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Nutritional Management of the Patient with Acute Respiratory Failure

Course Authors

Joel Mason, M.D., and Scott Epstein, M.D.

In the last three years, Dr. Mason has received grant/research support from Mead-Johnson Nutritional and also served as a consultant for Mead-Johnson Nutritional.

Dr. Epstein is Associate Professor of Medicine, Tufts University School of Medicine and Director, Medical Intensive Care Unit, Tufts-New England Medical Center, Boston.

Dr. Epstein reports no conflict of interest.

This activity is supported by an educational grant from Ross Products Division of Abbott Laboratories.

Estimated course time: 1 hour(s).

Albert Einstein College of Medicine – Montefiore Medical Center designates this enduring material activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

In support of improving patient care, this activity has been planned and implemented by Albert Einstein College of Medicine-Montefiore Medical Center and InterMDnet. Albert Einstein College of Medicine – Montefiore Medical Center is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.

 
Learning Objectives

Upon completion of this Cyberounds®, you should be able to:

  • Discuss the prevalence and impact that protein-calorie malnutrition has on the outcome of patients with acute respiratory failure

  • Describe which patients benefit most from aggressive nutritional support in the ICU setting, and some of the seminal principles involved in providing such support while minimizing its adverse side effects

  • Discuss the rationale behind the use of some of the newer liquid nutritional enteral formulations and discuss whether sufficient evidence exists at present to support their use.

 

I'd like to welcome our guest expert, Dr. Scott Epstein, who is a pulmonologist and Director of the Medical Intensive Care Unit at the chief teaching hospital for Tufts University, Tufts-New England Medical Center.

There certainly is an historical precedent for malnutrition playing a significant detrimental role in intensive care units. But given all the advances in modern medicine in the intensive care unit, why does malnutrition still play a key role in patient outcomes?

Malnutrition

Epstein

Joel, even with all the advances in intensive care unit medicine, malnutrition continues to be a major problem for several reasons. One reason is that, given the aging patient population and the chronic illnesses that accompany aging, many of the patients come to us in a malnourished state that precedes their acute illness.

Second, in our intensive care unit more than half the patients are mechanically ventilated, which makes it challenging to provide adequate nutrition for them. Also, acute illness, particularly of a the severe degree that we see in the ICU, rapidly induces a state of malnutrition. For all these reasons, malnutrition continues to be of major concern to us, and it's an issue that we need to address every day. Our ICU, like most tertiary care ICUs, has a nutritionist, who is an expert in critical care nutrition and rounds with us every day to help make recommendations on modalities of feeding and specific formulas.

Mason

Just to quantify your statement, Scott, recent nutrition surveys in hospitals continue to suggest that upwards of 40-50% of patients, particularly those in the intensive care unit, have a moderate to severe degree of malnutrition,(1) and it has been shown that this degree of malnutrition has a significant negative impact on clinical outcomes in the hospital.

Patients with Respiratory Compromise

Scott, let's begin by having you briefly review some of the adverse effects that malnutrition has on the physiologic and clinical capabilities of a patient with respiratory compromise.

Epstein

Malnutrition has a number of important consequences on physiological systems that are particularly significant for the patient in the ICU, specifically for the patient with respiratory failure. Respiratory muscle weakness is, by far, the most significant. We know that patients who are malnourished have both decreased respiratory muscle strength, probably from the decrease in muscle mass, as well as a decrease in respiratory muscle endurance.(2) The latter is especially important when trying to wean the patient from mechanical ventilation.

Similarly, there is reasonably good data to suggest that patients who are malnourished have an abnormal control of breathing. For example, studies have shown that patients who are malnourished have an inappropriate ventilatory response to hypoxemia.(3) That is, they do not ventilate enough. The other major issue we frequently encounter is that patients who are malnourished are at increased risk for respiratory tract infections, and this is usually an existing problem in the mechanically ventilated patient who is already a candidate for ventilator-associated pneumonia.

Mason

OK, so it's obvious that the physician needs to appreciate the adverse effects of malnutrition. But what can we do about it? Hasn't aggressive nutritional support been shown to improve the respiratory physiology of patients in a number of instances, particularly in the acute care setting?

Epstein

An interesting question, Joel. Let me begin by stating that systematic observations have demonstrated that we don't always do such a good job providing adequate nutritional support. In one retrospective study of patients who were ventilated for a minimum of six days, 88% of the patients were found to be receiving inadequate nutritional support.(4) There is evidence to suggest that nutritional repletion helps the patient with respiratory failure, especially those who come to the ICU already malnourished. In one study, for example, of critically ill patients who were mechanically ventilated and who received 2-4 weeks of TPN, researchers recorded a nearly 40% increase in respiratory muscle strength, an important parameter in determining whether or not a patient can come off a ventilator.(5) In addition, there are some older observational studies that suggested that adequate nutritional repletion can improve weaning from mechanical ventilation.(6) Unfortunately, to my knowledge, there are no randomized controlled trials yet showing that any given nutritional strategy will improve weaning outcome. Clearly, such studies are needed.

When to Start Nutritional Support?

Epstein

Joel, I'd actually like to pose a question to you. On rounds in the ICU, as we go bed to bed, one of the most frequently asked questions is, "How soon should we start nutritional repletion and what criteria should we use to determine when we should start?"

Mason

Scott, it's a very common clinical challenge and worth discussing. First, it is essential that each patient be considered individually -- algorithms for determining nutritional support in intensive care patients cannot account for all the nuances of each case. The randomized controlled clinical trials that have been performed uniformly indicate that it is the moderately to severely malnourished patient who benefits most from aggressive nutritional support, whether that be enteral or parenteral. There is considerably less evidence that a well-nourished patient is going to benefit from nutritional support. For instance, in the very large multi-center VA cooperative trial that was published in the New England Journal of Medicine in the early 1990s,(7) the benefit of preoperative nutritional support was only seen in those patients who had a substantial degree of malnutrition, and there was no significant benefit seen in patients who were either well nourished or mildly malnourished. Similar conclusions were arrived at by the large meta-analysis performed to examine the potential benefit of TPN in the intensive care unit.(8)

In the acute care setting, we frequently use as a criterion for moderate to severe malnutrition an unintentional weight loss from illness that is greater than or equal to 10% of the usual body weight. This is a very practical way of identifying those patients whose malnutrition is severe enough to warrant aggressive nutritional support and is, surprisingly, accurate when compared to more sophisticated methods of body composition analysis. Unfortunately, in the ICU, weight is artifactually altered by many factors, which sometimes confounds the use of this method. For instance, in the patient with excess body water, such as with ascites or congestive heart failure, artifactual increases in weight due to water are apparent.

Given the rapidity with which protein-calorie malnutrition develops in critical illness (a highly stressed ICU patient may lose nearly 3 kg of lean mass per day due to increased protein catabolism), I should add that we frequently do initiate aggressive nutritional support in the intensive care unit setting in well nourished or mildly malnourished patients if we project that the patient will not be able to meet at least 80% of their caloric and protein goals within five days after entering the intensive care unit. To date, there is inadequate evidence to prove the efficacy of this approach, but nevertheless it is one that is commonly followed.

Nutritional Issues After Extubation

Epstein

Joel, following up a point you just made: In the mechanically ventilated patient, there is very good data now to indicate that once a patient is extubated, swallowing dysfunction and a real risk of aspiration is present in the majority of patients, and may last up to several days especially in those patients who have been intubated for more than 48 hours.(9) Therefore, just because a patient is going to be intubated for only a short period doesn't mean that they will be able to take in oral nutrition immediately following extubation. Therefore, early nutritional support in a patient like this may be important because this patient may be unable to take conventional oral nutrition for several days after extubation. Along those lines, when a patient has been intubated for more than several days, we routinely will do a formal swallow evaluation (either a clinical evaluation by a therapist who is an expert in swallowing, or a modified barium swallow), just to ensure that this patient is not at high risk for aspiration.

Determining Appropriate Nutritional Support

The Risk of Hyperglycemia

Mason

As we discussed earlier, I think we both agree that there are potentially great benefits in providing nutritional support to appropriate patients in the intensive care unit with respiratory failure, but it has to be done intelligently if we are to minimize the likelihood of adverse effects.

When we institute nutritional support in the intensive care unit, it's frequently in a setting of a glucose intolerant patient (either secondary to pre-existing diabetes or to the effects of critical illness) and, as a result, hyperglycemia happens to be one of the most frequent consequences of enteral, and particularly parenteral, nutrition. There has been increasing attention to this issue over the past several years, and I was wondering if you could elaborate on this?

Epstein

A noteworthy study of a surgical ICU patient population, published in the New England Journal of Medicine by van den Berghe et al., showed that aggressive management of hyperglycemia, with a goal of achieving a serum glucose of 80-110 mg/dl, led to improved outcomes: shorter duration of mechanical ventilation and, most importantly, decreased mortality.(10) In order to achieve such tight serum glucose control, more than 90% of the patients required a continuous infusion of insulin, a much higher percentage than the control group's. Follow-up studies by the same investigators demonstrated that the beneficial effects relate more to normoglycemia than to the insulin therapy itself.(11) Therefore, aggressive nutritional support may not achieve better outcomes if hyperglycemia is not adequately controlled.

Mason

I would add, Scott, that this study substantiates a decade of animal studies which had demonstrated that even modest hyperglycemia impairs immune function in different tissues.(12) It is interesting to note that much of the increased morbidity and mortality in the clinical trial reported by van den Berghe was infection-related.

The Syndrome of Overfeeding

Epstein

Another potential pitfall of overly aggressive nutrition repletion is the syndrome of overfeeding. This is especially relevant in the patient with respiratory failure on mechanical ventilation. Overfeeding can be associated with a marked increase in carbon dioxide production. Therefore, in order to maintain normal blood gases, an overfed patient will have to increase their ventilation, a task that may be quite difficult if the patient has COPD or already has very high minute ventilation requirements. A related issue -- sedation in the ICU: nowadays, one of the more frequently used sedative medicines is diprivan (propofol). This drug is administered in a lipid emulsion and is, therefore, a rich source of calories (~900 kcal/liter). If nutritional support is implemented without the appropriate adjustment for the presence of propofol, the patient will be at risk for over feeding, excess CO2 production and respiratory acidosis.

Mason

As a consequence of this concern, overfeeding carbohydrate calories became a particular concern back in the 1980s since carbohydrates potentially have the highest respiratory quotient (moles of C02 produced per mole of O2 consumed), prompting the development of enteral feeding formulas that provide a greater proportion of calories as fat rather than carbohydrate. However, as long as overfeeding is avoided, and in particular, as long as carbohydrate is not infused either enterally or parenterally at a rate that exceeds 5 mg/kg/min (beyond which rate, the carbohydrate is converted to fatty acid), several studies have demonstrated that there is little concern that nutritional support will exacerbate or precipitate respiratory acidosis. Therefore, the use of these specialized formulas is not necessary as long as the ICU team is attentive to providing a reasonable amount of calories.

Positioning the Feeding Tube and the Patient

Mason

Scott, one other potential downside of aggressive nutritional support in the intensive care unit that I'd like to touch on is the issue of aspiration with enteral feedings through a nasoenteric tube. How important is it to place a nasoeenteric tube past the pylorus with the intent of minimizing aspiration risk?

Epstein

A few older studies suggested that post-pyloric feedings would decrease the risk for aspiration and there is some physiologic evidence in a randomized controlled trial by Heyland et al., showing that post-pyloric feeding decreased radiographically-detected gastroesophageal reflux as well as a trend towards a reduction in microaspiration.(13) However, larger randomized controlled trials and the meta-analysis of those trials(14) found no difference in clinically significant aspiration risk when comparing tubes that were placed in the stomach versus those placed beyond the pylorus.

Mason

Your points are well taken, Scott -- I'll make just one addition to what you said. I agree that with a few exceptions there is little evidence indicating that all patients should be fed post-pylorically. Nevertheless, that doesn't mean we shouldn't be attentive to the position of the nasoenteric tube. Given all the jostling and re-positioning that occurs in the critically ill patient, the tip of the tube can reposition itself up into the esophagus or into the cardia of the stomach, in which case it should be re-positioned in a more distal location within the stomach.

Epstein

Along these lines, there is one randomized controlled trial in which a single dose of erythromycin given to patients with a nasogastric feeding tube helped maintain the tube in the gastric position and, when compared to post-pyloric positioning, no difference was found in the ability of the groups to meet their nutritional goals.

A second point is that there is now abundant evidence to demonstrate the importance of body positioning in the prevention of aspiration. We know that patients who are cared for in the supine position are at increased risk for acquiring ventilator associated pneumonia. The experimental evidence shows that gastric contents in a supine patient will slowly make their way through the esophagus into the oropharynx and then into the lung. This process can be prevented, and in fact the risk for ventilator associated pneumonia can be significantly decreased, by keeping the patient upright at 45 degrees. So patient positioning, as well as tube positioning, may be important components of preventing complications of enteral feeding.

Mason

Certainly when patients are required to be in a supine position, either because of hypotension or because of an intra-aortic balloon pump, or some other such equipment, we withhold enteral feedings temporarily. Similarly, since prone positioning for the treatment of ARDS occasionally arises nowadays, we don't feed patients when they're placed in a prone position through an enteral route because of the very high risk of aspiration.

New Enteral Formulations: Are They Beneficial?

Mason

Scott, I would like to spend the remainder of our time discussing some of the newer enteral formulations that have appeared over the past several years. In particular, I'd like to first discuss the immunomodulatory formulas and second, I'd like to discuss a formulation that is enriched in fish oil.

Immunonutrition and Immunomodulatory Formulas

The immunomodulatory formulas (sometimes referred to as "immunoenhancing formulas"), of which there are several on the market, contain the conventional nutrients necessary for meeting the nutritional needs of the patient, but in addition contain supplemental quantities of specific nutrients in large quantities to convey pharmacologic actions. These so-called "nutriceuticals" include RNA, glutamine, arginine, and omega-3 fatty acids. There now exist many controlled clinical studies which demonstrate that a variety of immune- and inflammation-associated functions are modified by the administration of these immunomodulatory formulas. Nevertheless, given the complexity of the immune response as well as both survival benefits and risks associated with the inflammatory response, it has not been entirely clear in what settings and in what patients the modulation of the immune system actually improves clinical outcomes.

Mason

Scott, I was wondering whether you could provide us some perspective on the clinical studies that have examined immunomodulatory formulas and, more specifically, whether they truly are beneficial in the critically ill intensive care unit patient?

Epstein

Between 1990 and 2000, there were approximately 22 randomized controlled trials that examined the role of "immunonutrition" in either elective surgical patients or in critically ill patients. These studies have been analyzed in meta-analytic fashion by Heyland's group in Canada.(15) Looking at all the studies combined, immunonutrition seemed to have produced a significant reduction in the number of infectious complications and also in the length of stay. However, by stratifying the data, it became apparent that the significant reduction in infectious complications and hospital days occurred in the studies examining elective surgical patients rather than in those looking at critically ill patients. It should also be noted that in neither type of patient do these studies convincingly demonstrate that immunonutrition leads to a reduction in mortality.

Mason

Just to clarify for our audience, is it fair to say that the present state of knowledge does not support a large role for the use of immunomodulatory formulas in the intensive care unit?

Epstein

At the present time, the data would not support generalized use of immunonutrition in all critically ill patients. Of course, with further investigation, we may find subgroups of patients in the ICU who might benefit from this modality but, to date, we do not have good randomized controlled trials to help us identify such subgroups.

Supplemental Omega-3 Fatty Acids and Biotrauma

Mason

Scott, let's now move on to the other enteral formula that is frequently discussed these days: one that contains supplemental quantitites of omega-3 fatty acids alone. Acute respiratory distress syndrome is obviously a markedly inflammatory state. In this regard, there has been some thought that agents, like the omega-3 fatty acids, that could lessen the severity of this inflammation might be able to convey some clinical benefits to the patient. Now an enteral formulation has appeared on the market that is enriched with omega-3 fatty acids, thereby providing some suppression of the inflammatory response by diverting synthesis away from the pro-inflammatory prostanoids. Both human and animal trials have demonstrated that formulations of this nature are effective in modulating several immune mediators, including those in the lung.(16)

I was wondering whether you could give us some perspective on the state of our knowledge about this formula and whether it might provide real clinical benefits to the patient?

Epstein

Increasingly acute lung injury and ARDS are recognized as inflammatory states. This is particularly important because there is now very rigorous data to show that injurious mechanical ventilation strategies may not only injure the lung in the conventional sense of barotrauma and volutrauma, but also lead to a heightened inflammatory state. The term we use for this is "biotrauma."

The omega-3 fatty acid supplemented formulas have been studied in the setting of ARDS and it has been demonstrated that these formulas can reduce the amount of interleukin-8, leukotrienne-B4, as well as numbers of neutrophils and alveolar membrane permeability as studied by bronchopulmonary lavage fluid.(17) There is also one large randomized controlled trial in patients with ARDS that showed that these formulas, compared to conventional ones, are associated with a decrease in the number of days on mechanical ventilation, a decrease in organ failure and a decrease in the length of stay in the ICU.(18) I should also note that a reduction in mortality in patients with ARDS who were given the omega-3 acid formulations was not seen, although given the myriad of factors that determine mortality in the ICU this is perhaps not too surprising.

Mason

So observations to date suggest that omega-3 fatty acid- supplemented formulas might hold some genuine benefit to patients with ARDS, although we need some confirmatory studies that substantiate their benefit, since a single clinical trial is often not enough.

I think we've covered several of the seminal nutrition issues that come up frequently in the intensive care unit, although there are others which we simply did not have time to discuss, and which we may cover in future installments in Cyberounds®.

In summary:

  1. Malnutrition continues to play a very significant role in contributing to morbidity and mortality in the intensive care unit.
  2. In the appropriate patient, aggressive nutritional support can convey some true benefits to the patient.
  3. Although there are real benefits to aggressive nutritional support in the patient with acute respiratory failure (whether it be enteral or parenteral), the administration of the nutrition must be done in an intelligent and safe fashion to minimize the likelihood of adverse side effects.
  4. There are new formulations available for enteral use that are both provocative and potentially beneficial. It behooves the physician to remain abreast of the periodic literature since our knowledge about the potential benefits from these formulas is rapidly evolving.

Footnotes

1Souba, W. Nutritional support. N Engl J Med 1997;336:41.
2Kelly SM et al. Inspiratory muscle strength and body composition in patients receiving TPN therapy. Am Rev Respir Dis 1984;130:33.
3Palange P, et al. Effect of reduced body weight on muscle aerobic capacity in patients with COPD. Chest 1998;114: 12-18.
4Driver AG, LeBrun M. Iatrogenic malnutrition in patients receiving ventilatory support. JAMA 1980:244;2195.
5Rochester EF, Briscoe AM. Metabolism of the working diaphragm. Am Rev Respir Dis 1979; 119:101.
6Bassili HR et al. Effect of nutritional support on weaning patients off mechanical ventilation. J Parent Ent Nutr 1981;5: 161.
7Perioperative total parenteral nutrition in surgical patients. The VA TPN Cooperative Study Group. New Engl J Med 1991;325: 525-532.
8Heyland DK et al. Total parenteral nutrition in the critically ill patient: a meta-analysis. J Am Med Assoc 1998;280: 2013-2019.
9Ajemian MS et al. Routine fiberoptic endoscopic evaluation of swallowing following prolonged intubation: implications for management. Arch Surg 2001:136; 437.
10van den Berghe G et al. Intensive insulin therapy in the critically ill patients. N Engl J Med 2001;345:1359.
11van den Berghe et al. Outcome benefit of intensive insulin therapy in the critically ill: insulin dose versus glycemic control. Crit Care Med 2003;31: 359-366.
12Kwoun M et al. Immunologic effects of acute hyperglycemia in nondiabetic rats. J Parent Ent Nutr 1997;21: 91-95.
13Heyland DK et al. Effect of postpyloric feeding on gastroesophageal regurgitation and pulmonary microaspiration. Crit Care Med 2001;29: 1495-1501.
14Marik P, Zaloga G. Gastric versus post-pyloric feeding: a systematic review. Crit Care 2003;7:46.
15Heyland D et al. Should immunonutrition become routine in critically ill patients? A systematic review of the evidence. J. Am Med Assoc 2001: 286:944-953.
16Palombo JD et al. Effect of short-term enteral feeding with eicosopentaenoic and gamma-linoleic acids on alveolar macrophage eicosanoid sythesis. Crit Care Med 1999; 27: 1908-1915; also reference 10.
17Pacht ER et al. Enteral nutrition with eicosapentaenoic acid, gamma-linolenic acid, and antioxidants reduces alveolar inflammatory mediators and protein influx in patients with acute respiratory distress syndrome. Crit Care Med 2003;31:491.
18Gadek JE et al. Effect of enteral feeding with eicosapentaenoic acid, gamma-linolenic acid, and antioxidants in patients with acute respiratory distress syndrome. Enteral Nutrition in ARDS Study Group. Crit Care Med 1999;27:1409.