SAGES guidelines for the use of laparoscopy during pregnancy.

BACKGROUND: When pregnant patients present with nonobstetric pathology, the physicians caring for them may be uncertain about the optimal management strategy. The aim of this guideline is to develop evidence-based recommendations for pregnant patients presenting with common surgical pathologies including appendicitis, biliary disease, and inflammatory bowel disease (IBD). METHODS: The Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) Guidelines Committee convened a working group to address these issues. The group generated five key questions and completed a systematic review and meta-analysis of the literature. An expert panel then met to form evidence-based recommendations according to the Grading of Recommendations Assessment, Development, and Evaluation approach. Expert opinion was utilized when the available evidence was deemed insufficient. RESULTS: The expert panel agreed on ten recommendations addressing the management of appendicitis, biliary disease, and IBD during pregnancy. CONCLUSIONS: Conditional recommendations were made in favor of appendectomy over nonoperative treatment of appendicitis, laparoscopic appendectomy over open appendectomy, and laparoscopic cholecystectomy over nonoperative treatment of biliary disease and acute cholecystitis specifically. Based on expert opinion, the panel also suggested either operative or nonoperative treatment of biliary diseases other than acute cholecystitis in the third trimester, endoscopic retrograde cholangiopancreatography rather than common bile duct exploration for symptomatic choledocholithiasis, applying the same criteria for emergent surgical intervention in pregnant and non-pregnant IBD patients, utilizing an open rather than minimally invasive approach for pregnant patients requiring emergent surgical treatment of IBD, and managing pregnant patients with active IBD flares in a multidisciplinary fashion at centers with IBD expertise.

SAGES peritoneal dialysis access guideline update 2023.

BACKGROUND: Minimally invasive surgery has been used for both de novo insertion and salvage of peritoneal dialysis (PD) catheters. Advanced laparoscopic, basic laparoscopic, open, and image-guided techniques have evolved as the most popular techniques. The aim of this guideline was to develop evidence-based guidelines that support surgeons, patients, and other physicians in decisions on minimally invasive peritoneal dialysis access and the salvage of malfunctioning catheters in both adults and children. METHODS: A guidelines committee panel of the Society of American Gastrointestinal and Endoscopic Surgeons reviewed the literature since the prior guideline was published in 2014 and developed seven key questions in adults and four in children. After a systematic review of the literature, by the panel, evidence-based recommendations were formulated using the Grading of Recommendations Assessment, Development and Evaluation approach. Recommendations for future research were also proposed. RESULTS: After systematic review, data extraction, and evidence to decision meetings, the panel agreed on twelve recommendations for the peri-operative performance of laparoscopic peritoneal dialysis access surgery and management of catheter dysfunction. CONCLUSIONS: In the adult population, conditional recommendations were made in favor of: staged hernia repair followed by PD catheter insertion over simultaneous and traditional start over urgent start of PD when medically possible. Furthermore, the panel suggested advanced laparoscopic insertion techniques rather than basic laparoscopic techniques or open insertion. Conditional recommendations were made for either advanced laparoscopic or image-guided percutaneous insertion and for either nonoperative or operative salvage. A recommendation could not be made regarding concomitant clean-contaminated surgery in adults. In the pediatric population, conditional recommendations were made for either traditional or urgent start of PD, concomitant clean or clean-contaminated surgery and PD catheter placement rather than staged, and advanced laparoscopic placement rather than basic or open insertion.

Video-based Coaching: Current Status and Role in Surgical Practice, Part II- Practical Implementation and Risk Mitigation from the Society for Surgery of the Alimentary Tract, Health Care Quality and Outcomes Committee.

INTRODUCTION: Video-based surgical coaching is gaining traction within the surgical community. It has an increasing adoption rate and growing recognition of its utility, especially an advanced continuous professional growth tool, for continued educational purposes. This method offers instructional flexibility in real-time remote settings and asynchronous feedback scenarios. In our first paper, we delineated fundamental principles for video-based coaching, emphasizing the customization of feedback to suit individual surgeon's needs. METHOD: In this second part of the series, we review into practical applications of video-based coaching, focusing on quality improvements in a team-based setting, such as the trauma bay. Additionally, we address the potential risks associated with surgical video recording, storage, and distribution, particularly regarding medicolegal aspects. We propose a comprehensive framework to facilitate the implementation of video coaching within individual healthcare institutions. RESULTS: Our paper examines the legal and ethical framework and explores the potential benefits and challenges, offering insights into the real-world implications of this educational approach. CONCLUSION: This paper contributes to the discourse on integrating video-based coaching into continuous professional development. It aims to facilitate informed decision-making in healthcare institutions, considering the adoption of this innovative educational quality tool.

Percutaneous endoscopic gastrostomy in amyotrophic lateral sclerosis: outcomes of a dedicated anesthesia and surgery protocol.

BACKGROUND: Patients requiring percutaneous endoscopic gastrostomy (PEG) for amyotrophic lateral sclerosis (ALS) related dysphagia represent a clinical challenge. Diminished pulmonary function and aspiration risks can lead to anesthesia-related complications, and gastric displacement from hemidiaphragm elevation may preclude safe gastric access. This study reports the efficacy and outcomes of a dedicated anesthesia/surgery management protocol for ALS patients undergoing PEG. METHODS: In 2013, a PEG placement protocol for ALS patients was developed emphasizing efficient pre-operative evaluation, rapidly metabolized anesthetic agents, and minimization of opioid use. Outcomes were analyzed retrospectively. Preoperative weight loss, pulmonary function tests, total analgesia, procedural time, and 90-day morbidity and mortality were recorded. RESULTS: From 2013-2019, 67 ALS patients (mean age 65.3 years, 52.2% female) received a PEG under the protocol. Mean percentage weight loss 6 months before PEG was 9.3 ± 5.1% with 38.8% of patients meeting criteria for severe malnutrition. Mean anesthesia time (propofol induction to anesthesia emergence) was 34.5 ± 10.8 min and mean operative time (endoscope insertion to dressing placement) was 16.4 ± 8.2 min. Regional anesthesia with liposomal bupivacaine was performed in 76.1%. All attempts at PEG placement were successful. With a mean follow-up of 6.1 ± 6.8 months, all PEGs were functional and there were no surgical site complications. Thirty-day readmission rate was 7.0% and 90-day mortality was 22.4% (46.7% occurring within 30 days). Mean time from surgery to death was 8.8 ± 7.8 months. CONCLUSIONS: Protocols for optimizing PEG may help overcome challenges present in the ALS patient population. Despite patient comorbidities, protocol implementation and dedicated team members resulted in a high procedural success rate and low complication rate. Further study is warranted to optimize the timing of PEG placement in relation to ALS disease progression and determine the utility of regional anesthesia during PEG placement.

Endoscopic management of colovesical and colovaginal fistulas with over-the-scope clips: A single-institution case series.

AIM: Conventional surgical management of colovesical and colovaginal fistulas can be morbid and is contraindicated in many patients. Our aim in this work is to evaluate our experience in the management of colovesical and colovaginal fistulas with endoscopic over-the-scope (OTS) clips. METHOD: A retrospective review of all patients who underwent attempted endoscopic OTS clip management of colovesical and colovaginal fistulas between 2013 and 2020 was performed. Preoperative risk factors, operative details and postoperative outcomes are reported. RESULTS: Ten patients were identified. Fistula types were: colovesical (five), rectovesical (two), colovaginal (two) and rectovaginal (one). The aetiology of the fistula was diverticular disease in seven (70%) cases and surgical complication of pelvic surgery in three (30%). The mean defect age was 157 ± 98 days, the mean defect diameter was 4.5 mm (range 2-10 mm) and the mean fistula length was 15 mm (range 2-25 mm). In nine (90%) cases, fistula identification and cannulation were performed through the nonenteric lumen of the fistula. Initial management with an OTS clip was technically successful in eight (80%) patients. Of the eight patients who underwent OTS clip placement, long-term success (mean follow-up 218 days, range 25-673 days) was achieved after initial intervention in four (50%) patients. One patient underwent serial OTS clip procedures and achieved long-term success after four interventions; three patients have not undergone a repeat procedure after initial failure. CONCLUSION: Endoscopic management of colovesical and colovaginal fistulas with OTS clips offers a promising therapeutic option for patients with contraindications to conventional surgical management. Immediate technical success and long-term success rates are similar to other gastrointestinal tract applications of OTS clips.

Guidelines for the performance of minimally invasive splenectomy.

BACKGROUND: Minimally invasive splenectomy (MIS) is increasingly favored for the treatment of benign and malignant diseases of the spleen over open access approaches. While many studies cite the superiority of MIS in terms of decreased morbidity and length of stay over a traditional open approach, the comparative effectiveness of specific technical and peri-operative approaches to MIS is unclear. OBJECTIVE: To develop evidence-based guidelines that support clinicians, patients, and others in decisions on the peri-operative performance of MIS. METHODS: A guidelines committee panel of the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) including methodologists used the Grading of Recommendations Assessment, Development and Evaluation approach to grade the certainty of evidence and formulate recommendations. RESULTS: Informed by a systematic review of the evidence, the panel agreed on eight recommendations for the peri-operative performance of MIS for adults and children in elective situations addressing six key questions. CONCLUSIONS: Conditional recommendations were made in favor of lateral positioning for non-hematologic disease, intra-operative platelet administration for patients with idiopathic thrombocytopenic purpura instead of preoperative administration, and the use of mechanical devices to control the splenic hilum. Further, a conditional recommendation was made against routine intra-operative drain placement.

Revisional Bariatric Surgery.

Revisional bariatric surgery is a growing subset of all bariatric procedures. Although revisions can be associated with higher morbidity rates and less optimal outcomes than those seen with primary procedures, they can be safely performed, with excellent outcomes and improved quality of life for patients. Facility and familiarity with revisional principles and techniques are necessary components of bariatric surgical practice.

Over-the-scope clip management of non-acute, full-thickness gastrointestinal defects.

BACKGROUND: Endoscopic management of full-thickness gastrointestinal tract defects (FTGID) has become an attractive management strategy, as it avoids the morbidity of surgery. We have previously described the short-term outcomes of over-the-scope clip management of 22 patients with non-acute FTGID. This study updates our prior findings with a larger sample size and longer follow-up period. METHODS: A retrospective analysis of prospectively collected data was conducted. All patients undergoing over-the-scope clip management of FTGID between 2013 and 2019 were identified. Acute perforations immediately managed and FTGID requiring endoscopic suturing were excluded. Patient demographics, endoscopic adjunct therapies, number of endoscopic interventions, and need for operative management were evaluated. Success was strictly defined as complete FTGID closure. RESULTS: We identified 92 patients with 117 FTGID (65 fistulae and 52 leaks); 27.2% had more than one FTGID managed simultaneously. The OTSC device (Ovesco Endoscopy, Tubingen, Germany) was utilized in all cases. Additional closure attempts were required in 22.2% of defects. With a median follow-up period of 5.5 months, overall defect closure success rate was 66.1% (55.0% fistulae vs. 79.6% leaks, p = 0.007). There were four mortalities from causes unrelated to the FTGID. Only 14.9% of patients with FTGID underwent operative management. There were no complications related to endoscopic intervention and no patients required urgent surgical intervention. CONCLUSIONS: Over-the-scope clip management of FTGID represents a safe alternative to potentially morbid operative intervention. When strictly defining success as complete closure of all FTGID, endoscopy was successful in 64.4% of patients with only a small minority of patients ultimately requiring surgery.

Concomitant laparoscopic cholecystectomy and antegrade wire, rendezvous cannulation of the biliary tree may reduce post-ERCP pancreatitis events.

INTRODUCTION: For patients with a gallbladder in situ, choledocholithiasis is a common presenting symptom. Both two-session endoscopic retrograde cholangiopancreatography (ERCP) and subsequent cholecystectomy (CCY) and single-stage (simultaneous CCY/ERCP) have been described. We utilize an antegrade wire, rendezvous cannulation (AWRC) technique to facilitate ERCP during CCY. We hypothesized that AWRC would eliminate episodes of post-ERCP pancreatitis (PEP). METHODS: An IRB approved, retrospective review of patients who underwent ERCP via AWRC for choledocholithiasis during CCY was performed. Patient characteristics, pre/postoperative laboratory values, complications, and readmissions were reviewed. AWRC was conducted during laparoscopic or open CCY for evidence of choledocholithiasis with or without preoperative biliary pancreatitis or cholangitis. Following confirmatory intraoperative cholangiogram, a flexible tip guidewire was inserted antegrade into the cystic ductotomy, through the bile duct across the ampulla and retrieved in the duodenum with a duodenoscope. Standard ERCP maneuvers to clear the bile duct are then performed over the wire. RESULTS: Thirty-seven patients (27 female, age 19-77, BMI 21-50 kg/m2) underwent intraoperative ERCP via AWRC technique during CCY. Seventeen underwent CCY for acute cholecystitis. Fifteen patients underwent transgastric ERCP in the setting of previous Roux-en-Y gastric bypass. Mean total operative time was 214 min. Mean ERCP time was 31 min. Thirty-three patients had biliary stents placed. There were no cannulations or injections of the pancreatic duct. There were no intraoperative complications associated with the ERCP and no patients developed PEP. Three patients developed a postoperative subhepatic abscess requiring drainage. CONCLUSION: AWRC is a useful technique for safe and efficient bile duct cannulation for therapeutic ERCP in the setting of choledocholithiasis at the time of CCY. Despite supine (rather than the traditional prone) positioning, total ERCP times were short and we eliminated any manipulation of the pancreatic duct. No patients in our series developed PEP or post-sphincterotomy bleeding.

Optimizing Hospital Resource Utilization in Bariatric Readmission.

BACKGROUND AND OBJECTIVES: The prevalence of patients with a history of bariatric surgery is climbing. Medical and surgical questions arising in this patient population may prompt them to present to the nearest emergency department (ED), irrespective of that facility's experience with bariatric surgery. The emergency physician is the first to evaluate patients with a history of bariatric surgery who present with abdominal symptoms. As a quality improvement project aimed at reducing resource utilization, we sought to determine which patients presenting to the ED could be treated in an outpatient setting in lieu of hospital admission. METHODS: We conducted a retrospective review of bariatric patients admitted from our ED with abdominal symptoms, including abdominal pain, nausea, vomiting, dysphagia, obstruction, and hematemesis. We collected the following variables: type of bariatric operation, admission and discharge diagnoses, and all interventions performed during admission. RESULTS: One hundred sixty-nine patients (76.1%) had a history of laparoscopic Roux-en-Y gastric bypass. The time from bariatric operation to presentation averaged 42 ± 4.63 (SD) months. The most common symptom was abdominal pain (80.2%). Ninety-four percent of patients underwent invasive management via upper endoscopy, laparoscopy, or laparotomy. The most common postprocedural diagnoses were stricture, bowel obstruction, inflammatory findings, and cholecystitis. CONCLUSION: Most patient encounters resulted in invasive management (204/282; 72.3%). The subset of these patients requiring endoscopic evaluation or therapy (37.7%) may be suitable for outpatient management if appropriate measures are available for rapid follow-up and procedural scheduling.

Impact of incisional hernia development following abdominal operations on total healthcare cost.

BACKGROUND: Introduction of the category III CPT code (0437T) for prophylactic mesh augmentation (PMA) highlights efforts to reduce incisional hernia (IH). PMA's value in the context of value-based care requires understanding both the cost of IH development and the savings from prevention. We hypothesized large healthcare costs with IH development. Appreciating which subsets of patients are at highest risk for IH, and the subsets who have the costliest care is essential in targeting interventions for hernia prevention. METHODS: Retrospective cohort study utilizing data from Truven Health Analytic MarketScan Commercial Claims and Encounters Database from calendar years 2011-2014. Adults undergoing open abdominal operations with continued enrollment 3-year post-surgery were included. Inpatient and outpatient claims were tracked over 3 years to identify IH. Quantile regression estimated the association between conditional distribution of total cost and IH. A generalized linear model with gamma distribution estimated the association of conditional mean of total cost and IH. Models were adjusted for confounding cost covariates (e.g., age, gender, obesity, smoking, cancer). RESULTS: 14,290 patients were identified, 1294 (9.1%) developed IH, 48% within 1-year, 33% at 1-2 years, and 19% at 2-3 years post-surgery. 515 underwent stoma creation, 4579 colon resection, 2263 liver/kidney, 3890 peritoneal, 3043 other (foregut, appendectomy, cholecystectomy). Rate of IH formation was 25, 13, 5.9, 6.3, and 6.3%, respectively. The difference in median expenditures for IH development versus no IH was ostomies: $26,098, colorectal: $21,211, liver/kidney: $23,811, peritoneal: $25,554, others: $28,870 (p < 0.0.01). IH within 1 year was more expensive than within 3 years in the following categories: colorectal ($16,034, p = 0.0385), liver/kidney ($27,145, p = 0.0004), and ostomy ($18,992, p = 0.0035). CONCLUSION: IH is a common occurrence imposing significant healthcare burden. Higher costs occur when IH occurs within 1 year versus 3 years from the index-procedure. This highlights the importance of hernia prevention techniques and the question of whether temporizing closure adjuncts  are appropriate in high-risk patients.

Gastric Bypass and Influence on Improvement of NAFLD.

PURPOSE OF REVIEW: Obesity is recognized as a chronic and recurring disease, often accompanied by other weight-related comorbid conditions such as obstructive sleep apnea, hypertension, type 2 diabetes, and non-alcoholic fatty liver disease (NAFLD). This chapter will seek to focus on the effect of weight loss surgery (WLS), in particular Roux-en-Y gastric bypass (RYGB), on NAFLD. RECENT FINDINGS: Among several modalities available to treat NAFLD, the one most likely to achieve rapid, significant, and sustained improvement of liver disease is WLS. The most commonly studied WLS procedure at this time is RYGB, and there is significant evidence that this is a safe and effective procedure both for weight loss and to bring about improvement of multiple associated comorbid conditions, including NAFLD. Further research focusing on non-surgical approaches that might mimic the effect of WLS on liver pathology is needed.

Nineteen-year trends in incidence and indications for laparoscopic cholecystectomy: the NY State experience.

BACKGROUND: Since the introduction of laparoscopic cholecystectomy (LC), there has been continued evolution in technique, instrumentation and postoperative management. With increased experience, LC has migrated to the outpatient setting. We asked whether increased availability and experience has impacted incidence of and indications for LC. METHODS: The New York (NY) State Planning and Research Cooperative System longitudinal administrative database was utilized to identify patients who underwent cholecystectomy between 1995 and 2013. ICD-9 and CPT procedure codes were extracted corresponding to laparoscopic and open cholecystectomy and the associated primary diagnostic codes. Data were analyzed as relative change in incidence (normalized to 1000 LC patients) for respective diagnoses. RESULTS: From 1995 to 2013, 711,406 cholecystectomies were performed in NY State: 637,308 (89.58 %) laparoscopic. The overall frequency of cholecystectomy did not increase (1.23 % increase with a commensurate population increase of 6.32 %). Indications for LC during this time were: 72.81 % for calculous cholecystitis (n = 464,032), 4.88 % for biliary colic (n = 31,124), 8.98 % for acalculous cholecystitis (n = 57,205), 3.01 % for gallstone pancreatitis (n = 19,193), and 1.59 % for biliary dyskinesia (n = 10,110). The incidence of calculous cholecystitis declined (-20.09 %, p < 0.0001) between 1995 and 2013; meanwhile, other diagnoses increased in incidence: biliary colic (+54.96 %, p = 0.0013), acalculous cholecystitis (+94.24 %, p < 0.0001), gallstone pancreatitis (+107.48 %, p < 0.0001), and biliary dyskinesia (+331.74 %, p < 0.0001). Outpatient LC incidence catapulted to 48.59 % in 2013, from 0.15 % in 1995, increasing >320-fold. Analysis of LC through 2014 revealed increasing rates of digestive, infectious, respiratory, and renal complications, with overall cholecystectomy complication rates of 9.29 %. CONCLUSION: A shifting distribution of operative indications and increasing rates of complications should prompt careful consideration prior to surgery for benign biliary disease. For what is a common procedure, LC carries substantial risk of complications, thus requiring the patient to be an active participant and to share in the decision-making process.

The intestinal mucus layer is a critical component of the gut barrier that is damaged during acute pancreatitis.

Gut barrier failure has been implicated in the progression from single-organ injury to multiple-organ failure. The unstirred mucus layer is a major component of the physiological gut barrier; its role in acute pancreatitis (AP) is not clearly defined. Rats underwent biliopancreatic duct ligation-induced AP; two controls were used: biliopancreatic duct ligation with drainage and sham duct ligation. After 4.5 h, serum and ascitic amylase activity was measured. Mucus was analyzed for reactive nitrogen intermediate-mediated damage, reactive oxygen species-induced damage, and total antioxidant capacity. Mucus coverage and villous injury were assessed histologically. Ileum permeability was measured by diffusion of a fluorescent Dextran probe. Histology and morphology of the mucus layer were validated in a mouse AP model (intraductal taurocholate plus cerulein). Biliopancreatic duct ligation increased serum α-amylase, ascitic volume, and ascitic α-amylase. Intestinal permeability was increased, which was associated with loss of the unstirred mucus layer but not villous injury. These changes correlated with increased reactive oxygen species- and- reactive nitrogen intermediate-mediated mucus damage as well as decreased mucus total antioxidant capacity but were not present in the two control groups. Using a different model of AP in mice, the finding of mucus layer disruption was recapitulated at 6 h after AP, but by 24 h, rebound hypersecretion of inspissated mucus was seen. These results support the hypothesis that damage to the unstirred mucus layer with evidence of oxidative stress occurs during AP-induced gut barrier failure.

Intraluminal nonbacterial intestinal components control gut and lung injury after trauma hemorrhagic shock.

OBJECTIVE: To test whether the mucus layer, luminal digestive enzymes, and intestinal mast cells are critical components in the pathogenesis of trauma shock-induced gut and lung injury. BACKGROUND: Gut origin sepsis studies have highlighted the importance of the systemic component (ischemia-reperfusion) of gut injury, whereas the intraluminal component is less well studied. METHODS: In rats subjected to trauma hemorrhagic shock (T/HS) or sham shock, the role of pancreatic enzymes in gut injury was tested by diversion of pancreatic enzymes via pancreatic duct exteriorization whereas the role of the mucus layer was tested via the enteral administration of a mucus surrogate. In addition, the role of mast cells was assessed by measuring mast cell activation and the ability of pharmacologic inhibition of mast cells to abrogate gut and lung injury. Gut and mucus injury was characterized functionally, morphologically, and chemically. RESULTS: Pancreatic duct exteriorization abrogated T/HS-induced gut barrier loss and limited chemical mucus changes. The mucus surrogate prevented T/HS-induced gut and lung injury. Finally, pancreatic enzyme-induced gut and lung injury seems to involve mast cell activation because T/HS activates mast cells and pharmacologic inhibition of intestinal mast cells prevented T/HS-induced gut and lung injury. CONCLUSIONS: These results indicate that gut and gut-induced lung injury after T/HS involves a complex process consisting of intraluminal digestive enzymes, the unstirred mucus layer, and a systemic ischemic-reperfusion injury. This suggests the possibility of intraluminal therapeutic strategies.

Trauma-hemorrhagic shock induces a CD36-dependent RBC endothelial-adhesive phenotype.

OBJECTIVE: Microvascular dysfunction is a key element in the development of the multiple organ dysfunction syndrome. Although the mechanisms for this response are unclear, RBC adhesion to endothelium may initiate intravascular occlusion leading to ischemic tissue injury. Thus, we tested the hypothesis that trauma-hemorrhage induces RBC-endothelial cell adhesion. DESIGN: Prospective in vivo and in vitro animal study and analysis of patient blood samples. SETTING: University research laboratory and hospital emergency and trauma units. INTERVENTION: We initially assayed RBC adhesion to endothelial cells in vitro using RBCs obtained from rats subjected to trauma-hemorrhagic shock or sham shock as well as from severely injured trauma patients. Subsequently, we measured the role of putative RBCs and endothelial cell receptors in the increased RBC-endothelial cell adhesive response. MAIN RESULTS: In both rats and humans, trauma-hemorrhagic shock increased RBC adhesion to endothelium as well as increasing several putative RBC surface adhesion molecules including CD36. The critical factor leading to RBC-endothelial cell adhesion was increased surface RBC CD36 expression. Adhesion of trauma-hemorrhagic shock RBCs was mediated, at least in part, by the binding of RBC CD36 to its cognate endothelial receptors (αVß3 and VCAM-1). Gut-derived factors carried in the intestinal lymphatics triggered these trauma-hemorrhagic shock-induced RBC changes because 1) preventing trauma-hemorrhagic shock intestinal lymph from reaching the systemic circulation abrogated the RBC effects, 2) in vitro incubation of naïve whole blood with trauma-hemorrhagic shock lymph replicated the in vivo trauma-hemorrhagic shock-induced RBC changes while 3) injection of trauma-hemorrhagic shock lymph into naïve animals recreated the RBC changes observed after actual trauma-hemorrhagic shock. CONCLUSIONS: 1) Trauma-hemorrhagic shock induces rapid RBC adhesion to endothelial cells in patients and animals. 2) Increased RBC CD36 expression characterizes the RBC-adhesive phenotype. 3) The RBC phenotypic and functional changes were induced by gut-derived humoral factors. These novel findings may explain the microvascular dysfunction occurring after trauma-hemorrhagic shock, sepsis, and other stress states.

Oxidative modification of the intestinal mucus layer is a critical but unrecognized component of trauma hemorrhagic shock-induced gut barrier failure.

Recent studies demonstrate that mechanisms underlying gut barrier failure include systemic processes and less studied luminal processes. We thus tested the hypothesis that mucus layer oxidation is a component of trauma/hemorrhagic shock-induced gut injury and dysfunction. Male Sprague-Dawley rats underwent trauma/hemorrhagic shock. Controls underwent trauma only. Mucus from the terminal 30 cm of the ileum was collected, processed, and analyzed for reactive nitrogen intermediates (RNI)-mediated damage, reactive oxygen species (ROS)-induced damage, and total antioxidant capacity. The distal ileum was stained to quantify the mucus layer; gut permeability was assessed physiologically. A time course study was conducted to determine the temporal sequence of mucus layer damage. The role of free radical-mediated damage to the gut barrier was investigated by the effect of the free radical scavenger dimethyl sulfoxide on trauma/hemorrhagic shock-induced changes on the mucus and on gut permeability. Trauma/hemorrhagic shock increased intestinal permeability, which was associated with evidence of loss of the unstirred mucus layer. These changes correlated with increased ROS- and RNI-mediated mucus damage and loss of mucus total antioxidant capacity. Based on the time course study, ROS-mediated mucus damage and loss of total antioxidant capacity were present immediately following shock, whereas RNI-mediated damage was delayed for 3 h. Dimethyl sulfoxide ameliorated gut barrier loss, ROS-mediated changes to the mucus layer, and loss of total antioxidant capacity. There was no change in RNI-induced changes to the mucus layer. These results support the hypothesis that trauma/hemorrhagic shock leads to mucus damage and gut dysfunction through the generation of free radical species.