Clemens, K.E., & Klaschik, E. (2010). Dyspnoea associated with anxiety-symptomatic therapy with opioids in combination with lorazepam and its effect on ventilation in palliative care patients. Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer, 19(12), 2027-2033.

The objective of this study was to assess the safety of opioid and benzodiazepine combination for dyspnea management in patients receiving palliative care.

Patients in a palliative care unit were provided morphine or hydromorphone and lorazepam enterally every four hours, and rescue doses were given as needed every 15 minutes according to a titration schema. All patients were given 1 mg lorzepam sublingual with the first opioid dose during the clinical stay. Ratings of dyspnea were recorded at rest and on light exertion. PaCO ₂ and SaO₂ were monitored with earlobe sensors. Measurements were taken at baseline for 15 minutes after patients were admitted to the palliative care unit and for at least 240 minutes after starting the opioid and lorazepam combination. 

• The study reported on a sample of 26 participants.
• The mean age was 66 years (SD = 13.6 years).
• Of the sample, 53.8% were males and 46.2% were females.
• Patients had a variety of cancer types, with lung and breast the most frequent.
• All patients had advanced disease, with a mean survival time of 51.5 days.
• The mean length of stay in the palliative care unit was 12.8 days.
• No patients were on oxygen prior to the study.
• SaO₂ at study entry ranged from 85%–100%. 
• Of the participants, 42.3% were opioid naïve at study entry.
• All patients had at least moderate dyspnea, defined as at least 4 on the 11-point scale.
   

This single-site study was conducted in an inpatient setting in Germany.

• Patients were undergoing end-of-life care.
• The study has clinical applicability for end-of-life and palliative care.
   

The study was a prospective, nonrandomized trial.

• Numeric dyspnea rating scale (0–10)   
• Pulse oximetry
   

Mean morphine dose was 8.4 (SD = 7.2), and mean hydromorphone dose was 30 (SD = 35) morphine equivalents. Respiratory rate was significantly reduced 60 minutes after the combination of medications was delivered (from 40–30, p < .001), and dyspnea at rest declined from mean of 6.2 to 4.1 after 30 minutes and to 1.2 after 120 min (p < .001). No significant changes were seen in paCO₂  or SaO₂. 

The medication regimen used here was helpful in reducing symptoms of dyspnea in these patients.

• The study had a small sample size of less than 30.
• The study had no appropriate control or comparison. 
• Opioids have been shown to reduce dyspnea so as this study was designed, whether the lorazepam in addition was helpful is unclear. 
• Authors mention that patients were anxious, but no measure of anxiety was used or reported.
• All patients were opioid naïve on study entry, so symptoms improving with just the opioids is not surprising.
   

This study adds little new in terms of symptom management for dyspnea. The study design did not help to further define the role of anxiolytics versus opioids for dyspnea management.