A randomized pilot study to investigate the effect of opioids on immunomarkers using gene expression profiling during surgery

Wodehouse, Theresa; Demopoulos, Mary; Petty, Robert; Miraki-Moud, Farideh; Belhaj, Alla; Husband, Michael; Fulton, Laura; Randive, N.; Oksche, Alexander; Mehta, Vivek; Gribben, John G.; Langford, R. M.

doi:10.1097/j.pain.0000000000001677

Cited by 15 publications

(10 citation statements)

References 33 publications

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“…Procalcitonin (PCT) is a calcitonin-promoting hormone that is commonly used as a clinical infection index. The level of serum PCT in sepsis patients is signi cantly increased, and can be detected within 24 h post-infection, peaks at 12-24 h, and is closely related to the severity of infection [10]. PCT was detected in our mouse model of sepsis, which is in accordance with the response of clinical patients.…”

Section: Discussionsupporting

confidence: 77%

Establishment and Evaluation of a "Two-Hit" Mouse Model of Sepsis

et al. 2021

Preprint

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In recent years, researchers have turned their attention to the study of the mechanism of sepsis-induced immuneparalysis, but there is still a lack of appropriate animal models that reflect the process of sepsis-induced immuneparalysis. The purpose of this study was to explore and evaluate whether a "two-hit" model of sepsis can be used as an appropriate animal model to study the mechanism of sepsis-induced immunoparalysis. Firstly, we established a sepsis model in C57BL/6J mice via cecal ligation and puncture(CLP). Routine blood tests, serum ALT and PCT, etc. were analyzed to evaluate the establishment of a CLP sepsis model on day 1 post-CLP. Secondly, the surviving mice were treated with 40µL suspension of P.aeruginosa (Pa) under anesthetic on day 4 post-CLP to establish a "two-hit" model. Gross lung specimens, and pathological examination of the lung tissue, etc. were used to evaluate whether the "two-hit" model was successfully established on days 5 and 11 post-CLP. Finally, the level of serum TNF-α and IL-6, pathological examination of the spleen and the CD4+/CD8 + ratio in blood were detected to evaluate the immune status of the model mice. The above test results proved that the "two-hit" sepsis mouse model was successfully constructed. TNF-α, IL-6, pathological examination of the spleen and the CD4+/CD8 + ratio in blood confirmed that the model was in a state of immunoparalysis. We conclude that this "two-hit" sepsis mouse model is an appropriate animal model, which can successfully replicate the pathophysiological process of in clinical patients with sepsis-induced immunoparalysis.

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Section: Discussionsupporting

confidence: 77%

Establishment and Evaluation of a "Two-Hit" Mouse Model of Sepsis

et al. 2021

Preprint

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“…To validate sample quality, quality checks were conducted using Affymetrix Expression Console software. The intensity values were log2-transformed and imported into the Partek Genomics Suite 6.6 (Partek Incorporated, USA) (Wodehouse et al, 2019). Exons were summarized to genes and a 1-way ANOVA was performed to identify differentially expressed genes.…”

Section: Primary Cell Culturementioning

confidence: 99%

Regenerative Metaplastic Clones in COPD Lung Drive Inflammation and Fibrosis

Rao

Wang

Duleba

et al. 2020

Cell

108

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Chronic obstructive pulmonary disease (COPD) is a progressive condition of chronic bronchitis, small airway obstruction, and emphysema that represents a leading cause of death worldwide. While inflammation, fibrosis, mucus hypersecretion, and metaplastic epithelial lesions are hallmarks of this disease, their origins and dependent relationships remain unclear. Here we apply single-cell cloning technologies to lung tissue of patients with and without COPD. Unlike control lungs, which were dominated by normal distal airway progenitor cells, COPD lungs were inundated by three variant progenitors epigenetically committed to distinct metaplastic lesions. When transplanted to immunodeficient mice, these variant clones induced pathology akin to the mucous and squamous metaplasia, neutrophilic inflammation, and fibrosis seen in COPD. Remarkably, similar variants pre-exist as minor constituents of control and fetal lung and conceivably act in normal processes of immune surveillance. However, these same variants likely catalyze the pathologic and progressive features of COPD when expanded to high numbers.

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“…This impact on NK cell activity seems to be related to the dose of opioids. 20 , 21 In our study, regional anesthesia was used to ensure adequate analgesia while reducing the use of opioids to observe the effect of different doses of opioids on postoperative immunity.…”

Section: Discussionmentioning

confidence: 99%

Neutrophil-to-Lymphocyte Ratio as an Indicator of Opioid-Induced Immunosuppression After Thoracoscopic Surgery: A Randomized Controlled Trial

Chen¹,

Liang²,

Liu³

et al. 2022

JPR

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Purpose The neutrophil-to-lymphocyte ratio (NLR) is a useful prognostic marker for various diseases and surgery-induced immunosuppression. While opioids are important in general anesthesia, the association between immediate perioperative immune monitoring and opioid consumption for postoperative analgesia after video-assisted thoracoscopic surgery (VATS) is unknown. We aimed to investigate the effect of analgesic techniques on opioid-induced immune perturbation, and the feasibility of NLR as an indicator of opioid-induced immune changes. Patients and Methods Patients were randomly assigned to two groups: Group P (n=40) or Group C (n=40). Patients in group P received ultrasound-guided paravertebral block (PVB) before surgery, and followed by sufentanil patient-controlled intravenous analgesia (PCIA) after surgery, and group C received sufentanil PCIA only. The total and differential white blood cell counts, including CD4+ T lymphocyte counts, CD8+ T lymphocyte were recorded before surgery and at 24 and 72 hours after surgery. NLR was determined using the frequencies of lymphocyte subpopulations. The cumulative dose of sufentanil were recorded at 24 and 24h after surgery while the 40-item quality of recovery questionnaire (QoR-40) score were assessed at 48h after the surgery. Results At 24 and 48 hours after surgery, a lower sufentanil consumption, and higher QoR-40 recovery scores were found in group P than in group C (P<0.05). In biochemical analyses, the values of NLR were lower in group P compared to group C ( p <0.0001) and ratio of CD4/CD8 were higher in group P compared to group C ( p <0.05) on day three after surgery. NLR showed excellent predictive capability for immunosuppression, with an area under the curve (AUC) of 0.92 [95% confidence interval (CI), 0.86–0.98, P < 0.0001]. Conclusion Opioid-sparing pain management strategies may affect postoperative immunosuppression and NLR could be a reliable indicator of opioid-related immunosuppression. Moreover, opioid-sparing pain management strategies could improve patient’s satisfaction in VATS.

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A randomized pilot study to investigate the effect of opioids on immunomarkers using gene expression profiling during surgery

Cited by 15 publications

References 33 publications

Establishment and Evaluation of a "Two-Hit" Mouse Model of Sepsis

Establishment and Evaluation of a "Two-Hit" Mouse Model of Sepsis

Regenerative Metaplastic Clones in COPD Lung Drive Inflammation and Fibrosis

Neutrophil-to-Lymphocyte Ratio as an Indicator of Opioid-Induced Immunosuppression After Thoracoscopic Surgery: A Randomized Controlled Trial

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