Parenteral nutrition – Guidelines of the Israeli Society for Clinical Nutrition (ISCN)

lable at ScienceDirect

e-SPEN, the European e-Journal of Clinical Nutrition and Metabolism 4 (2009) e270–e288

Contents lists avai

e-SPEN, the European e-Journal ofClinical Nutrition and Metabolism

journal homepage: http: / /www.elsevier .com/locate/c lnu

Parenteral nutrition – Guidelines of the Israeli Society for Clinical Nutrition (ISCN)

Irit Chermesh a, Odile Azoulay b, Efrat Alpert c, Ronit Anbar d, Yitshal Berner e, Nir Barak f,Evgenia Chochrin a,g, Mirit Cohen a, Ruti Efargan a, Herbert Freund h, Miriam Ganon i, Salim Hadad j,Moshe Hersch k, Michal Kairi l, Asher Korzets m, Alon Lang n, Yshai Levi o, Eva Niv p, Irit Poraz l,Miryam Theilla d, Nachum Vaisman p, Pierre Singer d,*

a Clinical nutrition Unit, Gastroenterology Dept., Health Care Campus, Haifa, Israelb Clinical Dietician Department, Hasharon Hospital, Petah Tikva, Israelc Gastroenterology Dept., Clinical Nutrition Unit, Rambam Health Care, Haifa, Israeld Institute for Nutrition Research, General Intensive Care Department, Rabin Medical Center, Beilinson Hospital, Petah Tikva 49100, Israele Department of Geriatric Medicine, Meir Medical Center, Kfar Saba, Israelf Ward ‘‘D’’ Rabin Medical Center, Beilinson Hospital, Petah Tikva, Israelg Unit of Clinical Nutrition Souraski Medical Center, Tel-Aviv, Israelh Surgical Department, Hadassah Medical Center, Jerusalem, Israeli Hadassah Medical Center, Jerusalem, Israelj Pharmacy Department, Rambam Health Care Campus, Haifa, Israelk Intensive Care Unit, Shaare Zedek Hospital, Jerusalem, Israell Nutrition and Clinical Dietetic Schneider Children’s Medical Center of Israel, Petah Tikva, Israelm Nephrology Department, Hasharon Hospital, Petah Tikva, Israeln Gastroenterology Unit, Shiba Medical Center, Tel Hashomer, Israelo Word ‘‘D’’, Rambam Health Care Campus, Haifa, Israelp Gastroenterology Dept. and Clinical Nutrition Unit, Souraski Medical Center, Tel-Aviv, Israel

a r t i c l e i n f o

Article history:Received 25 March 2008Accepted 12 May 2009

Keywords:Total parenteral nutritionGuidelinesIntensive careRecommendations

* Corresponding author. Tel.: þ972 39376521; fax:E-mail address: [email protected] (P. Singer).

1751-4991/$ - see front matter � 2009 European Socdoi:10.1016/j.eclnm.2009.05.001

s u m m a r y

The Israel Ministry of Health was willing to update the National Recommendations for ParenteralNutrition administration and asked the Israel Society for Clinical Nutrition to write these guidelines. Agroup of experts in the field met and reviewed the literature before been separate in small workinggroups in purpose to write the recommendations of the society. These recommendations were proposedafter large agreement between the participants since the group believed that consensus was required.These guidelines are proposed to Clinical Nutrition.

� 2009 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rightsreserved.

1. Introduction

Parenteral nutrition is a nutritional regimen for in and outpatients and is a task for qualified health professionals. It providesnutrition when the gut fails to ensure sufficient nutrition. The timescale for a decision as to whether parenteral nutrition is mandatorydiffers from patient to patient, and depends upon the specificprimary diagnosis, comprehensive clinical status, time to normalintake, and basic nutritional status. Parenteral nutrition providespartial or full nutritional treatment. It includes macronutrients,micronutrients, electrolytes, and even ultra-trace micronutrients.Macronutrients include carbohydrates, proteins and lipids.

þ972 39232333.

iety for Clinical Nutrition and Met

Additional ingredients include water-soluble and lipid-solublevitamins, electrolytes and trace elements. Ultra-trace elementsinclude but are not limited to arsenic, boron, molybdenum andnickel.1 They are probably necessary but, for the time being, arecontaminants of other components of the parenteral nutritionformulation. Since parenteral nutrition is not the physiologic routefor the provision of nutrition, specific complications can occur, e.g.,metabolic, infectious and technical, due to line failure. Extra careshould be taken to prevent these complications as much as possibleand to treat them early if they do occur.

The aim of the ISCN guidelines on parenteral nutrition is toprovide practical guidelines based on evidence-based literature.

The aims of the guidelines are2:

1. Increasing knowledge, that is making physicians aware of theguidelines (education influence);

abolism. Published by Elsevier Ltd. All rights reserved.

mailto:[email protected]

www.sciencedirect.com/science/journal/17514991

http://www.elsevier.com/locate/clnu

I. Chermesh et al. / e-SPEN, the European e-Journal of Clinical Nutrition and Metabolism 4 (2009) e270–e288 e271

2. Changing attitudes, such that clinicians agree with and acceptthe recommendations as a better standard of care (personalfactors);

3. Changing behavior, such that physicians change their clinicalpractice to conform with the guidelines, such changesincluding patient influences (patient pressures), administrativeinfluences, and economic influences.

4. Changing outcomes, by improving patient health and quality ofcare.

The recommendations are graded by the level of evidence foundby the Consensus Committee and degree of importance. For gradingthe level of evidence, the ESPEN ECPC proposal of a method toproduce guidelines was adopted.3

A comprehensive recommendation was given, using the GCPN(Appendix 1) and CDC grading method respectively (Appendix 2).4

Recommendations and statements were graded 1A-5C by GCPNsystem or 1A-II by CDC.

A multi-disciplinary team (physician, nurse, dietician anda pharmacist) enables best care

3C
1B
Trained nursing teams should care for venous access devices inpatients receiving PN

3C
1B
1.1. Comments

The complexity of treatment with parenteral nutrition calls forthe cooperation of multi-disciplinary staff members. Parenteralnutrition treatment, when managed by a TPN team headed bya physician along with a dietician, nurse and pharmacist, has beenproven to lower rates of metabolic complications, meet nutritionalrequirements more often, and has been found to be cost-effective.5

Specialized nursing teams should care for venous access devices inpatients receiving PN6 (GCPN 3C; CDC 1B).

2. Nutritional status

Every patient should undergo screening for malnutrition
2B 1B
2.1. Comments

Defining the nutritional risk in every patient is mandatory(GCPN 2B; CDC 1B). Only then can an appropriate nutritionaltreatment plan be made. Screening for malnutrition should beinstituted in every patient, using an appropriate screening tool. Thescreening tool should have high predictive validity, high reliability,be reproducible, easy and inexpensive to use. Various nutritionalscreening tools have been assessed. ESPEN recommends the NRS2000 for hospitalized patients and the MUST for population-basedscreening.7 Since 2002, when the ESPEN guidelines were published,the MUST was validated for hospitalized patients as well.8–10 Twoadditional well-validated tools are the SGA and the NRI. Using anyof these tools to screen patients is bound to define adequately thepatients at nutritional risk (Appendix 3). Patients at nutritional riskshould undergo a full nutritional assessment by a professional.Then, a nutrition treatment plan can be made.

3. Indications for parenteral nutrition

Absolute indications for PN are irreversible intestinal failuree.g., post-resection

4C
1B
TPN should be considered in patients with partial intestinalfailure or transient prolonged (taking into account the timeto enteral feeding and basic nutritional state) situationssuch as pseudo-obstruction to Crohn’s disease

4C
1B
TPN should be given to a malnourished patient for 7 daysbefore surgery, when enteral route is not feasible

1A
1A
A severely stressed patient should be provided with nutritionwithin 24 h; if the enteral route fails, PN should be started

3C
1B
In a well-nourished patient
4C 1B A well-nourished patient should be given full alimentation to
fulfill his requirements
Follow-up 3C 1B Laboratory investigations before initiation of PN: electrolytes:
Na, K, P, Ca, Mg, kidney function, glucose, liver function, PT;TG in patients prone to develop hyperlipidemia, e.g.,patients with liver dysfunction

5C
1B
There are absolute and relative indications for parenteralnutrition. Absolute indications include any condition in which theenteral route is permanently dysfunctional. Such conditionsinclude but are not limited to extensive bowel resection, e.g., due toan ischemic mesenteric event or trauma. Functional problemsleading to the necessity of parenteral nutrition include chronicpseudo-obstruction. Transient situations in which parenteralnutrition is indicated include but are not limited to bowelobstruction, active Crohn’s disease and high output proximal fistula(GCPN 4C; CDC 1B). It has proved effective as a means of supportinga malnourished patient before surgery (GCPN 1A; CDC 1A).

4. Timing of initiation of parenteral nutrition

Patients who cannot eat or tolerate enteral feeding within 3days should receive parenteral nutrition according to theirrequirements.

5C
1B
4.1. Comments

There are no controlled studies to determine the ideal timepoint for initiation of parenteral nutrition in a patient who cannottolerate oral food or enteral alimentation, and no such studies canbe conducted. The current recommendations are based on knowl-edge of physiology and pathology of starvation.

According to the ESPEN enteral feeding guidelines, patients cantolerate no nutrition for 3–5 days unless one or more of thefollowing conditions exists (6 ESPEN guidelines)

� Severe stress or hypermetabolism� Recent 10% weight loss� BMI less than 22 kg/m2

� Albumin <3.5 g/Dl� Evidence of muscle wasting

It is important to identify patients who do not comply with ALLof the above, in whom parenteral nutrition should be started withno delay. Special consideration should be given to patients in theIntensive Care Unit, in whom it is advisable to begin nutritionaltreatment as soon as possible, preferably within 24 h (GCPN 1A;CDC 1A).

5. Defining nutritional needs

Calorimetry is the gold standard
1A 1A Equations such as Harris Benedict formulas or WHO equations
should be used
3C 1B

I. Chermesh et al. / e-SPEN, the European e-Journal of Clinical Nutrition and Metabolism 4 (2009) e270–e288e272

5.1. Comments

Meeting patients’ nutritional needs is of great importance. Multipleretrospective and cohort studies, specifically in patients in the Inten-sive Care Unit, have demonstrated worsening of outcome in patients inwhom provision of their calorie needs could not be established.11,12 Thegold standard for caloric nutritional requirements is indirect calo-rimetry (GCPN 1A; CDC 1A). Performing indirect calorimetry requiresequipment and a technician. Since these are not always available,equations have been developed to estimate the needs. The equationsare based on clinical and patient parameters, such as age, weight anddisease status. One of the following formulas could be used: HarrisBenedict, WHO or Ireton-Jones (GCPN 3C; CDC 1B) (Appendix 4).

Adaptations for special circumstances, such as mechanicalventilation and burns, should be made. The so-called ‘rule ofthumb’ is that basic metabolic requirements are 25–30 kcal/kg. Ina catabolic patient, estimation is elevated to 35–45 kcal/kg. Themost hypermetabolic states are severe and extensive burns andbone marrow transplantation.13–17

6. Protein needs

Practically, protein requirements are about 1–1.5 g/kg ideal bodyweight/day.18,19

A more accurate method to define the protein needs, whensteady-state nitrogen balance is assumed, is through 24 h urinarycollection for nitrogen excretion. This is used to determine thenitrogen balance and protein requirements are thereafter calcu-lated by using the following equation: urinary nitrogen loss¼ urineurea nitrogen (mg/dl)� daily urine volume (dl)/0.8.

Additional nitrogen losses are in the form of non-urea urinaryexcretion as well as fecal (~1–2 g/day) and skin losses (~0.3 g/day).

Total nitrogen losses (gr/day)¼NurineþNstoolþNskin¼Nurineþ 2Nitrogen balance: [Total protein given (gr)/6.25]� total nitrogenlosses

7. Evaluation of patient before implementation of parenteralnutrition

Clinical evaluation:

History concerning nutritional status and current clinicalsituationHas the patient experienced weight loss in the previous twoweeks?Previous 3 months?Did the patient eat less than normal?Are there gastrointestinal symptoms: diarrhea, vomiting orconstipation?How long has the patient been ill?What is the patient’s current clinical status? Is his metabolic rateconsidered normal or high (e.g., sepsis, extensive burns)?

Laboratory evaluation:

Compulsory before beginning parenteral nutrition unless thepatient has had recent acute trauma, judged to be in excellentnutritional status up to hospitalizationElectrolytes – Na, K, P, Ca, MgKidney function tests: serum creatinine, urea/BUNGlucose levelLiver function tests: ASAT, ALAT, alkaline phosphatase, total anddirect bilirubin, GGT

8. Beginning parenteral nutrition treatment

Before beginning parenteral nutrition, the patient is catego-rized as having a high or low risk for developing the refeedingsyndrome (see section on the Refeeding Syndrome). In a patientwith a low risk for developing the refeeding syndrome, paren-teral nutrition is begun according to calorimetry measurementsor calculations using one of the above equations. It is common forparenteral nutrition to be given around the clock when thepatient is unstable. Re-assessment of the need for 24-h infusionshould be made as soon as possible, with gradual shortening ofthe infusion time to 16–18 h per day. This is probably better interms of liver function (see section on liver dysfunction due toparenteral nutrition) and is more comfortable for the nursingstaff and the patient.

9. Follow-up of patient during parenteral nutrition treatment

Weigh the patient before initiating PN and once-twice weeklyafterward

5C
1B
Laboratory evaluation during PN: electrolytes every day for thefirst 3 days, twice weekly after stabilization

5C
1B
Triglycerides after 24 h; if >400 mg%, repeat after cessation ofparenteral lipids

In prolonged PN laboratory, evaluation should include: B12,folic acid, ferrum, ferritin, transferring, zinc, copper, TSH

4C
1B
9.1. Comments

Complete physical examination, particularly looking for signs offluid overload or dehydration, mental status with relation to elec-trolyte imbalance or nutritional deficiency, e.g., B1 deficiencycausing Wernicke-encephalopathy

Calorimetry whenever possible and, if unavailable, assessmentof needs using one of the equations24-h urine collection for urinary urea secretion to determineprotein requirements (see above)Weigh patient 1–2 times per weekElectrolytes: Na, K, P, Ca, Mg – every day for the first three days,2–3 times per week upon stabilization

It is best if glucose levels are kept at <110 mg%, except in dia-betic patients in whom levels probably should kept higher(but< 150 mg%).20 (Separate section on intensive insulin therapyand tight glucose control)

Renal function: serum creatinine and urea/BUNHepatic function: ASAT, ALAT, Total and direct bilirubin, alkalinephosphatase, GGT

Triglyceride levels should be taken the day after parenteralnutrition is given; if high (>400 mg/dl), repeat test adequate timeafter stopping the parenteral lipid emulsion (8–14 h); if normal,repeat twice a week. Care should be given to patients with liverfunction test abnormality.21

Coagulation tests (PT-INR) (GCPN 5C; CDC 1B)

10. Follow-up of patient during prolonged parenteralnutrition treatment

When parenteral nutrition is given for a prolonged period oftime, further follow-up and evaluation should be made. Thefollowing list includes suggested timing for laboratory tests:


Thyroid function tests – parenteral nutrition beyond a monthVitamin B12 levels – beyond a monthFolic acid levels – beyond a monthFerrum, transferrin and ferritin levels – beyond a monthZinc levels – beyond two weeksCopper levels – beyond two weeks

Assessment of bone metabolism should be considered inpatients with extensive parenteral nutrition, such as home paren-teral nutrition.22,23 (GCPN 4C; CDC 1B)

11. Refeeding syndrome

Before beginning alimentation in a patient who is high risk fordeveloping refeeding syndrome, 100 mg thiamine should begiven parenterally for the first 3 days

5C
1B
Alimentation of a patient who is high risk for developing therefeeding syndrome should be done gradually

4C
1B
A malnourished patient is prone to develop the refeedingsyndrome, therefore it is prudent that laboratory evaluationis kept strictly and electrolyte disorders corrected

4C
1B
The refeeding syndrome is a complex of clinical and laboratorycomplications that can develop in a malnourished patient whenfed.24 Crook and Panteli defined the refeeding syndrome as ‘apotentially lethal condition that can be defined as severe electrolyteand fluid shifts associated with metabolic abnormalities inmalnourished patients undergoing refeeding whether this is orally,enterally or parenterally’.25 Patients can develop fluid and elec-trolyte disorders, especially hypophosphatemia, along withneurological, pulmonary, cardiac, neuromuscular, and hematolog-ical complications. Insulin secretion is reduced during starvation.There is intracellular depletion of electrolytes, including phos-phorus. In malnourished patients, intracellular phosphate storescan be low despite normal serum phosphate levels. With initiationof alimentation, insulin secretion is caused with a shift of phos-phorus from the extracellular to the intracellular compartment.This, combined with utilization of phosphate for the production ofATP from ADP, glucose-6-phophate 2-3 DPG, etc., could result inhypophosphatemia. This hypophosphatemia could be severe andlife-threatening. Other components of the refeeding syndrome maybe hypomagnesemia, hypokalemia, thiamin deficiency resulting inWernicke’s encephalopathy, heart failure due to fluid retention ina patient with diminished cardiac function, and respiratory distressdue to weakness of the diaphragm. The most important steps are toidentify patients at risk for developing refeeding syndrome (seeabove), institute nutrition support cautiously, and correct andsupplement electrolyte and vitamin deficiencies to avoid therefeeding syndrome (GCPN 4C; CDC 1B).

Identifying and feeding patients at risk of developing therefeeding syndromeIdentification of patients at risk:Recent weight loss of >10%Diminished food intake for >1 weekBasal electrolyte imbalance – hypophosphatemia, hypomagne-semia or hypokalemiaCorrect electrolyte abnormalities with special consideration tophosphate. Phosphate level of <1.5 mmol/Dl can be dangerousFollow-up electrolyte levels at least once dailyGive parenteral thiamin (e.g., 100 mg) before beginningalimentationStart alimentation gradually. It is probably safe not to exceed20 kcal/kg (GCPN 4C; CDC 1B)

12. Parenteral nutrition formulation

Parenteral nutrition is a means of providing nutrition and, assuch, should include all the components of a well-balanced diet.Basically, carbohydrates should provide 40–60% of calories. Thekidney cortex, brain cortex and red blood cells use glucose as a soleenergy source; when there is a shortage of carbohydrates, ketonesare produced and utilized. A minimum of 150–200 g of glucoseshould be provided to avoid ketone production. 0.8–1.2 g of proteinshould be provided to a non-catabolic patient; some patients needas much as 2–3 g per kilogram. Protein requirements are bestcalculated after a 24-h urine collection for urea nitrogen excretion(see formula above for calculation). Fat should provide 30–40% but,in certain situations, could be as high as 60% (~ gr/kg/day). Bloodlevels of triglycerides (TG) should be followed to ensure that thequantity given does not exceed clearance capability. A minimum of3–5% of the calories provided by long chain polyunsaturated fattyacids (LCT) should be given to prevent essential fatty acid deficiency(linoleic acid and alpha linolenic acid). Parenteral nutritionformulas can contain carbohydrates, proteins and fats; theseformulations are called ‘3-in-1’ or ‘all-in-1’. If they contain carbo-hydrates and proteins alone, they are called ‘2-in-1’. ‘3-in-1’ solu-tions are emulsions, with some degree of stability, but separationcan occur, with the formation of fat globules.

12.1. Lipids

MCT/LCT solutions are clinically superior to LCT solutions alone
2B 1A Lipid emulsion with higher concentration is better than lower
concentration (e.g., 20% is better than 10%)
3C 1B
Lipid formulations are composed of triglycerides with phos-pholipids as emulsifiers. There are different formulations ofparenteral lipids:

Soybean oil-based LCT only (e.g., Intralipid, Livolipid)LCT and medium chain triglycerides (MCT) (e.g., Lipofundin)Olive oil-based (approximately 80%) and soybean oil-based LCT(Clinoleic)Structured lipids (with predetermined-structured chain length)Combination of lipids-SMOF, containing soybean oil, MCT, oliveoil and fish oilFish oil – omega-3, as supplement, given for its anti-inflam-matory qualities and not solely as an energy supplier (Ome-gaven) (see more data in Intensive Care and surgery sections)

The most abundant and studied formulas are the LCTs and thecombination of 50% LCT-50% MCT (LCT/MCT). Many studies haveproven the superiority of the LCT/MCT lipid emulsion. It improvesnutritional status better than the LCT solution alone26 – (GCPN 2B;CDC 1A). In a group of cancer patients undergoing surgery, LCT/MCTsignificantly improved plasma pre-albumin concentration27 andprovided a better nitrogen balance in another group.28 The LCT/MCT solution demonstrated a lower immunosuppressive effect inlaboratory studies29,30 and fewer clinical infections. In a group of 72severely malnourished surgical patients, those in the LCT/MCTgroup had a significantly lower incidence of intra- abdominalabscesses. Patients without cancer in the same study treated withLCT/MCT had a significantly lower rate of mortality.31 The LCT/MCTsolution was superior for patients in the ICU, especially those onmechanical ventilation. In 21 ICU patients treated with either LCT orLCT/MCT, cardiac output, oxygen consumption and oxygen deliveryincreased significantly only in the MCT/LCT group.32 In another


study, LCT infusion increased the mean pulmonary artery pressureand pulmonary venous admixture and decreased arterialPO2(PaO2)/ fractional inspired oxygen. Smyrniotis et al. demon-strated that the infusion of LCT/MCT 1:1 emulsions increasedoxygen consumption (VO2), cardiac output and CO2 production(VCO2).33 It was demonstrated that LCT/MCT increased the PaO (2)/fraction of inspired oxygen (FIO(2)) when compared to LCT emul-sion alone.34

One study found lower lipoprotein x in a MCT/LCT treated groupvs LCT alone.35 In a group of post-orthotopic liver transplantationpatients, RES function recovery was significantly better in the LCT/MCT group.36 These beneficial effects were observed while main-taining essential fatty acid status.37 On the whole, the use of LCT/MCT solutions is advocated.

As for the olive-based and the SMOF fat solutions, there isinsufficient information to recommend the routine use of olive-based solutions. Although there is a vast theoretical basis, there isonly very small direct clinical evidence showing it to be as safe as theLCT/MCT formulation37–40 (GCPN 5C). SMOF was tried in two clinicaltrials, one in healthy volunteers and one in an Intensive Care Unit.Both studies used the less than optimal LCTsolution as control. SMOFwas shown to be better than the LCT solution in terms of eliminationand tolerance in healthy volunteers41 and provided a better anti-oxidant status in stressed patients in the ICU.42

See section on Intensive Care regarding solutions with omega-3fatty acids.

Lipid formulations are produced in different concentrations,usually ranging from 10 to 30%. It is postulated that the deleteriouseffect on the lipid profile of patients given parenteral lipid solutionsis due to the emulsifier – phospholipid. In a solution with a higherconcentration, the ratio of the emulsifier to fat is lower and,therefore, is less toxic, ensuring: a lower median plasma concen-tration of triglycerides, phospholipids and free fatty acids. Whena lower concentration of lipids was used (Intralipid 10%), there wasan increase in the pathological LpX43,44 (GCPN 3C; CDC 1B).

13. Managing and preventing complications

13.1. Infectious complications

PN is an independent risk factor for developing CRI; therefore,utmost precautions should be taken to prevent infections

5C
1B
Parenteral nutrition is a risk factor for developing catheter-related infections (CRI) and blood stream infections (BSI). Theannual risk of infections in patients treated by home parenteralnutrition (HPN) is 3/1000 days of HPN.45 Parenteral nutrition is anindependent risk factor for CRI.46 Other risk factors includeundernutrition, hyperglycemia, and longer hospitalization beforecatheter insertion. The most common pathogens are Staph. epi-dermidis and Staph. aureus which tend to adhere to the catheteritself, other gram positive and negative pathogens as well asfungi.47,48 In the past, infection was found to originate from theinfusate itself.49,50 Nowadays, the lumen,51 the points of connec-tion52,53 and, mainly, the skin around the catheter insertion site arethe main ports of entry.54,55 Catheter sepsis should be suspectedwhen there is phlebitis, positive blood cultures for pathogens suchas Staph. Coagulase-negative or Candida, with no other cause. Thediagnosis of CRI relies on positive blood cultures. One reportdescribed w5% of false positive results and w2% of false negativeresults of cultures drawn through the central catheter.56,57 Anotherstudy reported that, while the positive predictive value of culturesdrawn through a central venous catheter is low compared with

peripheral venipuncture, the negative predictive value of culturesdrawn through a central venous catheter is 98%.58

The definition of CRI relies upon either quantitative or semi-quantitative blood cultures from the catheter and peripheral bloodwhen there is a higher bacterial load in the catheter (X5)59,60 or theblood culture from the catheter is positive at least 2 h before theblood cultures from the peripheral blood, if the samples were drawnat the same time61 or there is culture of >15 colony forming units(CFU) from the end of the catheter (after it has been taken out).62,63

14. Prevention of infections

Sterile techniques should be kept when dealing with PN linesand accessories

4C
1B
Use multi-modality strategy, including: expert PN team, hand-washing, gloves and face mask, clean with chlorhexidine 2%,avoid using a femoral vein

1A
1A
Washing hands before treating PN line is obligatory
2B 1B Clean site with chlorhexidine gluconate 2%; if not available, use
alcohol 70%
1A 1A
Always use sterile technique when inserting a catheter for PNuse

2B
1A
Give a 2 in one or 3 in one solution within 24 h
2B 1A Antibiotic lock is a proven means of preventing CRI 1A 1A Use antibiotic lock when there is a high rate of CRI 4C 1B Anti-infective coated catheter is not recommended for routine
use
1A 1A
Use of anti-infective coated catheter should be considered ifthere is a high rate of CRI

4C
1B
Prophylactic use of antibiotic ointment at the catheter exit siteshould be avoided

4C
1B
Use of 0.22 mm filters is not obligatory for infection control
3C 1B 0.22 mm filter should not be used with 3 in 1 solutions 3C 1B Either sterile gauze or sterile, transparent, semipermeable
dressing should be used to cover the catheter site
1A 1A
Healthcare workers should participate in a continuingeducation program to prevent infections

3C
1B
The CDC has published detailed guidelines regarding the controlof intravascular catheter-related infections.64 A multi-modalapproach lowered infection rates. This included a dedicated team(GCPN 1A, CDC 1A), surveillance of infections, hand washing (GCPN2B, CDC 1B), cleaning with chlorhexidine gluconate 2% (GCPN 1A,CDC 1A), and avoiding use of the femoral vein.65,66 Healthcareworker education and training is recommended to prevent infec-tions67–69 (GCPN 3C; CDC 1B).

Prevention of infections relies on strictly sterile manufacturingand handling69 (GCPN 2B, CDC 1A). Insertion of the catheter, alongwith changing the parenteral nutrition bags and infusion setsshould be done under sterile conditions and with full barrierprecautions, such as gloves and face mask.70 Hands should bewashed and sterile gloves used.71–73 The hub should be cleanedwith an antiseptic solution before every set/bag is changed. Chlo-rhexidine gluconate 2% was found to be the most effective. Adedicated catheter for the parenteral nutrition is recommended(this is important due to compatibility problems as well – seepharmacy section). Most of the studies regarding infection controlare retrospective and uncontrolled TPN solutions might becomeinfected; the longer the TPN bag is hung, the greater the risk ofinfection. Fat solutions have a higher tendency to become infecteddue to their lower osmolality than the 2-in-1 solutions. All-in-onesolutions should be given within 24 h of opening (GCPN 2B, CDC1A). Lipid solutions, when given alone, should be given within 12 hof opening the bottle (GCPN 2B, CDC 1A).74–76 An efficient tech-nique for preventing CRI is the use of an antibiotic lock (GCPN 1A,CDC 1A). Diluted vancomycin is flushed through the catheter andthe catheter is closed.77,78 In tunneled catheters, flushing the


catheter with antibiotics and heparin has proved to be beneficial(OR¼ 0.43, 95% CI 0.21–0.87). For intraluminal colonization, thebaseline infection rate is 15%, which leads to a number needed totreat (NNT) of 13 (95% CI 5–23).

There is a theoretical concern of development of vancomycin-resistant organisms; therefore, vancomycin locks are usually usedin units where there are high infection rates or in a patient who isprone to develop CRI (GCPN 4C, CDC 1B). Anti-infective coatedcatheters have been tried with various results79 (GCPN 1A, CDC 1A).The use of anti-infective coated catheter should be considered ifthere is a high rate of CRI (GCPN 4C; 1B). Common practice includesthe prophylactic use of antibiotic ointment at the catheter exit site;this encourages the development of resistant flora and should beavoided79 (GCPN 4C, CDC 1B). It was postulated that using a 0.22-mm filter could prevent in-line infections, but this was notsubstantiated, so that in-line 0.22 mm is not obligatory (GCPN 3C;1B) in 2-in-1 solutions and is totally inadequate for use with 3-in-1solutions (GCPN 3C, CDC 1B).80,81 It was found that there is nodifference in the usage of sterile gauze or sterile, transparent,semipermeable dressings to cover the catheter site.65,82 Eithersterile gauze or sterile, transparent, semipermeable dressingshould be used to cover the catheter site (GCPN 1A; CDC 1A).

15. Management of infectious complications

If a CRI is suspected, the catheter should be withdrawn if one ofthe following is present: polymicrobial infection, complexinfection, e.g., endocarditis or osteomyelitis, tunnelinfection, positive blood cultures for fungus, e.g., Candida

3C
1B
When CRI is suspected, two sets of cultures should be taken –peripherally and centrally

1A
1A
After blood cultures are drawn, empiric antibiotic treatmentshould be started and antibiotic lock considered

3C
1B
When there is evidence of an infected thrombus whena central catheter is involved, the catheter should bewithdrawn, drainage performed, antibiotic treatment andanticoagulant treatment given

4C
1B
For a peripheral PN catheter, a distal upper extremity(peripheral) site is chosen; lower extremity sites are avoided

4C
1B
When a CRI is suspected, blood cultures should be drawnsimultaneously through the catheter and through peripheral veins(GCPN 1A; CDC 1A). This will enable a considered decision ofwhether or not it is a CRI. Catheter removal is absolutely indicatedin the following situations: complex infection such as the presenceof septic emboli (osteomyelitis, endocarditis, etc.), polymicrobialinfection and candidal infection; a gram negative infection in itselfdoes not necessarily advocate catheter removal (GCPN 3C; CDC 1B).When catheter removal is not indicated, empiric antibiotic treat-ment should be started after cultures are drawn, and an antibioticlock should be considered83,84 (GCPN 3C; CDC 1B). If the catheterhas been removed, it is logical to assume that it is better to waituntil blood cultures are negative before reinsertion; if this is notpossible, it is better if the patient can be managed with a peripheralcatheter. Special consideration is needed for an infected thrombus.When this is diagnosed, the catheter should be removed. Heparintreatment is indicated in case of a central catheter only. There is noplace for thrombolytic therapy. Prolonged antibiotic therapy isgiven (GCPN 4C; CDC 1B).85–87

16. Prevention of thrombosis and thrombophlebitis

In a peripheral vein, osmolarity of solution should be kept at<800 milliosmole

3C
1B
Preventive peripheral catheter removal and reinsertion ina different site should be considered every 48 h

3C
1B
Anticoagulant flush solutions are recommended to preventcatheter thrombosis

2B
1A
Low-dose anticoagulant therapy should be used in patientsrequiring long-term catheterization

2B
1A
One of the major limits of parenteral nutrition througha peripheral vein is the development of thrombosis or thrombo-phlebitis. The chance of developing this condition is greater whenthe osmolarity of the solution is higher.88 When parenteral nutri-tion is given through a peripheral vein, osmolarity should be kept<800 miliosmole (GCPN 3C; CDC 1B). To optimize the use of theperipheral veins, the cannula should be removed and reinserted ata different site every 24–48 h (GCPN 3C; CDC 1B). The cannulashould be situated in the lower part of the hand and leg veinsshould never be used due to the very high rates of infection (GCPN4C; CDC 1B).89 In order to prevent thrombosis, anticoagulant flushsolutions are recommended90–92 (GCPN 2BBB; CDC 1A). In cases oflong-term cathetherization, low-dose anticoagulant therapy shouldbe used80,93,94 (GCPN 2B; CDC 1A).

17. Which catheter to use

On the whole, the type of the catheter used depends on theduration of the parenteral nutrition and the patient’s vein access.There are no double-blind control studies to describe the exact timelimit for each type of catheter. For short-term parenteral nutritionand when the patient’s veins are good, the peripheral route can beused; for longer terms but still within acute treatment, centralaccess is better. If the duration of treatment is intermediate, one canconsider a peripherally inserted central catheter (PICC). A PICC isprobably as good as a subclavian vein.95,96 A tunneled catheter, e.g.,Hickman, is needed for prolonged use, i.e., home parenteralnutrition.

18. Hepatic dysfunction

Cyclic PN may prevent liver dysfunction secondary toPN

2B
1B
Limit calories
5C Unresolved Limit carbohydrates 3C 1B Treat with metronidazole 2B 1B Treat with urodeoxicholic acid 3C 1B Give olive oil-based lipid emulsion or omega-3 fatty
acids containing solution
5C 1B
When cholestatic abnormalities are present andprolonged, with billirubin accumulation, refrainfrom giving manganese and copper

5C
1B
Three types of hepatic disorders have been related to TPNtreatment:

1. Cholestatic – more common in children2. Hepatocellular – initial manifestation is fatty infiltration –

more common in adults3. Biliary complications, including sludge and stones

The longer the treatment by parenteral nutrition, the greater thechance of developing a hepatic disorder. In a group of 90 patients,cholestasis was present in 55% and 72% of patients after two and sixyears, respectively.97 The rate of complicated liver disease wasmuch lower, 25% and 50%, after two and six years, respectively.Complicated liver disease was defined by extensive portal fibrosisor cirrhosis, liver complications such as bilirubin levels of >3.5 mg/


dl for longer than one month or ascites, hypertensive-related gas-tropathy, bleeding, portal hypertension, encephalopathy, or liverfailure with disturbed coagulation tests. Salvino et al. reporteda series of 208 patients treated by parenteral nutrition for anaverage of approximately two years (maximum w10 years). Almost75% had abnormal enzymes but only 3% had abnormal liver func-tion.98 The pathophysiology can be nutritional deficiencies, such ascarnitine, taurine or choline; the toxicity of a nutritional compo-nent (too much carbohydrates, lipids or manganese); change of theintestinal bacteria with resulting formation of toxic components;change in bile acid metabolism. Risk factors are premature birth,length of the remaining intestine (the shorter the intestine, thegreater the risk), duration of parenteral nutrition (the longer theduration, the greater the risk), overfeeding of lipids (>1 gr/kg/day),or too many calories.99,100

There are few treatment possibilities. The only prospectivecontrolled study assessed treatment by giving parenteral nutritionin a cyclic fashion101 (GCPN 2B, CDC 1B). A group of 65 patients wasdivided into three according to their bilirubin level (>5, >10,>20 mg%). Each group was then divided into cyclic and non-cyclicparenteral nutrition. Patients in the non-cyclic TPN group hadsignificant elevations of bilirubin and alkaline phosphatase,although in some there was a decline in albumin levels as well. Theconclusion of this study was that cyclic parenteral nutrition mayprevent deterioration of liver function. Two other modalities wereassessed in controlled studies with lower power: treatment withcholine102 was found to be effective but is not available on themarket and was given only in a trial setting with lowering of theamount of fat. Other treatment options are decreasing carbohy-drates (GCPN 3C; CDC 1B), keeping a balanced energy source (lipidsand carbohydrates)103 (GCP5C; CDC 1B), treatment with urso-deoxycholic acid104 (GCPN 3C; CDC 1B), and encouraging oral orenteral feeding. Treatment with metronidazole was tested in chil-dren with controversial results105 and in adults in a retrospectivestudy106 (GCPN 2B; CDC 1B). Changing to a different lipid solution,such as olive oil-based or omega-3-containing solution, can be tried(GCPN 5C; CDC II). If there is a further decline in liver function,transplantation is the only treatment option.

When there is a prolonged cholestatic disorder with bilirubinaccumulation, whether secondary to parenteral nutrition or, as ismore common, due to other reasons, care should be taken withtrace elements, as most are secreted through the biliary system(GCPN 5C; CDC 1B). The two trace elements which should begiven are selenium and zinc. When eliminating other traceelements, copper deficiency could ensue; therefore, serum coppershould be checked periodically. Laboratory signs of copper defi-ciency include pancytopenia.107,108 On the other hand, hyper-manganesemia has been described in patients with liverabnormalities. The diagnosis is based upon neurological symp-toms and MRI findings.109

19. In-line filters

In-line filters 0.22 mm should be considered in patients receiving2-in-1 solutions if they are in immunosuppressed, home PN orneonates. A 1.2-mm should be used in all patients receiving 3-in-1PN solutions110 (GCPN 4C; CDC 1B).

20. Guidelines on parenteral nutrition: intensive care

Recommended energy requirements are 25–30 kCal/kg afterstabilization and recovery

3C
1B
The enteral route is the preferred route
1A 1A
Mixed enteral and parenteral nutrition should be provided topatients who are unable to receive the calories required bythe enteraly

3C
II
Calorie requirements should be measured by indirectcalorimetry if possible

2B
1B
Parenteral nutrition is advocated in patients in whom nutritioncannot be supplied by the enteral route within 24 h

2B
1B
Adequate nutrition and calories should be provided while IIT isimplemented aiming at targeted glucose levels

1A
1A
Omega-3 fatty acids may be a valuable nutritional additive toimprove outcomes in patients with peritonitis, trauma,systemic inflammatory response and sepsis

3C
II
Glutamine supplementation (0.3–0.5 g/kg) for at least 5 daysmay be of benefit to ICU patients

1A
1A
Malnutrition is defined as a state of nutrition in which a defi-ciency or excess of energy, protein, or other nutrients causesmeasurable adverse effects on tissue/body form (body shape, sizeand composition) and function and clinical outcome.111 A vastmajority of critically ill patients present this condition and there-fore are considered as malnourished when they are admitted to theICU. This condition endangers them and they are at risk of increasedinfection, morbidity and mortality.112 The interaction betweennutritional status and immune state, as well as muscle massdeterioration, are important components of the risks of infectionand weaning problems, inducing more pulmonary infections andincreasing length of ventilation and length of ICU stay.113 In thenutritional screening score proposed by ESPEN,6 patients admittedto the ICU and scored with an APACHE II score of more than 10received a nutritional score of more than 3 and thus were consid-ered as nutritionally at risk and in need of a nutritional care plan.Enteral feeding recommendations for ICU patients have beendefined previously.114 These guidelines will focus on parenteralrequirements and administration in the critically ill.

20.1. Indications for parenteral nutrition in ICU

Patients suffering from GI failure should receive parenteralnutrition. This includes short bowel syndrome, high output fistula,ileus, or severe diarrhea. A second inclusion group is composed ofpatients requiring mixed enteral and parenteral nutrition (GCPN4C; CDC II).

20.2. How much energy should be administered to the ICU patient?

Energy requirements are usually determined by equations pre-dicting needs in calories. The oldest and most used equations arethe Harris Benedict equations, but others have been proposed in theICU: Ireton-Jones, Fagon and others115,116 introduce not only weightand height, but also minute volume (L/min) and fever. Indirectcalorimetry remains the gold standard for determination of energyrequirements and 17–20% of ICUs use this method despite the factthere are no guidelines for its use.117 A recent prospectiverandomized study argued in favor of tight calorie provision withsignificant improvement in the hospital survival.118 The preferredrecommendations for energy requirements are proposed by theACCN and ESPEN and are 25–30 kCal/kg after stabilization andrecovery (GCPN 3C; CDC 1B).119

20.3. Nutrition and tight glucose control (TGC) in ICU

Hyperglycemia impairs the cellular immune system, stimulatesinflammatory cytokines, and affects the microcirculation, thusincreasing the risk for infection and preventing normal woundhealing.120 Implementing TCG by intensive insulin treatment (IIT)aiming at euglycemia reduced morbidity and mortality in ICU


patients. Mebis summarized the data and specified that, ina subgroup of patients with prior diabetes, safety has not beenproved and might reduce survival in patients with prior insulindependant diabetes.121 In non-diabetic patients, the aim is to reacha state of euglycemia. It is beyond the scope of these guidelines todefine the optimal glucose level for diabetic patients. It has beenproven that providing the needed amount of calories is of benefitand that providing a low calorie diet does not prevent hypergly-cemia.11,122 Therefore, adequate nutrition and calories should beprovided while IIT is implemented, aiming at targeted glucoselevels (GCPN 1A; CDC 1A).

20.4. Route of administration and when to give parenteral nutritionin ICU

The enteral route is the preferred route (GCPN 1A; CDC 1A).However, many observational studies have demonstrated that therequirements are not reached with the enteral route and thata negative energy balance is associated with increased complica-tion rates and mortality.11,12,123 Early enteral feeding is preferredand recommended by ESPEN,117 but mixed enteral and parenteralnutrition in patients who are unable to receive the calories requiredhas been suggested recently124 (GCPN 3C; CDC II). Reaching therequirements according to indirect calorimetry measurements hasbeen proposed but prospective randomized studies are necessaryto demonstrate this point125 (expert opinion).

20.5. Is parenteral nutrition more dangerous than enteralnutrition?

In a meta-analysis comparing enteral to parenteral nutrition, theuse of enteral nutrition as opposed to parenteral nutrition resultedin an important decrease in the incidence of infectious complica-tions in the critically ill and may be less costly.126 Enteral nutritionshould be the first choice for nutritional support in the critically ill(GCPN 1A; CDC 1A). However, no difference in mortality rate wasobserved between the two groups. In addition, the consensus groupnoted that hyperglycemia and insulin requirements were observedfrequently in patients receiving parenteral nutrition. The Van denBerghe study was performed in patients receiving mixed enteraland parenteral nutrition and demonstrated improvement inmorbidity and mortality in patients receiving the mixed nutritionalsupport.21 Therefore, mixing enteral with parenteral nutrition toreach calorie targets in ICU patients is advised (GCPN 3C; CDC II).Anther meta-analysis of 11 trials127 showed no difference in termsof mortality if enteral feeding was started early and a beneficialeffect of parenteral nutrition on mortality if enteral feeding wasstarted later. Therefore, a recommendation can be generated forparenteral nutrition used in patients in whom enteral nutritioncannot be initiated within 24 h of ICU admission or injury (GCPN2B; CDC 1B). ESPEN enteral feeding guidelines also recommendadding parenteral nutrition carefully to ICU patients in whom thetarget level of enteral feeding could not be reached (GCPN 3C; CDCII), at a level equal to but not exceeding the nutritional needs of thepatient. Overfeeding should be avoided. The Canadian guidelinesare more cautious and suggest weighting indications in eachcase.128

20.6. Lipid emulsions as a part of the parenteral nutrition regimenin ICU

Lipid emulsions, including MCT, seem to be preferred in ICUpatients since they are metabolized faster and provide an energysource to the mitochondria. They improve nitrogen balance27 andoxygenation in ARDS patients receiving parenteral nutrition.34

Olive oil-based nutrition has been tested in trauma patientsrecently128 and showed a metabolic advantage regarding glucosecontrol when compared to glucose-based parenteral nutrition. Arecent meta-analysis129 compared the immune effects of all thelipid emulsions and did not find an advantage to any.

Parenteral fish oil supplements have been administered ina routine setting after major abdominal surgery.130 Analysis of thedata showed a decrease in mortality in patients receiving thissupplementation before and after surgery. Heller showed animprovement in the diagnosis-related clinical outcomes of criticallyill patients receiving omega-3 lipid-based parenteral nutrition.131

The survival rate was better and there was a decreased need forantibiotics. The supplementation with omega-3 fatty acids wasassociated with improved survival and accelerated recovery.Omega-3 fatty acids may be a valuable nutritional additive toimprove outcomes in patients with peritonitis, trauma, systemicinflammatory response and sepsis (GCPN 3C; CDC II).

20.7. Indication for Glutamine in ICU

A systematic review of the evidence regarding the use ofglutamine supplementation in serious illness was performed byNovak et al.132 and showed heterogeneous results. However, twostudies133,134 demonstrated a 6-month outcome improvement incritically ill patients, expressed in incidence of death within sixmonths. In addition, the addition of glutamine reduced infectiouscomplications and glucose intolerance in critically surgicalpatients.135 The recommendation of the consensus group was thatglutamine supplementation (0.3 g/kg) for at least 5 days may be ofbenefit to ICU patients (GCPN 2B; CDC 1B).

21. Short Bowel Syndrome (SBS)

Patients who underwent extensive small bowel resection areat nutritional risk.

3C
IB
Patients who underwent extensive small bowel resection mostlikely will need parenteral nutrition during first 7–10 daysto meet their nutritional and fluid-electrolyte demands.

3C
IB
Enteral nutrition should be re-introduced (along withparenteral nutrition) soon after the surgery and attempts ofweaning from parenteral nutrition should be started.

3C
IB
Enteral nutrition is an important factor in intestinal adaptationand therefore it should be an essential part of efforts inweaning from parenteral nutrition.

3C
IB
Patients with <150 cm of remaining small intestine (with nocolon in continuity) or <60–90 cm of remaining smallintestine (with colon in continuity) are unlikely to weanfrom parenteral nutrition and most likely will be completelyor partially dependent on parenteral nutrition.

3C
IB
Intestinal adaptation occurs usually during first 2 years afterthe small intestinal resection. Patients who did not succeedto wean from parenteral nutrition during first 2 years areunlikely to wean in the future.

3C
IB
Currently, the 5-year survival with parenteral nutrition isbetter than graft survival after small intestinaltransplantation. Therefore, only patients who failedparenteral nutrition or had life-threatening complications ofparenteral nutrition are considered to be candidates forintestinal transplantation.

3C
IB
SBS is a malabsorptive state for both macro- and micro-nutrients that may follow massive resection of the small intes-tine. In adults, this syndrome occurs most commonly aftersurgery for Crohn’s disease or mesenteric infarction. In children,the causes are different and the main reasons are surgicalresection due to necrotizing enterocolitis or congenital intestinalabnormalities.


Patients who undergo extensive small bowel resection are atnutritional risk136,137 (GCPN 4C) because both nutrient and fluidabsorptions are compromised. This data came from multiple, mainlydescriptive, studies from 1980 to 1990. For example, Bambach andHill136 and Hatakeyama et al.137 who evaluated patients whounderwent extensive resection of the small intestine found high ratesof underweight, low anthropometric parameters, low laboratorynutritional parameters, and excessive loss of macronutrients in feces.

The management of patients with SBS is different in theimmediate post-operative period than in a later period. Theimmediate post-operative period after intestinal resection is char-acterized by significant fluid and electrolytes losses. Therefore,these patients most likely will need parenteral nutrition during thefirst 7–10 days to meet their nutritional and fluid-electrolytedemands138–144 (GCPN 4C CDC 1B). While this statement is notsupported by prospective studies, it is common practice dictated byreal-life situations. After this critical period, enteral nutritionshould be re-introduced along with parenteral nutrition, andattempts at weaning from parenteral nutrition should be star-ted138–145 (GCPN 3C CDC 1B). For example, Levy et al.145 enrolled 32patients with a short bowel (30–150 cm) who started receivingenteral nutrition 14 days after surgery. Mean faecal volume did notincrease following enteral nutrition. Several additional prospectivestudies have explored this issue, but none were randomized.

The idea of early re-introducion of enteral nutrition is based onmany animal and in vitro studies, as well as some comparativehuman studies. They indicated that enteral nutrition is an importantfactor in intestinal adaptation and should be an essential part of theeffort in weaning from parenteral nutrition140–142,144,146 (GCPN 3CCDC 1B). However, only some patients with SBS will be able to weaneventually from parenteral nutrition. Patients with <150 cm ofremaining small intestine (with no colon in continuity) or <60–90 cm of remaining small intestine (with colon in continuity) areunlikely to wean from parenteral nutrition and are most likely to becompletely or partially dependent on parenteral nutrition147,148

(GCPN 4C CDC 1B). This data is supported by prospective andretrospective descriptive studies. Messing et al.148 created a Coxregression model to study the influence of anatomic variables. Itindicated that intestinal adaptation usually occurs during the firsttwo years after small intestinal resection and patients who did notsucceed to wean from parenteral nutrition during the first two yearsare unlikely to wean in the future. After two years of parenteralnutrition, the probability of permanent intestinal failure is 94%.

Another relevant issue is the possibility of intestinal trans-plantation to overcome parenteral nutrition dependence. Currently,the 5-year survival rate with parenteral nutrition is better thangraft survival after small intestinal transplantation. Therefore, onlypatients who fail parenteral nutrition or who have life-threateningcomplications from parenteral nutrition are considered to becandidates for intestinal transplantation (GCPN 4C CDC 1B).149–152

It should be noted that the results of intestinal transplantation areimproving so that this recommendation is likely to change in thefuture, when survival after transplantation exceeds that of pro-longed parenteral nutrition.

22. Intradialytic parenteral nutrition (IDPN)

IDPN has no place in routine treatment of dialytic patients.
1A 1A IDPN could be considered in specific patients when dialysis is
combined with intestinal failure.
5C
Hemodialysis is an active renal replacement treatment ofpatients with terminal renal failure. It consists of extra-corporal

flow of the patient’s blood through unidirectional filters. A patienton hemodialysis is in severe stress with increased nutritionalneeds. The energy expenditures of the dialysis patient are high: 30–35 kcal/kg are recommended, as 1–3 g of protein and 9–12 g ofamino acids may be lost in each dialysis cycle. An intake of 1.2 g perkg of weight of protein is recommended.153,154 Malnutrition isprevalent in 20–80% of patients on hemodialysis due to: low intakeof energy and proteins, loss of nutrient into the dialysis fluid,hypermetabolic state secondary to chronic state of diseaseincluding biocompatibility of the dialysis membranes and inflam-mation with elevated cytokines levels and endocrine reactionssecondary to the uremic state. Oral feeding with enteral formulasfortification is the method of choice to overcome the nutritionaldeficiency.

One long-term controlled study of IDPN has been conducted, inwhich 186 malnourished hemodialytic patients were treated eitherby oral supplements alone or by oral supplements with IDPN forone year. After two years, IDPN did not improve the 2-yearmortality, hospitalization rate, Karnofsky score, body mass index orlaboratory markers of nutritional status more than oral supple-mentation alone.155 It could be deducted that IDPN has no place inthe routine treatment of dialytic patients (GCPN 1A CDC 1A).

Despite dietary intervention in patients on hemodialysis,protein energy malnutrition (PEM) is prevalent. PEM mightaccompany acute disease states, such as major surgery of theabdomen or lower limbs, severe infections or cancer with activetreatment chemotherapy or radiotherapy.156,157 Signs of PEM in thedialysis patient are156,157,159–161:

1. Albumin lower than 34 g/L for � three months2. Serum creatinine< 8 mg/dL for � three months3. Weight loss of 20% over � six months4. BMI lower than 18.55. Intake of energy lower than 25 kcal/kg/day6. Intake of protein lower than 0.8 g/kg/day

With three of these and failure of enteral feeding and diet, IDPNmight considered. IDPN could be considered in specific patientswhen dialysis is combined with intestinal failure (GCPN 5C CDC: norecommendations).

22.1. The process of IDPN156,158,159

The protocol for IDPN is empiric. IDPN is given during thedialysis session of 4–6 h, 2–7 times a week. Frequency is deter-mined by the patient’s need for dialysis. IDPN is an adjuvanttreatment of dialysis, using the same venous access and time oftreatment.

IDPN solutions are parenteral nutrition solutions with aminoacids up to 10%, dextrose as needed, and lipids up to 20%. When thefat is given separately, the solutions should be given through a 0.22-mm filter; when all-in-one solutions are given, a 1.2-mm filter isused. The rate of infusion should not exceed 300 ml/h, starting withthe beginning of dialysis. The IDPN is connected to the venous poleof the dialysis and added to the patient’s water balance of eachdialysis.

Rate of infusion of amino acids: on the first time, patients willreceive only 500 ml consisting of 250 ml of 10% amino acids and250 ml of 50% dextrose. The staring rate is 150 ml/h and the rate isincreased by 25 ml/h every hour.

Lipid solution is given for the first time as a 20% solution and nomore than 100 ml. During the first 30 min, the rate is 1 ml/min.During the coming dialysis, lipids are given throughout the entiretreatment. From the fifth IDPN treatment, 500 ml of 20% lipids aregiven.


With all-in-one solutions giving amino acids, lipids anddextrose, 1 ml/min is given during the first 30 min; the rate isincreased but does not exceed 300 ml/h.

22.2. Monitoring the patient on IDPN

Glucose levels are checked before treatment, at 60 and 120 min,and at the end of treatment. If levels are higher than 300 mg/dL,insulin is considered. If continuous insulin treatment is started,glucose monitoring every 30 min is recommended. If glucose levelsare lower than 200 mg/dL, a small meal is given and glucose is re-examined 30 min after the end of the treatment before discharge ofthe patient home.

22.3. Terminating IDPN

IDPN is a temporary treatment and when dialysis and is stoppedwhen nutritional status is considered adequate.

Indications for discontinuation of IDPN158:

1. Albumin higher than 38 g/L � month2. Serum creatinine higher than 10 mg/dL � month3. BMI higher than 19.54. Intake of energy higher than 30 kcal/kg/day5. Intake of protein higher than 1 g/kg/day

When three criteria are fulfilled, IDPN should be stopped.Discontinuation can be immediate and there is no need forprogressive discontinuation.

The usual period for IDPN is 3–6 months, as it accompaniesacute disease; when the acute state resolves, the indication forIDPN ceases.

23. Conclusion

IDPN is not indicated routinely, only on a personal basis whenspecial and unique circumstances complicate end-stage renaldisease.

23.1. Inflammatory bowel disease (IBD)

Parenteral nutrition and bowel rest have no therapeuticbenefit as a primary therapy for Crohn’s disease orulcerative colitis.

1A
1A
TPN should be given to severely malnourished patients beforesurgery.

3C
1B
TPN is part of treatment for patients with Crohn’s disease withfistulae.

Expert opinion

Inflammatory bowel disease (IBD) includes Crohn’s disease (CD)and ulcerative colitis (UC). CD can involve any part of the gastro-intestinal (GI) tract, affecting the terminal ileum and/or colon inmost cases. Fistulae to other segments of the bowel or adjacentorgans and skin are common. Ulcerative colitis is restricted to thecolon. It begins in the rectum and spreads continuously moreproximally.

In the past, parenteral nutrition and bowel rest were the maintherapy for IBD. Ostro et al. demonstrated remission rates of 63–89%with TPN in a large retrospective series of refractory CD patients.162

However, Matuchansky et al. emphasized that there were highrelapse rates (40–62%) after two years.163 In most cases, parenteralnutrition induces temporary remission during acute attacks of IBDbut, upon resuming oral nutrition, the disease activity returns to theprevious level. Four prospective randomized controlled studies

have been conducted and support this statement.164–167 Lochset al.166 studied 12 patients with active Crohn’s disease who wererandomized to receive parenteral nutrition only or a combination ofparenteral and enteral low-residue nutrition. At the end of 28 daysof study, the improvement in the nutritional state and diseaseactivity was the same in both groups. The use of parenteral nutritionin many IBD patients was found to be unjustified and, in a retro-spective series, was associated with higher in-hospital mortality,longer length of stay, and higher hospital charges.140

Another historical concept was the use of bowel rest andparenteral nutrition aimed at inducing remission in the cases ofsevere UC so that colectomy was avoided. Prospective controlledstudies found that parenteral nutrition and bowel rest are inef-fective in inducing remission in IBD patients,164,165 but may be usedto promote a better peri-operative course (see below). Parenteralnutrition and bowel rest have no therapeutic benefit as a primarytherapy for CD or UC (GCPN 3C).162–167

Some defined clinical situations may justify parenteral nutrition.Parenteral nutrition should be preserved for severely malnourishedpatients with extensive CD or UC, or when oral or enteral feeding isnot tolerated or contra-indicated (intestinal obstruction) (GCPN 2BCDC 1B). It should be used in these cases as a bridge until remissioncan be achieved with medical or surgical therapy.

Parenteral nutrition and bowel rest may be used in cases of highoutput entero-cutaneous fistulae associated with Crohn’s disease.

There are no studies comparing enteral and parenteral nutritionand bowel rest in Crohn’s patients alone, only as a part of differenttreatment regimens in patients with fistulae. Nevertheless, paren-teral nutrition and bowel rest in patients with high output entero-cutaneous fistulae are standard treatment, because of its ability toreduce fistula output and decrease fluid and electrolytes losses.Parenteral nutrition is not the sole treatment and should be used inconjunction with medical treatment or as a part of surgical treat-ment. Parenteral nutrition may be indicated in patients withfistulae as part of a comprehensive treatment protocol includingmedical or surgical intervention (GCPN 4C CDC 1B).

Patients with IBD are at increased risk for operative interventionin comparison with the general population. In general, patientswith IBD do not need peri-operative parenteral preparation.However, peri-operative parenteral nutrition may be used inseverely malnourished patients with severe IBD in whom surgerymay be safely postponed (GCPN 3C CDC 1B).168–171 This issue hasbeen investigated primarily in retrospective studies that haveshown an improvement in albumin level, mean body weight, anda decreased length of bowel requiring resection, but at the expenseof longer hospitalization. Safety and feasibility of home parenteralnutrition in patients with IBD prior to surgery was described ina series of 15 patients with 80% success in delivering TPN (onepatient developed a TPN-related complication)167 pre-operativeparenteral nutrition has an effect when given for at least five days.

23.2. TPN for oncology patients

TPN should not be implemented routinely in all cancerpatients prior to surgery.

3C
2B
Nutrition support should be implemented in malnourishedcancer patients who are going for surgery for at least 7 daysprior to surgery.

1A
1A
TPN should be given to malnourished patients who do nottolerate enteral nutrition.

1A
1A
TPN should not be used routinely during radiation.
1A 1A TPN should be used for severe radiation enteritis or in
malnourished patients when the enteral route fails.
Expert opinion
TPN should not be administered routinely in patients withincurable cancer and total intestinal obstructions.

3C
II


In patients with incurable cancer and total intestinalobstructions treatment should be tailored personally takinginto account patient’s general performance status andpreferences.

5C
Expert opinion
The topic of parenteral nutrition for oncology patients isa controversial and sensitive issue. TPN for oncology patients isdealt with in three different situations:

1. Before surgery2. During chemotherapy or radiotherapy3. For non-curable patients:

a. With malfunction of the gastrointestinal tract, e.g. due toobstruction

b. Terminal patients with an intact and functioning gastroin-testinal tract

It seems that the type of malignancy is of minor importance,while differentiating according to disease stage and whether thegastrointestinal tract is functioning or not are the major consider-ations for or against TPN in these patients. The patient’s nutritionalstate is of major importance, of course.

Two previous position papers and one meta-analysis have beenpublished.172–174 None specified different recommendationsaccording to subgroup. The 1989 position paper of the AmericanCollege of Physicians172 states:

1. ‘‘Patients receiving parenteral nutritional support were only81% as likely to survive as control patients.’’

2. For short-term survival (3 months), the best estimate of theodds ratio is 0.74.

3. For tumor response rates, the best estimate was that nutri-tionally supported patients were only 68% as likely to achievecomplete or partial responses (p¼ 0.12).

The 2001 position paper of the American GastroenterologicalAssociation will be discussed in different subsections of thispaper.6

The 1990 meta-analysis by McGeer et al.174 states that TPN inthese patients has a detrimental effect: trend to decreased survival,poorer tumor response, significant increase in infectious compli-cations, and no clinical significant effect on gastrointestinal orhematological toxicity. TPN itself (not catheter-related septicemia)may increase susceptibility to infection.

In a review by Klein and Koretz from 1994175 of 70 prospectiverandomized controlled trials of nutritional support in general notspecific for TPN, the authors concluded that the many trials were ofpoor quality. The existing data failed to demonstrate the clinicalefficacy of providing nutrition support to most patients with cancerand that indications for nutritional treatment in cancer patientsshould be like the indications in benign diseases.

23.3. Peri-operative TPN support

A systemic retrospective review of patients undergoing pan-creaticoduodenectomy indicated that routine post-operative TPNadministration was associated with a higher incidence of compli-cations, while enteral nutrition reduced infective complications.176

Wu et al.177 prospectively studied 468 moderately or severelymalnourished patients with CRC based on the subjective globalassessment and randomly assigned them to seven days of pre-operative nutrition support (68% were put on PN). The nutritionregimen included 25 kcal/kg d and 0.25 g N/d 8–10 before surgeryand was continued for >7d after. Control patients received

a standard hospital oral diet before and hypocaloric PN after(600 kcal/d 60 g AA). The results indicated significantly lowermortality and complications (no difference in septic complica-tions), and lower total length of hospitalization and post-opera-tive stay. In another study, Bozzetti et al.178 prospectivelyincluded 90 patients with gastric or colo-rectal cancer (CRC).Patients who lost >10% of their usual body weight, wererandomly assigned to receive by TPN 34.6� 6.3 kcal/kg and0.25� 0.04 N/kg d for 10 days pre and nine days post-operativelyvs a control group that did not receive pre-operative nutrition butdid receive 940 kcal and 85 g AA/d post-operatively. The resultsindicated: lower mortality and a reduced rate of post-operativecomplications. There was no difference in post-operative lengthof hospitalization.

Muller et al.179 compared 10 days of pre-operative PPN toa regular hospital diet in 66 patients on PPN vs 59 controls.Significant reduction was noted for major complications andmortality. Rates of post-operative wound infections, pneumonia,major complications and mortality were generally lower in PPN. Ina recent retrospective historical study of 1410 subjects whounderwent major abdominal surgery for gastrointestinal cancerand received various types of nutritional support, nutritionalsupport reduced morbidity compared to standard intravenousfluids in an increasingly protective effect of TPN, enteral nutritionand immune-enhancing enteral nutrition.180

TPN should not be implemented routinely in all cancer patientswho are to undergo surgery (GCPN 3C CDC 2B), but should beimplemented in malnourished cancer patients scheduled forsurgery; TPN should be used in these patients for at least seven daysprior to surgery, when the enteral route is not feasible (GCPN 1ACDC 1A).

23.4. TPN during chemotherapy

Previous position papers and meta-analysis stated thefollowing:

1. American College of Physicians 1989172: in not undernourishedsubjects using TPN should be strongly discouraged.

2. AGA173: the routine use of parenteral nutrition for patientsundergoing chemotherapy should be strongly discouragedand, in deciding to use such therapy in individual patientswhose malnutrition is judged to be life-threatening, physi-cians should take into account the possible exposure toincreased risk.

In a meta-analysis by Klein et al. of 28 prospective randomizedcontrolled studies, no significant statistical differences were foundin survival, treatment tolerance, treatment toxicity or tumorresponse. However, patients on TPN had an increased risk fordeveloping infections.181

In the meta-analysis of McGeer et al.174 regarding TPN duringchemotherapy, the pooled data showed that total parenteralnutrition (TPN) has a detrimental effect: best estimates associateTPN use with trends to decreased survival (relative risk 0.81; 95%confidence limits [CL] 0.62, 1.0) and poorer tumor response (oddsratio 0.68; 95% CL 0.40, 1.1), with a significant increase in infectiouscomplications (odds ratio 4.1; 95% CL 2.4, 6.9), and no clinicallysignificant effect on gastrointestinal or hematological toxicity (datanot amenable to quantitative analysis).

De Cicco et al. studied 43 patients with RCT (24 malnourished),and randomly assigned them to a crossover intervention chemo-therapy� TPN support. The results indicated that TPN was unableto reduce chemotherapy-associated toxicity or to improve thenutritional indices in well-nourished patients. Their conclusion was


that TPN should be limited to severely malnourished neoplasticpatients.182 In a retrospective analysis of 45 patients with esopha-geal cancer who received chemotherapy with and without nutri-tional support, Sikora et al. found no differences in nutritionalparameters, response rate to chemotherapy, surgical morbidity orhospital stay. Their conclusion was that TPN should not be appliedroutinely.183

Bozzetti et al. subjected malnourished GI cancer patients post-operatively to enteral versus parenteral nutrition in a randomizedprospective study, and found a significantly better outcome inpatients treated with enteral nutrition vs the parenteral group:decreased in postoperative complications and shorter length ofstay. Their conclusion was that early enteral nutrition reducescomplications and duration of postoperative stay compared withPN, although PN is better tolerated.184

TPN during chemotherapy should only be used in malnourishedcancer patients when enteral nutrition fails to provide enoughcalories (GCPN 2B CDC 1B).

23.5. TPN during radiation therapy

In a meta-analysis of 28 prospective randomized controlledstudies by Klein et al., there were no significant statisticaldifferences in survival, treatment tolerance, treatment toxicity ortumor response.181 In a randomized prospective trial in childrenwith previously untreated malignancies requiring abdominal andpelvic radiation and chemotherapy, TPN was efficacious inmaintaining good nutritional status during combined treatment,but there was no beneficial effect on the ability to toleratetherapies in terms of decreased toxicity, although there was animproved adherence to chemotherapy and no difference inmortality rate.185

TPN should not be used routinely during radiation (GCPN 1ACDC 1A). TPN can be used for severe radiation enteritis or inmalnourished patients when the enteral route fails (Expertopinion).

23.6. Bowel obstruction and TPN

The Working Group of the European Association for PalliativeCare suggested that: TPN should not be considered as a routinepart of a terminal care regimen but should be used in selectedpatients. TPN should not be a substitute for appropriatepsychological support of the patient and family. Inoperablepatients being managed by drug therapy should be encouragedto drink and eat small amounts of their favorite beverages andfood. It is important for these patients to at least taste theirfavorite food and drinks.186

There are only retrospective studies on this field. The largestseries included 52 patients with various incurable malignancies.187

Median time from initiation of TPN to death was 5 months (range,1–154 months) and this historical series proves that prolongedsurvival with TPN in selected patients is feasible. In a cohort of 55patients with stage III/IV epithelial ovarian cancer hospitalized forterminal intestinal obstruction, median survival from time ofdiagnosis was 72 days for patients receiving TPN and 41 days forthose not receiving, but there was no difference after adjustingfor chemotherapy. Overall survival was shorter for patients on TPNfor 23 versus 35 months.188

In a retrospective review of nine patients considered for homeTPN, there was variable survival of 27–433 days. A survival rate oflonger than 60 days was noted in six patients, but there was noclear prediction of who would benefit from TPN.189 In anotherretrospective study of 21 patients with advanced epithelial ovariancarcinoma treated with chemotherapy in order to restore intestinal

function after small bowel obstruction, those on TPN and chemo-therapy had a median survival of 89 days compared to 71 days forthose on chemotherapy alone.190

TPN should not be administered routinely in patients withincurable cancer and total intestinal obstructions (GCPN 3C CDC II).

The group could not reach agreement regarding patients withincurable cancer, intestinal obstruction with fair or higher perfor-mance status, and life expectancy exceeding a few days. There is notenough data regarding this group of patients. Subjective experienceis that some of these patients might gain from being treated withTPN. Until more data is available, it is recommended that consid-erations should be patient-tailored and decisions taken on a one-to-one basis (GCPN 5C and expert opinion).

23.7. Incurable disease

Well-defined end-points and careful measures of nutritionalstatus, quality of life and survival are needed.

There seems little doubt that aggressive conventional nutri-tional support has limited benefits in the majority of cancerpatients.

Subjective reasons for giving TPN to terminally ill cancerpatients persist and include compassionate, ethical, religious oremotional reasons.

Conflict of interest

The Israel Society for Clinical Nutrition is proposing for publi-cation 2 manuscripts summarizing the guidelines for use of TPN inIsrael. The Society received a financial support to cover theexpenses related to meetings from Teva Medical representative ofBaxter, Cure representative of Fresenius, Luxembourg, representa-tive of B Braun and Abbott, as well as AMI technologies, represen-tative of Arrow in an equivalent way. The following authors have todeclare conflict of interest: I Chermesh, E Niv, N Vaisman arespeakers in the TNT course for Abbott, P Singer is on the speakerbureau of Baxter, Fresenius, Abbott and has research grants fromFresenius and B Braun.

Appendix 1. Level of literature scientific proof – GCPN

Level Grading

1
RCTs with strong power, Meta-analyses A 2 RCTs with low power B 3 Non-RCT comparative studies, Cohort studies C 4 Historical comparative studies 5 Case reports
Appendix 2. CDC categorizing recommendations

Category IA. Strongly recommended for all hospitals andstrongly supported by well-designed experimental or epide-miologic studies.Category IB. Strongly recommended for all hospitals and viewedas effective by experts in the, based on strong rationale andsuggestive evidence, even though definitive scientific studiesmay not have been done.Category II. Suggested for implementation in many hospitals.Recommendations may be supported by suggestive clinical orepidemiologic studies, a strong theoretical rationale, or defini-tive studies applicable to some, but not all, hospitals.No recommendation; unresolved issue. Practices for whichinsufficient evidence or consensus regarding efficacy exist.


Appendix 3. Screening tools


Change: duration ________ weeks ___ ____ months

Type: sub-optimal solid diet ________ full liquid diet ________ hypocaloric liquid diet _______ starvation ______

3. Gastrointestinal symptoms (persisting more than 2 weeks)

None Nausea ________ Vomiting Diarrhea ________ Anorexia _______

4. Functional capacity

No dysfunction ___________

Dysfunction: duration _______ weeks _______ months

Type: working sub-optimally ________ ambulatory _________ bedridden _________

5. Disease and its relationship to nutritional requirements

Primary diagnosis: ____________________________

Metabolic demand / Stress: none ________ low ________ moderate ________ high ________

B. Physical Examination

(for each specify: 0 = normal, 1+ = mild, 2+ = moderate, 3+ = severe)

Loss of subcutaneous fat (triceps, chest) ______________

Muscle wasting (quadriceps, deltoids) _________________

Ankle edema ________ Sacral edema ________ Ascites ________

C. Subjective Global Assessment Rating

Well nourished A

Moderately (or suspected)

of being) malnourished B

Severely malnourished C

Subjective Global Assessment of Nutritional Status

A. History

1. Weight change

Overall loss in past 6 months: ________ kg Percent loss ________

Change in past 2 weeks: increase no change decrease

2. Dietary intake change relative to normal

No change ________



Appendix 4. Energy requirements WHO

Age (years) Male Female

18–30
(15.3XW)þ679 (14.7XW)þ996 30–60 (11.6XW)þ879 (8.7XW)þ829 >60 (13.5XW)þ987 (10.5XW)þ596
Harris–Benedict:

BMRwomen ¼ 665þ ð9:6XWÞ þ ð1:8XHÞ � ð4:7XAÞ

BMRmen ¼ 66þ ð13:7XWÞ þ ð5XHÞ � ð6:8XAÞ

W¼actual weight (kg); H¼ height (cm); a¼ age (years)Original and revised Ireton-Jones equations20

Spontaneously breathing patients:

l JEEðsÞ ¼ 629� 11ðAÞ þ 25ðWÞ � 609ðOÞ

Ventilator-dependent patients (original)

l JEEðvÞ � 1925þ 10ðAÞ þ 5ðWÞ þ 281ðSÞ þ 292ðTÞ þ 851ðBÞ

Ventilator-dependent patients (revised)

l JEEðvÞ � 1784þ 11ðAÞ þ 5ðWÞ þ 244ðSÞ þ 239ðTÞ þ 804ðBÞ

I JEE: kcal/d; s¼ spontaneously breathing; v¼ ventilator-dependent; A¼ age (years); W¼ body weight (kilograms); S, sex(male¼ 1,female¼ 0); T, diagnosis of trauma (present¼ 1,absent¼ 0); B, diagnosis of burn (present¼ 1, absent¼ 0); and O,obesity 30% above ideal body weight or body mass index> 27 kg/m2

(present¼ 1, absent¼ 0).

References

1. Okada A, Takagi Y, Nezu R, Sando K, Shenkin A. Trace element metabolism inparenteral and enteral nutrition. Nutrition 1995;11:S106–13.

2. McKinlay EM, Dowell T, Howden-Chapman P. Clinical practice guidelines:a selective literature review, General Practice Department Working Paper No1, 2001. Prepared for the New Zealand Guidelines Group (www.otago.ac.nz/wsmhs/academic/gp/research/NZGGliteraturereview.pdf).

3. ECPC Proposal of a Method to produce Guidelines by Formal Consensus NCworking document 060504, Adapted from ANAES Formal Consensus Method,www.anaes.fr.

4. Agency for Health Care Policy and Research. Clinical Practice Guidelines No.1AHCPR Publication No. 92-0023; 1993.

5. Naylor CJ. Does a multidisciplinary total parenteral nutrition team improvepatient outcomes? A systematic review. J Parenter Enteral Nutr 2004;28:251–8.

6. ASPEN Board of Directors and the Clinical Guidelines Task Force. Guidelinesfor the use of parenteral and enteral nutrition in adult and pediatric patients.J Parenter Enteral Nutr 2002;26:1SA–138SA.

7. Kondrup J, Allison SP, Elia M, Vellas B, Plauth M, Educational and ClinicalPractice Committee, et al. ESPEN guidelines for nutrition screening 2002. ClinNutr 2003;22:415–21.

8. Kyle UG, Kossovsky MP, Karsegard VL, Pichard C. Comparison of tools fornutritional assessment and screening at hospital admission: a populationstudy. Clin Nutr 2006;25:409–17.

9. Stratton RJ, King CL, Stroud MA, Jackson AA, Elia M. Malnutrition universalscreening tool predicts mortality and length of hospital stay in acutely illelderly. Br J Nutr 2006;95:325–30.

10. Stratton RJ, Elia M. Deprivation linked to malnutrition risk and mortality inhospital. Br J Nutr 2006;96:870–6.

11. Villet S, Chiolero RL, Bollmann MD, Revelly JP, Cayeux RNMC, Delarue J, et al.Negative impact of hypocaloric feeding and energy balance on clinicaloutcome in ICU patients. Clin Nutr 2005;24:502–9.

12. Dvir D, Cohen J, Singer P. Computerized energy balance and complications incritically ill patients: an observational study. Clin Nutr 2006;25:37–44.

13. Frankenfield DC, Smith JS, Cooney RN. Validation of 2 approaches to predictingresting metabolic rate in critically ill patients. J Parenter Enteral Nutr2004;28:259–64.

14. Ireton-Jones C. Clinical dilemma: which energy expenditure equation to use?J Parenter Enteral Nutr 2004;28:282–3.

15. McClave SA, McClain CJ, Snider HL. Should indirect calorimetry be used as partof nutrition assessment? J Clin Gastroenterol 2001;33:14–9.

16. Barak N. Assessment of resting energy expenditure in mechanically ventilatedpatients. Am J Clin Nutr 2004;79:341–2.

17. Ireton-Jones C, Jones JD. Improved equations for predicting energyexpenditure in patients: the Ireton-Jones Equations. Nutr Clin Pract 2002;17:29–31.

18. Ishibashi N, Plank LD, Sando K, Hill GL. Optimal protein requirements duringthe first 2 weeks after the onset of critical illness. Crit Care Med 1998Sep;26(9):1529–35.

19. Greenberg GR, Jeejeebhoy KN. Intravenous protein-sparing therapy in patientswith gastrointestinal disease. J Parenter Enteral Nutr 1979 Nov–Dec;3(6):427–32.

20. Van den Berghe G, Wilmer A, Milants I, Wouters PJ, Bouckaert B, Bruyninckx F,et al. Intensive insulin therapy in mixed medical/surgical intensive care units:benefit versus harm. Diabetes 2006;55:3151–9.

21. Crook MA. Lipid clearance and total parenteral nutrition: the importance ofmonitoring plasma lipids. Nutrition 2000;16:774–5.

22. Haderslev KV, Tjellesen L, Haderslev PH, Staun M. Assessment of the longi-tudinal changes in bone mineral density in patients receiving home parenteralnutrition. J Parenter Enteral Nutr 2004;28:289–94.

23. Hamilton C, Seidner DL. Metabolic bone disease and parenteral nutrition. CurrGastroenterol Rep 2004;6:335–41.

24. Khardori R. Refeeding syndrome and hypophosphatemia. J Intensive Care Med2005;20:174–5.

25. Crook MA, Panteli JV. The refeeding syndrome and hypophosphataemia in theelderly. J Intern Med 2005;257:397–8.

26. Garnacho-Montero J, Ortiz-Leyba C, Jimenez-Jimenez FJ, Garcia-Garmendia JL,Jimenez-Jimenez LM, Garnacho-Montero MC, et al. Clinical and metaboliceffects of two lipid emulsions on the parenteral nutrition of septic patients.Nutrition 2002;18:134–8.

27. Chen FM, Wang JY, Sun LC, Juang RF, Huang TJ, Hsieh JS. Efficacy of medium-chain triglycerides compared with long-chain triglycerides in total parenteralnutrition in patients with digestive tract cancer undergoing surgery. KaohsiungJ Med Sci 2005;21:487–94.

28. Ball MJ. Parenteral nutrition in the critically ill: use of a medium chaintriglyceride emulsion. Intensive Care Med 1993;19:89–95.

29. Waitzberg DL, Bellinati-Pires R, Salgado MM, Hypolito IP, Colleto GM, Yagi O,et al. Effect of total parenteral nutrition with different lipid emulsions ofhuman monocyte and neutrophil functions. Nutrition 1997;13:128–32.

30. Iovinelli G, Marinangeli F, Ciccone A, Ciccozzi A, Leonardis M, Paladini A, et al.Parenteral nutrition in ventilated patients with chronic obstructive pulmo-nary disease: long chain vs medium chain triglycerides. Minerva Anestesiol2007;73:65–76.

31. Grau T, Ruiz de Adana JC, Zubillaga S, Fuerte S, Giron C. Randomized study oftwo different fat emulsions in total parenteral nutrition of malnourishedsurgical patients; effect of infectious morbidity and mortality. Nutr Hosp2003;18:159–66.

32. Masclans JR, Iglesia R, Bermejo B, Pico M, Rodriguez-Roisin R, Planas M. Gasexchange and pulmonary haemodynamic responses to fat emulsions in acuterespiratory distress syndrome. Intensive Care Med 1998;24:918–23.

33. Smyrniotis VE, Kostopanagiotou GG, Arkadopoulos NF, Theodoraki KA,Kotsis TE, Lambrou AT, et al. Long-chain versus medium-chain lipids inacute pancreatitis complicated by acute respiratory distress syndrome:effects on pulmonary hemodynamics and gas exchange. Clin Nutr2001;20:139–43.

34. Faucher M, Bregeon F, Gainnier M, Thirion X, Auffray JP, Papazian L. Cardio-pulmonary effects of lipid emulsions in patients with ARDS. Chest2003;124:285–91.

35. Hailer S, Jauch KW, Wolfram G. Influence of different fat emulsions with 10 or20% MCT/LCT or LCT on lipoproteins in plasma of patients after abdominalsurgery. Ann Nutr Metab 1998;42:170–80.

36. Kuse ER, Kotzerke J, Muller S, Nashan B, Luck R, Jaeger K. Hepatic reticulo-endothelial function during parenteral nutrition including an MCT/LCT or LCTemulsion after liver transplantation – a double-blind study. Transpl Int2002;5:272–7.

37. Buenestado A, Cortijo J, Sanz MJ, Naim-Abu-Nabah Y, Martinez-Losa M,Mata M, et al. Olive oil-based lipid emulsion’s neutral effects on neutrophilfunctions and leukocyte-endothelial cell interactions. J Parenter Enteral Nutr2006;30:286–96.

38. van Kempen AA, van der Crabben SN, Ackermans MT, Endert E, Kok JH,Sauerwein HP. Stimulation of gluconeogenesis by intravenous lipids inpreterm infants: response depends on fatty acid profile. Am J Physiol Endo-crinol Metab 2006;290:E723–30.

39. Reimund JM, Rahmi G, Escalin G, Pinna G, Finck G, Muller CD, et al. Efficacyand safety of an olive oil-based intravenous fat emulsion in adult patients onhome parenteral nutrition. Aliment Pharmacol Ther 2005;15:445–54.

40. Thomas-Gibson S, Jawhari A, Atlan P, Brun AL, Farthing M, Forbes A. Safe andefficacious prolonged use of an olive oil-based lipid emulsion (ClinOleic) inchronic intestinal failure. Clin Nutr 2004;23:697–703.

41. Schlotzer E, Kanning U. Elimination and tolerance of a new parenteral lipidemulsion (SMOF) – a double-blind cross-over study in healthy male volun-teers. Ann Nutr Metab 2004;48:263–8.

42. Antebi H, Mansoor O, Ferrier C, Tetegan M, Morvan C, Rangaraj J, et al. Liverfunction and plasma antioxidant status in intensive care unit patientsrequiring total parenteral nutrition: comparison of 2 fat emulsions. J ParenterEnteral Nutr 2004;28:142–8.

http://www.otago.ac.nz/wsmhs/academic/gp/research/NZGGliteraturereview.pdf

http://www.otago.ac.nz/wsmhs/academic/gp/research/NZGGliteraturereview.pdf


43. Kalfarentzos F, Kokkinis K, Leukaditi K, Maroulis J, Onoufriou A, Alexopoulos K.Comparison between two fat emulsions: Intralipid 30 percent vs intralipid 10cent in critically ill patients. Clin Nutr 1998;17:31–4.

44. Tashiro T, Mashima Y, Yamamori H, Sanada M, Nishizawa M, Okui K. Intra-venous intralipid 10% vs. 20%, hyperlipidemia, and increase in lipoproteinX inhumans. Nutrition 1992;8:155–60.

45. Reimund JM, Arondel Y, Finck G, Zimmermann F, Duclos B, Baumann R.Catheter-related infection in patients on home parenteral nutrition: results ofa prospective survey. Clin Nutr 2002;21:33–8.

46. Beghetto MG, Victorino J, Teixeira L, de Azevedo MJ. Parenteral nutrition asa risk factor for central venous catheter-related infection. J Parenter EnteralNutr 2005;29:367–73.

47. Marra AR, Opilla M, Edmond MB, Kirby DF. Epidemiology of bloodstreaminfections in patients receiving long-term total parenteral nutrition. J ClinGastroenterol 2007;41:19–28.

48. National Nosocomial Infections Surveillance (NNIS) System Report, datasummary from January 1992 through June 2004. Am J Infect Control2004;32:470–85.

49. Maki D, Rhame F, Mackel DC, Benett JV. Nationwide epidemic of septicemiacaused by contaminated intravenous products: I. Epidemiologic and clinicalfeatures. Am J Med 1976;60:471–85.

50. Goldmann D, Martin W, Worthington J. Growth of bacteria and fungi in totalparenteral nutrition solutions. Am J Surg 1973;126:314–8.

51. Dankner W, Spector S, Fierer J. Malassezia fungemia in neonates and adults:complication of hyperalimentation. Rev Infect Dis 1987;9:743–53.

52. Sitges-Serra A, Hernandez R, Maestro S, Pi-Suner T, Garces JM, Segura M.Prevention of catheter sepsis: the hub. Nutrition 1997;13(4 Suppl.):30S–5S.

53. Sitges-Serra A, Puig P, Linares J, Perez JL, Farrero N, Jaurrieta E, et al. Hubcolonization as the initial step in an outbreak of catheter-related sepsis due tocoagulase negative staphylococci during parenteral nutrition. J ParenterEnteral Nutr 1984;8:668–72.

54. Bjornson H, Colley R, Bower RH, Duty VP, Schwartz-Fulton JT, Fischer JE.Association between microorganism growth at the catheter insertion site andcolonization of the catheter in patients receiving total parenteral nutrition.Surgery 1982;92:720–7.

55. Atela I, Coll P, Rello J, Quintana E, Barrio J, March F, et al. Serial surveillancecultures of skin and catheter hub specimens from critically ill patients withcentral venous catheters: molecular epidemiology of infection and implica-tions for clinical management and research. J Clin Microbiol 1997;35:1784–90.

56. Felices FJ, Hernandez JL, Ruiz J, Mesequer J, Gomez JA, Molina E. Use of thecentral venous pressure catheter to obtain blood cultures. Crit Care Med1979;7:78–9.

57. Tonnesen A, Peuler M, Lockwood WR. Cultures of blood drawn by catheters vs.venipuncture. JAMA 1877;1976:235.

58. DesJardin JA, Falagas ME, Ruthazer R, Griffith J, Wawrose D, Schenkein D, et al.Clinical utility of blood cultures drawn from indwelling central venous cath-eters in hospitalized patients with cancer. Ann Intern Med 1999;131:641–7.

59. Wing EJ, Norden CW, Shadduck RK, Winkelstein A. Use of quantitativebacteriologic techniques to diagnose catheter-related sepsis. Arch Intern Med1979;139(4):482–3.

60. Quilici N, Audibert G, Conroy MC, Bollaert PE, Guillemin F, Welfringer P, et al.Differential quantitative blood cultures in the diagnosis of catheter-relatedsepsis in intensive care units. Clin Infect Dis 1997;25:1066–70.

61. Malgrange VB, Escande MC, Theobald S. Validity of earlier positivity of centralvenous blood cultures in comparison with peripheral blood cultures fordiagnosing catheter-related bacteremia in cancer patients. J Clin Microbiol2001;39:274–8.

62. Maki DG, Weise CE, Sarafin HW. A semiquantitative method for identifyingintravenous-catheter-related infection. N Engl J Med 1977;296:1305–9.

63. Maki DG, Jarrett F, Sarafin HW. A semiquantitative method for identifi-cation of catheter-related infection in the burn patient. J Surg Res1977;22:513–20.

64. O’Grady NP, Alexander M, Dellinger EP, Gerberding JL, Heard SO, Maki DG,et al. Guidelines for the prevention of intravascular catheter-related infec-tions. Centers for Disease Control and Prevention. MMWR Recomm Rep2002;51:1–29.

65. Gastmeier P, Geffers C. Prevention of catheter-related bloodstream infections:analysis of studies published between 2002 and 2005. J Hosp Infect2006;64:326–35.

66. Pronovost P, Needham D, Berenholtz S, Sinopoli D, Chu H, Cosgrove S, et al. Anintervention to decrease catheter-related bloodstream infections in the ICU. NEngl J Med 2006;28(355):2725–32.

67. Eggimann P, Hugonnet S, Sax H, Harbarth S, Chevrolet JC, Pittet D. Long-termreduction of vascular access-associated bloodstream infection. Ann Intern Med2005;142:875–6.

68. Sherertz RJ, Ely EW, Westbrook DM, Gledhill KS, Streed SA, Kiger B, et al.Education of physicians-in-training can decrease the risk for vascular catheterinfection. Ann Intern Med 2000;132:641–8.

69. Eggimann P, Harbarth S, Constantin MN, Touveneau S, Chevrolet JC, Pittet D.Impact of a prevention strategy targeted at vascular-access care on incidenceof infections acquired in intensive care. Lancet 2000;355:1864–8.

70. Raad II, Hohn DC, Gilbreath BJ, Suleiman N, Hill LA, Bruso PA, et al.Prevention of central venous catheter-related infections by using maximalsterile barrier precautions during insertion. Infect Control Hosp Epidemiol1994;15:231–8.

71. Pittet D, Dharan S, Touveneau S, Sauvan V, Perneger TV. Bacterial contami-nation of the hands of hospital staff during routine patient care. Arch InternMed 1999;159:821–6.

72. Salzman MB, Isenberg HD, Rubin LG. Use of disinfectants to reducemicrobial contamination of hubs of vascular catheters. J Clin Microbiol1993;31:475–9.

73. Cookson ST, Ihrig M, O’Mara EM, Denny M, Volk H, Banerjee SN, et al.Increased bloodstream infection rates in surgical patients associated withvariation from recommended use and care following implementation ofa needle less device. Infect Control Hosp Epidemiol 1998;19:23–7.

74. Didier ME, Fischer S, Maki DG. Total nutrient admixtures appear safer thanlipid emulsion alone as regards microbial contamination: growth properties ofmicrobial pathogens at room temperature. J Parenter Enteral Nutr1998;22:291–6.

75. Crocker KS, Noga R, Filibeck DJ, Krey SH, Markovic M, Steffee WP. Microbialgrowth comparisons of five commercial parenteral lipid emulsions. J ParenterEnteral Nutr 1984;8:391–5.

76. Mershon J, Nogami W, Williams JM, Yoder C, Eitzen HE, Lemons JA. Bacterial/fungal growth in a combined parenteral nutrition solution. J Parenter EnteralNutr 1986;10:498–502.

77. Safdar N, Maki DG. Use of vancomycin-containing lock or flush solutions forprevention of bloodstream infection associated with central venous accessdevices: a meta-analysis of prospective, randomized trials. Clin Infect Dis2006;43:474–84. Review.

78. van de Wetering M, van Woensel J. Prophylactic antibiotics for preventingearly central venous catheter Gram positive infections in oncology patients.Cochrane Database Syst Rev 2007;24:CD003295. Review.

79. Borschel DM, Chenoweth CE, Kaufman SR, Hyde KV, VanDerElzen KA,Raghunathan TE, et al. Are antiseptic-coated central venous catheters effectivein a real-world setting? Am J Infect Control 2006;34:388–93.

80. Driscol DF, Bacon MN, Bistrian BR. Effects of in-line filtration on lipid particlesize distribution in total nutrient admixture. J Parenter Enteral Nutr1996;20:296–301.

81. Mermel LA. Prevention of intravascular catheter-related infections. Ann InternMed 2000;132:391–402.

82. O’Grady NP, Alexander M, Dellinger EP, Gerberding JL, Heard SO, Maki DG,et al. Guidelines for the prevention of intravascular catheter-related infec-tions. The Hospital Infection Control Practices Advisory Committee, Center forDisease Control and Prevention, U.S. Pediatrics 2002;110:e51

83. Gillies D, O’Riordan L, Carr D, Frost J, Gunning R, O’Brien I. Gauze and tape andtransparent polyurethane dressings for central venous catheters. CochraneDatabase Syst Rev; 2003::CD003827.

84. Maki DG, Stolz SS, Wheeler S, Mermel LA. A prospective, randomized trial ofgauze and two polyurethane dressings for site care of pulmonary arterycatheters: implications for catheter management. Crit Care Med1994;22:1729–37.

85. Messing B, Man F, Colimon R, Thuillier F, Beliah M. Antibiotic-lock technique isan effective treatment of bacterial catheter-related sepsis during parenteralnutrition. Clin Nutr 1990;9:220–5.

86. Krzywda EA, Andris DA, Edmiston Jr CE, Quebbeman EJ. Treatment of Hickmancatheter sepsis using antibiotic lock technique. Infect Control Hosp Epidemiol1995;16:596–8.

87. Kaufman J, Demas C, Stark K, Flancbaum L. Catheter-related septic centralvenous thrombosis-current therapeutic options. West J Med 1986;145:200–3.

88. Garrison RN, Richardson JD, Fry DE. Catheter-associated septic thrombo-phlebitis. South Med J 1982;75:917–9.

89. Walsh TJ, Bustamente CI, Vlahov D, Standiford HC. Candidal suppurativeperipheral thrombophlebitis: recognition, prevention, and management.Infect Control 1986;7:16–22.

90. Randolph AG, Cook DJ, Gonzales CA, Andrew M. Benefit of heparin in centralvenous and pulmonary artery catheters: a meta-analysis of randomizedcontrolled trials. Chest 1998;113:165–71.

91. Timsit JF, Farkas JC, Boyer JM, Martin JB, Misset B, Renaud B, et al. Centralvein catheter-related thrombosis in intensive care patients: incidence, riskfactors, and relationship with catheter-related sepsis. Chest 1998;114:207–13.

92. Luna M, Khalil SA, Costerton JW, Lam C, Bodey GP. The relationship betweenthe thrombotic and infectious complications of central venous catheters. JAMA1994;271:1014–6.

93. Boraks P, Seale J, Price J, Bass G, Ethell M, Keeling D, et al. Prevention of centralvenous catheter associated thrombosis using minidose warfarin in patientswith haematological malignancies. Br J Haematol 1998;101:483–6.

94. Bern MM, Lokich JJ, Wallach SR, Bothe Jr A, Benotti PN, Arkin CF, et al. Very lowdoses of warfarin can prevent thrombosis in central venous catheters. Arandomized prospective trial. Ann Intern Med 1990;112:423–8.

95. Alhimyary A, Fernandez C, Picard M, Tierno K, Pignatone N, Chan HS, et al.Safety and efficacy of total parenteral nutrition delivered via a peripherallyinserted central venous catheter. Nutr Clin Pract 1996;11:199–203.

96. Cowl CT, Weinstock JV, Al-Jurf A, Ephgrave K, Murray JA, Dillon K. Compli-cations and cost associated with parenteral nutrition delivered to hospitalizedpatients through either subclavian or peripherally-inserted central catheters.Clin Nutr 2000;19:237–43.

97. Cavicchi M, Beau P, Crenn P, Degott C, Messing B. Prevalence of liver diseaseand contributing factors in patients receiving home parenteral nutrition forpermanent intestinal failure. Ann Intern Med 2000;132:525–32.


98. Salvino R, Ghanta R, Seidner DL, Mascha E, Xu Y, Steiger E. Liver failure isuncommon in adults receiving long-term parenteral nutrition. J ParenterEnteral Nutr 2006;30:202–8.

99. Luman W, Shaffer JL. Prevalence, outcome and associated factors of derangedliver function tests in patients on home parenteral nutrition. Clin Nutr2002;21:337–43.

100. Kelly DA. Intestinal failure-associated liver disease: what do we know today?Gastroenterology 2006;130(2 Suppl. 1):S70–7. Review.

101. Hwang TL, Lue MC, Chen LL. Early use of cyclic TPN prevents further deteri-oration of liver functions for the TPN patients with impaired liver function.Hepatogastroenterology 2000;47:1347–50.

102. Buchman AL, Ament ME, Sohel M, Dubin M, Jenden DJ, Roch M, et al. Cholinedeficiency causes reversible hepatic abnormalities in patients receivingparenteral nutrition: proof of a human choline requirement: a placebo-controlled trial. J Parenter Enteral Nutr 2001;25:260–8.

103. Buchmiller CE, Kleiman-Wexler RL, Ephgrave KS, Booth B, Hensley 2nd CE.Liver dysfunction and energy source: results of a randomized clinical trial.J Parenter Enteral Nutr 1993;17:301–6.

104. Spagnuolo MI, Iorio R, Vegnente A, Guarino A. Ursodeoxycholic acid fortreatment of cholestasis in children on long-term total parenteral nutrition:a pilot study. Gastroenterology 1996;111:716–9.

105. Kubota A, Okada A, Imura K, Kawahara H, Nezu R, Kamata S, et al. The effect ofmetronidazole on TPN-associated liver dysfunction in neonates. J Pediatr Surg1990;25:618–21.

106. Lambert JR, Thomas SM. Metronidazole prevention of serum liver enzymeabnormalities during total parenteral nutrition. J Parenter Enteral Nutr1985;9:501–3.

107. Spiegel JE, Willenbucher RF. Rapid development of severe copper deficiency ina patient with Crohn’s disease receiving parenteral nutrition. J Parenter EnteralNutr 1999;23:169–72.

108. Fuhrman MP, Herrman V, Masidonski P, Eby C. Pancytopenia after removalof copper from total parenteral nutrition. J Parenter Enteral Nutr2000;24:361–6.

109. Fitzgerald K, Mikalunas V, Rubin H, McCarthey R, Vanagunas A, Craig RM.Hypermanganesemia in patients receiving total parenteral nutrition. J ParenterEnteral Nutr 1999;23:333–6.

110. Bethune K, Allwood M, Grainger C, Wormleighton C, British PharmaceuticalNutrition Group Working Party. Use of filters during the preparation andadministration of parenteral nutrition: position paper and guidelines preparedby a British pharmaceutical nutrition group working party. Nutrition2001;17:403–8.

111. Stratton RJ, Green CJ, Elia M. Disease related malnutrition: an evidence-basedapproach to treatment. Oxon, UK: CABI Publishing; 2003. p. 3.

112. Dhaliwal R, Heyland DK. Nutrition and infection in the intensive care unit:what does the evidence show? Curr Opin Crit Care 2005;11:461–7.

113. Giner M, Laviano A, Meguid MM. A correlation between malnutrition and pooroutcome in critically ill patients still exists. Nutrition 1996;12:23–9.

114. Kreymann KG, Berger MM, Deutz NE, Hiesmayr M, Jolliet P, Kazandjiev G, et al.ESPEN guidelines on enteral nutrition: Intensive care. Clin Nutr 2006;25:210–23.

115. Singer P, Singer J, Cohen J. Tight energy balance control for preventingcomplications in the ICU. In: Vincent JL, editor. Yearbook of intensive care andemergency medicine; 2006. p. 561–8.

116. Fagon JY, Labrousse J, Diehl JL. Assessment of resting energy expwenditure injmechanically ventilated patients. Am J Clin Nutr 2003;78:241–9.

117. Reid CL. Poor agreement between continuous measurements of energyexpenditure and routinely used prediction equations in intensive care unitpatients. Clin Nutr 2007;26:649–57.

118. Anbar R, Theilla M, Fisher H, Madar Z, Cohen J, Singer P. Decrease in hospitalmortality in tight calorie balance control study: the preliminary results of theTICACOS study. Clin Nutr 2008;3(1):11.

119. Krishman JA, Parce PB, Martinez A, Diette GB, Brower RG. Caloric intake inmedical ICU patients: consistency of care with guidelines and relationship toclinical outcomes. Chest 2003;124:297–305.

120. Blondet JJ, Beilman GJ. Glycemic control and prevention of perioperativeinfection. Curr Opin Crit Care 2007;13:421–7.

121. Mebis L, Gunst J, Langouche L, Vanhorebeek I, Van den Berghe G. Indicationand practical use of intensive insulin therapy in the critically ill. Curr Opin CritCare 2007;13:392–8.

122. McCowen KC, Friel C, Sternberg J, Chan S, Forse RA, Burke PA, et al. Hypo-caloric total parenteral nutrition: effectiveness in prevention of hyperglycemiaand infectious complications-a randomized clinical trial. Crit Care Med2000;28:3606–11.

123. Petros S, Engelman L. Enteral nutrition delivery and energy expenditure inmedical intensive care patients. Clin Nutr 2006;25:51–9.

124. Heiddeger CP, Romand JA, Pichard C. Is it now time to promote mixed enteral andparenteral nutrition for critically ill patients? Intensive Care Med 2007;33:363–9.

125. Singer P. Comments on ‘‘Is it now time to promote mixed enteral and parenteralnutrition for critically ill patients?’’. Intensive Care Med 1856;2007:33.

126. Heyland DK, Dhaliwal R, Drover JW, Gramlich L, Dodek P. Canadian clinicalpractice guidelines for nutrition support in mechanically ventilated, criticallyill adult patients. J Parenter Enteral Nutr 2003;27:355–73.

127. Simpson F, Doig GS. Parenteral vs enteral nutrition in the critically ill patient:a meta-analysis of trials using the intention to treat principle. Intensive CareMed 2005;31:12–23.

128. Huschak G, Zur Nieden K, Hoell T, Riemann D, Mast H, Stuttmann R. Olive oilbased nutrition in multiple trauma patients: a pilot study. Intensive Care Med2005;31:1202–8.

129. Wirtitisch M, Wessner B, Spittler A, Roth E, Volk T, Bachmann L, et al. Effect ofdifferent lipid emulsions on the immunological function in humans:a systematic review with meta-analysis. Clin Nutr 2007;26:302–13.

130. Tsekos E, Reuter C, Stehle P, Boeden G. Perioperative administration ofparenteral fish oil supplements in a routine clinical setting improves patientoutcome after major abdominal surgery. Clin Nutr 2004;23:325–30.

131. Heller AR, Rossler S, Litz RJ, Stehr SN, Heller SC, Koch R, et al. Omega-3 fattyacids improve the diagnosis-related clinical outcome. Crit Care Med2006;34:972–9.

132. Novak F, Heyland DK, Avenell A, Crover JW, Su X. Glutamine supplementationin serious illness: a systemic review of the evidence. Crit Care Med2002;30:2022–9.

133. Griffiths RD, Allen KD, Andrews FJ, Jones C. Infection, multiple organ failure,and survival in the intensive care unit: influence of glutamine-supplementedparenteral nutrition on acquired infection. Nutrition 2002;18:546–52.

134. Goeters C, Wenn A, Mertes N, Wempe C, van Aken H, Stehle P, et al. ParenteralL-alanyl L glutamine improves 6 month outcome in critically ill patients. CritCare Med 2002;30:2032–7.

135. Dechelotte P, Hasselman M, Cynober L, Allauchiche B, Coeffier M,Hecketsweiler B, et al. L-Alanyl L-glutamine dipeptide-supplemented totalparenteral nutrition reduces infectious complications and glucose intolerancein critically ill patients: the French controlled randomized, double blind,multicenter study. Crit Care Med 2006;34:598–604.

136. Bambach CP, Hill GL. Long term nutritional effects of extensive resection of thesmall intestine. Aust N Z J Surg 1982;52(5):500–6.

137. Hatakeyama K, Oda Y, Shimoda S, Inoue Y, Yamadera Y, Sakai Y, et al. Nutri-tional assessments in the long-term survivors following massive resection ofthe small intestine. Nippon Geka Gakkai Zasshi 1988;89(9):1414–7.

138. Buchman A. Etiology and initial management of short bowel syndrome.Gastroenterology 2006;130:S5–15.

139. Nightingale J, Woodward JM, Small Bowel and Nutrition Committee of theBritish Society of Gastroenterology. Guidelines for management of patientswith a short bowel. Gut 2006;55(Suppl. 4):iv1–12.

140. DiBaise JK, Matarese LE, Messing B, Steiger E. Strategies for parenteral nutri-tion weaning in adult patients with short bowel syndrome. J Clin Gastroenterol2006;40(5 Suppl. 2):S94–8.

141. Steiger E. Guidelines for pharmacotherapy, nutritional management, andweaning parenteral nutrition in adult patients with short bowel syndrome:introduction. J Clin Gastroenterol 2006;40(5 Suppl. 2):S73–4.

142. Jeejeebhoy KN. Management of short bowel syndrome: avoidance of totalparenteral nutrition. Gastroenterology 2006;130(2 Suppl. 1):S60–6.

143. O’Keefe SJ, Buchman AL, Fishbein TM, Jeejeebhoy KN, Jeppesen PB, Shaffer J.Short bowel syndrome and intestinal failure: consensus definitions andoverview. Clin Gastroenterol Hepatol 2006;4(1):6–10.

144. Matarese LE, O’Keefe SJ, Kandil HM, Bond G, Costa G, Abu-Elmagd K. Shortbowel syndrome: clinical guidelines for nutrition management. Nutr Clin Pract2006;20(5):493–502.

145. Levy E, Frileux P, Sandrucci S, Ollivier JM, Masini JP, Cosnes J, et al. Continuousenteral nutrition during the early adaptive stage of the short bowel syndrome.Br J Surg 1988;75:549–53.

146. Crenn P, Morin MC, Joly F, Penven S, Thuillier F, Messing B. Net digestiveabsorption and adaptive hyperphagia in adult short bowel patients. Gut2004;53:1279–86.

147. Carbonnel F, Cosnes J, Chevret S, Beaugerie L, Ngo Y, Malafosse M, et al. Therole of anatomic factors in nutritional autonomy after extensive small bowelresection. J Parenter Enteral Nutr 1996;20:275–80.

148. Messing B, Crenn P, Beau P, Boutron-Ruault MC, Rambaud JC, Matuchansky C.Long-term survival and parenteral nutrition dependence in adult patientswith the short bowel syndrome. Gastroenterology 1999;117:1043–50.

149. Abu-Elmagd K, Reyes J, Todo S, Rao A, Lee R, Irish W, et al. Clinical intestinaltransplantation: new perspectives and immunologic considerations. J Am CollSurg 1998;186:512–25.

150. Abu-Elmagd K, Reyes J, Todo S, et al. Clinical intestinal transplantation: newperspectives and immunologic considerations. J Am Coll Surg 1997;186:512–25.

151. Grant D, Abu-Elmagd K, Reyes J, Tzakis A, Langnas A, Fishbein T, et al. 2003Report of the intestine transplant registry: a new era has dawned. Ann Surg2005;241(4):607–13.

152. Abu-Elmagd K, Reyes J, Todo S, Rao A, Lee R, Irish W, et al. Clinical intestinaltransplantation: new perspectives and immunologic considerations. J Am CollSurg 1998;186(5):512–25.

153. Foulks CJ, Goldstein DJ, Kelly MP, Hunt JM. Indications for use of intradialyticparenteral nutrition in the malnourished hemodialysis patient. J Renal Nutri-tion 1991;1:23–33.

154. Capelli JP, Kushnir H, Camiscioli TC, Chen SM, Torres MA. Effect of intradialyticparenteral nutrition on mortality rates in end-stage renal disease care. Am JKidney Dis 1994;23(6):808–16.

155. Cano NJ, Fouque D, Roth H, Aparicio M, Azar R, Canaud B, et al, FrenchStudy Group for Nutrition in Dialysis. Intradialytic parenteral nutrition doesnot improve survival in malnourished hemodialysis patients: a 2-yearmulticenter, prospective, randomized study. J Am Soc Nephrol 2007Sep;18(9):2583–91.


156. Chertow GM, Ling J, Lew NL, Lazarus JM, Lowrie EG. The association ofintradialytic parenteral nutrition administration with survival in hemodialysispatients. Am J Kidney Dis 1994;24(6):912–20.

157. Kopple JD. Nutritional status as a predictor of morbidity and mortality inmaintenance dialysis patients. ASAIO J 1997;43(3):246–50.

158. Lazarus JM. Recommended criteria for initiating and discontinuingintradialytic parenteral nutrition therapy. Am J Kidney Dis1999;33(1):211–6.

159. Korzets A, Azoulay O, Chagnac A, Weinstein T, Avraham Z, Ori Y, et al.Successful intradialytic parenteral nutrition after abdominal "catastrophes" inchronically hemodialysed patients. J Renal Nutrition 1999;9:206–13.

160. Laville M. Fouque. Nutritional aspects in hemodialysis. Kidney Int2000;76:S133–9.

161. Mitch WE. Cachexia in chronic kidney disease: a link to defective centralnervous system control of appetite. J Clin Invest 2005;115:1476–8.

162. Ostro MJ, Greenberg GR, Jeejeebhoy KN. Total parenteral nutrition andcomplete bowel rest in the management of Crohn’s disease. J Parenter EnteralNutr 1985;9:280–7.

163. Matuchansky C. Parenteral nutrition in inflammatory bowel disease. Gut1986;27(Suppl. 1):81–4.

164. Dickinson RJ, Ashton MG, Axon AT, Smith RC, Yeung CK, Hill GL. Controlledtrial of intravenous hyperalimentation and total bowel rest as an adjunct tothe routine therapy of acute colitis. Gastroenterology 1980;79:1199–204.

165. McIntyre PB, Powell-Tuck J, Wood SR, Lennard-Jones JE, Lerebours E,Hecketsweiler P, et al. Controlled trial of bowel rest in the treatment of severeacute colitis. Gut 1986;27:481–5.

166. Lochs H, Meryn S, Marosi L, Ferenci P, Hortnagl H. Has total bowel resta beneficial effect in the treatment of Crohn’s disease? Clin Nutr 1983;2:61–4.

167. Greenberg GR, Fleming CR, Jeejeebhoy KN, Rosenberg IH, Sales D,Tremaine WJ. Controlled trial of bowel rest and nutritional support in themanagement of Crohn’s disease. Gut 1988;29:1309–15.

168. Rombeau JL, Barot LR, Williamson CE, Mullen JL. Preoperative total parenteralnutrition and surgical outcome in patients with inflammatory bowel disease.Am J Surg 1982;143:139–43.

169. Eisenberg HW, Turnbull JRB, Weakley FL. Hyperalimentation as preparationfor surgery in transmural colitis (Crohn’s disease). Dis Colon Rectum1974;17:469–75.

170. Lashner BA, Evans AA, Hanauer SB. Preoperative total parenteral nutrition forbowel resection in Crohn’s disease. Dig Dis Sci 1989;34:741–74.

171. Gouma DJ, von Meyenfeldt MF, Rouflart M, Soeters PB. Preoperativetotal parenteral nutrition (TPN) in severe Crohn’s disease. Surgery1988;103(6):648–52.

172. Am College of Physicians. Parenteral nutrition in patients receiving cancerchemotherapy. Position paper. Ann Intern Med 1989;110:734–6.

173. American Gastroenterological Association Medical position statement:parenteral nutrition. Gastroenterology 2001;12:966–9.

174. McGeer AJ, Detsky AS, O’Rourke K. Parenteral nutrition in cancer patientsundergoing chemotherapy: a meta-analysis. Nutrition 1990;6:233–40.

175. Klein S, Koretz RL. Nutrition support in patients with cancer: what do the datareally show? Nutr Clin Pract 1994;9:91–100.

176. Goonetilleke KS, Siriwardena AK. Systemic review of peri-operative nutri-tional supplementation in patients undergoing pancreaticoduodenectomy. JOP2006;11:5–13.

177. Wu G-H, Liu Z-H, Wu Z-H, Wu Z-G. Peri-operative artificial nutrition in mal-nourished gastrointestinal cancer patients. World J Gastro 2006;12:2441–4.

178. Bozzetti F, Gavazzi C, Miceli R, Rossi N, Mariani L, Cozzaglio L, et al. Peri-operative total parenteral nutrition in malnourished gastrointestinal cancerpatients: a randomized, clinical trial. J Parenter Enteral Nutr 2000;24:7–14.

179. Muller JM, Brenner U, Dienst C, Pichlmaier H. Preoperative parenteral feedingin patients with gastrointestinal carcinoma. Lancet 1982;1(8263):68–71.

180. Bozzetti F, Gianotti L, Braga M, Di Carlo V, Mariani L. Postoperative compli-cations in gastrointestinal cancer patients: the joint role of the nutritionalstatus and the nutritional support. Clin Nutr 2007 Dec;26(6):698–709.

181. Klein S, Simes J, Blackburn GL. Total parenteral nutrition and cancer clinicaltrials. Cancer 1986;58:1378–86.

182. De Cicco M, Panarello G, Fantin D, Veronesi A, Pinto A, Zagonel V, et al.Pareneteral nutrition in cancer patients receiving chemotherapy: effects oftoxicity and nutritional status. J Parenter Enteral Nutr 1993;17:513–8.

183. Sikora SS, Ribeiro U, Kane JM, Laaandreneau RJ, Lembeersky B, Posner MC.Role of nutrition support during induction chemoradiation therapy inesophageal cancer. J Parenter Enteral Nutr 1998;22:18–21.

184. Bozzetti F, Braga M, Glanotti L, Gavazzi C, Mariani L. Postoperative enteralnutrition versus pareneteral nutrition in malnourished patients with gastro-intestinal cancer: a randomized multicentre trial. Lancet 2001;358:1487–92.

185. Ghavimi F, Shills E, Scott FB, Brown M, Tamaroff M. Comparison of morbidityin children requiring abdominal radiation and chemotherapy, with andwithout total parenteral nutrition. J Pediatr 1982;101:530–7.

186. Working Group of the European Association for Palliative Care Clinical –practice recommendations for the management of bowel obstruction inpatients with end-stage cancer. Support Care Cancer 2001;9:223–33.

187. Hoda D, Jatoi A, Burnes J, Loprinzi C, Kelly D. Should patients with advanced,incurable cancers ever be sent home with total parenteral nutrition? A singleinstitution’s 20-year experience. Cancer 2005 Feb 15;103(4):863–8.

188. Brard L, Weitzen S, Strubel-Lagan SL, Swamy N, Gordinier ME, Moore RG, et al.The effect of total parenteral nutrition on the survival of terminally ill ovariancancer patients. Gynecol Oncol 2006;103:176–80.

189. Duerksen DR, Ting E, Thomson P, McCurdy K, Linscer J, Larsen-Celhar S, et al. Isthere a role for TPN in terminally ill patients with bowel obstruction? Nutri-tion 2004;20:760–3.

190. Abu-Rustum NR, Barakat RR, Venkatraman E, Spriggs D. Chemotherapy andtotal parenteral nutrition for advanced ovarian cancer with bowel obstruction.Gynecol Oncol 1997;64:493–5.

Parenteral nutrition – Guidelines of the Israeli Society for Clinical Nutrition (ISCN)

Documents