From the Guidelines
Acute metabolic encephalopathy is primarily caused by systemic disturbances such as electrolyte imbalances, glucose disorders, acid-base disturbances, organ failures, toxins, nutritional deficiencies, and endocrine disorders, as identified in the most recent and highest quality study 1. The primary causes of acute metabolic encephalopathy include:
- Electrolyte imbalances (particularly sodium, calcium, and magnesium abnormalities)
- Glucose disorders (both hypoglycemia and hyperglycemia)
- Acid-base disturbances
- Organ failures (liver, kidney, or respiratory failure)
- Toxins (including medications, alcohol, and illicit drugs)
- Nutritional deficiencies (especially thiamine)
- Endocrine disorders like thyroid dysfunction Sepsis and systemic inflammatory responses can also trigger metabolic encephalopathy through inflammatory mediators that affect brain function, as noted in 2. These causes disrupt normal neuronal metabolism and neurotransmitter function, leading to altered mental status, confusion, and other neurological symptoms. The underlying pathophysiology typically involves changes in cellular energy production, membrane stability, or neurotransmitter balance that impair normal brain function. Treatment focuses on identifying and correcting the underlying metabolic disturbance, which often leads to rapid improvement in neurological symptoms once the metabolic abnormality is addressed, as emphasized in 3 and 1. It is essential to consider alternative or additional causes of neuropsychiatric impairment to improve prognostic accuracy and the results of treatment, as recommended in 1. A comprehensive diagnostic work-up, including blood tests, brain imaging, and screening for psychoactive drugs, is necessary to identify the underlying cause of acute metabolic encephalopathy, as suggested in 1.
From the FDA Drug Label
Hyponatremia can lead to acute hyponatremic encephalopathy characterized by headache, nausea, seizures, lethargy, and vomiting. The risk of hospital-acquired hyponatremia is increased in patients with cardiac or pulmonary failure, and in patients with non-osmotic vasopressin release (including SIADH) treated with high volume of hypotonic Lactated Ringer’s and 5% Dextrose Injection, USP Patients at increased risk for developing complications of hyponatremia such as hyponatremic encephalopathy, include pediatric patients, women (in particular, premenopausal women), patients with hypoxemia, and patients with underlying central nervous system disease.
Causes of Acute Metabolic Encephalopathy include:
- Hyponatremia: can lead to acute hyponatremic encephalopathy
- Hyperglycemia: can cause hyperosmolar hyperglycemic state, which may lead to encephalopathy
- Hypoglycemia: severe hypoglycemia can cause disorientation, seizures, unconsciousness, and death
- Electrolyte imbalances: such as hyperkalemia or hypokalemia can contribute to the development of encephalopathy
- Fluid overload: can cause electrolyte disturbances, including overhydration and congested states, which may lead to encephalopathy 4
- Diabetic ketoacidosis (DKA): a life-threatening emergency that can cause nausea, vomiting, stomach pain, dehydration, loss of consciousness, or death 5
From the Research
Causes of Acute Metabolic Encephalopathy
- Metabolic disturbances, including medications or illicit drugs, can cause toxic-metabolic encephalopathy (TME) 6
- Diabetic ketoacidosis (DKA) is a rare but potentially devastating complication that can lead to metabolic encephalopathy 7
- Inborn errors of metabolism can cause acute metabolic encephalopathy 8, 9
- Acute metabolic derangements, such as changes in blood flow and disturbances in neurotransmitter function, can contribute to the development of metabolic encephalopathy 9, 10
Mechanisms and Risk Factors
- Chronic hyperglycaemia can increase the risk of cerebral injury in diabetes mellitus 7
- Mechanisms of cerebral injury in diabetes mellitus are still being investigated 7
- Metabolic disorders, such as DKA, can pose a significant neurological risk to patients with diabetes mellitus 7
- Factors that contribute to acute brain dysfunction include changes in blood flow, disturbance in neurotransmitter function, failure of energy metabolism, and cellular depolarization 9
Diagnosis and Treatment
- A detailed history, examination, and investigations are necessary to identify patients with metabolic disorders 9
- Treatment of metabolic encephalopathy is largely supportive, with special attention to the management of cerebral perfusion pressure 9
- Resolution of brain dysfunction may be protracted despite normalization of laboratory values 10
- It is essential to search for and rule out structural injury to the brain, recognize confounding conditions, and acknowledge the potential for protracted recovery 10