Abstract
Background.
Acute pain may transition to chronic pain, a potentially debilitating illness.
Objectives.
We determined how often acute pain transitions to chronic pain among ED patients and whether persistent pain 1 week after the ED visit was associated with chronic pain.
Methods.
An observational cohort study conducted in two EDs. We included adults with acute pain (≤10 days) if an oral opioid was prescribed. Exclusion criteria were recent opioid use or use of any analgesics regularly prior to onset of the pain. Research associates interviewed patients during the ED visit, and 1 week and 6 months later. The primary outcome, chronic pain, was defined as pain on >50% of days since ED discharge. We constructed logistic regression models to evaluate the association between persistent pain 1 week after an ED visit and chronic pain while adjusting for demographic and treatment variables.
Results.
During a 9-month period, we approached 733 patients for participation and enrolled 484. 450/484(93%) provided one week outcome data and 410/484(85%) provided six month outcome data. One week after the ED visit, 348/453(77%, 95%CI:73, 80%) patients reported pain in the affected area. New onset chronic pain at six months was reported by 110/408 (27%, 95%CI: 23, 31%) patients. Presence of pain one week after ED visit was associated with chronic pain (OR3.6, 95%CI:1.6,8.5).
Conclusions.
About one-quarter of ED patients with acute pain transition to chronic pain within six months. Persistence of pain one week after the ED visit can identify patients at risk of transition.
Keywords: acute pain, chronic pain, transition
Introduction
Chronic pain, a potentially functionally disabling disease, affects 20% of the US population.(1) Appropriate treatment of patients with acute pain may prevent chronic pain. It is becoming increasingly clear from the surgical literature that interventions delivered at the time of the painful insult, or shortly thereafter, may reduce the incidence of persistent post-surgical pain.(2) If ED patients at risk of chronic pain could be identified and treated aggressively when they present to the ED with acute pain, it is possible that chronic pain could be prevented. Scant data are available to determine how often ED patients with acute pain transition to chronic pain and whether clinical features can predict which ED patients with acute pain transition. These data are essential to begin to determine which interventions may be appropriate for the primary prevention of chronic pain.
The goal of this work was to describe the frequency of new-onset chronic pain among a cohort of ED patients with acute pain, and to determine whether clinical features available earlier in the course of healing can be used to predict the transition to chronic pain. Specifically, we wished to test the hypothesis that persistent pain one week after an ED visit for acute pain would be associated with the development of chronic pain six months after the ED visit. This hypothesis is based on prior work among ED patients with acute low back pain.(3)
Materials and Methods
Overview.
This was a prospective observational cohort study of patients presenting to an ED for acute, new-onset pain for whom an opioid was prescribed upon discharge from the ED. We enrolled patients at the conclusion of the ED visit and followed them by telephone one and two weeks and three and six months later. The Albert Einstein College of Medicine Institutional Review Board reviewed and approved the study. All participants provided written informed consent.
Setting.
This study was performed in two academic EDs in the Bronx, NY which combined receive over 180,000 visits annually. Salaried, trained, bilingual (English and Spanish) technician-level research associates staff both EDs around the clock.
Subject selection.
We included adults aged 18 years and older with a chief complaint of acute pain from any cause who were discharged home from the ED and were prescribed an oral opioid. To participate, patients had to have pain for ≤ 10 days and could not have experienced pain in the same body region during the preceding six months. Individuals could only be enrolled once and were required to be opioid naive, which we defined as no use of any opioid (including methadone, buprenorphine or tramadol) within the previous six months. We excluded patients for use of any analgesic >10 days per month on average prior to the onset of acute pain, and any patients who required admission to the hospital.
Measures.
Research associates interviewed patients during the ED visit, obtaining basic sociodemographic data, information on the location and duration of pain, completed the PHQ9 depression instrument, and asked patients to predict how long they would continue to experience the pain that brought them to the ED. For this latter item, participants were asked, “Sometimes it’s difficult to predict, but what is your best guess for how long this episode of pain will last?” We recorded responses in number of days and dichotomized into ≤1 week versus > 1 week. This previously validated measure forces the patient to integrate a variety of components into one summary measure, including current pain relative to prior occurrences of pain as well as overall health, psychosocial stressors, general attitudes, and coping mechanisms such as catastrophization (defined as an overwhelming and irrational negative attitude about a disease process).(3) The research associates also collected data on morphine milligram equivalents of opioid prescribed.
During each of the telephone follow-ups, research associates collected data on pain intensity experienced using a four item ordinal scale (severe, moderate, mild, or none), frequency of pain at the time of follow-up (always, often, sometimes, rarely, or never),and whether or not the individual was able to resume all activities they had been able to perform prior to the ED visit. During the one and two week follow-up phone calls, the research associates collected data on whether or not the initial opioid prescription from the ED had been filled. We verified whether the initial opioid prescription had been filled using data from the state’s prescription monitoring program. During the six-month telephone follow-up, research associates inquired about the frequency of pain during the six months since the ED visit. Patients who reported pain on ≥50% of days since the ED visit were considered to have developed new onset chronic pain.(4)
Outcomes.
The primary outcome was new onset chronic pain. Important secondary outcomes included moderate or severe pain in the affected body part three or six months after the ED visit. Other three and six month outcomes included frequency of pain in the affected body part and whether or not the participant was able to resume all activities compared to prior to the ED visit.
Predictors.
The primary predictor was pain intensity at one-week. Co-variates of interest included age, sex, location of pain, duration of pain before ED visit, dose of opioid prescribed in oral morphine milligram equivalents (https://www.cdc.gov/drugoverdose/pdf/calculating_total_daily_dose-a.pdf), whether or not the patient filled the initial opioid prescription, depression, and the participant’s own anticipated duration of symptoms.
Analysis.
We reported the frequency of all baseline variables as n/N (%), mean (SD), or median (IQR) as appropriate. We report the frequencies of one and two week and three and six month outcomes as n/N (%). New onset chronic pain is reported as n/N (%, 95%CI)
We wished to test the hypothesis that pain at one week was associated with new onset chronic pain. This hypothesis was based on data from low back pain studies, which indicated that low back pain one week after an ED visit was associated with three month pain scores.(3)
In addition to our primary predictor variable (pain at one week), we analyzed the association between each of the following variables and new onset chronic pain: age, sex, location of pain, duration of pain, morphine milligram equivalents of opioids prescribed, whether or not the initial opioid prescription was filled, depression, and the participant’s own anticipated duration of symptoms. As has been done before, pain at one week was dichotomized into “some” or “none”.(3) We trichotomized the non-parametric continuous variables morphine milligram equivalents prescribed and dichotomized age at the median. We explored bivariable associations between each of these baseline variables and new onset chronic pain. We then built a multivariable logistic regression models in which new onset chronic pain was the dependent variable and all of the predictor variables discussed above were entered into each model. We report the results of these models as odds ratios (OR) with 95%CI. We considered independent variables to be associated statistically significantly with the dependent variable if the 95% CI did not cross 1.0.
Results
During a nine-month period beginning in November 2017, we approached 733 patients for participation; 484 met inclusion criteria and consented to participate (Figure 1). The most frequent reason for exclusion was use of opioids in the 6 months prior to the ED visit.
Figure 1.
Flow diagram
The location of acute pain participants reported most commonly was in the extremities, followed by back and neck, and abdomen and pelvis. On average, participants described experiencing pain for two days before presenting to the ED. We detail sociodemographic and other baseline characteristics in Table 1.
Table 1.
Baseline variables
| Characteristic | n (%) |
|---|---|
| Age in years, median (IQR) | |
| 45 (32, 57) | |
| Sex | |
| Male | 215 (44%) |
| Female | 269 (56%) |
| Location of pain | |
| Extremity | 224 (46%) |
| Neck and back | 103 (21%) |
| Abdomino-pelvic | 99 (20%) |
| Face including dental | 37 (8%) |
| Chest | 17 (4%) |
| Headache | 4 (1%) |
| Pain duration in days, median (IQR) | 2 (1, 4) |
| Morphine milligrams equivalents prescribed, median (IQR) | 75 (45, 90) |
| Depression | |
| None/ Mild | 457 (94%) |
| Moderate/ Severe | 27 (6%) |
| Anticipated duration of symptoms | |
| ≤ 1 week | 361 (75%) |
| > 1 week | 101 (21%) |
| Not sure | 22 (5%) |
IQR=interquartile range
During the six-month telephone follow-up, 110/408 participants (27%, 95%CI: 23, 31%) reported experiencing any pain on >50% of days since ED discharge, thus meeting criteria for new onset chronic pain.
As we report in Table 2, a large number of participants described continued pain and impaired functioning during the weeks and months after ED discharge. One week after ED discharge, 223/453 (49%) participants reported moderate or severe pain and nearly half had not yet resumed usual activities. Two weeks after ED discharge, 173/431 (40%) participants reported moderate or severe pain and more than one-third had not yet resumed usual activities. While the majority of patients had improved by three months, more than one in five reported moderate or severe pain at three months and one in six reported moderate or severe pain at six months.
Table 2.
Pain outcomes
| Outcome | One week n (%) | Two weeks n (%) | Three months n (%) | Six months n (%) |
|---|---|---|---|---|
| Worst pain in affected area during previous 24 hours | ||||
| Severe | 88 (19%) | 59 (14%) | 25 (6%) | 29 (7%) |
| Moderate | 135 (30%) | 114 (26%) | 64 (16%) | 42 (10%) |
| Mild | 125 (28%) | 113 (26%) | 75 (18%) | 70 (17%) |
| None | 105 (23%) | 145 (34%) | 244 (60%) | 269 (66%) |
| Missing | 31 | 53 | 76 | 74 |
| Pain frequency in affected area during previous 24 hours | ||||
| Often/ Always | 188 (42%) | 147 (34%) | 63 (16%) | 53 (13%) |
| Sometimes | 129 (29%) | 111 (26%) | 64 (16%) | 55 (13%) |
| Never/ Rarely | 133 (30%) | 173 (40%) | 277 (69%) | 302 (74%) |
| Missing | 34 | 53 | 80 | 74 |
| Able to resume usual activities | ||||
| Not able | 198 (44%) | 170 (39%) | 92 (23%) | 56 (14%) |
| Able | 252 (56%) | 261 (61%) | 313 (77%) | 353 (86%) |
| Missing | 34 | 53 | 79 | 75 |
We report bivariate associations between hypothesized predictors and chronic pain in Table 3. We report the results of the multivariable models in Table 4. Location of pain in the neck, back, or extremities, anticipating a pain duration of > 1 week, and persistent pain at one week were associated with poor outcomes, while depression and opioid variables were not. Substituting two-week pain (some or none) for one-week pain in the multivariable model resulted in a stronger association OR: 14.6 (95%CI: 5.1, 41.7).
Table 3.
Bivariate associations between early variables and chronic pain
| Characteristic | Frequency of new onset chronic pain n/N (%) | Odds of new onset chronic pain OR (95%CI) |
|---|---|---|
| Age in years | ||
| 18-45 | 53/ 202 (26%) | 1 |
| 46-96 | 57/ 206 (28%) | 1.1 (0.7, 1.7) |
| Sex | ||
| Male | 40/ 174 (23%) | 1 |
| Female | 70/234 (30%) | 1.4 (0.9, 2.2) |
| Location of pain | ||
| Chest/Abdomen/ pelvis | 16/96 (17%) | 1 |
| Neck and back | 29/ 92 (32%) | 2.3 (1.2, 4.6) |
| Head or face | 2/33 (6%) | 0.3 (0.1, 1.5) |
| Extremity | 63/187 (34%) | 2.5 (1.4, 4.7) |
| Duration of symptoms in hours | 1.1 (1.0, 1.2) | |
| Total morphine milligram equivalents of initial prescription | ||
| 9-54 | 27/ 119 (23%) | 1 |
| 60-75 | 55/ 186 (30%) | 1.4 (0.8, 2.4) |
| 90-390 | 28 / 103 (27%) | 1.3 (0.7, 2.3) |
| Filled initial ED opioid prescription | ||
| No | 8/ 36 (22%) | 0.8 (0.3, 1.7) |
| Yes | 102/ 372 (27%) | 1 |
| Depression | ||
| None or mild | 102/384 (27%) | 1 |
| Moderate or severe | 8/ 24 (33%) | 1.4 (0.6, 3.3) |
| Patient’s prediction of how long the pain would last | ||
| ≤ 1 week | 71/ 307 (23%) | 1 |
| >1 week | 32/ 80 (40%) | 2.2 (1.3, 3.7) |
| Pain at one week | ||
| None | 9/ 87 (10%) | 1 |
| Some | 96/ 308 (31%) | 3.9 (1.9, 8.2) |
OR=odds ratio
CI= confidence interval
Table 4.
Multivariable model
| Characteristic | Adjusted odds of new onset chronic pain OR (95%CI) |
|---|---|
| Age in years | |
| 18-45 | 1 |
| 46-96 | 0.8 (0.5, 1.3) |
| Sex | |
| Male | 1 |
| Female | 1.4 (0.8, 2.2) |
| Body region | |
| Head/ face/ Chest/Abdomen/ pelvis | 1 |
| Neck and back | 2.6 (1.3, 5.6) |
| Extremity | 2.4 (1.2, 4.7) |
| Duration of symptoms in hours | 1.0 (0.9, 1.2) |
| Total morphine milligram equivalents of initial prescription | |
| 9-54 | 1 |
| 60-75 | 1.5 (0.8, 2.8) |
| 90-390 | 1.4 (0.7, 2.8) |
| Filled initial opioid prescription | |
| No | 0.6 (0.2, 1.6) |
| Yes | 1 |
| Depression | |
| None or mild | 1 |
| Moderate or severe | 1.5 (0.6, 4.2) |
| Anticipated duration | |
| ≤ 1 week | 1 |
| >1 week | 1.9 (1.0, 3.4) |
| Pain at one week | |
| None | 1 |
| Some | 3.8 (1.6, 8.8) |
OR=Odds ratio
CI= confidence interval
Discussion
In this prospective cohort study conducted in two urban EDs, approximately one quarter of our patients with acute pain transitioned to chronic pain. More than 20% of the sample experienced moderate or severe pain in the affected body part three months later and more than 15% of the sample reported the same at six months. The transition to chronic pain was most pronounced among patients with extremity, neck or back pain, but even patients with torso pain were at risk. Persistent pain at one week, and even more so at two weeks, was associated with development of new onset chronic pain. In this dataset, depression and opioid use variables were not associated with poor pain outcomes.
Other ED-based studies reported similar rates of new-onset chronic pain after an initial ED visit for acute pain. Among adult patients with acute low back pain, 11%-24% report moderate or severe pain three months later.(3, 5, 6) Six months after a motor vehicle collision, 26% of elderly adults reported moderate or severe pain attributable to the MVC.(7) Among children and adolescents who suffered mild traumatic brain injury, 16% reported moderate or severe headache three months later.(8) Clearly, many injured ED patients continue to suffer long after ED discharge.
A variety of risk factors for progression of acute pain to chronic pain have been identified, mostly in the outpatient setting. Psychiatric disorders, such as depression, and psychological traits, such as catastrophizing, have been linked to poor long-term outcomes, though not among ED patients, and without robust magnitudes of association.(9–11) In this study, depression was not associated with poor outcomes. However, anticipating a pain duration > 1 week, a measure that incorporates catastrophizing, was associated modestly with chronic pain in this study. Among post-operative patients, worse pain or pain associated functional impairment at baseline, and worse tissue damage has also been associated with poor post-surgical outcomes.(12–15) However, none of these risk factors are associated strongly enough with long-term pain outcomes to enable clinicians to identify those patients most likely to continue to suffer.
Persistence of pain one week after the ED visit has previously been identified as a risk factor for poor long-term pain outcomes among ED patients with acute low back pain.(3) This study identified the same association in a broader sample of patients with acute pain. The association was even stronger when persistence of pain two weeks after the ED visit was used as the predictor. The challenge now is how to incorporate these data into interventions that can benefit patients.
There are models from other arenas that can inform this discussion. Persistent post-surgical pain has been decreased with a variety of different interventions, including regional anesthesia at the time of the surgery, and various medications in the post-operative period.(2) Similarly, low back pain outcomes have been improved modestly using targeted comprehensive interventions.(16) A compelling yet unproven hypothesis is that aggressive and tenacious treatment of pain initially can improve long-term outcomes.(17) The results of our study do not provide immediately actionable data for clinical emergency physicians, other than the ability to share with patients their odds of recovery. The twin goals of predicting which ED patients with acute pain might benefit from interventions, and what interventions to offer, require further study. There remains a lingering hope that early aggressive and comprehensive interventions will improve outcomes.
Persistence of pain one week after the initial event is an actionable risk factor in that it can theoretically be targeted. Though not relevant for individual emergency providers during a clinical shift, healthcare systems with an interest in the long-term health of their patients can devote more resources to ED patients with persistent pain at one week post-ED visit with the goal of improving long-term outcomes.
The interplay of opioids and new onset chronic pain is also incompletely understood. For some patients, persistent pain causes continued opioid use, placing patients at risk of opioid use disorder. Similarly, continued opioid use has been associated with neuroanatomical changes(18, 19) and increased risk of chronic pain.(20, 21) However, in our ED-based study, there was no relationship between dose of opioids and pain outcomes. The role of opioids for ED patients with acute pain is controversial. The long-term benefit of opioids for patients with acute pain is modest at best,(5) while the risk of progression from first-time opioid use to opioid use disorder, although quite low,(22) may be of some clinical importance.
Limitations
Limitations of this study include the following. First, we included patients with many different types of acute pain in one study instead of performing a disease specific study. It is clear that some types of pain require disease-specific treatment while others require more general treatments. Second, only 13% of the patients in this sample were 65 or older. Thus, these data may be less applicable to older patients. Third, 15% of our study population were lost-to-follow-up. We cannot determine whether these participants were fundamentally different from those from whom we were able to obtain follow-up data. Fourth, we determined our primary outcome using patient self-report rather than an objective measure of the impact of pain on functionality. These data may be inaccurate due to recall bias. Finally, our sample consisted of a socioeconomically depressed urban population. Because pain outcomes may be linked to access to care, the generalizability of these data to other patient populations is uncertain.
Conclusion
In conclusion, about one-quarter of ED patients with acute pain transition to chronic pain within six months. Persistence of pain one week after the ED visit can be used to identify those patients at risk of transition.
Supplementary Material
Article summary.
Why is this topic important? Chronic pain affects 20% of the US population. It is possible that chronic pain may be preventable if it could be anticipated.
What does this study attempt to show? This study attempts to show how frequently ED patients with acute pain transition to chronic pain within six months and whether persistence of pain one week after the ED visit is associated with new-onset chronic pain
What are the key findings? About one-quarter of ED patients with acute pain transition to chronic pain within six months. Persistence of pain one week after the ED visit can be used to identify those patients at risk of transition.
How is patient care impacted? Emergency physicians can counsel their patients with acute pain about their risk of transitioning to chronic pain. Healthcare systems with an interest in the long-term health of their patients can devote more resources to ED patients with persistent pain at one week post-ED visit with the goal of improving long-term outcomes.
Acknowledgments
This publication was supported in part by the Harold and Muriel Block Institute for Clinical and Translational Research at Einstein and Montefiore grant support (UL1TR001073)
Footnotes
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We have no conflicts of interest to report.
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