Abstract:

Objective To investigate the effect of analgesic dose on enteral feeding intolerance（EFI） in patients undergoing prone position ventilation（PPV），to determine the dose-response relationship，with aiming to provide evidence for balancing analgesia and nutrition management in critically ill patients. Methods We retrospectively collected clinical data from 630 patients receiving enteral nutrition（EN） support and PPV in the intensive care unit of a tertiary hospital in Nanjing between January 2020 and December 2024. Patients were divided into a tolerance group and an intolerance group based on the occurrence of EFI. Demographic data，disease and treatment-related information，and EN support data were collected. Logistic regression was used to explore the independent relationship between analgesic dose and EFI. Restricted Cubic Splines（RCS） were used to analyze the dose-response relationship between the daily cumulative dose of analgesic and EFI. A forest plot was used to visualize this relationship across subgroups. Results Among the 630 patients，366 tolerated EN and 264 did not，resulting in an EFI incidence of 41.90%. Among the 264 patients with EFI，70 presented with ≥2 symptoms of feeding intolerance，with a total of 336 episodes of EFI symptoms recorded. The most frequently reported symptom was gastric retention，occurring in 137 instances（40.8%，137/336）. The incidence of EFI was relatively higher within the first three days of initiating feeding，with rates of 19.0%，20.8%，and 19.6%，respectively. Multivariable regression analysis showed that the daily cumulative dose of remifentanil（OR=1.032，95%CI：1.005~1.061），use of ≥2 analgesics（OR=2.963，95%CI：1.557~5.640），extracorporeal membrane oxygenation（ECMO） therapy（OR=3.352，95%CI：1.819~6.175），higher number of antibiotic types used（OR=1.605，95%CI：1.329~1.939），and post-pyloric feeding（OR=1.564，95%CI：1.114~2.196） were independent risk factors for EFI. The model demonstrated good calibration （Hos-mer-Lemeshow test，P=0.259）. RCS analysis revealed a positive linear dose-response relationship between the daily cumulative dose of remifentanil and the risk of EFI（overall P=0.026；nonlinear P=0.379）. A daily cumulative dose exceeding 10.77 mg significantly increased EFI risk（OR>1.0）. Subgroup analysis showed that the effect of the remifentanil dose on EFI was consistent across patients of different ages，gender，APACHE Ⅱ scores，modified Nutrition Risk in the Critically Ill（mNUTRIC） scores，feeding routes，and types of analgesic agents（all interaction effects P>0.05）. However，the association was not statistically significant in the post-pyloric feeding，female，or ≥2 analgesics subgroups. Conclusion The dose of remifentanil is an independent risk factor for EFI in PPV patients，showing a dose-dependent effect. These findings provide a dose-threshold reference to support the balance between analgesia and nutrition management. Clinical practice should follow the principle of the lowest effective analgesic dose，and intensify EFI monitoring and prevention for the patients requiring high-dose analgesics to improve nutrition support outcomes.

Key words: Prone Position Ventilation, Remifentanil, Feeding Intolerance, Dose-Response Relationship, Nursing Care