Toxic Metabolic Encephalopathy in Clinical Practice

A 72-year-old nursing home resident develops progressive confusion over 48 hours. Her baseline is alert, conversational, and cognitively intact for her age. Now she is drowsy, disoriented to time and place, and intermittently agitated. The overnight intern pages the admitting team: “Patient is confused — possible dementia?” But her family insists this is not her normal state.

This is not dementia. This is the classic presentation of acute encephalopathy, specifically acute toxic-metabolic encephalopathy (TME) — an acute condition of global cerebral dysfunction in the absence of primary structural brain disease. TME is among the most common neurological disorders encountered in hospital medicine, yet it remains one of the most consistently underrecognized and undertreated conditions in clinical practice. Patients with TME who require mechanical ventilation are particularly vulnerable to missed diagnoses, as subtle alterations in mental status are frequently attributed to sedation or critical illness rather than to a treatable underlying cerebral dysfunction.

For mental health professionals, TME is not a remote consideration. It is a critical differential diagnosis that must be ruled out before attributing acute mental status changes to a primary psychiatric disorder. Missing TME can have catastrophic consequences: many metabolic encephalopathies are reversible with prompt recognition and treatment, but certain causes — including sustained hypoglycemia, hyperammonemia, and thiamine deficiency (Wernicke encephalopathy) — may result in permanent structural brain damage or death if left untreated.

This comprehensive guide is written for psychiatrists, psychologists, hospital clinicians, and other mental health professionals who encounter acute cognitive changes in medically ill patients. It covers the full spectrum of TME — definitions, etiologies, pathophysiology, clinical presentation, diagnostic workup, differential diagnosis, ICD-10 coding, documentation strategies, treatment principles, and prognosis — all with a focus on practical, actionable information for frontline practice.

Definitions and Terminology — Why Words Matter

The terminology surrounding TME is often used imprecisely, leading to diagnostic confusion and coding errors. Understanding the distinctions is essential.

Encephalopathy itself is a broad clinical syndrome — not a specific diagnosis — characterized by diffuse brain dysfunction resulting in altered mental status, cognitive impairment, and often behavioral changes. It is typically multifactorial or related to a specific underlying cause and is commonly associated with widespread, noninflammatory cerebral edema.

Toxic-metabolic encephalopathy (TME) results from an acute cerebral dysfunction due to different metabolic disturbances, including medications or illicit drugs. The term “toxic-metabolic encephalopathy” reflects the fact that many patients have both toxic and metabolic factors contributing to brain dysfunction, and distinguishing between the two is often clinically challenging. Toxic-metabolic encephalopathy, which encompasses delirium and the acute confusional state, is an acute condition of global cerebral dysfunction in the absence of primary structural brain disease.

Toxic encephalopathy is a broader term used to describe encephalopathy caused by endogenous or exogenous poisonous substances that lead to metabolic derangements. In contrast, the more specific term “toxin and metabolic encephalopathy” (TME) describes encephalopathy caused by exogenous toxins that have direct neurotoxic effects, though the two terms are often used interchangeably in the medical literature.

Metabolic encephalopathy refers specifically to brain dysfunction resulting from systemic metabolic derangements without external toxins — such as hepatic encephalopathy, uremic encephalopathy, hypoglycemic encephalopathy, or electrolyte disturbances.

Delirium and TME: Acute TME encompasses delirium and the acute confusional state. In clinical practice, the terms are often used interchangeably, but they carry different implications. Delirium describes the clinical syndrome of fluctuating attention, disorganized thinking, and altered arousal. TME implies a specific pathogenic mechanism (systemic metabolic or toxic insult). While the two labels refer to almost identical conditions, “toxic-metabolic encephalopathy” conforms to most neurologists‘ practice and emphasizes the underlying etiology. TME can be distinguished from dementia primarily by the patient’s level of consciousness acutely deteriorating and subsequently fluctuating.

Etiology — The Diverse Causes of TME

TME arises from a broad spectrum of etiologies, often involving complex and multifactorial mechanisms. The causative agents can be broadly categorized into exogenous (externally derived) or endogenous (internally generated) toxins.

Exogenous Toxins

Exogenous toxins can be environmental, industrial, or pharmaceutical.

Heavy metals:

• Lead: Common sources include contaminated water, soil, and lead-based paints. Occupational exposure in industries such as battery manufacturing is significant. Lead disrupts neuronal development and function, causing cognitive deficits, attention issues, and behavioral problems; severe cases can lead to encephalopathy with seizures and coma.

• Mercury: Exposure occurs primarily through contaminated fish or occupational settings. Mercury binds to proteins, leading to oxidative stress and neuronal damage, resulting in tremors, mood swings, and memory loss. Severe exposure can cause peripheral neuropathy and ataxia.

• Arsenic: Found in contaminated drinking water, pesticides, and some occupational settings, arsenic disrupts cellular respiration and energy production, leading to cognitive impairment and neurological symptoms such as confusion and peripheral neuropathy.

Organic solvents:

• Toluene: Used in industrial settings (e.g., paint thinners) and through inhalant abuse. Toluene disrupts neuronal membrane function and neurotransmitter activity, leading to cognitive deficits, motor disturbances, and behavioral changes. Chronic exposure can cause persistent cognitive impairment.

• Carbon tetrachloride: Causes oxidative stress and liver damage, potentially leading to toxic encephalopathy secondary to liver failure.

Pesticides:

• Organophosphates: Widely used in agriculture, these inhibit acetylcholinesterase, causing excessive cholinergic stimulation and neurotoxic effects, including cognitive dysfunction and motor impairment. Chronic exposure can lead to persistent neurological symptoms.

• Carbamates: Similarly inhibit acetylcholinesterase, causing symptoms such as nausea, headache, confusion, and tremors.

Alcohol and Medications: Includes alcohol-related Wernicke encephalopathy (thiamine deficiency) and medication toxicity from sedatives, anticonvulsants, lithium, and other drugs.

Endogenous Toxins

As organ function deteriorates, particularly in the liver or kidneys, the body struggles to filter toxins, allowing them to accumulate in the bloodstream and impact brain function.

• Ammonia: Elevated levels in liver disease can lead to hepatic encephalopathy, with symptoms ranging from confusion to coma. Approximately 50% of patients with cirrhosis develop hepatic encephalopathy, a specific form of toxic encephalopathy.

• Uremic toxins: Accumulation in kidney failure can cause cognitive and neurological impairments (uremic encephalopathy).

• Bilirubin: High levels in liver or biliary disorders can contribute to encephalopathy.

• Lactic acid: Elevated due to poor tissue oxygenation can lead to metabolic encephalopathy.

• Ketones: Increased in uncontrolled diabetes, potentially leading to brain dysfunction.

• Inflammatory mediators: In severe infections or autoimmune disorders, these can exacerbate neurological symptoms.

Pathophysiology of TME

Normal neuronal activity requires a balanced environment of electrolytes, water, amino acids, excitatory and inhibitory neurotransmitters, and metabolic substrates, as well as normal blood flow, temperature, osmolality, and physiologic pH. Complex systems mediating arousal, awareness, and higher cognitive functions are particularly vulnerable when the local milieu is deranged.

All forms of acute TME interfere with the function of the ascending reticular activating system and/or its projections to the cerebral cortex, leading to impairment of arousal and/or awareness. The mechanisms by which toxins disrupt the nervous system involve a complex interplay of direct neurotoxicity, metabolic derangements, and excitotoxicity. These processes often result in widespread, symmetric brain damage affecting multiple structures, most commonly the cerebral cortex, white matter, thalamus, caudate nucleus, and pons.

Clinical Presentation — Recognizing the Syndromes

The clinical presentation of TME can vary depending on the offending agent, duration of exposure, and individual susceptibility. However, core features are remarkably consistent across etiologies.

Cognitive and Behavioral Features:

• Acute or subacute onset of confusion and disorientation. Onset is typically within hours to days following exposure.

• Impaired attention and concentration — the patient cannot sustain focus or follow a conversation.

• Fluctuating course — symptoms wax and wane over minutes to hours. Patients may appear lucid during morning rounds but become confused and agitated by evening.

• Disorganized thinking — speech is tangential, rambling, or incoherent.

• Memory deficits — both short-term and working memory are impaired.

• Perceptual disturbances — illusions, hallucinations (often visual), and paranoia can occur.

• Personality change — patients may become irritable, withdrawn, or uncharacteristically aggressive.

Arousal and Consciousness Abnormalities:

• Altered level of arousal — ranging from drowsiness and lethargy to stupor and coma.

• Fluctuating alertness — patients may fall asleep mid-conversation and then awaken abruptly.

• In severe cases, coma and even sudden death can occur.

Motor and Neurologic Signs:

• Tremor — often coarse, irregular, or “flapping” (asterixis).

• Myoclonus — sudden, brief, involuntary jerking. Subacute delirium with myoclonus in the absence of focal neurological signs should suggest TME.

• Ataxia — unsteady gait (particularly relevant in Wernicke encephalopathy).

• Seizures — generalized or focal seizures may occur in severe cases.

• Extrapyramidal signs — rigidity, bradykinesia in some toxic exposures.

Other Associated Features:

• Sympathetic hyperactivity — tremor, tachycardia, diaphoresis, and mydriasis characterize the hyperactive subtype of delirium, which is common in toxic and withdrawal states.

• Headache — frequently reported in encephalopathy due to toxins.

• Nausea and vomiting.

• Sleep-wake cycle disturbance — excessive daytime drowsiness or insomnia with nocturnal agitation.

The “Subacute Delirium with Myoclonus” Red Flag: Although not specific, subacute delirium with myoclonus in the absence of focal neurologic sign should strongly suggest TME. This constellation is highly suggestive of a metabolic or toxic etiology and warrants urgent diagnostic evaluation.

Diagnostic Approach and Workup

TME is a clinical diagnosis of exclusion. The diagnostic approach must be systematic and thorough.

Step 1: Clinical Assessment and History

• Obtain collateral history from family, caregivers, or nursing staff to confirm that the mental status change is acute and represents a deviation from baseline.

• Review medication list for recent additions, dose adjustments, or high-risk medications (opioids, benzodiazepines, anticholinergics, anticonvulsants, lithium).

• Explore exposure history — occupational exposures (solvents, heavy metals, pesticides), environmental exposures (carbon monoxide, lead-based paint), substance use (alcohol, illicit drugs).

• Review recent medical events — falls, infections, surgeries, new medical diagnoses.

• Screen for alcohol withdrawal syndromes — alcohol withdrawal syndromes must be excluded in patients with suspected TME, as they require distinct management. Wernicke encephalopathy requires immediate IV thiamine (before glucose administration).

Step 2: Laboratory Evaluation

• Basic metabolic panel (BMP) — assess for electrolyte disturbances, renal dysfunction.

• Complete blood count (CBC) — screen for infection (elevated WBC), anemia.

• Liver function tests (LFTs) — assess for hepatic failure.

• Ammonia — indicated when hepatic encephalopathy is suspected, particularly with asterixis or elevated LFTs.

• Blood glucose — hypoglycemia and hyperglycemia are reversible causes of encephalopathy.

• Arterial blood gas (ABG) — assess for acidosis or hypoxia.

• Thyroid function tests and B12 — when indicated based on clinical suspicion.

• Toxicology screen — serum and urine toxicology for drugs of abuse and medications.

• Drug levels — for specific medications (lithium, phenytoin, valproate, digoxin, theophylline).

• Inflammatory markers (CRP, ESR) and blood cultures — when infection or sepsis is suspected.

Step 3: Imaging

• Non-contrast CT head — essential to rule out primary structural brain disease, such as large vessel stroke, intracranial hemorrhage, mass lesion, or hydrocephalus. TME is defined by the absence of primary structural brain disease.

• Brain MRI — may show characteristic findings in specific etiologies: symmetric T2 hyperintensities in the basal ganglia and thalami in hepatic encephalopathy; mamillary body involvement in Wernicke encephalopathy; diffuse cerebral edema in severe cases.

Step 4: Electroencephalography (EEG)

• EEG is a valuable adjunct in the evaluation of TME. It can help rule out nonconvulsive status epilepticus, which can mimic TME clinically. Generalised slowing of background activity is the most common finding in TME and can support the diagnosis when structural causes are excluded.

• Continuous EEG monitoring may be indicated in ICU patients with persistent impairment of consciousness or suspected subclinical seizures.

Step 5: Lumbar Puncture

• Indicated when CNS infection, inflammation (encephalitis), or subarachnoid hemorrhage is suspected, particularly in immunocompromised patients or when fever and meningismus are present.

Differential Diagnosis — The Exclusion of Primary Psychiatric Disorders

For mental health professionals, the critical differential is between TME and a primary psychiatric disorder presenting with acute behavioral changes. Mistaking TME for psychosis, mania, catatonia, or severe anxiety can have life-threatening consequences.

Comparison Table: TME vs. Psychiatric Disorders

High-Risk Scenarios for Missed TME

• Elderly patients with delirium attributed to “sundowning” or “dementia” without evaluation for underlying cause.

• Postoperative patients with confusion attributed to anesthesia or pain medications without metabolic workup.

• Patients with known psychiatric illness whose acute decompensation is attributed to their underlying disorder without medical evaluation.

• Nursing home residents with acute change in mental status attributed to “baseline dementia” without assessment for infection, dehydration, or medication toxicity.

Red Flags that Should Trigger Medical Evaluation Before Psychiatric Admission:

• Fever or hypothermia

• Tachycardia out of proportion to agitation

• Hypertension or hypotension

• New tremor, myoclonus, or asterixis

• Laboratory abnormalities (abnormal electrolytes, glucose, LFTs, renal function)

• Age >60 with no prior psychiatric history

• Acute onset of confusion in a patient with known dementia

• Fluctuating level of arousal

ICD-10 Coding and Documentation

Accurate coding is essential for reimbursement, quality tracking, and medical record clarity. Toxic-metabolic encephalopathy spans two primary ICD-10-CM codes, depending on the underlying cause.

Primary Codes

G92.8 is a billable/specific code that can be used to indicate a diagnosis for reimbursement purposes. The 2026 edition of ICD-10-CM G92.8 became effective on October 1, 2025. This is the American ICD-10-CM version of G92.8; other international versions of ICD-10 G92.8 may differ. Inclusion terms include “toxic encephalitis” and “toxic metabolic encephalopathy”.

Important: G92.8 is a manifestation code. Wherever there is a combination of an underlying etiology with multiple system manifestations, ICD-10-CM coding convention requires that the underlying condition be sequenced first, followed by the manifestation.

G93.41 is used for metabolic encephalopathy, including conditions such as sepsis-induced encephalopathy.

Code First and Use Additional Code Instructions

For G92.8 (toxic encephalopathy):

• Code first poisoning due to drug or toxin, if applicable (T36–T65 with fifth or sixth character 1–4).

• Use additional code for adverse effect, if applicable, to identify drug (T36–T50 with fifth or sixth character 5).

For G93.41 (metabolic encephalopathy):

• The underlying condition must be coded first.

G92.8 Code Tree

Ancillary Codes

When sepsis is the underlying cause of metabolic encephalopathy, code A41.9 (Sepsis, unspecified organism) should be used. When hepatic failure is the cause of toxic encephalopathy, code K72.90 (Hepatic failure, unspecified) should be used.

Documentation Requirements

To ensure proper reimbursement and compliance, documentation must establish clear clinical validation:

For G92.8 (Toxic Encephalopathy):

• Explicit mention of the toxin and its temporal relation to symptoms.

• Positive toxicology report.

• Documented exposure to toxin.

• Improvement of symptoms with toxin removal.

For G93.41 (Metabolic Encephalopathy):

• Documentation of acute onset with delirium, confusion, or altered consciousness.

• Laboratory findings such as elevated BUN/creatinine, low sodium, or hypoglycemia.

• Ensure documentation specifies the metabolic disturbance.

Coding Pitfalls

• Misclassification if toxin is not documented — G93.41 (metabolic) used when G92.8 (toxic) is appropriate, or vice versa.

• Incorrectly coding unspecified encephalopathy (G93.40) when documentation supports metabolic or toxic etiology.

• Failure to sequence underlying condition first — the underlying condition (e.g., poisoning, sepsis, hepatic failure) must be coded as primary, with encephalopathy as secondary.

• Misunderstanding the excludes notes: G93.41 excludes toxic encephalopathy (G92.8). G92.8 excludes metabolic encephalopathy (G93.41). These are mutually exclusive based on documented etiology.

Reimbursement Impact

“Metabolic encephalopathy” coded to G93.41 is a Major Complication or Comorbidity (MCC), capable of shifting MS-DRG reimbursement by thousands of dollars per case. For example, simple pneumonia DRG 195 may be reclassified to complex DRG 193 when metabolic encephalopathy is documented, significantly increasing hospital reimbursement. This underscores the importance of accurate, specific documentation.

Treatment — Correcting the Cause

The cornerstone of TME management is identifying and correcting the underlying cause. Treatment is cause-specific rather than syndromic.

Treatment by Etiology

Management of Acute Symptoms

While the underlying cause is being addressed, supportive care is essential:

• Airway, breathing, circulation (ABCs) must be secured, particularly in patients with depressed consciousness.

• Seizure management — antiepileptic drugs may be required for clinical or electrographic seizures. In TME patients with epileptiform abnormalities on EEG, increasing burden of epileptiform activity is associated with worse discharge neurologic outcomes; whether short-term treatment with anti-seizure medications improves outcomes requires further study.

• Agitation — non-pharmacologic measures (reorientation, familiar objects, family presence, calm environment) should be used first. If pharmacologic intervention is necessary, low-dose antipsychotics (quetiapine, olanzapine, haloperidol) may be used with caution, avoiding medications with significant anticholinergic or sedating properties.

• Prevention of complications — aspiration precautions, fall prevention, pressure ulcer prevention, deep vein thrombosis prophylaxis, early mobilization.

• Liaison with toxicology, occupational health, hepatology, or nephrology as indicated by the underlying etiology.

Prognosis and Outcomes

The prognosis for TME is highly variable and depends on several factors: the underlying etiology, the speed of recognition and treatment, the severity of the initial insult, and the patient’s baseline health status.

Reversibility

Most TME is reversible, making prompt recognition and treatment critically important. When the underlying cause is identified and corrected, many patients return to their baseline cognitive function.

However, certain metabolic encephalopathies, including those caused by sustained hypoglycemia and thiamine deficiency (Wernicke encephalopathy), may result in permanent structural brain damage if untreated. These are medical emergencies requiring immediate intervention.

Mortality and Neurologic Outcomes

A 2023 retrospective study of hospitalized patients with TME who underwent continuous EEG monitoring found:

• Overall cohort discharge mortality was 22%.

• 70% had a poor neurologic outcome (modified Rankin Score 4–6, indicating moderate to severe disability or death) at discharge.

• Presence of epileptiform abnormalities was associated with poor outcome (odds ratio 3.89; CI [1.05–14.2], p = 0.041).

• An increase in peak epileptiform abnormality burden from 0% to 100% increased the probability of poor discharge neurologic outcome by 30%.

These findings highlight that TME is a serious condition with substantial morbidity and mortality, particularly in critically ill patients.

Long-Term Cognitive Outcomes

Among elderly long-term care patients with cognitive impairment, approximately 6% to 12% have a reversible component to their impairment, with possible causes including adverse drug effects, depression, and metabolic encephalopathies. This underscores the importance of thorough evaluation for reversible causes even in chronically cognitively impaired populations.

Factors Associated with Better Outcomes

• Early recognition and diagnosis

• Rapid identification and correction of the underlying cause

• Younger age

• Absence of significant baseline cognitive impairment

• Absence of epileptiform abnormalities on EEG

• Treatment in a setting with appropriate monitoring and supportive care

The Role of the Psychiatrist in TME

Psychiatrists play a critical role in the recognition and management of TME, particularly in consultation-liaison psychiatry.

Recognition: Psychiatrists are often called to evaluate patients with acute behavioral changes in medical-surgical settings. A high index of suspicion for TME is essential. Any patient with acute onset of confusion, altered arousal, or behavioral change — especially in the setting of medical illness, surgery, or polypharmacy — should undergo evaluation for TME before a primary psychiatric diagnosis is assigned.

Differentiation from Primary Psychiatric Illness: The psychiatrist must distinguish TME from functional psychoses, mood disorders, catatonia, and other psychiatric conditions presenting with behavioral disturbance. The presence of altered arousal (lethargy, drowsiness, fluctuating consciousness) is the single most important differentiating feature pointing toward an organic etiology.

Management of Agitation: When agitation in TME requires pharmacologic intervention, the psychiatrist can guide medication selection, choosing agents with minimal anticholinergic and sedating properties, avoiding medications that may worsen the underlying encephalopathy (e.g., benzodiazepines in hepatic encephalopathy), and recommending lowest effective doses.

Recommendation of Further Workup: When the diagnosis is uncertain, the psychiatrist can recommend specific diagnostic tests (EEG, lumbar puncture, brain MRI, toxicology screening, metabolic panel, ammonia level) to clarify the etiology.

Differentiation of Psychiatric Syndromes Requiring Specialty Care: As part of the differential diagnosis, the psychiatrist should also consider catatonia (which may be secondary to an underlying medical condition or may be primary and require benzodiazepine trials or ECT), serotonin syndrome (often medication-induced, requires discontinuation of serotonergic agents and supportive care), neuroleptic malignant syndrome (antipsychotic-induced, requires supportive care and sometimes dantrolene), and alcohol withdrawal delirium (requires benzodiazepine-based protocols and thiamine supplementation).

Communication with the Medical Team: The psychiatrist serves as a bridge between the medical and psychiatric perspectives, ensuring that medical causes of mental status change are thoroughly investigated while also addressing the patient‘s behavioral symptoms.

Documentation for Audit Protection

Thorough, specific documentation is essential for both clinical care and reimbursement.

Essential elements to include in the medical record:

1. Description of acute onset — specify when symptoms began (e.g., “Patient was at baseline mental status 48 hours ago; over the past 2 days, she has developed progressive confusion and drowsiness”).

2. Description of altered mental status — note arousal level (lethargic, drowsy, stuporous), attention (easily distracted, unable to follow conversation), orientation (disoriented to time, place, or person), and thought process (disorganized, tangential).

3. Specific physical findings — document tremor, asterixis, myoclonus, focal neurologic signs, or their absence.

4. Cognitive assessment — brief bedside cognitive testing (e.g., “patient unable to recall 3 objects after 5 minutes“).

5. Laboratory confirmation — specify the specific metabolic or toxic derangement (e.g., ”ammonia level 150 mcg/dL,“ ”serum sodium 118 mEq/L,” ”lithium level 2.1 mEq/L”).

6. Temporal relationship — document the temporal relationship between toxin exposure or metabolic disturbance and symptom onset（例如，"symptoms began 48 hours after initiation of lithium therapy”).

Poor documentation (audit trigger):

“Patient confused due to encephalopathy.”

Good documentation (supports coding):

“Patient with acute onset of confusion, lethargy, and asterixis beginning 48 hours ago. Laboratory studies reveal ammonia level 165 mcg/dL, elevated LFTs. No focal neurologic findings on exam. Non-contrast CT head shows no acute intracranial pathology. Diagnosis: acute metabolic encephalopathy due to hepatic failure (G93.41). Treatment initiated with lactulose.”

FAQ

What is the difference between toxic encephalopathy and metabolic encephalopathy?

Toxic encephalopathy (G92.8) is caused by exogenous (external) toxins — medications, drugs of abuse, heavy metals, organic solvents, pesticides — that directly impair brain function. Metabolic encephalopathy (G93.41) is caused by endogenous (internal) metabolic disturbances — liver failure, kidney failure, electrolyte imbalances, hypoglycemia, sepsis. In clinical practice, many patients have both toxic and metabolic factors; the code “G92.8 Other toxic encephalopathy” includes “toxic metabolic encephalopathy” as an inclusion term to capture mixed presentations.

Is toxic-metabolic encephalopathy the same as delirium?

Acute toxic-metabolic encephalopathy encompasses delirium and the acute confusional state. However, the terms carry different implications. Delirium is a clinical syndrome defined by fluctuating attention, disorganized thinking, and altered arousal. TME implies a specific pathogenic mechanism (systemic metabolic or toxic insult). While the two labels refer to almost identical conditions, “toxic-metabolic encephalopathy” is the preferred term in neurology because it emphasizes the underlying etiology.

What is the prognosis for a patient with TME?

Prognosis varies widely depending on the underlying cause and timeliness of treatment. Most TME is reversible with prompt recognition and treatment of the underlying cause. However, certain etiologies — sustained hypoglycemia and thiamine deficiency (Wernicke encephalopathy) — may cause permanent brain damage if untreated. In hospitalized patients, overall discharge mortality is approximately 22%, and 70% have poor neurologic outcome at discharge. Early recognition and rapid correction of the underlying cause improve outcomes.

Can TME be coded as a primary diagnosis?

G92.8 (Other toxic encephalopathy) is a billable/specific code that can be indicated for reimbursement purposes. However, for many presentations, the underlying condition (e.g., poisoning, sepsis, hepatic failure) must be coded first, followed by the encephalopathy code. Manifestation codes like G92.8 are never permitted to be used as first-listed or principal diagnosis codes when an underlying etiology is known. Exception: when the encephalopathy is the primary reason for encounter and the underlying cause is not yet identified, G92.8 may be sequenced first.

When should a psychiatrist suspect TME rather than a primary psychiatric disorder?

Suspect TME rather than a primary psychiatric disorder when the patient presents with:

• Acute onset (hours to days rather than weeks to months).

• Altered level of arousal (lethargy, drowsiness, stupor) — this is the single most important distinguishing feature.

• Fluctuating course (waxing and waning symptoms, lucid intervals).

• Abnormal vital signs (fever, tachycardia, hypotension, hypertension).

• New neurologic signs (tremor, asterixis, myoclonus, ataxia).

• Laboratory abnormalities (electrolyte disturbances, abnormal LFTs, renal dysfunction, abnormal glucose).

• Age >60 with no prior psychiatric history.

• Poor response to antipsychotics — patients with TME may worsen or show paradoxical agitation with antipsychotic medications.

References

1. ICD-10 Data. (2026). 2026 ICD-10-CM Diagnosis Code G92.8: Other toxic encephalopathy.

2. ICD-10 Data. (2026). 2026 ICD-10-CM Diagnosis Code G93.41: Metabolic encephalopathy.

3. ICDcodes.ai. (2026). Toxic Metabolic Encephalopathy – ICD-10 Documentation Guidelines.

4. ICDcodes.ai. (2026). Metabolic Encephalopathy – ICD-10 Documentation Guidelines.

5. Unbound Medicine. (2026). G92.8 – Other toxic encephalopathy | ICD-10-CM.

6. MedGenius. (2026). G92.8: Other toxic encephalopathy – 2026 ICD-10-CM Codes.

7. AAPM&R PM&R KnowledgeNow. (2025). Toxin and Metabolic Encephalopathy.

8. ACDIS. (2024). Note from the CDI Education Director: Toxic encephalopathy, navigating internal and external threats to brain function.