Why may pressors (pressor medications) not be effective in the setting of severe acidosis?

Why Pressors May Not Work in the Setting of Extreme Acidosis

In severe acidosis (pH <7.1), vasopressor medications have significantly reduced effectiveness due to catecholamine receptor resistance, which can lead to refractory shock and increased mortality. 1, 2

Mechanisms of Reduced Pressor Effectiveness in Acidosis

• Severe acidosis causes catecholamine receptor resistance, reducing the binding efficacy of vasopressors to their target receptors 1
• Acidosis alters vascular smooth muscle responsiveness, diminishing the contractile response to vasopressors 2
• Extreme acidosis (pH <7.0) can lead to myocardial depression, further compromising cardiac output and blood pressure despite vasopressor administration 3
• Acidosis-induced peripheral vasodilation counteracts the vasoconstrictive effects of pressors, resulting in persistent hypotension 2

Clinical Evidence of Reduced Pressor Response

• Historical animal studies demonstrated that the pressor action of epinephrine, norepinephrine, and metaraminol was considerably reduced in the presence of acidosis 2
• Human studies have shown that patients with profound shock and acidosis have significantly decreased pressor response to vasopressor agents 2
• In critical care settings, patients with extreme acidosis (pH <7.0) often require escalating doses of vasopressors with limited hemodynamic improvement 3

Management Strategies

Correction of Acidosis

• For severe acidosis (pH <7.1 and bicarbonate <10 mEq/L), intravenous sodium bicarbonate administration is indicated to improve vasopressor efficacy 4
• The American Heart Association recommends sodium bicarbonate administration for special situations such as severe acidosis with pH <7.15 to overcome catecholamine receptor resistance-induced hypotension 1
• After correction of acidosis with sodium bicarbonate, vasopressor responsiveness can be restored in patients with shock 2

Alternative Vasopressors

• In refractory hypoxemia or acidosis where catecholamine vasopressors may be attenuated, vasopressin may be preferred as it works through non-adrenergic mechanisms 1
• For patients with shock and severe acidosis, consider using vasopressin as an adjunct or alternative to catecholamine vasopressors 1

Mechanical Support Considerations

• In patients with persistent shock despite 40 ml/kg of fluid and severe acidosis, consider elective intubation and ventilation to help manage acidosis 1
• Patients with severe acidosis may self-ventilate their PCO2 to very low levels as compensation; when initiating mechanical ventilation, avoid rapid rise of PCO2 before acidosis has been partly corrected 1
• For refractory shock with extreme acidosis, consider mechanical circulatory support if conventional therapies fail 1

Special Considerations

• Hyperlactatemia in combination with extreme acidosis is a predictor of poor prognosis and may require more aggressive intervention 3
• "Adapted alkalinization" treatment (combining hyperventilation, calcium supplementation, and slower sodium bicarbonate infusion) may be beneficial in cases of severe acidosis with hemodynamic instability 5
• In patients with mixed respiratory and metabolic acidosis, addressing both components simultaneously is crucial for restoring vasopressor efficacy 3

Pitfalls and Caveats

• Overly rapid correction of acidosis can lead to paradoxical central nervous system acidosis and cerebral edema 4
• Sodium bicarbonate administration can cause ionized hypocalcemia, which may further compromise cardiovascular function 5
• Excessive bicarbonate administration may cause hypernatremia and hyperosmolarity, potentially worsening outcomes 1
• Bicarbonate produces excess CO2, which can diffuse into myocardial and cerebral cells, potentially worsening intracellular acidosis 1