Drago Bonny B, Kimura Dai, Rovnaghi Cynthia R, Schwingshackl Andreas, Rayburn Mark, Meduri G Umberto, Anand Kanwaljeet J S
1Prohealth Pediatrics, New York, NY. 2Department of Pediatrics, University of Tennessee Health Science Center, Memphis, TN. 3Pain Neurobiology Laboratory, University of Tennessee Health Science Center, Memphis, TN. 4Department of Clinical Pharmacy, Le Bonheur Children's Hospital & College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN. 5Department of Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, Memphis Veterans Affairs Medical Center, Memphis, TN.
Pediatr Crit Care Med. 2015 Mar;16(3):e74-81. doi: 10.1097/PCC.0000000000000349.
Low-dose methylprednisolone therapy in adults with early acute respiratory distress syndrome reduces systemic inflammation, duration of mechanical ventilation, and ICU length of stay. We report a pilot randomized trial of glucocorticoid treatment in early pediatric acute respiratory distress syndrome.
Double-blind, placebo-controlled randomized clinical trial.
Le Bonheur Children's Hospital, Memphis, TN.
Children (0-18 yr) with acute respiratory distress syndrome undergoing mechanical ventilation.
Patients were randomly assigned to steroid or placebo groups within 72 hours of intubation. IV methylprednisolone administered as loading dose (2 mg/kg) and continuous infusions (1 mg/kg/d) on days 1-7 and then tapered over days 8-14. Both groups were ventilated according to the Acute Respiratory Distress Syndrome Network protocol modified for children. Daily surveillance was performed for adverse effects.
Thirty-five patients were randomized to the steroid (n = 17, no death) and placebo groups (n = 18, two deaths). No differences occurred in length of mechanical ventilation, ICU stay, hospital stay, or mortality between the two groups. At baseline, higher plateau pressures (p = 0.006) and lower Pediatric Logistic Organ Dysfunction scores (p = 0.04) occurred in the steroid group; other characteristics were similar. Despite higher plateau pressures on days 1 (p = 0.006) and 2 (p = 0.025) due to poorer lung compliance in the steroid group, they had lower PaCO2 values on days 2 (p = 0.009) and 3 (p = 0.014), higher pH values on day 2 (p = 0.018), and higher PaO2/FIO2 ratios on days 8 (p = 0.047) and 9 (p = 0.002) compared with the placebo group. Fewer patients in the steroid group required treatment for postextubation stridor (p = 0.04) or supplemental oxygen at ICU transfer (p = 0.012). Steroid therapy was not associated with detectable adverse effects.
This study demonstrates the feasibility of administering low-dose glucocorticoid therapy and measuring clinically relevant outcomes in pediatric acute respiratory distress syndrome. Changes in oxygenation and/or ventilation are consistent with early acute respiratory distress syndrome pathophysiology and results of similar clinical trials in adults. We propose and design a larger randomized trial to define the role of glucocorticoid therapy in pediatric acute respiratory distress syndrome.
低剂量甲泼尼龙治疗成人早期急性呼吸窘迫综合征可减轻全身炎症反应，缩短机械通气时间和重症监护病房（ICU）住院时间。我们报告一项关于糖皮质激素治疗小儿早期急性呼吸窘迫综合征的试点随机试验。
双盲、安慰剂对照随机临床试验。
田纳西州孟菲斯市的勒博内尔儿童医院。
接受机械通气的急性呼吸窘迫综合征患儿（0 - 18岁）。
患者在插管后72小时内随机分为类固醇组或安慰剂组。静脉注射甲泼尼龙，第1 - 7天给予负荷剂量（2 mg/kg）并持续输注（1 mg/kg/d），然后在第8 - 14天逐渐减量。两组均按照针对儿童修改后的急性呼吸窘迫综合征网络方案进行通气。每日监测不良反应。
35例患者被随机分为类固醇组（n = 17，无死亡）和安慰剂组（n = 18，2例死亡）。两组在机械通气时间、ICU住院时间、住院时间或死亡率方面无差异。基线时，类固醇组的平台压较高（p = 0.006），小儿逻辑器官功能障碍评分较低（p = 0.04）；其他特征相似。尽管由于类固醇组肺顺应性较差，第1天（p = 0.006）和第2天（p = 0.025）的平台压较高，但与安慰剂组相比，他们在第2天（p = 0.009）和第3天（p = 0.014）的PaCO2值较低，第2天（p = 0.018）的pH值较高，第8天（p = 0.047）和第9天（p = 0.002）的PaO2/FIO2比值较高。类固醇组需要治疗拔管后喘鸣（p = 0.04）或在转至ICU时需要补充氧气（p = 0.012）的患者较少。类固醇治疗未发现有可检测到的不良反应。
本研究证明了在小儿急性呼吸窘迫综合征中给予低剂量糖皮质激素治疗并测量临床相关结局的可行性。氧合和/或通气的变化与早期急性呼吸窘迫综合征的病理生理学以及成人类似临床试验的结果一致。我们提议并设计一项更大规模的随机试验，以确定糖皮质激素治疗在小儿急性呼吸窘迫综合征中的作用。
