Viva 5

Created on Thu, 06/04/2015 - 15:41
Last updated on Wed, 08/30/2017 - 00:40

You are asked to see a 72 year old lady in the ED who presented from home with a decreased level of consciousness. Bloods are not back yet, but the ED staff specialist is concerned about this ABG result.

Please interpret this ABG.

ABG of a HONK patient - BSL is 81

(This is one of the older vivas, back when the college did not even bother to give you their stem text. Their entry for this viva simply reads "Diagnosis and management of hyper-glycaemic, hyper-osmolar, non-ketotic coma. Twelve out of fifteen candidates passed this section". As the consequence of this, most of what you see here is generated de novo by yours truly.)

Anyway: that gas;

  • There is acidaemia
  • The CO2 is trying to be helpful
  • There is a metabolic acidosis
  • The compensation is inadequate (you'd expect a CO2 of around 27 if we used the SBE subtraction rule)
  • The anion gap is elevated (47.7 if you calculate it yourself, or 43.5 if you mindlessly read from the print-out)
  • The delta ratio is around 3.4, which means this is a high anion gap metabolic acidosis with an underlying metabolic alkalosis.
  • Lactate is raised, but not enough to explain the acidosis.
  • Renal function is deranged, which suggests that there may be a contribution from some uraemia
  • Of greastest concern is the glucose value, which is not given - but the machine helpfully printed a little ^^^ christmas tree symbol, indicating that the glucose-sensing electrode is maxed out. For the record, that sensor's normal operating range is from 0 to 60 mmol/L.
What are the differentials to explain this presentation?

The differentials must be broad, and this question tests whether the candidate will fixate on the BSL and HONK or whether they will produce a list of broad differentials. This HONKed-out patient might have also had a stroke, or a blow to the head from an elder-abusing grandchild, or they might have huffed some glue fumes,  or any number of other things. 

To aid the viva examiner, here is a broad list of differentials to tick off:

Differential Diagnosis of Unconsciousness

With focal  signs

Vascular causes:

  • Stroke
  • Vascular insufficiency of the brain, eg. critical vessel stenosis of some specific vessel
  • Intracranial haemorrhage

Infectious causes:

  • Brain abscess
  • Meningoencephalitis with focal crainal nerve damage

Neoplastic causes

  • Space-occuoing tumour

Intrinsic neurological causes

  • Pre-existing focal neurology, superimposed on an acute unconscious state

Autoimmune causes

  • Cerebral vasculitis

Traumatic causes

  • Focal neurological injury due to head trauma
    • That includes surgical injury due to retraction of structures, as in elective neurosurgery
  • Increased intracranial pressure, giving rise to false localising signs

Without focal  signs

Vascular causes:

  • Brainstem stroke, resulting in damage to the reticular activating system
  • Vascular insufficiency of the brain, eg. diffuse cerebral small vessel disease

Infectious causes:

  • Encephalitis without meningism
  • Neurological sequelae of systemic infection, eg. septic encephalopathy

Drug-related causes:

  • Persisting effects of sedatives in context of diminished clearance

Intrinsic neurological cause

  • Delirium of prolonged intensive care stay - a "hypoactive" form thereof
  • Seizures (post
  • Non-convulsive status epilepticus
  • Raised intracranial pressure

Autoimmune causes

  • Cerebral vasculitis

Traumatic causes

  • Sequelae of diffuse brain injury, eg. diffuse axonal injury
  • Hypothermia or hyperthermia

Endocrine and metabolic causes:

  • Hypoadrenalism
  • Hypothyroidism
  • Hepatic encephalopathy
  • Uremic encephalopathy
  • Wernicke's encephalopathy

With meningism

Vascular causes:

  • SAH

Infectious causes:

  • Meningitis
 
The following findings are revealed on your brief examination:

A - own and patent

B - RR 30, SpO2 88% on 15L via non-rebreather mask

C - BP 77/35, HR 120-150 (rapid AF)

D - E1 V1 M5, localising with both upper limbs. BSL by fingerprick glucometer reads "HI".

E - Cool to the touch; axillary temperature is 33.5°C. No obvious signs of trauma.

Describe your initial assessment and management

A - Protect the airway. This patient needs to be intubated.

B - Ventilate with mandatory mode initially; aim for a lower CO2  because the metabolic acidosis is particularly severe. 

C- Resucitate with fluid:

  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

D - sedate minimally; 

    - send this patient for a CT brain, particularly a CT venogram

    - consider anticonvulsants

E - measure osmolality

 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

F - Monitor renal function and urine output; consider dialysis

G - Insulin therapy may not be required, and may even be dangerous.
BSL may decrease at a satisfactory rate with fluid resuscitation alone.

May require anticoagulation for dural sinus thrombosis.

May require antibiotics, given that infection is a common precipitant.
A septic screen should be sent.

The patient is admitted under an endocrinologist, who variably refers to the diagnosis as "DKA", "HONK" and "HHS" as if these terms were interchangeable. What is the real difference between HHS and DKA?

How does one discriminate between DKA and HONK even when in about 30% of instances the two disorders coexist? Arbitrary definitions exist, proposed by the American Diabetes Association.

  • DKA is due to an absence of insulin; HONK is due to an insensitivity to insultin.
  • DKA is 3 times more common, but HONK has 3 times greater mortality
Discriminating Between HONK and DKA
Domain

Features suggestive of DKA

Features suggestive of HONK

Demographic
  • Young
  • Known Type 1 diabetic
  • Elderly
  • Known Type 2 diabetic
History
  • Rapid clinical course
  • History of noncompliance with insulin
  • Abdominal pain
  • Shortness of breath
  • Prolonged course
  • History of noncompliance with oral antihyperglycaemic agents and insulin
  • Polydipsia, polyuria, weight loss
  • Neurological symptoms
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
What are the possible precipitant causes for HHS?

Similarly to DKA, a stress response which mobilises metabolic substrates in a Type 2 diabetic will result in HONK.

Precipitating Factors for Hyperosmolar Hyperglycaemia

Mismanagement of diabetes

  • Poor treatment compliance
  • Dietary mismanagement

Drugs which trigger HONK

  • Corticosteroids
  • Diuretics
  • Phenytoin
  • Diazoxide
  • TPN
  • Lithium (by causing DI)

Physiological stress

  • Infection
  • Systemic inflammatory response
  • Myocardial infarction
  • Surgery
  • Substance abuse
  • Intracranial haemorrhage
  • Hepatic encephalopathy
What is the pathogenesis of this disease state?

The key distinction between DKA and HONK seems to be the fact that in HONk, there is still enough insulin to overcome the ketogenic effects of glucagon.

mechanisms of metabolic differences between DKA and HONK

Glucagon inhibits acetyl-CoA carboxylase, which normally converts acetyl-CoA into malonyl-CoA. Malonyl CoA inhibits acyl-carnitine synthesis; if this is uninhibited, it results in a stream of fatty acids being sucked up into the mitochondria to be converted into ketones.

Thus, we have a hyperglycaemic patient who remains reasonably asymptomatic because in them acidosis fails to develop (and thus, they are not short of breath). They remain hyperglycaemic for some time. As a result, they subject themselves to osmotic diuresis for a prolonged period, which allows them to become progressively more and more dehydrated.

The result is the hyperosmolar state which is usually associated with HONK.

This hyperosomolar hyperglycaemia is an intensely proinflammatory and prothrombotic state, which gives rise to the various complications of HONK.

What are the clinical manifestations of HHS?
Clinical Manifestations of Hyperosmolar Hyperglycaemia

Respiratory

Tachypnoea

Low PCO2

Cardiovascular

Tachycardia

Hypotension due to hypovolemia

Biochemical

High anion gap metabolic acidosis (with lactate and uremia rather than ketones)

Pseudohyponatremia

Hypokalemia (due to vomiting)

Hypophosphatemia

Hypomagnesemia

Neurological

Obtundation and coma

Weakness

Seizures

Stroke

Renal

Acute renal failure

Polyuria

Polydipsia

Hematological

Leucocytosis

Thrombosis

What are the potential complications of HHS?
  • HHS-specific physiological abnormalities
    • Hypotension and shock
    • Metabolic acidosis
    • Coma
  • Complications arising from the HHS disease state:
    • Cardiac arrest
    • Cardiovascular collapse
    • Myocardial infarction
    • Pulmonray oedema
    • Stroke
    • Cerebral oedema and brain injury
    • Venous thrombosis (DVT, PE)
    • Aspiration
  • Complications of therapy for HHS:
    • Dysnatraemia
    • Hyperchloremia from saline administration.
    • Phosphate depletion
    • Hypokalemia
    • Hypoglycaemia
What specific management would you offer this patient?

This question may not be specific or direct enough, and the candidate may need to be further prompted, "how will you resuscitate this hypotensive patient" or "how will you manage the hyperglycaemia". In short, they are expected to discuss fluid management.

Oh's Manual suggests that there is no specific difference between the fluid management in DKA and in HONK. On the basis of this consensus statement, they recommend the following fluid resuscitation schedule for both:

  • 15-20ml/kg in the first hour (and use colloid if they are shocked)
  • 4-14ml/kg in the second hour (of 0.45% NaCl)
  • 4-14ml/kg again in the third hour (use 0.9% NaCl if the sodium is low)
  • When glucose is under 15mmol/L, Oh's Manual recommends to start 5% dextrose 100-250ml/hr, as well as some other sort of sodium-containing fluid to prevent hyponatremia.
What are the possible complications of resuscitation in this condition?

Specifically, the answer should be:

  • circulatory overload, pulmonary oedema
  • cerebral oedema
What are the risk factors for cerebral oedema?

The college touched on this issue in Question 24 from the first paper of 2017. Specifically, the candidates were asked for "risk factors for all patients that predispose to the development of cerebral oedema" in HONK/HHS. Turns out, in adults this is a fairly uncommon complication (Matz, 1999).

Risk Factors for Cerebral Oedema in HONK
  • Children (esp. under 3s)
  • New diagnosis of diabetes
  • Down syndrome
  • Use of bicarbonate
  • Rapid change in serum sodium concentration
  • Severe acidosis
  • Severe hypoglycaemia
  • Severe dehydration
  • Low presenting PaCO2
  • High urea
  • Rate of rehydration (rapid)
What measures would you take to protect this patient from cerebral oedema?

How does one avoid cerebral oedema in HHS? Though there is a real risk of cerebral oedema with vigorous fluid resuscitation, there is only some vague mention of the need to be careful. Gouveia et al (2013) and Dhatariya (2014) both authored review articles which warn of cerebral oedema and central myelinolysis. A recent Diabetes UK Position Statement (Scott et al, 2015) recommends we reduce osmolality by 3–8 mOsm/kg/h, as a safe rate. 

The patient's family want to meet with you to discuss prognosis. Which features are associated with a poor outcome in HHS?

Mortality is higher for HONK than for DKA, and the patients tend to be older. One study sheds some light on poor prognostic indicators:

  • cardiovascular disease
  • old age
  • hypotension
  • hyponatremia
  • acidosis
  • high urea (the most important risk factor for death).
The patient's biochemistry gradually normalises in your ICU. However, the level of consciousness remains depressed in spite of minimal sedation. On day 3 of admission the patient has a prolonged generalised tonic-clonic seizure. What complication of HHS is likely responsible?
  • Stroke
  • Venous sinus thrombosis
  • Cerebral oedema

The candidate needs to demonstrate an awareness of the fact that his level of hyperglycaemia is profoundly pro-inflammatory and that ceberal venous thrombosis is something that needs to be ruled out.

Disclaimer: the viva stem above is the original CICM stem, acquired from their publicly available past papers. However, because the college do not make the rest of the viva text or marking criteria available, the rest has been confabulated. It sounds like a plausible viva and it can be used for the purpose of practice, but all should be aware that it does not represent the "true" canonical CICM viva station. 

 

References

Radiometer ABL 700 operator's reference manual 

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.

Hyperglycemic Comas by P. VERNON VAN HEERDEN from Vincent, Jean-Louis, et al. Textbook of Critical Care: Expert Consult Premium. Elsevier Health Sciences, 2011.

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.

Gerich, John E., Malcolm M. Martin, and Lillian Recant. "Clinical and metabolic characteristics of hyperosmolar nonketotic coma." Diabetes 20.4 (1971): 228-238.

Kitabchi, Abbas E., et al. "Hyperglycemic crises in adult patients with diabetes." Diabetes care 32.7 (2009): 1335-1343.

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.

Ellis, E. N. "Concepts of fluid therapy in diabetic ketoacidosis and hyperosmolar hyperglycemic nonketotic coma." Pediatric clinics of North America 37.2 (1990): 313-321.

Pinies, J. A., et al. "Course and prognosis of 132 patients with diabetic non ketotic hyperosmolar state." Diabete & metabolisme 20.1 (1993): 43-48.

Gouveia, Catherine F., and Tahseen A. Chowdhury. "Managing hyperglycaemic emergencies: an illustrative case and review of recent British guidelines." Clinical Medicine 13.2 (2013): 160-162.

Dhatariya, Ketan. "Diabetic ketoacidosis and hyperosmolar crisis in adults." Medicine 42.12 (2014): 723-726.

Scott, A. R. "Management of hyperosmolar hyperglycaemic state in adults with diabetes."Diabetic Medicine 32.6 (2015): 714-724.

Matz, R. O. B. E. R. T. "Management of the hyperosmolar hyperglycemic syndrome." American family physician 60.5 (1999): 1468-1476.

Matz, R. "How big is the risk of cerebral edema in adults with DKA." J Crit Illn 11 (1996): 768-772.

Kitabchi, Abbas E., et al. "Hyperglycemic crises in adult patients with diabetes." Diabetes care 32.7 (2009): 1335-1343.

Quintana, E. C. "Factors associated with adverse outcomes in children with diabetic ketoacidosis-related cerebral edema." Annals of Emergency Medicine 43.6 (2004): 793-794.

Bialo, Shara R., et al. "Rare complications of pediatric diabetic ketoacidosis."World journal of diabetes 6.1 (2015): 167.

Lawrence, Sarah E., et al. "Population-based study of incidence and risk factors for cerebral edema in pediatric diabetic ketoacidosis." The Journal of pediatrics 146.5 (2005): 688-692.

Marcin, James P., et al. "Factors associated with adverse outcomes in children with diabetic ketoacidosis-related cerebral edema." The Journal of pediatrics 141.6 (2002): 793-797.

Glaser, Nicole, et al. "Risk factors for cerebral edema in children with diabetic ketoacidosis." New England Journal of Medicine 344.4 (2001): 264-269.

Rosenbloom, Arlan L. "Intracerebral crises during treatment of diabetic ketoacidosis." Diabetes care 13.1 (1990): 22-33.