毒理性
◉ 母乳喂养期间使用概述：有限的数据表明，氢吗啡酮以少量排入乳汁中，但大剂量的母体用药会导致新生儿中枢神经系统抑制。通常情况下，哺乳期妇女使用口服麻醉剂可能会导致婴儿昏昏欲睡，严重的中枢神经系统抑制。哺乳期母亲应限制使用氢吗啡酮。新生婴儿似乎对即使是小剂量的麻醉性镇痛剂的影响也非常敏感。一旦母亲的乳汁开始分泌，最好使用非麻醉性镇痛剂来控制疼痛，并将母亲氢吗啡酮的摄入量限制在2到3天的小剂量，并密切监测婴儿。如果婴儿表现出过度困倦（比平时更甚）、哺乳困难、呼吸困难或无力，应立即联系医生。
◉ 对哺乳婴儿的影响：一名6天大的婴儿部分通过口服氢吗啡酮的母亲哺乳，该母亲在剖宫产后每隔4小时服用4毫克氢吗啡酮以止痛。由于过度困倦，婴儿被带到急诊科。婴儿出现了间歇性心动过缓，并有一次需要袋阀面罩干预的呼吸暂停事件。婴儿接受了0.36毫克纳洛酮，30秒内开始自主呼吸，心率达到165次/分钟，并变得更加警觉。15分钟后，他又出现了一次呼吸暂停，迅速用另一剂纳洛酮解决。进行了广泛的实验室检测，所有测试结果均为阴性，包括尿液阿片类药物筛查。作者指出，大多数尿液阿片类药物筛查测试对半合成的阿片类药物如氢吗啡酮不敏感，因为它们不会代谢成吗啡。婴儿的呼吸暂停可能是由于乳汁中的氢吗啡酮引起的。
一名出生于使用阿片类药物成瘾的母亲的婴儿，该母亲每天最多使用2克静脉注射芬太尼。在医院，她被转为静脉注射氢吗啡酮120毫克，每天三次，口服氢吗啡酮32毫克，按需服用，以及口服美沙酮70毫克，每天一次。在口服吗啡剂量减量9天后，婴儿被给予72毫升母亲的挤奶。在第10天，婴儿服用了两次0.1毫克的口服吗啡，然后在母亲注射110毫克静脉注射氢吗啡酮后3小时哺乳了30分钟。婴儿警觉活跃，进食和睡眠良好，婴儿的吗啡被停用。没有出现临床相关的呼吸暂停、心动过缓、低氧饱和度、呼吸抑制或过度镇静的发作。婴儿继续接受配方奶以及哺乳或挤奶，没有出现重要的不良反应。在47天内逐渐减少母亲的氢吗啡酮剂量，同时口服美沙酮和口服缓释吗啡的剂量分别增加到190毫克和1200毫克，她在分娩后第58天出院。出院后母乳喂养的情况没有报告。在4个月大时，婴儿在所有发展领域得分高于平均水平。
在加拿大安大略省的一项人口研究中，有85,852名在分娩出院后7天内填写阿片类药物处方的母亲与538,815名未填写的母亲进行了匹配。与出生时母亲未开阿片类药物处方的婴儿相比，出生时母亲开阿片类药物处方的婴儿在指数日期后30天内住院的可能性并不更高。出生时母亲在分娩后开阿片类药物处方的婴儿在随后的30天内去急诊科的可能性略高（危险比1.04）。没有婴儿死亡。开阿片类药物处方的母亲中有12%开了氢吗啡酮。值得注意的是，药物供应的中位数是3天（IQR 2-4）。
◉ 对泌乳和母乳的影响：麻醉剂可以增加血清催乳素。然而，已建立泌乳的母亲催乳素水平可能不会影响她哺乳的能力。
◉ Summary of Use during Lactation:Limited data indicate that hydromorphone is excreted into breastmilk in small amounts, but large maternal dosages have caused neonatal central nervous system depression. In general, Maternal use of oral narcotics during breastfeeding can cause infant drowsiness, and severe central nervous system depression. Hydromorphone use should be limited in nursing mothers. Newborn infants seem to be particularly sensitive to the effects of even small dosages of narcotic analgesics. Once the mother's milk comes in, it is best to provide pain control with a nonnarcotic analgesic and limit maternal intake of hydromorphone to 2 to 3 days at a low dosage with close infant monitoring. If the baby shows signs of increased sleepiness (more than usual), difficulty breastfeeding, breathing difficulties, or limpness, a physician should be contacted immediately.
◉ Effects in Breastfed Infants:A 6-day-old infant was being partially breastfed by a mother who was taking oral hydromorphone 4 mg every 4 hours for pain following a cesarean section. The infant was brought to the emergency department because of excessive drowsiness. The infant was having intermittent bradycardia and had an apneic event requiring bag-valve-mask intervention. The infant received 0.36 mg of naloxone and within 30 seconds developed spontaneous respirations, a heart rate of 165 beats/minute and increased alertness. Fifteen minutes later, he had another apneic episode that resolved rapidly with another dose of naloxone. Extensive laboratory testing was performed and all tests were negative, including a urine opiate screen. The authors note that most urine opiate screening tests are insensitive to semisynthetic opiates such as hydromorphone that are not metabolized to morphine. The infant's apnea was probably caused by hydromorphone in breastmilk.
An infant was born to a mother with opioid use disorder who was taking up to 2 grams of intravenous fentanyl daily. In the hospital she was transitioned to intravenous hydromorphone 120 mg three time daily, oral hydromorphone 32 mg every hour as needed, and methadone 70 mg daily by mouth. After 9 days of tapering the oral morphine dosage, the infant was given 72 mL of the mother’s expressed milk. On day 10, the infant received two doses of 0.1 mg of oral morphine and then breastfed for 30 minutes 3 hours after a maternal dose of 110 mg of intravenous hydromorphone. The infant was alert and active, feeding and sleeping well, and the infant’s morphine was discontinued. There were no clinically relevant episodes of apnea, bradycardia, desaturation, signs of respiratory depression, or excessive sedation. The infant continued to receive formula plus either breastfeeding or expressed milk with no clinically important adverse effects. The mother’s hydromorphone dose was tapered over 47 days while oral methadone and oral slow-release morphine were increased to 190 mg and 1200 mg daily, respectively, and she was discharged on day 58 postpartum. The extent of breastfeeding after hospital discharge was not reported. At 4 months of age, the infant scored above average on all developmental domains.
In population study in the province of Ontario, Canada, 85,852 who filled an opioid prescription within seven days of discharge after delivery were matched to 538,815 did not. Compared with infants born to mothers who were not prescribed an opioid, those born to mothers prescribed an opioid were no more likely to be admitted to hospital in the 30 days after the index date. Infants born to mothers prescribed opioids after delivery were slightly more likely to be taken to the emergency department in the subsequent 30 days (hazard ratio 1.04). No infant deaths occurred. Twelve percent of the mothers prescribed an opioid were prescribed hydromorphone. Of note is that the median drug supply was for 3 days (IQR 2-4).
◉ Effects on Lactation and Breastmilk:Narcotics can increase serum prolactin. However, the prolactin level in a mother with established lactation may not affect her ability to breastfeed.
来源:Drugs and Lactation Database (LactMed)
