Correlation between Catecholamine Levels and Outcome in Patients with Severe Head Trauma
Some studies have shown that catecholamines and the changes in their levels during and after head trauma can be useful in predicting the outcome in head trauma patients. The goal of this study is to search for a probable relation between urine levels of catecholamines and prognosis in patients with severe head trauma. Fifty four patients with severe head trauma Glasgow Coma Scale (GCS≤8) on admission time were recruited in Imam Reza Hospital within one. These patients were included when having no major accompanying trauma in other organs. Twenty four hour urine was collected after admission and levels of metanephrine and nor-metanephrine were measured. The relation between urine levels of these metabolites with final outcome and also with GCS at admission, 24, 48 h and 1 week after admission and discharge time and Glasgow Outcome Scale (GOS) were studied. Fifty two patients, 48 males and 4 females with a mean age of 32.3±14.7 (3-72) years were included. The main underlying etiologies were motorcycle (46.2%) and car accidents (25%). Diffuse axonal injury, brain contusion and subdural hematoma were three main diagnoses (28.8, 17.3 and 15.4% of the cases, respectively). 19 (36.5%) of the patients expired within the study period. The mean level of metanephrine and normetanephrine in urine were 207.9±200.5 and 330.2±218.4 μg in 24 h, respectively. There was no meaningful relation between urine levels of these metabolites and any of GCS and GOS. There was also no meaningful relation between these parameters and final prognosis in patients.
Received: May 10, 2010;
Accepted: July 09, 2010;
Published: August 05, 2010
Trauma is one of the major causes of death in all societies and only one of
its sub classifications, head trauma, has a prevalence of 200 to 300 cases in
100.000 people a year. In head trauma patients, the trauma is categorized into
two types. Primary brain injury that takes place in accident time and secondary
injury that develops following primary trauma so that cellular processes leading
to cellular death in brain and deterioration of clinical status of the patients
begin (Winn, 2003). By now, different prognostic factors
have been proposed in regard to the mortality and final prognosis of patients
with head trauma (Lingsma et al., 2010; Steyerberg
et al., 2008; Menon and Zahed, 2009;
Oh et al., 2006; Murray et al., 2007).
Catecholamine levels are one of the suggested items in trauma patients prognoses.
Trauma initiates a cascade of physiological procedures. Fear accompanied by
trauma provokes sympathetic system. On the other hand, pain is a powerful provoker
of sympathoadrenal axis which increases sympathetic tone and catecholamine release.
Sympathetic system activation can occur following injury, bleeding and hypovolemia.
Sympathetic effect and Catecholamines release, including epinephrine and nor-epinephrine,
have numerous effects such as increase in blood pressure, heart rate, heart
contractibility and ventilation per minute. Although these effects of catecholamines
after severe injuries increase survival probability in short term, sympathoadrenal
axis excitation in long term can lead to reverse physiological effects. High
catecholamine levels can cause arteriolar contraction and therefore decrease
oxygen and metabolic substrates delivery to the tissues and also catabolic metabolic
state which is seen in severe trauma (Fink et al.,
2005). To the best of knowledge there is only one study on catecholamine
metabolites in urine so for with no significant results (Kearney
et al., 1992). This study is to evaluate the relation between urine
catecholamine metabolites levels with GCS and prognosis in patients with severe
head trauma for the first time. Any significant finding would influence the
routine workup and management in these patients.
MATERIALS AND METHODS
Fifty four patient with severe head trauma were studied in a cross sectional,
descriptive-analytic study. Follow up was not possible for two patients; therefore
the study was carried out on 52 patients. Urine catecholamine metabolites levels
in first 24 h of admission were measured and their relation with prognoses of
patients was evaluated. The study was carried out in Tabriz Imam Reza Hospital
and primary data collection and analysis lasted for 12 months starting from
Jan 2009 to Jan 2010. Patients were entered the study immediately after being
examined by resident of neurosurgery in emergency ward if that they had GCS≤8
and surgical approval and did not have severe chest and/or abdomen traumas.
Urine catheters were inserted in all patients and 24 h urine was collected after
primary medical measurements and patient transfer to the ward. Urine samples
were collected and pH was adjusted to 1-3 with HCl. Urine samples were collected
by wringing the compresses, centrifuged at 4°C and acidified. All acidified
samples were kept at -20°C until analysis. The routine analysis of free
catecholamines (metanephrine and normetanephrine) was made by HPLC-EC (M515
pump, Wisp 740 autosampler and a M460 amperometric detector; Waters, Saint Quentin,
France) after extraction from urine by ion exchange. Urinary 24 h creatinine
concentrations were determined using a compensated rate-blanked Jaffé
based method on a Modular P900 (Roche Diagnostics) (Pussard
et al., 2009). Routine serum laboratory tests including determining
the serum levels of glucose, hematocrit, creatinine, Blood Urea Nitrogen (BUN),
Na and K were performed on admission, too (Fink et al.,
2005). Clinical examination and GCS estimation were performed by resident
of neurosurgery 24 and 48 h and one week after trauma. The GOS was also determined
when patients were discharged. The relation between the urinary levels of catecholamines
with the GCS and GOS scores, as well as the short-term outcome (discharge, expire)
was determined. Informed consents were signed by the first degree relatives
of the patients. This study is approved by the Ethics Committee of Tabriz University
of Medical Sciences. Obtained data are presented as Mean±SD and frequency
and percentage. SPSSTM Ver. 15 statistical software was used. Quantitative
variables were compared using student t-test (Independent samples), Mann Whitney
U-Test. Qualitative variables were compared using contingency tables and chi-square
test and or Fisher's Exact test considering the conditions. Correlation was
evaluated defining Spearman coefficient (rho). Results with p≤0.05 were considered
statistically meaningful in all studied items.
Fifty two cases with severe head trauma were studied. The mean age of the patients
was 32.3±14.7 (13-72, median 28) years including 10 (19.2%) cases ≤20
years, 27 (51.9%) cases between 21 and 40 years and 15 (28.8%) cases ≤41
years. Forty eight (92.3%) patients were male and 4(7.2%) were female. Thirty
three (63.5%) patients were hospitalized in trauma ward and 19 (36.5%) in the
Intensive Care Unit (ICU). Accompanied traumas existed in 8(15.4%) patients
which were all bone fractures. Thirteen (46.2%) patients were traumatized in
car, 9(17.3%) as pedestrians, 4(7.7%) with fall accidents and 2 (3.8%) in quarrel.
The hospitalization time was 16.1±10.8 (2-45) days. Regarding lab findings;
the mean hemoglobin level was 12.7±2.3 (8.4-19.2 median 12.9) mg dL-1
(15 decreased, 3 increased, 34 normal), mean hematocrit level was 34.2±6.6
(22-43 median 37) percent (8 decreased, 2 increased, 42 normal), mean blood
sugar level was 108.3±73.3 (94-444 median 163) mg dL-1 (18
increased, 34 normal), mean sodium level was 143.8±4.1 (128-151 median
144) meq dL-1 (2 decreased, 4 increased, 46 normal), mean potassium
level was 4.0±0.8(0.8-6.3 median 4) meq dL-1 (5 decreased,
2 increased, 45 normal), mean BUN level was 33.5±11.8 (12-82 median 33)
mg dL-1 (5 increased, 47 normal), mean serum creatinine level was
1.0±0.3 (0.6-1.7 median 0.9) mg dL-1 (2 increased, 50 normal),
mean 24 h urine creatinine level was 1.6±0.9 (0.2-3.5 median 1.6) mg
dL-1 (all normal), mean urine metanephrine level was 207.9±200.5
(30.5-1219 median 187.5) microg/24 h (14 increase, 38 normal), mean urine normetanephrine
level was 330.2±218.4 (54.1-1 median 282.9) microg/24 h (5 increased,
47 normal), mean GCS at admission time, 24 h after admission, 48 h after admission,
1 week after admission and at discharge time were respectively 6.4±1.5(median
7, 3-8), 6.8±1.7 (median 7, 3-11), 6.7±2.5 (median 7, 0-14), 6.4±5.1
(median 71, 0-15), 8.1±6.1 (median 10.5, 0-15) and the mean GOS was 2.6±1.4
(median 3, 1-5). Finally 33 patients (63.5%) were discharged and 19 (36.5%)
were expired. The final diagnoses are summarized in Table 1.
Accordingly, the diffuse axonal injury, brain contusion and subdural hematoma
were the three leading underlying causes. The correlation between urine catecholamine
levels and GCS and GOS in different age-groups and in all patients is summarized
in Table 2. Accordingly, there was no meaningful correlation
between urine metanephrine and normetanephrine and GCS on admission, 24, 48
h and 1 week after discharge. There was no meaningful correlation between urine
metanephrine and normetanephrine and GOS. The relations between studied criteria
and urine catecholamine levels with patients' outcome in different age-groups
and in all patients are summarized in Table 3.
|| Final diagnosis percentage among patients
|| The relation between urine catecholamine levels and GCS and
GOS in different age groups
|| The relation between basic variables and urine catecholamine
levels with prognosis in different age groups.
|Data are shown as Mean±SD (median)
Accordingly, there was no significant difference between the two groups regarding
gender, hospitalization ward, accompanying fractures in other parts of body
and the mean urine levels of metanephrine or normetanephrine.
Trauma initiates a cascade of physiological events and one of them is the catecholamines
release. Sympathoadrenal axis excitation in long term can lead to reverse physiological
effects such as decreased oxygen and metabolic substrates delivery to the tissues
and catabolic state in severe trauma (Fink et al.,
2005). Hamill et al. (1987) studied the plasma
levels of epinephrine, nor-epinephrine and dopamine in 33 patients with head
trauma and discovered that the levels of these indicators have reverse relation
with the level of consciousness and GCS of the patients and patients with lower
GCS had higher levels of these chemicals. Plasma catecholamine levels of patients
with very low GCS (Hamill et al., 1987; Koiv
et al., 1997) were 4 to 5 times more than normal people. They also
could predict the probability of recovery of patients measuring serum catecholamines
(Hamill et al., 1987). The relation between venous
epinephrine and norepinephrine levels in patients with head trauma with level
of consciousness were studied by Koiv et al. (1997)
and a reverse relation between serum epinephrine and norepinephrine levels with
GCS and consciousness levels was observed. They suggested that the evaluation
of these markers could be a useful method for early determination of prognosis
in patients with head trauma (Koiv et al., 1997).
In other studies, Clifton et al. (1981) and Woolf
et al. (1991) reported similar results. On the other hand, rapid
metabolism of epinephrine and norepinephrine, their very low concentrations
in plasma and also changes in their serum levels in different hours of day can
lower the validity and prognostic accuracy of measuring these chemicals in plasma.
Rapid catabolism of these materials and their turning into more stable metabolites
urges measuring the materials resulting from their catabolism (i.e. metanephrine,
nor-metanephrine and VMA) rather than direct measurement of epinephrine and
norepinephrine (Burtis et al., 2005; Defour
et al., 2001). Based on these facts and as the studies on plasma
catecholamine levels in patients with head trauma are not recent, we were to
study the probable relation between urine catecholamine metabolites levels 24
h after severe head trauma with patients' GCS in different stages, GOS and final
outcome of the patients. There was no meaningful relation between urine levels
of these metabolites and level of consciousness or final outcome of the patients.
A similar study has been carried out in this regard: Kearney
et al. (1992) studied 36 patients with severe head trauma (26 blunt
and 10 penetrating traumas, all having GCS lower than 9). Twenty four hour urine
metabolites after admission such as VMA, metanephrine and nor-metanephrine were
measured in this study. Half of the patients expired during the study. Five
candidates for elective neurosurgery were selected as the controls. There was
no meaningful relation between levels of catecholamine metabolites in urine
and patients' outcome. However, the levels of these chemicals were meaningfully
higher in patients with severe head trauma than the control group. As it is
seen, the results of our study are in accordance with this study. Feldman
et al. (1993) in a study carried out on 15 patients with severe head
trauma, showed that urine levels of catecholamine metabolites increase gradually
and reach their maximum level on day 7 to 10. Therefore, it is suggested that
urine levels of these metabolites can be measured in this period and their relation
with patient outcome can be evaluated.
There was no meaningful statistical relation between urine catecholamine levels (metanephrine and normetanephrine) in first 24 h of hospitalization and GCS at admission time and 24 and 48 h and 1 week after admission and GOS at discharge time. There was no meaningful statistical relation between level of catecholamine metabolites in urine and outcome in patients with severe head trauma. Based on the current study, measuring urine catecholamine metabolites 24 h after admission in patients with severe head trauma cannot predict their prognoses therefore is not suggested. Further studies in this regard on patients with different degrees of head trauma and are required. In future studies, urine metabolite levels should be measured continuously in hospitalization period until discharge or expiration of the patients.
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