妊娠期恶心呕吐 (NVP) 的治疗取决于就诊时症状的严重程度和持续时间。常见妊娠期恶心和呕吐的治疗方式可分为非药物和药物治疗。考虑到发育中的胎儿,最常推荐非药物治疗方案作为一线治疗。如果这些方法无效,则应考虑药物治疗。[16]Mahadevan U, Kane S. American Gastroenterological Association Institute medical position statement on the use of gastrointestinal medications in pregnancy. Gastroenterology. 2006;131:278-282.http://www.gastrojournal.org/article/S0016-5085%2806%2900864-X/fulltexthttp://www.ncbi.nlm.nih.gov/pubmed/16831610?tool=bestpractice.com目前没有充分的证据支持任何一种干预措施。[17]Matthews A, Haas DM, O'Mathúna DP, et al. Interventions for nausea and vomiting in early pregnancy. Cochrane Database Syst Rev. 2015;(9):CD007575.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD007575.pub4/fullhttp://www.ncbi.nlm.nih.gov/pubmed/26348534?tool=bestpractice.com此外,对于脱水患者应给予静脉补液。最后,对于妊娠剧吐患者,可能需要住院以及胃肠外营养治疗。如果检测表明患者有幽门螺杆菌感染,则应该给予选定患者适当的根除治疗方案。
无容量不足
初始非药物治疗方案包括饮食调整。患者发现少量多次的进餐方式更易于耐受。味道平淡、脂肪含量低、高碳水化合物的食物通常最易于耐受。女性通常主诉她们在上午更易于耐受含盐的食物。相比水,酸味液体可能更易于耐受。
如果饮食调整不能改善症状,则可尝试各种其他治疗方案(例如穴位按压、针灸、生姜)治疗妊娠恶心和呕吐,这些治疗方案都进行过评估。由于没有比较多数处理方式的头对头研究,故很难推荐一种一线治疗方法。应告知患者各种治疗选择,并鼓励其选择偏好的方法。穴位按压可能最大程度地减轻症状。[18]Rosen T, de Veciana M, Miller HS, et al. A randomized controlled trial of nerve stimulation for relief of nausea and vomiting in pregnancy. Obstet Gynecol. 2003;102:129-135.http://www.ncbi.nlm.nih.gov/pubmed/12850618?tool=bestpractice.com[19]Roscoe JA, Matteson SE. Acupressure and acustimulation bands for control of nausea: a brief review. Am J Obstet Gynecol. 2002;186(5 Suppl):S244-S247.http://www.ncbi.nlm.nih.gov/pubmed/12011894?tool=bestpractice.com[20]Lee EJ, Frazier SK. The efficacy of acupressure for symptom management: a systematic review. J Pain Symptom Manage. 2011;42:589-603.http://www.ncbi.nlm.nih.gov/pubmed/21531533?tool=bestpractice.com可在 P6 点处进行穴位按压(内关穴位,位于手掌面腕部上方 3 根手指宽度处)。[21]Allen TK, Habib AS. P6 stimulation for the prevention of nausea and vomiting associated with cesarean delivery under neuraxial anesthesia: a systematic review of randomized controlled trials. Anesth Analg. 2008;107:1308-1312.http://journals.lww.com/anesthesia-analgesia/Fulltext/2008/10000/P6_Stimulation_for_the_Prevention_of_Nausea_and.39.aspxhttp://www.ncbi.nlm.nih.gov/pubmed/18806045?tool=bestpractice.com症状减轻:质量差的证据显示,相比假穴位按压或未治疗,P6 穴位按压可能减轻患者自诉的晨吐。低质量的观察性(队列)研究或者受试者<200名且方法学存在缺陷的随机对照临床试验(RCT)。可佩戴市场出售的腕带以达到效果。针灸已用于治疗妊娠呕吐。[22]Smith CA, Cochrane S. Does acupuncture have a place as an adjunct treatment during pregnancy? A review of randomized controlled trials and systematic reviews. Birth. 2009;36:246-253.http://www.ncbi.nlm.nih.gov/pubmed/19747272?tool=bestpractice.com生姜补充剂也被证明能有效缓解症状。[23]Borelli F, Capasso R, Aviello G, et al. Effectiveness and safety of ginger in the treatment of pregnancy-induced nausea and vomiting. Obstet Gynecol. 2005;105:849-856.http://www.ncbi.nlm.nih.gov/pubmed/15802416?tool=bestpractice.com[24]Niebyl JR, Goodwin TM. Overview of nausea and vomiting of pregnancy with an emphasis on vitamins and ginger. Am J Obstet Gynecol. 2002;186(5 Suppl):S253-S255.http://www.ncbi.nlm.nih.gov/pubmed/12011896?tool=bestpractice.com[25]American College of Obstetricians and Gynecologists. Practice Bulletin: nausea and vomiting of pregnancy. Obstet Gynecol. 2004;103:803-814.http://www.ncbi.nlm.nih.gov/pubmed/15051578?tool=bestpractice.com[26]Mohammedbeigi R, Shahgeibi S, Soufizadeh N, et al. Comparing the effects of ginger and metoclopramide on the treatment of pregnancy nausea. Pak J Biol Sci. 2011;14:817-820.http://www.ncbi.nlm.nih.gov/pubmed/22545357?tool=bestpractice.com症状减轻:质量差的证据显示,相比安慰剂,生姜可能减轻妊娠早期的恶心和呕吐。低质量的观察性(队列)研究或者受试者<200名且方法学存在缺陷的随机对照临床试验(RCT)。可单独使用或随穴位按压一起使用,在妊娠各阶段均被认为是安全的。可直接生服,以茶水方式服用,或以药片/胶囊方式服用。[27]Ding M, Leach M, Bradley H. The effectiveness and safety of ginger for pregnancy-induced nausea and vomiting: a systematic review. Women Birth. 2013;26:e26-e30.http://www.womenandbirth.org/article/S1871-5192%2812%2900045-5/fulltexthttp://www.ncbi.nlm.nih.gov/pubmed/22951628?tool=bestpractice.com[28]Thomson M, Corbin R, Leung L. Effects of ginger for nausea and vomiting in early pregnancy: a meta-analysis. J Am Board Fam Med. 2014;27:115-122.http://www.jabfm.org/content/27/1/115.longhttp://www.ncbi.nlm.nih.gov/pubmed/24390893?tool=bestpractice.com
如果非药物治疗方法无效,可考虑药物疗法。一线治疗包括吡哆醇(维生素 B6)症状减轻:质量差的证据显示,相比安慰剂,吡哆醇可能减轻妊娠早期的恶心,但可能不减轻呕吐。低质量的观察性(队列)研究或者受试者<200名且方法学存在缺陷的随机对照临床试验(RCT)。和/或多西拉敏(doxylamin;一种抗组胺)。随机对照试验已证明这些组合治疗在控制 NVP 方面的有效性。[29]Koren G, Clark S, Hankins GD, et al. Effectiveness of delayed-release doxylamine and pyridoxine for nausea and vomiting of pregnancy: a randomized placebo controlled trial. Am J Obstet Gynecol. 2010;203:571;e1-e7.http://www.ncbi.nlm.nih.gov/pubmed/20843504?tool=bestpractice.com美国妇产科医师学会 (American Congress of Obstetricians and Gynecologists, ACOG) 和加拿大妇产科医师协会 (Society of Obstetricians and Gynecologists of Canada, SOGC) 的推荐认为这些药物安全有效,应考虑作为一线治疗。[25]American College of Obstetricians and Gynecologists. Practice Bulletin: nausea and vomiting of pregnancy. Obstet Gynecol. 2004;103:803-814.http://www.ncbi.nlm.nih.gov/pubmed/15051578?tool=bestpractice.com[30]Society of Obstetricians and Gynecologists of Canada. The management of nausea and vomiting of pregnancy. December 2016. http://www.sogc.org (last accessed 31 July 2017).http://sogc.org/guidelines/the-management-of-nausea-vomiting-of-pregnancy/然而由于考虑到高剂量的毒性问题,国家健康和保健优化研究所 (NICE) 目前并不推荐使用吡哆醇对妊娠女性进行治疗。[31]National Institute for Health and Care Excellence. Antenatal care for uncomplicated pregnancies. January 2017. http://www.nice.org.uk (last accessed 24 July 2017).https://www.nice.org.uk/guidance/CG62二线治疗包括替代性口服抗组胺药症状减轻:质量差的证据显示,相比安慰剂,抗组胺药物 [氯苯丁嗪 (buclizine) 、茶苯海明、多西拉敏、羟嗪和美其敏 (meclizine)] 可能减轻恶心和呕吐。低质量的观察性(队列)研究或者受试者<200名且方法学存在缺陷的随机对照临床试验(RCT)。或止吐剂。[25]American College of Obstetricians and Gynecologists. Practice Bulletin: nausea and vomiting of pregnancy. Obstet Gynecol. 2004;103:803-814.http://www.ncbi.nlm.nih.gov/pubmed/15051578?tool=bestpractice.com[32]Leathem A. Safety and efficacy of antiemetics used to treat nausea and vomiting in pregnancy. Clin Pharm. 1986;5:660-668.http://www.ncbi.nlm.nih.gov/pubmed/2874910?tool=bestpractice.com[33]Gill SK, O'Brien L, Koren G. The safety of histamine 2 (H2) blockers in pregnancy: a meta-analysis. Dig Dis Sci. 2009;54:1835-1838.http://www.ncbi.nlm.nih.gov/pubmed/19051023?tool=bestpractice.com
伴容量不足
按上述方案治疗仍不能控制液体的 NVP 患者经常脱水,并需要以静脉输液进行治疗。可使用生理盐水、5%的葡萄糖盐水或乳酸林格氏溶液。一项 RCT 表明患者使用生理盐水或 5% 葡萄糖溶液后,出现类似的结果。[34]Tan PC, Norazilah MJ, Omar SZ. Dextrose saline compared with normal saline rehydration of hyperemesis gravidarum: a randomized controlled trial. Obstet Gynecol. 2013;121:291-298.http://journals.lww.com/greenjournal/Fulltext/2013/02000/Dextrose_Saline_Compared_With_Normal_Saline.13.aspxhttp://www.ncbi.nlm.nih.gov/pubmed/23232754?tool=bestpractice.com如果考虑含葡萄糖的溶液,有些医生也建议在其之前给予硫胺素(维生素 B1)以预防韦尼克氏脑病 (Wernicke's encephalopathy) 。[1]Goodwin TM. Hyperemesis gravidarum. Clin Obstet Gynecol. 1998;41:597-605.http://www.ncbi.nlm.nih.gov/pubmed/9742356?tool=bestpractice.com[25]American College of Obstetricians and Gynecologists. Practice Bulletin: nausea and vomiting of pregnancy. Obstet Gynecol. 2004;103:803-814.http://www.ncbi.nlm.nih.gov/pubmed/15051578?tool=bestpractice.com[35]Eboue C, Carlier-Guerin C, de La Sayette V, et al. A rare complication of vomiting in pregnancy: Wernicke's encephalopathy. J Gynecol Obstet Biol Reprod. 2006;35:822-825.http://www.ncbi.nlm.nih.gov/pubmed/17151540?tool=bestpractice.com
对于容量不足患者,可能需要肠外(或直肠)止吐剂治疗。证据表明,昂丹司琼在控制严重呕吐方面可能比甲氧氯普胺更为有效。[36]Kashifard M, Basirat Z, Kashifard M, et al. Ondansetrone or metoclopromide? Which is more effective in severe nausea and vomiting of pregnancy? A randomized trial double-blind study. Clin Exp Obstet Gynecol. 2013;40:127-130.http://www.ncbi.nlm.nih.gov/pubmed/23724526?tool=bestpractice.com可使用质子泵抑制剂 (PPI) 作为肠外或直肠止吐剂的替代治疗选择,或联合使用。[37]Einarson A, Maltepe C, Boskovic R, et al. Treatment of nausea and vomiting in pregnancy: an updated algorithm. Can Fam Physician. 2007;53:2109-2111.http://www.cfp.ca/content/53/12/2109.fullhttp://www.ncbi.nlm.nih.gov/pubmed/18077743?tool=bestpractice.com数据表明质子泵抑制剂用于妊娠女性是安全的,与出生缺陷的明显增加并无关联。[38]Pasternak B, Hviid A. Use of proton-pump inhibitors in early pregnancy and the risk of birth defects. N Engl J Med. 2010;363:2114-2123.http://www.ncbi.nlm.nih.gov/pubmed/21105793?tool=bestpractice.com
妊娠剧吐被定义为持续性呕吐、容量不足及电解质失衡、酮症和体重减轻>5%。[1]Goodwin TM. Hyperemesis gravidarum. Clin Obstet Gynecol. 1998;41:597-605.http://www.ncbi.nlm.nih.gov/pubmed/9742356?tool=bestpractice.com为使情况稳定,这些患者将需要频繁住院治疗。对于初始治疗无效的患者,因胎儿在妊娠早期有皮质类固醇暴露可导致腭裂,可考虑在妊娠早期后使用皮质类固醇。[39]Park-Wyllie L, Mazzotta P, Pastuszak A, et al. Birth defects after maternal exposure to corticosteroids: prospective cohort study and meta-analysis of epidemiological studies. Teratology. 2000;62:385-392.http://www.ncbi.nlm.nih.gov/pubmed/11091360?tool=bestpractice.com在极端情况下,患者可能需要肠道喂养或全胃肠外营养以提供热量并补充电解质和营养成分。
幽门螺杆菌阳性患者
在严重病例中,幽门螺杆菌检测为阳性的患者可接受合适的根除方案。[12]Goldberg D, Szilagyi A, Graves L. Hyperemesis gravidarum and Helicobacter pylori infection: a systematic review. Obstet Gynecol. 2007;110:695-703.http://www.ncbi.nlm.nih.gov/pubmed/17766620?tool=bestpractice.com