Critically ill patients often require inotropic and/or pressor support to maintain adequate cardiac output and adequate blood pressure to sustain end-organ perfusion. Because end-organ perfusion has already likely been compromised and may continue to be problematic despite use of these agents, anaerobic metabolism rather than aerobic metabolism is likely to be generating a limited amount adenosine triphosphate (ATP) in the hypoperfused tissues. The consequence is lactic acid production and acidosis. Additionally, critically ill patients may have other causes of acidosis contributing to the overall acidotic state including renal failure, hyperchloremia, or ketoacidosis. The acidosis may be severe with pH values well below 7.0.

Binding of the inotropic or pressor agents to their receptors is influenced by pH, along with other factors such as temperature and concentration. Presumably, the greater the deviation in either direction from the optimal pH for the drug-ligand interaction, the less binding that will occur and hence, the less the effect of the drug. This has led to the widely held opinion that inotropes and vasopressors don’t work at the acidic pH values often encountered in critically ill patients. The actual relationship is much more complex since the target of the inotropes and vasopressors, the alpha and beta adrenergic receptors, includes several subtypes whose individual responsiveness to these agents is quite variable under acidic conditions.