Question 3.1

A 32-year-old male is admitted to your ICU after an appendicectomy for a perforated appendix. He has a background of schizoaffective disorder. On admission, he is receiving vasopressor support with noradrenaline at 7 mcg/min. and has a temperature of 41ºC. The first arterial blood gas on admission is given below:

Parameter Patient Value Adult Normal Range
FiO2 50%  



7.35 – 7.45


120.0 mmHg (16.4 kPa)


58.0 mmHg (9.6 kPa)*

35.0 – 45.0 (4.6 – 6.0)




14.0 mmol/L*

22.0 – 26.0

Base Excess

-15.0 mmol/L*

-2.0 to +2.0


8.5 mmol/L*

0.5 – 1.6


135 mmol/L

135 – 145


5.2 mmol/L*

3.5 – 5.0


99 mmol/L

95 – 105


8.0 mmol/L*

3.5 – 6.0

a)    Comment on the acid base status.    (10% marks)

b)    List four likely explanations for these findings other than sepsis.    (10% marks)

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College answer

  1. Comment on the acid base status. (1 mark)
  • Increased anion gap metabolic acidosis/lactic acidosis (AG 22, delta ratio 1)
  • Respiratory acidosis
  1. List four likely explanations for these findings other than sepsis (1 Mark)
    1. NMS
    2. MH
    3. Serotonin syndrome
    4. Haemolytic transfusion reaction
    5. Thyroid storm
    6. Illicit drug use


So: let's go through this ABG systematically.

  1. The A-a gradient is raised;  (0.6 x 713) - (58 x 1.25) - 120. = 235.3 mmHg.
    But given the FiO2 is 60% and the SpO2 is 96%, one did not need an equation to tell them that the patient has an oxygenation problem. Nor, for that matter, were we ever asked for a comment on this part of the gas. Anyway, the P/F ratio is 200.
  2. There is acidaemia.
  3. The PaCO2 is not compensating for the acidaemia. 
  4. The SBE is -15, suggesting a severe metabolic acidosis
  5. There is no respiratory compensation; the expected PaCO2 is (14 × 1.5) + 8 = 29, or 25 mmHg by the Copenhagen rules.
  6. The anion gap is raised:  (135) - (99 + 14) = 22, or 27.2 when calculated with potassium.
  7. The delta ratio, without using potassium and assuming a normal anion gap is 12 and a normal bicarbonate is 24, would therefore be (22 - 12) / (24 - 14) = 1.0. 

In summary, this is a severe high anion gap metabolic acidosis as well as a respiratory acidosis.

Four likely explanations for this? The college examiners have loaded this SAQ with plenty of background information. Specifically, they've given this patient a history of mental illness. The expectation here, of course, is that the candidates would form the impression of somebody who is likely to be using illicit drugs while recovering from appendicectomy. Because that's clearly what mentally ill people always do.

Anyway, the hints are:

  • Abdominal sepsis 
  • Recent exposure to an anaesthetic
  • Very high lactate
  • Very high CO2 (so, either not ventilating well, or producing tons of CO2 for some other reason)
  • Haemodynamic instability
  • Schizoaffective disorder (thus, likely antipsychotics)

Inevitably, the following elements must be in your list of differentials:

  • Malignant hyperthermia (high temperature, high lactate, excessive CO2 production, recent anaesthetic, what more do you want?)
  • Sepsis (fever, hypotension, a plausible abdominal source, a high lactate - come to think of it, how is this not just plain vanilla sepsis?)
  • Neuroleptic malignant syndrome (hypoventilation, high lactate and high temperature)
  • Serotonin syndrome (hypoventilation, high lactate, and also explains the temperature)

These are the four most likely culprits. The college throws thyrotoxicosis and transfusion reaction in there, but the history and biochemistry do nothing to promote those differentials. So if we're going to just throw random causes of lactic acidosis around, then, dear reader, have at you:

Type A lactic acidosis: impaired tissue oxygenation

  • Shock: circulatory collapse
  • Regional ischaemia
  • Severe hypoxia
  • Severe anaemia
  • Carbon monoxide poisoning

Type B1 lactic acidosis, due to a disease state

  • Malignancy
  • Thiamine deficiency
  • Ketoacidosis /HONK
  • Septic shock
  • Impaired hepatic or renal clearance

Type B2 drug-induced lactic acidosis

  • Beta-2 adrenoceptor agonists
  • Metformin
  • Isoniazid
  • Cyanide (and by extension nitroprusside)
  • Xylitol, sorbitol, fructose
  • Propofol
  • The toxic alcohols eg. methanol
  • Paracetamol
  • Salicylates
  • NRTIs (nucleoside reverse transcriptase inhibitors)

Type B3 : inborn errors of metabolism

  • Numerous possible defects:
    • Pyruvate dehydrogenase deficiency
    • Electron transport chain enzyme defects
    • G6PD


Narins RG, Krishna GG, Yee J, Idemiyashiro D, Schmidt RJ: The metabolic acidoses. In: Maxwell & Kleeman's Clinical Disorders of Fluid and Electrolyte Metabolism, edited by Narins RG, New York, McGraw-Hill, 1994, pp769 -825

Luft FC. Lactic acidosis update for critical care clinicians. J Am Soc Nephrol 2001 Feb; 12 Suppl 17 S15-9.

Ohs manual – Chapter 15 by D J (Jamie) Cooper and Alistair D Nichol, titled “Lactic acidosis” (pp. 145)

Cohen RD, Woods HF. Lactic acidosis revisited. Diabetes 1983; 32: 181–91.

Reichard, George A., et al. "Quantitative estimation of the Cori cycle in the human." Journal of Biological Chemistry 238.2 (1963): 495-501.

Andres, Reubin, Gordon Cader, and Kenneth L. Zierler. "The quantitatively minor role of carbohydrate in oxidative metabolism by skeletal muscle in intact man in the basal state. Measurements of oxygen and glucose uptake and carbon dioxide and lactate production in the forearm." Journal of Clinical Investigation 35.6 (1956): 671.

Phypers, Barrie, and JM Tom Pierce. "Lactate physiology in health and disease." Continuing Education in Anaesthesia, Critical Care & Pain 6.3 (2006): 128-132.