title: Prehospital Hypotension Is Associated With Altered Inflammation Dynamics and Worse Outcomes Following Blunt Trauma in Humans.
abstract: OBJECTIVE
  To define the impact of prehospital hypotension on the dynamic, systemic acute inflammatory response to blunt trauma.
  
  
  METHODS
  Retrospective study.
  
  
  METHODS
  Tertiary care institution.
  
  
  METHODS
  Twenty-two hypotensive blunt trauma patients matched with 28 normotensive blunt trauma patients.
  
  
  METHODS
  None.
  
  
  RESULTS
  From a cohort of 472 blunt trauma survivors studied following institutional review board approval, two stringently matched subcohorts were derived. Twenty-two patients who sustained prehospital hypotension following blunt trauma (15 males and 7 females; age, 45 ± 3.8; Injury Severity Score, 20.7 ± 1.8) were matched with 28 normotensive trauma patients (20 males and 8 females; age, 46.1 ± 2.5; Injury Severity Score, 20.8 ± 1.3). Serial blood samples (three samples within the first 24 hr and then from days 1 to 7 postinjury) were assessed for 24 inflammatory mediators using Luminex, and No2-/No3- was measured using the nitrate reductase/Griess assay. Two-way analysis of variance was used to compare groups. Dynamic Bayesian Network inference was used to infer causal relationships based on probabilistic measures. Statistically significant differences were observed in ICU length of stay, total length of stay, days on mechanical ventilator, and Marshall Multiple Organ Dysfunction score between hypotensive and normotensive patients. Shock markers (shock index, pH, lactate, and base deficit) were significantly altered in hypotensive patients. Plasma levels of chemokines (monocyte chemotactic protein-1/CCL2, inducible protein-10/CXCL10, macrophage inflammatory protein-1α/CCL3, and interleukin-8/CCL8) and cytokines (interleukin-6, interleukin-10, interleukin-17, granulocyte-macrophage colony-stimulating factor, interleukin-1β, and interleukin-7) as well as soluble interleukin-2 receptor-α were significantly elevated over the first 7 days postinjury in the hypotensive versus normotensive patients. Dynamic Bayesian Network suggested that the chemokines monocyte chemotactic protein-1/CCL2 and monokine induced by gamma interferon/CXCL9 in the hypotensive and normotensive patients, respectively, affect plasma interleukin-6 levels differentially in the initial 24 hours postinjury.
  
  
  CONCLUSIONS
  Studies in stringently matched patient cohorts suggest that an episode of prehospital hypotension post trauma leads to early, dynamic reprogramming of systemic inflammation (including differential upstream regulation of interleukin-6), which is associated with worse outcomes.
authors: 1Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA. 2Center for Inflammation and Regenerative Modeling, McGowan Institute for Regenerative Medicine, Pittsburgh, PA. 3Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA. 4Division of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI.
authors: Khalid
authors: K
authors: Almahmoud
authors: Rami A
authors: RA
authors: Namas
authors: Akram M
authors: AM
authors: Zaaqoq
authors: Othman
authors: O
authors: Abdul-Malak
authors: Rajaie
authors: R
authors: Namas
authors: Ruben
authors: R
authors: Zamora
authors: Jason
authors: J
authors: Sperry
authors: Timothy R
authors: TR
authors: Billiar
authors: Yoram
authors: Y
authors: Vodovotz
mesh_terms: D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007022:Hypotension / Q000150:complications* / Q000209:etiology; D007249:Inflammation / Q000209:etiology* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D014949:Wounds, Nonpenetrating / Q000150:complications*