lable at ScienceDirect

Clinical Nutrition Supplements 4 (2009) 3–7

Contents lists avai

Clinical Nutrition Supplements

journal homepage: ht tp: / /www.elsevier .com/locate/c lnu

Original Article

Enteral and parenteral nutrition for critically ill patients: A logicalcombination to optimize nutritional support

Claude Pichard a,*, Ronan Thibault a,c, Claudia-Paula Heidegger b,d, Laurence Genton a,e

a Clinical Nutrition Department, Geneva University Hospital, Avenue Micheli-du-Crest 24, 1211 Geneva 14, Switzerlandb Service of Intensive Care, Geneva University Hospital, CH-1211 Geneva 14, Switzerland

Keywords:Critical careEnteral nutritionMalnutritionParenteral nutrition

Abbreviations: ICU, intensive care unit; ESPEN, ENutrition and Metabolism; TEE, total energy expendituparenteral nutrition.

* Corresponding author. Tel.: þ41 22 3729345; fax:E-mail addresses: Claude.Pichard@unige.ch (C. Picha

(R. Thibault), Claudia-Paula.Heidegger@hcuge.ch (C.-P. Hhcuge.ch (L. Genton).

c Tel.: þ41 22 3723749; fax: þ41 22 3729363.d Tel.: þ41 22 3827440; fax: þ41 22 3827470.e Tel.: þ41 22 3729344; fax: þ41 22 3729363.

1744-1161/$ – see front matter � 2009 Elsevier Ltd adoi:10.1016/j.clnu.2009.04.007

s u m m a r y

Malnutrition is a common and serious problem in intensive care units. Negative energy balance has beenassociated with increased morbidity and mortality in critically ill patients. The increased incidence ofcomplications attributable to malnutrition correlates with increased length of hospital stay and overallhealth care costs. Although early enteral nutrition is the preferred method of feeding critically illpatients, enteral nutrition alone often fails to supply adequate calories and nutrients to critically illpatients, who are frequently hypermetabolic. Supplementation of insufficient enteral nutrition withparenteral nutrition may optimize nutritional support and avert negative energy balance in critically illpatients, thereby improving outcomes.

� 2009 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

1. Malnutrition: a common problem in hospitalized patients

Malnutrition continues to be a widespread problem in manyinpatient settings, including intensive care units (ICUs).1–4 Anumber of studies have shown that the prevalence of malnutritionamong hospitalized adults of all ages ranges from 20% to 69%,3–7

with a prevalence as high as 40% among critically ill patients.8

Pre-existing malnutrition may contribute to the frequency of thiscondition in the hospital setting. As many as 30% of hospitalizedpatients meet criteria for malnutrition at admission.9,10 In fact,patients with medical conditions that have been associated withmalnutrition in the hospital setting, such as gastrointestinaldisease, neuromuscular or arthritic impairment, hypoxic cardio-pulmonary disease, cancer, and infection, are often undernourishedat admission.6,7,10,11 However, additional stress during hospitaliza-tion may exacerbate any pre-existing nutritional deficits in patientswith these and other conditions.6,7,11 Critical illness, in particular, isassociated with a marked increase in metabolism, leading to

uropean Society for Clinicalre; EN, enteral nutrition; PN,

þ41 22 3729363.rd), Ronan.Thibault@hcuge.cheidegger), Laurence.Genton@

nd European Society for Clinical N

greater energy (i.e., caloric) requirements and loss of lean bodymass.12,13

Independent of the type and severity of disease, the duration ofhospitalization has also been shown to impact the risk of malnu-trition; as the length of hospital stay increases, so does the risk ofmalnutrition.6 Conversely, baseline nutritional status may influ-ence the duration of hospitalization, as was seen in a population-based study of 1907 hospitalized patients in whom the risk ofnutritional deficiency was evaluated at admission using the vali-dated Nutritional Risk Index (1.519� serum albumin concentration[g/L]þ [41.7� present/usual body weight]).14 In that study, patientswho were hospitalized for 16 days or longer were 3–4 times morelikely to have met criteria for a moderate-to-severe risk of nutri-tional deficiency (Nutritional Risk Index� 97.5) at admission thanpatients who were hospitalized for 15 days or less (P< 0.001).14

2. Consequences of malnutrition in the hospital setting

Malnutrition has been associated with increased morbidity andmortality in hospitalized patients. In a retrospective study of 709inpatients who were assessed for nutritional status within 72 h ofadmission, there was a significantly higher incidence of complica-tions in malnourished patients (27.0%) compared with well-nourished patients (16.8%; P< 0.01).15 Infectious complications,cardiac and respiratory failure, and cardiac arrest were all morecommon in malnourished patients (all P< 0.01; Fig. 1), andmalnutrition was identified as a significant independent risk factorfor the occurrence of complications, including death.15 Likewise,a state of negative energy balance has been associated with

utrition and Metabolism. All rights reserved.

***

*

Fig. 1. Comparative incidence of complications: malnourished versus well-nourishedhospitalized patients (N¼ 709).15 Infectious complications, respiratory and cardiacfailure, and cardiac arrest were all significantly more frequent in malnourished versuswell-nourished hospitalized patients in this study. *P< 0.01 versus well-nourishedpatients. ARepresentative of total infectious complications, including pulmonary,urinary, and wound infections; sepsis; intra-abdominal and extraperitoneal abscesses;and septic coagulopathy.

A

B

*** *

* * *

Fig. 2. Comparative length of hospital stay by fat-free mass index.17 Both men (A) andwomen (B) with a low fat-free mass index at admission were significantly more likelyto have a prolonged length of hospital stay. Men and women were analyzed separatelygiven differing norms for fat-free mass. OR, odds ratio. *P< 0.001. AOR adjusted for age.

C. Pichard et al. / Clinical Nutrition Supplements 4 (2009) 3–74

increased morbidity in ICU patients. In a recent prospective study of48 critically ill patients, energy deficit just 1 week after ICUadmission correlated with both total (P¼ 0.048) and infectious(P¼ 0.005) complications.16 These findings were confirmed inanother study of 50 critically ill patients that also showed a strongpositive relationship between increasing energy debt and thefrequency of complications, including adult respiratory distresssyndrome, renal failure, need for surgery, and pressure sores (allP< 0.01).2

The increased incidence of complications resulting frommalnutrition and energy deficit translates into a prolonged hospitalstay and increased health care costs. Notably, a low lean body massat hospital admission has been associated with an increase in thelength of hospital stay, regardless of disease or treatment course.10

In a prospective study of 995 hospitalized patients, the odds ofrequiring a hospital stay of more than 12 days were 4–5 timeshigher in patients with a low fat-free body mass index (defined asfat-free mass [kg]/height squared [m2]) versus a normal fat-freeindex at admission (P< 0.001; Fig. 2).17 A separate study of 709patients from 25 hospitals in Brazil confirmed these results; well-nourished patients stayed in the hospital for an average of 10 days,compared with 17 days for malnourished patients.15 This study alsoevaluated the health care costs attributable to malnutrition andfound that the mean per-patient daily costs were 61% higher formalnourished versus well-nourished patients.15 In a Europeanstudy that assessed the nutritional risk of hospitalized patientsusing the Nutritional Risk Screening–2002 method developed bythe European Society for Clinical Nutrition and Metabolism(ESPEN), mean overall hospital costs for nutritionally at-riskpatients were more than double those incurred by patients notconsidered as nutritionally at-risk (V4891 versus V2204, orapproximately US $6280 versus US $2800, respectively).18

3. Factors contributing to hospital-acquired malnutrition

Non–disease-related factors contributing to the development ofmalnutrition in hospitalized patients include a lack of propernutritional assessment or surveillance and underestimation of thenutritional requirements of these patients. Pre-existing malnutri-tion is rarely recognized because nutritional appraisals are infre-quently conducted at admission, as evidenced by a recent study of395 inpatients in which admission assessment of nutritional statusoccurred in less than 25% of the sample.4 In cases where malnu-trition is identified, ongoing nutritional surveillance is often

lacking. For example, of those patients considered as malnourishedin the aforementioned study of inpatients, 41% were weighed onlyonce or not at all during their hospital stay.4 In another prospectivestudy of hospitalized patients, out of 200 patients who wereconsidered undernourished at admission, only 55 were reassessedat discharge.19 Of those 55 patients, 41 (75%) had experienceda 5–10% weight loss from admission, while the remaining 14 (25%)experienced weight gain during their hospital stay, although nonewere able to achieve a normal body weight by discharge.19

Furthermore, only 10 of the 55 undernourished patients reassessedat discharge were referred for nutritional support; of thosepatients, 7 (70%) gained weight, compared with 5 (11%) of the 45not referred for nutritional support (P< 0.001).19

The lack of proper evaluation for and oversight of malnutritionin hospitalized patients is further compounded by a failure tooptimize nutritional support in these patients. Delays in the initi-ation of nutrition and/or the inadequate provision of calories andother nutritional substrates may also contribute to the develop-ment of malnutrition, particularly in critically ill patients, in whomcaloric requirements may be more difficult to predict and are mostoften increased.

4. Nutritional support in the ICU patient

A number of studies have investigated the total energy expen-diture (TEE) of critically ill patients. During the acute phase of

C. Pichard et al. / Clinical Nutrition Supplements 4 (2009) 3–7 5

illness, TEE is estimated at approximately 25–30 kcal/kg bodyweight per day.20–22 However, during the recovery phase and incertain groups of patients, such as those with severe sepsis ortrauma, TEE may increase to more than 40 kcal/kg per day.23 Thesevalues may vary substantially from patient to patient and shouldnot be considered as absolute nutritional targets but rather asindicators of the possible broad discrepancy between administeredand expended calories.20 This range of caloric expenditure alsohighlights the importance of methodically assessing energyexpenditure in critically ill patients over time.

4.1. Enteral nutrition

The enteral route is the preferred route for delivering nutritionalsupport in critically ill patients.24 The enteral route is thought tooffer several advantages over the parenteral route for the deliveryof nutrition; enteral nutrition (EN) is thought to be more physio-logical, may help restore or maintain normal gastrointestinalfunction, and has been associated with a reduced risk of infectiouscomplications in ICU patients relative to parenteral nutrition(PN).24–26 Enteral nutrition has also been associated with costsavings in the ICU.26,27 For example, it was estimated that an annualnet profit of $357,000 would result from optimizing the use of EN inlieu of PN in the ICU of a single hospital in Sweden.27

The timing for the initiation of EN appears to be a clinicallyimportant factor; specifically, early initiation of EN in critically illpatients has been associated with improved outcomes. In a retro-spective analysis of more than 4000 nonsurgical, mechanicallyventilated critically ill patients, ICU mortality, hospital mortality,and length of ICU stay were significantly reduced in patients whoreceived EN within 48 h of the onset of mechanical ventilationversus those who did not (Fig. 3).28 Early EN has additionally beenshown to decrease the rate of infectious complications, total lengthof hospital stay, and overall costs of patient management in post-surgical patients.29,30 Implementation of early EN has thereforebecome standard practice in ICU patients and is advocated ina number of clinical guidelines.24,31

However, optimal implementation of EN in the ICU remainsa challenge even when a well-trained and experienced nutritionteam is available. Enteral nutrition is frequently interrupted in ICUpatients for multiple and recurrent events, such as radiologic orendoscopic investigations, surgery, mechanical problems (e.g.,delivery pump malfunction, gastric tube occlusion or malposition),

*

Fig. 3. Comparative incidence of mortality: early versus delayed EN in mechanicallyventilated ICU patients.28 Early EN, defined as initiation of enteral feeding within 48 hof mechanical ventilation onset, was associated with significantly improved ICU andhospital mortality relative to delayed EN. ICU, intensive care unit; EN, enteral nutrition.*P¼ 0.01 versus early EN; yP¼ 0.001 versus early EN.

or gastrointestinal intolerance (e.g., vomiting, diarrhea, or abdom-inal distention).32 In fact, initiation of EN is often delayed because ofconcerns about gastrointestinal intolerance, which occurs in asmany as 46% of patients receiving nutrients by this route.33 Theultimate result of these interruptions or delays in the provision ofnutrition is an inability to match actual caloric intake to targetedcaloric intake. Analyses conducted in ICUs in US34 and Canadian35

hospitals found that, of total calories prescribed, only 52% and 56%,respectively, were actually delivered via the enteral route to thepatients in these units. In the US center, compliance with a stan-dardized enteral feeding protocol only improved the delivery ofcalories to 68% of the target amount.34 In contrast, PN has beenshown to deliver a significantly greater percentage of target caloriesthan EN in other studies of ICU patients.32,36

4.2. Parenteral nutrition

Parenteral nutrition has been associated with a number oftheoretical and actual complications, leading to restriction of itsuse. For example, intestinal mucosal atrophy, leading to bacterialtranslocation from the gut to the bloodstream, has been proposedas a theoretical complication of PN and has been implicated in theincreased incidence of infection and sepsis seen with PN versusEN.37 However, human studies have found that PN given in thesetting of complete bowel rest did not result in any intestinalatrophy, even after a month of no enteral intake.37 Furthermore, theactual observed incidence of bacterial translocation is similar inpatients treated with PN or EN.37 The complications that haveaccompanied the use of PN in the past are most likely the result ofexcess administration of calories, particularly from carbohydratesand fats, in an era when ‘‘superfeeding’’ was promoted as a meansto enhance recovery from disease (leading to the coining of theterm ‘‘hyperalimentation’’).37 In reality, PN can be successfully andsafely administered when overfeeding is avoided and carefulglycemic control by ‘‘intensive insulin therapy’’ is observed; in fact,PN appears to be associated with fewer complications than ENwhen administered by an experienced team.37,38 Moreover, a recentmeta-analysis suggested that, when compared with EN, PN isassociated with a reduced incidence of mortality in critically illpatients, in spite of an increased incidence of infectious complica-tions.39 Based on these findings, a grade Bþ evidence-basedrecommendation (level II trials, no heterogeneity) was made thatPN should be instituted in critically ill patients when initiation ofEN within 24 h of ICU admission is not feasible.39

4.3. Combined enteral and parenteral nutrition

Parenteral nutrition may also be used to supplement EN inpatients whose caloric needs are unmet by EN alone. The EuropeanSociety for Clinical Nutrition and Metabolism (ESPEN) guidelines onEN in the ICU recommend that, in the acute phase of critical illness,patients should receive a maximum of 20–25 kcal/kg per day,increasing to 25–30 kcal/kg per day during the post-acute phase.31

Severely malnourished patients should receive a maximum of25–30 kcal/kg per day from the time that feeding is initiated.31 Ifthese nutritional goals cannot be achieved using EN alone, theguidelines recommend that supplementary PN should beinitiated.31

The potential value of supplementing EN with PN was shown inthe aforementioned study16 correlating a negative energy balancewith increased complications in the ICU, in which patientsreceiving combined EN and PN achieved a significantly highermean caloric intake (2160 kcal/day) than did patients receiving ENalone (1365 kcal/day; P< 0.0001). In another study of 49mechanically ventilated, malnourished critically ill patients, the

*

Fig. 4. Comparative Maastricht Nutritional IndexA on ICU day 14 based on route of nutri-tional support.40 Relative to day 1, nutritional status as assessed by the Maastricht Nutri-tional Index was significantly improved by day 14 in ICU patients receiving combined ENand PN versus EN or PN alone. ICU, intensive care unit; EN, enteral nutrition; PN, parenteralnutrition. *P< 0.05, day 14 versus day 1. AThe Maastricht Nutritional Index incorporatesalbumin, prealbumin, absolute lymphocyte count, and percentage of ideal bodyweight to assess nutritional status, using the following formula: 20.68� (0.24� albumin[g/L])� (19.21� prealbumin [g/L])� (1.86� lymphocytes [109/L])� (0.04� percentage ofideal body weight). A Nutritional Index of >0 is consistent with malnutrition.

C. Pichard et al. / Clinical Nutrition Supplements 4 (2009) 3–76

mean prealbumin level improved significantly over the first 2weeks in patients treated with a combination of EN and PN(P< 0.05), whereas in patients receiving EN or PN alone, there wasno significant improvement.40 The combined nutrition grouplikewise experienced a significant increase in the Maastricht Index,a tool that incorporates prealbumin, albumin, lymphocyte count,and percentage of ideal weight to assess nutritional status, over thesame interval (P< 0.05), while the EN and PN groups did not(Fig. 4).40

The timing for initiating supplemental PN has been an issue ofconsiderable debate.1 In the context of a review of the literature,Heidegger and colleagues recently proposed that supplemental PNshould be initiated if EN fails to meet at least 60% of target caloricrequirements within 3 days of hospital admission.41 They furthersuggested that the addition of PN should permit attainment of 100%of target energy and protein levels by day 4 of hospitalization andthat PN should gradually be weaned over time as EN approachesnutritional goals.41 Given the association between hyperglycemiaand increased morbidity and mortality in critically ill patients, tightglycemic control should be ensured during combined EN and PN,with insulin administration as needed.41,42

5. Conclusions

Malnutrition continues to be a serious problem in intensive carefacilities and is associated with poor patient outcomes. AlthoughEN is the preferred method of feeding critically ill patients, it oftenfails to optimally meet nutritional needs. Supplementing insuffi-cient EN with PN may facilitate the achievement of nutritional goals(including target caloric intake) and may improve outcomes incritically ill patients. Ongoing clinical studies are expected to verifythis logical hypothesis. Given its association with decreasedmorbidity and mortality in ICU patients, a tight glycemic controlprotocol remains essential to the success of this combined nutri-tional approach.

Conflict of interest

Dr. Pichard and colleagues receive funding from various sources,including the Swiss National Research Fund, the public FoundationNutrition 2000Plus, the Societe Nationale Française de Gastro-enterologie (SNFGE), Abbott, Baxter, B. Braun, Danone, Fresenius-Kabi, and Nestle Medical Nutrition.

Acknowledgments

The authors would like to thank the public Foundation Nutrition2000Plus for its financial support. Lara Primak, MD, of MedErgyprovided editorial assistance with the preparation of this article.

Statement of authorship

All authors participated in the drafting of this manuscript andhave read and approved the final version.

References

1. de Aguilar-Nascimento JE, Kudsk KA. Early nutritional therapy: the role ofenteral and parenteral routes. Curr Opin Clin Nutr Metab Care 2008;11:255–60.

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

3. Singh H, Watt K, Veitch R, Cantor M, Duerksen DR. Malnutrition is prevalent inhospitalized medical patients: are housestaff identifying the malnourishedpatient? Nutrition 2006;22:350–4.

4. Bavelaar JW, Otter CD, van Bodegraven AA, Thijs A, Van Bokhorst-de van derSchueren MA. Diagnosis and treatment of (disease-related) in-hospitalmalnutrition: the performance of medical and nursing staff. Clin Nutr2008;27:431–8.

5. O’Flynn J, Peake H, Hickson M, Foster D, Frost G. The prevalence of malnutritionin hospitals can be reduced: results from three consecutive cross-sectionalstudies. Clin Nutr 2005;24:1078–88.

6. Waitzberg DL, Caiaffa WT, Correia MI. Hospital malnutrition: the Braziliannational survey (IBRANUTRI): a study of 4000 patients. Nutrition 2001;17:573–80.

7. Wyszynski DF, Perman M, Crivelli A. Prevalence of hospital malnutrition inArgentina: preliminary results of a population-based study. Nutrition 2003;19:115–9.

8. Giner M, Laviano A, Meguid MM, Gleason JR. In 1995 a correlation betweenmalnutrition and poor outcome in critically ill patients still exists. Nutrition1996;12:23–9.

9. Edington J, Boorman J, Durrant ER, et al. Prevalence of malnutrition onadmission to four hospitals in England. The Malnutrition Prevalence Group. ClinNutr 2000;19:191–5.

10. Pirlich M, Schutz T, Norman K, et al. The German hospital malnutrition study.Clin Nutr 2006;25:563–72.

11. Willard MD, Gilsdorf RB, Price RA. Protein-calorie malnutrition in a communityhospital. JAMA 1980;243:1720–2.

12. Hadley JS, Hinds CJ. Anabolic strategies in critical illness. Curr Opin Pharmacol2002;2:700–7.

13. Hill GL. Implications of critical illness, injury, and sepsis on lean body mass andnutritional needs. Nutrition 1998;14:557–8.

14. Kyle UG, Schneider SM, Pirlich M, Lochs H, Hebuterne X, Pichard C. Doesnutritional risk, as assessed by Nutritional Risk Index, increase during hospitalstay? A multinational population-based study. Clin Nutr 2005;24:516–24.

15. Correia MITD, Waitzberg DL. The impact of malnutrition on morbidity,mortality, length of hospital stay and costs evaluated through a multivariatemodel analysis. Clin Nutr 2003;22:235–9.

16. Villet S, Chiolero RL, Bollmann MD, et al. Negative impact of hypocaloric feedingand energy balance on clinical outcome in ICU patients. Clin Nutr 2005;24:502–9.

17. Pichard C, Kyle UG, Morabia A, Perrier A, Vermeulen B, Unger P. Nutritionalassessment: lean body mass depletion at hospital admission is associated withan increased length of stay. Am J Clin Nutr 2004;79:613–8.

18. Amaral TF, Matos LC, Tavares MM, et al. The economic impact of disease-relatedmalnutrition at hospital admission. Clin Nutr 2007;26:778–84.

19. McWhirter JP, Pennington CR. Incidence and recognition of malnutrition inhospital. BMJ 1994;308:945–8.

20. Griffiths RD, Bongers T. Nutrition support for patients in the intensive care unit.Postgrad Med J 2005;81:629–36.

21. Kan MN, Chang HH, Sheu WF, Cheng CH, Lee BJ, Huang YC. Estimation of energyrequirements for mechanically ventilated, critically ill patients using nutritionalstatus. Crit Care 2003;7:R108–15.

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

23. Uehara M, Plank LD, Hill GL. Components of energy expenditure in patientswith severe sepsis and major trauma: a basis for clinical care. Crit Care Med1999;27:1295–302.

24. Scurlock C, Mechanick JI. Early nutrition support in the intensive care unit: a USperspective. Curr Opin Clin Nutr Metab Care 2008;11:152–5.

25. Dominioni L, Rovera F, Pericelli A, Imperatori A. The rationale of early enteralnutrition. Acta Biomed 2003;74:41–4.

26. Gramlich L, Kichian K, Pinilla J, Rodych NJ, Dhaliwal R, Heyland DK. Does enteralnutrition compared to parenteral nutrition result in better outcomes in criti-cally ill adult patients? A systematic review of the literature. Nutrition 2004;20:843–8.

C. Pichard et al. / Clinical Nutrition Supplements 4 (2009) 3–7 7

27. Johansson C, Backman L, Jakobsson J. Is enteral nutrition optimally used inhospitalized patients? A study of the practice of nutrition in a Swedish hospital.Clin Nutr 1996;15:171–4.

28. Artinian V, Krayem H, DiGiovine B. Effects of early enteral feeding on theoutcome of critically ill mechanically ventilated medical patients. Chest 2006;129:960–7.

29. Neumayer LA, Smout RJ, Horn HG, Horn SD. Early and sufficient feeding reduceslength of stay and charges in surgical patients. J Surg Res 2001;95:73–7.

30. Hedberg AM, Lairson DR, Aday LA, et al. Economic implications of an earlypostoperative enteral feeding protocol. J Am Diet Assoc 1999;99:802–7.

31. Kreymann KG, Berger MM, Deutz NE, et al. ESPEN guidelines on enteralnutrition: intensive care. Clin Nutr 2006;25:210–23.

32. De Jonghe B, Appere-De-Vechi C, Fournier M, et al. A prospective survey ofnutritional support practices in intensive care unit patients: what isprescribed? What is delivered? Crit Care Med 2001;29:8–12.

33. Mentec H, Dupont H, Bocchetti M, Cani P, Ponche F, Bleichner G. Upperdigestive intolerance during enteral nutrition in critically ill patients:frequency, risk factors, and complications. Crit Care Med 2001;29:1955–61.

34. Spain DA, McClave SA, Sexton LK, et al. Infusion protocol improves delivery ofenteral tube feeding in the critical care unit. J Parenter Enteral Nutr 1999;23:288–92.

35. Sigalet DL, Mackenzie SL, Hameed SM. Enteral nutrition and mucosal immu-nity: implications for feeding strategies in surgery and trauma. Can J Surg 2004;47:109–16.

36. Woodcock NP, Zeigler D, Palmer MD, Buckley P, Mitchell CJ, Macfie J. Enteralversus parenteral nutrition: a pragmatic study. Nutrition 2001;17:1–12.

37. Jeejeebhoy KN. Total parenteral nutrition: potion or poison? Am J Clin Nutr2001;74:160–3.

38. Nardo P, Dupertuis YM, Jetzer J, Kossovsky MP, Darmon P, Pichard C. Clinicalrelevance of parenteral nutrition prescription and administration in 200hospitalized patients: a quality control study. Clin Nutr 2008;27:858–64.

39. 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.

40. Huang YC, Yen CE, Cheng CH, Jih KS, Kan MN. Nutritional status of mechanicallyventilated critically ill patients: comparison of different types of nutritionalsupport. Clin Nutr 2000;19:101–7.

41. Heidegger CP, Romand JA, Treggiari MM, Pichard C. Is it now time to promotemixed enteral and parenteral nutrition for the critically ill patient? IntensiveCare Med 2007;33:963–9.

42. Van den Berghe G, Wouters P, Weekers F, et al. Intensive insulin therapy in thecritically ill patients. N Engl J Med 2001;345:1359–67.