Pharmacist-Led Care in Palliative Settings: Using Anticholinergics Thoughtfully and Compassionately

The use of anticholinergic agents to manage terminal secretions, often referred to as the death rattle, remains a nuanced and evolving area of end-of-life care. While these medications are frequently used in hospice and palliative care settings to reduce secretion-related sounds that may be distressing to caregivers, their efficacy in improving patient comfort is less clear and often debated.

In this interview, Pharmacy Times spoke with Diana Violanti, PharmD, a clinical pharmacist specialist - supportive and palliative care at Roswell Park Comprehensive Cancer Center in Buffalo, New York, and Pamela S. Moore, PharmD, BCGP, a clinical lead pharmacist - pain and palliative care at Summa Health System in Akron, Ohio, about the practical considerations guiding anticholinergic selection, the optimal timing for intervention, and the risk-benefit balance in this vulnerable population. In advance of their discussion on this topic during the Jeff Fudin Debate at the Society of Pain & Palliative Care Pharmacists’ eighth annual Virtual Conference on Pain and Palliative Care, Violanti and Moore discuss the importance of individualized care, thoughtful caregiver communication, and cautious interpretation of limited evidence in guiding these decisions at the end of life.

Pharmacy Times: What are determining factors in assessing which anticholinergic agents are most effective in managing terminal secretions for patients in this setting?

Diana Violanti, PharmD, is a clinical pharmacist specialist - supportive and palliative care at Roswell Park Comprehensive Cancer Center in Buffalo, New York.

Diana Violanti, PharmD: This is an area of symptom management where “most effective” tends to be guided by practical practice considerations and side effects rather than a traditional application of relative effectiveness from a well-designed clinical trial. I work primarily with hospitalized patients who are followed by our palliative care team, so my first question is typically whether the goal is to get home with hospice services, or are we anticipating that the patient may continue to receive end-of-life care in the hospital? If the patient is likely remaining inpatient and still has some degree of alertness or ability to communicate with loved ones, I rely heavily on parenteral glycopyrrolate, which is less likely to cause delirium than some of the other anticholinergic agents.

Pamela S. Moore, PharmD, BCGP, is a clinical lead pharmacist - pain and palliative care at Summa Health System in Akron, Ohio.

Pamela S. Moore, PharmD, BCGP: We also rely on injectable glycopyrrolate in our inpatient palliative care and hospice patient population for the same reason and ease of administration. In our home population the decision making can be a bit more complicated. If the patient is not yet enrolled in hospice, then we still tend to lean on glycopyrrolate, but using the oral tablet formulation for the same reason. It can be extremely drying, so we start low dose and titrate. If the patient is enrolled in our hospice, and we are talking about end-of-life secretions, we use hyoscyamine orally disintegrating tablets. At this stage the patients are typically no longer alert, so the concerns for delirium are less. This formulation is designed for the sublingual route, so it is less burdensome on the caregivers as they don't need to crush the med. It also allows us to avoid introducing additional fluids which would be the case with administering a crushed tablet or the atropine eye drops.

Pharmacy Times: What is the optimal timing for initiating anticholinergic therapy to prevent or minimize terminal secretions effectively?

Moore: I've always considered the optimal timing to be as soon as possible after the sound is noticed, if it is determined to be distressing to the caregiver after non-pharmacological interventions such as repositioning and education. These medications do not dry the fluids that are already present but may minimize production going forward. Our inpatient team prefers to attempt prevention by minimizing fluids from all sources. After doing the deeper dive into the literature, there may be a role for preventative administration, prior to the sound occurring, for patients at high risk of developing terminal secretions. That would involve assessing for when the patient is entering the dying phase, is minimally responsive, and is only taking sips and is not eating or swallowing medications. The risk of delirium from glycopyrrolate would be minimal, but potential benefits of pre-treatment would have to be balanced with the risk of xerostomia and constipation or gastrointestinal (GI) obstruction. Given the short length of time from entering the dying phase until death in the study was less than 4 days, it is likely these risks are also minimal.

Pharmacy Times: How strong is the evidence supporting the efficacy of anticholinergics in improving patient comfort or caregiver distress at the end of life?

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Moore: The evidence on the use of anticholinergics for treating terminal secretions in general is mixed, leaning towards not being effective. The few articles describing prophylactic use are interesting and hypothesis generating. Many providers still likely feel it unnecessary given that not all nor most patients develop this symptom based on the studies. Many expect the symptom is not distressing to the patient, and that we should not administer medication to the patient that is not necessary for their comfort and could have side effects, only in hoping it may help to alleviate some distress for the caregiver. Others would argue that it is impossible to know if the patient is suffering from this symptom. Most would opt to treat demonstrations of pain or other symptoms that are known to be occurring prior to the patient becoming unresponsive and continuing after they can no longer communicate. So, the argument would go, why should we withhold a treatment that a patient would ask for if they were aware, since many patients with diseases such as Parkinson disease, amyotrophic lateral sclerosis, or post-stroke do for excessive drooling and inability to clear secretions? Given the long history in hospice of treating this symptom when it is determined to be distressing to the caregiver, the ongoing conduction of studies trying to determine if, when, and in which specific patient populations this intervention may be useful, either as treatment or prevention, is understandable.

Pharmacy Times: What are the most common adverse effects (AEs) of anticholinergics in this population, and how clinically significant are they in this patient population?

Violanti: I am most concerned about the impact of anticholinergic agents on sedation and cognition, although there can be multiple contributing factors to delirium and sedation as patients approach end-of-life. I strongly believe that the higher cost of glycopyrrolate is a small price to pay for less central nervous system AEs, as those hours or days can be critically important time with loved ones.

Moore: I agree that delirium would be the most concerning AE, but that can likely be avoided by waiting to initiate after the patient is unresponsive and using the quaternary amine, glycopyrrolate. In a patient with a longer life expectancy, delirium is still of concern, but glycopyrrolate can cause significant xerostomia which may cause the patient to discontinue therapy. This can be managed by starting a low dose and titrating based on tolerability and effectiveness. For these patients, the constipation would also need to be monitored for and treated when it occurs.

Pharmacy Times: How should pharmacists counsel caregivers and health care providers about the goals and limitations of anticholinergic use in managing death rattle?

Violanti: Although talking about the dying process can be uncomfortable (for staff as well as patients/family), knowing what to expect and normalizing some of the physiological changes that we anticipate can be reassuring. In addition to covering some of the standard counseling information (eg, name of the medication, route, potential benefits and burdens), I try to normalize that patients may continue to have audible secretions despite medications and that it is likely not bothersome to the patient.