Abstract
IntroductionSubstance P (SP) is a member of the tachykinin family of neuropeptides, which are widely distributed throughout the central nervous system (CNS) and actively involved in inflammatory processes. SP is released early following acute injury to the CNS, promoting a neurogenic inflammatory response characterized by an increase in the permeability of the blood–brain barrier and the development of vasogenic edema. High levels of SP could lead to an exacerbated inflammatory response that could be fatal for patients with traumatic brain injury (TBI). Thus, the main goal of the present study was to determine whether serum SP levels are associated with injury severity and mortality in patients with severe TBI.MethodsThis multicenter, observational, prospective study was carried out in six Spanish intensive care units and included patients with Glasgow Coma Scale (GCS) scores ≤8. Patients with an Injury Severity Score ≥10 in non-cranial aspects were excluded. Blood samples were collected on day 1 of TBI to measure serum SP levels. The endpoint was 30-day mortality.ResultsWe found higher serum SP levels (P =0.002) in non-surviving patients (n =27) than in surviving patients (n =73). The area under the curve for serum SP levels with regard to predicting 30-day mortality was 0.70 (95% confidence interval (CI), 0.60 to 0.79; P <0.001). Survival analysis showed that patients with serum SP levels >299 pg/ml had higher 30-day mortality than patients with lower levels (hazard ratio =3.7; 95% CI, 1.75 to 7.94; P <0.001). Multiple binomial logistic regression analysis showed that serum SP levels >299 pg/ml were associated with 30-day mortality when we controlled for APACHE II score and Marshall computed tomography lesion classification (odds ratio (OR) =5.97; 95% CI, 1.432 to 24.851; P =0.01) and for GCS score and age (OR =5.71; 95% CI, 1.461 to 22.280; P =0.01). We found a negative association between serum SP levels and GCS score (Spearman’s ρ = −0.22; P =0.03).ConclusionsWe report, for the first time to our knowledge, that serum SP levels were associated with injury severity and mortality in patients with severe TBI. These results open the possibility that SP antagonists may be useful in the treatment of patients with severe TBI.
Highlights
Substance P (SP) is a member of the tachykinin family of neuropeptides, which are widely distributed throughout the central nervous system (CNS) and actively involved in inflammatory processes
Multiple binomial logistic regression analysis showed that serum SP levels >299 pg/ml were associated with 30-day mortality when we controlled for Acute Physiology and Chronic Health Evaluation (APACHE) II score and Marshall computed tomography lesion classification (odds ratio (OR) =5.97; 95% Confidence interval (CI), 1.432 to 24.851; P =0.01) and for Glasgow Coma Scale (GCS) score and age (OR =5.71; 95% CI, 1.461 to 22.280; P =0.01)
We report, for the first time to our knowledge, that serum SP levels were associated with injury severity and mortality in patients with severe traumatic brain injury (TBI)
Summary
Substance P (SP) is a member of the tachykinin family of neuropeptides, which are widely distributed throughout the central nervous system (CNS) and actively involved in inflammatory processes. High levels of SP could lead to an exacerbated inflammatory response that could be fatal for patients with traumatic brain injury (TBI). Primary injury refers to the initial physical forces applied to the brain at the moment of impact and leads to shearing, laceration and stretching of nerve fibers [2,3]. Secondary injury is a term applied to the destructive and self-propagating biological changes in cells and tissues that lead to their dysfunction or death during the hours to weeks after the initial insult [4]. One of the process that contribute to these biological changes is neurogenic inflammation, characterized by the release of substances from primary sensory nerves, leading to vasodilation, protein extravasation and tissue swelling [5,6]. Substance P (SP), calcitonin gene-related peptide and neurokinin A are neuropeptides present in the sensory C fibers that densely surround cerebral blood vessels [7,8]
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