Intensive Versus Nonintensive Insulin Therapy for Hyperglycemia After Traumatic Brain Injury

Randomized Controlled Clinical Study of Intensive Versus Nonintensive Insulin Therapy for Hyperglycemia After Traumatic Brain Injury

An increase in blood glucose is a common clinical symptom in patients following traumatic brain injury. Studies confirm that death after traumatic brain injury was not only associated with nerve injury, but also correlated with abnormal physiological and metabolic reactions. Hyperglycemia is a manifestation of physiological and metabolic disorders after traumatic brain injury. Traumatic brain injury induced hyperglycemia, and then aggravated secondary injury to the brain. Therefore, it is of important clinical significance to study the treatment of hyperglycemia after traumatic brain injury.

Hyperglycemia induced by traumatic brain injury is directly correlated with patient prognosis. Previous studies showed that if blood glucose could be controlled < 6.11 mmol/L, prognosis would be good and mortality would be decreased by approximately 50%. Moreover, the incidence of ICU-related complications, especially infection, was obviously reduced. A study concerning severe traumatic brain injury analyzed the recovery of patients at 18 days, 3 months and 1 year after trauma, and demonstrated that the prognosis of patients with blood glucose levels < 11.1 mmol/L within 24 hours of hospital admission was apparently better than those whose blood glucose levels were > 11.1 mmol/L. Hyperglycemia occurred after traumatic brain injury and was treated with intensive insulin therapy. Thus, blood glucose levels were controlled between 4.4 and 6.1 mmol/L, which noticeably shortened insulin use and decreased the incidence of multiple organ dysfunction and mortality of patients with traumatic brain injury.

It is well known that hyperglycemia will appear after traumatic brain injury. However, there are few clinical studies addressing continuous dynamic monitoring of blood glucose of traumatic brain injury patients and the relationship between changes in blood glucose and the degree of traumatic brain injury. Insulin therapy for reducing injury to secondary nerve cells after traumatic brain injury and for improving functional prognosis has also not been explored.

When blood glucose level is > 7.0 mmol/L as measured twice by rapid examination within 2 hours of hospital admission, patients with hyperglycemia after severe closed traumatic brain injury will be randomly divided into the intensive therapy group and nonintensive therapy group according to the random number table.

Patients in both groups will be treated using the protocol as follows.

1. Craniotomy for traumatic brain injury to mainly decompress and remove hematoma. Standard trauma craniotomy and incision of trachea will be performed.
2. During the operation, all patients will undergo ventricular puncture. Cerebrospinal fluid will be obtained for biochemical analysis and cell culture.
3. All patients will be closely monitored in the ICU of the Department of Neurosurgery.
4. Therapeutic protocols for severe traumatic brain injury will be used.
5. Glucocorticoid can cause disorders of glucose metabolism, so glucocorticoids can not be regularly applied in these two groups.
6. When glucose was injected into the vein, insulin was added at the proportion of 5:1 to eliminate glucose effects on blood glucose.

Blood glucose measurement: Capillary blood will be obtained from the tip of the ring finger to measure blood glucose. For a period, the blood should be collected from the same finger to make sure an accurate measurement occurs. When blood glucose of a patient undergoing transfusion was measured, blood should be collected from the tip of the finger of the limb without transfusion to ensure the accuracy of measurement.

Monitoring of target blood glucose: insulin dose will be selected in accordance with the Yale Insulin Infusion Protocol.

1. Insulin will be infused into the vein using a micropump at 0.1 μ/kg•h;
2. When blood glucose levels are > 20.0 mmol/L, insulin will be infused at 10.0 μ/h;
3. When blood glucose levels are between 17.1 and 20.0 mmol/L, insulin will be infused at 8.0 μ/h;
4. When blood glucose levels are between 14.1 and 17.0 mmol/L, insulin will be infused at 6.0 μ/h;
5. When blood glucose levels are between 11.5 and 14.0 mmol/L, insulin will be infused at 4.0 μ/h;
6. Within 12 and 24 hours, blood glucose levels will be maintained within the range of target blood glucose. During this period, blood glucose levels will be monitored once every 2 hours, and insulin dose will be adjusted in time.
7. If blood glucose levels are higher than the target value, insulin dose could be gradually increased by 1-2 μ/h;
8. When blood glucose levels reach the target value, insulin dose could be gradually diminished until terminated.

Inclusion Criteria:

• Severe closed traumatic brain injury diagnosed in the clinic;
• Severe closed traumatic brain injury verified by CT examinations;
• Patients who are in accordance with the indications of craniotomy for severe traumatic brain injury;
• Blood glucose levels > 7.0 mmol/L measured twice by rapid examination within 2 hours of hospital admission;
• Glasgow coma score between 3 and 8;
• At the age of 18 - 80 years old;
• Irrespective of gender.

Exclusion Criteria:

• At the age of < 18 years old or > 80 years old;
• Glasgow coma score > 8;
• Patients combined with multiple site damage;
• Hemodialysis-dependent patients combined with diabetic nephropathy;
• Patients with nervous system disease before traumatic brain injury;
• Patients with a history of diabetes before suffering from a traumatic brain injury.