Bacterial translocation and the role of postoperative selective bowel decontamination in small intestinal transplantation.
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Animals↗
Biomedical subjects
M I Rowe
Publications and source records attributed to M I Rowe.
Effect of secretory IgA on transepithelial passage of bacteria across the intact ileum in vitro.
BACKGROUND: Bacterial translocation is a process believed to result in nosocomial infections. Secretory IgA (sIgA) may have a role in the prevention of translocation by its ability to bind and aggregate bacteria, a function termed "immune exclusion." The present study was done to determine the effect of specific binding of sIgA to bacteria on the movement of these organisms across the intact epithelial membrane. STUDY DESIGN: Bacterial translocation across intact intestinal segments of rats were assessed in vitro using the Ussing model. Secretory IgA (0.25 mg per mL) from pooled human colostrum was added to the perfused segments of ileum in the Ussing system. Subsequently, the membranes were exposed to 5 x 10(9) cfu per mL Escherichia coli on their mucosal side. A second experiment tested the effect of human IgG when perfused with E. coli using the same preparation. All experiments had paired matched rats in a control group without immunoglobulin. The ability of sIgA and IgG to bind to E. coli was studied by an in vitro assay, as well as by transmission electron microscopy and immunofluorescence of random IgA/E. coli experiments. Measurements obtained in all experimental and control groups were the incidence and amount of bacterial passage and the potential difference generated by the intestinal segments (an index of viability). RESULTS: There were no differences in potential difference between control and experimental groups in either of the two experiments. Secretory IgA bound E. coli and completely prevented passage of E. coli as compared with rats in the control group. IgG bound E. coli; however, the incidence of passage was equal to that of rats in the control group. However, the presence of IgG resulted in a significantly reduced number of bacteria that passed when compared with controls (p < 0.05). Electron microscopic studies revealed intact surface morphology and immunofluorescence revealed aggregates of IgA and E. coli on the mucosal, but not submucosal, surface of the ileal membranes. CONCLUSIONS: This study provides direct evidence of immune exclusion by sIgA. When bound to bacteria, it prevents passage across a morphologically intact segment of viable intestinal tissue.
Animals↗
Role of intestinal mucus in transepithelial passage of bacteria across the intact ileum in vitro.
BACKGROUND: Although gastrointestinal mucus is one of a number of putative host defense mechanisms that protect the gut barrier against microbial translocation, little experimental data are available to show its role in this process. The present study sought to determine the role of mucus depletion on the transepithelial passage of bacteria across viable segments of rat ileum mounted in Ussing chambers in vitro. METHODS: Intestinal mucus was depleted in 12 rats after injection with pilocarpine (160 mg/kg intraperitoneally) 45 minutes before intestinal harvest. The mucosal surfaces of the perfused gut segments mounted in the Ussing chamber were exposed to 5 x 10(9) CFU/ml Escherichia coli C-25. Viability was monitored by continuous measurements of the potential difference generated by the membranes. The electrical characteristics were unaltered by pilocarpine pretreatment or exposure to bacteria. RESULTS: Bacterial passage occurred in 100% of pilocarpine membranes as compared with 33.3% in controls (p < 0.05). Pilocarpine-treated membranes resulted in 19.9 +/- 7.5 mg of retrievable mucus as compared with 28.8 +/- 7.2 mg in controls (p < 0.05). Light and transmission electron microscopy revealed an intact epithelial surface in all membranes. There was a marked decrease in mucus on the surface of pilocarpine-treated membranes. CONCLUSIONS: Intestinal mucus secretion is a critical factor in the barrier function of the gut, and its depletion results in a dramatic increase in bacterial passage across the intact rat ileum.
Animals↗
Adaptation in short-bowel syndrome: reassessing old limits.
The improving survival of patients with severe short-bowel syndrome along with the advent of successful intestinal transplantation have accentuated the need to answer two questions. (1) Is there an intestinal length below which adaptation to full enteral nutrition can not be expected to occur? (2) How much time is necessary to complete intestinal adaptation? We reviewed the outcome of 21 infants with less than 50 cm of small intestine to answer these questions. Patients were divided into three groups based on intestinal length, regardless of ileocecal valve status: group I, < 10 cm (n = 3); group II, 10 to 30 cm (n = 11); and group III, 30 to 50 cm (n = 7). Data were collected to assess survival, incidence of adaptation, time to adaptation, and causes of mortality. Infants in group I did not achieve intestinal adaptation to full enteral nutrition. One survived and 2 died, one from varicella pneumonia and the other after intestinal transplantation. Eight of the 11 (73%) patients in group II survived and 5 of 8 (63%) survivors achieved full intestinal adaptation after a mean interval of 320 days (range, 148 to 506 days) on parenteral nutrition. Six of the seven patients (86%) in group III survived and all survivors (100%) achieved complete enteral adaptation after an average of 376 days (range, 58 to 727 days). The overall survival was 71% (15/21), but survival in patients with > 10 cm was 78%.(ABSTRACT TRUNCATED AT 250 WORDS)
Catheterization, Central Venous↗
Pathogenesis of pancreatic sepsis.
Although pancreatic sepsis is the most common cause of major morbidity and mortality associated with acute pancreatitis, the pathogenesis of such infections is unknown. Since intraperitoneal foci of inflammation are known to promote bacterial translocation, we hypothesized that acute pancreatitis promotes bacterial translocation that leads to infection of the inflamed pancreas and peripancreatic tissues. Non-lethal acute pancreatitis was induced in rats, and the translocation of live bacteria to the pancreas, mesenteric lymph nodes, liver, and spleen was determined. The presence of orally fed fluorescent beads, sensitive inert markers of translocation, was also determined in the pancreas and mesenteric lymph nodes. Live bacteria were recovered from 33% of the pancreata of rats with acute pancreatitis but from none of the control rats. Beads were visualized in 91% of the pancreata of rats with acute pancreatitis but in none of the pancreata from control rats. Beads were not visualized in the mesenteric lymph nodes of rats with acute pancreatitis, suggesting a transperitoneal route of migration. We conclude that acute pancreatitis promotes bacterial translocation leading to transperitoneal infection of the pancreas. These results support the use of selective decontamination of the gut and peritoneal lavage for the prevention of pancreatic infections in acute pancreatitis.
Animals↗
Renal artery occlusion in pediatric blunt abdominal trauma--decreasing the delay from injury to treatment.
The cases of seven children treated from 1980 through 1991 with blunt renal artery injuries were reviewed to determine (1) if computed tomography alone could eliminate the need for intravenous pyelography (IVP) or arteriography (ART); and (2) the causes of management delays. The diagnosis of arterial occlusion was suggested by the lack of renal contrast enhancement in six patients with CT scans and in two patients with IVP. In three patients ART was merely confirmatory. The diagnosis was suggested by IVP or CT scan within a mean of 4.7 hours of injury, but ART added an additional mean 2.3 hours to the diagnostic workup. There was an additional 3.9-hour average delay in the operating room before revascularization. Six patients underwent revascularization. Four had minimal function by postoperative renal scans. Renal artery occlusion is rapidly detected by contrast-enhanced CT scanning without IVP or ART. The time period from diagnosis to revascularization must be expedited to improve renal outcome.
Angiography↗
Selective decontamination in pediatric liver transplants. A randomized prospective study.
Although it has been suggested that selective decontamination of the digestive tract (SDD) decreases postoperative aerobic Gram-negative and fungal infections in orthotopic liver transplantation (OLT), no controlled trials exist in pediatric patients. This prospective, randomized controlled study of 36 pediatric OLT patients examines the effect of short-term SDD on postoperative infection and digestive tract flora. Patients were randomized into two groups. The control group received perioperative parenteral antibiotics only. The SDD group received in addition polymyxin E, tobramycin, and amphotericin B enterally and by oropharyngeal swab postoperatively until oral intake was tolerated (6 +/- 4 days). Indications for operation, preoperative status, age, and intensive care unit and hospital length of stay were no different in SDD (n = 18) and control (n = 18) groups. A total of 14 Gram-negative infections (intraabdominal abscess 7, septicemia 5, pneumonia 1, urinary tract 1) developed in the 36 patients studied. Mortality was not significantly different in the two groups. However, there were significantly fewer patients with Gram-negative infections in the SDD group: 3/18 patients (11%) vs. 11/18 patients (50%) in the control group, P < 0.001. There was also significant reduction in aerobic Gram-negative flora in the stool and pharynx in patients receiving SDD. Gram-positive and anaerobic organisms were unaffected. We conclude that short-term postoperative SDD significantly reduces Gram-negative infections in pediatric OLT patients.
Adolescent↗
Catheter sepsis in short-bowel syndrome.
Catheter sepsis with catheter removal is an important problem in patients with short-bowel syndrome. We determined the incidence of catheter sepsis and the catheter salvage rate in 20 pediatric patients with short-bowel syndrome. To evaluate the intestine as a source and translocation as the pathophysiologic mechanism for catheter sepsis, we identified the sepsis organisms, compared them with the fecal flora, and used mesenteric lymph node cultures to document translocation. The incidence of catheter sepsis was significantly higher in patients with short-bowel syndrome than in patients without short-bowel syndrome (7.8 vs 1.3 per 1000 catheter days). Overall catheter salvage was 42% and was highest in gram-negative sepsis (71%). Enteric organisms were responsible for 62% of cases of catheter sepsis in patients with short-bowel syndrome vs 12% in patients without short-bowel syndrome. Anaerobes were strikingly absent in 25 of 28 stool cultures. The sepsis organism was identified in the fecal flora in 19 of 28 cases. The dominant fecal organism or yeast was the septic organism in 12 of these 19 cases and was isolated in three of four mesenteric lymph node cultures. Our findings support translocation as a mechanism in catheter sepsis in patients with short-bowel syndrome.
Anti-Bacterial Agents↗
Liver transplantation for arteriohepatic dysplasia (Alagille's syndrome).
Thirteen out of 268 children (less than 18 years old) underwent hepatic transplantation (OLT) for end-stage liver disease (ESLD) associated with arteriohepatic dysplasia (AHD). Seven children are alive and well with normal liver function. Six children died, four within 11 days of the operation and the other two at 4 and 10 months after the OLT. Vascular complications with associated septicemia were responsible for the deaths of three children. Two died of heart failure and circulatory collapse, secondary to pulmonary hypertension and congenital heart disease. The remaining patient died of overwhelming sepsis not associated with technical complications. Seven patients had a portoenterostomy or portocholecystostomy early in life; five of these died after the OLT. Severe cardiovascular abnormalities in some of our patients suggest that complete hemodynamic monitoring with invasive studies should be performed in all patients with AHD, especially in cases of documented hypertrophy of the right ventricle. The improved quality of life in our surviving patients confirms the validity of OLT as a treatment of choice in cases of ESLD due to AHD.
Adolescent↗
Unique characteristics of the neonatal intestinal mucosal barrier.
The purpose of this study was to compare the newborn and weanling intestinal mucosa to determine differences in: (1) the electrophysiologic characteristics of the mucosal barrier; (2) the effects of glutamine supplementation on these physiological characteristics; and (3) transmucosal bacterial passage. The Ussing chamber was used to study ileal mucosa from newborn (1 to 4 days old) and weanling (21 days old) piglets. After the seromuscularis was stripped off the bowel wall, the mucosa was mounted in the chamber and perfused with Hanks Balanced Salt Solution (HBSS) or HBSS + 20 mmol/L of glutamine. Following initial stabilization, potential difference (PD) and resistance (R) were measured at 30-minute intervals for 2 hours. Transmucosal bacterial passage was measured by quantitative cultures of the mucosal and serosal reservoirs obtained 2 hours after adding 10(8) E coli C-25 to the mucosal reservoir. Six groups of membranes were studied: (1) newborn and HBSS; (2) weanling and HBSS; (3) newborn and HBSS + glutamine; (4) weanling and HBSS + glutamine; (5) newborn - HBSS + glutamine + E coli; and (6) weanling - HBSS + glutamine + E coli. Newborn ileal mucosa had significantly lower PD and R compared with weanling at all time points. Glutamine led to a significant increase in PD in both newborn and weanling. Newborn mucosa had a significantly increased incidence of transmucosal bacterial passage (4/7) compared with weanling (0/10). These findings suggest that: (1) newborn mucosal barrier has uniquely different electrophysiologic characteristics; (2) glutamine improves the metabolic activity as measured by PD in both newborn and weanling; and (3) the newborn mucosal barrier allows increased transmucosal passage of bacteria.
Animals↗
Mucosal glutamine utilization after small-bowel transplantation: an electrophysiologic study.
A short course of FK 506 after small bowel transplantation averts rejection in the rat and achieves indefinite survival of the recipient whose nutritional status is dependent on the function of the intestinal graft. Ex vivo electrophysiologic studies using the Ussing Cell were conducted to delineate functional competence of the graft by evaluating mucosal ion transport and glutamine utilization. Orthotopic small-bowel transplantation was performed in Lewis (LEW) rats as recipients of either Brown-Norway (BN) allografts or LEW syngeneic grafts. Allograft recipients received FK 506 either as a short course (2 mg/kg on Day 0-4 after transplantation) or continuously (2 mg/kg Day 0-4, then 0.5 mg/kg weekly). Ileal mucosa was harvested from small bowel grafts 9 and 60 days after transplantation and mounted in the Ussing Cell containing Hanks' balanced salt solution with/without L-glutamine (20 mM). Transmembrane potential difference (PD), which represents mucosal active ion transport, and mucosal resistance, an index of membrane integrity, were recorded. Nine days after transplantation, mucosal PD was the same in the ileum from syngeneic grafts, allografts treated with FK 506 and normal LEW and BN rats, and the addition of glutamine increased PD equally in all groups. In comparison, PD was markedly decreased in allografts undergoing rejection, and the glutamine response was blunted. Sixty days after transplantation, mucosal PD was reduced in allografts treated with a short course of FK 506, but normal in allografts receiving continuous immunosuppression with FK 506 and in syngeneic grafts. A decrease of mucosal resistance was not a feature of rejection nor a sequel of limited FK 506 therapy. Our data indicate that allograft rejection results in a significant decrease in mucosal PD and a poor response to glutamine. Control of rejection by FK 506 preserves normal electrophysiologic responses of the allograft mucosa.
Animals↗
The effect of E coli virulence on bacterial translocation and systemic sepsis in the neonatal rabbit model.
In the surgical neonate, three factors that promote bacterial translocation and systemic infection are: (1) intestinal bacterial colonization and overgrowth; (2) compromised host defenses; and (3) disruption of the mucosal epithelial barrier. The newborn rabbit provides an excellent model to study these factors. Like the human, there is early closure of the gut mucosa to macromolecules, and nutrition can be maintained by breast or formula feeding. This study examines translocation and systemic sepsis after colonization with virulent K1 and avirulent K100 strains of Escherichia coli. New Zealand white rabbit pups (2 to 5 days old) were studied. The gastrointestinal tracts of 12 were colonized with K1 E coli; 14 were colonized with K100 E coli; 12 control animals were not inoculated. Mesenteric lymph node (MLN), liver, spleen, and colon homogenate were cultured 72 hours postinoculation. No bacteria were isolated from the colons of all but one control animal. Translocation or systemic sepsis did not occur. Translocation to the MLN was significantly increased (P less than .03) in K1 (50%) and K100 (36%) groups compared with controls (0%). Translocation to liver and spleen (systemic sepsis) was significantly increased (P less than .03) in K1 animals (67%) compared with K100 (0%) or controls (0%). Colonization by both strains of E coli led to translocation to the MLN, but only K1 E coli caused systemic sepsis. This suggests that although colonization by E coli in the newborn leads to translocation to the MLN, progression to systemic sepsis is the result of characteristics of the bacteria and/or neonatal host responses.
Animals↗
Characterization of neonatal multisystem organ failure in the surgical newborn.
With advances in critical care, multisystem organ failure (MSOF) has replaced single organ failure as the major cause of death in adult patients. The purpose of this report is to characterize neonatal MSOF (NMSOF) in the surgical newborn. The records of 84 infants who died during a 5-year period in the surgical neonatal intensive care unit were reviewed. There was sufficient information available in 10 newborns to characterize the NMSOF syndrome. Criteria for renal, hepatic, microvascular, pulmonary, cardiac, and hematologic failure were developed. The sequence of organ failure was determined by calculating the number of days prior to death when these criteria were first noted. Systemic infections were recorded. The sequence of organ failure was as follows: microvascular (edema) 17 +/- 10 days, renal 14 +/- 7 days, hepatic 13 +/- 5 days, hematologic 8 +/- 4 days, pulmonary 5 +/- 2 days, and cardiac 3 +/- 2 days. Adult respiratory distress syndrome (ARDS) was absent. The 10 infants showed both culture-positive sepsis (8) and culture-negative sepsis (2). This is the first report to characterize NMSOF in newborn surgical patients. The earliest findings were edema, followed by renal and hepatic failure. In contrast to adult MSOF, anasarca is a prominent early finding, pulmonary failure develops late, and classic ARDS is absent.
Acute Disease↗
The newborn with hydrops and sacrococcygeal teratoma.
The combination of fetal hydrops and sacrococcygeal teratoma (SCT), is considered to be lethal. We report two such babies who survived. Case 1 exhibited oliguric acute renal failure (ARF) immediately after birth, and severe respiratory insufficiency despite maximal ventilatory support and vasodilator infusions. Tumor resection on the 2nd day of life resulted in an immediate improvement in pulmonary function as reflected by the ratio of arterial to alveolar oxygen. Renal function returned in a pattern typical of recovery from acute tubular necrosis. Case 2, less desperately ill, developed nonoliguric ARF, in part due to deliberate fluid restriction during the 7 days that followed birth and preceded surgery. This resolved following liberalization of fluid intake that occurred at the time of tumor removal on the 7th day of life. The baby also had respiratory insufficiency that improved after surgery. Respiratory insufficiency may be a severe and life-threatening complication of SCT and hydrops fetalis. Pulmonary function may improve dramatically by removal of the tumor. Why this improvement occurs is unclear. Improvement of respiratory function may result from the elimination of excess tumor blood volume with an improvement of the ventilation-perfusion ratio. Alternatively, the tumor may be a source of vasoactive substances or extremely desaturated blood that leads to pulmonary hypertension and right-to-left shunting. Uncertainties in postnatal fluid shifts and exaggerated fluid compartment volumes demand close attention to details of renal function.
Acute Kidney Injury↗
The effects of a hyperosmolar intravenous contrast medium on blood viscosity.
The effects of the hyperosmolar contrast medium, diatrizoate meglumine (Renografin-76) on blood viscosity and other metabolic parameters were measured in 20 immature piglets. Intravenous contrast medium caused a significant (P less than .5) increase in serum osmolality, cardiac output, and urine output, and a decrease in hematocrit. There was a fall in blood viscosity that was not statistically significant. These changes, which are attributed to an acute shift of fluid into the hyperosmolar vascular compartment, were greatest at 3 minutes following injection and subsequently returned towards baseline levels. We conclude that blood viscosity is not increased following intravenous injection of hyperosmolar radiocontrast media.
Animals↗
Serum endorphin levels in injured children.
Plasma beta-endorphin levels (PBEL) are known to be elevated in acutely injured adults, but this has not been studied in pediatric patients with trauma. We measured PBEL in 46 children who sustained blunt injury. The mean acute PBEL was significantly elevated compared with the mean convalescent PBEL (40.5 +/- 29.0 versus 5.4 +/- 2.1 picomoles per liter, p less than 0.05). PBEL were highest in patients with multiple injuries (60.5 +/- 33.2 picomoles per liter, n = 16). PBEL were also elevated with isolated injuries of the head, face or limbs, and even with less severe injuries, namely multiple abrasions. PBEL were low in patients with abdominal (two patients) or spinal (two patients) injuries. Convalescent PBEL were consistently low. Severely injured patients (Injury Severity Score [ISS] of more than ten) had significantly elevated PBEL compared with patients with minor injuries (ISS less than 10), but some children with low ISS had elevated PBEL. The presence of head injury did not influence PBEL and there was no correlation between PBEL and systolic blood pressure. We have demonstrated that the PBEL is elevated in pediatric patients with trauma.
Acute Disease↗
The hidden mortality in surgically treated necrotizing enterocolitis: fungal sepsis.
From 1979 to 1986, 82 infants underwent surgical treatment for necrotizing enterocolitis (NEC), with 36 deaths. The records of 30 of the 36 infants who died were available for review. Fungal colonization and sepsis, the sites of infection, and timing of diagnosis and therapy were determined. Sixteen of 30 (53%) neonates had no evidence of fungus. Six (20%) were colonized with Candida species. Eight (27%) had fungal sepsis, with two of these eight found only at necropsy. Positive fungal blood cultures were a late finding. In only four of the six patients with positive blood cultures were the results known in time to initiate treatment with amphotericin B. Two of these four babies received less than 2 days of amphotericin B treatment prior to death. Fungal sepsis is a significant lethal factor in the surgical mortality of NEC. Vigorous efforts at earlier diagnosis are mandatory.
Enterocolitis, Pseudomembranous↗
Selective bowel decontamination results in gram-positive translocation.
UNLABELLED: Colonization by enteric gram-negative bacteria with subsequent translocation is believed to be a major mechanism for infection in the critically ill patient. Selective bowel decontamination (SBD) has been used to control gram-negative infections by eliminating these potentially pathogenic bacteria while preserving anaerobic and other less pathogenic organisms. Infection with gram-positive organisms and anaerobes in two multivisceral transplant patients during SBD led us to investigate the effect of SBD on gut colonization and translocation. METHODS: Twenty-four rats received enteral polymixin E, tobramycin, amphotericin B, and parenteral cefotaxime for 7 days (PTA + CEF); 23 received parenteral cefotaxime alone (CEF), 19 received the enteral antibiotics alone (PTA), 21 controls received no antibiotics. Cecal homogenates, mesenteric lymph node (MLN), liver, and spleen were cultured. RESULTS: Only 8% of the PTA + CEF group had gram-negative bacteria in cecal culture vs 52% CEF, 84% PTA, and 100% in controls. Log Enterococcal colony counts were higher in the PTA + CEF group (8.0 + 0.9) vs controls (5.4 + 0.4) P less than 0.01. Translocation of Enterococcus to the MLN was significantly increased in the PTA + CEF group (67%) vs controls (0%) P less than 0.01. SBD effectively eliminates gram-negative organisms from the gut in the rat model. Overgrowth and translocation of Enterococcus suggests that infection with gram-positive organisms may be a limitation of SBD.
Animals↗