Dexamethasone

Clinical question 2c:

What is the effect of dexamethasone in the treatment of nausea and/or vomiting in patients in the palliative phase of cancer, heart failure, COPD, MS, ALS or renal failure?

Recommendation

The guideline development group is of the opinion that dexamethasone monotherapy may be used in the treatment of nausea and vomiting in the palliative phase if there is insufficient response to treatment with metoclopramide, domperidone or haloperidol.

Introduction

Dexamethasone is a corticosteroid. The agent has a broad area of application due to its anti-inflammatory action. The method of action with nausea and vomiting is not known.

It may be administered orally, subcutaneously or intravenously. The agent is registered for the symptomatic treatment of brain metastases and for the prevention and treatment of nausea and vomiting as a result of chemotherapy.

In the following text, the role of dexamethasone with brain metastases in the prevention and treatment of nausea and vomiting as a result of chemotherapy will not be discussed.

Literature discussion

During the literature research, one randomised study was found in which dexamethasone was compared to placebo, as a supplement to the use of metoclopramide [Bruera 2004]. In this study, 51 patients with an advanced stage of cancer were included who reported persistent complaints of nausea despite having used metoclopramide for 48 hours. Aside from 40-60 mg metoclopramide per day, 25 patients received additionally dexamethasone 10 mg twice daily per day, 26 patients received a placebo. After 8 days, there was a significant reduction in nausea in both groups. There was no significant difference in nausea between the two groups. It was concluded that dexamethasone does not provide additional value when using metoclopramide. The researchers indicated in the discussion that the period of 48 hours of treatment with metoclopramide was maybe too short to evaluate its effect and that the improvement in nausea in patients using a placebo could be a late effect of the treatment with metoclopramide.

Mystakidou conducted a randomised study in 280 patients in an advanced stage of cancer with nausea and vomiting, who did not respond to treatment with metoclopramide [Mystakidou 1998a]. The patients were randomised between treatment for a duration of 14 days with 1) metoclopramide 10 mg four times daily + dexamethasone 2 mg once daily (n=40), 2) tropisetron 5 mg once daily (n=40), 3) metoclopramide 10 mg twice daily + tropisetron 5 mg once daily (n=40), 4) metoclopramide 10 mg twice daily + tropisetron 5 mg once daily + dexamethasone 2 mg once daily (n=40), 5) chlorpromazine 25 mg twice daily + dexamethasone 2 mg once daily (n=40), 6) chlorpromazine 25 mg twice daily + tropisetron 5 mg once daily (n=40), and 7) chlorpromazine 2dd 25 mg twice daily + tropisetron 5 mg once daily + dexamethasone 2 mg once daily (n=40) [Mystakidou 1998a]. In a second publication, the results of groups 2, 5, 6 and 7 were outlined further [Mystakidou 1998b]. The patients completed a diary, in which they recorded how many hours per day they suffered from nausea and how often they vomited. In all groups treated with tropisetron, a maximum effect on both nausea and vomiting was achieved after 3 days of treatment. Complete control of the nausea after 3 days was seen in 10% of cases (metoclopramide + dexamethasone), 30% (tropisetron), 35% (metoclopramide + tropisetron), 55% (metoclopramide + tropisetron + dexamethasone), 10% (chlorpromazine + dexamethasone), 42% (chlorpromazine + tropisetron) and 60% (chlorpromazine + tropisetron + dexamethasone), respectively. Complete control of vomiting after 3 days was seen in 9% of cases (metoclopramide + dexamethasone), 42% (tropisetron), 65% (metoclopramide + tropisetron), 75% (metoclopramide + tropisetron + dexamethasone), 8% (chlorpromazine + dexamethasone), 67% (chlorpromazine + tropisetron) and 77% (chlorpromazine + tropisetron + dexamethasone), respectively. Comparisons between subgroups suggest that the addition of dexamethasone to the combination of metoclopramide or chlorpromazine and tropisetron leads to a slightly better control of nausea and vomiting. No correction was made for multiple testing.

The results from the study by Mystakidou suggest that tropisetron is effective in the treatment of nausea and vomiting, but the statistical analysis is questionable due to the lack of correction for the large number of comparisons.

Mystakidou also conducted a randomised study in 120 patients in an advanced stage of cancer with nausea and vomiting, who did not respond to treatment with metoclopramide [Mystakidou 1997]. All patients used opioids. They were randomised between metoclopramide10 mg four times daily + dexamethasone 2 mg once daily (n=40), metoclopramide 10 mg twice daily + tropisetron 5 mg once daily (n=40) and metoclopramide 10 mg twice daily + dexamethasone 2 mg once daily + tropisetron 15 mg once daily (n=40). The patients completed a diary, in which they recorded how many hours per day they suffered from nausea and how often they vomited. Complete control of nausea after 14 days was seen in 18%, 74% and 87% of patients, respectively, and complete control of vomiting in 24%, 84% and 92% of patients, respectively. Side effects (weakness, dizziness and constipation occurred in 22 patients.

In a review, no evidence was found for the effect of dexamethasone on nausea and vomiting due to other causes than ileus [Davis 2010]. The effect of dexamethasone monotherapy has not been researched.

In the Cleveland protocol [Gupta 2012], dexamethasone is only recommended if there is nausea and vomiting in patients with an ileus or brain metastases.

There are indications that the addition of dexamethasone does not have an effect in patients with an advanced stage of cancer, who suffer from persistent nausea despite treatment with metoclopramide for a duration of 48 hours.
[Bruera 2005]

No statemade can be made about the effectiveness of dexamethasone monotherapy for nausea and vomiting in patients in the palliative phase.

The use of dexamethasone in the treatment of nausea and vomiting due to other causes than ileus, brain metastases and chemotherapy is not supported by research. Despite this, the agent is often used successfully in daily practice in treating nausea and vomiting if an insufficient effect is achieved with metoclopramide and/or domperidone. An additional argument for the use of dexamethasone is that it also often has a favourable effect on other complaints that are also common in the palliative phase, such as anorexia, fatigue and pain.

Side effects as a result of long-term use of dexamethasone are less relevant for the patient population concerned.