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AIM: Recent evidence suggests that the provision of energy-containing fluids is safe and may impact positively on markers of recovery. The aims of this study were to assess the tolerance of preoperative carbohydrate fluid administration and to determine its effect on postoperative metabolic and clinical responses. METHODS: Patients admitted to the Royal Infirmary of Edinburgh for major, elective abdominal surgery were recruited to this double-blind, randomised study and received either a placebo drink or carbohydrate (12.6g/100ml) drink (CHOD). Patients consumed 800 ml of their drink on the evening before surgery and 400 ml on the day of surgery 2-3 h before the induction of anaesthesia. Nutritional status was determined using body mass index (BMI) and upper arm anthropometry; all measurements were taken preoperatively, postoperatively and at discharge. Blood glucose and insulin concentrations were also measured preoperatively and on the first post operative day. Length of hospital stay (LOS) and postoperative complications were recorded. RESULTS: Seventy-two patients were recruited and 65 (34 male:31 female) completed this study. Thirty-four patients were randomised to receive the placebo drink (control group) and 31 patients to receive the carbohydrate drink (CHOD group). Groups were well-matched in terms of gender and age. There were no differences between the two groups at baseline for BMI (control: -25.1+/-1.7 kg/m2; CHOD -25.2+/-1.2 kg/m2), upper arm anthropometry or surgical procedure. At discharge loss of muscle mass (arm muscle circumference) was significantly greater in the control group when compared with the CHOD group (control: -1.1+/-0.15 cm; CHOD: -0.5+/-0.16 cm; P<0.05). Baseline insulin (control: 20.7+/-4.9 mU/l; CHOD: 24.6+/-6.2 mU/l) and glucose (control: 6.0+/-1.4 mmol/l; CHOD 5.7+/-1.4 mmol/l) were comparable in the two groups and did not differ postoperatively. No complications were recorded as a result of preoperative fluid consumption. Postoperative morbidity occurred in six patients from each group. Median LOS in the control group was 10 days (IQR=6), and 8 days (IQR=4) in the CHOD group. CONCLUSION: Preoperative consumption of carbohydrate-containing fluids is safe. Provision of a carbohydrate energy source prior to surgery may attenuate depletion of muscle mass after surgery. Further studies are required to determine if this preservation of muscle mass is reflected in improved function and reduced rehabilitation time.

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After successful liver transplantation (LTx), excessive weight gain is common among recipients. This rapid change in body morphology has been attributed to immunosuppressive regimens. The liver's role as a metabolic sensor and its autonomic innervation are pivotal in relaying humoral and neural information to the hypothalamus, where ingestive behavior is determined and has largely been ignored. We examined and assessed the contribution of drugs, energy intake, and energy expenditure on weight gain after LTx. Twenty-three patients were followed up at 3-mo intervals after LTx. Energy expenditure was measured by indirect calorimetry and dietary intake by diet diaries, and body composition was assessed with anthropometry and multifrequency bioelectrical impedance analysis. Cumulative drug doses were calculated, and associations between body composition and immunosuppressive regimens and energy expenditure were examined. Nine months after LTx, 20 of 23 (87%) recipients were overweight or obese, despite three-fourths of this cohort being on weight-reduction regimens. After LTx, a decrease in measured energy expenditure was observed (60.3 +/- 1.6 kJ/kg of body cell mass pre-LTx versus 53.7 +/- 2.2 kJ/kg of body cell mass after 9 mo; P < 0.05). Multiple stepwise regression analysis showed that, when adjusted for body weight, the strongest predictor of fat mass at 9 mo after LTx was resting energy expenditure. Weight gain after LTx is not predicted by immunosuppressive drug dosage. The strong association between weight gain and energy economy might be a consequence of the loss of hepatic metabolic integration and accelerated further by increased energy intake. Effective management of weight gain will not be achieved until the mechanisms involved in altered energy homeostasis are elucidated.

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Anorexia in liver disease is common; however, its association with aberrant metabolism and the type of cirrhosis has not been considered. Dietary intake, nutritional status, fasting substrate oxidation, and macronutrient preference were examined in controls (n = 18) and 65 patients with hepatocellular (n = 31) or biliary cirrhosis (n = 34). Energy intakes were lowest in hepatocellular patients (controls: 9.0 +/- 0.48 megajoules/day compared with biliary: 7.0 +/- 0.40 MJ/day, P <.05; controls compared with hepatocellular 6.5 +/- 0.39 megajoules/day, P <.01). Triceps skinfold was lower only in hepatocellular patients (controls: 109 +/- 9.2% compared with hepatocellular 79 +/- 5.6%, P <.05). The fasting rate of lipid oxidation was elevated in hepatocellular patients when compared with controls and biliary patients (controls: 40.9 +/- 15.1 mg/min compared with hepatocellular 62.8 +/- 16.8 mg/min, P <.001, and biliary : 45.5 +/- 17.0 mg/min compared with hepatocellular, P <.001). Control subjects exhibited a greater preference for the high fat, moderate carbohydrate food (controls: median 7.0 IQR 2.0 compared with biliary: median 5.0 interquartile range [IQR] 4.7, P <.01) (controls compared with hepatocellular: median 6.0 IQR 4.0, P <.01). Cirrhotic patients' spontaneous dietary intake is lower than that of controls and recommended intakes. Although macronutrient preference ratings were different within cirrhotic patient groups it remains unclear whether associated nutrient deficits are metabolically driven and dictated by primary cause.

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BACKGROUND: The liver plays a central role in ingestive behavior; alterations in metabolic signaling to the brain stem as a result of chronic liver disease could influence intake. OBJECTIVE: We examined the influence of metabolic sequelae of liver disease on nutrient intake and nutritional status. DESIGN: Nutritional status and spontaneous dietary intake were examined in 65 cirrhotic patients and 14 control subjects. The response to feeding was investigated in 14 control subjects and a subgroup of 31 cirrhotic patients. Comparisons were made between patients with primary biliary cirrhosis (PBC) and hepatocellular cirrhosis (HC). RESULTS: Patients were nutritionally depleted. The fasting rate of lipid oxidation in the HC group was greater than in the control group (P < 0.01). In the fasting state, only HC patients were hyperinsulinemic [121.2+/-78.5 compared with 41.3+/-18.6 pmol/L in control subjects (P < 0.001) and 64.7+/-15.8 pmol/L in PBC patients (P < 0.05)] and this persisted during the response to feeding. In the fed state, the magnitude of change in carbohydrate oxidation was greatest in the HC group (HC: 34.6%; control: 23.1%; PBC: 25.2%). Carbohydrate and energy intakes of the HC group were lower than in control subjects (carbohydrate: 193+/-38.3 compared with 262+/-48.1 g/d, P < 0.05; energy: 6.29+/-1.40 compared with 9.0+/-2.12 MJ/d, P < 0.05). CONCLUSIONS: Reductions in carbohydrate intake could be mediated by hyperinsulinemia and compounded by preferential uptake of carbohydrate. This may enhance gastrointestinal satiety signaling and contribute to hypophagia.

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Motility was recorded from the corpus, antrum and small intestine of the urethane anaesthetised ferret. The gastrointestinal effects of the highly emetic cytotoxic anticancer agent, cisplatin were investigated following intravenous administration (10 mg/kg i.v.). Following injection, cisplatin induced a prompt onset (< 2 min) increase in motility (tone and contraction amplitude) in all regions with a duration of < 15 min. Acute vagotomy did not abolish the effect but reduced the peak amplitude in the antrum only. Chronic subdiaphragmatic vagotomy significantly enhanced the cisplatin-induced rise in tone in the corpus, the contraction amplitude in the antrum and the duration of the response in the duodenum. The stimulatory effect of cisplatin was blocked in all regions by atropine but not naloxone or the 5-HT3 receptor antagonist ondansetron. This study reports a previously undescribed gastrointestinal motility effect of cisplatin in vivo that is temporally dissociated from emesis. It is proposed that the results provide evidence for a neuroactive effect of cisplatin on enteric cholinergic neurones.

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In recent years the role of the area postrema in the emetic reflex has been predominant and the involvement of the abdominal visceral innervation has tended to be overlooked. This paper attempts to redress the balance reflex by reviewing aspects of the existing literature and complementing this with original studies from the ferret. In view of the widespread use of the ferret in studies of emesis and particularly in the characterization of the antiemetic actions of 5-HT3 receptor antagonist, the opportunity is taken to assess the suitability of this species for studies of emesis. It is concluded that the ferret is sensitive to a wide range of emetic stimuli including intragastric irritants, opiate and dopamine receptor agonists, many cytotoxic drugs, and radiation. For several stimuli it is more sensitive than other species and for radiation on the basis of its ED100 it appears to be the most sensitive of the laboratory animals studied. Using electrical stimulation of the central end of the dorsal vagal trunk in the abdomen in conscious and anaesthetized animals, the vagal afferents were shown to be capable of eliciting emesis. Using lesioning studies an involvement of the vagus in the emetic response to a number of cytotoxic drugs (e.g., cisplatinum, cyclophosphamide, mustine) and radiation was demonstrated, although the magnitude of the effect varied with the different stimuli. An attempt is made to reconcile these observations with previous studies of area postrema ablation. The problems of interpreting the effects of nerve lesions are critically discussed in light of preliminary evidence presented here that there may be a degree of plasticity in the emetic pathway following such lesions. The range of antiemetic effects of 5-HT3 receptor antagonists is reviewed and an attempt is made to identify the site(s) at which these agents act. Results are presented that suggest a link between the vagus and 5-HT3 receptor antagonism. These studies are discussed together with others and lead us to propose that (in the ferret) 5-HT3 receptor antagonists have their main antiemetic effect by acting on vagal afferent terminals in the wall of the upper gut with an additional minor site either in the nucleus tractus solitarius or presynaptically on the vagal afferent terminals in the medulla where binding sites for 5-HT3 receptor ligands have recently been demonstrated in this species.

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