Tweet

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

Tweet

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

Tweet

Tweet

Case:

Mr. R is a 65-year-old man who retired as a high-level executive at a large business. He had been hospitalized with worsening pulmonary fibrosis and had ultimately received a double lung transplant. Following transplant, Mr. R suffered multiple complications over a period of three months. In these months, Mr. R was a participant in his own care during times of relative medical improvement. Yet his primary team noticed at the present admission that, he seemed to be withdrawn and was not engaging well with physical or occupational therapy. The team also noted that he had more difficulty concentrating when they went into the room to see him. The team expressed concern that the stress of a prolonged hospitalization was getting to him and/or that Mr. R might be suffering from depression.

The team requested a palliative care consult and, as the psychiatrist on the service, I was asked to see Mr. R. When I first examined him, I indeed found him to be quiet and withdrawn and not at all the "go-getter" that his wife described. When the palliative care doctor had initially seen the patient, she was concerned that he appeared to be confused at times, and my examination bore this out. Mr. R was lethargic and would drift in and out of sleep while we talked. With a little prodding, he revealed that he had noticed a "problem" with his thinking and frequently found himself to be unsure of where he was and why people were coming in and out of his room. He denied any hallucinations or paranoia.

Discussion:

It is very common for doctors to identify hyperactive delirium in patients. Hyperactive delirium is the disturbance in thinking that results from physical illness, medications, or various other etiologies and is characterized by a previously stable individual becoming disoriented, agitated, paranoid, and hallucinatory. It frequently results in a disturbance on the medical unit, and is therefore usually diagnosed. Far more common, but less frequently noticed (estimates run from 32-66% missed) is the condition known as hypoactive delirium. Hypoactive delirium is also a disturbance of consciousness wherein the patient's mental status waxes and wanes, but it frequently manifests with symptoms more like those observed in Mr. R: patients become withdrawn, display less motivation, have lower energy, and are quietly confused.

It is not uncommon for patients with this symptom set to be mistaken for depressed or even as simply lacking the motivation to improve medically. The incidence of delirium among hospitalized patients has been estimated at around 10%. Among patients nearing the end of life, these numbers increase to approximately 60%. It is known that untreated delirium results in increased morbidity and mortality in the 6 months following a hospitalization. Identifying and treating hypoactive delirium is therefore an important component of improved quality and length of life for palliative care patients.

The treatment for both hyperactive and hypoactive delirium is the same: identification and treatment of the underlying cause, and short-term use of antipsychotic medications to reduce disruptive symptoms. Mr. R was started on risperidone 0.25mg twice a day with additional doses available as needed. Within two days of starting this regimen, he was interacting more with his providers, reengaging in rehab, and having conversations with his wife that both of them found to be more successful. Mr. R. never endorsed symptoms that would suggest depression. He was better able to communicate his needs and participate in his care.

References:

1. Casarett D, et al. Diagnosis and management of delirium near the end of life. Ann Int Med 2001; 135 (1): 32-40. (open access pdf)

2. Rea RS, et al. Atypical antipsychotics versus haloperidol for treatment of delirium in acutely ill patients. Pharmacotherapy 2007; 24 (4): 588-94.(no open access pdf)