JOURNAL OF PALLIATIVE MEDICINE Volume 18, Number 2, 2015 ª Mary Ann Liebert, Inc. DOI: 10.1089/jpm.2014.0375
Letters to the Editor
Midazolam in Palliative Care: At What Cost? Katherine Clark, MB, BS, FRACP1,2 and David Currow, PhD, MPH 3
Dear Editor: A review of the most prescribed injectable medications over a 12-month period in a 17-bed inpatient palliative care unit in regional New South Wales highlighted the frequency with which midazolam was used (see Table 1). While this is likely to reflect usual practice in Australian palliative care units, the evidence that supports the benefits and harms associated with the frequent use of this medication remains less than robust. One of the reasons for the frequent use of midazolam is that Australian clinical guidelines1 recommend it as the medication of choice for a number of situations including the palliation of anxiety, terminal crisis (e.g., acute airway obstruction, acute hemorrhage), seizures, delirium, and terminal agitation. The benefits attributed to midazolam include rapid onset and a relatively short duration of action with a half-life of two to five hours. This is increased when administered by continuous infusion. A well-documented effect of benzodiazepines is their impact on the acquisition and incorporation of new material into memory. A failure to incorporate memory results in a situation known as antegrade amnesia. Such memory loss is most likely to occur when the benzodiazepines with affinity to binding sites such as alprazolam, lorazepam, clonazepam, and midazolam are used.2 While there is a higher dose effect with the first three agents, the amnesic effects of midazolam have been observed when doses as low as 5mg are administered.3 However, despite this documented amnesic effect of low-dose midazolam in anesthesia, the real impact of midazolam on palliative care patients’ cognition has not been assessed. This is a knowledge gap that must be addressed, particularly given the recommendation that midazolam is an effective agent in the palliation of anxiety, even when people are not facing imminent death. Anxiety is a common problem among people living with life-limiting illnesses.4 Regardless of prognosis, it remains important to diagnose the anxiety disorder and implement appropriate management. Initially, this must be to engage with people, allowing them to articulate
1 2 3
their concerns and perhaps collaboratively developing practical solutions.5,6 While people may seemingly be able to participate in these conversations while receiving low-dose midazolam, the pharmacology of the medication raises the issue of whether people are actually able to build a memory of the interaction. Although speculative, it is possible to hypothesize that in the absence of capacity to store the memory of therapeutic discussions people may remain at risk of perpetual anxiety and distress. Previous observers have highlighted that people considering end-of-life treatment prefer to have their symptoms as well controlled as possible while remaining as alert as possible.7 While in times of life-threatening crises this may not be the case, at other times this must be respected. If there is a real commitment to providing patient-centered care at the end of life, the costs to the population we are serving of regularly prescribing midazolam must be investigated further.
Table 1. Injectable Medications Supplied in Palliative Care Unit September 2013 to September 2014 Medication and dosage Midazolam 5mg/ml Morphine 5mg/ml Hydromorphone 2mg/ml Hydromorphone 10mg/ml Levomepromazine 25mg/ml Morphine 10mg/ml Morphine 30mg/ml Clonazepam 1mg/ml Fentanyl 100mcg/2ml Morphine 120mg/1.5ml Morphine 15mg/ml Hydromorphone 50mg/5ml
Department of Palliative Care, Calvary Mater Newcastle, Newcastle, NSW, Australia. School of Medicine and Public Health, University of Newcastle, Newcastle, NSW, Australia. Discipline of Supportive and Palliative Care, Flinders University, Daw Park, South Australia, Australia.
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LETTERS TO THE EDITOR References
1. Palliative Care Expert Groups. Therapeutic Guidelines Limited: palliative care. Version 3. Melbourne: 2010. 2. Mejo S: Anterograde amnesia linked to benzodiazepines. Nurse Pract 1992;17:49–50. 3. Bulach R, Myles PS, Russnak M: Double-blind randomized controlled trial to determine extent of amnesia with midazolam given immediately before general anaesthesia. Br J Anaesth 2005;94:300–305. 4. Kolva E, Rosenfeld B, Pessin H, et al.: Anxiety in terminally ill cancer patients. J Pain Symptom Manage 2011;42:691–701. 5. Anderson T, Watson M, Davidson R: The use of cognitive behavioural therapy techniques for anxiety and depression in hospice patients: A feasibility study. Palliat Med 2008;22:814–821. 6. National Institute for Clinical Excellence: Guidance on Cancer Services: Improving Supportive and Palliative Care
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for Adults with Cancer; the Manual. London: NICE, 2004 www.nice.org.uk/nicemedia/live/10893/28816/28816.pdf. (Last accessed October 7, 2014.) 7. Steinhauser K, Christakis N, Clipp E, et al.: Factors considered important at the end of life by patients, family, physicians, and other care providers. JAMA 2000;284:2476–2482.
Address correspondence to: Katherine Clark, MB, BS, FRACP Department of Palliative Care Calvary Mater Newcastle Edith Street Waratah, Newcastle NSW Australia 2298 E-mail: [email protected]
Copyright of Journal of Palliative Medicine is the property of Mary Ann Liebert, Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
Letters to the Editor
Midazolam in Palliative Care: At What Cost? Katherine Clark, MB, BS, FRACP1,2 and David Currow, PhD, MPH 3
Dear Editor: A review of the most prescribed injectable medications over a 12-month period in a 17-bed inpatient palliative care unit in regional New South Wales highlighted the frequency with which midazolam was used (see Table 1). While this is likely to reflect usual practice in Australian palliative care units, the evidence that supports the benefits and harms associated with the frequent use of this medication remains less than robust. One of the reasons for the frequent use of midazolam is that Australian clinical guidelines1 recommend it as the medication of choice for a number of situations including the palliation of anxiety, terminal crisis (e.g., acute airway obstruction, acute hemorrhage), seizures, delirium, and terminal agitation. The benefits attributed to midazolam include rapid onset and a relatively short duration of action with a half-life of two to five hours. This is increased when administered by continuous infusion. A well-documented effect of benzodiazepines is their impact on the acquisition and incorporation of new material into memory. A failure to incorporate memory results in a situation known as antegrade amnesia. Such memory loss is most likely to occur when the benzodiazepines with affinity to binding sites such as alprazolam, lorazepam, clonazepam, and midazolam are used.2 While there is a higher dose effect with the first three agents, the amnesic effects of midazolam have been observed when doses as low as 5mg are administered.3 However, despite this documented amnesic effect of low-dose midazolam in anesthesia, the real impact of midazolam on palliative care patients’ cognition has not been assessed. This is a knowledge gap that must be addressed, particularly given the recommendation that midazolam is an effective agent in the palliation of anxiety, even when people are not facing imminent death. Anxiety is a common problem among people living with life-limiting illnesses.4 Regardless of prognosis, it remains important to diagnose the anxiety disorder and implement appropriate management. Initially, this must be to engage with people, allowing them to articulate
1 2 3
their concerns and perhaps collaboratively developing practical solutions.5,6 While people may seemingly be able to participate in these conversations while receiving low-dose midazolam, the pharmacology of the medication raises the issue of whether people are actually able to build a memory of the interaction. Although speculative, it is possible to hypothesize that in the absence of capacity to store the memory of therapeutic discussions people may remain at risk of perpetual anxiety and distress. Previous observers have highlighted that people considering end-of-life treatment prefer to have their symptoms as well controlled as possible while remaining as alert as possible.7 While in times of life-threatening crises this may not be the case, at other times this must be respected. If there is a real commitment to providing patient-centered care at the end of life, the costs to the population we are serving of regularly prescribing midazolam must be investigated further.
Table 1. Injectable Medications Supplied in Palliative Care Unit September 2013 to September 2014 Medication and dosage Midazolam 5mg/ml Morphine 5mg/ml Hydromorphone 2mg/ml Hydromorphone 10mg/ml Levomepromazine 25mg/ml Morphine 10mg/ml Morphine 30mg/ml Clonazepam 1mg/ml Fentanyl 100mcg/2ml Morphine 120mg/1.5ml Morphine 15mg/ml Hydromorphone 50mg/5ml
Department of Palliative Care, Calvary Mater Newcastle, Newcastle, NSW, Australia. School of Medicine and Public Health, University of Newcastle, Newcastle, NSW, Australia. Discipline of Supportive and Palliative Care, Flinders University, Daw Park, South Australia, Australia.
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Ampules 3900 2220 2094 1909 1815 1379 1051 1020 890 612 543 535
LETTERS TO THE EDITOR References
1. Palliative Care Expert Groups. Therapeutic Guidelines Limited: palliative care. Version 3. Melbourne: 2010. 2. Mejo S: Anterograde amnesia linked to benzodiazepines. Nurse Pract 1992;17:49–50. 3. Bulach R, Myles PS, Russnak M: Double-blind randomized controlled trial to determine extent of amnesia with midazolam given immediately before general anaesthesia. Br J Anaesth 2005;94:300–305. 4. Kolva E, Rosenfeld B, Pessin H, et al.: Anxiety in terminally ill cancer patients. J Pain Symptom Manage 2011;42:691–701. 5. Anderson T, Watson M, Davidson R: The use of cognitive behavioural therapy techniques for anxiety and depression in hospice patients: A feasibility study. Palliat Med 2008;22:814–821. 6. National Institute for Clinical Excellence: Guidance on Cancer Services: Improving Supportive and Palliative Care
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for Adults with Cancer; the Manual. London: NICE, 2004 www.nice.org.uk/nicemedia/live/10893/28816/28816.pdf. (Last accessed October 7, 2014.) 7. Steinhauser K, Christakis N, Clipp E, et al.: Factors considered important at the end of life by patients, family, physicians, and other care providers. JAMA 2000;284:2476–2482.
Address correspondence to: Katherine Clark, MB, BS, FRACP Department of Palliative Care Calvary Mater Newcastle Edith Street Waratah, Newcastle NSW Australia 2298 E-mail: [email protected]
Copyright of Journal of Palliative Medicine is the property of Mary Ann Liebert, Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
