The following cases and commentary, which address opioid therapy, are excerpted from ACP's Medical Knowledge Self-Assessment Program (MKSAP14).
Case 1: Hip surgery
An 84-year-old woman is hospitalized for surgical repair of a displaced right hip fracture. She has World Health Organization functional class IV pulmonary arterial hypertension treated with epoprostenol, bosentan, sildenafil, and oxygen supplementation.
Preoperatively, the patient is cognitively intact and conversant but has significant pain, which is difficult to control because of her hypotension and guarded respiratory status. She states that she would rather die than have to endure the hip pain, and both she and her family agree to surgery despite the significantly increased risk of worsening respiratory status and death associated with this procedure.
She remains stable during surgery but develops increasing hypotension, hypoxia, agitation, pulmonary edema, and renal failure postoperatively. Based on the patient's and family's wishes, her status is changed to “comfort care.” The surgical team is uncomfortable about giving pain medications because of concerns about worsening hypotension and respiratory failure.
On physical examination, blood pressure is 72/46 mm Hg, pulse rate is 113 beats/min and irregularly irregular, and respiration rate is 26 to 32 breaths/min with dyspnea. Arterial oxygen saturation is 80% by pulse oximetry (patient breathing oxygen, 10 L/min, by nonrebreathing face mask).
After discussion with the family and surgical team, which of the following should be done immediately to manage this patient?
A. Arrange for hospice care
B. Prescribe a low-dose fentanyl patch
C. Prescribe low-dose intravenous morphine
D. Withhold opioids
Case 2: End-stage metastatic prostate cancer
A 64-year-old man with end-stage metastatic prostate cancer is experiencing worsening skeletal pain throughout his back and bilateral lower extremities. He has already experienced disease progression with anti-hormonal therapy, has refused further chemotherapy, and has received the maximal dose of radiation to the spine and metastatic lesions. He had been controlling his pain with regular NSAID use but now requires short-acting narcotics almost every four to six hours. He is requesting a long-acting medication for his pain control, and his current health insurance does not include a pharmacy benefit.
On physical examination, no focal neurologic findings are noted. Results of renal function and liver chemistry tests are normal.
Which of the following is the most cost-effective choice for long-acting analgesia medication in this patient?
A. Long-acting morphine
B. Long-acting oxycodone
C. Transdermal fentanyl
Answers and commentary Case 1
Correct answer: C. Prescribe low-dose intravenous morphine.
End-of-life care has been identified by the Institute of Medicine as one of the priority areas to improve quality of health care, specifically in the area of pain control in patients with advanced cancer and advanced organ failure. Many clinicians think of the “end of life” as the short period when the patient is moribund just before death. However, clinicians and caregivers are encouraged to view the “end of life” as a phase of life when a patient is living with an illness that will worsen and eventually cause death. The primary goal should be to prevent or alleviate suffering for these patients by assessing symptoms and providing psychological and social support to patients and their families.
The American College of Physicians has recently published clinical practice guidelines for clinicians that provide evidence-based recommendations for interventions to improve the palliative care of pain, dyspnea, and depression at the end of life. These five recommendations are based on systematic evidence review.
Recommendation 1: In patients with serious illness at the end of life, clinicians should regularly assess for pain, dyspnea, and depression. (Grade: strong recommendation, moderate quality of evidence.)
Recommendation 2: In patients with serious illness at the end of life, clinicians should use therapies of proven effectiveness to manage pain. For patients with cancer, this includes non-steroidal anti-inflammatory drugs, opioids, and bisphosphonates. (Grade: strong recommendation, moderate quality of evidence.)
Recommendation 3: In patients with serious illness at the end of life, clinicians should use therapies of proven effectiveness to manage dyspnea, which include opioids in patients with unrelieved dyspnea and oxygen for short-term relief of hypoxemia. (Grade: strong recommendation, moderate quality of evidence.)
Recommendation 4: In patients with serious illness at the end of life, clinicians should use therapies of proven effectiveness to manage depression. For patients with cancer, this includes tricyclic antidepressants, selective serotonin reuptake inhibitors, or psychosocial intervention. (Grade: strong recommendation, moderate quality of evidence.)
Recommendation 5: Clinicians should ensure that advance care planning, including completion of advance directives, occurs for all patients with serious illness. (Grade: strong recommendation, low quality of evidence.)
The most appropriate next step in this patient's management is the immediate need to make her more comfortable. This can best be done by prescribing low-dose intravenous morphine to relieve the dyspnea and pain.
Although the patient is an excellent candidate for consideration of hospice care, making such arrangements will not immediately relieve her symptoms. Many clinicians believe that providing opiate-based pain relief for patients at the end of life will hasten their death. However, this does not constitute physician-assisted euthanasia. In addition, it is inappropriate to withhold measures that would make a patient more comfortable, even when a patient has severely impaired vital signs. Although a fentanyl patch will eventually relieve pain and dyspnea, the onset of action is several hours, and this medication is very difficult to titrate.
- In patients with serious illness at the end of life, clinicians should use therapies of proven effectiveness to manage pain and dyspnea.
Correct answer: A. Long-acting morphine.
This patient has chronic, progressive metastatic cancer-induced pain that is not alleviated by standard short-term pain management. He requires high-dose, escalating, long-acting narcotic analgesia, and in this setting, morphine would be appropriate.
There is no evidence that any long-acting narcotic is better than another such agent. In particular, oxycodone has an efficacy similar to that of morphine and is appropriate for use in patients with cancer-related pain. However, oxycodone is considerably more expensive than morphine, and because there is no evidence of its improved efficacy or a better side effect profile compared with morphine, it would be appropriate to first use the lowest-cost alternative of agents with comparable efficacy.
Transdermal fentanyl is also a useful long-acting narcotic but is considerably more expensive than long-acting morphine and is often used in patients who have limitations on oral intake or intolerance to other long-acting narcotics.
Duloxetine is a new antidepressant drug with an approved indication for some chronic pain syndromes but would not be an appropriate alternative to long-acting narcotic analgesia for the treatment of severe, progressive, cancer-related pain.
Methadone is another effective long-acting narcotic that is comparable in cost and efficacy to morphine and, therefore, would be an appropriate cost-effective alternative.
- Patients with progressive pain that ceases to respond to short-term pain management may require high-dose, escalating, long-acting narcotic analgesia.