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%
pH	7.01*	7.35 – 7.45
pO2	120.0 mmHg (16.4 kPa)
pCO2	58.0 mmHg (9.6 kPa)*	35.0 – 45.0 (4.6 – 6.0)
SpO2	96%
Bicarbonate	14.0 mmol/L*	22.0 – 26.0
Base Excess	-15.0 mmol/L*	-2.0 to +2.0
Lactate	8.5 mmol/L*	0.5 – 1.6
Sodium	135 mmol/L	135 – 145
Potassium	5.2 mmol/L*	3.5 – 5.0
Chloride	99 mmol/L	95 – 105
Glucose	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

Comment on the acid base status. (1 mark)

Increased anion gap metabolic acidosis/lactic acidosis (AG 22, delta ratio 1)
Respiratory acidosis

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

Discussion

So: let's go through this ABG systematically.

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.
There is acidaemia.
The PaCO₂ is not compensating for the acidaemia.
The SBE is -15, suggesting a severe metabolic acidosis
There is no respiratory compensation; the expected PaCO₂ is (14 × 1.5) + 8 = 29, or 25 mmHg by the Copenhagen rules.
The anion gap is raised: (135) - (99 + 14) = 22, or 27.2 when calculated with potassium.
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

References

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.

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