Geert Wanten

Lipid emulsions in parenteral nutrition of intensive care patients: current thinking and future directions

BackgroundEnergy deficit is a common and serious problem in intensive care units and is associated with increased rates of complications, length of stay, and mortality. Parenteral nutrition (PN), either alone or in combination with enteral nutrition, can improve nutrient delivery to critically ill patients. Lipids provide a key source of calories within PN formulations, preventing or correcting energy deficits and improving outcomes.DiscussionIn this article, we review the role of parenteral lipid emulsions (LEs) in the management of critically ill patients and highlight important biologic activities associated with lipids. Soybean-oil-based LEs with high contents of polyunsaturated fatty acids (PUFA) were the first widely used formulations in the intensive care setting. However, they may be associated with increased rates of infection and lipid peroxidation, which can exacerbate oxidative stress. More recently developed parenteral LEs employ partial substitution of soybean oil with oils providing medium-chain triglycerides, ω-9 monounsaturated fatty acids or ω-3 PUFA. Many of these LEs have demonstrated reduced effects on oxidative stress, immune responses, and inflammation. However, the effects of these LEs on clinical outcomes have not been extensively evaluated.ConclusionsOngoing research using adequately designed and well-controlled studies that characterize the biologic properties of LEs should assist clinicians in selecting LEs within the critical care setting. Prescription of PN containing LEs should be based on available clinical data, while considering the individual patient’s physiologic profile and therapeutic requirements.

Taurolidine lock is highly effective in preventing catheter-related bloodstream infections in patients on home parenteral nutrition: a heparin-controlled prospective trial.

BACKGROUND & AIMS Catheter-related bloodstream infections remain the major threat for Home Parenteral Nutrition programs. Taurolidine, a potent antimicrobial agent, holds promise as an effective catheter lock to prevent such infections. Aim of the present study was to compare taurolidine with heparin, the most frequently used lock, in this respect in these high-risk patients. METHODS Thirty patients from one referral centre for intestinal failure were enrolled after developing a catheter-related bloodstream infection. Following adequate treatment, either with or without a new access device (tunneled catheter or subcutaneous port), these patients were randomized to continue Home Parenteral Nutrition using heparin (n = 14) or taurolidine (n = 16) as catheter lock. RESULTS Whereas in controls 10 re-infections were observed, in the taurolidine group during 5370 catheter days only 1 re-infection occurred (mean infection-free survival 175 (95% CI 85-266; heparin) versus 641 (95% CI 556-727; taurolidine) days; log-rank p < 0.0001). No side effects or catheter occlusions were reported in either group. Moreover, after crossing-over of 10 patients with infections on heparin to taurolidine, only 1 new infection was observed. CONCLUSION Taurolidine lock dramatically decreased catheter-related bloodstream infections when compared with heparin in this high-risk group of Home Parenteral Nutrition patients.

18F-FDG PET/CT for Detection of Metastatic Infection in Gram-Positive Bacteremia

The timely detection of metastatic infectious foci in gram-positive bacteremia is crucial, because these foci often require prolonged antibiotic treatment or drainage. The diagnosis of metastatic infectious foci is difficult because localizing symptoms are often absent. We investigated whether 18F-FDG PET/CT was able to detect such foci and whether detection influenced clinical outcome. Methods: One hundred fifteen nonneutropenic patients with gram-positive bacteremia were prospectively included. Patients with positive blood cultures growing Staphylococcus aureus, Streptococcus species, or Enterococcus species were eligible when a risk factor for developing metastatic infectious foci was present. 18F-FDG PET/CT was performed within 2 wk after the first positive blood culture. Abnormal 18F-FDG uptake had to be confirmed by radiologic, microbiologic, or pathologic studies. Results were compared with a matched historical control group of 230 patients in whom no 18F-FDG PET/CT was performed. Results: Significantly more patients were diagnosed with metastatic foci in the study group (67.8% vs. 35.7%). Of the imaging investigations performed, 18F-FDG PET/CT was the first to delineate infectious foci in 35 patients (30%). In the remaining 70%, either symptoms on physical examination or other imaging techniques first revealed infectious foci. The sensitivity, specificity, negative predictive value, and positive predictive value of 18F-FDG PET/CT were 100%, 87%, 100%, and 89%, respectively. Relapse rates decreased from 7.4% to 2.6% among study patients (P = 0.09) and from 8.9% to 1.4% in patients with S. aureus (P = 0.04). Overall mortality after 6 mo decreased from 32.2% to 19.1% in the 18F-FDG PET/CT group (P = 0.014). Conclusion: In the diagnostic work-up of high-risk patients with gram-positive bacteremia, 18F-FDG PET/CT is a valuable technique that results in lower mortality rates. In patients with S. aureus bacteremia, relapse rates decreased significantly after the addition of 18F-FDG PET/CT.

Influence of structurally different lipid emulsions on human neutrophil oxygen radical production

The aim of this study was to evaluate immunomodulatory properties of lipid emulsions applied in parenteral nutrition by measuring neutrophil oxygen radical production (the ‘respiratory burst’) after lipid incubation.

Medium-chain triglyceride containing lipid emulsions increase human neutrophil beta2 integrin expression, adhesion and degranulation

BACKGROUND To test the hypothesis that lipid emulsions with different triglyceride structures have distinct immunomodulatory properties, we analyzed human neutrophil adhesion and degranulation after lipid incubation. METHODS Neutrophils, isolated from the blood of 10 healthy volunteers, were incubated in medium or physiologic (2.5 mmol/L) emulsions containing long-chain (LCT), medium-chain (MCT), mixed LCT/MCT, or structured (SL) triglycerides. Expression of adhesion molecules and degranulation markers was evaluated by flow cytometry. Also, functional adhesion was investigated by means of a flow cytometric assay using fluorescent beads coated with the integrin ligand intercellular adhesion molecule (ICAM)-1. RESULTS Although LCT and SL had no effect, LCT/MCT significantly increased expression of the beta2 integrins lymphocyte-function-associated antigen 1 (+18%), macrophage antigen 1 (+387%), p150,95 (+82%), and (alphaDbeta2 (+230%). Degranulation marker expression for azurophilic (CD63, +210%) and specific granules (CD66b, +370%) also significantly increased, whereas L-selectin (CD62L, -70%) decreased. The effects of LCT/MCT were mimicked by the MCT emulsion. ICAM-1 adhesion (% beads bound) was increased by LCT/MCT (34% +/- 4%), whereas LCT (19% +/-3%) and SL (20% +/- 2%) had no effect compared with medium (17% +/- 3%). CONCLUSIONS LCT/MCT and MCT, contrary to LCT and SL emulsions, increased neutrophil beta2 integrin expression, adhesion, and degranulation. Apart from other emulsion constituents, triglyceride chain length might therefore be a key feature in the interaction of lipid emulsions and the phagocyte immune system.

Metastatic infectious disease and clinical outcome in Staphylococcus aureus and Streptococcus species bacteremia

Early detection of metastatic infection in patients with Gram-positive bacteremia is important as morbidity and mortality are higher in the presence of these foci, probably due to incomplete eradication of clinically silent foci during initial treatment. We performed a prospective study in 115 patients with Staphylococcus aureus or Streptococcus species bacteremia with at least 1 risk factor for the development of metastatic foci, such as community acquisition, treatment delay, persistently positive blood cultures for >48 hours, and persistent fever >72 hours after initiation of treatment. An intensive search for metastatic infectious foci was performed including 18F-fluorodeoxyglucose-positron emission tomography in combination with low-dose computed tomography scanning for optimizing anatomical correlation (FDG-PET/CT) and echocardiography in the first 2 weeks of admission. Metastatic infectious foci were detected in 84 of 115 (73%) patients. Endocarditis (22 cases), endovascular infections (19 cases), pulmonary abscesses (16 cases), and spondylodiscitis (11 cases) were diagnosed most frequently. The incidence of metastatic infection was similar in patients with Streptococcus species and patients with S. aureus bacteremia. Signs and symptoms guiding the attending physician in the diagnostic workup were present in only a minority of cases (41%). An unknown portal of entry, treatment delay >48 hours, and the presence of foreign body material were significant risk factors for developing metastatic foci. Mean C-reactive protein levels on admission were significantly higher in patients with metastatic infectious foci (74 vs. 160 mg/L). FDG-PET/CT was the first technique to localize metastatic infectious foci in 35 of 115 (30%) patients. As only a minority of foci were accompanied by guiding signs or symptoms, the number of foci revealed by symptom-guided CT, ultrasound, and magnetic resonance imaging remained low. Mortality tended to be lower in patients without complicated infection compared to those with metastatic foci (16% vs. 25%, respectively). Five of 31 patients (16%) without proven metastatic foci died. In retrospect, 3 of these 5 patients likely had metastatic foci that could not be diagnosed while alive. In patients with Gram-positive bacteremia and a high risk of developing complicated infection, a structured protocol including echocardiography and FDG-PET/CT aimed at detecting metastatic infectious foci can contribute to improved outcome. AbbreviationsCI = confidence intervalCRP = C-reactive proteinCT = computed tomographyFDG-PET/CT = 18F-fluorodeoxyglucose-positron emission tomography in combination with low-dose computed tomographyMRI = magnetic resonance imagingTEE = transesophageal echocardiographyTTE = transthoracic echocardiography

Phagocytosis and killing of Candida albicans by human neutrophils after exposure to structurally different lipid emulsions.

BACKGROUND To test the hypothesis that structurally different lipid emulsions have distinct immune-modulating properties, we analyzed the elimination of Candida albicans by neutrophils after exposure to various emulsions. METHODS Neutrophils from 8 volunteers were incubated in physiologic 5 mmol/L emulsions containing long-chain- (LCT), medium-chain- (MCT), mixed LCT/MCT-, alpha-tocopherol-enriched LCT/MCT (LCT/MCT-E), or structured lipids (SL). After washing, the neutrophils were incubated with C. albicans. Phagocytosis was measured as the number of yeast-associated neutrophils relative to the total neutrophil count. Killing was expressed as the percentage of Candida survival relative to the initial yeast cell count. RESULTS No significant differences in yeast-neutrophil association could be demonstrated after neutrophil incubation in various lipid emulsions or medium, after correction for non-specific adhesion. However, although Candida survival after 1 hour incubation with non-lipid-exposed neutrophils amounted to 53% +/- 11% and was not influenced by LCT (60% +/- 11%), LCT/MCT (78% +/- 7%), LCT/MCT-E (72% +/- 12%), and SL (67% +/- 6%), pure MCT (70% +/- 13%) significantly impaired the killing capacity of neutrophils. CONCLUSIONS The decreased killing capacity of neutrophils after exposure to medium-chain fatty acid-containing emulsions and the absence of this effect with LCT suggest that lipid emulsions influence the elimination of C. albicans depending on the triglyceride chain length.

Nutritional status, food intake, and dysphagia in long-term survivors with head and neck cancer treated with chemoradiotherapy: a cross-sectional study.

The aim of this study was to evaluate nutritional status, food intake, and dysphagia in long‐term head and neck cancer survivors.

Managing adult patients who need home parenteral nutrition

#### Summary points Patients with intestinal failure—defined as failure to maintain protein-energy balance, fluid balance, electrolyte balance, or micronutrient balance when eating a normal diet as a result of surgery, bowel disease, or a congenital defect—require parenteral nutrition (see box 1 for full definition). Since its introduction in 1967, intravenous nutrition administered in the home has been the mainstay of treatment for patients with long term intestinal failure. Home parenteral nutrition is a clinically important way to supply certain patients with their long term nutritional requirements, but high rates of complications are a worry. Although patients’ survival largely depends on the underlying disease, adverse events related to venous access and metabolic disturbances associated with the delivery of parenteral nutrition may compromise quality of life. We provide an overview of the indications for and delivery of home parenteral nutrition and discuss advances that promise to limit complications and improve treatment outcomes. This review is based largely on recent guidelines and on observational evidence. #### Sources and selection criteria We searched PubMed for articles in English on home parenteral nutrition. We also consulted guidelines issued by the European Society for Clinical Nutrition and Metabolism (ESPEN) that are based on grade A (randomised controlled trials), grade B (non-randomised studies), and grade C (expert opinion) evidence.1 #### Box 1 Definition of intestinal failure and short bowel syndrome2 Intestinal failure is caused …

Taurolidine lock is superior to heparin lock in the prevention of catheter related bloodstream infections and occlusions.

Background and Aims Patients on home parenteral nutrition (HPN) are at risk for catheter-related complications; mainly infections and occlusions. We have previously shown in HPN patients presenting with catheter sepsis that catheter locking with taurolidine dramatically reduced re-infections when compared with heparin. Our HPN population therefore switched from heparin to taurolidine in 2008. The aim of the present study was to compare long-term effects of this catheter lock strategy on the occurrence of catheter-related bloodstream infections and occlusions in HPN patients. Methods Data of catheter-related complications were retrospectively collected from 212 patients who received HPN between January 2000 and November 2011, comprising 545 and 200 catheters during catheter lock therapy with heparin and taurolidine, respectively. We evaluated catheter-related bloodstream infection and occlusion incidence rates using Poisson-normal regression analysis. Incidence rate ratios were calculated by dividing incidence rates of heparin by those of taurolidine, adjusting for underlying disease, use of anticoagulants or immune suppressives, frequency of HPN/fluid administration, composition of infusion fluids, and duration of HPN/fluid use before catheter creation. Results Bloodstream infection incidence rates were 1.1/year for heparin and 0.2/year for taurolidine locked catheters. Occlusion incidence rates were 0.2/year for heparin and 0.1/year for taurolidine locked catheters. Adjusted incidence ratios of heparin compared to taurolidine were 5.9 (95% confidence interval, 3.9–8.7) for bloodstream infections and 1.9 (95% confidence interval, 1.1–3.1) for occlusions. Conclusions Given that no other procedural changes than the catheter lock strategy were implemented during the observation period, these data strongly suggest that taurolidine decreases catheter-related bloodstream infections and occlusions in HPN patients compared with heparin.