A Porcine Model of Early Adult Respiratory Distress Syndrome Induced by Endotoxaemia

To study the pathophysiology of early adult respiratory distress syndrome (ARDS) induced by sepsis, spontaneously breathing pigs under ketamine anaesthesia were investigated. Twenty animals were infused i.v. with E. coli endotoxin (10 micrograms . h-1 . kg-1) over 6 h, and ten control animals received physiological saline. In the controls, cardiac output (Qt) and O2 delivery decreased slightly. There were no changes in pulmonary gas exchange, pulmonary haemodynamics or extravascular lung water (EVLW). The polymorphonuclear (PMN) leucocyte count gradually increased, while the platelet count decreased slightly. Endotoxin infusion caused profound deterioration of pulmonary gas exchange, a marked rise in pulmonary vascular resistance (PVR) and a moderate increase in EVLW. The pulmonary dysfunction was not attributable to the pulmonary oedema per se, whereas a "dry" ventilation/perfusion inequality played an important role. The "responders" (peak venous admixture greater than 20%; n = 14) were characterized by higher Qt and lower PVR than the "non-responders". Qt declined progressively, especially in non-survivors. O2 delivery decreased considerably. Metabolic acidosis probably indicated oxygen deficit. Eleven of 20 animals died during the observation period. Mortality was related more to the imbalance between O2 delivery and oxygen demand than to the deterioration in pulmonary gas exchange. The PMN count decreased markedly while the gradual decline in platelet count was similar to that in the controls. Lung microscopy revealed PMN accumulation in the microvasculature, moderate interstitial oedema and microvascular blood stasis. Our porcine model, which closely mimics early ARDS in man, will be useful in further studies of the pathophysiological pathways and the treatment of this syndrome.     

Prophylactic and delayed treatment with indomethacin in a porcine model of early adult respiratory distress syndrome induced by endotoxaemia

The effects of prophylactic and delayed treatment with indomethacin were evaluated in a porcine model of early adult respiratory distress syndrome (ARDS) induced by endotoxaemia. Spontaneously breathing pigs under ketamine anaesthesia were infused i.v. with E. coli endotoxin (10 micrograms . h-1 . kg-1) over 6 h. Twenty animals received endotoxin without treatment. Eight animals were pretreated with indomethacin i.v., 5 mg . kg-1 in 30 min, followed by further infusion at a rate of 2 mg . h-1 . kg-1. Ten animals received the same dosage of indomethacin beginning 2 h after the start of endotoxin infusion. Pretreatment with indomethacin inhibited the endotoxin-induced impairment in pulmonary gas exchange, but did not prevent pulmonary oedema. The pulmonary hypertension was counteracted. Oxygen delivery did not improve, because of a marked reduction in cardiac output (Qt). Systemic vascular resistance (SVR) increased markedly, and mean arterial pressure (MAP) was higher. Survival was improved. Delayed indomethacin treatment prevented a further deterioration in pulmonary gas exchange and restored it towards the baseline level. The pulmonary oedema was not counteracted, while the pulmonary hypertension was reduced. O2 delivery was not restored, owing to the greater decrease in Qt compared with the untreated endotoxin group. SVR increased considerably, and MAP was better maintained. Survival was not improved. These results indicate that cyclo-oxygenase inhibitors might benefit pulmonary gas exchange in human ARDS. Drugs which interfere with arachidonate metabolism will probably be of great importance in the prophylaxis, in particular, and also in the treatment of ARDS.     

Endotoxemia and endotoxin tolerance in patients with ARDS

Background The significance of endotoxemia in man is controversial, induces cytokine release and stimulates the immune system. Exaggerated cytokine release of mononuclear cells was observed in acute lung injury/acute respiratory distress syndrome (ALI/ARDS). However, repetitive administration of endotoxin can cause tolerance. Objective To investigate endotoxemia, plasma TNFα, IL-1β, IL-6, the liberation capacity of those cytokines from mononuclear cells after LPS challenge (Δ values), and plasma antibodies to endotoxins and α-hemolysin of Staphylococcus aureus in ALI/ARDS. Design A prospective clinical study was conducted. Setting The study was carried out at the University Hospital Ulm, Ulm, Germany. Subjects The respondents were 23 patients with ALI/ARDS. Interventions ALI/ARDS was defined according to the American–European Consensus Conference on ARDS. Blood was collected periodically. Parameters were measured by LAL or ELISA. Results ARDS (P_aO₂/F_iO₂ < 200) revealed higher endotoxemia (0.22–0.46 [0.06–1.15] EU/mL vs 0.05–0.14 [0.02–0.63] EU/mL) than ALI (P_aO₂/F_iO₂ > 200) but lower ΔIL-6 (124–209 [10–1214] pg/mL vs 298–746 [5–1797] pg/mL), ΔTNFα (50–100 [6–660] pg/mL vs 143–243 [12–2795] pg/mL), and ΔIL-1 (2–3 [0–26] pg/mL vs 2–14 [0–99] pg/mL). Endotoxemia correlated negative with P_aO₂/F_iO₂ (r, −0.44 to −0.50). All patients presented antibodies to lipopolysaccharides and α-hemolysin, but the level did not correlate with P_aO₂/F_iO₂. Conclusions ALI/ARDS is associated with endotoxemia. The more severe the disease, the more intense is endotoxemia but the lower is the capacity of mononuclear cells to release cytokines (tolerance). Antibodies against Gram-positive and Gram-negative bacteria are detectable in the plasma but without relation to P_aO₂/F_iO₂.     

The Role of Polymorphonuclear Leucocytes in the Pulmonary Dysfunction Induced by Complement Activation

To determine the role of polymorphonuclear leucocytes (PMNs) in the pulmonary reaction induced by complement activation, pigs were infused with complement-activated plasma (CAP), cell-free supernatant from PMNs activated in vitro, or washed PMN aggregates produced in vitro. Infusion of CAP resulted in transient peripheral leucopenia, a reversible rise in pulmonary vascular resistance (PVR) and decreased arterial oxygen tension (PaO2). Indomethacin did not influence the CAP-induced drop in PMN count or the accumulation of PMNs in the lung, but significantly counteracted the rise in PVR and fall in PaO2. Antihistamines did not prevent the cellular or pulmonary reactions to CAP infusion. Methylprednisolone did not inhibit the decrease in PMN count, but modified the pulmonary reaction to CAP, although it did not prevent the rise in PVR to the same extent as indomethacin; it counteracted the fall in PaO2. Infusion of supernatant from activated PMNs did not influence the PMN count, but caused a reversible increase in PVR and a drop in PaO2. Indomethacin counteracted the pulmonary reaction to this infusion. Infusion of washed PMN aggregates did not result in any cellular or physiological changes. These findings suggest that the pulmonary reaction induced by complement activation is mediated by humoral components generated and/or released during activation of PMNs. Arachidonic acid metabolites play an important role and it is likely that substance(s) released from activated PMNs trigger prostanoid synthesis in other cells. It is conceivable, however, that PMNs exposed to activated complement factors also directly synthesize and release arachidonic acid metabolites.     

大剂量沐舒坦对急性呼吸窘迫综合征患者抗氧化能力的影响

目的　研究大剂量沐舒坦对急性呼吸窘迫综合征 (ARDS)患者抗氧化能力的影响。方法　选择ARDS患者 4 2例 ,随机分成对照组 (A组 ,n =2 0 )和观察组 (B组 ,n =2 2 )。A组每天给予单纯生理盐水 5 0 0ml静脉滴注 ,B组每天给予沐舒坦 2 0mg/kg加生理盐水 5 0 0ml静脉滴注 ,连续应用 7d。比较两组患者在肺损伤程度、血气指标和血清超氧化物歧化酶 (SOD)活力等方面的变化和差异。结果　用药后B组患者的血气指标和肺损伤评分明显改善 ,血清SOD活力显著升高 (P <0 0 5或P <0 0 1) ,与A组比较均有显著性差异 (P <0 0 5或P <0 0 1)。结论　临床应用大剂量沐舒坦可增强ARDS患者的抗氧化能力 ,有利于其呼吸功能的恢复     

Nebulized corticosteroid improves pulmonary function and outcome in experimental porcine septicemia

Nebulized beclomethasone dipropionate was administered to six anesthetized and artificially ventilated pigs at 6-hourly intervals after infusion of live S. aureus (aerosol group). Changes in pulmonary mechanics, gas exchange and hemodynamics during an observation period of 44 h were compared with those in six pigs subjected to the same insults but given no corticosteroid (non-treatment group). Six pigs served as controls, without sepsis or aerosol, but with the same general management (control group). The septic insult induced an acute 3-fold increase in mean pulmonary artery pressure (MPAP) in the aerosol and non-treatment group. MPAP fell to near baseline levels in the aerosol group, but remained significantly higher in the non-treatment group. Mean systemic arterial pressure fell more in the non-treatment than in the aerosol group, reaching its lowest level at 32 h. Pulmonary function was less affected in the aerosol group, with significantly better maintenance of arterial oxygenation, lower venous admixture and superior lung-thorax compliance than in the non-treatment group. Survival was significantly improved in the aerosol group. In this porcine model of septicemia-induced adult respiratory distress syndrome, nebulized corticosteroid thus attenuated the development of respiratory failure.     

Treatment of Early and Delayed Esophageal Perforation

Esophageal perforations are life threatening emergencies associated with high morbidity and mortality. We report on 22 consecutive patients (age 20–86; 13 female and 9 male) with an oesophageal perforation treated at the university hospital Duesseldorf. The patients' charts were reviewed and follow-up was completed for all patients until demission, healed reconstruction or death. Patients' history, clinical presentation, time interval to surgical presentation, and treatment modality were recorded and correlated with patients' outcome. Six esophageal perforations were due to a Boerhaave-syndrome, eleven caused by endoscopic perforation, two after osteosynthesis of the cervical spine and three foreign body induced. In 7 patients a primary local suture was performed, in 4 cases a supplemental muscle flap was interposed, and 7 patients underwent an oesophageal resection. Four patients were treated without surgery (three esophageal stent implantations, one conservative treatment). Eleven patients (50 %) were presented within 24 h of perforation, and 11 patients (50 %) afterwards. Time delay correlates with survival. In 17 (80.9 %) cases a surgical sufficient reconstruction could be achieved. One (4.7 %) patient is waiting for reconstruction after esophagectomy. Four (18.2 %) patients died. A small subset of patients can be treated conservatively by stenting of the Esophagus, if the patient presents early. In the majority of patients a primary repair (muscle flap etc.) can be performed with good prognosis. If the patient presents delayed with extensive necrosis or mediastinitis, oesophagectomy and secondary repair is the only treatment option with high mortality.     

Prophylactic treatment with an aerosolized corticosteroid liposome in a porcine model of early ARDS induced by endotoxaemia

The effects of prophylactic treatment with an aerosolized corticosteroid liposome (CSL) in high dose were evaluated in a porcine model of early Adult Respiratory Distress Syndrome (ARDS) induced by endotoxaemia. Intermittent positive pressure ventilated (IPPV) pigs under chlormethiazole anaesthesia were infused with E. coli endotoxin (18 micrograms.kg-1.h-1) over 4 h. Eight animals served as controls and were pretreated with aerosolized placebo liposomes, either 15 min or 2 h, before start of the endotoxin infusion. Eight animals were pretreated with CSL in aerosolized form 15 min before start of endotoxin, and eight animals were pretreated 2 h before start of endotoxin. Pretreatment with CSL, both 15 min and 2 h before endotoxin, modified and partly counteracted the late endotoxin-induced impairment in expiratory resistance (EXPres), dynamic compliance (Cdyn) and mean pulmonary artery pressure (MPAP). The administration of CSL did not seem to have a restrictive influence on the endogenous cortisol production estimated by repeated measurements of serum cortisol levels. These results indicate that CSL, administered prophylactically in an aerosolized form to the lung, might be valuable as a modulator without systemic side effects in regard to some of the endotoxin-induced pulmonary impairments seen in this experimental model of early ARDS.     

食管癌食管支气管瘘的外科治疗

目的总结外科治疗食管癌食管支气管瘘的技术特点和经验,探讨安全、有效的治疗方案。方法回顾性总结第四军医大学唐都医院2007年1月至2010年11月收治12例食管癌食管支气管瘘患者的临床资料,男9例,女3例;年龄37～62岁,平均年龄51.24岁。根据不同病情,12例患者分别采取4种手术方式治疗食管支气管瘘(:1)食管部分切除+食管胃隧道式吻合术+肺叶切除术2例;(2)食管部分切除+食管胃器械吻合术+肺叶切除术5例;(3)食管部分切除+结肠代食管术+肺叶切除术4例;(4)食管部分切除+食管胃吻合术+左全肺切除术1例。结果围手术期死亡2例,病死率为16.67%(2/12),其中1例为食管癌侵及左肺下叶支气管,行食管部分切除+食管胃隧道式吻合术+左肺下叶切除术后第4 d死于心力衰竭;另1例为食管癌侵及左肺上叶支气管行食管部分切除+食管胃器械吻合术+左肺上叶切除术后第11 d死于重症感染伴肾功能衰竭。术后并发轻度脓胸4例,总并发症发生率为41.67%(5/12),并发支气管吻合口瘘1例,经抗感染、引流等治疗后愈合出院。随访1个月～3年,死亡1例;其余患者未出现明显并发症,无死亡。结论依据患者的病情,选择个体化手术方式,是临床治疗食管癌食管支气管瘘患者安全有效的治疗方案。     

Revisiting extracorporeal membrane oxygenation for ARDS in burns: A case series and review of the literature

Introduction

Recent reports on the use of extracorporeal membrane oxygenation (ECMO) in critically ill burn patients with Acute Respiratory Distress Syndrome (ARDS) recommended against the use of ECMO. The authors cited the high mortality rates associated with the use of ECMO in these patients with no appreciable benefit. Accumulating evidence from referral centers suggests improved survival in patients with ARDS receiving ECMO. We report our recent experience treating patients with severe ARDS with ECMO in a burn intensive care unit.

右美托咪定对ARDS机械通气患者炎症因子及肺损伤的影响

目的观察右美托咪定对急性呼吸窘迫综合症(ARDS)机械通气患者炎症因子及肺损伤的影响。方法选择40例ARDS机械通气患者,根据患者使用和未使用右美托咪定,将患者分成右美托咪定组(右美托咪定组,n=20)和对照组(n=20)。前者静脉泵注右美托咪定负荷量1μg/kg 15 min,再以0.2~0.7μg/kg·h速率持续输注48 h;对照组患者静脉泵注丙泊酚3~5 mg/(kg·h)为48 h,两组均复合舒芬太尼0.1~0.2μg/(kg·h)。分别于插管前(T0)、插管后6 h(T1)、12 h(T2)、24 h(T3)、48 h(T4)各时间点抽取静脉血检测IL-6、IL-8、IL-10的浓度,同时记录Pa O2/Fi O2。结果与T0时比较,T1~T4时两组的IL-6、IL-8、IL-10的浓度显著升高(P0.05),D组Pa O2/Fi O2T2~T4时显著增高(P0.05)、C组T1~T4时显著降低(P0.05),HR在T1~T4时D组降低,C组增高(P0.05)。与C组比较,T2~T4时D组IL-6、IL-8显著降低、IL-10显著升高(P0.05);T2~T4时Pa O2/Fi O2升高(P0.05);T1~T4时D组HR降低,T2~T4时MAP升高(P0.05)。结论右美托咪定用于ARDS机械通气治疗患者,可以平衡炎症因子的释放,有利于减轻肺损伤。     

Continuous Renal Replacement Therapy Reduces the Systemic and Pulmonary Inflammation Induced by Venovenous Extracorporeal Membrane Oxygenation in a Porcine Model

Pulmonary changes in veno‐venous extracorporeal membrane oxygenation (VV‐ECMO) are rarely determined. We compared the contribution of VV‐ECMO and cannulation based on the observation of pulmonary inflammatory reaction and parenchymal construction in a porcine model of low tidal volume (V_T) ventilation. We also evaluated the effect of adding continuous renal replacement therapy (CRRT) to the ECMO circuit, because CRRT is known to reduce systemic cytokine release induced by VV‐ECMO. A total of 18 pigs undergoing low‐V_T ventilation were randomly divided into three groups (group 1, cannulation; group 2, VV‐ECMO; group 3, VV‐ECMO + CRRT) and studied for 24 h. Hemodynamic and ventilation parameters were recorded. We assessed plasma and alveolar cytokines, expression of pulmonary inflammatory genes, histopathological grading, and ultrastructural changes of the lungs. During the process, inspiratory volume increased and PaO₂ decreased in group 1. Systemic tumor necrosis factor‐α (TNF‐α) and interleukin 6 (IL‐6) levels increased at 2 h in group 2 and partly decreased in group 3. At 24 h, the levels of bronchoalveolar lavage fluid, TNF‐α, and IL‐6 in group 2 were remarkably higher than those in groups 1 and 3. Pulmonary mRNA expression of cytokines did not differ between the groups. We observed an increased score of pulmonary pathological findings in pro‐inflammatory cell infiltration and interstitial thickening of the lungs in group 2. The epithelium of the blood–air barrier after VV‐ECMO was swollen. In group 3, the pulmonary parenchyma and blood–air barrier were well preserved. We concluded that in a porcine model of low‐V_T ventilation, both VV‐ECMO and VV‐ECMO in combination with CRRT provided adequate oxygenation and carbon dioxide removal. Compared with VV‐ECMO alone, VV‐ECMO in combination with CRRT better preserved the lung parenchyma by eliminating systemic cytokines.     

早期眼眶骨折患者非手术治疗适应征选择体会

目的总结720例早期眼眶骨折患者分别经保守治疗和手术治疗的随访效果,为非手术治疗的适应征选择提供临床依据。方法收集2005年10月～2010年12月我科经临床及影像学资料证实的720例早期眼眶骨折患者资料,根据其CT表现及临床表现分别选择保守治疗以及手术治疗。非手术治疗适应征包括被动牵拉试验阴性、无眼球内陷,CT片示眼眶骨折破坏面积<1.0 cm2。结果随访结果表明,330例保守治疗患者,眼位均恢复正常;390例手术治疗患者双侧眼位、面颊对称、视功能基本恢复正常。结论熟悉眼眶骨折的CT表现,结合病史及临床表现,早发现,早诊断,适当选择保守或手术治疗,有助于制定对患者最为合适的治疗方案,避免过度手术。     

Doxycycline Treatment in a Model of Early Abdominal Aortic Aneurysm

Purpose. To evaluate the effects doxycycline (Dox) in animal models of early abdominal aortic aneurysm. Methods. Of 43 male Wistar rats, 33 underwent intraluminal perfusion of the abdominal aorta with thioglycolate plus plasmin to reproduce early aortic aneurysm. These rats then were treated for 7 days with subcutaneous injections of Dox or saline. The 10 remaining rats underwent intra-aortic perfusion with saline and were injected subcutaneously with saline. On day 7, the rats were killed after abdominal aortic diameters were measured. Some aortic specimens were examined microscopically after elastica van Gieson (EVG) and hematoxylin–eosin (H&E) staining. In other specimens, the matrix metalloproteinase (MMP) activity in tissue extracts was evaluated by gelatin zymography. Results. Among the thioglycolate plus plasmin-perfused rats, the degree of aortic dilation was less in Dox–treated than in saline-treated rats. EVG staining indicated that Dox maintained a nearly normal pattern of elastic lamellae and normal medial elastin thickness. The aortic inflammatory response was not suppressed by Dox in H&E staining. In gelatin zymography, Dox reduced the MMP-9 activity, but did not significantly change either MMP-2 or the percentage of activated MMP-2. Conclusions. Dox inhibited experimental aneurysmal dilation by preserving medial elastin. This effect involved the suppression of MMP-9 but not of the MMP-2 activity. Received: February 8, 2002 / Accepted: July 2, 2002 RID="*" ID="*" Reprint requests to: K. Kaito Acknowledgments. We gratefully acknowledge the helpful suggestions of Hiroshi Ohtake, M.D., Fuminari Kasashima, M. D., and Mrs. Yoko Tanaka.     

Renal Transplantation by Automatic Anastomotic Device in a Porcine Model

Automatic vascular staplers for vascular anastomoses in kidney transplantation may dramatically reduce the operative time and, in particular, warm ischemia time, thus increasing the outcome of transplantation. Ten pigs underwent kidney auto‐transplantation by automatic anastomotic device. Kidneys were collected by laparotomy with selective ligations at the renal hilum and perfused with cold storage solution. To overcome the shortage in length of renal hilum, a tract of the internal jugular vein was harvested to increase the length of the vessels. The anastomoses were totally performed by the use of the anastomotic device. On 10 kidney transplants, nine were successful and no complications occurred. Renal resistive indexes showed a slight increase in the immediate postoperative period returning normal at 10 days of follow‐up. We demonstrated the possibility to perform renal vascular anastomoses by means of an automatic anastomotic device. This instrument developed for coronary bypass surgery by virtue of the small caliber of the vessels could be adopted on a larger scale for renal transplantation. The reduced warm ischemia time needed for anastomosis may help to achieve a better outcome for the graft and expand the pool of marginal donors in renal transplantation.     

早期前列腺癌的诊断与治疗

随着前列腺癌发病率在我国的逐年升高,泌尿外科医生对此疾病的早期诊断与治疗也越来越关注。尽管美国的资料显示前列腺癌的筛查可以降低前列腺癌相关的死亡率,但对是否开展此项筛查依然存在争议。诊断方面依然以直肠指检(DRE)、前列腺特异性抗原(PSA)和B超引导的经直肠前列腺穿刺活检为主。治疗方面强调对这类患者实施治愈性治疗手段如前列腺癌根治术和放疗。严密的随访可以尽早发现肿瘤复发并及时开始二线治愈性治疗。本文对早期前列腺癌诊断与治疗的现状进行了综述。