What is the role of steroids, such as dexamethasone, in treating vomiting?

Role of Steroids in Treating Vomiting

Corticosteroids, particularly dexamethasone, are highly effective antiemetics that should be used as first-line therapy in combination with other antiemetic classes for chemotherapy-induced vomiting and postoperative nausea/vomiting, but have limited evidence for other causes of vomiting.

Chemotherapy-Induced Vomiting

Highly Emetogenic Chemotherapy (HEC)

• Dexamethasone 12 mg orally or IV on day 1 (reduced to 8 mg when combined with aprepitant due to drug interactions) is recommended as part of a multi-drug regimen including a 5-HT3 antagonist and NK1 receptor antagonist 1, 2
• For delayed emesis (days 2-4), dexamethasone 8 mg should be given twice daily 1
• The corticosteroid dose must be reduced by 50% when co-administered with aprepitant due to CYP3A4 interactions 1, 2

Moderately Emetogenic Chemotherapy (MEC)

• Dexamethasone alone is the preferred agent for preventing delayed nausea and vomiting after MEC 1
• A landmark Italian study demonstrated dexamethasone was statistically superior to placebo (87% vs 77% complete response) for delayed emesis, while adding ondansetron to dexamethasone provided no additional benefit (92% vs 87%) and caused more constipation 1
• For acute emesis with MEC, dexamethasone 12 mg combined with a 5-HT3 antagonist is recommended 1
• For anthracycline plus cyclophosphamide regimens in women, a three-drug regimen including dexamethasone 8 mg IV, a 5-HT3 antagonist, and aprepitant is recommended 1

Dosing Specifications

• For cisplatin-based HEC: single IV dose of 20 mg dexamethasone on day 1 1
• For cyclophosphamide/anthracycline-based chemotherapy: single IV dose of 8 mg dexamethasone on day 1 1
• Oral and IV routes are equally effective when dosed appropriately 1

Postoperative Nausea and Vomiting (PONV)

Prophylactic Use

• Dexamethasone 4-5 mg IV administered before the end of surgery is recommended as part of multimodal prophylaxis, preferably combined with ondansetron 4 mg 3, 4
• This combination provides superior prevention compared to either agent alone 3
• Dexamethasone significantly reduces PONV incidence in the first 24 hours and decreases the need for rescue antiemetics for up to 72 hours 3, 4
• A meta-analysis of 6,696 patients demonstrated that 4-5 mg dexamethasone has clinical effects similar to 8-10 mg doses for PONV prevention 4

Risk-Based Approach

• For patients with ≥2 PONV risk factors (female gender, history of PONV/motion sickness, non-smoking status, use of volatile anesthetics or opioids), a multimodal approach with dexamethasone plus ondansetron is first-line 3
• Consider adding a third antiemetic from a different class for very high-risk patients 3

Important Caveats

• Doses <4 mg may be less effective and should be avoided 3, 4
• The potential immunosuppressive effects of dexamethasone on long-term oncological outcomes remain unknown in cancer surgery 3, 4

Breakthrough/Rescue Treatment

• Dexamethasone 12 mg PO/IV daily can be added as breakthrough treatment when initial antiemetic therapy fails 1
• The principle is to add an agent from a different drug class than those used for prophylaxis 1

Other Causes of Vomiting

Limited Evidence

• For non-chemotherapy, non-surgical causes of vomiting (bowel obstruction, pancreatitis, viral syndromes, advanced cancer), data on corticosteroid efficacy are sparse 1
• Other causes to consider before using steroids include radiotherapy, infection, metabolic disorders, electrolyte disturbances, constipation, GI obstruction, brain/liver/bone metastases, and other emetogenic medications 1

Acute Gastroenteritis

• Corticosteroids are not recommended for gastroenteritis-related vomiting in children or adults 5, 6
• Ondansetron is the preferred agent in this setting 5, 6

Mechanism and Drug Class Considerations

• Corticosteroids work through anti-inflammatory mechanisms distinct from 5-HT3, dopamine, NK1, histamine, and muscarinic antagonists 1, 7
• This distinct mechanism makes them ideal for combination therapy 1, 8
• High-certainty evidence from network meta-analysis confirms dexamethasone reduces vomiting (RR 0.51,95% CI 0.44-0.57) compared to placebo 8

Safety Profile

• Dexamethasone has high-certainty evidence showing no effect on sedation compared to placebo (RR 1.00,95% CI 0.91-1.09) 8
• Evidence for serious adverse events is low certainty, with dexamethasone showing RR 1.16 (95% CI 0.28-4.85) compared to placebo 8
• Dexamethasone may reduce any adverse events (RR 0.77,95% CI 0.55-1.08, low certainty) 8

Common Pitfalls

• Failing to reduce corticosteroid dose by 50% when combining with aprepitant leads to excessive steroid exposure 1, 2
• Using single-agent therapy in high-risk chemotherapy or surgical patients is insufficient 1, 3
• Underdosing dexamethasone (<4 mg) reduces efficacy 3, 4
• Assuming steroids work for all causes of vomiting—evidence is strong only for chemotherapy and postoperative settings 1, 3