Does a 60-year-old African American male with diabetes, taking Mounjaro (tirzepatide), who presents to the emergency room (ER) with fatigue, lightheadedness, and nausea, and has a history of hypoglycemia, tachycardia, and metabolic acidosis with an elevated anion gap, require hospital admission for further evaluation and management?

Hospital Admission is Strongly Recommended

This patient requires hospital admission for persistent high anion gap metabolic acidosis despite correction of hypoglycemia, particularly given his use of tirzepatide (Mounjaro), which has been associated with hypoglycemic ketoacidosis. 1, 2

Critical Metabolic Abnormalities Requiring Admission

Persistent High Anion Gap Metabolic Acidosis

• The anion gap of 19 (normal <12) with bicarbonate of 19 mEq/L indicates ongoing metabolic acidosis that has only partially improved despite glucose correction from 63 to 169 mg/dL 1
• The American Diabetes Association guidelines specify that metabolic acidosis with signs of hypoperfusion (which includes altered mental status from hypoglycemia, tachycardia at 119 bpm) warrants ICU-level evaluation 1
• Admission criteria for diabetes-related metabolic complications include arterial pH <7.30 and serum bicarbonate <15 mEq/l, but persistent acidosis with anion gap >12 after initial treatment also requires inpatient monitoring 1

Tirzepatide-Associated Hypoglycemic Ketoacidosis Risk

• Recent case series demonstrate that tirzepatide can induce hypoglycemic ketoacidosis in patients, presenting with hypoglycemia (blood glucose <70 mg/dL), high anion gap metabolic acidosis, and ketosis 2
• All reported cases required inpatient treatment with intravenous fluids and correction of hypoglycemia and ketosis 2
• The combination of hypoglycemia (initial glucose 63 mg/dL), persistent metabolic acidosis (CO2 19, anion gap 19-26), and gastrointestinal symptoms (nausea) in a patient on tirzepatide is highly concerning for this complication 2

Hemodynamic Instability

• Tachycardia at 119 bpm in the setting of metabolic acidosis indicates inadequate compensation and potential ongoing volume depletion or hypoperfusion 1
• ICU admission criteria specifically include heart rate >120 bpm, metabolic acidosis, and signs of hypoperfusion 1
• While his blood pressure is currently normal, the persistent tachycardia despite glucose correction suggests ongoing metabolic stress 1

Specific Inpatient Management Required

Immediate Diagnostic Workup

• Measure serum and urine ketones immediately - this is crucial in patients with gastrointestinal symptoms taking dual GLP-1 and GIP receptor agonists like tirzepatide 2
• Obtain arterial blood gas to assess pH and degree of acidosis more precisely 1
• Check lactate level to rule out lactic acidosis as contributor to anion gap 1
• Repeat basic metabolic panel every 4-6 hours until acidosis resolves 1

Inpatient Treatment Protocol

• Intravenous fluid resuscitation is required for volume depletion contributing to metabolic acidosis and tachycardia 1, 2
• Continuous cardiac monitoring given persistent tachycardia and metabolic derangements 1
• Hold tirzepatide until metabolic acidosis fully resolves and etiology is clarified 2
• Dextrose-containing IV fluids to maintain euglycemia while correcting acidosis 1
• Serial monitoring of electrolytes, particularly potassium, during correction of acidosis 1

Level of Care Determination

• This patient meets criteria for telemetry or step-down unit admission at minimum given tachycardia >100 bpm, metabolic acidosis, and need for frequent laboratory monitoring 1
• Consider ICU admission if acidosis worsens, mental status changes develop, or hemodynamic instability progresses 1

Critical Pitfalls to Avoid

Do Not Discharge Based on Glucose Correction Alone

• The normalization of glucose does not address the underlying metabolic acidosis - the persistent anion gap of 19 and bicarbonate of 19 indicate ongoing acid production or inadequate clearance 1
• Patients with diabetes presenting with metabolic complications require careful evaluation of all physical findings and laboratory parameters before discharge, not just glucose levels 1

Do Not Assume Simple Hypoglycemia

• The combination of hypoglycemia with high anion gap acidosis in a patient on tirzepatide represents a specific syndrome requiring targeted evaluation 2
• Simple hypoglycemia from sulfonylureas warrants admission, but this patient's presentation with persistent acidosis is more concerning 1

Monitor for Progression

• Hypoglycemic ketoacidosis can worsen despite initial glucose correction if ketone production continues 2
• The reduction in anion gap from 26 to 19 shows improvement but not resolution - continued monitoring is essential 1

Discharge Criteria (Not Yet Met)

The patient should not be discharged until:

• Anion gap normalizes to <12 1
• Bicarbonate level returns to >22 mEq/L 1
• Heart rate normalizes to <100 bpm with symptom improvement 1
• Ketones (if elevated) clear from serum and urine 2
• Patient tolerates oral intake without recurrent nausea 2
• Clear plan established for diabetes management without tirzepatide if this medication is implicated 2

The combination of persistent metabolic acidosis, tachycardia, and tirzepatide use in this clinical context makes outpatient management unsafe and inappropriate. 1, 2