Objective To investigate the predictive value of serum Nod-like receptor protein 3 (NLRP3), calcitonin gene-related peptide (CGRP), and endothelial nitric oxide synthase (eNOS) for secondary intracranial infection and prognosis following craniotomy for cerebral hemorrhage.

Methods A case-control study was conducted. A total of 70 patients with secondary intracranial infection after craniotomy for cerebral hemorrhage in the hospital from January 2021 to May 2024 were selected as observation group, and 210 patients without secondary intracranial infection after craniotomy for cerebral hemorrhage were selected as control group. Surgical conditions and serum levels of NLRP3, CGRP, and eNOS were compared between the two groups, and clinical differences between died and surviving patients in the observation group were analyzed.

Results The observation group had significantly higher rates of tracheal intubation and surgical duration exceeding 4 hours, along with significant elevated serum levels of NLRP3, CGRP, and eNOS compared to the control group (P < 0.001). Logistic regression analysis revealed that tracheal intubation, NLRP3, CGRP, and eNOS were influencing factors for secondary intracranial infection (P < 0.05). In the observation group, there were 18 deaths and 52 survivors. The death group had significantly higher age, the Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE Ⅱ) score, and serum levels of NLRP3, CGRP, and eNOS compared to the surviving group (P < 0.05). Logistic regression analysis indicated that APACHE Ⅱ score and serum levels of NLRP3, CGRP, and eNOS were influencing factors for mortality in patients with secondary intracranial infection (P < 0.05). The areas under the curve of the receiver operating characteristic (ROC) curves for serum NLRP3, CGRP, and eNOS in predicting secondary intracranial infection were 0.805, 0.784, and 0.735 respectively, with significant differences (P < 0.001). The areas under the curve of ROC curves for serum NLRP3, CGRP, and eNOS in predicting mortality in patients with secondary intracranial infection were 0.684, 0.763, and 0.763, respectively, with significant differences (P < 0.05).

Conclusion Serum NLRP3, CGRP, and eNOS are influencing factors for secondary intracranial infection and poor prognosis following craniotomy for cerebral hemorrhage, exhibiting certain predictive values.