Multimodal Pain Management
Kyounghae Kim
The International Association for the Study of Pain (1994) defines pain as “an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage.” The definition represents that pain does not necessarily mean there is injury and implies the multidimensional nature of pain. Traditionally, management strategies for pain have predominantly focused on pharmacologic and interventional approaches. As pain research is evolving, there is a much greater emphasis on the biobehavioral approach targeting the behavioral/psychological aspects of pain in addition to analgesic medications (Department of Health and Human Services, 2016; Institute of Medicine, 2011). This approach is based on the biopsychosocial model of pain, which is now generally considered the most heuristic perspective on chronic pain (Gatchel, Peng, Peters, Fuchs, & Turk, 2007). As discussed in Chapter 1, the biopsychosocial model concentrates both health and illness, illness being considered the complex interactions of biologic, psychological, and social components (Gatchel, 2005). In brief, the bio portion of the model explains the physiology and neurobiology of the nociception and psychosocial components, which include both emotion and cognition (Gatchel et al., 2007). Emotion is the quicker response to nociceptive pain, which is midbrain based, whereas cognition is connected to the emotional experience and may then prompt additional emotional responses and thus magnify the pain experience, thereby perpetuating a vicious cycle of nociceptive stimulus, pain, and functional limitations (Gatchel et al., 2007). The multidimensional nature of chronic pain suggests that a logical management approach is multimodal, which is an integrated multidisciplinary treatment with closely coordinated somatic and psychotherapeutic components (Muller-Schwefe et al., 2017). This chapter provides an overview of the current research evidence on multimodal pain management in the context of perioperative pain, neck pain, chronic low back pain, fibromyalgia, and cancer pain. The reviewed evidence predominantly focuses on the findings from the meta-analyses of randomized controlled trials (RCTs) among adults aged 18 and older with pain conditions. Articles focusing on children and perinatal care were excluded.
▶ KEY POINT
Multimodal pain management provides the potential for a decrease in pain, opioid consumption, and opioid-related adverse effects by targeting biologic, psychological, and social factors associated with the pain mechanism.
Perioperative Pain
Figure 5-1 depicts the complementary mechanisms of action along the nociceptive pathway by which interventions exert their action to alleviate pain (Manworren, 2015). Multimodal analgesia may offer additive or synergistic effects on greater pain relief and less adverse effects found with analgesics than would a monomodal approach by combining a variety of analgesics and techniques, along with nonpharmacologic
approaches (Chou et al., 2016; Manworren, 2015). Traditional pharmacologic agents include local anesthetics, acetaminophen, and nonsteroidal anti-inflammatory drugs (NSAIDs) including cyclooxygenase-2 inhibitors and opioid analgesics. Nontraditional agents include anticonvulsants, N-methyl-D-aspartate receptor antagonists, α2-adrenergic agonists, and antidepressants. Per practice guidelines, the choice of medicine, dose, and duration of the treatment should be personalized, yet patients should receive around-the-clock regimens (Chou et al., 2016). Detailed information is provided in Chapter 7. Nonpharmacologic interventions, which are discussed in Chapter 8, generally include transcutaneous electrical nerve stimulation; cognitive behavioral therapy including relaxation methods, guided imagery, and hypnosis; and complementary approaches including acupuncture, massage, and music therapy.
approaches (Chou et al., 2016; Manworren, 2015). Traditional pharmacologic agents include local anesthetics, acetaminophen, and nonsteroidal anti-inflammatory drugs (NSAIDs) including cyclooxygenase-2 inhibitors and opioid analgesics. Nontraditional agents include anticonvulsants, N-methyl-D-aspartate receptor antagonists, α2-adrenergic agonists, and antidepressants. Per practice guidelines, the choice of medicine, dose, and duration of the treatment should be personalized, yet patients should receive around-the-clock regimens (Chou et al., 2016). Detailed information is provided in Chapter 7. Nonpharmacologic interventions, which are discussed in Chapter 8, generally include transcutaneous electrical nerve stimulation; cognitive behavioral therapy including relaxation methods, guided imagery, and hypnosis; and complementary approaches including acupuncture, massage, and music therapy.
 Figure 5-1. The effect of pain management interventions along the nociceptive pain pathway. Adapted with permission from Manworren, R. C. (2015). Multimodal pain management and the future of a personalized medicine approach to pain. AORN Journal, 101(3), 311. doi:10.1016/j.aorn.2014.12.009. Copyright ©2015, John Wiley and Sons. |
When NSAIDs are used as an adjunct to opioid therapy for perioperative pain, patients tend to have a greater pain reduction compared to the use of either NSAIDs or opioids alone. For example, meta-analysis of 13 RCTs (n = 782) supported the finding that single-dose perioperative, intravenous, or intramuscular ketorolac (30- or 60-mg dosage) is an effective adjunct to multimodal analgesia to relieve postoperative pain and reduce opioid consumption (De Oliveira, Agarwal, & Benzon, 2012). The combined regimen reduced immediate postoperative pain with a moderate weighted mean difference (WMD) of -0.64 (95% confidence interval [CI]: -1.11 to -0.18) but not late pain (WMD: -0.29, 95% CI: -0.88 to -0.29), and decreased opioid consumption when the 60-mg dose is used, with a difference in mean morphine equivalent dosing of -1.64 mg (95% CI: -2.90 to -0.37 mg). Compared to placebo, there was a greater opioid-sparing effect of ketorolac when intramuscular ketorolac was administered than when intravenous ketorolac was administered, with a difference in mean morphine equivalent dosing of -2.13 mg (95% CI: -4.1 to -0.21 mg). The addition of the 60-mg dose to the analgesic regimen reduced postoperative nausea and vomiting (odds ratio [OR]: 0.49, 95% CI: 0.29-0.81). Unlike the evidence of the effect of a ketorolac 60-mg dose that offers significant benefits in pain relief and opioid-related adverse effects, there is no sufficient evidence to conclude the effect of the 30-mg dose on postoperative pain and opioid outcomes.
Meta-analyses of 5 RCTs (n = 251 patients) did not support the lidocaine 5% patch as an adjunct for acute and postoperative pain care in pain intensity (MD: -9.1 mm, 95% CI: -23.31 to 5.20, Z = 1.24, P = 0.21; I2 = 99%), opioid consumption (MD: -8.2 mg, 95% CI: -28.68 to 12.24, Z = 0.79, P = 0.43; I2 = 88%), and days of hospital stay (MD: -0.2 days, 95% CI: -0.80 to 0.43, Z = 0.60, P = 0.55; I2 = 43%), compared to those without the lidocaine patch (Bai, Miller, Tan, Law, & Gan, 2015). Potential biases (e.g., unblinding), heterogeneity (high variability) among studies, and incomplete outcome data on adjunct analgesics remain concerns (Bai et al., 2015).
Zhou, Fan, Zhong, Wen, and Chen (2017) conducted a meta-analysis of 21 RCTs (n = 1980 patients) to compare their efficacy and safety of multimodal analgesic approaches to chronic postsurgical pain. The researchers particularly focused on four surgical types, including general, orthopedic, gynecologic, and thoracic. The multimodal anesthesia methods included regional analgesia such as epidural, wound infusion, topical application, plexus blocks, spinal blocks, peritoneal instillation, and paravertebral blocks. Regional analgesia has been shown to be effective in decreasing the frequency of postsurgical pain (relative risk [RR]: 0.69, 95% CI: 0.56-0.85,
P < 0.001), with moderate heterogeneity among the included studies (I2 = 50.1%, P = 0.007) and improving overall patient satisfaction (standardized mean difference [SMD]: 1.95, 95% CI: 0.83-3.06, P = 0.001), compared to traditional analgesia. No other outcomes were significant, such as opioid consumption, pain rating, functional activity, and mental health inventory. The authors conclude that further research should examine the long-term efficacy and safety of regional analgesic approaches to further verify the current evidence.
P < 0.001), with moderate heterogeneity among the included studies (I2 = 50.1%, P = 0.007) and improving overall patient satisfaction (standardized mean difference [SMD]: 1.95, 95% CI: 0.83-3.06, P = 0.001), compared to traditional analgesia. No other outcomes were significant, such as opioid consumption, pain rating, functional activity, and mental health inventory. The authors conclude that further research should examine the long-term efficacy and safety of regional analgesic approaches to further verify the current evidence.
In a meta-analysis of 11 RCTs (n = 899), use of anticonvulsant (i.e., pregabalin) as an adjunct for perioperative pain management yielded better outcomes, such as a decrease in opioid consumption and vomiting, and mixed results regarding other opioid-related adverse effects including nausea, dizziness and sedation, and headache (Zhang, Ho, & Wang, 2011). No significant difference in pain intensity exists. The use of pregabalin as an adjunct for acute postoperative pain was effective in decreasing cumulative opioid consumption at 24 hours but not pain intensity. A decrease in cumulative opioid consumption depends on pregabalin dosage. At pregabalin doses of less than 300 mg, the opioid-sparing effect was estimated at WMD: 8.8 mg (95% CI: -16.65 to -0.94) and at pregabalin doses 300 mg or more, the opioid-sparing effect was estimated at WMD: 13.40 mg (95% CI: -22.78 to -4.02), with high heterogeneity among the included studies (degrees of freedom = 2, P = 0.007). Pregabalin had a significant effect on reduction in vomiting (RR: 0.73, 95% CI: 0.56-0.95) but an increased risk of visual disturbance (RR: 3.29, 95% CI: 1.95-5.57). Similarly, meta-analysis of 132 RCTs (n = 9498) examined the pooled effects of perioperative gabapentin therapy versus placebo or active placebo on 24-hour opioid use and opioid-related adverse effects (Fabritius et al. 2016). A total of 13 RCTs with low risk of bias found a reduction in 24-hour morphine use of 3.1 mg (95% CI: 0.5-5.6, Trial Sequential Analysis [TSA]-adjusted CI: -0.2 to 6.3). When gabapentin was used as an add-on analgesic to another nonopioid treatment, there was a mean decrease in 24-hour opioid use of 1.2 mg (95% CI: -0.3 to 2.6, TSA-adjusted CI: -0.4 to 2.8) compared to the control group. Nine RCTs with low risk of bias found an RR of serious adverse effects of 1.61 (95% CI: 0.91-2.86, TSA-adjusted CI: 0.57-4.57). However, the interpretation of the results needs caution because of low or very low quality evidence. Strong evidence for the use of gabapentin in perioperative pain care is lacking, and serious adverse effects are forthcoming, particularly when it is added to multimodal regimen.
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