Peri-operative oral immunonutrition in malnourished ovarian cancer patients assessed by the nutritional risk screening.

OBJECTIVES: Aim of this study was to determine whether peri-operative immunonutrition can decrease complications and the length of stay (LOS) in malnourished ovarian cancer patients. STUDY DESIGN: Patients suspicious for advanced ovarian cancer before histopathological diagnosis and a nutritional risk score (NRS) ≥ 3 received oral immune-modulating diets (IMDs) for 5 days pre-operative and at least 5 days post-operative. Parameters for clinical outcome were infectious and non-infectious complications during hospital stay, and time of hospitalization. The results were compared with malnourished ovarian cancer patients of a previous study without any additive nutritional support (standard clinical diet/nutrition). RESULTS: The infectious and non-infectious complication rate in the interventional group (IG) N = 28 was 42.9%, similar to the control group (CG) N = 19 with 42.1%, whereas the rate of infectious complications in the IG (21.4%) was slightly lower compared to the CG (26.3%). The median LOS of the IG was 18 days, and therefore, longer than LOS of the CG (15 days). Regarding the patients' compliance pre-operative 78.6% of the patients took the IMDs in an optimal and sufficient amount. Whereas after surgery, only eight (28.6%) patients were able to take IMDs in optimal and sufficient amount. CONCLUSIONS: The current study showed no improvement of the complication rate or the time of hospitalization due to additional peri-operative immunonutrition in malnourished ovarian cancer patients. However, a trend towards the reduction of infectious complications could be seen in the IG.

Effects of malnutrition on complication rates, length of hospital stay, and revenue in elective surgical patients in the G-DRG-system.

OBJECTIVE: Malnutrition is known to independently affect patient outcomes. The aim of this study was to investigate the prevalence of patients at risk for malnutrition in an elective surgery patient cohort and to analyze the effects of malnutrition on morbidity, mortality, and hospital length of hospital (LOS). Furthermore, we aimed to evaluate the economic effect of a diligent coding of malnutrition, as a side diagnosis, in a simulation of the German Diagnosis-Related Group system. METHODS: The nutritional status of 1244 patients undergoing elective surgery was standardized on the day of admission by the Nutritional Risk Screening (NRS) 2002. To quantify the influence of malnutrition on revenue, the real DRGs of all patients were grouped. In simulation, an appropriate International Classification of Diseases code was used as a secondary diagnosis for all malnourished patients based on the NRS rating. A multivariate logistic regression analysis and a Cox regression were performed to identify potential confounders and to determine the adjusted effect of nutritional status on the occurrence of complications and hospital LOS. RESULTS: The prevalence of patients at risk for malnutrition (NRS ≥3) was 24.1% (300 of 1244). These patients showed a significant increase in hospital LOS (13 versus 7 d). Additionally, postoperative complications were significantly higher in this group (7.23% versus 6.91%). Including malnutrition in the Diagnosis-Related Group coding system resulted in a reimbursement of €1979.67 per patient at risk for malnutrition and a total reimbursement of €79,186.73 for all patients at risk for malnutrition in the present study. CONCLUSION: Establishment of a structured, comprehensive assessment of the nutritional status of hospitalized patients can repetitiously identify patients at risk for malnutrition. Additionally, the diligent codification of malnutrition can lead to cost compensation in the German Diagnosis-Related Group system.

Malnutrition and clinical outcome in gynecologic patients.

OBJECTIVES: An association between malnutrition and poor patient outcome has been established in various medical fields, but there is a general lack of data on the prevalence of malnutrition among gynecologic patients. Therefore an assessment of malnutrition is needed to detect malnourished patients in gynecology and initiate nutritional therapy if needed. STUDY DESIGN: Between 2011 and 2012 at our Gynecologic Department of a German University Hospital, 397 patients were evaluated regarding the risk of malnutrition and occurrence of complications during the time of hospitalization. The Nutritional Risk Screening (NRS) 2002 system was used to estimate the risk level for malnutrition. Of the 397 patients, 336 received surgery and 61 were treated conservatively. Patients were included independently of surgical intervention or age. The parameters for the clinical outcome were complications and time of hospitalization. RESULTS: A severe risk of malnutrition was diagnosed in 142 patients (35.8%) according to an NRS score of ≥3. Furthermore, a significantly higher complication rate among those patients who were at risk for malnutrition (NRS 1-2) (7.8%) or who were malnourished (NRS ≥3) (22.8%) was found (p<0.001 χ(2)). Regarding the length of stay (LOS) in hospital, the medial hospitalization time increased from 7 to 10 days when patients were malnourished (NRS score ≥3) (p<0.001). CONCLUSIONS: Malnutrition occurs frequently among gynecologic patients. Adequate perioperative nutritional supportive therapy should be considered in malnourished patients to improve their clinical outcome.

Use of gastric residual volume to guide enteral nutrition in critically ill patients: a brief systematic review of clinical studies.

OBJECTIVE: In critically ill patients, the optimal procedure to monitor upper gastrointestinal function is controversial. Several authors have proposed gastric residual volume (GRV) as a tool to guide enteral nutrition. The aim of this contribution is to briefly discuss corresponding studies. METHODS: We electronically searched MEDLINE, EMBASE, and CINAHL for studies relevant to the subject. RESULTS: Six randomized controlled trials (RCTs) and six prospective observational studies were identified. Each analyzed different thresholds of GRV to guide enteral nutrition and to avoid complications (e.g., vomiting, aspiration, nosocomial pneumonia) in artificially ventilated patients. Due to heterogeneity in outcome measures, patient populations, type and diameter of feeding tubes, and randomization procedures, combination of the results of the six RCTs into a meta-analysis was not appropriate. High-quality RCTs studying medical patients could not demonstrate an association between complication rate and the magnitude of GRV. The only observational study that adjusted results to potential confounders and that studied surgical patients found, however, that the frequency of aspiration increased significantly if a GRV > 200 mL was registered more than once. CONCLUSION: For mechanically ventilated patients with a medical diagnosis at admission to the intensive care unit, monitoring of GRV appears unnecessary to guide nutrition. Surgical patients might profit, however, from a low GRV threshold (200 mL).

Nutritional screening for risk prediction in patients scheduled for extra-abdominal surgery.

OBJECTIVE: The Nutritional Risk Screening-2002 (NRS-2000) is currently recommended by the European Society of Parenteral and Enteral Nutrition as a screening tool in hospitalized patients. However, for preoperative risk prediction, the usefulness of this tool is uncertain and may depend on the type of surgical disease. The present study investigated the relative prognostic importance of the NRS-2002 and of established medical and surgical predictors for postoperative complications in patients scheduled for non-abdominal procedures. METHODS: In this prospective observational study, we enrolled 581 patients scheduled for elective non-abdominal surgery. Data were collected on nutritional variables (body mass index, weight loss, and food intake), age, gender, type of surgery, extent of surgery, underlying disease, American Society of Anesthesiologists class, and comorbidity. We also evaluated a modification of the NRS-2002 (ordinal graduation according to <2 or ≥2 points) and the importance of individual parameter values. Relative complication rates were calculated with generalized linear models and cumulative proportional odds models. RESULTS: Forty-four patients (7.6%) sustained at least one postoperative complication. The frequency of this event increased significantly with a higher NRS-2002 score. However, the model that performed the best (sensitivity 81.8%, specificity 78.6%) included the modified NRS-2002 graduation (<2 or ≥2 points) and other factors such as American Society of Anesthesiologists class, the duration of the procedure, and the need for red blood cell transfusion. CONCLUSION: In surgical patients with non-abdominal diseases, a modified NRS-2002 classification may be required to preoperatively identify patients at a high nutritional risk. The NRS-2002 alone is insufficient to precisely predict complications.

Albumin synthesis rates are not responsive to hyperglycemic hyperinsulinemia in postoperative patients.

BACKGROUND: Insulin regulates albumin synthesis in vitro and in various experimental models. The current study was undertaken to determine the effects of a physiologic hyperinsulinemia on albumin synthesis in postoperative patients in whom plasma albumin concentrations are decreased. METHODS: Studies were performed in postabsorptive patients after major abdominal operations. Mass spectrometry techniques were used to directly determine the incorporation rate of 1-[(13)C]-leucine into albumin. Consecutive blood samples were taken during a continuous isotope (D-Glc) infusion (0.16 µmol/kg/min). Isotopic enrichments were determined at baseline (period I) and after a 4-hour D-glucose (D-Glc) infusion at currently recommended rates (170 mg/kg/h, n = 10) or after infusion of saline (control group, n = 8) (period II). RESULTS: After D-Glc infusion, plasma insulin concentrations increased significantly (period I, 6.6 ± 1.8 µU/mL; period II, 21.4 ± 2.1 µU/mL; P < .01). In contrast, plasma insulin concentration remained constant in control patients (period I, 3.8 ± 0.9 µU/mL(-1); period II, 5.9 ± 1.1 µU/mL; not significant vs period I, but P < .005 vs the corresponding value at the end of period II in the control group). Hyperinsulinemia was without effect on fractional albumin synthesis (period I, 12.8% ± 1.9%/d; period II, 11.9% ± 1.9%/d; not significant), and synthesis rates corresponded to those measured in controls (period I, 13.0% ± 1.2%/d; period II, 12.1% ± 0.1%/d; not significant vs period I and vs D-Glc infusion). CONCLUSIONS: A standard D-Glc infusion is insufficient to increase albumin synthesis in postoperative patients.

Differential regulation of protein synthesis in hepatic and intestinal tissues by amino acids: studies in patients recovering from major abdominal operations.

BACKGROUND: Currently, it is unknown whether recommended rates of amino acid infusion are sufficient to support hepatic or intestinal protein synthesis specifically after operation. The objective of the study was to determine the effect of a standard parenteral amino acid dose on serum albumin and ileum protein synthetic rates in postabsorptive patients recovering from major abdominal operations. METHODS: Mass spectrometry techniques were used to determine the incorporation rate of 1-[(13)C]-leucine directly into ileum protein and into serum albumin. Consecutive sampling from the same ileum and from blood was performed during continuous isotope infusion (0.16 micromol kg(-1) min(-1)). Isotopic enrichments were determined at baseline (period I) and after a 4-h infusion of amino acids (0.067 g kg(-1) h(-1), n = 8) or after infusion of saline (control group, n = 8) (period II). RESULTS: In controls, protein synthesis in the ileum declined during prolonged isotope infusion (period I: 1.14 +/- 0.13 %/h, period II: 0.47 +/- 0.14 %/h, P < .001). In contrast, during amino acid infusion, protein synthesis in the ileum remained constant (period I: 1.14 +/- 0.17 %/h, period II: 0.89 +/- 0.10 %/h not significant [n.s.] vs period I, but P < .05 vs period II in the control group). Amino acid infusion was without effect when fractional or absolute rates of serum albumin synthesis were studied. CONCLUSION: Currently, the recommended dosages for parenteral amino acid infusion are sufficient to support small-bowel protein synthesis during recovery from major abdominal operation but are ineffective with respect to the formation of new serum albumin.

Prospective assessment of malnutrition in urologic patients.

OBJECTIVES: The association between malnutrition and poor patient outcome has been established for different medical fields. There is a general lack of data on the prevalence of malnutrition in urologic patients. An assessment of malnutrition is needed to raise awareness of this condition and to initiate nutrition therapy if needed. METHODS: The nutritional state of 897 patients was assessed prospectively using the Nutritional Risk Screening 2002 (NRS) at a urologic department. Recruitment started in January 2007 and closed in July 2007. Of the 897 patients, 751 were men (84%) and 146 (16%) were women. The median age was 66 years (range 18-98). Of the 897 patients, 441 presented with benign disease and 456 with malignant disease. RESULTS: A severe risk of malnutrition was diagnosed in 144 patients (16%; NRS score >or=3). The NRS score was 0, 1-2, and 3-5 in 45, 708, and 144 patients, respectively. Age and malignant disease were significant risk factors for malnutrition (P < .001). Also, the type of surgery was significantly associated with the risk of malnutrition (P < .001). Sex and body mass index had no significant influence. Of the patients with an NRS score of >or=3, 94% presented with >or=1 of the 3 risk factors: older age, open surgery, and/or malignant disease (P < .001). CONCLUSIONS: In the present study, 16% of urologic patients were at a severe risk of malnutrition according to the NRS 2002. Older age, type of procedure, and malignant disease proved to be significant factors for a greater risk of malnutrition. Adequate nutritional supportive therapy should be considered in these patients to optimize their clinical outcome.

Dynamics of albumin synthesis after major rectal operation.

BACKGROUND: Major abdominal operations were found to be associated with long-lasting metabolic changes, such as accelerated release of stress hormones and carbohydrate turnover. It is unknown currently whether acute changes of hepatic protein metabolism persist in a similar way. We wanted to determine the long-term dynamics of albumin synthesis and its relationship to whole body protein breakdown and albumin concentration after major rectal operations. METHODS: We used stable isotope tracer techniques to determine albumin synthesis and whole body protein breakdown (rate of appearance of leucine, Ra) in postoperative patients about 1 week after low anterior rectal resection and also during convalescence (about 4 months after operation), and in healthy controls. Consecutive blood sampling was carried out during continuous isotope infusion (1-[(13)C]-leucine, 0.16 micromol/kg min). RESULTS: Serum albumin concentrations were close to the lower normal limit in patients early after operation but were comparable to controls in convalescent patients. Simultaneously, albumin synthesis was increased in the early postoperative phase (0.53 +/- 0.0.5%/h) compared with convalescent patients (0.32 +/- 0.04) and controls (0.28 +/- 0.04) (P < .01 each). A significant inverse correlation could be found between plasma albumin concentration and corresponding rates of albumin synthesis. Early after operation patients showed an increased leucine Ra (3.25 +/- 0.23 micromol/kg min) that was greater than that of convalescent patients (2.37 +/- 0.06 micromol/kg min, P < .05). Leucine Ra in both patient groups were greater than the rates in controls (2.01 +/- 0.07 micromol/kg min, P < .01) Albumin synthesis correlated weakly with whole body protein breakdown rate. CONCLUSIONS: Albumin synthesis and total body protein breakdown are increased after major abdominal operation, but albumin synthesis returns to control values only during convalescence. Hypoalbuminemia after rectal operations may be associated with high rates of albumin synthesis and is, therefore, not necessarily an indicator of insufficient hepatic function or poor nutritional status in that particular situation.

The effect of hyperglycemic hyperinsulinemia on small-intestinal mucosal protein synthesis in patients after surgical stress.

Hyperglycemic hyperinsulinemia cannot stimulate intestinal protein synthesis in healthy individuals but does so in conditions characterized by an altered somatotropic axis such as diabetes. Only in a state of growth hormone resistance (high growth hormone but low insulin like growth factor [IGF-1] concentrations), extra insulin may acutely reverse the impaired, growth-hormone-induced IGF-1 release, thereby exerting anabolic actions at the intestinal tract. Growth hormone resistance can be also found in patients after surgical stress. Therefore, we wanted to test the hypothesis whether hyperglycemic hyperinsulinemia would stimulate ileal protein synthesis in the latter condition. Mass spectrometry techniques (capillary gas chromatography/combustion isotope ratio mass spectrometry) were used to directly determine the incorporation rate of 1-[(13)C]-leucine into ileal mucosal protein. All subjects had an ileostomy, which allowed easy access to the ileal mucosa, and consecutive sampling from the same tissue was performed during continuous isotope infusion (0.16 mumol/kg min). Isotopic enrichments and fractional protein synthesis were determined at baseline (period I) and after a 4-hour glucose infusion (170 mg/kg/h) or after infusion of saline (control group) (period II). In controls, ileal protein synthesis declined significantly during prolonged isotope infusion (period I: 1.11 +/- 0.14%/h, period II: 0.39 +/- 0.13%/h, p < .01). In contrast, ileal protein synthesis remained constant during glucose infusion (period I: 1.32 +/- 0.35%/h, period II: 1.33 +/- 0.21%/h, n.s. vs period I, but p < .005 vs the corresponding value at the end of period II in the control group). Using the continuous tracer infusion technique, ileal protein synthesis seemingly declines over a short time in control subjects. We found evidence that this artificial decline was due to mass effects of a rapidly turning over mucosa protein pool in which an isotopic plateau was reached during the experiment and of which the size amounted to approximately 4% of the total mixed protein pool. Maintenance of ileal protein synthesis during glucose infusion therefore indicates a rise of ileal protein synthesis in a slowly turning over protein pool. This effect in postsurgical patients would be compatible with the concept of intestinal insulin action to depend on the specific clinical state (eg, growth hormone resistance).

Effect of amino acid infusion on human postoperative colon protein synthesis in situ.

BACKGROUND: Amino acids are an integral part of parenteral nutrition because of their anabolic action helping to conserve body protein after surgical stress. At the gastrointestinal tract, an adequate supply of amino acids may be particularly important because of the gut's high rate of protein turnover, cell division, and proliferation. However, no information is available about the effects of amino acids on human intestinal protein metabolism after surgery. METHODS: Studies were performed in postabsorptive patients 8-10 days after major abdominal surgery. Mass spectrometry techniques (capillary gas chromatography/combustion isotope ratio mass spectrometry) were used to directly determine the incorporation rate of 1-[13C]-leucine into colon mucosal protein. All subjects had a colostomy, which allowed easy access to the colon mucosa, and consecutive sampling from the same tissue was performed during continuous isotope infusion (0.16 micromol/kg min). Isotopic enrichments were determined at baseline and after a 4-hour infusion of amino acids or after infusion of saline (control group). RESULTS: Compared with baseline, infusion of amino acids reduced fractional colon protein synthesis significantly by -29.2 +/- 8.3%. This decrease was also significantly different from the corresponding (insignificant) change during saline infusion (+19.4 +/- 26.9%, p < .05 vs amino acid group). CONCLUSIONS: After surgery, an amino acid infusion acutely reduces postoperative colon protein synthesis. This effect possibly may be attributed to interactions of specific amino acids (glutamine) with an altered intestinal immune system and enterocyte activity.

Isolation of plasma albumin by ethanol extraction is inappropriate for isotope ratio measurements during the acute phase response.

Isolation of high-purity albumin from plasma is essential to study albumin kinetics in vivo with tracer techniques. Because of its simplicity ethanol extraction has been repeatedly used for albumin purification. However, it cannot be excluded that this single-step procedure completely prohibits contamination by other proteins, especially those known to be produced at an accelerated rate during the acute phase response. In the present study, we wanted to examine the reliability of ethanol extraction in different clinical conditions and to study the effects of potential impurities on albumin enrichment during stable isotope tracer studies. SDS-PAGE revealed a contaminating protein band at about 25,000 Da in healthy subjects and postoperative patients during the acute phase response, but not in critically ill patients. According to densitometry about 8% of proteins after ethanol extraction were contaminants. To examine potential contaminant effects on tracer enrichment 1-[13C]-leucine was given to healthy subjects and postoperative patients. Blood samples were taken after various amounts of time, and albumin enrichments (tracer/tracee ratios) were determined from isotope ratios obtained by mass spectrometry. Irrespective of the magnitude of tracer enrichment, postoperative tracer/tracee ratios were significantly higher (on average +10%) in samples exclusively analysed by ethanol extraction than in samples which had undergone additional electrophoretic purification. No significant effect of the contaminant was seen in healthy subjects. N-terminal protein sequencing revealed contaminants to mainly consist of apolipoprotein A-1. Its physiology and pathophysiology may sufficiently explain its variable effects of albumin enrichment. Our findings suggest that exclusive ethanol extraction is inappropriate for albumin isolation in tracer studies performed during the acute phase response. Ethanol extraction may also not be advisable in all other situations known to be associated with a rise in apolipoprotein A-1 turnover.

Use of the molecular adsorbent recycling system in the treatment of postoperative hepatic failure and septic multiple organ dysfunction--preliminary results.

PURPOSE OF THE STUDY: Molecular adsorbent recycling system (MARS) has been applied successfully in patients with a variety of liver diseases. However, preliminary results in patients with multiple organ failure (MOF) and sepsis were disappointing, possibly because the number of applied MARS cycles was too low. To determine potential effects of prolonged MARS treatment in patients with postsurgical MOF we evaluated five postoperative patients with acute liver failure and septic multiple organ dysfunction in a retrospective observational study. METHODS: MARS cycles (13.4+/-1.9) were applied during an average time period of 17.2+/-5.2 days. Fresh frozen plasma, thrombocyte units and blood units were transfused to maintain pre-MARS Quick values and thrombocyte counts, and to keep the hemoglobin concentration above 8 g/dl. MAIN FINDINGS: Plasma bilirubin concentrations declined significantly during treatment. In contrast, ammonia concentration remained constant, and parameters of the clotting system (Quick value) did not get better or even worsened (partial thromboplastin time) despite significantly increasing the substitution frequency of coagulatory factors. Due to poor clotting, we observed significant bleeding complications during MARS therapy causing a simultaneous rise in the number of transfused blood units. All patients demonstrated persistent, severe abdominal infection during MARS therapy. After discontinuing MARS treatment because of insufficient efficiency, all patients died of progressive septic organ malfunction. CONCLUSION: Our preliminary findings do not support use of MARS in patients with postoperative hepatic failure and progressive septic multiple organ dysfunction, particularly if the septic focus cannot be eliminated. If MARS is still applied, special attention should be paid to simultaneous clotting disorders and bleeding complications.

Effect of tumor removal on mucosal protein synthesis in patients with colorectal cancer.

It is currently controversial whether mucosal hyperproliferation is involved in colorectal cancerogenesis. The purpose of the present study was to examine protein synthetic rate as an indicator of potential tissue proliferation in grossly normal rectal mucosa from cancer-bearing subjects and to compare this rate with that in mucosa from subjects posttumor removal. Six postabsorptive patients with localized rectal cancer and five postsurgical control subjects received a primed constant infusion of [1-(13)C]leucine (0.16 micromol/kg min, 9.6 micromol/kg prime). Forceps biopsies from the mucosa were taken after 3 and 6 h. Protein synthesis was calculated from protein-bound leucine enrichment (determined by capillary GC-combustion IRMS) and from the enrichment of free intracellular leucine (determined by GC-quadrupole MS). In cancer-bearing subjects, mucosal protein synthesis amounted to 1.28 +/- 0.24%/h. This rate was significantly higher (P < 0.05) than the corresponding rate of mucosa from patients after cancer removal (0.69 +/- 0.09%/h). These findings do not support the concept that colorectal cancer originates from a proliferative disease of the whole colon. Increased mucosal protein synthesis appears to depend on the presence of the tumor itself and should therefore be considered a secondary phenomenon.