Hyperglycemia In Head Trauma عامر التواتي

Hyperglycemia In Head Trauma

K.S.M. Sayim,* Amer Altwati,* Mohamed H. Abdel-Latif,* Omran M. Abdrahman,*

Abstract:

Background: Severe head injury is associated with a stress response that includes hyperglycemia.

Objectives: To investigate the relationship between serum blood glucose and the severity of injury in patients suffering from closed head injury. Setting: The 2^nd March Teaching Hospital, Sebha, South Libya.

Materials and Methods: we reviewed the clinical course. Glasgow Coma Scale (GCS) and Injury Severity Score (ISS) and the Blood Glucose Level (BGL) of 297 consecutive head injured-patients. The patients were divided into two groups; group I (96 died patients) and group II (201 good outcome patients).

Results: We found that the major cause of traumatic brain injury was road traffic accidents (RTA). The admission blood glucose level in the fatal group was greater than in the good outcome group. Only 8.3 % of critical patients had euglycemia and 45% of good outcome patients had a normal BGLs. Euglycemia (4.2-6.4 mmol/L) was found in 33% of the patients. There was no significant difference between the admission BGL and that of 24 hours post-injury (P< 0.945 by paired t test). Blood glucose and ISS were significantly correlated only in good outcome patients. On the other hand, good outcome patients had a GCS, which was inversely correlated with blood glucose and the opposite was true in died patients.

Conclusion: Hyperglycemia is very common in sever TBI but has no effect in predicting the severity of brain injury. Nutrition and insulin therapy should be used in the treatment of patients with hyperglycemia to decrease its effect on traumatic brain in order to improve the prognosis.

Introduction:

Severe head injury is associated with a stress response that includes hyperglycemia. This has been shown in both experimental¹ and clinical studies.^2,3,4,5 Hyperglycemia exacerbates the severity of brain injury during ischemic condition.⁶ Patients with closed head injury were found to be hyperglycemic, with the highest levels of glucose concentration occurring on the day of injury.⁷ Previous studies showed that patients (adults or children) presented with hyperglycemia had poor prognosis.^3,4,8,9,10

The aim of this study is to examine the effect of severity of head trauma on blood glucose in a series of patients died as a result of head injury and to compare them with those who had been discharged with good outcome.

Materials and Methods:

Consecutive patients with head injury admitted by the trauma service at The Second March Teaching Hospital during the period 1998-1999. There were 297 patients eligible for this study. Most of these patients were transferred from other hospitals. Diabetic traumatized patients were excluded. Routine venous blood sample were taken on admission for serum electrolytes, urea and blood sugar level (BGL). Fasting early morning peripheral venous blood was drawn 24 hours post injury for serum glucose, urea and electrolytes.

Glucose was determined by glucose oxidase methodology. Admission Glasgow Coma Scale (GCS) and Injury Severity Score (ISS) were determined according to the 1985 version of the Abbreviated Injury Score (AIS).

Information include age, sex, cause of head injury, cranial and extracranial injuries and the fate of these patients were stored in personal computer.

Patients were divided into two major catego-ries, those with fatal head injury (Group I) and those with non-fatal head injury (Group II).

Clinical and blood values are presented as mean± standard deviation.

Relationships between variables were analyzed using multiple linear regression. Correlation and Pearson coefficients were calculated for relationships involving ISS and GCS as variables¹ (Packages Statistica Ver. 4.5).

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Results:

The major causes of traumatic brain injury were road traffic accidents (RTA), falls, assaults and trauma by hard object, Table 1. Euglycemia (4.2-6.4 mmol/L) were found in 33% of the patients. Only 8.3 % of critical patients had euglycemia and 45% of good outcome patients had a normal BGLs.

Group I includes ninety-six patients with fatal head injuries (68 males and 28 females) were studied, with ages ranging from 1.5 to 78 years (Table2), ISS 14 to 75, GCS 3 to 15 and blood glucose 4.3 to 42 mmo/L (Table 2). Fifty-six patients in the fatal group were first studied within 1hour of injury and after 24 hours post-injury. There was no significant difference between the admission BGL and that of 24 hours post-injury (P< 0.945 by paired t test), (Table 3).

The Severity of the trauma among the critical patients and good outcome groups were shown in Table 4 and 5. Head injuries were more severe in the fatal group. Table 5 showed a comparison between the two groups in regards to age groups, BGL, GCS, and ISS.

Two hundred-one patients (Group II) had been admitted after blunt trauma with good outcome (Group II). Their ages were ranging from 2 to 80 years, their ISS less than 16 and GCS 12 to 15.

The admission blood glucose level in the fatal group was greater than in the good outcome group, and there was a high correlation between GCS and ISS as represented by the regression equation: blood glucose (BGL) = 10.32-0.02 Age + 0.105 GCS + 0.095 ISS (P<0.24), r² = 0.038. However, in the good outcome group there was a significant correlation between ISS and blood glucose: BGL= 9.08-0.02 Age-0.17 GCS+ 0.252 ISS, r² =0.15, P<0.00001. The Correlation between BGL and ISS was stronger in the good outcome group than that of the fatal group. On the other hand, there was an inverse relationship between GCS and BGL among patients with good outcome, but the opposite was true in the fatal group. There was 44 patients in the good outcome group having GCS between 3 and 8 and their BGL was 10± 3.4 mmol/L, while 82 patients with the same severity in the fatal out come group had BGL of 13.3 ± 7.6 mmol/L, Table 6.

The age had no effect on BGL in both good outcome and fatal groups.

Tablet :Cause of Trauma

Road Traffic Accidents (RTA)	209 patients (70%)
Falls (FFH)	55 patients (19%)
Assault	26 patients (9%)
Trauma by Hard Object (THO)	7 Patients (2%)

Table 2: Clinical and blood glucose values.

	Group 1 (n=96)	Group II (n-201)
Patient age (years)	31±21 (range 1.5-78)	24.4±15(range 2-80)
Injury Severity Score (ISS)	37±11 (range 14-75)	11±4.4 (range 1-16)
Glasgow Coma Scale (GCS)	6±3 (range 3-15)	11±2.1 (range 12-15)
Blood Glusose (mmol/L)(admission) (BGL)	14±8.6 (range 4.3-42)	8±4.3 (range 1.6-36.3)

                                                                                                

Table 3: Blood Glucose Level in 56 patients of fatal group

Blood glucose admission	Blood glucose 24 hours post-injury
12.87 mmol/L ±6.09	12.96 mmol/L ±7.46

Table 4: The severity of trauma in Group I (Fatal outcome)

and Group II (Good outcome)

	AIS1		AIS2		AIS3		AIS4		AIS5
	G1	G2	G1	G2	G1	G2	G1	G2	G1	G2
Head/Neck	8	102	3	50	12	65	10		108
Face	9	94	26	47	7	1	5
Thorax	3	62	4	9	10	4	11		7
Abdomen	3	36	2	7		9			11
Extremitie		68	34	65	23	19	8	3	1
External	7	41	93	151

Table 5: The BGLs, GCSs and ISS of the Good outcome group  2 (n=201) and Fatal group 1.

Age group	No. pf Patients		Mean BGL		Mean GCS		Mean ISS
	G II	G1	G II	G1	G II	G1	G II	G1
1-5	12	9	10±4	14±3	10±3	3±4	14±5	29±11
6-10	28	7	8±3	17±8	11±3	5±4	11±5	33±11
11-15	18	9	9±4	9±3	11±3	5±2	11±8	33±6
16-20	37	7	10±7	13±7	11±2	3±2	12±5	33±8
21-25	37	12	7±3	14±10	11±3	5±3	10±6	33±8
26-30	20	12	7±2	13±9	12±2	5±4	11±4	33±9
31-35	8	8	8±4	9±4	11±4	4±2	11±4	31±6
36-40	11	2	6±2	12±7	11±2	8±7	12±7	41±2
41-45	5	5	9±7	14±4	13±2	10±5	7±6	50±23
46-50	9	6	7±2	13±4	13±2	9±5	8±4	48±15
51-55	5	3	6±2	25±10	12±3	5±2	9±5	38±12
56-60	4	6	13±8	10±6	12±3	4±2	11±7	34±9
61-65	5	4	8±2	11±4	12±2	7±4	12±4	42±9
66-70	1	3	6	6±5	12	5±2	12	33±8
71-75	1	2	6	25±21	12	3	8	31±3
76-80	0	1	0	18	0	7	0	38

Table 6: The mean BGL in patients with GCS 8 or less in the 2 Groups

	No. of patients	BGL in mmol/L
Good outcome group	47	10 ± 3.4
Fatal outcome group	82	13.3 ± 7.6

Discussion:

Traumatic brain injury affecting the younger and active age groups is the result of road traffic accidents. These crash injuries are usually associated with multiple body injuries, which may increase the severity of the brain injury.

In this study head injury was more severe in the fatal group. Much of the acute mortality and ultimate damage occurring after TBI results from a chain reaction of biochemical and physiologic events set in motion by the injury, which continue for hours and days. Although many mechanisms appear to be involved, many potential ischaemic insults result from changes in readily observable physiologic variables.⁶

Traumatic brain injury is associated with stress response that includes hyperglycemia, which has been shown to worsen neurological outcome during cerebral ischaemia and hypoxia.⁴

The regulation of blood glucose is generally stated to be under the control of the endocrine system. But the endocrine secretion is itself regulated by the central nervous system, especially the hypothalamus. The brain can sense the energy status of the body by using neural afferent signals and metabolic cues such as glucose. A variety of experimental evidences have been put forth to support the postulate that there are "glucoreceptors", sensitive to blood glucose and glucose utilization, in the hypothalamus.¹¹  

After TBI the there is autonomic and endocrine alterations. These include an increase in catecholamines; steroids; insulin; and glucagons.¹²

In the acute phase of severe head injury, many investigators found that there is an elevation of serum levels of catecholamines.^{8,13,14,15,16} The arterial level ofepinephrine was higher on post- injury day 3 and day 4 and norepinephrine was higher on days 3,4 and 5 in head injured patients. Both hormones tend to peak on day 3 or 4 after head injury. Furthermore, Yang, et al. (1995)⁸ found that the serum catecholamines was significantly higher in injured group than the controls. The serum NE and E levels were higher in patients with lower GCS and those who did not survive. Elevated plasma and CSF levels were observed in only %50 of the entire sample examined by Mautes et al (2001).¹³ These investigators found no correlation between GCS and the level of norepinephrine in CSF or plasma.

Cortiso is a common component of the stress response.^17,18 These hormones are significant indicators of severity and significant predictor of outcome. Glucagon and insulin levels increase as they do after extracranial injuries.^12,16,19,20

However, growth hormone changes seem to follow a pattern specific to head trauma.²¹  Calogero, Norton and Shepared (1992)²² showed a pulsatile elevation of the hypothamic- pitutary- adrenal axis during major surgery. However, patients with head injury exhibit lower plasma level of growth hormone, prolactine (PRL) and thyroid stimulating hormone (TSH) compared to patients without head injury. The decreased pituitary activity is probably secondary to hypothalamic dysfunction.²³

Stress hormones are known to enhance gluconeogenesis. Increase glucose production by this rout is modulated by elevation of catecholamines and glucagon, while adrenaline is rapidly increased, increments of glucagon have been shown to be slower. So glucose production is initiated by the former and maintained by both hormones. Glucocorticoides have also a gluconeogenic effect and act permissively with glucagon and adrenaline.²⁴

Kinoshita and his group (2002) studied the effect of posttraumatic hyperglycemia on contusion volume and neutrophil accumulation after experimental brain concussion. They found that hyperglycemia aggravates histopathological outcome and increase accumulation of PMNLs. Accordingly, acute hyperglycemia may worsen traumatic outcome by enhancing secondary injury processes, including inflammation. This inflammatory response may be due to the release of cytokines IL-1 and TNF alpha.

The local injury stimulates an inflammatory reaction that causes edema and depression of local metabolism (ebb phase). It has been shown that patients with severe head injury have a disruption in metabolic homeostasis that include increased energy expenditure and increased protein catabolism. These changes have been suggested to steroid administration, immobility and other factors.²⁵ This initial "ebb" phase is marked by diminished cardiac output, oxygen consumption, and body temperature i.e. heightened sympathetic activity. This autonomic hyperactivity found in severe closed head injury, usually associated with a decorticate state and wide spread axonal injury in the white matter. The proposed mechanism is a release of the hypothalamus from the inhibitory control of the cerebral Cortex.^1,8

Under the influence of circulating catecholamines and glucocorticoids primarily and in the setting of inhibited insulin secretion, lipolysis is activated.^26,27 The purpose is to supply endogenous substrates essential for survival and healing, glucose for wound repair and CNS function and keton bodies for cardiac, respiratory and skeletal muscle in absence of food.⁷ On the other hand hyperglycemia, at least theoretically, aggravates ischaemic brain damage by exaggerating intracellular acidosis, which enhance iron catalyzed free radical reactions. Furthermore hyperglycemia may lead to delayed damage because it enhances post-ischaemic acidosis.²⁸

Hyperglycemia is a frequent component of stress response to head injury, a significant indicator of severity of injury and a potent predictor of the outcome from head injury.^3,4 Similar to our finding, Yang, et al. (1995)⁸ found that 95% of patients with high blood glucose at admission died early.

Rovlias and Kotsou (2000)⁴ found a significant relationship between postoperative glucose level, papillary reaction, and maximum intracranial pressure during the first 24 hours. The prognostic potential of initial plasma glucose level may be beneficial in the management of severe head injury. (Alberty et al 2000).

Although age is a major independent factor affecting the mortality rate in head- injured patients,²⁹ our study showed that age had no effect on BGL in both good outcome and fatal groups. Age is not independently related to mortality. On the contrary, Jeremitsky et al (2003)² found that a higher hyperglycemia was associated with age. However, hyperglycemia and azotemia were common in elderly trauma patients studied by Frankfield et al (2000).

Glasgow Coma Scale (GCS) is the most widely used parameter for evaluating brain injury severity.³⁰ Although far from perfect, it has proved to be valuable in evaluating the prognosis of neurosurgical patients.³¹ In this study, blood glucose and ISS were significantly correlated only in good outcome patients. However, ISS alone may not adequately emphasize the importance of head injury in multiple injury patients. By combining ISS and GCS at 6 hours post-injury, physicians may then have the best available indicator of survival and functional outcome.³² On the other hand, GCS,ISS and age are not independently related to mortality.²

Margulies et al (1994)⁹ found that the peak glucose value was inversely related to GCS. They concluded that GCS and Simplified Acute Physiology Score (SAPS) have a powerful predicting power and hyperglycemia has not such power. Lam et al (1991)¹⁰ found that patients with lower GCS scores had higher serum glucose concentrations, and patients who remained in a persistent vegetative state or died had significantly higher glucose concentrations than those patients with good outcome. Recently, Geremitsky and his group (2003) studied 11 secondary brain injury factors as harbingers of poor outcome the day after severe brain injury. They found that hyperglycemia, hypotension and hypothermia were associated with increased mortality rate. Also hyperglycemia, episodes of hypocapnia, acidosis and hypoxia were related to length of hospital stay (LOS).²

Glucose and osmolality has been used as predictors of injury severity, (Kenny, Allen-Rowlands and Gann 1983). Inspite of these, many investigators have pursued the question of accurate prediction of outcome. Their results show that no single set of indications has been uniformly demonstrated to be useful in predicting patient outcome. However, this cannot explain those who died with euglycemia in our study. We can say that not all patients respond to head trauma have these metabolic changes.

Conclusion: 

Hyperglycemia is very common in sever TBI but has no effect in predicting the severity of brain injury. Nutrition and insulin therapy should be used in the treatment of patients with hyperglycemia to decrease its effect on traumatic brain in order to improve the prognosis.

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