Haloperidol for treatment of nausea and vomiting in palliative care patients
Abstract
This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:
To evaluate the efficacy and adverse events (both minor and serious) associated with the use of haloperidol for the treatment of nausea and vomiting in palliative care patients. Possible adverse events include sedation, movement disturbance and arrhythmias. Neuroleptic malignant syndrome is a more serious but less common adverse event. This has numerous features including fever, altered consciousness and muscle rigidity and can be fatal (Susman 2001).
Background
Nausea and vomiting are common symptoms of patients with terminal, incurable illnesses and can be distressing. Between 40 to 70 % of patients with advanced cancer (Twycross 1998) are troubled by these symptoms and they are also common in other terminal conditions, for example long‐standing lung diseases and heart failure (Edmonds 2001; Klinkenberg 2004). Antiemetic drugs can help control symptoms while actions are taken to try and treat the underlying cause. There are many such causes in patients with terminal illness including the underlying illness (for example the cancer they are suffering from); biochemical disturbance (for example kidney failure or electrolyte disturbance) or drugs (for example morphine). Doctors try to choose the best first choice antiemetic based on what is thought to be this underlying cause (Bentley 2001). While this is a common approach there is little evidence for many of the drugs used for these symptoms in this patient group (for example cyclizine, haloperidol or levomepromazine) (Glare 2004). Haloperidol is commonly used in this setting to treat nausea and vomiting (Critchley 2001). Haloperidol is in the butyrophenone class of drugs and acts as an antagonist on dopamine receptors at the chemoreceptor trigger zone in the brain (Mannix 2004). Haloperidol is used alone or in combination with other antiemetics (for example, cyclizine) orally, subcutaneously or intramuscularly. It is only licensed as an antiemetic by the intramuscular route.
All patients with terminal illness should have access to palliative care, independent of their diagnosis and we wanted to reflect this in our review. Defining this population has been identified as a problem in previous reviews. We used the same definition as Hirst 2001 to give some consistency with other Cochrane reviews: 'adult patients in any setting, receiving palliative care or suffering an incurable progressive medical condition'.
Objectives
To evaluate the efficacy and adverse events (both minor and serious) associated with the use of haloperidol for the treatment of nausea and vomiting in palliative care patients. Possible adverse events include sedation, movement disturbance and arrhythmias. Neuroleptic malignant syndrome is a more serious but less common adverse event. This has numerous features including fever, altered consciousness and muscle rigidity and can be fatal (Susman 2001).
Methods
Criteria for considering studies for this review
Types of studies
Randomised controlled trials (RCTs) of haloperidol for the treatment of nausea or vomiting, or both, in any setting.
Types of participants
Inclusion Criteria
Adults receiving palliative care or suffering from an incurable progressive medical condition. Adults suffering from nausea or vomiting, or both.
Exclusion Criteria
Nausea or vomiting, or both, thought to be secondary to pregnancy or surgery.
Types of interventions
We will include studies where haloperidol was used as an antiemetic (alone or in addition to other agents) including any dose of haloperidol, via any route, over any duration of follow up.
Acceptable comparators:
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placebo,
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other drug,
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non‐pharmacological intervention.
Types of outcome measures
Primary
1) Patient reported nausea severity,
2) Patient reported vomiting severity.
As there is little agreement about how to measure these symptoms any measure will be accepted.
Secondary
1) Quality of life measurement,
2) Acceptability of treatment,
3) Need for rescue antiemetic medication,
4) Adverse events,
5) Withdrawal from study because of side‐effects.
Ideally, valid outcome measures will have been used but we will not exclude studies on the basis of their outcome measures.
Search methods for identification of studies
We will search the electronic databases including CENTRAL, MEDLINE, EMBASE, CINAHL and AMED, using relevant search terms and synonyms. The basic search strategy will be ("haloperidol" OR "butyrophenone") AND ("nausea" OR "vomiting"), modified for each database. Handsearching will complement electronic searches (using reference lists of included studies, relevant chapters and review articles). We will not impose a language restriction on studies. Please see MEDLINE serach strategy in Appendix 1.
Data collection and analysis
Study Selection
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We will assess the potential relevance of studies based on their titles and abstracts, and obtain studies which may meet the inclusion criteria.
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We will both read these to assess suitability for inclusion. Discrepancies will be discussed to achieve consensus.
Data Extraction
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We will extract data using a data extraction form and judge study quality using the Oxford Quality Scale (Jadad 1996).
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We will enter data onto Revman independently to improve data input accuracy.
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We will assess studies for treatment effect (see outcome measures above) specifying numbers needed to treat to benefit (NNT) and numbers needed to treat to harm (NNH) if possible.
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If the heterogeneity of studies allows we will perform a meta‐analysis. If I2 test is < 50% we will use a fixed‐effect model. If I2 test is > 50% we will use a random‐effects model.
Subgroup Analysis
If there are sufficient data we will perform subgroup analyses for the following groups:
Population subgroups:
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diagnoses of patients,
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likely mechanism of nausea/vomiting,
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prognoses of patients,
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age of patients,
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gender of patients.
Intervention subgroups:
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route of administration,
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drug dose (< 2 mg /24 h; 2 to 5 mg /24 h; > 5 mg /24 h).
Outcome subgroups:
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nausea,
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vomiting.
