Palliative Volume Resuscitation in a Patient with Cancer and Hypercalcemia: Why Bother?

Introduction

Hypercalcemia of malignancy affects 2%–2.8% of cancer patients and is associated with an increased risk of mortality and other symptom-related complications.^1,2 Standard treatment consists of fluid resuscitation, intravenous bisphosphonates, and calcitonin. Little is known, however, about the benefits of treatment of malignant hypercalcemia in patients with late-stage terminal cancer. We present a case of a hospice patient with squamous cell lung cancer brought to our hospital with newly altered mental status who was found to have hypercalcemia of malignancy. Our discussion centers on the diagnostic dilemma of deciding which patients seeking comfort-focused care may benefit from fluid resuscitation for symptoms of hypercalcemia of malignancy while maintaining the unambiguous goal of comfort care.

Case Description

Mr. H was a 70-year-old man brought from a nursing home to the emergency room with request of transfer into an inpatient hospice associated with our hospital for a new complaint of altered mental status. History was provided by his daughter (also his medical power of attorney), the nursing home staff, and hospice staff. Mr. H had been diagnosed with metastatic lung cancer three months before current presentation. He had declined cancer treatment interventions at the time of diagnosis and enrolled in hospice care, stating that his primary goal was to remain comfortable. Per his daughter, they had also explicitly discussed that he would want to be moved to an inpatient hospice facility when he was unable to remain at home. Although discussions regarding general goals of care had previously taken place between the patient, his daughter, and his health care team, specific circumstances such as time-limited interventions to alleviate symptoms had not been fully discussed and clarified. Mr. H had remained in his private home until three days before admission, when the hospice chaplain reported increasing confusion and an inability of the patient to care for himself; he was subsequently moved to the nursing home for respite care while exploring placement options. At the nursing facility, the patient remained mostly asleep, with poor oral intake of food and liquids, but had also fallen twice when getting out of bed during periods of increased wakefulness. According to those around the patient the past few days, he was able to briefly focus on familiar voices such as family, but not oriented or able to answer questions.

Mr. H had a medical history significant for squamous cell lung cancer metastatic to the liver, mouth, and lymph nodes, advanced cirrhosis with esophageal varices, and chronic obstructive pulmonary disease. His social history was significant for alcohol abuse, with no signs of withdrawal since stopping drinking alcohol 1 week prior, and a 60 pack-year history of cigarette use. He had longstanding prescriptions for acetaminophen, hydrocodone, docusate, and lactulose. The patient had recently been prescribed chlordiazepoxide out of concern for his high risk of alcohol withdrawal, but, per nursing home staff, had not required the medication.

On physical examination, Mr. H was cachectic and appeared older than the stated age. He was lying in bed, somnolent, but able to focus on the examiner briefly with stimulation. He was unable to converse, instead mumbling unintelligible responses. His abdomen was scaphoid and nontender to palpation. His laboratory tests were notable for elevated serum white blood cell count of 18.4 × 10⁹ cells/L and calcium of 15.3 mg/dL (corrected to 16.1 mg/dL for albumin level of 3.0 g/dL). Other blood tests, including renal function, other electrolytes, glucose, and the remainder of his blood count, were otherwise normal. Testing for infection, including a full physical examination and blood cultures, was negative. Imaging of his head and lungs was negative for any acute abnormality. Our differential included delirium secondary to hypercalcemia, versus terminal delirium.

A meeting between patient's daughter and the palliative care team provided clarity that the patient's goals of care should focus primarily on comfort. Intravenous hydration was exclusively offered and agreed by family to treat potential mental status changes associated with hypercalcemia and hopefully preserve end-of-life comfort. Mr. H received treatment with one liter of intravenous normal saline as an attempt at palliation of his altered mental status. His mental status failed to improve at all and, in a shared decision with his daughter, he was transitioned to full inpatient hospice care with as-needed lorazepam for terminal delirium in the setting of alcoholic cirrhosis. He required only three 1 mg doses of this medication before dying comfortably five days after his initial admission.

Comment

Palliative care teams often meet patients for the first time near the end of their lives. We rely on family as surrogates for the patient's wishes and hope to help honor those wishes. At the same time, we often also serve as the gatekeepers in determining whether a patient is suffering from a truly life-ending symptom. Based on descriptions from his caregivers, Mr. H had enjoyed a relatively high quality of life before admission to our facility and treatments that could return him to this quality of life would honor his goals.

It is difficult but essential to help patients and their caregivers balance attempts at seeking further treatment of possibly reversible symptoms with focusing on pursuing a peaceful death. Such treatment is often perceived as aggressive by the health care team, and family members of terminally ill patients are often questioned whether their goals of care changed to pursuing aggressive care as their main focus. Examples of aggressive treatment might include antibiotics, ³ fluid resuscitation, radiation, physical therapy, limited trials of vasopressors, ⁴ and short intensive care unit stays, ⁵ among others.

Furthermore, health care teams often struggle when an aggressive treatment is given to terminally ill patients with the unique goal of improving symptoms, and may even consider such treatment as unethical ⁶ or contradictory to patient's wishes.

Hypercalcemia of malignancy is a well-known paraneoplastic syndrome; it is the most common cause of hypercalcemia in hospitalized patients and is usually a late manifestation of cancer. Patients frequently present with systemic symptoms, commonly remembered as “bones, stones, moans, and psychic overtones.” The associated altered mental status can range from decreased concentration to coma and is a common terminal event in patients with cancer; approximately half will die within a month of presentation. ⁷ Our patient had been highly functional and living independently until the week before admission, when he acutely decompensated. His goals of care while on hospice were clearly conveyed by his daughter—to be as comfortable as possible.

Treatment of hypercalcemia is well defined. The initial treatment of hypercalcemia is administration of intravenous fluids to correct hypovolemia and to improve symptoms of confusion. Effective intravenous hydration for severe hypercalcemia, however, often requires aggressive fluid administration up to several liters. Bisphosphonates are useful in lowering serum calcium levels in many patients but often take several days or repeated doses to work. ⁷ As palliative providers, our work often involves helping patients and their families determine risk versus benefit of attempting measures. We questioned, given the patient's known diagnosis and goals, whether administration of intravenous fluids would help to improve his symptoms and relieve suffering. Limited data exist to guide clinicians in this particular circumstance. A retrospective study of 126 patients presenting with hypercalcemia of malignancy reported that treatment did not improve mortality, except in cases wherein cancer-targeted treatments were available, but could help palliate symptoms of confusion, stupor, anorexia, polyuria, and polydipsia. ⁸

Mr. H presented a treatment dilemma, as his daughter's goal was to have him admitted to an inpatient hospice, whereas our team questioned whether fluid resuscitation could improve his mental status, thereby meeting his previously stated goals of symptomatic control. Treatment, however, would delay his disposition and potentially interfere with his goals of a comfortable death without significant intervention.

Clinicians can feel conflicted between offering hospice patients purely symptom-based care versus adding something “more.” Although palliative medicine often focuses on choosing less aggressive interventions, the ultimate goal remains to engage in shared decision making. Time-limited trials can offer a way to ensure that the patient has access to a full spectrum of treatments and symptom palliation without committing to major interventions. If the patient clinically improves, then disease-directed therapy can be continued, but if the patient deteriorates, the intervention can be ceased and goals may shift toward pure palliation. ⁹ The value of discussing these possibilities with patients while they are able to participate cannot be underestimated.

Given the acuity of the patient's decompensation, while acknowledging his overall prognosis and advance directives, we considered a reasonable approach to administer a trial of fluid administration and determine whether his mental status improved. Simply put, we believed that dying with the dignity of consciousness and ability to speak to his loved ones a final time would meet his goal of care focused on remaining comfortable. Limited data suggest that treatment of hypercalcemia may palliate symptoms but does not extend lifespan. A major question remains whether patients reported in the literature die from hypercalcemic crisis or whether the development of hypercalcemia is a manifestation of their advanced malignancy. Nevertheless, this case highlights a continued need for research into which patients with hypercalcemia of malignancy would benefit from treatment for palliation of symptoms. Furthermore, this case highlights the need to tailor the care of terminally ill patients exclusively to their goals of care and remain flexible in using limited trials of aggressive treatments to control their symptoms while maintaining dignity during their dying process. Early discussions and ethical thinking are critical components in the delivery of patient-centered care.