This hyperventilation was first described by Kussmaul in patients with diabetic ketoacidosis in 1874. The metabolic acidosis is detected by both the peripheral and central chemoreceptors and the respiratory center is stimulated. The initial stimulation of the central chemoreceptors is due to small increases in brain ISF [H+]. The subsequent increase in ventilation causes a fall in arterial pCO2 which inhibits the ventilatory response.
The chemoreceptor inhibition acts to limit and delay the full ventilatory response until bicarbonate shifts have stabilised across the blood brain barrier. The increase in ventilation usually starts within minutes and is usually well advanced at 2 hours of onset but maximal compensation may take 12 to 24 hours to develop. This is ‘maximal’ compensation rather than ‘full’ compensation as it does not return the extracellular pH to normal.
In situations where a metabolic acidosis develops rapidly and is short-lived there is usually little time for much compensatory ventilatory response to occur. An example is the acute and sometimes severe lactic acidosis due to a prolonged generalised convulsion: this corrects due to rapid hepatic uptake and metabolism of the lactate following cessation of convulsive muscular activity, and hyperventilation due to the acidosis does not occur.
The arterial pCO2 at maximal compensation has been measured in many patients with a metabolic acidosis. A consistent relationship between bicarbonate level and pCO2 has been found. It can be estimated from the following equation:
(Units: mmols/l for [HCO3], and mmHg for pCO2).
The limiting value of compensation is the lowest level to which the pCO2 can fall - this is typically 8 to 10mmHg, though lower values are occasionally seen.
If the measured HCO3 is 12 mmols/l, then the expected pCO2 (at maximal compensation) would be: (1.5 x 12) + 8 = 18 + 8 = 26 mmHg. If the actual pCO2 was within +/- 2 mmHg of this (and 12 to 24 hours have passed from onset) then the respiratory compensation has reached it maximal value (and there would be no evidence of a primary respiratory acid-base disorder).
If the actual pCO2 was say 40 mmHg in this situation, this is markedly different from the expected value of 26 mmHg and indicates the presence of quite a marked second primary acid-base disorder: a respiratory acidosis. A typical clinical situation may be a diabetic patient with ketoacidosis and severe pneumonia where the respiratory disease has resulted in the respiratory acid-base disorder. Note that in this situation, a severe respiratory acidosis has been diagnosed despite the presence of a pCO2 at the value (40 mmHg) typically considered ‘normal’!
If a patient with a severe metabolic acidosis requires intubation and controlled ventilation in hospital, the acidosis can markedly worsen unless the hyperventilation is maintained. The ventilation should be set to mimic the compensatory hyperventilation to keep the pCO2 low. If ventilation is set to some standard value and the pCO2 allowed to rise towards 40mmHg, then this represents the imposition of an acute respiratory acidosis and pH can fall rapidly!
Carbon dioxide crosses cell membranes readily so intracellular pH falls rapidly also, resulting in depression of myocardial contractility, arrhythmias and a rise in intracranial pressure. The patient may deteriorate soon after intubation and ventilation and the medical staff usually don’t appreciate how they have contributed to this outcome.
Beware when initiating ventilation in a patient with a significant acidosis: the situation described above is not widely appreciated and the outcome could be fatal. Set the ventilator settings so that the arterial pCO2 remains low. Use the "expected pCO2" formula as a guide to a suitable target level.