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Dosage Titration
Opioid doses should be adjusted in each patient to achieve pain relief with an acceptable level of adverse effects. Dosage typically requires adjustment over time. With the exception of fentanyl delivered by the transdermal route, there is no ceiling or maximal recommended dose for full opioid agonists, and in fact, very large doses of morphine, e.g., several hundred milligrams every 4 hours, may be needed for severe pain.161
Effective pain relief can be accomplished by the anticipation and prevention of pain. Because many patients have persistent or daily pain, it is important to use opioids on a regular schedule rather than only "as needed." Around-the-clock administration of analgesics allows each dose to become effective before the previous dose has lost its effectiveness. A patient should be given as-needed doses for the first 24 to 48 hours when a new drug is started to define the best daily dosing requirements for that individual patient.
In addition to the titration of individual drugs, the modalities for pain management are titrated when the pain is persistent and is moderate to severe in intensity.
Pain management for moderate to severe pain should begin with oral opioids in combination with an NSAID or acetaminophen. The optimal dose will control pain with the fewest side effects, such as sedation, mental clouding, nausea, or constipation.
Adjuvant drugs may be used to counteract the predictable side effects of opioids. For example, hydroxyzine may be added to opioids and NSAIDs to manage anxiety and nausea, especially when they occur simultaneously and are not intense. Dietary caffeine supplementation may provide additive analgesia and counteract opioid induced sedation. Antiemetic drugs such as phenothiazines and metoclopramide may be added to manage opioid-induced nausea.
It is usually advisable to observe the patient's response to several different opioids, sequentially, before switching routes of administration or trying an anesthetic, neurosurgical, or other invasive approach to relieve persistent pain.173 For example, patients who experience dose-limiting sedation, nausea, or mental clouding on oral morphine should be switched to an equianalgesic dose of hydromorphone or fentanyl. The dose of the second opioid should then be adjusted. Sequential analgesic trials should be based on regular assessments of pain, with continuous attention to antineoplastic and noninvasive nonpharmacologic therapies.
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