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Case:

Ms JB is a 32 year old woman with type 1 diabetes who underwent a living related donor renal transplant and a subsequent pancreas transplant. Unfortunately, both transplants were complicated by rejection and graft failure requiring re-initiation of hemodialysis in 2007. Since that time she has suffered with constant, intractable nausea with multiple episodes of vomiting throughout each day. Her symptoms were initially thought related to diabetic gastroparesis but they did not respond to metoclopramide, erythromycin or pylorus muscle botulinum toxin injections. An electrical gastric stimulator was to be placed but was aborted when a gastric emptying study was normal. Extensive workup, including laboratory studies, endoscopy, CNS imaging and abdominal imaging, was unrevealing. She received little or no benefit from adequate trials of domperidone, prochlorperazine, ondansetron, oral granisetron, promethazine, trimethobenzamide, scopolamine, mirtazapine, dronabinol, pancreatic enzymes and a proton pump inhibitor.

She underwent voluntary admission to a psychiatric hospital for treatment of any possible contributing eating disorder without any improvement. Since 2007, she has had more than 40 admissions to the hospital for nausea and vomiting. A feeding J-tube was placed to maintain adequate nutrition in 2008. She presented to the Palliative Care clinic in 2010 for further management of her nausea and vomiting. After a complete history and physical, the etiology of her symptoms remained somewhat elusive. She had nausea before her transplant and it had resolved when the kidney was working then recurred when it failed so the final conclusion was that her symptoms may be due to a poorly defined metabolic process related to her renal failure. Olanzapine was initiated on the first visit for refractory nausea and vomiting and the patient was referred to psychology and psychiatry to help with coping and to address underlying depression and anxiety. At the subsequent visit she noted some benefit so the olanzapine dose was increased and a granisetron transdermal patch was added. At the next visit her symptoms had improved dramatically with a clear temporal relation to starting the granisetron patch. She was only vomiting once or twice in the morning and was relatively asymptomatic through the day. In her first clinic visit she had vomited multiple times through the visit and appeared miserable.


At this visit she was asymptomatic, neatly dressed, wearing makeup and was thrilled at this new level of symptom control which was allowing her to re-engage her life.

Discussion: There were many factors that likely contributed to the dramatic improvement in Ms JB’s refractory nausea and vomiting. Better psychiatric care through the palliative care psychologist and psychiatrist almost certainly played a role in her overall clinical turn-around. The close attention, serial visits and supportive counseling she received in the Palliative Care clinic could also have been therapeutic. Up-titration of her olanzapine also likely was helpful. Olanzapine is an atypical antipsychotic that works on multiple receptors including dopaminergic, serotonergic, adrenergic, histaminergic and muscarinic receptors. Of particular interest is its antagonism of 5HT2 receptors which are located in the vomiting center and are not well targeted by other traditional antiemetics. Multiple small trials have demonstrated efficacy of olanzapine for chemotherapy-induced nausea and vomiting.¹ Many palliative care practitioners are now also starting to use olanzapine for refractory nausea and vomiting in patients with advanced cancer and other life-limiting conditions.^2-4

Even with all of these possible contributors to her improvement, there still seemed to be a clear benefit that came with initiation of the granisetron patch. While intravenous and oral granisetron have been available for some time, transdermal granisetron (Sancuso©) is a relatively new addition to the practitioner’s toolbox for difficult to control nausea and vomiting. Transdermal granisetron was approved by the FDA for chemotherapy-induced nausea and vomiting (CINV) in September of 2008 based largely on a trial of 582 patients receiving multi-day moderately or highly emetogenic chemotherapy. Patients received either oral or transdermal granisetron and achieved equally good control of their symptoms with either method (approximately 60% in each group achieving complete symptom control). The most common side effect in both groups was constipation.⁵ The patch is an 8x6cm clear, plastic-backed patch and is worn for 7 days. Pharmacokinectic studies suggest that the patch delivers a dose equivalent to 2 mg of oral granisetron each day it is worn.⁶

It is thought to exert its antiemetic effect through antagonism of 5HT3 receptors in the gut and chemoreceptor trigger zone.⁷ Experience with the patch outside of CINV, however, is limited. This case suggests that transdermal granisetron may have a role in other cases of refractory nausea and vomiting. It is unclear why the transdermal form of the drug worked so much better than the oral version for Ms JB. It could reflect absorption issues, especially if she was unable to keep the pills down. It could also reflect compliance issues and may bring into question the adequacy of her prior trial of oral granisetron. Whatever the mechanism, however, the result was dramatic. Further study of this agent in settings other than CINV is clearly needed. Hopefully these results can be replicated and other patients with difficult-to-control nausea and vomiting can achieve life-changing results similar to those achieved by Ms. JB.

References:
1. Navari RM, Einhorn LH, Loehrer PJ Sr, Passik SD, Vinson J, McClean J, Chowhan N, Hanna NH; Johnson CS (2007). A phase II trial of olanzapine, dexamethasone, and palonosetron for the prevention of chemotherapy-induced nausea and vomiting: a Hoosier oncology group study. Supportive Care in Cancer, 15 (11), 1285-91 PMID: 17375339

2.  Srivastava M, Brito-Dellan N, Davis MP, Leach M, Lagman R (2003). Olanzapine as an antiemetic in refractory nausea and vomiting in advanced cancer. Journal of Pain and Symptom Management, 25 (6), 578-82 PMID: 12782438

3.  Jackson WC, Tavernier L (2003). Olanzapine for intractable nausea in palliative care patients. Journal of Palliative Medicine, 6 (2), 251-5 PMID: 12854942

4.  Passik SD, Lundberg J, Kirsh KL, Theobald D, Donaghy K, Holtsclaw E, Cooper M, & Dugan W (2002). A pilot exploration of the antiemetic activity of olanzapine for the relief of nausea in patients with advanced cancer and pain. Journal of Pain and Symptom Management, 23 (6), 526-32 PMID: 12067777

5.  Boccia RV, Gordan LN, Clark G, Howell JD, Grunberg SM, on behalf of the Sancuso Study Group (2010). Efficacy and tolerability of transdermal granisetron for the control of chemotherapy-induced nausea and vomiting associated with moderately and highly emetogenic multi-day chemotherapy: a randomized, double-blind, phase III study. Supportive Care in Cancer PMID: 20835873

6.  Howell J, Smeets J, Drenth HJ, & Gill D (2009). Pharmacokinetics of a granisetron transdermal system for the treatment of chemotherapy-induced nausea and vomiting. Journal of Oncology Pharmacy Practice, 15 (4), 223-31 PMID: 19304880

7. Wood, G., Shega, J., Lynch, B., & Von Roenn, J. (2007). Management of Intractable Nausea and Vomiting in Patients at the End of Life: "I Was Feeling Nauseous All of the Time . . . Nothing Was Working" JAMA: The Journal of the American Medical Association, 298 (10), 1196-1207 DOI: 10.1001/jama.298.10.1196

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CASE:Mr. J was a 39 year-old white married male who came to the hospital for a tissue biopsy and was subsequently diagnosed with advanced adenocarcinoma of unknown primary origin. His disease had progressed to the point where the tumors could not be debulked. The previous week Mr. J had been working full time and leading a very active lifestyle, so his diagnosis and prognosis came as a shock to him and his family. The primary medical team consulted the Palliative Care Team (PCT) to assist with symptom management, discussion of treatment options and goals, and planning of end-of-life (EOL) care.

Once Mr. J became physically comfortable and accepting of his poor prognosis, he voiced concerns about how to talk to his 6 year-old son and 8 year-old daughter about his illness and likely death. The RN for the PCT provided Mr. J with books that aid parents in discussing death and dying with children, and the behavioral medicine specialist with the PCT assisted Mr. J in applying these materials to the conversation he would have with his children.

First, as a means of understanding each child’s developmental level, the behavioral medicine specialist asked Mr. J to simply talk about his two children – how they spent their time, what subjects were they good at in school, and what, if any, exposure they had to the death of a loved one or pet. This discussion naturally led into Mr. J identifying words and concepts about illness and death that his children would understand. Mr. J decided he would say the following to his children, “Sometimes people get sick and the doctors can cure them. Sometimes people get sick and the doctors can’t cure them. The doctors don’t think they can cure me, but I am hoping for a miracle because I don’t ever want to leave you.”

Although his message was brief, Mr. J feared he would emotionally break down when having this conversation with his children. He wanted to be “strong” for them so that they would not be too frightened. To promote his sense of self-control Mr. J practiced his conversation with the behavioral medicine specialist who in turn coached him on breathing techniques that would help him stay in control of his emotions.

The practice helped, but Mr. J still feared that “we’ll all end up crying and that’s not going to any of us any good in the long run.” So then the behavioral medicine specialist worked with him on identifying specific ways in which he was a father to his children, e.g., he helped his children with their homework and he read to them every night before they went to bed. She suggested that after he gives them the bad news and answers their questions, Mr. J might reassure his children that he’s still going to help them with their homework and read to them every night.

DISCUSSION:
Young children who are informed of their parents’ terminal illness are less anxious than those who are not told , but many terminally ill parents are daunted by this emotionally stressful task. Deciding how to break the news to children is made more difficult when taking into account the developmental level of each child. Palliative Care Teams often have several books available that guide parents through the process of discussing death and dying with their children. Parents’ abilities to apply the information in these books can be further enhanced with a session provided by the behavioral medicine consultant. The individual session allows parents to tailor their approach to their own families and to practice having and controlling very powerful feelings.

References
1. Rosenheim, E., Reicher, R. (1985). Informing children about a parent’s terminal illness. J Child Psychol Psychiatry Allied Disc. 26:995-998.

2. Siegel, K., Raveis, V., Karus, D. (1996). Pattern of communication with children when a parent has cancer. In L. Baider & L. Cooper (Eds) Cancer and the family, pp 109-128. John Wiley and Sons: New York.

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Case: During a weekly Palliative Care Consult meeting, it was discussed that if D, 53-year-old woman with congestive heart failure, did not receive a heart transplant within several weeks to a few months at the most, she would probably die. I felt led to visit her, even though she was not on my normal unit rounds. On the initial visit, D was welcoming when I stopped by her room. After introducing myself as a Protestant staff chaplain, I inquired about her pain. D told me how uncomfortable she was and how she felt so limited by her physical condition. When I asked how she was coping with any other areas of suffering in her life, her lips quivered and her eyes filled with tears as she told of the burdens in her soul…deep, personal stresses in her life that continued to that very day. She had tearfully vented for about an hour, as I reflectively listened and reassured her that every word was confidential and I was there for her to listen, if nothing else.

After hearing her life’s trials, it was important to let her know, as a chaplain and pastor representing Christ’s church, that God could help not only with the treatment of the pain in her heart but also with the trauma of her suffering soul. I prayed for her and the medical team that would work with her and those behind the scenes to care for her, to harvest the new heart and skillfully transplant it into her body; as well as for the opportunity to deal with some of the issues of suffering that were plaguing her. Thankfully, the issues that she was suffering from began to be addressed within her family as the real possibility of D’s death triggered the process of reconciliation. As those issues began to be resolved and forgiveness and harmony blessed her life, hope and new meaning for her life made the anticipated pain of transplant more tolerable. D was sent home with a VAD long enough to appreciate how some of the stress that existed in the home before had dissipated. Within 48 hours D was back in for her heart transplant.

Surgery went very well, and D was out of the ICU with few complications. Yet, once D was on a step-down unit and dealing with post-operative pain in her body and the anxiety and depression that ensues after transplantation, she was troubled by her years of living as a sufferer. It was reassuring when she made her suffering known.

Thankfully, the issues were addressed by those that contributed to her suffering within her family, and positive changes brought meaning back into her life. D did embrace her new life with meaning and purpose, and as she healed from the pain of the transplant, it was made bearable by the liberation from suffering.

This was a process that was not resolved as in our modern media. It was assisted in by others in the Palliative Care Team, the Transplant Team, Unit Staff, Pastoral Care, Providence, and, of vital importance, D’s family members who realized D’s mortality and took ownership of her suffering and their contribution to the dysfunction in their household.

In many of the rooms of the hospital are laminated Comparative Pain Scales with 1 being expressed as :) demonstrating No Pain to 10 being Unbearable/Excruciating Pain. Modern technology addresses this pain well. Suffering of the soul, mind, psyche, what ever terminology you are comfortable with, also needs to be addressed with awareness and compassion. Everyone should participate. According to Thomas R. Egnew, “Suffering arises from perceptions of a threat to the integrity of personhood, relates to the meaning patients ascribe to their illness experience, and is conveyed as an intensely personal narrative.”

While the medical community has established procedures, protocols, and treatment plans that factor in typical emotional responses, suffering is personal, individual and commonly expressed as a narrative that needs the freedom and respect to be presented and the dignity to be acted on to reestablish meaning and significance. Pastoral Care is one piece of the solution, but by far, not the only piece in total patient care.

References:

1. Mayo Clinic on Chronic Pain; Mayo Foundation for Medical Education and Research. Kensington Publishing Corp., NY, NY. 1999

2. Egne, TR. Annals of Family Medicine; Suffering, Meaning and Healing: Challenges of Contemporary Medicine. LICSW. Volume 7 No 2. March/April 2009

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Case:

You are asked to see Mrs. RT, a 44-year old woman with end-stage COPD. She was admitted to inpatient hospice with increased anxiety, hopelessness, and pain “all over.” She says she is tired of being sick and exhausted, and wants to be “put to sleep.” She has heard about “terminal sedation” and is angry it hasn’t been offered. She lives with her husband and adult children who work full-time and is upset they can’t all stay home with her. She experiences dyspnea with activity, and uses a wheelchair, but can independently transfer to bed and toilet. Your exam reveals she is awake and alert, neither delirious by the confusion assessment score (CAM), nor suicidal. She is cachectic, tachypnic, and has generalized muscle atrophy. She lacks signs of infection or localized pain. You estimate her prognosis in months. She takes medications erratically for symptom control.

What is Palliative Sedation Therapy (PST)?

Patients and families sometimes have heard or been told about “terminal sedation,” but it is a frequently misunderstood term and therapy. The term “terminal sedation” suggests the goal of the therapy is hastening death for terminally ill patients, when in fact the goal is symptom relief. Therefore, the term “palliative sedation therapy (PST)” is much preferred since the goal of PST is relief from intolerable and untreatable symptoms, not shortening a patient’s life. An international panel of palliative care experts recently reviewed the medical literature on PST and published their recommendations for standardizing our understanding of this therapy1. They recommend the following definition: “Palliative sedation therapy is the use of specific sedative medications to relieve intolerable suffering from refractory symptoms by a reduction in patient consciousness.” They emphasize that palliative sedation is distinct from euthanasia while acknowledging lively debate on this issue.

The panel’s position is based on their assertion that hastening a terminally ill patient’s death is not the goal of PST. Other points of difference between PST and euthanasia are the principle of titration to comfort rather than to death, and PST’s reversibility.

What are refractory symptoms?

Refractory symptoms are considered symptoms for which all possible treatments have failed. A patient experiencing refractory symptoms must be differentiated from a patient who has symptoms that are difficult to treat. Refractory symptoms are symptoms that the palliative care physician and team determine cannot safely be relieved by invasive or noninvasive interventions. Expert panel members recommend Cherney’s definition of refractory symptoms: “Refractory symptoms are symptoms for which all possible treatment has failed, or it is estimated that no other therapies exist within the patient’s time-frame or tolerable risk-benefit ratio.”

When is PST considered?

PST is considered for patients with refractory symptoms only after discussions with the patient and/or family, the caregiving team, and the palliative care expert. The most frequent reasons for PST have been refractory delirium or restlessness, dyspnea, pain, and nausea/vomiting. The use of PST or psychological or existential distress is rare, and initiated only under exceptional circumstances. PST is considered only in the last hours to days of life.

Experts recommend a systematic and inclusive process to determine if PST appropriate, which includes the patient, if possible, designated surrogate and caregivers, and addresses the patient’s values, beliefs, and goals. If PST is chosen, then the specific intervention is discussed and reviewed, instituted, and carefully monitored. Decisions about nutrition and hydration are discussed separately from the decision to offer PST.

Medications used for PST include benzodiazepines (usually midazolam), except for delirious patients, phenobarbital, or propofol. Opioids are not recommended for PST because even high doses may not result in sedation.

Since the aim of PST is the relief of refractory symptoms, doses of sedatives are carefully chosen to relieve distress by reducing a patient’s level of consciousness and are not excessive. The degree of sedation can vary from superficial to deep sedation. Initial doses of sedatives should be small enough to allow a patient to communicate periodically.

Refractory symptoms may respond to temporary sedation, since a patient’s ability to tolerate symptoms may be improved following rest provided by sedation. Experts identify three levels of continuous sedation. With mild sedation, the patient is awake, but has a lowered level of consciousness. Moderate sedation results in stupor, so that the patient is asleep, but can be awakened to communicate briefly. With deep PST, the patient is unconscious and unresponsive. PST is frequently monitored and assessed, with attention to the needs and goals of both patient and family.

Back to the Case:

You convene a meeting with the patient, her family, and the palliative care team. After asking open-ended questions and listening to concerns, you offer information about PST but say that you think her symptoms can be treated. You offer medication changes including around the- clock rather than as needed opioids for relief of dyspnea and pain, and a comprehensive treatment plan for her anxiety and depression. Her family finds ways for her to be less isolated, and the hospice team offers additional services and frequent monitoring. Although she is skeptical, she is willing to consider these options as possibly improving the quality of her life.

References:
1. De Graeff A. Dean M: Palliative Sedation Therapy in the Last Weeks of Life: A Literature Review and Recommendation for Standards. Journal of Palliative Medicine 2007; Vol10 (1); 67-84.

2. Cherny NI. Portenoy RK: Sedation in the management of refractory symptoms: guidelines for evaluation and treatment. Journal of Palliative Care 1994;10;31-38.

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Case:

Mr. L.O. was an elderly Russian immigrant to Canada, admitted to the Palliative Care Unit of a Canadian hospital with advanced rectal cancer. When L.O. was first presented to the multidisciplinary team, his major problems were identified as persistent rectal pain and anxiety. The initial workup of the pain suggested a neuropathic component, and adjustments were made to L.O.’s medications. His complaints of pain and anxiety persisted over the next several days.

L.O. then began to experience terrifying nightmares. Even during the day, when he was awake, he would have what he called “flashes” of frightening imagery, but the nightmares were the worst. L.O. was so fearful of them that he resisted falling asleep as much as he could. The images were horrific, often violent, with L.O. sometimes being the victim of the violence, sometimes the perpetrator. A CT scan was ordered to investigate the possibility of brain metastases as a contributing factor.

At the same time, the attending palliative care physician had a long interview with L.O., in which they explored the content of the nightmares in depth. L.O. was an amateur artist, and the physician suggested that he might sketch the images in his dreams, or, if not the exact images, some rendering of how they made him feel. L.O. did this. Subsequent conversations revealed that L.O. was estranged from his children; the main reason that he needed to be in the Palliative Care Unit was that none of his children cared enough about him to support him while he lived at home. L.O.’s sketches showed a small figure—himself—cowering at the bottom of a deep pit, with another figure standing far above, looking down.

The physician suggested that L.O., who had become physically well enough for a weekend pass, bring some of his previous paintings back with him to the Palliative Care Unit. Within a few days, the sound of hammering could be heard from L.O’s room. He was hanging his pictures, 15 or 20 in all. Most were landscapes, but there were also a portrait of a lovely young woman, and a winter scene, all in black and silvery white, of a snow- and ice-lined brook leading into a dark woods. The next morning L.O. reported that he had dreamed of eating a chicken dinner.

Discussion:

Two features of this case are striking. The first is the necessity of combining medical and psychosocial approaches to L.O.’s nightmares and overwhelming anxiety. Both the CT scan and several psychoactive medications were appropriate and helpful. But it was the in-depth exploration of the content of the imagery, and even more, the suggestion that L.O. use his art to capture his emotional state in drawings, that appeared to unlock the insights and emotions that lay beneath the anxiety and terror. The physician succeeded in helping L.O. find a language to express himself more effectively and concretely than he had been able to do at a purely verbal level. The physician found a form of expression that “fit” the patient, even though that form was somewhat unconventional.

The second feature concerns the possibility of creating a living space in the Palliative Care Unit where L.O. could work his way to a feeling of peace and safety, despite his estrangement. This use of the inpatient palliative care service would almost certainly be impossible in the United States, with our minimal lengths of stay and our restrictive utilization review requirements. L.O. died in this Canadian palliative care unit many days after his physical and emotional symptoms had been brought firmly under control. But the inpatient environment remained critical to his spiritual well-being. Even though the Canadian health care system faces some of the same economic pressures as that in the U.S., the possibility still exists there for more flexibility to respond to the broadest range of patient or family need, compared to the limits imposed by hospice and palliative care financing in the U.S.

References:

1. Pratt A, Wood M (eds). Art Therapy in Palliative Care. London: Routledge, 1998.

2. Lynn J. Serving patients who may die soon and their families: The role of hospice and other services. JAMA, 2001, 285:925-932. (No open access pdf)

3. Raphael C, Ahrens J, Fowler N. Financing end-of-life care in the USA. Journal of the Royal Society of Medicine, 2001, 94:458-461. (Open access PDF avail from Journal and PubMed Central)

(CS: Minor formatting edits for readability)