Simplified Norepinephrine Dosing for Septic Shock in Obese Patients


Weight based vs non weight based dosing of norepinephrine

Maintaining adequate perfusion in patients with septic shock is a critical component of their care. After volume resuscitation with crystalloid fluid fails to achieve adequate mean arterial pressure (MAP), norepinephrine is considered as a first-line inopressor.1

Depending on local or institutional practices, norepinephrine dosing may be weight-based (mcg/kg/min) or non-weight-based (mcg/min). Currently, guideline statements do not provide any recommendations on which dosing strategy is preferred.1

However, a new study from the University of Arizona suggests that the simpler non-weight-based strategy may be just as effective as weight-based dosing and deliver a similar amount of norepinephrine to septic shock patients.2

This retrospective cohort study involved adult patients admitted to medical and surgical intensive care units with septic shock. These patients received norepinephrine as the sole vasopressor for at least 1 hour to assess the norepinephrine infusion rate at 60 minutes after the start of treatment when titrated to a goal MAP ≥65 mm Hg.

Because MAP and norepinephrine dosing are interrelated, the researchers performed a log-transformation of the 2 variables into a single MAP:norepinephrine ratio, which was the secondary outcome at 60 minutes after the start of the infusion. In terms of the primary outcome, there was a difference in weight-based norepinephrine infusion rates between the obese group (0.09 mcg/kg/min, SD 0.08) and the non-obese group (0.13 mcg/kg/min, SD 0.14; p=0.006).

However, the equivalent non-weight-based doses of norepinephrine were similar between the 2 groups (8 mcg/min vs 9 mcg/min, p=0.72). Furthermore, the MAP:norepinephrine ratio at 60 minutes was similar between the obese group (2.5, SD 0.9) and the non-obese group (2.5, SD 0.8), which remained non-significantly different after adjustments for baseline MAP and weight.

Thus, the authors concluded that obese patients with septic shock require similar total norepinephrine dosing requirements to achieve MAP goals. Since norepinephrine’s pharmacokinetic properties produce great interpatient variability, low correlation between plasma concentration and clinical response coupled with poor perfusion of adipose tissue compared with lean body mass suggest that norepinephrine may not be an ideal agent for weight-based dosing.3,4

Unfortunately, obese patients are often not included in major sepsis and septic shock studies or critical care patient population studies to provide valuable pharmacokinetic and pharmacodynamic evidence for norepinephrine use.

The implications of these results on clinical practice may be significant in reducing the risks of medication errors associated with weight-based dosing. However, the study’s retrospective nature is a limitation, so prospective research should confirm these findings. Nevertheless, based on the known properties of norepinephrine and lack of evidence for weight-based versus non-weight-based dosing strategies, either practice may be acceptable.


1. Dellinger RP, et al. Surviving Sepsis Campaign Guidelines Committee including the Pediatric Subgroup. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med. 2013;41(2):580-637.

2. Radosevich JJ, et al. Norepinephrine dosing in obese and nonobese patients with septic shock. Am J Crit Care. 2016 Jan;25(1):27-32.

3. Beloeil H, et al. Norepinephrine kinetics and dynamics in septic shock and trauma patients. Br J Anaesth. 2005;95(6):782-788.

4. Lemmens HJ, et al. Estimating blood volume in obese and morbidly obese patients. Obes Surg. 2006;16(6):773-776.

Related Videos
Laboratory test tubes and solution with stethoscope background | Image Credit: Shutter2U -
Image credit: Andrea Izzotti
Inflation Reduction Act is shown using the text and the US flag - Image credit: Andrii |
Pharmacy Interior | Image Credit: Tyler Olson -
Male pharmacist selling medications at drugstore to a senior woman customer | Image Credit: Zamrznuti tonovi -
Pharmacist assists senior woman in buying medicine in pharmacy - Image credit: Drazen |
Pharmacy, medicine and senior woman consulting pharmacist on prescription. Healthcare, shopping and elderly female in consultation with medical worker for medication box, pills or product in store - Image credit: C Daniels/ |
Image credit: fidaolga -
Pharmacists checking inventory at hospital pharmacy- Image credit: Jacob Lund |
Young male pharmacist giving prescription medications to senior female customer in a pharmacy | Image Credit: Zamrznuti tonovi -
Related Content
© 2023 MJH Life Sciences

All rights reserved.