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.     

Methylprednisolone intravenously 1 day after surgery has sustained analgesic and opioid-sparing effects

BACKGROUND: In previous studies on glucocorticoids for postoperative pain, the test drug has been given perioperatively, usually before measurement of baseline pain. In order to evaluate the time course and magnitude of the analgesic effect of a glucocorticoid in well-established postoperative pain, we compared methylprednisolone with ketorolac and placebo, after assessment of baseline pain on the first postoperative day. METHODS: This was a double-blind, single dose, randomized, parallel comparison of intravenous (i.v.) methylprednisolone 125 mg, ketorolac 30 mg as an active control, and placebo in 75 patients with moderate to severe pain 1 day after orthopaedic surgery. Outcome variables were pain intensity (0-100 VAS), pain relief (0-4 PAR) and rescue opioid consumption. RESULTS: Methylprednisolone was not significantly different from ketorolac and gave significantly lower pain intensity from 1 h (0-6 h, P < 0.02), and more pain relief 2-6 h after test drugs (P < 0.05) compared with placebo. After 24 h, pain intensity was lower in both active drug groups compared with placebo (methylprednisolone, P < 0.0001; ketorolac, P < 0.007). Number needed to treat (NNT) calculated from patients having more than at least 50% of maximum obtainable total pain relief during the first 6 h (>50%maxTOTPAR(6 h)) was 3.6 for methylprednisolone and 3.1 for ketorolac. Number needed to treat calculated from the percentage reporting at least 50% pain relief for at least 4 h (>50%PAR(4 h)) was 2.8 for both groups. Opioid consumption was significantly reduced for 72 h after methylprednisolone compared with ketorolac (P < 0.02) and placebo (P < 0.003). CONCLUSION: Methylprednisolone 125 mg i.v. 1 day after surgery gave similar early reduction of pain as i.v. ketorolac 30 mg. Less pain than placebo 24 h after methylprednisolone, and lower opioid consumption for 72 h compared with ketorolac and placebo indicate sustained analgesic effects of methylprednisolone.     

卡贝缩宫素与欣母沛用于阴式分娩预防产后出血疗效观察

目的探讨卡贝缩宫素与欣母沛在阴式分娩中预防产后出血的临床效果,为临床治疗方案的选择提供理论依据。方法本研纳入2016年1~11月我院产科接收的有产后出血高危因素的产妇240例。按数字法随机分为两组,观察组(娩出后给予卡贝缩宫素)120例,对照组(胎儿娩出后应用欣母沛)120例,比较两组产妇产后2 h、4h出血量、分娩前后血红蛋白浓度下降幅度及两组不良反应情况。结果两组产时、产后2 h、4 h出血量比较差异无统学计意义(P0.05);两组分娩前后血红蛋白浓度变化比较差异无统学计意义(P0.05);观察组药物不良反应(恶心、呕吐、腹痛、面部潮红)发生率明显低于对照组(P0.05)。结论与欣母沛相比,卡贝缩宫素在预防阴式分娩产后出血方面有相同的疗效,且卡贝缩宫素不良反应较少。     

Emergency department analgesia without narcotics for adults with acute sickle cell pain crisis: Case reports and review of crisis management

Vaso-occlusive crises are one of the most debilitating features of sickle cell disease. There appears to be no standardization of care for adults with pain crisis, and some commonly utilized regimens, such as those employing intramuscular meperidine, are pharmacologically unsound. Parenteral narcotic use may be associated with respiratory compromise acutely and with dependence over the long term, but nonopioid preparations are often unsatisfactory in relieving pain. We have recently enjoyed success with a combination of a parenteral nonsteroidal anti-inflammatory medication and an oral tricyclic antidepressant. We report four representative cases and review the salient points of the management of pain crisis in adult patients in the emergency department.     

Double-masked study of the effects of nepafenac 0.1% and ketorolac 0.4% on corneal epithelial wound healing and pain after photorefractive keratectomy

Two NSAIDs—nepafenac 0.1% and ketorolac tromethamine 0.4%—were compared in terms of their effects on corneal reepithelialization and pain after photorefractive keratectomy (PRK) in a randomized, double-masked, contralateral eye, multicenter study. A total of 40 healthy adult patients who were undergoing sequential bilateral PRK received nepafenac 0.1% and ketorolac 0.4% in contralateral eyes, 1 drop 3 times daily for 3 d after bandage contact lens insertion. Patients were assessed on postoperative days 1, 3, 4, 5, and 7. At each visit, patients provided a general rating of pain. Each patient also assessed the sensation of each eyedrop following instillation (after-drop pain, irritation, burning/stinging, and overall comfort). Starting on day 3, epithelial defect size was assessed. Mean epithelial defect size was similar between treatments at each postoperative visit (P > .05). The average time-to-healing was 4.18 d for nepafenac 0.1 % and 4.00 d for ketorolac 0.4% (P=.3134). No statistical difference was observed between nepafenac 0.1% and ketorolac 0.4% in mean postoperative pain scores (P > .05). On day 3, the nepafenac 0.1% group had significantly lower mean sensation scores than did the ketorolac 0.4% group for after-drop pain (P=.0090), irritation (P=.0007), and burning/ stinging (P=.0003). Mean overall comfort score was also significantly better for nepafenac 0.1% on day 3 (7.43 vs 6.41; P < .0001). Nepafenac 0.1% and ketorolac 0.4% provide postoperative pain relief after PRK surgery without associated adverse effects on corneal epithelial healing. Nepafenac 0.1 % treatment may offer greater comfort upon instillation in patients who have undergone PRK.     

Bench-to-bedside review: treating acid-base abnormalities in the intensive care unit - the role of buffers

The recognition and management of acid-base disorders is a commonplace activity for intensivists. Despite the frequency with which non-bicarbonate-losing forms of metabolic acidosis such as lactic acidosis occurs in critically ill patients, treatment is controversial. This article describes the properties of several buffering agents and reviews the evidence for their clinical efficacy. The evidence supporting and refuting attempts to correct arterial pH through the administration of currently available buffers is presented.     

卡前列素氨丁三醇子宫肌内注射致产妇过敏性休克

1例27岁女性因产后出血,给予卡前列素氨丁三醇注射液250 μg子宫肌内注射.5 min后,患者突然出现胸闷、胸痛、心慌.先后给予地塞米松、麻黄碱、甲泼尼龙静脉滴注.症状未缓解并发展为大汗、意识模糊.心电监测T波振幅增高,血压降至70/40 mm Hg(1 mm Hg=0.133 kPa).诊断为过敏性休克.立即给予硝酸甘油及抗过敏治疗.3 h后症状逐渐缓解,血压升至100/60 mm Hg.     

反相高效液相色谱法测定酮咯酸氨丁三醇滴眼液的含量

目的 采用反相高效液相色谱法测定酮咯酸氨丁三醇滴眼液的含量.方法 采用RP-HPLC法,色谱柱为C8柱(4.6mm×250 mm,5μm);流动相为磷酸盐缓冲液-四氢呋喃(70 ∶ 30);流速为1.2 mL·min-1;检测波长313 nm.结果 酮咯酸氧丁三醇在0.24～0.56 mg·mL-1 (r=0.999 7)与峰面积呈良好线性关系,其平均回收率为100.3％,RSD=0.34％(n=9);仪器精密度RSD=0.23％(n=6);方法重复性RSD=0.43％(n=6).结论 该分析方法灵敏、准确,专属性强,重现性好,可以作为酮咯酸氨丁三醇滴眼液的质量控制方法.     

Neuroprotective effects of ketorolac tromethamine after spinal cord injury in rats: an ultrastructural study

Introduction The aim of this study was to investigate the effects of intrathecally administered ketorolac tromethamine on ultrastructural changes of the spinal cord in spinal cord-traumatised rats. Methods Male Wistar rats were used and divided into three groups for this study. The rats in Group S (n=6) were control animals and received 10 μl of saline. Groups K50 (n=6) and K400 (n=6) received intrathecally 50 μg and 400 μg of ketorolac tromethamine, respectively, immediately after trauma was induced. All rats underwent laminectomy and the spinal cord was traumatised using the clip-compression technique. Electron microscopic examination of the cord samples was carried out 3 days after spinal cord injury. Results Ultrastructural findings showed severe injury with extensive axoplasmic and cytoplasmic oedema in Group S. Minor neural damage occurred in Group K50 and increased ultrastructural protection was observed in the Group K400. Conclusion This study demonstrates that intrathecal administration of ketorolac tromethamine protects the spinal cord following injury in rats.