What are the side effects of methylprednisolone (corticosteroid) pulse therapy?

Methylprednisolone Pulse Therapy Side Effects

Methylprednisolone pulse therapy causes side effects in approximately 88% of patients, predominantly neuropsychiatric disturbances (especially insomnia in 50%), cardiovascular complications (bradycardia in 10%, hypertension in 3-4%, myocardial ischemia in 2%), and metabolic derangements (hyperglycemia and electrolyte shifts), with severe complications strongly related to underlying comorbidities. 1, 2

Common Side Effects (Occurring in >10% of Patients)

Neuropsychiatric Effects

• Insomnia occurs in approximately 50% of patients receiving pulse methylprednisolone, representing the most frequent adverse effect 2
• Neuropsychiatric reactions including mood swings, emotional instability, euphoria, depression, and personality changes are well-documented 1, 3
• Headache, vertigo, and paresthesias can occur during or after infusion 1

Cardiovascular Effects

• Bradycardia develops in approximately 10% of patients, occasionally symptomatic 2
• Cardiac arrhythmias and cardiac arrest have been reported, particularly with rapid administration of doses >0.5 grams over <10 minutes 1
• Hypertension (≥180/110 mmHg) occurs in 3-4% of patients, primarily those with pre-existing hypertension 2
• Myocardial ischemia occurs in 2% of patients with known coronary disease or high cardiovascular risk 2
• Tachycardia, thromboembolism, and thrombophlebitis are documented complications 1

Metabolic and Endocrine Effects

• Fasting glucose increases by a mean of 54% after the first pulse, with spontaneous return toward baseline in non-diabetics but progressive worsening in diabetics 2
• Serum potassium increases by approximately 5% (suggesting cellular potassium efflux), creating risk for subsequent hypokalemia 2
• Fluid retention and sodium retention with hypokalemic alkalosis can develop 1
• Development of cushingoid features, hirsutism, and menstrual irregularities with repeated courses 1

Serious but Less Common Side Effects (1-10%)

Gastrointestinal Complications

• Peptic ulcer with possible perforation and hemorrhage 1
• Pancreatitis, ulcerative esophagitis, and bowel perforation (particularly in inflammatory bowel disease) 1
• Abdominal distention and increased appetite 1

Hepatobiliary Toxicity

• Toxic hepatitis can occur with high-dose cyclically pulsed IV methylprednisolone (typically ≥1 gram/day), with onset several weeks or longer after treatment 1
• This can progress to acute liver failure and death; recurrence occurs with re-challenge 1
• Reversible elevation in serum liver enzymes 1

Infectious Complications

• Decreased resistance to infection due to immunosuppression 1
• Risk of opportunistic infections including fungal infections, strongyloides hyperinfection, and amebiasis activation 1
• Hepatitis B reactivation in carriers 1
• Varicella and measles can have serious or fatal courses in non-immune patients 1

Musculoskeletal Effects

• Aseptic necrosis of femoral and humeral heads 1
• Osteoporosis, pathologic fractures, and vertebral compression fractures 1
• Steroid myopathy with muscle weakness and loss of muscle mass 1

Rare but Severe Complications (<1%)

Ophthalmic

• Posterior subcapsular cataracts, glaucoma, and increased intraocular pressure 1
• Rare instances of blindness with periocular injections 1

Dermatologic

• Impaired wound healing, skin atrophy, striae, and ecchymoses 1
• Allergic dermatitis and urticaria 1

Hematologic and Allergic

• Anaphylaxis, anaphylactoid reactions, and angioedema 1
• Leukocytosis 1

Other Severe Reactions

• Kaposi's sarcoma development (may resolve with discontinuation) 1
• Fat embolism and pulmonary edema 1

Risk Factors for Severe Complications

Severe complications are strongly related to underlying comorbidities 2:

• Patients with known coronary insufficiency or high cardiovascular risk face increased myocardial ischemia risk 2
• Pre-existing hypertension increases risk of severe blood pressure elevation 2
• Diabetic patients experience progressive hyperglycemia rather than spontaneous normalization 2
• Cardiac disease patients are at risk from potassium shifts and arrhythmias 2

Monitoring Requirements During Pulse Therapy

Close clinical, blood pressure, and electrocardiographic monitoring is necessary during the entire treatment 2:

• Blood pressure and serum glucose should be monitored before, during, and after each infusion 4, 5, 2
• Daily electrocardiogram monitoring 2
• Fasting blood glucose and potassium levels daily 2
• Glucose monitoring is necessary only in diabetic patients for non-diabetics after initial assessment 2

Administration Considerations to Minimize Risk

• Doses >0.5 grams should be administered over at least 30 minutes (preferably 1 hour for 1 gram doses) to minimize acute cardiovascular complications 4, 1
• Avoid rapid administration (<10 minutes) which increases cardiac arrhythmia and arrest risk 1
• Consider antifungal prophylaxis in patients receiving prolonged steroid therapy 4

Atrial Fibrillation Risk

• Corticosteroids increase the risk of atrial fibrillation (OR 2.49), particularly with high-dose therapy (≥7.5 mg prednisone equivalents: OR 6.07) 6
• The risk is greatest at treatment initiation and with short-term high-dose use 6
• Case reports document atrial fibrillation after high-dose IV pulse methylprednisolone 6

Long-Term and Cumulative Effects

• More intense and prolonged pulse therapy results in higher toxicity rates (0-56% in different series) 3
• Immediate improvement may be followed by relapse, with transient effects even with maintenance therapy 7
• The theoretical benefits of pulse therapy over oral corticosteroids have not been conclusively demonstrated in all conditions 6, 4, 8