Assessment and Management of Pain at the End of Life _ ___________________________________________
should be low, and, if pain persists, the dose may be titrated up daily until pain is controlled. Opioid-naïve patients are those who are not receiving opioid analgesic daily and therefore have not developed significant tolerance. Opioid-tolerant patients are those who have been taking an opioid analgesic daily for at least one week. The FDA identifies tolerance as receiving at least 60 mg of morphine daily, 30 mg of oral oxycodone daily, 8 mg of oral hydromorphone daily, or an equianalgesic dose of another opioid for one week or longer [30]. Typical starting doses for patients who are opioid-naïve have been noted, but these doses should be used only as a guide, and the initial dose, as well as titrated dosing, should be done on an individual basis ( Table 1 ). The most serious potential adverse effect following initiation of opioids for treatment of pain is oversedation followed by respiratory depression. To mitigate this risk, clinicians should discuss the role of naloxone administration by caregivers in the event of sedation/respiratory depression and make naloxone available as indicated or as required by local regulations [30]. When initiating morphine, or any opioid agent for treatment of moderate/severe pain, the prescribing clinician should consider lower starting dose titration in frail or older patients and in any patient with renal insufficiency (reduced creatinine clearance). More than one route of opioid administration will be needed by many patients during end-of-life care, but in general, opioids should be given orally, as this route is the most convenient and least expensive. The transdermal route is preferred to the parenteral route, although dosing with a transdermal patch is less flexible and may not be appropriate for patients with unstable pain [8]. Intramuscular injections should be avoided
because injections are painful, drug absorption is unreliable, and the time to peak concentration is long [8]. Morphine is considered to be the first-line treatment for a Step 3 opioid [34]. Morphine is available in both immediate-release and sustained-release forms, and the latter form can enhance patient compliance. The sustained-release tablets should not be cut, crushed, or chewed, as this counteracts the sustained- release properties. Morphine should be avoided in patients with severe renal failure [28]. Buprenorphine (Butrans) has the general structure of mor- phine but differs from it in several ways [35]. The transdermal formulation of the drug was approved in 2010 for moderate-to- severe chronic pain in patients requiring an around-the-clock opioid for an extended period [8]. It may be used for people with renal impairment but is contraindicated in patients who have substantial respiratory depression [35; 37]. The sustained-release form of oxycodone (OxyContin) has been shown to be as safe and effective as morphine for cancer- related pain, and it may be associated with less common side effects, especially hallucinations and delirium [40]. Oxycodone is also available in an immediate-release form (Roxicodone). Oxycodone should be used in people with advanced chronic kidney disease only if alternative options are not available [28]. If the drug must be used, the intervals between doses should be increased, and the patient should be monitored closely [28]. Hydromorphone and fentanyl are the most potent opioids; neither drug should be given to an opioid-naïve patient. Hydromorphone, which is four times as potent as morphine, is available in immediate- and extended-release forms [41].
OPIOIDS FOR THE MANAGEMENT OF PAIN IN ADULTS a
Typical Starting Dose b
Drug
Onset of Action 30 to 60 minutes 10 to 20 minutes
Duration of Action
Codeine
15–60 mg 2.5–10 mg 15–30 mg
4 to 6 hours 4 to 8 hours 3 to 6 hours 3 to 4 hours 8 to 12 hours 4 to 5 hours 4 to 6 hours 4 to 6 hours
Hydrocodone
Morphine, immediate release
15 to 30 minutes (oral) 5 to 10 minutes (IV)
Oxycodone, immediate release Oxymorphone, sustained release
5–10 mg
10 to 30 minutes 5 to 10 minutes 15 to 30 minutes 30 to 60 minutes
10 mg
Hydromorphone
2–4 mg 5–10 mg
Methadone Tapentadol
50–100 mg 50–100 mg 100–200 mcg
<60 minutes
Tapentadol, extended release
—
—
Fentanyl (buccal tablet)
5 to 15 minutes 12 to 18 hours
2 to 4 hours
Fentanyl (transdermal patch)
25 mcg/hour (worn for 3 days) 5–10 mcg/hour (worn for 7 days)
48 to 72 hours
Buprenorphine (transdermal patch)
—
—
a All information is given for oral formulations unless otherwise specified. b Doses given are guidelines for opioid-naïve patients; actual doses should be determined on an individual basis. Source: [4; 8; 30; 37; 38; 39]
Table 1
6
MDNJ1525
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