Clemens, K.E., Quednau, I., & Klaschik, E. (2009). Use of oxygen and opioids in the palliation of dyspnoea in hypoxic and non-hypoxic palliative care patients: A prospective study. Supportive Care in Cancer, 17(4), 367-377.

The objective of the study is to compare the effects of oxygen application and use of opioid treatment on ventilation and palliation of chronic dyspnea in hypoxic and non-hypoxic palliative care patients.

Four liters per minute of oxygen were given via nasal cannula. After 60 minutes, patients rated dyspnea, and respiratory parameters were recorded for comparison to baseline. Patients initially received immediate release opioids every four hours and rescue doses as required for breakthrough dyspnea. Patients who had been pre-treated with opioids were switched to oral morphine equivalent doses, and the opioid dose was titrated to achieve a tolerable and stable level of symptoms. When stable, patients were changed to sustained release opioids.

The study reported on a sample of 46 patients. The median age was 66.5 years, with a range of 40-90 years, for hypoxic patients and a median age of 70.5 years, with a range of 40-86 years, for non-hypoxic patients. Twenty-three patients were females; 9 were hypoxic, and 14 were non-hypoxic. Twenty-three patients were males; 9 were hypoxic, and 14 were non-hypoxic. In the hypoxic group, participants were diagnosed with end-stage cancer of multiple types. Participants were included if they experienced dyspnea at rest, had a hemoglobin level of greater than or equal to 10 g/dl measured within 2 weeks, and had normal cognitive function. Of the participants included, 18 were noted to have been pre-treated with opioids for pain control, while 28 were opioid naive. In addition, four participants were noted to have a medical history of chronic obstructive lung disease. Seventeen patients reported intermittent pre-treatment with oxygen therapy (2-6 L/min).

The single-site study was conducted on a palliative care unit in Germany.

Patients were undergoing end-of-life and palliative care.

Prospective non-randomized study

• Numeric rating scale (NRS) of intensity of dyspnea (scale of 0-10)
• Karnofsky Performance Status Score to assess baseline level of function
• Transcutaneous measurement of carbon dioxide partial pressure, oxygen saturation, and pulse rate via an earlobe sensor

During 60-minute oxygen insufflation with the 4 L/min nasal cannula, no decrease in dyspnea was noted among the hypoxic and non-hypoxic patients. No significant correlation was seen between intensity of dyspnea and oxygen saturation. A significant increase was seen in SaO₂ in hypoxic patients after opioid application (P < 0.0001), and a significant decrease was seen in respiratory rate in both groups. In non-hypoxic patients, respirations in the opioid naïve ranged from 38 (SD = 5.6) per minute to 27 (SD = 4) per minute (P = <0.0001) after 120 minutes, while patients who were pre-treated with opioids ranged from 37 (SD = 4.5) per minute to 27 (SD = 3.4) per minute (P = 0.003) after 120 minutes.

• Use of opioids for the reduction of dyspnea was more effective than oxygen insufflation, even in hypoxic patients.
• Oxygen did not reduce dyspnea.
• Opioids appeared to reduce dyspnea both in opioid-naïve patients and those who had previous medication with opioids.

The study had a small sample of less than 100. Baseline measurement of dyspnea intensity, SaO₂, PaCO₂, and tcpaCo₂ during 60-minute oxygen administration obtained from the 17 participants who were known to have used as much as 6 L/min nasal cannula at home calls into question the accuracy of comparative data because study intervention used only 4 L/min nasal cannula. The results only pertain to patients experiencing “chronic” dyspnea and do not relay or compare the effects of increasing oxygen concentration or modes of oxygen delivery (i.e., greater than 4 L/min, face mask, FiO₂, etc.) in management of acute, chronic, or breakthrough dyspnea in hypoxic and non-hypoxic patients.

Oxygen therapy for the management of chronic dyspnea in patients with cancer with advanced disease may not be a cost-effective intervention and has no established long-term benefits for symptomatic relief of work of breathing. Intermittent use of opioids for the safe improvement of symptomatic dyspnea may be a better alternative with minimal likelihood of resulting respiratory depression.