CLINICAL SIGNIFICANCE OF ACUTE PHASE HYPERGLYCEMIA IN PATIENTS WITH SEVERE HEAD INJURY
作者：ZHANG Sai(张赛), YANG Shu-yuan(杨树源), WANG Ming-lu(王明璐)
单位：Department of Neurosurgery, ZHANG Sai(张赛), YANG Shu-yuan(杨树源), WANG Ming-lu(王明璐) Tianjin Neurological Center Hospital 300060
关键词：
CLINICAL SIGNIFICANCE OF ACUTE PHASE HYPERGLYCEMIA IN PATIENTS WITH SEVERE HEAD INJURY
Objective To study the relationship between severity and neurological outcome of severe head injury and hypergly-cemia.
, 百拇医药
Methods The acute phase serum glucose level was measured in 59 adult patients with severe head injury (GCS≤8) within 6 hours after injury. The relationship between the neurological outcome, Glasgow Coma Scale (GCS) scores and serum glucose level were assessed by statistical analysis.
Results The acute phase serum glucose level was significantly higher in the patients than the normal value (P<0.05). The patients with GCS score of 3-4, 5-6 and 7-8 had mean acute phase serum glucose level of 12.32±3.15, 9.08±2.98 and 6.24±1.07 mmol/L, respectively. The acute phase serum glucose level was correlated with neurological outcome of these patients (P<0.01). The patients in the 3 groups of the dead, poor recovery and good recovery within the first month after injury had mean acute phase serum glucose levels of 12.36±3.34, 8,39±1.79 and 6.11±1.01 mmol/L, respectively. The patients with acute phase serum glucose level ≥10 mmol/L had significantly higher mortality during the first month postinjury (P<0.001).
, 百拇医药
Conclusion The acute phase hyperglycemia is a frequent component of the stress response to severe head injury, a significant indicator of severity and a significant predictor of prognosis for severe head injury.
Severe head injury is associated with a stress response that includes hyperglycemia, which has been shown to worsen outcome after injury. In order to study the relationship between severe head injury and hyperglycemia, acute phase serum glucose level was measured in 59 adult patients with severe head injury within 6 hours after injury. It was found that there was a significant relationship between hyperglycemia and severity and neurological outcome of severe head injury.
, 百拇医药
MATERIALS AND METHODS
Fifty-nine patients, 46 male and 13 female, aging 16 to 73 (mean 39±15) had Glasgow Coma Scale (GCS) score ≤8 on admission within 6 hours after injury. No patients received corticosteroides or intravenous glucose solutions after injury and before admission. The patients with history of diabetes, long-bone fractures and chest/abdominal injury were excluded. Ninety-five percent of the patients had closed head injuries, including brain contusion and laceration (29%), diffuse axonal injury (17%), subdural hematoma (24%), extradural hematoma (13%), intracerebral hematoma (12%), and 5% of the patients had open head injuries. Surgical intervention was performed in 49 cases and conservative treatment in 10 cases. All the patients were classified into three groups according to GCS scores of 3-4,5-6 and 7-8 on admission. Outcome was judged by Glasgow Outcome Scale (GOS) at one month after injury: good recovery (good recovery and moderate disability of GOS), poor recovery (severe disability and persistent vegetative of GOS) and death. Serum glucose levels were obtained on admission to hospital.
, 百拇医药
Serum glucose levels on admission in patients with GCS scores of 3-4 were compared with those in patients with GCS scores of 5-6 and 7-8, respectively, using an unpaired t-test. Serum glucose levels on acute phase in patients with a good recovery were compared with those of patients with a poor recovery and death respectively using an unpaired t-test. Chi-square analysis was used to examine the neurological outcome (good/poor recovery vs. death) of the patients whose serum glucose level was less than 10 mmol/L as compared to the patients with a glucose value greater than 10 mmol/L. Relationships between the outcome, GCS score, and serum glucose levels were assessed with multiple linear regression analysis. A p value <0.05 is considered to be significant.
, 百拇医药
RESULTS
Of the studied patients, 24 cases (41%) died, 16 cases (27%) were in poor recovery, and 19 cases (32%) in good recovery during the first month after injury.
Acute phase serum glucose levels were significantly higher in the 59 patients (7.3～11.4 mmol/L, 95%Cl) than the normal value (P<0.05). The patients with GCS score of 3-4 had significantly higher acute phase serum glucose levels than that in the patients with GCS score of 5-6 and 7-8, respectively, (P<0.01, Table 1). The lower the GCS score, the higher the serum glucose level (P<0.001).
, 百拇医药
Table 1 Acute phase serum glucose level versus GCS score
GCS score
n
Serum glucose (
±s)
P
3～4
21
12.32±3.15
<0.01
, 百拇医药
5～6
18
9.08±2.98
<0.01
7～8
20
6.24±1.07
Table 2 and Fig 1 show that the comparison of patients in good recovery with patients in poor recovery or death demonstrated a significant difference on acute phase serum glucose levels (P<0.001). The higher the acute phase serum glucose levels, the poorer the outcome. The patients with acute phase serum glucose levels >10 mmol/L were associated with poor outcome (P<0.001, Fig 2). Nineteen of the 23 patients with acute phase serum glucose levels ≥10 mmol/L died in the first month after injury. The acute phase serum glucose level >10 mmol/L was evaluated as a prognostic test for neurological outcome (survival vs. death), which yielded a sensitivity of 79.1%, a specificity of 88.6%, a positive predictive value of 67.9%, and a negative predictive value of 77.6%. To assess the independent influence of acute phase serum glucose levels and GCS score on outcome, multiple linear regression analysis was used with both parameters as independent variables. It yielded the following relationship: GOS=3.59-0.36 (GCS score) + 0.054 (glucose level), with P<0.001 for both GCS score and serum glucose level. Table 2 Comparison of acute phase serum glucose level (mmol/L) in different outcome groups
, 百拇医药
Group
n
Serum glucose (±s)
P
Good
19
6.11±1.01
<0.01
Poor
16
, 百拇医药
8.39±1.79
<0.01
Death
24
12.36±3.34
Fig 1 Serum glucose levels in patients with good, poor and dead outcome.
, http://www.100md.com
Fig 2 Patients' outcome and the serum glucose level.
DISCUSSION
Our study demonstrated that hyperglycemia was frequently present in severely head-injured patients and the presence of hyperglycemia correlated with the severity of the initial injury. The results were similar to those of Lam et al.3. There is a considerable body of evidence from human and animal studies to show that hyperglycemia and increased blood catecholamins are causally related.1，2 The mechanism of acute phase hyperglycemia may be resulted from sympathetic system activation after severe head injury. Catecholamines increase glucagon secretion and inhibit insulin secretion. Glucagon stimulates the breakdown of glycogen stored in the liver into glucose. In addition, decreased glucose utilization associated with increased cortisol secretion by the adrenalglands, increased growth hormone leading to increased lipolysis, and insulin antagonism secondary to increased catecholamine levels, all of these may lead to hyperglycemia following head injury.1～3 In the present study, we have observed relationships between acute phase serum glucose levels and neurological outcome. The dead patients exhibited a significantly higher serum glucose value than the survival. Lam et al.3 have demonstrated that if the patients showed GCS score of 8 or less during 10 days after injury, their neurological outcome was as follows: GOS score=4.36-0.4 (GCS score )+0.004 (glucose level) with P<0.01. He suggested that the criterion of acute phase serum glucose level greater than 11.1mmol/L should act as a prognostic test for poor neurological outcome in patients with GCS score ≤8. Michaud et al.4 based on the study of children with head injury suggested a simple prognostic score: GCS score minus 2 if the acute phase blood glucose level is ≥ 13.8 mmol/L or GCS score minus 0 if it is <13.8 mmol/L.
, 百拇医药
Acute phase serum glucose level is a significant predictor of outcome for head injury because serum glucose levels correlate significantly with the severity of the brain injury and hyperglycemia may aggravate neurological outcome in severe head injury. It is generally agreed that an abundant supply of glucose substrate during hypoxemia condition in the patients with severe head injury allows continuation of anaerobic metabolism with accumulation of lactate and hydrogen ions. The resultant intracellular acidosis triggers a cascade that may involve activation of calcium influx into the cells, lipolysis, release of cytotoxic fatty acids and the glutamates, and eventual destruction of neurons.3，5～7 De Salles et al.8，9 found that increased lactate concentration in ventricular fluid was associated with hyperglycemia after severe head injury. Rosner et al.2 showed in acute head injury model that THAM infusion, which counters lactic acidosis, improved survival and morbidity. Some investigators1，3，4 have observed that treatment of hyperglycemia may improve neurological outcome. The routine use of dextrose infusions should be avoided and Lactated Ringers may be used following head trauma. Treatment with insulin to control serum glucose levels, when it is over 11.1 mmol/L has been used in management of traumatic brain injury.
, http://www.100md.com
REFERENCES
[1] Young B, Ott L, Haack D, et al. Relationship between acute phase hyperglycemia and neurologic outcome of severely brain-injured patients. Ann Surg 1989; 210∶466.
[2]Rosner MJ, Newsome HH, Becker DP, et al. Mechanical brain injury: the sympathoadrenal response. J Neurosurg 1984; 61∶76.
[3] Lam AM, Winn HR, Cullen BF, et al. Hyperglycemia and neurological outcome in patients with head injury. J Neurosurg 1991; 75∶545.
, 百拇医药
[4] Michaud LJ, Rivara FP, Longstreth WT, et al. Elevated initial blood glucose level and poor outcome following severe brain injury in children. J Trauma 1991; 31∶1356.
[5] McClain C, Cohen D, Ott L, et al. Ventricular fluid interleukin-1 activity in head-injury patients. J Lab Clin Med 1987; 21∶443.
[6] Marsh WR, Anderson RE, Sundt TM. Effect of hyperglycemia on brain pH levels in areas of focal incomplete cerebral ischemia in monkeys . J Neurosurg 1986; 65∶693.
, 百拇医药
[7] Deloof T, Berre, J Genette F, et al. Disturbances of the carbohydrate metabolism in acute head trauma. Acta Neurochir 1979; 28∶113.
[8] DeSalles AA, Kontos HA, BEcker DP, et al. Prognostic Significance of ventricular CSF lactic acidosis in severe head injury. J Neurosurg 1986; 65∶615.
[9] Ljunggren B, Norberg K, Sieso BK. Influence of tissue acidosis upon restitution of brain energy metabolism following total ischemia. Brain Research 1974; 77∶173., 百拇医药
单位：Department of Neurosurgery, ZHANG Sai(张赛), YANG Shu-yuan(杨树源), WANG Ming-lu(王明璐) Tianjin Neurological Center Hospital 300060
关键词：
CLINICAL SIGNIFICANCE OF ACUTE PHASE HYPERGLYCEMIA IN PATIENTS WITH SEVERE HEAD INJURY
Objective To study the relationship between severity and neurological outcome of severe head injury and hypergly-cemia.
, 百拇医药
Methods The acute phase serum glucose level was measured in 59 adult patients with severe head injury (GCS≤8) within 6 hours after injury. The relationship between the neurological outcome, Glasgow Coma Scale (GCS) scores and serum glucose level were assessed by statistical analysis.
Results The acute phase serum glucose level was significantly higher in the patients than the normal value (P<0.05). The patients with GCS score of 3-4, 5-6 and 7-8 had mean acute phase serum glucose level of 12.32±3.15, 9.08±2.98 and 6.24±1.07 mmol/L, respectively. The acute phase serum glucose level was correlated with neurological outcome of these patients (P<0.01). The patients in the 3 groups of the dead, poor recovery and good recovery within the first month after injury had mean acute phase serum glucose levels of 12.36±3.34, 8,39±1.79 and 6.11±1.01 mmol/L, respectively. The patients with acute phase serum glucose level ≥10 mmol/L had significantly higher mortality during the first month postinjury (P<0.001).
, 百拇医药
Conclusion The acute phase hyperglycemia is a frequent component of the stress response to severe head injury, a significant indicator of severity and a significant predictor of prognosis for severe head injury.
Severe head injury is associated with a stress response that includes hyperglycemia, which has been shown to worsen outcome after injury. In order to study the relationship between severe head injury and hyperglycemia, acute phase serum glucose level was measured in 59 adult patients with severe head injury within 6 hours after injury. It was found that there was a significant relationship between hyperglycemia and severity and neurological outcome of severe head injury.
, 百拇医药
MATERIALS AND METHODS
Fifty-nine patients, 46 male and 13 female, aging 16 to 73 (mean 39±15) had Glasgow Coma Scale (GCS) score ≤8 on admission within 6 hours after injury. No patients received corticosteroides or intravenous glucose solutions after injury and before admission. The patients with history of diabetes, long-bone fractures and chest/abdominal injury were excluded. Ninety-five percent of the patients had closed head injuries, including brain contusion and laceration (29%), diffuse axonal injury (17%), subdural hematoma (24%), extradural hematoma (13%), intracerebral hematoma (12%), and 5% of the patients had open head injuries. Surgical intervention was performed in 49 cases and conservative treatment in 10 cases. All the patients were classified into three groups according to GCS scores of 3-4,5-6 and 7-8 on admission. Outcome was judged by Glasgow Outcome Scale (GOS) at one month after injury: good recovery (good recovery and moderate disability of GOS), poor recovery (severe disability and persistent vegetative of GOS) and death. Serum glucose levels were obtained on admission to hospital.
, 百拇医药
Serum glucose levels on admission in patients with GCS scores of 3-4 were compared with those in patients with GCS scores of 5-6 and 7-8, respectively, using an unpaired t-test. Serum glucose levels on acute phase in patients with a good recovery were compared with those of patients with a poor recovery and death respectively using an unpaired t-test. Chi-square analysis was used to examine the neurological outcome (good/poor recovery vs. death) of the patients whose serum glucose level was less than 10 mmol/L as compared to the patients with a glucose value greater than 10 mmol/L. Relationships between the outcome, GCS score, and serum glucose levels were assessed with multiple linear regression analysis. A p value <0.05 is considered to be significant.
, 百拇医药
RESULTS
Of the studied patients, 24 cases (41%) died, 16 cases (27%) were in poor recovery, and 19 cases (32%) in good recovery during the first month after injury.
Acute phase serum glucose levels were significantly higher in the 59 patients (7.3～11.4 mmol/L, 95%Cl) than the normal value (P<0.05). The patients with GCS score of 3-4 had significantly higher acute phase serum glucose levels than that in the patients with GCS score of 5-6 and 7-8, respectively, (P<0.01, Table 1). The lower the GCS score, the higher the serum glucose level (P<0.001).
, 百拇医药
Table 1 Acute phase serum glucose level versus GCS score
GCS score
n
Serum glucose (
±s)P
3～4
21
12.32±3.15
<0.01
, 百拇医药
5～6
18
9.08±2.98
<0.01
7～8
20
6.24±1.07
Table 2 and Fig 1 show that the comparison of patients in good recovery with patients in poor recovery or death demonstrated a significant difference on acute phase serum glucose levels (P<0.001). The higher the acute phase serum glucose levels, the poorer the outcome. The patients with acute phase serum glucose levels >10 mmol/L were associated with poor outcome (P<0.001, Fig 2). Nineteen of the 23 patients with acute phase serum glucose levels ≥10 mmol/L died in the first month after injury. The acute phase serum glucose level >10 mmol/L was evaluated as a prognostic test for neurological outcome (survival vs. death), which yielded a sensitivity of 79.1%, a specificity of 88.6%, a positive predictive value of 67.9%, and a negative predictive value of 77.6%. To assess the independent influence of acute phase serum glucose levels and GCS score on outcome, multiple linear regression analysis was used with both parameters as independent variables. It yielded the following relationship: GOS=3.59-0.36 (GCS score) + 0.054 (glucose level), with P<0.001 for both GCS score and serum glucose level. Table 2 Comparison of acute phase serum glucose level (mmol/L) in different outcome groups
, 百拇医药
Group
n
Serum glucose (
±s)P
Good
19
6.11±1.01
<0.01
Poor
16
, 百拇医药
8.39±1.79
<0.01
Death
24
12.36±3.34
Fig 1 Serum glucose levels in patients with good, poor and dead outcome.
, http://www.100md.com
Fig 2 Patients' outcome and the serum glucose level.
DISCUSSION
Our study demonstrated that hyperglycemia was frequently present in severely head-injured patients and the presence of hyperglycemia correlated with the severity of the initial injury. The results were similar to those of Lam et al.3. There is a considerable body of evidence from human and animal studies to show that hyperglycemia and increased blood catecholamins are causally related.1，2 The mechanism of acute phase hyperglycemia may be resulted from sympathetic system activation after severe head injury. Catecholamines increase glucagon secretion and inhibit insulin secretion. Glucagon stimulates the breakdown of glycogen stored in the liver into glucose. In addition, decreased glucose utilization associated with increased cortisol secretion by the adrenalglands, increased growth hormone leading to increased lipolysis, and insulin antagonism secondary to increased catecholamine levels, all of these may lead to hyperglycemia following head injury.1～3 In the present study, we have observed relationships between acute phase serum glucose levels and neurological outcome. The dead patients exhibited a significantly higher serum glucose value than the survival. Lam et al.3 have demonstrated that if the patients showed GCS score of 8 or less during 10 days after injury, their neurological outcome was as follows: GOS score=4.36-0.4 (GCS score )+0.004 (glucose level) with P<0.01. He suggested that the criterion of acute phase serum glucose level greater than 11.1mmol/L should act as a prognostic test for poor neurological outcome in patients with GCS score ≤8. Michaud et al.4 based on the study of children with head injury suggested a simple prognostic score: GCS score minus 2 if the acute phase blood glucose level is ≥ 13.8 mmol/L or GCS score minus 0 if it is <13.8 mmol/L.
, 百拇医药
Acute phase serum glucose level is a significant predictor of outcome for head injury because serum glucose levels correlate significantly with the severity of the brain injury and hyperglycemia may aggravate neurological outcome in severe head injury. It is generally agreed that an abundant supply of glucose substrate during hypoxemia condition in the patients with severe head injury allows continuation of anaerobic metabolism with accumulation of lactate and hydrogen ions. The resultant intracellular acidosis triggers a cascade that may involve activation of calcium influx into the cells, lipolysis, release of cytotoxic fatty acids and the glutamates, and eventual destruction of neurons.3，5～7 De Salles et al.8，9 found that increased lactate concentration in ventricular fluid was associated with hyperglycemia after severe head injury. Rosner et al.2 showed in acute head injury model that THAM infusion, which counters lactic acidosis, improved survival and morbidity. Some investigators1，3，4 have observed that treatment of hyperglycemia may improve neurological outcome. The routine use of dextrose infusions should be avoided and Lactated Ringers may be used following head trauma. Treatment with insulin to control serum glucose levels, when it is over 11.1 mmol/L has been used in management of traumatic brain injury.
, http://www.100md.com
REFERENCES
[1] Young B, Ott L, Haack D, et al. Relationship between acute phase hyperglycemia and neurologic outcome of severely brain-injured patients. Ann Surg 1989; 210∶466.
[2]Rosner MJ, Newsome HH, Becker DP, et al. Mechanical brain injury: the sympathoadrenal response. J Neurosurg 1984; 61∶76.
[3] Lam AM, Winn HR, Cullen BF, et al. Hyperglycemia and neurological outcome in patients with head injury. J Neurosurg 1991; 75∶545.
, 百拇医药
[4] Michaud LJ, Rivara FP, Longstreth WT, et al. Elevated initial blood glucose level and poor outcome following severe brain injury in children. J Trauma 1991; 31∶1356.
[5] McClain C, Cohen D, Ott L, et al. Ventricular fluid interleukin-1 activity in head-injury patients. J Lab Clin Med 1987; 21∶443.
[6] Marsh WR, Anderson RE, Sundt TM. Effect of hyperglycemia on brain pH levels in areas of focal incomplete cerebral ischemia in monkeys . J Neurosurg 1986; 65∶693.
, 百拇医药
[7] Deloof T, Berre, J Genette F, et al. Disturbances of the carbohydrate metabolism in acute head trauma. Acta Neurochir 1979; 28∶113.
[8] DeSalles AA, Kontos HA, BEcker DP, et al. Prognostic Significance of ventricular CSF lactic acidosis in severe head injury. J Neurosurg 1986; 65∶615.
[9] Ljunggren B, Norberg K, Sieso BK. Influence of tissue acidosis upon restitution of brain energy metabolism following total ischemia. Brain Research 1974; 77∶173., 百拇医药