes: past history of DM has been documented
Unrecognised DM: patients with DM but previously undiagnosed
This requires confirmation by standard diagnostic criteria after hospitalisation
Hospital-related hyperglycaemia: hyperglycaemia occurring during hospitalisation but reverts to normal after discharge

Distinguishing between categories of hyperglycaemia at the bedside may be difficult, but in general does not impact fundamentally on management principles. Following discharge, it is important to investigate patients appropriately for DM.

HbA_1C MEASUREMENT

In patients without a history of diabetes, an elevated HbA_1C is suggestive of unrecognised DM, whilst a normal HbA_1C favours stress hyperglycaemia. It is also likely that patients with an elevated HbA_1C would require ongoing anti-hyperglycaemic therapy upon discharge from hospital. A normal HbA_1C would suggest that the hyperglycaemia may be resolved following resolution of the acute illness.

HbA_1C determination is recommended in all patients with IHH at the time of first detection, unless performed in the prior 2-3 months. Important caveats however do exist, and need to be taken into consideration when interpreting HbA_1C within the context of the underlying illness, use of blood products etc.

BLOOD GLUCOSE MONITORING

There are no data to support specific recommendations regarding glucose monitoring. Bedside blood-glucose (BG) monitoring is a useful tool to monitor response to therapy and helps to guide titration of antihyperglycaemic therapy, especially insulin. In addition, BG monitoring is vital in detecting hypoglycaemia, which is an obstruction to the achievement of good glycaemic control and an important cause of morbidity.

BG monitoring with use of point-of-care (POC) glucose meters is performed before meals and at bedtime in most inpatients who are eating usual meals^.2 However, the frequency and timing of bedside BG monitoring must be individualised. If intensification of insulin therapy is desired, 2-hour post-prandial BG levels should ideally also be performed.

Postprandial testing assists in optimal insulin dose titration. BG monitoring should also be performed at 2 am (overnight) if nocturnal hypoglycaemia is a concern. Patients who are receiving continuous enteral or parenteral nutrition require BG monitoring every 4 to 6 hours. Healthcare institutions should have standardised treatment protocols that aim to prevent and address mild, moderate and severe hypoglycaemia appropriately.

Healthcare workers should be educated about risk factors for hypoglycaemia, such as a sudden reduction/cessation of oral intake or discontinuation of enteral or parenteral nutrition.

Continuous glucose monitoring (CGM) systems have the potential to detect hypoglycaemia more effectively than POC meters. However, there is currently no evidence that employing CGM translates into better glycaemic control. Therefore, CGM is not recommended in adult hospitalised patients until studies are able to show greater efficacy and safety compared to POC meters.

GLYCAEMIC TARGETS IN NON-CRITICALLY ILL PATIENTS

Recommendations are based on clinical experience and judgement since there are no prospective, randomised, controlled trials providing clear evidence for specific blood glucose goals. Fasting and preprandial blood glucose targets generally should be < 8 mmol/l, and random glucose values < 10 mmol/l. More stringent targets may be appropriate for stable patients with previous tight glycaemic control, provided these targets can be safely achieved

PHARMACOLOGICAL THERAPY FOR HYPERGLYCAEMIA IN HOSPITALISED PATIENTS

Oral and non-insulin injectable agents

In general, oral agents are considered unsuitable for in-hospital management of hyperglycaemia. Sulphonylureas have been associated with severe and prolonged hypoglycaemia in patients with reduced or limited oral intake^.11 Thiazolidinediones have a delayed onset of action and are also contraindicated in patients with congestive heart failure or in those with haemodynamic instability^.12

Metformin has been associated with lactic acidosis, and risk factors for this complication include cardiac disease, decompensated chronic heart failure, hypoperfusion, renal insufficiency, advanced age, and chronic pulmonary disease.¹³ Many of these conditions cluster amongst hospitalised patients, and are either relative or absolute contraindications to metformin use, making metformin an unfavourable choice for therapy. Metformin should be suspended in patients requiring intravenous radio-contrast 48 hours before the planned administration and restarted no sooner than 48 hours after the procedure.

No large-scale studies have investigated the efficacy, safety and outcomes of oral agents in hospitalised patients. Furthermore, oral agents cannot be titrated rapidly to achieve the desired glycaemic targets, and therefore have a limited role to play in the treatment of IHH. They should be reserved for mild hyperglycaemia in non-critically ill patients with previously well-controlled diabetes who eat regular meals and in whom there are no specific contraindications to therapy.^1,5

Information on the use of incretin therapy including injectable non-insulin therapies such as glucagon-like peptide-1 (GLP-1) analogues and oral dipeptidyl-peptidase 4 (DPP-4) inhibitors are limited to small studies in specific groups of patients and are generally well tolerated. Treatment with sitagliptin plus basal insulin was shown to be as effective and safe as basal-bolus insulin regimen in patients with type 2 diabetes in the non-intensive care setting.¹⁰ However, insulin therapy remains the preferred method for achieving acceptable glucose control in the hospital setting.²

INSULIN

Insulin therapy forms the basis of treatment for IHH. It can facilitate more effective glycaemic control compared to oral and non-insulin injectable agents. Insulin is the most potent agent available against hyperglycaemia, has a more rapid onset of action compared to oral agents, and can easily be titrated and adapted to optimise the glycaemic control of in-hospital patients with varying therapeutic requirements. Although insulin is the ideal agent for IHH, the type of insulin regimen employed is crucial to the successful management of hyperglycaemia.

Insulin may be administered subcutaneously (SC) or intravenously (IV). SC insulin therapy can be administered as basal-bolus therapy, sliding-scale insulin therapy, a split-mixed regimen of neutral protamine Hagedorn (NPH) insulin and regular insulin, or basal insulin with correction doses of short-acting insulin.

Basal-bolus therapy, the most intensive regimen, is ideal for the management of IHH, since it addresses both basal requirements and prandial glucose excursions. Sliding-scale insulin therapy is inferior to basal-bolus therapy with respect to glycaemic control and is not recommended. Split-mixed NPH and regular insulin administered twice daily before breakfast and supper have been shown to be comparable to basal-bolus therapy, but lack the flexibility of basal-bolus, in that they require strict adherence to scheduled meals. IV insulin is generally reserved for the critical care environment. Caution should be exercised before implementing IV therapy outside the critical care setting, since inadequate monitoring and poorly trained staff can lead to morbidity and mortality from hypoglycaemia.

With respect to the selection of insulin type, most studies of IHH have employed the use of analogue insulins. Short-acting human insulins are likely to have similar efficacy but slower onset of action compared to rapid-acting insulin analogues. Rapid-acting insulin analogues, such as insulin aspart, lispro and glulisine, which can be injected just a few minutes before the meal, would be beneficial in the hospital setting where the timing of meals may vary.

MANAGEMENT IN NON CRITICALLY ILL PATIENTS

Oral agents are generally considered unsuitable and insulin remains the backbone of anti-hyperglycaemic therapy in-hospital. However, situations where oral agents would be acceptable do exist and include patients with mild hyperglycaemia and previously well-controlled diabetes who are eating regular meals and in whom there are no specific contraindications.^1,5 Stable patients with type 2 diabetes who use insulin at home should continue their pre-admission insulin regimen, with adjustment as required. Those on oral agents alone can safely be switched to insulin in-hospital.

Sliding-scale insulin (SSI) therapy, though widely utilised, is not recommended. It has been shown to be inferior to basal-bolus insulin therapy for glucose control in non-critically ill patients with type 2 diabetes.¹⁴ SSI therapy is reactive in its approach, due to the fact that hyperglycaemia is only treated after it has occurred. It has been associated with higher rates of both hyper- and hypoglycaemia.¹⁵ The Randomized Study of Basal Bolus Insulin Therapy in the Inpatient Management of Patients with Type 2 Diabetes (RABBIT 2 trial) clearly demonstrated that a proactive approach utilising the basal-bolus insulin algorithm is simple and more effective than SSI therapy with respect to glucose control in non-critically ill patients with type 2 diabetes.¹⁴

The preferred method for achieving and maintaining glucose control is scheduled SC insulin therapy consisting of three separate components ie. basal, nutritional (prandial), and correctional (supplemental) doses.¹⁶ Prandial insulin provides enough insulin to cover caloric exposure at mealtimes, during IV fluid therapy, total parenteral nutrition and enteral tube feeding. However, prandial insulin does not cater for pre-meal hyperglycaemia. Therefore, correction dose or “supplemental” insulin is needed in addition to scheduled prandial and basal insulin to correct pre-meal hyperglycaemia.¹⁶

HOW TO INITIATE SCHEDULED SC INSULIN THERAPY

When starting insulin therapy for the first time in hospital, it is appropriate to estimate the daily insulin requirement for each individual. Fifty per cent of the total daily dose (TDD) of Insulin should be prescribed as basal insulin and the remaining 50% should be divided equally between meals as either short or rapid-acting insulin.

The estimated TDD requirement can be based on a patient’s body weight and depends on the degree of insulin resistance. The initial dose should be between 0.2-0.5 units/kg body weight. It is important to note that the initial dose of insulin is only an estimate and does not usually provide ideal control. The response to insulin must be assessed frequently and on an ongoing basis, with appropriate titration of the insulin dose to achieve control.

Various factors may affect the optimal glycemic control in the in-patient setting. This includes but is not limited to: predetermined meal-times, sedentary behaviour as well as medications and therapies that may alter insulin sensitivity. Depending on the glycaemic target and response to insulin, the dose is adjusted accordingly. These dose alterations depend on the results of bedside glucose monitoring, whilst attempts are made to minimise the risk for hypoglycaemia.

SUPPLEMENTAL (CORRECTION DOSE) INSULIN

Patients receiving scheduled SC insulin may continue to have hyperglycaemia for a variety of reasons, and may principally be due to suboptimal insulinisation. In this instance, small supplementary doses of regular insulin or a rapid-acting analogue can be given, in addition to any scheduled insulin doses.

It cannot be overemphasised that supplemental insulin, also referred to as “correction dose” of insulin, is not intended to replace scheduled insulin,¹⁷,but rather to augment it. For example, if patients have been prescribed prandial insulin but continue to have hyperglycaemia, they should receive the scheduled prandial dose PLUS the correction dose. Patients being kept NPO that develop hyperglycaemia may also benefit from correction dose insulin at 6 hourly intervals.

Correction doses can either be based on a predetermined scale (Table I) or by calculation using accepted formulae. Using a predetermined scale to advise on correction (supplemental) dosing is simpler and takes the level of hyperglycaemia and clinical assessment of insulin sensitivity into consideration. An example of a correction dose scale is shown in Table I.

Another method to calculate the correction dose uses the correction factor (CF), also known as the insulin sensitivity factor. This provides an index of expected reduction in glucose with each unit of insulin administered. The CF is calculated using the so called “rule of 100” or “rule of 85”. This is done by dividing either 100 (for rapid-acting insulin) or 85 (for short-acting insulin) by the patient’s total daily insulin dose (TDD). Correction Dose = (Actual blood glucose - target blood glucose) divided by CF.

Correction doses should generally not be given within four hours of each other, and should be avoided if frequent, severe or recent episodes of hypoglycaemia have occurred. The amount of insulin used as correction dose therapy may be used to guide further changes in scheduled insulin doses.

Approximately 80% of the total daily correction dose can be added to the scheduled insulin for the following day, 50% of which can be added to the basal insulin component, and the remaining 50% added to prandial component with doses equally divided among the meals.

Table I: Insulin Correction Dose scale

Bedside BG (mmol/l)*	LEVEL 1	LEVEL 2	LEVEL 3
8.0-10.0	1	2	3
10.1-12.0	2	4	6
12.1-14.0	3	6	9
14.1-16.0	4	8	12
16.1-20.0	5	10	15
> 20	6	12	18

Use of this scale depends on fasting or pre-meal BG readings*
Select the level of the scale based on the patient profile :
LEVEL 1: Insulin sensitive patients (e.g. patients who are not eating, elderly patients, and those with impaired renal function)
LEVEL 2: Usual patients (e.g. patient who is able to eat all or most of his/her meals)
LEVEL 3: Insulin resistant patient (e.g. patients receiving glucocorticoids and those treated with more than 80 U/d before admission).
The “Correction Dose” is to be added to scheduled insulin dose.
Correction doses administered at bedtime should be reduced by 50%.
If a patient develops hypoglycaemia or has a history of hypoglycaemia, decrease regular or rapid-acting insulin from the insulin-resistant to the usual column or from the usual to the insulin-sensitive column.
Table I has been adapted from Umpierrez et al¹⁸ and Magaji et al.¹⁹

PATIENT RECEIVING ENTERAL FEEDS

Enteral feeding may cause or exacerbate IHH, resulting in adverse outcomes. In patients with diabetes, the use of diabetes specific formulas is associated with improved glycaemic control when compared to standard formulas.²⁰ Enteral feeds, may be administered on a continuous basis, as boluses or in some instances nocturnally scheduled. Various strategies of insulin administration including: daily long acting insulin analogues; pre-mixed insulins and 12 hourly NPH with or without scheduled regular insulin 6 hourly.

Bolus enteral feeds mimic the usual prandial glucose excursions, and are probably best treated with basal-bolus therapy. The timing of bolus doses must coincide with delivery of the bolus enteral feeds. In addition, basal insulin would still be required to address fasting and inter-feed glycaemia. Patients receiving only nocturnal enteral feeds can be managed with NPH insulin, administered upon commencement of the feed.

Any other prandial caloric exposure can be covered with scheduled bolus doses of regular insulin. The major concern with insulin therapy in patients receiving enteral feeds is the risk of hypoglycaemia if feeding is suspended. Therefore, protocols need to be in place that will enable staff to pre-empt and react to such occurrences promptly. If enteral feeding is stopped, insulin should also be immediately withheld and a 10% dextrose-containing infusion commenced to prevent hypoglycaemia.

PATIENTS RECEIVING TOTAL PARENTAL NUTRITION (TPN)

Total parenteral nutrition (TPN) associated hyperglycaemia has also been linked with adverse clinical outcomes.²¹ Regular insulin can be added to the TPN solution to maintain euglycaemia. The starting dose can be commenced at 0.1 units/g of carbohydrate contained in the TPN (one unit of regular insulin per 10 g of carbohydrate).

in cases of severe hyperglycaemia, it is advisable to use IV insulin therapy. In addition, IV insulin therapy may be a useful way of determining the total daily insulin requirements. Once glucose control has stabilised, IV insulin therapy can be replaced with the addition of regular insulin to the TPN, at a dose of approximately 80% of the TDD.

In patients with type 2 diabetes, it may be possible to provide half the TDD as basal insulin, and the remaining dose as regular insulin into the TPN. SC correction doses of regular insulin are also advise, to deal with hyperglycaemia related to an inadequate TDD prescription. Approximately 80% of the total daily corrective insulin dose can be added to the following day’s scheduled insulin.

PATIENTS BEING MAINTAINED NIL PER OS (NPO)

Previously prescribed scheduled prandial insulin doses should be suspended. However, patients who previously received basal insulin (including once-daily, long-acting analogues and once or twice-daily NPH insulin) should still be maintained on this therapy. Glycaemic targets are maintained with correction doses of regular or short-acting analogue insulin that can be given six hourly (see correction dose calculation). Patients being kept NPO for prolonged periods should be maintained on a dextrose infusion to prevent hypoglycaemia.

PATIENTS USING CONTINUOUS INSULIN INFUSION THERAPY (CSII)

Continuous subcutaneous insulin infusion (CSII) pump therapy, though infrequently utilised in South Africa, may be encountered in a few patients. Although continuation of pump therapy is desirable, it is in most instances not possible. The lack of expertise of most health care practitioners (HCP) with this modality renders it undesirable.

It is therefore recommended that during hospital admissions, CSII is temporarily stopped unless the attending HCP’s have the necessary accredited training and experience. Whenever CSII therapy is suspended, patients should be converted to subcutaneous insulin therapy until CSII can be recommenced.

Where staff and patient have the required competence in insulin pump therapy, CSII may be continued provided this can be accomplished safely and adequate supplies are available. It is necessary to clearly document the details of basal rates, bolus and correction dosing in the treatment chart.

PATIENTS RECEIVING GLUCOCORTICOID THERAPY

Steroid therapy has the potential to induce or exacerbate hyperglycaemia. The use of steroids necessitates greater vigilance with glucose monitoring. Some studies have reported multiple hyperglycemic episodes occurring in 52% of hospitalised patients.²²

The effects of steroids are not necessarily uniform, and its glycaemic consequences may possibly be affected by a number of patient factors, route of administration, total administered dose and these require further investigation. However, it has been shown that patients with multiple episodes of hyperglycaemia have more comorbid diseases, longer duration of corticosteroid therapy, and longer duration of hospital stay.²²

The management of glucocorticoid induced hyperglycaemia has not been adequately investigated. The most rational approach is to determine the degree of hyperglycaemia and appropriately intervene with insulin therapy. The type of insulin regimen to be employed is not stipulated but should be able to provide basal, nutritional and supplemental insulin (if required).

Current recommendations advise heightened vigilance for hyperglycaemia in the 48 hours after commencing steroids.²More frequent BG monitoring assists in determining the development and severity of hyperglycaemia, thereby guiding the need for insulin therapy as well as dosing. However, one important caveat to insulin therapy is to anticipate a reduction in glucose levels when steroid doses are reduced or steroids are withdrawn, which would then require an appropriate reduction in insulin dose or perhaps cessation, depending on BG monitoring.

PERIOPERATIVE GLYCAEMIC MANAGEMENT

Hyperglycaemia affects immune function and may increase the risk for infection^.7,8,9In patients undergoing surgery, hyperglycaemia per se may adversely affect outcomes by increasing the risk of wound infection. Hyperglycaemia also increases the risk of other postoperative infections^.²¹ In surgical wards, postoperative wound infections have been shown to be the most common nosocomial infection, an important contributor to morbidity and mortality. Furthermore, wound healing can also be affected.

Strict glycaemic control has been shown to improve surgical outcomes in patients undergoing cardiac surgery and critically ill surgical patients. However, more robust evidence is still needed to confirm the efficacy of tight glycaemic control in preventing perioperative infections.

DISCHARGING PATIENTS FROM HOSPITAL

Patients that were previously well controlled on oral agents and are clinically stable, may be recommenced on oral medication prior to discharge, provided they do not have contraindications to oral agents and are maintaining a regular eating pattern.

Patients with poor control or contraindications to oral antidiabetic therapy require continuation of insulin therapy. These patients require in-hospital education on insulin self-administration and titration. They also need to be taught to recognise and manage hypoglycaemia. Follow-up must be arranged to reassess control in patients with diabetes.

CRITICALLY ILL PATIENTS

Acute hyperglycaemia in the intensive care setting is not unusual and results from a number of factors, including stress-induced counter-regulatory hormone secretion, and medications administered in the ICU.²⁴ Hyperglycaemia in this setting has effects on multiple systems, including the cardiovascular, neurological and immune systems.²⁴

The results of early studies investigating the advantages of intensive insulin therapy in critical care patients were positive. The landmark study by Van den Berghe et al²⁵ demonstrated impressive benefits of intensive glycaemic control with IV insulin infusion, in predominantly surgical patients admitted to the ICU who required mechanical ventilation.

A subsequent analysis of a more heterogeneous ICU population with predominantly medical patients demonstrated a reduction in mortality, length of stay, renal dysfunction and requirement of transfusion among those receiving intensive glycaemic control with an IV insulin infusion protocol.²⁵ However, more recent randomised, controlled studies in critically ill patients have not shown the substantial mortality benefits that were previously described.

The largest randomised, controlled study, the Normoglycaemia in Intensive Care Evaluation-Survival Using Glucose Algorithm Regulation (NICE-SUGAR) study, included 6 104 critically ill patients. Patients were randomised to intensive and conventional treatment groups, with target glucose ranges of 4.5–6.0 mmol/l and ≤ 10.0 mmol/l, respectively. The final mean blood glucose values achieved in the two groups were 6.4 and 8.0 mmol/l respectively. Mortality at 90 days was unexpectedly higher in the intensively treated arm (27.5% vs. 24.9%, p = 0.02). The two groups did not differ in terms of days spent in the ICU, hospital stay or days on mechanical ventilation or renal dialysis. Of note, the risk of severe hypoglycaemia was significantly greater in the intensively treated arm (6.8% vs. 0.5%, P < 0.001).

There were no differences between the two groups for other outcomes. These findings do not diminish the advantages of glycaemic control, but instead indicate that targeting near normal glucose levels (< 6.0 mmol/l) is not advisable and may, in fact, be detrimental. A meta-analysis of 26 trials that included the NICE-SUGAR study, showed a mortality benefit for intensive glycaemic control among surgical ICU patients only albeit with a significant risk for hypoglycemia^.26Based on the available evidence, insulin therapy should be initiated for persistent hyperglycaemia, starting at a threshold of no greater than 10 mmol/l^.2 Once insulin therapy has been commenced, it is recommended that glucose values be maintained between 7.8-10 mmol/l.² Although lacking evidence, more stringent goals, such as 6.1–7.8 mmol/l, may be appropriate for selected patients, as long as this can be achieved without significant hypoglycaemia. Targets < 6.1 mmol/, however, are not recommended.

Critically ill patients in ICU and high-care settings are best managed with IV insulin using a well validated insulin infusion protocol. There are a number of published IV insulin infusion protocols that are safe and effective. Before commencement of IV insulin infusion therapy, clinicians should ensure that regular, accurate BG monitoring is feasible. An adequate staff complement and expertise are needed to ensure safe and successful implementation. The insulin infusion protocol must be readily accessible, legible and should specify the adjustments of insulin rates as well as the frequency of BG monitoring, based on the prevailing glucose level. Furthermore, nursing staff in the critical-care setting must be well educated on the selected insulin infusion protocol and importantly, the prevention and management of hypoglycaemia. Once stabilised and the patient is commenced on oral/enteral feeds, transitioning from IV insulin to scheduled SC insulin can be undertaken. SC insulin must overlap with IV insulin infusion for at least one (1) hour before discontinuing IV insulin infusion therapy.

HYPOGLYCAEMIA

Hypoglycaemia has unequivocally been associated with an increased mortality. A protocol should be in place to respond to hypoglycaemia in-hospital. Staff should be aware of the protocol and adequately trained in its implementation. The development of hypoglycaemia should prompt a review of current antihyperglycaemic therapy and adjustment if required. All incidents of hypoglycaemia and subsequent changes in treatment must be clearly documented.

Staff should be aware of known precipitants of hypoglycaemia such as NPO status, reduction in oral intake, increase in insulin, reduction or interruption in NGT or TPN feeds etc.

Author: Imran Paruk
Editors: Ankia Coetzee and Zaheer Bayat

References

Boord, J. B., Greevy, R. A., Braithwaite, S. S., Arnold, P. C., Selig, P. M., Brake, H., Cuny, J. and Baldwin, D. (2009), Evaluation of hospital glycemic control at US Academic Medical Centers. J. Hosp. Med., 4: 35–44.
Moghissi ES, Korytkowski MT, DiNardo MM, et al. American Association of Clinical Endocrinologists and American Diabetes Association Consensus Statement on Inpatient Glycemic Control. Diabetes Care. 2009; 32: 1119-1131.
Wexler DJ, Meigs JB, Cagliero E, et al. Prevalence of hyper- and hypoglycaemia among inpatients with diabetes: a national survey of 44 U.S. hospitals. Diabetes Care. 2007; 30: 367-369.
Leite SA, Locatelli SB, Niece SP, Oliveira AR, Tockus D, Tosin T. Impact of hyperglycaemia on morbidity and mortality, length of hospitalization and rates of re-hospitalization in a general hospital setting in Brazil. Diabetol Metab Syndr. 2010 Jul 21;2:49.
Clement S, Braithwaite SS, Magee MF, et al. Management of diabetes and hyperglycaemia in hospitals. Diabetes Care. 2004; 27: 553-591.
Cheung NW, Li S, Ma G, Crampton R. The relationship between admission blood glucose levels and hospital mortality. Diabetologia. 2008 Jun;51(6):952-5. Epub
2008 Apr 16.
Stegenga ME, van der Crabben SN, Blumer RME, et al. Hyperglycaemia enhances coagulation and reduces neutrophil degranulation, whereas hyperinsulinemia
inhibits fibrinolysis during human endotoxemia. Blood. 2008; 112:82-89.
Pickup JC, Chusney GD, Thomas SM, Burt D. Plasma interleukin-6, tumour necrosis factor alpha and blood cytokine production in type 2 diabetes. Life Sci.2000;67:291–300.
Marhoffer W, Stein M, Maeser E, Federlin K. Impairment of polymorphonuclear leukocyte function and metabolic control of diabetes. Diabetes Care. 1992;15:256–260.
Pasquel FJ et al. Efficacy of sitagliptin for the hospital management of general medicine and surgery patients with type 2 diabetes (Sita-Hospital): a multicentre, prospective, open-label, non-inferiority randomised trial. The Lancet Diabetes & Endocrinology , Volume 5 , Issue 2 , 125 - 133
Bodmer M, Meier C, Krahenbuhl S, et al. Metformin, sulfonylureas, or other antidiabetes drugs and the risk of lactic acidosis or hypoglycemia: a nested case
-control analysis. Diabetes Care. 2008; 31: 2086-2091
Bolen S, Feldman L, Vassy J, et al. Systematic review: comparative effectiveness and safety of oral medications for type 2 diabetes mellitus. Ann Intern Med. 2007; 147: 386-399.
Dunham DP, Baker D. Use of an electronic medical record to detect patients athigh risk of metformin -induced lactic acidosis. Am J Health Syst Pharm. 2006;63: 657-660.
Umpierrez G, Smiley D, Zisman A, et al. Randomized study of basal-bolus insulintherapy in the inpatient management of patients with type 2 diabetes (RABBIT 2
trial). Diabetes Care. 2007;30:2181-2186.
Queale WS, Seidler AJ, Brancati FL. Glycemic control and sliding scale insulin use in medical inpatients with diabetes mellitus. Arch Intern Med. 1997;157:545-552.
Magee MF, Clement S. Subcutaneous insulin therapy in the hospital setting: issues, concerns, and implementation. Endocr Pract. 2004;10(suppl 2):81-88.
Campbell KB, Braithwaite SS. Hospital Management of Hyperglycaemia. Clinical Diabetes. Volume 22, Number 2, 2004
Elia M, Ceriello A, Laube H, et al. Enteral nutritional support and use of diabetes-specific formulas for patients with diabetes: a systematic review and meta-analysis. Diabetes Care. 2005;28:2267–2279.
Pasquel FJ, Spiegelman R, McCauley M, et al. Hyperglycaemia during total parenteral nutrition: an important marker of poor outcome and mortality in hospitalized patients. Diabetes Care. 2010;33(4):739-741.
Donihi AC, Raval D, Saul M, Korytkowski MT, DeVita MA. Prevalence and predictors of corticosteroid-related hyperglycaemia in hospitalized patients.Endocrine Practice: July 2006, Vol. 12, No. 4, pp. 358-362.
Ramos M, Khalpey Z, Lipsitz S, Steinberg J, Panizales MT, Zinner M, Rogers SO. Relationship of perioperative hyperglycaemia and postoperative infections in patients who undergo general and vascular surgery. Ann Surg. 2008;248:585–591.
Lewis KS, Lane-Gill SL, Bobek MG, et al. Intensive insulin therapy for critically ill patients. Ann Pharmacother. 2004;38: 1243-1251.
Van den Berghe G,Wouters P,Weekers F, et al. Intensive insulin therapy in the critically ill patients. N Engl J Med. 2001;345: 1359-1367.
Griesdale DEG, De Souza RJ, Van Dam RM, et al. Intensive insulin therapy and mortality among critically ill patients: a meta-analysis including NICE-SUGAR data. Can Med Assoc J. 2009;180:821-827
Guillermo E. Umpierrez, Richard Hellman, Mary T. Korytkowski, Mikhail Kosiborod, Gregory A. Maynard, Victor M. Montori, Jane J. Seley, and Greet Van den Berghe. Management of Hyperglycaemia in Hospitalized Patients in Non-Critical Care Setting: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 97: 16–38, 2012.
Magaji V, Johnston JM. Inpatient Management of Hyperglycaemia and Diabetes. Clinical Diabetes 2011 Jan; 29(1): 3-9.

In-hospital Management of Hyperglycaemia

Drugs mentioned