Management of hyperglycaemic

emergenciesUkandu Igwe,

Senior Registrar,Endocrinology, Diabetes and Metabolism Unit,

Lagos University Teaching Hospital.

Outline

•Goals of management•Fluid therapy• Insulin•Electrolytes•General measures

•Summary

•Goals of management•Fluid therapy• Insulin•Electrolytes•General measures

•Summary

Goals of management

•Rehydrating the patient•Correcting hyperglycaemia•Correcting acidosis and ketonaemia•Correcting electrolyte abnormalities• Identifying and managing precipitants•Avoiding and managing complications

Typical deficits DKA HHS Corresponding losses (in a 70-kg man)

DKA HHS

Water (ml/kg) 100 100-200 7l 7-14l

Na+ (meq/kg) 7-10 5-13 490-700meq 490-980meq

Cl- (meq/kg) 3-5 4-6 210-350meq 280-420meq

K+ (meq/kg) 3-5 3-7 210-350meq 210-490meq

PO4 (meq/kg) 5-7 1-2 350-490meq 70-140meq

Mg++ (meq/kg) 1-2 1-2 70-140meq 70-140meq

Ca++ (meq/kg) 1-2 1-2 70-140meq 70-140meq

Severe DKA

Features of severe DKA:• Ketones > 6mmol/l• HC03

- > 5mmol/l• K+ < 3.5mmol/l• Glasgow Coma Score <12• O2 < 92%• Systolic blood pressure < 90mmHg• Pulse rate > 100/mn or < 60/mn• Anion gap > 16mmol/l

Manage in Intensive Care Unit

Severe DKA

Fluid therapy

• Intravascular, interstitial and intracellular fluid are all depleted•Typical deficits 100-200ml/kg•Estimated deficits should be corrected within 24h•Pass 2 wide bore intravenous cannulas

Fluid therapy

• Fluid replacement alone will lower the blood glucose• Typical fluid regimen (through intravenous route)• 1l in first hour• 1l over next 1h• 1l over next 2h• 1l over next 3h• 1l over next 4h

• If patient able to drink, give 20ml/kg of the fluid (water) orally• Modify regimen based on input/output, cardiac status

Fluid

• 0.9% saline is fluid of choice• Change to 5% or 10% glucose when RBS < 250mg/dl• If patient still volume depleted 0.9% saline may be continued

concurrently• If random blood glucose > 250mg/dl after changing,

continue glucose infusion and increase insulin. Do not revert to normal saline• If acidosis slow to resolve and RBG < 180mg/dl (euglycaemic

ketoacidosis) change 5% to 10% dextrose to allow faster insulin rate

Insulin therapy

• Insulin therapy is effective regardless of route of administration• Should be instituted about 1h after commencing fluid therapy• Continuous intravenous infusion is preferred route• Short half life• Easy titration

• Start at 0.1unit/kg/h (e.g. 6 units for 60kg man)• Target blood glucose reduction 50-75mg/dl per hour• If reduction rate is slower, increase insulin infusion rate till steady decline

by 50%• Continue long-acting insulin analogues

Insulin infusion pump

Buretrol

Insulin therapy

• In DKA, when serum glucose falls to ≤250 mg/dl• The insulin infusion is decreased to 0.02 to 0.05

units/kg/h•5% dextrose with 0.45% NaCl is initiated at a rate of

150 to 250 mL/h• Titrate to keep serum glucose between 150 and 200

mg/dl until DKA is resolved

Insulin therapy

• In HHS, when the glucose falls to ≤300 mg/dl• The rate of insulin is switched to 0.02 to 0.05

units/kg/h•And 5% dextrose with 0.45% NaCl is infused at a

rate of 150 to 250 mL/h• Titrate to keep serum glucose between 200 and 300

mg/dl until HHS has resolved

Insulin therapy

Transition to subcutaneous insulin• Run continuous intravenous insulin till:• For DKA, RBS < 200mg/dl and 2 of• HCO3

- ≥ 15mmol/l• Venous pH > 7.3• Anion gap ≤ 12mmol/l

• For HHS• Normal osmolality• Regaining of normal mental status

Insulin therapy

Transition to subcutaneous insulin•When ketosis is resolved and patient eating, change to

subcutaneous • Overlap with IV 1-2h• Basal-bolus regimen• Lispro/aspart + glargine have lower incidence of

hyperglycaemia than regular + NPH• Same dose as pre-crisis, or 0.5-0.8 units/kg/day

Insulin therapy

•32 patients with hyperglycaemic emergencies in Lagos (Anumah-Ehusani, Ohwovoriole)•40.6% DKA•34.4% HHS•25% non-ketotic normoosmolar hyperglycaemic state

Insulin therapy

•Mean time to RBS < 250mg/dl• IV: 3.2h• IM: 4.2h

• Longer in HHS• Rate of reduction more gradual and more predictable in IM

• Another study in Cameroun: IM insulin and careful rehydration leads to reduced mortality

Insulin therapy

• Hourly subcutaneous lispro insulin vs hourly intramuscular regular insulin• No difference in outcome, hypoglycaemia, mortality (Adesina et al)• Sc lispro or aspart insulin in mild-moderate HE are as safe as IV regular

insulin in non-ICU patients• But use only IV regular insulin in• ICU• Hypotension• Anasarca• Severe critical illness

Insulin therapy

Insulin therapy

Potassium correction

• Total K+ depleted but hyperkalaemia common at presentation• K+ replacement when < 5.0mmol/l, target 4-5mmol/l• Generally, add 20-30meq to each litre of IVF• If hypokalaemia, omit till > 3.5mmol/l• Hypokalaemia can result from• Insulin therapy• Correction of acidosis• Volume expansion

Potassium correction

Serum potassium Action

<3.5mmol/l Withhold insulinAdd 30mmol KCl to each litre of IVF

3.5-5.2mmol/l Add 20-30mmol KCl to each litre of IVF

>5.2mmol/l Withhold KCl and reassess every 2h

Bicarbonate correction• Usually no replacement• Self-correction in mild-moderate• Adequate fluid and insulin usually will resolve acidosis• But severe acidosis causes• Impaired myocardial contractility• Cerebral vasodilatation• Coma

• If pH < 6.9• 100mmol of 1.4% NaHCO3 in 400ml sterile water • + 20mmol KCl • Run at 200ml/h until pH >7.0

Phosphate correction

•Normal at presentation•Reduced by insulin therapy•No benefit of replacement. Can cause hypocalcaemia•But replace if: anaemia, respiratory depression,

cardiac dysfunction•20-30meq/l of IVF, at 4-5mmol/h•No role in HHS

Metabolic treatment targets

•Reduce capillary blood glucose by 50-75mg/dl per hour•Reduce blood ketones by 0.5mmol/l per hour• Increase HC03

- by 3mmol/l per hour•Maintain K+ 4-5mmol/l•Reduce Na+ by 10mmol/l in 24h

General measures

•Diabetologist’s involvement shortens hospital stay•Weight-based, fixed rate insulin infusion better than sliding scale

General measures

•Management of DKA focused on ketones, not glucose•Portable ketone metres for bedside

ketone (β-hydroxybutyrate)•Resolution of DKA depends on

suppression of ketonaemia• So measurement of blood ketones

now represent best practice

Monitoring

•Monitor blood glucose hourly• Serum electrolytes, urea and creatinine 2-6 hourly•Cardiac monitoring•Use blood ketone metre (bedside)•Monitor fluid input/output•Routine catheterisation not advised

Other measures

•Identify and treat precipitating factors•Routine anticoagulation (unless contraindication)•Treat complications•Prevent recurrence

Treat complications

• Hypoglycaemia. Can result to:• Rebound ketosis (increased counter-regulatory hormones)• Arrhythmia, brain injury

• Cerebral oedema: Intravenous mannitol, dexamethasone• Cardiac arrhythmias: correct precipitant (hypokalaemia,

acidosis…), cardiac monitoring• Pulmonary oedema: cautious fluid correction, diuretics,

oxygen

Prevention

• Proper patient education• Early access to medical care• effective communication with a health care provider

during intercurrent illness• Education of family members on sick day rule

• Self blood glucose monitoring• Urine ketone testing• Better access to medical care• Provision of guidelines reduce mortality

Summary…

•Early involvement of diabetologist •Adequate hydration initial therapeutic intervention•Continuous intravenous insulin therapy preferred •Emphasis on serum ketones over glucose (in DKA)•Correction of electrolyte abnormalities

References

• Kitbachi AE, Milez JM, Umpierrez GE, Fisher JN. Hyperglycaemic crises in adult patients with diabetes. Diabetes Care 2009; 32(7): 1335-1343• Sobngwi E, Lekoubou Al, Dehayem MY, Nouthe BE, Balti EV, Nwastock

F, et al. Evaluation of a simple management protocol for hyperglycaemic crises using intramuscular insulin in a resource-limited setting. Diabetes & Metabolism 2009 (35) 404-409.• Ehusani_Anumah FO, Ohwovoriole AE. Plasma glucose response to

insulin in hyperglycaemic crisis. Int J Diabetes & Metabolism 2007 (15): 17-21

References

• Canadian Diabetes Association Clinical Practice Guidelines Expert Committee. Hyperglycemic emergrncies in adults. Can J Diabetes 2013 (37): S72-S76• Chinenye S, Ofoegbu EN, Onyemelukwe GC, Uloko AE, Ogbera AO.

Clinical practice guidelines for diabetes management in Nigeria. Published by Diabetes Association of Nigeria, 2013. Accessed at diabetesnigeria.org on 14-02-15• Joint British Diabetes Societies Inpatient Care Group. The management

of diabetic ketoacidosis in adults, 2013. Available at http://www.diabetologists-abcd.org.uk/JBDS/JBDS.htm and the Diabetes UK website at www.diabetes.org.uk

References

• Anumah FO. Management of hyperglycaemic emergencies in the tropics. Ann Afr Med 2007;6:45-50• Fasanmade OA, Odeniyi IA, Ogbera AO. Diabetic ketoacidosis:

diagnosis and management. Afr J Med Sci 2008; 37 (2): 99-105• Joint British Diabetes Societies Inpatient Care Group. The

management of the hyperosmolar hyperglycaemic state in adults with diabetes, 2012. Available at http://www.diabetologists-abcd.org.uk/JBDS/JBDS_IP_HHS_Adults.pdf.

References

• Adesina OF, Kolawole BA, Ikem RT, Adebayo OJ, Soyoye DO. Comparison of lispro insulin and regular insulin in the management of hyperglycaemic emergencies. Afr J Med Sci 2011; 40(1): 59-66

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