Hyperglycaemic emergencies in Diabetes mellitus

1. PATHOPHYSIOLOGY AND MANAGEMENT
OF HYPERGLYCAEMIC EMERGENCIES IN
DIABETES MELLITUS
Presenter : Dr. Kapil Dhingra

2. 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

3. 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

4. Role of Insulin

5. Hyperglycaemic Emergencies
• Diabetic Ketoacidosis
(DKA)
• Hyperglycaemic
Hyperosmolar State
(HHS)

6. Triad of Diabetic Ketoacidosis
HYPERGLYCAEMIA
DKA
KETOSIS ACIDOSIS

7. Hyperglycaemic Hyperosmolar
State (HHS)
– Distinguishing characteristics
• Hyperglycemia
• Hyperosmolarity
• Altered sensorium
– Patients are typically Type 2 diabetics

8. Epidemiology
DKA HHS
• 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%

9. Pathophysiology of DKA

10. Pathophysiology of HHS
Brain
Hyperglycemia
Hyperosmolality
Pancreas
Kidney
Liver Muscle
Impaired
insulin
secretion
Decreased GFR
Gluconeogenesis
Impaired glucose
uptake
Impaired thirst

11. 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

12. 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

13. 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

14. HHS: Precipitating Factors
1. Age > 70 years
Contributing Factor- debilitating
condition (prior stroke or
dementia) or social situation that
compromises water intake
2. Infection
3. Myocardial infarction
4. Stroke
5. Undiagnosed/untreated Type 2 diabetes
6. Drugs (corticosteroids, thiazides, dobutamine,
terbutaline, second generation antipsychotic agents)

15. 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

16. HHS: Signs
1. Altered mental status (confusion to coma)
2. Dehydration
3. Hypotension/“Normal” BP in hypertensive
patient
4. Tachycardia
5. Fever/Hypothermia

17. 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

18. 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).

19. 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.

20. Labs: Glucose
• Usually between 250-600mg/dl (DKA)
and 600-1200mg/dl (HHS)
• Euglycaemic DKA:
1. Nutritional deficiency/starvation
2. Pregnancy

21. Labs: Anion Gap
• Anion Gap= Na – (Cl + HCO3)
• Normal <14 mEq/L; DKA >20 mEq/L
• Accumulation of β hydroxybutyrate and
acetoacetate

22. Acidosis
• Sine qua non of DKA
• s/ HCO3 < 10 mEq/L
• pH = 6.8-7.3
• Production and accumulation of ketones
in serum

23. 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)

24. 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) ]

25. 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

26. Labs: Others
• Phosphate
– Usually body depleted, but initial levels may be
normal or high
• Amylase
– May be elevated (DKA), even without pancreatitis. If
pancreatitis is suspected , s/lipase should be done.
• Elevated WBC
• Hypertriglyceridemia and hyperlipoproteinemia

27. ADA Diagnostic Criteria
DKA
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
Kitabchi AE et al. Diabetes Care (2001) 24:131.

28. Therapeutic goals
Treatment involves 5 key components:
1. Fluid resuscitation
2. Insulin and dextrose infusion
3. Electrolyte repletion
4. Monitoring
5. Treating underlying cause

29. Fluids, fluids, fluids!
• Restores circulatory volume
• Diminish concentration of catecholamines, glucagon
• ↑ urinary glucose loss

30. Caution!
Excessive therapy may result in
• ARDS
• Cerebral edema
• Hyperchloremic acidosis

31. 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

32. 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

33. 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)

34. 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.

35. Who saved me: the insulin or the
nurse ?

36. 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

37. Potassium Replacement
.
• Normal or elevated at the time of diagnosis
• Goal : s/K= 4 -5mEq/L
• Establish adequate renal function (UO = 50 ml/ hr)
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 betn
4-5 mEq/L
Check s/K every 2
hrs

38. 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

39. 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.

40. 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

41. Data Flowsheet

42. 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

43. DKA Mortality
• Mortality primarily due to precipitating
illness
• Prognosis worse with
– Old Age
– Coma
– Hypotension
– Severe comorbidities

44. DKA HHS
Type of DM T1DM>T2DM T2DM>T1DM
Ketosis/acidosis Present Absent
Age group Any age Typically elderly
Onset Rapid Insidious
Nausea/vomiting/abdo
Present Absent
minal pain
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%

45. Prevention
• Patient education
1. symptoms of DKA
2. precipitating factors
3. management of diabetes during a concurrent
illness.

46. 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.

47. 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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48. THANK YOU &