Background

Persistent postsurgical pain after total knee arthroplasty is a common problem and a major reason for patient dissatisfaction. This secondary analysis aimed to investigate the effects of anesthesia (spinal vs. general) and tourniquet use on persistent pain after total knee arthroplasty.

Methods

In this secondary analysis of a previously presented parallel, single-center, randomized trial, 404 patients scheduled for total knee arthroplasty were randomized to spinal versus general anesthesia and no-tourniquet versus tourniquet groups. Patients assessed pain using the Brief Pain Inventory–short form preoperatively and 3 and 12 months postoperatively. The prespecified main outcome was the change in “average pain” measured with numerical 0 to 10 rating scale 1 yr postoperatively. The threshold for clinical importance between groups was set to 1.0.

Results

The change in average pain scores 1 yr postoperatively did not differ between the spinal and general anesthesia groups (–2.6 [SD 2.5] vs. –2.3 [SD 2.5], respectively; mean difference, –0.4; 95% CI, –0.9 to 0.1; P = 0.150). The no-tourniquet group reported a smaller decrease in the average pain scores than the tourniquet group (–2.1 [SD 2.7] vs. –2.8 [SD 2.3]; mean difference, 0.6; 95% CI, 0.1 to 1.1; P = 0.012). After 1 yr, the scores concerning the mean of four pain severity variables (numerical rating scale) decreased more in the spinal than in the general anesthesia group (–2.3 [SD 2.2] vs. –1.8 [SD 2.1]; mean difference, –0.5; 95% CI, –0.9 to –0.05; P = 0.029) and less in the no-tourniquet than in the tourniquet group (–1.7 [SD 2.3] vs. –2.3 [SD 2.0]; mean difference, 0.6; 95% CI, 0.2 to 1.0; P = 0.005). None of the differences in pain scores reached the threshold for clinical importance.

Conclusions

The type of anesthesia (spinal vs. general) or tourniquet use has no clinically important effect on persistent postsurgical pain after total knee arthroplasty.

Editor’s Perspective
What We Already Know about This Topic
  • Persistent pain after total knee arthroplasty is common and adversely affects outcomes

  • The choice of anesthesia and use of a tourniquet during knee arthroplasty may have an impact on complication rates, but the effects on persistent pain are poorly known

What This Article Tells Us That Is New
  • In a secondary analysis of a study involving 404 patients, no clinically important differences in pain scores 1 yr after arthroplasty were found between the spinal and general anesthesia groups

  • In the same study, no clinically meaningful differences in 1-yr pain scores were found between the no-tourniquet and tourniquet use groups

Total knee arthroplasty is a common procedure with good long-term outcomes.1,2  Despite its benefits, moderate to severe persistent postsurgical pain remains a challenge, affecting 13 to 31% of patients.3–9  Persistent postsurgical pain after total knee arthroplasty is a major reason for patient dissatisfaction.3,10  Moreover, pain is an independent risk factor for revision surgery.11 

Several studies have investigated factors that may affect the risk of persistent postsurgical pain.7–9,12–19  However, data on the effects of spinal and general anesthesia on persistent pain after total knee arthroplasty are highly limited. A retrospective, multicenter study including patients who underwent hip or knee arthroplasty found no difference in the prevalence of persistent postsurgical pain between the regional and general anesthesia groups.13  In this study, however, regional anesthesia methods and perioperative pain management were variable, and most general anesthesia patients underwent a hip replacement.13  Similarly, in a recent prospective cohort study, the anesthesia type was not a predictor for persistent postsurgical pain after total knee arthroplasty; however, only 11% of patients received other than neuraxial anesthesia.8  Nevertheless, spinal anesthesia is recommended over general anesthesia for total knee arthroplasty mainly because of its lower risk of complications.20–22 

The effects of no-tourniquet versus tourniquet use on persistent postsurgical pain after total knee arthroplasty have been investigated in three randomized controlled trials.12  Only two of these trials reported separate pain scores, with no significant differences 6 to 12 months after surgery.14,15 

The increasing annual number of total knee arthroplasties underlines the need for adequately sized randomized investigations targeted at comparing the effects of spinal and general anesthesia and no-tourniquet and tourniquet use on persistent postsurgical pain. In addition, the overall prevalence of persistent postsurgical pain after total knee arthroplasty should be reassessed, given that some of the previous results might not reflect the current situation due to the implementation of fast-track protocols, such as multimodal analgesia, which appear to improve outcomes after total knee arthroplasty.23,24 

In this secondary analysis of a previously presented randomized trial, we investigated whether spinal versus general anesthesia and no-tourniquet versus tourniquet use would lead to differences in persistent postsurgical pain after total knee arthroplasty.25  We also explored possible interaction effects between these anesthesia and tourniquet regimens. The primary in-hospital results concerning the same patients and study groups have been published previously.25  In the current study, we further evaluated the overall prevalence of moderate to severe persistent postsurgical pain after total knee arthroplasty and possible major differences in long-term pain management by investigating analgesic prescriptions. We hypothesized that anesthesia and tourniquet methods would not differ in their effects on the outcomes.

Materials and Methods

This study was a secondary analysis of a trial that was approved by the ethics committee of HUS Helsinki University Hospital, Surgery (Helsinki, Finland) (June 8, 2016; reference No. HUS1703/2016) and the Finnish Medicines Agency Fimea (Kuopio, Finland) (May 20, 2016; reference No. KL72/2016). The study was registered to EudraCT (reference No. 2016-002035-15, principal investigator: Anne Vakkuri) on May 12, 2016. We obtained written informed consent from every participant.

Study Setting and Participants

This study was a secondary analysis of an open-label, parallel, longitudinal, single-center, randomized controlled trial conducted at the Arthroplasty Center of HUS Helsinki University Hospital, Vantaa, Finland. A separate study description and in-hospital results, including the primary outcome concerning the use of intravenous (IV) oxycodone with a patient-controlled analgesia device, have been published.25,26 

Patients aged 18 to 75 yr with a body mass index of 40 kg/m2 or less and who were referred for primary total knee arthroplasty due to Kellgren–Lawrence grade III to IV knee arthritis were included in the study. We excluded patients with severe malalignment, extension or flexion deficit, or previous major surgery of the same knee. In addition, we excluded patients with American Society of Anesthesiologists (Schaumburg, Illinois) physical status class IV or higher, those with contraindications to the study medications or to either anesthesia method, those with a need for bridging anticoagulation, those who underwent a bilateral operation, or those with ongoing usage of strong opioids.26 

Randomization and Blinding

Sealed and opaque randomization envelopes were created in blocks of 20 by a nonparticipating physician. The patients were randomized into the following four groups in a 1:1:1:1 allocation ratio: spinal anesthesia + no tourniquet, spinal anesthesia + tourniquet, general anesthesia + no tourniquet, and general anesthesia + tourniquet. The envelopes were opened at the earliest 2 h before the operation by a nurse not associated with the study. Blinding the medical staff or patients was infeasible.

Perioperative Care

Premedication included 5 mg oral diazepam, 1 g acetaminophen, and 400 to 800 mg ibuprofen according to the ideal body weight.26  Induction of spinal anesthesia was performed with 15 mg isobaric bupivacaine, and patients received propofol infusion for light sedation. Target-controlled infusions of propofol and remifentanil were used for general anesthesia. At the end of the surgery, the patients under general anesthesia received 0.1 mg/kg IV oxycodone based on their ideal body weight. When used, tourniquets were maintained at 250 mmHg and applied for no more than 2 h. Surgeons injected local infiltration analgesia with 30 mg ketorolac, 300 mg ropivacaine, and 0.5 mg epinephrine to every patient with an organized multipuncture method and 100 mg of ropivacaine to subcutaneous wound edges. Surgeons used a single type of cemented implant with patellar resurfacing and operated through a midline incision and with a medial parapatellar approach.26 

Postoperatively, acetaminophen and ibuprofen were administered three times daily with premedication doses. A patient-controlled analgesia device was used with no baseline infusion and a preset dose of 0.04 mg/kg IV oxycodone for a maximum of four doses per hour for the first 24 h. Subsequently, the patients received one extended-release oxycodone tablet of 5 to 15 mg. Repeated immediate-release oxycodone (5 to 15 mg orally or 4 to 12 mg intramuscularly) was allowed upon request. All oxycodone doses were predefined according to the ideal body weight.26  From the second postoperative morning, the patients received 50 mg oral tramadol or a combination of 500 mg acetaminophen and 30 mg codeine (one to two tablets up to three times daily). If the immediate-release oxycodone was insufficient, 75 to 300 mg pregabalin orally twice daily was allowed as a rescue analgesic. Peripheral nerve block was allowed if treatment with analgesics proved insufficient.

Prescriptions for Pain Management after Discharge

Patients received prescriptions for acetaminophen, a nonsteroidal anti-inflammatory drug, and either tramadol or a combination of acetaminophen and codeine. Possible contraindications, such as the permanent use of anticoagulants, were noted. Strong opioids or gabapentinoids were prescribed only if the surgeon or anesthesiologist assessed that routine medication was insufficient. Once discharged, patients were allowed to obtain prescriptions from other physicians and healthcare organizations.

Data Collection

The patients completed the Brief Pain Inventory–short form27  and Oxford Knee Score28,29  questionnaires median 7 days preoperatively and 3 and 12 months postoperatively. The Brief Pain Inventory–short form is a self-administered, validated, and widely used questionnaire in clinical studies for assessing pain. Patients evaluate four pain severity variables (average pain, worst and least pain in the last 24 h, and current pain) and seven pain interference variables with a numerical rating scale (0 = no pain/pain interference, and 10 = worst imaginable pain/pain interference). The Oxford Knee Score is a self-administered and validated questionnaire designed to measure knee pain and function after total knee arthroplasty. From the Oxford Knee Score questionnaire, we extracted responses to the question concerning the description of usual knee pain during the past 4 weeks. The responses were rated on a 5-point scale (none, very mild, mild, moderate, and severe).28 

We obtained information on opioid and gabapentinoid prescriptions up to 12 months after the operation from the National Prescription Center. This database includes all prescriptions concerning these analgesics. If additional information was necessary to check the indications on prescriptions, we investigated the electronic patient records.

Outcomes

The prespecified main outcome of this secondary analysis was the change in the “average pain” 12 months postoperatively, measured using the Brief Pain Inventory–short form (numerical rating scale).26  Other prespecified secondary outcomes included the change in the average pain 3 months postoperatively and the change in the other three (worst and least pain in the last 24 h and current pain) Brief Pain Inventory–short form pain severity variables, in the arithmetic mean of the four pain severity variables, and in the arithmetic mean of the seven pain interference variables 3 and 12 months postoperatively. The scores of the respective Brief Pain Inventory–short form pain variables at 3 and 12 months were also explored in a post hoc sensitivity analysis.

The prevalence of moderate to severe knee pain at 3 and 12 months postoperation, as defined by the Oxford Knee Score question, was added as a secondary outcome post hoc.28  Given the wide variations in the presented cutoff values for moderate to severe pain, we further included the prevalence of average pain (Brief Pain Inventory–short form) with three different cutoffs (numerical rating scale of 3 or higher, 4 or higher, and 5 or higher) at 3 and 12 months as secondary outcomes post hoc.4,9,30  In addition, the secondary post hoc outcomes included the number of patients who were prescribed gabapentinoids or opioids (except tramadol and codeine) because of the study operation during the 12-month follow-up.

Statistical Analysis

We conducted sample size calculations of the primary trial with parametric methods to address the prespecified main outcome of this secondary analysis, “average pain” of the Brief Pain Inventory–short form, with the estimated mean numerical rating scale of 5.5 (SD 2.2) and used two-tailed tests with an α level of 0.05 and a power of 80%.26  Subsequently, we increased sample sizes by 16% to adjust for possible nonparametric analyses. We set numerical rating scale 1.0 as the minimal clinically important difference between groups, for which a sample size of at least 90 patients/group was required for nonparametric comparisons.26 

Categorical data were expressed as frequencies with percentages, normally distributed data as means with standard deviations, and nonnormally distributed data as medians with interquartile ranges. The analysis plan was finalized after the completion of data collection. Comparisons of patient characteristics between the four randomization groups were conducted using the chi-square test or Fisher’s exact test and Bonferroni adjustments in further pairwise comparisons for categorical data and one-way ANOVA for continuous data. The prespecified main outcome of this secondary analysis, the change in average pain 12 months after the operation, and changes in other continuous pain outcome variables at 3 and 12 months after the operation were analyzed using the two-way ANOVA, with the main effects for anesthesia (spinal vs. general) and tourniquet (no tourniquet vs. tourniquet) and an interaction effect between anesthesia and tourniquet. Post hoc sensitivity analyses concerning pain scores at 3 and 12 months after surgery were conducted using the analysis of covariance, with the main effects for anesthesia and tourniquet, an interaction effect between anesthesia and tourniquet, and the preoperative pain score of the respective postoperative score as a covariate. The results from the two-way ANOVA and analysis of covariance were reported as estimated marginal mean differences (95% CI). The comparisons concerning dichotomous secondary outcome data were conducted using binary logistic regression, and the results were presented as odds ratios (95% CI). All statistical tests were two-sided, and P values less than 0.05 were considered statistically significant.

We reported mean pain interference scores if data were available on at least four of the seven items.27  We imputed the scores concerning the mean of four pain severity variables if at least three of the four items were reported. We did not analyze data on patients with randomization deviations because of their low number. Statistical analyses were performed using IBM SPSS Statistics 26 (IBM Corp., USA).

Results

Patient recruitment began in October 2016. A total of 2,783 patients referred for knee arthroplasty were evaluated, 413 patients signed informed consent forms, and 404 were randomized. Preoperative data were eventually analyzed from 395 patients (table 1). The 3- and 12-month follow-ups of this secondary analysis ended in March and December 2019 with data from 391 and 387 patients, respectively (fig. 1). Pain scores of the randomization groups at different time points are presented in table 2. We derived information on prescriptions from 390 patients.

Table 1.

Patient Characteristics by Randomization Group

Patient Characteristics by Randomization Group
Patient Characteristics by Randomization Group
Table 2.

Pain before and after Total Knee Arthroplasty in the Randomization Groups

Pain before and after Total Knee Arthroplasty in the Randomization Groups
Pain before and after Total Knee Arthroplasty in the Randomization Groups
Fig. 1.

Consolidated Standards of Reporting Trials flow diagram.

Fig. 1.

Consolidated Standards of Reporting Trials flow diagram.

Spinal versus General Anesthesia

The change in average pain scores (Brief Pain Inventory–short form) 1 yr after the operation did not differ significantly between the anesthesia groups (tables 3 and 4; fig. 2). At 12 months, the spinal anesthesia group reported greater decreases in scores concerning least pain in the last 24 h and arithmetic means of the four pain severity variables and seven pain interference variables, compared with the general anesthesia group (tables 3 and 4). These differences, however, did not reach the predefined threshold (numerical rating scale of 1.0 or more) for clinical importance. The interaction effect between anesthesia and tourniquet was not significant in any pain variable at 3 or 12 months after total knee arthroplasty, indicating that the effect of anesthesia on pain variables was not different in the no-tourniquet and the tourniquet groups (table 4).

Table 3.

Preoperative Pain Scores and Change Scores 3 and 12 Months after Total Knee Arthroplasty in the Spinal and General Anesthesia Groups

Preoperative Pain Scores and Change Scores 3 and 12 Months after Total Knee Arthroplasty in the Spinal and General Anesthesia Groups
Preoperative Pain Scores and Change Scores 3 and 12 Months after Total Knee Arthroplasty in the Spinal and General Anesthesia Groups
Table 4.

Comparisons of Change Scores 3 and 12 Months after Total Knee Arthroplasty in the Spinal and General Anesthesia and in the No-Tourniquet and Tourniquet Groups

Comparisons of Change Scores 3 and 12 Months after Total Knee Arthroplasty in the Spinal and General Anesthesia and in the No-Tourniquet and Tourniquet Groups
Comparisons of Change Scores 3 and 12 Months after Total Knee Arthroplasty in the Spinal and General Anesthesia and in the No-Tourniquet and Tourniquet Groups
Fig. 2.

Bar charts of changes in preoperative average pain scores 12 months after total knee arthroplasty by study groups. The values present means (SD). P = 0.150 for spinal versus general anesthesia, P = 0.012 for no tourniquet versus tourniquet, and P = 0.551 for anesthesia × tourniquet interaction from the two-way ANOVA.

Fig. 2.

Bar charts of changes in preoperative average pain scores 12 months after total knee arthroplasty by study groups. The values present means (SD). P = 0.150 for spinal versus general anesthesia, P = 0.012 for no tourniquet versus tourniquet, and P = 0.551 for anesthesia × tourniquet interaction from the two-way ANOVA.

In the post hoc sensitivity analysis, the differences between the anesthesia groups in pain scores at 3 and 12 months were consistent with the main analysis, except for the scores concerning the mean of four pain severity variables, which did not differ significantly between the groups (Supplemental Digital Content 1, http://links.lww.com/ALN/C663).

Regardless of the cutoff value (numerical rating scale of 3 or higher, 4 or higher, and 5 or higher), no significant differences in the prevalence of moderate to severe average pain at 3 and 12 months emerged between the groups (Supplemental Digital Content 2, http://links.lww.com/ALN/C664). However, the prevalence of Oxford Knee Score–derived moderate to severe knee pain at 12 months appeared lower in the spinal than in the general anesthesia group (Supplemental Digital Content 2, http://links.lww.com/ALN/C664). The number of patients who received prescriptions for gabapentinoids or oxycodone did not differ significantly between the two groups (Supplemental Digital Content 3, http://links.lww.com/ALN/C665).

No Tourniquet versus Tourniquet

The average pain scores decreased less in the no-tourniquet than in the tourniquet group during the 12-month follow-up (tables 4 and 5; fig. 2). In addition, all other pain severity scores and the scores concerning the arithmetic mean of the four pain severity variables in 12 months decreased less in the no-tourniquet than in the tourniquet group (tables 4 and 5). Nevertheless, these differences did not reach the level of minimal clinical importance. The interaction effect between anesthesia and tourniquet was not significant in any pain variable at 3 or 12 months after surgery, indicating that the effect of tourniquet on pain variables was not different in the spinal and the general anesthesia groups (table 4). In the post hoc sensitivity analysis, none of the differences in pain scores between the tourniquet groups at 3 and 12 months were statistically significant (Supplemental Digital Content 1, http://links.lww.com/ALN/C663).

Table 5.

Preoperative Pain Scores and Change Scores 3 and 12 Months after Total Knee Arthroplasty in the No-Tourniquet and Tourniquet Groups

Preoperative Pain Scores and Change Scores 3 and 12 Months after Total Knee Arthroplasty in the No-Tourniquet and Tourniquet Groups
Preoperative Pain Scores and Change Scores 3 and 12 Months after Total Knee Arthroplasty in the No-Tourniquet and Tourniquet Groups

The number of patients with moderate to severe average pain with different cutoff values or knee pain at 3 or 12 months did not differ significantly between the groups (Supplemental Digital Content 4, http://links.lww.com/ALN/C666). Furthermore, the groups did not differ regarding the number of patients receiving prescriptions for oxycodone and gabapentinoids (Supplemental Digital Content 3, http://links.lww.com/ALN/C665).

Total Rates of Post Hoc Outcomes

The total prevalence of moderate to severe knee pain, as defined by the Oxford Knee Score question, was 77% (303 of 395 patients) preoperatively, 24% (93 of 389 patients) 3 months after surgery, and 7% (27 of 387 patients) 12 months after surgery. At the cutoff values (numerical rating scale) of 3 or higher, 4 or higher, and 5 or higher, the total prevalence of moderate to severe pain was 45% (175 of 388 patients), 28% (108 of 388 patients), and 18% (71 of 388 patients), as defined by the Brief Pain Inventory–short form 3 months after surgery, and 37% (144 of 386 patients), 24% (94 of 386 patients), and 15% (58 of 386 patients) 12 months after surgery, respectively.

Only one patient was prescribed buprenorphine, and eight patients (2%) were prescribed oxycodone for postoperative knee pain. No other strong opioids were prescribed. In addition, because of knee pain after the study operation, 40 patients (10%) were prescribed gabapentinoids.

Discussion

In this secondary analysis of a previously presented randomized trial, the change in average pain scores 1 yr after total knee arthroplasty did not differ between the spinal and general anesthesia groups. The no-tourniquet group reported a smaller decrease in the average pain scores 1 yr after surgery than the tourniquet group; however, this difference was not clinically important. The scores concerning the arithmetic means of the four pain severity variables and seven pain interference variables decreased more in the spinal anesthesia group during the 12-month follow-up compared with the general anesthesia group, although the differences remained below the borderline of clinical importance. In addition to average pain, the no-tourniquet group had smaller decreases in the scores of the other three pain severity variables (worst and least pain in the last 24 h and current pain) and in the arithmetic mean of all four severity variables 12 months after total knee arthroplasty compared with the tourniquet group, but without clinical importance. No interaction effects between anesthesia and tourniquet methods were detected in the pain variables.

In the post hoc sensitivity analysis with the analysis of covariance, the differences in pain scores between the anesthesia groups were mostly in line with the main analysis. However, in the comparison of the no-tourniquet and tourniquet groups, no differences in pain scores at 3 and 12 months were observed. In the other post hoc analyses, the spinal anesthesia group had a lower prevalence of Oxford Knee Score–based moderate to severe knee pain 12 months after total knee arthroplasty compared with the general anesthesia group. However, the prevalence of Brief Pain Inventory–short form–based moderate to severe average pain did not differ between these groups at any time point. Comparing the no-tourniquet and tourniquet groups, the prevalence rates of moderate to severe pain did not differ significantly at 3 or 12 months. The number of patients receiving prescriptions for oxycodone or gabapentinoids for postoperative knee pain did not differ in either comparison.

This secondary analysis of a previously presented trial included both prespecified and post hoc outcomes. Our previously published primary in-hospital results from the same patient cohort revealed that during the hospital stay (median of 2.2 days after surgery), pain management did not differ between the study groups.25  In addition, even though general anesthesia patients reported more pain during the immediate postoperative phase in the recovery room, the differences in pain scores were not clinically important 24 h after surgery.25 

Previous cohort studies have suggested no differences in the prevalence of persistent postsurgical pain after total knee arthroplasty between regional and general anesthesia groups.8,13  The main results of this secondary analysis are in line with these studies. Thus, the recommendations to use spinal anesthesia as the primary method in total knee arthroplasty seem to remain unaffected by the outcomes concerning persistent pain.20–22 

Our results seem consistent with two smaller randomized trials showing no significant differences in persistent postsurgical pain after total knee arthroplasty between tourniquet and no-tourniquet groups.14,15  Compared with the Brief Pain Inventory–short form–based results of the current trial, some prospective studies have presented lower prevalence rates for moderate to severe or for “significant” persistent postsurgical pain 1 yr after total knee arthroplasty.4,6,8  Studies of 63 and 116 patients reported prevalence rates of 27% (numerical rating scale of 3 or higher) and 13% (visual analog scale greater than 40 of 100).4,6  Furthermore, a recent study of 288 patients reported that 16% suffered from moderate to severe persistent postsurgical pain (Western Ontario McMaster Universities Osteoarthritis Index pain score of 30 of 100 or higher).8  However, based on the Oxford Knee Score question, the prevalence of persistent postsurgical pain appeared much lower in our analysis. These differences may have arisen from differences in the definitions of persistent postsurgical pain, surgery and anesthesia protocols, sample sizes, and patient characteristics. Questionnaires also play a crucial role, as observed in our results. Oxford Knee Score and Brief Pain Inventory–short form questionnaires involve different time frames. Furthermore, the Oxford Knee Score focuses on the knee, whereas the Brief Pain Inventory–short form is a universal instrument for assessing pain.

Our findings on prescriptions are in line with a recent study reporting a very low proportion of patients receiving postoperative prescriptions for strong opioids.31  This result suggests that prescribing strong opioids routinely for pain after total knee arthroplasty may be unnecessary, at least in some populations.

The strengths of this study include its randomized design, adequate sample size, and very low (2%) dropout rate during the follow-up. In addition, this study was conducted in a publicly funded, high volume, tertiary hospital, and numerous arthroplasty surgeons and anesthesiologists treated patients who underwent total knee arthroplasty with modern fast-track protocols.

Among the limitations of this study, its open-label design is the most obvious. Blinding, however, was not feasible. Personnel had either first-hand knowledge or free access to information on operating room events, and patients were undoubtedly aware of the anesthesia method. In addition, we regarded blinding the tourniquet use in the spinal anesthesia group as unreliable. The single-center design and high exclusion rate are also noteworthy limitations. Of 1,583 patients who failed to meet the inclusion criteria, 51% were either over 75 yr, referred for a unicompartmental knee replacement, underwent a bilateral operation, or received a nonprotocol prosthesis, such as a hinge prosthesis.25  In addition, due to randomization deviations, five patients were excluded from the analyses, which might have biased the results.

A further limitation concerns the type of pain. A recent definition for chronic postsurgical pain refers to pain that develops after surgery and persists longer than 3 months.32  In this study, we used the term “persistent postsurgical pain” to describe the combination of residual pain from the preoperative period and possible chronic pain caused by the surgery. Estimating the proportions of these two pain modalities or their precise nature was not possible with the questionnaires used in this study, and this should be noted in interpreting the results.

In the current analysis, we used numerical rating scale 1.0 as the threshold for minimal clinically important differences between the groups. This was consistent with previous studies assessing the minimal clinically significant changes in pain scores.33,34  However, for persistent pain after total knee arthroplasty, the optimal threshold for clinically important differences between groups remains to be established. In addition, for data comparability, a consensus should be reached on time points for measuring persistent pain after total knee arthroplasty. We suggest 1 yr as the primary timepoint for future studies, given the current and previous results, which strongly indicate that pain continues to decrease up to 12 months after the operation.4,6,8  Furthermore, studies with longer follow-up times have not presented lower prevalence rates for persistent postsurgical pain.3,7,35 

In conclusion, the results from this secondary analysis of a randomized trial concerning total knee arthroplasty suggest that spinal and general anesthesia do not lead to clinically important differences in persistent postsurgical pain. Similarly, operating with or without a tourniquet has no clinically important impact on persistent pain. Prescriptions for strong opioids may be rarely necessary after total knee arthroplasty.

Acknowledgments

The authors thank Arja Mäkelä, R.N., and Katarina Lahtinen, M.D. (Department of Anesthesiology, Intensive Care and Pain Medicine, Peijas Hospital, University of Helsinki and HUS Helsinki University Hospital, Vantaa, Finland), for their help in data collection. They thank Eero Pesonen, M.D., Ph.D. (Department of Anesthesiology, Intensive Care and Pain Medicine, University of Helsinki and HUS Helsinki University Hospital, Helsinki, Finland), Tatu Mäkinen, M.D., Ph.D. (University of Helsinki and Pihlajalinna, Helsinki, Finland), and Vesa Kontinen, M.D., Ph.D. (Department of Anesthesiology, Intensive Care and Pain Medicine, University of Helsinki and HUS Helsinki University Hospital, Espoo, Finland), for their advice concerning the study design. The authors also thank Pekka Kairaluoma, M.D., Ph.D. (Department of Anesthesiology, Intensive Care and Pain Medicine, Peijas Hospital, University of Helsinki and HUS Helsinki University Hospital, Vantaa, Finland), for helping in patient recruitment; Eliisa Nissilä, M.D. (Department of Anesthesiology, Intensive Care and Pain Medicine, University of Helsinki and HUS Helsinki University Hospital, Helsinki, Finland), for creating the randomization envelopes; and all of the anesthesiologists, surgeons, other participating personnel, and patients who made this study possible.

Research Support

Supported by HUS Helsinki University Hospital (Helsinki, Finland) grant No. Y102011095 and HUS Helsinki University Hospital Finnish government science grants Nos. TYH 2017239 and TYH 2019113. Personal grants for dissertation research, including the preparation of this article, were granted to Dr. Palanne by the Paulo Foundation (Espoo, Finland), Finnish Medical Foundation (Helsinki, Finland), Finnish Arthroplasty Society (Helsinki, Finland), Research Foundation for Orthopaedics and Traumatology (Finland), and Finnish Society of Anaesthesiologists (Helsinki, Finland). In addition, Dr. Palanne received a travel grant from the University of Helsinki (Helsinki, Finland).

Competing Interests

Dr. Madanat has received fees for consultancy and lectures from Pfizer (Helsinki, Finland) and Stryker (Vantaa, Finland) and holds stock options and is a medical advisor for Osgenic Ltd. (Helsinki, Finland). Dr. Reponen has received personal grants from the Foundation for Economic Education, Pulsus Foundation, Finnish Medical Association, and Finnish Society of Anaesthesiologists (all in Helsinki, Finland). Dr. Linko has received a fee from Fisher&Paykel (Helsinki, Finland) for a lecture concerning nasal high flow therapy. The other authors declare no competing interests.

Reproducible Science

Full protocol available at: riku.palanne@ksshp.fi. Raw data available at: riku.palanne@ksshp.fi.

References

1.
Williams
SN
,
Wolford
WM
,
Bercovitz
A
:
Hospitalization for total knee replacement among inpatients aged 45 and over: United States, 2000–2010
.
NCHS Data Brief
2015
;
210
:
1
8
2.
Jenkins
PJ
,
Clement
ND
,
Hamilton
DF
,
Gaston
P
,
Patton
JT
,
Howie
CR
:
Predicting the cost-effectiveness of total hip and knee replacement: A health economic analysis.
Bone Joint J
2013
;
95-B
:
115
21
3.
Baker
PN
,
van der Meulen
JH
,
Lewsey
J
,
Gregg
PJ
;
National Joint Registry for England and Wales
:
The role of pain and function in determining patient satisfaction after total knee replacement: Data from the National Joint Registry for England and Wales.
J Bone Joint Surg Br
2007
;
89
:
893
900
4.
Fletcher
D
,
Stamer
UM
,
Pogatzki-Zahn
E
,
Zaslansky
R
,
Tanase
NV
,
Perruchoud
C
,
Kranke
P
,
Komann
M
,
Lehman
T
,
Meissner
W
;
euCPSP group for the Clinical Trial Network group of the European Society of Anaesthesiology
:
Chronic postsurgical pain in Europe: An observational study.
Eur J Anaesthesiol
2015
;
32
:
725
34
5.
Vuorenmaa
M
,
Ylinen
J
,
Kiviranta
I
,
Intke
A
,
Kautiainen
HJ
,
Mälkiä
E
,
Häkkinen
A
:
Changes in pain and physical function during waiting time and 3 months after knee joint arthroplasty.
J Rehabil Med
2008
;
40
:
570
5
6.
Brander
VA
,
Stulberg
SD
,
Adams
AD
,
Harden
RN
,
Bruehl
S
,
Stanos
SP
,
Houle
T
:
Predicting total knee replacement pain: A prospective, observational study
.
Clin Orthop Relat Res
2003
;
416
:
27
36
7.
Wylde
V
,
Hewlett
S
,
Learmonth
ID
,
Dieppe
P
:
Persistent pain after joint replacement: Prevalence, sensory qualities, and postoperative determinants.
Pain
2011
;
152
:
566
72
8.
Rice
DA
,
Kluger
MT
,
McNair
PJ
,
Lewis
GN
,
Somogyi
AA
,
Borotkanics
R
,
Barratt
DT
,
Walker
M
:
Persistent postoperative pain after total knee arthroplasty: A prospective cohort study of potential risk factors.
Br J Anaesth
2018
;
121
:
804
12
9.
Gungor
S
,
Fields
K
,
Aiyer
R
,
Valle
AGD
,
Su
EP
:
Incidence and risk factors for development of persistent postsurgical pain following total knee arthroplasty: A retrospective cohort study.
Medicine (Baltimore)
2019
;
98
:
e16450
10.
Scott
CE
,
Howie
CR
,
MacDonald
D
,
Biant
LC
:
Predicting dissatisfaction following total knee replacement: A prospective study of 1217 patients.
J Bone Joint Surg Br
2010
;
92
:
1253
8
11.
Sadoghi
P
,
Liebensteiner
M
,
Agreiter
M
,
Leithner
A
,
Böhler
N
,
Labek
G
:
Revision surgery after total joint arthroplasty: A complication-based analysis using worldwide arthroplasty registers.
J Arthroplasty
2013
;
28
:
1329
32
12.
Beswick
AD
,
Dennis
J
,
Gooberman-Hill
R
,
Blom
AW
,
Wylde
V
:
Are perioperative interventions effective in preventing chronic pain after primary total knee replacement?: A systematic review.
BMJ Open
2019
;
9
:
e028093
13.
Liu
SS
,
Buvanendran
A
,
Rathmell
JP
,
Sawhney
M
,
Bae
JJ
,
Moric
M
,
Perros
S
,
Pope
AJ
,
Poultsides
L
,
Della Valle
CJ
,
Shin
NS
,
McCartney
CJ
,
Ma
Y
,
Shah
M
,
Wood
MJ
,
Manion
SC
,
Sculco
TP
:
A cross-sectional survey on prevalence and risk factors for persistent postsurgical pain 1 year after total hip and knee replacement.
Reg Anesth Pain Med
2012
;
37
:
415
22
14.
Ejaz
A
,
Laursen
AC
,
Kappel
A
,
Laursen
MB
,
Jakobsen
T
,
Rasmussen
S
,
Nielsen
PT
:
Faster recovery without the use of a tourniquet in total knee arthroplasty.
Acta Orthop
2014
;
85
:
422
6
15.
Huang
Z
,
Xie
X
,
Li
L
,
Huang
Q
,
Ma
J
,
Shen
B
,
Kraus
VB
,
Pei
F
:
Intravenous and topical tranexamic acid alone are superior to tourniquet use for primary total knee arthroplasty: A prospective, randomized controlled trial.
J Bone Joint Surg Am
2017
;
99
:
2053
61
16.
Høvik
LH
,
Winther
SB
,
Foss
OA
,
Gjeilo
KH
:
Preoperative pain catastrophizing and postoperative pain after total knee arthroplasty: A prospective cohort study with one year follow-up.
BMC Musculoskelet Disord
2016
;
17
:
214
17.
Lewis
GN
,
Rice
DA
,
McNair
PJ
,
Kluger
M
:
Predictors of persistent pain after total knee arthroplasty: A systematic review and meta-analysis.
Br J Anaesth
2015
;
114
:
551
61
18.
Puolakka
PA
,
Rorarius
MG
,
Roviola
M
,
Puolakka
TJ
,
Nordhausen
K
,
Lindgren
L
:
Persistent pain following knee arthroplasty.
Eur J Anaesthesiol
2010
;
27
:
455
60
19.
Thomazeau
J
,
Rouquette
A
,
Martinez
V
,
Rabuel
C
,
Prince
N
,
Laplanche
JL
,
Nizard
R
,
Bergmann
JF
,
Perrot
S
,
Lloret-Linares
C
:
Predictive factors of chronic post-surgical pain at 6 months following knee replacement: Influence of postoperative pain trajectory and genetics.
Pain Physician
2016
;
19
:
E729
41
20.
Memtsoudis
SG
,
Cozowicz
C
,
Bekeris
J
,
Bekere
D
,
Liu
J
,
Soffin
EM
,
Mariano
ER
,
Johnson
RL
,
Hargett
MJ
,
Lee
BH
,
Wendel
P
,
Brouillette
M
,
Go
G
,
Kim
SJ
,
Baaklini
L
,
Wetmore
D
,
Hong
G
,
Goto
R
,
Jivanelli
B
,
Argyra
E
,
Barrington
MJ
,
Borgeat
A
,
De Andres
J
,
Elkassabany
NM
,
Gautier
PE
,
Gerner
P
,
Gonzalez Della Valle
A
,
Goytizolo
E
,
Kessler
P
,
Kopp
SL
,
Lavand’Homme
P
,
MacLean
CH
,
Mantilla
CB
,
MacIsaac
D
,
McLawhorn
A
,
Neal
JM
,
Parks
M
,
Parvizi
J
,
Pichler
L
,
Poeran
J
,
Poultsides
LA
,
Sites
BD
,
Stundner
O
,
Sun
EC
,
Viscusi
ER
,
Votta-Velis
EG
,
Wu
CL
,
Ya Deau
JT
,
Sharrock
NE
:
Anaesthetic care of patients undergoing primary hip and knee arthroplasty: Consensus recommendations from the International Consensus on Anaesthesia-Related Outcomes after Surgery group (ICAROS) based on a systematic review and meta-analysis.
Br J Anaesth
2019
;
123
:
269
87
21.
Weinstein
SM
,
Baaklini
LR
,
Liu
J
,
Poultsides
L
,
Cozowicz
C
,
Poeran
J
,
Saleh
JN
,
Memtsoudis
SG
:
Neuraxial anaesthesia techniques and postoperative outcomes among joint arthroplasty patients: Is spinal anaesthesia the best option?
Br J Anaesth
2018
;
121
:
842
9
22.
Soffin
EM
,
Gibbons
MM
,
Ko
CY
,
Kates
SL
,
Wick
E
,
Cannesson
M
,
Scott
MJ
,
Wu
CL
:
Evidence review conducted for the Agency for Healthcare Research and Quality safety program for improving surgical care and recovery: Focus on anesthesiology for total knee arthroplasty.
Anesth Analg
2019
;
128
:
441
53
23.
Berg
U
,
BüLow
E
,
Sundberg
M
,
Rolfson
O
:
No increase in readmissions or adverse events after implementation of fast-track program in total hip and knee replacement at 8 Swedish hospitals: An observational before-and-after study of 14,148 total joint replacements 2011-2015.
Acta Orthop
2018
;
89
:
522
7
24.
McDonald
DA
,
Siegmeth
R
,
Deakin
AH
,
Kinninmonth
AW
,
Scott
NB
:
An enhanced recovery programme for primary total knee arthroplasty in the United Kingdom: Follow up at one year.
Knee
2012
;
19
:
525
9
25.
Palanne
R
,
Rantasalo
M
,
Vakkuri
A
,
Madanat
R
,
Olkkola
KT
,
Lahtinen
K
,
Reponen
E
,
Linko
R
,
Vahlberg
T
,
Skants
N
:
Effects of anaesthesia method and tourniquet use on recovery following total knee arthroplasty: A randomised controlled study.
Br J Anaesth
2020
;
125
:
762
72
26.
Rantasalo
MT
,
Palanne
R
,
Juutilainen
K
,
Kairaluoma
P
,
Linko
R
,
Reponen
E
,
Helkamaa
T
,
Vakkuri
A
,
Olkkola
KT
,
Madanat
R
,
Skants
NKA
:
Randomised controlled study comparing general and spinal anaesthesia with and without a tourniquet on the outcomes of total knee arthroplasty: Study protocol.
BMJ Open
2018
;
8
:
e025546
27.
Cleeland
CS
:
The Brief Pain Inventory: User Guide, 2009.
28.
Dawson
J
,
Fitzpatrick
R
,
Murray
D
,
Carr
A
:
Questionnaire on the perceptions of patients about total knee replacement.
J Bone Joint Surg Br
1998
;
80
:
63
9
29.
Murray
DW
,
Fitzpatrick
R
,
Rogers
K
,
Pandit
H
,
Beard
DJ
,
Carr
AJ
,
Dawson
J
:
The use of the Oxford hip and knee scores.
J Bone Joint Surg Br
2007
;
89
:
1010
4
30.
Kapstad
H
,
Hanestad
BR
,
Langeland
N
,
Rustøen
T
,
Stavem
K
:
Cutpoints for mild, moderate and severe pain in patients with osteoarthritis of the hip or knee ready for joint replacement surgery.
BMC Musculoskelet Disord
2008
;
9
:
55
31.
Rajamäki
TJ
, Jr
,
Puolakka
PA
,
Hietaharju
A
,
Moilanen
T
,
Jämsen
E
:
Use of prescription analgesic drugs before and after hip or knee replacement in patients with osteoarthritis.
BMC Musculoskelet Disord
2019
;
20
:
427
32.
Schug
SA
,
Lavand’homme
P
,
Barke
A
,
Korwisi
B
,
Rief
W
,
Treede
RD
;
IASP Taskforce for the Classification of Chronic Pain
:
The IASP classification of chronic pain for ICD-11: Chronic postsurgical or posttraumatic pain.
Pain
2019
;
160
:
45
52
33.
Salaffi
F
,
Stancati
A
,
Silvestri
CA
,
Ciapetti
A
,
Grassi
W
:
Minimal clinically important changes in chronic musculoskeletal pain intensity measured on a numerical rating scale.
Eur J Pain
2004
;
8
:
283
91
34.
Myles
PS
,
Myles
DB
,
Galagher
W
,
Boyd
D
,
Chew
C
,
MacDonald
N
,
Dennis
A
:
Measuring acute postoperative pain using the visual analog scale: The minimal clinically important difference and patient acceptable symptom state.
Br J Anaesth
2017
;
118
:
424
9
35.
Petersen
KK
,
Simonsen
O
,
Laursen
MB
,
Nielsen
TA
,
Rasmussen
S
,
Arendt-Nielsen
L
:
Chronic postoperative pain after primary and revision total knee arthroplasty.
Clin J Pain
2015
;
31
:
1
6