Central venous catheters for parenteral nutrition: A double-edged sword

STEPHEN L. GANS VISITING GUEST LECTURE

Central

Venous Catheters for Parenteral A Double-Edged Sword

Nutrition:

By David A. Lloyd Liverpool, England

I

AM DEEPLY conscious of the great honor you have accorded me in inviting me to deliver the Stephen L. Gans Distinguished Visiting Guest Lecture, and I thank you most sincerely for this. I am humbled when I look at the list of illustrious Pediatric Surgeons who have preceded me, including two of my mentors, Jannie Louw and Sid Cywes from Capetown, South Africa. This Overseas Lecture has taken place for a number of years, but became the Stephen Gans eponymous lecture only last year in recognition of a man who did so much for pediatric surgery. I did not meet Steve until after I moved to Pittsburgh, but of course his name was already familiar to me, as it was to pediatric surgeons the world over, wherever the Journal of Pediatric Sztrgery is read. Although I did not know him well, I was always impressed that he knew who I was and had time to exchange a few words. With this lecture, all of us here today salute the memory of Stephen L. Cans. The ability to feed a patient intravenously has been one of the most significant developments in the past 25 years. In neonatal surgery this has been a key factor accounting for the decreased mortality for conditions associated with prolonged postoperative intestinal dysmotility such as gastroschisis and duodenal atresia. From the early days of total parenteral nutrition (TPN), when the solution was administered through delicate peripheral veins, parenteral nutrition has developed to the point where a sterile process accurately provides a customized solution that is delivered to the patient through a long-term in-dwelling catheter. It is now so much a part of pediatric care that often it is taken for granted, and the potential risks of the TPN solution and the catheter may be overlooked. Nothing comes without a price. The disadvantages of TPN include the metabolic complications associated with delivering high concentrations of carbohydrate, fat, and protein directly into the systemic circulation, bypassing the natural route through the intestine to the liver, where the most serious damage occurs. In addition, there is the need to deliver TPN solutions through a centrally positioned venous catheter. These catheters are the focus of this paper. INTRAVENOUS

ACCESS

In the early days of TPN the solutions were delivered peripherally. Access was obtained with steel butterfly Journal

of Pediatric

Surgery,

Vol32,

No 7 (July),

1997: pp 943-948

needles and later by plastic cannulae. Despite frequent rotation of access sites, phlebothrombosis and thrombophlebitis were frequent problems, and the life-span of a peripheral line was measured in days and sometimes in hours. This resulted in numerous needlesticks for the infant and many hours of frustration for interns striving to regain access before the infant became hypoglycemic. The concept of cannulating the internal jugular vein was not new to pediatric surgeons accustomed to inserting ventriculoatrial catheters for hydrocephalus, and this route was adopted for providing TPN. The advent of the Broviac catheter in 1973 was a major advance, not only in providing long-term access but also enabling even more concentrated solutions to be delivered and thus the ability to meet the full nutritional needs of the patient.’ In the last several years, the peripheral long line has increased in popularity enabling central access to be achieved for as long as 3 weeks through a line inserted peripherally. The complications of central venous catheters are mechanical problems (displacement, occlusion, fracture) and infection. Potentially the most serious of these is catheterrelated infection, which may require removal of the catheter. Catheter Material When I first used a central line the only catheters of suitable size were polyethylene feeding tubes, which I inserted by cut-down into the internal jugular vein and brought out directly through a short tunnel in the neck. The anterior chest tunnel had not yet been popularized. Not surprisingly, these catheters soon became occluded, infected, or dislodged, but they were all that was available at the time. Today, silicone elastomer is the most widely used material for central venous catheters, being relatively inert and strong, yet flexible. Claims for other materials have been made, notably polyurethane. but none has yet replaced silicone. In a study we carried out in rats with Presented at the 1996 Annual Meeting of the Section on Surgery oj the Amencan Academy of Pediatrics. Boston, Massachusetts, October 26-30, 1996. Address reprint requests to Professor D.A. Lloyd, Institute of Child Health, Alder Hey Children’s Hospital, Liverpool L12 2AE: England. Copyright o 1997 by WB. Saunders Company 0022.3468/97/3207-0001$03.00/0 943

944

DAVID A. LLOYD

nonperfused central venous catheters, we found a significantly higher rate of infection in polyurethane catheters compared with silicone catheters (Table 1). THE FIBRINOUS

SHEATH

Much attention has been paid to the so-called fibrinous sheath that forms ‘around the intravenous part of the catheter and its relationship with catheter-related sepsis. The layer of fibrin, albumin, ‘and platelets that coats all catheters after insertion is a natural phenomenon that occurs on all intravascular implants, presumably an effort by the body to isolate these foreign materials. The fibrinous coating is initially thin and fragile, but with time becomes more substantial, and radiological studies in rabbits have shown the intact sheath in the vein after removal of the catheter. The fibrinous sheath is thought to contribute to catheter infection by providing a surface onto which bacteria could adhere, and it was further speculated that this nidus for ongoing infection could only be eliminated by lysing the fibrinous sheath or removing the catheter. This led to attempts to prevent sheath formation on the catheter by using heparin-bonded catheters, but these had no proven beneficial effect on catheter-related sepsis. To test the hypothesis that the fibrin sheath promoted catheter infection, we undertook a study that was reported to the American Pediatric Surgical Association in 1991.’ For this study we used a rat model in which a segment of silicone catheter was inserted into the interior jugular vein, positioning the tip in the superior vena cava/right atrium. The external end of the catheter was tied off and buried under the skin. A strain of Staphylococcus aureus isolated from a clinical catheter infection was injected through the tail vein to induce bacteremia. There were two groups of rats. In the first group, the bacteria were injected immediately after inserting the catheter, and in the second group, the bacteremia was induced 7 days after the catheter was inserted. We postulated that in the second group, the delayed group, a definite fibrinous sheath would have developed around the catheter, whereas in the first immediate group there would not have been time for this to have occurred before the bacteria were Table 1. Streptococcus

feca/kPositive

Cultures

Blood Culture Group

No. of Cases

24 h

Day 8

Silicone Immediate

12

3

0

Delayed

12

5

0

Polyurethane immediate

12

6

4

Delayed

12

12

5

NOTE. Posltw cultures urethane central venous immediately after catheter

Catheter

Culture

0 1 3 6

in rats with nonperfused sillcone or polycatheter after inoculation with S faecalis Insertion or after a delay of 7 days.

injected. This was confirmed by electron microscopic examination of the catheters. Contrary to our expectations, we found that in the delayed group there was no significant difference in the number of positive blood cultures, but there was a significant reduction in the number of positive catheter cultures compared with the immediate group. The number of animals with both catheter culture and blood culture positive was also less in the delayed group. We concluded from these findings that the fibrinous sheath did not promote infection and indeed appeared to have a protective effect, which we speculated was by preventing bacteria from adhering to the catheter. For that study we used a strain of S aureus. A better choice would have been a coagulase-negative Staphylococczts, but it is extremely difficult to induce infection with this organism in the rat. Recently we have repeated the study using a species of Streptococcus fecalis. This time we found no significant difference in the incidence of infected catheters between the immediate group (no fibrinous sheath) and the delayed group (fibrinous sheath present, Table 1). Our suggestion that the fibrin sheath may have a protective role therefore was not confirmed, but from the findings of both these studies it seems that the presence of the fibrin sheath does not appear to promote infection. In this study we also compared silicone and polyurethane catheters. In each of the immediate and delayed groups, half the rats received polyurethane and half received silicone catheters and we found that there were significantly more positive cultures among the polyurethane catheters. Within the lumen of the catheter the situation is different. Here, there is interaction between the hyperosmolar TPN solution and blood that has refluxed into the catheter, leading to clot formation and possibly calcium deposition. In turn this leads to occlusion of the catheter lumen and the development of vegetative thrombi at the catheter opening. There are also important changes in the cannulated vein. In our rat studies we found severe damage to the endothelium of the superior vena cava adjacent to the catheter tip. These damaged areas predispose to thrombus formation and superior vena cava occlusion (Fig 1). I speculate that the pathological thrombus in the catheter lumen and in the veins is more likely to predispose to catheter-related infection than the fibrinous sheath. Indirect evidence for this is the fact that for resistant or recurrent catheter infection, antibiotics may be more effective if given in combination with a fibrinolytic agent such as streptokinase or urokinase.3 SOURCES

OF INFECTION

Exogenous Infections During the early TPN era, in the 1970s and early 1980s. catheter infection sometimes was attributed to

CENTRAL

VENOUS

CATHETER

945

INFECTION

Fig 1. Thrombus formation in central venous catheters showing the external fibrinous sheath (F), intra-luminal thrombus (IT) and vein wall damage with thrombus formation (V).

contamination of the administration system from an external source. The pharmacy solution itself was a potential source of infection, particularly when solutions were prepared on the ward. When I began to use TPN in Durban, South Africa, the amino-acid solution and a 50% dextrose solution were supplied in separate containers by the Pharmacy and were mixed by me every day on the ward. A multivitamin preparation, trace elements and minerals also had to be added. The lipid suspension entered the line via a Y connection near the patient, as is still commonly practiced. In spite of our best efforts with antiseptic technique, there was a high risk of contamination, and infection was common. Now with the preparation of TPN solutions in centralized sterile pharmacy units this danger has almost been eliminated. Other potential portals for external infection were the connection sites in the system, particularly points where the line had to be disconnected to replace comp,onents such as the burette or for injecting medications. The exit site of the catheter was also recognized to be an important portal for infection, which was thought to spread subcutaneously along the outside of the catheter to reach the vein. The bacteria commonly responsible for catheter infection via these external routes were S uzuvus and Stuphylococcus epidermidis, both common surface commensals. The incidence of these external infections has been greatly reduced, and in some units virtually eradicated, by developing practice guidelines for aseptic care. The introduction of the TPN nurse, with responsibility for training and supervising nursing staff and other caretakers and for monitoring the quality of care, has also had a major impact on catheter-related infection. Audits of clinical practice have led to positive changes, such as reducing the frequency with which the intravenous administration line is broken, and in the way the TPN solution is packaged. In our unit in Liverpool, the TPN solution for neonates is supplied in a syringe, which is

simply connected to the central line and controlled by a syringe pump. Two technical innovations had an important effect on catheter infection. The first was the introduction of the subcutaneous tunnel to increase the distance between the exit site on the skin and the site of entry into the vein.4 The rationale for this was twofold; to help stabilize the catheter and prevent it from becoming dislodged and to place any exit site infection as far away as possible from the vein. Dislodgement of the fine silicone catheters in use at the time remained a major problem, and the second innovation was the Teflon cuff. By becoming densely adherent to the subcutaneous tissues, the cuff was postulated to act as a barrier to infection from the exit site spreading along the catheter toward the vein. The cuff does appear to have a role in preventing infection, not by acting as a barrier, but by stabilizing and fixing the catheter in the subcutaneous tunnel and preventing it from moving in and out at the exit site. Endogenous Infections A central venous catheter may become infected as a result of continuous or intermittent bacteraemia from a distant focus of infection, such as an abscess. In general it is advised that catheters should not be inserted in the presence of systemic infection because of the theoretical risk that it would immediately become infected, but this has not been confirmed. Our work in the rat model, in which bacteremia was induced within minutes of inserting the catheter, suggests that the risk of catheter infection is not increased, However, it seems sensible to use peripheral access until the bacteraemia has cleared. There is increasing recognition of the importance of the gut as an internal source of infection. Translocation of enteric organisms into the mesenteric lymphatics and hence into the systemic circulation is a well-established event.5 This may occur in two different situations, The first situation is one in which there is an abnormality of the gut mucosa as a result of infection, ischemia, or trauma, which are associated with destruction of the gut mucosal integrity, allowing movement of bacteria from the lumen through the wall of the bowel into the circulation, either directly or via the mesenteric lymphatics. Necrotizing enterocolitis is an example of this situation. The second situation, and the one in which we are particularly interested, is where there is no disease of the gut and the mucosa is essentially “intact,” but the gut mucosal barrier is impaired. This leads to true translocalion of viable enteric organisms. The mechanisms by which this occurs include movement through the enterocytes by pinocytosis and passage between enterocytes. The phenomenon of translocation is well established, and its role in systemic infection has lead to the concept of selective decontamination of the digestive tract (SDD) to

946

prevent the translocation of potentially pathogenic organisms by selectively eliminating them using specific enteral antibiotics.5 My first encounter with bacterial translocation occurred when I was in Pittsburgh and was involved with the care of the second child to undergo a multi-visceral transplant by Dr Starzl. One of the features of her posttransplant course was repeated episodes of catheterrelated infection caused by streptococci, which was concurrently cultured from enteral swabs in high concentrations (>105 cfu). This impressed on me the value of regular surveillance cultures from the throat, rectum, and stomas. The risk of bacterial translocation occurring in immunocompromised patients is now well recognized, and SDD is an integral part of the care of these patients during their most vulnerable periods. The factors predisposing to bacterial translocation include enteric bacterial overgrowth resulting in high concentrations of potentially pathogenic bacteria, and impairment of the gut mucosal barrier. In the surgical patient, bacterial overgrowth may result from the use of systemic or enteral antibiotics, or as a result of intestinal stasis caused by a mechanical obstruction or postoperative intestinal dysmotility. The gut mucosal integrity is impaired because the patients are starved of enteral nutrition and are receiving TPN that is deficient in specific enteral nutrients, notably glutamine. Infants with a major gastrointestinal disorder such as gastroschisis are a potential model for catheter-related sepsis because they have all the conditions predisposing to translocation of enteric bacteria, notably long-term TPN which lacks essential substrates, and intestinal dysfunction and stasis leading to bacterial overgrowth. Tramlocation and Catheter Infection We undertook a study in newborn infants to explore the relationship between septicaemia caused by bacterial translocation and catheter-related infection6 We studied all patients admitted to our Neonatal Surgical Unit over 2 years who had gastrointestinal abnormalities and received parenteral nutrition. Surveillance cultures of the oropharynx and gut were obtained at the start of parenteral nutrition and twice weekly thereafter. When a catheter infection was suspected clinically, blood was taken for culture from both the central venous catheter and from a peripheral vein where possible. We diagnosed bacterial translocation when the organism isolated from blood cultures had also been identified in the throat or rectum within the 2 weeks preceding the episode of septicemia. Of the 94 infants in the study, 24 episodes of septicemia developed in 10 patients (11%). Six of these ten infants had 15 episodes of infection caused by enteric organisms normally encountered in the intestine, namely Escherichia coli, Klebsiella, Candida, and enterococci. The other four infants had infection caused by coagulase-

DAVID

A. LLOYD

negative staphylococci (CNS). The enteric organisms causing the septicemia were always present in the throat or rectum, and in 60% they were present in high concentrations (>105 cfu). The episodes of infection occurred after patients had been on parenteral nutrition for a median of 58 days (range 32 to 286 days). These observations strongly suggested that in infants on longterm parenteral nutrition septicemia was related to translocation of enteric organisms. It is of interest that all but one episode of septicemia occurred in infants who had elevated serum bilirubin levels (defined as >30 mmol/L). At this time, our surveillance cultures were not routinely processed for semiquantitative cultures for coagulase-negative staphylococci, and therefore we were not in a position to evaluate translocation of this organism. We are now performing routine quantitative cultures for CNS and recently reported these findings.7 Nine newborn infants on TPN had ten episodes of septicemia caused by CNS, which was also present in the surveillance cultures. None of the patients had evidence of infection at the entry site or in the infusion system. We concluded that the catheter infections caused by CNS were the result of translocation from the gut. In one infant the blood culture grew S aureus, which was not present in the surveillance cultures, and therefore was considered to be of exogenous origin. The enteric organisms that translocated were normal gut flora. In our study population of 94 surgical neonates, 44% had abnormal gut flora identified on the surveillance cultures. There were 24 episodes of catheter infection caused by translocation, 23 of which were in neonates with abnormal gut flora (Table 2). It is of particular interest that, although the abnormal flora were present in high concentrations, it was only the normal flora that translocated. The abnormal flora were assumed to be present as a result of prolonged intestinal dysmotility and antibiotic use, and we do not know the reason they did not translocate. The clinical significance of this finding is that the presence of abnormal gut flora on routine surveillance cultures identifies patients who are at risk of translocating normal gut flora. We demonstrated a correlation between the bacteria cultured from the central venous catheters and bacteria in the gut in surgical newborn infants who had been on TPN longer than 3 weeks, from which we conclude that in this specific population, catheter sepsis usually is caused by translocation of endogenous bacteria. We also were able Table 2. Septicemia

in Infants

Abnormal Flora (rl = 41)

Patients Episodes TPN davsieolsode NOTE. septicemia

The Impact in newborn

on TPN Normal Flora (n = 53)

9 (22%) 23

1(2%)

111.5

617.0

1

of abnormal carriage on infants raceivlng long-term

PVdlJe

,005 ,001 ,001

the occurrence TPN.

of

CENTRAL

VENOUS

CATHETER

INFECTION

to identify patients at risk of bacterial translocation. The value of routine surveillance cultures therefore is to identify patients with abnormal gut flora who are at high risk of bacterial translocation, and secondly, to indicate the likely cause of the catheter infection and guide initial antibiotic therapy. PREVENTION AND MANAGEMENT OF BACTERIAL TRANSLOCATION

If, as our evidence suggests, translocation is the mechanism for catheter-related infection in surgical infants receiving long-term TPN, the following prophylactic and therapeutic options are available. Gut Motility Infants on prolonged TPN with recurrent catheter sepsis should be investigated for evidence of gut dysmotility. Contrast gastrointestinal radiographs may demonstrate evidence of partial mechanical obstruction, such as a persistently dilated dysfunctional loop of bowel secondary to an inflammatory stricture or a localized ischemic injury, in which case resection may resolve the problem. Bacterial Overgrowth If surveillance cultures from infants with recurrent episodes of catheter infection identify overgrowth of bacteria (normal or abnormal flora), selective decontamination of the gut with enteral antibiotics should be considered. The recommended antibiotics are colistin, tobramycin and amphotericin by mouth or by nasogastric tube and as a gel applied to the oral cavity. When coagulase-negative Staphylococcus is present, vancomytin should be added to the antibiotic regimen. Mucosal Integrity Much research has been directed toward understanding the factors responsible for maintaining gut mucosal integrity. Work performed on rats has clearly demonstrated gut atrophy in animals receiving TPN, either enterally or intravenously, and similar changes occur in humans. Substrates that play a major role in promoting mucosal growth and reversing mucosal atrophy include glutamine, short chain fatty acids (SCFA), arginine, purines, pyramidines, and w(omega)-fatty acids8 In 1993 we reported on an infant with persistent malabsorption requiring long-term TPN after operations for gastroschisis and necrotizing enterocolitis, including intestinal resection.1° Endoscopic suction biopsy of the small intestine showed an inflammatory response and moderate mucosal atrophy. After intravenous glutamine for 35 days, the inflammatory changes had resolved and the mucosal atrophy was less prominent with a marked increase in the villus-crypt ratio and partial recovery of mucosal disaccharidases. The infant’s nutritional status

947

improved, although the intestinal transit time remained rapid, and stool volume was unchanged. There is clear experimental evidence that TPN is associated with bacterial translocation to the mesenteric lymph nodes and that this can be prevented or reduced by providing substrates such as glutamine, but there have been no studies on the effect of this on catheter-related infection.8 We therefore studied bacterial translocation and catheter infection in rats receiving TPN alone or supplemented with glutamine, SCFA, or epidermal growth factor (EGF). Glutamine is the preferred energy source for the intestine and in the enterocyte is metabolized to yield 30 mol of adenosine triphosphate (ATP) per mol of glutamine, compared with 2 mol of ATP per mol of carbohydrate.8 SCFA are also an important energy source for both the large and small intestine, and EGF has a trophic effect on the intestinal mucosa. In this rat model, a silicone catheter was inserted via the right internal jugular vein into the superior vena cava and tunnelled around the neck to exit on the back. The catheter was passed through a protective tether and swivel and connected to the infusion syringe. After a 3-day recovery period, during which access to chow was allowed, TPN was started and the chow withdrawn. After 7 days of TPN the animals were killed and tissues were harvested for microbiological and histological studies. A longer period of TPN was not possible because of the high rate of catheter-related complications after 7 days, in particular catheter displacement and catheter occlusion. In rats receiving TPN only, histological examination of the intestine confirmed that gut mucosal atrophy was present by 7 days, and cultures of the mesenteric nodes confirmed that translocation of enteric bacteria had occurred in 80% of animals. We then studied the effects of adding the specific trophic substrates to the TPN solution. Mucosal atrophy was reduced by glutamine and SCFA, and EGF-promoted mucosal growth. The microbiological studies showed that all three substances decreased bacterial translocation to the mesenteric nodes and the number of positive blood cultures, compared with the TPN-only group, but the difference was not significant for SCFA (Fig 2). There were no infected catheters in the glutamine supplemented group and only one each in the SCFA and EGF groups. Supplementation of the TPN

Mucosal

atrophy

Translocation Catheter

infection

EGF

GLU

SCFA

c

1

4

ns

1

4

4

1

Fig 2. The effects of intravenous glutamine fatty acids (SCFA), and epidermal growth factor ing TPN.

14

(GLU), short chain (EGF) in rats receiv-

DAVID

948

with glutamine, SCFA, or EGF reduced the incidence of infected catheters, although translocation was not always prevented. While we were developing this model, we administered by gavage a specific antibiotic resistant strain of E coli to demonstrate that the bacteria cultured from the mesenteric nodes had originated in the gut. We found that in rats on TPN, only the indigenous E coli translocated and not the specific antibiotic resistant strain that had been gavaged. We have no explanation for this. In our final model, we did not use gavaged bacteria and studied translocation of the resident flora only. SUMMARY

OF THERAPEUTIC

OPTIONS

The therapeutic strategies for treating infants on longterm TPN who are unable to tolerate enteral feeds and who have had or are at risk of experiencing catheterrelated infection include (1) correcting intestinal stasis and associated bacterial overgrowth by identifying and treating intestinal abnormalities amenable to operation, (2) reducing bacterial overgrowth of potentially pathological organisms and eliminating abnormal intestinal flora using SDD, (3) providing intravenously nutritional substrates and growth factors to promote mucosal growth, maintain mucosal integrity, and prevent or reduce translocation, (4) treating established catheter sepsis with systemic antibiotics, with or without urokinase, and (5) removing the catheter.

A. LLOYD

bilirubin levels with episodes of catheter-related septicemia in individual infants, and found that almost every infective episode was associated with a rise in the serum bilirubin level.6 Although the bilirubin level subsequently fell, it did not return to the presepticemia level. There is evidence in rats and humans of impaired mucosal integrity and increased translocation in the presence of obstructive jaundice, which is reversed when bile flow is restored.‘O With long-term TPN, therefore, there may be a spiral of cholestasis, reduced bile flow into the intestine, impaired mucosal integrity, translocation, septicemia, and further damage to the liver, The premature infant with neonatal necrotizing enterocolitis is an excellent model for cholestasis because all major risk factors are present, namely immaturity of the immune system, sepsis, longterm TPN, and absence of enteral feeding. CONCLUSION

The central venous catheter is a double-edged sword. On the one hand, it is a vital route for delivering TPN, a life-saving measure for many newborn infants deprived of enteral feeding. However, it has potentially lifethreatening complications, of which infection is the foremost. Catheter-related infection is considerably more complex than was thought 20 years ago when the problem was attributed to contamination of the hub.” We are now in a position to define therapeutic strategies that require scientific evaluation.

CHOLESTASIS

ACKNOWLEDGMENT

I would like to discuss a possible link between catheter sepsis and TPN-related cholestasis. In our study of translocation and catheter infection, we correlated serum

The authors acknowledges the important contributions made by Agostino Pierro. Rick van Saene, Fiona McAndrew, and Ragu Shanbhogue.

REFERENCES 1. Broviac JW. Cole JJ. Scribner BH: A silicone rubber atria1 catheter for prolonged parenteral alimentation. Surg Gynecol Obstet 136:602606,1973 2. Lloyd DA, Shanbogue LKR, Doherty PJ. et al: Does the fibrin coat around a central venous catheter influence catheter related sepsis? J Pediatr Surg 28:345-349, 1993 3. Jones GR, Konsler GK, Dunaway RP. et al: Prospective analysis of Urokinase in the treatment of catheter sepsis in pediatric hematologyoncology patients. J Pediatr Surg 28:350-357, 1993 4. Keohane PP. Attrill H, Northover J. et al: Effect of catheter tunnellmg and a nutrition nurse on catheter sepsis during parenteral nutrition. Lancet 11:1388-1390, 1983 5. Smith SD. Simmons RL: Gut flora m health and disease, in Najanan J, Delaney J (eds): Progress in Trauma and Critical Care. St Louis, MO. Mosby-Yearbook. 1996, pp 347-354 6. Pierro A, Van Saene HKF, Donnell SC, et al: Microbial transloca-

tion in neonates and infants receiving long-term parenteral nutrition. Arch Surg 131:176-179. 1996 7. Modi N, Catahan N, van Saene HKF, et al: Coagulase-negative staphylococcal translocation in neonates and infants receiving long term parenteral nutrition. J Parenter Enter Nutr (in press) 8. Fischer JE: Nutritional support of the intensive care unit patient. in Najarian J, Delaney J (eds): Progress in Trauma and Critical Care, St Louis. MO. Mosby-Year Book, 1996, pp 355-370 9. Allen SJ. Pierro A, Cope L, et al: Glutamine supplemented parenteral nutrition m a child with short bowel syndrome. J Pediatr Gastroenterol Nutr 17:329-332, 1993 10. Parks RW, Clements EDB. Smye MG, et al: Intestinal barrier dysfunction in clinical and experimental obstructive jaundice and its reversal by internal drainage. Br J Surg 83:1345-1340, 1996 11. Sitges-Serra A, Linares J. Garau J: Catheter sepsis: The clue is the hub. Surgery 97:355-357, 1985