JOURNAL OF PALLIATIVE MEDICINE Volume 17, Number 9, 2014 ª Mary Ann Liebert, Inc. DOI: 10.1089/jpm.2013.0610
Prescribing for Nausea in Palliative Care: A Cross-Sectional National Survey of Australian Palliative Medicine Doctors Timothy H.M. To, BM, BS, FRACP,1,2 Meera Agar, MBBS, FRACP, FAChPM, MPC, PhD,1,3 Patsy Yates, PhD, MSocSc, BA,4 and David C. Currow, BMed, MPH, FRACP1
Abstract
Background: Nausea can be a debilitating symptom for patients with a life-limiting illness. While addressing reversible components, nonpharmacological strategies and antiemetics are the main therapeutic option. The choice of medication, dose, and route of administration remain highly variable. Objective: The aim of this study was to codify the current clinical approaches and quantify any variation found nationally. Methods: A cross-sectional study utilizing a survey of palliative medicine clinicians examined prescribing preferences for nausea using a clinical vignette. Respondent characteristics, the use of nonpharmacological interventions, first- and second-line antiemetic choices, commencing and maximal dose, and time to review were collected. Results: Responding clinicians were predominantly working in palliative medicine across a range of settings with a 49% response rate (105/213). The main nonpharmacological recommendation was ‘‘small, frequent snacks.’’ Metoclopramide was the predominant first-line agent (69%), followed by haloperidol (26%), while second-line haloperidol was the predominant agent (47%), with wide variation in other nominated agents. Respondents favoring metoclopramide as first-line tended to use haloperidol second-line (65%), but not vice versa. Maximal doses for an individual antiemetic varied up to tenfold. Conclusion: For nausea, a commonly encountered symptom in palliative care, clinicians’ favored metoclopramide and haloperidol; however, after these choices, there was large variation in antiemetic selection. While most clinicians recommended modifying meal size and frequency, use of other nonpharmacological therapies was limited. Introduction
N
ausea, with or without vomiting, can be persistent, distressing, and disabling for people with a life-limiting illness. Therapeutic strategies include addressing reversible components, nonpharmacological strategies, antiemetics and, in a small number of cases, surgery in bowel obstruction. Antiemetics work through effects on neurotransmitters including dopamine, histamine, acetylcholine, and serotonin. Across palliative care, there is variability in clinical practice, even for frequently encountered symptoms. Although some variation is of no consequence, at times it may lead to unwarranted differences in clinical outcomes. In 2010, the Australian Palliative Care Clinical Studies Collaborative (PaCCSC) performed a cross-sectional survey
examining prescribing practices for a number of frequently encountered symptoms. This study examines the prescribing preferences for the treatment of nausea in palliative care patients. The aim of the study was to codify the current clinical approaches and quantify any variation found nationally. Methods Study setting
Specialist palliative care services (SPCS) in Australia span a range of service delivery models, from large multidisciplinary teams covering all care within a geographical region through to single clinical nurses in small rural locations. SPCS may service public and private hospitals with inpatient and/or consultative services, free-standing hospice/palliative care units,
1
Discipline, Palliative and Supportive Services, Flinders University, Bedford Park, Australia. Southern Adelaide Palliative Services, Repatriation General Hospital, Daw Park, Australia. 3 Palliative Care, Braeside Hospital, New South Wales, Australia. 4 Faculty of Health Sciences, Queensland University of Technology, Brisbane, Australia. Accepted April 7, 2014. 2
1032
PRESCRIBING FOR NAUSEA IN PALLIATIVE CARE
outpatient clinics, and community care teams. SPCS may be the primary health provider but most commonly works in consultation to support general practitioners, other specialists, and community services. Study design and respondents
This cross-sectional study was part of a larger survey examining prescribing, including off-label prescribing1 and preferences for nausea, malignant bowel obstruction, and pain. A single invitation to participate on paper or online was sent in July 2010 to all Australian-based members of the Australia and New Zealand Society of Palliative Medicine (ANZSPM), a society open to doctors with an interest in palliative medicine. Membership does not require specialist qualifications in palliative medicine; however the majority are palliative medicine specialists. The survey included respondents’ demographics, scope of palliative medicine practice, and level of experience. Using the standard clinical vignette below, respondents were asked if they would use any of four nonpharmacological interventions, and their first- and second-line medication for nausea, commencing and maximum dose, and time to review of effect. ‘‘Mr. T is a 72-year-old man with pancreatic cancer with local spread, and metastatic liver disease. He has a biliary stent in situ. He has mildly abnormal aspartate aminotransferase (AST) and alanine aminotransferase (ALT), but normal bilirubin. His other electrolytes are normal. He describes continuous nausea, worse with the sight and smell of food. He is not vomiting and bowels are working normally. He is currently on a stable dose of sustained release opioids, aperients, and an antihypertensive.’’
Data analysis
Data were analyzed using PWAS 18.0 (SPSS Corp. Inc., Chicago, IL). Descriptive statistics are reported. Categorical variables were compared using chi square. The study complies with reporting guidelines for surveys.2 Ethical approval for this study was granted by the Flinders University Social and Behavioural Research Ethics Committee. Consent was implied by participation. Results
In July 2010, 213 of 220 registered ANZSPM members had a valid contact address, and of these, 105 (49%) provided valid responses for analysis. Respondent characteristics are summarized in Table 1. Not all respondents answered all questions. Of note, 68% had palliative medicine training and 91% had been practicing medicine for more than 10 years, and 78% had been practicing palliative medicine for more than 5 years. Most respondents worked in multiple care settings—most commonly hospital liaison (64%) and hospice/palliative care units (55%). Nonpharmacological management options
For nonpharmacological measures, 94/100 (94%) of respondents would offer small, frequent snacks, relaxation techniques 46/91 (51%), liquid/pureed foods 41/92 (45%), and cognitive behavioral therapy 17/85 (20%).
1033
Table 1. Respondent Characteristics (n = 105) n (%) Gender Male Female Age 20–30 years 31–40 years 41–50 years 51–60 years >60 years Training Palliative medicine General practitioner Medical oncology Radiation oncology Other Years since specialization 0–5 years 6–10 years 11–15 years 16–20 years 21–25 years >25 years Duration of practice of palliative medicine 0–5 years 6–10 years 11–20 years >20 years Practice Acute hospital inpatient Acute hospital consultative/liaison Community Outpatient Hospice/palliative care unit Other
40 (39) 64 (62) 1 26 32 28 17
(1) (25) (31) (27) (16)
70 18 4 2 9
(68) (18) (4) (2) (9)
28 29 15 8 8 4
(30) (32) (16) (9) (9) (4)
23 18 47 17
(22) (17) (45) (16)
37 67 49 48 58 5
(35) (64) (46) (46) (55) (5)
69% chose metoclopramide and 26% haloperidol. For second-line therapy, 47% chose haloperidol with much wider variation in the other nominated agents. Training in palliative medicine did not influence the choice of first-line therapy (metoclopramide with training versus without, 82% versus 65%, p = 0.11; haloperidol 15% versus 30%, p = 0.13). When first- and second-line medications were combined, 73% were either metoclopramide or haloperidol (see Fig. 1). For respondents who nominated metoclopramide as their first-line therapy, haloperidol was the predominant secondline medication (see Fig. 2). For respondents who nominated haloperidol first-line, there was wide variation on second-line medications (see Fig. 3). No relationship was found between first-line choice and years of experience; however there was difference in first-line choice in those practicing in New South Wales (NSW) (n = 24) compared with the rest of Australia (n = 74) (metoclopramide 35% versus 78%; haloperidol 65% versus 15%, p < 0.01). Choice of dose
Choice of medication
Ninety-eight respondents (93%) provided first- and second-line antiemetic agent preferences. For first-line therapy,
Even for commonly used antiemetics in palliative care, there was up to tenfold variation in the maximal doses nominated (see Table 2). No relationship between dose of a
1034
TO ET AL.
FIG. 1.
Medication choices for nausea in palliative care.
particular antiemetic and years of experience or training in palliative medicine was found. Time to review
The majority of respondents would review response by 24 hours (59%), with a further 28% reviewing by 48 hours. Discussion
When clinicians with an interest in palliative medicine were presented with an identical clinical vignette on a palliative care patient with nausea, there was wide variation in medication and dose choices. The response rate of 49% and responder characteristics mean these data are likely to represent a broad cross-section of Australian practitioners. Many current reviews and guidelines support a mechanistic approach to nausea management, targeting a presumed etiology for nausea to a medication’s dominant mechanism of
FIG. 2.
action; examples include the prokinetic metoclopramide for patients with gastric stasis, or serotonin receptor antagonist for chemotherapy-induced nausea.3–6 However it must be noted that the evidence to support the use of antiemetics in palliative care patients is limited, with few controlled clinical trials outside of chemotherapy-induced nausea and vomiting. Furthermore, in practice it is often difficult to determine a single etiology for nausea, and frequently it will be multifactorial. Even if a single etiology has been identified, few of the medications used actually target a single receptor, but have effects across multiple receptors. Therefore it is recognizd that an empiric approach based on prescriber preference is a reasonable approach.3,5 This study did not attempt to determine a clinician’s preference for the mechanistic or empirical approach to treatment for nausea. In the absence of high-quality evidence for nausea management in palliative care patients, variation in medication selection and dosing for a single clinical vignette is not
Treatment for nausea after metoclopramide in palliative care (n = 68).
PRESCRIBING FOR NAUSEA IN PALLIATIVE CARE
FIG. 3.
Treatment for nausea after haloperidol in palliative care (n = 25).
surprising. The preference for dopamine antagonists and the interquartile range of maximal doses seem reasonable. However the choice of other medications as first- and secondline choices, and the more extreme maximal dose ranges seen (metoclopramide and haloperidol dose ranges varied by sixfold and tenfold, respectively), are of concern given the uncertain benefit and potential for increasing toxicity with increasing dose. Given the majority of these respondents had training in palliative medicine, would there be even greater variation if the same questions were asked of clinicians from outside palliative care? Interestingly, while many respondents prescribing metoclopramide first-line went on to prescribe haloperidol (65%), metoclopramide was rarely used second-line to haloperidol (12%). The most common second-line agent after haloperidol was cyclizine, an antihistamine. The choice of cyclizine is intriguing, given that at the time of the study, cyclizine was not registered for use in Australia and thus required extra administrative steps to access. Such prescribing also raises issues around access and prescribing appropriately in the context of national licensing and subsidy regulations, as seen with off-label prescribing.1 The reason for different prescribing preferences in NSW, a state representing one-third of the Australian population, is unclear.
Table 2. Nominated Medications for Nausea and Dose, First- and Second-Line Combined Medication (number of respondents) Metoclopramide (n = 73) Haloperidol (n = 71) Dexamethasone (n = 21) Cyclizine (n = 14)
Median maximal dose Interquartile per day (mg) range (mg)
Range (mg)
80
47.5–80.0
40–240
5
4–5
1.5–15.0
8
8–16
4–16
150–250
100–300
175
1035
The variations in antiemetic prescribing practices highlight the need for well-designed clinical studies to evaluate the benefits and toxicities of individual antiemetics and doses with carefully selected comparators. Furthermore there needs to be comparative effectiveness studies of current antiemetics. Equally, the mechanistic versus empiric approaches need to be subjected to similarly robust evaluation. Yates et al., in conjunction with Palliative Care Clinical Studies Collaborative (PaCCSC), are currently running two studies evaluating nausea pharmacotherapy—one is a mechanistic versus empirical approach to antiemetic prescribing for nausea (ANZCTR 12610000481077) and the other looks at treatment of refractory nausea (ANZCTR 12610000482066). Given many of the antiemetics used in palliative care are already in widespread use, high-quality pharmacovigilance programs to assess net clinical effect in real-world clinical practice are also required.7–9 Limitations
This study relies on clinician self-report, not actual practice. While using a patient vignette only provides a limited picture of the clinical situation, each respondent was presented with the same information. This study focussed on pharmacological strategies for symptom management, and did not address other confounders such as psychological distress. The list of nonpharmacological therapies included in the survey was also limited. It was not specified whether second-line treatment would be added to or replace first-line treatment. Conclusion
This study examines prescribing preferences for nausea in palliative medicine. The dopamine antagonists metoclopramide and haloperidol were preferred agents; however after these, there was wide variation in the treatment given. Nearly all respondents recommended changes to size and frequency of meals, although use of other nonpharmacological therapies was not common.
1036 Acknowledgments
The Australian Palliative Care Clinical Studies Collaborative is supported by funding from the Palliative Care Branch of the Australian government’s Department of Health. We thank all the responders to the prescribing preferences survey. Author Disclosure Statement
This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. The authors declare that no competing financial interests exist. References
1. To TH, Agar M, Shelby-James T, et al.: Off-label prescribing in palliative care: A cross-sectional national survey of palliative medicine doctors. Palliat Med 2013;27:320–328. 2. Kelley K, Clark B, Brown V, Sitzia J: Good practice in the conduct and reporting of survey research. Int J Qual Health Care 2003;15:261–266. 3. Glare P, Miller J, Nikolova T, Tickoo R: Treating nausea and vomiting in palliative care: A review. Clin Interv Aging 2011;6:243–259. 4. Palliative Care Expert Group: Therapeutic Guidelines: Palliative Care, 3rd ed. Melbourne: Therapeutic Guidelines Limited, 2010.
TO ET AL.
5. NCCN: Clinical Practice Guidelines in Oncology: Palliative Care Version 1. NCCN, 2013. 6. Nausea / Vomiting in Palliative Care. http://www.palliative careguidelines.scot.nhs.uk/documents/NauseaVomiting.pdf (last accessed June 3, 2013). 7. Currow DC, Rowett D, Doogue M, To TH, Abernethy AP: An international initiative to create a collaborative for pharmacovigilance in hospice and palliative care clinical practice. J Palliat Med 2012;15:282–286. 8. Currow DC, Vella-Brincat J, Fazekas B, et al.: Pharmacovigilance in hospice/palliative care: Rapid report of net clinical effect of metoclopramide. J Palliat Med 2012;15: 1071–1075. 9. Crawford GB, Agar MM, Quinn SJ, et al.: Pharmacovigilance in hospice/palliative care: Net effect of haloperidol for delirium. J Palliat Med 2013;16:1335–1341.
Address correspondence to: Timothy H.M. To, BM, BS, FRACP Department of Rehabilitation and Aged Care Repatriation General Hospital Daw Park, South Australia 5041 E-mail: [email protected]
Prescribing for Nausea in Palliative Care: A Cross-Sectional National Survey of Australian Palliative Medicine Doctors Timothy H.M. To, BM, BS, FRACP,1,2 Meera Agar, MBBS, FRACP, FAChPM, MPC, PhD,1,3 Patsy Yates, PhD, MSocSc, BA,4 and David C. Currow, BMed, MPH, FRACP1
Abstract
Background: Nausea can be a debilitating symptom for patients with a life-limiting illness. While addressing reversible components, nonpharmacological strategies and antiemetics are the main therapeutic option. The choice of medication, dose, and route of administration remain highly variable. Objective: The aim of this study was to codify the current clinical approaches and quantify any variation found nationally. Methods: A cross-sectional study utilizing a survey of palliative medicine clinicians examined prescribing preferences for nausea using a clinical vignette. Respondent characteristics, the use of nonpharmacological interventions, first- and second-line antiemetic choices, commencing and maximal dose, and time to review were collected. Results: Responding clinicians were predominantly working in palliative medicine across a range of settings with a 49% response rate (105/213). The main nonpharmacological recommendation was ‘‘small, frequent snacks.’’ Metoclopramide was the predominant first-line agent (69%), followed by haloperidol (26%), while second-line haloperidol was the predominant agent (47%), with wide variation in other nominated agents. Respondents favoring metoclopramide as first-line tended to use haloperidol second-line (65%), but not vice versa. Maximal doses for an individual antiemetic varied up to tenfold. Conclusion: For nausea, a commonly encountered symptom in palliative care, clinicians’ favored metoclopramide and haloperidol; however, after these choices, there was large variation in antiemetic selection. While most clinicians recommended modifying meal size and frequency, use of other nonpharmacological therapies was limited. Introduction
N
ausea, with or without vomiting, can be persistent, distressing, and disabling for people with a life-limiting illness. Therapeutic strategies include addressing reversible components, nonpharmacological strategies, antiemetics and, in a small number of cases, surgery in bowel obstruction. Antiemetics work through effects on neurotransmitters including dopamine, histamine, acetylcholine, and serotonin. Across palliative care, there is variability in clinical practice, even for frequently encountered symptoms. Although some variation is of no consequence, at times it may lead to unwarranted differences in clinical outcomes. In 2010, the Australian Palliative Care Clinical Studies Collaborative (PaCCSC) performed a cross-sectional survey
examining prescribing practices for a number of frequently encountered symptoms. This study examines the prescribing preferences for the treatment of nausea in palliative care patients. The aim of the study was to codify the current clinical approaches and quantify any variation found nationally. Methods Study setting
Specialist palliative care services (SPCS) in Australia span a range of service delivery models, from large multidisciplinary teams covering all care within a geographical region through to single clinical nurses in small rural locations. SPCS may service public and private hospitals with inpatient and/or consultative services, free-standing hospice/palliative care units,
1
Discipline, Palliative and Supportive Services, Flinders University, Bedford Park, Australia. Southern Adelaide Palliative Services, Repatriation General Hospital, Daw Park, Australia. 3 Palliative Care, Braeside Hospital, New South Wales, Australia. 4 Faculty of Health Sciences, Queensland University of Technology, Brisbane, Australia. Accepted April 7, 2014. 2
1032
PRESCRIBING FOR NAUSEA IN PALLIATIVE CARE
outpatient clinics, and community care teams. SPCS may be the primary health provider but most commonly works in consultation to support general practitioners, other specialists, and community services. Study design and respondents
This cross-sectional study was part of a larger survey examining prescribing, including off-label prescribing1 and preferences for nausea, malignant bowel obstruction, and pain. A single invitation to participate on paper or online was sent in July 2010 to all Australian-based members of the Australia and New Zealand Society of Palliative Medicine (ANZSPM), a society open to doctors with an interest in palliative medicine. Membership does not require specialist qualifications in palliative medicine; however the majority are palliative medicine specialists. The survey included respondents’ demographics, scope of palliative medicine practice, and level of experience. Using the standard clinical vignette below, respondents were asked if they would use any of four nonpharmacological interventions, and their first- and second-line medication for nausea, commencing and maximum dose, and time to review of effect. ‘‘Mr. T is a 72-year-old man with pancreatic cancer with local spread, and metastatic liver disease. He has a biliary stent in situ. He has mildly abnormal aspartate aminotransferase (AST) and alanine aminotransferase (ALT), but normal bilirubin. His other electrolytes are normal. He describes continuous nausea, worse with the sight and smell of food. He is not vomiting and bowels are working normally. He is currently on a stable dose of sustained release opioids, aperients, and an antihypertensive.’’
Data analysis
Data were analyzed using PWAS 18.0 (SPSS Corp. Inc., Chicago, IL). Descriptive statistics are reported. Categorical variables were compared using chi square. The study complies with reporting guidelines for surveys.2 Ethical approval for this study was granted by the Flinders University Social and Behavioural Research Ethics Committee. Consent was implied by participation. Results
In July 2010, 213 of 220 registered ANZSPM members had a valid contact address, and of these, 105 (49%) provided valid responses for analysis. Respondent characteristics are summarized in Table 1. Not all respondents answered all questions. Of note, 68% had palliative medicine training and 91% had been practicing medicine for more than 10 years, and 78% had been practicing palliative medicine for more than 5 years. Most respondents worked in multiple care settings—most commonly hospital liaison (64%) and hospice/palliative care units (55%). Nonpharmacological management options
For nonpharmacological measures, 94/100 (94%) of respondents would offer small, frequent snacks, relaxation techniques 46/91 (51%), liquid/pureed foods 41/92 (45%), and cognitive behavioral therapy 17/85 (20%).
1033
Table 1. Respondent Characteristics (n = 105) n (%) Gender Male Female Age 20–30 years 31–40 years 41–50 years 51–60 years >60 years Training Palliative medicine General practitioner Medical oncology Radiation oncology Other Years since specialization 0–5 years 6–10 years 11–15 years 16–20 years 21–25 years >25 years Duration of practice of palliative medicine 0–5 years 6–10 years 11–20 years >20 years Practice Acute hospital inpatient Acute hospital consultative/liaison Community Outpatient Hospice/palliative care unit Other
40 (39) 64 (62) 1 26 32 28 17
(1) (25) (31) (27) (16)
70 18 4 2 9
(68) (18) (4) (2) (9)
28 29 15 8 8 4
(30) (32) (16) (9) (9) (4)
23 18 47 17
(22) (17) (45) (16)
37 67 49 48 58 5
(35) (64) (46) (46) (55) (5)
69% chose metoclopramide and 26% haloperidol. For second-line therapy, 47% chose haloperidol with much wider variation in the other nominated agents. Training in palliative medicine did not influence the choice of first-line therapy (metoclopramide with training versus without, 82% versus 65%, p = 0.11; haloperidol 15% versus 30%, p = 0.13). When first- and second-line medications were combined, 73% were either metoclopramide or haloperidol (see Fig. 1). For respondents who nominated metoclopramide as their first-line therapy, haloperidol was the predominant secondline medication (see Fig. 2). For respondents who nominated haloperidol first-line, there was wide variation on second-line medications (see Fig. 3). No relationship was found between first-line choice and years of experience; however there was difference in first-line choice in those practicing in New South Wales (NSW) (n = 24) compared with the rest of Australia (n = 74) (metoclopramide 35% versus 78%; haloperidol 65% versus 15%, p < 0.01). Choice of dose
Choice of medication
Ninety-eight respondents (93%) provided first- and second-line antiemetic agent preferences. For first-line therapy,
Even for commonly used antiemetics in palliative care, there was up to tenfold variation in the maximal doses nominated (see Table 2). No relationship between dose of a
1034
TO ET AL.
FIG. 1.
Medication choices for nausea in palliative care.
particular antiemetic and years of experience or training in palliative medicine was found. Time to review
The majority of respondents would review response by 24 hours (59%), with a further 28% reviewing by 48 hours. Discussion
When clinicians with an interest in palliative medicine were presented with an identical clinical vignette on a palliative care patient with nausea, there was wide variation in medication and dose choices. The response rate of 49% and responder characteristics mean these data are likely to represent a broad cross-section of Australian practitioners. Many current reviews and guidelines support a mechanistic approach to nausea management, targeting a presumed etiology for nausea to a medication’s dominant mechanism of
FIG. 2.
action; examples include the prokinetic metoclopramide for patients with gastric stasis, or serotonin receptor antagonist for chemotherapy-induced nausea.3–6 However it must be noted that the evidence to support the use of antiemetics in palliative care patients is limited, with few controlled clinical trials outside of chemotherapy-induced nausea and vomiting. Furthermore, in practice it is often difficult to determine a single etiology for nausea, and frequently it will be multifactorial. Even if a single etiology has been identified, few of the medications used actually target a single receptor, but have effects across multiple receptors. Therefore it is recognizd that an empiric approach based on prescriber preference is a reasonable approach.3,5 This study did not attempt to determine a clinician’s preference for the mechanistic or empirical approach to treatment for nausea. In the absence of high-quality evidence for nausea management in palliative care patients, variation in medication selection and dosing for a single clinical vignette is not
Treatment for nausea after metoclopramide in palliative care (n = 68).
PRESCRIBING FOR NAUSEA IN PALLIATIVE CARE
FIG. 3.
Treatment for nausea after haloperidol in palliative care (n = 25).
surprising. The preference for dopamine antagonists and the interquartile range of maximal doses seem reasonable. However the choice of other medications as first- and secondline choices, and the more extreme maximal dose ranges seen (metoclopramide and haloperidol dose ranges varied by sixfold and tenfold, respectively), are of concern given the uncertain benefit and potential for increasing toxicity with increasing dose. Given the majority of these respondents had training in palliative medicine, would there be even greater variation if the same questions were asked of clinicians from outside palliative care? Interestingly, while many respondents prescribing metoclopramide first-line went on to prescribe haloperidol (65%), metoclopramide was rarely used second-line to haloperidol (12%). The most common second-line agent after haloperidol was cyclizine, an antihistamine. The choice of cyclizine is intriguing, given that at the time of the study, cyclizine was not registered for use in Australia and thus required extra administrative steps to access. Such prescribing also raises issues around access and prescribing appropriately in the context of national licensing and subsidy regulations, as seen with off-label prescribing.1 The reason for different prescribing preferences in NSW, a state representing one-third of the Australian population, is unclear.
Table 2. Nominated Medications for Nausea and Dose, First- and Second-Line Combined Medication (number of respondents) Metoclopramide (n = 73) Haloperidol (n = 71) Dexamethasone (n = 21) Cyclizine (n = 14)
Median maximal dose Interquartile per day (mg) range (mg)
Range (mg)
80
47.5–80.0
40–240
5
4–5
1.5–15.0
8
8–16
4–16
150–250
100–300
175
1035
The variations in antiemetic prescribing practices highlight the need for well-designed clinical studies to evaluate the benefits and toxicities of individual antiemetics and doses with carefully selected comparators. Furthermore there needs to be comparative effectiveness studies of current antiemetics. Equally, the mechanistic versus empiric approaches need to be subjected to similarly robust evaluation. Yates et al., in conjunction with Palliative Care Clinical Studies Collaborative (PaCCSC), are currently running two studies evaluating nausea pharmacotherapy—one is a mechanistic versus empirical approach to antiemetic prescribing for nausea (ANZCTR 12610000481077) and the other looks at treatment of refractory nausea (ANZCTR 12610000482066). Given many of the antiemetics used in palliative care are already in widespread use, high-quality pharmacovigilance programs to assess net clinical effect in real-world clinical practice are also required.7–9 Limitations
This study relies on clinician self-report, not actual practice. While using a patient vignette only provides a limited picture of the clinical situation, each respondent was presented with the same information. This study focussed on pharmacological strategies for symptom management, and did not address other confounders such as psychological distress. The list of nonpharmacological therapies included in the survey was also limited. It was not specified whether second-line treatment would be added to or replace first-line treatment. Conclusion
This study examines prescribing preferences for nausea in palliative medicine. The dopamine antagonists metoclopramide and haloperidol were preferred agents; however after these, there was wide variation in the treatment given. Nearly all respondents recommended changes to size and frequency of meals, although use of other nonpharmacological therapies was not common.
1036 Acknowledgments
The Australian Palliative Care Clinical Studies Collaborative is supported by funding from the Palliative Care Branch of the Australian government’s Department of Health. We thank all the responders to the prescribing preferences survey. Author Disclosure Statement
This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. The authors declare that no competing financial interests exist. References
1. To TH, Agar M, Shelby-James T, et al.: Off-label prescribing in palliative care: A cross-sectional national survey of palliative medicine doctors. Palliat Med 2013;27:320–328. 2. Kelley K, Clark B, Brown V, Sitzia J: Good practice in the conduct and reporting of survey research. Int J Qual Health Care 2003;15:261–266. 3. Glare P, Miller J, Nikolova T, Tickoo R: Treating nausea and vomiting in palliative care: A review. Clin Interv Aging 2011;6:243–259. 4. Palliative Care Expert Group: Therapeutic Guidelines: Palliative Care, 3rd ed. Melbourne: Therapeutic Guidelines Limited, 2010.
TO ET AL.
5. NCCN: Clinical Practice Guidelines in Oncology: Palliative Care Version 1. NCCN, 2013. 6. Nausea / Vomiting in Palliative Care. http://www.palliative careguidelines.scot.nhs.uk/documents/NauseaVomiting.pdf (last accessed June 3, 2013). 7. Currow DC, Rowett D, Doogue M, To TH, Abernethy AP: An international initiative to create a collaborative for pharmacovigilance in hospice and palliative care clinical practice. J Palliat Med 2012;15:282–286. 8. Currow DC, Vella-Brincat J, Fazekas B, et al.: Pharmacovigilance in hospice/palliative care: Rapid report of net clinical effect of metoclopramide. J Palliat Med 2012;15: 1071–1075. 9. Crawford GB, Agar MM, Quinn SJ, et al.: Pharmacovigilance in hospice/palliative care: Net effect of haloperidol for delirium. J Palliat Med 2013;16:1335–1341.
Address correspondence to: Timothy H.M. To, BM, BS, FRACP Department of Rehabilitation and Aged Care Repatriation General Hospital Daw Park, South Australia 5041 E-mail: [email protected]
