Hypercalcemia of Malignancy: An Emergency Medicine Simulation.

Hypercalcemia is a poor prognostic factor associated with malignancy. The signs and symptoms of hypercalcemia that the patients present to the emergency department are vague and often overlap with the general symptoms of cancer itself or the adverse effects of the chemotherapy. Given that the development of hypercalcemia of malignancy can present with imminent danger to the patient and is a treatable condition, emergency physicians should know how to recognize and treat it. It also marks a time at which discussions regarding plans of care should be initiated with the patients. In this report, we describe a simulation case that can be used to train emergency medicine residents to both recognize and treat hypercalcemia of malignancy and to initiate the discussion of goals of care.

Introduction

Hypercalcemia associated with malignancy is relatively common, occurring in up to 20-30% of the patients with cancer [1]. The leading cause of hypercalcemia in hospitalized patients is hypercalcemia associated with cancer [2]. This condition can occur in patients with both solid and hematologic malignancies, with the most common malignancies being breast cancer, lung cancer, multiple myeloma, and renal cell carcinoma [2-3].

The main pathogenesis of the hypercalcemia is increased osteoclastic bone resorption, however, the renal tubular resorption and intestinal absorption of calcium can contribute as well [1-2]. The bone resorption can occur due to increased tumor secretion of parathyroid hormone-related protein (PTHrP), osteolysis secondary to bone metastasis, or tumor production of calcitriol [4-5].

The signs and symptoms of hypercalcemia are often nonspecific, such as fatigue, nausea, constipation, and confusion [2], making the diagnosis challenging. These clinical features often mimic general symptoms of underlying cancer itself or adverse effects from the treatments such as chemotherapy. This simulation was created to assist emergency medicine residents to consider hypercalcemia when oncology patients present with acute changes in symptoms.

The development of hypercalcemia of malignancy indicates a poor prognosis for the patients with cancer. It is reported that 80% of the patients die within a year [2] and 50% die within 30 days of presentation [1]. For this reason, when a diagnosis of hypercalcemia is made in the patient population, a discussion regarding the goals of care needs to be initiated. There is a lack of formal palliative care training in many emergency medicine residency programs [6]. Case-based simulation, bedside teaching have been shown to be the most effective educational methods to provide palliative care teaching to these residents [6]. Therefore, this simulation case was also created to provide emergency medicine residents with effective methods of initiating palliative care discussions.

The learning objectives covered by this simulation case are:

1. Recognize acute illness in an oncology patient

2. Recognize the signs and symptoms of hypercalcemia in an oncology patient and consider the differential diagnosis

3. Order appropriate labs and diagnostic imaging

4. Initiate treatment for hypercalcemia of malignancy

5. Deliver bad news and initiate discussion around goals of care.

Technical report

Context

The simulation session was conducted in the Clinical Learning and Simulation Centre (CLSC) at the Faculty of Medicine, Memorial University. It can be, however, performed in any medical school or hospital-based simulation lab, or in an emergency department. The simulation was conducted to train emergency medicine residents; however, other physicians, medical students, and the nurses may benefit from the case.

Inputs

This simulation case requires standardized patients (SPs) playing the roles of the patient and her husband, and another SP playing the role of the emergency room nurse. Instructors will be present to control the patient’s vitals and to observe the scenario unfold. This case is preferably performed where there is an examining table, a cardiac monitor, an intravenous (IV) setup, and a screen to display X-rays to preserve the reality of the scenario.

A detailed stepwise scenario template (Table 1), as well as a script for each SP (Appendices A-C) were created. An electrocardiogram (ECG) tracing of hypercalcemia (Figure 1) and multiple X-rays demonstrating bone metastasis (Figures 2-5) were also obtained. Prior to the training session with the residents, a mock scenario was completed with the SPs and an instructor to ensure the learning objectives would be appropriately demonstrated by the case.

Table 1

A stepwise, detailed scenario template to be submitted to the simulation lab and the standardized patient coordinators, who then train the standardized patients and supply the necessary materials for the case

Legend: L4-5 – 4th and 5th lumbar vertebrae, ECG – electrocardiogram, IV – intravenous, CBC – complete blood count, BUN – blood urea nitrogen, PTH – parathyroid hormone, TSH – thyroid stimulating hormone, CXR – chest X-ray, CT – computed tomography, AST – aspartate transaminase, ALT – alanine transaminase, ALP – alkaline phosphatase, INR – international normalized ratio, PTT – partial thromboplastin time, SC – subcutaneously, SPIKES: S- setting up the interview (ensure privacy, involve family, make a connection with the patient and avoid interruptions), P- assess the patient’s perception (open-ended questions and correct misinformation), I- obtain the patient’s invitation (information disclosure, does the patient want all information?), K- giving knowledge (warn the patient of bad news, give facts in small chunks and avoid bluntness), E- address the patient’s emotions (observe and identify), S- strategy and summary (the treatment plan and the goals of care).

Pre-Scenario:
You are a family physician in a rural emergency department. A 59-year-old female with stage 4 metastatic breast cancer presents to you confused and complaining of increased nausea and fatigue over the past week. She has had a double mastectomy with chemotherapy five years ago for Stage 2 breast cancer. However, six months ago, she had a recurrence and is once again being treated with chemotherapy. The patient has not been connected with any pain or symptom management teams.
History: Over past week, the patient was more confused, complaining of nausea and fatigue.
Allergies	No known allergies
Medications	Hydrochlorothiazide, ondansetron, dexamethasone, cyclophosphamide, doxorubicin, 5-Fluorouracil (FAC)
Past medical history	Stage 2 breast cancer, unilateral modified radical mastectomy, hypertension, cesarean section, appendectomy
Social history	Married, two children (18 & 20 years old), previous smoker (10 pack-year history), no alcohol. Prior to cancer, worked as a teacher.
Review of systems	General – weight loss (~5-10 lbs over past few weeks), lethargic, decreased appetite, no fever/chills; eyes – no visual changes; ears, nose, throat – no hearing changes, no sore throat; cardiovascular – no chest pain, no palpitations, no shortness of breath, no peripheral edema; respiratory – no cough, no shortness of breath, no wheezing; gastrointestinal – nausea, decreased appetite, no vomiting, no abdominal pain, no change in bowel movements; genitourinary – no change in urination; musculoskeletal – pain in the chest and lower back; neurologic – drowsiness, dizziness on standing, no headache, no numbness or tingling; skin – no rash
Physical: Appears thin, lethargic, and cachectic, in some discomfort
Initial vitals	Temperature 37 (oral), heart rate 59 (sinus), blood pressure 85/50, respiratory rate 18
Head, eyes, ears, nose, throat	Pale, dry mucous membranes, no thyroid nodules on palpation
Central nervous system	Alert, oriented to person and place – not oriented to time, Glasgow Coma Scale 14, cranial nerves I-XII intact, reflexes normal in upper and lower limbs
Cardiovascular system	Heart sounds normal, slow heart rate, jugular venous pressure flat (difficult to see), pain to palpation across chest wall (rib metastasis), mastectomy scar on the chest
Respiratory system	Normal breath sounds, no wheezes, no crackles, mastectomy scar on the chest
Abdomen	Cesarean section scar, appendectomy scar, otherwise benign
Musculoskeletal System	Lower back tenderness (L4-5 region) (vertebral metastasis)
Expected actions (immediate)
Assign to bed space with cardiac monitor, connect to cardiac monitor and oxygen saturation probe
Check bedside glucose
Obtain 12-lead ECG
Start 2 large bore IVs, order IV normal saline 1 L bolus
Order labs (CBC, electrolytes, glucose, BUN, creatinine, calcium, magnesium, phosphate, albumin, liver function panel, PTH, TSH, toxicology screen, urinalysis)
Order diagnostic imaging (CXR, the abdominal series, lumbar series, the CT head scan)
Engage family member (husband)
Objective 1: Recognize acute illness in an oncology patient
Stage 1: Initial Assessment
Stage	Findings	Expected action
Recognize acute presentation	Confusion, nausea and lethargy x one week	Get new set of vitals, order labs
Get new set of vitals	Same as above	Start two large bore IVs, order IV normal saline 1 L bolus
With fluid bolus	Heart rate 59, blood pressure 90/60	IV normal saline 1 L bolus
Without fluid bolus	Heart rate 59, blood pressure 80/48
Assess for pain	Pain to palpation across the chest wall, lower back tenderness	Pain control should be given (IV Ketorolac or Morphine) + Anti-emetic (IV dimenhydrinate 25-50 mg, ondansetron 4-8 mg, or metoclopramide 10 mg) Order CXR, abdominal series, lumbar series
Objective 2: Recognize the signs and symptoms of hypercalcemia in an oncology patient and consider the differential diagnosis Objective 3: Order appropriate labs and diagnostic imaging
Stage 2: Recognize cause of symptoms
Results of ordered labs	Hemoglobin 125, Hematocrit 0.39, Platelets 200, White blood cell count 5.0, Sodium 135, Chloride 100, Potassium 4.3, Calcium 3.5 (corrected for albumin = 3.6), Magnesium 0.9, Phosphate 0.98, Glucose 4.8, BUN 5.0, Creatinine 79, Albumin 35, AST 35, ALT 30, ALP 309, Total bilirubin 15, INR 1.2, PTT 32, PTH <2.5, TSH 2.5, toxicology screen negative	Recognize elevated calcium level. Recognize acute presentation may suggest hypercalcemia of malignancy. Consult patient for the internal medicine.
Objective 4: Initiate treatment for hypercalcemia of malignancy
Stage 3: Initiation of the treatment
Initiate normal saline rehydration		200-500 mL/h IV
Initiate Bisphosphonate (Zoledronate)		4-8 mg IV over 15 mins
Initiate calcitonin	May or may not be initiated	2-8 units/kg SC every six-12 hours (52 kg = 104-416 units SC every six-12 hours) or 100 units SC three times a day
Discontinue hydrochlorothiazide	Hydrochlorothiazide can contribute to hypercalcemia	Change to another anti-hypertensive
Objective 5: Deliver bad news and initiate discussion around goals of care
Results of CXR, abdominal & lumbar series	Extensive bone metastasis to ribs, lumbar vertebrae, pelvis present	Discuss with the patient
Use strategy (such as “six steps”, SPIKES, CLASS) to explain cancer has spread to bones and is incurable		Assess patient’s understanding of the disease. Assess patient’s goals of care. Is there an advance care directive?
Disposition		Consult internal medicine

Figure 1

The electrocardiogram showing marked shortening of the QT interval (260 ms) from hypercalcemia.

Source: Life in the fastlane - http://lifeinthefastlane.com/ecg-library/basics/hypercalcaemia/

Figure 2

The chest X-ray, anteroposterior (AP) view, demonstrating bone metastasis.

Source: A Dixit

Figure 5

The lumbar X-ray demonstrating bone metastasis.

Source: A Dixit

The chest X-ray, lateral view demonstrating bone metastasis.

The abdominal X-ray demonstrating bone metastasis.

Process

The resident is given pre-scenario information, along with initial vitals prior to entering the scene. Upon entering, the patient is already in a hospital gown and connected to a cardiac monitor. The emergency room nurse and the patient’s husband are also present in the room. The residents proceed with their assessment.

Product

The scenario was completed as a formative exercise for the residents at Memorial University. However, there is the potential to have it formally evaluated using the five objectives that the case is expected to achieve.

Pre-briefing

A pre-briefing was held with the residents before they began the case. The instructors involved in the case were identified. The residents participating in the case were determined; in this case, two residents completed the simulation. The fiction contract was reviewed, which encourages residents and instructors to proceed as if the case was real, while concurrently identifying it is not real. This provides a safe environment for residents to learn.

Case

This simulation takes place in a community hospital. A 59-year-old female is brought to the emergency department by her husband. She has a history of breast cancer and presents with worsening symptoms over the past week. She complains of increased nausea and fatigue, along with feeling confused.

Debriefing

Upon conclusion of the scenario, the instructor completes a formal debriefing exercise with the residents. Each resident is given an opportunity to safely express his or her feelings and reflections of the case, the events of the case are reviewed, and the SPs provide feedback. The debriefing with a good judgment approach can be used to create a safe environment where the instructor can provide feedback without being penalized, or without eliciting a defensive response from the residents [7]. This method involves the instructor clarifying actions of the residents that they may question, by assessing the resident’s reasons for the action. This avoids a single “right” or “wrong” answer, and instead maintains respect for the resident as a capable physician. An example dialogue could include, “During the case, I noticed you did (action). Can you help me understand why you chose to do (action) at that point?”. The debriefing with good judgment approach helps residents integrate their insights and experiences so that they can improve their performance when a similar situation presents in the future [7].

Post-scenario didactics

After the debriefing, a didactic session is held to focus on knowledge gaps identified throughout the simulation case and debriefing session. The objectives are used to strengthen and solidify the knowledge learned from the simulation exercise.

Objective 1

To recognize acute illness in an oncology patient. Recognizing acute illness in the patients with cancer can be difficult, as they are often quite sick at baseline. In addition to assessing the patient’s new or worsening symptoms, it is also helpful to assess the patient’s functional status. The Palliative Performance Scale (PPS) is an 11-point scale (Appendix D) describing the patient’s level of ambulation, level of activity, evidence of the disease, ability to perform self-care, nutritional intake, and level of consciousness [8-9].

Objective 2

To recognize the signs and symptoms of hypercalcemia in an oncology patient and consider the differential diagnosis. These patients often present with nonspecific clinical features such as fatigue, nausea, constipation, and confusion, making diagnosis challenging. Severe symptoms that are important for the emergency physician to recognize include seizures, cardiovascular collapse, and coma [1-2]. The differential diagnosis will depend on the patient’s symptoms. In this, the patient with nausea, fatigue, and confusion, some diagnoses to consider are adverse effects of chemotherapy, the progression of breast cancer, dehydration, hypo/hyperglycemia, electrolyte disturbances, delirium, and gastrointestinal disorders or infections.

Objective 3

To order appropriate labs and diagnostic imaging. The symptomatic cancer patients should always have plasma calcium measured. The calcium levels can be classified as mild (2.6-2.9 mmol/L), moderate (3.0-3.4 mmol/L), and severe (≥ 3.5 mmol/L) [1]. The formula to correct calcium for the albumin level should be reviewed and is: measured calcium (mmol/L) + ( [40 – albumin (g/L) ] x 0.02) [2]. The levels of parathyroid hormone (PTH) should be undetectable or extremely low unless primary hyperparathyroidism is also present. For diagnostic imaging, a chest x-ray, the abdominal and lumbar series are reasonable to investigate bone pain and the possibility of bone metastasis, looking for lytic or sclerotic lesions. A computed tomography (CT) scan of the head may also be reasonable to investigate the new onset of confusion and weakness and to rule out brain metastasis.

Objective 4

To initiate treatment for hypercalcemia of malignancy. The reduction of tumor mass usually corrects hypercalcemia, but this is not always possible, as is the case in this scenario with metastatic disease [10]. The mainstay of the treatment of hypercalcemia is hydration with normal saline and IV bisphosphonates (zoledronate or pamidronate). The IV bisphosphonates should be started right away, as they take 12 hours for onset, with full effect reached by four-seven days. They block osteoclast activity and reduce bone pain. The zoledronate requires 15-minute infusions and pamidronate requires two-four hour infusions. Both need to be dose-adjusted for the renal dysfunction. The calcitonin works rapidly, but the effect is short-lived as the patients develop tolerance in two-three days. It may be started initially, especially in the patients with severe symptoms, while waiting for the bisphosphonate to take effect. The calcitonin is administered subcutaneously. It used to be standard practice to administer loop diuretics (furosemide) in hypercalcemia; however, there is a lack of evidence for effectiveness [3]. Thiazide diuretics, like the hydrochlorothiazide that this patient takes for hypertension increases renal calcium resorption, so these medications should be discontinued/switched to an alternative [11].

Objective 5

To deliver bad news and initiate discussion around the goals of care. Hypercalcemia of malignancy has a poor prognosis and is associated with advanced disease. When diagnosed, the physicians should discuss the goals of care and advance care directives with the patient and family. Strategies such as SPIKES are helpful: S- setting up the interview (ensure privacy, involve family, make a connection with the patient and avoid interruptions), P- assess the patient’s perception (open-ended questions and correct misinformation), I- obtain the patient’s invitation (information disclosure, does the patient want all information?), K- giving knowledge (warn the patient of bad news, give facts in small chunks and avoid bluntness), E- address the patient’s emotions (observe and identify), S- strategy and summary (the treatment plan and the goals of care) [12]. A referral to palliative care may be appropriate.

Discussion

Teaching emergency medicine residents how to recognize and manage hypercalcemia of malignancy using case-based simulation is a valuable teaching tool. Hypercalcemia of malignancy is an indicator of poor prognosis and the recognition and initiation of discussions regarding goals of care are important.

The learning objectives covered by this simulation case include:

1. Recognize acute illness in an oncology patient 2. Recognize the signs and symptoms of hypercalcemia in an oncology patient and consider the differential diagnosis 3. Order appropriate labs and diagnostic imaging 4. Initiate treatment for the hypercalcemia of malignancy 5. Deliver bad news and initiate discussion around the goals of care.

This case scenario is outlined in a stepwise approach for replication. It is adaptable and can be altered based on the needs of the trainees, level of training of those involved, and the resources available at the site.

In addition to the simulation case, the residents will also benefit from the debriefing session and post-scenario didactics. These sessions allow residents to reflect on their experience and allow instructors to identify knowledge gaps and provide necessary teaching. Collectively, this will provide the emergency medicine residents with the knowledge and confidence to provide appropriate care to the patients with hypercalcemia of malignancy in the future.

Conclusions

Hypercalcemia of malignancy can be challenging to recognize, and once diagnosed will involve a no doubt difficult discussion with the patient regarding their condition. Therefore, providing the emergency medicine residents with a case-based simulation training session allows for a controlled and safe environment to learn the techniques of approaching this situation. We have presented a simulation case of hypercalcemia of malignancy using a stepwise algorithm, along with an approach to debriefing and providing didactic teaching.

Table 2

The Palliative Performance Scale.

PPS - Palliative Performance Scale

Source: Lau F, Downing F, Michael G, Lesperance M: A reliability and validity study of the palliative performance scale. BMC Palliative Care. 2008, 7:10. 10.1186/1472-684X-7-10.

PPS level	Ambulation	Activity and evidence of the disease	Self-care	Intake	Conscious level
100%	Full	Normal activity and work. No evidence of the disease	Full	Normal	Full
90%	Full	Normal activity and work. Some evidence of the disease	Full	Normal	Full
80%	Full	Normal activity with the effort. Some evidence of disease	Full	Normal or reduced	Full
70%	Reduced	Unable normal job/work. Significant disease	Full	Normal or reduced	Full
60%	Reduced	Unable hobby/housework. Significant disease	Occasional assistance necessary	Normal or reduced	Full or confusion
50%	Mainly sit/lie	Unable to do any work. Extensive disease	Considerable assistance required	Normal or reduced	Full or confusion
40%	Mainly in bed	Unable to do the most activity. Extensive disease	Mainly assistance	Normal or reduced	Full or drowsy +/- confusion
30%	Totally bed bound	Unable to do any activity. Extensive disease	Total care	Normal or reduced	Full or drowsy +/- confusion
20%	Totally bed bound	Unable to do any activity. Extensive disease	Total care	Minimal to sips	Full or drowsy +/- confusion
10%	Totally bed bound	Unable to do any activity. Extensive disease	Total care	Mouth care only	Drowsy or coma +/- confusion
0%	Death	-	-	-	-