US Pharm. 2024;49(3):HS2-HS7.

ABSTRACT: Even with advances in surgical techniques, the prevention and minimization of postoperative pain continue to be a topic of clinical discussion and research. Although pain is a subjective state, multimodal interventions have been developed that allow clinicians to tailor pain-management therapies to the individual patient. The implementation of pain assessments, analgesics, and nonpharmacologic approaches along with pharmacologic therapies optimizes pain management, and it can also contribute to reductions in opioid dependence, adverse effects, and long-term complications. As part of the healthcare team, pharmacists should offer recommendations on analgesic options, participate in opioid-stewardship programs, and assist in the formulation of postoperative pain protocols.

Surgical interventions have become a foundational component of modern healthcare’s clinical advances in the improvement of patient quality and quantity of life. Postoperative pain is experienced by most patients who undergo invasive procedures; the U.S. Institute of Medicine stated that 80% of surgical patients in the United States had pain postoperatively, and in a national survey, 75% of participants reported experiencing moderate to extreme pain immediately following surgery. Furthermore, mismanagement of postoperative pain compromises patient recovery by increasing morbidity and delaying recovery.¹

The use of multimodal analgesic regimens has become the standard method for addressing both acute and chronic postoperative pain. Although acute pain and chronic pain are managed differently, the medications utilized for both are divided into nonopioid and opioid regimens. The incorporation of nonpharmacologic approaches enhances the effectiveness of analgesic therapies.² Multidisciplinary collaboration, coupled with the use of multimodal strategies, has made it possible to tailor treatment plans based on the patient’s medical status and type of surgical intervention.²

Despite the push to develop standardized algorithms for pain management, pain is necessarily a subjective state. Pain-assessment tools are clinical instruments used to conceptualize and objectively describe a patient’s pain experience. Establishing a multimodal regimen provides thorough pain coverage from multiple drug mechanisms, and the use of nonopioid analgesics reduces the development of opioid dependence. Regardless of whether the approach is pharmacologic or nonpharmacologic, the goal of the management of both acute and chronic postoperative pain is to alleviate symptoms and prevent complications.³

ACUTE POSTOPERATIVE PAIN

Acute postsurgical pain (APSP) is a symptom that develops within 7 days after surgery and lasts for less than 3 months.⁴ The UK Perioperative Quality Improvement Programme 2017–2018 annual report noted that 48% of patients across the United Kingdom experienced severe APSP within the first 24 hours after surgery.⁵ Prolongation of APSP can lead to clinical complications, including chronic pain and morbidity. A literature review found that when multianalgesic regimens were considered, the overall incidence of moderate-to-severe APSP was 30%.⁶

Preoperative patient screening that identifies pertinent comorbidities and risk factors for decreased postoperative pain control and increased opioid use can assist in achieving optimal pain management through preoperative interventions, patient education, and early specialist management.⁵ Presurgical assessments aim to address both physiological and psychological contributors to APSP. In a German cross-sectional longitudinal study, younger age increased the risk of APSP.⁷ Psychological factors including fear of the surgery reduced recovery, increased disability, and increased analgesic nonadherence following surgery.

Anxiety, depression, and restlessness, which are psychological phenotypes that predict the likelihood of developing APSP, are measured by quantitative sensory testing (QST) and temporal summation of pain. Because of the subjective nature of pain, self-reporting subjective pain scales and standardized objective assessment tools are used to surmount the challenges of developing individualized pain-management regimens.⁵ The Visual Analogue Scale (VAS), Numeric Rating Scale (NRS), and Verbal Rating Scale (VRS) pinpoint a patient’s perception of pain, whereas the Critical Pain Observation Tool (CPOT) and Behavioral Pain Scale (BPS) do not require the patient’s cognitive input, which is beneficial for patients with dementia and cognitive impairments.^4,5 Overall, suboptimal presurgical evaluation and APSP management impede patient recovery and prolong pharmacologic interventions, leading to the development of chronic postoperative pain.¹

CHRONIC POSTOPERATIVE PAIN

Chronic postsurgical pain (CPSP) is defined as physiological discomfort in which pain intensifies following a surgical procedure and persists beyond the healing process for at least 3 months post surgery.⁸ On average, one in five patients undergoing surgery will develop CPSP.⁹ To be classified as having CPSP, a patient must meet certain criteria. The pain must develop after a surgical procedure and last for at least 2 months, and other causes of pain—such as from a preexisting condition—are excluded.¹⁰ The questions surrounding the mechanisms behind CPSP have not been fully researched because of the diversity of study designs, definitions, surgical techniques, and so on.¹¹ Despite the lack of evidence for accurately predicting the mechanisms of CPSP, risk factors for the development of CPSP have been identified. These risk factors include the patient’s gene expression profile and several preoperative, intraoperative, and postoperative aspects.

At present, the strongest and most consistent predictor of CPSP is acute postoperative pain.⁹ The severity of pain in the days and weeks after surgery is thought to contribute to the transition from acute to chronic pain. Additionally, studies have found that more chronic pain and overall poorer outcomes occur in operations lasting longer than 3 hours.¹¹ In other words, the intensity of the procedure plays a role in the development of CPSP. From a preoperative standpoint, younger age, lower educational level, and socioeconomic status have been considered major risk factors.⁹ Genetic polymorphisms are likely to be involved in the development of CPSP. The single nucleotide polymorphism coding for the catechol-O-methyltransferase enzyme is correlated with the development of chronic pain conditions such as temporomandibular joint disorder.¹² Finally, patients with poor inhibitory systems are more susceptible to developing CPSP after thoracotomy or major abdominal surgery.⁹

ASSESSING POSTOPERATIVE PAIN

The characterization of acute and chronic postoperative pain is based on the onset and prolongation of symptoms. However, the development of pain-management regimens requires several methods of measuring pain severity, chronicity, and pain experience.¹³ Although pharmacologic therapies are an important component of treatment, subjective and objective pain-assessment tools are important because they provide a comprehensive evaluation of a patient’s pain intensity and surgical outcome. Using the data collected, clinicians can better design multimodal treatment plans that meet the patient’s needs.

Subjective Assessment Tools

The VAS is a 10-cm to 15-cm scale that maps the patient’s pain severity, ranging from “no pain at all” to “pain as bad as it could be.”¹³ Patients rank their pain between these endpoints, and the VAS uses this ranking to identify the actual difference in pain magnitude. Collecting several measurements over time allows the clinician to record initial pain and monitor treatment responsiveness.¹⁴ However, one drawback is that the scale’s design does not accommodate patients who experience more pain than they thought possible. Additionally, because confusion and errors can affect its accuracy, the VAS requires sufficient instructions for patients.¹³

Other pain-assessment tools include the NRS and the VRS. The NRS, simpler than the VAS, scales pain from “no pain at all” to “the worst pain ever possible,” with patients identifying their pain level numerically on one of three scales: 0 to 10, 0 to 20, or 0 to 100.¹³ The NRS can be conducted verbally in person or over the telephone. A drawback is that, unlike the VAS, NRS data cannot be organized as a ratio. In the VRS, the patient selects one from a small number of specific adjectives (“no,” “mild,” “moderate,” or “severe”) to describe pain intensity. With its simpler structure, the VRS is easy to explain and understand; however, some patients find that the limited number of pain categories makes it difficult to accurately describe their pain level.¹³

Objective Assessment

The objective component of pain assessment is used primarily in nonverbal or incapacitated patients. One tool, the BPS, incorporates facial expression, upper-limb movement, and ventilation status into its evaluation; after each behavior is scored (from 1-4), the patient is assigned a level of pain intensity. A prospective, observational cohort trial noted, however, that the BPS is limited in its ability to categorize pain apart from nonpainful and painful procedures.¹⁵ Similar to the BPS, the CPOT incorporates upper and lower muscle tension into patient assessments. The greater comprehensibility of the CPOT makes it a more reliable resource than the BPS; however, both tools are vulnerable to observer bias.¹⁶ Biological markers can provide clear evidence of disease progression. Using proteomics, researchers hope to identify specific cytokines and biomarkers that may be able to establish levels of inflammation and pain.¹⁷ QST encompasses sensory phenotyping to identify the progression of acute pain to chronic pain.

PHARMACOLOGIC MANAGEMENT

Standardized pain management is based on the pain location and ranges of physiological coverage. CPSP management differs from APSP in various ways. Nonopioid, noninvasive, and nonpharmacologic therapies; mind-body interventions; and exercise are some common modalities for managing chronic pain. Opioids are not considered first-line or routine therapy for chronic pain.¹ In the acute setting, pain management is implemented immediately to minimize the patient’s exposure to severe discomfort. In contrast to chronic management, opioids are considered a staple in acute postoperative pain control. The medication regimen is tailored to the patient and is decided jointly by the patient and the medical personnel involved in the patient’s care. The simultaneous use of various pain-relieving medications and nonpharmacologic interventions is known as multimodal therapy. These regimens have been proven to result in superior pain relief and decreased opioid consumption compared with the use of a single medication.² A key part of the medication-selection decision is the drug’s route of administration, as the drug’s bioavailability is important. The goal in determining a regimen is to implement the quickest and most effective drug delivery with the fewest side effects.

Regional Anesthesia: Regional anesthesia numbs a specific area of the body, whereas general anesthesia induces central sedation. The use of regional anesthetic techniques has proven to be advantageous as a component of multimodal analgesia for postoperative pain management in patients undergoing various surgical procedures.² Procedures that commonly use peripheral regional anesthesia include thoracotomy, lower-extremity joint surgery, shoulder surgery, cesarean section, hemorrhoid surgery, and circumcision. In peripheral nerve block, a local anesthetic (e.g., mepivacaine, bupivacaine, ropivacaine, lidocaine) is used to alter the sensorium in the brain, resulting in decreased sensation of the nerves in a site-specific manner. It is thought that the incorporation of peripheral nerve block into specific procedures will reduce postoperative opioid consumption and pain scores; however, further studies are needed to validate this assumption.

Neuraxial Therapies: Neuraxial analgesia may be used for major thoracic and abdominal procedures, cesarean section, and hip and lower-extremity surgeries.² The use of epidural or spinal analgesia is particularly useful in patients who are at risk for cardiac or pulmonary complications or prolonged ileus. Epidural analgesia is beneficial in acute postoperative pain management because a continuous infusion of local anesthetic is provided along with opioids, lowering the dose requirement for each individual drug and reducing the frequency of side effects.³ In contrast, spinal analgesia is limited to only a single dose of opioids.² A review of nine randomized, controlled trials that compared IV patient-controlled analgesia (PCA) and continuous epidural analgesia (CEA) concluded that CEA achieved better pain control in the first 72 hours after abdominal surgery.

PCA Versus Non-PCA: PCA is a form of IV administration of opioids that is employed when postoperative systemic pain management is required for more than a few hours.² PCA allows the patient to administer bolus doses of a basal amount of opioid with the push of a button. Healthcare-provider administration of intermittent pain medications at various times is considered non-PCA therapy. PCA therapy is considered only if the patient has the necessary cognitive function to understand the proper use of the PCA pump.

Opioids

Opioid analgesics provide pain relief by agonizing mu opioid receptors and inhibiting ascending pain pathways. Current guidelines do not specify particular medications that should be utilized. Rather, the guideline recommendations are to use oral over IV medications when feasible; employ short-acting over long-acting agents; utilize the lowest effective dose for the shortest period of time; and assess the patient’s preoperative opioid use.² Patients should be monitored for adverse effects associated with opioid use, including sedation, respiratory depression (hypoventilation and hypoxia), nausea/vomiting, and constipation. Many opioid medications are currently available in a variety of dosages and formulations. Options include agents such as morphine, hydrocodone, hydromorphone, oxycodone, and methadone, which are full mu opioid agonists; buprenorphine, which is a mixed opioid agonist-antagonist; and tramadol, which is a centrally acting opioid.^18-20 Other classification systems used may refer to the compound structure or the relative opioid strength compared with morphine, the standard by which other opioids are compared. Pharmacokinetic characteristics dictate the dosing frequency, renal and hepatic dose adjustment requirements, and the onset of action. Lower dosages are recommended for frail and elderly patients.

Nonopioid Therapy

Nonsteroidal Anti-Inflammatory Drugs: Nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, naproxen, and ketorolac have a unique mechanism of action in pain management. These medications nonselectively or selectively inhibit the cyclooxygenase pathways, resulting in the inhibition of inflammation. NSAIDs have been evaluated as part of multimodal analgesia for the management of postoperative pain.² However, because these medications are associated with increased risks of gastrointestinal bleeding, ulceration, cardiovascular events, renal dysfunction, and more, they should be used with caution.

Celecoxib: This analgesic, anti-inflammatory, and antipyretic drug is a potent inhibitor of prostaglandin synthesis via the cyclooxygenase-2 pathway.²¹ Prostaglandins are the primary mediators of inflammation; therefore, the general outcome of celecoxib use is inhibition of inflammation. Celecoxib is not recommended for use in patients with severe renal insufficiency. Celecoxib carries the risk of serious cardiovascular and gastrointestinal events.

Gabapentin and Pregabalin: Traditionally utilized in the treatment of neuropathic pain, gabapentanoids are currently recommended for postoperative pain management.² Initially studied specifically for their use in polyorthopedic, spine, and rib fracture patients, these oral agents are recommended by current guidelines for use in major and minor surgical procedures.^2,19 Preoperative and postoperative utilization should be considered; however, there are no specific target doses. Patients should be monitored for sedation and dizziness, and the dosing should be adjusted for renal dysfunction.

Ketamine: Ketamine is a nonbarbiturate rapid-acting general anesthetic.²² This medication produces an anesthetic state that is caused by its antagonistic mechanisms of N-methyl-d-aspartate receptors in the central nervous system. The anesthetic state that is produced is termed dissociative anesthesia. Ketamine is contraindicated in patients who may have negative consequences from significant elevations in blood pressure.

NONPHARMACOLOGIC MANAGEMENT

Multimodal analgesics are the primary form of pain management for postoperative pain. The use of both nonpharmacologic methods and pharmacologic methods is recommended to reduce the patient’s pain.² Nonpharmacologic therapies used alone do not provide the same benefit as pharmacologic therapies, but they are beneficial when combined with pharmacologic therapy. Aerobic exercise, strength training, and flexibility/balance exercises (e.g., tai chi) are examples of beneficial nonpharmacologic therapies.²³ Aside from exercise, proper sleep hygiene, the Mediterranean diet, and physical therapy are other lifestyle recommendations that can improve the patient’s health outcomes. Cognitive-behavioral modalities such as guided imagery, relaxation techniques, hypnosis, and musical relaxation have been evaluated and have demonstrated positive effects on postoperative pain control. It should be noted that these modalities have been studied primarily in adults; evidence in adolescent populations is insufficient.²

PREVENTING AND MINIMIZING POSTOPERATIVE PAIN

Acute postoperative pain can lead to the development of chronic physiological and psychological outcomes. To minimize the risk of postsurgical complications, adequate pain-management therapy is crucial. Steps for formulating a multimodal regimen consider both nonpharmacologic and pharmacologic therapies. However, optimal pain-management strategies stem from comprehensive assessment of patient comorbidities, risk factors, and contraindications from a multidisciplinary standpoint. Collaboration between healthcare professionals and patients fosters positive health outcomes and results in a postoperative pain-management plan that is tailored to the individual patient.²⁴

To reduce acute and chronic postoperative pain, hospitals have implemented several types of clinical protocols, including acute pain service (APS) and enhanced recovery after surgery (ERAS) programs.²⁴ Each method provides a standardized approach to postsurgical monitoring and parameters. APS is a cost-effective protocol in which clinicians educate patients about acute pain management.²⁵ Although APS committees may consist of various disciplines, the overarching goal is to ease the patient’s transition from surgery to discharge through counseling and follow-ups. APS encourages healthcare professionals to become more proactive in providing quality care. ERAS focuses on early recovery by maintaining preoperative organ function and reduced stress response postoperatively. As implemented into invasive surgical protocols, ERAS monitors all stages of surgical interventions: preoperative, intraoperative, and postoperative.²⁶ It has been shown that the incorporation of ERAS is clinically beneficial and reduces both direct and indirect costs.

CONCLUSION

Even with advances in surgical techniques, the prevention and minimization of postoperative pain continue to be a topic of clinical discussion and research. The various pharmacologic and nonpharmacologic therapies associated with pain control should be individualized to each patient. As part of the healthcare team, pharmacists should offer recommendations on analgesic options, participate in opioid-stewardship programs, and assist in the formulation of postoperative pain protocols.

REFERENCES

1. Gan TJ. Poorly controlled postoperative pain: prevalence, consequences, and prevention. J Pain Res. 2017;10:2287-2298.
2. Chou R, Gordon DB, de Leon-Casasola OA, et al. Management of postoperative pain: a clinical practice guideline from the American Pain Society, the American Society of Regional Anesthesia and Pain Medicine, and the American Society of Anesthesiologists’ Committee on Regional Anesthesia, Executive Committee, and Administrative Council. J Pain. 2016;17(2):131-157.
3. Garimella V, Cellini C. Postoperative pain control. Clin Colon Rectal Surg. 2013;26(3):191-196.
4. Gupta A, Kaur K, Sharma S, et al. Clinical aspects of acute post-operative pain management & its assessment. J Adv Pharm Technol Res. 2010;1(2):97-108.
5. Small C, Laycock H. Acute postoperative pain management. Br J Surg. 2020;107(2):e70-e80.
6. Dolin SJ, Cashman JN, Bland JM. Effectiveness of acute postoperative pain management: I. Evidence from published data. Br J Anaesth. 2002;89(3):409-423.
7. Riecke J, Zerth SF, Schubert AK, et al. Risk factors and protective factors of acute postoperative pain: an observational study at a German university hospital with cross-sectional and longitudinal inpatient data. BMJ Open. 2023;13(5):e069977.
8. Segelcke D, Rosenberger DC, Pogatzki-Zahn EM. Prognostic models for chronic postsurgical pain—current developments, trends, and challenges. Curr Opin Anaesthesiol. 2023;36(5):580-588.
9. Shipton EA. The transition of acute postoperative pain to chronic pain: part 1—risk factors for the development of postoperative acute persistent pain. Trends Anaesth Crit Care. 2014;4(2-3):67-70.
10. Bruce J, Quinlan J. Chronic post surgical pain. Rev Pain. 2011;5:23-29.
11. Macrae WA. Chronic post-surgical pain: 10 years on. Br J Anaesth. 2008;101(1):77-86.
12. Searle RD, Simpson KH. Chronic post-surgical pain. Contin Educ Anaesth, Crit Care Pain. 2010;10(1):12-14.
13. Haefeli M, Elfering A. Pain assessment. Eur Spine J. 2006;15(Suppl 1):s17-s24.
14. Bird SB, Dickson EW. Clinically significant changes in pain along the visual analog scale. Ann Emerg Med. 2001;38(6):639-643.
15. Rijkenberg S, Stilma W, Endeman H, et al. Pain measurement in mechanically ventilated critically ill patients: Behavioral Pain Scale versus Critical-Care Pain Observation Tool. J Crit Care. 2015;30(1):167-172.
16. Linde SM, Badger JM, Machan JT, et al. Reevaluation of the critical-care pain observation tool in intubated adults after cardiac surgery. Am J Crit Care. 2013;22(6):491-497.
17. Sluka KA, Wager TD, Sutherland SP, et al. Predicting chronic postsurgical pain: current evidence and a novel program to develop predictive biomarker signatures. Pain. 2023;164(9):1912-1926.
18. Drewes AM, Jensen RD, Nielsen LM, et al. Differences between opioids: pharmacological, experimental, clinical and economical perspectives. Br J Clin Pharmacol. 2013;75(1):60-78.
19. Kay AB, White T, Baldwin M, et al. Less Is more: a multimodal pain management strategy is associated with reduced opioid use in hospitalized trauma patients. J Surg Res. 2022;278:161-168.
20. Edinoff AN, Kaplan LA, Khan S, et al. Full opioid agonists and tramadol: pharmacological and clinical considerations. Anesth Pain Med. 2021;11(4):e119156.
21. Celebrex (celecoxib) product information. New York, NY: Pfizer, Inc; June 2018.
22. Ketalar (ketamine) product information. Chestnut Ridge, NY: Par Pharmaceutical; April 2017.
23. Fenske JN, Berland DW, Chandran S, et al. Pain Management. Ann Arbor, MI: Michigan Medicine University of Michigan; January 2021.
24. Horn R, Kramer J. Postoperative Pain Control. In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; 2024 Jan–.
25. Kishore K, Agarwal A, Gaur A. Acute pain service. Saudi J Anaesth. 2011;5(2):123-124.
26. Melnyk M, Casey RG, Black P, Koupparis AJ. Enhanced recovery after surgery (ERAS) protocols: time to change practice? Can Urol Assoc J. 2011;5(5):342-348.

The content contained in this article is for informational purposes only. The content is not intended to be a substitute for professional advice. Reliance on any information provided in this article is solely at your own risk.

To comment on this article, contact rdavidson@uspharmacist.com.