Impact of Auricular Neurostimulation in Patients Undergoing Colorectal Surgery with an Enhanced Recovery Protocol: A Pilot Randomized, Controlled Trial.

BACKGROUND: Narcotics are the cornerstone of postoperative pain control, but the opioid epidemic and the negative physiological and psychological effects of narcotics implore physicians to utilize nonpharmacological methods of pain control. OBJECTIVE: This pilot study investigated a novel neurostimulation device for postoperative analgesia. We hypothesized that active neurostimulation would decrease postoperative narcotic requirements. DESIGN: This was a placebo-controlled, double-blinded trial. SETTINGS: This trial was conducted at an academic medical center and a Veterans Affairs hospital. PATIENTS: This trial included adult patients who underwent elective bowel resection between December 2016 and April 2018. INTERVENTIONS: Patients were randomly assigned to receive an active or inactive (sham) device, which was applied to the right ear before surgery and continued for 5 days. MAIN OUTCOME MEASURES: The primary outcome was total opioid consumption. The secondary outcomes included pain, nausea, anxiety, return of bowel function, complications, 30-day readmissions, and opioid consumption at 2 weeks and 30 days. RESULTS: A total of 57 patients participated and 5 withdrew; 52 patients were included in the analysis. Twenty-eight patients received an active device and 24 received an inactive device. There was no difference in total narcotic consumption between active and inactive devices (90.79 ± 54.93 vs 90.30 ± 43.03 oral morphine equivalents/day). Subgroup analyses demonstrated a benefit for patients after open surgery (p = 0.0278). When patients were stratified by decade, those aged 60 to 70 and >70 years derived a benefit from active devices in comparison with those aged 30 to 40, 40 to 50, and 50 to 60 years old (p = 0.01092). No serious adverse events were related to this study. LIMITATIONS: This study was limited by the small sample sizes. CONCLUSIONS: No difference in opioid use was found with auricular neurostimulation. However, this pilot study suggests that older patients and those with larger abdominal incisions may benefit from auricular neurostimulation. Further investigation in these high-risk patients is warranted. See Video Abstract at http://links.lww.com/DCR/B452.ClinicalTrials.gov identifier: NCT02892513. IMPACTO DE LA NEUROESTIMULACIN AURICULAR EN PACIENTES SOMETIDOS A CIRUGA COLORRECTAL CON UN PROTOCOLO DE RECUPERACIN MEJORADA UN ENSAYO PILOTO ALEATORIZADO Y CONTROLADO: ANTECEDENTES:Los narcóticos son la piedra angular del control del dolor postoperatorio, pero la epidemia de opioides y los efectos fisiológicos y psicológicos negativos de los narcóticos incentivan a los médicos a que utilicen métodos no farmacológicos de control del dolor.OBJETIVO:Este estudio piloto investigó un nuevo dispositivo de neuroestimulación para analgesia postoperatoria. Hipotetizamos que la neuroestimulación activa disminuiría los requerimientos narcóticos postoperatorios.DISEÑO:Este fue un ensayo doble ciego controlado con placebo.ESCENARIO:Esto se llevó a cabo en un centro médico académico y en un hospital de Asuntos de Veteranos (Veterans Affairs hospital).PACIENTES:Este ensayo incluyó pacientes adultos que se sometieron a resección intestinal electiva entre diciembre de 2016 y abril de 2018.INTERVENCIONES:Los pacientes fueron asignados al azar para recibir un dispositivo activo o inactivo (falso), que se aplicó al oído derecho antes de la cirugía y se mantuvo durante 5 días.PRINCIPALES MEDIDAS DE RESULTADO:El resultado primario fue el consumo total de opioides; los resultados secundarios incluyeron dolor, náusea, ansiedad, retorno de la función intestinal, complicaciones, reingresos a 30 días y consumo de opioides a 2 semanas y a 30 días.RESULTADOS:Participaron un total de 57 pacientes y 5 se retiraron; Se incluyeron 52 pacientes en el análisis. Veintiocho pacientes recibieron un dispositivo activo y 24 recibieron un dispositivo inactivo. No hubo diferencias en el consumo total de narcóticos entre los dispositivos activos e inactivos (90.79 ± 54.93 vs 90.30 ± 43.03 equivalentes de morfina oral [OME] / día). Los análisis de subgrupos demostraron un beneficio para los pacientes después de cirugía abierta (p = 0.0278). Cuando los pacientes se estratificaron por década, aquellos de 60-70 y > 70 años obtuvieron un beneficio de los dispositivos activos en comparación con los de 30-40, 40-50 y 50-60 años (p = 0.01092). No hubo eventos adversos graves relacionados con este estudio.LIMITACIONES:Este estudio estuvo limitado por los pequeños tamaños de muestra.CONCLUSIONES:No se encontró diferencia en el uso de opioides con la neuroestimulación auricular. Sin embargo, este estudio piloto sugiere que los pacientes mayores y aquellos con incisiones abdominales más grandes pueden beneficiarse de la neuroestimulación auricular. Está justificada la investigación adicional en estos pacientes de alto riesgo. Consulte Video Resumen en http://links.lww.com/DCR/B452. (Traducción-Dr. Jorge Silva Velazco).

Radiation-induced changes in intestinal and tissue-nonspecific alkaline phosphatase: implications for recovery after radiation therapy.

BACKGROUND: Exogenous replacement of depleted enterocyte intestinal alkaline phosphatase (IAP) decreases intestinal injury in models of colitis. We determined whether radiation-induced intestinal injury could be mitigated by oral IAP supplementation and the impact on tissue-nonspecific AP. METHODS: WAG/RjjCmcr rats (n = 5 per group) received lower hemibody irradiation (13 Gy) followed by daily gavage with phosphate-buffered saline or IAP (40 U/kg/d) for 4 days. Real-time polymerase chain reaction, AP activity, and microbiota analysis were performed on intestine. Lipopolysaccharide and cytokine analysis was performed on serum. Data were expressed as a mean ± SEM with P greater than .05 considered significant. RESULTS: Intestine of irradiated animals demonstrates lower hemibody irradiation and is associated with upregulation of tissue-nonspecific AP, downregulation of IAP, decreased AP activity, and altered composition of the intestinal microbiome. CONCLUSIONS: Supplemental IAP after radiation may be beneficial in mitigating intestinal radiation syndrome as evidenced by improved histologic injury, decreased acute intestinal inflammation, and normalization of intestinal microbiome.

Anti inflammatory and anti angiogenic effect of black raspberry extract on human esophageal and intestinal microvascular endothelial cells.

Polyphenolic compounds (anthocyanins, flavonoid glycosides) in berries prevent the initiation, promotion, and progression of carcinogenesis in rat's digestive tract and esophagus, in part, via anti-inflammatory pathways. Angiogenesis has been implicated in the pathogenesis of chronic inflammation and tumorigenesis. In this study, we investigated the anti-inflammatory and anti-angiogenic effects of black raspberry extract (BRE) on two organ specific primary human intestinal microvascular endothelial cells, (HIMEC) and human esophageal microvascular endothelial cells (HEMEC), isolated from surgically resected human intestinal and donor discarded esophagus, respectively. HEMEC and HIMEC were stimulated with TNF-α/IL-1ß with or without BRE. The anti-inflammatory effects of BRE were assessed based upon COX-2, ICAM-1 and VCAM-1 gene and protein expression, PGE2 production, NFκB p65 subunit nuclear translocation as well as endothelial cell-leukocyte adhesion. The anti-angiogenic effects of BRE were assessed on cell migration, proliferation and tube formation following VEGF stimulation as well as on activation of Akt, MAPK and JNK signaling pathways. BRE inhibited TNF-α/IL-1ß-induced NFκB p65 nuclear translocation, PGE2 production, up-regulation of COX-2, ICAM-1 and VCAM-1 gene and protein expression and leukocyte binding in HEMEC but not in HIMEC. BRE attenuated VEGF-induced cell migration, proliferation and tube formation in both HEMEC and HIMEC. The anti-angiogenic effect of BRE is mediated by inhibition of Akt, MAPK and JNK phosphorylations. BRE exerted differential anti-inflammatory effects between HEMEC and HIMEC following TNF-α/IL-1ß activation whereas demonstrated similar anti-angiogenic effects following VEGF stimulation in both cell lines. These findings may provide more insight into the anti-tumorigenic capacities of BRE in human disease and cancer.

Mechanisms of endotoxin tolerance in human intestinal microvascular endothelial cells.

Lipopolysaccharide (endotoxin) tolerance is well described in monocytes and macrophages, but is less well characterized in endothelial cells. Because intestinal microvascular endothelial cells exhibit a strong immune response to LPS challenge and play a critical regulatory role in gut inflammation, we sought to characterize the activation response of these cells to repeated LPS exposure. Primary cultures of human intestinal microvascular endothelial cells (HIMEC) were stimulated with LPS over 6-60 h and activation was assessed using U937 leukocyte adhesion, expression of E-selectin, ICAM-1, VCAM-1, IL-6, IL-8, manganese superoxide dismutase, HLA-DR, and CD86. Effect of repeat LPS stimulation on HIMEC NF-kappaB and mitogen-activated protein kinase (MAPK) activation, generation of superoxide anion, and Toll-like receptor 4 expression was characterized. LPS pretreatment of HIMEC for 24-48 h significantly decreased leukocyte adhesion after subsequent LPS stimulation. LPS pretreatment inhibited expression of E-selectin, VCAM-1, IL-6, and CD86, while ICAM-1, IL-8, and HLA-DR were not altered. Manganese superoxide dismutase expression increased with repeated LPS stimulation, with a reduction in intracellular superoxide. NF-kappaB activation was transiently inhibited by LPS pretreatment for 6 h, but not at later time points. In contrast, p44/42 MAPK, p38 MAPK, and c-Jun N-terminal kinase activation demonstrated inhibition by LPS pretreatment 24 or 48 h prior. Toll-like receptor 4 expression on HIMEC was not altered by LPS. HIMEC exhibit endotoxin tolerance after repeat LPS exposure in vitro, characterized by diminished activation and intracellular superoxide anion concentration, and reduced leukocyte adhesion. HIMEC possess specific mechanisms of immunoregulatory hyporesponsiveness to repeated LPS exposure.