BMP4 and LGL1 are Down Regulated in an Ovine Model of Congenital Diaphragmatic Hernia.

BACKGROUND/PURPOSE: The molecular pathophysiology of lung hypoplasia in congenital diaphragmatic hernia (CDH) remains poorly understood. The Wnt signaling pathway and downstream targets, such as bone morphogenetic proteins (BMP) 4 and other factors such as late gestation lung protein 1 (LGL1), are essential to normal lung development. Nitrofen-induced hypoplastic CDH rodent lungs demonstrate down regulation of the Wnt pathway including BMP4 and reduced LGL1 expression. The aim of the current study was to examine the molecular pathophysiology associated with a surgically induced CDH in an ovine model. METHODS: Left thoracotomy was performed at 80 days in 14 fetal sheep; CDH was created in seven experimental animals. Lungs were harvested at 136 days (term = 145 days). Lung weight (LW) and mean terminal bronchiole density (MTBD) were measured to determine the degree of pulmonary hypoplasia. Quantitative real time PCR was undertaken to analyze Wnt2, Wnt7b, BMP4, and LGL1 mRNA expression. RESULTS: Total LW was decreased while MTBD was increased in the CDH group (p < 0.05), confirming pulmonary hypoplasia. BMP4 and LGL1 mRNA was significantly reduced in CDH lungs (p < 0.05). Wnt2 mRNA was decreased, although not significantly (p < 0.06). CONCLUSION: For the first time, down regulation of BMP4 and LGL1 are reported in an ovine CDH model. In contrast to other animal models, these changes are persistent to near term. These findings suggest that mechanical compression from herniated viscera may play a more important role in causing pulmonary hypoplasia in CDH, rather than a primary defect in lung organogenesis.

Management of chest tubes after pulmonary resection: a systematic review and meta-analysis.

BACKGROUND: We performed a systematic review and meta-analysis to determine the effect of suction with water seal, compared with water seal alone, applied to intra pleural chest tubes on the duration of air leaks in patients undergoing pulmonary surgery. METHODS: We searched MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials to find randomized controlled trials (RCTs) comparing the effect of the 2 methods on the duration of air leaks. Trials were systematically assessed for eligibility and validity. Data were extracted in duplicate and pooled across studies using a random-effects model. RESULTS: The search yielded 7 RCTs that met the eligibility criteria. No difference was identified between the 2 methods in duration of air leak (weighted mean difference [WMD] 1.15 days, favours water seal; 95% confidence interval [CI] -0.64 to 2.94), time to discharge (WMD 2.19 d, favours water seal; 95% CI -0.63 to 5.01), duration of chest tubes (WMD 0.96 d, favours water seal; 95% CI -0.12 to 2.05) or incidence of prolonged air leaks (absolute risk reduction [ARR] 0.04, favours water seal; 95% CI -0.01 to 0.09). Water seal was associated with a significantly increased incidence of postoperative pneumothorax (ARR -0.14, 95% CI -0.21 to -0.07). CONCLUSION: No differences were identified in terms of duration of air leak, incidence of prolonged air leak, duration of chest tubes and duration of hospital stay when chest tubes were placed to suction rather than water seal. Chest tube suction appears to be superior to water seal in reducing the incidence of pneumothorax; however, the clinical significance of this finding is unclear.

Better late than never? Impact of local analgesia timing on postoperative pain in laparoscopic surgery: a systematic review and metaanalysis.

BACKGROUND: This study aimed to determine the effect of local anesthesia administered before laparoscopic surgery (preemptive anesthesia) on postoperative pain. METHODS: The authors searched Medline, EMBase, and the Cochrane Central Register of Controlled Trials, as well as reference lists of textbooks and relevant articles. They contacted experts in the field of anesthesia and laparoscopic surgery for randomized controlled trials comparing preemptive administration of local anesthesia at the incision site or intraperitoneally with postoperative anesthesia administration or placebo. Trials were systematically assessed for eligibility and validity, and data were extracted in duplicate. The data were pooled across studies using a random effects model. RESULTS: The 26 studies that met the inclusion criteria were included in the analysis. Preemptive incisional local anesthetic was superior to placebo in terms of visual analog pain scores (VAS) at 4 h (weighted mean difference [WMD], -9.49 mm; 95% confidence interval [CI], -15.50 to -3.48) and 24 h (WMD, -4.75 mm; 95%CI, -8.90 to 0.60). However, no difference was found between these measures and those for postoperative incision-site infiltration. Preemptive intraperitoneal local anesthetic was superior to placebo in terms of VAS at 4 h (WMD, 5.76 mm; 95%CI, -11.27 to -0.25), 8 h (WMD, -9.64 mm; 95%CI, -13.68 to -5.60), 12 h (WMD, -4.68 mm; 95%CI, -5.86 to -3.49), and 24 h (WMD, -5.57 mm; 95%CI, -8.35 to -2.79), and superior to postoperative anesthesia administration at 8 h (WMD, -7.42; 95%CI, -13.40 to -1.45), 12 h (WMD, -7.27 mm; 95%CI, -10.26 to -4.28), and 24 h (WMD, -7.95 mm; 95%CI, -12.33 to -3.56). CONCLUSION: Preemptive administration of local anesthetic at the incision site reduces postoperative pain compared with placebo but achieves an analgesic effect similar to that of postincisional anesthetic infiltration. Preemptive local anesthetic administered intraperitoneally decreases postoperative pain compared with both placebo and postoperative infiltration. Surgeons should use local analgesia in laparoscopic surgery to decrease postoperative pain, but the timing of administration is significant only for intraperitoneal infiltration.