Beta-glucan attenuates inflammatory cytokine release and prevents acute lung injury in an experimental model of sepsis

Sepsis is one of the most important risk factors in acute respiratory distress syndrome (ARDS). beta-Glucan is a potent reticuloendothelial modulating agent, the immunobiological activity of which is mediated in part by an increase in the number and function of macrophages. In this study, we investigated the putative protective role of beta-glucan against sepsis-induced lung injury. Sepsis was induced by cecal ligation and puncture (CLP) in Wistar rats. The control group received saline, and the treatment groups received beta-glucan or beta-glucan + beta-1,3-D-glucanase. Five hours thereafter, plasma tumor necrosis factor (TNF) alpha, interleukin (IL) 1beta, and IL-6 levels were determined. Presence of lung injury was determined via lung tissue myeloperoxidase (MPO) activity, intercellular adhesion molecule (ICAM) 1 levels, and histopathological examination at 18 h after CLP. In a separate set of experiments, survival was monitored for 7 days after CLP. beta-Glucan treatment led to a significant increase in survival rate (63% in glucan-treated rats vs 38% in saline-treated rats). Administration of the beta-glucan inhibitor abrogated beta-glucan's survival benefit (50%). After CLP, plasma TNF-alpha, IL-1beta, and IL-6 concentrations were increased in control animals. When beta-glucan was administered, it completely blocked the elevation of TNF-alpha, IL-1beta, and IL-6. Administration of beta-1,3-D-glucanase suppressed glucan-induced decrease in cytokines. Animals treated with beta-glucan showed a significant reduction in lung injury score, a marked decrease in ICAM-1 expression, and a significant decrease in MPO levels. In contrast, beta-1,3-D-glucanase caused a significantly increased MPO and ICAM-1 levels in the lung. These data reveal that beta-glucan treatment improved the course of CLP-induced peritonitis and attenuated the lung injury. Administration of beta-glucanase inhibited the beta-glucan activity and resulted in enhanced lung injury.     

Role of peroxynitrite in sepsis-induced acute kidney injury in an experimental model of sepsis in rats

ABSTRACT: The mechanisms involved in sepsis-induced acute kidney injury (AKI) are unknown. We investigated the role of nitrosative stress in sepsis-induced AKI by studying the effects of manganese (III) tetrakis-(1-methyl-4-pyridyl) porphyrin pentachloride (MnTMPyP), a peroxynitrite decomposition catalyst, and aminoguanidine (AG), a selective nitric oxide synthase 2 (NOS2) inhibitor and peroxynitrite scavenger, on kidney function of rats subjected to cecal ligation and puncture (CLP). Sprague-Dawley rats (weighing 350 [SD, 50] g) were treated with MnTMPyP (6 mg/kg i.p.) or AG (50 mg/kg i.p.) at t = 12 and 24 h after CLP or sham procedure. At t = 36 h, mean arterial pressure and aortic blood flow were measured, and blood and urine samples were obtained for biochemical determinations, including creatinine clearance, fractional excretion of sodium, and neutrophil gelatinase-associated lipocalin concentration in the urine. Kidney tissue samples were obtained for (i) light microscopy, (ii) immunofluorescence and Western blot for 3-nitrotyrosine and NOS2, (iii) gene expression (quantitative real-time polymerase chain reaction) studies (NOS1, NOS2, NOS3, and superoxide dismutase 1), and (iv) matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Mean arterial pressure was unchanged and aortic blood flow decreased 25% in CLP animals. The sepsis-induced (i) decreased urine output and creatinine clearance and increased fractional excretion of sodium and urinary neutrophil gelatinase-associated lipocalin concentration, (ii) increased protein nitration and NOS2 protein, and (iii) NOS1 and NOS2 upregulation were all significantly attenuated by treatment with MnTMPyP or AG. Nitrated proteins in renal tissue from CLP animals (matrix-assisted laser desorption ionization time-of-flight mass spectrometry) were glutamate dehydrogenase, methylmalonate-semialdehyde dehydrogenase, and aldehyde dehydrogenase, mitochondrial proteins involved in energy metabolism or antioxidant defense. Nitro-oxidative stress is involved in sepsis-induced AKI, and protein nitration seems to be one mechanism involved.     

Evaluating abdominal oedema during experimental sepsis using an isotope technique

Purpose: Abdominal oedema is common in sepsis. A technique for the study of such oedema may guide in the fluid regime of these patients. Procedures: We modified a double‐isotope technique to evaluate abdominal organ oedema and fluid extravasation in 24 healthy or endotoxin‐exposed (‘septic’) piglets. Two different markers were used: red blood cells (RBC) labelled with Technetium‐99m (^99mTc) and Transferrin labelled with Indium111 (¹¹¹In). Images were acquired on a dual‐head gamma camera. Microscopic evaluation of tissue biopsies was performed to compare data with the isotope technique. Results: No ^99mTc activity was measured in the plasma fraction in blood sampled after labelling. Similarly, after molecular size gel chromatography, ¹¹¹In activity was exclusively found in the high molecular fraction of the plasma. Extravasation of transferrin, indicating the degree of abdominal oedema, was 4·06 times higher in the LPS group compared to the healthy controls (P<0·0001). Abdominal free fluid, studied in 3 animals, had as high ¹¹¹In activity as in plasma, but no ^99mTc activity. Intestinal lymphatic vessel size was higher in LPS (3·7 ± 1·1 μm) compared to control animals (0·6 + 0·2 μm; P<0·001) and oedema correlated to villus diameter (R² = 0·918) and lymphatic diameter (R² = 0·758). A correlation between a normalized index of oedema formation (NI) and intra‐abdominal pressure (IAP) was also found: NI = 0·46*IAP?3·3 (R² = 0·56). Conclusions: The technique enables almost continuous recording of abdominal oedema formation and may be a valuable tool in experimental research, with the potential to be applied in the clinic.     

Protective role of heme oxygenase-1 in the intestinal tissue injury in an experimental model of sepsis

OBJECTIVE: The aim of this study was to examine the role of heme oxygenase-1 induction in the intestinal tissue injury in a rat model of sepsis. DESIGN: Randomized, masked, controlled animal study. SETTING: University-based animal research facility. SUBJECTS: Sprague-Dawley male rats, weighing 220-250 g (n = 126). INTERVENTIONS: Rats were injected with lipopolysaccharide (10 mg/kg) intraperitoneally. Another group of rats was injected with interleukin-6 (10 microg/kg) intravenously. In some rats, tin mesoporphyrin (1 micromol/kg) was administered intravenously 1 hr before lipopolysaccharide treatment. MEASUREMENTS AND MAIN RESULTS: Following lipopolysaccharide treatment, expression of heme oxygenase-1 and nonspecific delta-aminolevulinate synthase (ALAS-N), the rate-limiting enzymes of heme catabolism and biosynthesis, respectively, was examined in various regions of the intestine. Lipopolysaccharide treatment markedly increased heme oxygenase-1 messenger RNA and protein concentrations in the mucosal epithelial cells in the duodenum and the jejunum, whereas its expression in the ileum and the colon was hardly detectable and was not influenced by the treatment. ALAS-N messenger RNA was also more markedly increased in the duodenum, the jejunum, and the ileum than in the colon following lipopolysaccharide treatment. Interleukin-6 administration also induced heme oxygenase-1 and ALAS-N gene expression in a pattern similar to that following lipopolysaccharide treatment. In contrast to the marked heme oxygenase-1 expression in the upper intestine, lipopolysaccharide-induced mucosal injury and inflammation in the upper intestine were far less than observed in the lower intestine as judged both by tumor necrosis factor-alpha gene expression and by histologic analysis. Of note, inhibition of heme oxygenase activity by tin mesoporphyrin produced a significant tissue injury in the upper intestine of the lipopolysaccharide-treated animals. CONCLUSIONS: Intestinal heme oxygenase-1 and ALAS-N gene expression was regulated in a site-specific manner in a rat model of sepsis. Our findings also suggest that heme oxygenase-1 induction may play a fundamental role in protecting mucosal epithelial cells of the intestine from oxidative damages that occur in sepsis.     

A novel animal model of sepsis after acute lung injury in sheep

OBJECTIVE: Patients with acute lung injury after smoke inhalation often develop pneumonia subsequently complicated by sepsis. This often is a fatal complication. The aim of this study was to develop a standardized and reproducible model of hyperdynamic sepsis after smoke inhalation in sheep. DESIGN: Prospective, experimental study in sheep. SETTINGS: Experimental laboratory in a university hospital. SUBJECTS: Twenty-one female Merino ewes. INTERVENTION: Animals were anesthetized and surgically prepared for this chronic study. After a week of recovery, baseline data were collected. After tracheostomy was performed, sheep were connected to a volume-controlled ventilator. Acute lung injury was produced by insufflating the lungs with 48 breaths of cotton smoke. During halothane anesthesia, live bacteria suspended in a 30-mL saline solution containing 2-5 x 10(11) colony-forming units were instilled through a bronchoscope into the right lower and middle lung lobes (10 mL each) and left lower lung lobe (10 mL; n = 10). Eleven sheep were given smoke but not bacteria. After injury and the bacterial challenge, the animals were ventilated mechanically with 100% oxygen. The animals were monitored for 48 hrs. was detected in blood cultures after 14-48 hrs. MEASUREMENTS AND MAIN RESULTS: The sheep developed a hyperkinetic cardiovascular response concomitant with a decrease in Pao similar to severe sepsis in human patients who meet the criteria for acute respiratory distress syndrome (PaO2 /FIO2 <200). These changes were more severe than in animals exposed to smoke inhalation alone. Mean arterial pressures at 48 hrs in the smoke-alone and the smoke + sepsis group were 85.5 +/- 5.2 and 68.1 +/- 7.6 mm Hg, respectively (mean +/- se, p<.05). CONCLUSION: This animal model closely resembles hyperdynamic sepsis in humans and may be of great value for studies of sepsis with smoke inhalation.     

Characterization of S. pneumoniae pneumonia-induced multiple organ dysfunction syndrome: an experimental mouse model of gram-positive sepsis

Streptococcus pneumoniae, a gram-positive bacteria, is the most common cause of community-acquired pneumonia. It is a common cause of septic shock with multiple organ dysfunction syndrome (MODS) resulting in significant mortality. Gram-positive mouse models of sepsis with MODS are required to examine mechanisms of immune responses in severe sepsis. To assess whether lung infection due to S. pneumoniae in a nonventilated mouse model can induce multiple organ dysfunction. S. pneumoniae, SPN 15814 strain, harvested at log phase, was injected intratracheally in C57BL/6 mice at OD 600 between 0.35 and 0.63. A dose of bacteria at OD 600 = 0.63 conferred approximately 30% mortality in 36 h. Lung pneumonia was assessed by histology, lung myeloperoxidase activity, and lung bacterial load; intestinal epithelial barrier integrity was assessed by measuring blood-to-lumen clearance of Cr-EDTA; renal function was assessed by measuring plasma creatinine and urea; and myocardiac function was assessed using an isolated perfused mouse heart model. S. pneumoniae-induced pneumonia resulted in neutrophil infiltration into the lungs and increased lung bacterial load. Although relatively few bacteria gained access to the blood stream, the pneumonia was accompanied by increased intestinal epithelial barrier permeability, increased plasma creatinine, and decreased cardiac output and stroke volume. These data clearly show that intratracheal S. pneumoniae induced not only pneumonia but also MODS, despite the fact that few organisms gain access to the blood stream. This model can be used as a good gram-positive model of sepsis and MODS for further studies.     

Inhibition of poly (ADP-ribose) polymerase attenuates acute lung injury in an ovine model of sepsis

It is known that in various pathophysiological conditions, reactive oxidants cause DNA strand breakage and subsequent activation of the nuclear enzyme poly(ADP ribose) polymerase (PARP). Activation of PARP results in cellular dysfunction. We hypothesized that pharmacological inhibition of PARP reduces the damage in the ovine model of acute lung injury (ALI). After smoke inhalation, Pseudomonas aeruginosa (5 x 109 cfu/kg) was instilled into both lungs. All of the animals were mechanically ventilated with 100% O2. The infusion of the PARP inhibitor (INO-1001, n = 6) began 1 h after the injury and thereafter through 24 h (3 mg bolus + 0.3 mg/kg/h, i.v.). Control animals (n = 6) were treated with saline. Sham injury animals (n = 8) received sham smoke and were mechanically ventilated in the same fashion. One-half of those sham animals (n = 4) were given the same dose of INO-1001. PaO2/FiO2 ratio at 24 h in saline and in the INO-1001-treated groups were 95 +/- 22 and 181 +/- 22, respectively (P < 0.05). Peak airway pressure at 24 h in the saline- and INO-1001-treated groups was 32.6 +/- 3.0 and 24.4 +/- 2.2, respectively (P < 0.05). Pulmonary shunt fraction was also significantly attenuated. INO-1001 treatment reduced pulmonary histological injury and attenuated poly (ADP-ribose) accumulation in the lung. In conclusion, inhibition of PARP improved the ALI after smoke inhalation and pneumonia. The results suggest that the activation of PARP plays a role in the pathophysiology of ALI in sheep.     

Massive brain injury enhances lung damage in an isolated lung model of ventilator-induced lung injury

OBJECTIVE: To assess the influence of massive brain injury on pulmonary susceptibility to injury attending subsequent mechanical or ischemia/reperfusion stress. DESIGN: Prospective experimental study. SETTING: Animal research laboratory. SUBJECTS: Twenty-four anesthetized New Zealand White rabbits randomized to control (n = 12) or induced brain injury (n = 12) group. INTERVENTIONS: After randomization, brain injury was induced by inflation of an intracranial balloon-tipped catheter, and animals were ventilated with a tidal volume of 10 mL/kg and zero end-expiratory pressure for 120 mins. Following heart-lung block extraction, isolated and perfused lungs were subjected to injurious ventilation with peak airway pressure 30 cm H2O and positive end-expiratory pressure 5 cm H2O for 30 mins. MEASUREMENTS AND MAIN RESULTS: No difference was observed between groups in gas exchange, lung mechanics, or hemodynamics during the 2-hr in vivo period following induction of brain injury. However, after 30 mins of ex vivo injurious mechanical ventilation, lungs from the brain injury group showed greater change in ultrafiltration coefficient, weight gain, and alveolar hemorrhage (all p < .05). CONCLUSIONS: Massive brain injury might increase lung vulnerability to subsequent injurious mechanical or ischemia-reperfusion insults, thereby increasing the risk of clinical posttransplant graft failure.     

Diagnosis and management of blunt abdominal solid organ injury

PURPOSE OF REVIEW: Nonoperative management of solid organ injuries has become the standard of care for over 25 years. Benefits of this practice include reduced operative complications, reduced transfusions, lower infectious morbidity, and shorter length of stay. Patients eligible for this management practice include those who are hemodynamically stable and who do not have associated injuries that require celiotomy. Operative interventions need to occur expeditiously in hemodynamically unstable patients with hepatic and splenic injuries. RECENT FINDINGS: Recent literature has focused on the continued success with nonoperative management of blunt solid organ injuries. The role of angioembolization for both splenic and hepatic injuries continues to be explored. Other authors are also questioning the appropriateness of clinical decisions for selection of hemodynamically unstable patients for nonoperative management. Operative management of blunt pancreatic trauma remains the rule. SUMMARY: Nonoperative management of solid organ injuries continues to have high success rates in the appropriate patient population. Minimally invasive adjuncts have a definite role in management of this patient population. Pancreatic trauma remains an operative injury. Surgeons must, however, temper the enthusiasm for nonoperative management of patients with solid organ injury, and exclude from this management scheme patients who would best be treated with surgery.     

脓毒症急性肺损伤大鼠肺组织细胞凋亡的研究

目的观察脓毒症急性肺损伤（ALI）大鼠肺组织的细胞凋亡情况。方法24只SPF级SD大鼠采用盲肠结扎穿孔术（CLP）复制脓毒症模型,分别于CLP后0、12、36和72h颈椎脱臼法处死大鼠,取肺组织。行肺组织HE染色,观察病理变化,以透射电镜、TUNEL法检测细胞凋亡。结果HE染色可见,CLP后12、36、72h肺泡间隔增宽,间质充血水肿,肺泡腔变窄,炎症细胞渗出。TUNEL法检测发现,CLP后12、36、72h肺组织内细胞凋亡指数（Al）增加,其中36hAl值最高（P〈0．01）。透射电镜证实细胞凋亡的特征性改变。结论脓毒症大鼠肺组织的Al明显增加,细胞凋亡可能在脓毒症ALI发生、发展中起着重要作用。     

Ketamine delays mortality in an experimental model of hemorrhagic shock and subsequent sepsis

BackgroundIn previous studies ketamine was reported to improve survival and decrease serum interleukin-6 (IL-6) concentration after sepsis alone and after burn injury followed by sepsis. The aim of this study was to determine whether ketamine alters survival and/or IL-6 after hemorrhagic shock alone or hemorrhagic shock followed by sepsis.Materials and methodsRats were subjected to hemorrhagic shock with or without subsequent Gram-negative bacterial sepsis and were either treated with ketamine 5 mg/kg or were not treated. Blood was sampled for IL-6 determination prior to hemorrhage, at the completion of resuscitation, and at 6 and 30 h later. Mortality was recorded for 7 days following hemorrhage or hemorrhage + sepsis.ResultsAfter hemorrhage + sepsis the time to median mortality was significantly later in the ketamine-treated group (36 h) than in the control group (12 h). At 12 h the survival rate of the ketamine-treated group (100%) was significantly higher than in the control group (55%). There were no significant differences between groups with respect to IL-6 or 7-day survival after either hemorrhage + sepsis or hemorrhage alone.ConclusionKetamine improved 12 h survival and delayed mortality after hemorrhage + sepsis without significantly altering IL-6, and did not alter survival or IL-6 after hemorrhage alone.     

Norepinephrine and vital organ blood flow during experimental hyperdynamic sepsis

OBJECTIVE: To study the effect of norepinephrine (NE) infusion on cerebral, coronary, renal and mesenteric blood flow during sepsis. DESIGN AND SETTING: Randomised placebo-controlled animal trial in the animal laboratory of university physiology institute. ANIMALS: Seven merino cross-ewes. INTERVENTIONS: Chronic implantation of flow probes (aorta, renal, mesenteric and coronary artery and sagittal sinus). Induction of sepsis by intravenous bolus of E. coli (3 x 10(9)). After the onset of hyperdynamic sepsis sheep were randomly allocated to either NE (0.4 microg kg(-1) min(-1)) or placebo for 6 h. MEASUREMENTS AND RESULTS: E. coli induced hypotension, fever, oliguria, tachycardia and tachypnoea. It increased cardiac output and renal, mesenteric and coronary blood flows. Sagittal flow remained unchanged. Compared to placebo NE infusion restored mean arterial blood pressure and further increased cardiac output. The increases in renal, mesenteric and coronary blood flow were unaffected. Sagittal flow was also unaltered. Compared to placebo NE increased myocardial performance, mean urine output and creatinine clearance at 2 h. CONCLUSIONS: We conclude that hyperdynamic sepsis increases blood flow to heart, gut and kidney and that NE further increases cardiac output, blood pressure, myocardial performance, and urine output and creatinine clearance while maintaining regional blood flow.     

乌司他丁对脓毒症大鼠肺损伤的保护作用

目的探讨乌司他丁(UTI)对脓毒症性急性肺损伤(ALI)的保护作用。方法采用盲肠结扎穿孔(CLP)制作SD大鼠脓毒症ALI模型,随机分ALI组、糖皮质激素(GC)治疗(GC)和UTI治疗(UTI)组。成模后3 h、6 h、12 h开腹抽血行动脉血气分析,提取支气管肺泡灌洗液(BALF)检测总蛋白(TP)、总磷脂(TPL)、饱和磷脂酰胆碱(DSPC)含量,测定肺组织湿/干重(W/D)比值和肺组织匀浆中髓过氧化物酶(MPO)、丙二醛(MDA)含量,血浆中肿瘤坏死因子(TNF-α)、白介素-6(IL-6)含量,观察与比较各组肺组织病理改变。结果UTI组PaCO_2、PaO_2、HCO_3~-、BE与GC组差异无统计学意义(P＞0．05),但高于ALI组(P＜0．05);两组W/D均明显低于ALI组(P＜0．01),BALF中TP显著低于ALI组(P＜0．01),TPL和DSPC/TPL高于ALI组(P＜0．05、P＜0．01),但两组间差异无统计学意义(P＞0．05);两组肺组织匀浆中MPO、MDA含量均明显低于ALI组(P＜0．01),UTI组MPO含量还明显高于GC组(P＜0．05);两组血浆TNF-α、IL-6水平均低于ALI组(P＜0．01),UTI组IL-6高于GC组(P＜0．05);两组病理变化均较ALI组轻(P＜0．01)。结论UTI能改善缺氧、过度通气和酸中毒,减轻肺水肿和肺组织病理损伤,具有抗氧化和抑制炎性细胞因子释放作用,其抗炎作用与GC相似。     

Abdomen release in prone position does not improve oxygenation in an experimental model of acute lung injury

OBJECTIVE: To analyze the effect of abdomen release in the prone position on oxygenation in an experimental model of acute lung injury. DESIGN: Experimental randomized controlled study. SETTING: Experimental laboratory of a tertiary university hospital. PARTICIPANTS: Mixed-breed adolescent pigs weighing between 25-31 kg. INTERVENTIONS: Thirty minutes after pulmonary edema was produced with oleic acid, the animals were turned prone and randomized into two groups: group I or control (n = 9), lying directly on the operating table; and group II (n = 11) with abdomen release, with positioning rolls under the upper part of the chest wall and the pelvis to allow free movement of the abdomen. MEASUREMENTS AND RESULTS: The gas exchange, respiratory mechanics, hemodynamics, intra-abdominal pressure (IAP) and the extravascular lung water (EVLW), determined by double indicator dilution method (DI), were recorded at baseline (time 0) and at 30, 60, 90, 120 and 150 min. The PaO2/FIO2 increased in both groups at 30 min after the pigs were placed in the prone position (time 60) and then decreased progressively until the end of the experimental period, with no statistical differences between the groups at any time (73.1 +/- 14.5 vs 79.5 +/- 14.9 at 150 min). Abdomen release was not associated with changes in the respiratory mechanics, EVLW or intra-abdominal pressure. CONCLUSIONS: Abdomen release in prone position does not improve oxygenation in an experimental model of acute lung injury.     

Influence of respiratory rate and end-expiratory pressure variation on cyclic alveolar recruitment in an experimental lung injury model

Introduction  

Cyclic alveolar recruitment/derecruitment (R/D) is an important mechanism of ventilator-associated lung injury. In experimental models this process can be measured with high temporal resolution by detection of respiratory-dependent oscillations of the paO₂ (ΔpaO₂). A previous study showed that end-expiratory collapse can be prevented by an increased respiratory rate in saline-lavaged rabbits. The current study compares the effects of increased positive end-expiratory pressure (PEEP) versus an individually titrated respiratory rate (RR_ind) on intra-tidal amplitude of Δ paO₂ and on average paO₂ in saline-lavaged pigs.     

脓毒症相关性肺损伤治疗进展

近年来,随着药物治疗学及生物细胞学的快速发展,有关脓毒症相关性肺损伤治疗的新方法也相应出现,并且在动物模型中的相关干预效果令人鼓舞,临床试验有待进一步证实.临床上急性肺损伤定义的更新和发展及共识的达成,对指导相应机械通气策略的应用有帮助.     

Retroperitoneal organ injury caused by anterior penetrating abdominal injury in children.

OBJECTIVE: To describe the retroperitoneal organ injury pattern after anterior penetrating abdominal injury in children. SETTING: The paediatric surgical department of a university teaching hospital. PATIENTS AND METHODS: All children presenting with firearm and stab wounds to the anterior abdomen between January 1983 and April 2001. RESULTS: Forty-nine children (34%) with penetrating anterior abdominal wounds had retroperitoneal organ injury. The most injured organs were the descending colon in 17 patients (35%), ascending colon in eight patients (16%), and kidney in seven (14%). The most commonly associated injured organ was the small bowel. Postoperative septic complications were seen in 10 patients (20%). The most common postoperative complication was wound infection. When we compared patients with intraperitoneal organ injury with patients with retroperitoneal injury, there was no difference in parameters such as age, associated organ injury, morbidity and mortality between both groups. The main causative factor of retroperitoneal injuries was shotgun wounds, whereas it was stabbing in intra-abdominal injuries (P<0.05). The number of injured organs and the hospital stay is significantly greater in retroperitoneal organ injuries, and the trauma scores such as the Injury Severity Score (P<0.001) and the Penetrating Abdominal Trauma Index (P<0.001) were found to be significantly higher. CONCLUSION: Retroperitoneal organ injury is commonly associated with anterior penetrating abdominal trauma. Even if there is no preoperative sign of retroperitoneal organ injury, an exploratory laparotomy and a meticulous retroperitoneal exploration should also be performed for associated retroperitoneal organ injury.