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 Table of Contents  
ORIGINAL ARTICLE
Year : 2020  |  Volume : 7  |  Issue : 2  |  Page : 235-239

Plasma epinephrine as a prognostic marker in traumatic brain injury


1 Resident of Critical Care in Alexandria University Students Hospital, Alexandria, Egypt
2 Critical Care Medicine Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt

Date of Submission01-Oct-2019
Date of Acceptance08-Apr-2020
Date of Web Publication27-Jun-2020

Correspondence Address:
MBBCh Ahmed E Elshewy
Faculty of Medicine, Alexandria University, 7 Syria Street, Roushdy, Alexandria, 21529
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/roaic.roaic_82_19

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  Abstract 

Background Traumatic brain injury is an international health problem with high morbidity and mortality. It is associated with catecholamine release (catecholamine surge).
Objective The purpose of the work was to study plasma epinephrine as a prognostic marker in traumatic brain injury.
Patients and methods The authors enrolled 60 adult persons of both sexes [30 patients with diagnosis of isolated traumatic brain injury with Glasgow coma score (GCS) ≤11 and 30 volunteers as a control group]. Plasma epinephrine levels were measured on admission and after 24 h. Then the patients were classified into two groups at the end of the study (3 months) according to the GOS: group I (favorable outcome; GOS IV, V) which included 11 (36.6%) patients and group II (unfavorable outcome; GOS I, II, III) which included 19 (63.3%) patients.
Results Receiver operating characteristic curves were used to describe the prognostic value of plasma epinephrine on admission and after 24 h to predict unfavorable outcome and mortality. Higher levels of epinephrine on admission were associated with a higher rate of unfavorable outcome [areas under the curve (AUC)=0.921, confidence interval (CI): 0.828–1.014, P<0.001] and mortality (AUC=0.855, CI: 0.707–1.003, P=0.003). Also, higher levels of epinephrine after 24 h were associated with a higher rate of unfavorable outcome (AUC=0.971, CI: 0.912–1.030, P<0.001) and mortality (AUC=0.884, CI: 0.752–1.02, P=0.002).
Conclusion Plasma epinephrine could be used as a prognostic marker in traumatic brain injury.

Keywords: catecholamine surge, Glasgow outcome score, plasma epinephrine, traumatic brain injury


How to cite this article:
Elshewy AE, Nabil AM, El-Reweny EM. Plasma epinephrine as a prognostic marker in traumatic brain injury. Res Opin Anesth Intensive Care 2020;7:235-9

How to cite this URL:
Elshewy AE, Nabil AM, El-Reweny EM. Plasma epinephrine as a prognostic marker in traumatic brain injury. Res Opin Anesth Intensive Care [serial online] 2020 [cited 2020 Oct 28];7:235-9. Available from: http://www.roaic.eg.net/text.asp?2020/7/2/235/288001


  Background Top


Traumatic brain injury (TBI) is a leading cause of morbidity and mortality worldwide. The overall incidence of TBI worldwide is estimated to be 69 million patients each year. It is a devastating condition in terms of personal, social and economic impact [1].

Despite the relationship of many variables and outcome, prognostications are difficult to make. Multivariate analysis has identified age, degree of coma, CT findings, hypotension, hypoxia, and some laboratory studies as important factors for prediction of outcome in brain injury [2].

Epinephrine is a hormone and neurotransmitter [3]. It is responsible for many functions, the most important one being those accompanied with the ‘fight or flight’ response to perceived danger [4]. In addition, it has a role in catecholamine surge which occurs after TBI [5],[6].

Elevated catecholamines level after TBI lead to peripheral vasoconstriction which results in arterial hypertension and increase in cerebral blood flow. These mechanisms and the loss of blood brain barrier integrity in TBI can lead to secondary brain injury and brain edema formation [7]. In addition, catecholamines induce disturbance of cytokine release, resulting in systemic organs damage [8].


  Objective Top


The purpose of our work was to study plasma epinephrine as a prognostic marker in traumatic brain injury.


  Patients and methods Top


After approval by the Medical Ethics Committee of Alexandria Faculty of Medicine, we conducted this prospective observational study on 60 adults of both sexes [30 patients with diagnosis of isolated traumatic brain injury with Glasgow coma score (GCS)≤11 who were admitted to the units of Critical Care Medicine Department in Alexandria Main University Hospital and 30 volunteers as a control group]. Informed consent was taken from the next of kin. Patients were classified into two groups at the end of the study (3 months) according to the Glasgow outcome score (GOS) [9]. Group I (favorable outcome; GOS IV, V) included 11 (36.6%) patients and group II (unfavorable outcome; GOS I, II, III) included 19 (63.6%) patients.

We excluded pregnant women, patients aged below 18 years of age, patients with associated injuries, for example chest trauma, abdominal trauma and fractures, postarrest patients, or any patient requiring surgical intervention .

Data collection

All patients included in the study were subjected to complete history taking and complete physical examination including vital signs and investigations.

Neurological assessment for the patients included the GCS that was recorded on admission and daily during the period of the study (3 months). Computed tomography (CT) brain was done on admission and as needed, Marshall classification [10] was done on admission only and GOS was done at the end of the study.

Epinephrine measurement

Plasma epinephrine was measured immediately after admission and after 24 h. A sample of 5 ml venous blood samples was collected on admission and again at 24 h of TBI. Venous blood samples were drawn into 10 ml K2edta vacutainers. Specimens were immediately centrifuged at 1600×g for 15 min (4C). The plasma was separated into aliquots and frozen at −70°C until measurement. Plasma epinephrine levels were determined from duplicate samples using a direct competitive enzyme immunoassay method according to the manufacturer’s instructions (Bi-CAT EIA; Alpco Diagnostics, Salem, New Hampshire, USA) [11].

Statistical analysis

Data were fed into the computer and were analyzed using IBM SPSS software package version 20.0 (IBM Corp., Armonk, New York, USA). Qualitative data were described using number and percentage. The Kolmogorov–Smirnov test was used to verify the normality of distribution. Quantitative data were described using range (minimum and maximum), mean, SD, and median. Significance of the obtained results was judged at the 5% level.


  Results Top


Regarding demographic data, there was statistically significant difference between the two groups as regards age (P=0.042), while there was no statistically significant difference between the two groups as regards sex (P=1.000) ([Table 1]).
Table 1 Comparison between two studied groups as regards demographic data

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As regards routine laboratory investigations: there were no statistical difference between both studied groups except that white blood cell counts was higher in group II and the difference between two groups was significant (P=0.038), while the other parameters showed no statistically significant difference between the two groups.

As regards CT findings, a CT brain was done on admission for each patient of the two groups and the findings were classified according to the Marshall classification of CT in brain injury. The Marshall score was higher in group II (the unfavorable group) and the difference between the two groups was statistically significant (P<0.001) ([Table 2]).
Table 2 Comparison between two studied groups as regards computed tomography findings (Marshall score)

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Regarding GCS on admission, the mean GCS in group I was 9.91±1.45, while in group II it was 5.32±1.77. There was statistical significance between the two groups according to GCS on admission (P<0.001), the mean GCS on admission was higher in group I (favorable) than in group II (unfavorable) ([Figure 1]).
Figure 1 Comparison between two studied groups as regards Glasgow coma score on admission.

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Epinephrine level

It was found that the mean value of plasma epinephrine on admission in group II was higher than group I and this difference was statistically significant (P<0.001). Furthermore, the relationship between epinephrine levels on admission and mortality was also statistically significant (P<0.001) ([Table 3], [Figure 2]).
Table 3 Comparison between two studied groups as regards epinephrine level

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Figure 2 Comparison between two studied groups as regards epinephrine level.

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When comparing the plasma level of epinephrine withdrawn after 24 h of admission between the two groups, it was found that the mean value in group II was higher than group I and the difference was statistically significant (P<0.001). Moreover, the relationship between epinephrine level after 24 h and mortality was also statistically significant (P=0.002).

We observed that the difference between the amounts of reduction in both groups was statistically insignificant. However, the percentage of reduction from baseline was statistically significant (P=0.007).

Receiver operating characteristic curves for plasma epinephrine level on admission and after 24 h

Regarding plasma epinephrine on admission, the receiver operating characteristic (ROC) curve was used to describe the prognostic values of plasma epinephrine on admission to predict the unfavorable outcome, the areas under the curve (AUC) for epinephrine on admission calculated from the ROC curves were 0.921 (P<0.001). Also, sensitivity and specificity were 73.68 and 81.82%, respectively, with 87.5% positive predictive value (PPV) and 64.3% negative predictive value (NPV) ([Table 4]).
Table 4 Agreement (sensitivity, specificity) for epinephrine on admission and after 24 h to predict unfavorable outcome and mortality

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In addition, the ROC curve for plasma epinephrine level on admission was used to predict mortality and the AUC for plasma epinephrine levels as a predictor of mortality was 0.855 (P=0.003). Also, sensitivity and specificity were 87.5 and 68.18%, respectively, with 50% PPV and 93.7% NPV ([Table 4]).

Regarding plasma epinephrine level after 24 h, the ROC curve was used to describe the prognostic values of plasma epinephrine after 24 h to predict the unfavorable outcome. AUC for epinephrine after 24 h were calculated from the ROC curves were 0.971 (P<0.001). Also, sensitivity and specificity were 94.74 and 96%, respectively, with 98% PPV and 91.7% NPV ([Table 4]).

Moreover, in the study, the ROC curve for plasma epinephrine level after 24 h was used to predict the mortality, the AUC for plasma epinephrine levels after 24 h as a predictor of mortality was 0.884 (P=0.002). In addition, sensitivity and specificity were 87.50 and 68.18%, respectively, with 50% PPV and 93.7% NPV ([Table 4]).


  Discussion Top


The results of this study showed that the mean age was27.82±9.34 years in group I (favorable outcome) and 35.42±12.63 years in group II (unfavorable outcome). There was statistically significant difference between the two groups regarding age (P=0.042). In agreement with our study, Czosnyka et al. [12] in their study about the outcome of traumatic brain injury found that the elderly people had a worse outcome after brain trauma.

As regards routine laboratory investigations, the white blood cell counts were higher in group II and there was a significant difference between two groups (P=0.038). The development of high white cell counts during the clinical course of the patient is due to infection which worsen the prognosis. In consistent with our study, Piek et al. [13] has shown that during their study that pulmonary infections and septicemia were independent predictors of an unfavorable outcome in severe traumatic brain injury.

In our research, the GCS was done on admission, the mean GCS in group I was 9.91±1.45, while in group II it was 5.32±1.77. There was statistical significance between the two groups according to GCS on admission (P<0.001). The relation between GCS and GOS was also demonstrated by Bordbar et al. [14] during their study which revealed that presenting GCS is reliable indicator of long term outcome.

Regarding Marshall Classification of CT in brain injury, the Marshall score was higher in group II and the difference between two groups was statistically significant (P<0.001). Similar to our study, Maas et al. [15] found that the Marshall score was strongly related to the outcome, with worst outcome for patients with diffuse injuries in CT class III or CT class IV.

Epinephrine level

In our study, it was found that the mean value of plasma epinephrine on admission in group II was higher than group I and this difference was statistically significant (P<0.001). Furthermore, the relationship between epinephrine level at admission and mortality was also statistically significant (P<0.001).

Similar to our study the Rizoli et al. [11] study have found during their study about catecholamines as outcome markers in isolated traumatic brain injury that higher admission levels of epinephrine were associated with a higher risk of unfavorable outcome and mortality. Also, in agreement with our study, the Ko et al. [16] study showed that the use of propranolol (nonselective beta blockers) which blocks the effect of catecholamines (epinephrine and norepinephrine) early in traumatic brain injury improves mortality.

Regarding epinephrine withdrawn after 24 h, it was found that the mean value was higher in group II and the difference between two groups was statistically significant (P<0.001). Moreover, the relationship between epinephrine levels after 24 h and mortality was also statistically significant (P=0.002).

In consistent with our study, the Woolf et al. [17] study about the predictive of catecholamines in assessing outcome in traumatic brain injury found that the mean value of epinephrine in the first 48 h were significantly higher in patients who died or remained persistently vegetative than in those with better outcomes.

In contrast to our study, the Rizoli et al. [11] study found that there was no relationship between the changes in epinephrine levels over time and mortality or unfavorable outcome. This may be explained by the small size of the sample in our study and the duration of their study was 6 months while in our study, it was 3 months.

The strength of our study was that enrolled patients with isolated traumatic brain injury (GCS ≤11) and with certain exclusion criteria to avoid any confounders, such as postarrest patients, patients with associated injuries (e.g. chest trauma, abdominal trauma), and patients requiring surgical interventions. Another advantage in our study is that we classified the patients into two categories according to the GOS which allowed to evaluate the role of plasma epinephrine in the prediction of unfavorable outcome and mortality.

Our study had some limitations; the main limitation of this study is that it is a single-center study. A multicenter study may be required to extrapolate our findings to other clinical settings. Other limitations can be the small sample size and the short duration of the study (3 months).


  Conclusion Top


Our study illustrated that plasma epinephrine could be a clue about the prognosis in isolated traumatic brain injury. In addition, it has been demonstrated that plasma epinephrine level has good sensitivity and specificity for the prediction of functional outcome and mortality in isolated traumatic brain injury.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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    Figures

  [Figure 1], [Figure 2]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

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