R. I. C. Wesdorp

Randomised trial of glutamine-enriched enteral nutrition on infectious morbidity in patients with multiple trauma

BACKGROUND Infections are an important cause of morbidity and mortality in patients with multiple trauma. Studies in both animals and human beings have suggested that glutamine-enriched nutrition decreases the number of infections. METHODS Patients with multiple trauma with an expected survival of more than 48 h, and who had an Injury Severity Score of 20 or more, were randomly allocated glutamine supplemented enteral nutrition or a balanced, isonitrogenous, isocaloric enteral-feeding regimen along with usual care. Each patient was assessed every 8 h for infection, the primary endpoint. Data were analysed both per protocol, which included enteral feeding for at least 5 days, and by intention to treat. FINDINGS 72 patients were enrolled and 60 received enteral feeding (29 glutamine-supplemented) for at least 5 days. Five (17%) of 29 patients in the glutamine-supplemented group had pneumonia compared with 14 (45%) of 31 patients in the control group (p<0.02). Bacteraemia occurred in two (7%) patients in glutamine group and 13 (42%) in the control group (p<0.005). One patient in the glutamine group had sepsis compared with eight (26%) patients in the control group (p<0.02). INTERPRETATION There was a low frequency of pneumonia, sepsis, and bacteraemia in patients with multiple trauma who received glutamine-supplemented enteral nutrition. Larger studies are needed to investigate whether glutamine-supplemented enteral nutrition reduces mortality.

Glutamine-Enriched Enteral Diet Increases Renal Arginine Production

BACKGROUND Arginine (Arg) is generated in the kidney by the conversion of circulating citrulline. The most important source for circulating citrulline is the metabolism of glutamine (Gln) by the gut. In this study, we investigated the influence of an enteral diet enriched with Gln on renal Arg synthesis in the rat. METHODS Rats were fed a 12.5% Gln-enriched diet or an isocaloric, isonitrogenous control diet for 14 days. Kidney plasma flow and arterial and renal venous plasma levels of a number of amino acids were measured, and kidney amino acid fluxes were calculated. RESULTS Compared with the control diet, Gln enrichment resulted in significantly higher arterial plasma levels of circulating citrulline (30%, p < .0001) and Arg (31%, p < .0005). The uptake of circulating citrulline and the subsequent production of Arg by the kidneys were significantly higher in the Gln-enriched group (40% and 38%, respectively) and showed an equimolar relationship in both the control (r = .84, p < .0001) and the Gln-enriched group (r = .83, p < .0001). CONCLUSIONS The findings indicate that enteral Gln supplementation caused significantly increased arterial plasma levels of Arg as a result of increased renal Arg production from circulating citrulline. Considering the multiple important biologic properties of Arg, the reported beneficial effects of Gln in catabolic states might be explained in part by increased renal Arg production.

TPN Catheter Sepsis: Lack of Effect of Subcutaneous Tunnelling of PVC Catheters on Sepsis Rate

In an effort to diminish the incidence of catheter related sepsis in total parenteral nutrition, the effect of a 10-cm long subcutaneous tunnel was studied in a prospective randomized manner. This tunnel created a longer anatomical distance between puncture site of the catheter and the subclavian vein. In the control group, a direct puncture technique was employed. Eighty-one catheters (group A) were inserted according to the direct technique, 69 (group B) were tunnelled. Catheter sepsis was defined as an episode of clinical sepsis for which no other cause can be identified and which resolves upon removal of the catheter. No significant differences were noted between the two groups, suggesting that tunnelling of subclavian PVC catheters does not diminish the incidence of catheter related sepsis.

GASTRIN AND GASTRIC ACID SECRETION IN RENAL FAILURE

In 10 anephric patients awaiting transplantation, 15 patients with chronic renal failure and 30 patients with acute renal failure, daily basal plasma gastrin levels and basal and stimulated gastric acid secretion were measured. Significant elevated plasma gastrin levels were found in all of the anephric patients and in 50 percent of the patients with acute and 55 percent of those with chronic renal failure. Elevated plasma gastrin levels decreased to normal after kidney transplantation or when kidney function returned to normal in the patients with acute renal failure. Gastric acid secretion studies showed a consistent pattern in all three groups of patients with a low basal acid output, a high basal intragastric pH and a very significant peak acid output, perhaps secondary to elevated plasma gastrin levels due to inadequate renal inactivation of gastrin. This may partly explain the increased incidence of gastrointestinal bleeding and gastritis seen in patients with different degrees of renal failure.

Use of a mixture of medium-chain triglycerides and long-chaintriglycerides versus long-chain triglycerides in critically ill surgical patients: a randomized prospective double-blind study

Twenty critically-ill surgical patients who needed total parenteral nutrition were randomly enrolled in a double-blind study comparing two intravenous fat emulsions: one containing a mixture of 50% medium-chain triglycerides and 50% long-chain triglycerides and another containing 100% longchain triglycerides. The purpose of this study was to investigate metabolic and biochemical differences between both emulsions with special reference to liver enzymes. After a baseline period of 24 h with only glucose and NaCl infusion, the lipid emulsion was added continuously during 24 h over 5 days. The parenteral nutrition was administered in mixture bags containing amino-acids, glucose and lipids together. Two-thirds of the non-protein calories were administered as glucose 40% and one third as either long-chain triglycerides or a mixture of medium-chain triglycerides and long-chain triglycerides. The total amount of non-protein calories received was the measured energy expenditure during the baseline period plus 10% and was fixed during the study. Plasma substrate concentrations, energy expenditure, and nitrogen balance were determined and arterial blood samples were taken. No toxic effects or complications attributable to one of the two emulsions were observed. There was no significant difference in energy expenditure, nitrogen balance, liver function tests, carnitine, transferrin, pre-albumin, albumin, cholesterol, triglycerides and free fatty acids. The only parameter that showed a different pattern of reaction between the two emulsions was serum bilirubin concentration. In this study no evidence of any advantageous effect of a mixture of medium-chain triglycerides and long-chain triglycerides was seen.

Radioimmunoassay of vasoactive intestinal peptide

Abstract A sensitive and specific radioimmunoassay for vasoactive intestinal peptide is described. Normal levels appear to be under 100 pg/ml with an upper range of normal of approximately 200 pg/ml. Values are elevated in liver disease, and slightly following portacaval shunt. In six patients with a syndrome of watery diarrhea, three had no tumor found at autopsy, and VIP levels were normal. Large amounts of VIP were recovered from two tumors in patients with the syndrome, but normal plasma levels were recovered from one, and only mildly elevated levels in another, who was being treated with steroids. The results suggest that while VIP may be involved in the causation of the WDHA Syndrome, there apparently exists a form of watery diarrhea which is not associated with a tumor, and in these patients, normal levels of VIP are detectible.

Percutaneous transhepatic drainage and insertion of an endoprosthesis for obstructive jaundice

As a consequence of the good results with percutaneous transhepatic cholangiography using the Chiba needle, a similar technique was employed for percutaneous transhepatic drainage and insertion of a percutaneous transhepatic endoprostheses. Herein we have described the technique and results of percutaneous transhepatic cholangiography with the Chiba needle in 45 patients and of combined percutaneous transhepatic drainage and insertion of an endoprosthesis in a consecutive group of 69 patients with obstructive jaundice. In the latter group, 50 patients had a malignant lesion. Of these, 38 were subject to continuous drainage, 14 externally and 24 with an endoprosthesis. The percutaneous transhepatic drainage and insertion of an endoprosthesis procedure brings a new dimension to preoperative decompression of the bile ducts and palliative treatment of obstructive jaundice in high-risk patients.

L-dopa in hepatic coma.

The use of L-Dopa in hepatic coma has been the subject of numerous reports since 1970. The following represents our experience with a rather heterogenous group of patients treated at the Massachusetts General Hospital over the past 4 years. Thirty-five patients with severe liver disease, a mean age of 53 PM 3.5 years, including nutritional cirrhosis with acute coma and acute hepatitis were treated. Four patients were judged grade III, 31 patients grade IV. All patients had previously been treated with protein restriction, orally administered non-absorbable antibiotics, fluid and electrolytes, and in some cases, steroids. L-Dopa was given orally in 21 patients, and as a retention enema in 14. Thirteen of the 35 patients did not respond to therapy. Seventeen responded, but did not survive, and 5 patients responded and survived. There was no difference between any of the groups as far as dosage of L-Dopa and clinical features. The one striking finding as the differences between groups was the time of initiation of L-Dopa therapy. In Group I, the survivors, therapy was started within 1.4 ± 0.8 days after the onset of coma. In Group II, there was an initiation of therapy at 6.7 ± 1.6 days, and in the non-responders 9.5 ± 1.6 days. These differences are highly significant. The results suggest that coma may pass from a reversible to an irreversible stage, and that L-Dopa therapy initiated early in the course of hepatic coma, may be of some benefit

Gut endotoxin restriction prevents catabolic changes in glutamine metabolism after surgery in the bile duct-ligated rat.

OBJECTIVE The objective of this study was to investigate the role of gut-derived endotoxemia in postoperative glutamine (GLN) metabolism of bile duct-ligated rats. SUMMARY BACKGROUND DATA Postoperative complications in patients with obstructive jaundice are associated with gut-derived endotoxemia. In experimental endotoxemia, catabolic changes in GLN metabolism have been reported. Glutamine balance is considered important in preventing postsurgical complications. METHODS Male Wistar rats were treated orally with the endotoxin binder cholestyramine (n = 24, 150 mg/day) or saline (n = 24). On day 7, groups received a SHAM operation or a bile duct ligation (BDL). On day 21, all rats were subjected to a laparotomy followed 24 hours later by blood flow measurements and blood sampling. Glutamine organ handling was determined for the gut, liver, and one hindlimb. Intracellular GLN muscle concentrations were determined. RESULTS Compared to the SHAM groups, BDL rats showed lower gut uptake of GLN (28%, p < 0.05); a reversal of liver GLN release to an uptake (p < 0.05); higher GLN release from the hindlimb (p < 0.05); and lower intracellular muscle GLN concentration (32%, p < 0.05). Cholestyramine treatment in BDL rats maintained GLN organ handling and muscle GLN concentrations at SHAM levels. CONCLUSIONS Disturbances in postoperative GLN metabolism in BDL rats can be prevented by gut endotoxin restriction. Gut-derived endotoxemia after surgery in obstructive jaundice dictates GLN metabolism.

Basal and meat extract plasma gastrin before and after parietal cell vagotomy and selective gastric vagotomy with drainage in patients with duodenal ulcer.

Basal and meat extract stimulated plasma gastrin (PG) levels and basal and stimulated gastric acid secretion were evaluated pre and postoperatively in duodenal ulcer patients who underwent parietal cell vagotomy without antral drainage (normal duodena) (PC, n = 32) or selective vagotomy with drainage (pyloric stenosis) (SV + P, n = 11). Before operation, both groups had comparable basal PG values of 52 ± 13 pg/ml (PCV) and 51 ± 18 pg/ml (SV + P), while the peak gastrin level to meat extract stimulation was 173 ± 40 pg/ml for the total group of patients. After both operations basal PG levels increased (107 ± 18 pg/ml (PCV) and 152 ± 45 pg/ml (SV + P)) and the gastrin response to meat extract stimulation was augmented after PCV, while the response after SV + P was the same as before operation. Patients with PCV often demonstrated an acid response following meat extract stimulation (3.6 ± 0.9 mEq HCl/hr), and pentapeptide stimulation (18.8 ± 2.0 mEq/hr) while patients with SV + P showed a minimal response (1.3 ± 1.2 mEq HCl/hr meat extract), and 10.7 ± 1.8 mEq/hr pentapeptide stimulation. The comparatively intact acid responses in the PCV patients may augur a high ultimate recurrence rate.