PATHOPHYSIOLOGY AND MANAGEMENT OF HYPERGLYCAEMIC EMERGENCIES IN

DIABETES MELLITUS

Presenter : Dr. Kapil Dhingra

Diabetes Mellitus : An overview

• Diabetes mellitus (DM) refers to a group of common metabolic disorders that share the phenotype of hyperglycemia

• Factors contributing to hyperglycemia include :

1. reduced insulin secretion,

2. decreased glucose utilization,

3. increased glucose production

Classification of Diabetes

• Type 1 diabetes

– β-cell destruction

• Type 2 diabetes

– Progressive insulin secretory defect

• Other specific types of diabetes

– Genetic defects in β-cell function, insulin action

– Diseases of the exocrine pancreas

– Drug- or chemical-induced

• Gestational diabetes mellitus

Role of Insulin

Hyperglycaemic Emergencies

• Diabetic Ketoacidosis (DKA)

• Hyperglycaemic Hyperosmolar State (HHS)

Triad of Diabetic Ketoacidosis

HYPERGLYCAEMIA

KETOSIS ACIDOSIS

DKA

Hyperglycaemic Hyperosmolar State (HHS)

– Distinguishing characteristics

• Hyperglycemia

• Hyperosmolarity

• Altered sensorium

– Patients are typically Type 2 diabetics

Epidemiology

• Average of ~ 100,000 hospitalizations/yr

• Annual hospital costs exceed $1 billion

• Mortality rate 2-5%

• Lack of population-based studies

• Less than 1% of diabetes-related admissions

• Mortality rate ~ 15%

DKA HHS

Pathophysiology of DKA

Hyperglycemia

Hyperosmolality

Pancreas

Liver Muscle

Pathophysiology of HHS

Kidney

Impaired insulin secretion

Decreased GFR

Gluconeogenesis

Impaired glucose

uptake

Brain

Impaired thirst

DKA: Precipitating Events

1. Insulin omission /inadequate administration

2. Infection – Pneumonia, UTI

3. Infarction – ACS, Stroke

4. Trauma

5. New diagnosis of Diabetes- often misdiagnosed

DKA: Symptoms

Evolves rapidly within a few hours of the precipitating event(s).

1. Nausea/ vomiting

2. Thirst , polyuria

3. Abdominal pain

4. Shortness of breath

5. Full alertness to profound lethargy or coma

DKA: Physical Findings

1. Dry buccal mucosa, sunken eye balls, poor skin turgor

2. Tachycardia

3. Hypotension/Shock

4. Tachypnea/Kussmaul respirations/respiratory distress

5. Abdominal tenderness (may resemble acute pancreatitis or surgical abdomen)

6. Lethargy/obtundation/cerebral edema/possibly coma

HHS: Precipitating Factors

1. Age > 70 years

2. Infection

3. Myocardial infarction

4. Stroke

5. Undiagnosed/untreated Type 2 diabetes

6. Drugs (corticosteroids, thiazides, dobutamine, terbutaline, second generation antipsychotic agents)

Contributing Factor- debilitatingcondition (prior stroke ordementia) or social situation thatcompromises water intake

HHS: Symptoms

• Onset- insidious

• Several-week history of polyuria, weight loss, and diminished oral intake

• Mental confusion, lethargy, or coma

• Focal neurological deficit

• Seizure

•Notably absent are nausea, vomiting and abdominal pain

HHS: Signs1. Altered mental status (confusion to coma)

2. Dehydration

3. Hypotension/“Normal” BP in hypertensive patient

4. Tachycardia

5. Fever/Hypothermia

Initial evaluation

• History and physical examination should assess

1. Airway patency

2. Cardiovascular/hydration status

3. Mental status

4. Sources of infection

• Urgent assessment

1. Finger-stick glucose

2. Urinalysis (glucose, ketones)

3. IV access

4. ECG- arrhythmias, signs of hypo and hyperkalemia

Five I’s in a Hyperglycaemic crisis

1. Infection

2. Infarction

3. infant (pregnancy)

4. indiscretion (including cocaine ingestion)

5. insulin lack (nonadherence or inappropriate dosing).

Initial Laboratory Tests

1. Arterial blood gas

2. Blood glucose and electrolytes (with calculated anion gap)

3. Creatinine and BUN

4. Serum osmolality

5. Serum ketones

6. Complete blood count

7. Blood and urine cultures

8. Urine pregnancy test -women with childbearing potential.

Labs: Glucose

• Usually between 250-600mg/dl (DKA) and 600-1200mg/dl (HHS)

• Euglycaemic DKA:

1. Nutritional deficiency/starvation

2. Pregnancy

Labs: Anion Gap

• Anion Gap= Na – (Cl + HCO3)

• Normal <14 mEq/L; DKA >20 mEq/L

• Accumulation of β hydroxybutyrate and acetoacetate

Acidosis

• Sine qua non of DKA

• s/ HCO3 < 10 mEq/L

• pH = 6.8-7.3

• Production and accumulation of ketones in serum

Ketosis

• Three types of ketones:

a) 2 ketoacids ( β hydroxybutyrate and acetoacetate)

b) Neutral ketone acetone

• Detected in serum and urine

• Nitroprusside reaction converts AA to acetone

– Theoretically possible to have ketoacidosis from mainly BHB & have a negative test

– Can test by adding Hydrogen Peroxide to urine (converts BHB to AA & allows NP reaction)

Labs: Sodium

• Variable sodium levels

• Direct effect of hyperglycemia leads to hyponatremia (1.6 meq reduction in serum sodium for each 100 mg/dL rise in the serum glucose)

• Secondary effect of osmotic diuresis which causes loss of free water→ hypernatremia

• Mostly [ 125-135 (DKA), 135-145 (HHS) ]

Labs: Potassium

• Overall potassium deficit– Renal loss with osmotic diuresis – ketone excretion (DKA)– GI loss

• However, on initial evaluation, K level is usually normal or elevated– Acidosis– Hyperosmolarity– Insulin deficiency

• Take great care in monitoring/repleting K

Labs: Others

• Phosphate

– Usually body depleted, but initial levels may benormal or high

• Amylase

– May be elevated (DKA), even without pancreatitis. Ifpancreatitis is suspected , s/lipase should be done.

• Elevated WBC

• Hypertriglyceridemia and hyperlipoproteinemia

ADA Diagnostic Criteria

Mild Moderate Severe HHS

Glc (mg/dL) > 250 > 250 > 250 > 600

pH 7.25-7.30 7.00-7.24 < 7.00 > 7.30

HCO3- (mM) 15-18 10-14 < 10 > 18

Urine ketones + + + Small

Serum ketones + + + Small

Osmolality Varies Varies Varies > 320

Anion gap > 10 > 12 > 12 < 12

Sensorium Alert Drowsy Stupor/Coma Stupor/Coma

DKA

Kitabchi AE et al. Diabetes Care (2001) 24:131.

Therapeutic goals

Treatment involves 5 key components:

1. Fluid resuscitation

2. Insulin and dextrose infusion

3. Electrolyte repletion

4. Monitoring

5. Treating underlying cause

Fluids, fluids, fluids!

• Restores circulatory volume• Diminish concentration of catecholamines, glucagon• ↑ urinary glucose loss

Caution!

Excessive therapy may result in • ARDS• Cerebral edema• Hyperchloremic acidosis

Fluid replacement

• Initial fluid = 0.9% saline– 15ml to 20ml/kg/hr, about 1-1.5L in 1 hour

– 500 ml/h for next 2 hours or 1L /h if in shock

– 250-500 ml/h according to hydration status

• Subsequent change in fluids– 0.45% saline, 250-500ml/hr

• START when urine output improves and BP stable

– 5% dextrose, 0.45% saline, 150-250ml/hr

• START when blood glucose <200 mg/dl (DKA) and <300mg/dl (HHS)

• Endpoint – resolution of DKA/HHS

Insulin administration

• Withhold insulin therapy until the serum potassium

concentration has been determined (s/K >3.3meq/L)

• Initial regular insulin

– Goal = reduce hourly glucose by 50-70 mg/dl

– Bolus = 0.1U/kg IV

– IV infusion = 0.1U/kg/hr

– Goal not achieved in 1st hr = double the insulin dose

Insulin administration

• BS: 200 mg/dl (DKA) or 300 mg/dl (HHS) IVF – D5, ½ NS Insulin rate - 0.05 U/kg/hr

• Maintenance blood glucose 150-200 mg/dl (DKA) and 250-300 mg/dl (HHS)

• End Point Resolution of DKA/HHS

• It is important to give the first s.c. injection of insulin approximately 2 hours before stopping the i.v. route. (Long-acting insulin + SC short-acting insulin)

Resolution

DKA

1. blood glucose is < 200 mg/dl

2. serum bicarbonate is > 18

3. pH is > 7.30

4. anion gap is < 12

HHS

1. osmolarity is < 320 mOsm/kg

2. gradual recovery to mental alertness.

Who saved me: the insulin or the nurse ?

Clinical Formulae

• Anion gap– Na - (Cl + HCO3)

– Normal 7-9 (ion-specific electrodes), 8-12 (absorption spectroscopy)

• Osmolality– 2(Na+K) + glucose/18 + BUN/2.8

– Approximation is 2(Na+K) + glucose/20 + BUN/3

– Normal 290 + 5 mOsm/kg

• Corrected sodium– {[(Glc-100)/100]x1.6}+Na+

meas

Potassium Replacement

.

K < 3.3 mEq/L K=3.3 mEq/L-5.3 mEq/L

K > 5.3mEq/L

Withhold insulin 10 mEq of K/hr Do not give K

40mEq of K/hr till K > 3.3 mEq/L

20-30mEq/L of IVF till s/K betn4-5 mEq/L

Check s/K every 2 hrs

• Normal or elevated at the time of diagnosis

• Goal : s/K= 4 -5mEq/L

• Establish adequate renal function (UO = 50 ml/ hr)

Bicarbonate Therapy

pH< 6.9

100 mmol sodium bicarbonate in 400 ml sterile water (an isotonic solution) with 20 mEq KCl

200 ml/h for two hours

pH= 6.9-7.0

50 mmol of bicarbonate in 200 ml of sterile water with 10 mEq KCL

Infuse over 1 hr

pH>7.0

No sodium bicarbonate

•Controversial subject

•In patients with pH > 7.0, insulin therapy inhibits lipolysis and also corrects ketoacidosis without use of bicarbonate

•Adverse effects

1. hypokalemia

2. decreased tissue oxygen uptake

3. cerebral edema

4. delay in the resolution of ketosis

Venous pH should be assessed every 2 hours until the pH

rises to 7.0; treatment can be repeated every 2 hours if necessary

Phosphate therapy

• Phosphate deficiency– Osmotic diuresis → urinary phosphate losses– Insulin therapy → serum phosphate reenters intracellular compartment

• RCT have not demonstrated that phosphate replacement is beneficial in DKA

• Adverse complications may occur if P < 1.0 mg/dl– Respiratory depression– Skeletal muscle weakness– Hemolytic anemia– Cardiac dysfunction

• May be useful to replace 1/3 potassium as K3PO4,reduce chloride load, prevent hyperchloremic acidosis.

Monitoring

1. Don’t expect much sleep

2. Clinical Status

3. Capillary glucose every 1–2 h

4. Electrolytes (especially K+, bicarbonate, phosphate) and anion gap every 4 h for first 24 h.

5. Blood pressure, pulse, respirations, mental status, fluid intake and output every 1–4 h

6. Venous pH q2-4 hrs

7. Ketones?

8. Consider use of flowsheet

Data Flowsheet

Complications

• Lactic acidosis– Due to prolonged dehydration, shock, infection and tissue hypoxia– Should be suspected in pt with refractory metabolic acidosis and

persistent anion gap

• Arterial thrombosis– Stroke, MI, or an ischemic limb

• Cerebral edema– Over hydration of free water, excessively rapid correction of

hyperglycemia are risk factors

• ARDS– Excessive crystalloid infusion– Pulmonary rales, increased AaO2 gradient

DKA Mortality

• Mortality primarily due to precipitating illness

• Prognosis worse with

– Old Age

– Coma

– Hypotension

– Severe comorbidities

DKA HHS

Type of DM T1DM>T2DM T2DM>T1DM

Ketosis/acidosis Present Absent

Age group Any age Typically elderly

Onset Rapid Insidious

Nausea/vomiting/abdominal pain

Present Absent

Mental changes Less common common

Focal neurological deficit uncommon common

Seizures uncommon common

Prerenal Azotemia mild marked

Blood Glucose 250-600 800-1200

Fluid deficit 3-5L 8-10L

Addition of dextrose S glucose=200mg/dL s/glucose=300mg/dl

Bicarbonate therapy needed Not needed

Mortality 2-5% 15%

Prevention

• Patient education

1. symptoms of DKA

2. precipitating factors

3. management of diabetes during a concurrent illness.

Prevention

• During illness or when oral intake is compromised, patients should

1. frequently measure the capillary blood glucose

2. measure urinary ketones when the serum glucose > 16.5 mmol/L (300 mg/dL)

3. drink fluids to maintain hydration

4. continue or increase insulin; and

5. seek medical attention if dehydration, persistent vomiting, or uncontrolled hyperglycemia develop.

Three Take Home Messages

1. DKA &HHS may be life threatening

2. Fluids and Insulin along with frequent

monitoring is essential

3. Watch for hypokalemia and cerebral

edema

11/13/2014 5:44:25 AM

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