Rationale for and approach to preoperative opioid weaning: a preoperative optimization protocol

Pain is a complex and subjective experience now well-known to occur outside of the context of nociception, and with considerable potential for both amplification and suppression from the central nervous system (Latremoliere and Woolf 2009; Tracey and Mantyh 2007; Heinricher et al. 2009). While acute/nociceptive pain comprises a warning system alerting the organism to adopt avoidant behavior, it is now widely accepted (and supported by functional imaging evidence) that chronic pain for the most part represents maladaptive neuroplastic changes at the dorsal horn, and multiple higher (brain) centers including amygdala, hippocampus, insula, cingulate, and other parietal cortex areas and the prefrontal cortex (Flor et al. 1997; Tinazzi et al. 1998; Apkarian et al. 2004; Apkarian et al. 2005; Schmidt-Wilcke 2008; Rodriguez-Raecke et al. 2009; Baliki et al. 2010; Malinen et al. 2010; Apkarian et al. 2011; Farmer et al. 2012; Baliki et al. 2012).

Chronic opioid use is believed to reinforce this pathology, and again, functional neuroimaging studies seem to support shared neuroanatomic pathways and perturbances (Wanigasekera et al. 2011; Younger et al. 2011).

Chronic opioid use has also been shown to increase pain sensitivity via a process known as opioid-induced hyperalgesia (OIH). Distinct from tolerance, which represents an increasing threshold for analgesic responsiveness, OIH represents a reduced threshold for pain perception. Teleologically, the prolonged and imbalanced exogenous suppression of pain impulses to the brain should result in a reactionary increase in sensitivity to maintain homeostasis of this most critical protective sense. OIH is likely multifactorial with a host of postulated mechanisms including structural and functional alterations in opioid receptors, long-term potentiation at the dorsal horn, glial-mediated neuroinflammation, enhanced descending pain facilitation, and epigenetic factors (Lee et al. 2011; Roeckel et al. 2016; Weber et al. 2017). Once thought to require months of exposure to opioids, it is now recognized from animal and human investigations that OIH may occur with exposure as brief as days (Angst and Clark 2006; Compton et al. 2003; Cooper et al. 2012) and the recent widespread use of intraoperative remifentanil infusions has demonstrated that exposure on the order of hours is sufficient (Guignard et al. 2000; Angst et al. 2003). There may be a dose-response effect (Salengros et al. 2010; Fechner et al. 2013; Fletcher and Martinez 2014; Mauermann et al. 2016).

A specific association between chronic preoperative opioid use and postoperative hyperalgesia has been demonstrated recently (Hina et al. 2015; Chapman et al. 2011). This may result from preoperative OIH persisting into the postoperative period or may be mediated more acutely by requisite increased intra- and postoperative opioid doses. The association may also be confounded in the perioperative setting by inadequate analgesia resulting from tolerance; increased immediate postoperative pain intensity has been shown to correlate with increased incidence of persistent postoperative hyperalgesia (Malik et al. 2017; Weinbroum 2017).

Regardless of the mechanisms involved, the study by Nguyen et al. (2016) showing improved pain and functional outcomes after even a 50% reduction in preoperative opioid burden argues convincingly in the context of the other literature reviewed herein for a concerted effort toward preoperative opioid reduction if not elimination. Additional supporting evidence for this tactic comes from the recent demonstration that downtitration of remifentanil infusion rates is associated with a lower incidence of OIH (Comelon et al. 2016).

Chronic pain is also associated with psychological distress such as anxiety, post-traumatic stress disorder, borderline personality disorders, and to a lesser degree depression (Fishbain et al. 1998; Von Korff et al. 2005; Gureje et al. 2008; Bushnell et al. 2013; Simons et al. 2014). The reported severity of such chronic pain has been shown to correlate much more closely with these psychosocial variables than with somatic contributors including injury severity, which has in fact been shown in several studies to be non-predictive (Harris et al. 2007; Jenewein et al. 2009; Trevino et al. 2013). These psychological/behavioral comorbidities have also been shown to predict chronic postoperative pain specifically (Kleiman et al. 2011; Theunissen et al. 2012; Attal et al. 2014; Hoofwijk et al. 2015).

The distinct construct of pain catastrophizing has received significant attention recently in the arenas of pain management and perioperative medicine. Pain catastrophizing is defined as persistent negative cognitive and affective responses to actual or anticipated pain (Quartana et al. 2009) and incorporates various degrees of magnification, rumination, and perception of helplessness (Sullivan et al. 1995). Pain catastrophizing and learned helplessness correlate with many of the underlying psychiatric comorbidities mentioned above and also independently confer worsened postoperative pain (Theunissen et al. 2012; Ip et al. 2009; Khan et al. 2011; Vissers et al. 2012; Denison et al. 2004) and surgical outcomes (Abbot et al. 2011, Coronado et al. 2015, Teunis et al. 2015)

All of these behavioral comorbidities are strongly associated with chronic opioid use, misuse, and dependence (Turk et al. 2008; Becker et al. 2008; Goldner et al. 2014; Gross et al. 2016; Arteta et al. 2016; McAnally 2017) and in fact have been shown repeatedly to be the most robust predictors (Martins et al. 2012; Katz et al. 2013; Blanco et al. 2013).

A final consideration related to the complex association of psychopathology, chronic pain, opioid use, and the perioperative arena is that patients suffering with chronic pain are more likely to seek not only opioid prescriptions, but also operative intervention. Among those patients struggling with chronic pain is a disproportionate number of individuals plagued with catastrophic thinking regarding pain, as well as poor self-efficacy. To quote Beth Darnall, a leading contemporary researcher in the field, “pain catastrophizing may speed the path to surgery while simultaneously undermining surgical response” (Darnall 2016). In other words, the path to the operating room may be disproportionately self-selected by the very people who are least likely to benefit from it, or who are the least prepared at any rate.

Over-eager desire for surgical intervention and persistent seeking of opioid prescriptions are both more likely to be associated with an external locus of control. While impossible to measure objectively, this lack of self-efficacy may in fact be the most important independent variable.

An increasing number of publications as well as our local survey of surgeons indicate the importance of preoperative opioid reduction. The survey results may be biased somewhat in terms of the importance associated to preoperative opioid reduction or elimination given our reputation and that of our preoperative optimization program within the community. Nonetheless, the literature does support both plausibility and rationality of this objective, and at an anecdotal level, anyone involved in perioperative care for more than a handful of years has learned the challenges involved in rendering opioid-tolerant patients comfortable in the post-anesthesia care unit and the ward, and surgeons and pain physicians are well aware of the difficulties they face afterward. As discussed above, there is growing recognition also that chronic preoperative opioid use confers postoperative problems beyond simple analgesic compromise. However, answering the question at hand, whether preoperative opioid reduction/elimination is beneficial in terms of outcome may be more difficult than appears on the surface. First of all, randomization is almost certainly not going to occur—patients either are or are not willing to reduce or eliminate their opioids preoperatively. Second, blinding would be nearly impossible in that the high probability of withdrawal symptoms would likely unmask treatment arms. Whether or not preoperative opioid reduction is beneficial must then most likely be judged from non-randomized prospective or retrospective studies, the plausibility of compelling “reverse” evidence such as the studies discussed herein, and common sense given the known associations between chronic opioid use and its harms.

Beyond mere opioid reduction/cessation, in view of the complex risk factors for chronic pain discussed briefly above, it stands to reason (and has been advocated by numerous experts, consensus groups, and clinical practice guidelines) (Veterans Health Administration and Department of Defense 2002; Chou et al. 2007; Federation of State Medical Boards 2013; United States Department of Health and Human Services 2016; Manchikanti et al. 2017) that a biopsychosocial-spiritual paradigm with particular focus upon enhancing resilience and diversify coping skills is required. Simply removing opioids without providing effective substitute coping mechanisms will invariably lead to non-compliance and dropout. A systematic, rigorous (e.g., weekly visit) program of opioid reduction/withdrawal palliation needs to be coupled with basic preoperative counseling addressing the replacement of multifactorial “wellness-killers” (e.g., poor self-valuation and esteem, unaddressed psychopathology, poor sleep, poor nutrition, sedentary lifestyle, tobacco use) with proactive steps supporting personal responsibility for health and wellness.

Growing recognition of the disproportionate impact of chronic pain syndromes upon operative outcomes in Canada has led to the establishment of what appears to be a promising, comprehensive approach to perioperative pain management for chronic pain patients with the Toronto General Transitional Pain Service (TPS) (Katz et al. 2015). The current iteration of the TPS involves five anesthesiology-based pain physicians, a palliative care specialist/family physician, two clinical psychologists and trainees, three acute pain nurse practitioners, two physical therapists with expertise in acupuncture, an exercise physiologist, and administrative staff (Katz et al. 2015).

The American Society of Anesthesiologists, among other organizations, has championed the concept of a Perioperative Surgical Home (PSH) (Desebbe et al. 2016) which is intended to address multiple perioperative health deficits at an institutional level. One of the theoretical functions of a PSH would be to address perioperative chronic pain management optimization including opioid reduction (Vetter and Kain 2017). A significant practical barrier however in the USA (with payer source fragmentation and limitations of reimbursement allocation) is actually coming up with the resources for such an effort. As noted by Vetter and Kain,

How will an organization finance these additional resources necessary for a Transitional Pain Service? …A small community hospital may be hard-pressed to mobilize the comprehensive services and personnel required to successfully implement a full-scale perioperative Transitional Pain Service.

We propose that moving such perioperative chronic pain optimization functions outside of the institution to a smaller, leaner paradigm shaped by market pressures including outcomes-driven referral patterns will result in more efficient use of resources and improved care. Toward that end, we have created and begun implementation of a multidisciplinary preoperative optimization program for chronic pain patients focusing on a few high-yield areas of intervention, with opioid reduction and pain catastrophizing as two of the top priorities (as well as tobacco cessation and diet and activity improvements). The current iteration of the program comprises a 10–12-week course and incorporates traditional preoperative assessment and consultation issues (e.g., cardiac clearance and endocrinologic optimization) into a basic “wellness program” with simple, graded, measurable objectives including gentle opioid weaning along the lines of the fairly standard 10% per week paradigm (Manchikanti et al. 2017). Evidence from the behavioral world indicates that it takes at least 12 weeks to change habits (Lally et al. 2010); moving such “pain prehabilitation” into the outpatient realm and allowing for adequate optimization time beforehand allows for such and furthermore overcomes the institutional-level problem of lack of resources by placing this critical component of healthcare into the hands of invested providers. While the cost of a dozen or so outpatient follow-up visits may seem formidable up front, it is exceeded by the cost of a single extra day in the hospital and pales in comparison to a canceled operation, or worst of all an adverse outcome.