Background
Weight loss and muscle wasting are commonly found in patients with end-stage liver disease. Since there is an association between malnutrition and poor clinical outcome, such patients (or those at risk of becoming malnourished) are often given parenteral nutrition, enteral nutrition, or oral nutritional supplements. These interventions have costs and adverse effects, so it is important to prove that their use results in improved morbidity or mortality, or both.

Objectives
To assess the beneficial and harmful effects of parenteral nutrition, enteral nutrition, and oral nutritional supplements on the mortality and morbidity of patients with underlying liver disease.

Search methods
The following computerised databases were searched: the Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE, EMBASE, and Science Citation Index Expanded (January 2012). In addition, reference lists of identified trials and review articles and Clinicaltrials.gov were searched. Trials identified in a previous systematic handsearch of Index Medicus were also considered. Handsearches of a number of medical journals, including abstracts from annual meetings, were done. Experts in the field and manufacturers of nutrient formulations were contacted for potential references.

Selection criteria
Randomised clinical trials (parallel or cross-over design) comparing groups of patients with any underlying liver disease who received, or did not receive, enteral or parenteral nutrition or oral nutritional supplements were identified without restriction on date, language, or publication status. Six categories of trials were separately considered: medical or surgical patients receiving parenteral nutrition, enteral nutrition, or supplements.

Data collection and analysis
The following data were sought in each report: date of publication; geographical location; inclusion and exclusion criteria; the type of nutritional support and constitution of the nutrient formulation; duration of treatment; any nutrition provided to the controls; other interventions provided to the patients; number, sex, age of the study participants; hospital or outpatient status; underlying liver disease; risks of bias (sequence generation, allocation concealment, blinding, incomplete outcome reporting, intention-to-treat analysis, selective outcome reporting, others (vested interests, baseline imbalance, early stopping)); mortality; hepatic morbidity (development or resolution of ascites or hepatic encephalopathy, occurrence of gastrointestinal bleeding); quality of life scores; adverse events; infections; lengths of stay in the hospital or intensive care unit; costs; serum bilirubin; postoperative complications (surgical trials only); and nutritional outcomes (nitrogen balance, anthropometric measurements, body weight). The primary outcomes of this review were mortality, hepatic morbidity, quality of life, and adverse events. Data were extracted in duplicate; differences were resolved by consensus.

Data for each outcome were combined in a meta-analysis (RevMan 5.1). Estimates were reported using risk ratios or mean differences, along with the 95% confidence intervals (CI). Both fixed-effect and random-effects models were employed; fixed-effect models were reported unless one model, but not the other, found a significant difference (in which case both were reported). Heterogeneity was assessed by the Chi2 test and I2 statistic. Subgroup analyses were planned to assess specific liver diseases (alcoholic hepatitis, cirrhosis, hepatocellular carcinoma), acute or chronic liver diseases, and trials employing standard or branched-chain amino acid formulations (for the hepatic encephalopathy outcomes). Sensitivity analyses were planned to compare trials at low and high risk of bias and trials reported as full papers. The following exploratory analyses were undertaken: 1) medical and surgical trials were combined for each nutritional intervention; 2) intention-to-treat analyses in which missing dichotomous data were imputed as best- and worst-case scenarios; 3) all trials were combined to assess mortality; 4) effects were estimated by absolute risk reductions.

Main results
Thirty-seven trials were identified; only one was at low risk of bias. Most of the analyses failed to find any significant differences. The significant findings that were found were the following: 1) icteric medical patients receiving parenteral nutrition had a reduced serum bilirubin (mean difference (MD) -2.86 mg%, 95% CI -3.82 mg% to -1.89 mg%, 3 trials) and better nitrogen balance (MD 3.60 g/day, 95% CI 0.86 g/day to 6.34 g/day, 1 trial); 2) surgical patients receiving parenteral nutrition had a reduced incidence of postoperative ascites only in the fixed-effect model (RR 0.65, 95% CI 0.48 to 0.87, 2 trials, I2 = 70%) and one trial demonstrated a reduction in postoperative complications, especially infections (pneumonia in particular); 3) enteral nutrition may have improved nitrogen balance in medical patients (although a combination of the three trials was not possible); 4) one surgical trial of enteral nutrition found a reduction in postoperative complications; and 5) oral nutritional supplements had several effects in medical patients (reduced occurrence of ascites (RR 0.57, 95% CI 0.37 to 0.88, 3 trials), possibly (significant differences only seen in the fixed-effect model) reduced rates of infection (RR 0.49, 95% CI 0.24 to 0.99, 3 trials, I2 = 14%), and improved resolution of hepatic encephalopathy (RR 3.75, 95% CI 1.15 to 12.18, 2 trials, I2 = 79%). While there was no overall effect of the supplements on mortality in medical patients, the one low risk of bias trial found an increased risk of death in the recipients of the supplements. Three trials of supplements in surgical patients failed to show any significant differences. No new information was derived from the various subgroup or sensitivity analyses. The exploratory analyses were also unrevealing except for a logical conundrum. There was no difference in mortality when all of the trials were combined, but the trials of parenteral nutrition found that those recipients had better survival (RR 0.53, 95% CI 0.29 to 0.98, 10 trials). Either the former observation represents a type II error or the latter one a type I error.

Authors' conclusions
The data do not compellingly justify the routine use of parenteral nutrition, enteral nutrition, or oral nutritional supplements in patients with liver disease. The fact that all but one of these trials were at high risks of bias even casts doubt on the few benefits that were demonstrated. Data from well-designed and executed randomised trials that include an untreated control group are needed before any such recommendation can be made. Future trials have to be powered adequately to see small, but clinically important, differences.

/pdf/nutritional-support-for-liver-disease-1yll0cdp0m.pdf

Nutritional support for liver disease

Effect of Ischemic Preconditioning on Rat Liver Microcirculation Monitored with Laser Doppler Flowmetry

Background In order to improve perioperative subjective quality of care it seems desirable to shorten preoperative fasting times as much as possible within acceptable safety limits. These efforts should result in a measurable reduction of preoperative thirst and hunger as well as in improvements of patient well-being. It is unknown to what extent preoperative patient comfort is limited by thirst and hunger from a patient point of view. The purpose of this study was to determine the impact of a traditional fasting regimen on preoperative patient discomfort. Patients and methods We conducted a survey on preoperative thirst and hunger in 412 adult American Society of Anesthesiologists ASA I and II patients scheduled for minor elective surgery. Results Of the patients 33% complained of moderate to strong thirst, whereas 19% had moderate to strong hunger, 47% of the participants would have liked to have been able to drink and 72% would have appreciated a light breakfast before surgery. Mean preoperative fasting times were 12.8+/-3.4 h for fluids and 15.5+/-4.4 h for solids. "Thirst" was named by 3.3% and "hunger" by 0.8% of patients as the most important factor for preoperative discomfort but "long wait" (8.5%), "tenseness" (6.5%) and "anxiety" (4.8%) were the most frequently named factors. Answers were independent of the duration of preoperative fasting. Conclusion Patient comfort is compromised by traditional fasting rules and liberalization of these policies is desired by patients. However, efforts to reduce preoperative anxiety and tenseness might have an additional, important potential to improve perioperative quality of care from a patient's perspective.

/pdf/preoperative-fasting-times-patients-perspective-3jzgl22a5o.pdf

[Preoperative fasting times: patients' perspective].

Hintergrund
Mit dem Ziel der subjektiven perioperativen Qualitatsverbesserung scheint es wunschenswert, die praoperativen Nuchternzeiten im Rahmen der als sicher geltenden Grenzen so kurz als moglich zu halten. Diese Masnahmen sollten mit einer messbaren Verminderung von praoperativem Hunger und Durst einhergehen und v. a. in einer Verbesserung der praoperativen Befindlichkeit resultieren. Welchen Einfluss Durst und Hunger aus Patientensicht auf den praoperativen Komfort haben, ist jedoch weit gehend unbekannt. Ziel dieser Studie war es, das Ausmas der Beeintrachtigung der Patienten durch eine traditionelle Nuchternheitsregelung abzuschatzen.

/pdf/praoperative-nuchternzeiten-pjmnip1vuy.pdf

Präoperative Nüchternzeiten

Anesthesiology societies have issued various guidelines on preoperative fasting since 1990, not only to decrease the incidence of lung aspiration and anesthetic morbidity, but also to increase patient comfort prior to anesthesia. Some of these societies have been updating their guidelines, as such that, since 2010, we now have 2 evidence-based preoperative fasting guidelines available. In this article, an attempt is made to review these updated guidelines, as well as the current instructions for more controversial patients such as infants, the obese, and a particular type of ophthalmic surgery.

Guías de ayuno preoperatorio: actualización

Postoperative infectious complications are nowadays a major problem in liver surgery. Better surgical outcomes with a consequent reduction in treatment and hospitalisation costs are a primary objective. The aim of this prospective, randomised study was to evaluate the cytokine response during and after portal clamping in patients undergoing liver resection and continuously fed with enteral nutrition as compared to patients receiving parenteral nutritional support. Forty patients with liver tumours were divided into two groups of 20 on the basis of the presence or absence of chronic liver disease. Furthermore, the latter group of 20 were randomised to two subgroups A and B of 10 patients on the basis of the different perioperative nutrition modalities. Group A patients were fed by so-called uninterrupted enteral nutrition, which means without interruption from the day before surgery with a nutritional solution delivered via a nasojejunal tube. The patients in group B were submitted to hepatic resection with parenteral nutritional support. Liver resection had to consist in resection of at least 30% of the parenchyma in non-cirrhotic patients or in segmental resection in cirrhotic ones. Ten milliliter blood samples were harvested before operation, and 10, 30 and 60 min after declamping and at 24 h. Interleukin 6 and a-tumour necrosis factor values were detected in blood samples. The values of C reactive protein and of prealbumin were recorded at 72 h postoperatively. We also evaluated postoperative complications, resumption of bowel movements, oral intake of nourishment, and patient discharge. Values in blood samples in the two groups showed a statistically significant difference in interleukin 6 values only after 24 h (10 min: group A 121 +/- 25.3, group B 156 +/- 31.4; after 24 h: group A 31.5 +/- 12, group B 105.1 +/- 24.1), while the a-tumour necrosis factor assay showed no significant difference between the two groups. However, there was an appreciably longer hospital stay (group A 10.9 +/- 3.1 days (range: 7-21 days), group B 13.2 +/- 2.7 days (range: 8-19 days) (P < 0.02) and a quicker resumption of bowel movements in group A. The data available show that uninterrupted enteral nutrition produces a modulation of the cytokine response following portal clamping. A lower cytokine activation cascade reduces the impact of the action of cytokines on the hepatic parenchyma with consequent enhancement of the hepatic Kupffer cell component. These factors thus substantially reduce the length of the patient's hospital stay and consequently the cost of medical care.

Influence of enteral nutrition on cytokine response in resective liver surgery

Enteral nutrition (EN) is increasingly used to minimize the rate of septic complications related to bacterial translocation, due to its effectiveness and low cost. Bengmark's self-propelling auto-positioning feeding tube (SPT) absorbs and uses gut motility for rapid transport to the upper small intestine, thereby allowing uninterrupted EN both in surgical and critically ill patients. We report on our experience with 175 SPTs applied over the period from December 1996 to February 2000, and analyse the safety, compliance, and indications of SPT in surgical and ICU practice. Open study: feasibility of insertion, time and rate of placement, compliance and complications related to the tube or to EN were studied. SPTs were successfully placed in 40 patients before liver resection, in 32 patients before extensive maxillo-facial surgery MFS and prior to colon resections in 10 cases. SPTs were also applied in 56 patients with acute vascular neurological diseases, 22 in pancreatic diseases and in another 15 critically ill patients. 92.5% of SPT's crossed the pylorus, while only 7.5% stopped in the stomach and 3.4% in the duodenum; 89.14% reached the first jejunal loop. The tip of the tube reached its final position within a mean period of 5.2 hours, 8% instantly and all within 24 hours. Enteral nutrition was started immediately after introduction of the tube into the stomach. The compliance was excellent, even in maxillo-facial surgery patients: only 2/76 patients (2.6%) showed poor compliance. There were no cases of aspiration pneumonia or other complications related to SPT. Polymeric nutrition was usually supplied at a starting flow rate of 45 ml/hour and rapidly increasing over the following 48 h. Eleven patients experienced diarrhoea and 6 abdominal distension, leading to a temporary reduction of the EN flow rate. Clogging of the SPT occurred in 13 patients: 7/13 were cleansed with pancreatic enzymes, but 6 had to be replaced. SPT is ideal for intensive EN and is characterised by minimal complications and excellent patient compliance.

The Bengmark tube in surgical practice and in the critically ill patient

The concept of perioperative starvation requires an update on a more balanced physiological bias. The old British dictum "nil by mouth from midnight" is a thing of the past. We need to administer food and fluids as early as possible both before both before and after surgery and to avoid or reduce hospital infections. Resumption of bowel movements is very rapid, and the patients are fed and experience no thirst and thus have better compliance during their hospital stay. Moreover, the social cost is reduced. A short review of the rules of various Associations of Anaesthetists both in Europe and the US shows that today the starvation time is reduced, and re-feeding after surgery is implemented early. For clear fluids a 2-h period before surgery without ingestion of clear fluids is enough, whilst in most countries a 6-h period of starvation for solid foods is the rule, but if proper distinctions are made between the various nutrients given to the patients, this time could be reduced to 2-3 hours.

[What is new in fasting guidelines of surgical patients? Review of the literature].

Enteral nutrition, as demonstrated by the many published papers, is not only safer and cheaper than parenteral supply of nutrients, but modulates an exaggerated cytokine response related to surgical trauma that leads to an increase in intestinal permeability, bacterial translocation and infection. The aim of enteral nutrition is to reduce the impact of cytokines on surgical patients and the related infectious complications. Via the enteral route the nutrients can reach the bowel lumen where enterocytes draw upon their fuel, preserving the barrier effect and modulating the cytokine response. Parenteral supply does not achieve this target since the blood supply of nutrients is not as important as the luminal supply. It is only via the enteral supply route that we can preserve the barrier effect. Since the cytokine response sets in immediately after a trauma such as surgery, we implement uninterrupted enteral nutrition, which means before, during and after surgery, plus parenteral support till the full calorie intake is achieved. In a hepatic resection study, we have demonstrated that enteral nutrition modulates the interleukin-6 immunological response and shortens both the period to bowel movement resumption and the duration of hospital stay. Aggressive enteral nutrition has also been implemented in severe pancreatitis, allowing control of the disease without the onset of septic complications. The most important target is not to achieve full calorie intake rapidly, but to supply the enteric mucosa continuously with useful immuno-nutrients, such as glutamine and fibres, to preserve the barrier effect, the mucus layer, and immunological status of the mucosa. In this way we have obtained significant results in the surgical treatment of these patients, reducing the infection rate and hospital stay. New prospects may be,possible in the fight against surgical infections by adding probiotics to enteral nutrition in order to improve the microenvironment of the colon.

Perioperative enteral nutrition

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Influence of enteral nutrition on cytokine response in resective liver surgery

The Bengmark tube in surgical practice and in the critically ill patient

[What is new in fasting guidelines of surgical patients? Review of the literature].

Perioperative enteral nutrition