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Pain Medicine  |   May 2017
A Prospective Study of Chronic Pain after Thoracic Surgery
Author Notes
  • From the Department of Anesthesia (E.O.B., T.J.B.), Department of Biostatistics (E.O.B.), Department of Cardiothoracic Surgery (K.R.P., J.K.), and Department of Pharmacology (T.J.B.), University of Iowa, Iowa City, Iowa; and Istanbul University, Cerrahpasa Medical Faculty, Istanbul, Turkey (A.S.).
  • This article is featured in "This Month in Anesthesiology," page 1A.
    This article is featured in "This Month in Anesthesiology," page 1A.×
  • Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are available in both the HTML and PDF versions of this article. Links to the digital files are provided in the HTML text of this article on the Journal’s Web site (www.anesthesiology.org).
    Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are available in both the HTML and PDF versions of this article. Links to the digital files are provided in the HTML text of this article on the Journal’s Web site (www.anesthesiology.org).×
  • Submitted for publication September 16, 2016. Accepted for publication January 27, 2017.
    Submitted for publication September 16, 2016. Accepted for publication January 27, 2017.×
  • Address correspondence to Dr. Bayman: University of Iowa Hospitals and Clinics, 6439 JCP, 200 Hawkins Drive, Iowa City, Iowa 52242-1081. emine-bayman@uiowa.edu. This article may be accessed for personal use at no charge through the Journal Web site, www.anesthesiology.org.
Article Information
Pain Medicine / Clinical Science / Pain Medicine / Thoracic Anesthesia
Pain Medicine   |   May 2017
A Prospective Study of Chronic Pain after Thoracic Surgery
Anesthesiology 5 2017, Vol.126, 938-951. doi:10.1097/ALN.0000000000001576
Anesthesiology 5 2017, Vol.126, 938-951. doi:10.1097/ALN.0000000000001576
Abstract

Background: The goal of this study was to detect the predictors of chronic pain at 6 months after thoracic surgery from a comprehensive evaluation of demographic, psychosocial, and surgical factors.

Methods: Thoracic surgery patients were enrolled 1 week before surgery and followed up 6 months postsurgery in this prospective, observational study. Comprehensive psychosocial measurements were assessed before surgery. The presence and severity of pain were assessed at 3 and 6 months after surgery. One hundred seven patients were assessed during the first 3 days after surgery, and 99 (30 thoracotomy and 69 video-assisted thoracoscopic surgery, thoracoscopy) patients completed the 6-month follow-up. Patients with versus without chronic pain related to thoracic surgery at 6 months were compared.

Results: Both incidence (P = 0.37) and severity (P = 0.97) of surgery-related chronic pain at 6 months were similar after thoracotomy (33%; 95% CI, 17 to 53%; 3.3 ± 2.1) and thoracoscopy (25%; 95% CI, 15 to 36%; 3.3 ± 1.7). Both frequentist and Bayesian multivariate models revealed that the severity of acute pain (numerical rating scale, 0 to 10) is the measure associated with chronic pain related to thoracic surgery. Psychosocial factors and quantitative sensory testing were not predictive.

Conclusions: There was no difference in the incidence and severity of chronic pain at 6 months in patients undergoing thoracotomy versus thoracoscopy. Unlike other postsurgical pain conditions, none of the preoperative psychosocial measurements were associated with chronic pain after thoracic surgery.

What We Already Know about This Topic
  • Chronic pain after thoracic surgery is common

  • Both psychosocial measures and quantitative sensory testing results have been proposed as factors predictive of chronic pain after other types of surgery

What This Article Tells Us That Is New
  • In a study of 107 patients undergoing thoracotomy and thoracoscopy, the incidence and severity of pain 6 months after surgery were similar

  • Acute postoperative pain was the strongest predictor of pain at 6 months

CHRONIC pain is the most common symptom for which patients seek medical care (26% in the United States),1,2  and surgery is the cause of chronic pain for 22.5% of these patients.3  The International Association for the Study of Pain (Washington, D.C.) defines chronic postsurgical pain as pain persisting at least 3 months after surgery.4 
Despite advances in medical care, meta-analyses of prospective studies on chronic pain at 3 months (17 studies; 1,439 patients) and 6 months (15 studies; 1,354 patients) after thoracotomy demonstrate that the incidence of chronic pain at 3 and 6 months after thoracotomy were 57% (95% CI, 51 to 64%) and 47% (95% CI, 39 to 56%), respectively.5  A few studies evaluated results for chronic pain after video-assisted thoracic surgery ([VATS], thoracoscopy)5,6 ; however, the data were not sufficient to summarize.
The goal of this study was to detect the predictors of chronic pain at 6 months after thoracic surgery, both from thoracotomy and VATS, from a comprehensive evaluation of demographic, psychosocial, and surgical factors. Our hypothesis was that the chronic pain related to thoracic surgery is not only related to surgery- and anesthesia-related factors, but also associated with psychosocial measures assessed before the surgery. The primary outcome of the current study was the presence of chronic pain (yes/no) at 6 months after thoracic surgery. This is the primary analysis of this prospective, observational study.
Materials and Methods
Study Design and Subjects
This prospective, observational study was approved by the University of Iowa (Iowa City, Iowa) Institutional Review Board (201202796). Thoracic surgery patients were recruited from the University of Iowa Hospitals and Clinics and the Iowa City Veterans Affairs Medical Center, both located in Iowa City, Iowa. The Iowa City Veterans Affairs Medical Center thoracic surgery clinic was staffed by the University of Iowa Hospitals and Clinics thoracic surgery clinic, and patient care was similar in these two hospitals. Patients were approached for consent during their preoperative visit approximately 1 week before their thoracic surgery.
To be eligible, patients must have spoken English, been 18 to 80 yr old, and been scheduled for thoracic surgery. The surgical procedures included thoracotomy; pneumonectomy; removal of lung other than bilobectomy, pneumonectomy, completion pneumonectomy, sleeve lobectomy, and segmentectomy; single- or multiple-wedge resection; or thoracoscopy with excision-plication of bullae, with lobectomy, with partial or total pulmonary decortication, or with wedge resection of lung. Patients with limitations of self-expression or visual dysfunction or having emergency surgery, a severe psychiatric illness, or chronic pain problems in the chest area for longer than 2 months before the thoracic surgery were excluded. Pregnant women and prisoners were also excluded.
Preoperative Psychosocial Assessments
After informed consent, the research nurse asked patients to complete five computer-adaptive Patient-Reported Outcomes Measurement Information System (PROMIS)7  questionnaires for (1) anxiety (PROMIS Bank v1.0: anxiety); (2) depression (PROMIS Bank v1.0: depression); (3) physical role function (PROMIS Bank v1.0: physical function); (4) fatigue (PROMIS Bank v1.0: fatigue); and (5) sleep disturbance (PROMIS Bank v1.0: sleep disturbance). These computer-adaptive questionnaires contain a large collection of items measuring one characteristic; each subsequent question is chosen depending on the patient’s responses to previous queries, thus limiting the number of questions to approximately six per questionnaire. The results of the PROMIS questionnaires are presented as standardized T scores with a mean of 50 and an SD of 10. Therefore, a patient with a physical function T score of 40 is 1 SD below the U.S. general population mean.8  Patients then completed three additional computer questionnaires examining (1) posttraumatic stress disorder (Post-traumatic Stress Disorder CheckList—Civilian Version9 ), (2) catastrophizing (Pain Catastrophizing Scale10 ), and (3) psychologic acceptance (Acceptance and Action Questionnaire II [higher scores indicate greater emotional distress]11 ).
Preoperative Pain Assessments
During the preoperative visit, patients were asked to rate their current pain at rest using the numerical rating scale (NRS, 0 to 10) based on the following question: “Please rate your current pain at rest by indicating the number that best describes your pain where 0 means no pain and 10 is the worst imaginable pain.” Next, we asked patients to cough strongly two times and rate pain with coughing using the NRS (0 to 10) by asking “Please rate your current pain during coughing by indicating the number that best describes your pain where 0 means no pain and 10 is the worst imaginable pain.” In addition, they were asked to rate their average expected postoperative pain severity for each of their first 3 postoperative days (NRS, 0 to 10; “Please rate your expected average pain on day 1 [2 or 3] after surgery”). Severities of pain are reported as overall NRS when it includes all patients’ assessments even if pain severities were 0 (zero).
Quantitative Sensory Testing
Preoperative pain threshold to cold was measured by the Thermal Sensory Analyzer-II (Medoc Inc., Israel) via 30 × 30 mm contact thermode. During this procedure, a probe starting from 30°C (86°F) was applied to the forearm and the temperature was decreased by 1°C/s (1.8°F/s) increments until the patient experiences pain. The patient was asked to click a button when the nonpainful cold sensation changes to a painful cold sensation. At this time, the temperature of the probe returned to 30°C (86°F). If the patient did not stop the test, the lowest temperature reached would be 10°C (50°F), and at that time, the temperature rapidly returns to 30°C (86°F). This process was repeated three times, and the average of three measurements (°C) was presented as the pain threshold to cold.
Pain magnitude to suprathreshold cold was estimated in terms of an NRS (0 to 10). This time, the thermal testing device cooled to 10°C (50 °F) and stayed at that temperature for 15 s. At the end of the 15 s, patients were asked to rate their pain in terms of the NRS (0 to 10). This process was repeated three times, and the average of three measurements (NRS) was presented as the pain magnitude to suprathreshold cold.
Anesthesia and Surgery
The type of surgery was determined by surgeons based on their usual practice. Surgeons and anesthesiologists performed their usual intraoperative care. The usual postoperative pain management for patients undergoing VATS was patient-controlled analgesia using hydromorphone or morphine. Generally, when patients tolerated oral nutrition, oral opioid pain medications were initiated. For open thoracotomy, unless contraindicated, a thoracic epidural catheter was placed at approximately T5 to T6, and 0.05 or 0.10% bupivacaine was infused at 8 to 14 ml/h as tolerated, based on blood pressure and pain scores.12  Patient-controlled analgesia was utilized for rescue in patients receiving epidural local analgesia. If converted from VATS to open thoracotomy, a patient was given patient-controlled analgesia and offered thoracic epidural analgesia in the recovery room or on postoperative day 1. Postoperative opioid analgesic use during the first 24 h was recorded in oral morphine equivalents.
Electronic Medical Records
Age, American Society of Anesthesiologists physical status (general medical condition), preexisting medical conditions, preoperative opioid usage, preoperative radiation or chemotherapy within 6 weeks of the surgery, duration and type of surgery, postoperative analgesic use, and postoperative radiation or chemotherapy within 6 months after surgery were obtained from the electronic medical records.
First 3 Postoperative Days
Research assistants visited patients during the first 3 days after surgery to collect the severity of average pain during the previous 24 h (NRS, 0 to 10; “Please rate your pain by indicating the number that best describes your pain on average in the last 24 h”) and the number of chest tubes present for each day. The chest tube management was at the discretion of the surgical team, and it was counted present if the patient had a chest tube at 6:00 am that day. When patients were discharged during the weekend, the data collection form to measure the severity of average pain during the previous 24 h and the number of chest tubes present for each day for the first 3 postoperative days was sent with the patient with a stamped return envelope.
Follow-up Assessment
At 3 and 6 months after thoracic surgery, patients were mailed three questionnaires. The intensity of their average pain during the previous week (NRS, 0 to 10) was assessed based on the following question: “Please rate your thoracic surgery pain only by indicating the number that best describes your pain on average in the last 1 week using the NRS (0 to 10; 0 = no pain and 10 = worst possible pain).” Forms for physical functioning and chronic pain acceptance questionnaires13  were also sent. In addition, the presence of pain from thoracic surgery and extent of pain limiting daily activities were identified by telephone interview with the following questions: (1) “Do you currently have pain related to your thoracic surgery?”; and (2) “Does the pain limit your daily activities?” (yes/no).
Statistical Analyses
The primary outcome variable and the statistical analysis plan were defined before data collection. The primary outcome variable of the study is chronic pain related to thoracic surgery at 6 months after surgery, based on the following question: “Do you currently have pain related to your thoracic surgery?” Those patients with chronic pain related to thoracic surgery at 6 months after surgery were compared to those patients without such pain at that time.
The two-sided 95% CI for the incidence of chronic pain related to thoracic surgery at 6 months after surgery was calculated according to Clopper and Pearson.14 
The normality of the continuous data was statistically tested by the Shapiro–Wilk test and by examining the quantile–quantile plot. Normally distributed continuous variables were presented as mean ± SD and univariately compared using a two-sample Student’s t test. When the distribution was not normal, median along with the first (Q25) and third (Q75) quartiles was presented and the groups were compared using a Wilcoxon rank sum test. Categorical data were presented as frequency and percentage and were statistically tested using the chi-square test or the Fisher exact test, where appropriate. Those subjects with any response to the phone interview at 6 months were included in the analyses. Missing data points were not imputed. Analyses of repeated measures were performed with mixed-effects models with unstructured covariance structures.
Univariate and multivariate statistical analyses are performed with both traditional frequentist and Bayesian analyses. In Bayesian analyses, unknown parameters are random variables and therefore prior probability distributions should be defined. The Bayesian model combines the prior distribution with data and produces a posterior distribution. Inferences are made from the posterior distribution. Prior distributions used for the overall mean and the coefficients for the fixed-effect terms such as severity of acute pain and the presence of preoperative pain at rest were assumed normal, as usual for these types of analyses, and were not very informative (Supplemental Digital Content 1, Appendix, http://links.lww.com/ALN/B387).
Those covariates with a univariate P < 0.20 were examined in the frequentist multivariate model. The corresponding Bayesian analog for the P = 0.20 is to examine whether the 80% two-sided posterior credible interval of the slope term excludes zero. This enables us to work with a smaller subset of the covariates that are most likely to be significant in the multivariate model. The covariates considered for the frequentist and Bayesian multivariate models were age at surgery, preoperative pain at rest (or preoperative pain with coughing), preoperative opioid usage, average expected pain severity, any chest tube on day 3 (D3) after surgery, severity of acute postoperative pain during the first 3 days after surgery, standardized sleep disturbance score, and the pain catastrophizing scale total score.
A model with all potential covariates can be written as follows:
where μ is the intercept in the logit scale and β1 to β8 are coefficients to adjust for the potential model covariates that were introduced before. Note that, since preoperative pain with coughing and preoperative pain at rest are correlated (weighted κ = 0.47; P < 0.0001), we separately examined these two variables in the model.
Those covariates with multivariate P < 0.01 were included in the final multivariate models. Backward model selection techniques were applied to find the most parsimonious model. Models were compared with a stepwise approach based on their Akaike Information Criterion15  for frequentist models and Deviance Information Criterion16  for Bayesian models. Relative risks and associated 99% CI and credible intervals were provided for key covariates of chronic pain. Relative risk estimates and associated confidence or credible intervals were calculated using the modified Poisson regression approach17–19  for the frequentist multivariate model and using the log-binomial model20  for the Bayesian multivariate model. Sensitivity to prior distributions was examined to test the robustness of the model for Bayesian models.
The goodness of fit of the final multivariate logistic regression model was evaluated by the Hosmer–Lemeshow test,21  where P < 0.05 indicates lack of fit. The area under the receiver operating characteristics curve (C statistic) for the multivariate logistic regression model was provided.
The sample size of the study was assessed based on the logistical challenges, instead of a priori power calculations, in this study. The main goal of the study was to collect preliminary data for a future larger study. We aimed to have complete data from 100 patients in this prospective longitudinal study.
Frequentist analyses were performed using SAS 9.4 software (SAS Institute, USA). Plots were created using SigmaPlot version 12.5 (Systat Software, USA) and R version 3.2.5 (The R Foundation, https://www.R-project.org/).22  Bayesian analysis were performed in WinBUGS 1.4.3 software (Imperial College and Medical Research Council, United Kingdom).23  WinBUGS uses Markov chain Monte Carlo methods. To represent the extreme regions of the parameter space, three parallel chains of equal lengths with disperse initial values were used in WinBUGS analyses. Convergence was judged by Brooks–Gelman–Rubin diagnostics plots,24  density and history plots, and autocorrelations. Bayesian results were based on 5,000 iterations after a burn-in period of 5,000 iterations in each chain.
Results
Four hundred ninety patients were screened between March 8, 2013, and December 21, 2015. From these, 124 patients were consented and 107 patients were assessed during the first 3 days after surgery. One hundred two patients completed the follow-up interviews at 3 months, and 99 patients completed the follow-up interviews at 6 months (fig. 1). From these, 30 patients had thoracotomy (19 scheduled for thoracotomy and 11 converted from VATS) and 69 patients had VATS. Two surgeons (K.R.P. and J.K.) performed 74% of the operations. Data from 99 patients with 6-month follow-up are presented.
Fig. 1.
Flowchart of patients. VATS = video-assisted thoracic surgery.
Flowchart of patients. VATS = video-assisted thoracic surgery.
Fig. 1.
Flowchart of patients. VATS = video-assisted thoracic surgery.
×
Acute and Chronic Pain: Thoracotomy Versus VATS
The overall NRS during the acute postoperative period for all patients is plotted from the preoperative period to the 3rd postoperative day in figure 2 for both thoracotomy and VATS patients. There were no differences between the average NRS preoperatively and for the 3 days after surgery in thoracotomy patients compared to patients undergoing VATS.
Fig. 2.
Numerical rating scale (NRS, 0 to 10) for patients during the 6 months of the study separately for thoracotomy versus video-assisted thoracic surgery (VATS) patients. Note that those patients with zero pain scores were included in this plot. When analyzed longitudinally, the time effect was significant (P < 0.0001). Neither surgery (P = 0.13) nor the interaction (P = 0.53) effects were significant. One-sided error bars represent SD. POD = postoperative day; pre-op = preoperative.
Numerical rating scale (NRS, 0 to 10) for patients during the 6 months of the study separately for thoracotomy versus video-assisted thoracic surgery (VATS) patients. Note that those patients with zero pain scores were included in this plot. When analyzed longitudinally, the time effect was significant (P < 0.0001). Neither surgery (P = 0.13) nor the interaction (P = 0.53) effects were significant. One-sided error bars represent SD. POD = postoperative day; pre-op = preoperative.
Fig. 2.
Numerical rating scale (NRS, 0 to 10) for patients during the 6 months of the study separately for thoracotomy versus video-assisted thoracic surgery (VATS) patients. Note that those patients with zero pain scores were included in this plot. When analyzed longitudinally, the time effect was significant (P < 0.0001). Neither surgery (P = 0.13) nor the interaction (P = 0.53) effects were significant. One-sided error bars represent SD. POD = postoperative day; pre-op = preoperative.
×
Incidences of chronic pain at 3 and 6 months after thoracotomy were 47% (14 of 30; 95% CI, 28 to 66%) and 33% (10 of 30; 95% CI, 17 to 53%), respectively. The incidences of chronic pain after VATS at 3 and 6 months were 29% (21 of 72; 95% CI, 19 to 41%) and 25% (17 of 69; 95% CI, 15 to 36%), respectively. The incidences of chronic pain both at 3 (P = 0.09) and 6 (P = 0.37) months were not different for thoracotomy and VATS patients (fig. 3).
Fig. 3.
Incidences of chronic pain related to thoracotomy and video-assisted thoracic surgery (VATS) at 3 and 6 months after surgery.
Incidences of chronic pain related to thoracotomy and video-assisted thoracic surgery (VATS) at 3 and 6 months after surgery.
Fig. 3.
Incidences of chronic pain related to thoracotomy and video-assisted thoracic surgery (VATS) at 3 and 6 months after surgery.
×
When the average NRS is calculated for those patients with chronic pain related to thoracic surgery, the severities of pain at 3 and 6 months after thoracotomy were 3.9 ± 2.3 (n = 9) and 3.3 ± 2.1 (n = 9), respectively. Similarly, for VATS patients, the NRS for those patients with chronic pain related to thoracic surgery at 3 and 6 months were 2.8 ± 2.2 (n = 17) and 3.3 ± 1.7 (n = 16), respectively. For those patients with chronic pain related to thoracic surgery, differences between thoracotomy and VATS patients at 3 (P = 0.18) and 6 (P = 0.93) months were not statistically significant. Severities of pain at 3 and 6 months after surgery are also presented as mild (NRS, 0 to 2), moderate (NRS, 3 to 5), and severe (NRS, >5) in table 1.
Table 1.
Three- and 6-Month Follow-up for Pain Assessments
Three- and 6-Month Follow-up for Pain Assessments×
Three- and 6-Month Follow-up for Pain Assessments
Table 1.
Three- and 6-Month Follow-up for Pain Assessments
Three- and 6-Month Follow-up for Pain Assessments×
×
Because there were no differences between thoracotomy and VATS patients for both incidences of chronic pain and the average NRS at 3 and 6 months after thoracic surgery, we present results by combining thoracotomy and VATS patients for the remainder of the article.
Chronic Pain Related to Thoracic Surgery: Thoracotomy and VATS Combined
Altogether, the incidence of chronic pain at 3 months after either type of thoracic surgery was 34% (35 of 102; 95% CI, 25 to 44%), and the severity of pain among those patients with chronic pain related to thoracic surgery at 3 months was 3.3 ± 2.4 (n = 35). Pain limited the daily activities of 16% (16 of 102) of patients at 3 months after surgery. For the 6-month assessment, the incidence was 27% (27 of 99; 95% CI, 19% to 37%) and the severity of pain among those patients with chronic pain related to thoracic surgery was 3.3 ± 1.8. Pain limited the daily activities of 8.2% (8 of 98) of the patients.
The severity of acute and chronic pain (NRS) is plotted for those patients with and without thoracic surgery-related chronic pain at 6 months after surgery in figure 4. Those patients with chronic pain related to thoracic surgery at 6 months consistently reported higher NRS preoperatively, for 3 days postoperatively, and at 3 and 6 months (all P < 0.05). When analyzed longitudinally, both the time effect (P < 0.0001) and the group effect (chronic thoracic surgery pain at 6 months; P < 0.0001) were significant, but the interaction (P = 0.62) term was not.
Fig. 4.
Severity of pain for those patients with and without chronic pain related to thoracic surgery at 6 months after surgery. Note that those patients with zero pain scores were included in this plot. When analyzed longitudinally, both the time effect (P < 0.0001) and the presence of pain at 6 months (P < 0.0001) were significant, but not the interaction (P = 0.62) term. Note that, one patient (¥) was sedated during the first 3 days. Some (5 patients at 3 months and 8 patients at 6 months) patients completed phone interviews at 3 and 6 months but did not return the mail including the numerical rating scale (NRS). One-sided error bars represent SD. POD = postoperative day; pre-op = preoperative. *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001, ****P ≤ 0.0001.
Severity of pain for those patients with and without chronic pain related to thoracic surgery at 6 months after surgery. Note that those patients with zero pain scores were included in this plot. When analyzed longitudinally, both the time effect (P < 0.0001) and the presence of pain at 6 months (P < 0.0001) were significant, but not the interaction (P = 0.62) term. Note that, one patient (¥) was sedated during the first 3 days. Some (5 patients at 3 months and 8 patients at 6 months) patients completed phone interviews at 3 and 6 months but did not return the mail including the numerical rating scale (NRS). One-sided error bars represent SD. POD = postoperative day; pre-op = preoperative. *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001, ****P ≤ 0.0001.
Fig. 4.
Severity of pain for those patients with and without chronic pain related to thoracic surgery at 6 months after surgery. Note that those patients with zero pain scores were included in this plot. When analyzed longitudinally, both the time effect (P < 0.0001) and the presence of pain at 6 months (P < 0.0001) were significant, but not the interaction (P = 0.62) term. Note that, one patient (¥) was sedated during the first 3 days. Some (5 patients at 3 months and 8 patients at 6 months) patients completed phone interviews at 3 and 6 months but did not return the mail including the numerical rating scale (NRS). One-sided error bars represent SD. POD = postoperative day; pre-op = preoperative. *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001, ****P ≤ 0.0001.
×
At 6 months after surgery, the NRS of patients without chronic pain related to thoracic surgery was 0.5 (95% CI, 0.05 to 0.98) units higher compared to preoperative pain at rest (P = 0.03). On the other hand, for those patients with chronic pain related to thoracic surgery, the NRS at 6 months after surgery was 2.3 units (95% CI, 1.4 to 3.2) higher compared to preoperative pain at rest (P < 0.0001). Therefore, statistically, neither group returned to baseline pain levels at 6 months after their surgery.
Note that, because of the exclusion criteria, preoperatively, no patients had chronic pain in their chest region, but many had a non-zero NRS (fig. 5). Similarly, some patients without chronic pain related to thoracic surgery at 6 months still reported a non-zero NRS at that time. Even if we specifically asked for the presence of thoracic surgery-related pain for the primary outcome variable, the NRS may reflect other symptoms or be affected by other conditions.
Fig. 5.
Severity of preoperative pain at rest (numerical rating scale [NRS], 0 to 10) for those patients with (red triangles) versus without (black circles) chronic pain related to thoracic surgery at 6 months.
Severity of preoperative pain at rest (numerical rating scale [NRS], 0 to 10) for those patients with (red triangles) versus without (black circles) chronic pain related to thoracic surgery at 6 months.
Fig. 5.
Severity of preoperative pain at rest (numerical rating scale [NRS], 0 to 10) for those patients with (red triangles) versus without (black circles) chronic pain related to thoracic surgery at 6 months.
×
Preoperative Evaluations
Preoperative evaluations comparing patients with and without chronic pain related to thoracic surgery at 6 months are presented in table 2. Based on the preoperative evaluations, those patients who report higher preoperative pain scores at rest (P = 0.025; fig. 5) and pain upon coughing (P = 0.014; Supplemental Digital Content 2, Figure 1, http://links.lww.com/ALN/B388), as well as those patients who expect to have a higher severity of acute pain after the surgery (P = 0.026) tend to have a higher likelihood of reporting chronic pain related to thoracic surgery at 6 months. Other demographics, quantitative sensory testing measurements, or preoperative radiation or chemotherapy evaluated during the preoperative visit were not associated with the presence of chronic pain at 6 months after surgery.
Table 2.
Preoperative Evaluation, Approximately 1 Week before Surgery
Preoperative Evaluation, Approximately 1 Week before Surgery×
Preoperative Evaluation, Approximately 1 Week before Surgery
Table 2.
Preoperative Evaluation, Approximately 1 Week before Surgery
Preoperative Evaluation, Approximately 1 Week before Surgery×
×
Expected Versus Observed Postoperative Pain
Scatterplots, Pearson correlation coefficients, and the associated P values between the expected and observed pain scores (NRS) for each postoperative day for those patients with versus without chronic pain related to thoracic surgery at 6 months are presented in Supplemental Digital Content 2, Figure 2 (http://links.lww.com/ALN/B388). Correlation coefficients among those patients having chronic pain related to thoracic surgery at 6 months were all less than or equal to 0.21 and were all nonsignificant (P ≥ 0.3). On the other hand, correlation coefficients among those patients not having chronic pain related to thoracic surgery at 6 months were all greater than or equal to 0.4 and were significant (P ≤ 0.001). The differences between observed and expected acute pain scores for those patients with chronic pain related to thoracic surgery at 6 months were not different (P = 0.70).
Early Postoperative Evaluations
Assessments measured during the day of surgery and the first 3 days after the surgery, as well as the postoperative radiation and chemotherapy within 6 months of surgery, are presented in table 3. Most of the patients had lobectomy (49%) or wedge resection (43%). Note that 83% (25 of 30) of thoracotomy patients had epidural analgesia compared to 12% (8 of 69) of VATS patients. In addition to higher severity of average acute pain (P = 0.001), the presence of chest tube on the 3rd postsurgical day (P = 0.02) was also univariately associated with the higher chance of developing chronic pain at 6 months.
Table 3.
Intraoperative and Early Postoperative Evaluation (Days 0 to 3 after Surgery) and Postoperative Therapy
Intraoperative and Early Postoperative Evaluation (Days 0 to 3 after Surgery) and Postoperative Therapy×
Intraoperative and Early Postoperative Evaluation (Days 0 to 3 after Surgery) and Postoperative Therapy
Table 3.
Intraoperative and Early Postoperative Evaluation (Days 0 to 3 after Surgery) and Postoperative Therapy
Intraoperative and Early Postoperative Evaluation (Days 0 to 3 after Surgery) and Postoperative Therapy×
×
Preoperative Psychosocial Measurements
Associations of preoperative psychosocial measurements with the presence of chronic pain related to thoracic surgery at 6 months are presented in table 4. Even if scales, such as pain catastrophizing, indicated some trend, when the type I error rate of 0.05 level is used, none of the preoperative psychosocial evaluations indicated a difference for those patients with versus without chronic pain related to thoracic surgery at 6 months.
Table 4.
Preoperative Psychosocial Assessments
Preoperative Psychosocial Assessments×
Preoperative Psychosocial Assessments
Table 4.
Preoperative Psychosocial Assessments
Preoperative Psychosocial Assessments×
×
Psychosocial Measurements at 3- and 6-month Follow-ups
As a part of the follow-up, at 3 and 6 months after surgery, patients were also asked to complete the short form PROMIS physical function and chronic pain acceptance questionnaires25  (table 5). Even if at the baseline, both groups of patients reported similar standardized physical function scores (P = 0.43; table 4); at 6 months after surgery, the standardized physical function scores for those patients with chronic pain related to thoracic surgery was 5.7 units (95% CI of the difference, 2.4 to 9.1) lower compared to those patients without such pain at that time (P = 0.007). However, within the chronic pain and no chronic pain related to thoracic surgery groups, the changes in physical function scores from baseline to 3 and 6 months were not statistically significant (P > 0.05 for each). For example, for those patients with thoracic surgery-related pain at 6 months, the reductions on standardized physical function scores from baseline to 6 months were 4.3 units (95% CI, –0.5 to 9.0).
Table 5.
Three- and 6-Month Follow-up for Psychosocial Assessments
Three- and 6-Month Follow-up for Psychosocial Assessments×
Three- and 6-Month Follow-up for Psychosocial Assessments
Table 5.
Three- and 6-Month Follow-up for Psychosocial Assessments
Three- and 6-Month Follow-up for Psychosocial Assessments×
×
Frequentist Multivariate Model
When those covariates with univariate P < 0.2 were included in the multivariate model and stepwise backward model selection procedures were applied, a reduced frequentist multivariate model was obtained (table 6). According to the multivariate model, the only factor associated with the presence of chronic pain related to thoracic surgery at 6 months is the severity of acute postoperative pain during the first 3 days after surgery (NRS, 0 to 10).
Table 6.
Frequentist and Bayesian Multivariate Models for the Presence of Chronic Pain at 6 Months after Thoracic Surgery
Frequentist and Bayesian Multivariate Models for the Presence of Chronic Pain at 6 Months after Thoracic Surgery×
Frequentist and Bayesian Multivariate Models for the Presence of Chronic Pain at 6 Months after Thoracic Surgery
Table 6.
Frequentist and Bayesian Multivariate Models for the Presence of Chronic Pain at 6 Months after Thoracic Surgery
Frequentist and Bayesian Multivariate Models for the Presence of Chronic Pain at 6 Months after Thoracic Surgery×
×
Based on the multivariate model, those patients with higher severity of acute pain during the first 3 days after surgery have a higher likelihood of developing chronic pain related to thoracic surgery. Each point of increase on the severity of the acute postoperative pain (NRS, 0 to 10) score increased the chance of developing chronic pain related to thoracic surgery 1.3 times (99% CI, 1.1 to 1.4). The Hosmer–Lemeshow test indicated the model’s adequacy for the data (P = 0.24). The area under the curve (AUC; C statistic) of the multivariate model is 0.73.
Bayesian Multivariate Model
When those covariates in which 80% two-sided posterior credible interval of the slope term excludes zero (age at surgery, preoperative pain at rest [or preoperative pain with coughing], preoperative opioid usage, average expected pain severity, any chest tube on day 3 after surgery, severity of acute postoperative pain during the first 3 days after surgery, standardized sleep disturbance score, and the pain catastrophizing scale total score) were included in the Bayesian logistic regression model and stepwise backward model selection procedures were applied, a reduced Bayesian multivariate model was obtained (table 6). Parallel to the frequentist multivariate model, the Bayesian multivariate model also only included the severity of acute postoperative pain during the first 3 days after surgery (NRS, 0 to 10) as a significant covariate associated with the presence of chronic pain related to thoracic surgery at 6 months. Relative risk estimates from the Bayesian model were similar to frequentist estimates and are presented in the last two columns of table 6. Different prior distributions provided similar results (Supplemental Digital Content 1, Appendix, http://links.lww.com/ALN/B387).
Type of Surgery
Even though there were not univariate differences between thoracotomy and VATS patients for developing chronic pain, to inspect the impact of surgery on outcome, the surgery effect was examined in the final Bayesian and frequentist multivariate models. When treatment effect is added to the model, there was no increase on the AUC or differences on the inferences from the multivariate models compared to the model not including the treatment effect.
In addition, model selection was repeated within the open surgery and VATS groups separately. Within the VATS group (n = 69), the severity of acute postoperative pain during the first 3 days after surgery was the only predictor for both frequentist (P = 0.001) and Bayesian (99% credible interval, 0.21 to 1.17) models. Because of the small sample size (n = 30), none of the covariates were significant within the open thoracotomy group with either the frequentist or Bayesian models.
Discussion
This is the first prospective study to consider a comprehensive list of preoperative, demographic, psychosocial, and surgical variables for thoracic surgery patients. We surveyed patients through 6 months with a small (7.5%) loss to the follow-up rate and almost no missing data. Our broad inclusion criteria allowed us to generalize our results to all thoracic surgery patients, including those patients converted from VATS to thoracotomy. There was no difference in the incidence and severity of chronic pain 6 months after thoracic surgery in patients undergoing VATS versus thoracotomy. Based on both the frequentist and the Bayesian multivariate models, the covariate associated with the chronic pain related to thoracic surgery was higher severity of average acute pain during the first 3 days after surgery. Preoperative psychosocial factors were not associated with the development of chronic pain.
Thoracotomy Versus VATS
Several studies propose that nerve injury is associated with chronic postsurgical pain26 ; yet both chronic neuropathic (20 to 30%) and nonneuropathic pain occur after thoracic surgery,27,28  suggesting that postthoracic surgery pain is not simply due to direct nerve injury. VATS is considered less invasive than open thoracotomy and would seem to be less likely to cause nerve injury. However, accumulating data indicate that VATS and thoracotomy have similar rates of chronic pain.28–33  Also, consistent with a previous study,32  during the course of 6-month follow-up, among those patients with chronic pain related to thoracic surgery, NRS scores for thoracotomy patients were not different compared to those of VATS patients.
Even though some patients reported that they do not have chronic pain related to thoracic surgery at 3 and 6 months, some did report a positive NRS at those times. NRS scores at 3 and 6 months may reflect other sources of pain that patients undergoing thoracic surgery experience.
Preoperative Pain at Rest
The majority (75%) of patients reported zero pain at the preoperative assessment. Preoperative pain is identified as a risk factor to chronic pain after total knee replacement,34  as well as other surgeries.35,36  In our study, we excluded those patients with preexisting chronic pain in the chest area, and the indication for surgery does not usually contribute to preoperative pain. However, we do not have detailed information regarding other preexisting pain conditions. Approximately 25% of the patients in our study had a preoperative NRS > 0. If those patients with preexisting pain conditions such as back pain and fibromyalgia were excluded from the study, the generalizability of study results to the patient population would be diminished.
Acute Pain
Consistent with the thoracic surgery37,38  and other postsurgical chronic pain conditions,35,39,40  we report that a higher severity of acute pain is associated with a greater likelihood of developing chronic pain. Much chronic pain can be initiated by an inciting event like surgery, trauma, or infection and begins as acute pain. In general, studies show that reducing pain with various analgesic regimens has been successful in the acute postoperative period.41,42  When those patients were followed up to examine the long-term effect, incidences of chronic pain were usually not different.43–48  Regional techniques such as epidural analgesia continue to have a role in reducing acute pain and acute postoperative morbidity. Although many assume that good treatment of acute pain will prevent chronic pain, this association with acute pain may be a marker for a patient prone to poor longer term outcomes that may not be prevented through better acute inpatient management. Reducing acute pain using either regional anesthesia or other techniques and examining the incidence and severity of chronic pain after surgery remain important areas of investigation.49,50 
Preoperative Psychosocial Assessments
In general, chronic pain after surgery is associated with preoperative psychosocial factors.51–53  A previous study reported higher anxiety and/or depression scores among those patients with versus without chronic pain related to thoracic surgery.54  However, it is currently unknown if the psychosocial factors were different before the surgery or if those patients with chronic pain after surgery developed anxiety or depression after surgery or after developing chronic pain. Measuring psychosocial factors before surgery enabled us to test this hypothesis in our study. Contrary to our expectations and consistent with a recent observational study on VATS patients,6  none of the preoperative psychosocial variables were significantly associated with the presence of chronic pain. Our negative results may be due to the small sample size in our study and the large number of associations tested. To examine the role of psychosocial factors, in future studies, batteries of psychosocial factors could be assessed both before and after the surgery in larger samples. In addition, measures of neuropathic pain, mood, and function can be added to longitudinally assess the impact of these factors on pain outcome and impact of pain on psychosocial factors.
Quantitative Sensory Testing
A few studies have examined quantitative sensory testing to predict chronic pain for thoracic surgeries. Wildgaard et al.6  preoperatively enrolled 47 patients and followed them at 3 months after VATS. Preoperative sensory thresholds to warmth, cool, and heat pain on the thorax were not predictive of chronic pain. Yarnitsky et al.38  preoperatively enrolled 62 patients and followed them up around 29 weeks after thoracotomy. During the preoperative period, heat pain threshold, suprathreshold pain magnitude to heat, and diffuse noxious inhibitory control were measured. They showed that pain threshold and suprathreshold pain scores were not associated with chronic pain. Only diffuse noxious inhibitory control and acute pain were predictors of chronic pain. In our study, finding cold pain threshold and suprathreshold pain magnitude to cold not associated with chronic pain is consistent with the results of Yarnitsky et al.38 
Multivariate Model
Both frequentist and Bayesian multivariate models revealed that severity of average acute pain during the first 3 days after surgery (NRS, 0 to 10) is the only measure associated with the presence of chronic pain related to thoracic surgery at 6 months. Because we examined a large number of associations with a sample size of only 99 patients, we used a type I error rate of 0.01 instead of 0.05. Despite a small sample size in this study, the AUC for the final multivariate model discriminating between patients with and without chronic pain is 0.73. Larger, multicenter studies are needed to examine if the severity of acute pain remains as the only predictor associated with the presence of chronic pain related to thoracic surgery.
Observational Study
During the last 2 decades, the number of surgeons preferring less invasive VATS to open thoracotomy has increased.31  Recently, Bendixen et al.31  completed a randomized controlled trial for patients undergoing lobectomy for stage I lung cancer. They reported episodes of moderate to severe pain being more frequent after anterolateral thoracotomy compared to VATS at 52 weeks after surgery. They reported strict exclusion criteria that limited the eligible patient pool. Using strict exclusion criteria and randomizing only a subgroup of patients are remarkably difficult. On the other hand, with a prospective, observational study, all thoracic surgery patients can be included, which likely increases the generalizability of the study results.
Study Limitations
First, because of the observational nature of the study, the numbers of patients in the thoracotomy (n = 30) and VATS (n = 69) groups are different. Type of surgery is based on surgical preference. However, the type of surgery was not a significant factor affecting the incidence and severity of chronic pain. Second, since the choices of anesthetic and postoperative analgesic regimens utilized during the first few days after surgery are not likely to influence the development of chronic pain after thoracotomy,43–48  they were not rigorously standardized, but followed the usual care. For example, the use of acetaminophen and nonsteroidal antiinflammatory drugs was not standardized. Third, we do not have detailed information about other comorbid chronic pain problems that were present before surgery or developed during the 6-month follow-up. Fourth, we did not examine specifically for evidence of nerve injury during the 3- and 6-month follow-up assessments. Fifth, during the follow-up interview at 3 and 6 months after surgery, we asked patients if thoracic surgery-related pain limits their daily activities. Pain limited daily activities of 16 and 8.2% of the patients at 3 and 6 months after surgery, respectively. We do not have detailed information using a validated questionnaire in a U.S. population33  about specific functions that were limited.
Conclusions
The incidence of chronic pain related to thoracic surgery at 6 months is 27%, and pain limited the daily activities of 8.2% of patients at that time. The incidence of chronic pain is similar for thoracotomy and VATS patients. Patients with a higher severity of pain during the first 3 days after surgery have a higher likelihood of developing chronic pain related to thoracic surgery at 6 months. Unlike other postsurgical pain conditions, none of the preoperative psychosocial measurements were associated with the presence of chronic pain. Psychosocial factors may become evident after surgery or as chronic pain develops. Therefore, future studies should examine psychosocial factors not only preoperatively, but also at other time points during the follow-up.
Acknowledgments
The authors appreciate the help of Alicia Manning, A.D.N. (Department of Anesthesia, University of Iowa, Iowa City, Iowa), Pam Jacobs, R.N. (Department of Anesthesia, University of Iowa, Iowa City, Iowa), and Joan Ricks-McGillin, R.N., B.S.N., (Department of Cardiothoracic Surgery, University of Iowa, Iowa City, Iowa) for the patient enrollment. We also appreciate edits suggested by Paul Casella, M.F.A. (Department of Internal Medicine, University of Iowa, Iowa City, Iowa).
Research Support
Supported by grant No. NS080110-01A1 from the National Institute of Neurological Disorders and Stroke of the National Institutes of Health (Bethesda, Maryland). Support was also provided by the Department of Anesthesia at the University of Iowa (Iowa City, Iowa).
Competing Interests
The authors declare no competing interests.
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Fig. 1.
Flowchart of patients. VATS = video-assisted thoracic surgery.
Flowchart of patients. VATS = video-assisted thoracic surgery.
Fig. 1.
Flowchart of patients. VATS = video-assisted thoracic surgery.
×
Fig. 2.
Numerical rating scale (NRS, 0 to 10) for patients during the 6 months of the study separately for thoracotomy versus video-assisted thoracic surgery (VATS) patients. Note that those patients with zero pain scores were included in this plot. When analyzed longitudinally, the time effect was significant (P < 0.0001). Neither surgery (P = 0.13) nor the interaction (P = 0.53) effects were significant. One-sided error bars represent SD. POD = postoperative day; pre-op = preoperative.
Numerical rating scale (NRS, 0 to 10) for patients during the 6 months of the study separately for thoracotomy versus video-assisted thoracic surgery (VATS) patients. Note that those patients with zero pain scores were included in this plot. When analyzed longitudinally, the time effect was significant (P < 0.0001). Neither surgery (P = 0.13) nor the interaction (P = 0.53) effects were significant. One-sided error bars represent SD. POD = postoperative day; pre-op = preoperative.
Fig. 2.
Numerical rating scale (NRS, 0 to 10) for patients during the 6 months of the study separately for thoracotomy versus video-assisted thoracic surgery (VATS) patients. Note that those patients with zero pain scores were included in this plot. When analyzed longitudinally, the time effect was significant (P < 0.0001). Neither surgery (P = 0.13) nor the interaction (P = 0.53) effects were significant. One-sided error bars represent SD. POD = postoperative day; pre-op = preoperative.
×
Fig. 3.
Incidences of chronic pain related to thoracotomy and video-assisted thoracic surgery (VATS) at 3 and 6 months after surgery.
Incidences of chronic pain related to thoracotomy and video-assisted thoracic surgery (VATS) at 3 and 6 months after surgery.
Fig. 3.
Incidences of chronic pain related to thoracotomy and video-assisted thoracic surgery (VATS) at 3 and 6 months after surgery.
×
Fig. 4.
Severity of pain for those patients with and without chronic pain related to thoracic surgery at 6 months after surgery. Note that those patients with zero pain scores were included in this plot. When analyzed longitudinally, both the time effect (P < 0.0001) and the presence of pain at 6 months (P < 0.0001) were significant, but not the interaction (P = 0.62) term. Note that, one patient (¥) was sedated during the first 3 days. Some (5 patients at 3 months and 8 patients at 6 months) patients completed phone interviews at 3 and 6 months but did not return the mail including the numerical rating scale (NRS). One-sided error bars represent SD. POD = postoperative day; pre-op = preoperative. *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001, ****P ≤ 0.0001.
Severity of pain for those patients with and without chronic pain related to thoracic surgery at 6 months after surgery. Note that those patients with zero pain scores were included in this plot. When analyzed longitudinally, both the time effect (P < 0.0001) and the presence of pain at 6 months (P < 0.0001) were significant, but not the interaction (P = 0.62) term. Note that, one patient (¥) was sedated during the first 3 days. Some (5 patients at 3 months and 8 patients at 6 months) patients completed phone interviews at 3 and 6 months but did not return the mail including the numerical rating scale (NRS). One-sided error bars represent SD. POD = postoperative day; pre-op = preoperative. *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001, ****P ≤ 0.0001.
Fig. 4.
Severity of pain for those patients with and without chronic pain related to thoracic surgery at 6 months after surgery. Note that those patients with zero pain scores were included in this plot. When analyzed longitudinally, both the time effect (P < 0.0001) and the presence of pain at 6 months (P < 0.0001) were significant, but not the interaction (P = 0.62) term. Note that, one patient (¥) was sedated during the first 3 days. Some (5 patients at 3 months and 8 patients at 6 months) patients completed phone interviews at 3 and 6 months but did not return the mail including the numerical rating scale (NRS). One-sided error bars represent SD. POD = postoperative day; pre-op = preoperative. *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001, ****P ≤ 0.0001.
×
Fig. 5.
Severity of preoperative pain at rest (numerical rating scale [NRS], 0 to 10) for those patients with (red triangles) versus without (black circles) chronic pain related to thoracic surgery at 6 months.
Severity of preoperative pain at rest (numerical rating scale [NRS], 0 to 10) for those patients with (red triangles) versus without (black circles) chronic pain related to thoracic surgery at 6 months.
Fig. 5.
Severity of preoperative pain at rest (numerical rating scale [NRS], 0 to 10) for those patients with (red triangles) versus without (black circles) chronic pain related to thoracic surgery at 6 months.
×
Table 1.
Three- and 6-Month Follow-up for Pain Assessments
Three- and 6-Month Follow-up for Pain Assessments×
Three- and 6-Month Follow-up for Pain Assessments
Table 1.
Three- and 6-Month Follow-up for Pain Assessments
Three- and 6-Month Follow-up for Pain Assessments×
×
Table 2.
Preoperative Evaluation, Approximately 1 Week before Surgery
Preoperative Evaluation, Approximately 1 Week before Surgery×
Preoperative Evaluation, Approximately 1 Week before Surgery
Table 2.
Preoperative Evaluation, Approximately 1 Week before Surgery
Preoperative Evaluation, Approximately 1 Week before Surgery×
×
Table 3.
Intraoperative and Early Postoperative Evaluation (Days 0 to 3 after Surgery) and Postoperative Therapy
Intraoperative and Early Postoperative Evaluation (Days 0 to 3 after Surgery) and Postoperative Therapy×
Intraoperative and Early Postoperative Evaluation (Days 0 to 3 after Surgery) and Postoperative Therapy
Table 3.
Intraoperative and Early Postoperative Evaluation (Days 0 to 3 after Surgery) and Postoperative Therapy
Intraoperative and Early Postoperative Evaluation (Days 0 to 3 after Surgery) and Postoperative Therapy×
×
Table 4.
Preoperative Psychosocial Assessments
Preoperative Psychosocial Assessments×
Preoperative Psychosocial Assessments
Table 4.
Preoperative Psychosocial Assessments
Preoperative Psychosocial Assessments×
×
Table 5.
Three- and 6-Month Follow-up for Psychosocial Assessments
Three- and 6-Month Follow-up for Psychosocial Assessments×
Three- and 6-Month Follow-up for Psychosocial Assessments
Table 5.
Three- and 6-Month Follow-up for Psychosocial Assessments
Three- and 6-Month Follow-up for Psychosocial Assessments×
×
Table 6.
Frequentist and Bayesian Multivariate Models for the Presence of Chronic Pain at 6 Months after Thoracic Surgery
Frequentist and Bayesian Multivariate Models for the Presence of Chronic Pain at 6 Months after Thoracic Surgery×
Frequentist and Bayesian Multivariate Models for the Presence of Chronic Pain at 6 Months after Thoracic Surgery
Table 6.
Frequentist and Bayesian Multivariate Models for the Presence of Chronic Pain at 6 Months after Thoracic Surgery
Frequentist and Bayesian Multivariate Models for the Presence of Chronic Pain at 6 Months after Thoracic Surgery×
×