Strategies to Prevent the Transition From Postoperative Acute Pain to Chronic Pain

The high variability of postoperative pain is thought to partly underlie the discrepancies in results across studies.

In a talk titled “Preventing persistent post-surgical pain and promoting opioid cessation after discharge,” given at the annual meeting of the American Academy of Pain Medicine, March 15-19, 2017, in Orlando, Florida, Jennifer Hah, MD, MS, an anesthesiologist and pain specialist at the Pain Management Center at Stanford Health Care, California, provided an overview of postoperative care, its shortcomings, and current research in the field.¹

“When we think of pain after surgery, we often think of acute vs chronic pain, but perhaps there is more of a continuum with no clear delineation,“ stated Dr Hah. A number of shortcomings are associated with systematic reviews and meta-analyses on postoperative care. These include highly variable dosing protocols in studies investigating the effects of gabapentin and pregabalin, as well as treatment duration and drug bioavailability (which was shown to range from 3% to 90% for gabapentin), all of which can influence treatment outcomes. In addition, evidence is scarce regarding the efficacy of nonsteroidal anti-inflammatory agents (NSAIDs), ketamine infusions, or local anesthetics on postoperative pain.

What treatments have shown efficacy in relieving post-surgical pain? Results from an evidence-based review indicate that thoracic epidural infusions and paravertebral nerve blocks provide a reduction in persistent pain related to breast cancer surgery for a period lasting from 2.5 to 12 months after surgery.² In addition, these treatments were found to provide an opioid-sparing effect, thus decreasing the incidence of opioid-related adverse events. Another review that looked at the efficacy of epidural anesthesia on post-thoracotomy pain showed that the number to treat in order to prevent chronic pain was 4.³

“What else can we add to the picture [as these treatments all belong to the local analgesic realm]?” asked Dr Hah. A 3-month cognitive behavioral-based physical therapy regimen initiated 6 weeks after surgery led to reductions in pain and pain-related disability in patients undergoing lumbar spine surgery for chronic pain.⁴

“Is pain resolution more than pain intensity? I would hope so,” said Dr Hah. The high variability of postoperative pain is thought to partly underlie the discrepancies in results across studies. To palliate this issue, Dr Hah and her colleagues sought to ameliorate the way in which patients are classified, using data mining algorithms. This approach led to the identification of 2 patient clusters: patients with low- and high-pain.⁵ The investigators examined postoperative pain trajectories for a period of 10 days following surgery in 106 patients.⁵ Upon stratification by surgery type, clusters were found to separate patients in a 50:50 ratio. This categorization, achieved with a data mining algorithm, was shown to predict both pain- and opioid cessation with a highly significant threshold. The researchers hope to develop additional biomarkers to identify patients at risk for prolonged pain and opioid use after surgery.

Among the generally recognized risk factors for persistent post-surgical pain are anxiety, catastrophizing, preoperative pain, acute postoperative pain, pre-existing opioid use, and depressive symptoms. Patients taking illicit opioids pre-operatively were found to be at higher risk for prolonged pain.⁵ Extensive literature reflects this trend: in a study focusing on veterans, non-medical prescription opioid use was associated with pain interference.⁶ Another study in primary care clinics indicated an association between self-reported opioid use and chronic pain,⁷ and in the US adult population as a whole, non-medical prescription analgesic use is significantly associated with pain.⁸

Anxiety sensitivity, in which patients feel that unusual body sensations may harm them, is usually perceived as negative. However, anxiety sensitivity was found to predict short duration of pain.⁹This counterintuitive finding may be due to the fact that patients are so focused that they are more compliant than other patients with following rehabilitation directions, and taking their medications as directed.

A number of strategies have been proposed to address postoperative pain, including “transitional pain service,” which is instituted by identifying patients prior to surgery who are at risk for prolonged pain and opioid use following surgery.¹⁰ In those patients, enhanced communication and close monitoring may prevent a transition from acute to chronic postoperative pain.

In a double-blind placebo-controlled randomized clinical trial, the Stanford Accelerated Recovery Trial (ClinicalTrials.gov Identifier: NCT01067144), 410 patients undergoing a variety of surgical procedures were randomly assigned to treatment consisting of 1200 mg of preoperative gabapentin, followed by 300 mg of postoperative gabapentin, 3 times per day, for a total of 10 doses (3 days total), or placebo. Patients receiving gabapentin showed a lower risk of opioid abuse (as indicated by their opioid risk tool score), as well as lower levels of psychiatric comorbidities (including anxiety, depression,and impulsivity) than patients in the placebo arm. Although gabapentin had no effect on time to pain cessation — the trial’s primary outcome — it had an impact on the secondary outcome: time to opioid cessation, which was significantly decreased by gabapentin treatment (P <.05). Per-protocol analysis of time to opioid cessation (which only took into account patients who had received the 10 doses of potoperative gabapentin) showed a stronger clinical effect (P <.01).

Gabapentin was also found to reduce the use of illicit opioids during a 10-day detoxification regimen with buprenorphine,¹² and pre-clinical studies in animal models indicate that gabapentin may help prevent opioid-induced hyperalgesia,¹³ thus pointing to potential opioid-sparing effects of this drug.

The common standard of care in patients undergoing surgery may contribute to persistent opioid use and lead to non-medical use of opioids and addiction, according to Dr Hah. In addition, the main source of opioid diversion is over-prescribing for acute pain — and that includes surgical patients. “Are we really placing patients at risk?” asked Dr Hah. The risk of opioid addiction might be as high as 10%, and 31% to 84% of patients addicted to prescription opioids were initially given a legitimate opioid prescription that they later went on to abuse.

In a preliminary study, Dr Hah and her colleagues used motivational interviewing, defined as “a collaborative, goal-oriented style of communication with particular attention to the language of change… designed to strengthen personal motivation for and commitment to a specific goal by eliciting and exploring the person’s own reasons for change within an atmosphere of acceptance and compassion.”¹⁴ The researchers sought to compare the effects of motivational interviewing with guided opioid weaning on persistent opioid use after surgery.

A number of studies indicate that motivational interviewing can help patients with treatment engagement, improve treatment outcomes, increase medication adherence, and decrease drug use. In another trial conducted at Stanford, the “Perioperative Recovery of Opioids, Mood and Pain Trial” or PROMPT (ClinicalTrials.gov Identifier: NCT02070003), opioid-naïve patients undergoing hip or knee replacement surgery were randomly assigned to receive usual care or motivational interviewing, combined with physician-guided opioid tapering. Tapering involved a short conversation (usually ≤15 min) during which the physician discusses with the patient their medication use adherence, and response (presence of adverse effects), and provides advice on opioid weaning.

Preliminary data from the PROMPT trial (n=34) indicate that the median time to opioid cessation in patients who were tapered is about 30 days, compared with 55 days for usual care. Expert guidelines recommend that patients be weaned off opioids within 6 weeks of surgery, but no evidence-based method is currently available to reach this goal.

“Our hope is that studies like this or other evidence-based clinical trials will continue to complement the expert guidelines, so we can prevent the catastrophies that are happening,” concluded Dr Hah.

References

1. Hah J. Preventing persistent post-surgical pain and promoting opioid cessation after discharge. Presented at: the American Academy of Pain Medicine 33rd Annual Meeting; March 16-19, 2017; Orlando, Florida.
2. Cheng GS, Ilfeld BM. An evidence-based review of the efficacy of perioperative analgesic techniques for breast cancer-related surgery. Pain Med. 2016. pii: pnw172. [Epub ahead of print]
3. Andreae MH, Andreae DA. Local anaesthetics and regional anaesthesia for preventing chronic pain after surgery. Cochrane Database Syst Rev. 2012;10:CD007105.
4. Archer KR, Devin CJ, Vanston SW, et al. Cognitive-behavioral-based physical therapy for patients with chronic pain undergoing lumbar spine surgery: A randomized controlled trial. J Pain 17:76-89, 2016. J Pain. 2017;18(4):477.
5. Carroll IR, Hah JM, Barelka PL, et al. Pain duration and resolution following surgery: an inception cohort study. Pain Med. 2015;16(12):2386-2396.
6. Barry DT, Goulet JL, Kerns RK, et al. Nonmedical use of prescription opioids and pain in veterans with and without HIV. Pain. 2011;152(5):1133-1138.
7. Becker WC, Fiellin DA, Gallagher RM, Barth KS, Ross JT, Oslin DW. The association between chronic pain and prescription drug abuse in Veterans. Pain Med. 2009;10(3):531-536.
8. Novak SP, Herman-stahl M, Flannery B, Zimmerman M. Physical pain, common psychiatric and substance use disorders, and the non-medical use of prescription analgesics in the United States. Drug Alcohol Depend. 2009;100(1-2):63-70.
9. Keogh E, Book K, Thomas J, Giddins G, Eccleston C. Predicting pain and disability in patients with hand fractures: comparing pain anxiety, anxiety sensitivity and pain catastrophizing. Eur J Pain. 2010;14(4):446-451.
10. Clarke H, Poon M, Weinrib A, Katznelson R, Wentlandt K, Katz J. Preventive analgesia and novel strategies for the prevention of chronic post-surgical pain. Drugs. 2015;75(4):339-351.
11. Carroll I, Barelka P, Wang CK, et al. A pilot cohort study of the determinants of longitudinal opioid use after surgery. Anesth Analg. 2012;115(3):694-702.
12. Sanders NC, Mancino MJ, Gentry WB, et al. Randomized, placebo-controlled pilot trial of gabapentin during an outpatient, buprenorphine-assisted detoxification procedure. Exp Clin Psychopharmacol. 2013;21(4):294-302.
13. Wei X, Wei W. Role of gabapentin in preventing fentanyl- and morphine-withdrawal-induced hyperalgesia in rats. J Anesth. 2012;26(2):236-241.
14. Miller WR, Rollnick S. Motivational interviewing: helping people change. 3rd ed. New York, NY. Guilford Press, 2013.