Nakagawa T A, Morris A, Gomez R J, Johnston S J, Sharkey P T, Zaritsky A L
Division of Pediatric Critical Care Medicine, Children's Hospital, King's Daughters, Norfolk, VA 23607, USA.
J Pediatr. 1997 Jul;131(1 Pt 1):63-9. doi: 10.1016/s0022-3476(97)70125-2.
To determine the pulmonary vascular functional dose response to inhaled nitric oxide (NO) for infants and children with acute respiratory distress syndrome and pulmonary artery hypertension.
Prospective, clinical observational study.
Thirteen-bed pediatric intensive care unit at a 168-bed children's hospital.
Infants and children requiring mechanical ventilation with an oxygenation index greater than 10.
Children with severe acute respiratory distress syndrome received inhalation therapy with NO after conventional mechanical ventilation failed to result in improvement. Inhaled NO was sequentially titrated from 10 parts per million to 20, 40, 60, and 80 ppm at 10-minute intervals. A reduction of at least 30% in the pulmonary vascular resistance index (PVRI), or a reduction in mean pulmonary artery pressure of at least 10%, or an increase in the hypoxemia score of at least 20%, or a decrease in the oxygenation index of at least 20% from pretreatment values was considered a therapeutic response. After sequential titration, children who responded received continuous inhaled NO at the lowest dose associated with a therapeutic response.
Fourteen children received 15 trials with inhaled NO (median age, 63.4 months; range, 0.4 to 201 months). One patient's condition deteriorated during the titration phase, unrelated to NO treatment, and the patient was withdrawn from the study protocol. The mean (+/- SD) pretreatment oxygenation index was 35 +/- 15, which decreased to 32 +/- 20 at 80 ppm of inhaled NO (p = 0.01). Ten children had pulmonary artery catheter measurements. The PVRI decreased by 30% or greater in seven children (70%). One child had a minimal decrease in PVRI during the titration phase but demonstrated an increase of more than 30% after NO therapy was discontinued. Mean pretreatment PVRI (270 +/- 106) decreased to 207 +/- 92 dynes/sec per cubic centimeter per square meter at 80 ppm of inhaled NO (p = 0.06). Pretreatment mean pulmonary artery pressure (31 +/- 7) decreased to 28 +/- 5 mm Hg at 80 ppm of inhaled NO (p = 0.04). Six trials (43%) showed an increase of 20% or greater in their hypoxemia score. Maximum improvement in the hypoxemia score and reduction in OI, PVRI, and mean pulmonary artery pressure occurred at 20 to 40 ppm of NO. Ten trials led to continuous inhaled NO therapy ranging from 7 to 661.5 hours, with a median of 47 hours. Systemic hypotension was not observed in any patient, and the maximum methemoglobin level was 5%.
Inhaled NO appears to be a safe, although variably effective, therapy for the treatment of infants and children with acute respiratory distress syndrome. The maximum dose response occurs between 20 and 40 ppm of inhaled NO. Systemic side effects did not occur in any child who received NO therapy.
确定吸入一氧化氮（NO）对患有急性呼吸窘迫综合征和肺动脉高压的婴幼儿的肺血管功能剂量反应。
前瞻性临床观察研究。
一家拥有168张床位的儿童医院的13张床位的儿科重症监护病房。
需要机械通气且氧合指数大于10的婴幼儿。
患有严重急性呼吸窘迫综合征的儿童在常规机械通气未能改善病情后接受NO吸入治疗。吸入的NO以百万分之10开始，每隔10分钟依次滴定至20、40、60和80 ppm。肺血管阻力指数（PVRI）至少降低30%，或平均肺动脉压至少降低10%，或低氧血症评分至少增加20%，或氧合指数较治疗前值至少降低20%，被视为治疗反应。在依次滴定后，有反应的儿童接受与治疗反应相关的最低剂量的持续吸入NO。
14名儿童接受了15次NO吸入试验（中位年龄63.4个月；范围0.4至201个月）。1名患者在滴定阶段病情恶化，与NO治疗无关，该患者退出研究方案。治疗前平均（±标准差）氧合指数为35±15，在吸入80 ppm NO时降至32±20（p = 0.01）。10名儿童进行了肺动脉导管测量。7名儿童（70%）的PVRI降低了30%或更多。1名儿童在滴定阶段PVRI降低最小，但在停止NO治疗后增加超过30%。治疗前平均PVRI（270±106）在吸入80 ppm NO时降至207±92达因/秒每立方厘米每平方米（p = 0.06）。治疗前平均肺动脉压（31±7）在吸入80 ppm NO时降至28±5 mmHg（p = 0.04）。6次试验（43%）显示低氧血症评分增加20%或更多。低氧血症评分的最大改善以及OI、PVRI和平均肺动脉压的降低发生在20至40 ppm的NO时。10次试验导致持续吸入NO治疗7至661.5小时，中位时间为47小时。未在任何患者中观察到全身性低血压，高铁血红蛋白最高水平为5%。
吸入NO似乎是治疗患有急性呼吸窘迫综合征的婴幼儿的一种安全但效果不一的疗法。最大剂量反应发生在吸入20至40 ppm的NO之间。接受NO治疗的儿童均未出现全身性副作用。
