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.

Ultrasound and nerve stimulator guided continuous femoral nerve block analgesia after total knee arthroplasty: a multicenter randomized controlled study / Bloqueio contínuo do nervo femoral guiado por ultrassom e estimulador de nervo para analgesia após artroplastia total de joelho: estudo multicêntrico, randomizado e controlado / Bloqueo continuo del nervio femoral guiado por ultrasonido y estimulador de nervio para analgesia posterior a la artroplastia total de rodilla: estudio multicéntrico, aleatorizado y controlado

BACKGROUND AND OBJECTIVES: Postoperative analgesia is crucial for early functional excise after total knee arthroplasty. To investigate the clinical efficacy of ultrasound and nerve stimulator guided continuous femoral nerve block analgesia after total knee arthroplasty. METHODS: 46 patients with ASA grade I-III who underwent total knee arthroplasty received postoperative analgesia from October 2012 to January 2013. In 22 patients, ultrasound and nerve stimulator guided continuous femoral nerve block were performed for analgesia (CFNB group); in 24 patients, epidural analgesia was done (PCEA group). The analgesic effects, side effects, articular recovery and complications were compared between two groups. RESULTS: At 6 h and 12 h after surgery, the knee pain score (VAS score) during functional tests after active exercise and after passive excise in CFNB were significantly reduced when compared with PCEA group. The amount of parecoxib used in CFNB patients was significantly reduced when compared with PCEA group. At 48 h after surgery, the muscle strength grade in CFNB group was significantly higher, and the time to ambulatory activity was shorter than those in PCEA group. The incidence of nausea and vomiting in CFNB patients was significantly reduced when compared with PCEA group. CONCLUSION: Ultrasound and nerve stimulator guided continuous femoral nerve block provide better analgesia at 6 h and 12 h, demonstrated by RVAS and PVAS. The amount of parecoxib also reduces, the incidence of nausea and vomiting decreased, the influence on muscle strength is compromised and patients can perform ambulatory activity under this condition. .

JUSTIFICATIVA E OBJETIVOS: Analgesia pós-operatória é fundamental para o exercício funcional precoce logo após a artroplastia total de joelho. O objetivo foi investigar a eficácia clínica do bloqueio contínuo do nervo femoral guiado por ultrassom e estimulador de nervo em analgesia após artroplastia total do joelho. MÉTODOS: Receberam analgesia pós-operatória, de outubro de 2012 a janeiro de 2013, 46 pacientes, estado físico ASA I-III, submetidos à artroplastia total de joelho. Em 22 pacientes, o bloqueio femoral contínuo foi guiado por ultrassom e estimulador de nervo para analgesia (grupo BFC); em 24 pacientes, analgesia foi administrada por via epidural (grupo ACP). Os efeitos analgésicos, efeitos colaterais, a recuperação articular e as complicações foram comparados entre os dois grupos. RESULTADOS: Às seis e 12 horas após a cirurgia, os escores de dor no joelho (escore EVA) durante os testes funcionais após exercício ativo e passivo foram significativamente menores no grupo BFC do que no grupo ACP. A quantidade usada de parecoxib nos pacientes do grupo BFC foi significativamente menor em comparação com o grupo ACP. Quarenta e oito horas após a cirurgia, o grau de força muscular no grupo BFC foi significativamente maior e o tempo de atividade ambulatória foi menor do que no grupo ACP. A incidência de náusea e vômito em pacientes do grupo BFC foi significativamente menor em comparação com o grupo ACP. CONCLUSÃO: O bloqueio femoral contínuo guiado por ultrassom e estimulador do nervo proporcionou melhor analgesia às seis e 12 horas, demonstrada por EVA-R e EVA-P. A quantidade de parecoxib também foi menor, a incidência de náusea e vômito diminuiu, a influência sobre a força muscular é comprometida e os pacientes podem fazer atividade ambulatorial sob essa condição. .

JUSTIFICACIÓN Y OBJETIVOS: La analgesia postoperatoria es fundamental para el ejercicio funcional precoz posteriormente a la artroplastia total de rodilla. El objetivo fue investigar la eficacia clínica del bloqueo continuo del nervio femoral guiado por ultrasonido y estimulador de nervio en analgesia después de la artroplastia total de la rodilla. MÉTODOS: Cuarenta y seis pacientes, con estado físico ASA I-III, sometidos a artroplastia total de rodilla recibieron analgesia postoperatoria de octubre de 2012 a enero de 2013. En 22 pacientes, el bloqueo femoral continuo fue guiado por ultrasonido y estimulador de nervio para analgesia (grupo BFC); en 24 pacientes, la analgesia fue administrada por vía epidural (grupo ACP). Los efectos analgésicos, efectos colaterales, recuperación articular y las complicaciones fueron comparados entre los 2 grupos. RESULTADOS: A las 6 y 12 h después de la operación, las puntuaciones de dolor en la rodilla (puntuación EVA) durante los test funcionales después del ejercicio activo y pasivo fueron significativamente menores en el grupo BFC que en el grupo ACP. La cantidad usada de parecoxib en los pacientes del grupo BFC fue significativamente menor en comparación con el grupo ACP. Cuarenta y ocho horas después de la operación, el grado de fuerza muscular en el grupo BFC fue significativamente mayor y el tiempo de actividad ambulatoria fue menor que en el grupo ACP. La incidencia de náuseas y vómitos en pacientes del grupo BFC fue significativamente menor en comparación con el grupo ACP. CONCLUSIÓN: El bloqueo femoral continuo guiado por ultrasonido y estimulador del nervio proporcionaron una mejor analgesia a las 6 y 12 horas, lo que quedó demostrado por EVA-R y EVA-P. La cantidad de parecoxib también fue menor, la incidencia de náuseas y vómito disminuyó, la influencia sobre la fuerza muscular está comprometida y los pacientes pueden realizar una actividad ambulatoria bajo esa condición. .

Cyclooxygenase-2 inhibitors modulate skin aging in a catalytic activity-independent manner

It has been proposed that the pro-inflammatory catalytic activity of cyclooxygenase-2 (COX-2) plays a key role in the aging process. However, it remains unclear whether the COX-2 activity is a causal factor for aging and whether COX-2 inhibitors could prevent aging. We here examined the effect of COX-2 inhibitors on aging in the intrinsic skin aging model of hairless mice. We observed that among two selective COX-2 inhibitors and one non-selective COX inhibitor studied, only NS-398 inhibited skin aging, while celecoxib and aspirin accelerated skin aging. In addition, NS-398 reduced the expression of p53 and p16, whereas celecoxib and aspirin enhanced their expression. We also found that the aging-modulating effect of the inhibitors is closely associated with the expression of type I procollagen and caveolin-1. These results suggest that pro-inflammatory catalytic activity of COX-2 is not a causal factor for aging at least in skin and that COX-2 inhibitors might modulate skin aging by regulating the expression of type I procollagen and caveolin-1.

Efficacy of etoricoxib for pain relief during endometrial biopsy; a double blind randomized controlled trial.

OBJECTIVE: To compare the efficacy of oral etoricoxib and placebo for pain relief during endometrial biopsy. MATERIAL AND METHOD: A double-blind, randomized controlled trial that included 80 women who underwent endometrial biopsy was done at Thammasat University Hospital between 1 September 2005 and 30 June 2006. Forty women were randomly allocated to the etoricoxib group (120 mg, tablet) and 40 to the placebo group. The main outcome was the patient's assessment of intensity of pain measured by visual analog scale (VAS) before speculum insertion, during endometrial biopsy, immediately after endometrial biopsy, and 30 minutes after endometrial biopsy. Satisfactory score was also evaluated. RESULTS: Demographic data including age, BMI, previous vaginal deliveries, previous pelvic surgery and history of curettage were not significantly different between the etoricoxib group and the placebo group. Mean pain score in the etoricoxib group was not significantly lower when compared with the placebo group during endometrial biopsy (5.0 +/- 1.7 versus 5.25 +/- 2.2, p = 0.7) and immediately after endometrial biopsy (2.1 +/- 2.2 versus 2.8 +/- 1.7, p = 0.1) but significantly lower at 30 minutes after endometrial biopsy (0.2 +/- 0.5 versus 0.6 +/- 0.8, p = 0.01). Mean satisfactory score was significantly higher in the etoricoxib group (6.9 +/- 1.8 versus 5.1 +/- 2.3, p = 0.001). CONCLUSION: A single oral dose of etoricoxib for reduction of pain during endometrial biopsy had not significantly lower the pain score during the procedure compared with the placebo. However mean satisfactory score in the etoricoxib group was higher with statistically significant difference. Also the authors found no serious adverse effects of this drug.

Prevention of post operative pain after abdominal hysterectomy by single dose etoricoxib.

OBJECTIVE: To test whether a reduction in post operative morphine consumption could be achieved by a single-dose of etoricoxib before induction of anesthesia. DESIGN: Randomized, double-blind, placebo-controlled study. MATERIAL AND METHOD: Two hours before surgery, patients undergoing transabdominal hysterectomy (under general anesthesia) were randomized to a single oral dose of 1) etoricoxib 120 mg (n = 17), 2) etoricoxib 180 mg (n = 17), or 3) placebo (n = 15). Intravenous morphine was given for patient-controlled analgesia (PCA) device. Morphine consumption, pain scores both at rest and on coughing, and side-effects were recorded at 1, 2, 4, 8 and 24 h after surgery. Patients' global evaluation of study medication was assessed at the end of the present study. RESULTS: Etoricoxib provided greater clinical benefit than the placebo in terms of mean morphine in milligram at 24 hour consumption (stardard deviation): a) 26.4 mg (SD of 11.2) for etoricoxib 120 mg; b) 27.2 mg (SD of 9.9) for etoricoxib 180 mg; and, c) 36.6 mg (SD of 8.9) for the placebo group. At 8 h post surgery, pain both at rest and on coughing in the active drug groups was significantly less than in the placebo, while pain on coughing was significantly less at 24 h. Patients reported better global satisfaction and less somnolence in the etoricoxib groups. CONCLUSION: Single dose etoricoxib 180 mg given before surgery provides the same analgesic effect as 120 mg for post operative pain after an abdominal hysterectomy.

Oral etoricoxib for pain relief during fractional curettage: a randomized controlled trial.

OBJECTIVE: To compare the efficacy of oral etoricoxib and placebo combined with paracervical block for pain relief during fractional curettage MATERIAL AND METHOD: A double-blind, randomized controlled trial that included 220 women who underwent fractional curettage and received paracervical block for pain relief was done at Ramathibodi Hospital between September 2005 and June 2006. One hundred and ten women were randomly allocated to the etoricoxib group (90 mg, tablet) and 110 to the placebo group. The main outcome was the patient's assessment of intensity of pain measured by verbal rating scales after speculum insertion, during fractional curettage, immediately after curettage, and 30 minutes after curettage. RESULTS: Demographic data including age, previous vaginal deliveries, and history of curettage were not significantly different between etoricoxib group and placebo group. Most common indication for fractional curettage was menometrorrhagia in both groups. Pain score in etoricoxib group was significant lower during fractional curettage (5 vs. 6, p = 0.04), immediately after curettage (2 vs. 3, p = 0. 009), and 30 minutes after curettage (0 vs. 1, p = 0.003). Comparing the number of patients with mild pain (score 0-3), there were significant higher number of mild pain patient at the time during curettage (39 vs. 20 cases), immediate after curettage (78 vs. 60 cases), and 30 minutes after curettage (107 vs. 100 cases) in etoricoxib group. CONCLUSION: Combination of etoricoxib with paracervical block for reduction of pain during fractional curettage had statistically significant lower pain scale when compared with placebo with paracervical block. However the difference was small and may have questionable clinical significance.

Quantitative structure-activity relationship study of orally active cyclooxygenase-2 (COX-2) inhibitors of derivatives of 3-phenoxypyran-4-one.

The cyclooxygenase (COX) inhibition activities of the derivatives of 3-phenoxypyran-4-one were analyzed through multiple-regression analysis (MRA). Appropriate physicochemical parameters, identified for the substitutents of phenyl ring, attached to 3-phenoxypyran-4-one moiety were quantitatively correlated with COX-2 and COX-1 inhibition activities of these compounds. The derived significant correlation equation for COX-2 inhibition suggested that the ortho-substituent with negative resonance parameter, the para-substituent with lower dipole moment and the meta-substituent having higher resonance parameter were advantageous for the activity. The derived correlation equation for COX-1 inhibition suggested the significance of resonance effect for ortho-substituents and electron-donating effect for para-substituent. A few potential congeners were also suggested for further synthesis.

A Case of Complete Regression of Hepatocellular Carcinoma during Administration of COX-2 Inhibitor / 대한간학회지

Overexpression of cyclooxygenase-2 (COX-2) has been associated with hepatocarcinogenesis. Inhibitors of COX-2 have proapoptotic and antiproliferative effects on malignant tumors and inhibit tumor invasion to the surrounding tissues. We report here a case of complete regression of advanced hepatocellular carcinoma (HCC) during COX-2 inhibitor administration. An eighty-year-old female was diagnosed as an advanced HCC, which was associated with HCV infection. She received COX-2 inhibitor for 3 months due to degenerative arthritis of both knees. Tumor enhancement on arterial phase CT completely disappeared without specific treatment for the HCC, and the tumor size decreased on the follow-up CT scan.