Catecholamines as outcome markers in isolated traumatic brain injury: the COMA-TBI study

Sandro B Rizoli, Blessing N R Jaja, Alex P Di Battista, Shawn G Rhind, Antonio Capone Neto, Leodante da Costa, Kenji Inaba, Luis Teodoro da Luz, Bartolomeu Nascimento, Adic Perez, Andrew J Baker, Airton Leonardo de Oliveira Manoel, Sandro B Rizoli, Blessing N R Jaja, Alex P Di Battista, Shawn G Rhind, Antonio Capone Neto, Leodante da Costa, Kenji Inaba, Luis Teodoro da Luz, Bartolomeu Nascimento, Adic Perez, Andrew J Baker, Airton Leonardo de Oliveira Manoel

Abstract

Background: Elevated catecholamine levels might be associated with unfavorable outcome after traumatic brain injury (TBI). We investigated the association between catecholamine levels in the first 24 h post-trauma and functional outcome in patients with isolated moderate-to-severe TBI.

Methods: A cohort of 174 patients who sustained isolated blunt TBI was prospectively enrolled from three Level-1 Trauma Centers. Epinephrine (Epi) and norepinephrine (NE) concentrations were measured at admission (baseline), 6, 12 and 24 h post-injury. Outcome was assessed at 6 months by the extended Glasgow Outcome Scale (GOSE) score. Fractional polynomial plots and logistic regression models (fixed and random effects) were used to study the association between catecholamine levels and outcome. Effect size was reported as the odds ratio (OR) associated with one logarithmic change in catecholamine level.

Results: At 6 months, 109 patients (62.6%) had an unfavorable outcome (GOSE 5-8 vs. 1-4), including 51 deaths (29.3%). Higher admission levels of Epi were associated with a higher risk of unfavorable outcome (OR, 2.04, 95% CI: 1.31-3.18, p = 0.002) and mortality (OR, 2.86, 95% CI: 1.62-5.01, p = 0.001). Higher admission levels of NE were associated with higher risk of unfavorable outcome (OR, 1.59, 95% CI: 1.07-2.35, p = 0.022) but not mortality (OR, 1.45, 95% CI: 0.98-2.17, p = 0.07). There was no relationship between the changes in Epi levels over time and mortality or unfavorable outcome. Changes in NE levels with time were statistically associated with a higher risk of mortality, but the changes had no relation to unfavorable outcome.

Conclusions: Elevated circulating catecholamines, especially Epi levels on hospital admission, are independently associated with functional outcome and mortality after isolated moderate-to-severe TBI.

Keywords: Catecholamines; Epinephrine; Functional outcome; Norepinephrine; Traumatic brain injury.

Figures

Fig. 1
Fig. 1
Flow diagram of the screening process. LA Los Angeles County General Hospital and the University of Southern California Medical Center, SHSC Sunnybrook Health Sciences Centre, SMH St. Michael’s Hospital, WC withdrawal of consent
Fig. 2
Fig. 2
Bar plot showing temporal changes in mean catecholamine levels. a Epinephrine levels. b Norepinephrine levels
Fig. 3
Fig. 3
a and b Fractional polynomial plots of the relation of hospital-admission catecholamine levels to Marshall CT score of brain injury. c and d Fractional polynomial plots of the relation of catecholamine levels to outcomes at the different time points. Epi epinephrine, NE norepinephrine

References

    1. Boto GR. Severe head injury and the risk of early death. J Neurol Neurosurg Psychiatry. 2006;77:1054–1059. doi: 10.1136/jnnp.2005.087056.
    1. Shackford SR, Mackersie RC, Holbrook TL, et al. The epidemiology of traumatic death. A population-based analysis. Arch Surg. 1993;128:571–575. doi: 10.1001/archsurg.1993.01420170107016.
    1. Langlois JA, Rutland-Brown W, Wald MM. The epidemiology and impact of traumatic brain injury: a brief overview. J Head Trauma Rehabil. 2006;21:375–378. doi: 10.1097/00001199-200609000-00001.
    1. Molina PE. Neurobiology of the stress response: contribution of the sympathetic nervous system to the neuroimmune axis in traumatic injury. Shock. 2005;24:3–10. doi: 10.1097/01.shk.0000167112.18871.5c.
    1. Elenkov IJ, Wilder RL, Chrousos GP, Vizi ES. The sympathetic nerve: an integrative interface between two supersystems: the brain and the immune system. Pharmacol Rev. 2000;52:595–638.
    1. Woolf PD, Hamill RW, Lee LA, Cox C, McDonald JV. The predictive value of catecholamines in assessing outcome in traumatic brain injury. J Neurosurg. 1987;66:875–882. doi: 10.3171/jns.1987.66.6.0875.
    1. Chesnut RM, Marshall LF, Klauber MR, et al. The role of secondary brain injury in determining outcome from severe head injury. J Trauma. 1993;34:216–222. doi: 10.1097/00005373-199302000-00006.
    1. Teasdale G, Jennett B. Assessment of coma and impaired consciousness. A practical scale. Lancet. 1974;2:81–84.
    1. Elm VE, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Lancet. 2007;370:1453–57.
    1. Marshall LF, Marshall SB, Klauber MR, Clark MB. A new classification of head injury based on computerized tomography. J Neurosurg. 1991;1:S14–S20.
    1. Wilson JT, Pettigrew LE, Teasdale GM. Structured interviews for the Glasgow Outcome Scale and the extended Glasgow Outcome Scale: guidelines for their use. J Neurotrauma. 1998;15:573–585. doi: 10.1089/neu.1998.15.573.
    1. Wilson JTL, Edwards P, Fiddes H, Stewart E, Teasdale GM. Reliability of postal questionnaires for the Glasgow Outcome Scale. J Neurotrauma. 2002;19:999–1005. doi: 10.1089/089771502760341910.
    1. Chesnut RM, Marshall SB, Piek J, Blunt BA, Klauber MR, Marshall LF. Early and late systemic hypotension as a frequent and fundamental source of cerebral ischemia following severe brain injury in the Traumatic Coma Data Bank. Acta Neurochir Suppl (Wien) 1993;59:121–125.
    1. Hamill RW, Woolf PD, McDonald JV, Lee LA, Kelly M. Catecholamines predict outcome in traumatic brain injury. Ann Neurol. 1987;21:438–443. doi: 10.1002/ana.410210504.
    1. Clifton GL, Ziegler MG, Grossman RG. Circulating catecholamines and sympathetic activity after head injury. Neurosurgery. 1981;8:10–14. doi: 10.1227/00006123-198101000-00003.
    1. Woolf PD, McDonald JV, Feliciano DV, Kelly MM, Nichols D, Cox C. The catecholamine response to multisystem trauma. Arch Surg. 1992;127:899–903. doi: 10.1001/archsurg.1992.01420080033005.
    1. Toutant SM, Klauber MR, Marshall LF, et al. Absent or compressed basal cisterns on first CT scan: ominous predictors of outcome in severe head injury. J Neurosurg. 1984;61:691–694. doi: 10.3171/jns.1984.61.4.0691.
    1. Ristagno G, Sun S, Tang W, et al. Effects of epinephrine and vasopressin on cerebral microcirculatory flows during and after cardiopulmonary resuscitation. Crit Care Med. 2007;35:2145–2149. doi: 10.1097/01.CCM.0000280427.76175.D2.
    1. Ristagno G, Tang W, Huang L, et al. Epinephrine reduces cerebral perfusion during cardiopulmonary resuscitation. Crit Care Med. 2009;37:1408–1415. doi: 10.1097/CCM.0b013e31819cedc9.
    1. Di Battista AP, Rhind SG, Hutchison MG, et al. Inflammatory cytokine and chemokine profiles are associated with patient outcome and the hyperadrenergic state following acute brain injury. J Neuroinflammation. 2016;13:1–14. doi: 10.1186/s12974-016-0500-3.
    1. Di Battista AP, Rizoli SB, Lejnieks B, et al. Sympathoadrenal activation is associated with acute traumatic coagulopathy and endotheliopathy in isolated brain injury. Shock. 2016;46:93–106. doi: 10.1097/SHK.0000000000000642.
    1. Hammerle AF, Hackl JM, Brücke T, Rumpl E, Hörtnagl H. The activity of the sympathetic nervous system following severe head injury. Intensive Care Med. 1980;6(3):169–7. doi: 10.1007/BF01757299.
    1. McLeod AA, Neil-Dwyer G, Meyer CH, Richardson PL, Cruickshank J, Bartlett J. Cardiac sequelae of acute head injury. Br Heart J. 1982;47:221–226. doi: 10.1136/hrt.47.3.221.
    1. Larremore T, Markovchick V. Cardiac sequelae of acute head injury. Br Heart J. 1983;49:101–102. doi: 10.1136/hrt.49.1.101.
    1. Dunser MW, Hasibeder WR. Sympathetic overstimulation during critical illness: adverse effects of adrenergic stress. J Intensive Care Med. 2009;24:293–316. doi: 10.1177/0885066609340519.
    1. Dunser MW, Ruokonen E, Pettilä V, et al. Association of arterial blood pressure and vasopressor load with septic shock mortality: a post hoc analysis of a multicenter trial. Crit Care. 2009;13:R181. doi: 10.1186/cc8167.
    1. Herndon DN, Hart DW, Wolf SE, Chinkes DL, Wolfe RR. Reversal of catabolism by beta-blockade after severe burns. N Engl J Med. 2001;345:1223–1229. doi: 10.1056/NEJMoa010342.
    1. Arbabi S, Ahrns KS, Wahl WL, et al. Beta-blocker use is associated with improved outcomes in adult burn patients. J Trauma. 2004;56:265–269. doi: 10.1097/01.TA.0000109859.91202.C8.
    1. Diaz EC, Herndon DN, Porter C, Sidossis LS, Suman OE, Børsheim E. Effects of pharmacological interventions on muscle protein synthesis and breakdown in recovery from burns. Burns. 2015;41:649–657. doi: 10.1016/j.burns.2014.10.010.
    1. Monk DN, Plank LD, Franch-Arcas G, Finn PJ, Streat SJ, Hill GL. Sequential changes in the metabolic response in critically injured patients during the first 25 days after blunt trauma. Ann Surg. 1996;223:395–405. doi: 10.1097/00000658-199604000-00008.
    1. Asgeirsson B, Grände PO, Nordström CH. A new therapy of post-trauma brain oedema based on haemodynamic principles for brain volume regulation. Intensive Care Med. 1994;20:260–267. doi: 10.1007/BF01708961.
    1. Naredi S, Eden E, Zäll S, Stephensen H, Rydenhag B. A standardized neurosurgical neurointensive therapy directed toward vasogenic edema after severe traumatic brain injury: clinical results. Intensive Care Med. 1998;24:446–451. doi: 10.1007/s001340050594.
    1. Park E, Bell JD, Baker AJ. Traumatic brain injury: can the consequences be stopped? CMAJ. 2008;178:1163–1170. doi: 10.1503/cmaj.080282.
    1. Alali AS, McCredie VA, Golan E, Shah PS, Nathens AB. Beta blockers for acute traumatic brain injury: a systematic review and meta-analysis. Neurocrit Care. 2014;20:514–523. doi: 10.1007/s12028-013-9903-5.

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