Adding propacetamol to ketorolac increases the tolerance to painful pressure.

Combining an NSAID and paracetamol (acetaminophen) has in some studies given superior analgesia compared with the single drugs. In other trials no additive effect has been found. We have investigated the effect of this drug combination on the pressure pain tolerance threshold (PPTT), a reproducible correlate to clinical pain. The aim of this double blind, randomised, placebo controlled, crossover study was to evaluate the effect of i.v. propacetamol 2 g (= paracetamol 1 g) and ketorolac 30 mg, individually and in combination, on PPTT in 16 volunteers on four separate days. PPTT was measured 15 min before and at 45, 60, 90 and 150 min after the start of test drug administration. The pressure stimuli were applied on the base of a fingernail, increasing by 30 kPa/s until the pressure pain tolerance threshold was reached. For the total observation period (150 min), only the combination (propacetamol+ketorolac) increased significantly PPTT compared with baseline (P<0.04), while PPTT decreased significantly after placebo (P<0.01). The combination (propacetamol+ketorolac) and ketorolac alone increased PPTT compared with placebo (combination vs. placebo and ketorolac vs. placebo, P<0.001) and with propacetamol (combination vs. propacetamol and ketorolac vs. propacetamol, P<0.001). The combination was significantly better than ketorolac alone (P<0.04). After propacetamol 2 g, PPTT did not change significantly neither compared with placebo or baseline. CONCLUSIONS: Tolerance to repeated painful pressure (PPTT) decreased after placebo. Ketorolac 30 mg caused an increase in PPTT compared with placebo but not with baseline. Adding propacetamol 2 g to ketorolac 30 mg significantly increased PPTT. These findings support the practice of combining paracetamol with an NSAID for relief of acute pain.     

高效液相色谱法测定人血浆中酮咯酸浓度

目的建立测定人血浆中酮咯酸浓度的高效液相色谱法。方法 24例健康志愿者口服单剂量(20 mg)酮咯酸氨丁三醇胶囊试验制剂。以奥硝唑为内标,待测血浆用甲醇沉淀法进行处理,色谱柱采用PlatisilODS柱(250 mm×4.6 mm,5μm),流动相为0.05 mol/L磷酸二氢钠溶液-乙腈(70∶30)(2 mol/L氢氧化钠调节pH值至5.14±0.01),波长为330 nm,进行HPLC分析。结果试验制剂的主要药动学参数:t1/2为(6.08±1.82)h,Cmax为(1 351.7±310.9)ng/mL,Tmax为(1.86±0.58)h,AUC0-t为(7 735±1 718)ng.h/mL,AUC0-∞为(8183±1 939)ng.h/mL,无内源性物质干扰测定,酮咯酸在24.8～2 480.0 ng/mL范围内与内标物峰面积之比线性关系良好,定量下限为24.8 ng/mL。提取回收率为83.9%～94.6%。结论该方法操作简便、准确,灵敏度高,专属性强,适用于人血浆中酮咯酸浓度的测定。     

酮咯酸氨丁三醇注射液治疗急性胆绞痛的疗效观察

目的：观察酮咯酸氨对胆绞痛患者的疗效及不良反应。方法：将180例患者随机分为3组,分别应用酮咯酸氨丁三醇（治疗组）、奈福泮（对照组1）和盐酸哌替啶（对照组2）进行肌内注射,观察比较三种药物的镇痛效果及不良反应。结果：酮咯酸氨丁三醇在镇痛效果与盐酸哌替啶比较,无显著性差异,但优于奈福泮。不良反应比较,酮咯酸氨丁三醇与奈福泮无显著性差异;两者与盐酸哌替啶比较,均有显著性差异,且副作用小。结论：酮咯酸氨丁三醇治疗急性胆绞痛时,镇痛疗效确切,不良反应少,值得临床推广。     

临床药师干预对规范酮铬酸氨丁三醇注射液合理使用的效果分析

〔摘 要〕 目的：分析临床药师干预对规范酮铬酸氨丁三醇注射液合理使用的效果。方法：收集南京医科大学康达学院附属涟水人民医院 2021 年 1 月至 2021 年 5 月（干预前）和 2022 年 1 月至 2022 年 5 月（干预后）住院患者的酮咯酸氨丁三醇注射液使用资料,其中 2022 年 1 月至 2022 年 5 月临床药师通过分析酮咯酸氨丁三醇注射液应用不合理用药的原因并进行干预。随机抽取两个时间段酮咯酸氨丁三醇注射液使用患者的病历各 100 份,比较干预前后住院患者的酮咯酸氨丁三醇注射液的使用数量、使用合理率和不合理用药类型情况。结果：干预后,酮咯酸氨丁三醇注射液使用量下降幅度达 81.33 %;用药合理率明显高于干预前,差异具有统计学意义（P ＜ 0.001）。结论：临床药师干预有利于规范酮咯酸氨丁三醇注射液的合理使用,促进临床合理用药。     

The effect of post-operative NSAID administration on bone healing after elective foot and ankle surgery

BackgroundPost-operative pain is a common concern following elective foot and ankle surgery. NSAIDs used for pain relief have led to bone-healing complications in animal models and in vitro studies. This retrospective study examined the rate of bone-healing complications in post-surgical patients using NSAIDs.MethodsParticipants underwent elective foot surgeries between January 2016 and May 2018. Radiographs were used to identify bony nonunion at osteotomy sites 12 weeks post-surgery.ResultsTwo-hundred thirty-two patients were evaluated; 59 (25.43%) were prescribed ibuprofen, 62 (27%) ketorolac, 15 (6.47%) acetaminophen, and 92 (40%) hydrocodone-acetaminophen. Two-hundred and twelve (91.38%) patients exhibited radiographic evidence of osseous union at 12 weeks and 20 (8.62%) had radiographic evidence of non-union of the osteotomy sites. There was no significant relationship between NSAID use and osseous non-union (p < 0.05).ConclusionsShort-term use of oral ibuprofen and ketorolac in the post-operative period was not associated with bony non-union.     

Safety of ketorolac in surgical neonates and infants 0 to 3 months old

Background

Ketorolac is a nonsteroidal antiinflammatory drug widely used as an adjunct to postoperative pain control in adult and pediatric patients. Minimal safety data exist regarding the use of ketorolac in neonates.

Methods

The charts of 57 postsurgical neonates between 0 and 3 months of age were retrospectively reviewed for bleeding events associated with ketorolac. Data included gestational age (GA), corrected gestational age (CGA) at the time of ketorolac, serum creatinine, platelet count, urine output (in milliliters per kilogram per hour), concomitant medications, enteral feeds, number of ketorolac doses, and surgical procedure performed.

Results

Of 57 patients, 10 (17.2%) demonstrated a bleeding event. Mean CGA and serum creatinine for those with bleeding events was 39.4 weeks (P = .69) and 0.64 mg/dL (P = .03), respectively. Patients with a bleeding event received ketorolac at a mean of 20.7 days of life with 70% receiving the drug at less than 14 days of age, whereas those without a bleeding event received ketorolac at a mean of 31.9 days (P = .04). Bleeding events correlated with glomerular filtration rate of less than 30 mL/min/1.73 m² or concomitant medications in all but 1 patient.

Conclusions

Infants younger than 21 days and less than 37 weeks CGA are at significantly increased risk for bleeding events and should not be candidates for ketorolac therapy.     

曲安奈德和酮咯酸氨丁三醇对缺氧视网膜Müller细胞上水通道蛋白-4及VEGF表达的影响

背景 曲安奈德(TA)玻璃体腔内注射可引起高眼压、白内障及眼内炎等并发症.酮咯酸氨丁三醇(Ketorolac)是一种作用机制与TA相似、不良反应较少的新型非甾体类抗炎药,其在治疗视网膜水肿方面可能替代或部分替代TA. 目的 研究TA和Ketorolac对CoCl2诱导的缺氧条件下兔视网膜Müller细胞上水通道蛋白-4(AQP4)及血管内皮生长因子(VEGF)表达的影响,探讨其治疗视网膜水肿的作用机制. 方法 收集健康新西兰白兔20只,采用酶消化法培养兔视网膜Müller细胞并进行鉴定.取第2代细胞用于实验.分别用含500μmol/L CoCl2的DMEM 2 ml孵育细胞0、6、12、24 h建立视网膜Müller细胞缺氧模型,采用半定量逆转录PCR(RT-PCR)法观察缺氧对Müller细胞中AQP4 mRNA及VEGF mRNA表达的影响,确定造模的最佳时间点.将培养24 h的细胞分为正常对照组,缺氧对照组,缺氧+50、100、200 mg/L TA组,缺氧+50、100、200 mg/L Ketorolac组,分别在缺氧细胞培养基中加入相应的药物进行共培养,采用半定量RT-PCR法观察TA和Ketorolac对Müller细胞中AQP4 mRNA及VEGF mRNA表达的影响. 结果 培养的细胞呈不规则形、星形,细胞核呈卵圆形,培养14 ～25 d时细胞达到80％以上融合.95％的培养细胞中间丝波形蛋白(vimentin)、α-平滑肌肌动蛋白(α-SMA)和神经胶质纤维酸性蛋白(GFAP)阳性表达,呈绿色荧光.RT-PCR法检测结果显示,培养后各时间点间Müller细胞中AQP4 mRNA和VEGF mRNA表达的吸光度(A)值总体比较差异均有统计学意义(F=18.70、53.20,P＜0.01),CoCl2作用6、12、24 h值均明显高于正常Müller,差异均有统计学意义(P＜0.05),其中24 h时AQP4 mRNA和VEGF mRNA的表达量达峰值.缺氧24 h时8个组Müller细胞中AQP4 mRNA和VEGF mRNA表达(A)值的总体比较差异均有统计学意义(F=27.98、10.03,P＜0.01);与缺氧对照组比较,除缺氧+50 mg/L TA组、缺氧+50 mg/L Ketorolac组外,其他各缺氧实验组Müller细胞中AQP4mRNA、VEGF mRNA表达量均明显下降,差异均有统计学意义(P＜0.05);缺氧+100 mg/L TA组和缺氧+100 mg/LKetorolac组以及缺氧+200 mg/L TA组和缺氧+200 mg/L Ketorolac组AQP4mRNA、VEGF mRNA的表达,组间差异均无统计学意义(P＞0.05). 结论 TA和Ketorolac均可下调化学性诱导的缺氧Müller细胞中AQP4和VEGF的表达水平,二者对视网膜水肿的治疗作用类似.     

Analgesic and antiemetic effect of ketorolac vs. betamethasone or dexamethasone after ambulatory surgery

BACKGROUND: Glucocorticoids are known to provide slower onset and more prolonged duration of analgesic effect than ketorolac. In the present study, we wanted to evaluate the effect over time from a single dose of either intravenous (i.v.) dexamethasone or an intramuscular (i.m.) depot formulation of betamethasone compared with i.v. ketorolac. MATERIALS AND METHODS: One hundred and seventy-nine patients admitted for mixed ambulatory surgery were included in the study. After induction of general i.v. anaesthesia, the patients were randomized to receive double-blindly either dexamethasone 4 mg i.v. (Group D) or betamethasone depot formulation 12 mg i.m. (Group B) or ketorolac 30 mg i.v. (Group K). Fentanyl was used for rescue analgesic medication in the post-operative care unit (PACU) and codeine with paracetamol after discharge, for a study period of 3 days. RESULTS: There was significantly less post-operative pain in the ketorolac group during the stay in the unit (88% with minor or less pain in Group K vs. 74% and 67% in Groups D and B, respectively, P < 0.05), significantly less need for rescue medication (P < 0.05) and significantly less nausea or vomiting (12% in Group K vs. 30% in the other groups pooled, P < 0.05). The ketorolac patients were significantly faster for ready discharge, median 165 min vs. 192 min and 203 min in Groups D and B, respectively (P < 0.01). There were no differences between the groups in perceived pain, nausea, vomiting or rescue analgesic consumption in the 4- to 72-h period. CONCLUSION: Dexamethasone 4 mg or bethamethasone 12 mg did not provide prolonged post-operative analgesic effect compared with ketorolac 30 mg, which was superior for analgesia and antiemesis in the PACU.     

酮咯酸氨丁三醇用于腹腔镜胆囊切除术对患者超前镇痛的观察

目的观察酮咯酸氨丁三醇对于腹腔镜胆囊切除术(LC)患者的超前镇痛作用。方法 60例择期行LC患者随机分为T组、R组、C组3组,各20例。T组分别于切皮前30 min缓慢静脉推注酮咯酸氨丁三醇30 mg(0.9%氯化钠溶液稀释至10 ml),手术结束前30 min缓慢静脉推注0.9%氯化钠溶液10 ml;R组切皮前30 min缓慢静脉推注0.9%氯化钠溶液10 ml,手术结束前30 min缓慢静脉推注酮咯酸氨丁三醇30 mg;C组分别于切皮前30 min、手术结束前30 min缓慢静脉推注0.9%氯化钠溶液10 ml。采用视觉模拟量表(VAS)评价3组各时点的疼痛强度,采用Ramsay系统进行术后镇静评分,并观察术后的不良反应。结果在术后30 min、1 h、3 h、6 h,T组和R组的VAS均比C组的低,差异有统计学意义(P<0.05),在其余时点,两组VAS的差异无统计学意义。而T组和R组的VAS的差异无统计学意义(P>0.05),术后C组曲马多用量明显大于T组和R组(P<0.05)。结论酮咯酸氨丁三醇能效缓解腹腔镜手术的术后疼痛,且无明显不良反应,但在LC中超前镇痛的效果与给药时点无明显关系。