Simplified Norepinephrine Dosing for Septic Shock in Obese Patients

FEBRUARY 16, 2016
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.
 
References
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.

Craig Cocchio, PharmD
Craig Cocchio, PharmD
Craig Cocchio, PharmD, BCPS, is an Emergency Medicine Clinical Pharmacist at Trinity Mother Frances Hospital in Tyler, Texas. Follow on Twitter @iEMPharmD and on his blog at empharmd.blogspot.com
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