Posted by Dr. Jim Joyner
Can opioids be administered by nebulizer for shortness of breath (dyspnea)?
Opioids are the mainstay of treatment for management of severe dyspnea in hospice patients with late stage CHF and COPD. The use of opioids in dyspnea is supported by extensive experience as well as clinical studies with the use of both oral and parenteral opioids, specifically morphine. The mechanism of action is unclear and it is interesting that opioids can alleviate dyspnea in many patients without changing the respiratory rate or producing any measurable changes in blood gas parameters. The rationale for considering nebulized opioids centers on the belief that dyspnea can be relieved while avoiding potential systemic side effects associated with oral or parenteral routes. The current medical literature does not support this belief. A review article by Foral (1) and colleagues in 2004 evaluated a number of clinical studies in patients being treated for dyspnea with inhaled nebulized opioids. The authors concluded that the evidence did not support the use of nebulized morphine for the relief of dyspnea. They also reported that in all cases opioid side effects were present from mild to moderate degree. There are several other options available for conventional opioid administration routes for hospice patients, including: oral, subcutaneous, intramuscular, intravenous, rectal, transmucosal, and sublingual.
(1) Nebulized Opioids use in COPD. Chest 2004;125:363-365
Posted by Dr. Jim Joyner
Pain Management in Hospice Patients: Morphine
Morphine exerts potent analgesic effects via agonist activity at the mu-opioid receptor in the central nervous system. Morphine is extensively metabolized in the liver by UDP-glucuronosyltransferase enzymes (UGTs) to water-soluble metabolites that are eliminated by the kidneys. In hospice patients with good renal function, these metabolites are usually cleared from the body promptly, exerting minimal pharmacological effects. In the presence of impaired renal function, these metabolites will accumulate to varying degrees depending upon the level of impairment.
Two primary morphine metabolites are active and may contribute significantly to both the analgesic effectiveness and some of the potential adverse effects observed with morphine. Approximately 55% of a morphine dose is converted to morphine-3-glucuronide (M3G) and 15% is converted to morphine-6-glucuronide (M6G).
M6G has significant analgesic effects and is actually more potent than the parent compound, morphine. M3G has little or no analgesic effects (no mu-opioid receptor affinity). However, it has been shown to have significant neuroexcitatory activity. This neuroexcitatory activity is thought to be responsible for some of the adverse effects encountered with the use of morphine in the hospice patient.
Accumulation of M6G may result in increased analgesia, as well as increased levels of sedation and respiratory depression. M3G, on the other hand, will not add to analgesia, sedation, or respiratory depression, but may result in a variety of adverse effects related to neuroexcitatory activity. Specifically, myoclonus, seizures, and delirium are problems believed to be brought on by excessive M3G levels. There is also evidence of an "anti-analgesic" effect associated with M3G accumulation. It has been linked to morphine-induced allodynia and hyperalgesia. (See previous blog article on this topic.)
The argument for avoiding morphine in hospice patients with renal impairment is compelling based upon what we know of morphine pharmacokinetics. In addition, clinicians should also be vigilant in monitoring for similar problems of morphine metabolite accumulation in hospice patients who do not have renal impairment, but are receiving high-dose morphine. In such patients the corresponding high levels of M6G and, more importantly M3G, may be great enough that accumulation will occur, even in the face of normal renal function.
Opioid rotation to an agent that does not have active metabolites may be the best approach to address this problem. Methadone is good option, however, hydromorphone and meperidine should be avoided because they have similar neuroexcitatory metabolites that will accumulate in the presence of impaired renal function.
Morphine Oral Sulfate Solution Approved by FDA
Just this week, the FDA has officially approved the use of Morphine Oral Sulfate Solution for the relief of moderate to severe, acute and chronic pain in opioid-tolerant patients. This medicine will be available in 100 milligrams per 5 mL or 20 milligrams per 1 mL. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm198667.htm
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