Evaluation of the Effect of Dexmedetomidine on Phenylephrine Response During Refractory Septic Shock
Status:
Recruiting
Trial end date:
2023-07-01
Target enrollment:
Participant gender:
Summary
Septic shock is common in patients admitted to intensive care and hospital mortality occurs
in close to 50% of these patients. In half of the cases, death occurs within the first 72
hours in a context of multiple organ failure that does not respond to conventional therapies,
particularly circulatory therapies, despite increasing doses of catecholamines. Vasopressor
resistance in septic patients defines refractory septic shock. In one study (Conrad et al.
2015), the increase in blood pressure observed with an infusion of increasing doses of
phenylephrine (dose-response curve) made it possible to quickly and clearly identify patients
resistant to vasopressors at a high risk of death by refractory shock (ROC AUC 0.92). This
resistance is due in particular to a downregulation of α1 adrenergic receptors, linked to
sympathetic hyper activation associated with septic shock. To date, there is no validated
therapy in this situation. However, experimental data have shown that the administration of
α2 agonists, usually used for their sedative (dexmedetomidine) or anti-hypertensive
(clonidine) effect, normalizes sympathetic activity towards basal values. In animals, α2
agonists restore the sensitivity of alpha1 adrenergic receptors, resulting in improved
vasopressor sensitivity and survival. In humans, a beneficial effect on mortality was
suggested in the first trial testing dexmedetomidine in septic patients in 2017. This effect
was observed especially in the most severe patients, suggesting a restoration of sensitivity
to vasopressors.
The hypothesis is that the administration of dexmedetomidine in patients in refractory septic
shock may improve response to phenylephrine and decrease resistance to vasopressors. This
pilot study could lay the foundation for a randomized controlled trial.