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State of the Art Opioid-Sparing Strategies for Post-Operative Pain in Adult Surgical Patients

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State of the Art Opioid-Sparing Strategies for Post-Operative Pain in Adult Surgical Patients UC San Diego UC San Diego Previously Published Works Title State of the art opioid-sparing strategies for post-operative pain in adult surgical patients. Permalink https://escholarship.org/uc/item/3z9800kv Journal Expert opinion on pharmacotherapy, 20(8) ISSN 1465-6566 Authors Gabriel, Rodney A Swisher, Matthew W Sztain, Jacklynn F et al. Publication Date 2019-06-01 DOI 10.1080/14656566.2019.1583743 Peer reviewed eScholarship.org Powered by the California Digital Library University of California EXPERT OPINION ON PHARMACOTHERAPY https://doi.org/10.1080/14656566.2019.1583743 REVIEW State of the art opioid-sparing strategies for post-operative pain in adult surgical patients Rodney A. Gabriela,b,c, Matthew W. Swishera,c, Jacklynn F. Sztaina, Timothy J. Furnisha, Brian M. Ilfelda,c and Engy T. Saida aDepartment of Anesthesiology, Division of Regional Anesthesia and Acute Pain, University of California, San Diego, La Jolla, CA, USA; bDivision of Biomedical Informatics, University of California, San Diego, La Jolla, CA, USA; cOutcomes Research Consortium, Cleveland, OH, USA ABSTRACT ARTICLE HISTORY Introduction: There are various important implications associated with poorly controlled postoperative Received 17 October 2018 pain in the adult surgical patient – this includes cardiopulmonary complications, opioid-related side Accepted 13 February 2019 effects, unplanned hospital admissions, prolonged hospital stay, and the subsequent development of KEYWORDS chronic pain or opioid addiction. With the ongoing national opioid crisis, it is imperative that perio- Multimodal analgesia; acute perative providers implement pathways for surgical patients that reduce opioid requirements and pain- pain service; opioid; related complications. perioperative Areas covered: In this review, the authors discuss the components of a multimodal opioid-sparing analgesia pathway as it pertains to the perioperative environment. Medications reviewed include gabapentinoids, acetaminophen, non-steroidal anti-inflammatory drugs, ketamine, intravenous lido- caine, dexmedetomidine, and glucocorticoids. The use of peripheral nerve blocks and neuraxial analge- sia are also discussed. Expert opinion: In appropriate cases, regional anesthetic interventions are extremely useful for post- operative analgesia, including peripheral nerve blocks and neuraxial analgesia and while newer post- operative analgesics have been postulated, the literature on such is presently controversial. Coordinated approaches to pain management are recommended to reduce the need for opioids and to improve patient satisfaction post-surgery. 1. Introduction acute postoperative period. Preemptive analgesia is defined as a preoperative antinociceptive treatment that prevents the estab- Pain is one of the most common and significant postopera- lishment of central sensitization caused by incisional and inflam- tive events experienced by many surgical patients. The matory injuries [3], and is achieved by administering analgesics implications of poorly controlled postoperative pain are prior to the surgical insult. Intravenous or oral analgesic medica- substantial, including cardiopulmonary complications, tions most commonly studied in the context of opioid-sparing opioid-related side effects, unplanned hospital admissions, preemptive analgesia include gabapentinoids, non-steroidal anti- prolonged hospital stay, and the subsequent development inflammatory medications (NSAIDs), acetaminophen, ketamine, of chronic pain or opioid addiction [1]. With the ongoing dexamethasone, magnesium, and dextromethorphan. Many of national opioid crisis [2], it is in both the patients’ and the agents commonly used in both pre-emptive analgesia and public’s interest for perioperative providers to implement intraoperative management may be continued during the post- pathways for surgical patients that reduce opioid require- operativeperiod.Here,wesummarizesomeofthoseagentsand ments and pain-related complications. In this review, we discuss the evidence behind their utilization. discuss the components of multimodal opioid-sparing analgesia pathways as it pertains to the perioperative environment in the adult patient (Figure 1). We focus on 2.1. Gabapentinoids evidence-based medicine and discuss process changes that may aid in the implementation of such clinical pathways Gabapentinoids, such as gabapentin and pregabalin, have and promising novel therapies. been studied as part of a multimodal analgesic regimen to provide analgesia in the perioperative period. Their mechan- ism of action involves the presynaptic voltage-gated calcium 2. Non-opioid medication for perioperative channel receptor in both the central and peripheral nervous analgesia systems [4]. A number of meta-analyses have been performed Multimodal analgesia should begin in the preoperative period, to investigate the effect of preoperative administration of extend into intraoperative management, and finally during the gabapentinoids on postoperative analgesia. CONTACT Rodney A. Gabriel [email protected] Department of Anesthesiology, University of California, 200 W Arbor Dr, MC 8770, San Diego, CA 92103, USA © 2019 Informa UK Limited, trading as Taylor & Francis Group 2 R. A. GABRIEL ET AL. 2.1.2. Pregabalin Article highlights There is no consensus regarding the optimal type (e.g. gaba- ● Multimodal opioid-sparing analgesia is an effective approach to pentin versus pregabalin) or dose for gabapentinoids. In postsurgical care a meta-analysis investigating 11 RCTs, they reported that peri- ● Pharmacological non-opioid agents for pain control include the operative pregabalin was not associated with postoperative gabapentinoids, non-steroid anti-inflammatory drugs, magnesium, lidocaine, NMDA-antagonists, glucocorticoids, and alpha2-agonists. pain intensity; however, it reduced 24-h opioid consumption ● When appropriate, regional anesthesia interventions are extremely and some opioid-related adverse events [12]. In a more recent useful for postoperative analgesia, including peripheral nerve blocks meta-analysis that included 43 studies, they also reported and neuraxial analgesia ● Newer agents for postoperative analgesia include HTX-011, SABER- reduction in analgesic usage associated with perioperative bupivacaine, and liposomal bupivacaine, although the literature is pregabalin usage [13]. One placebo-controlled RCT demon- still controversial strated no analgesic superiority between gabapentin (600 mg) ● A coordinated approach to pain management, including an Acute Pain Service or Enhanced Recovery After Surgery pathway, may aid in and pregabalin (150 mg) during the first 48 postoperative hours reducing opioid requirements and improving patient satisfaction in following laparoscopic cholecystectomy in terms of postopera- the surgical population. tive shoulder pain, although it failed to evaluate opioid con- This box summarizes key points contained in the article. sumption [14]. In contrast, another RCT involving lumbar spine surgery showed improved postoperative opioid consumption for preoperative pregabalin in comparison to gabapentin [15]. This study used a higher dose of pregabalin (300 mg) in com- parison. Similarly, a comparative randomized trial did find 2.1.1. Gabapentin decreased opioid consumption and pain scores with pregabalin Two meta-analyses found significantly lower pain scores and/ (150 mg) compared to gabapentin (900 mg) [16]. Comparative or opioid consumption for 24 h with preoperative gabapentin results for other surgical populations have also shown conflict- [5,6]. An additional systematic review and meta-regression ing results. Given the lack of consensus and limited data, further analysis of 133 placebo-controlled RCTs revealed improved prospective controlled trials are required. postoperative nausea and vomiting, pruritis, preoperative anxiety, and patient satisfaction [7]. Possible side effects with gabapentinoids include sedation 2.2. Non-steroidal anti-inflammatory drugs and respiratory depression: one retrospective review found a 50% increased risk of respiratory depression [8]. Relatedly, Both nonselective non-steroidal anti-inflammatory drugs this class of analgesics has also been associated with an (NSAIDs) and selective cyclooxygenase-2 (COX-2) inhibitors increased risk of naloxone administration and delayed recov- improve postoperative analgesia in a myriad of surgical popu- ery room discharge [9,10]. Although distinct from preoperative lations. A recent meta-analysis of 20 randomized controlled gabapentinoid administration, recent data demonstrate an trials (RCT) documented a decrease in 24-h opioid consump- association between outpatient opioid-related deaths and tion, pain scores, and postoperative nausea and vomiting with concomitant treatment with opioids and gabapentin [11]. preoperative celecoxib administration for non-cardiac surgery Thus, caution must be exercised, especially with the continua- [17]. Similarly, a systematic review of 22 placebo-controlled tion of gabapentinoids past the perioperative period. RCTs involving preoperative COX-2 inhibitors also found Figure 1. Diagram illustrating components of a multimodal opioid-sparing regimen. EXPERT OPINION ON PHARMACOTHERAPY 3 improved postoperative pain scores, analgesic consumption, for abdominal hysterectomies [29]. Another RCT compared and patient satisfaction [18]. Another meta-analysis of eight preoperative oral acetaminophen to postoperative rectal acet- RCTs involving specifically lumbar spine surgery similarly aminophen for pediatric tonsillectomies and
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