What blood glucose level can cause brain injury?

Blood Glucose Thresholds for Brain Injury

Both severe hypoglycemia (≤40 mg/dL or 2.2 mmol/L) and severe hyperglycemia (≥200 mg/dL or 11.1 mmol/L) can cause brain injury, with hypoglycemia posing immediate risk of permanent neurological damage and hyperglycemia worsening outcomes in acute brain injury. 1

Hypoglycemic Thresholds That Cause Brain Injury

Critical Danger Zone

• Severe hypoglycemia at ≤40 mg/dL (2.2 mmol/L) is independently associated with increased mortality and can cause permanent brain injury or death 1
• Symptoms typically develop when blood glucose falls below 50-60 mg/dL (2.8-3.3 mmol/L), including confusion, slurred speech, and altered consciousness 1
• Untreated severe hypoglycemia can lead to seizures, status epilepticus, unconsciousness, permanent cognitive dysfunction, and death 1, 2

Moderate Hypoglycemia Risk

• Blood glucose ≤70 mg/dL is associated with increased mortality in critically ill patients 1
• In brain-injured patients, even brief episodes of severe hypoglycemia carry greater risk than in patients with normal brains 1
• The injured brain is particularly vulnerable to glucose deficit because it has increased metabolic demands and limited ability to utilize alternative fuel sources 3

Special Considerations in Brain Injury

• In traumatic brain injury (TBI) patients, tight glycemic control (<6 mmol/L or 108 mg/dL) causes decreased interstitial brain glucose, triggering cerebral energy crisis with elevated lactate, glutamate, and lactate/pyruvate ratios 1, 4
• Strict glucose control (4.4-6.1 mmol/L or 80-110 mg/dL) in TBI patients resulted in increased cerebral metabolism markers of energy crisis compared to more liberal targets 1, 4

Hyperglycemic Thresholds That Cause Brain Injury

Severe Hyperglycemia

• Blood glucose ≥200 mg/dL (11.1 mmol/L) is associated with 3.6-fold increased risk of hospital mortality in severe TBI patients 5
• In brain-injured patients, peak admission glucose >200 mg/dL correlates with worse neurological outcomes at 18 days, 3 months, and 1 year post-injury 6
• Hyperglycemia ≥11.1 mmol/L is an independent risk factor for mortality, infection, and prolonged ICU stays in TBI patients 4

Moderate Hyperglycemia

• Treating moderate to severe hyperglycemia (>180-200 mg/dL or >10.0-11.1 mmol/L) is reasonable to improve outcomes in intracerebral hemorrhage 1
• In trauma patients, blood glucose ≥150 mg/dL should trigger insulin therapy initiation 1

Mechanisms of Hyperglycemic Brain Injury

• Hyperglycemia compromises microcirculatory blood flow, increases blood-brain barrier permeability, and promotes inflammation 3
• It triggers intracellular lactic acidosis, with hydrogen ions being directly injurious to neurons and glia 7
• Additional complications include osmotic diuresis, hypovolemia, and immunosuppression 3

Recommended Target Ranges by Clinical Context

Traumatic Brain Injury

• Target serum glucose between 8-10 mmol/L (144-180 mg/dL) for TBI patients 1, 4
• Maintain blood glucose absolutely <180 mg/dL using protocols that achieve low rates of hypoglycemia 1
• Seven randomized controlled trials found that strict glucose control did not improve neurological outcome or mortality in TBI but increased hypoglycemia risk 1

Intracerebral Hemorrhage

• Monitor serum glucose to reduce risk of both hyperglycemia and hypoglycemia 1
• Treat hypoglycemia <40-60 mg/dL (2.2-3.3 mmol/L) to reduce mortality 1
• Treat hyperglycemia >180-200 mg/dL (10.0-11.1 mmol/L) to improve outcomes 1

General Critical Care

• The NICE-SUGAR trial demonstrated that intensive glucose control (81-109 mg/dL) resulted in increased mortality compared to conventional control (<180 mg/dL) 1
• Severe hypoglycemic events (≤40 mg/dL) were significantly more common with intensive control (6.8% vs 0.5%) 1

Critical Pitfalls to Avoid

The U-Shaped Mortality Curve

• Both extreme hypoglycemia and hyperglycemia create a U-shaped mortality curve in brain-injured patients 1
• Overly aggressive glucose control attempting to achieve tight targets (80-110 mg/dL) increases hypoglycemia risk without improving outcomes 1

Regional vs. Systemic Glucose

• Tight systemic glycemic control can cause regional cerebral neuroglycopenia even when serum glucose appears adequate 1
• Cerebral microdialysis studies show that systemic glucose 80-110 mg/dL can be associated with critically low brain interstitial glucose 1

Monitoring Requirements

• Regular blood glucose monitoring from venous or arterial blood samples is essential in brain-injured patients 1, 4
• Use protocols that achieve low rates of hypoglycemia (≤70 mg/dL) rather than aggressive targets 1

Neonatal Considerations

• In neonates, severe (<36 mg/dL or 2 mmol/L) and recurrent hypoglycemia (3 or more episodes) can cause neurological injury and developmental delays 8
• Recent studies suggest neurological injury occurs with glucose <36 mg/dL (<2 mmol/L) in early school age and <30-36 mg/dL in mid-childhood 8