Acute Pain Management in Patients With Opioid Tolerance

Adebola Adesoye, PharmD, BCPS; Nakia Duncan, PharmD, BCGP, BCPS


US Pharmacist. 2017;42(3):28-33. 

In This Article

Approach to Pain Management

Acute pain management in opioid-tolerant patients often requires a multimodal and multidisciplinary approach; therefore, it is necessary to maintain careful coordination and effective communication between disciplines, as well as between each discipline and the patient.[17] Early identification through a careful assessment and history in patients at risk for opioid tolerance is essential for adequate pain-management planning.[17,18] Upon identification of such a patient, steps should be taken to formulate an effective treatment plan in the preoperative or similarly acute phase to ensure adequate pain management during the acute period and prevention of withdrawal symptoms or other treatment-related complications.[17,18] Similarly, appropriate discharge and transition-of-care planning should be considered.[17,18]

As with the general patient population, a multimodal pain regimen with a combination of pharmacologic and nonpharmacologic approaches is ideal. Opioids remain the drug of choice for severe pain and are a common option for moderate pain, but multimodal pain management with acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), and adjuvant medications ( Table 1 ) remains the mainstay of effective analgesia. In order to prevent delays in care and the risk of untreated pain, analgesics should be administered on a scheduled basis rather than an as-needed basis.


Patients with opioid tolerance will likely require more opioids than opioid-naïve patients.[4,5] Opioids should be administered in an amount sufficient to achieve analgesia without harmful side effects, such as excessive sedation or respiratory depression.[4] Opioid rotation (substitution with a different opioid when one opioid in increasing doses does not provide desired analgesic effect) may be employed when needed in patients with opioid tolerance, as cross-tolerance is uncommon.[4,5] The recommended approach for opioid rotation is to initially substitute with one-half to two-thirds equianalgesic opioid and then monitor for safety and effectiveness.[4] It should be kept in mind that switching from a long-acting opioid to a short-acting opioid may precipitate withdrawal symptoms in the patient.[4]

Opioid-related side effects are less common in opioid-tolerant patients; however, if opioid therapy is selected as analgesia of choice in these patients, monitoring for side effects or complications related to opioid therapy remains just as important as with the general population.[4,5] The risk of adverse drug events is greater with rapid escalation of opioid therapy, even in opioid tolerance.[5] In fact, opioid-tolerant patients are said to be more susceptible to the sedative properties of opioids and should be monitored.[5,17]

In the selection of opioids as analgesia of choice, patient-controlled analgesia (PCA) offers a convenient method of delivery, as it minimizes the risk of undertreatment, allows self-titration, and negates possible conflicts with nursing staff.[4,5] Additionally, a retrospective study found that opioid-tolerant patients who had PCA were less likely to report adverse effects—with the exception of sedation—compared with the opioid-naïve group.[19] By nature of their condition, opioid-tolerant patients likely require higher bolus doses with PCA.

Recognizing Acute Withdrawal

Opioid withdrawal can occur in opioid-dependent patients receiving a reduced amount of their usual opioid or using an opioid antagonist. The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, lists four criteria for opioid withdrawal: 1) previously heavy and prolonged opioid use ceases or is reduced, or an opioid antagonist is administered after a period of opioid use; 2) at least three signs and symptoms (e.g., dysphoric mood, nausea, vomiting, diarrhea, muscle aches, rhinorrhea, lacrimation, pupillary dilation, piloerection, sweating, yawning, fever, insomnia) develop within minutes to several days of the previous criteria; 3) symptoms are clinically significant or impair social, occupational, and other important areas of functioning; and 4) signs and symptoms cannot be attributed to any other medical or mental disorder, including withdrawal from or intoxication with another drug.[20]

NSAIDs and Acetaminophen

NSAIDs and acetaminophen are often included in the multimodal approach to pain management in opioid-naïve patients because of their opioid-sparing property. Similarly, this approach should be employed in maximally tolerated doses in opioid-tolerant individuals.[17] It is suggested that use of these agents will decrease the need and increase the time for rescue medications required for breakthrough pain.[7] Both subgroups of medications may be given orally or parenterally.