Reply to: phenylephrine and cardiac output
We thank Dr. Gelman and colleagues1 for their interest in our study and their constructive comments. In our study in anaesthetised patients, we demonstrated that the effects of phenylephrine on stroke volume depended on the preload-dependent state of the heart.2 A decrease in stroke volume in preload-independent patients was described, whereas the stroke volume remained constant in preload-dependent patients.2
In preload-dependent patients, we demonstrated that phenylephrine induced an increase of preload as suggested by the decrease in pulse pressure variation and an increase in oesophageal time-corrected Doppler flow. Oesophageal Doppler is a noninvasive beat-to-beat cardiac index monitor that is well validated in comparison with thermodilution3 in perioperative haemodynamic optimisation studies,4 free from the influence of vasopressors on vasomotor tone,5 and permitting calculation of haemodynamic parameters, which facilitates the assessment of preload, afterload and myocardial contractility.6 Pulse pressure variation decrease is well known to be associated with an increase in stroke volume after fluid loading in preload-dependent patients.7 The Sarnoff curve easily explains what might be called the venous–ventricular coupling.
In our study, pulse pressure variation decreased and time-corrected oesophageal Doppler flow increased in preload-dependent patients suggesting a preload increase, whereas stroke volume remained unchanged. Indeed, phenylephrine induced increased left ventricular afterload [systemic vascular resistance index], which may decrease stroke volume and thus cardiac index. We showed that in the preload-dependent patients, phenylephrine preload increase counteracts phenylephrine afterload increase, thus resulting in the stroke volume stability. The effects of phenylephrine on cardiac index because of possible action on both preload and afterload cannot be explained by venous–ventricular coupling alone, but requires a veno–ventriculoarterial coupling approach.8
What physiologically happened that can explain the decrease in stroke volume in preload-independent patients? The dose of phenylephrine administered was comparable between preload-dependent [1.5 (0.6) μg kg−1] and preload-independent groups [1.4 (0.4) μg kg−1; P = 0.279]. Moreover, the α1-adrenergic receptor density is heterogeneous regarding the species, age or vessels. But the concentration of drug required to produce 50% of the maximal α-adrenergic response of most arteries and veins is similar, between 10−7 and 10−8 nmol l-1.9 Taking into account the increase in the systemic vascular resistance index and the decrease in time-corrected oesophageal Doppler flow, we suggested that phenylephrine-induced increase in cardiac afterload was the main cause of the decreases in both stroke volume and cardiac index. Finally, we strongly suggest that anaesthesiologists evaluate preload dependency before phenylephrine administration in clinical practice.