Effect of stress and trauma on bacterial translocation from the gut

Previously, we established that bacteria contained within the gut can cross the GI mucosal barrier and spread systemically, a process termed bacterial translocation. Three models were used to extend this work: cold exposure (up to 16 hr at 4 degrees C), a nontissue injury stress model; femoral fracture-amputation, a trauma model; and thermal injury (30% third-degree burn), a trauma model with retained necrotic tissue. CD-1 mice either with a normal GI microflora or who were monoassociated with Escherichia coli C-25 were subjected to sham or actual stress or trauma. The animals were sacrificed at various times postinsult and the ceca, mesenteric lymph nodes (MLN), spleens, and livers were quantitatively cultured. Neither the incidence nor the magnitude of bacterial translocation was increased in the cold-exposed animals compared to control mice. The incidence of bacterial translocation to the systemic organs was higher in the animals with a normal flora receiving femoral fracture amputation (11%) (P less than 0.02) than in animals receiving a thermal injury (1%) or sham-injured control mice (0%). In contrast, the incidence of translocation to the liver or spleen was higher in burned mice monoassociated with E. coli C-25 (60%) (P less than 0.01) than in E. coli monoassociated mice sustaining femoral fracture amputation (17%). Stress alone (cold exposure) does not promote bacterial translocation; however, trauma, especially in combination with retained necrotic tissue, promotes bacterial translocation. Thus bacteria colonizing the gut can invade systemic organs after trauma, especially when the normal ecology of the gut flora has been disrupted.     

Lethal burn-induced bacterial translocation: role of genetic resistance

Since genetic factors may influence outcome after trauma or during infection, the current experiments were performed to examine the resistance of three genetically different mouse strains to burn-induced bacterial translocation. Outbred ICR, inbred Balb/c, and inbred C57/B1 mice, with a normal or disrupted (monoassociated with Escherichia coli C25) GI tract microflora, were subjected to sham or actual 25% body burns. In Balb/c, but not ICR mice, replacing the normal intestinal microflora with E. coli C25 converted the thermal injury from a nonlethal (0% mortality) to a lethal (68% mortality) injury. The increased mortality of the burned Balb/c mice monoassociated with E. coli C25 was associated with a higher incidence (p less than 0.05) and magnitude (p less than 0.05) of E. coli C25 translocation from the GI tract. The C57/B1 mice were intermediate between the Balb/c and ICR strains, in that C57/B1 mice monoassociated with E. coli C25 had a higher mortality and greater E. coli C25 translocation than mice with a normal microflora after thermal injury. Thus the composition of the intestinal microflora as well as the genetic background of the host influence the susceptibility of the host to burn-induced bacterial translocation and survival.     

Thermal injury promotes bacterial translocation from the gastrointestinal tract in mice with impaired T-cell-mediated immunity

We have shown previously that after thermal trauma viable bacteria will cross the intact gastrointestinal mucosa (bacterial translocation) to invade the mesenteric lymph nodes and other organs if the normal indigenous microflora is disrupted, allowing bacterial overgrowth. To determine whether T-cell-mediated immunity (T-CMI) was important in preventing translocation after thermal injury in animals with an intact normal flora, conventional (+/+), athymic (nu/nu), and heterozygous (nu/+) mice receiving a 30% third-degree burn were killed at various intervals after burn and their organs cultured. Bacterial translocation did not occur in control or burned specific pathogen-free mice with intact T-CMI but did occur in athymic mice with deficient T-CMI. Both the incidence of positive organs and the numbers of translocated bacteria per gram of organ were increased after thermal injury. Bacterial overgrowth was not responsible for these findings, since the levels of cecal enteric bacteria were not different between the burned and nonburned groups. Since translocation occurred to a greater extent in athymic burned mice than control athymic mice, it appears that a thermal injury promotes translocation by impairing other host defense systems in addition to the T-CMI.     

Endotoxin but not malnutrition promotes bacterial translocation of the gut flora in burned mice

Previously we have shown that under certain conditions, bacteria can pass through the intact epithelial mucosa to the mesenteric lymph nodes (MLN), liver, spleen, and bloodstream to cause infection, a process termed bacterial translocation. To extend these studies, we determined the influence of protein malnutrition and endotoxemia on bacterial translocation in burned (25% TBSA) and unburned mice. The results of these experiments documented that protein malnutrition did not promote bacterial translocation from the gut in either burned or unburned animals, although it did disrupt the normal indigenous gut flora. In contrast, a nonlethal dose of endotoxin (IP) promoted bacterial translocation to the mesenteric lymph nodes in burned and unburned mice, but only in burned mice did the bacteria translocate from the gut to other systemic organs (p less than 0.01). Furthermore, the mortality rate of mice receiving only endotoxin or burn was less than 10%, while the combination of endotoxin plus a thermal injury increased the mortality rate to 100% (p less than 0.01). These studies support the concept that bacteria may translocate from the gut to other organs and be a potential source of lethal infections after thermal injury.     

Effect of oral antibiotics and bacterial overgrowth on the translocation of the GI tract microflora in burned rats

Infections in burned patients have generally been considered to arise from exogenous organisms. Consequently, the therapy of burned patients has emphasized the use of infection control policies and topical antimicrobial agents to reduce bacterial colonization. Even though enteric bacteria are frequently found in the burn wound little attention has been paid to the patient's own GI tract microflora as a potential source of organisms colonizing the burn wound. The current experiments were carried out to determine if the bacteria present in the GI tract of healthy animals would penetrate (translocate) through the GI mucosa and spread to visceral organs after a moderate or major thermal injury. The results of these experiments indicated that bacteria can translocate across the wall of the GI tract and survive in the mesenteric lymph nodes in healthy rats. Furthermore, when the GI tract microflora is altered, either due to bacterial overgrowth or under the influence of oral antibiotic therapy, not only will bacteria translocate to the mesenteric lymph nodes but bacteria will also spread to other visceral organs. The results of these experiments support the hypothesis that the GI tract can serve as a reservoir for nosocomial infections in the burned patient, since bacteria can translocate across the mucosal barrier of the GI tract after thermal injury and survive in visceral organs before colonization of the burn wound occurs.     

Intestinal bacterial overgrowth induces the production of biologically active intestinal lymph

OBJECTIVE: We have previously documented that gut-derived lymph from rats subjected to trauma plus hemorrhagic shock (T/HS) is injurious to vascular endothelial cells and activates neutrophils (PMNs), two key events in postshock organ injury. Because T/HS leads to gut injury, intestinal bacterial overgrowth, and the loss of gut barrier function, the relative role of gut injury as opposed to intestinal bacterial overgrowth per se in the pathogenesis of biologically active intestinal lymph is unclear. We therefore studied whether mesenteric lymph can injure endothelial cells and/or active PMNs in an intestinal bacterial overgrowth model where there is no gut injury (monoassociation). METHODS: Bacterial overgrowth was established in male rats by treating the animals with 4 days of oral antibiotics followed by administration of a nonpathogenic, streptomycin-resistant strain of Escherichia coli C25. Mesenteric lymph was then collected from rats with normal flora and from E. coli C25 monoassociated rats. Its effects were tested on human umbilical vein endothelial cells (HUVECs) and human PMNs. As an additional control, lymph was collected from antibiotic-decontaminated rats that received antibiotics but were not colonized with E. coli C25. RESULTS: As compared with medium, normal flora intestinal lymph, antibiotic-decontaminated lymph, or portal plasma from the monoassociated rats, mesenteric lymph from the monoassociated rats killed HUVECs and increased the permeability of a HUVEC monolayer. In contrast to the effects on HUVECs, lymph from the monoassociated rats did not increase PMN CD11b expression or prime PMNs for an augmented respiratory burst, as compared with lymph from the rats with normal flora or from antibiotic-decontaminated rats. The effects of lymph from the monoassociated rats was not caused by bacteria, because these lymph samples were sterile. CONCLUSION: These results indicate that disruption of the normal intestinal microflora resulting in bacterial overgrowth with enteric bacilli may participate in the production of mesenteric lymph that is injurious to endothelial cells in shock, but this mechanism does not appear to be significantly involved in the activation of PMNs.     

Altered gut flora and environment in patients with severe SIRS

BACKGROUND: The gut is considered an important target organ of injury after severe insult such as sepsis, trauma, and shock. The impact of bacterial translocation or mesenteric lymph on systemic inflammatory response and multiple organ damage has been investigated in animals, but dynamic changes in the gut flora and environment have not been fully clarified in critically ill patients. In the present study, we quantitatively evaluated changes in the gut microflora and environment in patients with severe systemic inflammatory response syndrome (SIRS). METHODS: Twenty-five patients with severe SIRS, who fulfilled the criteria for SIRS, had a serum CRP level >10 mg/dL, and were treated in the intensive care unit for more than 2 days, were included in our study. SIRS was a result of sepsis in 18 patients, trauma in 6, and burn in 1. A fecal sample was used for quantitative evaluation of microflora (bacterial counts of 10 key groups including Bifidobacterium and Lactobacillus) by plate or tube technique and of the gut environment (pH and 9 organic acids by high speed liquid chromatography). Data obtained from patients were compared with corresponding data from healthy volunteers. RESULTS: Analysis of fecal flora confirmed that patients with severe SIRS had significantly lower total anaerobic bacterial counts (especially 2-4 log fewer "beneficial" Bifidobacterium and Lactobacillus) and 2 log higher "pathogenic" Staphylococcus and Pseudomonas group counts than those of healthy volunteers. Concentrations of total organic acids (especially "beneficial" short-chain fatty acids such as acetic acid, propionic acid, and butyric acid) in the feces were significantly decreased in the patients, whereas pH was markedly increased. CONCLUSIONS: The gut flora and environment are significantly altered in patients with severe SIRS. Abnormal gut flora and environment may affect systemic inflammatory response after severe insult.     

Influence of S. aureus and Str. pyogenes wound colonization on bacterial translocation in a burn model

Summary Bacterial translocation (BT) and release of endotoxin from the gut may contribute to septic complications in severely burned patients. In earlier experiments, it was shown in a burn model that BT exceeded the role of wound dissemination when burn wounds were colonized with Pseudomonas aeruginosa. Burn wound colonization with Pseudomonas aeruginosa also enhanced BT. It was concluded that endotoxin from gram-negative micro-organisms colonizing the burn wound appeared to play a role in the increased BT. In this study, the contribution of burn wound colonization with the gram-positive micro-organisms S. aureus and Str. pyogenes to BT and endotoxemia has been examined in Escherichia coli monoassociated mice with a 30% scald. The animals were sacrificed two days post-burn. The peritoneal cavity, the heart, one lung, the liver, the spleen and the cecum were cultured. Endotoxin in plasma was determined by means of the Limulus amoebocyte lysate assay. It appeared that dissemination of E. coli from the gut played a more important role than S. aureus or Str. pyogenes dissemination from the burn wound in this model. In only one of the 15 surviving Str. pyogenes contaminated animals dissemination had taken place from the burn wound. Dissemination of S. aureus was not seen in the S. aureus contaminated group. The incidence of E. coli translocation two days postburn, to the spleen (p<0.05) and liver (p<0.01) was enhanced in the Str. pyogenes group compares to the control group. Wound colonization by S. aureus did not increase the incidence of E. coli translocation. Endotoxemia was found in three of the 15 Str. pyogenes and in none of the S. aureus contaminated animals. In one of the 15 control animals, endotoxin was detected in plasma. These differences are not significant. The cause of the enhanced BT to the spleen and the liver in the Str. pyogenes contaminated group remains as yet unclear.Abbreviations BT bacterial translocation - SPF specific pathogen free - CFU colony forming unit - GI gastrointestinal - BHI brain heart infusion - LPS Lipopolysaccharide     

The effect of albumin or crystalloid resuscitation on bacterial translocation and endotoxin absorption following experimental burn injury.

Burn injury induces immune suppression and increases susceptibility to infection. Hypoalbuminemia is an early and consistent finding following thermal injury and is independently associated with gastrointestinal dysfunction and increased rates of infectious morbidity. This study assessed the effects of albumin resuscitation on burn-induced immunosuppression, bacterial translocation, and absorption of gut endotoxin. Male Sprague-Dawley rats, presensitized to keyhole limpet hemocyanin (KLH), underwent a 20% dorsal scald burn injury, followed by laparotomy and IVC catheterization for fluid resuscitation. Animals were randomized to one of three resuscitative regimens: Ringer's lactate 3 ml/kg/% burn, Ringer's lactate 9 ml/kg/% burn, or 5% human albumin 3 ml/kg/% burn. Delayed hypersensitivity (DTH) responses to KLH were depressed 24 hr following injury (preburn 8.9 +/- 0.2 mm, post-burn 3.1 +/- 0.3 mm, P less than 0.001) and were significantly lower in animals in whom gram-negative bacterial translocation had occurred (2.3 +/- 0.4 vs 3.6 +/- 0.2 mm, P less than 0.005). Serum albumin levels were lower and rates of gram-negative bacterial translocation higher for those animals receiving low volume crystalloid resuscitation; animals resuscitated with albumin or high volume crystalloid experienced similar degrees of postinjury hypoalbuminemia and bacterial translocation. Uptake of radiolabeled endotoxin was maximal in animals resuscitated with albumin. Bacterial translocation is believed to be responsible for a significant number of late nosocomial infections following trauma. These data suggest that the adequacy of early resuscitation rather than the type of resuscitative solution is the more important factor in minimizing translocation.     

Bacterial translocation and its relationship to visceral blood flow, gut mucosal ornithine decarboxylase activity, and DNA in pigs

The relationship of bacterial translocation to gut blood flow and mucosal integrity was studied in pigs. Three groups of miniature pigs were studied: sham injured (controls) (n = 7), 50% mechanical reduction in blood flow to the superior mesenteric artery (SMA) and celiac artery (CA) (n = 6), and a 40% third-degree cutaneous flame burn (n = 9). Forty-eight hours after injury, animals were killed and organ samples obtained for analysis. Bacteria of the same biotype as that found in the intestinal lumen were present in the mesenteric lymph nodes (MLN) of 9 of 9 burned pigs and 5 of 6 pigs undergoing partial vascular occlusion. The DNA content and ornithine decarboxylase (ODC) activity were increased in the colon mucosa of animals from both the reduced-flow and burn-injured groups compared with control animals. Decreased blood flow to the gut may contribute to the development of bacterial translocation. In addition, intestinal regenerative capacity remains intact 48 hours after injury.     

Role of bacterial adherence and the mucus barrier on bacterial translocation: effects of protein malnutrition and endotoxin in rats.

OBJECTIVE: The purpose of the study was to investigate the potential relations between mucosal bacterial adherence, intestinal mucus and mucin content, and bacterial translocation. SUMMARY BACKGROUND DATA: The attachment of bacteria to mucosal surfaces is the initial event in the pathogenesis of most bacterial infections that originate at mucosal surfaces, such as the gut. The intestinal mucus layer appears to function as a defensive barrier limiting micro-organisms present in the intestinal lumen from colonizing enterocytes. Consequently, studies focusing on the biology of bacterial adherence to the intestinal mucosa likely are to be important in clarifying the pathogenesis of gut origin sepsis. METHODS: To explore the relations between intestinal bacterial adherence, mucus bacterial binding, and bacterial translocation, two models were used. One (protein malnutrition) in which profound alterations in intestinal morphology occurs in the absence of significant translocation and one (endotoxin challenge) in which bacterial translocation occurs and intestinal morphology is relatively normal. RESULTS: Protein malnutrition was not associated with bacterial translocation and measurement of enteroadherent, mucosally associated bacterial population levels documented that the total number of gram-negative enteric bacilli adherent to the ileum and cecum was less in the protein-malnourished rats than in the normally nourished animals (p < 0.01). Furthermore, there was an inverse relation between the duration of protein malnutrition and bacterial adherence to the intestinal mucosa (r = 0.62, p < 0.002). In contrast, after endotoxin challenge, the level of enteroadherent bacteria was increased and bacterial translocation was observed. The binding of Escherichia coli to immobilized ileal mucus in vitro was decreased significantly in protein-malnourished rats, whereas E. coli binding to insoluble ileal mucus was increased in the rats receiving endotoxin. CONCLUSIONS: This study indicates that the adherence of bacteria to the intestinal mucosal surface is an important factor in bacterial translocation, that intestinal mucus modulates bacterial adherence, and that increased levels of mucosally associated bacteria are associated with a loss intestinal barrier function to bacteria.     

Bacterial translocation from the gastrointestinal tract and endogenous infection induced by immunosuppression after burn

This study described the endogenous infections and bacterial translocation from GI tract caused by immunosuppression after burn. In the group of burned plus injected dexamethasone (DXM) (BIS, n = 31), the rate of enteric bacteria translocation was 67.4%, the rate of visceral abscess was 65.5%, much more higher than in the group of only DXM (IS, n = 15). The translocation of intestinal bacteria also was found in the group of only burned (BU 3/15) and control (ck, 1/23), but endogenous infection did not occur in both group. The bacteria cultured from the rat organs are mainly enteric bacilli and corynebacterium. It was assumed that the endogenous infection was originated from the conditions in which the micro-ecologic system of indigenous intestinal flora was disturbed, immunologic function was suppressed by the overlapped effect of burn and injection of DXM, the biological antagonism among the intestinal flora was attenuated, and the intestinal bacilli overgrew, passed through the epithelia of intestine into lymphatic vessel and mesenteric lymph nodes, then colonized and multiplied in other organs, resulting in endogenous infection.     

The role of interdigestive small bowel motility in the regulation of gut microflora, bacterial overgrowth, and bacterial translocation in rats.

OBJECTIVE: To clarify the role of the migrating motor complex (MMC) in the regulation of small intestinal microflora and bacterial translocation. SUMMARY BACKGROUND DATA: The intestinal microflora may serve as a source of infectious microorganisms. Failure of regulatory mechanisms of the intestinal flora could therefore play an important role in the pathogenesis of gut-derived infections. METHODS: Rats were fitted with small intestinal myoelectrodes. MMCs were measured on a control day and 3 consecutive days during continuous administration of morphine or placebo. Mesenteric lymph nodes, liver, spleen, peripheral blood, duodenum, and ileum samples were cultured quantitatively. RESULTS: The mean MMC cycle length in placebo-treated animals was 15.1+/-0.5 minutes. MMCs were completely disrupted after morphine treatment. Total bacterial growth in the duodenum was 7.27+/-0.34 10log colony-forming units (CFU)/g with placebo and 8.28+/-0.27 CFU/g with morphine. In placebo-treated animals, the mean MMC cycle length the day before culturing correlated with total bacterial growth in the duodenum. Translocation incidences to the mesenteric lymph nodes, liver, spleen, and blood were 0/8, 1/8, 0/8, and 0/8 with placebo and 7/8, 6/8, 5/8, and 0/8 with morphine. The overall translocation incidence was 1/8 in placebo-treated animals and 8/8 in morphine-treated animals. CONCLUSIONS: The MMC is an important mechanism controlling bacterial growth in the upper small bowel. Its disruption with morphine promotes duodenal bacterial overgrowth and bacterial translocation.     

Bacterial translocation in trauma patients

Sepsis and multiple system organ failure (MSOF) are major causes of morbidity and mortality in trauma patients. Bacterial translocation induced by hypotension, endotoxemia, or burns is a reproducible phenomenon in the laboratory. The incidence of bacterial translocation to mesenteric lymph nodes (MLNs) in 29 critically ill patients was evaluated to determine its relationship to subsequent sepsis and MSOF. Bacterial translocation was documented in 3 of 4 patients who underwent laparotomy for gastrointestinal (GI) disease. No trauma patient (25 patients), even at second exploration 3-5 days after injury, had a positive MLN culture. Five patients died; 4 trauma patients, one with GI disease. Forty percent of the trauma patients had major complications, predominantly pulmonary infections with gram-negative bacteria. However, infectious complications and outcome were not related to MLN culture results. The classical progression of bacteria from the gut to the bloodstream via the MLNs may require time and gut mucosal injury. The data suggest that bacterial translocation to the MLNs is not a common occurrence in acutely injured trauma patients.     

Endotoxin-induced bacterial translocation: a study of mechanisms

Previously, we documented that nonlethal doses of endotoxin cause the translocation (escape) of bacteria from the gut to systemic organs. The purpose of this study was to determine which portion(s) of the endotoxin molecule induces bacterial translocation and to examine the role of xanthine oxidase activity in the pathogenesis of endotoxin-induced bacterial translocation. Nonlethal doses of Salmonella endotoxin preparations (wild type, Ra, or Rb), containing the terminal portion of the core polysaccharide, induced bacterial translocation, whereas those preparations lacking the terminal-3 sugars (Rc, Rd, Re, or lipid A) did not induce bacterial translocation. Additionally, only those endotoxin preparations that induced bacterial translocation injured the gut mucosa, increased ileal xanthine dehydrogenase and oxidase activity, and disrupted the normal ecology of the gut flora, resulting in overgrowth with enteric bacilli. Inhibition of xanthine oxidase activity by allopurinol prevented endotoxin (Ra)-induced mucosal injury and reduced the incidence of bacterial translocation from 83% to 30% (p less than 0.01). These results suggest that endotoxin-induced bacterial translocation requires the presence of the terminal core lipopolysaccharide moiety and that xanthine oxidase-generated oxidants are important in the pathogenesis of endotoxin-induced mucosal injury and bacterial translocation.     

Experimental study of the effects of splenectomy and partial splenectomy on bacterial translocation.

BACKGROUND: The aim of this study is to evaluate the effect of splenectomy and partial splenectomy in a burn-induced bacterial translocation model and to study Kupffer cell (KC) morphology and number. METHODS: Mice were divided into sham-burn and burn groups. Each group was also subdivided to sham-splenectomy, partial-splenectomy, and splenectomy subgroups. At day 0, operations were performed. At the postoperative 10th day, a sham burn or burn injury was made in all animals. Twenty-four hours later, cultures for bacterial translocation were obtained and livers were evaluated for the quantity and morphology of KCs. RESULTS: Burned-splenectomized animals had significantly decreased bacterial translocation when compared with sham-splenectomized animals (p = 0.031). Interestingly, in both the sham-burned and burned groups, splenectomy subgroups had significantly higher numbers of KCs compared with partial-splenectomy and sham-splenectomy subgroups (p<0.00000). Burn injury caused a significant decrease of KC numbers in all subgroups compared with their correspondent sham-burned subgroups (p<0.05). CONCLUSION: Results revealed that splenectomy decreases bacterial translocation and also increases the number of KCs.     

Promotion by burn stress of the translocation of bacteria from the gastrointestinal tracts of mice

A mouse burn model was established to test the effect of nonlethal thermal injury on the translocation of indigenous bacteria from the gastrointestinal (GI) tract to other organs. Specific pathogen-free (SPF) mice were given 15% or 30% total body surface area burns, and the mesenteric lymph nodes (MLNs), spleens, livers, blood, and peritoneal cavities were cultured for translocated bacteria at various time intervals. No viable aerobic, facultatively anaerobic, or strictly anaerobic bacteria of the indigenous flora grew in cultures from the MLNs of these mice. Consequently, SPF mice were antibiotic decontaminated and then colonized with Escherichia coli to develop a model in which E coli maintains abnormally high cecal population levels and translocates continuously to the MLN. These mice received 15% or 30% thermal burns four days after colonization with E coli. The incidence of bacterial translocation and the numbers of E coli translocating to the MLN, spleen, liver, blood, and peritoneal cavity increased with increasing burn area compared with controls. Mice receiving 15% burns could not clear intravenously challenged E coli from their bloodstream, MLN, or liver. Thus, burn stress promotes the translocation of bacteria from the GI tract to other organs to cause bacteremia.     

Intestinal bacterial translocation in experimentally burned mice with wounds colonized by Pseudomonas aeruginosa.

Translocation of micro-organisms from the gastrointestinal tract may play a role in the pathogenesis of septic complications in severely burned patients. We therefore investigated the influence of burn wound infection with Pseudomonas aeruginosa on translocation in experimentally burned mice. The P. aeruginosa disseminated in 15% of the animals on the second day and in 20% of the animals on the third day postburn in the Pseudomonas-seeded group. Wound colonization with P. aeruginosa, compared with a control group, led to an increased incidence of translocation of Escherichia coli from the GI tract to the spleen (p < 0.005), liver (p < 0.03), lungs (p < 0.005), and peritoneal cavity (p < 0.03) on the second day postburn but not on the third day postburn. On both the second and third days, the number of viable E. coli in the organs in the Pseudomonas-seeded group exceeded that in the organs in the control group. In this model translocation of E. coli from the GI tract played a more important role than did hematogeneous dissemination of P. aeruginosa from the burn wound.     

The effect of major thermal injury and carbohydrate-free intake on serum triglycerides, insulin, and 3-methylhistidine excretion.

The severely burned patient responds differently to starvation ketosis in the early stage of injury as compared to the normal individual. A similar response has been observed in the patient after skeletal trauma and sepsis. In order to determine the extent of muscle protein contribution and the mechanism(s) involved, 11 burn patients with 35% to 80% BSA burn were resuscitated using carbohydrate-free solutions for 3 days followed by unrestricted intake. Blood was drawn daily and 24-hour urinary nitrogens were determined. Controls consisted of 10 preoperative elective surgical patients and two normal volunteers. The burned patients lost a mean +/- SEM of 17.1 +/- 1.72 g nitrogen per day on the third day. The mean +/- SEM ketone body response on the third day for burned patients was 385 +/- 77 mumol/l compared to 727 +/- 81 mumol/l for control patients. The mean +/- SEM 3-methylhistidine loss for burned patients on the third day was 9.83 +/- 0.82 mumol/kg compared to 3.6 mol/kg for control patients. Insulin levels on the third day of fast were three times the normal group. This insulin increase may be the modulating factor that suppresses excessive fat mobilization. This metabolic response causes a lower plasma ketone level, which may then necessitate the need for continued protein catabolism for glucose production for certain tissues. The protein contribution to the hypercatabolic response as assessed by increased urinary nitrogen losses is in part supported by an increased muscle protein breakdown as indicated by increased 3-methylhistidine excretion.     

Gut barrier function and the surgeon

There is accumulating evidence that multiple organ failure is not always the result of an established septic focus. Increasing attention has centred on the gut as a reservoir of bacteria (and bacterial endotoxins) that can traverse the intestinal mucosal barrier (a process called 'bacterial translocation') and initiate the septic state. Although the link between haemorrhagic shock and sepsis was recognized decades ago, the full experimental demonstration of this phenomenon is more recent. It was shown to occur in three main settings: physical disruption of the gut mucosa, impaired defence mechanisms and altered gut microbial ecology. Conditions such as haemorrhagic shock, burns, protein malnutrition and sepsis are seen in the severely ill surgical patient or the multiply injured, and are known to cause various combinations of circumstances favourable to bacterial translocation and endotoxin absorption. These may play an important role in the mortality of the critically ill.