Paul A M van Leeuwen

VU University Medical Center, Amsterdam, North Holland, Netherlands

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Publications (250)1056.91 Total impact

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    ABSTRACT: Asymmetric dimethylarginine (ADMA) is an analog of arginine and functions as an endogenous inhibitor of the nitric oxide synthase, which forms nitric oxide. Nitric oxide is crucial for perfusion of vital organs and is an important signaling agent in the development of critical illness. The role of ADMA in the pathophysiological mechanisms underlying critical illness is widely studied in the last decades, and recently it has become clear that ADMA should not be overlooked by clinicians working at the ICU. The aim of this review is to describe new insights into the role of ADMA in critical illness and its clinical relevance. High levels of ADMA are found in critically ill patients, because of higher levels of protein methylation, increased rate of protein turnover, decreased activity of dimethylamine dimethylaminohydrolase, and impaired renal and hepatic clearance capacity. These high levels are an independent risk factor for cardiac dysfunction, organ failure, and ICU mortality. The arginine : ADMA ratio in particular is of clinical importance and the restoration of this ratio is expedient to restore several functions that are disturbed during critical illness. Elevated ADMA levels occur in critically ill patients, which is detrimental for morbidity and mortality. The arginine : ADMA ratio should be restored to maintain nitric oxide production and therewith improve the clinical outcome of the patient.
    Current opinion in clinical nutrition and metabolic care. 11/2013;
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    Nikki Buijs, Mechteld Vermeulen, Paul van Leeuwen
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    ABSTRACT: To the Editor: Heyland et al. (April 18 issue)(1) have shown that glutamine supplementation (approximately 65 g daily) of a diet that does not supply adequate energy (910 kcal) or protein (45 g) did not affect clinical outcome and increased mortality. However, the addition of a supplement that constituted 60% of total dietary protein introduced an amino acid imbalance with the potential for toxicity. Other, similar examples, such as the lack of arginine as part of dietary protein(2) or the use of essential amino acids only(3) in otherwise complete diets, have been shown to produce hyperammonemia in humans. Furthermore, glutamine . . .
    New England Journal of Medicine 08/2013; 369(5):482-5. · 51.66 Impact Factor
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    ABSTRACT: Delayed gastric emptying limits the administration of enteral nutrition, leading to malnutrition, which is associated with higher mortality and morbidity. Currently available prokinetics have limitations in terms of sustained efficacy and side effects. To summarise the mechanisms of action and to discuss the possible utility of gastrointestinal hormones to prevent or treat delayed gastric emptying in critically ill patients. We searched PubMed for articles discussing 'delayed gastric emptying', 'enteral nutrition', 'treatment', 'gastrointestinal hormones', 'prokinetic', 'agonist', 'antagonist' and 'critically ill patients'. Motilin and ghrelin receptor agonists initiate the migrating motor complex in the stomach, which accelerates gastric emptying. Cholecystokinin, glucagon-like peptide-1 and peptide YY have an inhibiting effect on gastric emptying; therefore, antagonising these gastrointestinal hormones may have therapeutic potential. Other gastrointestinal hormones appear less promising. Manipulation of endogenous secretion, physiological replacement and administration of gastrointestinal hormones in pharmacological doses is likely to have therapeutic potential in the treatment of delayed gastric emptying. Future challenges in this field will include the search for candidates with improved selectivity and favourable kinetic properties.
    Alimentary Pharmacology & Therapeutics 07/2013; · 4.55 Impact Factor
  • Nutritional Therapy and Metabolism 07/2013;
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    ABSTRACT: Pharmaco-nutrients have beneficial effects on protective and immunological mechanisms in patients undergoing surgery, which are important for recovery after injury and in combating infectious agents. The aim of this review article was to outline the potential of the administration of nutritional substrates to surgical patients and the underlying mechanisms that make them particularly important in peri-operative care. Surgery causes a stress response, which has catabolic effects on the body's substrate stores. The amino acid glutamine is a stimulating agent for immune cells. It activates protective mechanisms through its role as a precursor for antioxidants and it improves the barrier function of the gut. Arginine also enhances the function of the immune system, since it is the substrate for T-lymphocytes. Furthermore, n-3 PUFA stabilise surgery-induced hyper-inflammation. Taurine is another substrate that may counteract the negative effects of surgical injury on acid-base balance and osmotic balance. These pharmaco-nutrients rapidly become deficient under the influence of surgical stress. Supplementation of these nutrients in surgical patients may restore their protective and immune-enhancing actions and improve clinical outcome. Moreover, pre-operative fasting is still common practice in the Western world, although fasting has a negative effect on the patient's condition and the recovery after surgery. This may be counteracted by a simple intervention such as administering a carbohydrate-rich supplement just before surgery. In conclusion, there are various nutritional substrates that may be of great value in improving the condition of the surgical patient, which may be beneficial for post-operative recovery.
    Proceedings of The Nutrition Society 02/2013; · 3.67 Impact Factor
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    ABSTRACT: Loss of body tissue resulting in undernutrition can be caused by reduced food intake, altered metabolism, ageing, and physical inactivity. The predominant cause of undernutrition before cardiac operations is unknown. First, we explored the association of reduced food intake and inactivity with undernutrition in patients before elective cardiac operations. Second, we assessed if adding these reversible, cause-based items to the nutritional screening process improved diagnostic accuracy. A prospective observational study was performed. Undernutrition was defined by low fat-free mass index (LFFMI) measured by bioelectrical impedance spectroscopy and/or unintended weight loss (UWL). Reduced food intake was defined as the patient having a decreased appetite over the previous month. Patients admitted to hospital preoperatively were assumed to be less physically active than patients awaiting cardiac operations at home. Using these data, we developed a new tool and compared this with an existing cardiac surgery-specific tool (Cardiac Surgery-Specific Malnutrition Universal Screening Tool [CSSM]). A total of 325 patients who underwent open cardiac operations were included. Reduced food intake and inactivity were associated with undernutrition (odds ratio [OR], 4.2; 95% confidence interval [CI], 2.1-8.5 and OR, 2.0; 95% CI, 1.0-4.0). Reduced food intake and inactivity were integrated with body mass index (BMI) and UWL into a new scoring system: the Cardiac Surgery-Specific Undernutrition Screening Tool (CSSUST). Sensitivity in identification of undernourished patients was considerably higher with the CSSUST (90%) than with the CSSM (71%) (receiver operating characteristic [ROC] curve-based area under the curve [AUC], 0.79; 95% CI, 0.73-0.86 and ROC AUC, 0.71; 95% CI, 0.63-0.80). Results suggest that reduced food intake and inactivity partly explain undernutrition before cardiac operations. Our new cause-based CSSUST, which includes reduced food intake and inactivity, is superior to existing tools in identifying undernutrition in patients undergoing cardiac operations.
    The Annals of thoracic surgery 02/2013; 95(2):642-7. · 3.74 Impact Factor
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    ABSTRACT: The patients’ condition prior to surgery is of major importance for clinical outcome. It is believed nowadays that artificial nutrition in the form of a preoperative drink may improve postoperative outcome. Until now, a clear overview concerning the effects of preoperative supplementation on patients’ well-being has been lacking. The aim of this review is to summarize the results of randomized clinical trials investigating the effects of different preoperative supplements such as carbohydrate (CHO)-rich beverages, oral nutritional supplements (ONSs), immunonutrition and lemonades on clinical, metabolic and immunological parameters. We reviewed the relevant articles published between 1995 and 2012. Preoperative CHO-rich drinks appear to be safe, do not affect gastric emptying time and switch the fasted state to a fed state. Moreover, a significant reduction of postoperative insulin resistance, an improved well-being of the patient and prevention of surgery-induced immunodepression was found. For ONSs, beneficial effects were found according to muscle metabolism and strength, glucose storage and cost-effectiveness. Preoperative supplementation of immunonutrition resulted in improved immune function, restricted inflammatory response after surgery, prevention of organ damage, improved nutritional status with subsequently decreased postoperative complication rates and reduced length of hospital stay. Preoperative oral supplements have beneficial effects on many aspects of patient’s well-being and recovery. Different supplements, preferably in combination with each other, can help to reduce postoperative complications after surgery and length of hospital stay. Nutritional support must not be overlooked when considering optimal surgical care. Keywords: Preoperative, Oral supplements, Surgery, Carbohydrates,
    CAB Reviews Perspectives in Agriculture Veterinary Science Nutrition and Natural Resources 01/2013;
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    ABSTRACT: BACKGROUND & AIMS: A carbohydrate (CHO) drink given preoperatively changes the fasted state into a fed state. The ESPEN guidelines for perioperative care include preoperative CHO loading and re-establishment of oral feeding as early as possible after surgery. An intestinal ischaemia reperfusion (IR) animal model was used to investigate whether preoperative CHO loading increases spontaneous postoperative food intake, intestinal barrier function and the catabolic response. METHODS: Male Wistar rats (n = 65) were subjected to 16 h fasting with ad libitum water and: A) sham laparotomy (Sham fasted, n = 24); B) intestinal ischaemia (IR fasted, n = 27); and C) intestinal ischaemia with preoperatively access to a CHO drink (IR CHO, n = 14). Spontaneous food intake, intestinal barrier function, insulin sensitivity, intestinal motility and plasma amino acids were measured after surgery. RESULTS: The IR CHO animals started eating significantly earlier and also ate significantly more than the IR fasted animals. Furthermore, preoperative CHO loading improved the intestinal barrier function, functional enterocyte metabolic mass measured by citrulline and reduced muscle protein catabolism, as indicated by normalization of the biomarker 3-methylhistidine. CONCLUSIONS: Preoperative CHO loading improves food intake, preserves the GI function and reduces the catabolic response in an IR animal model. These findings suggest that preoperative CHO loading preserves the intestinal function in order to accelerate recovery and food intake. If this effect is caused by overcoming the fasted state or CHO loading remains unclear.
    Clinical nutrition (Edinburgh, Scotland) 11/2012; · 3.27 Impact Factor
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    ABSTRACT: Despite the development of consensus-based frameworks to define cancer cachexia, the validity and usefulness of these frameworks are relatively unknown. The aim of the present study was to study the presence of pre-cachexia and cachexia in patients with stage III non-small-cell lung carcinoma (NSCLC) by using a cancer-specific framework and a general framework for cachexia, and to explore the prognostic value of pre-cachexia and cachexia. In forty patients at diagnosis of stage III NSCLC, weight loss, fat-free mass, handgrip strength, anorexia and serum biochemistry, assessed before the first chemotherapy, were used to define 'cancer cachexia' or 'cachexia'. The cancer-specific framework also classified for pre-cachexia and refractory cachexia. Additionally, quality of life was assessed by the European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire C30. Groups were compared using independent t tests, ANOVA, Kaplan-Meier and Cox survival analyses. Based on the cancer-specific framework, pre-cachexia was present in nine patients (23 %) and cancer cachexia was present in seven patients (18 %). Cancer cachexia was associated with a reduced quality of life (P = 0·03) and shorter survival (hazard ratio (HR) = 2·9; P = 0·04). When using the general framework, cachexia was present in eleven patients (28 %), and was associated with a reduced quality of life (P = 0·08) and shorter survival (HR = 4·4; P = 0·001). In conclusion, pre-cachexia and cachexia are prevalent in this small population of patients at diagnosis of stage III NSCLC. For both frameworks, cachexia appears to be associated with a reduced quality of life and shorter survival. Further studies are warranted to more extensively explore the validity and prognostic value of these new frameworks in cancer patients.
    The British journal of nutrition 11/2012; · 3.45 Impact Factor
  • Clinical Nutrition Supplements 09/2012; 7(1):19.
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    ABSTRACT: An important complication of allo-SCT is GVHD, which commonly affects the skin, liver and digestive tract. Clinical symptoms of GVHD of the digestive tract (GVHD-DT) include excessive diarrhoea, abdominal pain and cramps, nausea and vomiting, gastrointestinal bleeding, dysphagia, and weight loss. Treatment is complicated and regarding nutritional support, only a few guidelines are available. Our aim was to critically appraise the literature on nutritional assessment, nutritional status and nutritional support for patients with GVHD-DT. Evidence shows that GVHD-DT is often associated with malnutrition, protein losing enteropathy, magnesium derangements, and deficiencies of zinc, vitamin B(12) and vitamin D. Limited evidence exists on derangements of magnesium, resting energy expenditure, bone mineral density and pancreatic function, and some beneficial effects of n-3 polyunsaturated fatty acids and pancreatic enzyme replacement therapy. Expert opinions recommend adequate amounts of energy, at least 1.5 g protein/kg body weight, supplied by total parenteral nutrition in cases of severe diarrhoea. When diarrhoea is <500 mL a day, a stepwise oral upgrade diet can be followed. No studies exist on probiotics, prebiotics, dietary fibre and immunonutrition in GVHD-DT patients. Future research should focus on absorption capacity, vitamin and mineral status, and nutritional support strategies.Bone Marrow Transplantation advance online publication, 9 July 2012; doi:10.1038/bmt.2012.124.
    Bone marrow transplantation 07/2012; · 3.00 Impact Factor
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    ABSTRACT: BACKGROUND & AIMS: In cardiac surgical patients, undernutrition increases the risk of adverse clinical outcome. We investigated whether the bioelectrical impedance phase angle is an indicator of undernutrition and clinical outcome in cardiac surgery. METHODS: In 325 cardiac surgical patients, we prospectively analyzed the associations between a preoperative low phase angle, measured by bioelectrical impedance spectroscopy, and well-established indicators of undernutrition such as body mass index (kg/m(2)), unintended weight loss, and fat free mass index (kg/m(2)), and muscle strength (handgrip strength (kg)), immune function (C-reactive protein and albumin), and adverse clinical outcomes. RESULTS: A low phase angle (<5.38°) was present in 29.8% (n = 96) of the patients, and was associated with low body mass index (p < 0.001), low fat free mass index (p < 0.001), and less handgrip strength (p = 0.063), but not with unintended weight loss or immune function. Furthermore, a preoperative low phase angle was associated with a prolonged intensive care unit and hospital stay (adj. hazard ratio: 0.68; 95%CI: 0.49-0.94; p = 0.020 and adj. hazard ratio: 0.74; 95%CI: 0.55-0.99; p = 0.048, respectively). CONCLUSIONS: A preoperative low bioelectrical impedance phase angle is associated with undernutrition, and increases the risk of adverse clinical outcome after cardiac surgery. The phase angle might help to identify undernourished cardiac surgical patients.
    Clinical nutrition (Edinburgh, Scotland) 05/2012; · 3.27 Impact Factor
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    ABSTRACT: BACKGROUND: Poor nutrition status is considered a risk factor for postoperative complications in the adult population. In elderly patients, who often have a poor nutrition status, this relationship has not been substantiated. Thus, the aim of this systematic review was to assess the merit of preoperative nutrition parameters used to predict postoperative outcome in elderly patients undergoing general surgery. METHODS: A systematic literature search of 10 consecutive years, 1998-2008, in PubMed, EMBASE, and Cochrane databases was performed. Search terms used were nutrition status, preoperative assessment, postoperative outcome, and surgery (hip or general), including their synonyms and MeSH terms. Limits used in the search were human studies, published in English, and age (65 years or older). Articles were screened using inclusion and exclusion criteria. All selected articles were checked on methodology and graded. RESULTS: Of 463 articles found, 15 were included. They showed profound heterogeneity in the parameters used for preoperative nutrition status and postoperative outcome. The only significant preoperative predictors of postoperative outcome in elderly general surgery patients were serum albumin and ≥10% weight loss in the previous 6 months. CONCLUSIONS: This systematic review revealed only 2 preoperative parameters to predict postoperative outcome in elderly general surgery patients: weight loss and serum albumin. Both are open to discussion in their use as a preoperative nutrition parameter. Nonetheless, serum albumin seems a reliable preoperative parameter to identify a patient at risk for nutrition deterioration and related complicated postoperative course. (JPEN J Parenter Enteral Nutr. XXXX;xx:xx-xx).
    Journal of Parenteral and Enteral Nutrition 05/2012; · 2.49 Impact Factor
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    ABSTRACT: BACKGROUND & AIMS: Both undernutrition - low fat free mass (FFM) - and obesity - high fat mass (FM) - have been associated with adverse outcome in cardiac surgical patients. However, whether there is an additional effect on outcome of these risk factors present at the same time, that is sarcopenic obesity (SO), is unknown. Furthermore, the association between SO and muscle function is unidentified. METHODS AND RESULTS: In 325 cardiac surgical patients, we prospectively analysed the association between preoperative FFM and FM, measured by bioelectrical impedance spectroscopy, and postoperative adverse outcomes, and their correlation with muscle function - handgrip strength (HGS). SO was associated with postoperative infections (28.2% vs. 5.3%, adj. odds ratio (OR): 7.9; 95% confidence interval (CI): 1.2-54.1; p=0.04). Further, a low FFM index (FFMI; kgm(-2)) was associated with postoperative infections (18.5% vs. 4.7%, adj. OR: 6.6; 95% CI: 1.7-25.2; p=0.01) while a high FM index (FMI; kgm(-2)) was not. Both components of SO, FFMI and FMI, correlated with HGS (FFMI: r=0.570; p<0.001, FMI: r=-0.263; p<0.001). CONCLUSION: SO is associated with an increased occurrence of adverse outcome after cardiac surgery. Our results suggest an additional risk of a low FFMI and high FMI present at the same time. Furthermore, SO is characterised by less muscle function. We advocate determining body composition in cardiac surgical patients to classify and treat undernourished patients, in particular those who are also obese.
    Nutrition, metabolism, and cardiovascular diseases: NMCD 03/2012; · 3.52 Impact Factor
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    ABSTRACT: Our objective was to investigate effects of an oral nutritional supplement containing n-3 polyunsaturated fatty acids (FAs) on quality of life, performance status, handgrip strength and physical activity in patients with non-small cell lung cancer (NSCLC) undergoing multimodality treatment. In a double-blind experiment, 40 patients with stage III NSCLC were randomised to receive 2 cans/day of a protein- and energy-dense oral nutritional supplement containing n-3 polyunsaturated FAs (2.02 g eicosapentaenoic acid+0.92 g docosahexaenoic acid/day) or an isocaloric control supplement, during multimodality treatment. Quality of life, Karnofsky Performance Status, handgrip strength and physical activity (by wearing an accelerometer) were assessed. Effects of intervention were analysed by generalised estimating equations. P-values <0.05 were regarded as statistically significant. The intervention group reported significantly higher on the quality of life parameters, physical and cognitive function (B=11.6 and B=20.7, P<0.01), global health status (B=12.2, P=0.04) and social function (B=22.1, P=0.04) than the control group after 5 weeks. The intervention group showed a higher Karnofsky Performance Status (B=5.3, P=0.04) than the control group after 3 weeks. Handgrip strength did not significantly differ between groups over time. The intervention group tended to have a higher physical activity than the control group after 3 and 5 weeks (B=6.6, P=0.04 and B=2.5, P=0.05). n-3 Polyunsaturated FAs may beneficially affect quality of life, performance status and physical activity in patients with NSCLC undergoing multimodality treatment.
    European journal of clinical nutrition 03/2012; 66(3):399-404. · 3.07 Impact Factor
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    ABSTRACT: Proteolytic activity in whole blood may lead to release of the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA). We investigated the role of the human erythrocyte in storage and generation of ADMA in healthy controls (n = 36) and critically ill patients (n = 38). Both free and total (sum of free and protein-incorporated) ADMA were measured. Upon incubation of intact erythrocytes with extracellular ADMA (0 to 40 μmol/l), equilibrium between intra- and extracellular ADMA was reached within 3 h. Compared with controls, patients had significantly higher basal concentrations of ADMA in plasma (0.88 ± 0.75 vs. 0.41 ± 0.07 μmol/l) and erythrocytes (1.28 ± 0.55 vs. 0.57 ± 0.14 μmol/l). Intracellular and plasma ADMA were significantly correlated in the patient group only (r = 0.834). Upon lysis, followed by incubation at 37°C for 2 h, free ADMA increased sevenfold (to 8.60 ± 3.61 μmol/l in patients and 3.90 ± 0.78 μmol/l in controls). In lysates of controls, free ADMA increased further to 9.85 ± 1.35 μmol/l after 18 h. Total ADMA was 15.43 ± 2.44 μmol/l and did not change during incubation. The increase of free ADMA during incubation corresponded to substantial release of ADMA from the erythrocytic protein-incorporated pool (21.9 ± 4.6% at 2 h and 60.8 ± 7.6% at 18 h). ADMA was released from proteins other than hemoglobin, which only occurred after complete lysis and was blocked by combined inhibition of proteasomal and protease activity. Neither intact nor lysed erythrocytes mediated degradation of free ADMA. We conclude that intact erythrocytes play an important role in storage of ADMA, whereas upon erythrocyte lysis large amounts of free ADMA are generated by proteolysis of methylated proteins, which may affect plasma levels in hemolysis-associated diseases.
    AJP Heart and Circulatory Physiology 02/2012; 302(8):H1762-70. · 3.63 Impact Factor
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    ABSTRACT: Taurine is involved in numerous biological processes. However, taurine plasma level decreases in response to pathological conditions, suggesting an increased need. Knowledge on human taurine metabolism is scarce and only described by arterial-venous differences across a single organ. Here we present taurine organ fluxes using arterial-venous concentration differences combined with blood flow measurements across the 3 major organ systems involved in human taurine metabolism in patients undergoing hepatic surgery. In these patients, we collected blood from an arterial line, portal vein, hepatic vein, and renal vein, and determined blood flow of the hepatic artery, portal vein, and renal vein using Doppler ultrasound. Plasma taurine was determined by high-performance liquid chromatography, and net organ fluxes and fractional extraction rates were calculated. Seventeen patients were studied. No differences were found between taurine concentrations in arterial, portal venous, hepatic venous, and renal venous plasma. The only significant finding was a release of taurine by the portally drained viscera (P = .04). Our data show a net release of taurine by the gut. This probably is explained by the enterohepatic cycle of taurine. Future studies on human taurine metabolism are required to determine whether taurine is an essential aminosulfonic acid during pathological conditions and whether it should therefore be supplemented.
    Metabolism: clinical and experimental 02/2012; 61(7):1036-40. · 3.10 Impact Factor
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    ABSTRACT: The objective of this study was to compare the quick-and-easy undernutrition screening tools, ie, Short Nutritional Assessment Questionnaire and Malnutrition Universal Screening Tool, in patients undergoing cardiac surgery with respect to their accuracy in detecting undernutrition measured by a low-fat free mass index (FFMI; calculated as kg/m(2)), and secondly, to assess their association with postoperative adverse outcomes. Between February 2008 and December 2009, a single-center observational cohort study was performed (n=325). A low FFMI was set at ≤14.6 in women and ≤16.7 in men measured using bioelectrical impedance spectroscopy. To compare the accuracy of the Malnutrition Universal Screening Tool and Short Nutritional Assessment Questionnaire in detecting low FFMI sensitivity, specificity, and other accuracy test characteristics were calculated. The associations between the Malnutrition Universal Screening Tool and Short Nutritional Assessment Questionnaire and adverse outcomes were analyzed using logistic regression analyses with odds ratios and 95% confidence intervals (CI) presented. Sensitivity and receiver operator characteristic-based area under the curve to detect low FFMI were 59% and 19%, and 0.71 (95% CI: 0.60 to 0.82) and 0.56 (95% CI: 0.44 to 0.68) for the Malnutrition Universal Screening Tool and Short Nutritional Assessment Questionnaire, respectively. Accuracy of the Malnutrition Universal Screening Tool improved when age and sex were added to the nutritional screening process (sensitivity 74%, area under the curve: 0.72 [95% CI: 0.62 to 0.82]). This modified version of the Malnutrition Universal Screening Tool, but not the original Malnutrition Universal Screening Tool or Short Nutritional Assessment Questionnaire, was associated with prolonged intensive care unit and hospital stay (odds ratio: 2.1, 95% CI: 1.3 to 3.4; odds ratio: 1.6, 95% CI: 1.0 to 2.7). The accuracy to detect a low FFMI was considerably higher for the Malnutrition Universal Screening Tool than for the Short Nutritional Assessment Questionnaire, although still marginal. Further research to evaluate the modified version of the Malnutrition Universal Screening Tool, ie, the cardiac surgery-specific Malnutrition Universal Screening Tool, is needed prior to implementing.
    Journal of the American Dietetic Association 12/2011; 111(12):1924-30. · 3.80 Impact Factor
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    ABSTRACT: In shock, organ perfusion is of vital importance because organ oxygenation is at risk. NO, the main endothelial-derived vasodilator, is crucial for organ perfusion and coronary patency. The availability of NO might depend on the balance between a substrate (arginine) and an inhibitor (asymmetric dimethylarginine; ADMA) of NO synthase. Therefore, we investigated the relationship of arginine, ADMA and their ratio with circulatory markers, disease severity, organ failure and mortality in shock patients. In forty-four patients with shock (cardiogenic n 17, septic n 27), we prospectively measured plasma arginine and ADMA at intensive care unit admission, Acute Physiology and Chronic Health Evaluation (APACHE) II-(predicted mortality) and Sequential Organ Failure Assessment (SOFA) score, and circulatory markers to investigate their relationship. Arginine concentration was decreased (34·6 (SD 17·9) μmol/l) while ADMA concentration was within the normal range (0·46 (SD 0·18) μmol/l), resulting in a decrease in the arginine:ADMA ratio. The ratio correlated with several circulatory markers (cardiac index, disseminated intravascular coagulation, bicarbonate, lactate and pH), APACHE II and SOFA score, creatine kinase and glucose. The arginine:ADMA ratio showed an association (OR 0·976, 95 % CI 0·963, 0·997, P = 0·025) and a diagnostic accuracy (area under the curve 0·721, 95 % CI 0·560, 0·882, P = 0·016) for hospital mortality, whereas the arginine or ADMA concentration alone or APACHE II-predicted mortality failed to do so. In conclusion, in shock patients, the imbalance of arginine and ADMA is related to circulatory failure, organ failure and disease severity, and predicts mortality. We propose a pathophysiological mechanism in shock: the imbalance of arginine and ADMA contributes to endothelial and cardiac dysfunction resulting in poor organ perfusion and organ failure, thereby increasing the risk of death.
    The British journal of nutrition 12/2011; 107(10):1458-65. · 3.45 Impact Factor

Publication Stats

4k Citations
1,056.91 Total Impact Points


  • 2002–2013
    • VU University Medical Center
      • • Department of Surgery
      • • Department of Internal Medicine
      Amsterdam, North Holland, Netherlands
  • 1995–2013
    • VU University Amsterdam
      • • Department of Surgery
      • • Department of Clinical Chemistry
      Amsterdamo, North Holland, Netherlands
  • 1988–2013
    • University of Amsterdam
      • Faculty of Medicine AMC
      Amsterdam, North Holland, Netherlands
    • Maastricht Universitair Medisch Centrum
      Maestricht, Limburg, Netherlands
  • 1999–2012
    • Academisch Medisch Centrum Universiteit van Amsterdam
      • Department of Surgery
      Amsterdamo, North Holland, Netherlands
  • 2010
    • University Medical Center Utrecht
      • Department of Metabolic and Endocrine Disease
      Utrecht, Provincie Utrecht, Netherlands
  • 2008
    • National and Kapodistrian University of Athens
      • Division of Surgery V
      Athens, Attiki, Greece
    • KU Leuven
      • Department of Cellular and Molecular Medicine
      Leuven, VLG, Belgium
  • 1986–2008
    • Maastricht University
      • Algemene Heelkunde
      Maastricht, Provincie Limburg, Netherlands
  • 2006
    • Medisch Centrum Alkmaar
      • Department of Surgery
      Alkmaar, North Holland, Netherlands
  • 2005
    • Erasmus MC
      Rotterdam, South Holland, Netherlands
  • 1997–2000
    • Freie Universität Berlin
      Berlín, Berlin, Germany
  • 1991
    • Brigham and Women's Hospital
      • Department of Medicine
      Boston, MA, United States
    • Memorial Sloan-Kettering Cancer Center
      • Department of Surgery
      New York City, NY, United States