Opioids are a critical means of relieving pain and shortness of breath in people with serious illnesses. While non-opioid analgesics such as acetaminophen (Tylenol) and ibuprofen (Advil, Motrin) may partially or fully relieve mild to moderate pain, these agents have no effect on shortness of breath, and opioids are usually required for more severe pain.
Before describing different opioids and how and when to use them, let’s review some broadly held concerns about this class of medication.
First, and perhaps most importantly, is the belief that opioids cause respiratory depression and hasten dying. There is no question that opioids can slow respiration, especially if used incorrectly or given in high doses. However, the reality is that respiratory depression with opioids in the setting of life-limiting illness is rare. A well-conducted study of opioids in cancer patients with shortness of breath conducted 30 years ago showed that these medications were effective in relieving symptoms and resulted in no significant respiratory depression (Bruera E, MacEachern T, Ripamonti C, Hanson J. Subcutaneous morphine for dyspnea in cancer patients. Ann Intern Med. 1993;119(9):906–907). Another study, conducted in 2002, showed that opioids are also safe and effective for the treatment of shortness of breath or pain in patients with chronic obstructive pulmonary disease and heart failure (Jennings AL, Davies AN, Higgins JP, Gibbs JS, Broadley KE. A systematic review of the use of opioids in the management of dyspnoea. Thorax. 2002;57(11):939–944).
Unfortunately, the belief that opioids hasten dying persists among both medical and nursing professionals and the public at large. The physicians and nurse practitioners at The Connecticut Hospice, Inc. are highly experienced in the safe use of opioids, making this concern unnecessary for the care of you or a loved one. While the use of very high doses of opioids at the very end of life in patients who are not conscious may result in some respiratory slowing, this is never the reason they are used, which is solely to effect relief of pain and shortness of breath in patients who are suffering.
Another widely held perception about opioids is that they necessarily cause addiction, or opioid use disorder (OUD). Unfortunately, as with beliefs about respiratory depression, the consensus around the medical use of opioids and OUD is nuanced and merits closer examination.
CDC Guidelines: Shaping the Landscape of Opioid Use
First, there is no question that the inappropriate use of opioids in the medical setting, especially in the 2000s, contributed to the spread of OUD and the opioid epidemic, which in 2021 took the lives of 106,000 of our friends, neighbors, and family members. Aggressive marketing of opioids for medical use and the overprescribing of opioids for both acute pain (“acute” meaning of recent onset, such as for a broken bone or dental problem) and chronic pain clearly resulted in OUD and death in some patients. Partially in response to this, the CDC (Centers for Disease Control) issued guidelines in 2016 on the use of opioids for pain. While the report made clear that the evidence on harm related to the medical use of opioids was less than optimal, they recommended nonopioid pharmacologic therapy as preferred for chronic pain, with numerous caveats and warnings for those patients with chronic pain who were prescribed opioids. For people with acute pain, no more than a 3-to-7-day supply of opioids was recommended. A wave of legislation and regulatory actions on the medical use of opioids followed, resulting in an almost 50% decline in opioid prescribing from 2016 to 2019. The CDC updated these guidelines in 2022, still recommending non-opioid therapy for chronic pain, though also stating, “No validated, reliable way exists to predict which patients will experience serious harm from opioid therapy and which patients will benefit from opioid therapy.” The report softened its position regarding acute pain, stating, “When opioids are needed for acute pain, clinicians should prescribe no greater quantity than needed for the expected duration of pain severe enough to require opioids.”
Unfortunately, these reports – and the legislation that followed -- created barriers to effective pain relief for many people with chronic pain who previously had good symptom relief with little or no harm from opioids prescribed by experienced clinicians. In the hospice context, the risk of OUD-related harm is exceedingly low when seriously ill patients with moderate to severe pain are managed by appropriately trained medical staff. This is not because expected death renders the development of OUD irrelevant, but because -- at least in my experience with thousands of patients -- OUD does not occur when pain and shortness of breath are appropriately managed with opioids. This includes many patients who were treated for and cured of serious illness or painful orthopedic conditions who successfully stopped taking appropriately prescribed opioids without developing OUD.
In short, OUD is not a concern for hospice patients – and it should be noted that both CDC guidelines specifically exclude patients at the end of life from their recommendations.
Opioids fall into three distinct chemical categories, those related to morphine, such as codeine, oxymorphone (Opana), oxycodone (including OxyContin), buprenorphine (various brand names, including Suboxone), hydromorphone (Dilaudid), and hydrocodone (Vicodin, Lortab), those related to fentanyl, and those related to methadone.
Practically, the opioids are divided by duration of action and potency. Most, including those commonly used in hospice, such as morphine and hydromorphone, provide relief of pain and shortness of breath for about 4 hours. Some of these come in longer-acting oral formulations, such as MSContin and OxyContin, which last 6 to 8 hours and only exist in oral form (remember that long-acting pills will lose their 6 – 8 hour duration of action if they are crushed). Morphine and hydromorphone also come in oral concentrates, which need only be taken under the tongue to work (making them effective for people who have difficulty swallowing), and injected forms. Typically, oral opioids (swallowed or under the tongue) take about 30 to 45 minutes to take effect, IV forms work in 5 – 15 minutes, and those given by intramuscular injection or under the skin (“sub-q”) take about 15 – 20 minutes to work. Oxycodone only has an oral form. The potency of opioids is usually contrasted with morphine and referred to as oral morphine milligram equivalent, or MME. Hydromorphone is roughly 4 – 7 times as potent as morphine, and oxycodone about 1.5 times as potent. Injected opioids are more potent than oral opioids – doses of oral opioids are reduced by half to a third when patients are no longer able to take them by mouth and they are given by injection.
At Connecticut Hospice, we generally start with lower opioid doses given on an as-needed basis for patients who have not previously used opioids (“opioid-naïve”), and we escalate the dose and give it on a scheduled rather than as needed basis as the opioid requirement becomes clear in the first day or two of their use. We always try to schedule these medications to prevent pain or shortness of breath before it starts, rather than relieving it after it has started. Opioid-experienced patients will be escalated as needed from prior dose regimens.
What’s a normal opioid dose? – very variable. Often we start at a dose of morphine 2 mg injected every 4 hours (“Q4H”) in our inpatient unit with the same dose available every 20 minutes as needed (“PRN”) should the scheduled dose be ineffective and an “in-between” dose needed for persistent pain. Hydromorphone 0.4 mg injected Q4H and Q20min PRN is also typical. We then escalate the dose as needed to fully control pain or shortness of breath. While most people need about 5 – 20 mg of injected morphine Q4H or 4 – 8 mg of injected Dilaudid Q4H for effective symptom relief, it is not unusual to get into the thousands of MMEs per day. For this reason, we often say that there is no “ceiling dose” for opioids. (Once, a patient in home care was taking 1300 mg of methadone a day for pain. She was wide awake and able to get around without sleepiness and without pain. Her only complaint was the need to take 130 ten-milligram tablets of methadone every day. By way of comparison, the dose of methadone typically used for the treatment of OUD ranges from about 50 to 150 mg daily.)
Opioid dose is adjusted based on several factors. First, does the dose relieve all the pain? If not, it needs to be increased. Second, does the pain relief last until the next dose? If not, we may need to either increase the dose or decrease the dose interval (e.g., from every 4 to every 3 hours).
How do we choose which opioid to use? Often, this depends on our pharmacy supply. Sometimes, one opioid is preferred over another, depending on a patient’s medical problem. For example, morphine is generally avoided in patients with kidney failure because it can accumulate with a resulting increased likelihood of toxicity or side effects.
Fentanyl is also commonly used in hospice. Fentanyl, which comes in a patch or “transdermal” form that is applied to the skin and replaced every three days, can be very convenient. People need a bit of body fat under the skin for it to work properly, and the medicine will not last 3 days in very underweight people with no fat under the skin.
Methadone is also a very effective opioid. Generally, it is reserved for use in patients still experiencing pain on high doses of short-acting medications such as hydromorphone and morphine. Methadone helps reverse the development of tolerance to other opioids, helping them work in patients who may have been using opioids for a prolonged period and are experiencing reduced effectiveness despite increasing dose – “tolerance.” Methadone can also help people with the painful numbness in the hands and feet – “neuropathy”-- that can affect many patients on chemo- and immune-therapy.
All opioids have side effects – though not the problems with respiratory depression and addiction often ascribed to them, as reviewed above. ALL opioids cause constipation, and patients who are not taking preventive laxatives such as senna or docusate will develop constipation that can be severe and difficult and uncomfortable to overcome. (In fact, most anti-diarrhea medications are weak opioids.) All opioids also cause sleepiness, though the effect usually wears off after a week to 10 days. In hospice, opioid-induced somnolence can be very distressing to families who want to engage with an awake and lucid loved one who is at the end of life, and finding a balance between sedation and pain control can be tricky. For some, a dose of oral methylphenidate, a mild stimulant best known as Ritalin, used for attention deficit disorder, taken in the morning and early afternoon, can help maintain wakefulness while still offering effective pain relief and allowing a night of sleep. Opioids may also cause nausea and a cloudy sensorium. While meds exist to counter these effects, such as haloperidol for nausea, rotating the opioid from, say, morphine to hydromorphone, is often all that is necessary.
Finally, there is the phenomenon of opioid-induced hyperalgesia – a rare condition in which the opioid increases pain sensitivity, resulting in sometimes severe pain from both painful and non-painful stimuli – such as simply being gently touched. This tends to be seen in patients whose pain does not get better – and seems to be getting worse – despite escalating opioid dose, sometime to very high levels. Once hyperalgesia is diagnosed and opioid dose reduced, pain often goes away.
Adjuvants are medications used to help opioids work. A benzodiazepine such as Ativan, for example, used in conjunction with an opioid in a patient with anxiety, can make the opioid more effective. NSAIDS, such as the over-the-counter analgesics ibuprofen and naproxen, have an anti-inflammatory effect and help opioids work. NSAIDS must be used with caution however, as they can cause gastrointestinal bleeding and kidney failure (typically, NSAIDs used for more than a few days are given with an antacid like omeprazole). The literature cites upwards of 16,000 deaths annually due to NSAID-induced gastrointestinal bleeding. Corticosteroid medications such as prednisone and dexamethasone (Decadron) are also powerful anti-inflammatory drugs commonly used as adjuvants for opioids, especially in people with cancer and in those with metastases (spread of cancer) to bone, which can be very painful. Like NSAIDS, corticosteroids have toxicities, including GI bleeding, and are usually used with antacids.