Table 1.
Strategies for Mitigating Opioid Tolerance or Opioid-Induced Hyperalgesia.*
| Appropriate use of opioids |
| Use of valid assessment scales of pain before and during administration of the analgesic drug |
| Use of intermittent opioid therapy (oral or intravenous) rather than continuous infusions, when possible |
| Opioid rotation |
| Use of remifentanil for short-term analgesia (because of potent induction of opioid-induced hyperalgesia), except when rapid offset of effect is required, as in evaluation of head injury |
| Minimal use of benzodiazepines (because of delirium and potential opioid-induced hyperalgesia associated with long-term use) |
| Avoidance of excessive dose escalation; supplementation of opioid with nonopioid analgesics |
| Addition of methadone to attenuate or delay opioid tolerance |
| Coadministration of nonopioid analgesics as rescue therapy during procedures or to potentiate the effects of opioids |
| N-methyl-d-aspartate receptor antagonists (ketamine) |
| α2-Adrenergic receptor agonists (clonidine or dexmedetomidine) |
| Gabapentinoids (gabapentin or pregabalin) |
| Continuous administration of nerve blocks by means of a catheter |
| Neuraxial: thoracic or lumber epidural blocks for thoracic, abdominal, or bilateral leg analgesia |
| Regional: brachial plexus block for arm analgesia; femoral or obturator block or both, with or without sciatic nerve block for lower-limb analgesia |
| Local: paravertebral block for rib fractures or chest-tube–associated pain; transversus abdominis block for lower abdominal surgery |
| Prevention or reversal of opioid-induced hyperalgesia and opioid-withdrawal symptoms |
| Tapering of opioid dose when pain score goal is achieved (10–20% dose reduction every 1–4 days) |
| Use of valid withdrawal assessment scales |
| Use of adjuncts to opioids (ketamine, dexmedetomidine, or gabapentinoids [gabapentin or pregabalin]) |
| Use of methadone |
| Reduction of inflammation |
| Scheduled acetaminophen therapy |
| Short-term use of ketorolac† |
*
The nonopioid strategies that are listed are usually used in combination with opioids; dosing regimens and routes of drug administration are provided in Tables S2 and S3 in the Supplementary Appendix.
†
Other nonsteroidal antiinflammatory drugs (e.g., ibuprofen) have limited use in the intensive care unit because of cardiovascular, nephrotoxic, and gastrointestinal side effects.