What are the side effects of dexamethasone?

Side Effects of Dexamethasone

Dexamethasone has significant side effects including hyperglycemia, gastrointestinal complications (including ulcers and perforations), psychiatric disturbances, and increased risk of infections, with severity and frequency directly related to dosage and duration of treatment.

Common Side Effects by System

Metabolic Effects

• Hyperglycemia: Occurs in up to 76% of patients receiving high-dose dexamethasone in ICU settings 1
• Weight gain/increased appetite: Reported in 16-19% of patients 2
• Altered lipid metabolism: Changes in serum lipids and upregulation of acylcarnitines 3
• Fluid retention: Can lead to edema and hypertension

Gastrointestinal Effects

• Gastric/duodenal ulcers: Can be severe and potentially fatal, especially with high doses
• Gastrointestinal perforations: Reported in 14.3% of patients receiving high-dose dexamethasone (96 mg) for spinal cord compression 4
• Indigestion/epigastric discomfort: Affects approximately 27% of patients 2
• Rectal bleeding: Documented in high-dose treatment regimens 4

Neuropsychiatric Effects

• Insomnia: Affects up to 45% of patients 2
• Agitation: Reported in 27% of patients 2
• Psychosis: More common with high-dose therapy
• Memory impairment: Particularly concerning in pediatric patients 5

Musculoskeletal Effects

• Osteoporosis: With prolonged use
• Reduced alkaline phosphatase: Indicating altered bone metabolism 3
• Increased hydroxyproline levels: Reflecting abnormal bone metabolism 3

Immunologic Effects

• Increased infection risk: New infections (pneumonia, sepsis) occur in approximately 24% of patients 1
• Immunosuppression: Particularly concerning in already immunocompromised patients 6

Dermatologic Effects

• Acne: Affects approximately 15% of patients 2
• Skin thinning/bruising: With prolonged use

Dose-Dependent Side Effects

High-Dose Regimens (>0.5 mg/kg/day)

High-dose dexamethasone (such as 96 mg IV daily) is associated with:

• Serious gastrointestinal complications: 14.3% incidence of serious side effects including fatal ulcers with hemorrhage and gastrointestinal perforations 4
• Significantly higher risk of overall adverse events: 29% compared to 8% with moderate doses 4

Moderate-Dose Regimens (0.2-0.5 mg/kg/day)

• Lower risk of serious complications: Standard dexamethasone dose of 16 mg daily showed no serious side effects in the same patient population that experienced 14.3% serious complications with high doses 4
• Better safety profile: While still maintaining efficacy for many indications

Low-Dose Regimens (<0.2 mg/kg/day)

• Reduced risk of adverse effects: Particularly important in pediatric patients 5
• May still be effective: For certain indications like extubation facilitation 7

Special Considerations

Pediatric Patients

• Neurodevelopmental concerns: High-dose dexamethasone has been associated with neurodevelopmental impairment 7
• Hippocampal damage: Dexamethasone binds only to glucocorticoid receptors, which can result in hippocampal neuron degeneration 7
• Alternative considerations: Hydrocortisone may be safer for young children as it has not shown the same adverse effects on hippocampal volume or memory 5

Patients with Malignancy

• Thromboembolism risk: Particularly when combined with thalidomide or lenalidomide 7
• Prophylactic anticoagulation: Recommended when dexamethasone is used in combination therapies for multiple myeloma 7

Patients with Spinal Cord Compression

• Benefit vs. risk assessment: While high-dose dexamethasone (96 mg/day) improves ambulation in 81% vs. 63% of patients compared to controls, it carries an 11% risk of serious toxicity 7
• Moderate dosing consideration: Standard dose of 16 mg daily tapered over 14 days provides benefit with significantly lower risk of serious complications 4

Duration-Related Considerations

• Short-term, high-dose therapy (as in COVID-19 ARDS) may be justified when benefits outweigh risks 1
• Long-term therapy requires careful monitoring and potentially dose reduction to minimize cumulative adverse effects 6

Monitoring Recommendations

• Regular blood glucose monitoring
• Blood pressure checks
• Gastrointestinal symptom assessment
• Mental status evaluation
• Infection surveillance
• Bone health assessment with prolonged use

Practical Approach to Minimizing Side Effects

1. Use the lowest effective dose for the shortest duration possible
2. Consider alternative corticosteroids (e.g., hydrocortisone) for pediatric patients
3. Implement prophylactic measures (e.g., proton pump inhibitors for GI protection)
4. Monitor for early signs of adverse effects
5. Taper gradually after prolonged use to prevent adrenal insufficiency

The decision to use dexamethasone should carefully weigh the potential benefits against these significant side effects, particularly when considering high-dose or prolonged therapy regimens.