Bronchoalveolar lavage with pulmonary surfactant/dextran mixture improves meconium clearance and lung functions in experimental meconium aspiration syndrome

Surfactant lung lavage is a promising approach in the treatment of meconium aspiration syndrome (MAS). We hypothesise that the enrichment of modified natural surfactant with dextran will enhance meconium clearance from the airspaces during lung lavage and improve lung function in experimental MAS. Human meconium (30 mg/ml; 4 ml/kg) was instilled into the tracheal cannula of anaesthetised and paralysed adult rabbits to induce respiratory failure. The animals were then lavaged with saline (Sal), surfactant without (Surf) and with dextran (Surf+dex). Lung lavage (10 ml/kg in three portions) was performed with diluted surfactant (Curosurf(R), 10 mg/ml, 100 mg/kg) without or with dextran (3 mg/mg of surfactant phospholipids) or saline and the animals were conventionally ventilated with 100% O(2) for an additional hour. Lung functions were measured prior to and after meconium instillation, and 10, 30 and 60 min after lavage. The recovery of meconium in bronchoalveolar lavage (BAL) fluid was quantified. More meconium solids was recovered in the surfactant-lavaged than in the saline-lavaged groups (Surf: 12.4 +/- 3.9% and Surf+dex: 17.5 +/- 3.5% vs. Sal: 4.8 +/- 1.0%; both P < 0.01). Moreover, more meconium solids was obtained by Curosurf/dextran than by Curosurf-only lavage (P < 0.05). In the Surf group, the values for PaO(2)/FiO(2) were significantly higher than in the controls (at 60 min: 24.5 +/- 4.2 kPa vs.9.1 +/- 2.2 kPa, P < 0.01). An additional increase in oxygenation was seen in the Surf+dex group (at 60 min: 34.2 +/- 8.1 kPa, P vs. Surf group <0.01). The lung-thorax compliance was higher in the Surf+dex group in comparison with the Sal and Surf groups (at 60 min: 9.6 +/- 0.9 vs.7.6 +/- 1.2, P < 0.01 and 8.0 +/- 0.7 ml/kPa/kg, P < 0.05). The enrichment of Curosurf with dextran improves meconium clearance and lung functions in surfactant-lavaged rabbits with meconium aspiration.     

Complement activation reflects severity of meconium aspiration syndrome in newborn pigs

Meconium aspiration syndrome (MAS) is a serious condition in newborns, associated with a poorly characterized inflammatory reaction. The aim of this study was to investigate a possible role for complement in pulmonary pathophysiology and systemic inflammation in experimental MAS. MAS was induced by instillation of meconium into the lungs of 12 hypoxic piglets. Six controls received saline under otherwise identical conditions. Hemo- and lung dynamics were recorded for 5 h. Plasma complement activation, revealed by the terminal sC5b-9 complex (TCC), and cytokines were measured by enzyme immunoassays. TCC increased substantially in MAS animals compared with controls (p <0.0005). The increase in TCC correlated with lung dysfunction: closely with oxygenation index (r=0.51, p <0.0001) and ventilation index (r=0.64, p < 0.0001) and inversely with lung compliance (r=-0.22, p=0.05). IL-1beta and tumor necrosis factor-alpha increased significantly in MAS animals compared with the controls (p=0.004 and 0.008, respectively). The cytokine increase occurred later than TCC and showed correlations with lung dysfunction similar to TCC. IL-10 did not discriminate between MAS animals and controls (p=0.32). Finally, the subgroup of MAS animals that died (n=5) had substantially higher TCC concentration compared with the surviving MAS animals (n=7; p <0.0005). TCC increased substantially in MAS and was closely correlated to lung dysfunction. Complement activation preceded cytokine release, which may suggest a primary role for complement in the pathophysiology of MAS.     

Effect of surfactant lavage in a rabbit model of meconium aspiration syndrome

Meconium aspiration syndrome (MAS) is a frequent cause of respiratory distress in neonates. Recent reports have suggested that surfactant dysfunction contributes to the pathophysiology of MAS and surfactant therapy improves oxygenation of infants with MAS. We evaluated the effect of bronchial lavage with surfactant solution in a rabbit model of meconium aspiration. All animals were given 5 mL/kg of a 20% slurry of human meconium into the endotracheal tube and mechanically ventilated. The animals were then divided into saline lavage (n = 5) or surfactant lavage (n = 5). Lavage was performed an hour after meconium instillation. After the lavage the total amount of meconium recovered was measured. Blood gas was monitored during the experiment. The amount of meconium recovered by saline lavage was 14%, and by surfactant lavage was 57%. The surfactant group had a significant improvement in gas exchange, whereas the saline group had no improvement. It was concluded that the lavage with surfactant solution effectively washed out meconium and improved gas exchange in rabbit model of MAS.     

Effects of dexamethasone on meconium aspiration syndrome in newborn piglets.

We examined the effects of dexamethasone on lung function in a piglet model of meconium aspiration syndrome. We induced lung injury in 10 newborn piglets (age 5 +/- 0.2 d) with 4 mL/kg body weight of 20% sterile human meconium in normal saline given via tracheostomy. Ventilator management was aimed at maintaining comparable values of end tidal carbon dioxide, Hb saturation, and arterial blood gases. Lung function was assessed using a BICORE CP100 neonatal monitor. Five piglets received 0.5 mg/kg of dexamethasone 2 and 8 h after meconium administration, whereas control piglets received normal saline at similar times. Ventilator settings, oxygen requirements, and lung compliance were similar between groups at the start of the study. Two hours after the instillation of meconium, there was marked lung dysfunction in both groups as evidenced by increased oxygen requirements [fraction of inspired oxygen (FiO2) 0.98 +/- 0.01 versus FiO2 0.21 +/- 0, p < 0.0001] and reduced lung compliance (0.35 +/- 0.03 versus 0.8 +/- 0.03 mL x kg(-1) x cm(-1) H2O, p < 0.0001). Administration of dexamethasone resulted in lower oxygen requirements (FiO2 0.27 +/- 0.01 versus FiO2 1.0 +/- 0.0, p < 0.00001), lower oxygenation index (2.17 +/- 0.17 versus 22.64 +/- 3.39, p < 0.0001), ventilatory efficiency index (0.30 +/- 0.01 versus 0.07 +/- 0.01, p < 0.0001), and improved lung compliance (0.68 +/- 0.04 versus 0.34 +/- 0.05 mL x kg(-1) x cm(-1) H2O, p < 0.001) compared with the control group. In summary, a two-dose course of 0.5 mg/kg of dexamethasone improved blood gases and lung function in a piglet model of meconium aspiration syndrome.     

Albumin mixed with meconium attenuates pulmonary dysfunction in a newborn piglet model with meconium aspiration

We hypothesized that lipids and bile acids in meconium may induce pulmonary insufficiency in newborns. Because albumin may bind these components we studied the effect of albumin on meconium-induced lung injury in piglets. We measured concentration of FFA in the meconium (110 mg dry weight/mL) and added albumin to provide a molar FFA to albumin ratio of 1:1. Newborn piglets, 0-2 d of age, artificially ventilated and exposed to hypoxemia by ventilation with 8% O2, were randomized to group A receiving meconium (n = 12) or group B receiving meconium + albumin (n = 12), 3 mL/kg intratracheally. The animals were reoxygenated for 8 h. Reoxygenation was started when mean blood pressure was <20 mm Hg or base excess was <-20 mM. Pulmonary function was assessed in parallel with pulmonary hemodynamics. From the start of reoxygenation and the next 8 h we found a significant difference (by ANOVA) between the two groups in oxygenation index (p = 0.005), with an increase from 1.6 +/- 0.2 to 6.1 +/- 6.8 (p = 0.04) in the meconium group and from 1.8 +/- 0.3 to 3.1 +/- 3.1 (NS) in meconium + albumin group. There were also significant differences (by ANOVA) between the groups in favor of the treatment group concerning need of inspired fraction of O2, mean airway pressure, dynamic compliance of the respiratory system, time constant, ventilation index, and pulmonary vascular resistance. In conclusion, albumin given concurrently with meconium significantly reduced detrimental effects of meconium aspiration in the lungs of newborn piglets.     

Surfactant lavage decreases systemic interleukin‐1β production in meconium aspiration syndrome

Background: Surfactant lavage has been used to remove meconium debris in meconium aspiration syndrome (MAS), but the influence of surfactant lavage on pro‐inflammatory cytokines and cellular apoptosis is unclear. The aim of this study was to investigate the response of pro‐inflammatory cytokine and the influence on alveolar cellular apoptosis using therapeutic bronchoalveolar lavage with diluted surfactant to treat MAS. Methods: Twelve newborn piglets were anesthetized, intubated via tracheostomy, and artificially ventilated. MAS was induced by intratracheal instillation of 3–5 mL/kg of 20% human meconium. The piglets were then randomly assigned to a surfactant lavage group (n= 6) or a control group (n= 6). Piglets in the lavage group received bronchoalveolar lavage with 30 mL/kg diluted surfactant (5 mg/mL) in two aliquots. Cardiopulmonary parameters were monitored continuously. Serum was obtained hourly to measure concentrations of pro‐inflammatory cytokines, including interleukin (IL)‐Iβ, IL‐6, and tumor necrosis factor α. Lung tissue was histologically examined after experiments, and terminal deoxynucleotidyl transferase‐mediated nick‐end labeling assay for apoptotic cell death was also performed. Results: The animals in the lavage group displayed significantly better gas exchange and lower serum concentrations of IL‐1β than the animals in the control group (P < 0.05). The number of apoptotic cells in lung tissues was significantly lower in the lavage group than the control group, and also in the nondependent than the dependent site. Conclusion: Therapeutic surfactant lavage improves oxygenation, decreases production of systemic pro‐inflammatory cytokine IL‐1β, and alleviates the severity of lung cell apoptosis in newborn piglets with experimentally‐induced MAS.     

Efficacy of three treatment schedules in severe meconium aspiration syndrome

Aim: To compare three different schedules in severe meconium aspiration syndrome (MAS) treatment: standard, bronchoalveolar lavage (BAL) with diluted surfactant, and diluted surfactant BAL plus a single early dexamethasone dose. Methods: Twenty-four full-term newborns with severe MAS (needing mechanical ventilation and with oxygenation index ≥15) were divided into three groups: group I (historical control group; n = 6) treated with standard therapy; group II (n = 7) treated in the first hours of life with one BAL using diluted surfactant (beractant 5 mg/mL) in a volume of 15 mL/kg in four aliquots; and group III (n = 11) treated with one diluted surfactant BAL and a previous single dose of intravenous dexamethasone (0.5 mg/kg) Results: At 12 h, groups II and III showed a significant improvement in oxygenation index (OI) compared with group I (14.7% and 27.0% vs -19.6% respectively; p = 0.012). Group III also showed a significantly lower OI than group I at 24 h (63.6% vs -27.9%) and at 48 h (87.1% vs 49.6%). Group III, in comparison to group I, showed a lower FiO ₂ requirement at 12 h (0.66 vs 1), at 24 h (0.4 vs 0.87) and at 48 h (0.35 vs 0.67), and a decrease in the number of days of inhaled nitric oxide administration, mechanical ventilation, oxygen therapy and hospitalisation period. All patients from groups II and III survived and none developed pneumothorax or respiratory infections.

Conclusion: Diluted surfactant BAL in the first hours of life combined with an intravenous single dose of dexamethasone may be an effective treatment for severe MAS.     

比例辅助通气对重症胎粪吸入幼兔肺组织肿瘤坏死因子-α和白细胞介素-8水平的影响

目的探讨比例辅助通气(PAV)对胎粪吸入幼兔肺组织中肿瘤坏死因子-α(TNF-α)和白细胞介素-8(IL-8)水平的影响。方法将30只日龄20～30天的幼兔随机分为灌入胎粪后实施PAV组和灌入胎粪后实施同步间歇指令通气(SIMV)组,并与胎粪吸入不予通气组(MAS组)及灌生理盐水组(对照组)进行比较,各组分别于8h后处死,ELISA法检测肺组织匀浆及肺泡灌洗液中TNF-α、IL-8的含量。结果 (1)肺组织湿干比PAV组(7.81±0.52)、SIMV组(8.79±0.96)、MAS组(7.12±0.74)均高于对照组(4.22±0.30),SIMV组高于PAV组和MAS组,差异有统计学意义(P均<0.05);PAV组与MAS组差异无统计学意义(P>0.05)。(2)PAV组、SIMV组和MAS组肺组织匀浆TNF-α含量(pg/ml)[(872.6±104.0)、(973.9±114.5)和(707.1±39.1)]及IL-8含量(pg/ml)[(787.0±89.3)、(872.9±87.0)和(641.4±60.3)]均高于对照组[(401.1±74.5)和(381.3±63.3)],SIMV组高于PAV组和MAS组,PAV组高于MAS组,差异有统计学意义(P均<0.05)。(3)PAV组、SIMV组及MAS组肺泡灌洗液TNF-a含量[(644.4±89.3)、(787.1±100.6)和(536.0±28.5)]均高于对照组(301.8±75.9),SIMV组高于PAV组,差异有统计学意义(P均<0.05);PAV组、SIMV组及MAS组IL-8含量[(653.0±93.3)、(744.7±81.8)和(532.4±60.1)]均高于对照组(280.9±70.8),SIMV组高于PAV组和MAS组,PAV组高于MAS组,差异有统计学意义(P均<0.05)。结论胎粪在炎症反应中可促进TNF-α、IL-8释放,PAV治疗MAS时所致肺损伤程度较SIMV小。     

猪肺表面活性物质联合布地奈德混悬液气管内滴入治疗新生儿胎粪吸入综合征的疗效观察

目的探讨猪肺表面活性物质(PS)联合布地奈德混悬液气管内滴入治疗新生儿胎粪吸入综合征(MAS)的临床效果。方法采用前瞻性研究法,将70例MAS新生儿随机分成治疗组与对照组(n=35)。对照组常规给予气管内滴入PS(100 mg/kg)治疗,治疗组在此基础上加用布地奈德(0.25 mg/kg)治疗。结果治疗组在治疗后12 h需重复使用PS的比例明显低于对照组(P0.05)。治疗组在治疗后6 h、12 h、24 h动脉氧分压与吸入氧浓度比值(Pa O_2/Fi O_2)、经皮血氧饱和度(Tc Sa O_2)、动脉血氧分压(Pa O_2)、动脉血二氧化碳分压(Pa CO_2)的改善情况明显优于对照组(P0.05)。治疗后48 h胸片显示治疗组肺部炎症吸收明显优于对照组(P0.05);治疗组并发症的发生率明显低于对照组(P0.05),平均住院时间也较对照组明显缩短(P0.01)。结论与单用PS比较,PS联合布地奈德混悬液气管内滴入治疗新生儿MAS能更好改善血气指标和临床症状,缩短住院时间,减少并发症。     

Airway lavage with exogenous surfactant in an animal model of meconium aspiration syndrome

BACKGROUND: Meconium aspiration syndrome (MAS) is a major cause of respiratory morbidity and mortality in term infants, and occasionally causes serious respiratory disturbance. Viscous meconium debris in the trachea interferes with ventilation, and chest physiotherapy (CPT) is effective for removing secretions from the trachea. The effects of conventional exogenous diluted surfactant lavage combined with CPT were evaluated in a MAS animal model in a randomized controlled study. METHODS: Twenty-three MAS model adult Japanese rabbits were randomized into three groups and artificially ventilated for 3 h with the following treatments: group 1, suction only (n = 7); group 2, surfactant lavage (n = 7); group 3, surfactant lavage with CPT (n = 7). Surfactant lavage was performed by infusing 2 mL/kg of diluted Surfactant TA (Surfacten; 6 mg/mL) into the trachea over approximately 5 s, then performing gentle manual bagging six times, and aspirating the tracheal contents using a suction catheter. This procedure was performed four times in four different positions (total, 8 mL/kg). In group 3, CPT (squeezing) was performed during expiration of manual bagging in surfactant lavage. RESULTS: In group 3, PaO(2) improved significantly (P < 0.05) at all time points compared with those in the other groups. Oxygenation index (OI) in group 3 improved significantly (P < 0.05) at all time points except after 0.5 h compared with that in group 1, and at 2, 2.5, and 3 h compared with that in group 2. CONCLUSIONS: A combination of exogenous surfactant lavage and CPT (squeezing) improves respiratory disturbance in MAS.     

CC10 reduces inflammation in meconium aspiration syndrome in newborn piglets

Complications from meconium aspiration syndrome (MAS) remain significant despite a variety of therapeutic interventions. Clara cell protein (CC10) is a novel anti-inflammatory agent that can also inhibit phospholipase A2 (PLA2) (an important component of meconium). The present study examined whether administration of recombinant human CC10 (rhCC10) would reduce inflammation and improve lung function in a piglet model of MAS. Following meconium instillation, piglets exhibited significant physiologic dysfunction that improved significantly after surfactant administration. Analysis of tracheal aspirates revealed significant increases in both tumor necrosis factor (TNF) alpha and interleukin (IL)-8 after meconium instillation. rhCC10-treated animals had significantly lower TNF-alpha levels at 24 h (561 +/- 321 versus 1357 +/- 675 pg/mL, p < 0.05) compared with saline controls. There were no differences between rhCC10-treated and untreated groups with respect to other measured physiologic variables or inflammatory markers, including secretory PLA2 activity. Histologic analyses revealed marked inflammatory infiltrates and thickened alveolar walls, but no significant differences among rhCC10 and control animals. Newborn piglets with MAS have significant physiologic dysfunction, marked inflammatory changes and histologic abnormalities, which was partially counteracted by a single dose of exogenous surfactant and rhCC10.     

Dexamethasone treatment attenuates pulmonary injury in piglet meconium aspiration

To investigate the pulmonary effects of steroid treatment in neonates with meconium aspiration, 25 10- to 12-d-old piglets were studied for 6 h after an intratracheal bolus of human meconium. Dexamethasone (0.5 mg/kg) was given in two treatment schedules, either 1 h before (n = 6) or 1 h after meconium instillation (n = 8). Eight piglets served as controls. Three additional piglets were given dexamethasone without meconium instillation. Pulmonary hemodynamics and oxygenation were followed, and lung tissue samples investigated for signs of inflammation and ultrastructural injury, including apoptosis. Pulmonary artery pressure and vascular resistance increased after meconium instillation, but this rise was significantly prevented after prophylactic dexamethasone. This treatment also improved the acutely deteriorated oxygenation of the piglets after meconium insufflation. Prophylactic, but not early, dexamethasone treatment further protected the lungs from the ultrastructural changes caused by meconium instillation. Additionally, the increase of apoptotic epithelial cell deaths was significantly prevented by both dexamethasone treatments. These results show that prophylactic dexamethasone treatment significantly attenuates the early pulmonary hemodynamic deterioration and structural lung damage caused by meconium aspiration. Further studies on the apoptosis-inhibiting effect of dexamethasone administration in neonatal lungs exposed to heavy meconium are warranted.     

Surfactant tracheobronchial lavage for the management of a rabbit model of meconium aspiration syndrome

We evaluated the effect of tracheobronchial lavage with diluted surfactant solution (bovine lipid extract surfactant, bLES) in a rabbit model of meconium aspiration. All animals were anaesthetized, tracheotomized and given 3-4 ml/kg of 25% slurry of human meconium into the endotracheal tube and mechanically ventilated for 1 h. The animals were then randomly assigned to surfactant lavage (n = 12) with 15 ml/kg of diluted surfactant at a concentration of 5.4 mg phospholipid/ml administered in aliquots of 2 ml; or simple endotracheal suction (control n = 12) when the oxygenation index (OI) was >/=15. Changes in the arterial blood gases and the histomorphological and radiological appearances of the lungs were recorded. The OI and arterial/alveolar oxygen tension (a/A PO2) of the surfactant lavage group improved significantly at 5 min post-treatment, and these improvements were observed throughout the ensuing 4 h of ventilation. There was significantly more solid content recovered by surfactant lavage compared with the control group (p = 0.0001). Radiologically, the post-treatment air space opacification scores of the lavage group were significantly lower compared with the control (p = 0.002). The post-treatment radiographs of the lavage-treated rabbits were rated by the radiologist, who was blinded to the treatment groups, as much improved in 5 and improved in 4, whereas the control rabbits were rated as much worse in 3 and worse in 4. Histological examination showed the lungs of the lavaged rabbits had significantly more normal airway (p < 0.0001), more fields showing completely normal airspace (p = 0.0001) and less fields showing severe overdistension with meconium (p = 0.0005). We concluded that lavage with diluted surfactant solution effectively washed out the meconium, improved gases exchanges, and improved the histological and radiological appearances in the rabbit model of MAS.     

Gas trapping with high-frequency ventilation: jet versus oscillatory ventilation

Gas trapping was evaluated during high-frequency jet ventilation (HFJV) and high-frequency oscillatory ventilation (HFOV) in nine adult rabbits under basal conditions and after instillation of a mixture of 20% human meconium (2 mL/kg). The anesthetized animals underwent tracheostomy and were placed inside a body plethysmograph. Respiratory compliance and resistance were calculated from airway pressure and simultaneous flow, and volume was measured with a pneumotachograph. Gas trapping was measured as the change in volume observed in the plethysmograph after clamping the jet or the oscillatory line at respiratory rates of 10 and 15 Hz and tidal volumes of 1.0 and 2.0 mL/kg. Mean airway pressure was similar with both ventilators. Inspiratory/expiratory ratios were 1:4 at 10 Hz and 1:2 at 15 Hz with HFJV, and 1:1 during HFOV. Under all conditions, gas trapping was significantly greater with HFJV than with HFOV. More gas trapping was observed with higher tidal volume (2 mL/kg) and respiratory rate (15 Hz) during HFJV, before and after meconium instillation. After meconium instillation, gas trapping during HFJV at 15 Hz and tidal volume 2 mL/kg decreased significantly (32.7 +/- 10.4 to 24.9 +/- 10.3; P less than 0.05), compared with basal conditions. This finding may be explained by the shorter time constant of the respiratory system after meconium instillation (0.118 vs 0.083 seconds, P less than 0.01). Thus gas trapping was significantly greater with HFJV than with HFOV, a difference most likely related to the active expiratory phase of HFOV.     

胎粪吸入性肺炎应用常频与高频通气的研究

目的　 评估常频通气和高频通气治疗胎粪吸入性肺炎 (MAS)所致呼吸衰竭的临床与实验对比疗效。 方法 　实验方面 :健康白兔 ,气管注入胎粪混悬液 ( 3～ 5ml/kg) ,呼吸衰竭模型出现后随机分组 :①继续常频通气 (CMV) 3h后转为高频通气 (HFV) 3h(CMV HFV组 ) ;②转为HFV 3h后再转为CMV 3h(HFV CMV组 )。 2 0例MAS患儿入院后即用CMV治疗 ,当所用吸入氧浓度 (FiO2 ) >0 82h左右 ,经皮氧饱和度 (TcPO2 )仍 <90 %,改为HFV治疗 ;当FiO2 >0 82h左右 ,TcPO2 能维持在90 %以上 ,继续用CMV治疗。 10例继续应用CMV治疗 ,10例改用HFV治疗。 结果 　动物出现呼吸衰竭模型时 ( 0h)的氧合指数 (OI)二组无差异 ,CMV HFV组在治疗后 3hOI无明显变化 ,至 6hOI有上升 ;HFV CMV组治疗后 3hOI较 0h时有下降 ,两组动物治疗后 3h的OI的组间比较有差异。 2 0例患儿中 ,CMV组治愈 7例 ,死亡 2例 ,放弃 1例 ;HFV组治愈 7例 ,放弃 2例 ,死亡1例。HFV组患儿治疗后 1hOI较 0h有下降 ,至治疗后 6h ,OI与 0h比较差异显著 ;CMV组治疗后 1hOI有明显下降 ,但至治疗后 6h下降幅度不明显。二组患儿的呼吸机应用时间和用氧时间均无差异。 结论 　MAS用HFV治疗后的氧合作用较CMV改善明显和吸入氧浓度下降迅速     

Exudative lung injury is associated with decreased levels of surfactant proteins in a rat model of meconium aspiration

OBJECTIVE: Meconium aspiration syndrome remains a common cause of respiratory failure in neonates. The acute effects of meconium aspiration are inactivation of lung surfactant in vivo and in vitro. This study investigated the delayed effects of meconium on alveolar surfactant phospholipids and protein levels in spontaneously breathing animals. METHODS: Twenty-two adult rats were given 4.3 mg of dry weight human meconium after endotracheal intubation. Rats were briefly mechanically ventilated in room air, extubated, then killed after 16 (n = 6), 24 (n = 6), 48 (n = 6), and 72 hours (n = 4). Control animals received the same volume of normal saline (n = 7) or no meconium (n = 7). Bronchoalveolar lavage and tissue specimens were evaluated for inflammatory cells, total proteins, surfactant phospholipids, and surfactant proteins. RESULTS: Meconium caused exudative lung injury that was reflected in increased cell counts and proteins in alveolar lavage fluid. The peak injury occurred at 16 hours after instillation, whereas recovery occurred by 72 hours. Although total lavage fluid phospholipids did not change over time, phospholipid and dipalmitoyl phosphatidylcholine in large aggregates tended to decrease at 24 hours. Western blot analysis demonstrated time-dependent qualitative decreases in surfactant proteins A and B (SP-A, SP-B) in meconium-instilled animals compared with the controls. ELISA for SP-B confirmed the Western blot findings with total SP-B in large aggregate decreasing from 25 +/- 4 microg in controls to 6.6 +/- 0.8 microg at 24 hours of injury. CONCLUSIONS: Our study suggests that the exudative lung injury with meconium instillation is associated with decreased levels of SP-A and SP-B in the large aggregate fraction of lung surfactant. We speculate that decreased secretion and/or increased degradation accounts for lower levels of SP-B in bronchoalveolar lavage fluid.     

胎粪污染羊水新生儿发生重度胎粪吸入综合征的临床特征及预警因素分析北大核心CSCD

目的探讨胎粪污染羊水(meconium-stained amniotic fluid,MSAF)新生儿发生重度胎粪吸入综合征(meconium aspiration syndrome,MAS)的临床特征及预警因素。方法纳入2018年1月至2019年12月因Ⅲ°MSAF住院的新生儿295例为研究对象,按是否并发MAS分为无MAS组(n=199)、轻度/中度MAS组(n=77)和重度MAS组(n=19),回顾性收集3组患儿一般临床资料、血气分析结果、感染指标、母亲围生期临床资料等进行分析,并比较3组患儿出生后的呼吸支持方案。应用受试者工作特征曲线及多因素logistic回归分析MSAF新生儿发生重度MAS的预警因素。结果295例MSAF新生儿中32.5%(96/295)发生MAS,其中20%(19/96)为重度。重度MAS组出生5min Apgar评分低于轻度/中度MAS组及无MAS组(P<0.05),脐动脉血乳酸水平高于轻度/中度MAS组和无MAS组(P<0.05),生后1h外周血白细胞介素6(interleukin-6,IL-6)水平高于无MAS组(P<0.017)。重度MAS组患儿79%(15/19)出生无活力(其中13例行胎粪吸引术),100%在24h内开始机械通气。生后1 h外周血IL-6水平>39.02 pg/mL及生后1 h白细胞计数>30.345×10^(9)/L为MSAF新生儿发生重度MAS的预警指标(P<0.05)。结论胎粪吸引不能完全阻止MSAF新生儿严重MAS的发生;重度MAS患儿在出生早期即发生严重呼吸窘迫需要机械通气。监测脐动脉血乳酸及生后1 h外周血IL-6水平、白细胞计数有助于预警MAS的发生及严重程度。     

重组人超氧化物歧化酶对胎粪诱导肺损伤的保护作用及其机制研究

目的探讨胎粪诱导急性肺损伤的发病机制及抗氧化剂重组人超氧化物歧化酶(recombinant human superoxide dismutase, rhSOD)的保护作用.方法 32只雄性SD大鼠,随机取出8只经气管置管注入生理盐水1 ml/kg 作为对照(生理盐水组),24只大鼠由气管置管注入20%胎粪1 ml/kg复制大鼠胎粪肺损伤模型,随机分为胎粪组(8只);胎粪+生理盐水组(8只,气管内注入生理盐水1 ml/kg);胎粪+rhSOD组(8只,气管内注入rhSOD 20 mg/ml/kg).24 h后分别行大鼠支气管肺泡灌洗液(BALF)细胞计数和蛋白含量、肺通透指数(BALF蛋白含量/血浆蛋白含量,pulmonary permibility index, PPI)、乳酸脱氢酶(LDH),肺组织匀浆髓过氧化物酶(MPO)活性和丙二醛(MDA)、一氧化氮(NO)含量及超氧化物歧化酶(SOD)活性检测,并观察光镜下动物肺损伤的程度.结果与生理盐水组比较,胎粪组和胎粪+生理盐水组BALF细胞计数、蛋白含量、PPI、LDH及肺组织MPO活性、MDA、NO含量、肺损伤病理评分均显著增高(P均<0.01),肺匀浆SOD活性略有上升,但差异无意义(P>0.05);胎粪组与胎粪+生理盐水组比较,上述指标差异均无显著意义(P均>0.05);与胎粪+生理盐水组比较,胎粪+rhSOD组大鼠BALF细胞计数、LDH、肺匀浆MPO活性、MDA、NO含量、肺损伤病理评分均显著下降(P<0.01或0.05),SOD活性显著增加(P<0.05),而两组间蛋白含量、PPI差异无显著意义(P均>0.05).结论炎症和脂质过氧化损伤参与胎粪诱导肺损伤的发病机制,早期单剂20 mg/kg rhSOD气管内给药可减轻胎粪诱导的大鼠肺炎症反应和脂质过氧化损伤.     

Surfactant phosphatidylcholine metabolism in neonates with meconium aspiration syndrome

OBJECTIVE: Because meconium directly inhibits surfactant function, we sought to determine the effect of meconium on endogenous surfactant synthesis and clearance. STUDY DESIGN: We studied surfactant phosphatidylcholine kinetics with the use of stable isotopes in 11 newborn infants with meconium aspiration syndrome (MAS) who required extracorporeal membrane oxygenation (ECMO). For comparison we studied 6 neonates with persistent pulmonary hypertension (PPHN) on ECMO and 10 term neonates ventilated for non-pulmonary indications and not on ECMO. All patients received a 24-hour [U- 13C]glucose infusion as precursor for the palmitic acid in surfactant phosphatidylcholine. RESULTS: In the meconium group, the maximal 13C-incorporation in phosphatidylcholine (PC) was half of that in controls (0.09 +/- 0.01 vs 0.18 +/- 0.03 atom percent excess [APE], P = .027). There was a trend toward lower surfactant synthesis in the MAS group (3.3 +/- 0.7%/day) and PPHN group (2.6 +/- 0.3%/day) compared with controls 8.0 +/- 2.4%/day, P = .058). Significantly lower PC concentrations in tracheal aspirates were found in the MAS group (4.4 +/- 2.6 mg/mL) and PPHN group (3.6 +/- 2.0 mg/mL) compared with controls (12.8 +/- 2.6 mg/mL, P = .01). Endogenously synthesized surfactant had a similar half-life in all groups, ranging from 63 to 98 hours. CONCLUSION: We conclude that surfactant synthesis is disturbed and that surfactant PC concentrations are low in infants with MAS on ECMO.     

Randomized trial of volume infusion during resuscitation of asphyxiated neonatal piglets

Despite its use, there is little evidence to support volume infusion (VI) during neonatal cardiopulmonary resuscitation (CPR). This study compares 5% albumin (ALB), normal saline (NS), and no VI (SHAM) on development of pulmonary edema and restoration of mean arterial pressure (MAP) during resuscitation of asphyxiated piglets. Mechanically ventilated swine (n=37, age: 8 +/- 4 d, weight: 2.2 +/- 0.7 kg) were progressively asphyxiated until pH <7.0, Paco2 >100 mm Hg, heart rate (HR) <100 bpm, and MAP <20 mm Hg. After 5 min of ventilatory resuscitation, piglets were randomized blindly to ALB, NS, or SHAM infusion. Animals were recovered for 2 h before euthanasia and lung tissue sampled for wet-to-dry weight ratio (W/D) as a marker of pulmonary edema. SHAM MAP was similar to VI during resuscitation. At 2 h post-resuscitation, MAP of SHAM (48 +/- 13 mm Hg) and ALB (43 +/- 19 mm Hg) was higher than NS (29 +/- 10 mm Hg; p=0.003 and 0.023, respectively). After resuscitation, SHAM piglets had less pulmonary edema (W/D: 5.84 +/- 0.12 versus 5.98 +/- 0.19; p=0.03) and better dynamic compliance (Cd) compared with ALB or NS (Cd: 1.43 +/- 0.69 versus 0.97 +/- 0.37 mL/cm H2O, p=0.018). VI during resuscitation did not improve MAP, and acute recovery of MAP was poorer with NS compared with ALB. VI was associated with increased pulmonary edema. In the absence of hypovolemia, VI during neonatal resuscitation is not beneficial.