Serum substance P levels are associated with severity and mortality in patients with severe traumatic brain injury.
BACKGROUND
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. 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.


METHODS
This 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.


RESULTS
We 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).


CONCLUSIONS
We 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.
Intensive Care Unit, Hospital Universitario de Canarias, Ofra, s/n La Laguna, 38320, Tenerife, Spain. lorentemartin@msn.com.
Leonardo
L
Lorente
Intensive Care Unit, Hospital Universitario Nuestra Señora Candelaria, Carretera del Rosario s/n, 38010, Santa Cruz Tenerife, Spain. mar.martinvelasco@gmail.com.
María M
MM
Martín
Unidad de Genética, Instituto de Enfermedades Tropicales y Salud Pública de Canarias, Universidad de La Laguna, Avenida Astrofísico Francisco Sánchez s/n, Campus de Anchieta, La Laguna, 38071, Tenerife, Spain. tacosalm@ull.edu.es.
Teresa
T
Almeida
Unidad de Genética, Instituto de Enfermedades Tropicales y Salud Pública de Canarias, Universidad de La Laguna, Avenida Astrofísico Francisco Sánchez s/n, Campus de Anchieta, La Laguna, 38071, Tenerife, Spain. mnhdez@ull.edu.es.
Mariano
M
Hernández
Intensive Care Unit, Hospital General La Palma, Buenavista de Arriba s/n, Breña Alta, 38713, La Palma, Spain. lramosgomez@gmail.com.
Luis
L
Ramos
Intensive Care Unit, Hospital Clínico Universitario de Valencia, Avenida Blasco Ibáñez n° 17-19, 46004, Valencia, Spain. moni_begasa@hotmail.com.
Mónica
M
Argueso
Intensive Care Unit, Hospital Insular, Plaza Dr Pasteur s/n, 35016, Las Palmas de Gran Canaria, Spain. juanjose.caceresagra@gobiernodecanarias.org.
Juan J
JJ
Cáceres
Intensive Care Unit, Hospital Universitario Dr Negrín, Centro de Investigación Biomédica en Red Enfermedades Respiratorias (CIBERES), Barranco de la Ballena s/n, 35010, Las Palmas de Gran Canaria, Spain. jsolvio@gobiernodecanarias.org.
Jordi
J
Solé-Violán
Research Unit, Hospital Universitario de Canarias, Ofra, s/n, La Laguna, 38320, Santa Cruz de Tenerife, Spain. ajimenezsosa@gmail.com.
Alejandro
A
Jiménez
D000328:Adult; D000368:Aged; D015415:Biomarkers; D001930:Brain Injuries / Q000097:blood* / Q000175:diagnosis / Q000401:mortality*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009026:Mortality / Q000639:trends; D011446:Prospective Studies; D012720:Severity of Illness Index; D013373:Substance P / Q000097:blood*
D015415:Biomarkers; D013373:Substance P