Norepinephrine Equivalent Dose of Vasopressin, Phenylephrine and Epinephrine in Septic Shock Patients: A Prospective Study

Sepsis is a life-threatening state of organ dysfunction caused by dysregulated response of host to infection. It is the most common form of circulatory shock encountered in patients admitted in intensive care unit. In physiological state, blood pressure is maintained by the interplay of three major mechanisms namely sympathetic nervous system, vasopressin system and renin aldosterone system. However in the states of vasodilatory shock, these homeostatic mechanisms are disturbed. The initial management involves fluid resuscitation but if hypotension doesn't get resolved solely by it, then vasopressors become the mainstay of the management of shock to maintain adequate mean arterial pressure (MAP).

Norepinephrine has been recommended as the first line vasopressor for management of septic shock since 2004 and the latest guideline recommends addition of vasopressin along with norepinephrine when the target MAP is not achieved. However, in clinical practice various other vasopressors are used in the management of septic shock. Different vasopressors have different modes of action and pharmacological effects on hemodynamics. Therefore, there evolved the need of development of a formula that would reflect the potency of each vasopressor in a standardized manner. Thus, the concept of Norepinephrine Equivalence (NEE) came into existence. It is a scale to quantify the exposure to various vasopressors, by converting their dose as an equivalent of norepinephrine. It allows us to combine the dose of other vasopressors in a single scale and quantitatively assess the severity of shock when norepinephrine is being used along with other vasopressors.

Annane et al conducted a study in 2007 in 330 patients of septic shock with the primary objective of comparing the efficacy and safety of norepinephrine plus dobutamine with those of epinephrine alone in septic shock. They inferred from their study that the doses of vasopressors needed to achieve the MAP target were same for epinephrine and norepinephrine. Similarly, Myburgh et al studied in 280 patients of circulatory shock in the year 2008 to determine whether there was any difference between epinephrine and norepinephrine in achievement of MAP goal in the ICU patients and found that the maximal daily infusion of epinephrine and norepinephrine didn't have difference to achieve a target MAP. De Becker et al conducted a study in 2003 on 20 septic shock patients with the primary objective to assess the effects of different doses of dopamine, norepinephrine and epinephrine on the splanchnic circulation in patients of septic shock. They found that the final infusion rate of epinephrine was 0.62 mcg/kg/min, which was comparable to 0.45 mcg/kg/min rate of norepinephrine infusion to achieve the target MAP, suggesting a conversion ratio of 1.4:1. Hussain et al found in their study on 42 patients of septic shock in 2014 to determine the efficacy of phenylephrine in comparison to norepinephrine in patients of septic shock in ICU, that phenylephrine was 1.1 times equipotent to norepinephrine. Gordon et al studied on 409 patients of septic shock in 2016 to compare the effect of early vasopressin versus norepinephrine on kidney failure. They concluded from their study that 0.04U/min of vasopressin to be equivalent to 0.1 mcg/kg/min of norepinephrine.

Goradia et al proposed a norepinephrine equivalent formula in 2021 in their review article as Norepinephrine dose (mcg/kg/min) + epinephrine dose (mcg/kg/min) + 2.5 x vasopressin (U/min) + 0.1 × phenylephrine dose (mcg/kg/min). Kotani et al proposed a different norepinephrine equivalent formula in 2023 as follows Norepinephrine dose (µg/kg/min) + epinephrine dose (µg/kg/ min) + 0.06 × phenylephrine dose (µg/kg/min) + 2.5 × vasopressin dose (U/min).

However, since these calculations of NEE are based on assumptions and not standardized, there are several different formulae for calculation of the same. Different studies were conducted in different parts of the world with different primary objectives, the authors proposed different NEE formulas of the used vasopressor as an inference from their studies.