毒理性
哺乳期使用概述：通常口服剂量的酮洛酸在乳汁中的水平较低，但在更高剂量的注射剂或鼻喷剂使用后，乳汁中的水平尚未经过测量。在一些医院的协议中，酮洛酸注射液在剖宫产后短时间使用（通常24小时），没有证据表明对哺乳婴儿有害。然而，由于初乳产量小，婴儿在初乳中接收到的酮洛酸剂量非常低。一些证据表明，与基于患者控制的静脉吗啡的镇痛相比，作为多模式剖宫后镇痛一部分的静脉注射酮洛酸可以减少未能进行纯母乳喂养的母亲比例。酮洛酸具有强烈的抗血小板活性，可能导致胃肠道出血。制造商指出，在哺乳期间酮洛酸是禁忌的，所以在产生较多乳汁的头24到72小时后，尤其是在哺乳新生儿或早产儿时，应优先选择其他药物。
母亲使用酮洛酸眼药水不会预期对哺乳婴儿造成任何不良影响。为了大幅减少使用眼药水后到达乳汁中的药物量，可以在眼角处对泪管施加压力1分钟或更长时间，然后用吸收性纸巾去除多余的溶液。
对哺乳婴儿的影响：一项随机双盲研究比较了接受剖宫产的标准护理的母亲（n = 60）与在筋膜闭合时接受标准护理加多模式疼痛管理，包括单次肌肉注射60毫克酮洛酸的母亲（n = 60）。在产后第一个月，两组在异常新生儿生长、喂养困难、新生儿镇静或呼吸抑制率方面没有显著差异。
对泌乳和乳汁的影响：一项随机双盲研究比较了接受剖宫产的标准护理的母亲（n = 60）与在筋膜闭合时接受标准护理加多模式疼痛管理，包括单次肌肉注射60毫克酮洛酸的母亲（n = 60）。在产后第一个月，两组的母乳喂养率（分别为78%和79%）没有显著差异。
在一项比较剖宫产后标准护理与加强恢复的研究中，固定剂量的酮洛酸15毫克每6小时静脉注射24小时是加强恢复方案的一部分，而在标准方案中，按需静脉注射酮洛酸15毫克。加强恢复方案中的患者（n = 58）纯母乳喂养的频率（67%）高于标准方案中的患者（48%; n = 60）。
一项回顾性研究评估了1349名接受剖宫产并在手术结束15分钟内给予酮洛酸的女性。结果表明，在手术后的前6小时内疼痛控制没有差异，也没有差异的是出院时正在哺乳的女性比例。
一项前瞻性队列研究比较了剖宫后疼痛控制，一组是吗啡PCA和定期服用布洛芬12小时，然后继续定期服用布洛芬，必要时使用氢可酮-对乙酰氨基酚，另一组是多模式疼痛管理方案，包括口服对乙酰氨基酚1000毫克每8小时一次，首次静脉注射酮洛酸30毫克，然后每8小时静脉注射15毫克，持续24小时，然后口服布洛芬600毫克每8小时一次，在整个术后过程中仅在必要时给予阿片类药物。计划在入院时纯母乳喂养的女性中，与传统的组相比，多模式组在出院前使用配方奶的女性较少（9%对12%）。
◉ Summary of Use during Lactation:Milk levels of ketorolac are low with the usual oral dosage, but milk levels have not been measured after higher injectable dosages or with the nasal spray. Ketorolac injection is used for a short time (typically 24 hours) after cesarean section in some hospital protocols with no evidence of harm to breastfed infants. However, the ketorolac dose an infant receives in colostrum is very low because of the small volume of colostrum produced. Some evidence suggests that IV ketorolac as part of a multimodal post-cesarean section analgesia reduces percentage of mothers who fail exclusive breastfeeding compared to patient-controlled IV morphine-based analgesia. Ketorolac has strong antiplatelet activity and can cause gastrointestinal bleeding. The manufacturer indicates that ketorolac is contraindicated during breastfeeding, so an alternate drug is preferred after the first 24 to 72 hours when larger volumes of milk are produced, especially while nursing a newborn or preterm infant.
Maternal use of ketorolac eye drops would not be expected to cause any adverse effects in breastfed infants. To substantially diminish the amount of drug that reaches the breastmilk after using eye drops, place pressure over the tear duct by the corner of the eye for 1 minute or more, then remove the excess solution with an absorbent tissue.
◉ Effects in Breastfed Infants:A randomized, double-blind study compared standard care of mothers receiving a cesarean section delivery (n = 60) to those receiving standard care plus multimodal pain management that included a single dose of 60 mg of intramuscular ketorolac given at the time of fascial closure (n = 60). No significant differences in abnormal neonatal growth, difficulty feeding, neonatal sedation, or respiratory depression rates between the two groups were seen during the first month postpartum.
◉ Effects on Lactation and Breastmilk:A randomized, double-blind study compared standard care of mothers receiving a cesarean section delivery (n = 60) to those receiving standard care plus multimodal pain management that included a single dose of 60 mg of intramuscular ketorolac given at the time of fascial closure (n = 60). No significant differences in breastfeeding rates (78% and 79%, respectively) were seen during the first month postpartum.
In a study comparing standard of care to enhanced recovery after cesarean section deliveries, a fixed dose of ketorolac 15 mg every 6 hours intravenously for 24 hours postpartum was part of the enhanced recovery protocol whereas as needed ketorolac 15 mg intravenously was part of the standard protocol. Patients in the enhanced recovery protocol (n = 58) had a greater frequency of exclusive breastfeeding (67%) than those in the standard protocol (48%; n = 60).
A retrospective study evaluated 1349 women who had undergone a cesarean section and were given ketorolac within 15 minutes of the end of surgery. The results indicated that there was no difference in pain control in the first 6 hours after surgery nor in the percentage of women who were breastfeeding at discharge.
A prospective cohort study of postcesarean pain control compared (1) morphine PCA and scheduled ibuprofen for the first 12 hours followed by continued scheduled ibuprofen with hydrocodone-acetaminophen as needed to a multimodal pain management regimen consisting of (2) acetaminophen 1000 mg orally every 8 hours, ketorolac 30 mg IV once initially, then 15 mg IV every 8 hours for 24 hours, then ibuprofen 600 mg orally every 8 hours for the remainder of the postoperative course with opioids given only as needed. Of women who planned to exclusively breastfeed on admission, fewer women used formula prior to discharge in the multimodal group compared to the traditional group (9% vs. 12%).
来源:Drugs and Lactation Database (LactMed)
