From the Guidelines
Hypoglycemia in a septic patient with altered mental status is most commonly caused by a combination of increased glucose utilization, decreased gluconeogenesis, inadequate nutritional intake, and medication effects, as evidenced by the high incidence of hypoglycemia in septic patients, particularly those with impaired mental state 1. The primary causes of hypoglycemia in these patients include:
- Increased glucose utilization due to the hypermetabolic state of sepsis
- Decreased gluconeogenesis from hepatic dysfunction
- Inadequate nutritional intake
- Medication effects, such as insulin, sulfonylureas, and certain antibiotics Sepsis creates a high-energy demand state where glucose consumption increases dramatically, especially in tissues fighting infection, as noted in the context of sepsis management in resource-limited settings 1. Simultaneously, the liver's ability to produce glucose through gluconeogenesis becomes impaired as sepsis progresses. Many septic patients experience poor oral intake or interruptions in enteral/parenteral nutrition, further contributing to the risk of hypoglycemia. Medications that commonly contribute to hypoglycemia include insulin (particularly if dosing isn't adjusted for decreased nutritional intake), sulfonylureas like glipizide or glyburide, and certain antibiotics like fluoroquinolones. Additionally, adrenal insufficiency secondary to sepsis can reduce cortisol levels, impairing the normal counterregulatory response to low blood glucose, and renal failure, which often accompanies severe sepsis, can prolong the half-life of insulin and other hypoglycemic agents, as supported by the recommendations for sepsis management 1. The combination of these factors creates a perfect storm for hypoglycemia, which can worsen the patient's altered mental status and complicate the clinical picture of sepsis. Given the harmful effects of hypoglycemia, it is crucial to monitor blood glucose levels closely and provide a glucose calorie source to prevent hypoglycemia, aiming to keep blood glucose above 70 mg/dL, as recommended in the management of sepsis 1.
From the Research
Causes of Hypoglycemia in Sepsis
- Depleted glycogen stores, impaired gluconeogenesis, and increased peripheral glucose utilization may contribute to hypoglycemia in sepsis 2
- Spontaneous hypoglycemia, which may occur in the early stages of sepsis, is associated with a higher mortality rate 3
- Dysglycemia, including hypoglycemia, is a marker of illness severity in sepsis 4
- Relative adrenal insufficiency or critical illness-related corticosteroid insufficiency (CIRCI) can occur in sepsis, leading to decreased mental status, unexplained fever, or hypotension refractory to fluids, and may contribute to hypoglycemia 5
- Early hypoglycemic episodes during sepsis are associated with poor outcomes, including increased in-hospital mortality, especially in nondiabetic patients 6
Associated Factors
- Altered mental status is a common feature in patients with sepsis and hypoglycemia 2
- Metabolic acidosis, leukopenia, abnormal clotting studies, and bacteremia are also common in these patients 2
- Certain pathogens, such as Streptococcus pneumoniae and Hemophilus influenzae, type b, are more commonly associated with hypoglycemia in sepsis 2
- Premorbid glycemia and the dynamic pathophysiologic consequences of dysglycemia throughout the course of sepsis can influence the development of hypoglycemia 4