The Daily Dose • Sunday, March 20, 2022

Debating the Opioid Sparing Anesthetic Approaches for Controlling Pain

Cameron Bosinski, MD, MS

The opioid crisis has made anesthesiologists acutely aware of the consequences of excessive opioid use. Enhanced Recovery After Surgery (ERAS) protocols were developed in the 1990s to reduce opioid use and length of stay after surgery. During a live debate session, Shobana Rajan, MD and Rebecca Rigel Donald, MD discussed whether opioid sparing anesthetic approaches can effectively control pain and reduce opioid use in spine surgery during the session entitled, “Opioid Free Anesthesia for Spine Surgery: Harmful Hoax or Imperative Innovation?,” held on Saturday, March 19 at the IARS 2022 Annual Meeting.

Letha Mathews, MBBS, Professor of Clinical Anesthesiology, Chief, Neuroanesthesiology, and Medical Director II of Neuro Anesthesiology Team at Vanderbilt University Medical Center, set the stage for the debate to start off the session.  In her introduction, Dr. Mathews noted that there has recently been an exponential increase in spine surgeries, especially in the United States. This has been paralleled by an increasing awareness of an epidemic of opioid misuse. ERAS has been successfully applied to multiple surgeries including colorectal, hepatobiliary, breast, urologic, gynecologic, thoracic and head and neck, but the literature is mixed on whether there are benefits after spine surgery.

Shobana Rajan, MD, Associate Professor in the Department of Anesthesiology at UTHealth Houston McGovern Medical School, noted that spine surgery is highly variable and may extend from a single level to multiple levels with varying degrees of instrumentation and blood loss. In addition, patients undergoing spine surgery may possess varying risk factors such as preoperative opioid use or sleep apnea that impact the risk-benefit ratio of opioid administration. Importantly, uncontrolled pain in the postoperative period is the greatest risk factor for the development of chronic postoperative pain. This year, Dr. Rajan has published a review of alternatives to opioids in spine surgery in the Journal of Neurosurgical Anesthesiology. In this article, she discussed the options to reduce opioid use, including pre-emptive analgesia, intravenous adjuvants, neuraxial blockade, regional nerve blocks and local anesthetics.

Preemptive Analgesia:

NSAIDs have anti-inflammatory effects and reduce the development of central and peripheral sensitization in nociceptive pathways. Multiple studies have shown that NSAIDs lower pain scores and reduce opioid consumption. However, NSAIDs increase the risk of renal failure, gastrointestinal problems and can impair wound healing. There have been equivocal results as to whether acetaminophen decreases opioid consumption and length of stay. Recent systematic reviews and meta-analyses have shown that gabapentin and pregabalin have no benefit in spine surgery. This is in part due to an increased risk of side effects, such as respiratory depression, dizziness and vision changes.

Perioperative Intravenous Adjuvants:

A randomized placebo-controlled trial showed that intraoperative infusion of ketamine (5 mcg/kg/min) and lidocaine (1.5 mg/kg/hr) did not reduce pain within the first 48 hours after surgery. In addition, no benefit was seen in quality of recovery 3 months later. Methadone has action in the μ-opioid receptor and the NMDA receptor. Multiple studies have shown that a single 20mg dose of methadone lasts for 20 hours without any increased risk of respiratory depression. A recent study has shown that patients may have improved pain control when administered methadone and ketamine intraoperatively. Dexmedetomidine has been shown to reduce intraoperative opioid consumption, but this was not associated with a reduction in pain scores at 24 hours. A recent study of dexmedetomidine was stopped prematurely due to a high incidence of bradycardia, prolonged extubation and prolonged PACU stay.

Neuraxial Blockade:

When compared to patient controlled analgesia, epidural catheters placed by surgeons have been shown to reduce pain, reduce opioid consumption, improve patient satisfaction and lead to earlier mobilization. Epidurals frequently malfunction, are not in adequate position and can cause hypotension and bradycardia when used at high doses.

Regional Blockade:

The erector spinae plane block targets the dorsal rami of the thoracic spinal nerves. A recent randomized control trial found that patients with an erector spinae plane block had greater satisfaction compared to controls and reported 6-8 hours of analgesia. However, this block can also lead to motor blockade, spinal instability and neurologic complications.

Local Anesthetics:

Studies have not shown any benefit to infiltration of local anesthetics in spine surgery, including liposomal bupivacaine.

Opioid sparing interventions such as oral gabapentinoids and intravenous methadone are not recommended due to a high risk of adverse effects. In addition, other interventions have limited evidence that they provide any benefit including, erector spinae plane block, thoracolumbar interfascial plane block, intravenous lidocaine, glucocorticoids, dexmedetomidine, magnesium, epidural opioids, intrathecal opioids and local anesthetics.

Dr. Evan Kharasch, Vice Chair, Innovation, Director, Academic Entrepreneurship, Duke University School of Medicine and Professor of Anesthesiology at Duke University, published “Opioid-free Anesthesia: Time to Regain Our Balance” to address the possibility of opioid free anesthesia. At this time, opioid free strategies have not shown any benefit over opioid reduction strategies, nor do they reduce the risk of postoperative opioid use. Poorly controlled acute postoperative pain is the most important risk factor for developing chronic postoperative pain. Dr. Rajan recommended that anesthesiologists take a more patient-centric and balanced approach that tries to optimize pain control and minimize opioid usage when possible.

Rebecca Rigel Donald, MD, an Assistant Professor of Anesthesiology and Pain Medicine at Vanderbilt University Medical Center, explained that although opioids have traditionally been the main analgesic in spine surgery, practice patterns vary across institutions and have impacts on surgical outcomes.

Nearly every year since 2000, the number of deaths from opioid overdose has increased from the previous year. This trend has accelerated during the COVID-19 pandemic. One major contributor to opioid misuse can be traced to over-prescription of opioids. There is a positive correlation between the number of opioid pills initially prescribed and the probability of needing opioids 1 and 3 years after the initial prescription. A 10-day supply of opioids corresponds to a 20% probability that the patient will still require opioids to control pain after one year. A recent systematic review found that most patients only take 29-58% of prescribed opioids. Importantly, 50% of people who misuse opioids obtain them from a relative or friend. Eighty percent of these patients were prescribed opioids by only one doctor.

Surgery places opioid-naïve patients at a risk of developing persistent postoperative opioid use, this risk is even higher for patients that chronically use opioids. Twenty-five percent of opioid naïve patients and 59% of patients that were using opioids preoperatively developed persistent postoperative opioid use. Regardless of the type of surgery performed, patients with anxiety, depression, sleeping problems, prior trauma, substance misuse, preoperative pain or who use psychotropic medications are all at an increased risk of developing persistent postoperative opioid use.

Opioids have short-term and long-term negative effects. Chronic opioid use can lead to pharmacologic tolerance, hyperalgesia and disruption of the hypothalamic-pituitary-gonadal and hypothalamic-pituitary-adrenal axes. In addition, suppression of the innate and adaptive immune system can allow the progression of cancer and delay bone and wound healing.

When reviewing the literature, Dr. Donald found that there are many contradictory studies, in which some show a benefit of nonopioid analgesics, while others do not show any benefit. Gabapentin and pregabalin have been shown to lead to prolonged analgesia compared to placebo and reduce opioid consumption. Intravenous lidocaine has been shown to reduce pain scores at all time points postoperatively up to 3 months after surgery, opioid consumption and length of stay. Ketamine reduces pain scores and is opioid-sparing. A case report has been published of erector spinae block successfully managing the pain of a patient who was unable to tolerate opioids. Most studies have not shown motor weakness to be a complication in appropriately placed erector spinae blocks.

Combining multiple opioid-sparing interventions may lead to a synergistic effect on the reduction of pain and opioid use. The combination of acetaminophen, pregabalin and ketorolac given preoperatively led to lower opioid requirements, earlier ambulation and decreased length of stay. Numerous studies have shown that implementing a standardized ERAS pathway decreases postoperative opioid consumption and length of stay. In the future, it will be important to determine the best combination of pharmacologic and nonpharmacologic interventions to control postoperative pain. Dr. Donald noted that patients undergoing spine surgery are at a high risk of persistent postoperative opioid use. She recommended that anesthesiologists take this risk into account when developing an anesthetic plan.

Overall, spine surgery can produce moderate to severe pain. ERAS protocols have been developed to reduce intraoperative and postoperative opioid requirements. Although opioid sparing strategies have been developed, opioids should not be withheld in a patient with uncontrolled pain. For patients at a high risk of developing persistent postoperative pain, opioid alternatives and nonpharmacologic interventions should be implemented preoperatively, intraoperatively and postoperatively. When discharged, patients should not be prescribed more opioids than they need due to the risk of persistent pain and misuse by others.