Acute Pain Management in Patients With Opioid Tolerance

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

US Pharmacist. 2017;42(3):28-33.

Abstract and Introduction

Abstract

Prescription opioid use has significantly increased globally in the past two decades and has led to an increased number of patients who have become tolerant to opioids. Analgesia in this patient population poses a challenge, and there is a risk of undertreatment. In addition to providing effective analgesia, it is important to prevent withdrawal symptoms and address any related psychosocial issues. Therefore, a multidisciplinary and multimodal approach in pain management is necessary to provide effective analgesia in this patient population.

Introduction

Prescription opioids are some of the most commonly prescribed pain medications in the United States, and they are usually the drugs of choice for managing moderate-to-severe pain. The number of opioids prescribed in the U.S. sky-rocketed from 76 million in 1991 to 216 million in 2012, with one-half of opioid sales accounting for treatment of chronic noncancer pain.^[1,2]

The FDA defines a patient as opioid tolerant if for at least 1 week he or she has been receiving oral morphine 60 mg/day; transdermal fentanyl 25 mcg/hour; oral oxycodone 30 mg/day; oral hydromorphone 8 mg/day; oral oxymorphone 25 mg/day; or an equianalgesic dose of any other opioid.^[3]Opioid tolerance implies a lesser susceptibility to the effects of opioids—both therapeutic and adverse—and it may develop in individuals with longterm use of opioids.^[3–6] Patients who are prescribed opioids for management of cancer pain or chronic noncancer pain or who have an opioid addiction may become opioid tolerant.^[5,6]

Acute pain may present postoperatively because of the traumatic surgical injury, or in other acute conditions. Acute pain in patients with opioid tolerance makes pain management a challenge, and perhaps one of the greatest risks associated with pain management in this population is the risk of undertreatment due to stigma and bias. Further, data on pain management in this patient population are limited.^[7] This review focuses primarily on acute pain management in opioid-tolerant patients, including those with chronic opioid use for chronic noncancer pain and those who abuse opioids.

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Next Section

Abstract and Introduction
Pathophysiology
Consequences of Unrelieved Pain
Treatment Goals for Acute Pain
Approach to Pain Management
Special Populations and Acute Pain Management
Conclusion
References

Table 1. Multimodal Analgesia for Acute Pain Management
Drug Class	Drugs	Clinical Considerations
NSAIDs	Ibuprofen, naproxen, diclofenac, meloxicam, sulindac	Antiplatelet effects. GI bleeding risk; consider PPI use. CV risk; renal and hepatic considerations. Interactions with lithium. Available in topical, oral, and parenteral formulations
Acetaminophen		Maximum-dose considerations. Analgesic ceiling effects. Hepatic considerations. Available in oral and parenteral formulations
Opioids	Morphine, hydromorphone, oxycodone, hydrocodone, fentanyl, methadone	May be given as long-acting or short-acting formulation. Side effects and withdrawal symptoms. Assess renal and hepatic function. Available in topical, oral, and parenteral formulations
Mixed-acting analgesics	Tramadol, tapentadol	Low affinity for opioid receptors. Analgesic ceiling effect. Risk of lowering seizure threshold. May be considered adjuvant for neuropathic pain
NMDA receptor antagonists	Ketamine, methadone	May inhibit opioid tolerance. May be considered as adjuvant in opioid-tolerant patients. Ketamine shown to enhance morphine analgesic effects. Methadone administered as adjuvant to prevent opioid withdrawal
Anticonvulsants	Carbamazepine, gabapentin, pregabalin	Slow onset of pain relief. Gabapentin and pregabalin useful for neuropathic symptoms. Utility in opioid-tolerant patients not well established
Antidepressants	Venlafaxine, duloxetine, milnacipran, nortriptyline, amitriptyline	Greater evidence with neuropathic pain. Risk of serotonin syndrome with SNRIs. Risk of unpleasant side effects. Renal and hepatic considerations
Alpha₂ agonists	Dexmedetomidine, clonidine	Helps suppress opioid-withdrawal symptoms. Considered opioid-sparing and antihyperalgesic. Potentiates systemic analgesics
Corticosteroids	Dexamethasone	Possible analgesic adjuvant in opioid tolerance. Place in therapy unclear

CV: cardiovascular; GI: gastrointestinal; NMDA: N-methyl-D-aspartate; NSAID: nonsteroidal anti-inflammatory drug; PPI: proton pump inhibitor; SNRI: serotonin-norepinephrine reuptake inhibitor. Source: References 4, 5, 7, 8, 28–30, 32.

Table 2. Acute Pain Management Considerations in Older Adults
Drug Class	Considerations
Acetaminophen	Consider initial treatment for mild pain. Maximum: 3 g/day from all sources
NSAIDs	Several safety warnings exist for NSAIDs (GI bleeding, kidney disease, HF, CAD). Advise against using NSAIDs systemically. Consider topical NSAID if pain localized, unless safer therapies have failed
Opioids	Assess for renal or hepatic impairment and select opioid accordingly. Frequently evaluate pain and adverse effects. Frequently assess for therapeutic goal, and plan to titrate off once goals are achieved. Patient should have a stool softener and laxative available to prevent OIC
Adjuvants	Enhance analgesic effect of other medications. Avoid TCAs because of profound anticholinergic effects

CAD: coronary artery disease; GI: gastrointestinal; HF: heart failure; NSAID: nonsteroidal anti-inflammatory drug; OIC: opioid-induced constipation; TCA: tricyclic antidepressant.
Source: References 21, 24.

Table 3. Abuse-Deterrent Opioids
Brand Name	Generic Name	Abuse-Deterrent Mechanism
Arymo ER	Morphine	Crush/extraction-resistant
Embeda ER	Morphine-naltrexone	Agonist-antagonist
Hysingla ER	Hydrocodone	Crush/extraction-resistant
Morphabond	Morphine	Crush/extraction-resistant
Opana ER	Oxymorphone HCl	Crush/extraction-resistant
Oxaydo	Oxycodone	Crush/extraction-resistant
Targiniq ER	Oxycodone-naloxone	Agonist-antagonist
Troxyca ER	Oxycodone-naltrexone	Agonist-antagonist
Vantrela ER	Hydrocodone	Crush/extraction-resistant
Xtampza ER	Oxydocone	Crush/extraction-resistant
Zohydro ER	Hydrocodone	Crush/extraction-resistant

ER: Extended-release; HCl: hydrochloride.
Source: Reference 27.

Table 4. Treatment Strategies for Patients in Opioid-Abuse Programs
Drugs	Planned Minor/Elective Surgery	Unplanned Trauma/Surgery
Methadone	Continue usual maintenance dose; use short-acting opioids. Consider PCA	Continue usual maintenance dose; use short-acting opioids. Consider PCA
Buprenorphine	Discontinue 24–36 h prior; use short-acting opioids during/after surgery. Daily dose may be divided every 6–8 h	Start methadone 20–40 mg to treat opioid addiction. Use short-acting opioids for pain. Naloxone must be available at bedside. Switch back to buprenorphine at discharge
Naltrexone	Discontinue 72 h prior (oral). Discontinue 30 days prior for ER IM formulation; may use oral temporarily. Wait 3–7 days after discontinuing opioid before resuming naltrexone	Give regional analgesia. Use nonopioids (NSAIDs, IV acetaminophen), benzodiazepines, ketamine, clonidine. Wait 3–7 days after discontinuing opioid before resuming naltrexone