a) List the features which distinguish diabetic ketoacidosis (DKA) from the hyperosmolar hyperglycaemic state (HHS).

b) Describe your specific treatment for a 62-year-old female presenting with a decreased conscious state secondary to HHS.

[Click here to toggle visibility of the answers]

College Answer

a)
1. History
i. Known type 1 DM; discontinuation of insulin therapy
ii. Presentation: DKA evolves rapidly (24 hours); HHS typically days-weeks with polydipsia, polyuria and weight loss.
2. Clinical features
i. Neurological symptoms more common in HHS.
ii. Abdominal pain and hyperventilation more common in DKA.
3. Laboratory features
i. Degree of hyperglycaemia (HHS typical higher, exceeding 56 mmol/l; DKA usually < 44 mmol/L)
ii. Degree of acidosis: severe in DKA, mild in HHS
iii. Anion gap acidosis present in DKA; absent (or mild in case of concomitant lactic acidosis) in HHS
iv. Ketones: HHS small ketonuria, absent to low ketonaemia [there is sufficient basal insulin secretion to prevent ketogenesis]; both high in DKA
v. Hyperosmolality more severe in HHS, typically > 320 mosm/L
4. NOTE: Significant overlap can occur in 30% of patients – represent part of a spectrum
b)
1. Fluid replacement
i. Expect fluid replacement of up to 10 litres, but GO SLOW (replace over 48 hours)
ii. Start with isotonic crystalloids (boluses if in shock, infusion rate up to 1L/hour). Need justification for choice of fluid, while recognising there is substantial controversy in this area.
iii. Continue isotonic if serum Na+ low; change to 0.45% NaCl if serum Na+ is normal or elevated.
iv. Change to 5% dextrose with 0.45% NaCl when serum glucose reaches 15 mmol/L or below
v. Individual tailoring based on heart rate, blood pressure, peripheral perfusion, urine output
2. Insulin infusion 0.05 U/kg/hr. initially following adequate fluid resuscitation aiming for steady but slow reduction in blood sugar levels (e.g. 5 mmol/hr)
3. Electrolyte replacement
i. Expect potassium deficit even if level appears normal
ii. Give 20 - 30 mmol K+ in each Litre of fluid or use separate infusion; aim for serum K+ 4 – 5 mmol/L
iii. Phosphate depletion only requires treatment if levels are very low (e.g. < 0.3 mmol/L) or symptomatic (Ref: BMJ best practice)
4. Treat possible precipitating cause (infection? need for broad spectrum antibiotics? Think about underlying precipitant in this case – there is a long list of possible causes (e.g. pancreatitis). What about drugs [both β blockers and HMGCo-A reductase inhibitors have been associated with HHS. Other common precipitating drugs e.g. antipsychotics, steroids…] Does she even have diabetes? [Check HbA1C].
5. Thromboprophylaxis mandatory – consider risks and benefits of heparin infusion.

6. Monitor
i. Haemodynamic situation
ii. Mental state
iii. Urine output
iv. Levels of glucose and electrolytes every 1 – 4 hours
v. Levels of ketones in DKA
7. Consider CT brain scan (possibility of ischaemic stroke).

Discussion

a)

In summary:

  • DKA presents with acidosis as the major feature
  • HONK presents with hyperglycaemia as the major feature
Discriminating Between HONK and DKA
Domain

Features suggestive of DKA

Features suggestive of HONK

History
  • Known Type 1 diabetic
  • Rapid clinical course
  • Abdominal pain
  • Known Type 2 diabetic
  • Prolonged course
  • Polydipsia, polyuria, weight loss
Examination
  • Tachypnoea
  • Normal level of consciousness, or only slightly decreased
  • Coma
  • Seizures
Biochemistry
  • Severe acidosis
  • Severe ketosis
  • Mild hyperglycaemia
  • Renal function normalises rapidly
  • Mild acidosis
  • Little ketosis; mainly lactate is raised
  • Severe hyperglycaemia
  • Established renal failure

b)

A stereotypical approach to management is offered below:

  1. Assess airway patency. Intubate to protect the airway if comatose.
  2. Ventilate with mandatory mode initially; aim for normocapnea if the metabolic acidosis is not particularly severe.
  3. Insert arterial line for frequent sampling and haemodynamic monitoring.
    Insert central line to manage electrolyte and fluid infusions.
    Check ECG/serial enzymes  for MI (common complication)
    Expect a 200ml/kg total water deficit
    Commence fluid resuscitation:
    1. 15-20ml/kg in the first hour
    2. 4-14ml/kg in the second hour (of 0.45% NaCl)
    3. 4-14ml/kg again in the third hour (use 0.9% NaCl if the sodium is low)
    4. When glucose is under 15mmol/L, start 5% dextrose 100-250ml/hr
  4. May require benzodiazepines or anticonvulsants if the presentation history included seizures.
    May require a head CT venogram to rule out dural sinus thrombosis / venous infarction
  5. Watch for a precipitous drop in serum osmolality.
    A safe drop is 3–8 mOsm/kg/h
    Correct electrolyte deficit:
    1. Sodium deficit: 5-13mmol/kg
    2. Potassium deficit: 5-15mmol/kg
    3. Chloride deficit: 3-7mmol/kg
    4. Phosphate deficit: 1-2mmol/kg
    5. Magneisum deficit: 1-1.5mmol/Kg
    6. Calcium deficit: 1-2mmol/Kg
  6. Monitor renal function and consider dialysis
  7. Insulin therapy may not be required, and may even be dangerous.
    BSL may decrease at a satisfactory rate with fluid resuscitation alone.
  8. May require anticoagulation for dural sinus thrombosis.
  9. May require antibiotics, given that infection is a common precipitant.
    A septic screen should be sent.

Key issues of "specific therapy:

  • Fluid resuscitation
  • Electrolyte replacement
  • Careful slow reduction of serum osmolality
  • Investigation for complications:
    • Myocardial infarction
    • Stroke
    • Cerebral oedema and brain injury
    • Venous thrombosis
  • Management of other possible precipitating causes:
    • Infection, systemic inflammatory response
    • Intracranial haemorrhage
    • Hepatic encephalopathy
    • Drugs, including illicit substances, steroids, phenytoin, diuretics, TPN, lithium

References

References

UpToDate has a nice summary of this topic for the paying customer.

Oh's Intensive Care manual: Chapter 58  (pp. 629) Diabetic  emergencies  by Richard  Keays

Umpierrez, Guillermo E., Mary Beth Murphy, and Abbas E. Kitabchi. "Diabetic ketoacidosis and hyperglycemic hyperosmolar syndrome." Diabetes Spectrum15.1 (2002): 28-36.

ARIEFF, ALLEN I., and HUGH J. CARROLL. "Nonketotic hyperosmolar coma with hyperglycemia: clinical features, pathophysiology, renal function, acid-base balance, plasma-cerebrospinal fluid equilibria and the effects of theraphy in 37 cases." Medicine 51.2 (1972): 73-94.

Alberti, K. G. M. M., et al. "Role of glucagon and other hormones in development of diabetic ketoacidosis." The Lancet 305.7920 (1975): 1307-1311.

Kitabchi, Abbas E., et al. "Management of hyperglycemic crises in patients with diabetes." Diabetes care 24.1 (2001): 131-153.

Foster, Jennifer Ruth, Gavin Morrison, and Douglas D. Fraser. "Diabetic ketoacidosis-associated stroke in children and youth." Stroke research and treatment 2011 (2011).

Edge, J. A., et al. "The risk and outcome of cerebral oedema developing during diabetic ketoacidosis." Archives of disease in childhood 85.1 (2001): 16-22.

Woodrow, G., A. M. Brownjohn, and J. H. Turney. "Acute renal failure in patients with type 1 diabetes mellitus." Postgraduate medical journal 70.821 (1994): 192-194.

Bonfanti, R., et al. "Disseminated intravascular coagulation and severe peripheral neuropathy complicating ketoacidosis in a newly diagnosed diabetic child." Acta diabetologica 31.3 (1994): 173-174.

Chua, Horng-Ruey, et al. "Plasma-Lyte 148 vs 0.9% saline for fluid resuscitation in diabetic ketoacidosis." Journal of critical care 27.2 (2012): 138-145.

Stowe, Michele L. "Plasma-Lyte vs. Normal Saline: Preventing Hyperchloremic Acidosis in Fluid Resuscitation for Diabetic Ketoacidosis." (2012).

Jivan, Daksha. "A comparison of the use of normal saline versus Ringers lactate in the fluid resuscitation of diabetic ketoacidosis." (2013).

Basnet, Sangita, et al. "Effect of Normal Saline and Half Normal Saline on Serum Electrolytes During Recovery Phase of Diabetic Ketoacidosis." Journal of intensive care medicine 29.1 (2014): 38-42.

Hillman, K. "Fluid resuscitation in diabetic emergencies—a reappraisal."Intensive care medicine 13.1 (1987): 4-8.

Wagner, Arnd, et al. "Therapy of severe diabetic ketoacidosis. Zero-mortality under very-low-dose insulin application." Diabetes care 22.5 (1999): 674-677.

Chiasson, Jean-Louis, et al. "Diagnosis and treatment of diabetic ketoacidosis and the hyperglycemic hyperosmolar state." Canadian Medical Association Journal 168.7 (2003): 859-866.

Kitabchi, Abbas E., et al. "Hyperglycemic crises in adult patients with diabetes a consensus statement from the American Diabetes Association." Diabetes care 29.12 (2006): 2739-2748.