Association of circulating gene expression signatures with stiffness following total knee arthroplasty for osteoarthritis: a pilot study.

A subset of patients undergoing total knee arthroplasty (TKA) for knee osteoarthritis develop debilitating knee stiffness (reduced range of motion) for poorly understood reasons. Dysregulated inflammatory and immune responses to surgery correlate with reduced surgical outcomes, but the dysregulated gene signatures in patients with stiffness after TKA are poorly defined. As a consequence, we are limited in our ability to identify patients at risk of developing poor surgical outcomes and develop preventative approaches. In this pilot study we aimed to identify perioperative blood gene signatures in patients undergoing TKA for knee osteoarthritis and its association with early surgical outcomes, specifically knee range of motion. To do this, we integrated clinical outcomes collected at 6 weeks after surgery with transcriptomics analyses in blood samples collected immediately before surgery and at 24 h after surgery. We found that patients with stiffness at 6 weeks after surgery have a more variable and attenuated circulating gene expression response immediately after surgery. Our results suggest that patients with stiffness following TKA may have distinct gene expression signatures detectable in peripheral blood in the immediate postoperative period.

Identification of biological risk factors for persistent postoperative pain after total knee arthroplasty.

BACKGROUND: There is growing evidence that cytokines and adipokines are associated with osteoarthritis (OA) severity, progression, and severity of associated pain. However, the cytokine response to total knee arthroplasty (TKA) and its association with persistent postoperative pain is not well understood. This study aims to describe the perioperative systemic (plasma) and local (synovial fluid) cytokine profiles of patients who do and do not develop persistent pain after TKA. METHODS: Patients undergoing primary unilateral TKA for end-stage OA were prospectively enrolled. Demographic and clinical data were gathered preoperatively and postoperatively. Synovial fluid was collected pre arthrotomy and plasma was collected at multiple time points before and after surgery. Persistent postoperative pain (PPP) was defined as Numerical Rating Score≥4 at 6 months. Cytokine levels were measured using the V-Plex Human Cytokine 30-Plex Panel (Mesoscale-Rockville, Maryland, USA). Cytokine levels were compared between PPP and minimal pain groups. Given that the study outcomes are exploratory, no adjustment was performed for multiple testing. RESULTS: Incidence of persistent pain at 6 months post TKA was 15/162 (9.3%). Postoperative plasma levels of four cytokines were significantly different in patients who developed persistent postoperative pain: interleukin (IL)-10, IL-1ß, vascular endothelial growth factor, and IL12/IL23p40. Significantly lower IL-10 levels in the prearthrotomy synovial fluid were associated with development of postoperative persistent pain. CONCLUSIONS: This prospective cohort study described a distinct acute perioperative inflammatory response profile in patients who developed persistent post-TKA pain, characterized by significant differences in four cytokines over the first 2 postoperative days. These results support the growing evidence that the patient-specific biologic response to surgery may influence longer-term clinical outcomes after TKA. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov NCT02626533.

[The effect of emotional stressors on postoperative skin conductance indices: a prospective cohort pilot study]. / Efeito dos estressores emocionais nos índices de condutância cutânea no pós­operatório: estudo piloto de coorte prospectivo.

BACKGROUND: Skin conductance response reflects the activity of the sympathetic nervous system and is used to measure acute pain. This pilot study examines correlations of skin conductance response with emotional stressors postoperatively. METHODS: The correlation of skin conductance response with pain, anxiety, nausea and intellectual task performance was analyzed in postoperative patients. RESULTS: Significant correlations were observed between anxiety and pain during physical activity on both postoperative day 1 and 2. No significant correlations were found between skin conductance response versus mild pain, nausea, anxiety or intellectual task performance. CONCLUSION: This pilot study suggests that when the pain is well-controlled in the early postoperative period, skin conductance response monitoring may not be influenced by other emotional stressors.

The effect of emotional stressors on postoperative skin conductance indices: a prospective cohort pilot study / Efeito dos estressores emocionais nos índices de condutância cutânea no pós-operatório: estudo piloto de coorte prospectivo

Abstract Background: Skin conductance response reflects the activity of the sympathetic nervous system and is used to measure acute pain. This pilot study examines correlations of skin conductance response with emotional stressors postoperatively. Methods: The correlation of skin conductance response with pain, anxiety, nausea and intellectual task performance was analyzed in postoperative patients. Results: Significant correlations were observed between anxiety and pain during physical activity on both postoperative day 1 and 2. No significant correlations were found between skin conductance response versus mild pain, nausea, anxiety or intellectual task performance. Conclusion: This pilot study suggests that when the pain is well-controlled in the early postoperative period, skin conductance response monitoring may not be influenced by other emotional stressors.

Resumo Justificativa: A variação da condutância da pele reflete a atividade do sistema nervoso simpático e é usada para avaliar dor aguda. Este estudo piloto examinou as correlações entre a variação da condutância da pele e estressores emocionais no pós-operatório. Método: A correlação entre a variação da condutância da pele e dor, ansiedade, náusea e desempenho de tarefa intelectual foi analisada em pacientes no pós-operatório. Resultados: Correlações significantes foram observadas entre ansiedade e dor durante atividade física nos dias 1 e 2 pós-operatórios. Não foram encontradas correlações significantes entre a variação da condutância da pele e dor leve, náusea, ansiedade ou desempenho de tarefa intelectual. Conclusão: Este estudo piloto sugere que, quando a dor é bem controlada no pós-operatório inicial, o monitoramento empregando a variação da condutância da pele pode não ser influenciado por outros estressores emocionais.

Pregabalin Did Not Improve Pain Management After Spinal Fusions.

BACKGROUND: The treatment of postoperative pain is a challenge after posterior spinal fusions. Pain management using predominantly opioids is often associated with multiple adverse effects, while multimodal postoperative analgesia may provide adequate pain relief with fewer opioid side effects. QUESTIONS/PURPOSES: The purpose of this review is to determine whether addition of 150 mg pregabalin daily would reduce narcotic requirements and improve outcomes after posterior lumbar fusion (PLF). METHODS: The method used is a randomized, controlled trial of elective PLF patients who received pregabalin or placebo. With institutional review board (IRB) approval, 86 patients undergoing elective posterior lumbar fusion, ASA I-III, were randomized to receive either a placebo or pregabalin after obtaining written informed consent. Both arms, i.e., placebo and pregabalin, consisted of 43 patients each.The 86 patients for elective PLF were randomly assigned to receive 150 mg of pregabalin 1 h before surgery and then 150 mg daily, or a placebo tablet. All patients received a similar general anesthetic and in the post-anesthesia care unit (PACU), started on intravenous (IV) patient-controlled analgesia (PCA) of hydromorphone (0.2 mg/ml). Postoperative pain was assessed daily until discharge using a Numerical Rating Scale (NRS) at rest and with physical therapy (PT). Patients were also assessed twice daily for level of sedation and nausea and/or vomiting and expected PT milestones. All narcotics (IV, oral) were documented. RESULTS: Demographics and operative time between groups were similar. PCA hydromorphone administration and oral narcotic intake were not statistically different between the two groups. However, an increased incidence of nausea and vomiting in the placebo group reached statistical significance (p < 0.05). In addition, there was no statistical difference between groups with respect to achieving PT milestones and hospital discharge day. CONCLUSION: After PLF, patients receiving pregabalin 150 mg/day did not have reduced IV narcotic usage, improved PT milestones, or reduced length of hospital stay. We were unable to demonstrate an analgesic advantage to prescribing pregabalin to patients undergoing lumbar spinal fusions.

Post-Dural Puncture Headache is Uncommon in Young Ambulatory Surgery Patients.

BACKGROUND: The incidence of post-dural puncture headache (PDPH) arising from spinal anesthesia in the general population is low. However, patients under 45 years have been shown to exhibit a higher incidence of PDPH, even with small needles. QUESTIONS/PURPOSES: This study aimed to estimate the incidence of PDPH from a 27G pencil-point needle in ambulatory surgery patients between the ages of 15-45 years and compare incidence of PDPH by age group, sex, and history of headache. METHODS: In this prospective cohort study, 300 patients (15-45 years old) who underwent simple knee arthroscopy under spinal anesthesia with a 27G pencil-point needle were enrolled. Verbal consent was obtained during the initial phone conversation between post-operative days (PODs) 2-5. A PDPH questionnaire was administered during this conversation and between PODs 7-10. Patients who reported a positional headache were contacted by a physician co-investigator, who determined PDPH diagnosis. RESULTS: Five patients were excluded from analysis due to complicated operative procedures or spinal needle size. The overall PDPH incidence was 2.0% (95% CI 0.9-4.4; 6/295). PDPH incidence in 15-19-year-old patients was 16.7% (95% CI 4.7-44.8; 2/12). The crude relative risk of PDPH was 15.4 (95% CI 2.8-114.4) for patients with and without history of headache and 2.5 (95% CI 0.5-14.8) for females vs. males. Overall, 16.3% (95% CI 12.5-20.9) of patients reported post-operative, non-positional headaches. CONCLUSIONS: There was a low overall incidence of PDPH among patients aged 15-45. Pre-planned subgroup analyses of PDPH incidence by age group revealed a high risk of PDPH among a small sample of 15-19-year-olds.