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Cardiac pressors

Critically ill patients often require cardiac inotrope and/or cardiac pressors 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 cardiac inotropes or cardiac pressors 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 cardiac inotropes and cardiac pressors 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 cardiac inotropes and cardiac pressors, the alpha and beta adrenergic receptors, includes several subtypes whose individual responsiveness to these agents is quite variable under acidic conditions.

The variability in responsiveness stems from not only changes in affinity for binding to the receptors but also because acidic conditions have been shown to change receptor numbers on cell surfaces as well as alter the downstream regulation mediated by G-coupled proteins.

Some receptors are upregulated while their binding affinity may drop. Others exhibit no change in their affinity or overall responsiveness to cardiac inotropes and cardiac pressors.

Still others increase their responsiveness. Different blood vessels in different tissue beds also are highly variable in their responsiveness since the predominant population of the receptor subtype present varies with the site and even caliber of the vessel.

The degree of pH change influences these results dramatically. Mild acidemia actually stimulates the sympathetic nervous system output, increasing ventricular function and vasomotor tone.

As the acidemia becomes more severe, changes in ligand binding and pharmacological effect of circulating catecholamines may become more prominent. The final clinical effect will be a balance between the two competing phenomena.

Overall, pH values as low as 7.15 do not have an appreciable clinical effect on the activity of these drugs. Below this value, however, reductions in overall effectiveness may become clinically apparent.

It is often noted that when bicarbonate is given, blood pressure improves and cardiac pressors can be titrated. One explanation for this benefit is that an ampule of sodium bicarbonate acts as a hypertonic fluid bolus expanding plasma volume.

Additionally, the change in pH alone can have effects on vasomotor tone separate from any effects on drug binding and this may be prominent when a certain pH threshold is crossed. Treatment of an acidotic pH with bicarbonate, with the goal of improving cardiac inotropes and cardiac pressors effectiveness, should be reserved for when the pH is below 7.1.

Other reasons for wanting to correct the acidosis when the pH is above this value may exist (such as facilitating weaning from a mechanical ventilator) but significant improvement in the effectiveness of cardiac inotropes and cardiac pressors with bicarbonate administration should not be expected at less acidotic pH values.

As always, simply relying on bicarbonate infusion to correct pH should not alter an aggressive search for and treatment of the underlying cause of the acidosis.

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