Protective efficacy of combined use of parecoxib and dexmedetomidine on postoperative hyperalgesia and early cognitive dysfunction after laparoscopic cholecystectomy for elderly patients

Abstract Purpose: To investigate efficacy of combined use of parecoxib and dexmedetomidine on postoperative pain and early cognitive dysfunction after laparoscopic cholecystectomy for elderly patients. Methods: The present prospective randomized controlled study included a total of 80 patients who underwent laparoscopic cholecystectomy surgery during January 2016 to November 2017 in our hospital. All patients were randomly divided into 4 groups, the parecoxib group, the dexmedetomidine group, the parecoxib and dexmedetomidine combined group, and the control group. Demographic data and clinical data were collected. Indexes of heart rate (HR), mean arterial pressure (MAP), levels of jugular venous oxygen saturation (SjvO2) and jugular venous oxygen pressure (PjvO2) were recorded at different time points before and during the surgery. The mini-mental state examination (MMSE) score, Ramsay score and Visual Analogue Score (VAS) were measured. Results: Levels of both SjvO2 and PjvO2 were significantly higher in parecoxib group, dexmedetomidine group and the combined group than the control group. Meanwhile, levels of both SjvO2 and PjvO2 in the combined group were the highest. VAS scores were significantly lower in the combined group than all other groups, and total patient controlled intravenous analgesia (PCIA) pressing times within 48 h after surgery were the lowest in the combined group. Both Ramsay and MMSE scores were the highest in the combined group compared with other groups, while were the lowest in the control group. Conclusion: The combined use of parecoxib and dexmedetomidine could reduce the postoperative pain and improve the postoperative sedation and cognitive conditions of patients after laparoscopic cholecystectomy.

Efficiency of bupivacaine and association with dexmedetomidine in transversus abdominis plane block ultrasound guided in postoperative pain of abdominal surgery / Eficácia de bupivacaína e associação com dexmedetomidina em bloqueio do plano transverso abdominal guiado por ultrassom na dor após cirurgia abdominal

Abstract Background and objectives We aimed to evaluate the effect of bupivacaine and dexmedetomidine added to bupivacaine used in tranversus abdominis plane (TAP) block on postoperative pain and patient satisfaction in patients undergoing lower abdominal surgery. Methods Patients submitted to lower abdominal surgery were enrolled in the study. After anesthesia induction, ultrasound guided TAP block was performed. TAP block was obtained with 21 mL 0.9% saline in Group C (n = 31), 20 mL 0.5% bupivacaine + 1 mL saline in Group B (n = 31), and 20 mL 0.5% bupivacaine + 1 mL dexmedetomidine (100 µg) in Group BD (n = 31). Results Visual analog scale scores were lower in Group BD compared to Group C, at all time points (p < 0.05); it was lower in group BD than in group B at 10-24 h. In Group B, it was lower than Group C at 2-8 h (p < 0.05). Total morphine consumption was lower in Group BD compared to other groups and lower in group B than in the controls (p < 0.001). Patient satisfaction was higher in Group BD than in other groups and was higher in both study groups than in the controls (p < 0.001). Nausea-vomiting scores, antiemetic requirement, or additional analgesic administration were not significant among groups (p > 0.05). Conclusions The addition of dexmedetomidine to bupivacaine on TAP block decreased postoperative pain scores and morphine consumption; it also increased patient satisfaction in patients undergoing lower abdominal surgery. Dexmedetomidine did not have any effect on nausea and vomiting score and antiemetic requirement.

Resumo Justificativa e objetivos O objetivo do estudo foi avaliar o efeito de bupivacaína e dexmedetomidina adicionada à bupivacaína para bloqueio do plano transverso abdominal (TAP) no controle da dor e satisfação do paciente após cirurgia abdominal inferior. Métodos Pacientes submetidos à cirurgia abdominal inferior foram incluídos no estudo. Após a indução da anestesia, o bloqueio TAP guiado por ultrassom foi feito com 21 mL de solução salina a 0,9% no Grupo C (n = 31), 20 mL de bupivacaína a 0,5% + 1 mL de solução salina no Grupo B (n = 31) e 20 mL de bupivacaína a 0,5% + 1 mL de dexmedetomidina (100 µg) no grupo BD (n = 31). Resultados Os escores da escala visual analógica foram menores no Grupo BD comparado com o Grupo C em todos os tempos mensurados (p < 0,05); foi menor no Grupo BD do que no Grupo B em 10-24 horas. No Grupo B, os escores VAS foram menores do que no Grupo C em 2-8 horas (p < 0,05). O consumo total de morfina foi menor no Grupo BD em comparação com outros grupos e menor no Grupo B do que nos controles (p < 0,001). A satisfação do paciente foi maior no Grupo BD do que nos outros grupos e maior em ambos os grupos de estudo do que nos controles (p < 0,001). Os escores de náusea e vômito, necessidade de antiemético ou de analgésicos adicionais não foram significativos entre os grupos (p > 0,05). Conclusões A adição de dexmedetomidina à bupivacaína em bloqueio TAP reduziu os escores de dor e o consumo de morfina no pós-operatório, além de aumentar a satisfação em pacientes submetidos à cirurgia abdominal inferior. Dexmedetomidina não apresentou efeito sobre os escores de náusea e vômito e a necessidade de antiemético.

Effect of dexmedetomidine on acute lung injury in experimental ischemia-reperfusion model / Efeito de dexmedetomidina sobre lesão pulmonar aguda em modelo experimental de isquemia-reperfusão

Abstract Purpose: Ischemia-reperfusion injury is one of the consequences of tourniquet application for extremity surgery. The aim of the study was to establish the effect of dexmedetomidine on the acute lung injury following lower extremity experimental ischemia-reperfusion model in rats. Methods: Twenty-eight Wistar-Albino breed Rats were recruited after Ethics Committee approval and allocated into 4 groups, each with 7 subjects. Group 1 (SHAM) received only anesthesia. Group 2 (IR) had experienced 3 h of ischemia and 3 h of reperfusion using left lower extremity tourniquet after anesthesia application. Groups 3 (D-50) and 4 (D-100) had undergone the same procedures as in the Group 2, except for receiving 50 and 100 mg·kg-1, respectively, dexmedetomidine intraperitoneally 1 h before the tourniquet release. Blood samples were obtained for the analysis of tumor necrosing factor-α and interleukin-6. Pulmonary tissue samples were obtained for histological analysis. Results: No significant difference regarding blood tumor necrosing factor-α and interleukin-6 values was found among the groups, whereas pulmonary tissue injury scores revealed significant difference. Histological scores obtained from the Group 2 were significantly higher from those in the Groups 1, 3 and 4 with p-values 0.001 for each comparison. Moreover, Group 1 scores were found to be significantly lower than those in the Groups 3 and 4 with p-values 0.001 and 0.011, respectively. No significant difference was observed between the Groups 3 and 4. Conclusion: Dexmedetomidine is effective in reduction of the experimental ischemia-reperfusion induced pulmonary tissue injury in rats, formed by extremity tourniquet application.

Resumo Objetivo: A lesão de isquemia-reperfusão é uma das consequências da aplicação do torniquete em cirurgias de extremidades. O objetivo do estudo foi determinar o efeito de dexmedetomidina em lesão pulmonar aguda após modelo experimental de isquemia-reperfusão em extremidade inferior de ratos. Métodos: Vinte e oito ratos albinos Wistar foram recrutados após aprovação do Comitê de Ética e alocados em quatro grupos, cada um com sete indivíduos. O Grupo 1 (Sham) recebeu apenas anestesia. O Grupo 2 (IR) foi submetido a 3 horas de isquemia e 3 horas de reperfusão com o uso de torniquete em extremidade inferior após a aplicação da anestesia. Os grupos 3 (D-50) e 4 (D-100) foram submetidos aos mesmos procedimentos do Grupo 2, exceto por receberem 50 e 100 mg.kg-1 de dexmedetomidina, respectivamente, por via intraperitoneal uma hora antes da liberação do torniquete. Amostras de sangue foram coletadas para análise de TNF-α e Interleucina-6 (IL-6). Amostras de tecido pulmonar foram coletadas para análise histológica. Resultados: Não houve diferença significativa quanto aos valores sanguíneos de TNF-α e IL-6 entre os grupos, enquanto os escores de lesão em tecidos pulmonares revelaram diferença significativa. Os escores histológicos obtidos no Grupo 2 foram significativamente maiores do que os dos grupos 1, 3 e 4, com valores-p de 0,001 para cada comparação. Além disso, os escores do Grupo 1 foram significativamente menores do que os dos grupos 3 e 4, com valores-p de 0,001 e 0,011, respectivamente. Não houve diferença significativa entre os grupos 3 e 4. Conclusão: Dexmedetomidina mostrou eficácia na redução de lesão em tecido pulmonar induzida por isquemia-reperfusão experimental em ratos, ocasionada por aplicação de torniquete em extremidade.

Dexmedetomidina genera óxido nítrico mediante un mecanismo independiente de la óxido nítrico sintasa inducible / Dexmedetomidine protects the heart against ischemia-reperfusion injury by an endothelial eNOS/NO dependent mechanism

El infarto del miocardio es una de las principales causas de muerte a nivel mundial y se produce a consecuencia de procesos de isquemia-reperfusión (IR). El daño miocárdico generado por IR puede ser atenuado a través del pre-condicionamiento isquémico (PI) temprano, mediado por la vía RISK o PI tardío, que se asocia a una respuesta genómica en la que se activan proteínas como óxido nítrico sintasa inducible (iNOS). Las vías de señalización que median el PI también pueden ser activadas farmacológicamente. Dexmedetomi-dina (Dex) es un agonista alfa2-adrenérgico, que se ha descrito como un potente agente cardioprotector frente a IR. Recientemente, nuestro grupo describió que Dex requiere el endotelio y la activación de la vía óxido nítrico sintasa endotelial (eNOS)-óxido nítrico (NO) para pre-condicionar el miocardio. Sin embargo, no existen estudios que muestren la posible participación de iNOS en la protección conferida por Dex. La presente adenda tiene por objetivo evaluar si Dex activa iNOS en el corazón y en cardiomiocitos. Para esto, corazones de rata adulta fueron estimulados con Dex 10 nM y se observó que el fármaco aumentó la producción de NO medida por cuantificación de nitritos, mas no estimuló la activación de iNOS medida por Western blot. Además, Dex tampoco indujo el aumento de mRNA de iNOS en cardiomiocitos adultos. Por lo tanto, Dex genera NO independiente a iNOS durante su efecto pre-condicionante agudo. Sin embargo, se requieren más estudios que clarifiquen su papel en una posible protección a largo plazo frente a IR generada por Dex.

Myocardial infarction is one of the leading causes of death worldwide and is generated as a consequence of ischemia-reperfusion (IR). Myocardial damage inflicted by IR can be attenuate by early ische-mic pre-conditioning (IP), which is mediated by the RISK pathway or late IP, which is associated to a genomic response involving the activation of proteins such as inducible nitric oxide synthase (iNOS). The signaling pathways mediating IP can also be pharmacologically activated. Dexmedetomidine (Dex) is an alpha2-adrenergic receptor agonist, which has been described as a strong cardio protective agent against IR. Recently, our group reported that Dex requires the endothelium and the activation of the endothelial nitric oxide synthase (eNOS)-ni-tric oxide (NO) pathway to precondition the myocardium. However, there are no studies showing the involvement of iNOS in the protection elicited by Dex. The aim of this Addendum is to evaluate if Dex activates iNOS in the heart and cardiomyocytes. To test this, adult rat hearts were stimulated with Dex 10 nM and we observed that NO production measured by quantification of nitrites was increased, but Dex did not activate iNOS measured by Western blot. Moreover, Dex did not induce an increase in the mRNA levels of iNOS in adult cardiomyocytes. Therefore, Dex generates NO independent of iNOS during its early pre-conditioning effect. Nevertheless, more studies are required to clarify its role in a possible long term protection against IR generated by Dex.