critical care, ICU, intensive care, mediation analysis, norepinephrine, pressure injury, vasoconstrictor agents



  1. Argenti, Graziela MSc, RN
  2. Ishikawa, Gerson DEng
  3. Fadel, Cristina Berger DMD


OBJECTIVE: To estimate the direct effects of norepinephrine administration on pressure injury (PI) incidence in intensive care patients.


METHODS: This is a secondary and exploratory analysis of a retrospective cohort study of intensive care patients discharged in 2017 to 2018. Observational cases only included patients who received primary PI preventive care during intensive care (N = 479). As a first-choice vasopressor drug, norepinephrine administration was approximated with days of norepinephrine. Linear path models were examined from norepinephrine administration to PI development. The identification of confounding variables and instrumental variables was grounded on directed acyclic graph theory. Direct effects were estimated with instrumental variables to overcome bias from unobserved variables. As models were re-specified with data analysis, the robustness of path identification was improved by requiring graph invariance with sample split.


RESULTS: Norepinephrine caused PI development from one stage to another after 4.0 to 6.3 days of administration in this cohort as a total effect (90% CI). The direct effect was estimated to advance the stage of PI at a rate of 0.140 per day of norepinephrine administered (standard error, 0.029; P < .001). The direct effect accounted for about 70% of the total effect on PI development.


CONCLUSIONS: Estimations with instrumental variables and structural equation modeling showed that norepinephrine administration directly and substantially affected hospital-acquired PI incidence in intensive care patients in this cohort.