CA PALLIMED DYSPNEA

More than half of patients with advanced cancer have difficulty breathing, and this chronic dyspnea can be highly debilitating and challenging to manage, thanks to the lack of evidence-based treatment options or a standard of care, say experts interviewed by Medscape Medical News for this feature article.

Dyspnea is prevalent in 50% to 60% of patients with advanced cancer generally and in up to 74% of patients with lung cancer. Prevalence increases during the last 6 weeks of life and can cause significant psychological and emotional distress, they noted.

Many patients report feelings of suffocation or "air hunger,” while others describe a choking sensation or chest tightness that makes breathing difficult and exhausting. Chronic refractory dyspnea can lead to overwhelming feelings of helplessness, anxiety, and depression.

The social isolation that comes with breathlessness can be equally traumatic, said David C. Currow, MD, professor of palliative and supportive services at Flinders University in Adelaide, South Australia.

People describe dying a social death long before they die a physical death,” he commented in an interview. "Their symptoms are progressively worsening, their exercise tolerance is decreasing, and their friends aren't coming around anymore because breathlessness is very difficult to watch."

Even in the general population, dyspnea may be more prevalent than previously thought. In Australia, population studies independent of health service access revealed that 1 in 100 people had severe chronic breathlessness on a day-to-day basis, and 1 in 300 people had breathlessness so severe that it precluded them from leaving the house.

The primary underlying cause was related to lung disease, particularly chronic obstructive pulmonary disease (COPD), followed by cardiac failure, cancer, neuromuscular diseases, and other respiratory diseases.

"At present, optimum management involves pharmacological treatment that has not changed in years and consists of the use of opioids and, occasionally, oxygen and anxiolytics,” said Marcin Chwistek, MD, director of the Pain and Palliative Care Program at Fox Chase Cancer Center, Philadelphia, Pennsylvania, when asked to comment.

The second was a pilot study of prophylactic fentanyl buccal tablets for episodic exertion dyspnea. The drug was associated with a reduction in exertional dyspnea and was well tolerated, supporting "the need for larger trials to confirm the therapeutic potential of rapid-onset opioids," they said.

they concluded that opioids are the drug of choice for treating refractory dyspnea in patients with advanced cancer.

Neither benzodiazepines nor oxygen showed significant benefit," they concluded. "In addition, there is insufficient literature available to draw a conclusion about the effectiveness of steroids for treating persistent dyspnea in advanced cancer patients."

Reducing Symptom Burden

High-level evidence shows that treating breathlessness systematically can result in significant reductions in symptom burden, said Dr Currow. "Most important, regular oral low-dose sustained release morphine is safe and effective for the relief of breathlessness."

The results showed that daily extended-release (ER) morphine was safe and improved symptoms compared with placebo. Breathlessness improved significantly, both in the whole patient population with COPD receiving ER morphine compared with placebo (6.30 mm; P = .012) and in the most severely affected patients, with COPD and a modified Medical Research Council score of 3 or 4 (11.47 mm; P < .001).

Second, nonpharmacologic interventions with a strong evidence base should be considered. These include conditioning exercises for those who can tolerate them, use of a walker, and other options (such as medical air, fans, and techniques to optimize breathing).

To come back to the three-step plan, the third step, which is reached when other measures have failed, involves the use of opioids. Specifically, oral sustained-release morphine at doses between 10 mg and 30 mg every 24 hours is required to reduce breathlessness, said Dr Currow. Approximately two of three patients will notice an improvement at the initial dose of 10 mg daily, and a smaller number will require 20 or even 30 mg.

Patients should also have regular laxatives introduced at the same time as regular morphine, he said.

Medications to prevent nausea and emesis can also be prescribed for the first few days, said Dr Kreye, "as [they are] in treating pain."

For patients who are already receiving opioids for cancer pain, the dose can be increased by 25% to 50% until the patient reports a reduction of dyspnea, she suggested. If symptoms persist, a benzodiazepine, such as lorazepam (Ativan, Wyeth) 2.5 mg sublingually can be added with a half-tablet or one tablet every 3 hours.

In rare circumstances, breathlessness may be sufficient to warrant sedation in the terminal hours and days of life using higher doses of benzodiazepines in combination with other sedatives, said Dr Currow. "Their role as an anxiolytic as well as an amnesiac may be of benefit to some patients."

I will never forget when a colleague refused to give opioids to a patient, being afraid that the patient would die from respiratory depression, and instead the patient died suffocating," she told Medscape Medical News. "Education about the value of opioids for refractory dyspnea is of utmost importance," she emphasized.

Dyspnea is a complex symptom that requires a team to manage it properly. 

Breathlessness isn't just a symptom, it's a distinct clinical entity

My primary message to clinicians is that dyspnea in palliative care patients is an absolute emergency.

People describe dying a social death long before they die a physical death.