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

Abstract

BackgroundElevated 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.MethodsA 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.ResultsAt 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.ConclusionsElevated circulating catecholamines, especially Epi levels on hospital admission, are independently associated with functional outcome and mortality after isolated moderate-to-severe TBI.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-017-1620-6) contains supplementary material, which is available to authorized users.

Beta-adrenergic blockade for attenuation of catecholamine surge after traumatic brain injury: a randomized pilot trial

“…Our group verified these results and showed that the odds of mortality were reduced with beta-blockers in patients with TBI by 65% in the adjusted regression model 14. These findings are consistent across multiple retrospective studies,9 10 12 14 15 19 20 32 but all share a similar weakness. Patients in most of these studies received ‘2 or more doses’, ‘greater than one dose’, or scheduled doses instead of actually titrating the dose of beta-blockers to a target 10 14 16 24 33 34.…”

“…The etiology for the syndrome of dysautonomia or paroxysmal sympathetic hyperactivity18 is a catecholamine surge leading to tachycardia, fever, hypertension, diaphoresis, tachypnea, and mydriasis from cerebral disconnection 15. Multiple authors have shown the both central and peripheral catecholamines are elevated after TBI 4 6 13 17 32 41–43. The elevation of catecholamines is directly proportional to the severity of brain injury 4 13.…”

“…The elevation of catecholamines is directly proportional to the severity of brain injury 4 13. Catecholamine elevation seems to be highest in plasma immediately after injury, but this elevation may persist for up to 14 days 13 32 41–43. In this study, we measured urinary catecholamines and pooled the results for total analysis as well as examined the individual results of dopamine, epinephrine, and norepinephrine.…”

Innate immune responses to trauma

“…Microglia in the injured brain as well as neutrophils in extra-cerebral areas generate inducible nitricoxide synthase early after TBI, which contributes to hemodynamic instability through vasodilation 148 . In contrast, vasoconstriction is induced by catecholamines from the TBI-activated HPAA, which results in a stress reaction that modulates extra-cerebral immune responses (for example, activation of neutrophils and immunological-metabolic shifts) and is also associated with a poor outcome 149 .…”

Using propranolol in traumatic brain injury to reduce sympathetic storm phenomenon: A prospective randomized clinical trial

“…Another study by Rizoli et al . [ 25 ] confirmed that higher admission levels of E were associated with a higher risk of unfavorable outcome which was assessed at 6 months by the extended Glasgow outcome scale score (odds ratio [OR], 2.04, 95% confidence interval [CI]: 1.31–3.18, P = 0.002) and that 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). Other investigators have not found such a correlation.…”