000068
10.3205/000068
urn:nbn:de:0183-0000683
Review Article
Non-surgical oncology – Guidelines on Parenteral Nutrition, Chapter 19
Nichtchirurgische Onkologie – Leitlinie Parenterale Ernährung, Kapitel 19
Arends
Arends
J.
J
Dept. of Medical Oncology, Tumour Biology Center, University of Freiburg, Germany
author
Zuercher
Zuercher
G.
G
Dept. of Internal Medicine I, University of Freiburg, Germany
author
Dossett
Dossett
A.
A
Dept. of Medical Oncology, Tumour Biology Center, University of Freiburg, Germany
author
Fietkau
Fietkau
R.
R
Depts. Paediatric Surgery and Radiation Therapy, University of Rostock, Germany
author
Hug
Hug
M.
M
Pharmacy, University Hospital Freiburg, Germany
author
Schmid
Schmid
I.
I
Dept. Metabolic Diseases & Nutritional Medicine, Dr. von Hauner Children's Hospital, University of Munich, Germany
author
Shang
Shang
E.
E
Dept Surgery, University Hospital of Mannheim, Germany
author
Zander
Zander
A.
A
Dept. of Oncology and Haematology, University of Hamburg, Germany
author
Working group for developing the guidelines for parenteral nutrition of The German Association for Nutritional Medicine
Working group for developing the guidelines for parenteral nutrition of The German Association for Nutritional Medicine
author
German Medical Science GMS Publishing House
Düsseldorf
610
tumour
radiotherapy
chemotherapy
stem cell transplantation
Tumor
Radiotherapie
Chemotherapie
Stammzelltransplantation
Special Issue
20090114
20091118
engl
1612-3174
7
GMS German Medical Science
GMS Ger Med Sci
09
Ein reduzierter Ernährungszustand ist mit einer eingeschränkten Prognose und verminderter Lebensqualität assoziiert. Patienten mit aktiver Tumorerkrankung haben häufig eine unzureichende Nährstoffaufnahme. Der Ruhe-Energieumsatz kann im Vergleich zum Erwartungswert unverändert, gesteigert oder vermindert sein. Bei manifesten Tumorerkrankungen kommt es in unterschiedlichem Ausmaß zu systemischen proinflammatorischen Prozessen mit sekundären Auswirkungen auf alle wesentlichen Stoffwechselwege. Durch eine parenterale Ernährung (PE) soll der Ernährungszustand stabilisiert und ein fortschreitender Gewichtsverlust verhindert oder reduziert werden. Weitere Ziele sind der Erhalt oder eine Verbesserung der Lebensqualität und eine Erhöhung der Effektivität sowie eine Reduktion von Nebenwirkungen der antitumoralen Therapie. Prinzipiell sind die Indikationen für eine PE bei Tumorpatienten identisch mit den Indikationen bei Patienten mit gutartigen Erkrankungen, wobei bei Tumorpatienten eine orale oder enterale Nahrungszufuhr immer vor einer PE eingesetzt werden sollte. Bei möglicher oraler oder enteraler Zufuhr ergibt sich ein kombiniertes Ernährungskonzept. Für die optimale Energie- und Nährstoffzufuhr onkologischer Patienten, besonders für die ausschließliche künstliche Ernährung, gibt es keine allgemein akzeptierten Standards. Der generelle Einsatz einer PE begleitend zum Strahlentherapieverfahren oder zur Chemotherapie ist nicht sinnvoll, ist jedoch indiziert bei chronischer schwerer radiogener Enteritis oder nach allogener Transplantation wegen einer ausgeprägten Mukositis und GvH-bedingten Gastrointestinalschäden mit besonderer Rücksicht auf das erhöhte Blutungs- und Infektionsrisiko. In der Sterbephase ist keine PE erforderlich.
Reduced nutritional state is associated with unfavourable outcomes and a lower quality of life in patients with malignancies. Patients with active tumour disease frequently have insufficient food intake. The resting energy expenditure in cancer patients can be increased, decreased, or remain unchanged compared to predicted values. Tumours may result in varying degrees of systemic pro-inflammatory processes with secondary effects on all significant metabolic pathways. Therapeutic objectives are to stabilise nutritional state with oral/enteral nutrition and parenteral nutrition (PN) and thus to prevent or reduce progressive weight loss. The maintenance or improvement of quality of life, and the increase in the effectiveness and a reduction in the side-effects of a<![CDATA[nt</PlainText></TextGroup>it<TextGroup><PlainText>umo</PlainText></TextGroup>r therapy are further objectives. Indications for PN in tumour patients are essentially identical to those in patients with benign illnesses, with preference given to oral or enteral nutrition when feasible. A combined nutritional concept is preferred if oral or enteral nutrition are possible but not sufficient. There are generally no accepted standards for ideal energy and nutrient intakes in oncological patients, particularly when exclusive artificial nutrition is administered. The use of PN as a general accompaniment to radiotherapy or chemotherapy is not indicated, but PN is indicated in chronic severe radiogenic enteritis or after allogenic transplantation with pronounced mucositis or GvH-related gastrointestinal damage for prolonged periods, with particular attention to increased risk of bleeding and infection. No PN is necessary in the terminal phase.</Pgraph>
</Abstract>
<TextBlock linked="yes" name="The nutritional state influences the clinical outcome">
<MainHeadline>The nutritional state influences the clinical outcome</MainHeadline>
<Pgraph>
<UnorderedList>
<ListItem level="1">Reduced nutritional state is associated with unfavourable outcomes and a lower quality of life in patients with malignancies (IIa).</ListItem>
</UnorderedList>
</Pgraph>
<SubHeadline>Commentary</SubHeadline>
<Pgraph>Adult tumour patients who have lost weight or are malnourished show an unfavorable outcome in longitudinal studies. The response to antitumor treatment is decreased while treatment-associated side effects are more frequent; physical performance and quality of life are compromised; overall survival is significantly shorter than in patients without weight loss <TextLink reference="1"></TextLink>, <TextLink reference="2"></TextLink>, <TextLink reference="3"></TextLink>, <TextLink reference="4"></TextLink>, <TextLink reference="5"></TextLink>, <TextLink reference="6"></TextLink>, <TextLink reference="7"></TextLink>, <TextLink reference="8"></TextLink>, <TextLink reference="9"></TextLink>, <TextLink reference="10"></TextLink>, <TextLink reference="11"></TextLink>. Cachexia is the most common cause of death in tumour patients other than sepsis <TextLink reference="12"></TextLink>.</Pgraph>
<Pgraph>In a recent study body nitrogen content was found to be the strongest predictor for protection against bone marrow toxicity during chemotherapy in patients with breast cancer <TextLink reference="13"></TextLink>.</Pgraph>
<Pgraph>The effect of malnutrition on the rate of cure in children with cancer is controversial. While a significantly lower rate of healing is reported in malnourished patients (Ib) <TextLink reference="14"></TextLink>, <TextLink reference="15"></TextLink>, <TextLink reference="16"></TextLink>, <TextLink reference="17"></TextLink>, <TextLink reference="18"></TextLink>, there appears to be no influence on patients’ survival (IIa) <TextLink reference="19"></TextLink>, <TextLink reference="20"></TextLink>, <TextLink reference="21"></TextLink>, <TextLink reference="22"></TextLink>. These differences depend on the various definitions of malnutrition, the type and extent of the tumour, tumour therapy, supportive measures and the socio-economic status of the family. Malnutrition is known to decrease immunocompetence (IIa) <TextLink reference="23"></TextLink>, <TextLink reference="24"></TextLink>, decrease the tolerance to chemotherapy (IIa) <TextLink reference="25"></TextLink> and increase the rate of infection (IIa) <TextLink reference="26"></TextLink>, <TextLink reference="27"></TextLink>. Information on organ dysfunction as a result of malnutrition in children with cancer is scarce. In malnourished children there is an increased risk of cardiomyopathy after the administration of anthracyclines (IV) <TextLink reference="28"></TextLink>.</Pgraph>
</TextBlock>
<TextBlock linked="yes" name="Influence of malignancies on energy expenditure">
<MainHeadline>Influence of malignancies on energy expenditure</MainHeadline>
<Pgraph>
<UnorderedList>
<ListItem level="1">Patients with active tumours frequently have insufficient food intake (II).</ListItem>
<ListItem level="1">The resting energy expenditure in cancer patients can be increased, decreased, or remain unchanged in comparison to the predicted value (II).</ListItem>
</UnorderedList>
</Pgraph>
<SubHeadline>Commentary</SubHeadline>
<Pgraph>Food intake is lower than the usual even in patients with early stage tumour disease, and there is often a large discrepancy between the actual energy and protein intake and the calculated requirements in advanced tumour stages <TextLink reference="10"></TextLink>, <TextLink reference="29"></TextLink>. </Pgraph>
<Pgraph>In approximately 25% of patients with active tumours, resting energy expenditure (REE), as measured by indirect calorimetry, is more than 10% above, and in another 25% more than 10% below the predicted value. A prediction as to the direction and extent of the deviation is not possible <TextLink reference="30"></TextLink>, <TextLink reference="31"></TextLink>. The mean value of total energy expenditure in cancer patients is similar to that of a healthy reference group <TextLink reference="31"></TextLink>, <TextLink reference="32"></TextLink>. Studies in patients with various tumour entities showed a normal REE in people with stomach or colorectal carcinomas, and an increased REE in patients with pancreatic or bronchial carcinomas <TextLink reference="33"></TextLink>, <TextLink reference="34"></TextLink>, <TextLink reference="35"></TextLink>, <TextLink reference="36"></TextLink>. More detailed investigations in patients with advanced bronchial and pancreatic carcinomas revealed an increased REE coupled with diminished physical activity and a slightly lower overall energy expenditure when compared to healthy subjects <TextLink reference="35"></TextLink>, <TextLink reference="36"></TextLink>.</Pgraph>
<Pgraph>Therefore, in adult patients normal energy expenditure should be assumed if the actual resting energy expendi<TextGroup><PlainText>tur</PlainText></TextGroup>e cannot be measured in individual cases. Formulae (i.e. Harris Benedict, cf. chapter “Energy expenditure and energy intake” (<Hyperlink href="http://www.egms.de/en/journals/gms/2009-7/000084.shtml">http://www.egms.de/en/journals/gms/2009-7/000084.shtml</Hyperlink>)) may be used to calculate the normal resting energy expenditure. In patients, the overall energy requirement is also determined by physical activity and may be estimated as 100–120% of REE (cf. chapters “Energy expenditure and energy intake” (<Hyperlink href="http://www.egms.de/en/journals/gms/2009-7/000084.shtml">http://www.egms.de/en/journals/gms/2009-7/000084.shtml</Hyperlink>) and “Neonatology/Paediatrics” (<Hyperlink href="http://www.egms.de/en/journals/gms/2009-7/000074.shtml">http://www.egms.de/en/journals/gms/2009-7/000074.shtml</Hyperlink>) for children’s energy expenditure).</Pgraph>
<Pgraph>Studies have shown that children with leukaemia have a near normal resting energy expenditure at diagnosis and during anti-cancer treatment <TextLink reference="24"></TextLink>, <TextLink reference="37"></TextLink>, <TextLink reference="38"></TextLink>, <TextLink reference="39"></TextLink>, <TextLink reference="40"></TextLink>. Resting energy expenditure, however, is increased in leukaemic children with large tumour mass <TextLink reference="38"></TextLink>, and in children with solid tumours <TextLink reference="24"></TextLink>, <TextLink reference="41"></TextLink>. However, the data are inconsistent. </Pgraph>
</TextBlock>
<TextBlock linked="yes" name="Malignancies may influence metabolic parameters">
<MainHeadline>Malignancies may influence metabolic parameters</MainHeadline>
<SubHeadline>Clinically-relevant metabolic changes </SubHeadline>
<Pgraph>Manifest tumours result in varying degrees of systemic pro-inflammatory processes with secondary effects on all significant metabolic pathways <TextLink reference="42"></TextLink>. A large body of data suggests that the primary reaction of the tumour-bearing host is to release cytokines, catabolic hormones and other regulatory peptides locally and systemically <TextLink reference="42"></TextLink>, <TextLink reference="43"></TextLink>, <TextLink reference="44"></TextLink>. </Pgraph>
<Pgraph>The resulting systemic inflammatory reaction contributes significantly to the loss of appetite <TextLink reference="45"></TextLink>, <TextLink reference="46"></TextLink> and weight <TextLink reference="47"></TextLink>, <TextLink reference="48"></TextLink>, <TextLink reference="49"></TextLink>, <TextLink reference="50"></TextLink>. These cytokine-induced metabolic changes prevent a recovery of body cell mass <TextLink reference="51"></TextLink>, and are associated with reduced life expectancy <TextLink reference="52"></TextLink> in cachectic patients <TextLink reference="52"></TextLink>, <TextLink reference="53"></TextLink>.</Pgraph>
<SubHeadline>Effects on carbohydrate metabolism</SubHeadline>
<Pgraph>
<UnorderedList>
<ListItem level="1">Insulin resistance and increased glucose production can often be detected in tumour patients (II). </ListItem>
</UnorderedList>
</Pgraph>
<SubHeadline>Commentary</SubHeadline>
<Pgraph>Impaired glucose tolerance due to insulin resistance is common in tumour patients <TextLink reference="54"></TextLink>. The plasma ratio of insulin to catabolic hormones is abnormal with typical findings of increased cortisol secretion and a decreased insulin-cortisol ratio <TextLink reference="44"></TextLink>, <TextLink reference="55"></TextLink>. This results in increased glucose turnover and gluconeogenesis <TextLink reference="43"></TextLink>. Concomitant medication with high-dose glucocorticoids intensifies these changes. </Pgraph>
<SubHeadline>Effects on lipid metabolism</SubHeadline>
<Pgraph>
<UnorderedList>
<ListItem level="1">Weight loss in cancer patients is accompanied by a loss of lipid stores and increased serum triglycerides. The ability to oxidise lipids is normal to increased (II).</ListItem>
</UnorderedList>
</Pgraph>
<SubHeadline>Commentary</SubHeadline>
<Pgraph>The reasons for changes in lipid metabolism have not yet been clearly determined <TextLink reference="44"></TextLink> although increased lipolysis is often observed <TextLink reference="56"></TextLink>, <TextLink reference="57"></TextLink>. Increased <TextLink reference="57"></TextLink>, <TextLink reference="58"></TextLink>, <TextLink reference="59"></TextLink> or at least normal <TextLink reference="60"></TextLink>, lipid oxidation is often detectable at the same time, while glucose oxidation is compromised. These observations may support the recommendation to increase the lipids to glucose ratio when composing nutrition for cancer patients.</Pgraph>
<SubHeadline>Effects on protein metabolism</SubHeadline>
<Pgraph>
<UnorderedList>
<ListItem level="1">Protein expenditure is usually increased, resulting in a loss of muscle mass and an increased production of acute phase proteins (II).</ListItem>
</UnorderedList>
</Pgraph>
<SubHeadline>Commentary</SubHeadline>
<Pgraph>While the underlying processes are complex, usually increases in overall body protein turnover and in proteolysis are measured <TextLink reference="43"></TextLink>, <TextLink reference="61"></TextLink>. The ATP consuming and ubiquitin-dependent proteolysis system of proteasomes is activated at an early stage <TextLink reference="62"></TextLink>, <TextLink reference="63"></TextLink>, <TextLink reference="64"></TextLink>. These changes are triggered by inflammatory mediators and, possibly, additional substances released by the tumour <TextLink reference="65"></TextLink>, <TextLink reference="66"></TextLink>.</Pgraph>
</TextBlock>
<TextBlock linked="yes" name="Treatment aims for parenteral nutrition (PN) in cancer patients">
<MainHeadline>Treatment aims for parenteral nutrition (PN) in cancer patients</MainHeadline>
<Pgraph>
<UnorderedList>
<ListItem level="1">PN should stabilise the nutritional state and prevent or reduce progressive weight loss (C). </ListItem>
<ListItem level="1">PN should maintain or improve the quality of life (C).</ListItem>
<ListItem level="1">PN might increase the effectivity and reduce the side-effects of anti-cancer therapies (C).</ListItem>
</UnorderedList>
</Pgraph>
<SubHeadline>Commentary</SubHeadline>
<Pgraph>After curative antitumour treatment, PN can enhance survival chances in patients with severe gastrointestinal defects e.g. with radiation enteritis <TextLink reference="67"></TextLink>. Due to the accompanying non-specific inflammatory processes in patients with active cancers anabolism usually cannot be achieved by only supplying energy and substrates <TextLink reference="44"></TextLink>, <TextLink reference="50"></TextLink>, <TextLink reference="51"></TextLink>. According to data collected on body compartments, artificial nutrition results in a stabilisation of or an increase in body weight <TextLink reference="68"></TextLink>, <TextLink reference="69"></TextLink>, <TextLink reference="70"></TextLink>, <TextLink reference="71"></TextLink> and body fat mass, while an improvement in lean body or muscle mass is observed only rarely <TextLink reference="72"></TextLink>.</Pgraph>
<Pgraph>Numerous studies reported a median overall survival of 50 to 150 days <TextLink reference="69"></TextLink>, <TextLink reference="70"></TextLink>, <TextLink reference="71"></TextLink>, <TextLink reference="73"></TextLink>, <TextLink reference="74"></TextLink>, <TextLink reference="75"></TextLink>, <TextLink reference="76"></TextLink>, <TextLink reference="77"></TextLink>, <TextLink reference="78"></TextLink> when using PN in patients with advanced cancer and chronic small bowel defects. In the majority of these patients weight <TextLink reference="69"></TextLink>, <TextLink reference="70"></TextLink>, <TextLink reference="71"></TextLink>, and parameters to measure quality of life may be stabilized <TextLink reference="69"></TextLink>, <TextLink reference="70"></TextLink>, <TextLink reference="71"></TextLink>, <TextLink reference="75"></TextLink>. The rate of PN-associated infectious complications is between 0.34 and 2.68 per 1000 catheter days <TextLink reference="74"></TextLink>, <TextLink reference="76"></TextLink>, <TextLink reference="77"></TextLink>, <TextLink reference="78"></TextLink>.</Pgraph>
<Pgraph>Orreval et al. reported that the provision of home PN was perceived as a positive alternative to progressive weight loss due to the inability to eat in a small group of patients with advanced tumours <TextLink reference="79"></TextLink>. </Pgraph>
<Pgraph>Meta-analyses indicate that PN may reduce postoperative complications in malnourished, but not in normally nourished, patients after extensive abdominal surgery <TextLink reference="80"></TextLink>. In contrast, only few studies have evaluated the influence of PN on the therapeutic effects of non-surgical oncology. Parenteral nutrition in orally nourished patients undergoing chemotherapy may increase body weight <TextLink reference="68"></TextLink> (Ib), but does not improve anticancer treatment <TextLink reference="68"></TextLink>, <TextLink reference="81"></TextLink> (Ib). The quality of these few studies, however, is restricted by the inhomogeneity of the patient groups and by the inclusion of patients without malnutrition or patients who were able to eat normal amounts of food <TextLink reference="81"></TextLink>.</Pgraph>
</TextBlock>
<TextBlock linked="yes" name="Indication for parenteral nutrition in cancer patients">
<MainHeadline>Indication for parenteral nutrition in cancer patients</MainHeadline>
<Pgraph>Indications for PN in tumour patients are essentially identical to those in patients with benign illnesses. Considering the limited data available in this area <TextLink reference="82"></TextLink>, <TextLink reference="83"></TextLink>, <TextLink reference="84"></TextLink>, <TextLink reference="85"></TextLink>, <TextLink reference="86"></TextLink>, <TextLink reference="87"></TextLink>, <TextLink reference="88"></TextLink> the following recommendations are given:</Pgraph>
<Pgraph>
<UnorderedList>
<ListItem level="1">PN is indicated if oral and enteral food intake <TextLink reference="83"></TextLink>, <TextLink reference="84"></TextLink> provide <500 kcal per day and this is expected to continue for >5 days, or for between 3 and 5 days in case of severe malnutrition, or if oral and enteral food intake reach <60% of calculated requirement and this is expected to last for 10–14 days in adult patients (C). </ListItem>
<ListItem level="1">PN should be commenced immediately when indicated, and increased to target dosages over 2–4 days if considered necessary (C). </ListItem>
<ListItem level="1">The amount of PN should supplement oral or enteral nutrition, providing full nutritional requirements in combination (C). </ListItem>
<ListItem level="1">PN in children is indicated (C):</ListItem>
<UnorderedList>
<ListItem level="2">in severe malnutrition </ListItem>
</UnorderedList>
<UnorderedList>
<ListItem level="2">in borderline malnutrition and high risk for malnutrition through therapy, etc.</ListItem>
</UnorderedList>
<UnorderedList>
<UnorderedList>
<ListItem level="3">when oral food intake is <60% of the energy and protein requirements and there is a high risk for treatment-induced malnutrition, etc.</ListItem>
</UnorderedList>
</UnorderedList>
<ListItem level="1">PN is used in children if digestion or absorption of food is impaired and it is expected that the patient will require nutritional therapy for at least 7 days. PN should be commenced as soon as possible and continued until the gastrointestinal tract is fully functioning. Regular checks should be carried out if it is expected that the patient will require a nutrition therapy for less than 7 days (C). </ListItem>
</UnorderedList>
</Pgraph>
<SubHeadline>Commentary</SubHeadline>
<Pgraph>In tumour patients, who are not able to eat, digest or absorb foods, the nutritional state may be maintained or improved by PN <TextLink reference="71"></TextLink>, <TextLink reference="75"></TextLink>, <TextLink reference="89"></TextLink>, <TextLink reference="90"></TextLink>, <TextLink reference="91"></TextLink>. This includes situations with severe intestinal defects caused by radiation enteritis, chronic ileus, severe adhesions, short bowel syndrome, peritoneal carcinosis or the occurrence of chylothorax.</Pgraph>
<Pgraph>In 1994 Klein and Koretz analysed several prospective randomised-controlled studies on the effects of PN regimes in tumour patients, including 22 studies on perio<TextGroup><PlainText>per</PlainText></TextGroup>ative nutrition, 18 studies using PN during the course of chemotherapy, and 4 studies using PN during radiotherapy <TextLink reference="81"></TextLink>. They found no general advantage of PN regarding morbidity or mortality, but an increased rate of infection in patients receiving chemotherapy.</Pgraph>
<Pgraph>Definitive conclusions on the role of PN in the three treatment modalities, however, were not possible due to major flaws in most studies. Most studies had included only few subjects of heterogeneous patient groups undergoing various antitumor therapies. Individual studies were not comparable as they had used different criteria for initiation of artificial nutrition as well as different nutrition regimens and different treatment durations. In addition, patients in these studies were treated despite having a normal, or only a slightly impaired, nutritional state <TextLink reference="85"></TextLink>, <TextLink reference="86"></TextLink>.</Pgraph>
<Pgraph>PN increases tumour cell proliferation <TextLink reference="92"></TextLink>, <TextLink reference="93"></TextLink>, <TextLink reference="94"></TextLink>, <TextLink reference="95"></TextLink>, <TextLink reference="96"></TextLink>, <TextLink reference="97"></TextLink> and sensitivity to chemotherapy <TextLink reference="94"></TextLink>, <TextLink reference="97"></TextLink> in in-vitro models. In malnourished patients with gastric cancer, concomitant administration of PN with preo<TextGroup><PlainText>per</PlainText></TextGroup>ative chemotherapy improved nutritional state, reduced post-operative complications, but did not influence the pre-operative tumour cell proliferation <TextLink reference="97"></TextLink>. </Pgraph>
<Pgraph>Using PN during tumour therapy improved the nutritional state of children (Ib) <TextLink reference="23"></TextLink>, <TextLink reference="98"></TextLink>, <TextLink reference="99"></TextLink>, <TextLink reference="100"></TextLink>. Several studies indicate that chemotherapy is better tolerated when accompanied by PN, resulting in fewer therapy delays, dose reductions and shorter myelosuppression (Ib) <TextLink reference="15"></TextLink>, <TextLink reference="100"></TextLink>, <TextLink reference="101"></TextLink>, <TextLink reference="102"></TextLink>, <TextLink reference="103"></TextLink>. However, other data suggest that the use of PN does not lower the incidence of therapy-related complications (IIa) <TextLink reference="98"></TextLink>, <TextLink reference="104"></TextLink>. In addition, there is no evidence that targeted nutritinal therapy might increase the chance of healing <TextLink reference="105"></TextLink> (UICC 34). On the contrary, PN is associated with an increased rate of infection (Ia) <TextLink reference="106"></TextLink>, <TextLink reference="107"></TextLink>. Therefore, in nutritional therapy whenver possible preference should be given to the oral or enteral route <TextLink reference="108"></TextLink>.</Pgraph>
</TextBlock>
<TextBlock linked="yes" name="Volume and substrate quantities in parenteral nutrition of cancer patients">
<MainHeadline>Volume and substrate quantities in parenteral nutrition of cancer patients</MainHeadline>
<Pgraph>
<UnorderedList>
<ListItem level="1"><Mark1>Energy</Mark1> expenditure is usually comparable to that of healthy subjects; only rarely is it necessary to supply daily energy exceeding 35 kcal per kg body weight (C) (for children’s intake, cf. chapter “Neonatology/Paediatrics” (<Hyperlink href="http://www.egms.de/en/journals/gms/2009-7/000074.shtml">http://www.egms.de/en/journals/gms/2009-7/000074.shtml</Hyperlink>)).</ListItem>
<ListItem level="1">A daily <Mark1>amino acid</Mark1> supply of 1.2 to 1.5 g per kg body weight is usually appropriate in cancer patients (C) (for the appropriate dose for children, cf. chapter “Neonatology/Paediatrics” (<Hyperlink href="http://www.egms.de/en/journals/gms/2009-7/000074.shtml">http://www.egms.de/en/journals/gms/2009-7/000074.shtml</Hyperlink>)). </ListItem>
<ListItem level="1">There is no agreement on an ideal ratio of <Mark1>lipids</Mark1> and carbohydrates; the proportion of lipids can be above 35% of the overall energy intake without disadvantages (C).</ListItem>
<ListItem level="1">Glucose should be the preferred parenteral carbohydrate (B).</ListItem>
<ListItem level="1"><Mark1>Micronutrients</Mark1> should be supplied in sufficient amounts; this should not be less than the iv doses recommended for healthy persons (C). </ListItem>
<ListItem level="1">Monitoring of PN should be carried out following the usual protocol for all PN patients (C).</ListItem>
</UnorderedList>
</Pgraph>
<SubHeadline>Commentary</SubHeadline>
<Pgraph>There are generally no accepted standards for the optimal energy and nutrient intake in oncological patients, particularly when artificial nutrition is administered exclusively. </Pgraph>
<Pgraph>The energy intake should be adapted to the potentially increased energy requirements and the level of physical activity. Total energy expenditure of cancer patients was measured to be comparable to that of healthy subjects, even though REE was incresed in cancer patients <TextLink reference="30"></TextLink>. The cause of this is perhaps an adaptive decrease in physical activity in metabolically altered cancer patients <TextLink reference="36"></TextLink>. </Pgraph>
<Pgraph>The basis for dosing macro- and micronutrients currently remains the same as for healthy persons. There is no indication that an intake of protein above the normal dose (max. 1.5 g protein/kg body weight) has an anticatabolic effect in oncological patients <TextLink reference="109"></TextLink>. </Pgraph>
<Pgraph>Tumour patients show increased lipid oxidation and utilisation of exogenously administered lipids <TextLink reference="58"></TextLink>. Tumour cells preferentially utilise glucose for their energy requirements while healthy tissues display high lipid oxidation <TextLink reference="110"></TextLink>. Therefore, it is recommended to increase the proportion of lipids to over 35% of the total energy supply in the nutrition of oncological patients <TextLink reference="58"></TextLink>. More recent studies, however, showed that post-absorptive glucose turnover of malignant tissues is high and does not increase during an intravenous glucose infusion <TextLink reference="111"></TextLink>; thus, the theoretical benefit of lipid over glucose solutions may be clinically irrelevant. </Pgraph>
<Pgraph>Metabolic and immunological effects of various lipid solutions (LCT, MCT) have been compared mainly in surgical environments. The postulated benefit of medium-chained triglycerides (MCT) over long-chained triglycerides (LCT) could not be established in various clinical studies <TextLink reference="112"></TextLink>, <TextLink reference="113"></TextLink>. There are no data in cancer patients undergoing radiotherapy or chemotherapy substantiating benefits of more recently developed parenteral lipid emulsions, with increased contents of n-9 or n-3 fatty acids. </Pgraph>
<Pgraph>Attention should be given to providing a sufficient supply of micronutrients. The recommendations for intake in other patient population should be followed (cf. chapter “Water, electrolytes, vitamins and trace elements” (<Hyperlink href="http://www.egms.de/en/journals/gms/2009-7/000080.shtml">http://www.egms.de/en/journals/gms/2009-7/000080.shtml</Hyperlink>)). There are no data supporting a clinical advantage of very high doses of micronutrients.</Pgraph>
</TextBlock>
<TextBlock linked="yes" name="Special substrates">
<MainHeadline>Special substrates</MainHeadline>
<Pgraph>
<UnorderedList>
<ListItem level="1">The provision of special substrates such as glutamine, arginine, taurine, branched-chain amino acids or n-3 fatty acids is not recommended due to lack of convincing data supporting their use (C).</ListItem>
</UnorderedList>
</Pgraph>
<SubHeadline>Commentary</SubHeadline>
<Pgraph>Glutamine has been studied as a possible oral supplement to reduce toxic side-effects of radiation or chemotherapy <TextLink reference="114"></TextLink>. Parenteral glutamine has been used in haematopoietic stem cell transplantations (HSCT). Findings to date are inconsistent.</Pgraph>
<Pgraph>In a randomized study of patients after allogeneic HSCT Ziegler et al. showed a significantly improved nitrogen balance, reduced infection rate and shorter length of stay (LOS) for patients supplemented with glutamine (0.57 g/kg/d) compared a control group on an isonitrogenic and isocaloric diet (Ib) <TextLink reference="115"></TextLink>. In a randomized follow-up study these data, however, could only be repeated with respect to a reduction in LOS (Ib) <TextLink reference="116"></TextLink>. In a later study, the same working group was not able to document any advantage of parenteral glutamine (0.57 g/kg/d) in a similar clinical situation <TextLink reference="117"></TextLink> (Ib).</Pgraph>
<Pgraph>In a further randomised study patients after HSCT receiving 3–4 weeks of glutamine-enriched PN showed significant increases in total lymphocyte counts, T-lymphocytes, CD4 and CD8 cells, while the clinical outcome was unchanged <TextLink reference="118"></TextLink> (Ib). In a randomised study in patients after autologous HSCT, high daily doses of intravenous alanyl-glutamine dipeptide (30 g glutamine) resulted in increased relapse and mortality rates as well as increased costs <TextLink reference="119"></TextLink> (Ib). </Pgraph>
<Pgraph>One randomised study, which highlighted the possible protective role of glutamine infusions on hepatic functions during HSCT justifies further studies, especially with a focus on the prevention of veno-occlusive disease <TextLink reference="120"></TextLink> (Ib).</Pgraph>
<Pgraph>In hematological patients undergoing intensive chemotherapy supplementation with glutamine dipeptide had no effect on hematological parameters or clinical toxicity; the glutamine group, however, showed significantly more weight gain during the study period <TextLink reference="121"></TextLink>. </Pgraph>
<Pgraph>In a randomised study of patients with acute myeloid leukaemia requiring PN supplementation with glutamine (20 g) resulted in a more rapid recovery of neutrophils after myelosuppressive chemotherapy, but no reduction in the incidence of neutropenic fever and no improvement in other immunological parameters <TextLink reference="122"></TextLink> (Ib). </Pgraph>
<Pgraph>According to the current ASPEN guidelines <TextLink reference="123"></TextLink>, there is no indication for the administration of pharmacological doses of glutamine in patients after HSCT. Other recent recommendations agree with this <TextLink reference="124"></TextLink>.</Pgraph>
<Pgraph>There is only scarce evidence concerning other special substrates; particularly, there are no relevant data on the parenteral use of n-3 fatty acids.</Pgraph>
</TextBlock>
<TextBlock linked="yes" name="Indications for parenteral nutrition during radiotherapy">
<MainHeadline>Indications for parenteral nutrition during radiotherapy</MainHeadline>
<Pgraph>
<UnorderedList>
<ListItem level="1">PN should not be used as a general accompaniment of radiotherapy (B), but PN is indicated if sufficient enteral intake cannot be achieved (B).</ListItem>
<ListItem level="1">PN is indicated in chronic severe radiation enteritis (C).</ListItem>
</UnorderedList>
</Pgraph>
<SubHeadline>Commentary</SubHeadline>
<Pgraph>During the last 10 years no prospective randomised studies have been published on the use of PN as an accompaniment to radiotherapy. So far it has not been demonstrated that routine PN during radiotherapy or radio-chemotherapy improves prognosis <TextLink reference="81"></TextLink>, <TextLink reference="125"></TextLink>, <TextLink reference="126"></TextLink>. During radiation treatment, especially when treating head and neck areas, whenever possible, sufficient enteral nutrition should be supplied including the use of sip feeds or enteral tube feeding <TextLink reference="109"></TextLink>, <TextLink reference="125"></TextLink>, <TextLink reference="127"></TextLink>, <TextLink reference="128"></TextLink>. </Pgraph>
<Pgraph>PN is indicated if sufficient enteral nutrition is not possible, e.g. as a result of acute radioation enteritis; if nutritional deficits exist and radiation is intended to cover the upper gastrointestinal tract such that an intended PEG would need to be placed within the radiation field; and during neoadjuvant treatment, if insertion of a PEG system is not recommended, e.g. in oesophageal resections and planned gastric interposition. Chronic radiation enteritis develops in approx. 5% of cases subjected to abdominal radiation; this may be accompanied by intestinal failure, fistulae, perforation or chylous ascites and these cases frequently require long-term PN <TextLink reference="67"></TextLink>, <TextLink reference="129"></TextLink>, <TextLink reference="130"></TextLink>, <TextLink reference="131"></TextLink>, <TextLink reference="132"></TextLink>.</Pgraph>
<Pgraph>No benefit of special parenteral substrates such as glutamine has been established for radiotherapy procedures.</Pgraph>
</TextBlock>
<TextBlock linked="yes" name="Indications for parenteral nutrition during chemotherapy">
<MainHeadline>Indications for parenteral nutrition during chemotherapy</MainHeadline>
<Pgraph>
<UnorderedList>
<ListItem level="1">The indications for PN during chemotherapy are not different from general indications in malignant diseases. Routine PN therapy as an accompaniment to chemotherapy is not indicated (B).</ListItem>
</UnorderedList>
</Pgraph>
<SubHeadline>Commentary</SubHeadline>
<Pgraph>In 1990 McGeer et al. published a meta-analysis on the use of PN during chemotherapy (Ia) <TextLink reference="133"></TextLink>. They reported that PN is associated with a trend towards shorter survival and reduced tumour response. They concluded that routine PN is not advisable in patients undergoing chemotherapy. Klein and Koretz analysed 18 randomised studies with clinically relevant end points on the effect of PN in patients treated with chemotherapy. They concluded that there were no evident advantages of PN with regards to overall survival, tumour responses and toxicity of chemotherapy, but there was an increased rate of infection in those receiving PN (Ib) <TextLink reference="81"></TextLink>. </Pgraph>
<Pgraph>It is difficult to draw reliable conclusions from the existing data due to serious flaws in most study designs, such as insufficient number of patients treated, inclusion of extremely inhomogeneous patient groups, large variability of the nutrient solutions used, large variability of antitumor therapies, and inclusion of patients who were not suffering from malnutrition as well as patients who maintained normal oral food intake <TextLink reference="81"></TextLink>. Randomised studies, i.e. by De Cicco et al, which differentiated between normal and malnourished patients undergoing chemotherapy, were able to detect an improvement in the nitrogen balance in severely malnourished patients while no effect was seen in patients without malnutrition <TextLink reference="134"></TextLink> (Ib). </Pgraph>
<Pgraph>Recent recommendations by the American Gastroenterological Association (AGA) and the American Society for Parenteral and Enteral Nutrition (ASPEN) have come to similar conclusions. The AGA report reviewed 19 randomised studies and concluded that PN had no influence on the survival of patients who were treated with chemotherapy or radiation treatment, although a positive influence may be possible after bone marrow transplants. Accompanying PN has an unfavourable effect on other parame<TextGroup><PlainText>ter</PlainText></TextGroup>s in patients treated for chemotherapy, radiotherapy or bone marrow transplants, mainly an increase in infectious complications and a decrease of the response to chemotherapy (Ib) <TextLink reference="85"></TextLink>.</Pgraph>
<Pgraph>The ASPEN recommendations specify that PN as routine accompaniment of chemotherapy is not justified and potentially dangerous due to the increased risk of infection. It is pointed out, however, that PN should be offered to patients who are malnourished and who are unable to absorb sufficient nutrients over a long time period <TextLink reference="135"></TextLink>.</Pgraph>
<Pgraph>Regarding all published recommendations it is important to note that all randomised studies on which they are based were performed more than 10 years ago and that many are flawed as mentioned above. More recent studies report fewer complications of long-term PN <TextLink reference="67"></TextLink>, <TextLink reference="76"></TextLink>, <TextLink reference="77"></TextLink>, <TextLink reference="78"></TextLink>, <TextLink reference="136"></TextLink>, <TextLink reference="137"></TextLink>, suggesting that the benefits and risks of PN administration during chemotherapy should be reviewed again in the near future.</Pgraph>
</TextBlock>
<TextBlock linked="yes" name="Indications for parenteral nutrition during autologous/allogeneic stem cell transplantion">
<MainHeadline>Indications for parenteral nutrition during autologous/allogeneic stem cell transplantion</MainHeadline>
<Pgraph>
<UnorderedList>
<ListItem level="1">PN is required only in selected patients after autologous transplantations, while after allogeneic transplantation PN is usually required in most patients and for prolonged time periods due to the development of pronounced mucositis and GvH-related gastrointestinal damage (C).</ListItem>
<ListItem level="1">Particular attention must be paid to the increased risk of bleeding and infection associated with PN (C).</ListItem>
</UnorderedList>
</Pgraph>
<SubHeadline>Commentary</SubHeadline>
<Pgraph>In patients after autologous transplantations impaired food intake is usually of short duration (2–3 weeks). Nutritional problems in allogenic transplant patients usually are more severe and prolonged. Thus, there is no need for routine PN after autologous transplantations, but PN may be necessary if complications develop such as prolonged mucositis <TextLink reference="138"></TextLink>. After allogenic transplantations, PN is routinely administered in most transplantation centres <TextLink reference="138"></TextLink>. In 1987 Weisdorf et al. showed that prophylactic standardised PN significantly improved survival three years after HSCT <TextLink reference="106"></TextLink>. The control group received only minerals and vitamins intravenously until a reduced nutritional state was detected. Because patients receiving early PN had a lower relapse rate, it was speculated that the better overall survival observed might have been caused by a possible positive effect of PN on transplant function, resulting e.g. in an increased graft versus leukaemia effect. </Pgraph>
<Pgraph>Enteral nutrition is not well tolerated in most cases after complete conditioning regimens <TextLink reference="139"></TextLink>; if tolerated, however, enteral nutrition in patients with a functioning gastrointestinal tract has effects on nutritional status that are comparable to those of PN <TextLink reference="124"></TextLink>, <TextLink reference="140"></TextLink> <TextLink reference="141"></TextLink> (Ib). The French Federation of Cancer Centres, as well as the authors of a review of relevant randomised studies recommend enteral nutrition as the primary approach in non-myeloablative conditioning, and PN only in cases of gastrointestinal complications <TextLink reference="141"></TextLink>. It has been recommended to initiate PN when oral or enteral food intake provides less than 50–60% of calculated requirements <TextLink reference="67"></TextLink>, <TextLink reference="141"></TextLink>.</Pgraph>
<Pgraph>American and French panels on gastroenterology and nutrition emphasize that all HSCT patients carry a high nutritional risk and should, therefore, be monitored regularly for nutritional deficits before and after transplantation <TextLink reference="123"></TextLink>, <TextLink reference="141"></TextLink>.</Pgraph>
<Pgraph>A small randomised study has observed that a high dose of lipid (lipid:glucose ratio 80:20) after allogenic transplantation lowered the incidence of lethal acute graft–versus-host disease and hyperglycaemia <TextLink reference="142"></TextLink>. This study has yet to be confirmed. </Pgraph>
<Pgraph>Certin et al. <TextLink reference="143"></TextLink> reported that supplying total rather than partial PN after autologous transplantation resulted in a delyed rise in thrombocytes. At the same time, there were more cases of infection and hyperglycaemia associated with total PN as compared to partial PN, whilst a drop in the level of albumin was prevented. The study was not randomized and patients receiving total PN may have been more severely ill. The observation, however, may support the recommendation not to provide total PN as a standard treatment after autologous transplantations.</Pgraph>
<Pgraph>In children an autologous blood stem cell transplantation usually has only a low impact on nutritional status (III) <TextLink reference="144"></TextLink>, <TextLink reference="145"></TextLink>. Thus, a targeted nutritional therapy should be based primarily on the above-mentioned criteria (see: Indication for PN in cancer patients) or be initiated if a conditioning therapy is chosen, which is associated with a high risk for severe mucositis. </Pgraph>
<Pgraph>In allogenic transplantations the criteria for using PN are usually given, and PN has been shown to have positive effects on maintaining the body weight <TextLink reference="146"></TextLink>, <TextLink reference="147"></TextLink> (Ib). Enteral nutrition is possible in many cases and then is as effective as PN. In a study by Hopman et al., enteral tube feeding was possible during 60% of the study period, although it could be used as the sole form of nutrition only in 3 of 12 children <TextLink reference="148"></TextLink> (Ib). In a retrospective analysis, Langdana et al. reported on their positive experiences and the high patient acceptance rate for a similar concept with the preferrential use of enteral nutrition <TextLink reference="149"></TextLink> (III). In all cases the risks of enteral tube feeding (aspiration, bleeding, diarrhoea, sinusitis, intestinal perforation) should be weighed against the risks of PN (catheter sepsis and metabolic complications). </Pgraph>
<Pgraph>In most cases it appears to be sufficient to restrict the amount of energy provided to be slightly more than the resting energy expenditure (see: Influence of malignancies on energy expenditure) <TextLink reference="150"></TextLink>, <TextLink reference="151"></TextLink>, <TextLink reference="152"></TextLink>.</Pgraph>
<Pgraph>There are no generally accepted indications for the use of glutamine (see Special substrates).</Pgraph>
</TextBlock>
<TextBlock linked="yes" name="Indications for parenteral nutrition independent of antitumor therapies in incurable cancer patients">
<MainHeadline>Indications for parenteral nutrition independent of antitumor therapies in incurable cancer patients</MainHeadline>
<Pgraph>
<UnorderedList>
<ListItem level="1">If food intake is insufficient survival of patients in advanced cancer stages may be compromised more by inadequate nutrition than by the underlying illness (C).</ListItem>
<ListItem level="1">Long-term PN should be initiated if intestinal absorption is severely impaired and if allof the following 4 criteria are fulfilled (C): </ListItem>
</UnorderedList>
</Pgraph>
<Pgraph>
<OrderedList>
<ListItem level="1" levelPosition="1" numString="1.">enteral nutrition is insufficient to maintain nutritional state,</ListItem>
<ListItem level="1" levelPosition="2" numString="2.">the expected survival is more than 4 weeks,</ListItem>
<ListItem level="1" levelPosition="3" numString="3.">PN is expected to stabilise or improve quality of life,</ListItem>
<ListItem level="1" levelPosition="4" numString="4.">the patient explicitely wishes to receive PN.</ListItem>
</OrderedList>
</Pgraph>
<SubHeadline>Commentary</SubHeadline>
<Pgraph>Oncological treatments today may allow patients with incurable cancer disease to survive up to a point at which further survival is significantly affected the nutritional state <TextLink reference="153"></TextLink>. An inadequate oral or enteral intake results in progressive weight loss and impaired clinical outcome (see: The nutritional state influences the clinical outcome). Randomised studies on the value of PN appear unethical in these situations <TextLink reference="87"></TextLink>. </Pgraph>
<Pgraph>Despite a lack of effective antitumor treatment options, patients with advanced cancers may have a life expectancy of several weeks or months. If the expected survival exceeds 2 to 3 months (e.g. the period of survival in total starvation <TextLink reference="154"></TextLink>, <TextLink reference="155"></TextLink>, <TextLink reference="156"></TextLink>), it can be reasonably assumed that PN will lengthen the survival of a patient who does not tolerate enteral nutrition <TextLink reference="87"></TextLink>. In this situation PN, by providing essential nutrition, constitutes a basic care rather than a medical therapy <TextLink reference="87"></TextLink>, <TextLink reference="157"></TextLink>.</Pgraph>
<Pgraph>Specialised centres providing long-term PN to patients with advanced cancer disease report a median survival period of 2–5 months <TextLink reference="69"></TextLink>, <TextLink reference="70"></TextLink>, <TextLink reference="71"></TextLink>, <TextLink reference="73"></TextLink>, <TextLink reference="74"></TextLink>, <TextLink reference="75"></TextLink>, <TextLink reference="76"></TextLink>, <TextLink reference="77"></TextLink>, <TextLink reference="78"></TextLink>. This means that a large proportion of patients cared for in this manner have a longer period of survival than that assumed for conditions of complete starvation. Weight stabilisation was successful in a majority of patients <TextLink reference="69"></TextLink>, <TextLink reference="70"></TextLink>, <TextLink reference="71"></TextLink>. </Pgraph>
<Pgraph>Quality of life scores are poorer in parenterally nourished cancer patients than in healthy subjects undergoing PN; cancer patients are further burdened by accompanying depressions and opoid requirements <TextLink reference="158"></TextLink>. PN, however, may stabilise parameters determining quality of life <TextLink reference="69"></TextLink>, <TextLink reference="70"></TextLink>, <TextLink reference="71"></TextLink>. Orreval et al. reported that the provision of PN was perceived as a positive alternative to progressive weight loss by a small group of patients with advanced tumours and their relatives <TextLink reference="79"></TextLink>. </Pgraph>
<Pgraph>Since the benefits of PN can only have an impact when life expectancy is impaired more by insufficient food intake than by the tumour itself, several expert groups recommend considering PN when the expected survival is at least 4 weeks <TextLink reference="135"></TextLink> or 2–3 months depending on the tumour <TextLink reference="85"></TextLink>, <TextLink reference="87"></TextLink>, <TextLink reference="159"></TextLink>, <TextLink reference="160"></TextLink>. No advantage of PN should be expected when survival is shorter.</Pgraph>
<Pgraph>It is extremely difficult to estimate the life expectancy of a cancer patient and, hence, the possible advantages of artificial nutrition. These patients should, therefore, be seen and evaluated cooperatively by their consultant oncologist, the nutrition specialist and the palliative care consultant in order to design a treatment plan that is in agreement with the patients expectations and wishes.</Pgraph>
</TextBlock>
<TextBlock linked="yes" name="Parenteral nutrition in terminally ill patients">
<MainHeadline>Parenteral nutrition in terminally ill patients</MainHeadline>
<Pgraph>
<UnorderedList>
<ListItem level="1">No PN is necessary in dying patients (B). </ListItem>
<ListItem level="1">The occurrence of agitated confusion induced by dehydration can be controlled by parenteral infusion of saline solutions (or the appropriate paediatric solutions, respectively) (B).</ListItem>
</UnorderedList>
</Pgraph>
<SubHeadline>Commentary</SubHeadline>
<Pgraph>During the phase of dying the most important aims of treatment and care are the alleviation of agonising discomfort and the feelings of thirst and hunger. Fluids and nutrition are part of the basic care; however, the patient needs to consent to such offers <TextLink reference="157"></TextLink>. Most patients do not feel hungry in the terminal phase of life and only require minimal quantities of fluid <TextLink reference="161"></TextLink>. It is counterproductive since it may strain the patient severely and thus it should be avoided at all cost to continue standardised infusion regimens into the terminal phase without further consideration <TextLink reference="162"></TextLink>. </Pgraph>
<Pgraph>Regulation of fluid balance should be observed closely. Both dehydration, induced by diuretics or limited drinking, and hyperhydration caused by infusions can have adverse affects on a person’s well-being. The “dry mouth” is one of the main symptoms of the dying <TextLink reference="163"></TextLink>. However, thirst and “dry mouth” do neither correlate with the degree of hydration <TextLink reference="164"></TextLink> nor with the volume of intravenous infusion <TextLink reference="165"></TextLink>. Terminal patients appear to receive too much fluid in general <TextLink reference="162"></TextLink>, increasing the risks for peripheral oedema, ascites, pleural effusions and the development of a pulmonary oedema.</Pgraph>
<Pgraph>Dehydration can result in drying of the mucous membranes with subsequent injuries and infections <TextLink reference="163"></TextLink>, it reduces alertness and promotes the occurrence of restlessness and confusion <TextLink reference="166"></TextLink>, thus contributing to the burden of the patients and their relatives <TextLink reference="167"></TextLink>. Retrospective studies provided evidence that intravenous flids may reduce neuropsychiatric symptoms like sedation, hallucinations, myoclonus and agitation <TextLink reference="168"></TextLink>, <TextLink reference="169"></TextLink>. A randomised trial in dehydrated terminal cancer patients could show that subjective discomfort was significantly improved with the infusion of 1000 ml per day as compared to no infusions and only minimal oral fluid intake of 100 ml per day <TextLink reference="170"></TextLink>.</Pgraph>
<Pgraph>Recommendations for terminal care, therefore, emphasize that fluid intake should always be prescribed on an individual basis and should target the prevention of intolerable symptoms. Fluid quantities of 1000 ml per day are recommended in symptomatic dehydration <TextLink reference="170"></TextLink>, <TextLink reference="171"></TextLink>; in children this corresponds to supplying approx. 50% of the daily fluid requirements.</Pgraph>
</TextBlock>
<TextBlock linked="yes" name="Notes">
<MainHeadline>Notes</MainHeadline>
<Pgraph>This article is part of the publication of the Guidelines on Parenteral Nutrition from the German Society for Nutritional Medicine (overview and corresponding address under <Hyperlink href="http://www.egms.de/en/journals/gms/2009-7/000086.shtml">http://www.egms.de/en/journals/gms/2009-7/000086.shtml</Hyperlink>).</Pgraph>
<Pgraph>English version edited by Sabine Verwied-Jorky, Rashmi Mittal and Berthold Koletzko, Univ. of Munich Medical Centre, Munich, Germany.</Pgraph>
</TextBlock>
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