Intensive Care Med
https://doi.org/10.1007/s00134-024-07446-z
CORRESPONDENCE
Norepinephrine dose and concentration
reporting: the devil is in the details
Eduardo Kattan1, Miguel Ibarra‑Estrada2 and Christian Jung3,4*
© 2024 The Author(s)
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 interpreta-
tion errors. While we also advocate on a standardized
dosing reporting, caution should be taken when re-ana-
lyzing previously reported data. If overlooked, multiple
factors could induce bias, such as drug shortages [5], dif-
ferent 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 effec-
tively leveling the playing field and becoming agents of
change.
*Correspondence: christian.jung@med.uni-duesseldorf.de
3
Medical Faculty, Department of Cardiology, Pulmonology and Vascular
Medicine, Heinrich-Heine-University Duesseldorf, Moorenstraße 5,
40225 Duesseldorf, Germany
Full author information is available at the end of the article
This comment refers to the article available online at https://​doi.​org/​10.​
1007/​s00134-​024-​07374-y.
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 norepi-
nephrine 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 norepi-
nephrine preparations stability that we could not explore
due to word-count constraints. Interestingly, this phe-
nomenon 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 pharma-
cists have a pivotal role in optimizing safe and effective
drug administration [9].
We are glad that the discussion around the use of nor-
epinephrine is gaining momentum, which will undoubt-
edly 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.
Author details
1
Departamento de Medicina Intensiva, Facultad de Medicina, Pontificia
Universidad Católica de Chile, Santiago, Chile. 2 Unidad de Terapia Intensiva,
Hospital Civil Fray Antonio Alcalde, Universidad de Guadalajara, Guadalajara,
Jalisco, México. 3 Medical Faculty, Department of Cardiology, Pulmonology
and Vascular Medicine, Heinrich-Heine-University Duesseldorf, Moorenstraße
5, 40225 Duesseldorf, Germany. 4 CARID (Cardiovascular Research Institute
Düsseldorf ), Duesseldorf, Germany.
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.
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Accepted: 11 April 2024
References
1. Goyer I, Levy B, Leone M (2024) Norepinephrine dose and concentration
reporting a closer look at the fine print. Intensive Care Med. https://​doi.​
org/​10.​1007/​s00134-​024-​07425-4
2. Kattan E, Ibarra-Estrada M, Jung C (2024) Knowing the ropes of vasopres‑
sor dosing: a focus on norepinephrine. Intensive Care Med. https://​doi.​
org/​10.​1007/​s00134-​024-​07374-y
3. Yerke JR, Mireles-Cabodevila E, Chen AY, Bass SN, Reddy AJ, Bauer SR
et al (2024) Peripheral administration of norepinephrine: a prospective
observational study. Chest 165(2):348–355. https://​doi.​org/​10.​1016/j.​
chest.​2023.​08.​019
4. Auchet T, Regnier MA, Girerd N, Levy B (2017) Outcome of patients with
septic shock and high-dose vasopressor therapy. Ann Intensive Care
7(1):43. https://​doi.​org/​10.​1186/​s13613-​017-​0261-x
5. Vail E, Gershengorn HB, Hua M, Walkey AJ, Rubenfeld G, Wunsch H (2017)
Association between US norepinephrine shortage and mortality among
patients with septic shock. JAMA 317(14):1433–1442. https://​doi.​org/​10.​
1001/​jama.​2017.​2841
6. Ibarra-Estrada M, Veith J, Mireles-Cabodevila E (2022) Implementing
change is a science. Med Intensiva (Engl Ed) 46(7):359–362. https://​doi.​
org/​10.​1016/j.​medine.​2022.​05.​011
7. Kenakin T, Williams M (2014) Defining and characterizing drug/com‑
pound function. Biochem Pharmacol 87:40–63. https://​doi.​org/​10.​1016/j.​
bcp.​2013.​07.​033
8. Ibarra-Estrada M, Kattan E, Aguirre-Avalos G, Hernández G (2023) Drug
diluent and efficacy of methylene blue in septic shock: authors’ reply. Crit
Care 27(1):345. https://​doi.​org/​10.​1186/​s13054-​023-​04633-0
9. McKenzie C, Spriet I, Hunfeld N (2024) Ten reasons for the presence of
pharmacy professionals in the intensive care unit. Intensive Care Med
50:147–149. https://​doi.​org/​10.​1007/​s00134-​023-​07285-4