On February 1, the European Academy of Palliative Care (EAPC) updated its Guidelines on Opioids for the Treatment of Cancer Pain, published in The Lancet? Oncology (Lancet Oncol 2012, 13: e58). The guideline summarizes recommendations in 16 areas by combining the latest evidence and the expert group’s assessment (△ indicates a stronger level of evidence, * indicates a weaker level of evidence). 1, WHO Second-step opioids For people with mild to moderate pain and inadequate pain control with regular oral acetaminophen or oral nonsteroidal anti-inflammatory drugs (NSAIDs), it is expected that the addition of second-step oral opioids (e.g., codeine, tramadol) may provide pain relief without serious adverse effects, and that small doses of third-step opioids (e.g., morphine, oxycodone) can also be used as an alternative medications*. Pei Wenzhong, Department of Oncology, Beijing Luhe Hospital, Capital Medical University, Beijing, China Evidence shows that there is no significant difference in the analgesic efficacy of morphine, oxycodone, and hydromorphone when administered orally, and that all three drugs can be used as the first choice of third-order opioids for moderate and severe cancer pain*. Oral immediate-release and extended-release dosage forms of morphine, oxycodone and hydromorphone can be used for opioid dosage titration*. When titrating with these two dosage forms, oral immediate-release opioids should be supplemented as needed to control the pain outbreak. 4, The role of transdermally administered opioids Transdermally administered fentanyl and buprenorphine are alternatives to oral opioids, and these two drugs may be the preferred third-step opioid in some patients*; they are also an effective, noninvasive route of analgesia for those with swallowing disorders. 5. Effects of Methadone Methadone has complex pharmacokinetics with a long and unpredictable half-life. It may be used as the first choice of third-step opioid in patients with moderate to severe cancer pain or as a subsequent option* for experienced professionals only. 6. Switching between opioids Substitution of other opioids may be beneficial for those who are treated with third-step opioids but do not obtain adequate pain relief and who have serious adverse effects and/or are difficult to treat effectively*. 7. Opioid Equivalent Dose When making an opioid switch, dose conversion ratios exist at different levels of confidence. These conversion ratios are based on the premise that opioid pain relief prior to conversion is satisfactory. Therefore, when a patient undergoes opioid conversion because of unsatisfactory opioid analgesia and/or comorbid serious adverse effects, clinical experience suggests that the starting dose after conversion should be lower than the value based on published equianalgesic ratios (EAR) calculations. All patients require dose titration after opioid conversion based on clinical pain efficacy. The subcutaneous route of administration is simple and effective for morphine, diacetylmorphine, and hydromorphone and should be the preferred route for those who cannot be administered orally or percutaneously △; intravenous infusion can be used in combination with contraindications to subcutaneous administration (e.g., peripheral edema, coagulation disorders, poor peripheral circulation, large volumes of fluids to be infused, and high opioid dosages) △; and intravesical routes of opioid titration should only be used when there is a clinical need for rapid pain control △. clinical need for rapid pain control △. Intravenous and subcutaneous infusions can be used for optimal pain relief in those who cannot obtain adequate pain relief orally or transdermally*; Patient-controlled analgesia can be used for both subcutaneous and intravenous routes of administration if the patient is able and willing to control the antidote dose*; Morphine conversion ratios are essentially the same when switching from oral to subcutaneous and intravenously administered morphine, with ratios ranging from 3:1 to 2:1*; Although opioid administration is effective when administered rectally, suitable doses are often not readily available. Although opioids are effective when administered rectally, they are often not readily available in suitable dosage forms and are unacceptable to many patients, so they are only a second choice*. 9. Oral immediate-release opioids should be given for pain exacerbation due to uncontrolled underlying pain; when opioids are given on a regular basis, the antidote dose for flare-ups should be predetermined △. Explosive pain (e.g., episodic pain) can be effectively managed with oral, immediate-release opioids or fentanyl lozenges or nasal sprays. For some patients, fentanyl tablets or nasal sprays are preferable to immediate-release oral opioids because of their more rapid onset of action and shorter duration of pain relief. Alternatively, immediate-release opioids with a short half-life can be used to treat anticipatory flare-ups of pain and can be given within 20-30 minutes before the onset of pain*. 10. Treatment of opioid-associated vomiting Some antidopamine drugs (e.g., haloperidol) and other types of drugs with combined antidopamine function (e.g., metoclopramide) should be used in the treatment of opioid-induced vomiting*. 11. Treatment of opioid-associated constipation Light laxatives should be routinely used to combat opioid-induced constipation Δ. There is no evidence to suggest that any one laxative is significantly superior. For refractory constipation, a combination of drugs with different mechanisms of action may be more effective than a single mode of action. Subcutaneous injection of methylnaltrexone may be considered when traditional laxatives are ineffective. 12. Treatment of opioid-associated CNS symptoms Methylphenidate may be used to ameliorate opioid-induced over-sedation, but there is a narrow dosage range between effective doses and overdose*. Patients with opioid-associated neurotoxic effects (delirium, hallucinations, clonus, and nociceptive sensitization) should be considered for dose reduction or switching to other opioids*. 13. Use of opioids in patients with renal failure Opioids should be used with caution in patients with severe renal impairment (glomerular filtration rate <30 ml/min) *. Subcutaneous or intravenous administration of fentanyl or buprenorphine should be preferred in this case, and should be initiated in small doses and followed by slow titration of the dose. Expedient measures, such as temporary reduction of morphine dose or frequency of administration, may also be used as a short-term coping strategy. 14. Acetaminophen and NSAID pain relief on top of third-order opioids NSAIDs* may be added to improve the pain relief of third-order opioids or when opioid dose reduction is needed, but given the risk of serious adverse events with these medications, their use should be restrictive, especially in the elderly and in those with comorbid renal, hepatic, or cardiac failure. In combination with third-order opioids, acetaminophen is superior to NSAID due to fewer adverse events, but its efficacy is not certain*. 15. Adjuvant medications for neuropathic pain (antidepressants, anticonvulsants) Opioids are only partially effective in the treatment of cancer neuropathic pain, at which point amitriptyline or gabapentin∆ should be considered. Without careful titration, the combination of these drugs with opioids may cause additional CNS adverse events. Intraspinal administration of opioids Intraspinal (epidural or intradural) administration of opioids in combination with local anesthetics or colistin should be considered for the treatment of persons who, despite optimal oral/non-oral opioid and non-opioid therapy, continue to experience unsatisfactory pain relief or intolerable adverse effects*. Opioids are the centerpiece of cancer pain pharmacotherapy. As early as 1996, the EAPC issued the Guidelines for the Treatment of Cancer Pain with Morphine, which were updated and renamed the Guidelines for the Treatment of Cancer Pain with Opioids in 2001.3 years ago, the EAPC formally initiated the updating of the Guidelines by first discussing and defining the main structure and content of the Guidelines, which is to list the 22 major issues facing the treatment of opioid pain in cancer pain, and then answering the systematic review of the findings after the systematic review of the Guidelines respectively and publishing the results of 19 of the findings in 2010. The results of 19 of these were published in 2010. On this basis, the expert group comprehensively evaluated the evidence obtained from the systematic review according to the criteria for categorizing the level of evidence, and reached a consensus and wrote the new version of the guideline after full discussion. Compared with many current guidelines in the field of cancer pain treatment, this guideline is more concise, organized, objective, and refreshing. Its main features are summarized in 3 aspects: 1) more intuitive question-oriented, i.e., questions are listed first, then evidence is provided, followed by clear answers, which makes it easy for readers to review quickly; 2) more scientific evidence-oriented, based on systematic review, rather than simple listing and citing of evidence; 3) more clear clinical orientation, in which the guideline expert group combines the limited evidence with their rich clinical experience and objectively recommends clinical strategies. recommend clinical strategies. The process of updating the guideline was a comprehensive review by the EAPC expert group of the major studies in the field of opioid therapy for cancer pain over the past 10 years. From the initial identification of 22 major issues, to the publication of 19 reviews, to the 16 items listed in the guideline, it is not difficult to find that the major limiting factor for the gradual reduction of the number of entries is the insufficient evidence of evidence-based medicine, which has prompted us to learn and learn from the guideline, This also encourages us to learn from the guideline and improve the treatment of cancer pain, and to design clinical trials in a more targeted manner, and to adopt randomized, controlled, and blinded studies as much as possible if possible, so as to comprehensively improve the overall level of clinical research in this field.