ERAS Pain Management

Enhanced Recovery in Spine Surgery and Perioperative Pain Management

Vikram Chakravarthy, MDa, Hana Yokoi, BSb, Mariel R. Manlapaz, MDc, Ajit A. Krishnaney, MDa,*

KEYWORDS Enhanced recovery after surgery Pain management Spine surgery Opioid Postoperative outcomes Acetaminophen Gabapentin Analgesia

KEY POINTS Enhanced recovery after surgery is an interdisciplinary, multimodal approach to improve postoperative outcomes by applying multiple evidenced-based interventions. Multimodal analgesia begins preoperatively with the consumption of acetaminophen and gabapentin, and continues intraoperatively and postoperatively. Intraoperative medications include ketamine, ketorolac, epidural analgesia, bupivacaine liposome injectable suspension, and lidocaine. For patients undergoing spinal fusion, there was no difference in long term rates of spinal fusion found between groups provided with normal dose (<120 mg/d) nonsteroidal anti-inflammatory therapy versus those without nonsteroidal anti-inflammatory therapy. Enhanced recovery after surgery and chronic pain management in the surgical spine patient requires a multidisciplinary, team-based approach with increasing accountability from the patient.

INTRODUCTION been effective in other specialties such as colorectal and orthopedic surgery, showing decreased Enhanced recovery after surgery (ERAS) is an postoperative complications and outcomes.1,3 interdisciplinary, multimodal approach to improve ERAS has been recently adapted for spine sur- postoperative outcomes by applying multiple gery at multiple institutions in the United States. evidenced-based interventions. These interven- The Hospital for Special Surgery showed tions are incorporated into preoperative, intrao- decreased length of stay, reduced complications, perative, and postoperative protocols based on and no readmissions in their cohort study looking identified risk factors for high-risk patients and at 15 standardized ERAS elements.4 For lumbar surgeries. These protocols have been shown to spine fusions, there was decreased length of reduce complications, hospital stays by 30% to stay, decreased blood loss, and improved pain 50%, readmissions, and costs.1–3 ERAS has

Disclosure: The authors have nothing to disclose. a Department of Neurosurgery, Cleveland Clinic, S40, Cleveland, OH 44195, USA; b Case Western Reserve Uni- versity School of Medicine, S40, Cleveland, OH, USA; c Department of General Anesthesiology, Cleveland Clinic, E31, Cleveland, OH 44195, USA * Corresponding author. Department of Neurosurgery, Cleveland Clinic, S40, 9500 Euclid Avenue, Cleveland, OH. E-mail address: [email protected]

Neurosurg Clin N Am 31 (2020) 81–91 https://doi.org/10.1016/j.nec.2019.08.010

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control in a retrospective cohort performed by decreasing a patient’s risk of opioid dependence, Wang and colleagues.5 Other studies have identi- as well as decreasing the possibility of opioid fied decreased postoperative intensive care unit diversion.15 Implementation of protocols and admissions, a shorter length of stay, reduced reducing the quantity of opioids necessary for cost, and decreased opioid consumption adequate pain control will only further reduce the throughout the duration of the hospital stay. In quantity of opioids prescribed after hospital addition, some studies have shown improved discharge. mobilization and ambulation rates at the 1-month Decreased opioid use is not only beneficial in follow-up.6–8 Ali and colleagues7 identified addi- decreasing drug-related adverse outcomes such tional postoperative benchmarks that were as addiction, diversion, or death, but also advanta- impacted positively by implementation of ERAS geous for outcomes in spine surgery. Animal at University of Pennsylvania, including decreased models have shown decreased rates of healing urinary catheter use and decreased opioid con- and fusion with opioid use.16 In spine surgery, sumption at the 1-month follow-up. higher opioid prescriptions are associated with The recent opioid epidemic in the United states an increased risk of deep venous thrombosis, has seen drug overdoses triple from 1999 to postoperative infection, gastrointestinal and respi- 2014.9 Sixty-three percent of drug overdose- ratory complications, increased hospital length of related deaths in 2015 involved use of an opioid stay, and higher overall hospital costs. medication.9 Narcotic-based postoperative proto- The ERAS paradigm is an ideal framework in cols for pain management have contributed to the which to incorporate the needed changes in post- opioid epidemic with surgery being a key risk fac- operative pain management for spine surgery. Us- tor for chronic opioid use.10,11 Despite focusing on ing evidence-based and best practice principles, this postoperative issue, studies continue to show rational pain management protocols can and that the management of postoperative pain re- have been created. ERAS pain management pro- quires significant modifications.12,13 As a result, tocols emphasize a multidisciplinary approach current practices in perioperative pain manage- across the operative episode to improve pain con- ment must be addressed to reduce opioid use trol and minimize narcotic consumption. One such while improving pain control for patients. The Joint protocol has been developed at the Cleveland Commission recommends establishing protocols Clinic and can serve as an example of an using “multi-modal adjuvant therapies,” including evidence-based rational spine surgery pain man- nonopioid analgesics to decrease the dose of opi- agement protocol. oids needed for optimal pain control. The National Action Plan to Prevent Adverse Drug Events states PREOPERATIVE PAIN MANAGEMENT that federal agencies should use evidence-based INTERVENTIONS strategies to optimize safe opioid prescribing including “multimodal, team-based care” and non- Preemptive analgesia has been shown to reduce opioid pharmacologic therapies to “personalize postoperative pain and narcotic consumption pain management.” This multimodal approach is (Fig. 2). ERAS pain protocols therefore, should defined as 2 or more analgesic drugs that act via include preemptive analgesia on the day of sur- different mechanisms administered in conjunc- gery before initiation of the operation. A number tion14 (Fig. 1). The American Society of Anesthesi- of medications have been shown to be helpful pre- ologists Task Force recommends that multimodal operatively, including acetaminophen, gabapen- pain management be used whenever possible.14 tin, and cyclooxygenase (COX)-2 inhibitors. Improvements in pain management for spine Acetaminophen surgery can play a significant role in decreasing opioid use and improving pain management. The Multiple studies have demonstrated benefit of potential impact of multimodal protocols to treat acetaminophen as part of a greater multimodal spine surgery pain is large, between 2001 to pain management protocol. The American Society 2011 there was a 70% increase in the overall num- of Anesthesiologists recommend administering ber of spine surgeries.10 A 2018 study showed that scheduled acetaminophen with a maximum dose patients undergoing minimally invasive spine sur- not to exceed 4 g/d to prevent the risk of gery consumed less than one-half the opioids hepatotoxicity.14 they were prescribed postoperatively.15 These re- The benefits of acetaminophen include sults highlight the need for continuous monitoring decreased opioid use, increased analgesic con- and evaluation of patient pain management needs trol, and more cost-effective care.17 After lower to decrease unnecessary opioid prescriptions. extremity surgery, the addition of preoperative This finding has positive implications for acetaminophen has been shown to decrease

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Fig. 1. A representation of various levels of analgesia from the site of local tissue manipulation to the feedback loop in the central nervous system.

opioid consumption and reduce the need for anal- that has been corroborated by a Cochrane gesic rescue.18 This low-cost analgesic medica- review of 75 studies presenting high-quality tion provides effective pain relief after surgery, evidence.22–24 indicating a cheaper alternative.19 A systematic review of acetaminophen in combination with nonsteroidal anti-inflammatory drugs (NSAIDS) Gabapentin by Ong and colleagues20 demonstrates superior Gabapentin has been shown to decrease pain analgesia compared with either drug alone. Acet- scores, decrease morphine use, and decrease aminophen has few contraindications including rates of postoperative nausea, vomiting, and pru- severe liver disease, and few drug interactions. ritis with minimal side effects.25–28 The significant Current recommendations advise administering decrease in postoperative nausea and vomiting oral acetaminophen over intravenous (IV) adminis- provides additional justification for its use as a pre- tration with some studies showing little benefit of emptive measure.29 Other studies have confirmed IV infusion.17,21 However, there is controversy in decreased rates of opioid consumption without the literature, with studies indicating a clear benefit additional side effects and decreased rates of

Fig. 2. Schematic representation of the progression from preoperative to intraoperative to postoperative medications available for administration. PCA, patient-controlled analgesia.

the use of rescue pain medications.30,31 Hegarty INTRAOPERATIVE AND POSTOPERATIVE PAIN and Shorten31 in a randomized placebo- MANAGEMENT INTERVENTIONS controlled trial found that a single dose of pregabalin decreased postoperative morphine con- An effective intraoperative pain management pro- sumption, with an absolute difference of 42.3%. tocol requires collaboration with anesthesiology to Gabapentin not only prevents hyperalgesia, but create a rational multimodal series of intraopera- also acts as an anxiolytic, addressing the associa- tive interventions to improve postoperative pain tion between preoperative anxiety and postsur- control. This collaboration is an integral aspect of gical pain.25 Based on these findings, The the multimodal ERAS protocol. Various intraopera- American Society of Anesthesiologists recom- tive specifications were delineated to aid in the mends that gabapentin be administered in the postoperative management of all patients under- perioperative period.14 going elective spine surgery.

Cyclooxygenase-2 Inhibitors Ketamine The use of COX-2 inhibitors has had a significant The American Society of Anesthesiologists Task impact on postoperative pain control when admin- Force recommends the use of ketamine combined istered before surgery.32 This is mediated by a with IV morphine, which has demonstrated decrease in prostaglandin synthesis, decreased improved pain scores, decreased analgesic use, tissue inflammation, and by preventing the sensiti- and improved nausea scores compared with IV zation of nociceptive receptors.25 Furthermore, morphine alone.14 Previous studies have shown these agents are preferred to nonselective COX in- ketamine infusions to be effective in spine surgery hibitors owing to the preservation of platelet func- and other surgical specialties with improved pain tion and decreased risk of gastric bleeding. COX-2 control and decreased opioid use.35,36 A system- inhibitors were not shown to increase the risk of atic review by Laskowski and colleagues36 found bleeding in the perioperative period and have a ketamine to be of particular benefit in painful pro- decreased incidence of gastrointestinal side ef- cedures, including upper abdominal, thoracic, and fects compared with nonselective NSAIDs.33 major orthopedic procedures. Pendi and col- The American Society of Anesthesiologists Task leagues35 reviewed a total of 14 randomized Force recommends COX-2 inhibitors and nonse- controlled trials, finding supplemental periopera- lective NSAIDS to be added to the perioperative tive ketamine to decrease postoperative opioid pain management regimen.14 Pain management consumption up to 24 hours postoperatively in protocols combining COX-2 inhibitors and gaba- spine surgical patients. pentin have been shown to have effective anal- The use of ketamine is recommended for pa- gesic control, improved patient satisfaction, and tients with chronic pain owing to its opioid- decreased opioid use with fewer side effects sparing effect. Therefore, this therapy confers the when compared with gabapentin monotherapy greatest advantage in the patient population that as found by Vasigh and colleagues.34 is expected to require high doses of postoperative

opioids.36 Major side effects include neuropsychi- 2 weeks after spinal fusion does not have adverse atric symptoms and postoperative nausea and effects on fusion rates; however, high doses vomiting. (>120 mg/d) of ketorolac were associated with impaired spinal fusion rates.42 In animal models, Lidocaine NSAIDs have also been shown to significantly inhibit fracture healing process; however, these ef- Intraoperative IV lidocaine infusion has been fects depend on their timing, dose, and duration, shown to improve pain outcomes, decrease hos- supporting the recommendation that they should pital length of stay, and has been associated only be administered for short periods.43 with a decreased 30-day complication rate.37,38 The clinical effects of lidocaine, by attenuation of Ketorolac and hemostasis the proinflammatory system to decrease pain Interestingly, the only side effect that has been and ileus, may outlast the infusion by hours or documented to occur with single-dose or short- days.39 This pain attenuation has an opioid- term administration of ketorolac is increased oper- sparing effect and additionally reduces postopera- ative site bleeding after surgical procedures with tive nausea and vomiting. These effects have been raw surface areas (eg, tonsillectomy, adenoidec- demonstrated in multilevel and major spine sur- tomy, total joint replacements, and major plastic gery where infusions resulted in decreased post- surgery).44 There are no controlled studies in the operative pain, decreased opioid consumption, peer-reviewed literature demonstrating an in- and improved functional outcomes.39 crease in blood loss during or after surgery when standard doses of ketorolac were administered at Ketorolac the end of surgery or in the early postoperative period. It is our practice for the anesthesiologist Ketorolac is an IV NSAID that has demonstrated to confirm with the surgeon before ketorolac significant effectiveness in controlling postopera- administration and withhold the dose if there tive pain and decreasing opioid consumption were any intraoperative concerns with hemostasis. when administered perioperatively. It is typically given at the end of the case and continued into Ketorolac and renal failure the postoperative period. For patients younger The transient decrease in renal function postoper- than 65 years of age, a 30-mg dose is given; pa- ative is clinically insignificant for patients with tients 65 and older a 15-mg bolus is given. Contra- normal renal function. There is no greater risk of indications for administration include a creatinine acute renal failure when administered for short pe- of more than 1.3 mg/dL, a bleeding disorder, or riods in the acute postoperative setting. However, surgeon discretion based on intraoperative patients with preexisting low creatinine clearance hemostasis. may be at greater risk for postoperative renal The American Society of Anesthesiologists Task failure.45 Force recommends NSAIDs to be administered around the clock, with improved pain scores Narcotic Analgesia when IV morphine is combined with ketorolac Short-acting narcotic anesthetic agents such as 14 compared with IV morphine alone. A meta- remifentanil, fentanyl, or sufentanil are routinely 40 analysis by Gobble and colleagues demon- given intraoperatively during surgery to provide strated that ketorolac was equivalent to opioids intraoperative analgesia. Remifentanil has consis- for pain control after surgery and should be admin- tently been shown to induce hyperalgesia in the istered in the perioperative period to decrease 24 hours after surgery.46 However, based on a ran- opioid use. In a randomized, double-blind trial by domized controlled trial by de Hoogd and col- 41 Cepeda and colleagues, adding 30 mg IV of leagues47 in the cardiac surgery literature, it is ketorolac to an analgesic regimen for treating suggested that intraoperative administration is postoperative pain decreased morphine rescue associated with increased narcotic use for up to dose requirements and opioid-related side effects 3 months postoperatively. Using long-acting IV in the early postoperative period. narcotics intraoperatively can provide analgesia Ketorolac and spinal fusion that extends into the immediate postoperative For patients undergoing spinal fusion, there was period, thereby diminishing the need for rescue no difference in long-term rates of spinal fusion narcotic doses in the recovery room. found between groups provided with normal Epidural Analgesia dose (<120 mg/d) NSAID therapy versus those without NSAID therapy.32 A meta-analysis showed In a meta-analysis by Wu and colleagues,48 that normal dose NSAID exposure for less than epidural analgesia provided a statistically and

clinically significant improvement in postoperative States encapsulates the drug in liposomes made pain control compared with IV patient-controlled of biodegradable cholesterols that breakdown analgesia with opioids regardless of analgesic slowly over a desired time period.50,51 It is our regimen, measured pain outcomes, type of practice to infiltrate the incision before skin closure epidural analgesia, or surgical site. Attempts at with a combination of both liposomal bupivacaine enhancing the analgesic potential of patient- and marcaine to provide both immediate and controlled analgesia demonstrated that a combi- delayed pain relief. nation solution (local anesthetic with opioid) compared with opioid alone resulted in improved Nonpharmacologic Interventions for Pain pain scores but greater motor weakness. Patients Management who received infusions of opioid alone had greater Nonpharmacologic interventions that have been 14 amount of pruritus. Epidural analgesia (combina- used to manage postoperative pain include preop- tion solution) provides more significant analgesia erative counseling with cognitive–behavioral ther- and higher patient satisfaction compared with IV apy, biofeedback visualization, and chiropractic patient-controlled analgesia after spinal fusion Fig. 3 49 manipulation ( ). A case series by Archer surgery. In addition, it has been found to and colleagues51 reviewed 8 postoperative pa- decrease postoperative opioid consumption. Con- tients who suffered from a high fear of movement traindications include occurrence of intraoperative who underwent 6-session cognitive-behavioral– durotomy and/or if the epidural space is deemed based physical therapy. This therapy addresses too small to advance an epidural catheter (eg, mul- the fear of movement through behavior self- tiple revisions or fibrosis of epidural space). Anal- control and cognitive restructuring techniques gesic infusion begins in the postanesthetic care aiming to increase physical activity. At the unit once a stable neurologic examination has 6-month follow-up, 7 patients demonstrated a been obtained. clinically significant decrease in pain and all 8 patients had significant reduction in disability. This Local Anesthetics was quantified by 5 patients demonstrating clini- The American Society of Anesthesiologists Task cally significant improvement on the 10-m walk Force recommends regional blockade with test. Nicholls and colleagues52 found 6 papers local anesthetic.14 Meta-analysis of randomized in their systematic review citing a decrease in controlled trials report improved pain scores and postoperative pain disability and intensity in decreased analgesic use with preincisional infiltra- cognitive–behavioral therapy–based psychologi- tion of ropivacaine and bupivacaine.49 cal interventions. Recently, liposomal bupivacaine (Exparel), an Biofeedback therapy encourages relaxation and amide local anesthetic that targets the voltage helps to alleviate various conditions associated gated sodium ion channels, has emerged as an with stress. In a case series of Taiwanese patients extended release form that may last up to 72 hours after total knee arthroplasty, Wang and col- after infiltration. Since its approval by the US Food leagues53 found that the group receiving biofeed- and Drug Administration, it has been used in back training twice daily for 5 days demonstrated thoracic, orthopedic, and abdominal surgeries, significantly less pain from continuous passive demonstrating decreased pain, decreased opioid motion therapy compared with the control group. requirement, and improved patient satisfaction.49 Although pain is a subjective measure, this modal- In spine surgery liposomal bupivacaine was ity may offer patients an additional option when shown to decrease pain in the immediate postop- seeking nonpharmacologic care. erative period and decrease the total opioid con- In a European study of patients undergoing sur- sumption.5,49 The formulation used in the United gical correction of adolescent idiopathic scoliosis,

Fig. 3. The nonpharmacologic interventions available to patients during the postoperative period to decrease the use of narcotic medications.

a novel cooling brace was used postoperatively to patients receive a physical therapy evaluation minimize opioid consumption. The Game Ready automatically to ensure maximal mobilization device is connected to an external circuit with ice and recovery. It is encouraged to remove the uri- cold water cooled to 4C. The brace is applied in nary catheter early in the postoperative period the postanesthetic care unit and is kept on for (ie, postoperative day 1). Prolonged immobiliza- 24 hours. Bellon and colleagues54 found that in tion has deleterious effects on pulmonary func- their consecutive cohort of 22 patients, the cooling tion and decreases the integrity of muscles, the brace allowed for decreased opioid use after sur- urinary tract, and the skin. Immobilization pro- gical correction in children. longs hospital stay and carries an increased risk of deep venous thrombosis, pulmonary em- bolism, pulmonary infection, and urinary tract in- Early Mobilization fections. Early mobilization has been shown to All patients are mobilized by nursing staff within decrease perioperative complications and 8 hours of arriving to the regular nursing floor. If decrease length of stay by 34%. Additionally, the patient is unable to mobilize an automatic patients mobilized early were more likely to be physical therapy order is sent out. High-risk discharged to home.

Fig. 4. A schematic of the various components of the ERAS protocol at the Cleveland Clinic Foundation, demonstrating the multidisciplinary approach.

Table 1 Pain-specific ERAS protocol at the Cleveland Clinic

Morning of Surgery Acetaminophen Gabapentin Dose 1 g PO 300–600 mg PO Epidural Local Anesthetic at Ketamine Lidocaine IV Ketorolac Analgesia incision Site Pre-incision 0.25 mg/kg 1.5 mg/kg bolus Lidocaine 1% bolus 1 mL/kg or 2.5 mg/kg max dose During surgery 5 mg/kg/min 1.5 mg/kg/h infusion infusion After closure 15–30 mg IV Fentanyl 0.25% bupivacaine bolus morphine 1 mL/kg or 2.5 mg/kg max Postoperative Ketorolac Acetaminophen Dose <120 mg/d for 72 h 1 g q6h until discharge

Abbreviations: PO, per os; q6h, every 6 hours.

DISCUSSION confounding factors. The various components of the protocol may need to be introduced in different Enhanced recovery after spine surgery is an itera- phases to improve compliance. Working across tive, innovative systems-based care approach that multiple disciplines is a potential barrier owing to has demonstrated effectiveness and statistically different methods of charting and decreased inter- significant outcomes at different tiers of care specialty communication. Pain is a subjective (Fig. 4). The growing opioid epidemic has placed physical examination finding and the subjectivity pressure on health care administrators and is what drives the challenge to both study and providers to find effective non-narcotic, pain man- effectively treat the entity. agement options for postoperative patients. Multi- The effectiveness of ERAS protocols at modal analgesia has been shown in the literature improving outcomes, efficiency, and patient satis- across different health care disciplines to faction remains to be seen. Early studies of ERAS decrease opioid consumption and improve post- protocols have shown that implementation of a operative mobilization. As discussed, there are multitiered approach to improving patient out- various pharmacologic and nonpharmacologic comes is possible, and may be effective and bene- perioperative interventions available to patients ficial to the surgical spine patient. Multidisciplinary (Table 1). Although previous studies have identi- collaboration has been found to improve patient fied the need to overhaul the postoperative pain and provider satisfaction with greater confidence management regimen of patients undergoing sur- that each aspect of the patient’s preoperative gery, few data have been published on the most and postoperative care benchmarks has been effective strategy to do so. Various ERAS met. protocols have been published citing standardiza- Future studies are needed to analyze effi- tion as a common theme leading to improved ciency, efficacy, and cost effectiveness. outcomes. Emerging research and innovation will help to Although the creation of a standardized, iterative determine the optimal protocols to use the protocol is possible, there are challenges to imple- various pain management options available to mentation and compliance. One such challenge to the clinician today. implementing this type of program is compliance owing to individual surgeon preference and a limited ability to monitor adherence to the pro- REFERENCES gram. Additionally, the implementation of multilevel reforms makes for difficult analysis for 1. Wainwright Thomas W, Immins T, Middleton causation with the potential for a variety of Robert G. Enhanced recovery after surgery

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