Why is hyperglycemia allowed to increase slightly in acute stroke management?

Why Hyperglycemia is Allowed to Increase Slightly in Acute Stroke Management

In acute stroke management, blood glucose is allowed to remain moderately elevated (140-180 mg/dL) rather than aggressively normalized because there is no clinical evidence that targeting lower glucose levels improves outcomes, while aggressive correction significantly increases the risk of hypoglycemia, which can cause additional brain damage and requires intensive monitoring resources. 1

The Evidence Against Aggressive Glucose Lowering

Lack of Proven Benefit from Tight Control

• The only large randomized trial (GIST-UK) testing hyperglycemia treatment in acute stroke showed no difference in clinical outcomes between insulin-treated and control groups, though the trial was underpowered and stopped early 1
• There is currently no clinical evidence that targeting blood glucose to a particular level during acute ischemic stroke will improve outcomes 1
• The SHINE trial analyzing intensive glucose control (80-130 mg/dL) versus standard treatment (140-180 mg/dL) in patients undergoing endovascular treatment found no beneficial effect on death rates or favorable outcomes at 90 days 2

The Primary Risk: Hypoglycemia

• The main risk from aggressive hyperglycemia correction in acute stroke is hypoglycemia, which can cause permanent brain damage and worsen ischemic injury 1, 3
• Meta-analyses of intensive glucose control revealed increased rates of severe hypoglycemia (blood glucose <40 mg/dL) and mortality in tightly controlled cohorts compared to moderate control 1, 4
• Avoidance of hypoglycemia requires frequent glucose monitoring (every 1-2 hours), and in many hospitals this necessitates ICU admission, which may otherwise not be needed 1

The Recommended Target Range: 140-180 mg/dL

Why This Range Was Chosen

• It is reasonable to follow the American Diabetes Association recommendation to maintain blood glucose in a range of 140 to 180 mg/dL in all hospitalized patients with acute stroke 1
• This target balances the known association between hyperglycemia and poor outcomes against the proven risks of hypoglycemia from aggressive treatment 1, 4
• Insulin therapy should be initiated for persistent hyperglycemia starting at a threshold of 180 mg/dL, with a target range of 140-180 mg/dL for critically ill patients 1, 4

Resource and Safety Considerations

• Subcutaneous insulin protocols can safely lower and maintain blood glucose levels below 180 mg/dL in acute stroke patients without excessive use of healthcare resources 1
• The 140-180 mg/dL range can be achieved with standard nursing care and monitoring protocols, avoiding the need for intensive care unit admission solely for glucose management 1

The Association Between Hyperglycemia and Poor Outcomes

Observational Evidence

• Multiple observational studies consistently found an association between acute stroke hyperglycemia and worse outcomes, including increased infarct volume on MRI and higher mortality 1
• Among stroke patients treated with intravenous rtPA, hyperglycemia has been associated with symptomatic intracranial hemorrhage and worse clinical outcomes 1
• Admission hyperglycemia was present in 40% of acute stroke patients and independently increased the risk for death at 30 days (HR 1.87), 1 year (HR 1.75), and 6 years (HR 1.41) 5

Why Correlation Doesn't Prove Causation

• It cannot be determined whether this is a cause-and-effect relationship based on observational studies alone 1
• Hyperglycemia may simply be a marker of stroke severity and physiological stress rather than a direct cause of poor outcomes 1, 6
• Blood glucose elevations during acute stroke are related in part to a nonfasting state and in part to a stress reaction with impaired glucose metabolism 1

Practical Implementation

When to Treat

• Treat hyperglycemia when blood glucose persistently exceeds 180 mg/dL 1, 4
• Hypoglycemia (blood glucose <60 mg/dL) should be treated immediately in patients with acute ischemic stroke, with the goal to achieve normoglycemia 1

How to Treat

• For most patients, subcutaneous insulin protocols are sufficient and can safely maintain glucose levels in the 140-180 mg/dL range 1
• Patients who are critically ill, treated with thrombolytic therapy, or have extreme hyperglycemia should receive intravenous insulin with frequent monitoring 7
• Monitor blood glucose every 1-2 hours initially when using intravenous insulin 1, 4

Common Pitfalls to Avoid

• Avoid targeting normoglycemia or glucose levels <140 mg/dL in the acute stroke setting, as this increases hypoglycemia risk without proven benefit 1
• Do not delay treatment of severe hyperglycemia (>180 mg/dL), as persistent hyperglycemia during the first 24 hours is associated with poor outcomes 1, 7
• Avoid using sliding scale insulin alone without basal insulin coverage, as this approach is ineffective for glycemic management 8
• Be particularly vigilant for hypoglycemia in patients with type 1 diabetes, hepatic or renal impairment, or those on complicated feeding regimens 7