Question 18.1

A previously well 23-year-old male has been an inpatient on your ICU for six days following an isolated traumatic brain injury. He has been extremely agitated and required constant infusions of propofol and fentanyl. A full workup has confirmed there are no other injuries, and he has been stable from a haemodynamic, respiratory and metabolic standpoint since admission. This morning he has become hypotensive, and the following results are available. 

  1. List the significant abnormalities.                                                               (30% marks)
  2. What is the likeliest diagnosis?                                                                  (10% marks)


Patient Value

Adult Normal Range





7.35 – 7.45


120 mmHg (16 kPa)


35.0 mmHg (4.7 kPa)

35.0 – 45.0 (4.6 – 6.0)




12.0 mmol/L*

22.0 – 26.0 

Base Excess 

-15 mmol/L*

-2.0 – +2.0 


9.2 mmol/L*

0.5 – 1.6


145 mmol/L

135 – 145


6.3 mmol/L*

3.5 – 5.0


98 mmol/L

95 – 105


12.0 mmol/L*

22.0 – 26.0 


10.2 mmol/L*

3.5 – 6.0


6.7 mmol/L

3.0 – 8.0


70 μmol/L

45 – 90 

Creatinine Kinase 

43,500 U/L*

55 – 170 

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College answer

High anion gap metabolic acidosis 
Associated respiratory acidosis 
Delta ratio 1.9 suggesting pure HAGMA 
Elevated Aa gradient 
Propofol Infusion Syndrome 



To approach this systematically:

1) The A-a gradient is raised;  (0.4 × 713) - (35 / 0.8) - 120 = 121.5 mmHg.

2) There is severe acidaemia.

3) There is a severe metabolic acidosis (SBE is -15)

4) There is minimal effort at respiratory compensation - the expected CO2 is  25 mmHg by the Copenhagen SBE rules, or 26 using Winter's rule where expected CO2 = (1.5 ×12)+ 8. Thus, there is also a respiratory acidosis.

5) The anion gap is elevated; it is 35 if you omit potassium from the equation, or 41.3 if you do not. The delta ratio therefore also changes. Assuming a normal albumin of 40g/L, the delta ratio is either 2.4 (with potassium) or 1.9 (without). Thus, depending on whether or not you include that electrolyte in your anion gap equation, you'd either develop the impression that there is a co-existing metabolic alkalosis, or that this is a pure HAGMA. The evils of the anion gap and whether or not one ought to involve the potassium ions are debated elsewhere.

Other abnormalities which can be seen:

  • High lactate 
  • Rhabdomyolysis

The diagnosis of propofol infusion syndrome is suggested by the story, where this young man is pickled in propofol for some days following his traumatic brain injury. Other features of PRIS are :

  •     Acute bradycardia leading to asystole.
    • A prelude to the bradycardia is a sudden onset RBBB with ST elevation in V1-V3; Kam’s article has the picture of this ECG. 
  •     Arrhythmias    
  •     Heart failure, cardiogenic shock
  •     Metabolic acidosis (HAGMA) with raised lactate (and also due to fatty acids)
  •     Rhabdomyolysis
  •     Hyperlipidaemia
  •     Fatty liver and hepatomegaly
  •     Coagulpathy
  •     Raised plasma malonylcarnitine and C5-acylcarnitine


 Underwood, Ao H., and E. A. Newsholme. "Properties of phosphofructokinase from rat liver and their relation to the control of glycolysis and gluconeogenesis." Biochemical Journal 95.3 (1965): 868.

Kam, P. C. A., and D. Cardone. "Propofol infusion syndrome." Anaesthesia62.7 (2007): 690-701.

Marinella, Mark A. "Lactic acidosis associated with propofol." CHEST Journal109.1 (1996): 292-292.

Vasile, Beatrice, et al. "The pathophysiology of propofol infusion syndrome: a simple name for a complex syndrome." Intensive care medicine 29.9 (2003): 1417-1425.

Schenkman KA, Yan S. Propofol impairment of mitochondrial respiration in isolated perfused guinea pig hearts determined by reflectance spectroscopy. Critical Care Medicine 2000; 28: 172–7.