MANAGEMENT OF HYPERGLYCEMIA IN HOSPITALIZED PATIENTS IN NON-CRITICAL CARE SETTING: AN ENDOCRINE SOCIETY CLINICAL PRACTICE GUIDELINE

(J Clin Endocrinol Metab 97: 1638, 2012)

Introduction
Stress hyperglycaemia generally refers to transient hyperglycaemia

during illness and is usually restricted to patients without previous evidence of diabetes.
No guidelines specifically define stress hyperglycaemia.

In a technical review written by the Diabetes in Hospitals Writing

Committee of the American Diabetes Association (ADA), (Clement S, Diabetes Care 2004; 27: 55391) patients are classified into one of three groups known diabetes, newly diagnosed diabetes, and hospital-related hyperglycaemia.

Defining Stress Hyperglycemia

According to the ADA consensus definition (fasting

glucose >125 mg% or random glucose >200 mg% without evidence of previous diabetes)
Also pre-existing diabetes with deterioration of pre-illness

glycaemic control.
The most appropriate cut off point for stress

hyperglycaemia in patients with pre-existing diabetes needs to be established.

ESC guidelines 2012

In-hospital hyperglycemia is defined as any glucose value greater than 7.8 mmol/liter

(140 mg/dl)
Observational studies report that hyperglycemia is present in 32 to 38% of patients in

community hospitals
41% of critically ill patients with acute coronary syndromes 44% of patients with heart failure 80% of patients after cardiac surgery

Hyperglycemia was found in 1/3 of non-intensive care unit (ICU) patients and

approximately 80% of ICU patients had no history of diabetes before admission

Glycemic Targets and Approaches to Management of the Patient with Critical Illness

The statistical association in observational studies between blood glucose level and risk of death follows a J-shaped curve, with normal, fasting blood levels associated with lowest risk of death. In patients with diabetes mellitus this curve is blunted and shifted toward higher blood glucose level
Dieter Mesotten & Greet Van den Berghe Curr Diab Rep (2012) 12:101107

The NICE-SUGAR (Normoglycemia in Intensive Care Evaluation and Survival Using Glucose Algorithm Regulation) trial was not a true confirmation study of the Leuven surgical intensive care unit (SICU) study. Despite using similar blood glucose targets for the intervention group, the Leuven SICU and NICE-SUGAR differed in the targets for the control group. Whereas in the Leuven SICU study hyperglycemia up to the renal threshold was accepted, NICESUGAR, already affected by the results from the Leuven SICU study, used an intermediate blood glucose target for the control group

Lessons from NICE-SUGAR AND Leuven studies

Either hypoglycemia is a marker of severity of critical

illness or hypoglycemia may actually cause the increased risk of death.

Hypoglycemia is still independently associated with

mortality risk after correction of insulin therapy.

E, French CJ, Hart GK, Taori G, et al. Hypoglycemia and outcome in critically ill patients. Mayo Clin Proc. 2010;85(3):217 24]

[Egi M, Bellomo R, Stachowski

Kansagara et al.
Meta-analysis of 21 RCTs in ICU, myocardial infarction, perioperative care,

stroke or brain injury.

14,768 hospitalized patients.

Results of this analysis showed that IIT (intensive insulin therapy) did not

affect short-term mortality or the need for renal replacement therapy, infection rates, or hospital LOS.
Moreover, a high risk for severe hypoglycemia was identified in all hospital

settings.

Kansagara, D., R. Fu, M. Freeman, et al., Intensive insulin therapy in hospitalized patients: a systematic review. Ann Intern Med, 2011; 154(4): p. 26882.

ACP recommendations
The American College of Physicians (ACP) recently published recommendations

for the management of inpatient hyperglycemia based on the systematic review by Kansagara et al. sponsored by the Department of Veterans Affairs.
The ACP advocates for target blood glucose level of 7.811.1 mmol/L (140200

mg/dL) when insulin therapy is used in SICU/ MICU patients.

Their recommendations are based on current evidence demonstrating no

reductions in mortality with target blood glucose levels of 4.46.1 mmol/L (80110 mg/dL) when compared with higher targets.

These tight targets are associated with a higher risk for hypoglycemia. They also recommend allowing blood glucose levels to rise above 10.011.1

mmol/L (180200 mg/dL) before initiating therapy

Qaseem, A., L.L. Humphrey, R. Chou, et al., Use of intensive insulin therapy for the management of glycemic control in hospitalized patients: a clinical practice guideline from the American College of Physicians. Ann Intern Med, 2011; 154(4): p. 2607.

SUMMARY OF RECOMMENDATIONS
ESC 2012

Diagnosis and recognition of hyperglycemia and diabetes in the hospital setting

Recommend that clinicians assess all patients

admitted to the hospital for a history of diabetes.

All patients, independent of a prior diagnosis of

diabetes, have laboratory blood glucose (BG) testing on admission.

Non Diabetic with BG>140MG% be monitored

bedside for 24-48 hrs. Sustained elevation requires treatment.

Diagnosis and recognition of hyperglycemia and diabetes in the hospital setting

Previously normoglycemic patients receiving therapies

associated with hyperglycemia, such as corticosteroids or octreotide, enteral nutrition (EN) and parenteral nutrition (PN) be monitored with bedside POC testing for at least 24 to 48 h after initiation of these therapies.

Recommended that all inpatients with known diabetes or

with hyperglycemia (>140mg%) be assessed with a hemoglobin A1C (HbA1C) level if this has not been performed in the preceding 23 months.

Monitoring glycemia in the non-critical care setting

Bedside capillary POC testing as the preferred method. Timing of glucose measures match the patients nutritional

intake and medication regimen.

Before meals and at bedtime in patients who are eating. Every 46 h in patients who are NPO or receiving

continuous enteral feeding.

Glycemic targets in the non-critical care setting

Premeal glucose target of <140 mg/d and a random BG of

< 180 mg/dl for the majority of hospitalized patients with non-critical illness.
Modified according to clinical status and condition. For patients who are able to achieve and maintain

glycemic control without hypoglycemia, a lower target range may be reasonable.

For avoidance of hypoglycemia, antidiabetic therapy be

reassessed when BG values fall below 100 mg/dl.

Management of hyperglycemia in the non-critical care setting

MNT (medical nutrition therapy) be included as a

component of the glycemic management program for all.

Providing meals with a consistent amount of carbohydrate

at each meal can be useful in coordinating doses of rapidacting insulin

Transition from home to hospital

Insulin therapy as the preferred method for achieving

glycemic control in hospitalized patients with hyperglycemia.

Discontinuation of oral hypoglycemic agents, and non

insulin injectables in acute illness.

Patients treated with insulin before admission have their

insulin dose modified according to clinical status as a way of reducing the risk for hypoglycemia and hyperglycemia

Pharmacological therapy
Prolonged use of sliding scale insulin (SSI) therapy be

avoided as the sole method for glycemic control in hyperglycemic patients with history of diabetes during hospitalization.
Scheduled sc insulin therapy consist of basal or

intermediate-acting insulin given once or twice a day in combination with rapid- or short-acting insulin administered before meals in patients who are eating.
Correction insulin be included as a component of a

scheduled insulin regimen for treatment of BG values above the desired target

Starting Basal Bolus (1/2)

Discontinue oral diabetes drugs and non-insulin injectable diabetes medications upon hospital admission

Starting insulin: calculate the total daily dose as follows

0.2 to 0.3 U/kg of body weight in patients: aged 70 yr and/or glomerular filtration rate less than 60 ml/min.

0.4 U/kg of body weight per day for patients not meeting the criteria above who have BG concentrations of 7.8 11.1 mmol/liter (140200 mg/dl).

Start of Basal Bolus (2/2)

0.5 U/kg of body weight per day for patients not meeting the criteria above when BG concentration is 11.222.2 mmol/liter (201400 mg/dl).

Distribute total calculated dose as approximately 50% basal insulin and 50% nutritional insulin.

Give basal insulin once (glargine/detemir) or twice (detemir/ NPH) daily, at the same time each day.

Give rapid-acting (prandial) insulin in three equally divided doses before each meal. Hold prandial insulin if patient is not able to eat.

Adjust insulin dose(s) according to the results of bedside BG measurements.

Supplement Insulin
If a patient is able and expected to eat all or most of his/ her

meals, give regular or rapid-acting insulin before each meal and at bedtime following the usual column

If a patient is not able to eat, give regular insulin every 6 h (6

12612) or rapid-acting insulin every 4 to 6 h following the sensitive column.

Supplement Insulin
If fasting and premeal plasma glucose are persistently above

7.8 mmol/liter (140 mg/dl) in the absence of hypoglycemia, increase insulin scale of insulin from the insulin-sensitive to the usual or from the usual to the insulin-resistant column.

If a patient develops hypoglycemia BG 3.8 mmol/liter (70

mg/dl), decrease regular or rapid-acting insulin from the insulinresistant to the usual column or from the usual to the insulinsensitive column.

Transition from hospital to home

We suggest reinstitution of preadmission insulin regimen

or oral and non-insulin injectable antidiabetic drugs at discharge.provided sugars are under control.
We suggest that initiation of insulin administration be

instituted at least one day before discharge to allow assessment of the efficacy and safety of this transition.
Patients and their family or caregivers receive both written

and oral instructions regarding their glycemic management regimen at the time of hospital discharge.

SPECIAL SITUATIONS

Transition from iv continuous insulin infusion (CII) to sc insulin therapy

All patients with type 1 and type 2 diabetes be

transitioned to scheduled sc insulin therapy at least 12 h before discontinuation of CII.

Specially for hyperglycemia requiring more than 2 U/h. Close monitoring and regular adjustments are needed.

Transition from ICU to Ward 1/3

Calculate total IV insulin dose over last 6 hrs For e.g if Insulin dose is stable per hour of 3 iu then 6x3 =

18 units over 6 hrs

18 x 4= 72 which is the 24 hr requirement of basal insulin 80% of 72 is the basal analogue shot to be given

Schmeltz LR, DeSantis AJ, Schmidt K, et al. Conversion of intravenous insulin infusions to subcutaneously administered insulin glargine in patients with hyperglycemia. Endocr Pract. 2006;12(6):64150.

Transition from ICU to Ward 2/3

If patient has been receiving dextrose solution and it will

be discontinued, consider using 60% instead of 80%.

If BG is fluctuating, > 1 unit/hour variability between

measurement within last 6 h, consider continuing the drip and reassess later or calculate TDD based on 6 stable doses (insulin units/hour) within the last 12 h

Schmeltz LR, DeSantis AJ, Schmidt K, et al. Conversion of intravenous insulin infusions to subcutaneously administered insulin glargine in patients with hyperglycemia. Endocr Pract. 2006;12(6):64150.

Transition from ICU to Ward 3/3

Divide TDD into basal (half of TDD) and prandial (half of

TDD) for patients eating.

If glucose level >180 mg/dL and just taking clear liquids,

start 25% of TDD divided equally between meals.

When full diet is started increment dose by 1020% and

adjust on a daily basis

Schmeltz LR, DeSantis AJ, Schmidt K, et al. Conversion of intravenous insulin infusions to subcutaneously administered insulin glargine in patients with hyperglycemia. Endocr Pract. 2006;12(6):64150.

Patients receiving EN or PN
POC testing be initiated even in non diabetics Can be stopped if sugars are <140 mg% after 48 hrs of

adequate caloric intake in non diabetics

For all others start insulin therapy if sugars >140mg%

Perioperative BG control
All patients with type 1 diabetes who undergo minor or

major surgical procedures receive either CII or sc basal insulin with bolus insulin as required to prevent hyperglycemia during the perioperative period.
We recommend discontinuation of oral and noninsulin

injectable antidiabetic agents before surgery with initiation of insulin therapy.

When instituting sc insulin therapy in the postsurgical

setting, we recommend that basal (for patients who are NPO) or basal bolus (for patients who are eating) insulin therapy be instituted as the preferred approach

Glucocorticoid-induced diabetes
Bedside POC testing be initiated for patients with or

without a history of diabetes receiving glucocorticoid therapy.

Can be stopped if sugars are <140 mg% after 48 hrs in

non diabetics
Insulin is preferred means of control Severe uncontrolled sugars may require CSII if basal

bolus not effective.

Recognition and management of hypoglycemia in the hospital setting

Must have fixed hospital protocols developed with adequately trained staff. Prompt immediate therapy of any recognized hypoglycemia, defined as a BG

below 70 mg/dl.

Nurses Protocol

Other Recommendations
Proper BG device handling and training of personnel Standard protocols be set up regarding Glycemia Mgmt Patient counseling and education groups

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