Dataset Information

The Role of Cytokines in Acute and Chronic Postsurgical Pain in Pediatric Patients after Major Musculoskeletal Surgeries.

ABSTRACT:

Study objective

To determine if baseline cytokines and their changes over postoperative days 0-2 (POD0-2) predict acute and chronic postsurgical pain (CPSP) after major surgery.

Design

Prospective, observational, longitudinal nested study.

Setting

University-affiliated quaternary children's hospital.

Patients

Subjects (≥8 years old) with idiopathic scoliosis undergoing spine fusion or pectus excavatum undergoing Nuss procedure.

Measurements

Demographics, surgical, psychosocial measures, pain scores, and opioid use over POD0-2 were collected. Cytokine concentrations were analyzed in serial blood samples collected before and after (up to two weeks) surgery, using Luminex bead arrays. After data preparation, relationships between pre- and post-surgical cytokine concentrations with acute (% time in moderate-severe pain over POD0-2) and chronic (pain score>3/10 beyond 3 months post-surgery) pain were analyzed. After adjusting for covariates, univariate/multivariate regression analyses were conducted to associate baseline cytokine concentrations with postoperative pain, and mixed effects models were used to associate longitudinal cytokine concentrations with pain outcomes.

Main results

Analyses included 3,164 measures of 16 cytokines from 112 subjects (median age 15.3, IQR 13.5-17.0, 54.5% female, 59.8% pectus). Acute postsurgical pain was associated with higher baseline concentrations of GM-CSF (β=0.95, SE 0.31; p=.003), IL-1β (β=0.84, SE 0.36; p=.02), IL-2 (β=0.78, SE 0.34; p=.03), and IL-12 p70 (β=0.88, SE 0.40; p=.03) and longitudinal postoperative elevations in GM-CSF (β=1.38, SE 0.57; p=.03), IFNγ (β=1.36, SE 0.6; p=.03), IL-1β (β=1.25, SE 0.59; p=.03), IL-7 (β=1.65, SE 0.7, p=.02), and IL-12 p70 (β=1.17, SE 0.58; p=.04). In contrast, CPSP was associated with lower baseline concentration of IL-8 (β= -0.39, SE 0.17; p=.02), and the risk of developing CPSP was elevated in patients with lower longitudinal postoperative concentrations of IL-6 (β= -0.57, SE 0.26; p=.03), IL-8 (β= -0.68, SE 0.24; p=.006), and IL-13 (β= -0.48, SE 0.22; p=.03). Furthermore, higher odds for CPSP were found for females (vs. males) for IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, and TNFα, and for pectus (vs. spine) surgery for IL-8 and IL-10.

Conclusion

We identified pro-inflammatory cytokines associated with increased acute postoperative pain and anti-inflammatory cytokines associated with lower CPSP risk, with potential to serve as predictive and prognostic biomarkers.

SUBMITTER: Chidambaran V

PROVIDER: S-EPMC10996732 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature

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Publications

The Role of Cytokines in Acute and Chronic Postsurgical Pain in Pediatric Patients after Major Musculoskeletal Surgeries.

Chidambaran Vidya V Duan Qing Q Pilipenko Valentina V Glynn Susan M SM Sproles Alyssa A Martin Lisa J LJ Lacagnina Michael J MJ King Christopher D CD Ding Lili L

medRxiv : the preprint server for health sciences 20240328

<h4>Study objective</h4>To determine if baseline cytokines and their changes over postoperative days 0-2 (POD0-2) predict acute and chronic postsurgical pain (CPSP) after major surgery.<h4>Design</h4>Prospective, observational, longitudinal nested study.<h4>Setting</h4>University-affiliated quaternary children's hospital.<h4>Patients</h4>Subjects (≥8 years old) with idiopathic scoliosis undergoing spine fusion or pectus excavatum undergoing Nuss procedure.<h4>Measurements</h4>Demographics, surgi ...[more]

PMID: 38585987

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Project description:Reliable, clinic-friendly screening for Chronic postsurgical pain (CPSP) risk is unavailable. Within a prospective, observational study, we evaluated Pediatric Pain Screening Tool (PPST), a concise 9-item questionnaire, as a preoperative screening tool to identify those at higher risk for CPSP (Numerical Rating Scale > 3/10 beyond 3 months post-surgery) and poor function (disability/Functional Disability Inventory [FDI]/quality of life/ Pediatric Quality of Life) after spine fusion and Nuss procedures. Incidence of CPSP was 34.86% (38/109). We confirmed PPST scale stability, test re-test reliability (ICC = 0.68; P< .001); PPST measures were positively correlated with known CPSP risk factors (P< .001) preoperative pain (Pearson or Spearman Correlation Coefficient [SCC]:0.672), Child anxiety sensitivity index (SCC:0.357), Patient Related Outcome Measures Information System pain interference (SCC:0.569), Patient Related Outcome Measures Information System depression (SCC:0.501), Pediatric Quality of Life (SCC:-0.460) and insomnia severity index (SCC0.567). Preoperative PPST and PPST physical sub-scores (median(IQR) were higher in CPSP (2[0.5,4], 1[0,2]) compared to non-CPSP (1[0,3], 0[0,1.5]) groups (P= .026, P= .029) respectively. PPST scores/sub-scores positively correlated with higher FDI at 6 months but only PPST total and PPST psychosocial subscore correlated with higher FDI at 12 months. Based on ROC, optimal PPST cutoff for CPSP was 2 (63.9% sensitivity, 64.7% specificity). CPSP risk was high (48.94% risk) if PPST ≥ 2 (n = 47) and medium (22.81%) if PPST < 2 (n = 57) after spine/pectus surgery. General and risk-strata specific, targeted psychosocial non-pharmacological interventions, need to be studied. Findings need validation in diverse, larger cohorts. CLINICALTRIALS.GOV IDENTIFIER: NCT02998138. PERSPECTIVE: The article supports Pediatric Pain Screening Tool, a simple 9-item questionnaire, as a preoperative screening tool for CPSP and function 6-12 months after spine/pectus surgeries. PPST measures correlate with known risk factors for CPSP. Risk stratification and targeted preventive interventions in high-risk subjects are proposed.

Project description:BackgroundChronic postsurgical pain (CPSP) is a clinical problem, and large prospective studies are needed to determine its incidence, characteristics, and risk factors.ObjectiveTo find predictive factors for CPSP in an international survey.DesignObservational study.SettingMulticentre European prospective observational trial.PatientsPatients undergoing breast cancer surgery, sternotomy, endometriosis surgery, or total knee arthroplasty (TKA).MethodStandardised 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 measureThe primary goal of NIT-1 was to propose a scoring system to predict those patient likely to have CPSP at 6 months after surgery.ResultsA 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.ConclusionUnfortunately, 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 registrationclinicaltrials.gov ID: NCT03834922.

Dataset Information

The Role of Cytokines in Acute and Chronic Postsurgical Pain in Pediatric Patients after Major Musculoskeletal Surgeries.

Study objective

Design

Setting

Patients

Measurements

Main results

Conclusion

Publications

The Role of Cytokines in Acute and Chronic Postsurgical Pain in Pediatric Patients after Major Musculoskeletal Surgeries.

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