Prophylactic antiemetics for adults receiving intravenous opioids in the acute care setting New

Abstract

Background

Physicians often prescribe opioids for pain in the acute care setting. Nausea and vomiting are well‐described adverse events, occurring in over one‐third of patients. Prophylactic antiemetics may be one option to reduce opioid‐associated nausea and vomiting. However, these medications also have their own adverse effects, so it is important to understand their efficacy and safety prior to routine use. This is a review of randomized controlled trials comparing prophylactic antiemetics versus placebo or standard care for preventing opioid‐associated nausea and vomiting.

Objectives

To assess the effects of prophylactic antiemetics for nausea and vomiting in adults (aged 16 years or older) receiving intravenous opioids in the acute care setting.

Search methods

We searched CENTRAL (the Cochrane Library), MEDLINE (OVID), Embase (OVID) from inception to January 2022, and Google Scholar (17 January 2022). We also searched the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) and screened reference lists.

Selection criteria

We included randomized controlled trials of prophylactic antiemetics versus placebo or standard care in adults prior to receiving an intravenous opioid.

Data collection and analysis

Two review authors (MG, JNC) independently determined the eligibility of each study according to the inclusion criteria. Two review authors (MG, GDP) then independently extracted data, assessed risk of bias, and determined the certainty of evidence using GRADE. Our primary outcomes were the occurrence of nausea, vomiting, and adverse events. Secondary outcomes included nausea severity, number of vomiting episodes, and number of participants requiring antiemetic rescue therapy. We presented outcomes as risk ratios (RR) for dichotomous data (e.g. presence of vomiting, presence of nausea, number of participants requiring rescue medication, adverse events) and mean difference (MD) or standardized mean difference for continuous data (e.g. number of vomiting episodes, nausea severity) with 95% confidence intervals (CI).

Main results

We included three studies involving 527 participants (187 women and 340 men) with a mean age of 42 years.  All studies used intravenous metoclopramide (10 mg) as the intervention and a placebo for the comparator. No studies assessed any other antiemetic or compared the intervention to standard care.

Compared to placebo, metoclopramide did not reduce vomiting (RR 1.18, 95% CI 0.26 to 5.32; low‐certainty evidence) or nausea (RR 0.55; 95% CI 0.15 to 2.03; low‐certainty evidence) and there was no difference in adverse events (RR 2.34, 95% CI 0.47 to 11.61; low‐certainty evidence).  No data were available regarding the number of vomiting episodes. Metoclopramide did reduce the severity of nausea compared with placebo (MD −0.49, 95% CI −0.75 to −0.23; low‐certainty evidence) but did not reduce the need for rescue medication (RR 1.86, 95% CI 0.17 to 20.16; low‐certainty evidence). 

Two studies were at unclear risk of bias for random sequence generation, one for blinding of outcome assessors, one for incomplete outcome data, and two for selective reporting. The studies were at low risk of bias for all remaining components.

Authors' conclusions

There was no evidence that prophylactic metoclopramide affected the risk of vomiting, nausea, or the need for rescue medication when provided prior to intravenous opioids in the acute care setting. There was a clinically insignificant difference in nausea severity when comparing prophylactic metoclopramide with placebo. Overall, the evidence was of low certainty. Future research could better delineate the effects of prophylactic antiemetics on specific populations, and new studies are needed to evaluate the use of other prophylactic antiemetic agents, for which there were no data.

Author(s)

Michael Gottlieb, Jestin N Carlson, Gary D Peksa

Abstract

Plain language summary

Prophylactic antiemetics for adults receiving intravenous opioids in the acute care setting 

Key messages 

Metoclopramide did not reduce the risk of vomiting, nausea, or the need for rescue medication when provided prior to intravenous opioids in the emergency department. 

In terms of the severity of nausea, metoclopramide did not help patients any more than placebo (sham treatment).

What is opioid‐induced emesis? 

Physicians often give patients opioids for pain in emergency departments, but over a third experience the side effects of nausea and vomiting (emesis). Some experts have suggested that taking antiemetics before receiving the opioid (that is, as a prophylactic) could prevent these symptoms from occurring. However, these medications have their own side effects, so it is important to understand whether they are effective and safe before routinely using them.

What did we want to find out? 

This review looks at whether taking antiemetics (medications to treat or prevent nausea and vomiting) before receiving an intravenous opioid reduces the risk of experiencing nausea and vomiting as side effects.

What did we do? 

We looked for studies involving adults (aged 16 years or older) who received prophylactic antiemetics compared with either placebo or standard care before receiving an intravenous opioid.

What did we find? 

We found three studies with a total of 527 patients. All the studies used metoclopramide as the antiemetic. Compared with placebo, metoclopramide did not reduce the risk of vomiting, nausea, or the need for an antiemetic later on. There was also no difference in side effects between those who received antiemetics and those who did not.

What are the limitations of the evidence? 

The studies investigated only one medication (metoclopramide) and did not report all the information we were interested in. The intervention probably makes little or no difference in terms of experiencing nausea or vomiting.

How up to date is this evidence? 

This evidence is up to date to 17 January 2022.

Author(s)

Michael Gottlieb, Jestin N Carlson, Gary D Peksa

Reviewer's Conclusions

Authors' conclusions 

Implications for practice 

For people receiving opioids

There is low‐certainty evidence that prophylactic metoclopramide does not reduce vomiting, nausea, or the need for rescue or antiemetic medications compared with placebo. Therefore, current data do not support the routine use of prophylactic metoclopramide in patients receiving intravenous opioids. Importantly, the overall rates of vomiting and nausea after intravenous opioids were very low across all three studies, suggesting that a very large sample would be necessary to detect a statistically significant difference. While no differences were identified for adverse events, it is possible a larger sample size could change this result, so it would be important to weigh the risks and benefits of such treatment if future research were to demonstrate a benefit. There is a lack of evidence regarding the harms or benefits of other antiemetic agents.

For clinicians

While antiemetics continue to be used for treating nausea or vomiting after opioid delivery, the current data do not support clinicians routinely prescribing prophylactic metoclopramide to prevent these adverse events in patients being given intravenous opioids. As the data were limited to metoclopramide, it remains unclear whether other antiemetics may be beneficial. Clinicians should be aware of the current data regarding metoclopramide and consider devoting their efforts elsewhere, including toward addressing the underlying etiology of the pain as well as earlier recognition and treatment of nausea or vomiting resulting from intravenous opioids. There is a lack of evidence regarding the harms or benefits of other antiemetic agents.

For policymakers

Based on the findings from this study, prophylactic metoclopramide does not appear to meaningfully prevent nausea or vomiting in people receiving intravenous opioids. Policymakers should be aware of these findings, and future policies for intravenous opioid and nausea or vomiting management should not include recommendations for prophylactic antiemetics. There is a lack of evidence regarding the harms or benefits of other antiemetic agents. 

For funders

While current data do not demonstrate evidence of a benefit for prophylactic antiemetics, published studies are currently restricted to metoclopramide. Funders should be aware of these limitations and consider additional research funding to assess the safety and efficacy of other antiemetics and alternate interventions to reduce the risk of nausea or vomiting in people receiving intravenous opioids. 

Implications for research 

General implications

The current data show no evidence of a benefit with regard to dopamine antagonist antiemetics compared with placebo. While these results do not currently support the use of prophylactic antiemetics, future research is needed to better delineate whether other agents may be more effective or if specific patient populations may benefit from this treatment.

Design

Future research may be beneficial to better delineate the effect of prophylactic antiemetics for specific populations. For example, while the overall rate of vomiting and nausea was low in the included studies, it is unclear whether patients with a higher likelihood or prior history of opioid‐induced nausea and vomiting could benefit from prophylactic antiemetics.

Additionally, as all three studies assessed a single agent, other agents (e.g. serotonin receptor antagonists, neurokinin receptor antagonists, corticosteroids, histamine receptor antagonists, or anticholinergics) may yet demonstrate a benefit. Future studies should therefore assess the efficacy and safety of these other antiemetic agents in comparison with placebo and other agents.

Moreover, investigators should ensure that they preregister their studies to ensure transparency and adequately describe randomization and blinding.

Measurement (endpoints)

Only two studies reported nausea severity postintervention, and they used different scales (Choo 2019; Talbot‐Stern 2000). Future studies should use consistent and previously validated scales for assessing nausea. Authors should also ensure that studies are powered to identify a clinically meaningful difference in nausea severity.

Finally, most studies were underpowered to detect a difference in adverse events. Future studies should be adequately powered to identify a difference in adverse events in order to inform a determination of the risk and benefit of this intervention. It will also be important for authors to use a standardized tool and adequate follow‐up when assessing adverse events.

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