Association of norepinephrine with pressure ulcer development in critically ill patients with COVID-19-related acute respiratory distress syndrome: A dose-response analysis.

To investigate the correlation between varying doses of norepinephrine (NE) and the incidence of pressure injuries (PIs) in COVID-19 patients in intensive care units (ICUs). A retrospective multicenter study was conducted on 1,078 COVID-19 patients admitted to ICUs with acute respiratory distress syndrome (ARDS) requiring mechanical ventilation. The research spanned from March 2020 to April 2021 across five university-affiliated hospitals in Iran. Univariate and multivariate binary logistic regression analyses, along with linear and non-linear dose-response assessments, were utilized to evaluate the relationship between NE dosages and the probability of PI development. The multivariate analysis revealed a significant association between higher doses of NE administered over 24 h (OR: 1.832, 95 % CI: 1.218-2.754, P=0.004) and cumulative doses (OR: 1.408, 95 % CI: 1.204-1.975, P=0.048) with the occurrence of PIs. Moreover, patients receiving high NE doses had a nearly fourfold increased risk of developing PIs, regardless of PIs stage, compared to those on low or moderate doses (>15 µg/min vs. ≤ 15 µg/min; OR: 4.401, 95 % CI: 3.339-5.801, P=0.001). Although the linear dose-response analysis did not show a significant correlation between NE doses (µg/min) and PI development (P>0.05), the non-linear analysis indicated that NE doses ≤ 9 µg/min were associated with a reduced risk of PI development. Maintaining NE infusion within the range of 1-9 µg/min appears to be most effective in reducing the likelihood of PIs in ICU patients with COVID-19. Lower NE doses (≤9 µg/min) were associated with a lower risk of PI development, suggesting that factors beyond NE dosage or the use of other vasopressors may play a crucial role in PI formation in this patient cohort. Rather than suggesting a specific threshold, clinicians should consider further studies to determine the optimal dose that balances microvascular perfusion and patient outcomes. It is crucial to comprehensively evaluate additional factors and selectively use vasopressors. Individualized care, including regular monitoring and personalized treatment plans, is essential for achieving the best outcomes in this patient population.

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Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.