See Article, page 1192

Despite substantial advances in the perioperative care of cardiac surgical patients that have led to enhanced recovery and improved quality of life, there continues to be a subset of patients who develop chronic postsurgical pain (CPSP). The incidence of CPSP after cardiac surgery has been reported to be as high as 37% at 6 months and up to 17% at 2 years.1 As with any perioperative complication, identifying which patients may be at greatest risk for CPSP is an essential element in developing a plan to reduce or even eliminate this risk. Knowing which patients are highest risk before surgery is one of the ultimate goals of precision perioperative medicine. While this goal is still yet unrealized, the predictive instruments available to clinicians for this purpose continue to evolve.

Postoperative pain trajectory analyses are tools that facilitate the categorization of patients who are recovering well with mild or resolving pain scores and those with persistently high pain scores who are not meeting expected pain resolution “milestones.”2 Categorizing patients by pain trajectories has been previously validated in multiple studies examining patients in noncardiac surgery, and a persistently high acute pain trajectory has been associated with CPSP and persistent postoperative opioid use.2 Less is currently known about pain trajectories after cardiac surgery and their associations with long-term outcomes.

In this issue of Anesthesia & Analgesia, Pagé et al3 sought to address this question by characterizing patient-reported pain trajectories and their associated 1-year rate of CPSP in a diverse cohort of cardiac surgical patients. The authors followed over 1000 patients undergoing median sternotomy for cardiac surgery and assessed their reported pain intensity each day for the first 6 postoperative days (PODs). Using Growth Mixture Modeling, an advanced statistical technique designed to create patient groupings based on pain trajectories, the authors were able to categorize their cohort into 3 groups: 41% of patients reported mild pain scores immediately after surgery which remained mild (“mild-staying-mild” group); 47% of patients reported moderate pain scores immediately after surgery which improved to mild (“moderate-becoming-mild” group); and 12% of patients reported moderate pain immediately after surgery which remained moderate through POD6 (“moderate-staying-moderate” group). Overall, 6% of patients reported CPSP in the chest region at 1 year postoperatively. After adjusting for confounders, patients in the mild-staying-mild trajectory had substantially lower odds of developing CPSP at 1-year compared to those in the moderate-staying-moderate pain trajectory (odds ratio [OR], 0.23, 95% confidence interval [CI], 0.06–0.88).

This study supports findings from multiple other cohorts in cardiac surgery, which have reported that 18% to 23% of patients report ongoing, persistent pain beyond the immediate postoperative period.4,5 A major gap in the previously-published literature has been linking these pain trajectories with longer term outcomes; this is where the work by Pagé et al3 expands our knowledge. In their study, the association of a moderate-staying-moderate pain trajectory with CPSP at 1 year is simultaneously impressive and concerning; it suggests that patients who are failing to meet early postoperative pain management milestones (ie, experiencing pain resolution) have higher odds of becoming patients with chronic pain a year later. These data, when combined with other studies in both cardiac and noncardiac surgery populations, convincingly demonstrate that patients with persistently high pain trajectories after surgery should be carefully observed for the development chronic pain and persistent opioid use.2,6

The study by Pagé et al3 has numerous strengths. This is the first study in cardiac surgery that has linked an early postoperative pain trajectory with CPSP at 1 year, providing clinicians with a potential “warning light” to trigger additional interventions. Next, all patients in the study received consultation with an acute pain service and had access to a range of pain therapies including intravenous patient-controlled opioid analgesia, if necessary. Finally, the data were prospectively collected using standardized tools.

While well-executed, the study also has a number of important limitations to consider. First, the study had an approximately 40% drop-out rate for the 1-year follow-up end point, and younger patients were more likely to drop-out than older ones. This is important because younger age is more likely to be associated with CPSP, so the study results may actually underestimate the incidence of CPSP in their cohort.4,6 Second, the study only examines chronic postsurgical chest pain and did not assess other potential sites of CPSP (eg, lower leg from saphenous vein harvesting); if other sites were included, the overall rate of CPSP may have been higher. Third, while the authors have done well to assess CPSP at 1-year, the association of CPSP with chronic opioid use such as active opioid prescriptions at 1-year was not assessed and remains unknown. Fourth, much of the study era (August 2012 to June 2020) includes data now 5 to 10 years old. Although it is possible that changes in care pathways over the past decade may have affected patients’ short- and longer-term outcomes, this study does provide an important estimate of CPSP risk and an association with a postoperative pain trajectory that clinicians and researchers can focus on going forward.7,8

Despite these limitations, there is much to be learned from these results. As noted now in multiple studies, there are certain patients after cardiac surgery who do not steadily progress towards surgical pain resolution as expected. Importantly, these patients may have characteristics that allow them to be identified early in the postoperative period. This failure to achieve adequate early pain resolution is associated with increased CPSP at 1-year. Armed with this understanding, we propose a comprehensive call to action aiming to reduce CPSP in the cardiac surgical population (Figure). First, and in accordance with current guidance, all scheduled preoperative patients should be screened for risk factors associated with CPSP. High-risk patients should be assessed preoperatively by a pain specialist to aid in perioperative pain management planning, identifying and addressing underlying mental health issues, and setting realistic patient expectations for the postoperative pain experience.9,10 Specifically, patients with preexisting chronic pain of any type, patients on preoperative long-term opioid therapy, and patients with substance use disorders merit special preoperative attention as these patients are at higher risk of developing CPSP. Ideally, patient pain management plans should be coordinated with preexisting outpatient clinicians, including their pain management and mental health specialists.10 Furthermore, patients receiving preoperative opioid therapy should be continued on their baseline opioid dose throughout the perioperative period, supplemented by additional opioid and nonopioid analgesia. These patients should be discharged with a plan for postoperative tapering of opioids back to their baseline preoperative dosage.10

Figure.:

Comprehensive action plan to reduce chronic postsurgical pain in cardiac surgery. All patients should be screened for risk factors for chronic postsurgical pain (CPSP) and receive standardized analgesic therapy with enhanced recovery protocols. Patients reporting moderate postoperative pain on postoperative day 2 are at highest risk of CPSP, and should receive more intensive in-hospital pain management as well as postdischarge follow-up with a transitional pain service.

High-risk patients may also be well-suited for a new model of pain medicine, the transitional pain service.11–13 A transitional pain service is primarily an outpatient-based multidisciplinary physician-led team that may be composed of anesthesiologists, pain physicians, nurse practitioners, pain psychologists, and other health care professions capable of providing multimodal psychological, pharmacological, and procedural pain interventions in an outpatient setting.11,12 The transitional pain service bridges the gaps in perioperative pain care by providing: (a) pre- and postsurgical care coordination with outpatient chronic pain clinicians and inpatient acute pain service teams; (b) preoperative pain education and expectation setting for complex patients, such as those on long-term opioid therapy; and (c) individualized pain management recommendations for the in-hospital acute pain service. After hospital discharge, the team provides close outpatient follow-up for high-risk patients, often via telehealth, to guide the titration of pain medications, monitor for persistent pain, and recommend in-person evaluation and intervention when necessary.

A critical element to potentially reduce CPSP is optimizing acute pain management. This entails providing effective perioperative multimodal analgesia for all patients, not just high-risk patients. Consensus- and evidence-based pain management recommendations for cardiac surgery have been included in published guidelines issued by relevant medical organizations.7,8 Multimodal analgesia targets pain transmission and pain processing at various sites through the use of agents with different mechanisms. Scheduling nonopioid analgesics such as acetaminophen are now recommended for all patients undergoing cardiac surgery unless contraindicated.7,8 Gabapentinoids have been reported to reduce postoperative pain, but they are likely not appropriate for all patients.7,8 Additionally, randomized trials comparing intravenous intraoperative methadone to fentanyl have demonstrated both improved immediate postoperative pain control and quality of recovery, as well as durable reductions in postsurgical pain at 1- and 3-month time points.14,15 Accordingly, it has now been recommended to consider intraoperative methadone for pain management in cardiac surgery patients.7

Despite optimized care pathways, we expect that some patients will still remain in the higher postoperative pain trajectory.16 In their cohort of patients who reported moderate pain immediately after surgery, Pagé et al3 identified a critical divergence on POD 2: in the group that followed the “moderate-becoming-mild” pain trajectory, patients reported a decrease in the numeric rating scale pain intensity score (0 = no pain; 10 = worst possible pain) of approximately 1.5 points compared to the prior day, down to less than 3. The other group of patients who followed the “moderate-staying-moderate” trajectory continued to report a pain intensity of at least 4, essentially unchanged from the previous day.3 This pain trajectory separation at POD2 to 3 has also been described in other cardiac surgery studies.4,6 Accordingly, cardiac surgery patients on POD2 with ongoing moderate pain (pain score ≥4), or with pain that is not resolving, merit early intervention. Earlier intervention could also be considered for patients with moderate pain on POD1, although at least some of these patients likely would have trended towards “mild” pain with standard therapies based on the present study.

For these patients with ongoing or worsening pain on POD2, we advise consultation with an inpatient acute pain service, if not already involved, to evaluate the effectiveness of the pain management plan and offer additional treatments that may steer the patient towards a “moderate-becoming-mild” pain trajectory. An acute pain team offers numerous different services, including both pharmacologic and nonpharmacologic therapies to reduce pain. One important procedural adjunct that may be offered by acute pain anesthesiologists is peripheral nerve blockade of chest wall nerves, which has been shown in a recent meta-analysis to reduce postoperative pain after cardiac surgery.17 For patients who may benefit from longer duration of nerve blockade, a catheter for perineural local anesthetic infusion is a powerful tool against postoperative pain. While not yet studied in patients stratified by pain trajectories, adding peripheral nerve blockade with or without a catheter offers great potential for patients in the “moderate-staying-moderate” pain trajectory, and improving acute pain management in this population may very well “redirect” them towards the “moderate-becoming-mild” pain trajectory.

Patients who do not initially meet their pain milestones should be followed by the acute pain service for the duration of their hospitalization or until their pain has resolved. Patients approaching discharge with ongoing pain issues should be referred to a transitional pain service, if available, with early clinical evaluation of their pain and opioid use postdischarge.11 The transitional pain team can help coordinate pain management strategies, provide psychological and mental health services, combine pharmacologic and nonpharmacologic therapies, and if necessary, offer procedurally based pain interventions. Transitional pain service referral may be associated with reduced CPSP and persistent postoperative opioid use.18 Furthermore, transitional pain clinicians can monitor opioid consumption and offer personalized opioid tapering strategies postoperatively. For patients continuing to experience ongoing pain at 3 months despite these interventions, referral to a chronic pain specialist will offer needed longitudinal care and other supportive services.

Pagé et al are to be commended for their work elucidating patient-specific postsurgical pain trajectories in cardiac surgery and linking them to CPSP at 1 year. Their work provides clinically-relevant guidance for identifying patients who are not meeting pain resolution milestones and may be at increased risk of CPSP. Why and how specific subsets of patients diverge in terms of their postoperative pain trajectories remains an active field of investigation.19 Fully understanding the genetic contribution to the development of chronic pain after surgery remains elusive, as pain itself is recognized as having biophysical and psychosocial components with current measurement tools mostly dependent on patient response.20–22 For now, early detection of greater-than-expected acute pain and intervention in the critical window around POD 2 (or perhaps earlier) represents an opportunity to affect longer-term outcomes in some patients. Optimizing pre- and peri-procedural pain management via implementation of and adherence to published recommendations will hopefully reduce the number of patients in the “moderate-staying-moderate” trajectory. For patients with persistent moderate pain despite optimal standard therapy, a progressive approach is indicated with pain therapy intensification, acute pain service consultation, transitional pain service referral with postdischarge follow-up, and chronic pain services if needed. While it is unknown if this approach will succeed in eliminating CPSP after cardiac surgery, the problem is now better defined, paving the way for future research studies and clinical innovations aimed at utilizing postoperative pain trajectory data to guide actionable therapeutic escalation in pain management to improve patient outcomes.

ACKNOWLEDGEMENTS

This material is in part the result of work supported with resources and the use of facilities at the Veterans Affairs Palo Alto Health Care System (Palo Alto, California, USA). The contents do not represent the views of the Department of Veterans Affairs or the United States Government.

DISCLOSURES

Name: Matthew W. Vanneman, MD.

Contribution: This author helped develop the concept, drafted the initial article, revised the draft, and reviewed and approved the submitted article.

Conflicts of Interest: M. W. Vanneman receives royalties from Dana-Farber Cancer Institute/Novartis for novel preclinical cancer immunotherapy.

Name: Larissa M. Kiwakyou, MD.

Contribution: This author helped create the figure, revised the draft, and reviewed and approved the submitted article.

Conflicts of Interest: None.

Name: T. Kyle Harrison, MD.

Contribution: This author helped revise the draft, and reviewed and approved the submitted article.

Conflicts of Interest: T. K. Harrison receives research funding from Lucid Lane, Inc.

Name: Edward R. Mariano, MD, MAS, FASA, FASRA.

Contribution: This author helped develop the concept, revised the draft, and reviewed and approved the submitted article.

Conflicts of Interest: None.

This manuscript was handled by: Nikolaos J. Skubas, MD, DSc, FACC, FASE.

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