卡前列素氨丁三醇注射液和缩宫素在剖宫产产后出血中的应用

目的观察卡前列素氨丁三醇注射液（欣母沛）和缩宫素在预防和减少剖宫产产后出血的疗效及其不良反应比较。方法选择2013年11月至2014年3月同济大学附属第一妇婴保健院足月妊娠并行子宫下段剖宫产术的40例产妇为研究对象,并按胎儿娩出后宫体注射药物的不同,将剖宫产术中使用卡前列素氨丁三醇注射液的20例产妇纳入Ⅰ组,将术中使用缩宫素的20例产妇纳入Ⅱ组。观察两组产妇的手术情况和生命体征变化情况。两组产妇年龄、孕龄、体质量等一般情况比较,差异无统计学意义（P〉0.05）。本研究遵循的程序符合同济大学附属第一妇婴保健院人体试验委员会所制定的伦理学标准,得到该委员会批准,分组征得受试对象本人的知情同意,并与之签署临床研究知情同意书。结果Ⅰ组产妇术中出血量显著少于Ⅱ组,两组比较,差异有统计学意义（P〈0.05）。两组产妇用药10min后生命体征变化情况比较,差异有统计学意义（P〈0.05）。Ⅰ组产妇恶心、呕吐、胸闷和颜面潮红等药物不良反应发生率显著高于Ⅱ组,两组比较,差异也有统计学意义（P〈0.01）。结论卡前列素氨丁三醇注射液用于剖宫产术能有效的减少产后出血,但该药物使用时应预防和避免其药物不良反应的发生。     

IN VIVO/IN VITRO CORRELATIONS FOR FOUR DIFFERENTLY DISSOLVING KETOROLAC TABLETS

This study assesses whether in vitro immediate release ketorolac tablet dissolution profiles (utilizing the recently proposed USP dissolution test for ketorolac tablets) can be correlated with in vivo plasma pharmacokinetic parameters. Four batches of ketorolac tablets were utilized: a ketorolac tablet batch that demonstrated a rapid dissolution rate during USP in vitro dissolution testing, two tablet batches that were manufactured such that they dissolved at moderate rates, and a tablet batch that was manufactured such that it dissolved at a distinctly slow rate. The single-dose mean pharmacokinetic characteristics and relative bioavailability of the four different 10 mg ketorolac tromethamine tablets were evaluated in 12 healthy volunteers in a randomized study of Latin square design. The amount dissolved of the various tablets at 10, 20, and 30 min was in the order of fast-dissolving tablets > medium-1-dissolving tablets=medium-2-dissolving tablets > slow-dissolving tablets. In general, the profiles of the average plasma concentrations for ketorolac were similar for the fast- and the two medium-dissolving tablet batches (even though a statistically significant difference was found between the t_max of the fast-dissolving tablet and one of the medium-dissolving tablet batches). The mean plasma concentrations for the slow-dissolving tablet, however, reached peak levels much later, with the peak also being significantly smaller. There were no statistically significant differences in the total AUC or in the mean plasma half-lives among the four formulations. Good correlations were obtained for mean t_max versus the percentage dissolved at 20, 30, and 45 min. Correlations were generally weaker for percentage dissolved versus C_max or percentage bioavailability. This indicates that in vitro dissolution testing for immediate release ketorolac tablets can be a useful indicator of in vivo time to maximum plasma concentration when comparing similarly formulated tablets. Further, the proposed USP dissolution test and specification would have appropriately failed the slow-dissolving tablet batch, which demonstrated a significantly slower rate of absorption as per t_max and C_max.     

羟考酮降低剖宫产术中卡前列素氨丁三醇所致不良反应的效果

目的观察羟考酮降低剖宫产术中卡前列素氨丁三醇不良反应的效果。方法选取2018年3月至2019年3月廊坊市第四人民医院产科诊治的80例宫缩乏力剖宫产产妇为研究对象,将其随机分为观察组和对照组,每组40例产妇。两组产妇均于胎儿娩出后立即行卡前列素氨丁三醇250μg宫体注射。观察组产妇镇痛泵输入0.5mg·kg-1羟考酮,对照组产妇于胎儿娩出后静脉注射生理盐水2 mL。观察两组产妇卡前列素氨丁三醇注射后2 min(T1)、5 min(T2)、10 min(T3)平均动脉压(MAP)、心率(HR)、血氧饱和度(SpO2)。记录两组产妇术后6h、12h、24h时的视觉模拟疼痛评分(visual analogue scale,VAS)静息痛评分和Ramsay镇静评分,以及两组产妇不良反应发生情况。结果①两组产妇T1、T3时MAP、HR、SpO2比较,其差异均无统计学意义(均P>0.05),观察组产妇T2时MAP、HR明显低于对照组产妇,其差异均具有统计学意义(均P<0.05)。②观察组产妇6h、12h、24 h时的VAS评分明显低于对照组产妇,其差异均具有统计学意义(均P<0.05);12h时的Ramsay评分明显高于对照组产妇,其差异具有统计学意义(P<0.05)。③观察组产妇恶心、呕吐、面部潮红、胸闷憋气、血压升高、头痛眩晕的发生率明显低于对照组产妇,其差异均具有统计学意义(均P<0.05)。结论羟考酮对剖宫产术中卡前列素氨丁三醇所致的不良反应有一定防治作用,有利于产妇生命体征的稳定,具有确切的镇痛和镇静效果。     

不同选择性环氧合酶抑制剂对瑞芬太尼麻醉后痛觉过敏的影响

目的探讨不同选择性环氧合酶抑制剂对瑞芬太尼麻醉后痛觉过敏的影响。方法选择瑞芬太尼维持的全麻下行全子宫切除术的患者60例,根据麻醉诱导前15 min用药不同分为2组,A组30例给予帕瑞昔布钠40mg,B组30例给予酮咯酸氨丁三醇30 mg,观察术后15、30 min的疼痛评分和术后4、8、12、24 h的疼痛评分,病人自控镇痛(PCA)按压次数、镇痛药物消耗量。结果 A组在术后15 min疼痛评分小于B组(P<0.05);术后4 h内A组的镇痛药物消耗量和PCA按压次数均少于B组(P<0.05)。结论麻醉诱导前给予帕瑞昔布钠相比酮咯酸氨丁三醇能更有效地抑制瑞芬太尼所致的痛觉过敏。     

The efficacy of postoperative pain management with ketorolac for day case oral surgery

The efficacy of the non-steroidal anti-inflammatory analgesic, ketorolac (Toradol), was investigated in 52 day case patients undergoing removal of impacted third molar teeth under intravenous sedation and local analgesia. The study was double-blind, randomized and placebo-controlled. A single 30 mg dose of ketorolac was administered intravenously just prior to induction of sedation with midazolam. Ketorolac was well tolerated and provided good postoperative analgesia. It is suggested that ketorolac is a useful addition to the analgesic armamentarium and appropriately prescribed, provides good pain relief following day case oral surgery.     

非甾体抗炎药酮咯酸的脊髓镇痛作用

采用小鼠温浴法研究非甾体抗炎药（ＮＳＡＩＤ）酮咯酸氨了三醇的脊髓镇痛作用及其机制，发现脊髓内注射酮咯酸氨了三醇０．４ｍｇ·ｋｇ－１有明显镇痛作用，但全身给药（ｉｐ）需８ｍｇ·ｋｇ－１才能达到同样镇痛效果，脊髓与腹腔注射有效剂量比为１：２０，证实酮咯酸具有脊髓镇痛作用，该作用可被ｓｃ利血平、呱唑嗪或育亨宾取消，表明酮咯酸脊髓镇痛作用机制与内源镇痛系统中的去甲肾上腺素能神经有密切关系。本文研究结果为了解ＮＳＡＩＤｓ的中枢镇痛作用及其机制提供了新资料。     

Effect of pretreatment with ketorolac on propofol injection pain

BACKGROUND: : Pain on injection is still a major problem with propofol. We performed this study to compare different doses of intravenous (i.v.) ketorolac with and without venous occlusion and its effect on the incidence and the severity of the pain after propofol injection. METHODS: We conducted a prospective, randomized and double-blind study of 180 patients (20-60 years of age.) scheduled to undergo elective surgery. Six groups of patients were generated: group A received normal saline (NS) 2 ml i.v.; groups B, C, D received ketorolac 10 mg in 2 ml NS with venous occlusion (VO) and a subsequent propofol injection at either 30, 60 or 120 s; groups E and F received ketorolac 15 mg and 30 mg in 2 ml NS and propofol was injected after 60 s. The pain perception was assessed during injection of propofol in all patients. RESULT: : The incidence of propofol-associated injection pain was for A: 46.7%; B: 43.4%; C: 23.3%; D:16.7%; E: 20%, and F: 10%. The incidence of pain following propofol injection was reduced by i.v. ketorolac 10 mg with venous occlusion for 120 s. Furthermore, i.v. ketorolac 15 mg and 30 mg but not 10 mg following propofol injection after 60 s without venous occlusion revealed significant pain reduction when compared to saline group. There was no difference in venous sequelae at 7 days postoperatively between the groups. CONCLUSION: Our results suggested that pretreatment with i.v. 15 and 30 mg ketorolac reduces pain following propofol injection. Moreover, pretreatment with i.v. ketorolac 10 mg with venous occlusion for 120 s achieves the same pain relief effect.     

酮咯酸氨丁三醇胶囊溶出度测定方法的研究

目的建立酮咯酸氨丁三醇胶囊溶出度测定方法。方法以水为溶出介质,转速为50 r.min-1,分光光度法检测,检测波长为322 nm。结果酮咯酸氨丁三醇在3.16~12.64μg.mL-1浓度与其吸收度呈良好线性关系(r=0.999 5),平均回收率为99.01%,RSD为0.20%。结论该方法操作简便,准确可靠。     

Effect of adding ketorolac to intravenous morphine patient-controlled analgesia on bowel function in colorectal surgery patients--a prospective, randomized, double-blind study

BACKGROUND: Postoperative ileus (PI) is the transient impairment of bowel motility due to surgical trauma and the associated physiological responses. Postoperative ileus results in patient discomfort, increases gastrointestinal risks, prolongs hospital stay and increases medical expenses. In this study, we investigated the effect of patient-controlled analgesia (PCA) morphine with or without ketorolac on bowel functions in patients after colorectal surgeries. METHODS: A total of 79 patients who received elective colorectal resection were randomly allocated into two groups receiving either intravenous PCA morphine (M group) or intravenous PCA morphine plus ketorolac (K group). Recovery of bowel functions (bowel movement, passage of flatus, and soft diet intake), pain scores, morphine consumption, time for first ambulation, and opioid-related side-effects were recorded. RESULTS: Patients in the K group received 29% less morphine than patients in the M group with comparable pain scores. The first bowel movement (1.5 [0.7-1.9] vs. 1.7 [1.0-2.8] days, P < 0.05) and the first ambulation (2.2 +/- 1.0 vs. 2.8 +/- 1.2 days, P < 0.05) were significantly earlier in the K group than in the M group. The time of the first flatus passing, the first intake of soft diet, and duration of hospital stay were not significantly different between the two groups. CONCLUSIONS: The results of this study suggest that addition of ketorolac to intravenous morphine PCA provides an opioid-sparing effect but has limited benefit in shortening the duration of bowel immobility and time to first ambulation. These findings imply that postoperative ileus is attributable to multiple factors in addition to morphine consumption.     

Prostaglandin-mediated control of rat brain kynurenic acid synthesis – opposite actions by COX-1 and COX-2 isoforms

Summary. Kynurenic acid (KYNA), an endogenous glutamate-receptor antagonist preferentially blocking NMDA-receptors, has analgesic properties and has also been implicated in the pathophysiology of schizophrenia. Recently, the non-steroid anti-inflammatory drug (NSAID) diclofenac was found to increase rat brain KYNA. Here, we analyze whether cyclooxygenase (COX)-1 or COX-2 modulate the levels of rat brain KYNA. The non-selective COX-inhibitor diclofenac (50mg/kg, i.p.) or indomethacin (50mg/kg, i.p.), a non-selective inhibitor with a preferential selectivity for COX-1, produced an elevation in brain KYNA. In contrast, the COX-2 selective inhibitors parecoxib (25mg/kg, i.p.) or meloxicam (5mg/kg, i.p.) decreased brain KYNA. Both elevation and lowering of brain KYNA by indomethacin or parecoxib, respectively, were prevented by the prostaglandin E₁/E₂ agonist misoprostol (1mg/kg, s.c.). It is proposed that increased brain KYNA formation induced by NSAIDs displaying an inhibitory action on COX-1 contribute to their analgesic efficacy as well as to their psychiatric side effects.