Using Haloperidol as an Antiemetic in Palliative Care: Informing Practice Through Evidence From Cancer Treatment and Postoperative Contexts

ABSTRACT

Nausea and vomiting are common symptoms in palliative care. Haloperidol is often used as an antiemetic in this context, although direct evidence supporting this practice is limited. To evaluate the efficacy and clinical use of haloperidol as an antiemetic in nonpalliative care contexts to inform practice, the authors conducted a rapid review of (i) published evidence to supplement existing systematic reviews, and (ii) practical aspects affecting the use of haloperidol including formulations and doses that are commonly available internationally. In nausea and vomiting related to cancer treatment, haloperidol was superior to control in two small studies. In postoperative nausea and vomiting (PONV), two randomized controlledtrials found treatment with haloperidol comparable to ondansetron. In palliative care, an observational study found a complete response rate of 24% with haloperidol (one in four patients) which would be consistent with a number needed to treat (NNT) of 3 to 5 derived from PONV. There remains insufficient direct evidence to definitively support the use of haloperidol for the management of nausea and vomiting in palliative care. However, generalizing evidence from other clinical contexts may have some validity.     

Intravenous haloperidol for tranquilization in critical care patients: a review and critique

The management of agitated, combative, fearful critically ill patients is a significant challenge for critical care nurses. Intravenously administered haloperidol can be effective in treating these patients. Because the U.S. Food and Drug Administration has not approved the use of haloperidol intravenously, there are no widely accepted guidelines for intravenous use of this drug. This chapter reviews the literature and provides information to critical care nurses in the use of intravenous haloperidol. Haloperidol's pharmacologic properties are described; several published case studies are reviewed; and potential adverse effects associated with haloperidol's use are presented.     

Complicated delirium in a cancer patient successfully treated with olanzapine

Delirium is common among cancer patients, especially those with advanced disease. Typical treatment involves addressing the underlying cause if possible; eliminating nonessential and/or other drugs that can worsen confusion, manipulating the environment; and administering antipsychotic drugs to control symptoms and agitated behavior, and attempt to clear the patient's sensorium. The newer atypical antipsychotics may have potential in the treatment of delirium and also have the added benefit of causing less akithisia and other extrapyramidal side effects. This is illustrated by the case of a 59-year-old woman with leukemia and pain of unclear etiology who developed a delirium and a moderate to severe extrapyramidal syndrome (EPS) in the setting of escalation of her pain medications and concomitant escalation of prochlorperazine. The patient presented with confusion and moderate to severe cogwheeling rigidity, masked facies, bradykinesia, and tremor. Additionally, the patient had a relatively recent history of subdural hematoma and one seizure. Conservative management including eliminating multiple nonessential medications (including the prochlorperazine); changing her opioid analgesic; providing a 24-hour companion: and administering low doses of haloperidol (0.5 mg-2.0 mg) were not effective in treating the patient's delirium. The patient's EPS was dramatically worse following haloperidol doses. After approximately I week without improvement, the patient was started on olanzapine 5 mg daily with initial improvement but with residual confusion in the evenings and overnight. The dose was titrated up to 10 mg nightly with 2.5 mg as needed during the day. After 3 days on this regimen, the patient's mental status exam was normal and she was discharged home. We discuss the potential utility of this atypical antipsychotic in the palliative care setting.     

The Activity of Palliative Care Team Pharmacists in Designated Cancer Hospitals: A Nationwide Survey in Japan

ContextThe role of pharmacists in palliative care has become more important now that they are able to provide medication review, patient education, and advice to physicians about a patient's pharmacotherapy. However, there is little known about pharmacists' activity on palliative care teams.ObjectivesThe present study aimed to examine the clinical, educational, and research activities of pharmacists on palliative care teams and pharmacist-perceived contributions to a palliative care team or why they could not contribute.MethodsWe sent 397 questionnaires to designated cancer hospitals, and 304 responses were analyzed (response rate 77%).ResultsOf the pharmacists surveyed, 79% and 94% reported attending ward rounds and conferences, respectively. Half of the pharmacists provided information/suggestions to the team about pharmacology, pharmaceutical production, managing adverse effects, drug interactions, and/or rotation of drugs. In addition, 80% of the pharmacists organized a multidisciplinary conference on palliative care education. Furthermore, 60% of the pharmacists reported on palliative care research to a scientific society. Seventy percent of the pharmacists reported some level of contribution to a palliative care team, whereas 16% reported that they did not contribute, with the main perceived reasons for no contribution listed as insufficient time (90%) and/or staff (68%).ConclusionIn Japan, pharmacists exercise a moderate level of clinical activity on palliative care teams. Many pharmacists believe that they contribute to such a team and generally place more emphasis on their educational and research roles compared with clinical work.     

Palliative care in Parkinson's disease: implications for neuroscience nursing.

Parkinson's disease (PD) is a chronic, progressive neurological disease affecting 1.5 million Americans. The modern success of pharmacology and deep-brain stimulation surgery to treat the motor symptoms of tremor, rigidity, and bradykinesia provide PD patients with longer lives and increased motor functioning. However, in the moderate and advanced stages of disease, the therapeutic benefits of pharmacology diminish and motor symptoms are more complicated to treat. The nonmotor symptoms of PD receive little attention in clinical settings, although they can lead to disability and caregiver burden. The Center to Advance Palliative Care advocates applying the principles of palliative care to chronic disease. Likewise, the World Health Organization has redefined palliative care to include life-threatening illness. The Parkinson's Disease Model of Care (PDMC) takes the precepts of palliative care and presents a model for the neuroscience nurse to use in individual care planning across the trajectory of disease. The PDMC guides the nurse in providing relief from suffering for PD patients and their families, from diagnosis through bereavement, with an emphasis on advance care planning.     

HALOPERIDOL FOR NAUSEA AND VOMITING

ABSTRACT.?

Timely and important studies are reviewed and commentaries provided by leading palliative care clinicians. Symptoms, interventions, and treatment-related adverse events addressed in this issue are haloperidol for nausea and vomiting; transdermal fentanyl and cachexia; drugs impact on opioid efficacy; denosumab for bone metastases; and cognitive behavioral insomnia therapy.     

Efficacy and undesirable effects of corticosteroid therapy experienced by palliative care specialists in Japan: a nationwide survey

BACKGROUND AND METHODS: Corticosteroids are commonly used for symptom relief in the treatment of patients with advanced cancer. Consistent efficacy of corticosteroid treatment in palliative care remains controversial. A cross-sectional anonymous survey was mailed to representative managing physicians in certified palliative care units in Japan to clarify the physician-perceived efficacy of steroid treatment on anorexia, fatigue, and dyspnea in terminal cancer patients, to clarify physicians' experience of side effects of corticosteroid use, and to determine the Japanese palliative care physician-reported predictive factors for efficacy and lack of efficacy. RESULTS AND CONCLUSIONS: Many Japanese palliative care specialists perceived that corticosteroids are effective for each of the symptoms, are aware of the prevalence and importance of serious adverse effects, and predict the effectiveness of steroid therapy by etiological factors.     

The use of haloperidol and associated complications in the agitated, acutely ill pediatric burn patient

The use of haloperidol to induce sedation and control agitation in the acutely ill adult patient has been well documented. There are few reports, however, of the use of this neuroleptic agent to control the severe delirium and agitation that may occur in critically ill pediatric patients or acute pediatric patients suffering from burn wounds. We assessed the effectiveness and safety of the use of haloperidol by completing a retrospective chart review of 855 acutely ill children treated consecutively during the period from April 1999 to May 2002, during which time 26 children received haloperidol. The safe use of haloperidol was assessed by documenting any adverse effects or reactions observed after the administration of the drug. Of patients given haloperidol, 23% had adverse effects. This result suggests that the use of haloperidol to treat the acutely agitated and delirious pediatric burn patients is fraught with a number of difficulties and is not completely safe and effective.     

Palliation and liver failure: palliative medications dosage guidelines

Palliation of symptoms is important in a variety of conditions, both malignant and nonmalignant. These symptoms may be present in patients with chronic or acute liver failure. However, to date there is a notable lack of reliable information on the use of medications that are commonly required in the palliative care of these patients. To facilitate care, a literature review was conducted with extensive searches of MEDLINE and Micromedex as well as reviews of the major textbooks of pharmacology, palliative care, gastroenterology and hepatology. A table is presented that includes medications organized in groupings of functional importance in palliative medicine such as opioids, antiarrhythmics, antidepressants, aperients, and other medications as selected for use at a Sydney palliative care unit. Data have been collected on the pharmacologic half-life in normal liver function and in cirrhosis. The latter, where suitable data could be obtained, were divided into three subgroups, using the Child-Pugh criteria. The further development of this information may help limit difficulties in choice of medication and reduce potential complications and improve palliation.     

Risperidone versus haloperidol in the treatment of schizophrenia: a meta-analysis comparing their efficacy and safety

The aim of this study was to compare the shortterm clinical efficacy and safety of risperidone with haloperidol and placebo. A meta-analysis of seven published randomized double-blind controlled trials was carried out. Study quality was assessed. The proportion of patients failing to reach at least 20% improvement on the positive and negative syndrome scale (PANSS) or brief psychiatric rating scale (BPRS), the proportion of patients discontinuing treatment because of adverse effects and the number of patients who needed antiparkinsonian medication were abstracted for use as outcome measures.
Treatment failure was present in 50% of risperidone-treated patients compared to 66% in those treated with haloperidol and 83% in those treated with placebo. It would be necessary to treat 11 patients with risperidone to prevent one treatment failure in those patients treated with haloperidol (Odds ratio (OR) = 0.74, 95% CI of 0.58-0.94, P =0.02). Pooling of the three multicentre trials which included placebo as a treatment arm, showed that one in three patients treated with risperidone 4–16 mg/day (OR=0.22, 95% CI of 0.13-0.39, P <0.00001) and one in six treated with haloperidol 10–20 mg/day (OR=0.44, 95% CI of 0.22-0.84, P =0.02) would derive significant benefit. Moreover, there was a highly significant greater need for anticholinergic medication due to extrapyramidal symptoms (EPS) in the haloperidol-treated patients compared to risperidone (OR=0.54, 95% CI of 0.42-0.70, P <0.00001). In conclusion, risperidone seems to be more effective and causes less EPS than haloperidol, as suggested by the significantly lower requirement for antiparkinsonian medication.     

Physical compatibility of binary and ternary mixtures of morphine and methadone with other drugs for parenteral administration in palliative care

The parenteral administration of combinations of drugs is often necessary in palliative medicine, particularly in the terminal stage of life, when patients are no longer able to take medication orally. The use of infusers to administer continuous subcutaneous infusions is a well-established practice in the palliative care setting and enables several drugs to be given simultaneously, avoiding the need for repeated administrations and the effects of peaks and troughs in the doses of medication. The method is also appreciated by patients and caregivers in the home care setting because the devices and infusion sites are easy to manage. Despite their frequent use, however, the mixtures of drugs adopted in clinical practice are sometimes not supported by reliable data concerning their chemical and physical compatibility. The present study investigates the chemical compatibility of binary mixtures (morphine with ketorolac) and the physical compatibility of binary (morphine or methadone with ketorolac) or ternary mixtures (morphine with ketorolac and/or haloperidol, and/or dexamethasone, and/or metoclopramide, and/or hyoscine butylbromide) with a view to reducing the aleatory nature of the empirical use of such combinations, thereby increasing their safety and clinical appropriateness.     

Atypical antipsychotics for the treatment of ICU delirium

Delirium is commonly described in critically ill patients as 1 factor contributing to increased length of intensive care unit and hospital stay, secondary complications, and increased mortality. Initial screening tools for delirium in hospitalized patients are generally easy to use; however, many centers have struggled with implementing these tools in a consistent and systematic manner. Haloperidol has traditionally been prescribed as the primary agent of choice for the treatment of delirium in critically ill patients. Clinicians have been challenged to consider alternative agents due to adverse effects such as extrapyramidal symptoms, QTc prolongation, and possible torsades de pointes with haloperidol use. The atypical antipsychotics are attractive alternatives to haloperidol with improved safety profiles but are flawed by limited data to support dosing and efficacy in this patient population. Future studies that provide large, prospective, double-blinded, placebo-controlled data to support the implementation of these agents as standard therapy over haloperidol are needed.     

Symptom Control and Palliative Care in Chile

As in other developed and developing countries, the most common chronic disorders affecting the Chilean population are cardiovascular disease, cancer, cirrhosis, diabetes, chronic obstructive pulmonary disease and external injuries. Availability of oncology services is not extensive and there are no academic programs to adequately train practitioners in either palliative medicine or comprehensive palliative care for allied health professionals including nurses, psychologists and chaplains. Major efforts have been made to incorporate palliative care as an important health care focus in the last decade and in the development of effective policies for opioid availability. Chile now meets 84% of the 17 criteria outlined by the World Health Organization and the International Narcotics Control Board for opioid availability. Postgraduate medical education in symptom control, clinical use of opioids and end-of-life care remains relatively poor as judged by the results of a questionnaire administered to 158 resident physicians at the Pontificia Universidad Católica de Chile. Improvements in symptom control and the development of palliative care in Chile will depend on the effective assessment of symptom control effectiveness and improved education and training of health professionals in clinical pharmacology, symptom control, clinical ethics, and end-of-life care.     

Symptom control and palliative care in Chile

As in other developed and developing countries, the most common chronic disorders affecting the Chilean population are cardiovascular disease, cancer, cirrhosis, diabetes, chronic obstructive pulmo- nary disease and external injuries. Availability of oncology services is not extensive and there are no academic programs to adequately train practitioners in either palliative medicine or comprehensive palliative care for allied health professionals including nurses, psychologists and chaplains. Major efforts have been made to incorporate palliative care as an important health care focus in the last decade and in the development of effective policies for opioid availability. Chile now meets 84% of the 17 criteria outlined by the World Health Organization and the International Narcotics Control Board for opioid availability. Postgraduate medical education in symptom control, clinical use of opioids and end-of-life care remains relatively poor as judged by the results of a questionnaire administered to 158 resident physicians at the Pontificia Universidad Católica de Chile. Improvements in symptom control and the development of palliative care in Chile will depend on the effective assessment of symptom control effectiveness and improved education and training of health professionals in clinical pharmacology, symptom control, clinical ethics, and end-of-life care.     

Evidence-Based Review Of Pharmacotherapy For Acute Agitation. Part 2: Safety

Background

The management of acute agitation in the emergency department often requires the administration of rapid-acting antipsychotic agents. However, there are few comparative studies and little guidance regarding the risks associated with use of such drugs in the acute setting.

Pharmacologic treatment of schizophrenia.

The literature on the pharmacologic treatment of schizophrenia and schizoaffective disorders is reviewed (116 references). All clinically active antipsychotic drugs share the ability to block postsynaptic dopamine receptors in the central nervous system. Their potencies vary, chlorpromazine and thioridazine being the least potent and fluphenazine and haloperidol the most potent. The adverse effects of the neuroleptics include acute dystonia, parkinsonian symptoms (extrapyramidal symptoms), akathisia, tardive dyskinesia, and tardive dystonia. When used at equipotent doses, all classic neuroleptics now available are equally effective in the treatment of schizophrenia. Choice of drug is based on adverse effects and patient response. The neuroleptics are effective in most acute exacerbations of schizophrenia and for the prevention or mitigation of relapse. Their effects are more pronounced on the positive symptoms of schizophrenia, such as hallucinations, delusions, disordered thinking, and paranoia, than on the negative symptoms, such as deficits in social interaction, emotional expression, and motivation. Strategies for acute and maintenance treatment and for the management of treatment-resistant patients are reviewed. The pharmacology and clinical use of the newer atypical neuroleptics, particularly clozapine, and their adverse effects are discussed.     

Acute confusional states in patients with advanced cancer.

In 39 of 100 cancer patients admitted to the palliative care unit at Edmonton General Hospital, the presence of delirium during their last week of life required psychotropic drug treatment. In 10 of the 39 delirious patients, symptoms were only controllable by sedation; this was achieved in 9 patients by a continuous subcutaneous infusion of midazolam. Although haloperidol is considered to be the treatment of choice in agitated, delirious cancer patients, our data suggest that palliative care treatment strategies for these patients may be different.     

Acute extrapyramidal syndrome in Cebus monkeys: development mediated by dopamine D2 but not D1 receptors

The present study assessed the role of dopamine D1 and D2 receptors in the production of an extrapyramidal syndrome (EPS) in Cebus apella monkeys. Previous studies have shown the development of EPS in both old and new world monkeys with haloperidol administration. We now report that repeated weekly administration of a selective D1 antagonist, SCH 23390, does not produce this syndrome in cebus monkeys. Cebus monkeys were treated with either vehicle (n = 6), the specific D2 antagonist haloperidol (0.3 mg/kg p.o., n = 9) or the specific D1 antagonist SCH 23390 (10.0 mg/kg p.o., n = 9) once a week for approximately 1 year and behavioral effects were observed and scored. The drug doses used in this study produced similar sedative scores when given acutely and sedation increased over the first 12 weeks of the study for both treatment groups. However, by the 12th week of dosing with haloperidol all the monkeys showed a profound EPS characterized by limb extensions, head pushing, tongue protrusions and sometimes severe biting movements. In contrast, none of the SCH 23390-treated monkeys showed any abnormal movements, suggesting D1 antagonists have a low EPS side-effect liability. The profile of the incidence of EPS seen with classical neuroleptic drugs in cebus monkeys and their blockade of EPS by anticholinergic drugs mimics the profile seen in humans. The models presented appear to be predictive of the production of the EPS in humans and could be used to screen neuroleptics for EPS liability. Furthermore, the EPS is probably due to the selective blockade of dopamine D2 receptors with its associated enhancement of cholinergic neurotransmission.(ABSTRACT TRUNCATED AT 250 WORDS)