Is Norepinephrine Infusion during Intraoperative Period Justified?

The study by Wuethrich et al.¹  has interesting physiological background and important clinical implications. Veins, particularly splanchnic veins, are much more compliant than arteries.^2,3  Density of α-adrenergic receptors within the veins is much higher than in the arteries.⁴  Therefore, veins are more sensitive to sympathetic activation than arteries.^4,5  The reported study has demonstrated that the use of relatively small doses of norepinephrine is not associated with any clinical or biochemical signs of tissue hypoperfusion.¹ 

Sympathetic nervous system and α-adrenergic receptors play the main role in maintaining a certain ratio between stressed (Vs) and unstressed (Vu) blood volumes.^2,3  α-Adrenergic agonists induced constriction of compliant veins, resulting in a decrease in Vu and a concomitant increase in Vs.^3,6  General and, particularly, epidural anesthesia decreases the overall sympathetic discharge followed by venodilation, increase in Vu, and decrease in Vs, which could lead to a decrease in venous return and cardiac output. In addition, controlled ventilation with concomitant increase in intrathoracic pressure might decrease venous return and therefore must be associated with an increase in Vs to maintain adequate hemodynamics. The body achieves this by several mechanisms, main and immediate of which is an increase in sympathetic discharge. Such compensation also might be impaired to different degrees by general and epidural anesthesia. This study illustrates that norepinephrine induced reduction in enlarged Vu and restoration of the Vs can maintain adequate hemodynamics. Fluid infusion also can restore the Vs. Thus, an increase in Vs can be achieved by an increase in fluid load (to fill up an increased venous capacity) and/or by restoration of the sympathetic tone that would reduce the increased Vu. The use of norepinephrine in this situation decreases the Vu but not the blood flow to the tissues. The current study demonstrates clinical benefits of such an approach.¹ 

Clinical implications of these observations are also important. Use of relatively small doses of vasopressors to restore what has general and epidural anesthesia impaired seems logical. The clinical advantage of such an approach is relatively simple: it allows avoiding additional, not needed infusion of fluid. However, the clinician should realize that such approach might decrease the margin of safety. The main function of the Vu is to serve as a reservoir of blood to be mobilized when needed, for example, during blood loss. However, when the mobilization of blood from Vu to Vs is approximately complete, hemodynamics deteriorate. We all have observed the initial blood loss of 800 to 900 ml not being associated with serious hemodynamic consequences; however, when blood loss reaches approximately 1 l, even minor additional blood loss quickly leads to hemodynamic deterioration. This happens at the time when Vu becomes very low. Low Vu per se is not harmful, but unexpected blood loss in condition of decreased Vu could lead quickly to hemodynamic deterioration.

Routine use of such technique might aggravate other unexpected complications. For example, some minor cardiac insufficiency might need an increase in preload to maintain adequate cardiac output. An already decreased Vu might postpone the effective treatment of such unexpected complications. Other events, such as compression of inferior caval vein, unexpected pneumothorax, and others, could also result in a decreased ability of the body to respond adequately and timely. Also, use of norepinephrine in situations during anesthesia and surgery might confuse a clinician and delay correct clinical diagnosis or one or another deviation from the expected uncomplicated course.

Finally, the differences between the experimental (norepinephrine infusion) and control groups in this study are quite drastic; the dramatic degree of these differences partially might be due to the overloading of the patients in the control group: the protocol rather than the clinical situation required infusion of fluid to a greater extent than usually is done in clinical setting. We hardly ever infuse up to 8 to 9 l of fluid during surgical procedures that are not associated with severe blood loss.

The main lesson from this interesting study is that the administration of small doses of vasopressors during anesthesia and surgery is physiologically justified because it can counteract the iatrogenic impairment of sympathetic nervous system and may provide our patients with certain advantages. However, such techniques might become dangerous when some deviations from the expected clinical course occur. As always, vigilance and clinical judgment remain to be crucially important in patient care.

The author declares no competing interests.