先兆子痫管理基于疾病的严重程度和进展情况。主要治疗包括监测、决定分娩日期和方式、降血压 (BP)、控制癫痫发作和产后液体管理。孕产妇死亡的主要原因是脑血管意外和肺水肿;因此无论是否存在其他并发症(例如子痫或 HELLP 综合征),降血压和产后液体管理是最重要的治疗方法。HELLP 综合征是重度子痫前期的一种亚型,以溶血 (H)、肝酶升高 (EL)、低血小板 (LP) 为特征。
治疗应当在三级医疗环境中或请有处理高危妊娠经验的产科/妇科医生会诊。[1]American College of Obstetricians and Gynecologists; Task Force on Hypertension in Pregnancy. Hypertension in pregnancy: report of the American College of Obstetricians and Gynecologists’ Task Force on Hypertension in Pregnancy. Obstet Gynecol. 2013 Nov;122(5):1122-31.http://www.acog.org/Resources-And-Publications/Task-Force-and-Work-Group-Reports/Hypertension-in-Pregnancyhttp://www.ncbi.nlm.nih.gov/pubmed/24150027?tool=bestpractice.com 不同国家之间的治疗不同;然而,基本的治疗原则相同。
住院
所有妇女,无论疾病严重程度如何,都应当住院接受治疗。[1]American College of Obstetricians and Gynecologists; Task Force on Hypertension in Pregnancy. Hypertension in pregnancy: report of the American College of Obstetricians and Gynecologists’ Task Force on Hypertension in Pregnancy. Obstet Gynecol. 2013 Nov;122(5):1122-31.http://www.acog.org/Resources-And-Publications/Task-Force-and-Work-Group-Reports/Hypertension-in-Pregnancyhttp://www.ncbi.nlm.nih.gov/pubmed/24150027?tool=bestpractice.com[3]National Institute for Health and Care Excellence. Hypertension in pregnancy: diagnosis and management. January 2011 [internet publication].http://www.nice.org.uk/guidance/cg107[2]Tranquilli AL, Dekker G, Magee L, et al. The classification, diagnosis and management of the hypertensive disorders of pregnancy: a revised statement from the ISSHP. Pregnancy Hypertens. 2014 Apr;4(2):97-104.http://www.ncbi.nlm.nih.gov/pubmed/26104417?tool=bestpractice.com 然而,对于控制良好的轻至中度病例,可以考虑门诊治疗,但需要在日间病房或类似场所实施密切的门诊监测。[1]American College of Obstetricians and Gynecologists; Task Force on Hypertension in Pregnancy. Hypertension in pregnancy: report of the American College of Obstetricians and Gynecologists’ Task Force on Hypertension in Pregnancy. Obstet Gynecol. 2013 Nov;122(5):1122-31.http://www.acog.org/Resources-And-Publications/Task-Force-and-Work-Group-Reports/Hypertension-in-Pregnancyhttp://www.ncbi.nlm.nih.gov/pubmed/24150027?tool=bestpractice.com[3]National Institute for Health and Care Excellence. Hypertension in pregnancy: diagnosis and management. January 2011 [internet publication].http://www.nice.org.uk/guidance/cg107[34]Lowe SA, Bowyer L, Lust K, et al. SOMANZ guidelines for the management of hypertensive disorders of pregnancy 2014. Aust N Z J Obstet Gynaecol. 2015 Oct;55(5):e1-29.https://somanz.org/downloads/HTguidelineupdatedJune2015.pdfhttp://www.ncbi.nlm.nih.gov/pubmed/26412014?tool=bestpractice.com
住院后,需要进一步评估。应当定期监测血压水平是否升高,是否需要干预以及对治疗的反应;然而,有关监测频率方面的指南很少。最好是在病房每日至少 4 次监测,或在重症监护病房持续监测。[3]National Institute for Health and Care Excellence. Hypertension in pregnancy: diagnosis and management. January 2011 [internet publication].http://www.nice.org.uk/guidance/cg107
分娩计划
子痫前期的最终治疗方法是终止妊娠;然而,这不一定总是能够立即实施。此外,即使在分娩后,疾病完全缓解可能也需要几天。只有全面评估母亲和婴儿的风险和收益后才能决定是否终止妊娠。对于婴儿的主要风险是早产,是新生儿发病和死亡的一个原因。[3]National Institute for Health and Care Excellence. Hypertension in pregnancy: diagnosis and management. January 2011 [internet publication].http://www.nice.org.uk/guidance/cg107 在即刻分娩情况下,新生儿医护费用也会大幅上涨。[43]van Baaren GJ, Broekhuijsen K, van Pampus MG, et al. An economic analysis of immediate delivery and expectant monitoring in women with hypertensive disorders of pregnancy, between 34 and 37 weeks of gestation (HYPITAT-II). BJOG. 2017 Feb;124(3):453-61.https://obgyn.onlinelibrary.wiley.com/doi/full/10.1111/1471-0528.13957http://www.ncbi.nlm.nih.gov/pubmed/26969198?tool=bestpractice.com
如果认为患者病情稳定(例如不存在癫痫发作,血压控制良好),通常采取保守方法,根据孕龄决定何时终止妊娠。[3]National Institute for Health and Care Excellence. Hypertension in pregnancy: diagnosis and management. January 2011 [internet publication].http://www.nice.org.uk/guidance/cg107[1]American College of Obstetricians and Gynecologists; Task Force on Hypertension in Pregnancy. Hypertension in pregnancy: report of the American College of Obstetricians and Gynecologists’ Task Force on Hypertension in Pregnancy. Obstet Gynecol. 2013 Nov;122(5):1122-31.http://www.acog.org/Resources-And-Publications/Task-Force-and-Work-Group-Reports/Hypertension-in-Pregnancyhttp://www.ncbi.nlm.nih.gov/pubmed/24150027?tool=bestpractice.com[34]Lowe SA, Bowyer L, Lust K, et al. SOMANZ guidelines for the management of hypertensive disorders of pregnancy 2014. Aust N Z J Obstet Gynaecol. 2015 Oct;55(5):e1-29.https://somanz.org/downloads/HTguidelineupdatedJune2015.pdfhttp://www.ncbi.nlm.nih.gov/pubmed/26412014?tool=bestpractice.com
<32 孕周:延长妊娠时间有益于胎儿,只要孕妇和胎儿评估令人满意。在孕妇或胎儿情况亟需终止妊娠前,抗高血压治疗平均可使用 15 天。[3]National Institute for Health and Care Excellence. Hypertension in pregnancy: diagnosis and management. January 2011 [internet publication].http://www.nice.org.uk/guidance/cg107 采用这种方案时,需要在院内仔细监测孕妇和胎儿状况。[44]Publications Committee, Society for Maternal-Fetal Medicine; Sibai BM. Evaluation and management of severe preeclampsia before 34 weeks' gestation. Am J Obstet Gynecol. 2011 Sep;205(3):191-8.https://www.ajog.org/article/S0002-9378(11)00918-5/fulltexthttp://www.ncbi.nlm.nih.gov/pubmed/22071049?tool=bestpractice.com 建议在 34 孕周前使用产前皮质类固醇,促进胎儿肺成熟。[3]National Institute for Health and Care Excellence. Hypertension in pregnancy: diagnosis and management. January 2011 [internet publication].http://www.nice.org.uk/guidance/cg107
在第 32 至 36 孕周:可指导治疗的证据有限,因此应当根据具体情况决定。一项研究在妊娠 34 至 37 周非重度子痫前期妇女中比较了立即分娩与期待治疗。[45]Broekhuijsen K, van Baaren GJ, van Pampus MG, et al; HYPITAT-II study group. Immediate delivery versus expectant monitoring for hypertensive disorders of pregnancy between 34 and 37 weeks of gestation (HYPITAT-II): an open-label, randomised controlled trial. Lancet. 2015 Jun 20;385(9986):2492-501.http://www.ncbi.nlm.nih.gov/pubmed/25817374?tool=bestpractice.com 延迟分娩对孕产妇并发症的发生并没有显著影响,但提前分娩可增加婴儿呼吸窘迫综合征的发生。[45]Broekhuijsen K, van Baaren GJ, van Pampus MG, et al; HYPITAT-II study group. Immediate delivery versus expectant monitoring for hypertensive disorders of pregnancy between 34 and 37 weeks of gestation (HYPITAT-II): an open-label, randomised controlled trial. Lancet. 2015 Jun 20;385(9986):2492-501.http://www.ncbi.nlm.nih.gov/pubmed/25817374?tool=bestpractice.com 这表明,若产妇临床情况稳定,可在监测下继续妊娠,最长到 37 周。但是,当将这些结果与另一项随机临床试验相结合时发现,计划提前分娩可降低产妇在达到妊娠 34 周后的发病率和死亡率,不过作者承认数据有限。[46]Cluver C, Novikova N, Koopmans CM, et al. Planned early delivery versus expectant management for hypertensive disorders from 34 weeks gestation to term. Cochrane Database Syst Rev. 2017;(1):CD009273.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD009273.pub2/abstracthttp://www.ncbi.nlm.nih.gov/pubmed/28106904?tool=bestpractice.com 若母亲疾病的严重程度有所增加,则需要立即分娩。为了减少呼吸窘迫综合征,建议在妊娠达 34 周前,于产前使用皮质类固醇以促胎儿肺成熟。[3]National Institute for Health and Care Excellence. Hypertension in pregnancy: diagnosis and management. January 2011 [internet publication].http://www.nice.org.uk/guidance/cg107 在第 34 至 36 周给予产前皮质类固醇,可能有益,但受益不明确,应当根据具体的病例决定。[3]National Institute for Health and Care Excellence. Hypertension in pregnancy: diagnosis and management. January 2011 [internet publication].http://www.nice.org.uk/guidance/cg107
>36 孕周:终止妊娠是最合理的方法。
如果认为患者病情不稳定(即,存在癫痫发作、未得到控制的高血压),在考虑分娩前,应对患者进行硫酸镁和降压治疗。[2]Tranquilli AL, Dekker G, Magee L, et al. The classification, diagnosis and management of the hypertensive disorders of pregnancy: a revised statement from the ISSHP. Pregnancy Hypertens. 2014 Apr;4(2):97-104.http://www.ncbi.nlm.nih.gov/pubmed/26104417?tool=bestpractice.com 应在患者稳定后考虑分娩,因为不稳定患者仓促分娩可能有危险。
分娩的方式取决于孕龄,应当根据患者的具体情况决定。[3]National Institute for Health and Care Excellence. Hypertension in pregnancy: diagnosis and management. January 2011 [internet publication].http://www.nice.org.uk/guidance/cg107[1]American College of Obstetricians and Gynecologists; Task Force on Hypertension in Pregnancy. Hypertension in pregnancy: report of the American College of Obstetricians and Gynecologists’ Task Force on Hypertension in Pregnancy. Obstet Gynecol. 2013 Nov;122(5):1122-31.http://www.acog.org/Resources-And-Publications/Task-Force-and-Work-Group-Reports/Hypertension-in-Pregnancyhttp://www.ncbi.nlm.nih.gov/pubmed/24150027?tool=bestpractice.com[34]Lowe SA, Bowyer L, Lust K, et al. SOMANZ guidelines for the management of hypertensive disorders of pregnancy 2014. Aust N Z J Obstet Gynaecol. 2015 Oct;55(5):e1-29.https://somanz.org/downloads/HTguidelineupdatedJune2015.pdfhttp://www.ncbi.nlm.nih.gov/pubmed/26412014?tool=bestpractice.com
如果实施剖宫产,在孕妇能够耐受并且没有凝血障碍的情况下,首选局部麻醉。如使用全身麻醉,应当谨慎,以预防对插管和拔管的高血压反应以及喉水肿风险。[47]Hein HA. Cardiorespiratory arrest with laryngeal oedema in pregnancy-induced hypertension. Can Anaesth Soc J. 1984 Mar;31(2):210-2.http://www.ncbi.nlm.nih.gov/pubmed/6704786?tool=bestpractice.com
高血压的管理
如果收缩压≥160 mmHg 和/或舒张压≥110 mmHg,应当开始降压治疗。[1]American College of Obstetricians and Gynecologists; Task Force on Hypertension in Pregnancy. Hypertension in pregnancy: report of the American College of Obstetricians and Gynecologists’ Task Force on Hypertension in Pregnancy. Obstet Gynecol. 2013 Nov;122(5):1122-31.http://www.acog.org/Resources-And-Publications/Task-Force-and-Work-Group-Reports/Hypertension-in-Pregnancyhttp://www.ncbi.nlm.nih.gov/pubmed/24150027?tool=bestpractice.com 口服单一降压药对大多数病例有效,但有些妇女可能需要联合治疗,使用两种不同的抗高血压药物或静脉治疗,取决于临床情况。如果在开始治疗后 1 小时内不能充分降低血压,应当再次给予 1 剂,联合用药,或开始静脉注射给药方案。不需要将血压降得太快或太低;目的是阻止血压上升,将血压逐步降到收缩压<150 mmHg 和舒张压<100 mmHg。
拉贝洛尔被认为是首选抗高血压药物,[3]National Institute for Health and Care Excellence. Hypertension in pregnancy: diagnosis and management. January 2011 [internet publication].http://www.nice.org.uk/guidance/cg107[1]American College of Obstetricians and Gynecologists; Task Force on Hypertension in Pregnancy. Hypertension in pregnancy: report of the American College of Obstetricians and Gynecologists’ Task Force on Hypertension in Pregnancy. Obstet Gynecol. 2013 Nov;122(5):1122-31.http://www.acog.org/Resources-And-Publications/Task-Force-and-Work-Group-Reports/Hypertension-in-Pregnancyhttp://www.ncbi.nlm.nih.gov/pubmed/24150027?tool=bestpractice.com[48]Committee on Obstetric Practice. Committee opinion no. 514: emergent therapy for acute-onset, severe hypertension with preeclampsia or eclampsia. Obstet Gynecol. 2011 Dec;118(6):1465-8.http://www.ncbi.nlm.nih.gov/pubmed/22105295?tool=bestpractice.com[2]Tranquilli AL, Dekker G, Magee L, et al. The classification, diagnosis and management of the hypertensive disorders of pregnancy: a revised statement from the ISSHP. Pregnancy Hypertens. 2014 Apr;4(2):97-104.http://www.ncbi.nlm.nih.gov/pubmed/26104417?tool=bestpractice.com 且作为单药治疗时,在 80% 的患者中有效。[6]Tuffnell DJ, Jankowicz D, Lindow SW, et al. Outcomes of severe pre-eclampsia/eclampsia in Yorkshire 1999/2003. BJOG. 2005 Jul;112(7):875-80.http://onlinelibrary.wiley.com/doi/10.1111/j.1471-0528.2005.00565.x/fullhttp://www.ncbi.nlm.nih.gov/pubmed/15957986?tool=bestpractice.com 它能安全有效地治疗子痫前期;但是,应当避免用于加勒比黑人妇女,因为她们对 β 受体阻滞剂的反应不佳,也应当避免用于患有哮喘或其他任何使用禁忌症的妇女。[1]American College of Obstetricians and Gynecologists; Task Force on Hypertension in Pregnancy. Hypertension in pregnancy: report of the American College of Obstetricians and Gynecologists’ Task Force on Hypertension in Pregnancy. Obstet Gynecol. 2013 Nov;122(5):1122-31.http://www.acog.org/Resources-And-Publications/Task-Force-and-Work-Group-Reports/Hypertension-in-Pregnancyhttp://www.ncbi.nlm.nih.gov/pubmed/24150027?tool=bestpractice.com
如果重度高血压对口服拉贝洛尔无反应,那么口服硝苯地平可能与静脉用拉贝洛尔一样有效。[49]Shekhar S, Gupta N, Kirubakaran R, et al. Oral nifedipine versus intravenous labetalol for severe hypertension during pregnancy: a systematic review and meta-analysis. BJOG. 2016 Jan;123(1):40-7.http://onlinelibrary.wiley.com/doi/10.1111/1471-0528.13463/fullhttp://www.ncbi.nlm.nih.gov/pubmed/26113232?tool=bestpractice.com 如需要,硝苯地平还可与拉贝洛尔或甲基多巴安全地联合使用。在极端情况下,可把拉贝洛尔、硝苯地平和甲基多巴联合使用。
肼屈嗪广泛用于治疗重度妊娠期高血压;然而,它能使血压急剧下降,使用时应同时扩容。可以少量多次给药;然而,认为拉贝洛尔是首选药物。[3]National Institute for Health and Care Excellence. Hypertension in pregnancy: diagnosis and management. January 2011 [internet publication].http://www.nice.org.uk/guidance/cg107[1]American College of Obstetricians and Gynecologists; Task Force on Hypertension in Pregnancy. Hypertension in pregnancy: report of the American College of Obstetricians and Gynecologists’ Task Force on Hypertension in Pregnancy. Obstet Gynecol. 2013 Nov;122(5):1122-31.http://www.acog.org/Resources-And-Publications/Task-Force-and-Work-Group-Reports/Hypertension-in-Pregnancyhttp://www.ncbi.nlm.nih.gov/pubmed/24150027?tool=bestpractice.com
子痫的治疗
硫酸镁是子痫妇女的首选治疗。[3]National Institute for Health and Care Excellence. Hypertension in pregnancy: diagnosis and management. January 2011 [internet publication].http://www.nice.org.uk/guidance/cg107[1]American College of Obstetricians and Gynecologists; Task Force on Hypertension in Pregnancy. Hypertension in pregnancy: report of the American College of Obstetricians and Gynecologists’ Task Force on Hypertension in Pregnancy. Obstet Gynecol. 2013 Nov;122(5):1122-31.http://www.acog.org/Resources-And-Publications/Task-Force-and-Work-Group-Reports/Hypertension-in-Pregnancyhttp://www.ncbi.nlm.nih.gov/pubmed/24150027?tool=bestpractice.com[2]Tranquilli AL, Dekker G, Magee L, et al. The classification, diagnosis and management of the hypertensive disorders of pregnancy: a revised statement from the ISSHP. Pregnancy Hypertens. 2014 Apr;4(2):97-104.http://www.ncbi.nlm.nih.gov/pubmed/26104417?tool=bestpractice.com 一些临床试验证明,肌内注射或静脉给药的疗效相同。[50]Which anticonvulsant for women with eclampsia? Evidence from the Collaborative Eclampsia Trial. Lancet. 1995 Jun 10;345(8963):1455-63.http://www.ncbi.nlm.nih.gov/pubmed/7769899?tool=bestpractice.com 美国建议使用较高剂量;然而,这没有随机试验证明有额外的益处,但观察性研究支持这一点。[3]National Institute for Health and Care Excellence. Hypertension in pregnancy: diagnosis and management. January 2011 [internet publication].http://www.nice.org.uk/guidance/cg107 虽然癫痫发作很可怕,但大多数妇女无需治疗即可恢复,大多数不会再次惊厥,也没有方法预防将来的癫痫发作。
[Figure caption and citation for the preceding image starts]: 重症监护病房中,癫痫发作后的重度子痫前期患者来自 Dr James J. Walker 的个人收集;经获准使用 [Citation ends].
如果使用低剂量方案,仅当患者有肾损害时需要监测血清镁水平。[3]National Institute for Health and Care Excellence. Hypertension in pregnancy: diagnosis and management. January 2011 [internet publication].http://www.nice.org.uk/guidance/cg107 如果使用高剂量方案,应当在给药后 6 小时检查血清镁水平,然后根据需要检查。治疗浓度是 4 至 7 mEq/L(4.8 至 8.4 mg/dL)。[1]American College of Obstetricians and Gynecologists; Task Force on Hypertension in Pregnancy. Hypertension in pregnancy: report of the American College of Obstetricians and Gynecologists’ Task Force on Hypertension in Pregnancy. Obstet Gynecol. 2013 Nov;122(5):1122-31.http://www.acog.org/Resources-And-Publications/Task-Force-and-Work-Group-Reports/Hypertension-in-Pregnancyhttp://www.ncbi.nlm.nih.gov/pubmed/24150027?tool=bestpractice.com 一旦浓度达到 10 mEq/L,可能发生呼吸抑制,膝反射可能消失;然而,可以使用葡萄糖酸钙逆转这些作用。
尽管硫酸镁有益于已经发生的癫痫发作,但预防癫痫发作的作用尚不确定。[50]Which anticonvulsant for women with eclampsia? Evidence from the Collaborative Eclampsia Trial. Lancet. 1995 Jun 10;345(8963):1455-63.http://www.ncbi.nlm.nih.gov/pubmed/7769899?tool=bestpractice.com 在美国,推荐在所有重度子痫前期女性中使用。[1]American College of Obstetricians and Gynecologists; Task Force on Hypertension in Pregnancy. Hypertension in pregnancy: report of the American College of Obstetricians and Gynecologists’ Task Force on Hypertension in Pregnancy. Obstet Gynecol. 2013 Nov;122(5):1122-31.http://www.acog.org/Resources-And-Publications/Task-Force-and-Work-Group-Reports/Hypertension-in-Pregnancyhttp://www.ncbi.nlm.nih.gov/pubmed/24150027?tool=bestpractice.com 在其他国家,包括英国,建议使用更有针对性的方法,允许医生根据患者的具体危险因素(例如存在未得到控制的高血压、蛋白尿 ≥5 g/24 小时、孕妇状况恶化)实施个体判断。[3]National Institute for Health and Care Excellence. Hypertension in pregnancy: diagnosis and management. January 2011 [internet publication].http://www.nice.org.uk/guidance/cg107
产后管理
分娩后需要继续控制高血压和癫痫发作,直到明显恢复。在这个阶段,产妇的主要风险是体液潴留。虽然美国建议使用有创性血液动力学监测,[1]American College of Obstetricians and Gynecologists; Task Force on Hypertension in Pregnancy. Hypertension in pregnancy: report of the American College of Obstetricians and Gynecologists’ Task Force on Hypertension in Pregnancy. Obstet Gynecol. 2013 Nov;122(5):1122-31.http://www.acog.org/Resources-And-Publications/Task-Force-and-Work-Group-Reports/Hypertension-in-Pregnancyhttp://www.ncbi.nlm.nih.gov/pubmed/24150027?tool=bestpractice.com 在英国,指南是基于 80 mL/h 的限液方案。[3]National Institute for Health and Care Excellence. Hypertension in pregnancy: diagnosis and management. January 2011 [internet publication].http://www.nice.org.uk/guidance/cg107 使用这个方案没有发生因肺水肿导致的死亡,且入住重症监护病房的患者减少。[6]Tuffnell DJ, Jankowicz D, Lindow SW, et al. Outcomes of severe pre-eclampsia/eclampsia in Yorkshire 1999/2003. BJOG. 2005 Jul;112(7):875-80.http://onlinelibrary.wiley.com/doi/10.1111/j.1471-0528.2005.00565.x/fullhttp://www.ncbi.nlm.nih.gov/pubmed/15957986?tool=bestpractice.com[21]Centre for Maternal and Child Enquiries (CMACE). Saving mothers' lives: reviewing maternal deaths to make motherhood safer: 2006-08. The Eighth Report on Confidential Enquiries into Maternal Deaths in the United Kingdom. BJOG. 2011 Mar;118(suppl 1):1-203.http://onlinelibrary.wiley.com/doi/10.1111/j.1471-0528.2010.02847.x/epdfhttp://www.ncbi.nlm.nih.gov/pubmed/21356004?tool=bestpractice.com 应当使用液体出入量表记录产妇的液体情况。只要尿液正常,静脉输液应当限制到 80 mL/小时,直到患者自由饮水。不需要治疗尿排出量低,除非经过仔细考虑并且在严格监护下,否则不应当给予液体冲击。只要心血管情况稳定,有充足的尿排出量,氧饱和度得到维持,就无需有创性监测。[3]National Institute for Health and Care Excellence. Hypertension in pregnancy: diagnosis and management. January 2011 [internet publication].http://www.nice.org.uk/guidance/cg107
如果怀疑分娩期间,尤其是剖宫产期间液体给药导致的体液潴留,建议审慎使用利尿剂。[3]National Institute for Health and Care Excellence. Hypertension in pregnancy: diagnosis and management. January 2011 [internet publication].http://www.nice.org.uk/guidance/cg107
中心静脉置管的动画演示