M. H. Irving

Hormonal and Metabolic Responses to Glucose Infusion in Sepsis Studied by the Hyperglycemic Glucose Clamp Technique

Although nutritional support is vital to treatment of severe sepsis, the septic patient does not respond normally to glucose infusion. We have used the hyperglycemic glucose clamp technique to investigate the initial hormonal and metabolic responses of the septic patient to glucose under controlled conditions. The plasma glucose concentration was raised to and maintained at 12 mmol/liter for 2 hr in 12 septic patients and 11 normal controls. Glucose utilization, assessed from the amount infused, was significantly depressed in the patients, despite similar plasma insulin concentrations in the two groups. Forearm glucose uptake was similarly impaired. Despite very similar plasma free fatty acid concentrations in the two groups, which were suppressed equally by the glucose infusion, whole-body fat oxidation was elevated in the patients compared with the controls, and suppressed to a lesser extent in response to glucose. Glycerol and ketone body concentrations were elevated in the patients in keeping with a picture of accelerated release, clearance, and oxidation of fatty acids. Plasma cortisol, epinephrine, and norepinephrine concentrations were elevated in the septic patients in a severity-related manner, but not to high levels compared with experimental work. Norepinephrine showed no response to the glucose infusion in either group. Plasma glucagon concentrations were not significantly elevated in the septic patients. We conclude that the hyperglycemic glucose clamp provides a useful model for studying glucose intolerance in sepsis. Impaired glucose utilization in septic patients is associated with increased fat oxidation, although the hormonal basis for these changes is still unclear.

Mechanisms of intestinal failure in Crohn's disease.

PURPOSE: The purpose of this study was to determine the mechanisms by which patients with Crohns disease develop intestinal failure and, in particular, to assess the relative importance of severe primary disease, repeated uncomplicated elective small intestine resection, and resection performed as a consequence of intra-abdominal septic surgical complications. METHODS: This was a retrospective analysis of 41 patients with Crohns disease referred to a specialized intestinal failure unit between January 1987 and September 1998 for permanent home parenteral nutrition. To compare the surgical activity in patient groups, a resection index was calculated by dividing the number of intestinal resections by the interval in years between the first resection for Crohns disease and referral for management of intestinal failure. RESULTS: Extensive primary Crohns disease was responsible for intestinal failure in 7 cases (17 percent). The remainder (n=34, 83 percent) developed intestinal failure after intestinal resection. Nine of the “surgical” Crohns patients developed intestinal failure after uncomplicated sequential resection, (median small-bowel length 65 (range, 60–120) cm) after a median of 3 (range, 2–8) operations over a median of 17 (range, 3–27) years. By contrast, the other 25 surgical Crohns patients developed intestinal failure after multiple unplanned laparotomies for intra-abdominal sepsis (median small-bowel length 70 (range, 60–200) cm), with a median of 4 (range, 2–7) laparotomies performed over a median of 0.5 (range, 0.1 to 1.5) years (P<0.001). The resection index for the 25 Crohns patients undergoing laparotomies for intra-abdominal sepsis was significantly greater than that of the 9 patients who had planned sequential resections (2.1 (0.27–25)vs. 0.23 (0.1–1.0);P < 0.002, Mann-WhitneyU test). CONCLUSION: Intestinal failure develops in Crohns disease primarily as a result of complications of surgical treatment. The largest group of patients at risk consists of those who are undergoing multiple unplanned laparotomies to control intra-abdominal sepsis.

Parenteral nutrition in Crohn's disease.

A retrospective study of 50 consecutive patients admitted to hospital with Crohns disease has been undertaken in order to assess the place of parenteral nutrition in our management of this disease. Following treatment, median weight, hemoglobin, and plasma albumin were the same in three treatment groups—parenteral nutrition (12), low-residue diet (9), and normal diet (29). Of 13 courses of parenteral nutrition used in 12 patients, 10 were for periods of less than 14 days (median four days). Most patients with nutritional problems associated with Crohns disease can be treated successfully by one or other form of enteral nutrition. Parenteral nutrition, if required, is usually only necessary for periods of less than two weeks, to support patients over a critical period in their illness. Occasionally prolonged parenteral nutrition is required for short-bowel syndrome or advanced fistulous disease. In these cases, training the patient to infuse himself with nutrients at home has much to recommend it.

Urinary 3 -Methylhistidine: Creatinine Ratio in Patients on Long-Term Parenteral Nutrition

The urinary 3-methylhistidine (3-MH) and creatine excretion were measured serially in two patients on total parenteral nutrition for 201 and 225 days, respectively. Variations in excretion were related to clinical events, such as sepsis; 3-MH excretion and the 3-MH:creatinine ratio were raised in association with some episodes of infection, but not all. It is concluded that, although infection is often associated with increased myofibrillar protein breakdown, this is not always the case. It is suggested that in susceptible patients a high 3-MH:creatine ratio may indicate occult infection not detectable by other means.

Cyclic neutropenia—Unusual cause of acute abdomen

Cyclic neutropenia, a rare blood disorder, may be complicated by spontaneous necrosis of the cecum and ascending colon. We describe one such case, where a staged surgical approach achieved a successful outcome. The importance of recognition of this disorder is stressed, since this allows both performance of appropriate surgery and consultation with hematologic colleagues.

Response of plasma amino acids to elective surgical trauma.

Venous plasma amino acids have been measured before, during, and after surgical operation in 17 patients. There were no statistically significant changes in plasma amino acid levels during the operation itself, but in the 3 days following operation the concentration of many of the amino acids were altered compared with the preoperative levels. Because some of the changes resemble those seen in early starvation, further studies are necessary to determine whether trauma or starvation is the prime stimulus to the changes observed.