Norepinephrine Dose and Pulse Oximetry Agreement During Critical Illness: A Prospective Repeated-Measures Study.

Background and Objectives: Pulse oximetry is essential in ICUs but may be less accurate when peripheral perfusion is impaired. Norepinephrine, the primary vasopressor for shock, may exacerbate vasoconstriction and microcirculatory alterations, increasing discrepancy between pulse oximetry saturation (SpO2) and arterial oxygen saturation (SaO2). This study aimed to evaluate whether norepinephrine dose is associated with disagreement between SpO2 and SaO2, with particular attention to measurement variability and large discrepancies. Materials and Methods: We analyzed 1050 paired SpO2-SaO2 measurements from 196 adult ICU patients receiving norepinephrine. Dose was weight-adjusted (µg/kg/min). Based on the clinically relevant thresholds defined in the 2021 Surviving Sepsis Campaign guidelines for initiating vasopressin, doses were categorized as low (≤0.25 µg/kg/min), moderate (0.25-0.50 µg/kg/min), or high (≥0.50 µg/kg/min). A large discrepancy was defined as |SpO2 - SaO2| ≥ 5%. A generalized estimating equation (GEE) model was applied to account for repeated measurements within patients. Results: Overall mean bias was 0.91 ± 3.58%. In the primary GEE analysis accounting for repeated measurements within patients, norepinephrine dose was not significantly associated with large SpO2-SaO2 discrepancies when analyzed as a continuous variable (adjusted OR 0.964, 95% CI 0.916-1.014, p = 0.158). Categorical analyses showed a non-monotonic pattern, with only the comparison between the moderate- and high-dose groups reaching statistical significance and with wide confidence intervals limiting the precision of this finding. Unadjusted descriptive analyses suggested greater measurement variability across dose ranges, which was largely attributable to within-patient clustering. ROC analysis demonstrated limited discriminatory ability for norepinephrine dose alone (AUC 0.60). Conclusions: After accounting for repeated measurements and relevant clinical covariates, norepinephrine dose did not demonstrate a consistent dose-dependent association with large SpO2-SaO2 discrepancies. Although large SpO2-SaO2 discrepancies may occur in critically ill patients receiving norepinephrine, norepinephrine infusion rate alone should not be used as a surrogate marker of pulse oximetry reliability.