Role of Neuromuscular Blocking Agents in Acute Respiratory Distress Syndrome: An Updated Meta-Analysis of Randomized Controlled Trials
- 作者列表："Xue-biao Wei","Zhong-hua Wang","Xiao-long Liao","Wei-xin Guo","Tie-he Qin","Shou-hong Wang
BackgroundThe therapeutic role of neuromuscular blocking agents (NMBA) in patients with acute respiratory distress syndrome (ARDS) remains controversial.MethodsWe systematically reviewed randomized controlled trials investigating the use of NMBA in ARDS patients from inception to July 2019. Relative risk (RR) was calculated for the incidence of barotrauma and mortality using the random-effect or fixed-effect model according to heterogeneity analysis.ResultsData were combined from five randomized controlled trials that included 1,461 patients (724 in the NMBA group and 737 in the control group). Pooled analysis showed that NMBA infusion did not reduce 28-day mortality (RR = 0.72, 95% confidence interval (CI) 0.44 to 1.17, P=0.180, I-squared = 62.8%), but was associated with lower intensive care unit (ICU) mortality (RR = 0.60, 95% CI 0.41 to 0.88, P = 0.009, I-squared = 9.2%). In addition, the incidence of barotrauma was significantly lower in patients treated with NMBA (RR = 0.53, 95% CI 0.33 to 0.84, P = 0.007, I-squared = 0). However, infusion of NMBA might increase the risk of ICU-acquired weakness (RR = 1.34, 95% CI 0.97 to 1.84, P = 0.066, I-squared = 0).ConclusionInfusion of NMBA could reduce ICU mortality and the incidence of barotrauma. The risk of ICU-acquired weakness was higher in moderate-to-severe ARDS patients treated with NMBA. The real effects of NMBA need to be further evaluated and confirmed by a study with a stricter design.
研究背景神经肌肉阻滞剂 (NMBA) 对急性呼吸窘迫综合征 (ARDS) 患者的治疗作用仍存在争议。根据异质性分析，使用随机效应或固定效应模型计算气压伤发生率和死亡率的相对危险度 (RR)。结果数据来自 5 个随机对照试验，包括 1,461 例患者 (NMBA 组 724 例，对照组 737 例)。合并分析显示，NMBA 输注未降低 28 天死亡率 (RR = 0.72，95% 置信区间 (CI) 0.44 ~ 1.17，P = 0.180，I-平方 = 62.8%), 但与较低的重症监护病房 (ICU) 死亡率相关 (RR = 0.60，95% CI 0.41 ~ 0.88，P = 0.009,I-平方 = 9.2%)。此外，接受 NMBA 治疗的患者气压伤的发生率显著较低 (RR = 0.53，95% CI 0.33 ~ 0.84，P = 0.007，I 平方 = 0)。然而，输注 NMBA 可能会增加 ICU 获得性衰弱的风险 (RR = 1.34，95% CI 0.97 ~ 1.84，P = 0.066，I-squared = 0)。结论输注 NMBA 可降低 ICU 病死率和气压伤的发生率。接受 NMBA 治疗的中重度 ARDS 患者发生 ICU 获得性衰弱的风险较高。NMBA 的真实效果需要进一步评估，并通过设计更严格的研究来证实。
METHODS::Acute respiratory distress syndrome (ARDS), characterized by acute hypoxic respiratory dysfunction or failure, is a manifestation of multiple organ failure in the lung, and the most common risk factor is sepsis. We previously showed that blocking α2 -adrenoceptor (α2 -AR) could attenuate lung injury induced by endotoxin in rats. α2A -adrenoceptor (α2A -AR), a subtype of α2 -AR plays a key role in inflammatory diseases, but the mechanism remains unknown. Here, we explored the effect of BRL-44408 maleate (BRL), a specific α2A -AR antagonist, on cecal ligation puncture (CLP)-induced ARDS in rats and the underlying mechanism. Preadministration of BRL-44408 maleate significantly alleviated CLP-induced histological injury, macrophage infiltration, inflammatory response, and wet/dry ratio in lung tissue. However, there was no statistical difference in survival rate between the CLP and CLP+BRL groups. Extracellular regulated protein kinase (ERK1/2), p38MAPK, and p65 were activated in the CLP group, and BRL-44408 maleate inhibited the activation of these signal molecules, c-Jun N-terminal kinase (JNK) and protein kinase A (PKA) showed no changes in activation between these two groups. BRL-44408 maleate decreased lipopolysaccharide (LPS)-induced expression of cytokines in NR8383 rat alveolar macrophages and reduced phosphorylation of ERK1/2, p38MAPK, and p65. JNK and PKA were not influenced by LPS. Together, these findings suggest that antagonism of α2A -AR improves CLP-induced acute lung injury and involves the downregulation of ERK1/2, p38MAPK, and p65 pathway independent of the activation of JNK and PKA.