Association Between Pain, Agitation, and Intracranial Pressure with Cerebral Near-Infrared Spectroscopy in Critically Ill Children: A Prospective Pilot Study

Background/Objectives: Invasive intracranial pressure (ICP) monitoring is standard in pediatric neurocritical care, but the potential of non-invasive near-infrared spectroscopy (NIRS) and the bedside drivers of ICP remain under-explored. We evaluated the association between cerebral NIRS (rSO2), pain and agitation, systemic hemodynamics, inflammatory markers, and invasive ICP in critically ill children. Methods: In this prospective pilot study, children undergoing external ventricular-drain-based ICP monitoring were followed with repeated measurements. Linear Mixed Models (LMM) with a random patient intercept were used to assess the NIRS–ICP association, adjusting for hemodynamic (mean arterial pressure (MAP), heart rate) and clinical variables. The Mann–Whitney U test compared parameters across a 20 mmHg ICP threshold, and the Kruskal–Wallis test compared ICP burden across etiology and outcome subgroups. Inflammatory markers (CRP, WBC, procalcitonin) were evaluated separately. Results: A total of 596 measurements from 21 patients were analyzed. Cerebral NIRS was the strongest independent predictor of ICP, showing a significant inverse association (estimate −0.609, p < 0.001). Agitation was independently associated with higher ICP (estimate 0.856, p < 0.001), and this effect was significantly modified by the patient’s behavioral state, being attenuated during sleep and calm wakefulness compared with agitated wakefulness (sleep × agitation interaction, p = 0.002). MAP retained an independent positive association with ICP (estimate 0.044, p = 0.019), whereas pain score did not. After adjustment for etiology and sex, these associations remained unchanged; etiology was itself an independent predictor of ICP (p = 0.001), whereas sex was not. Serum CRP independently predicted ICP (t = 2.382, p = 0.018), whereas WBC and procalcitonin did not. ICP burden differed by etiology, with intracranial masses and leukemia showing the highest loads (p < 0.001), but not across clinical-outcome groups (p = 0.192). Conclusions: Cerebral NIRS-derived rSO2 was an independent inverse correlate of invasive ICP, and agitation was independently associated with ICP in a state-dependent manner, with its effect attenuated during sleep and calm wakefulness. CRP and etiology further shaped ICP burden. These findings support integrating non-invasive cerebral oximetry into multimodal pediatric neuromonitoring and highlight the value of managing distress to mitigate intracranial hypertension.