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Tissue oxygenation and hemodynamic response to NO synthase inhibition in septic shock
A Broccard1, J M Hurni, P Eckert
1Department of Medicine, University Hospital, Lausanne, Switzerland.
Abstract:
The objective of the study was to evaluate the tissue oxygenation and hemodynamic effects of NOS inhibition in clinical severe septic shock. Eight patients with septic shock refractory to volume loading and high level of adrenergic support were prospectively enrolled in the study. Increasing doses of NOS inhibitors [N(G)-nitro-L-arginine-methyl ester (L-NAME) or N(G)-monomethyl-L-arginine (L-NMMA)] were administered as i.v. bolus until a peak effect = 10 mmHg on mean blood pressure was obtained or until side effects occurred. If deemed clinically appropriate, a continuous infusion of L-NAME was instituted and adrenergic support weaning attempted. The bolus administration of NOS inhibitors transiently increased mean blood pressure by 10 mm Hg in all patients. Seven out of eight patients received an L-NAME infusion, associated over 24 h with a progressive decline in cardiac index (P < 0.001) and an increase in systemic vascular resistance (P < 0.01). Partial or total adrenergic support weaning was rapidly possible in 6/8 patients. Oxygen transport decreased (P < 0.001), but oxygen consumption remained unchanged in those patients in whom it could be measured by indirect calorimetry (5/8). Blood lactate and the difference between tonometric gastric and arterial PCO2 remained unchanged. There were 4/8 ICU survivors. We conclude that nitric oxide synthase inhibition in severe septic shock was followed with a progressive correction of the vasoplegic hemodynamic disturbances with finally normalization of cardiac output and systemic vascular resistances without any demonstrable deterioration in tissue oxygenation.
Insights
Nitric oxide synthase (NOS) inhibition improved hemodynamics in severe septic shock by correcting vasoplegia. This treatment normalized cardiac output and vascular resistance without impairing tissue oxygenation, aiding in weaning from adrenergic support.
Area of Science:
- Critical Care Medicine
- Pharmacology
- Physiology
Background:
- Severe septic shock is characterized by vasoplegia and refractory hypotension.
- Nitric oxide synthase (NOS) plays a key role in the pathophysiology of septic shock.
- Effective therapeutic strategies for refractory septic shock remain limited.
Purpose of the Study:
- To evaluate the hemodynamic and tissue oxygenation effects of NOS inhibition in patients with severe septic shock.
- To assess the potential for weaning from adrenergic support following NOS inhibition.
Main Methods:
- Prospective study of eight patients with severe septic shock refractory to standard treatments.
- Administration of NOS inhibitors (L-NAME or L-NMMA) via intravenous bolus and infusion.
- Monitoring of hemodynamic parameters, oxygen transport and consumption, and clinical outcomes.
Main Results:
- NOS inhibition transiently increased mean blood pressure.
- Continuous infusion of L-NAME led to a progressive increase in systemic vascular resistance and a decrease in cardiac index.
- Adrenergic support could be weaned in 6/8 patients.
- Tissue oxygenation, measured by oxygen transport and consumption, remained stable.
- Lactate levels and gastric-arterial PCO2 difference were unchanged.
Conclusions:
- NOS inhibition effectively corrected vasoplegic hemodynamic disturbances in severe septic shock.
- This approach normalized cardiac output and systemic vascular resistance without compromising tissue oxygenation.
- NOS inhibition facilitates weaning from adrenergic support in septic shock patients.