Intratracheal budesonide supplementation in addition to surfactant improves pulmonary outcome in surfactant‐depleted newborn piglets

Severe respiratory distress syndrome (RDS) is still a major cause of mortality and morbidity in premature infants. The combined use of intratracheal corticosteroid and surfactant in severe RDS, which bypasses the systemic circulation, may not only help recruit the lungs but also alleviates pulmonary inflammation without an increase in systemic adverse effects. Twelve newborn piglets received repeated pulmonary saline lavage to create surfactant‐depleted lungs that mimic neonatal RDS, and then were randomly grouped into a control group (standard intratracheal instillation of surfactant‐Survanta 100 mg/kg); and a budesonide (Bude) group (intratracheal instillation with the mixed suspension of Budesonide 0.25 mg/kg and Survanta 100 mg/kg). Blood samples were examined, and the observation period was 24 hr. The results showed that oxygenation was significantly better in Bude group compared to the control group over time (P = 0.016). The proinflammatory cytokines tumor necrosis factor‐α and interleukin‐1 β showed a reduced trend in the Bude group, but was not significantly different from the control group (P > 0.05). Comparing the histological lung injury scores, the Bude group had a significantly lower score than the control group at both dependent and non‐dependent sites (P < 0.05). In conclusion, in piglets with severe RDS, intratracheal instillation of budesonide in addition to surfactant seems to results in a sustained improvement in pulmonary outcome over 24 hr. Pediatr Pulmonol. 2013; 48:151–159. © 2012 Wiley Periodicals, Inc.     

体外膜肺氧合在成人严重呼吸衰竭中应用的系统评价

目的 评价体外膜肺氧合(ECMO)对成人严重呼吸衰竭患者病死率的影响.方法 计算机检索PubMed(1966年1月至2012年1月)、Cochrane Library(1966年1月至2012年1月)、CNKI (1979年至2012年1月)和万方数据库(1982年至2012年1月),手工检索初步入选文献的全文和参考文献中所列的相关文献,收集国内外关于ECMO对成人严重呼吸衰竭患者影响的随机对照研究(RCT)和观察性对照研究,利用RevMan5.0软件对RCT进行Meta分析,对观察性对照研究进行统计描述.结果 共纳入3篇RCT文献,5篇观察性对照研究文献.3个RCT合并分析结果显示,与对照组相比ECMO不能降低成人严重呼吸衰竭患者的病死率(OR =0.70,95％CI:0.42～1.16,P=0.17).单个RCT的结果显示ECMO能降低残疾率(RR =0.69,95％CI:0.50～0.97,P=0.03).5个观察性对照研究结果均显示,与对照组相比应用ECMO不能降低成人严重呼吸衰竭患者的病死率.结论 目前证据表明ECMO不能降低成人严重呼吸衰竭患者病死率.ECMO治疗严重呼吸衰竭的有效性及可能获益人群需要进一步的研究确定.     

Intrapulmonary application of a 5-lipoxygenase inhibitor using surfactant as a carrier reduces lung edema in a piglet model of airway lavage

Leukotriene-generated effects on microvascular integrity and polymorphonuclear leukocytes (PMNL) play a key role in the inflammatory process of the alveolar-capillary unit in neonatal acute respiratory distress syndrome. We asked if intrapulmonary application of MK886, a 5-lipoxygenase inhibitor, and the use of a porcine surfactant preparation (Curosurftrade mark) as a carrier substance would improve lung function in a neonatal piglet model of airway lavage. Anesthetized, mechanically ventilated newborn piglets (n = 19) underwent repeated airway lavage to induce acute lung injury. Piglets then received either surfactant alone (S, n = 6), or MK886 admixed with surfactant (S + MK, n = 7), or an air-bolus injection as control (C, n = 6). Measurements of gas exchange, lung function, extravascular lung water (EVLW), cell counts, and leukotriene B(4) (LTB(4)) concentrations in bronchoalveolar lavage fluid (BAL) were performed during 6 hr of mechanical ventilation. Arterial oxygen partial pressure (PaO(2)) (S, 13.8 +/- 4.2 kPa, vs. S + MK, 20 +/- 6.6; P < 0.05), functional residual capacity (S, 15.1 +/- 6.8 ml/kg, vs. S + MK, 18.8 +/- 3.7 ml/kg; P < 0.05), and EVLW (S, 29 +/- 14 ml/kg, vs. S + MK 24 +/- 4 ml/kg; P < 0.05) were significantly improved in the MK886 group. This clinical effect was linked with a decrease in LTB(4) concentration in BAL (S, 3.5 (1.9-5.4) pg/ml, vs. S + MK, 1.6 (0.7-4.7) pg/ml; P < 0.05) and an increase in IL-8 (S, 2,103 (852-4,243) pg/ml, vs. S + MK, 3,815 (940-26,187) pg/ml; P < 0.05). PMNL counts in BAL were reduced (S, 570 +/- 42 cells/ml, vs. 275 +/- 35 cells/ml; P < 0.05). In conclusion, intrapulmonary application of the 5-lipoxygenase inhibitor MK886 with surfactant as a carrier improves lung function by decreasing EVLW as the main response to LTB(4) reduction.     

房间隔造口术联合体外膜肺治疗急性呼吸窘迫综合征的大动物实验研究

目的:探索房间隔造口术(ASD)联合体外膜肺(ECMO)治疗急性呼吸窘迫综合症(ARDS)的效果,以便为治疗新型冠状病毒肺炎(COVID-19)重症患者寻找一条有效的新方法。方法:应用静脉泵入脂多糖(LPS)方法制作成年绵羊的ARDS大动物模型5只,在全麻体外循环下完成房间隔缺损(1~2 cm),在应用体外循环机模拟静脉-静脉体外膜肺(VV-ECMO)工作状态下,对比观察在ASD闭合和开放状态下动物的外周血氧合情况和体循环状态,以及心脏功能情况,评价ASD分流对改善心肺功能的意义。结果:在闭合ASD的情况下,未见房水平分流,仅应用VV-ECMO辅助下可见动物吸入100%氧的情况下心率(93±26)次/min,平均血压(MAP):(51.6±16.5)mmHg(1 mmHg=0.133 kPa),肺动脉压(PAP):(27.3±14.5)mmHg,肺血管阻力指数(PVRI):(47.6±9.6)N·s·m^-2·L^-1,外周动脉PaO2为(134.2±21.3)mmHg,SaO2:(96.3±0.3)%,氧合指数(PaO2/FiO2)为335.0±53.3,心脏饱胀,运动幅度较小,显得无力;在其他实验条件不变的情况下,仅打开ASD后房水平出现右向左分流,平均血压(MAP):(70.4±18.2)mmHg,PAP:(19.1±9.3)mmHg, PVRI:(32.1±8.1)N·s·m^-2·L^-1,外周动脉PaO2明显上升至(171.1±22.2)mmHg,SaO2:(98.2±0.3)%, PaO2/FiO2为427.5±55.5,心率(77±18)次/min,心脏运动幅度明显加大,心脏跳动显得轻松,体循环状态明显好转。统计学分析显示:与ASD关闭时比较,在ASD开放后MAP, PaO2, SaO2, PaO2/FiO2明显上升;PAP,PVRI明显下降。二者之间存在明显差异(P<0.01)。结论:房间隔造口术联合VV-ECMO是治疗ARDS的一种有效方法,对于COVID-19引起的重症ARDS治疗有一定的借鉴意义,需要临床应用进一步验证。     

AA genotype of IL‐8 −251A/T is associated with low PaO2/FiO2 in critically ill patients and with increased IL‐8 expression

Background and Objective: Interleukin‐8 (IL‐8) is a central chemokine in acute respiratory distress syndrome (ARDS), and the IL‐8 gene contains a functional single nucleotide polymorphism (SNP) ?251A/T in its promoter region. We hypothesized that IL‐8 ?251A/T SNP is associated with PaO₂/FiO₂ in critically ill patients. Methods: We conducted genetic‐association studies in intensive care units at academic teaching centres using a derivation septic shock cohort (vasopressin and septic shock trial (VASST), n = 467) and a validation post‐cardiopulmonary bypass surgery cohort (CPB, n = 739) of Caucasian patients. Patients in both cohorts were genotyped for IL‐8 ?251A/T. The primary outcome variable in both cohorts was the fraction of patients who had a PaO₂/FiO₂ < 200. IL‐8 mRNA expression was measured in genotyped lymphoblastoid cells in vitro. Results: The frequency of the patients with PaO₂/FiO₂ <200 was significantly greater in patients who had the AA genotype of ?251A/T than in patients who had the AT or TT genotypes in both VASST (AA = 60.8% vs AT and TT = 53.8% and 48.0%, P = 0.038) and the CPB cohort (AA = 37.0% vs AT and TT = 27.0% and 26.0%, P = 0.039). Patients having the AA genotype had a higher probability to remain on mechanical ventilation (P = 0.047) in the first 14 days. Lymphoblastoid cells having the AA genotype had significantly higher IL‐8 mRNA expression than cells having the AT or TT genotype (P = 0.022). Conclusions: Critically ill Caucasian patients who had the AA genotype of IL‐8 ?251A/T had an increased risk of PaO₂/FiO₂ <200. The AA genotype was associated with greater IL‐8 mRNA expression than the AT or TT genotypes.     

固尔苏联合鼻塞式持续气道正压通气治疗新生儿呼吸窘迫综合征的疗效观察

目的探讨固尔苏联合鼻塞式持续气道正压通气(NCPAP)治疗新生儿呼吸窘迫综合征(NRDS)的临床疗效。方法 72例NRDS患儿按数字表随机分为两组,对照组(n=36例)在综合治疗措施上采用沐舒坦联合NCPAP治疗,观察组(n=36例)在综合治疗措施上采用固尔苏联合NCPAP治疗。观察两组患儿临床疗效,治疗前后临床表现,比较两组患儿治疗后1、12、24h NCPAP参数(Fi O2、PIP、PEEP、Flow)、动脉血气指标(p H、Pa O2、Pa CO2、Pa O2/Fi O2)的变化。结果观察组治疗总有效率(88.9%)明显高于对照组治疗总有效率(72.2%)(P0.05);随着治疗时间延长,两组患儿动脉血气指标和NCPAP参数均得到改善,且观察组动脉血气指标和NCPAP参数(Fi O2、PIP)改善较对照组更为显著(P0.05)。结论固尔苏联合NCPAP治疗NRDS患儿疗效显著,可明显改善动脉血气指标和NCPAP参数,值得临床推广应用。     

Efficacy and safety of Nuwiq® (human‐cl rhFVIII) in patients with severe haemophilia A undergoing surgical procedures

Introduction

Haemophilia A patients are at a high risk of excess bleeding during surgeries. The aim of haemostatic therapy during the perioperative period is to normalize FVIII level perioperatively and postoperatively to maintain normal haemostasis until wound healing is complete.

Aims/Methods

To examine the efficacy of Nuwiq^® (simoctocog alfa, human‐cl rhFVIII), a 4^th generation recombinant FVIII produced in a human cell line, for surgical prophylaxis in patients with severe haemophilia A. This analysis assessed the efficacy of Nuwiq^® during surgical procedures and in the postoperative period in seven clinical studies of previously treated patients (PTPs) with severe haemophilia A.

Results

Thirty‐six patients, aged 3‐55 years, received surgical prophylaxis with Nuwiq^® for 60 surgeries (28 major and 32 minor). Efficacy was evaluated for 52 surgeries (25 major and 27 minor). The success rate of Nuwiq^® treatment was 98.1% (51 of 52 evaluated surgeries); haemostatic efficacy was assessed as “excellent” or “good” in all but one major surgery (assessed as “moderate”). The number of infusions ranged from 1 to 19 for minor surgeries and from 3 to 76 for major surgeries. The median (range) daily doses were 42.0 (28.2‐100.9) IU kg^?1 for minor surgeries and 69.3 (43.3‐135.6) IU kg^?1 for major surgeries. There were no serious treatment‐related adverse events, and none of the patients developed FVIII inhibitors.

Conclusions

The results of this pooled analysis show that Nuwiq^® was efficacious in maintaining haemostasis during and after major and minor surgical procedures in PTPs with severe haemophilia A.