断指再植术后3种镇痛方法的临床效果观察比较

目的探索断指再植术后最佳镇痛方法。方法选择断指再植手术75例,随机分成3组。每组25例,A组:自控式镇痛泵;B组:酮咯酸氨丁三醇30mg,im,tid;C组:静脉滴注盐酸哌替啶100mg加入500mL 0.9%NS中持续缓慢滴注。视疼痛情况调节滴速。结果 A组镇痛效果最佳,好于B组、C组(P<0.05),C组费用最低。结论断指再植术后使用自控式镇痛泵的镇痛效果优于其他2组术后镇痛方法。     

Comparison of cyclooxygenase inhibitory activity and ocular anti-inflammatory effects of ketorolac tromethamine and bromfenac sodium

ABSTRACT

Objective: To compare the cyclooxygenase (COX) activity and anti-inflammatory effects of the nonsteroidal anti-inflammatory drugs (NSAIDs) ketorolac tromethamine (ketorolac) and bromfenac sodium (bromfenac).

Methods: Cyclooxygenase activity and selectivity was determined in vitro by measuring prostaglandin E₂ (PGE₂) production following incubation of varying concentrations of NSAID with human recombinant COX‐1 or COX‐2 and arachidonic acid. Anti-inflammatory effects were evaluated in a rabbit model in which an ocular inflammatory response was induced by intravenous injection of 10?µg/kg lipopolysaccharide (LPS). In study animals, one eye was treated with 50?µL (+/–) ketorolac 0.4% (Acular LS) or bromfenac 0.09% (Xibrom) and the other eye with 50?µL buffered saline. In control animals, both eyes were treated with vehicle. All animals were treated twice: 2 hours and 1 hour before LPS.

Main outcome measures: PGE₂ production in vitro, measured by enzyme immunoassay; fluorescein isothiocyanate (FITC)-dextran leakage into the anterior chamber, measured by fluorophotometry; aqueous PGE₂ levels in vivo, measured by ELISA immunoassay.

Results: Ketorolac was six times more active against COX‐1 (?IC₅₀ = 0.02?µM) than COX‐2 (?IC₅₀ = 0.12?µM) while bromfenac was ≈ 32 times more active against COX‐2 (?IC₅₀ = 0.0066?µM) than COX‐1 (?IC₅₀ = 0.210?µM). In the animal model, both drugs resulted in nearly complete inhibition of FITC-dextran leakage and PGE₂ production in the anterior chamber of treated eyes. There was also a 79% inhibition (?p < 0.001) of FITC-dextran leakage in the contralateral eyes of bromfenac-treated rabbits, and a 22.5% inhibition (not statistically significant) in the contralateral eyes of ketorolac-treated rabbits.

Conclusions: Ketorolac is relatively COX‐1 selective while bromfenac is potently selective for COX‐2 over COX‐1. In the animal model, both ketorolac 0.4% and bromfenac 0.09% demonstrated maximal anti-inflammatory activity in treated eyes. Only bromfenac 0.09% had a significant effect on the contralateral eye, suggesting possible systemic absorption of this drug.     

Efficacy of topical ketorolac tromethamine 0.4% for control of pain or discomfort associated with cataract surgery

SUMMARY

Objective: To evaluate the efficacy of ketorolac 0.4% ophthalmic solution for control of pain and discomfort associated with cataract surgery.

Methods: This was a single-center, double-masked, randomized, fellow-eye placebo-controlled clinical study of 25 patients (mean age 72?years; 76% female) requiring bilateral cataract surgery. Patients received either ketorolac tromethamine 0.4% ophthalmic solution (Acular LS*) or placebo, 1 drop QID for 3?days prior to and 1?day following phacoemulsification and intraocular lens implantation on their first eye, and the other treatment for surgery on the second, fellow eye 1?week–4?weeks later. The physician rated patient cooperation and ocular pain or discomfort during surgery, and patients rated ocular pain or discomfort immediately and 24?h after surgery.

Results: Patients reported significantly less ocular pain during the 24?h following surgery when treated with ketorolac 0.4% than with placebo (?p = 0.02). Ocular pain was reported for only a single ketorolac 0.4%-treated eye (4%) during that period, compared with 39% of placebo-treated eyes (?p = 0.004). No significant differences between eyes treated with ketorolac 0.4% and placebo were observed in patient cooperation, and ocular pain or discomfort during or immediately after surgery. No adverse events occurred during the study.

Limitations: Evaluation of pain is subjective, and the severity of pain experienced in the control, vehicle-treated eyes was low.

Conclusions: The reduction in pain associated with cataract surgery afforded by ophthalmic ketorolac 0.4%, together with its favorable safety profile, make it an important tool to help surgeons meet the high expectations of today's cataract and refractive surgery patients.     

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.     

Development and Evaluation of Nasal Formulations of Ketorolac

Ketorolac tromethamine is a potent non-narcotic analgesic with moderate anti-inflammatory activity. Clinical studies indicate that ketorolac has a single dose efficacy greater than morphine for postoperative pain and has excellent applicability in the emergency treatment of pain. Due to incomplete oral absorption of ketorolac, several approaches have been tried to develop a nonoral formulation in addition to injections, especially for the treatment of migraine headache. The aim of our study was to develop a nasal formulation of ketorolac with a dose equivalent to the oral formulation. A series of spray and lyophilized powder formulations of ketorolac were administered into the nasal cavity of rabbits, and their pharmacokinetics profiles were assessed. The spray and powder formulations were compared through their pharmacokinetics parameters and absolute bioavailability. Drug plasma concentration was determined using solid phase extraction, followed by an HPLC analysis. Nasal spray formulations were significantly better absorbed than powder formulations. A nasal spray formulation of ketorolac tromethamine showed the highest absorption with an absolute bioavailability of 91%. Within 30 min of administration, the plasma concentration was comparable to that resulting from an intravenous injection. The absolute bioavailability of a solution of ketorolac acid was 70%. Apparently, the dissolution of ketorolac acid into the mucous layer limits its absorption. There were no significant differences in absorption between different powder formulations. Even the reduction of particle size from 123 θ m to 63 θ m did not indicate better absorption of ketorolac tromethamine from powder formulations. Interestingly, the absolute bioavailability of ketorolac tromethamine from a powder formulation is only 38%, indicating that the drug may not be totally released from the polymer matrix before it is removed from nasal epithelium by mucociliary clearance.     

酮咯酸氨丁三醇与曲马多对小儿七氟醚全麻术后躁动的影响

目的观察酮咯酸氨丁三醇与曲马多对小儿七氟醚全麻术后躁动的影响。方法选择全麻下行扁桃体和腺样体切除术的患儿80例,年龄2⁷岁、ASAⅠ7岁、ASAⅠ^Ⅱ级。根据手术结束前静脉注入的药物分为4组,每组20例,曲马多组(T组,手术结束前30 min静注曲马多1 mg/kg),酮咯酸氨丁三醇组(K组,手术结束前30 min静注酮咯酸氨丁三醇0.5 mg/kg),曲马多+酮咯酸氨丁三醇组(T+K组,手术结束前30 min静注曲马多1mg/kg和酮咯酸氨丁三醇0.5 mg/kg),对照组(C组,手术结束前30 min静注盐水5 mL)。记录各组手术时间、术后拔管时间,拔管后5 min(T5)、10 min(T10)的躁动评分,入PACU后记录疼痛和镇静评分,以及术后恶心呕吐的情况。结果各组间患儿手术时间、拔管时间比较差异无统计学意义(P>0.05);T5和T10 2个时点的躁动发生率排序:C组>T组>T+K组,C组>K组>T+K组,差异有统计学意义(P<0.05)。K组躁动发生率高于T组,但差异无统计学意义(P>0.05);入PACU后患儿疼痛评分排序:C组>T组>T+K组,C组>K组>T+K组,差异有统计学意义(P<0.05)。K组疼痛评分高于T组,但差异无统计学意义(P>0.05);术后恶心呕吐发生率T组和T+K组明显高于C组和K组(P<0.05)。结论酮咯酸氨丁三醇和曲马多可减轻术后疼痛,减少小儿七氟醚麻醉后躁动的发生。两种药物联合应用降低术后躁动的效果更显著。     

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。     

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.     

Low dose ketorolac infusion improves postoperative analgesia combined with patient controlled fentanyl analgesia after living donor hepatectomy – Randomized controlled trial

BackgroundHepatectomy elaborates significant post-operative pain. Opioids represent cornerstone for post-operative analgesia in such cases. This study examined the therapeutic effect and outcome of adding low dose ketorolac tromethamine infusion to PO intravenous patient controlled fentanyl analgesia IV-PCA.Patients and methodsSixty right lobe donors were randomized into either fentanyl or ketorolac groups (30 patients each). Patients in both groups received fentanyl (2 μg/ml) solution in normal saline as IV-PCA with background infusion in a rate adjusted to deliver 0.25 μg kg h^?1 and boluses of 10 ml with a lock-out time of 20 min. They received 15 mg ketorolac IV bolus in ketorolac group and similar placebo injection in the control. Patients in both groups received a continuous intravenous infusion of 240 ml normal saline solution that is either free in the FENT group or containing 60 mg ketorolac in ketorolac group, adjusted to a rate of 0.2 ml kg h^?1. Visual analogue score (VAS) and hemodynamic profile were recorded at 1, 6, 12, 24, 36 and 48 h while laboratory results were recorded after 48 h and 7 days post-operatively.ResultsVAS was significantly lower in ketorolac group compared to fentanyl group from 6 to 36 h post-operatively while sedation score was significantly higher in fentanyl group compared to fentanyl–ketorolac group between 12 and 36 h post-operatively. Fentanyl consumption was significantly lower in ketorolac group at 24 (318.7 ± 66 vs 468.3 ± 79) and 48 (211.5 ± 59 vs 369.1 ± 68) h. Hemodynamic data and laboratory parameters were comparable in both groups. Nausea had a significantly higher incidence in FENT compared to KETR groups while other complications (vomiting and blood loss) were homogenous in both groups.ConclusionAdding ketorolac to IV PCA fentanyl improved the analgesic state and reduced the dose of fentanyl used without adding any side effects or risks to donors subjected to right lobe hepatectomy.