Mechanisms of intestinal failure in Crohn's disease.

PURPOSE: The purpose of this study was to determine the mechanisms by which patients with Crohn's 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 Crohn's 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 Crohn's disease and referral for management of intestinal failure. RESULTS: Extensive primary Crohn's 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" Crohn's 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 Crohn's 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 Crohn's 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-Whitney U test). CONCLUSION: Intestinal failure develops in Crohn's 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.

Patient quality of life after successful restorative proctocolectomy is normal.

OBJECTIVE: To measure quality of life (QoL), using validated health status instruments, of patients with functioning IPAA for CUC. PATIENTS AND METHODS: Between 1986 and 1997, a total of 77 patients had an IPAA. Thirteen patients were excluded [6 excised, 3 awaiting ileostomy closure, 2 lost to follow up, 2 serious unrelated illnesses]. Postal survey using SF36 and EuroQol questionnaires. Age, sex, year of pouch construction and stool frequency were documented. RESULTS: Fifty-six patients (87.5%) replied. Male:female ratio; 3:2. Median age; 34 years (range 13-64). Median time since pouch construction; 4 years (range 1-10 years). Median SF36 scores (range); physical function 86.6 (0-100), physical role 81.6 (0-100), body pain 78.4 (22-100), general health 61.6 (5-100), vitality 57.6 (5-100), social function 75.4 (25-100), emotional role 83.5 (0-100), mental health 70.7 (16-100). All the SF36 scores were within the normal range, as were the EuroQol scores. Median EuroQol score (range); 0.85 (-0.07-1.0). Median EuroQol thermometer score (range); 83.3 (20-100). There was no correlation between objective QoL score and age, gender, stool frequency and year of pouch construction. CONCLUSION: The QoL for patients with a functioning IPAA for CUC measured using validated health status instruments is normal. Age, gender, stool frequency and year of construction do not affect QoL outcome after the IPAA for ulcerative colitis.

Selective impairment of glucose storage in human sepsis.

BACKGROUND: Glucose utilization in sepsis is impaired but the mechanisms are unclear. This study examined the effect of sepsis on total glucose utilization, oxidation and storage, and the energetic costs of these metabolic processes. METHODS: Glucose infusion rate (GIR), glucose oxidation rate (GOR), non-oxidative disposal rate and the energetic cost of glucose storage were studied in 24 patients with abdominal sepsis and in 26 healthy controls, using indirect calorimetry and the euglycaemic hyperinsulinaemic clamp with insulin infusion rates of 40 and 240 mU m-2 min-1. RESULTS: Basal GOR was significantly lower in septic patients than in controls (1.5 versus 2.3 mg per kg fat-free mass (FFM) per min, P < 0.001). Septic patients had a significantly lower GIR at 40 mU m-2 min-1 (4.2 versus 9.1 mg per kg FFM per min) and at 240 mU m-2 min-1 (7.5 versus 11.8 mg per kg FFM per min), relative to controls (P < 0.001). GOR was similar in septic and control subjects at both rates of insulin infusion whereas non-oxidative disposal was significantly lower in septic patients (P < 0.001) and accounted entirely for the reduction in GIR. The energetic cost of glucose disposal was unaffected by sepsis. CONCLUSION: Sepsis is associated with selective impairment of glucose storage but the energetic cost of non-oxidative disposal is unaffected.

Serum leptin concentrations and their relation to metabolic abnormalities in human sepsis.

Circulating leptin concentrations are raised in animal models of inflammation and sepsis. The purpose of this study was to determine the effect of sepsis on serum leptin concentration in humans and to examine the relationship between leptin and the metabolic consequences of sepsis. Resting energy expenditure, insulin sensitivity, and fasting serum leptin, plasma insulin, and cortisol concentrations were measured in 20 subjects with intra-abdominal sepsis and 20 healthy control subjects, before and during a 2-h period of euglycemic hyperinsulinemia. Fasting serum leptin concentrations were similar in septic and control subjects. In simple regression analysis, serum leptin concentrations correlated significantly with percent body fat in both septic patients (r = 0. 64, P < 0.005) and healthy subjects (r = 0.75, P < 0.0001). Multiple regression analyses additionally indicated that percent body fat, fasting plasma insulin, and plasma cortisol, but not sepsis, were significant and independent determinants of serum leptin concentration. No relationship between leptin and resting energy expenditure or insulin sensitivity was identifiable. A major metabolic role for leptin in human sepsis therefore appears unlikely.

Thermogenic, hormonal and metabolic effects of intravenous glucose infusion in human sepsis.

BACKGROUND: Sepsis is associated with alterations in glucose metabolism and the effect of intravenous feeding on energy expenditure is unclear. Many studies of glucose metabolism in humans with sepsis have employed techniques that are not relevant to the practice of intravenous feeding. METHODS: The thermogenic, hormonal and metabolic effects of glucose were evaluated in a prospective experimental study of septic (n = 6) and non-septic (n = 6) subjects, by administering glucose intravenously under conditions and at a rate similar to those used in total parenteral nutrition. RESULTS: Patients with sepsis had a higher fasting metabolic rate than control subjects (P < 0.001) and a lower fasting respiratory quotient (P < 0.03). The thermic effect of glucose in both groups was small and not statistically significant (median 3.2 and 0.4 per cent in septic and non-septic subjects respectively, P > 0.1). Patients with sepsis had an attenuated plasma insulin response to glucose administration compared with control subjects (P < 0.001) and less marked suppression of plasma fatty acid and glycerol concentrations (P < 0.001). Glucose administration was not associated with significant changes in plasma catecholamine concentrations in either group of patients. CONCLUSION: Intravenous infusion of glucose at clinically relevant rates is associated with a negligible thermogenic response, with no activation of the sympathetic nervous system.

Successful management of external duodenal fistula in a specialized unit.

BACKGROUND: High-output external duodenal fistula remains a challenging condition to treat. Despite advances in metabolic and nutritional care, mortality rates remain high. METHOD: Retrospective casenote review of patients managed on a specialised unit. RESULTS: Thirteen of 388 admissions (3.4%, 11 males, median age 51 years) had an external duodenal fistula. Management was by eradication of abdominal and systemic sepsis and maintenance of nutritional status by the administration of total parenteral nutrition. The majority of fistulas followed surgery for peptic ulcer disease. Eight of 13 fistulas closed spontaneously, and of those requiring operative closure, surgery was successful in 4 of 5 cases. There were 2 mortalities. CONCLUSION: High-output external duodenal fistula may be successfully managed in a specialised unit.

A prospective evaluation of central venous blood flow using Doppler ultrasound in patients with a long-term central venous catheter.

Using Doppler ultrasound, we prospectively evaluated the relationship between central venous blood flow and the development of central venous thrombosis in ten patients with a long term central line. The presence of turbulent blood flow around the catheter was followed by the development of central venous thrombosis in two patients but neither had subsequent clinical sequelae. More surprisingly, however, normal blood flow was demonstrated in eight patients, two of whom subsequently developed intravascular thrombi.

Assessing the quality of life of patients with intestinal failure on home parenteral nutrition.

BACKGROUND: A study was performed to measure the quality of life of patients receiving home parenteral nutrition (HPN). Quality of life is an important determinant of the effectiveness of health technologies, but it has rarely been assessed in patients receiving HPN. AIMS: To measure quality of life and highlight any moderating factors. PATIENTS AND METHODS: Quality of life was measured using two validated instruments (SF 36 and EuroQol) in 51 patients with intestinal failure. All patients had benign disease, the commonest being Crohn's disease (n = 35). RESULTS: HPN patient scores were worse for six of eight SF 36 domains (p < 0.05) compared with standard population scores. Younger patients (< 45) had good scores but older patients (> 55 years) scored significantly less. Patients addicted to narcotic substances had very low scores. EuroQol utility scores confirmed the SF results. Forty one patients reported that they felt too ill to work and only five were in full time work or education. CONCLUSIONS: The health status profile of our young patients on HPN was good compared with the normal population. The poorest scores were in older patients and those dependent on narcotic drugs. This has clinical and economic relevance when considering such patients for HPN.

Cost-utility analysis of home parenteral nutrition.

An economic evaluation of home parenteral nutrition (HPN) for intestinal failure is presented. The cost-utility of HPN and factors affecting the cost-utility ratio were examined to determine whether current practice is the most efficient way of treating intestinal failure. Quality-adjusted life-years (QALYs) gained were measured using a validated health status questionnaire. The cost of treating a patient with intestinal failure was calculated, and marginal cost per QALY gained ratios were obtained. The cost per QALY for an average patient was approximately 68,975 pounds, but the value for patients over 55 years of age of about 126,865 pounds compared with approximately 58,233 pounds for those under 44 years. Treating a patient in hospital rather than at home increased the estimated cost per QALY to approximately 190,000 pounds. The current practice of home care is about 65 per cent more cost-effective than hospital care.

Prolonged peripheral parenteral nutrition with an ultrafine cannula and low-osmolality feed.

Peripheral parenteral nutrition is an attractive alternative to centrally delivered parenteral nutrition because it obviates the need for central venous cannulation and its attendant complications. Some 45 consecutive patients were fed peripherally using a 22-G polyurethane catheter and a fat-based, low-osmolality feed. Of these patients, 36 were fed for a median of 8.5 (range 3-31) days without peripheral vein thrombophlebitis (PVT). Seven patients developed PVT after a median of 6 (range 5-7) days. The cumulative daily risk of PVT was 0.016 episodes per day. These results suggest that prolonged (more than 7 days) problem-free peripheral parenteral nutrition is possible.

Management of intra-abdominal abscesses in Crohn's disease.

Over a 5-year period, 54 intra-abdominal abscesses were observed in 40 (20.8%) of 192 patients with Crohn's disease. The median age was 39 years (range 17-76 years); median interval from diagnosis, 7.5 years (range 0-24 years) and the median number of surgical operations was 2 (range 0-7). Forty abscesses (74.1%) were spontaneous and 14 (25.9%) were postoperative. Thirty abscesses were initially managed by laparotomy, 14 by percutaneous drainage, nine by incision and drainage and in one case the abscess drained spontaneously. Intra-abdominal abscesses were managed successfully by laparotomy in 23 (76.7%) of 30 patients, with a 93% success rate (13 of 14) for spontaneous abscesses managed by resection and primary anastomosis. Three of 8 (37.5%) spontaneous abscesses were managed successfully by percutaneous drainage, a temporising effect being achieved in a further two cases. There was no significant difference in sepsis score or duration of hospital stay for patients managed initially by laparotomy and those managed by drainage. However, patients with stricturing or fistulating Crohn's disease were much more likely to have initial management by laparotomy and in these patients surgical intervention was found to be an effective initial strategy.

Quality of life on home parenteral nutrition: a single centre study of 37 patients.

Quality of life was assessed in 37 patients receiving home parenteral nutrition (HPN) for intestinal failure. A questionnaire was developed specifically for this purpose and the results were compared with those obtained by subjective assessment using a simple linear scale. The majority of patients (n = 26, 70.3%) had a good objective quality of life and most (n = 16, 53.3%) of those eligible (n = 30, 81.1%) did not express an interest in intestinal transplantation. Despite the apparent good quality of life enjoyed by patients receiving HPN, there were numerous areas in which patients with intestinal failure felt that their quality of life left much to be desired: many patients reported significant psychological symptoms (n = 15, 40.5%) sexual (n = 10, 27.0%) and social dysfunction (n = 19, 51.3%) and most patients with intestinal failure were unable to return to work (n = 24, 88.9%). Detailed quality of life assessment reveals that there is much still to be done to ensure that provision of care for patients with intestinal failure involves not only prolongation of life but also an improvement in quality of life.

Effect of lateral sphincterotomy on internal anal sphincter function. A computerized vector manometry study.

PURPOSE: This study was designed to investigate the effect of lateral sphincterotomy on internal anal sphincter function in patients with chronic anal fissure. METHODS: Using an eight-channel perfusion catheter and computerized data analysis, a prospective manometric study was performed on patients with chronic anal fissure undergoing lateral sphincterotomy (LS). RESULTS: Mean resting pressure (MRP) in patients with anal fissure (85.1 mmHg) was significantly higher (P = 0.012) than control subjects (63.3 mmHg). One week following LS there was a significant reduction in MRP (50.0 mmHg; P = 0.0014), and this was maintained when reassessed five weeks later (MRP = 56.4 mmHg; P = 0.0019). There was no significant difference in coefficient of variation (a measure of the degree of manometric asymmetry of the anal canal) in the control group (mean, 8.9 percent) and in patients with anal fissure (mean, 7.7 percent; P = 0.43). LS created a significant increase in anal canal resting manometric asymmetry when assessed at one (mean, 17.3 percent; P = 0.0013) and six weeks (mean, 11.7 percent; P = 0.027) after the procedure. CONCLUSION: LS produces a global and symmetric decrease in anal canal resting pressure. In addition, it produces a significant increase in manometric asymmetry of the resting anal canal by creating a detectable segmental defect.

Total parenteral nutrition modifies the acute phase response to Crohn's disease.

Measurements of the acute phase proteins, C-reactive protein (CRP) and orosomucoid are widely used to monitor the activity of Crohn's disease. The effect of TPN upon the levels of acute phase proteins is unknown. Serum levels of CRP and orosomucoid were measured simultaneously over a four year period in 13 patients receiving TPN for Crohn's disease, nine patients with noninflammatory causes of intestinal failure, and 16 patients with Crohn's disease treated without TPN. An acute phase response was found with a similar frequency in both groups of patients with Crohn's disease (73.6% and 83.9% for Crohn's with and without TPN respectively), but was less prevalent in patients receiving TPN for non-inflammatory causes of intestinal failure (56.1%, P < 0.01). In this latter group, the acute phase response consisted primarily of an isolated elevation of orosomucoid (78.4%), compared with patients with Crohn's disease alone (21.1%, P < 0.001) and with Crohn's disease and TPN (46.6%, P < 0.05). Liver function abnormalities were seen on 68.8% of occasions in patients with noninflammatory causes of intestinal failure who had elevated levels of orosomucoid, compared with 34.9% of occasions on which orosomucoid levels were normal (P < 0.001). TPN may lead to isolated elevation of serum levels of orosomucoid, reducing the value of this acute phase protein in monitoring the activity of Crohn's disease in patients receiving TPN.

Catheter-related morbidity in patients on home parenteral nutrition: implications for small bowel transplantation.

Until recently, Home Parenteral Nutrition (HPN) has been the only real option for patients with intestinal failure. Small bowel transplantation (SBT) is advancing rapidly, however, and may soon provide an alternative for these patients. One of the arguments in favour of SBT is the alleged morbidity of prolonged parenteral nutrition. We have assessed the catheter-related morbidity in a large cohort of patients on HPN. A total of 88 central venous catheters were required in 50 patients. The main complications were sepsis (24 episodes) and occlusion (18 episodes). The overall incidence of catheter-related morbidity was one episode per 46 patient-months of HPN.

Reconstructive abdominal operations after laparostomy and multiple repeat laparotomies for severe intra-abdominal infection.

Between 1980 and 1993, 18 patients underwent formal laparotomy after laparostomy and healing of the peritoneal cavity by granulation. The majority (12 patients) were men and the median age was 47 (range 22-67) years. Intraabdominal infection following surgery for Crohn's disease (four patients) and necrotizing pancreatitis (six) was the most common primary condition requiring laparostomy. A total of 23 reconstructive operations were carried out on the 18 patients a median of 6 (range 1-18) months after laparostomy. The indication for surgery was for closure and/or resection of an enteric fistula in 13 patients. The site of the fistula included three gastric, two duodenal, 11 small bowel and seven colonic. A further four patients required operation for closure or refashioning of a stoma. Five patients subsequently required a second laparotomy: two for elective restoration of bowel continuity, two for recurrent fistula and one for an acute abdomen. After reconstructive surgery following laparostomy 16 patients were discharged home alive and well, one requiring home parenteral nutrition for short bowel syndrome. In contrast, the two oldest patients in the series died from multiple organ failure immediately after initial reconstructive surgery. Both had pre-existing medical problems and in neither was there evidence of further intra-abdominal infection after reconstruction.