Selecting an Agent in the ED: the Evidence (or Lack Thereof)
Nontreatment-Related Nausea and Vomiting
A 2011 systematic review of cancer nausea unrelated to chemotherapy or radiotherapy found level B evidence that metoclopramide is the most effective first-line empiric agent. In patients with bowel obstruction, dexamethasone, hyoscine butylbromide (scopolamine), and octreotide are effective. While dexamethasone is often thought to improve the effects of antiemetic drugs, this review showed it did not improve nausea when added to chlorpromazine or metoclopramide. Furthermore, neither metoclopramide nor ondansetron were shown to reduce opioid-induced emesis.13 The review further pointed out the lack of good evidence for expert opinion guideline recommendations in breakthrough vomiting—eg, dose titration of the same drug, switching to a different drug class, or using two or more drugs together at once.13
Another review had similar findings, while pointing out that an “absence of evidence is not evidence of absence,” and noting that many of these treatments have been used for years—ie, the problem is lack of evidence, but not negative evidence.17 Both studies are notable in that they were all done in palliative-care units in which time to relief from nausea and/or vomiting was typically measured in days, not hours, making their application to the emergency setting—where time is a factor—difficult.
Due to the potential for drug toxicity, using the same antiemetic drug repeatedly within a short amount of time in a patient refractory to therapy may not be the best strategy in the ED. It is most likely more beneficial and effective to switch drugs or use a combination of drugs right away—though this approach has theoretical concerns with drug-drug interactions. Again, this is an area in which further study is needed.
Treatment-Related Nausea and Vomiting
A recent review on breakthrough CINV again cited the paucity of clinical trials for this entity. Based on few studies, olanzapine and metoclopramide seem to be of value when prophylactic antiemetic regimens have failed. The review further noted that treatment of breakthrough CINV with an agent from same drug class as that used in the prophylactic regimen (usually 5-HT3 and NK1 antagonists) is unlikely to be successful.32 This review also mentioned an interesting phase 2 study using a transdermal gel consisting of diphenhydramine, haloperidol, and lorazepam to the wrist, in which 27 of 33 patients in the study reported a decrease in nausea within a 4-hour period.33 The same combination of drugs in IV form (lorazepam 0.5 mg, diphenhydramine 12.5 mg, and haloperidol 1 mg) is frequently used in the ED at the authors’ institution to treat breakthrough vomiting refractory to metoclopramide, antihistamines, or 5-HT3 antagonists. To the authors’ knowledge, this combination treatment has not been previously cited in the medical literature.
Recommendations and Summary
Cancer patients presenting to the ED with nausea and vomiting should be thoroughly evaluated regarding the possible etiology of their symptoms. A careful history must include recent chemotherapy, radiation, medications, as well as knowledge of the potential complications associated with the specific type of cancer. The EP also should keep in mind that delayed nausea and vomiting can be present several days after chemotherapy, and that CINV may not manifest until after the initial prophylactic medications have worn off. Moreover, he or she should be aware that some individuals have unique responses to chemotherapy and radiation and may experience more nausea and vomiting symptoms than is considered typical.
In addition to CINV, other etiologies, including GI issues such as delayed gastric emptying, partial bowel obstruction, and constipation should also be carefully considered. When evaluating the patient, the EP should also consider non-GI causes such as elevated ICP, kidney obstruction, infection, silent cardiac ischemia, steroid withdrawal, Addisonian crisis, and electrolyte abnormalities.
The lack of conclusive evidence for the treatment of cancer-related nausea and vomiting in any circumstance—except for prophylaxis prior to chemotherapy—precludes the recommendation of a specific treatment algorithm. However, the evidence is abundant that there are multiple effective agents with different, if not overlapping, mechanisms of action available. The EP, therefore, should be familiar with the most commonly used antiemetic drugs from several different categories and their side effects, and tailor the approach based on the assumed etiology of the symptoms. When treating CINV or cancer-related nausea and vomiting, it is not uncommon that patients may require multiple agents, either simultaneously or in sequence, to obtain symptom resolution.
Dr Sandoval is an assistant professor, department of emergency medicine, division of internal medicine at The University of Texas MD Anderson Cancer Center, Houston. Dr Rice is an assistant professor and clinical medical director in the department of emergency medicine, division of internal medicine at The University of Texas MD Anderson Cancer Center, Houston.