How to work up and treat a 56-year-old female with hypertension (High Blood Pressure), hyperlipidemia (Elevated Lipid Levels), and type 2 diabetes mellitus, presenting with acute vomiting, inability to eat, and hyponatremia (Low Sodium Levels) likely secondary to a medication-related adverse effect of a Glucagon-Like Peptide-1 (GLP-1) receptor agonist due to delayed gastric emptying?

Management of GLP-1 Receptor Agonist-Induced Gastroparesis with Acute Vomiting and Hyponatremia

Immediate Management: Discontinue the GLP-1 Receptor Agonist

Immediately discontinue the GLP-1 receptor agonist, as this is causing delayed gastric emptying leading to acute vomiting and subsequent hyponatremia. 1, 2 The American College of Cardiology states that immediate discontinuation is required when true adverse reactions occur, and while nausea/vomiting are common with GLP-1 therapy, the severity described here (unable to eat, with hyponatremia) warrants stopping the medication. 1, 2, 3

Workup for Hyponatremia

Assess Severity and Symptom Status

• Determine if hyponatremia is symptomatic or asymptomatic. Severe symptoms include delirium, confusion, impaired consciousness, ataxia, seizures, or cardiorespiratory distress—these constitute a medical emergency. 4, 5 Mild symptoms include nausea, vomiting, weakness, headache, and mild neurocognitive deficits. 4, 5
• Classify severity by serum sodium level: mild (130-134 mEq/L), moderate (125-129 mEq/L), or severe (<125 mEq/L). 5

Determine Volume Status

• Categorize the patient as hypovolemic, euvolemic, or hypervolemic based on physical examination findings. 4, 5, 6 In this case, acute vomiting with inability to eat strongly suggests hypovolemic hyponatremia due to gastrointestinal losses and inadequate oral intake. 5, 6
• Look for signs of volume depletion: orthostatic hypotension, dry mucous membranes, decreased skin turgor, tachycardia. 5, 6

Laboratory Evaluation

• Serum sodium, serum osmolality, urine sodium, and urine osmolality are essential. 4, 5, 6
• In hypovolemic hyponatremia from GI losses, expect: low serum sodium, low serum osmolality (<280 mOsm/kg), urine sodium typically <40 mEq/L (kidneys retain sodium), and variable urine osmolality. 5, 6
• Check serum glucose to exclude hyperglycemia as a cause of hypertonic hyponatremia. 6, 7
• Assess renal function (BUN, creatinine) as dehydration may cause prerenal azotemia. 5

Treatment Algorithm

For Severely Symptomatic Hyponatremia (Somnolence, Seizures, Coma)

This is a medical emergency requiring immediate hypertonic saline. 4, 5

• Administer 3% hypertonic saline boluses to increase serum sodium by 4-6 mEq/L within 1-2 hours, but do not exceed 10 mEq/L correction in the first 24 hours. 4, 5
• Use calculators to guide fluid replacement to avoid overly rapid correction and osmotic demyelination syndrome. 5
• Monitor serum sodium every 2-4 hours during active correction. 4, 5

For Asymptomatic or Mildly Symptomatic Hypovolemic Hyponatremia

Treat with normal saline (0.9% NaCl) infusions to restore intravascular volume and correct sodium deficit. 5, 6

• Initiate normal saline at 100-150 mL/hour initially, adjusting based on clinical response and sodium levels. 5, 6
• Target correction rate of 0.5 mEq/L/hour in chronic hyponatremia (>48 hours or unknown duration) to prevent osmotic demyelination syndrome. 6, 7
• Do not exceed 10-12 mEq/L correction in 24 hours and 18 mEq/L in 48 hours. 4, 6, 7
• Check serum sodium every 4-6 hours during correction phase. 5, 6

Address Gastroparesis and Vomiting

Antiemetic Therapy

• Administer metoclopramide 10 mg IV slowly over 1-2 minutes for acute symptom relief and to promote gastric emptying. 8 Metoclopramide is specifically indicated for diabetic gastroparesis and can be given IV initially, then transitioned to oral when tolerated. 8
• Monitor for dystonic reactions with metoclopramide; if they occur, administer diphenhydramine 50 mg IM. 8
• Alternative antiemetics include ondansetron 4-8 mg IV if metoclopramide is contraindicated or not tolerated. 8

Nutritional Support

• Keep patient NPO initially if severe vomiting persists, then advance to clear liquids as tolerated. 8
• Consider nasogastric tube placement if vomiting is intractable and gastric decompression is needed. 8
• Once vomiting resolves, advance diet slowly: clear liquids → full liquids → small, frequent low-fat meals. 3

Diabetes Management During Acute Illness

Adjust Glucose-Lowering Medications

• Temporarily hold metformin if the patient is NPO or has significant volume depletion (risk of lactic acidosis). 1
• Reduce insulin doses by 20-50% to prevent hypoglycemia during acute illness with poor oral intake. 1, 3
• Monitor blood glucose every 4-6 hours and adjust insulin accordingly. 3
• Do not restart the GLP-1 receptor agonist. Consider alternative diabetes medications once the patient recovers. 1

Monitoring and Follow-Up

Inpatient Monitoring

• Serial serum sodium measurements every 4-6 hours until stable, then every 12-24 hours. 5, 6
• Daily weights, strict intake/output monitoring. 5, 6
• Assess volume status with vital signs including orthostatic measurements. 5, 6
• Monitor for signs of osmotic demyelination syndrome if correction was rapid: dysarthria, dysphagia, paraparesis, behavioral changes. 4, 6, 7

Transition to Oral Intake

• Once vomiting resolves and sodium is stable, transition from IV fluids to oral hydration. 5, 6
• Ensure adequate sodium intake through diet (avoid very low-salt diets). 5
• Restart oral diabetes medications as appropriate, avoiding GLP-1 receptor agonists. 1

Alternative Diabetes Therapy Selection

Choose an alternative glucose-lowering agent based on the patient's cardiovascular and renal risk profile. 1

• If the patient has established cardiovascular disease, consider an SGLT2 inhibitor (if eGFR ≥30 mL/min/1.73 m²) for cardiovascular and renal protection. 1
• If SGLT2 inhibitors are contraindicated, consider DPP-4 inhibitors, which have lower risk of GI side effects than GLP-1 agonists. 1
• Optimize metformin (if eGFR ≥30 mL/min/1.73 m²) as first-line therapy once the patient is stable. 1
• Add basal insulin if glycemic targets are not met with oral agents. 1

Critical Pitfalls to Avoid

• Do not correct sodium too rapidly (>10 mEq/L in 24 hours or >18 mEq/L in 48 hours) as this causes osmotic demyelination syndrome with permanent neurological damage or death. 4, 6, 7
• Do not use hypotonic fluids (D5W, 0.45% saline) in hypovolemic hyponatremia—use normal saline. 5, 6
• Do not restart the GLP-1 receptor agonist after this severe adverse reaction; the American College of Cardiology states that a history of serious adverse reaction is an absolute contraindication. 1, 2
• Do not delay treatment while pursuing diagnostic workup if the patient is severely symptomatic. 5
• Do not use vaptans in hypovolemic hyponatremia—they are indicated only for euvolemic or hypervolemic hyponatremia (SIADH, heart failure). 4, 6