Forrest J B, Heitlinger E L, Revell S
McMaster University Medical Centre, Hamilton, Ontario, Canada.
Drug Saf. 1997 May;16(5):309-29. doi: 10.2165/00002018-199716050-00003.
Ketorolac is a nonsteroidal anti-inflammatory drug (NSAID) with potent analgesic effects and a relatively low incidence of adverse effects. Numerous clinical trials of postoperative pain treatment in children have shown that ketorolac is as effective as the major opioid analgesics, such as morphine, and more effective than codeine. The pharmacokinetics of ketorolac differ in children compared with adult patients after surgery. In children, the volume of distribution (Vd) of ketorolac is increased by as much as 2-fold relative to that in adults. The plasma clearance (CL) of ketorolac is also higher in children, probably because of lower binding to plasma proteins. However, the elimination half-life (t 1/2 beta) of ketorolac is similar in children and adults because t 1/2 beta is directly proportional to Vd but inversely proportional to CL. These pharmacokinetic differences indicate that a higher relative dosage is required in children, but the dosage interval is similar in children and adults. Ketorolac can be administered intravenously, intramuscularly or orally. The intravenous route is preferred during the immediate postoperative period, until the patient can tolerate oral medication. Intramuscular injections are not recommended in children, unless the intravenous route is unavailable. The recommended intravenous dosage of ketorolac in children is 0.5 mg/kg, followed either by bolus injections of 1.0 mg/kg every 6 hours or an intravenous infusion of 0.17 mg/kg/h. The maximum daily dosage is 90mg, and the maximum duration of treatment is 48 hours. The recommended oral dosage is 0.25 mg/kg to a maximum of 1.0 mg/kg/day, with a maximum duration of 7 days. Older children may require somewhat lower dosages, while infants and young children may require slightly higher dosages to achieve the same level of pain relief. Ketorolac is not recommended for use in infants aged < 1 year. Unlike opioid analgesics ketorolac does not depress ventilation, and is not associated with nausea and vomiting, urinary retention or sedation. When combined with an opioid, ketorolac exhibits marked opioid-sparing effects, allowing a lower dosage of opioid to be used. Clinical studies in children and adults show that the synergistic action of ketorolac and opioids improves the degree and quality of pain relief, and reduces the incidence of opioid-related adverse effects such as respiratory depression, nausea/vomiting and ileus. Recovery of bowel function after abdominal surgery occurs sooner in ketorolac-compared with opioid-treated patients. Ketorolac reversibly inhibits cyclo-oxygenase, and decreases the hypersensitisation of tissue nociceptors that occurs with surgery. It also has reversible antiplatelet effects, which are attributable to the inhibition of thromboxane synthesis. Bleeding time is usually slightly increased, but in most patients it remains within normal values. There is conflicting evidence of the potential for increased surgical-site bleeding after tonsillectomy but, for other types of paediatric surgery, numerous clinical studies have confirmed that ketorolac is not associated with increased bleeding. Thus, ketorolac is well suited for the treatment of postoperative pain in children, either alone or in combination with opioids or local anaesthetics, because of its analgesic potency and relatively low incidence of adverse effects.
酮咯酸是一种具有强效镇痛作用且不良反应发生率相对较低的非甾体抗炎药(NSAID)。众多针对儿童术后疼痛治疗的临床试验表明,酮咯酸与主要的阿片类镇痛药(如吗啡)效果相当,且比可待因更有效。与术后的成年患者相比,酮咯酸在儿童体内的药代动力学有所不同。在儿童中,酮咯酸的分布容积(Vd)相对于成年人增加了多达2倍。酮咯酸的血浆清除率(CL)在儿童中也更高,这可能是由于其与血浆蛋白的结合较低。然而,酮咯酸的消除半衰期(t1/2β)在儿童和成年人中相似,因为t1/2β与Vd成正比,但与CL成反比。这些药代动力学差异表明儿童需要相对更高的剂量,但儿童和成年人的给药间隔相似。酮咯酸可以静脉注射、肌肉注射或口服。在术后即刻,直到患者能够耐受口服药物,静脉途径是首选。除非无法采用静脉途径,否则不建议对儿童进行肌肉注射。儿童酮咯酸的推荐静脉剂量为0.5mg/kg,随后每6小时静脉推注1.0mg/kg或静脉输注0.17mg/kg/h。最大日剂量为90mg,最大治疗时长为48小时。推荐的口服剂量为0.25mg/kg,最大剂量为1.0mg/kg/天,最大疗程为7天。年龄较大的儿童可能需要稍低的剂量,而婴儿和幼儿可能需要稍高的剂量才能达到相同的疼痛缓解水平。不建议1岁以下婴儿使用酮咯酸。与阿片类镇痛药不同,酮咯酸不会抑制通气,也不会引起恶心、呕吐、尿潴留或镇静。与阿片类药物联合使用时,酮咯酸具有显著的阿片类药物节省作用,可使用较低剂量的阿片类药物。儿童和成年人的临床研究表明,酮咯酸与阿片类药物的协同作用可提高疼痛缓解的程度和质量,并降低与阿片类药物相关的不良反应(如呼吸抑制、恶心/呕吐和肠梗阻)的发生率。与接受阿片类药物治疗的患者相比,接受酮咯酸治疗的患者腹部手术后肠功能恢复更快。酮咯酸可逆性抑制环氧化酶,并减少手术时发生的组织伤害感受器的超敏反应。它还具有可逆的抗血小板作用,这归因于对血栓素合成的抑制。出血时间通常略有增加,但在大多数患者中仍保持在正常范围内。关于扁桃体切除术后手术部位出血增加的可能性存在相互矛盾的证据,但对于其他类型的儿科手术,众多临床研究已证实酮咯酸与出血增加无关。因此,由于其镇痛效力和相对较低的不良反应发生率,酮咯酸非常适合单独或与阿片类药物或局部麻醉剂联合用于治疗儿童术后疼痛。
Drug Saf. 1997-5
Acta Anaesthesiol Belg. 1996
Acta Anaesthesiol Scand. 1998-8
J Post Anesth Nurs. 1992-8
Ann Burns Fire Disasters. 2021-3-31
J Clin Med. 2021-4-23
J Pediatr Pharmacol Ther. 2021
Plast Reconstr Surg Glob Open. 2019-8-21
Open Access Maced J Med Sci. 2019-3-29
Cochrane Database Syst Rev. 2018-7-7
GMS Curr Top Otorhinolaryngol Head Neck Surg. 2014-12-1
Korean J Anesthesiol. 2014-3
Reg Anesth. 1996
Arch Otolaryngol Head Neck Surg. 1996-9
Adv Immunol. 1996
Can J Anaesth. 1996-6
Can J Anaesth. 1996-6
Semin Thromb Hemost. 1995