Optimal Postoperative Analgesia for the Opiate-Tolerant Patient

INTRODUCTION

Opioid tolerance, the physiologic process of diminishing effects combined with rising dose requirements over time with long-term opioid usage, has increased in prevalence in the developed world over the past two decades as opioid use has risen in the same period. Likewise, the proportion of opioid-tolerant patients presenting for surgery has increased and is estimated to be between one-fifth to one-third of patients, and even higher in certain populations such as spine surgery patients, where rates of over 70% have been reported. These patients present a unique challenge in perioperative pain management, often requiring a multimodal approach with significant coordination between care teams.

Opioid-tolerant patients can be grouped into three nonmutually exclusive categories: patients with current or prior cancer; patients with chronic noncancer pain; and patients with history of or current opioid addiction or misuse. Significant overlap between the first two and the last categories can occur, with as many as 20% of cancer patients prescribed opioids reporting misuse, and the rate of misuse among noncancer patients ranging from 21% to 29%, with the rate of addiction in the latter group between 8% and 12%. Furthermore, opioid tolerance and long-term use are associated with an elevated risk for psychiatric conditions such as depression, anxiety, psychosis, and post-traumatic stress disorder (PTSD). Patients with a history of opioid abuse are at especially high risk for poor pain control and withdrawal and may receive less opioids than other patients because of stigmatization from health care providers.

Additionally, opioid tolerance is associated with physiologic changes and increased risk for medical comorbidities that may affect perioperative care. Opioid-induced hyperalgesia (OIH) can be common in these patients; opioid-tolerant individuals often report higher pain scores and use higher opioid doses after surgery. Physical dependence can also be a significant factor because opioid-tolerant patients are at an increased risk for withdrawal with abrupt cessation or dose reduction. It also may be difficult to distinguish symptoms of withdrawal from OIH in the postoperative period in these patients, but the latter should be suspected when pain is perceived to increase with increasing opioid use. Furthermore, opioid-tolerant patients are at greater risk for respiratory depression with postoperative opioid use as a result of differential tolerance to analgesia versus respiratory drive compounded by increased opioid requirement in the acute period. As many as 70% to 85% of patients taking long-term opioids exhibit sleep-disordered breathing, with central sleep apnea being more common.

Opioids have also been shown to exert endocrine effects; of particular concern in these patients may be a blunted stress response after surgery from secondary adrenal suppression and reduced bone mineral density from hypogonadism. Opioids, morphine in particular, have been shown to suppress immune system responses in preclinical studies, ¹ and impact wound healing through impaired angiogenesis, lower recruitment of immune cells, decrease in myofibroblasts, and alteration of neuropeptide activity through receptors in the skin in peripheral nervous system. Overall, observational studies have found a higher risk for postoperative infections with long-term opioid use and a higher risk for poorer surgical outcomes, longer hospital stays, and higher health care costs.

OPTIONS

Opioid-tolerant patients tend to have poorer outcomes, more complications, longer hospital stays, and higher health costs than their opioid-naïve counterparts. For these reasons, coordination of care and preoperative planning are of elevated importance in these patients. The American perioperative surgical home (PSH) is one model of coordinated care for these patients, offering preoperative risk stratification, resources for addressing biopsychosocial factors, employment of evidence-based perioperative pathways, and interdisciplinary management that can improve outcomes both in hospital and after discharge. The 2016 American Pain Society (APS) guidelines also strongly recommend pain specialist consultation for opioid-tolerant patients undergoing surgery, particularly those patients with a history of substance abuse or addiction.

Multimodal analgesia has increasingly become a mainstay for patients undergoing surgery and those with opioid tolerance in particular. As in opioid-naïve patients, a variety of agents targeting different pain receptors may be employed. Evidence for the use of epidural analgesia, nonsteroidal antiinflammatory drugs (NSAIDs), continual peripheral nerve blocks, and lidocaine in multimodal analgesia can be found in the previous chapter on opiate-naïve patients and remain relevant therapies for opioid-tolerant patients. In this chapter, we will address the role of ketamine, gabapentinoids, and alpha-2 agonists in multimodal analgesia with particular regard toward opioid-tolerant patients and also discuss the use of perioperative opioids, including medication-assisted therapy (MAT), in this cohort.

EVIDENCE