Nebulizing morphine has been a topic of debate in hospice over the years. The use seems cyclical, where it garners lots of attention, then the use rapidly falls out of favor only to show back up again. I’ll attempt to explain why that cyclical phenomena occurs.

The data on the use of morphine nebulized is weak. Larger studies showcased that morphine nebs are no more effective than nebulized normal saline. Small case studies have shown some possible benefit, however as previously discussed, morphine is hydrophilic and typically you need more of a lipophilic substance to readily get across the membrane surface and be absorbed. So, the amount of morphine absorbed systemically via the lungs is lower than if given orally or parentally. This makes sense since we often see little to no sedation with nebulized morphine. Herein lies the problem. Dyspnea at end of life is often centrally mediated in the brain, so if you can’t achieve a blood level high enough via nebulization, you are probably fighting an uphill battle.

Some studies theorized a mechanism of action via opioid receptor binding in the lungs that might impact smooth muscles and help with shortness of breath. The data however is pretty sparse to make a solid conclusion for morphine. Also keep in mind, relaxation of smooth muscle in the airway would most likely benefit those having dyspnea non-centrally mediated. There is actually more data to support that nebulized furosemide (Lasix) and its binding affinity for a different set of receptors might be a better option. So, if you’re practicing evidenced based medicine, morphine nebs would be reserved for last line therapy.

My general recommendations over the years for end-of-life dyspnea are: use opioids via the oral route first with the alternative being subcutaneous/parental, manage anxiety with use of a benzodiazepine, then try adding in normal saline nebs (don’t sleep on the value of nebulized normal saline especially in COPD patients), then a bronchodilator like albuterol or furosemide nebs, then morphine nebs or fentanyl nebs. Fentanyl being more lipophilic may actually be more readily absorbed.

Clinical pearl wise, the biggest challenge with all of this data is you have to normalize for various patient conditions, in addition to the medications used. For example, a patient with dyspnea who has COPD, a disease that causes damage to the lungs, might not absorb at the same rate as someone who has dyspnea and dementia and no lung impairment. Alternatively, those with lung diseases might actually express more or less of these alternative receptors making their use and results questionable.

These and many other factors have led us here to the present where we have the occasional case report of success aka the ‘one off’, but on the other hand many reported treatment failures. That case report phenomena can be contributed to the cyclical response we see in the hospice space, but due to wide variability and study bias the results are hard to be extrapolated to hospice in general. One such bias that is important to understand is when nebulizing morphine, you bring the volume up to 3mls with normal saline and normal saline alone has shown benefit in dyspnea. So are morphine nebs wrong to use, not necessarily, but best practice would be to not use as first line or second line, keeping in mind this is in general and there can always be patient level exceptions.

If morphine nebs are to be used, the best recommendation would be to use injectable morphine. Preservative free morphine has been suggested to reduce risk of bronchospasms, but in clinical practice the preservative free often is not necessary. Some use the oral liquid morphine concentrate mixed with normal saline. This is not recommended as the oral solution, even the sugar free, is formulated for oral administration and contains other ingredients that actually do increase the risk of bronchospasms, cough, etc.

Note: This is part 4 of the morphine mini-article series.