Management of diabetic hyperglycaemic emergencies and hyperglycaemia in

acute coronary syndrome, stroke and end of life

Dr Paul Smith

Consultant Endocrinologist

University Hospitals Morecambe Bay NHS Trust

Diabetic Ketoacidosis

•Defined by biochemical triad• ketonaemia• hyperglycaemia• acidaemia

Pathophysiology of Diabetic ketoacidosisInsulin deficiency Stress

Increased glucocorticoid, glucagon& catecholamine release

Hyperglycaemia

DehydrationElectrolyte loss

Hypovolaemia Increased mineralocorticoidrelease

Potassiumloss

Intracellular dehydration/lossinsulin effects cell membranes

Potassium leak from cells

Mobilisation NEFA from adipose tissue

liver

Glucagon

Ketogenesis & inhibition fatty acid synthesis

Ketone body metabolismimpaired

Ketone accumulation

Acidosis

Hyperkalaemia

Increased giycogenolysis & hepatic gluconeogenesis

Osmoticdiuresis

DKA

Diagnostic criteria

• Blood ketones (bhydroxybutyrate) >3mmol/l or ketonuria >2+

• Blood glucose >11mmol/l or known diabetes mellitus

• Venous pH <7.3 and, or venous HCO3 <15mmol/l

Typical deficits at diagnosis• Water – 100ml/kg

• Sodium – 7-10mmol/kg

• Chloride – 3-5mmol/kg

• Potassium – 3-5mmol/kg

Fundamentals of national guideline

• Blood ketone monitoring in diagnosis and treatment

• Aggressive rehydration with crystalloid

• Fixed rate insulin infusion based on body weight

• Maximise near patient testing - Venous samples through gas analyser for pH, bicarbonate, electrolytes and glucose

• Continuation of sc basal insulin therapy

• Add in K+ when serum K+ <5.5mmol/l

• Add 10% dextrose when glucose <14mmol/l

• Early involvement of diabetes specialist team

• Resolution of DKA• pH >7.3; HCO3>15mmol/l• Blood ketones <0.6mmol/l

Severe DKAPresence of one or more of the following should prompt review by a consultant physician and consideration of referral to Level 2 (HDU) care

• Blood ketones >6mmol/l

• HCO3 < 5mmol/l

• pH <7.0

• Hypokalaemia on admission (<3.5mmol/l)

• GCS <12

• O2 saturation <92% on air

• Systolic BP <90mmHg

• Pulse <60min-1 or >100min-1

• Anion gap >16

Controversial Areas (1)• Arterial vs Venous monitoring?

• Negligible differences in pH - 0.02-0.15 pH units and HCO3 - 1.88mmol/l1

• Benefits blood vs urine ketone monitoring 2

• Reduced assessment time in ED & fewer admissions

• Shorter time to recovery

• Bedside monitoring• Facilitates regular monitoring - Reduces delays in results

• Colloid vs crystalloid?• Recent data suggests crystalloid superior to colloid in fluid resuscitation of the critically ill3,4

• 0.9% saline vs Hartmann’s• Evidence of superiority in clinical outcomes lacking5,6

• Risk of hyperchloraemic acidosis with excess saline infusion

• Hartmann’s solution lacks flexibility in K+ concentration

1. Gokel et al, Am J Nephrol 2000:202. Klocker et al, Diab Med 2013:30 3. Reinhart et al, Int Care Med 2013:384. Perel et al, Cochrane Database Syst Rev 2007; Issue 45. Mahler et al, Am J Emerg Med 2011:296. Van Zyl et al, QJM 2012: 105

Controversial Areas (2)

• Rate of fluid replacement• Concern that rapid fluid replacement may lead to cerebral oedema in the young

so more cautious fluid resuscitation advised in non-shocked young adults

• Continuation long acting basal insulins• Provides background insulin - reduces risk rebound hyperglycaemia when IV

therapy stopped• Facilitates earlier discharge on resolution DKA• No evidence continuation human basal insulins less safe than analogues

• Weight based fixed rate insulin infusion (FRII)• Compensates insulin resistance of obesity• Leads to more rapid clearance ketonaemia

• Priming bolus of IV insulin• No evidence of benefit• Only indicated if there is a delay in commencing FRII

Controversial Areas (3)

• Intravenous bicarbonate• Acidosis will resolve with rehydration and adequate insulin1

• Excessive HCO3 may increase CO2 partial pressure in CSF and paradoxical CSF acidosis2

• Some evidence bicarbonate therapy increases risk of cerebral oedema in children3

• Intravenous phosphate• Phosphate deficiency common in patients presenting with DKA but no evidence

of benefit from replacement

• Rate of glucose lowering• No evidence glucose lowering with 0.1U/kg insulin causes harm

• Discontinuation SC insulin pump therapy• Occlusion of giving set and/or infection at introducer site may have led to DKA• Negligible benefit from continuation

1. Chua et al, Ann Int Care 2013, 1(23)2. Morris et al, Ann Int Med, 1986, 105(6)3. Glaser et al, NEJM 2001, 344(4)

Serious complications (1)

• Hypokalaemia and hyperkalaemia• Avoid potassium with initial fluid resuscitation & monitor electrolytes 2 hourly

• Add potassium 40mmol/l to 0.9% saline when K+ <5.5mmol/l

• Review replacement and consider HDU if K+ falls <3.5mmol/l

• Review treatment DKA in 2014 in UK 55% patients developed hypokalaemia1

• Hypoglycaemia• Hypoglycaemia - release of counter-regulatory hormones can cause rebound

ketosis

• Severe hypoglycaemia may lead to cardiac arrhythmia, acute brain injury and death

• Hourly monitoring of blood glucose & introduction 10% dextrose infusion when <14mmol/l minimises risk

• Review of 2014 -26% patients experienced hypoglycaemia1

1. Dhatariya et al, Diabetic Medicine 2016:33(2)

Serious complications (2)

• Cerebral oedema• Uncommon in adults - when occurs does so within a few hours of treatment

• Cause is unknown

• Consider more cautious fluids in non-shocked young adults and, or use of paediatric DKA guideline

• Pulmonary oedema• Rare

• Elderly/those with a cardiac history most at risk - consider HDU care/invasive monitoring

Hyperosmolar hyperglycaemic state (HHS)

• Hyperglycaemic emergency characterised by• Hypovolaemia• Severe hyperglycaemia (>30mmol/l) without significant hyperketonaemia

(<3mmol/l) or acidosis (pH>7.3, HCO3>15)• Hyperosmolality usually >320mosmol/kg

• Previously referred to as hyperosmolar non-ketotic coma (HONK)

• Less common than DKA but higher mortality (15-20%)1

• Typically occurs in the elderly but also young adults/middle-aged

• Usually presents with AKI

• Vascular complications include MI, stroke, peripheral arterial thrombosis

• Other complications include seizures, cerebral oedema, central pontine myelinolysis (CPM)

1. Kitabachi et al, Diabetes Care 2009:32

Principles of treatment HHS (1)• Diagnosis with laboratory blood samples

• Check blood ketones and lactate

• Monitor venous electrolytes, pH, (glucose) using ABG machine

• Calculate osmolality (2xNa+ + glucose + urea) for diagnosis and every hour

• Rehydrate with IV 0.9% saline

• Fluid losses likely to be 100-220ml/kg body weight – estimate from clinical and biochemical measures

• Strict fluid balance monitoring needed

• Aim positive fluid balance 3-6 litres at 12 hours and replacement remaining deficit next 12-72 hours

• Switch to 0.45% saline only if osmolality is not declining• An initial rise in serum Na+ is inevitable as falling osmolality with declining glucose

leads to an intracellular osmotic shift of water

Principles of treatment HHS (2)

• Rate of fall of serum Na+ to be kept <10mmol/l/24 hours

• Fall in blood glucose should be kept at <5mmol/l/hour

• Commence fixed rate IV insulin at 0.05U/kg body weight only when blood glucose stops falling with rehydration OR with commencement of IV fluids if blood ketones >1mmol/l or urine ketones 2+

• Commence K+ 40mmol/l of 0.9% saline once serum K+ <5.5mmol/l

• Assessment for complications of treatment: fluid overload, cerebral oedema, CPM every 1-2 hours

• Underlying precipitants identified and treated

• Prophylactic anticoagulation with LMWH

• High risk of foot ulceration – heels examined and protected

HHS -Identification of patients for consideration of level 2/HDU care

One or more of:

• Osmolality >350mosmol/kg

• Na+ >160mmol/l

• pH <7.1

• Hypokalaemia <3.5mmol/l or hyperkalaemia >6mmol/l on admission

• GCS < 12

• Oxygen saturations <92% on air

• Systolic BP <90mmHg

• Pulse <60min-1 or >100min-1

• Urine output <0.5ml/kg/hour

• Serum creatinine >200mmol/l

• Hypothermia

• Macrovascular event

• Other serious comorbidity

Diabetes and hyperglycaemia in patients presenting with acute coronary syndromes

• long-term outcome after AMI is worse for patients with diabetes due to increased mortality and nonfatal cardiovascular end points1

• Approximately 30% of patients with AMI have undiagnosed diabetes2

• In study of >4000 patients with STEMI, the admission blood glucose showed a U shaped relationship with mortality and morbidity3

Admission blood sugar

Hypoglycaemia(<4.5mmol/l)

Euglycaemia(4.5-5.5mmol/l)

Severe hyperglycaemia(>11mmol/l)

30 day mortality rate

4.6 1.0 4.7

30 day recurrent MI or death rate

10.5 4.2 7.2

1. Haffner et al, NEJM 1998:3392. Norhammar et al, Lancet 2002:3593. Pinto et al, J Am Coll Cardiol 2005:46

NICE recommendations managing hyperglycaemia in inpatients within 48 hours of ACS

• Manage hyperglycaemia in patients admitted to hospital for an ACS by keeping blood glucose levels <11.0 mmol/litre while avoiding hypoglycaemia.

• Consider variable rate insulin infusion with regular monitoring of blood glucose levels.

• Do not routinely offer intensive insulin therapy (IV insulin and glucose +/- potassium)

Hyperglycaemia in patients with stroke

• Hyperglycaemia predicts a worse outcome in patients experiencing stroke

• Studies of intensive lowering of blood sugar with intravenous insulin/GKI infusions have not been proven to improve outcomes in hyperglycaemic stroke patients1,2

• Such intensive therapies increase risks of hypoglycaemia and significantly increase nursing staff workload1,2

1. Gray et al, Lancet Neurology 20072. Bruno et, Stroke 2008; 39

Recommendations for the management of hyperglycaemia in the context of acute stroke

• 4-6 hourly capillary blood glucose (CBG)monitoring all patients presenting with stroke and diabetes or newly recognised hyperglycaemia.

• Refer patient to diabetes inpatient specialist nurse/diabetes inpatient team at earliest opportunity

• Patients with type 1 diabetes must continue basal insulin

• Patients with type 2 diabetes should continue subcutaneous basal analogue insulin therapies if treated with the same on admission.

• Target CBG 6-12 mmol/l.

Key principles of treatment of diabetes at the end of life

• Provision of a painless and symptom-free death

• Tailor glucose-lowering therapy to minimise adverse treatment effects, avoid metabolic de-compensation and diabetes-related emergencies:• hypoglycaemia

• DKA

• HHS

• persistent symptomatic hyperglycaemia

• Avoidance foot complications in frail, bed-bound patients

• Avoidance symptomatic clinical dehydration

• Intervention appropriate to stage of illness, symptoms and respect for dignity

• Supporting patients in diabetes self-management to the last possible stage

Diabetes management in last few days of life1

1. End of Life Diabetes CareClinical Care RecommendationsSecond Edition Oct 2013Diabetes UK