Change the Equation: Polyanalagesic Options in the Perioperative Period

Although Americans comprise roughly 5 percent of the world’s population, they consume 99 percent of the world’s hydrocodone and 83 percent of its oxycodone, resulting in one opioid-related death every 35 minutes (1). In the setting of an on-going national opioid crisis and continued restrictions placed on prescribers, alternative pain management therapies are essential. This is particularly true for neurosurgeons, who regularly treat patients with chronic back pain.

Whether our patients come to us opioid naïve or with years of chronic, high-dose opioid use, the medications we give them perioperatively play a role in this opioid epidemic. New, chronic opioid use appears to be the most common complication of many surgical procedures (2).

Extensive evidence exists on the benefits of non-opioid therapies for the management of post-surgical patients (1,3-9). Here we offer a brief look at some of the available options, that neurosurgeons can easily implement in their daily practices:

Prescribe preoperative and postoperative gabapentin in patients who are not taking them and have no history of adverse effects.
Preoperative gabapentin or pregabalin is associated with decreased postoperative pain and opioid use at 24 hours following surgery (1,10,11). Doses vary, but consider a gabapentin starting dose of 100mg three times daily on week one increasing to 200 mg three times daily by week two, followed by 300mg three times daily thereafter. Advise patients that it may take several weeks to appreciate the benefit and to develop a tolerance to the side effects such as fatigue. If there is not adequate time to titrate the dosing, even a single dose of 900 mg of gabapentin in the holding area has been shown to reduce early postoperative pain and opioid use in patients undergoing lumbar spine surgery (12).

Work with anesthesia to give intraoperative and/or postoperative N-methyl-D-aspartate (NMDA) antagonists.
Ketamine, magnesium and dextromethorphan have all been associated with a reduction in postoperative opioid use, as well as postoperative nausea and vomiting (1,13-15).

Work with anesthesia to determine how intraoperative opioids should be managed.
There is significant controversy over whether certain opioids, especially remifentanil, can cause opioid-induced hyperalgesia (OIH) (8).  There is some evidence that how quickly the medication is turned off may influence the development of OIH (19).

Consider the use of lidocaine and bupivacaine.
Lidocaine and other local anesthetics can be used as preoperative regional blocks, epidural infusions, incisional agents at the beginning and end of cases and even postoperatively intravenously or via patches (1).

Prescribe around the clock postoperative acetaminophen.
When prescribed with opioids, the effects may be additive, or even synergistic, and may decrease the use of opioids (1,16). Current recommendations from the Food and Drug Administration (FDA) are to not administer more than 3000 mg total a day to adults with normal hepatic function.

Prescribe postoperative NSAIDs.
If not contraindicated for your patient, these medications can result in a substantial reduction of pain, and many randomized controlled trials have not shown a difference in postoperative bleeding with the administration of NSAIDs (17,18).

Use tramadol when possible, especially in opioid-naïve patients, as an alternative to opioids.
This medication acts as a weak mu receptor binding opioid as well as a serotonin and norepinephrine reuptake inhibitor (1). Although less potent, there is a lower risk of addiction, less constipation and minimal respiratory depression.

Work with your hospitals to develop a polyangalgesic protocol that fits your practice.
Multiple centers are collaborating with their anesthesiologists, hospitalists and physician extenders to implement a policy that works for their patients.

1. Wick, E. C., Grant, M. C., & Wu, C. L. (2017). Postoperative multimodal analgesia pain management with nonopioid analgesics and techniques. JAMA Surgery, 152(7), 691.

2. Brummett, C. M., Waljee, J. F., Goesling, J., Moser, S., Lin, P., Englesbe, M. J., . . . Nallamothu, B. K. (2017). New persistent opioid use after minor and major surgical procedures in US adults. JAMA Surgery, 152(6).

3. Armaghani, S. J., Lee, D. S., Bible, J. E., Archer, K. R., Shau, D. N., Kay, H., . . . Devin, C. J. (2014). Preoperative opioid use and its association with perioperative opioid demand and postoperative opioid independence in patients undergoing spine surgery. Spine, 39(25).

4. Cron, D. C., Englesbe, M. J., Bolton, C. J., Joseph, M. T., Carrier, K. L., Moser, S. E., . . . Brummett, C. M. (2017). Preoperative opioid use is independently associated with increased costs and worse outcomes after major abdominal surgery. Annals of Surgery, 265(4), 695-701.

5. Menendez, M. E., Ring, D., & Bateman, B. T. (2015). Preoperative opioid misuse is associated with increased morbidity and mortality after elective orthopaedic surgery. Clinical Orthopaedics and Related Research®, 473(7), 2402-2412.

6. Loftus, R. W., Yeager, M. P., Clark, J. A., Brown, J. R., Abdu, W. A., Sengupta, D. K., & Beach, M. L. (2010). Intraoperative ketamine reduces perioperative opiate consumption in opiate-dependent patients with chronic back pain undergoing back surgery. Anesthesiology, 1.

7. Blaudszun, G., Lysakowski, C., Elia, N., & Tramèr, M. R. (2012). Effect of perioperative systemic ?2 agonists on postoperative morphine consumption and pain intensity: systematic review and meta-analysis of randomized controlled trials. Anesthesiology, 116(6), 1312-1322.

8. Rivosecchi, R. M., Rice, M. J., Smithburger, P. L., Buckley, M. S., Coons, J. C., & Kane-Gill, S. L. (2014). An evidence based systematic review of remifentanil associated opioid-induced hyperalgesia. Expert Opinion on Drug Safety, 13(5), 587-603.

9. Dworkin, R. H., O’Connor, A. B., Backonja, M., Farrar, J. T., Finnerup, N. B., Jensen, T. S., . . . Wallace, M. S. (2007). Pharmacologic management of neuropathic pain: Evidence-based recommendations. Pain, 132(3), 237-251.

10. Hurley, R. W., Cohen, S. P., Williams, K. A., Rowlingson, A. J., & Wu, C. L. (2006). The analgesic effects of perioperative gabapentin on postoperative pain. Regional Anesthesia and Pain Medicine, 31(3), 237-247.

11. Mishriky, B. M., Waldron, N. H., & Habib, A. S. (2014). Impact of pregabalin on acute and persistent postoperative pain: A systematic review and meta-analysis. British Journal of Anaesthesia, 114(1), 10-31.

12. Yu, L., Ran, B., Li, M., & Shi, Z. (2013). Gabapentin and pregabalin in the management of postoperative pain after lumbar spinal surgery. Spine, 38(22), 1947-1952.

13. Bell, R. F., Dahl, J. B., Moore, R. A., & Kalso, E. A. (2006). Perioperative ketamine for acute postoperative pain. Cochrane Database of Systematic Reviews.

14. De Oliveira, G. S., Castro-Alves, L. J., Khan, J. H., & Mccarthy, R. J. (2013). Perioperative systemic magnesium to minimize postoperative pain. Anesthesiology, 119(1), 178-190.

15. King, M. R., Ladha, K. S., Gelineau, A. M., & Anderson, T. A. (2016). Perioperative dextromethorphan as an adjunct for postoperative pain. Anesthesiology, 124(3), 696-705.

16. Apfel, C. C., Turan, A., Souza, K., Pergolizzi, J., & Hornuss, C. (2013). Intravenous acetaminophen reduces postoperative nausea and vomiting: A systematic review and meta-analysis. Pain, 154(5), 677-689.

17. Gobble, R. M., Hoang, H. L., Kachniarz, B., & Orgill, D. P. (2014). Ketorolac does not increase perioperative bleeding. Plastic and Reconstructive Surgery, 133(3), 741-755.

18. Strom, B. L., Berlin, J. A., Kinman, J. L., Spitz, P. W., Hennessy, S., Feldman, H., . . . Carson, J. L. (1997). Parenteral ketorolac and risk of gastrointestinal and operative site bleeding. Survey of Anesthesiology, 41(1), 32.

19. Comelon, M., Raeder, J., Stubhaug, A., Nielsen, C. S., Draegni, T., & Lenz, H. (2016). Gradual withdrawal of remifentanil infusion may prevent opioid-induced hyperalgesia. British Journal of Anaesthesia, 116(4), 524-530.