Chronic postsurgical pain: A European survey.

BACKGROUND: Chronic postsurgical pain (CPSP) is a clinical problem, and large prospective studies are needed to determine its incidence, characteristics, and risk factors. OBJECTIVE: To find predictive factors for CPSP in an international survey. DESIGN: Observational study. SETTING: Multicentre European prospective observational trial. PATIENTS: Patients undergoing breast cancer surgery, sternotomy, endometriosis surgery, or total knee arthroplasty (TKA). METHOD: Standardised questionnaires were completed by the patients at 1, 3, and 7 days, and at 1, 3, and 6 months after surgery, with follow-up via E-mail, telephone, or interview. MAIN OUTCOME MEASURE: The primary goal of NIT-1 was to propose a scoring system to predict those patient likely to have CPSP at 6 months after surgery. RESULTS: A total of 3297 patients were included from 18 hospitals across Europe and 2494 patients were followed-up for 6 months. The mean incidence of CPSP at 6 months was 10.5%, with variations depending on the type of surgery: sternotomy 6.9%, breast surgery 7.4%, TKA 12.9%, endometriosis 16.2%. At 6 months, neuropathic characteristics were frequent for all types of surgery: sternotomy 33.3%, breast surgery 67.6%, TKA 42.4%, endometriosis 41.4%. One-third of patients experienced CPSP at both 3 and 6 months. Pre-operative pain was frequent for TKA (leg pain) and endometriosis (abdomen) and its frequency and intensity were reduced after surgery. Severe CPSP and a neuropathic pain component decreased psychological and functional wellbeing as well as quality of life. No overarching CPSP risk factors were identified. CONCLUSION: Unfortunately, our findings do not offer a new CPSP predictive score. However, we present reliable new data on the incidence, characteristics, and consequences of CPSP from a large European survey. Interesting new data on the time course of CPSP, its neuropathic pain component, and CPSP after endometriosis surgery generate new hypotheses but need to be confirmed by further research. TRIAL REGISTRATION: clinicaltrials.gov ID: NCT03834922.

Operation-specific risk of postoperative nausea: a cross-sectional study comparing 72 procedures.

OBJECTIVES: Determination of the procedure-specific, risk-adjusted probability of nausea. DESIGN: Cross-sectional analysis of clinical and patient-reported outcome data. We used a logistic regression model with type of operation, age, sex, preoperative opioids, antiemetic prophylaxis, regional anaesthesia, and perioperative opioids as predictors of postoperative nausea. SETTING: Data from 152 German and Austrian hospitals collected in the Quality Improvement in Postoperative Pain Treatment (QUIPS) registry from 2013 to 2022. Participants completed a validated outcome questionnaire on the first postoperative day. Operations were categorised into groups of at least 100 cases. PARTICIPANTS: We included 78 231 of the 293 947 participants from the QUIPS registry. They were 18 years or older, willing and able to participate and could be assigned to exactly one operation group. MAIN OUTCOME MEASURES: Adjusted absolute risk of nausea on the first postoperative day for 72 types of operation. RESULTS: The adjusted absolute risk of nausea ranged from 6.2% to 36.2% depending on the type of operation. The highest risks were found for laparoscopic bariatric operations (36.2%), open hysterectomy (30.4%), enterostoma relocation (29.8%), open radical prostatectomy (28.8%), laparoscopic colon resection (28.6%) and open sigmoidectomy (28%). In a logistic regression model, male sex (OR: 0.39, 95% CI 0.37 to 0.41, p<0.0001), perioperative nausea and vomiting prophylaxis (0.73, 0.7 to 0.76, p<0.0001), intraoperative regional anaesthesia (0.88, 0.83 to 0.93, p<0.0001) and preoperative opioids for chronic pain (0.74, 0.68 to 0.81, p<0.0001) reduced the risk of nausea. Perioperative opioid use increased the OR up to 2.38 (2.17 to 2.61, p<0.0001). CONCLUSIONS: The risk of postoperative nausea varies considerably between surgical procedures. Patients undergoing certain types of operation should receive special attention and targeted prevention strategies. Adding these findings to known predictive tools may raise awareness of the still unacceptably high incidence of nausea in certain patient groups. This may help to further reduce the prevalence of nausea. TRIAL REGISTRATION NUMBER: DRKS00006153; German Clinical Trials Register; https://drks.de/search/de/trial/DRKS00006153.

Responsiveness of multiple patient-reported outcome measures for acute postsurgical pain: primary results from the international multi-centre PROMPT NIT-1 study.

BACKGROUND: Postsurgical outcome measures are crucial to define the efficacy of perioperative pain management; however, it is unclear which are most appropriate. We conducted a prospective study aiming to assess sensitivity-to-change of patient-reported outcome measures assessing the core outcome set of domains pain intensity (at rest/during activity), physical function, adverse events, and self-efficacy. METHODS: Patient-reported outcome measures were assessed preoperatively, on day 1 (d1), d3, and d7 after four surgical procedures (total knee replacement, breast surgery, endometriosis-related surgery, and sternotomy). Primary outcomes were sensitivity-to-change of patient-reported outcome measures analysed by correlating their changes (d1-d3) with patients' global impression of change and patients' specific impression of change items as anchor criteria. Secondary outcomes included identification of baseline and patient characteristic variables explaining variance in change for each of the scales and descriptive analysis of various patient-reported outcome measures from different domains and after different surgeries. RESULTS: Of 3322 patients included (18 hospitals, 10 countries), data from 2661 patients were analysed. All patient-reported outcome measures improved on average over time; the median calculated sensitivity-to-change for all patient-reported outcome measures (overall surgeries) was 0.22 (range: 0.07-0.31, scale: 0-10); all changes were independent of baseline data or patient characteristics and similar between different procedures. CONCLUSIONS: Pain-related patient-reported outcome measures have low to moderate sensitivity-to-change; those showing higher sensitivity-to-change from the same domain should be considered for inclusion in a core outcome set of patient-reported outcome measures to assess the effectiveness and efficacy of perioperative pain management.

Pain After Outpatient Surgical Procedures.

BACKGROUND: Approximately 8.1 million outpatient surgical procedures were performed in Germany in 2021. Little is known about the quality of postoperative pain treatment in the outpatient sector. METHODS: The AQS1 project comprises a combined survey of patients and staff in the framework of quality control for ambulatory surgery. The primary endpoint of this study was the prevalence of relevant incisional pain (≥ 4/10 on the numerical rating scale) up to postoperative day 3. Secondary endpoints included prognostic variables for pain and pain-associated outcomes, based on the AQS1 patient questionnaire. Moreover, mixed regression models were used to analyze potential prognostic variables and associations of pain with other outcomes (study registration number DRKS00028052). RESULTS: Data from 330 008 patients were evaluated (from 1 July 2001 to 31 December 2021). The overall prevalence of relevant incisional pain up to postoperative day 3 was 22.5%, with major differences between different types of procedure (3.2%-51.2%). Pain was most common after hemorrhoid surgery (51.2%) and the laparoscopic lysis of large and small bowel adhesions (45.4%). The main associations of relevant pain were with younger age (odds ratio [OR] 1.87, 95% confidence interval [1.82; 1.91]), early postoperative pain (1.34, [1.30; 1.39]), inadequate provision of analgesics (2.90, [2.71; 3.09]), and surgical wound infections (2.60, [2.43; 2.78]). Patients with pain reported lower overall satisfaction with the procedure and a longer inability to work. CONCLUSION: These data have not been tested for representativeness. They can serve as a point of departure for the optimization of individualized perioperative pain therapy and for the planning of prospective studies.

Endoplasmic reticulum stress and the unfolded protein response in skeletal muscle of subjects suffering from peritoneal sepsis.

We provide a descriptive characterization of the unfolded protein response (UPR) in skeletal muscle of human patients with peritoneal sepsis and a sepsis model of C57BL/6J mice. Patients undergoing open surgery were included in a cross-sectional study and blood and skeletal muscle samples were taken. Key markers of the UPR and cluster of differentiation 68 (CD68) as surrogate of inflammatory injury were evaluated by real-time PCR and histochemical staining. CD68 mRNA increased with sepsis in skeletal muscle of patients and animals (p < 0.05). Mainly the inositol-requiring enzyme 1α branch of the UPR was upregulated as shown by elevated X-box binding-protein 1 (XBP1u) and its spliced isoform (XBP1s) mRNA (p < 0.05, respectively). Increased expression of Gadd34 indicated activation of PRKR-Like Endoplasmic Reticulum Kinase (PERK) branch of the UPR, and was only observed in mice (p < 0.001) but not human study subjects. Selected cell death signals were upregulated in human and murine muscle, demonstrated by increased bcl-2 associated X protein mRNA and TUNEL staining (p < 0.05). In conclusion we provide a first characterization of the UPR in skeletal muscle in human sepsis.

Association of Perioperative Regional Analgesia with Postoperative Patient-Reported Pain Outcomes and Opioid Requirements: Comparing 22 Different Surgical Groups in 23,911 Patients from the QUIPS Registry.

(1) Background: In many surgical procedures, regional analgesia (RA) techniques are associated with improved postoperative analgesia compared to systemic pain treatment. As continuous RA requires time and experienced staff, it would be helpful to identify settings in which continuous RA has the largest benefit. (2) Methods: On the basis of 23,911 data sets from 179 German and Austrian hospitals, we analyzed the association of perioperative RA with patient-reported pain intensity, functional impairment of movement, nausea and opioid use for different surgeries. Regression analyses adjusted for age, sex and preoperative pain were performed for each surgery and the following groups: patients receiving continuous RA (surgery and ward; RA++), RA for surgery only (RA+-) and patients receiving no RA (RA--). (3) Results: Lower pain scores in the RA++ compared to the RA-- group were observed in 13 out of 22 surgeries. There was no surgery where pain scores for RA++ were higher than for RA--. If maximal pain, function and side effects were combined, the largest benefit of continuous RA (RA++) was observed in laparoscopic colon and sigmoid surgery, ankle joint arthrodesis, revision (but not primary) surgery of hip replacement, open nephrectomy and shoulder surgery. The benefit of RA+- was lower than that of RA++. (4) Discussion: The additional benefit of RA for the mentioned surgeries is larger than in many other surgeries in clinical routine. The decision to use RA in a given surgery should be based on the expected pain intensity without RA and its additional benefits.

Developing consensus on core outcome domains for assessing effectiveness in perioperative pain management: results of the PROMPT/IMI-PainCare Delphi Meeting.

ABSTRACT: Postoperative pain management is still insufficient, leading to major deficits, including patient suffering, impaired surgical recovery, long-term opioid intake, and postsurgical chronic pain. Yet, identifying the best treatment options refers to a heterogeneous outcome assessment in clinical trials, not always reflecting relevant pain-related aspects after surgery and therefore hamper evidence synthesis. Establishing a core outcome set for perioperative pain management of acute pain after surgery may overcome such limitations. An international, stepwise consensus process on outcome domains ("what to measure") for pain management after surgery, eg, after total knee arthroplasty, sternotomy, breast surgery, and surgery related to endometriosis, was performed. The process, guided by a steering committee, involved 9 international stakeholder groups and patient representatives. The face-to-face meeting was prepared by systematic literature searches identifying common outcome domains for each of the 4 surgical procedures and included breakout group sessions, world-café formats, plenary panel discussions, and final voting. The panel finally suggested an overall core outcome set for perioperative pain management with 5 core outcome domains: physical function (for a condition-specific measurement), pain intensity at rest, pain intensity during activity, adverse events, and self-efficacy. Innovative aspects of this work were inclusion of the psychological domain self-efficacy, as well as the specific assessment of pain intensity during activity and physical function recommended to be assessed in a condition-specific manner. The IMI-PROMPT core outcome set seeks to improve assessing efficacy and effectiveness of perioperative pain management in any clinical and observational studies as well as in clinical practice.

Desire to Receive More Pain Treatment - A Relevant Patient-Reported Outcome Measure to Assess Quality of Post-Operative Pain Management? Results From 79,996 Patients Enrolled in the Pain Registry QUIPS from 2016 to 2019.

Acute postoperative pain is frequently evaluated by pain intensity scores. However, interpretation of the results is difficult and thresholds requiring treatment are not well defined. Additional patient-reported outcome measures (PROMs) might be helpful to better understand individual pain experience and quality of pain management after surgery. We used data from the QUIPS pain registry for a cross-sectional study in order to investigate associations between the desire to receive more pain treatment (D2RMPT) with pain intensity ratings and other PROMs. Responses from 79,996 patients were analyzed, of whom 10.7% reported D2RMPT. A generalized estimating equation Poisson model showed that women had a lower risk ratio (RR) to answer this question with "yes" (RR: .92, P < .001). Factors that increased the risk most were "maximal pain intensity ≥ 6/10 on a numerical rating scale" (RR: 2.48, P < .001) and "any pain interference" (RR: 2.48, P < .001). The largest reduction in risk was observed if patients were "allowed to participate in pain treatment decisions" (RR: .41, P < .001) and if they felt that they "received sufficient treatment information" (RR: .58, P < .001). Our results indicate that the (easily assessed) question D2RMPT gives additional information to other PROMs like pain intensity. The small proportion of patients with D2RMPT (even for high pain scores) opens the discussion about clinicians' understanding of over- und under-treatment and questions the exclusive use of pain intensity as quality indicator. Future studies need to investigate whether asking about D2RMPT in clinical routine can improve postoperative pain outcome. PERSPECTIVE: This article presents characteristics of the patient-reported outcome measure "Desire to receive more pain treatment." This measure could be used to apply pain treatment in a more individualized way and lead to improved treatment strategies and quality.

Developing consensus on core outcome domains and measurement instruments for assessing effectiveness in perioperative pain management after sternotomy, breast cancer surgery, total knee arthroplasty, and surgery related to endometriosis : The IMI-PainCare PROMPT protocol for achieving a consensus on core outcome domains.

INTRODUCTION: Evidence synthesis of clinical trials requires consistent outcome assessment. For pain management after surgery, inconsistency of effectiveness assessment is still observed. A subproject of IMI-PainCare (Innovative Medicine Initiatives, www.imi-paincare.eu ) aims for identifying core outcome domains and measurement instruments for postoperative pain in four surgical fields (sternotomy, breast cancer surgery, total knee arthroplasty, and surgery related to endometriosis) in order to harmonize outcome assessment for perioperative pain management. METHODS: A multifaceted process will be performed according to existing guidelines (Core Outcome Measures in Effectiveness Trials (COMET), COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN)). In a first step, outcome domains will be identified via systematic literature review and consented on during a 1-day consensus meeting by 10 stakeholder groups, including patient representatives, forming an IMI PROMPT consensus panel. In a second step, outcome measurement instruments regarding the beforehand consented core outcome domains and their psychometric properties will be searched for via systematic literature review and approved by COSMIN checklist for study quality and scale quality separately. In a three-step online survey, the IMI PROMPT consensus panel will vote for most suitable measurement instruments. The process is planned to be conducted between 11/2017 (systematic literature review on common outcome domains) and 3/2022 (final voting on core outcome measurement).

[Postoperative pain therapy after total knee arthroplasty : Is the local infiltration anesthesia the best therapy?] / Schmerz nach Knietotalendoprothese : Ist die lokale Infiltrationsanästhesie die beste Therapieoption?

BACKGROUND: Optimal perioperative pain management after total knee arthroplasty is necessary to promote mobilization and achieve early rehabilitation. The aim of this study was to determine whether local infiltration anesthesia (LIA) is the better postoperative pain therapy compared to a femoral nerve block (FNB) or a sciatic nerve block (SNB) using routine data. METHODS: Data from the acute pain registry "Qualitätsverbesserung in der postoperativen Schmerztherapie" (QUIPS) were analyzed. The endpoints included postoperative maximal pain, frequency of pain-related movement impairment, nausea, and number of patients requesting opioids postoperatively. The influence of regional anesthesia in addition to general anesthesia was analyzed in 5 groups. RESULTS: In total, the data of 8754 patients could be examined. It was found that the addition of LIA (ß = -0.087 p = 0.000) or FNB (ß = -0.137 p = 0.000) to general anesthesia is associated with a small but significant reduction of postoperative maximum pain. Between LIA, FNB, and SNB no relevant differences could be detected. DISCUSSION: The pain reduction achieved by adding LIA or FNB in patients after total knee arthroplasty is relatively small. Comparison of techniques is hindered as there exists no widely accepted standard for performing LIAs yet.

Non-Pharmacological Methods and Post-Operative Pain Relief: An Observational Study.

BACKGROUND: Non-pharmacological methods (NPMs) like cold packs, acupuncture, meditation or distractions are supposed to ease acute post-surgical pain. OBJECTIVES: This study assessed how frequently these methods are used in clinical routine and if their use is associated with pain relief or with the wish for more pain treatment. METHODS: Data from the world's largest acute post-operative pain registry, PAIN OUT, was used for this study. In PAIN OUT, patients report their pain levels and side effects related to pain therapy after surgery. Overall, 15 different NPMs were tested for their association with pain relief and the wish for more pain treatment using Mann-Whitney U test, Kruskal-Wallis test, General Linear Model, and Logistic Regression. The researchers adjusted for age and gender, and specifically looked at the three most frequent surgeries: total knee replacement, total hip replacement, and laparoscopic cholecystectomy. RESULTS: Data of 14 767 patients from 12 European hospitals were analyzed. Overall, 6563 (44.4%) patients used at least one NPM; with distraction and cold packs being the most frequently used. The 8204 (55.6%) patients, who did not use NPMs had little yet significantly more pain relief than patients, who used them (means of 71.2% ± 27.9% versus 68.6% ± 25.7%, P < 0.001). Using NPMs does not affect the wish for more pain treatment. This is true for every single NPM. The only exceptional sub-group included total knee replacement patients, where a positive effect of NPMs was observed. CONCLUSIONS: Some NPMs are widely used while others are rarely applied. Their association with pain relief is doubtful. These findings add to a rather contradictory literature. Advantages and disadvantages of applying NPMs solely for pain relief should thus be considered carefully.

Howling at the moon? The effect of lunar phases on post-surgical pain outcome.

OBJECTIVE: Many people are convinced that lunar phases influence their lives - despite the fact that a lot of studies have shown that this belief is wrong. In this article, we investigate the effect of lunar phases on acute post-surgical pain and on treatment-related side effects. We hypothesize that there is no influence. METHODS: The data for the study were collected in 2010 and 2011 in 10 international hospitals participating in the research project PAIN OUT. Hospitalized patients were asked for their pain after surgery and pain treatment side effects using numerical ratings scales from 0 to 10. We applied Kurskal-Wallis H-tests to find out if the four moon phases show significant differences in 14 outcome variables. Afterwards, we adjusted for age, gender and three tracer surgeries. RESULTS: A total of 12,224 patient data sets were assessed. For most variables and sub-groups, there is no lunar effect on the observed outcome variables. The only items that show statistically significant differences are pain interference with sleep (p = 0.01) and drowsiness (p = 0.01). The only sub-groups that show statistically significant connections to lunar phases in some variables are men (7 out of 14 variables significant) and elderly people (4 out of 14 variables significant). DISCUSSION: Even in the statistically significant sub-groups, the differences are small and only show up in some variables. We conclude that lunar phases have no effect on post-surgical pain or its side effects. The hypothesis holds. Thus, there is no reason for patients to postpone surgeries or to fear surgeries on any given date.

Fine structure of spermatozoa of some labidognath spiders (Filistatidae, Segestriidae, Dysderidae, Oonopidae, Scytodidae, Pholcidae; Araneae; Arachnida) with remarks on spermiogenesis.

The present study reports on the spermiogenesis and spermatozoa of seven labidognath spiders: Filistata insidiatrix (Filistatidae), Segestria senoculata (Segestriidae), Dysdera sp., Harpactea hombergi (Dysderidae), Oonops domesticus (Oonopidae), Scytodes thoracica (Scytodidae), and Pholcus phalangioides (Pholcidae). Filistata insidiatrix is the first cribellate spider whose spermatology is described electron microscopically. A common characteristic of the spermatozoa of the cribellate spider and the remaining species, often referred to as haplogyne spiders, is the coiling process that occurs at the end of spermiogenesis. As a result of coiling, an elongated spermatid is converted into a lens-shaped structure with the flagellum bearing a 9 × 2 + 3 axoneme becoming incorporated into the cell body. Remarkable differences regarding the main components (shape of nucleus, acrosomal vacuole, implantation fossa, and centriolar complex) probably reflect systematic relationships. The formation of sperm capsules and sperm balls is described for the first time in detail. Sperm capsules occur in Filistata, in which numbers of individual spermatozoa are grouped together by a common secretory envelope established in the distal vas deferens. In contrast, in the sperm balls, two (Harpactea) or four (Segestria, Dysdera, Seytodes) spermatids fuse completely at the end of spermiogenesis. These sperm balls, considered unique in the animal kingdom, are also provided with an envelope. A further peculiarity not reported previously is the occurrence of a large vesicular area in the sperm balls of Dysdera and Harpactea; this area is also found in Oonops, which, however, possesses individual spermatozoa. Components of the spermatozoa such as the acrosomal vacuole, part of the nucleus, and the axoneme protrude into this area and are thus secondarily covered with a membrane. A detailed study of the individual spermatozoa of Pholcus phalangioides completes earlier investigations and stresses the exceptional position of the genus in comparison to that of other spiders.