Diabetic Ketoacidosis and Hyperglycemia Hyperosmolar Syndrome

1. Diabetic Emergencies
DR ADIB MURSYIDI IM
EMERGENCY AND TRAUMA DEPARTMENT, HCTM

2. Diabetic
Ketoacidosis
(DKA)

3. Introduction and Epidemiology
 Acute, life threatening complication of DM in predominant in Type 1
 Overall mortality is <1%, but a mortality rate >5% in the elderly has been reported
 Mortality in patients with DKA is frequently related to the underlying etiological
precipitant rather than the metabolic sequelae of hyperglycaemia or ketoacidosis

4. Precipitating Factors
 Common - infection (often pneumonia or urinary tract infection) &
discontinuation of or inadequate insulin therapy
 Acute major illnesses such as myocardial infarction, cerebrovascular accident,
sepsis, or pancreatitis.
 New-onset type 1 diabetes, in which DKA is a common presentation.
 Poor compliance with the insulin regimen.

5. Physiology

6. Insulin
 Ingested glucose is primary stimulant of
insulin release from B-cells of pancreas
 Insulin main action : Liver, adipose tissue
and skeletal muscle

7.  Deficiency in insulin secretion due to loss of islet cell mass in type 1 DM
 Initial stage  secretory failure of B cells impairs fuel storage
 Evident during glucose tolerance test
 Later stage  as level of insulin decrease, fuel stores are mobilized during fasting
 resulting hyperglycemia
 As disease progression  increase blood glucose level can no longer trigger
insulin activity  lead to cell starvation

8. Pathogenesis
 Complex relationship between insulin and
counterregulatory hormones
 DKA is a response to cellular starvation
due to insulin deficiency
 Relative absence insulin and excess
counterregulatory hormones result in
hyperglycemia
Insulin
Glucagon
Cortisol
Catecholamines
GH

9. Pathophysiology

10. Ketone Body Formation
 Lipolysis
 B-oxidation splits fatty acids into Acetyl-
CoA
 Acetyl-CoA either:
 Enter Kreb’s cycle to produce ATP
 Enters Ketogenic pathway to produce
acetoacetic acids (ketones body)

11.  Ketones bodies
 Acetoacetic acid (20%)  urine ketone strip
 B-hydroxybutyric acid (78%)  blood ketone strip
 Acetone (2%)  lungs

12. Clinical Presentation
 Diabetic ketoacidosis (DKA) usually evolves rapidly - over a 24-hour period.
 In contrast, symptoms of HHS develop more insidiously, often persisting for
several days before hospital admission.
 Clinical manifestation of DKA related directly to
 Hyperglycemia
 Volume depletion
 Acidosis
 Osmotic diuresis gradually led to volume loss, in addition to renal losses of Na, Cl,
K, Phos, Ca, Mg

13. Clinical Features
 Alteration of consciousness seems to correlate better with elevated serum
osmolality (>320mmol/kg) than with severity of metabolic acidosis
 Kussmaul respiration (increase rate and depth of breathing)
 Acetone produce fruity odor breathing
 Abdominal pain and tender in DKA correlate with level of acidosis
 Pain can be due to gastric dilatation, ileus or pancreatitis

14. Diagnosis
 Blood glucose >13.9 mmol/L
 Anion gap >10 mmol/L
 Bicarbonate <15 mmol/L
 pH <7.3

15. Differential Diagnosis
 Alcoholic ketoacidosis
 Starvation ketoacidosis
 Renal failure
 Lactic acidosis
 Ingestion
 Salicylates
 Ethylene glycol
 Methanol

16. Investigation
 FBC, renal profile, electrolyte (Ca, Mg, Phos)
 Blood glucose
 Urinalysis
 ECG
 VBG
 Calculate anion gap [Na – (Cl + HCO3)]
 Blood C&S as per indicated

17. Principles of Management
1. Volume repletion
2. Reversal of metabolic consequences of
insulin insufficiency
3. Correction of electrolyte and acid-base
balance
4. Recognition and treatment of
precipitating cause
5. Avoidance complications

18. Algorithm

19. Algorithm

20. Algorithm

21. DKA data flowsheet

22. Complications
Related to acute disease
 In general, the greater initial
 Serum osmolality
 BUN
 Blood glucose
 Serum HCO3 (<10 mEq/L)
 Infection and myocardial infarction main
contributors for mortality
Greater mortality

23. Complications - Related to therapy

24. Complication

25. Complications of DKA (summary)
Related to Acute Disease Related to Therapy Later Complication
Loss of airway Hypokalemia Recurrent anion gap
metabolic acidosis
Sepsis Hypophosphatemia Non-anion gap metabolic
acidosis
Myocardial infarction Acute respiratory distress
syndrome
Vascular thrombosis
Hypovolemic shock Cerebral edema Mucormycosis
Hypoglycemia

26. Disposition and follow up
 Required hospitalization in a monitored setting (ICU)
 Nursing experienced with IV Insulin infusion

27. What to monitor? Our treatment aim?
Parameters Rate Aim
DXT Hourly Drop by 3
VBG (HCO3, K) 1H
4H
6H
HCO3 rise by 3
K : 3-5 mmol/L
Ketone 4 hourly 0.5 mmol/L/H
BUSE 6 hourly
Vital signs, I/O charting Hourly Aim positive balance
Urine output >0.5ml/kg/H
Cardiac monitor
SPO2
Continuous

28. What else to monitor?
Clinical Monitor Possible causes
A
B
Respiration Tachypneic Worsening acidosis
C Circulation Hypotension
Arrythmias
Dehydration
Electrolyte
imbalance
D GCS Drop of GCS Hypoglycemia
Cerebral edema
Hyponatremia

29. Input/output aim?
 For I/O, how much of positive balance?
 Estimated deficit in DKA up to 100ml/kg (estimated 10% of body weight), in HHS up to
200ml/kg)
 Aim to replace this deficit within the next 24-48 hours
 Aim positive balance 2-3L within this period

30. If DXT < 14
 Once blood glucose falls below 14 mmol/L
 Switch to 5% dextrose at 125ml/H and reduce insulin infusion rate to 0.05
units/kg/hour; or
 Switch to 10% dextrose at 125ml/H with no change in insulin infusion rate
 If equipment is working but response to treatment inadequate, increase insulin
infusion rate by 1 unit/hr increments hourly until target achieved

31. When to stop/overlap IVI insulin?
 Resolution of DKA:
 Patient able to eat
 Blood ketone <0.3 mmol/L
 pH. >7.3
 Do not discontinue intravenous infusion until 30 minutes after S/C short acting
insulin has been given

32.  Calculating SC insulin:
 Estimated dose = patient’s weight (kg) x 0.5
 50% of dose as bedtime, another 50% to 3 basal bolus
 Example: 80 kg required approximately 80kg x 0.5 = 40 units in 24 hours
 Eg: short acting insulin 7u & 20 units bedtime

33. Hyperosmolar
Hyperglycemic
State (HHS)

34. Background
 HHS : characterized by progressive hyperglycemia and hyperosmolarity
 Mostly in poor controlled or undiagnosed Type 2 DM
 Occurred in elderly, with common risk factors being obesity

35. Pathophysiology
Insulin resistance
and/or deficiency
Osmotic diuresis
followed by impaired
renal excretion of
glucose
Inflammatory state with marked
elevation in proinflammatory
cytokines vs counter-regulatory
stress hormones (catecholamines,
GH, glucagon, cortisol)

36. As serum glucose
concentration
increases
Osmotic gradient
develops
Shifting water
from intracellular
into intravascular
compartment
Cellular
dehydration

38. Clinical features
 History and comorbidities
 Elderly, baseline cognitive impairment, multiple comorbid, referred for abnormalities in
V/S
 Mostly evolved over days to weeks
 Nonspecific complaints
 Malaise, weakness, anorexia, fatigue, vomiting, cognitive impairment
 15% may present with seizures (typically focal)

39. Diagnosis
Severe hyperglycemia (>33.3 mmol/L)
Elevated plasma osmolality (>315 mmol/kg)
Serum HCO3 >15 mmol/L
pH >7.3
Serum ketones negative to mild positive
* Important to recognize the potential for a variety of mixed acid-base patterns in patients with
HHS

40. Diagnostic Criteria

41. Treatment

42. Treatment
 Improvement of tissue perfusion is the key to effective recovery in HHS
 The therapeutic plan must be carefully considered and adjusted for concurrent
medical illnesses such as cardiac, renal, and pulmonary disease.
 Overzealous resuscitation can result in significant harms and should be avoided.
 Treating severely ill patients likely requiring intensive care unit

43. Correction of hypovolemia
Identifying and treating precipitating causes
Correcting electrolyte abnormalities
Gradual correction of hyperglycemia and hyperosmolarity
Frequent monitoring

44.  Begin normal saline infusion before insulin therapy is started.
 The average fluid deficit in HHS is in the range of 20% to 25% of total body water, or 8
to 12L.
 One half of the fluid deficits should be replaced over the initial 12 hours and the
balance over the next 24 hours when possible.
 Begin fluid resuscitation with 0.9% normal saline at a rate of 15 to 20 mL/kg/h during
the first hour, followed by rates from 4 to 14 mL/kg/h.
 Limit the rate of volume repletion during the first 4 hours to <50 mL/kg of normal
saline. Once hypotension, tachycardia, serum hyponatremia, and urinary output
improve, 0.45% NaCl can be used to replace the remaining free water deficit.
 Hourly glucose, electrolyte, and osmolality measurements should be taken to monitor
progress in the critically ill.

45. Any questions? NO PLEASE.
PROCEED.

46. “
”
Blood gas: VBG or ABG?

47. Blood gas: VBG or ABG?
 Kelly AM et al. Review Article – Can Venous Blood Gas Analysis Replace
Arterial in Emergency Medical Care. Emery Med Australas 2010; 22: 493 – 498
 For pH, 3 studies of patients with DKA (265 patients) were reviewed showing a
weighted mean difference of 0.02 pH units. Only one study, which was the largest
study (200 patients) reported 95% limits of agreement of pH that were -0.009 – 0.02 pH
units.
 For bicarbonate, 7 studies with just over 900 patients were reviewed showing a
weighted mean difference of -1.41 mmol/L. Only 2 studies (246 patients and 95
patients) reported 95% limits of agreement which ranged from -5.8 to +5.3 mmol/L.

48. Blood gas: VBG or ABG?
 Ma OJ et al. Arterial Blood Gas Results Rarely Influence Emergency Physician
Management of Patients with Suspected Diabetic Ketoacidosis. Acad Emerg Med
Aug 2003; 10(8): 836 – 41.
 ABG analysis changed ED physicians diagnosis in 1% (95% CI 0.3 – 3.6%) of patients
 ABG analysis changed ED physicians treatment in 3.5% (95% CI 0.3 – 3.6%) of patients
(Change from SQ to IV insulin or vice versa)
 ABG analysis changed patient disposition in 2.5% (95% CI 1.1% – 5.7%) of patients
 Venous pH correlated well with arterial pH with difference of -0.015 +/- 0.006 pH units

49. “
”
Insulin versus Electrolyte?

50. Insulin versus Electrolyte?
 Patients with DKA will have total body potassium depletion from osmotic diuresis
and electrolyte losses.
 Measured levels of serum potassium may be falsely normal or elevated due to
extracellular shifts of potassium from secondary acidosis.
 The American Diabetes Association (ADA) actually recommends obtaining a a
serum potassium level before initiating insulin, but this is based on anecdotal
evidence.
 That being said, according to Arora et al, approximately 5% of patients with DKA
will have hypokalemia.

51. Insulin versus Electrolyte?
 Eg: In VBG you will see your K+ is 2.8.
 If you start insulin therapy before electrolyte replacement, you will worsen
hypokalemia which is a very real cause of morbidity and mortality from cardiac
arrhythmias and respiratory muscle weakness.
 Why?
 Don’t forget that insulin will activate your Na-K ATPase which will shift potassium
intracellular and worsen your hypokalemia.

52. “
”
Do Sodium Bicarbonate really
benefit?

53. Do Sodium Bicarbonate really benefit?
 Chua et al. Bicarbonate in Diabetic Ketoacidosis – A Systematic Review. Ann
Intensive Care 2011; 1 (23). 44 studies of DKA patients reviewed which showed:
 Transient improvement in metabolic acidosis
 No improved glycemic control
 Risk of cerebral edema in pediatric patients
 No studies with pH <6.85

54. Do Sodium Bicarbonate really benefit?
 Duhon et al. Intravenous Sodium Bicarbonate Therapy in Severely Acidotic
Diabetic Ketoacidosis. Ann Pharmacother 2013. 47(7 – 8): 970 – 5.
 Retrospective study of 86 patients with DKA which showed:
 No difference in: Time to resolution of acidemia, time to hospital discharge, time on IV
insulin, potassium requirement in 1st 24hrs
 Subgroup Analysis of pH < 6.9 (n = 20) showed no statistical difference in time to
resolution of acidemia

55. “
”
Should We Bolus Insulin Before
Starting the Infusion?

56. Should We Bolus Insulin Before Starting
the Infusion?
 Is there any benefit to an initial insulin bolus in Diabetic Ketoacidosis?
 Goyal et al. Utility of Initial Bolus Insulin in the Treatment of Diabetic Ketoacidosis. J
Emerg Med 2010; 38(4): 422 – 7.
 Prospective, Observational Study of 157 patients with DKA:
 Insulin bolus at the start of an insulin infusion IS EQUIVALENT to no insulin bolus at the start
of an insulin infusion in several endpoints including:
 Decrease normalization of glucose
 Affect the rate of change of anion gap
 Reduce ED or hospital length of stay
 Insulin bolus at the start of an insulin infusion DOES:
 Increase hypoglycemic events by 6 fold (6% vs 1%) [NOT Statistically Significant]

57. References
 Tintinalli’s Emergency Medicine (Chapter 225, 227, 9th Edition)
 Up-to-date
 Medscape

58. Thank you