Intensive Care Med (2003) 29:1861–1864 DOI 10.1007/s00134-003-2006-6
Peter Varga Richard Griffiths René Chiolero Gérard Nitenberg Xavier Leverve Marek Pertkiewicz Erich Roth Jan Wernerman Claude Pichard Jean-Charles Preiser
EDITORIAL
Is parenteral nutrition guilty?
Received: 25 July 2003 Accepted: 12 August 2003 Published online: 10 September 2003 © Springer-Verlag 2003 P. Varga · R. Griffiths · R. Chiolero · G. Nitenberg · X. Leverve M. Pertkiewicz · E. Roth · J. Wernerman · C. Pichard J.-C. Preiser (✉) Department of Intensive Care, Centre Hospitalo-universitaire de Liège, Domaine du Sart Tilman B35, 4000 Liege 1, Belgium e-mail:
[email protected] Tel.: +32-4-3667495, Fax: +32-4-3668898
Introduction “Death by parenteral nutrition” was the title of the controversial editorial published in the June issue of Intensive Care Medicine by P.E. Marik and M. Pinsky [1]. One might believe that a real event was being described by the authors. Imagine our astonishment, which quickly turned to dismay, when we read the words: “...a poison or toxin is a substance that through its chemical action usually kills, injures or impairs an organism... and by this definition TPN meets all criteria of a poison/toxin, in the critically ill patient receiving parenteral nutrition.” We are surprised and perturbed that the authors have missed some important issues regarding the nutrition of patients in intensive care units (ICUs), exchanging sensationalism for sound scientific discussion. It would appear that the authors believe that the seriously ill patients in ICUs all over the world who due to their condition must receive total parenteral nutrition (TPN) are in fact being poisoned by their professional carers. This frightful accusation, which is a gross generalization and insinuation lacks in our view solid scientific evidence. Furthermore, it can potentially produce a great deal of harm by introducing possible confusion
among intensivists and doubt among patients and relatives. Something that has been given safely to patients in ICUs and at home for many years cannot be called a poison. In contrast, anything used incorrectly or in excess may do harm. Exhibiting a dose response and toxicity with excess is a feature of most active therapies, especially in the ICU setting. Even normal food intake has these characteristics, as shown by Western morbidity and mortality changes subsequent to overfeeding. Indeed, overfeeding is easy to achieve with parenteral nutrition (PN), but there is no evidence that PN not given in excess is harmful. What is true with PN is the loss of the benefit related to normal eating, a benefit which cannot be achieved in the patients unable to feed enterally. Even if we fully agree that enteral feeding should be preferred to PN in critically ill patients whenever possible, we would like to refute many of the arguments of the editorial suggesting that PN is a poison, using a scientific approach.
Proof of the toxicity of PN No one argues that parenteral feeding is without inherent risks. Naturally over the past decades those working in this field became keenly aware of the potential clinical complications of TPN and established practical guidelines to minimize their impact. Many of the risks of indiscriminate and inappropriate use of PN have been recognized and demonstrated, and there is no doubt that they increase the chance of iatrogenic complications. However, it is possible to avoid such conditions as overfeeding, resulting in hyperglycemia, hypertriglyceridemia, uremia, metabolic acidosis, and electrolyte imbalances by conscientious monitoring and titrating the quality and quantity of nutrients provided. Careful cannulation and maintenance of sterile techniques will prevent or minimize infections or sepsis, immunosuppression can be attenuated by supplementation of glutamine, in
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other words careful respecting guidelines will go a long way to reduce the rate of complication. Not surprisingly, several recent studies on TPN in surgical and critically ill patients report very low rates of metabolic complications. One of the real landmark outcome studies in recent years showed the great benefits of glycemic control in patients receiving early enteral nutrition or PN [2]. The use of closely applied, best evidence nutrition protocols was central to this process and involved enteral nutrition and PN. Such benefits seen in the long-stay patients would not have occurred if PN were a cumulative poison. Outcome was related to the tight glycemic control achieved, but this was established with insulin, and not by underfeeding. Interestingly, although parenterally fed patients required more insulin (+23%) to achieve normoglycemia, quality of glycemia control did not differ in enterally fed patients. We know that underfeeding by omitting lipids and delivering hypocaloric parenteral feeds prevents neither hyperglycemia nor its infectious complications [3], confirming the lack of the doserelated effected implied by the authors of the editorial. There is a large body of evidence showing that enteral feeding is superior to parenteral feeding in trauma and surgical patients, particularly for septic morbidity. Marik and Pinsky cite the meta-analysis by Heyland et al. [4] on PN vs. no artificial nutrition and state that “in critically ill patients TPN almost doubles the risk of dying.” This analysis covered 21 studies with surgical patients and only 6 studies with surgical patients requiring ICU management. Most of these studies had methodological problems: inclusion of non-critically ill surgical patients [5, 6], overfeeding in the PN group [7], combined parenteral and enteral feeding [7, 8], early postoperative parenteral feeding in unstable patients [9], and some probably no longer reflected current practice or were very old studies [9]. This suggests that the strength of evidence of this part of the meta-analysis is low. Similarly, a study of TPN published only as an abstract and quoted in the editorial [10], which seriously limits its impact, showed that the addition of trickle enteral nutrition to PN reduces the toxicity of TPN. This suggests, again, that the problem is not the toxicity of TPN, but that it may be more related to the absence of enteral feeding.
PN is often necessary in critically ill surgical patients The authors state: “we believe that based on evidence, TPN has no place in the management of the critically ill who can otherwise be fed enterally” and then: “Enteral nutritional support may not be possible in patients with short-bowel syndrome. However, these patients are exceedingly rare.” We do not agree with the authors’ categorical statement, although it means that the authors accept the existence of patients who cannot be fed enteral-
ly. The working group of nutrition and metabolism of the European Society of Intensive Care Medicine (ESICM) has published in this journal a position paper on enteral nutrition describing the limit of enteral nutrition [11]. Also Berger et al. [12] have described the change in TPN and enteral nutrition in their surgical ICU during 10 years: in spite of the authors’ conviction that enteral nutrition is the first choice, they found that there are still about 8–10% of the patients who need TPN because enteral nutrition is not possible or not safe. What should we do with them? Let them starve without nutritional support and then die of the complications? Drs. Marik and Pinsky offer little solutions to this problem! All would agree that there is no place for PN in well nourished patients able to be fed adequately by the enteral route after a reasonable delay. The real problem is encountered when patients do not or can only poorly tolerate enteral feeding. Regrettably a large number of patients can be found in ICUs every day who for various reasons cannot tolerate adequate quantity and quality of nutrients enterally for many days. A recent survey by Preiser et al. [13] published in this journal on behalf of the Working Group of Nutrition and Metabolism of the ESICM found that among 2,774 ICU patients 23% were receiving PN! Let us not forget that underfeeding is a debt that must eventually be repaid and, as with all debts, it is made worse when it is compounded [14].
All routes of feeding should be used in ICU patients We completely agree that all patients are to be fed as close to “normal” as possible, preferably by mouth, nasogastrically or postpylorically. We also agree that TPN should be complemented with enteral feeding when possible. We stand by our established opinion that malnourished patients who for whatever reason are unable to tolerate enteral feeding must be fed parenterally. When used wisely TPN can deliver adequate nutrition safely! Depriving the seriously ill of nutrition, underfeeding or starving them, is dangerous and therefore should be avoided. TPN and enteral nutrition are not mutually exclusive. It is our considered opinion that patients requiring nutritional support should be fed accordingly to the adequacy of gastrointestinal function [15]. All artificial nutrition modalities carry risks and this must be balanced with advantages to be gained. Encouraging adequate nutrition by any route is important, but an overzealous or inappropriate promotion of enteral feeding may blind one to its many risks [14]. Enteral feeding also has risks. Many studies show that most of the time enteral feeding provides only partial nutrition [16] for reasons that include setting targets too low, not using protocols [17], slow initiation, and a tendency to stop too readily [18].
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It is unclear whether the authors of the editorial believe that the “nutrient cocktail” of amino acids, lipids, carbohydrates, vitamins, and trace elements are poisons or if the lack of intraluminal availability is the problem. The selected evidence that they cite, however, suggests that the nutrients are not to blame, but that the method of delivery is the culprit. The routes do matter and we agree normal is better than abnormal. They cite the elegant work of Li et al. [19] to show us the importance of luminal nutrition in mice. However, the authors fail to mention that the same laboratory demonstrated that the deleterious effects of the standard PN are due in part to its nutrient composition, since many of the features are prevented by the inclusion of glutamine in the amino acid mixture [19]. In addition, there is presently little evidence from clinical studies that TPN causes mucosal atrophy of the gut or bacterial translocation [20]. The central issue is whether there is solid evidence in the literature to support the view that TPN increases morbidity and mortality in the critically ill who cannot be fed enterally. We believe the evidence cited is weak. Indeed, as nearly all the data regarding the risks of TPN come from surgical studies, it is interesting that the authors confirm in the most recent studies that TPN is risk neutral. The authors fail to mention that there is very strong evidence from larger meta-analyses that failing to give PN to a malnourished patient unable to tolerate EN significantly increases mortality [21]. Heyland et al. [4] showed that TPN significantly reduced morbidity in malnourished patients. It is difficult to see how TPN could be considered a poison, and it is wiser to consider that this term comes from erroneous interpretations of studies suffering from important methodological biases [20]. It is
difficult to see how TPN could be considered a poison! Well controlled studies in similar mixed-fed patients having enteral feed show that there is no evidence of harm but possible benefit from supplemental PN [22]. Drs. Marik and Pinsky, in other situations where good studies are lacking, would you agree with the scientific statement by us... and with a famous Nobel prize that “the absence of evidence is not the evidence of absence”? Following the paper by Woodcock et al. [23] in which they state: “Indeed, now when correctly applied, the complications of parenteral feeding are less likely to result in death compared with those of enteral nutrition,” we expected other editorials and reviews [14, 24], and after the statement “[T]he time has come for the EN vs. TPN to be finally laid to rest. Patients with questionable gastrointestinal function should be fed using a combination of EN and TPN. The enteral feed is increased or decreased according to tolerance of EN and TPN, with the TPN adjusted accordingly” [15]. According to Drs. Marik and Pinsky, it seems that we were wrong. We are of course ready for further discussion based on sound scientific evidence. We definitely reject their statement: “In conclusion, for the intensivist the acronym ‘TPN’ may represent ‘total poisonous nutrition’.” This statement is neither correct nor justified. It has potentially disturbing effects and is unworthy of publication in a highly respected medical journal. It is also unworthy of the authors, whatever their aim was in the first place. We too have looked in a dictionary, namely the Oxford English Dictionary 2003 and found a definition for poison more applicable to the editorial: wicked, dangerous; hateful, objectionable. Say no more.
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