Viva 5

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.

(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.

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 may be an original CICM stem, acquired from their publicly available past papers. Or, perhaps it is a slightly altered version of the original CICM stem. Or, it is a completely original viva stem, concocted by the monstrously amoral author of Deranged Physiology for nothing more than his own personal amusement. In either case, because the college do not make the main viva text or marking criteria available, almost everything here has been confabulated. It might sound like a plausible viva and it could be used for the purpose of practice, but all should be aware that it does not represent the "true" canonical CICM viva station.