Effect of pre-administered flurbiprofen axetil on the EC50 of propofol during anesthesia in unstimulated patients: a randomized clinical trial / Efeito da pré‐ administração de flurbiprofeno axetil na CE50 do propofol durante anestesia em pacientes não estimulados: estudo clínico randomizado

Abstract Background and objectives Preoperative use of flurbiprofen axetil (FA) is extensively adopted to modulate the effects of analgesia. However, the relationship between FA and sedation agents remains unclear. In this study, we aimed to investigate the effects of different doses of FA on the median Effective Concentration (EC50) of propofol. Methods Ninety-six patients (ASA I or II, aged 18-65 years) were randomly assigned into one of four groups in a 1:1:1:1 ratio. Group A (control group) received 10 mL of Intralipid, and groups B, C and D received 0.5 mg.kg−1, 0.75 mg.kg−1 and 1 mg.kg−1 of FA, respectively, 10 minutes before induction. The depth of anesthesia was measured by the Bispectral Index (BIS). The "up-and-down" method was used to calculate the EC50 of propofol. During the equilibration period, if BIS ≤ 50 (or BIS > 50), the next patient would receive a 0.5 µg.mL−1-lower (or -higher) propofol Target-Controlled Infusion (TCI) concentration. The hemodynamic data were recorded at baseline, 10 minutes after FA administration, after induction, after intubation and 15 minutes after intubation. Results The EC50 of propofol was lower in Group C (2.32 µg.mL−1, 95% Confidence Interval [95% CI] 1.85-2.75) and D (2.39 µg.mL−1, 95% CI 1.91-2.67) than in Group A (2.96 µg.mL−1, 95% CI 2.55-3.33) (p = 0.023, p = 0.048, respectively). There were no significant differences in the EC50 between Group B (2.53 µg.mL−1, 95% CI 2.33-2.71) and Group A (p > 0.05). There were no significant differences in Heart Rate (HR) among groups A, B and C. The HR was significantly lower in Group D than in Group A after intubation (66 ± 6 vs. 80 ± 10 bpm, p < 0.01) and 15 minutes after intubation (61 ± 4 vs. 70 ± 8 bpm, p < 0.01). There were no significant differences among the four groups in Mean Arterial Pressure (MAP) at any time point. The MAP of the four groups was significantly lower after induction, after intubation, and 15 minutes after intubation than at baseline (p < 0.05). Conclusion High-dose FA (0.75 mg.kg−1 or 1 mg.kg−1) reduces the EC50 of propofol, and 1 mg.kg−1 FA reduces the HR for adequate anesthesia in unstimulated patients. Although this result should be investigated in cases of surgical stimulation, we suggest that FA pre-administration may reduce the propofol requirement when the depth of anesthesia is measured by BIS.

Resumo Justificativa e objetivos A administração pré‐operatória de Flurbiprofeno Axetil (FA) é amplamente usada para a modulação da analgesia. No entanto, a relação entre FA e fármacos sedativos permanece obscura. Neste estudo, nosso objetivo foi investigar os efeitos de diferentes doses de FA na Concentração Efetiva mediana (CE50) do propofol. Métodos Noventa e seis pacientes (ASA I ou II, com idades de 18-65 anos) foram alocados aleatoriamente em quatro grupos na proporção de 1:1:1:1. Dez minutos antes da indução, o Grupo A (grupo controle) recebeu 10 mL de Intralipid, enquanto os grupos B, C e D receberam FA na dose de 0,5 mg.kg‐1; 0,75 mg.kg‐1 e 1 mg.kg‐1, respectivamente. A profundidade da anestesia foi medida pelo Índice Bispectral (BIS). O método up‐and‐down foi usado para calcular a CE50 do propofol. Durante o período de equilíbrio, se o valor do BIS fosse ≤ 50 ou BIS > 50, o próximo paciente tinha a infusão de propofol ajustada para uma concentração alvo‐controlada 0,5 µg.mL‐1 inferior ou superior, respectivamente. Os dados hemodinâmicos foram registrados no início do estudo, 10 minutos após a administração de FA, após a indução, após a intubação e 15 minutos após a intubação. Resultados A CE50 do propofol foi menor no Grupo C (2,32 µg.mL‐1, Intervalo de Confiança de 95% [95% IC] 1,85-2,75) e D (2,39 µg.mL‐1, 95% IC 1,91-2,67) do que no Grupo A (2,96 µg.mL‐1; 95% IC 2,55-3,33) (p = 0,023, p = 0,048, respectivamente). Não houve diferenças significantes na CE50 entre o Grupo B (2,53 µg.mL‐1, 95% IC 2,33-2,71) e o Grupo A (p > 0,05). Não houve diferenças significantes na Frequência Cardíaca (FC) entre os grupos A, B e C. A FC foi significantemente menor no grupo D do que no grupo A após a intubação (66 ± 6 vs. 80 ± 10 bpm, p < 0,01) e 15 minutos após a intubação (61 ± 4 vs. 70 ± 8 bpm, p < 0,01). Não houve diferenças significantes entre os quatro grupos na Pressão Arterial Média (PAM) em qualquer momento. A PAM dos quatro grupos foi significantemente menor após a indução, após a intubação e 15 minutos após a intubação do que na linha de base (p < 0,05). Conclusão FA em altas doses (0,75 mg.kg‐1 ou 1 mg.kg‐1) reduz a CE50 do propofol, e 1 mg.kg‐1 de FA reduz a FC durante níveis adequados de anestesia em pacientes não estimulados. Embora esse resultado deva ser investigado na presença de estimulação cirúrgica, sugerimos que a pré‐administração de FA pode reduzir a necessidade de propofol durante anestesia cuja profundidade seja monitorada pelo BIS.

Formulation Optimization And Evaluation Of Flurbiprofen Emulgel

Objective: The objective of the present study was to formulate flurbiprofen (FLB) emulgel, evaluation of the formulations and the selection of an optimized formulation through in vitro drug release and drug content studies. Flurbiprofen is a non-steroidal anti-inflammatory drug (NSAID) requiring frequent administration and its chronic intake can lead to systemic side effects like gastric irritation and GI bleeding. The development of a dermal drug delivery system can overcome these side effects. Methods: The emulgel formulations were produced using different combinations of oil and emulsifying agents. Carbopol 940 was used as a gelling agent. The prepared emulgels were evaluated for general appearance, pH, spreadability, extrudability, drug content, in vitro drug release, average globule size and viscosity. Results: Optimized formulation F7 showed a better in vitro drug release compared to the marketed gel preparation. The stability study for the optimized formulation was carried out at 25 °C/60 % RH for 3 mo and the emulgel was found to be stable concerning the physical appearance, pH and drug content. Conclusion: The study revolved around the formulation of emulgel containing Flurbiprofen for dermal delivery of the drug. Emulgel was formulated with the purpose to enhance the permeation of poorly water-soluble drug FLB. The study concluded that the optimized emulgel containing FLB exhibited better in vitro drug release profile compared to the marketed formulation.

Effect of dexmedetomidine combined with flurbiprofen axetil on postoperative pain and cognitive function of patients after thyroid gland surgery / 中国基层医药

Objective@#To investigate the effect of dexmedetomidine combined with flurbiprofen axetil on pain and cognitive function of patients after thyroidectomy.@*Methods@#A total of 80 patients with thyroid gland surgery in the People's Hosptial of Shouguang from January 2016 to December 2017 were selected and randomly divided into four groups according to the digital table: saline control group(C), dexmedetomidine group(D), flurbiprofen axetil group(F), dexmedetomidine combined with flurbiprofen axetil group(DF), with 20 casess in each group.The extubation time and wake-up time of the four groups were observed.The VAS scores were used to assess the analgesic effect after surgery, and the Riker sedation scale was used to assess postoperative anxiety.@*Results@#The extubation time of the C, D, F and FD group were (16.66±3.37)min, (24.63±2.80)min, (14.55±3.74)min, (26.22±3.45)min, respectively, which of group D and group DF was significantly longer than that in group C and group F(F= 4.59, P<0.01). The recovery time of group D[(17.98±2.54)min] and group DF[(17.84±3.63)min] was significantly longer than that of group F[(10.92±2.21) min] and group C[(9.95±2.16)min] (F=5.01, P<0.01). The VAS scores of group DF at 30 min, 3 h, 6 h and 24 h after recovery were significantly lower than those of group F and group D (F=4.53, 4.59, 4.61, 4.35, all P<0.01). The Rick sedation scores of C, D, F and FD groups were (5.28±1.81)points, (4.20±1.56)points, (4.24±2.01)points and (3.76±1.43)points, respetively, which of group DF was significantly lower than those of the other three groups(F=3.01, P<0.01). The MMSE scores of cognitive function in group DF at 3 h, 1 d and 3 d after surgery were significantly higher than those in group C (F=5.89, 4.95, 4.56, all P<0.01).@*Conclusion@#The combined use of dexmedetomidine and flurbiprofen axetil significantly reduces pain and relieves postoperative cognitive impairment after thyroid surgery.

A prospective evaluation of efficacy and safety of topical bromfenac 0.09% over topical flurbiprofen 0.03% after cataract surgery

Background: Different medications are used to reduce pain and inflammation after cataract surgery. Hence this study was taken up to compare the efficacy and safety of topical bromfenac 0.09% over topical flurbiprofen 0.03% in reducing anterior chamber inflammation and pain after cataract surgery.Methods: Total of 100 patients who underwent uneventful cataract surgery with posterior chamber intra ocular lens (IOL) implantation were randomly allocated to receive bromfenac 0.09% and flurbiprofen 0.03% topically from first post-operative day onwards for 6 weeks. Assessment of anterior chamber inflammation and pain was done by slit lamp and visual analogue scale respectively on each follow up days. Analysis was done by unpaired t test and Fischer’s exact test.Results: The response to treatment was earlier in bromfenac group for all the inflammatory changes (significant difference was found on day 7, p<0.05) except for corneal edema where both the groups showed similar response. On 7th day after surgery, 72% patients in flurbiprofen group and 12% in bromfenac group had pain (score1), while on the 14th day none in the bromfenac group complained of pain whereas 4% in flurbiprofen group still had pain. Both the drugs were safe and no clinically serious adverse effects were observed in either of the groups.Conclusions: This study showed both the medications, topical bromfenac 0.09% and topical flurbiprofen 0.03% effective and safe in reducing pain and anterior chamber inflammation after cataract surgery but the response was earlier with bromfenac 0.09%.

Effects of preemptive analgesia by nalbuphine combined with flurbiprofen on pain and platelet activity in patients with decompensated cirrhosis / 吉林大学学报(医学版)

Objective: To observe the influence of preemptive analgesia by nalbuphine combined with flurbiprofen in the platelet activity indexes of the patients with decompensated cirrhosis, and to explore its quality of analgesia in the patients with decompensated cirrhosis. Methods: A total of 120 patients with decompensated cirrhosis were randomly divided into combination group (40 cases, given nalbuphine combined with flurbiprofen before anesthesia), nalbuphine group (40 cases, given nalbuphine before anesthesia) and flurbiprofen group (40 cases, given flurbiprofen before anesthesia). The postoperative patient-controlled intravenous analgesia (PCIA) was carried out with sufentanil in all the patients. The indexes of visual analog score (VAS), PCIA compression number, sufentanil consumption, Ramsay score, thrombelastogram (TEG) indexes (R value, K value, a angle, MA value and CI value) and the maximum aggregation rate by arachidonic acid (MARAA) and β-endorphin (β-EP) level, recovery time, and agitation occurrence rate of the patients in various groups were recorded 12 h and 24 h after operation. Results: The indexes of VAS, PCIA compression number, sufentanil consumption and 3-EP level of the patients in combination group were lower than those in the other groups 12 and 24 h after operation (P0. 05). The Ramsay scores of the patients in three groups had no differences at 12 and 24 h after operation (P>0. 05). Compared with nalbuphine group, the R values and K values of the patients in combination group and flurbiprofen group at 12 and 24 h after operation were increased (P 0. 05). The recovery time of the patients among three groups had no significant difference (F=2. 054, P=0. 102). The agitation occurrence rate during recovery period of the patients in case group was the highest (F=5. 624, P= 0. 001), and there was no significant difference in the agitation occurrence rate during recovery period of the patiens between nalbuphine group and flurbiprofen group (χ2 =3. 020, P=0. 091). Conclusion: Combination of nalbuphine and flurbiprofen in the patients with decompensated cirrhosis before analgesia can improve the quality of postoperative analgesia and can' t inhibit the activity of platelet obviously.

Postoperative administration of flurbiprofen helps rapid rehabilitation of the patient following minimally invasive esophagectomy / 医学研究生学报

Objective Pain is an important factor affecting rapid rehabilitation of the patient after minimally invasive esophagectomy (MIE), and few studies are reported on the analgesic effect of intravenous administration of flurbiprofen (FBP) following MIE. This study was to investigate the role of FBP analgesia in rapid rehabilitation of the patients after MIE. Methods Sixty-four patients with esophageal cancer underwent MIE in the General Hospital of Eastern Theater Command from October 2015 to October 2016. Thirty-two of them received analgesia with a patient-controlled analgesia (PCA) pump (the control group) and the other 32 with FBP plus a PCA pump (the FBP group) postoperatively. We measured the concentrations of serum interleukin 6 (IL-6) and procalcitonin (PCT) at 12, 24, 48 and 72 hours after surgery, recorded the visual analog scale (VAS) pain scores at rest, and compared the parameters obtained between the two groups of patients. Results Compared with the control group, the FBP group showed significantly decreased concentrations of serum IL-6 ([156.53 ± 13.46] vs [120.19±13.52] μg/L, P < 0.05) and PCT ([1.99 ± 0.12] vs [1.89 ± 0.18] μg/L, P < 0.05) at 12 hours after MIE, even more significantly at 24, 48 and 72 hours (P < 0.05). And the VAS scores were markedly lower in the FBP than in the control group at all the four time points (P < 0.05). Conclusion Postoperative intravenous administration of flurbiprofen can significantly reduce inflammatory reaction, relieve pain and contribute to rapid rehabilitation after minimally invasive esophagectomy.

Optimum compatibility of nabufine mixed with flurbiprofen for patient-controlled intravenous analgesia after gynecological laparoscopic surgery: a multicenter, randomized, controlled clinical trial / 中华麻醉学杂志

Objective To evaluate the optimum compatibility of nabufine mixed with flurbiprofen for patient-controlled intravenous analgesia (PCIA) after gynecological laparoscopic surgery.Methods A total of 210 patients,aged 18-64 yr,with body mass index of 18-30 kg/m2,of American Society of Anesthesiologist physical status Ⅰ or Ⅱ,scheduled for gynecological laparoscopic surgery under general anesthesia,were divided into 4 groups using a random number table method:sufentanil 2.0 μg/kg+flurbiprofen axetil 2.0 mg/kg group (SF group,n =55),nalbuphine 1.5 mg/kg+flurbiprofen axetil 2.0 mg/kg group (N1 F group,n=49),nalbuphine 2.0 mg/kg+flurbiprofen axetil 2.0 mg/kg group (N2F group,n =55) and nalbuphine 3.0 mg/kg +flurbiprofen axetil 2.0 mg/kg group (N3F group,n=51).PCIA solution was prepared correspondingly after surgery in each group.The PCA pump was set up to deliver a 1 ml bolus dose with a 15-min lockout interval and background infusion at 2.0 ml/h.Nalbuphine 5 mg or sufentanil 5 μg was intravenously injected as a rescue analgesic to maintain visual analogue scale score at rest ＜4 at 48 h after surgery in SF and N1 F-N3F groups.Ramsay sedation scores were recorded on admission to post-anesthesia care unit (T1),at the time of post-anesthesia care unit discharge (T2) and at 6,24 and 48 h after surgery (T3-5).The total pressing times of PCIA in 0-6 h,6-24 h and 24-48 h periods after surgery and requirement for rescue analgesics were recorded.The incidence of adverse reactions such as nausea and vomiting,drowsiness and shivering within 48 h after surgery was also recorded.Results Compared with group SF,the incidence of nausea and vomiting was significantly decreased in N1 F and N2F groups,the requirement for rescue analgesics was significantly decreased,and the total pressing times of PCIA was reduced in N2F and N3 F groups,and Ramsay sedation scores at T3,4 were significantly increased in group N3F (P＜0.05).Compared with group N1 F,the requirement for rescue analgesics was significantly decreased,and the total pressing times of PCIA was reduced in N2F and N3F groups,and the incidence of nausea and vomiting and Ramsay sedation scores at T3,4 were significantly increased in group N3F (P＜0.05).Compared with group N2F,the incidence of nausea and vomiting was significantly increased (P＜ 0.05),and no significant change was found in the requirement for rescue analgesics,total pressing times of PCIA or Ramsay sedation scores in group N3F (P＞0.05).Conclusion Nabufine 2.0 mg/kg mixed with flurbiprofen 2.0 mg/kg is the optimum compatibility when used for PCIA after gynecological laparoscopic surgery.

A comparative study on efficacy of nepafenac and flurbiprofen in maintenance of intraoperative mydriasis during cataract surgery: an open label randomized controlled trial

Background: Surgery on the ocular tissue brings about activation of phospholipase A3 thereby releasing prostaglandins and leukotrienes. Prostaglandins bring about meiosis during surgery, changes in IOP, conjunctival hyperaemia. Newer topical NSAID抯 Nepafenac and Flurbiprofen are potent inhibitors of the cyclooxygenase enzyme thereby inhibiting the biosynthesis of prostaglandins. Objective of this study was to compare the efficacy of preoperative use of topical Nepafenac (0.1%) and Flurbiprofen (0.03%) in maintenance of intraoperative mydriasis during cataract surgery.Methods: A randomised, comparative study was performed on 104 patients, 52 were allocated in each group and were given either of the topical NSAID抯 Nepafenac or Flurbiprofen prior to cataract surgery. Pupillary diameter was measured at the beginning and at the end of the surgery and the values were compared between the groups. Mean and standard deviation was calculated and between two groups comparison was done using students t-test.Results: The mean pupillary diameter of the two groups were comparable at the beginning of surgery (p=0.34). The mean change in the pupillary diameter was 1.86�71mm in the Nepafenac group and 1.77�72mm in the Flurbiprofen group. There was no statistically significant difference among both the groups in maintenance of intraoperative mydriasis (p=0.47).Conclusions: Pre-operative use of Nepafenac and Flurbiprofen were equally effective in preventing meiosis during cataract surgery.

Development of fast dissolving tablets of flurbiprofen by sublimation method and its in vitro evaluation

Flurbiprofen belongs to Biopharmaceutical Classification System (BCS) class II drugs which are poorly soluble in water. The objective of present research work was to prepare fast dissolving tablets of Flurbiprofen using varying concentrations of three different sublimating agents to improve the dissolution rate. Seven formulations were prepared containing different concentrations of camphor, ammonium bicarbonate and thymol as sublimating agent along with primogel as a superdisintegrant. Tablets were manufactured by direct compression method. The prepared tablets were evaluated for pre-compression and post-compression parameters result, For all formulations result was within official limits. FTIR studies revealed that there were no interactions between the drug and the excipients used. From in vitro drug release studies it was concluded that the formulations F6 and F7 containing 10% and 15% of thymol showed fast drug release of 100.00% and 100.84% respectively in 30 minutes. Formulations containing camphor (F2 & F3) and ammonium bicarbonate (F4 & F5) as sublimating agents showed a drug release of less than 80%, while the control formulation F1 having no sublimating agent showed 49.14% of drug release in 30 minutes. Thus thymol can successfully be used to formulate fast dissolving tablets of flurbiprofen by sublimation method with much better dissolution profile

Efficacy and Economic Evaluation of Tramadol and Hydromorphone Combined with Flurbiprofen Axetil in the Treatment of PCIA for Postoperative Cesarean / 中国药学杂志

OBJECTIVE: To evaluate the efficacy, safety and economy of tramadol and hydromorphone combined with flurbiprofen axetil in the treatment of PCIA for postoperative cesarean through the empirical study, optimize the drug treatment program and provide certain evidence-based medicine and pharmacoeconomics basis for clinical use of drugs. METHODS: Included 240 cases of maternal, these maternal need to use PCIA for postoperative analgesia and meet the inclusion and exclusion criteria. The maternal samples included in the study were divided into two groups: tramadol(tramadol 2 mg •kg-1 + flurbiprofen axetil 5 mg•kg-1) and hydromorphone(hydromorphone 0.04 mg •kg-1 + flurbiprofen axetil 5 mg•kg-1). The efficacy index, safety index and cost index of the two groups were observed. The effectiveness, adverse reactions and cost data were collected. Statistical analysis and cost effectiveness analysis were used to evaluate the economic effects of the two groups. RESULTS: The analgesic effect of tramadol group was same as the hydromorphone group, but the total cost of analgesia in tramadol group was lower than that in hydromorphone group, the results of the minimum cost analysis showed that the tramadol regimen was superior and the results were stable. CONCLUSION: The PCIA regimen of tramadol group is superior to that of the hydromorphone group, considering the efficacy, safety and economy.

Effect of flurbiprofen axetil for postoperative analgesia on blood coagulation: a meta-analysis / 中华创伤骨科杂志

Objective To analyze the effect of flurbiprofen axetil (FA) on blood coagulation in patients undergoing surgery through systematic review and meta-analysis.Methods PubMed,WanFang and CNKI databases were searched from their establishment to August 2017 by computer retrieval for relevant literature on the blood coagulation effect of FA.The references of the studies included were also searched by hand.Two reviewers independently screened the literature,extracted data from full-text articles,and evaluated the methodological quality of included studies.All data were analyzed by Review Manager 5.3.Results Altogether 11 studies were finally included,consisting of 10 RCTs and one case-control study,involving 643 patients undergoing surgery.The mean Jadad score for all the studies included were less than 3,suggesting low methodological quality of the studies included.The pool analysis of 4 blood coagulation indexes (prothrombin time,thrombin time,activated partial thromboplastin time and fibrinogen) and platelet count showed that there were no significant differences between the control group and flurbiprofen axetil group before treatment and at 30 min,1-2 h,6-8 h,12 h,24 h and 48 h after treatment(P ＞ 0.05).As for other outcomes like Sonoelot coagulation indexes [activated clotting time of whole blood,coagulation rate and platelet function (PF)],time to peak,mean platelet volume,maximum platelet aggregation rate,platelet aggregation rate at 1 min (PAG1),platelet aggregation rate at 5 min (PAG5) and platelet aggregation rate maximum,no significant differences were found except in one study where PF was found to be lower at 2 h after treatment in the FA group than in the control group.Conclusion Use of FA in common clinical doses is safe for postoperative analgesia,because blood coagulation may not be significantly affected.

Analgesia,Sedation Effects and Safety of Flurbiprofen Axetil Combined with Hydromorphone for PCIA after Orthopedics Surgery / 中国药房

OBJECTIVE:To observe analgesia,sedation effects and safety of flurbiprofen axetil combined with hydromorphone for postoperative patient-controlled intravenous analgesia (PCIA) after orthopedics surgery. METHODS:Totally 90 patients with combined spinal epidural anesthesia underwent lower limb surgery were selected from anesthesology department in the Affiliated Hospital of Chengde Medical College during May 2016-Jan. 2018. They were divided into SF group,H group and KH group according random number table,with 30 cases in each group. The postoperative PCIA pump drug liquid formula of SF group included Sufentanil citrate injection 2-3 μ g/kg+Tropisetron hydrochloride for injection 10 mg+0.9% Sodium chloride injection diluted to 100 mL;that of H group included Hydromorphone hydrochloride injection 0.12 mg/kg+Tropisetron hydrochloride for injection 10 mg+0.9% Sodium chloride injection diluted to 100 mL;that of KH group included Hydromorphone hydrochloride injection 0.12 mg/kg+Flurbiprofen axetil injection 50 mg+Tropisetron hydrochloride for injection 10 mg+0.9% Sodium chloride injection diluted to 100 mL. The operation time, intraoperative medication (epidural application frequency of additional ropivacaine,frequency of ephedrine and atropine),effective pressing times of analgesic pump and the analgesic effect of PCIA were observed in 3 groups. VAS score and Ramsay sedation score were observed 2,6,12,24,48 h after surgery. The hospital anxiety and depression scale (HAD) score,profile of mood states (POMS) score and the occurrence of ADR were observed before and after surgery. RESULTS:There was no statistical significance in operation time,epidural application frequency of additional ropivacaine or frequency of ephedrine and atropine among 3 groups (P＞0.05). The effective pressing times of analgesic pump in KH group were significantly lower than SF group and H group. The proportion of patients with excellent and good anesthesia effect in KH group was significantly higher than SF group and H group (P＜0.05);there was no statistical significance between SF group and H group(P＞0.05). VAS score of 3 groups 48 h after surgery were significantly lower than 6, 12,24 h after surgery;that of KH group was significantly lower than SF group and H group(P＜0.05);there was no statistical significance between SF group and H group(P＞0.05). There was no statistical significance in Ramsay score among 3 groups at different time points(P＞0.05). Before surgery,there was no statistical significance in HAD score or POMS score among 3 groups (P＞0.05). After surgery,HAD score and POMS score of KH group and H group were significantly lower than before surgery and SF group(P＜0.05);there was no statistical significance in KH group and H group,before and after surgery in SF group(P＞0.05). No vomiting,respiratory depression,pruritus and digestive tract bleeding were observed in 3 groups. The incidence of dizziness and nausea in H group and KH group were significantly lower than SF group (P＜0.05);there was no statistical significance between KH group and H group(P＞0.05). CONCLUSIONS:The flurbiprofen axetil combined with hydromorphone show good analgesic and sedative effect for PCIA after orthopedics operation,and can significantly improve emotion and mood of patients with good safety.

Clinical effect of flurbiprofen axetil in the postoperative analgesia of cervical cancer surgery / 实用肿瘤学杂志

Objective The objective of this study was to investigate the analgesic effect of flurbiprofen axetil and its effect on immune factors after cervical cancer surgery.Methods Ninety patients with cervical cancer undergoing laparoscopic surgery were ran-domly divided into three groups with 30 patients in each group in Zhongshan Hospital Affiliated to Dalian University from January 2016 to June 2017.The indexes of assessment were visual assessment of visual analog scale(VAS)pain assessment and postoperative adverse reaction at 2,12,24 and 48 h after operation.The levels of CD4,CD8,IL-1,IL-6,CD4/CD8 and PGEs in the serum at 12,24 and 48 h after operation were measured.Results The VAS scores in the A group were significantly lower than those in the B and C groups dur-ing 12 and 24 h after operation(P<0.05).But there were no significant differences in the levels of CD4,CD8,IL-1,IL-6,CD4/CD8 and PGEs amongst the three groups(P>0.05).The levels of IL-1 and IL-6 at 2,12 and 24 h after operation were significantly higher than those in the baseline(P<0.05).However,the levels of IL-1 and IL-6 in the C group was significantly higher than those in the A and B groups(P<0.05).Compared to before operation,the ratio of CD4/CD8 was decreased and the level of PGE2 was increased in the three groups after operation.After 24 h operation,the ratio of CD4/CD8 in the B group were significantly lower than that in the C group(P<0.05).The level of PGE2 at 12 h after operation was significantly increased in the B and C groups(P<0.05).Conclusion The combination of flurbiprofen axetil and sufentanil in the laparoscopic surgery of cervical cancer can improve postoperative analgesia and reduce adverse reactions,effectively reduce the secretion of inflammatory mediators and minor affect on cellular immune function.

Effects of postoperative PCIA with or without background infusion of dezocine plus flurbiprofen axetil in-jection in patients undergoing laparoscopic colorectal cancer operation / 实用医学杂志

Objective To compare the effectiveness of patient-controlled intravenous analgesia with or without background infusion of dezocine plus flurbiprofen axetil injection in patients undergoing laparoscopic colorectal cancer operation. Methods Sixty patients scheduled for laparoscopic colorectal cancer surgery,35 males and 25 females,aged 18-65 years,ASA physical status Ⅰ or Ⅱ,were randomly divided into 2 groups:common-dose background infusion group(Group CB,n = 30),and no background infusion group(Group NB, n = 30). All patients were intravenously administered a PCA pump containing dezocine 0.6 mg/kg,flurbiprofen axetil 3 mg/kg and normal saline in a volume of 120 mL.Patients in Group CB were given background infusion rate of 2 mL/h with PCA bolus dose 2 mL,patients in Group NB were given PCA bolus dose 4 mL only.NRS scores, Ramsay sedation scores,pressing times,consumption of analgesic,supplementary analgesics,incidence of ad-verse reactions,time of first exhaust,time of first leaving bed and patients'satisfaction scores were recorded after surgery. The influence factors of time of first exhaust and time of first leaving bed were also analyzed. Results Compared with group CB,the NRS scores in group NB were higher both at rest and during movement(P<0.05), the Ramsay sedation scores in group NB were lower at 24 and 48 h after surgery(P<0.05),the pressing times in group NB were higher(P < 0.05),the consumption of analgesic in group NB were lower after surgery,and the incidence of using supplementary analgesics was higher(P < 0.05). No statistical difference was found on the in-cidence of adverse reactions between the two groups(P > 0.05). Moreover,the time of first leaving bed in group NB was longer than that in group CB(P<0.05).The satisfaction scores in group NB was lower than that in group CB(P<0.05).The main influence factors of the time of first leaving bed were gender and NRS score during move-ment at 24 h after the operation(P<0.05).The main influence factors of the time of first exhaust were age,BMI and fluid infusion volume(P < 0.05). Conclusion Postoperative patient-controlled intravenous analgesia with background infusion of dezocine and flurbiprofen axetil injection was more efficacious and satisfactory,and more suitable in postoperative pain management.

Effects of dezocine or flurbiprofen combined with propofol-remifentanil in cervical precancerosis conization / 中国癌症杂志

Background and purpose: Cervical conization is a common operation to treat precancerous tissues performed under non-intubated anesthesia. As common opioid analgesics have side effects of inhibiting respiration and circulation, other kinds of analgesic drugs should be coordinated to improve the anesthetic effect, without interfering the respiration and circulation. This study aimed to evaluate the effects of dezocine or flurbiprofen combined with propofolremifentanil in cervical precancerosis conization. Methods: Sixty patients who underwent cervical conization were equally randomized into dezocine group (group D), flurbiprofen group (group F) and 0.9％ natural saline (group N) with 20 patients in each group, and received dezocine 0.1 mg/kg, flurbiprofen 1 mg/kg or 0.9％ natural saline in 5 mL respectively before anesthesia induction. During the anesthesia induction, the targeted control infusion of remifentanil in effect concentration was set at 1.5 ng/mL, and the plasma concentration of propofol was set at 2 μg/mL. Heart rate (HR), respiratory rate (RR), surplus pulse O2 (SPO2) and mean arterial pressure (MAP), MAP were monitored before the anesthesia induction (T0) and after (T1), at the start of cervical conization (T2), and at the end of operation (T3). The incidence of respiratory depression and body movements during surgery were observed. The satisfaction degree of the surgeon to the opening status of cervix was evaluated. The post-operative recovery time, visual analogue scale (VAS) scores, nausea and vomiting in the following 12 hours were also recorded. Results: The HR, RR, SPO2 and MAP in three groups did not have any significant change (P＞0.05) at T0, T1 and T3. At T2 the HR and MAP decreased significantly in group D and group F compared with group N (P＜0.05), and there was no significant difference between group D and group F (P＞0.05). The surgical satisfaction degree of "Good" in group D was 80％, significantly higher than that in group N (30％) and group F (50％), indicating a better cervix opening in group D. The recovery time in three groups had no significant difference, and the VAS scores in group D and group F were lower than those in group N (P＜0.05) after operation, and patients did not have nausea or vomiting in the following 12 hours. Conclusion: Both the dezocine and flurbiprofen could improve the anesthetic effect in cervical conization and post-operative comfort, with less respiratory or circulation depression. Dezocine showed better improvement than flurbiprofen in cervix opening and the inhibition of stress response and body movements during surgery.

Solubility and dissolution enhancement of flurbiprofen by solid dispersion using hydrophilic carriers

ABSTRACT The intent of the current work is to study the effect of polyethylene glycol 8000 and polyethylene glycol 10000 as hydrophilic carriers on dissolution behaviour of flurbiprofen. In the present study, solvent evaporation method was used to prepare flurbiprofen solid dispersions and evaluated for physico-chemical properties, drug-carrier compatibility studies and dissolution behaviour of drug. Solubility studies showed more solubility in higher pH values and formulations SD4 and SD8 were selected to prepare the fast dissolving tablets. FTIR and DSC study showed no interaction and drug was dispersed molecularly in hydrophilic carrier. XRD studies revealed that there was change in the crystallinity of the drug. The results of In vitro studies showed SD8 formulation confer significant improvement (p<0.05) in drug release, Q20 was 99.08±1.35% compared to conventional and marketed tablets (47.31±0.74% and 56.86±1.91%). The mean dissolution time (MDT) was reduced to 8.79 min compared to conventional and marketed tablets (25.76 and 22.22 min.) indicating faster drug release. The DE (% dissolution efficiency) was increased by 2.5 folds (61.63%) compared to conventional tablets (23.71%). From the results, it is evident that polyethylene glycol solid dispersions in less carrier ratio may enhance the solubility and there by improve the dissolution rate of flurbiprofen.

Investigation of the parameters affecting the release of flurbiprofen from chitosan microspheres

ABSTRACT Flurbiprofen (FLB), a NSAID, widely used for preventing pain generally for arthritis or dental problems. In this study, FLB loaded chitosan microspheres were prepared by ionotropic gelation method. In this method, microspheres were formed by dropping chitosan solutions containing FLB into sodium alginate solutions including sodium tripolyphosphate (TPP). A variety of formulation parameters like drug:polymer ratio, drug concentration, polymer's molecular weight, polymer concentration, pH and the concentration of TPP solutions, drying method and stirring time were analyzed. The dissolution studies were performed in a shaking water bath in pH 7.4 phosphate buffer saline (PBS) at 37 °C. Laser diffractometer was used for particle size analysis, and scanning electron microscope (SEM) was used for morphological properties. Drug loading and loading efficiency were calculated by using UV spectrophotometer. The particles obtained were spherical with 0.7-1.3 mm size range, and the loading efficiency was approximately 21-79%. The dissolution studies conducted revealed that drug:polimer ratio and the polymer type and concentration affected the drug release from microspheres. It was observed that increasing the polymer concentration, polymer's molecular weight and TPP concentration decreased the FLB release from microspheres, which was according to Higuchi kinetics.

Investigation of flurbiprofen axetil on analgesic efficacy in nerve-injured rats / 中国基层医药

Objective To investigate the influence of different doses of flurbiprofen axetil on neurological behavior in CCI rats.Methods All SD rats were randomly assigned to 3 groups:control group(C group),operation but without CCI,n=5;CCI group,without injection,n=5;flurbiprofen axetil (FA) group,different doses of flurbiprofen axetil were intraperitoneally administered every 12 hours for 7 days beginning on postoperative 6 hours in CCI rats (FA1 group:2mg/kg,FA2 group:4mg/kg,FA3 group:8mg/kg,FA4 group:16mg/kg),5 rats in each subgroup.The thermal withdrawal latency(TWL) and mechanical withdrawal threshold(MWT) were tested on preoperative 1,3,5 and 7 days and postoperative 1,3,5 and 7 days.Results Firstly,compared with C group[TWL:(12.396±1.144)s;MWT:(12.801±0.494)g],the TWL and MWT of CCI and FA groups[TWL:(5.645±1.144)s,(5.901±0.914)s,(6.300±0.835)s,(7.631±0.597)s,(7.894±0.526)s;MWT:(5.14±0.71)g,(5.28±0.60)g,(6.74±0.50)g,(6.74±0.25)g,(6.70±0.42)g]were significantly declined after surgery (tTWL=26.973,31.047,31.176,30.373,30.772;tMWT=44.192,48.132,51.136,54.326,46.937,all P0.05).However,the TWL and MWT of FA2 group,FA3 group and FA4 group[TWL:(6.300±0.835)s,(7.631±0.597)s,(7.894±0.526)s;MWT:(6.74±0.50)g,(6.74±0.25)g,(6.70±0.42)g] increased significantly compared with CCI group(tTWL=-3.768,-11.569,-13.867,tMWT=-3.898,-15.233,-14.801,all P0.05).Conclusion Over 4mg/kg of flurbiprofen axetil can significantly reduce the thermal hyperalgesia and mechanical allodynia in CCI rats,however,there is a ceiling effect of flurbiprofen axetil,and the dosage of 8mg/kg can provide a maximum analgesic effect.

Optimal dose of dexmedetomidine for intravenous analgesia after open radical resection of intestinal neoplasms when mixed with flurbiprofen axetil and butorphanol / 中华麻醉学杂志

Objective To determine the optimal dose of dexmedetomidine for intravenous analgesia after open radical resection of intestinal neoplasms when mixed with flurbiprofen axetil and butorphanol.Methods A total of 120 patients of both sexes,of American Society of Anesthesiologists physical status Ⅰ or Ⅱ,aged 20-60 yr,weighing 45-80 kg,undergoing elective open radical resection of intestinal neoplasms,were divided into 4 groups (n =30 each) using a random number table:control group (group C)and different doses of dexmedetomidine groups (group DEX1,group DEX2,group DEX3).Group C received flurbiprofen axetil 2 mg/kg and butorphanol 0.05 mg/kg for intravenous analgesia.In DEX1,DEX2 and DEX3 groups,dexmedetomidine 0.3 μg/kg was intravenously infused starting from 30 min before the end of surgery,and the analgesia solution contained dexmedetomidine 1,2 and 3 μg/kg,respectively,which was mixed with flurbiprofen axetil 2 mg/kg and butorphanol 0.05 mg/kg in 100 ml of 0.9％ normal saline,and the mixture was infused at a rate of 2 ml/h.Butorphanol 0.5 mg was intravenously injected as a rescue analgesic,postoperative pain was assessed using the visual analog scale at coughing,and visual analog scale score was maintained ＜4.The requirement for rescue analgesics was recorded within 48 h after operation.The occurrence of postoperative adverse reactions such as nausea and vomiting,respiratory depression,somnolence,bradycardia,hypotension and over-sedation,patient's satisfaction with analgesia and length of postoperative hospital stay were recorded.Results Compared with group C,the rate of rescue analgesia after operation was significantly decreased,and the degree of satisfaction with analgesia was increased in DEX2 and DEX3 groups,and the incidence of postoperative somnolence was significantly increased in group DEX3 (P＜0.05).No other adverse effects were found in DEX1,DEX2 and DEX3 groups.Conclusion When mixed with flurbiprofen axetil and butorphanol,the optimal dose of dexmedetomidine for intravenous analgesia after open radical resection of intestinal neoplasms is 2 μg/kg.

Effect of flurbiprofen axetil pretreatment on level of central β-endorphin in a rat model of incisional pain / 中华麻醉学杂志

Objective To evaluate the effect of flurbiprofen axetil pretreatment on the level of central β-endorphin in a rat model of incisional pain.Methods Fifty-four SPF male healthy Sprague-Dawley rats,aged 6-7 weeks,weighing 180-230 g,were divided into 3 groups (n=18 each) using a random number table:control group (group C),incisional pain group (group Ⅰ) and flurbiprofen axetil pretreatnent group (group FA).At 30 min before the model of incisional pain was established,fat emulsion 1 ml was injected via the caudal vein in group Ⅰ,and flurbiprofen axetil 6 mg/kg (diluted to 1 ml in fat emulsion) was injected via the caudal vein in group FA.The mechanical paw withdrawal threshold (MWT) was measured at 1 day before establishment of the model and 1,6 and 12 h after establishment of the model (T1-3).The rats were sacrificed after measurement of pain threshold at T1-3,and the lumbar enlargement segment of the spinal cord and hypothalamic arcuate nucleus specimens were obtained for determination of β-endorphin content (by enzyme-linked immunosorbent assay) and β-endorphin expression (by immunohistochemistry).Results Compared with group C,the MWT was significantly decreased at T1-3 in I and FA groups,the content and expression of β-endorphin in the spinal cord were significantly decreased at T2,3,and the content and expression of β-endorphin in the hypothalamic arcuate nucleus were increased at T1 in group Ⅰ,and the content and expression of β-endorphin in the spinal cord and hypothalamic arcuate nucleus were significantly increased at T1-3 in group FA (P＜0.05).Compared with group Ⅰ,the MWT was significantly increased,and the content and expression of β-endorphin in the spinal cord and hypothalamic arcuate nucleus were increased at T1-3 in group FA (P＜0.05).Conclusion The mechanism by which flurbiprofen axetil pretreatment produces analgesic effect may be related to the increased level of central β-endorphine in a rat modal of incisional pain.