Abstract:ObjectiveTo explore the application effect of nurse-led early comfort using analgesia, minimal sedatives and maximal humane care (eCASH) model in patients with multiple injuries, so as to provide a new reference for nursing of multiple injuries. Methods Multiple injury patients who received treatment at Jiangsu Province Hospital from February to December 2023, February to December 2022 were selected as the experimental group and the control group, respectively, with 102 cases in each group. The experimental group was subjected to the nurse-led eCASH model, while the control group received conventional nursing interventions. The clinical indexes and prognosis iudexes of the two groups were recorded. After two weeks of intervention, the levels of consciousness, physiological health status, pain intensity, pain factors ［serotonin (5-HT), neuropeptide Y (NPY)］, negative emotions, and nursing satisfaction were compared between the two groups. Results The duration of mechanical ventilation ［(8.03 ± 1.67) d vs (10.45 ± 2.01) d］, hospital stays ［(26.91 ± 4.03) d vs (30.58 ± 4.81) d］, dosage of butorphanol tartrate ［(107.25 ± 30.51) mg /(kg·h) vs (172.69 ± 35.08) mg/ (kg·h)］, and dosage of dexmedetomidine ［(271.83 ± 60.29) mg /(kg·h) vs (502.73 ± 72.15) mg /(kg·h)］ in the experimental group were lower than those in the control group (P＜0.05). The incidence of post-traumatic stress syndrome and delirium of patients in the experimental group (14.71% vs 26.47%, 1.96% vs 8.82%) were lower than those in the control group (P＜0.05). After intervention, the Glasgow Coma Scale (GCS) scores of both groups increased compared to before intervention, and the experimental group was higher than the control group (P＜0.05). Acute Physiological and Chronic Health Evaluation Ⅱ (APACHE Ⅱ) scores, Richmond Agitation-Sedation Scale (RASS) scores, and pain Numeric Rating Scale (NRS) scores, Hamilton Anxiety Scale (HAMA) scores, Hamilton Depression Scale (HAMD) scores, 5-HT and NPY levels all decreased compared to before intervention, and the experimental group were lower than the control group (P＜0.05). The nursing satisfaction of both groups of patients was 100.00%. Conclusion The application of nurse-led eCASH model in the clinical practice of multiple injuries patients is beneficial in reducing the use of anesthesia drugs, shortening mechanical ventilation time, alleviating patient pain responses, relieving negative emotions, and ensuring good safety and high nursing satisfaction.