Introduction
Multimodal analgesia protocols, including gabapentin, aim to minimize opioid consumption and reduce postoperative pain (Chou et al., 2016). Early studies suggested gabapentin provided opioid-sparing effects and decreased postoperative pain with minimal side effects (Kharasch et al., 2020). Its use was adopted as part of Enhanced Recovery After Surgery Protocols (ERAS) in many surgical specialties, including total joint arthroplasty (TJA). In 2020, the American Association of Hip and Knee Surgeons (AAHKS), American Society of Regional Anesthesia and Pain Medicine (ASRA), American Academy of Orthopaedic Surgeons (AAOS), Hip Society, and Knee Society provided recommendations for its use in the management of pain in TJA surgical procedures.
Background
TJA is the most common elective surgical procedure performed in the United States (Pelkowski, 2020) and is associated with significant postoperative pain. Opioids effectively treat acute pain but have multiple side effects, including tolerance and addiction. Pain management continues to challenge healthcare providers, and effective management is important to both patients and providers (Pulos & Sheth, 2014). Patient satisfaction is directly linked to pain control postoperatively (Pulos & Sheth, 2014). In addition to patient satisfaction, inadequate pain management contributes to patient anxiety, sleep disturbance, decreased mobility, and increased hospital length of stay (Goode et al., 2019). The American Pain Society (APS) has published recommendations for managing postoperative pain, including multimodal therapies. Multimodal therapies combine medications from different drug classes to target pain at different pathways to reduce postoperative pain and opioid consumption and provide superior pain relief (Chou et al., 2016) while avoiding side effects associated with opioid use.
Multimodal therapies include neuraxial and regional techniques, intravenous opioids and nonopioids, and oral medications, including acetaminophen, nonsteroidal anti-inflammatory drugs, and gabapentinoids (Li et al., 2019). Gabapentin belongs to the drug class gabapentinoids. It is an oral medication approved by the Food and Drug Administration for postherpetic neuralgia and as an antiepileptic drug. The mechanism of action is unclear; yet, it is believed that it elicits its effect by binding to the alpha2-delta site on the voltage-gated calcium channels, altering neurotransmission, and reducing the effects of hyperexcitability caused by tissue damage (Goode et al., 2019). Originally thought of as a benign drug, its off-label use expanded to treat mental illness, migraines, fibromyalgia, and postoperative pain (Peckham et al., 2018).
In 2020, the AAHKS published evidence-based practice (EBP) guidelines for using gabapentinoids in TJA. AAHKS practice guidelines noted that existing evidence found gabapentin does not reduce postoperative pain or opioid consumption in the acute perioperative phase or postdischarge regardless of dosing. Gabapentin, combined with central nervous system depressants and opioids, increases the risk of respiratory depression and altered mental status, especially in the elderly or patients with underlying respiration conditions. In the outpatient setting, the combined use of gabapentinoids and opioids increases the patient's risk of an emergency department evaluation or inpatient hospital stay (Patel et al., 2022). Growing evidence suggests that gabapentin is associated with intentional misuse, especially in patients with substance use disorders (Patel et al., 2022). Gabapentin provides a euphoria-like effect and potentiates the high experience of opioids (Campbell et al., 2021). Based on evolving evidence and on the adverse consequences of gabapentin, as well as its potential for abuse, AAHKS recommends gabapentinoids be used cautiously in patient undergoing TJA (see Table 1).
Purpose
In 2012, a multimodal analgesia protocol for TJA was implemented at our center. The protocol included oral administration of OxyContin (oxycodone) 10 mg, gabapentin 300 mg, and celecoxib 400 mg administered 1 hour preoperatively. Since its inception, the effectiveness of this protocol, specifically oral gabapentin 300 mg, had not been reevaluated for its efficacy in treating postoperative pain in TJA. This work describes the evidence of the ineffectiveness of gabapentin in reducing postoperative pain and an advanced practice registered nurse (APRN)-led EBP change in a Western Connecticut preadmission testing center.
Literature Search
Key words were used to search four literature databases to answer the PICOT question: Do patients undergoing TJA (P) who receive preoperative oral gabapentin (I) compared with similar patients who do not receive oral gabapentin (C) have less pain (O) postoperatively (T)? To answer this PICOT question, a systematic literature search was performed using four electronic databases (see Tables 2 and 3): Cumulative Index to Nursing and Allied Health Literature (CINAHL), PubMed, Cochrane Database of Systematic Reviews, and APA PsycINFO. Key terms used were "total joint arthroplasty," "total joint replacement," "total hip replacement," "total hip arthroplasty," and "total knee replacement" and "total knee arthroplasty," "gabapentin," and "multimodal" and "postoperative pain" and "pain."
A current and comprehensive literature search was performed following AAHKS, ASRA, AAOS, Hip Society, and Knee Society guidelines to search for any studies that may have been published following their release until the completion of this project. One systematic review and meta-analysis and one meta-analysis were identified. The evidence from these two analyses, Hannon et al. (2020) and Kang et al. (2020), was consistent with existing evidence and AAKHS guideline recommendations. In addition, multiple themes emerged in the literature search regarding pain management in TJA, including (1) regional analgesia techniques, (2) differences in surgical approaches, (3) behavior and physical therapy techniques, and (4) multimodal analgesia, including nonsteroidal anti-inflammatories and steroids.
Evidence
Paul et al. (2015) performed a randomized controlled trial (RCT) of 102 patients to evaluate the effectiveness of gabapentin as an adjunct to morphine for postoperative pain management in total hip arthroplasty. Patients were given oral gabapentin 600 mg (treatment group, n = 48) or placebo (control group, n = 54) and acetaminophen 1,000 mg 2 hours preoperatively, and 30 mg of ketorolac intravenously. A regional neuraxial technique of fentanyl 20 [mu]g and 0.5% or 0.75% of bupivacaine was administered. The study results found no statistically significant difference in pain scores, opioid consumption, side effects, and range of motion between the control and gabapentin groups (Paul et al., 2015).
Lunn et al. (2015) performed an RCT of 300 opioid-naive patients to evaluate dose-dependent gabapentin postoperative pain in total knee arthroplasty. The treatment began 2 hours preoperatively on the day of surgery in addition to the multimodal analgesic regimen of oral Tylenol (acetaminophen) 2 g and celecoxib 400 mg. Participants were divided into three groups. Group A received a total of 1,300 mg gabapentin per day, Group B received 900 mg total per day, and Group C received the placebo at the exact times as the comparison groups. Neuraxial anesthesia of bupivacaine 0.5% and propofol, and local infiltration of 150 ml ropivacaine 0.2% with epinephrine (10 [mu]g/ml), was administered to all patients. The findings demonstrated no statistical difference between the three groups in postoperative pain or morphine consumption in the first 48 hours and Days 2-6. Sedation and dizziness were experienced in the higher dose gabapentin group (Lunn et al., 2015).
Paul et al. (2013) performed an RCT of 101 participants to evaluate the efficacy of gabapentin in reducing morphine requirements and pain scores in total knee arthroplasty. Patients were given gabapentin (n = 52) or placebo (n = 49) and a multimodal anesthesia plan that included oral acetaminophen 1,000 mg and ketorolac 15 mg, neuraxial anesthesia with combined hyperbaric bupivacaine and fentanyl, and no other opioids or local infiltrations, and Patient-care analgesia (PCA) morphine postoperatively. The findings demonstrated no statistically significant difference in postoperative morphine consumption or pain scores at 72 hours (Paul et al., 2013).
Clarke et al. (2014) performed an RCT of 179 patients to determine the effectiveness of celecoxib in combination with gabapentin at improving in-hospital rehabilitation, physical function, pain, and opioid consumption. A multimodal approach was used, including femoral, sciatic nerve blocks, spinal anesthesia neuraxial techniques, and postoperative PCA. The results showed a statistically significant decrease in morphine use in the first 24 hours after surgery in the celecoxib/gabapentin group compared with the placebo group: G = 38.3 (29.5 mg), P = 48.2 (29.4 mg (p < .0125). There was no statistically significant difference in pain or sedation between the groups (Clarke et al., 2014).
Verret et al. (2020) performed a systematic review and meta-analysis to assess the analgesic effect and adverse events of perioperative use of gabapentinoids, including gabapentin and pregabalin, in adult patients. The review analyzed 281 RCTs with 24,682 patients across multiple surgical specialties. Orthopaedic patients and patients with spine injuries represented 27% of total patients. This study found that regardless of timing point, dosage regimen, or if pregabalin or gabapentin was used, there was no statistically significant difference in postoperative pain compared with placebo. The use of gabapentinoids was associated with increased dizziness and visual disturbance (Verret et al., 2020).
Synthesis of Evidence
One systematic review and meta-analysis and four RCTs were critically appraised. Four RCTs evaluated the effectiveness of gabapentin compared with placebo at reducing postoperative pain after TJA and used similar regional anesthesia techniques. Three studies found that gabapentin did not reduce pain or morphine consumption. Clarke et al. (2014) saw a slight decrease in opioid consumption of approximately 10 mg in the first 24 hours (p = .0125) between the gabapentin and placebo groups, with no differences in pain scores. Verret et al. (2020), who conducted a meta-analysis of 281 RCTs trials evaluating perioperative gabapentinoids, found no difference in postoperative pain compared with placebo. Clarke et al. (2014) and Paul et al. (2013) found an increased incidence of nausea and pruritus in the placebo group. Verret et al. (2020) and Lunn et al. (2015) noted visual disturbance, dizziness, and sedation in the gabapentinoid group. This evidence, along with recent clinical practice guideline recommendations, and our patient demographics, supported a change in practice.
Description of the Evidence-Based Project
Table 4 details the timeline of this EBP project, which occurred at a Level II Trauma Center in Western Connecticut in three phases using the Melnyk EBP model (Melnyk & Fineout-Overhold, 2019): preimplementation, implementation, and postimplementation. The institutional review board exemption determinations were obtained during the preimplementation phase. Several meetings were held with the key stakeholders, the Anesthesia Medical Director and the Pain Management Director, to discuss the evidence and feasibility of a practice change. In addition, the Pharmacy manager was consulted on the feasibility of collecting aggregate data. Key stakeholders also included the Preadmission Testing APRNs, orthopaedic surgeons, physician assistants, and the manager of postanesthesia care unit (PACU) nurses, who were presented with the evidence and the recommendations for a practice change. Phase II consisted of piloting the change in practice over 30 days, where APRNs manually removed gabapentin from the preoperative order sets. Pharmacy reports were used to determine the number of doses of gabapentin 300 mg dispensed from the ASU Phase II automated medication dispensing system 30 days before implementation and 30 days following implementation.
Results
This EBP project demonstrated essential EBP competencies used by the APRNs to implement a change in practice for preadmission APRNs with minimal change in the workflow. Traditionally, patients presenting to the surgical center would receive OxyContin 10 mg, gabapentin 300 mg, and celecoxib 400 mg by mouth 1 hour prior to surgery. After implementation, there was a 23.8% reduction in gabapentin administered preoperatively. Two of the three APRNs removed gabapentin from the preoperative order set. The Anesthesia Medical Director observed no complaints of increased pain or increase in opioid use. In addition, the orthopaedic service line manager reported no complaints of increased pain postoperatively. After the EBP results were communicated, the TJA protocol was modified, excluding preordered gabapentin 300 mg from the TJA preoperative order set.
Discussion
Gabapentin has many benefits; however, when combined with other central nervous system depressants, it can have adverse consequences, yet have limited benefit in reducing postoperative pain in TJA. If used in this patient population, special consideration should be given to patients with underlying respiration conditions, the elderly, and those with substance use disorder. As we continue to search for the most effective multimodal regimen for this patient population, APRNs must utilize and embrace EBP to move from practice based on tradition or outdated protocols. This work highlights the APRN's role in identifying knowledge gaps, critically appraising evidence, and applying new evidence to clinical practice settings to improve patient outcomes and lead EBP change.
References