Cardiologie Pédiatrique (AF), Hôpital de la Timone-Enfants, Marseille Cedex, France.
Pediatr Crit Care Med. 2010 Mar;11(2 Suppl):S37-40. doi: 10.1097/PCC.0b013e3181c8e6e9.
Pharmacologic strategies to reduce pulmonary vascular tone and to treat pulmonary hypertension originally aimed to enrich vascular smooth muscle cyclic adenosine monophosphate levels. Alternatively, increasing cyclic guanosine monophosphate (cGMP) also reduces pulmonary vascular tone. Inhaled nitric oxide is extremely efficacious in increasing cGMP and selectively reducing mean pulmonary arterial pressure in pediatric cardiac patients. It is considered standard treatment in most centers. However, not all patients respond to inhaled nitric oxide and withdrawal is sometimes problematic. This has prompted investigation of alternative methods to increase intracellular vascular smooth muscle cGMP. Phosphodiesterase type 5 is particularly abundant in the lung vasculature of patients with severe pulmonary hypertension. Its inhibition with the sildenafil class of drugs is now commonplace. Drugs that affect cGMP metabolism in children with acute pulmonary hypertension are the subject of this review and consensus statement. Oral sildenafil is recommended in postoperative pulmonary hypertension after failed withdrawal of inhaled NO (class I, level of evidence B). The effectiveness of prolonged treatment with sildenafil in documented postoperative pulmonary hypertension is not well established (class IIb, level of evidence C). Sildenafil is indicated in idiopathic pulmonary hypertension, although data have been extrapolated mainly from adult trial (class I, level of evidence A, extrapolated). Recently, completed pediatric trials have seemed to support this recommendation. Longer-acting and intravenous forms of phosphodiesterase type 5 inhibitors, brain natriuretic peptides, and direct soluble guanylate cyclise activators all have appeal, but there is insufficient experience in children with acute pulmonary hypertensive disorders for recommendations on treatment.
药理学策略旨在降低肺血管张力和治疗肺动脉高压，最初旨在丰富血管平滑肌环磷酸腺苷水平。或者，增加环鸟苷酸（cGMP）也可以降低肺血管张力。吸入一氧化氮在增加 cGMP 和选择性降低儿科心脏病患者平均肺动脉压方面非常有效。它被认为是大多数中心的标准治疗方法。然而，并非所有患者对吸入一氧化氮都有反应，有时停药也存在问题。这促使人们研究增加细胞内血管平滑肌 cGMP 的替代方法。磷酸二酯酶 5 在严重肺动脉高压患者的肺血管中特别丰富。其抑制剂西地那非类药物现在已很常见。本文和共识声明讨论了影响儿童急性肺动脉高压中 cGMP 代谢的药物。在吸入 NO 停药失败后出现术后肺动脉高压的情况下，推荐口服西地那非（I 类，证据水平 B）。在有记录的术后肺动脉高压中延长西地那非治疗的有效性尚未得到很好的证实（IIb 类，证据水平 C）。西地那非适用于特发性肺动脉高压，尽管数据主要从成人试验中推断而来（I 类，证据水平 A，推断）。最近，已完成的儿科试验似乎支持这一建议。作用时间更长的和静脉内的磷酸二酯酶 5 抑制剂、脑利钠肽和直接可溶性鸟苷酸环化酶激活剂都很有吸引力，但急性肺动脉高压疾病儿童的治疗经验不足，无法提出建议。
