Persistently High Serum Substance P Levels and Early Mortality in Patients with Severe Traumatic Brain Injury

BACKGROUND: Substance P is a neuropeptide belonging to the tachykinin family and is involved in neuroinflammation. In a previous study by our team, we found higher serum substance P levels on day 1 of traumatic brain injury (TBI) in nonsurviving than in surviving patients. Thus, the objective of this study was to determine whether serum substance P levels during the first week of TBI could predict early mortality. METHODS: This was a multicenter, observational, and prospective study. We included patients with an isolated severe TBI, defining isolated as <9 points in non-cranial aspects of Injury Severity Score and severe as <9 points of Glasgow Coma Scale. We determined serum substance P concentrations at days 1, 4, and 8 of TBI. We performed receiver operating characteristic analyses to determine the capacity of serum substance P levels at day 1, 4, and 8 of TBI to predict 30-day mortality. RESULTS: Nonsurviving (n = 34) compared with surviving patients (n = 90) had greater serum substance P levels on day 1 (P < 0.001), 4 (P < 0.001), and 8 (P < 0.001) of TBI. The areas under curve of serum substance P concentrations at days 1, 4, and 8 of TBI to predict 30-day mortality were 76% (P < 0.001), 87% (P < 0.001), and 89% (P < 0.001), respectively. CONCLUSIONS: The new finding of our study is that the presence of elevated serum substance P levels during the first week of TBI is associated with increased mortality.