Norepinephrine dose and concentration reporting: the devil is in the details

We thank Goyer et al. [1] for their interest in our recent article about norepinephrine [2]. They further described the nuances and complexities of this ubiquitous drug [1].

They highlight that “the exact reporting units are rarely specified and leave room for interpretation errors.” For the very same reason, and to avoid adding bias or error to the examples we gave in this educational piece, we maintained the original values proposed by the authors, since we did not have certainty about the compounds used. This was not specified in the study performed in the United States [3]. Interestingly, Goyer et al. mention that since the study from Auchet et al. is French [4], the dosing unit is in norepinephrine tartrate. However, on a closer look at the original paper, the authors specified that reported units were based on bitartrate. This further proves our point: assumptions could induce interpretation errors. While we also advocate on a standardized dosing reporting, caution should be taken when re-analyzing previously reported data. If overlooked, multiple factors could induce bias, such as drug shortages [5], different suppliers within hospitals or regions, or changes in suppliers through time. Since we know that adoption of recommendations to routine clinical practice takes a long time [6], efforts on norepinephrine reporting as base molecule should be focused on prospective studies and the recommendations that build upon them, thus effectively leveling the playing field and becoming agents of change.

The authors correctly mention that potency is the same for a given equivalent dose in mgs of norepinephrine base. We acknowledge that “weakest” was an inadequate term, as potency involves a complex interaction between efficacy and receptor affinity of molecules [7], and we thank the authors for the precision, but this should be read within the clinical context. We intended to raise awareness of the fact that at a given dose of different salts, the dose of norepinephrine base would be lower for tartrate (i.e. 0.25 mcg/kg/min of hydrochloride norepinephrine equates to 0.20 mcg/kg/min of base, while the same dose of tartrate formulation equates only to 0.125 mcg/kg/min of base).

We also thank the authors for expanding on norepinephrine preparations stability that we could not explore due to word-count constraints. Interestingly, this phenomenon is not particular to norepinephrine only. A similar discussion was recently raised regarding the administration of methylene blue in septic shock [8]. This underscores the relevance of efficient interdisciplinary teams caring for critically ill patients, in which pharmacists have a pivotal role in optimizing safe and effective drug administration [9].

We are glad that the discussion around the use of norepinephrine is gaining momentum, which will undoubtedly nurture the research agenda and our understanding of this fascinating drug. Hopefully, this will translate into homogenizing our practice throughout the world and providing safer and more efficient patient care.

Funding

Open Access funding enabled and organized by Projekt DEAL.

Data availability

Not applicable.

Declarations

Conflicts of interest

The authors declare that they have no competing interests.