This new protocol updates a previous review, 'Hydromorphone for acute and chronic pain', published in The Cochrane Library (Issue 1, 2002). This review will only focus on cancer pain.
Description of the condition
Pain is defined as "an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage" (IASP 2011).
Cancer pain is an important and distressing symptom of the disease, which tends to increase in frequency and intensity as the cancer advances. For cancer patients, pain can arise from the progression of the cancer itself as well as from treatments designed to alleviate the condition such as radiotherapy, chemotherapy and surgery. Cancer-related pain can be classified as acute or chronic, though is sometimes thought to be an ongoing acute pain. Acute pain is defined as having "a temporal pattern of onset... generally associated with subjective and objective physical signs," whereas chronic pain is more continuous, lasting three months or longer.
Increasingly, the treatment of cancer-related pain has become a major challenge within the healthcare sector. A previous systematic review has indicated the prevalence of pain to be more than 50% in all cancer types (Van den Beuken-van Everdingen 2007). For patients with advanced cancer, the prevalence of pain can be as high as 90% (Laird 2008). It has been estimated that 30% to 50% of cancer patients categorise their pain as moderate to severe and that between 75% to 90% of cancer sufferers experience pain, which has a major impact on their daily life (Portenoy 1999). Epidemiological studies suggest that approximately 15% of patients who experience pain fail to experience acceptable pain relief with conventional management (Running 2011; Yakovlev 2008). Uncontrolled pain can lead to physical and psychological distress and can, consequently, have a drastic effect on patients' quality of life.
Description of the intervention
The options available for managing cancer-related pain include pharmacological treatments (e.g. opioid analgesics), psychological therapy (e.g. cognitive behavioural therapy) and alternative treatments (e.g. acupuncture or massage). Opioid pharmacotherapies (such as morphine, oxycodone, fentanyl, hydromorphone and methadone) have been put forward as the most effective of these therapies (Portenoy 2011).
The World Health Organization (WHO) has recommended oral morphine as the first choice for the management of moderate to severe cancer-related pain (WHO 1986). This has been stated to be largely due to its cost and availability rather than proven superiority (Caraceni 2012), with a previous review suggesting that a significant proportion of patients do not achieve sufficient pain relief by taking morphine due to unmanageable adverse effects, including nausea, delirium or myoclonus (Murray 2005). However, evidence from a recent Cochrane review on oral morphine for cancer pain suggests that only around 5% stopped taking morphine due to lack of pain relief or unacceptable adverse effects (Wiffen 2013). Morphine may also be associated with toxicity in patients with renal impairment (King 2011).
Hydromorphone (also know as dihydromorphinone) is a semi-synthetic derivative of morphine. It is marketed in various countries under various brand names. Since its clinical introduction in 1926, it has been used as an alternative opioid analgesic to morphine, as it has a similar chemical structure but is more soluble (Urquhart 1988) and potent (Twycross 1994). High solubility is beneficial for opioid-resistant patients who require higher doses (Portenoy 2011) and OROS® hydromorphone extended-release is five times as potent as morphine, and has 8.5 times the equianalgesic effect when administered intravenously (Binsfeld 2010; Sarhill 2001). This also allows a smaller dose of hydromorphone to be used for an equianalgesic effect. Hydromorphone is administered through oral, intravenous, subcutaneous, epidural, intrathecal and other routes (Murray 2005).
How the intervention might work
Like morphine, hydromorphone is primarily an agonist at μ receptors, displaying weak affinity for κ-opioid receptors. μ receptors mediate the pain-relieving properties but they can also result in adverse effects like nausea, constipation and respiratory depression (Murray 2005). One systematic review has shown that hydromorphone has similar analgesic and side effects to morphine (Miller 1999), while a more recent review concludes that no study can clearly demonstrate whether hydromorphone is better than oral morphine (Pigni 2011).
Hydromorphone, in common with other opioid analgesics, has the potential to produce adverse effects that include respiratory depression, nausea, vomiting, constipation and itching. Tolerance may develop during chronic opioid therapy such that larger doses may be required to sustain the analgesic effect. In addition, patients can be at risk of physiological dependence and experience opioid withdrawal syndrome upon sudden cessation of the opioid or administration of an antagonist. Side effects from opioid analgesics are not always seen as adverse effects, however. When used for the relief of pain in malignant disease, the actions of relieving anxiety, producing drowsiness and allowing sleep may be welcome (Grahame-Smith 2002).
Why it is important to do this review
This is one of a suite of reviews looking at analgesics for cancer pain. Although WHO recommends oral morphine as first-line analgesia for cancer-related pain, the use of hydromorphone remains a consideration in some circumstances (Wiffen 2013). Previous systematic reviews have compared the efficacy and side effects of hydromorphone with other medications, but the inconsistency of their conclusions and the low quality of the studies that were included suggest that further research is needed. This review will update the evidence by evaluating the effectiveness of hydromorphone for cancer-related pain and examining the incidence and severity of its side effects.