May 162014
Nutritional Support During Critical Illness

This PulmCCM topic review will be periodically updated and expanded as new research is published. Originally published September 22, 2013. Most recent update: January 24, 2019.

During critical illness, catabolism (breakdown of muscle protein, fat and other complex molecules) occurs faster than anabolism (synthesis of these same macromolecules). Historically, the major goal of nutritional support during this period of acute illness was to ensure the body has adequate energy and nutrients available to slow down this process of fat and muscle loss. Loss of lean muscle mass during acute illness has been associated with worsened outcomes including prolonged mechanical ventilation and debility. The goal of nutrition support has traditionally been to preserve protein and energy stores, bolstering bodily processes needed to survive critical illness without lasting impairment.

However, it's unknown whether muscle wasting causes poor outcomes (suggesting nutritional support can be preventive or curative) or is simply a marker for severe illness (in which case nutrition may not matter all that much). Randomized trials have not shown a benefit from approaches that try to counteract the natural catabolic state that occurs in the acute phase of critical illness (i.e., forcing patients to reach their calculated caloric goals, through combinations of enteric and parenteral feedings).

Non-randomized prospective trials have suggested improved outcomes among patients considered at high nutritional risk (using the NUTRIC score or the NRS score) who were provided targeted additional nutrition support. (NUTRIC score calculator)

Randomized trials testing particular enteral nutritional preparations, delivery methods, and timing have not shown any superiority of one intervention or method over another in terms of improving measurable clinical outcomes.

The knowledge base and recommendations regarding nutrition and critical illness can be roughly summarized as follows:

Feed the gut early, if you can.

Providing enteral nutrition early to people with critical illness may reduce their infection risk, as compared to delaying enteral nutrition or not providing any. Enteral nutrition should be provided within 48 hours to people with critical illness who are not at high risk for bowel ischemia. The evidence supporting this recommendation is weak, however.

You usually can.

Most critically ill patients with impaired gut motility can tolerate “trophic” enteral feedings (tube feeds provided at 10 mL/hour or so) during critical illness. One randomized trial suggested monitoring gastric volumes may be unnecessary in most patients receiving mechanical ventilation.

It is better not to quickly reach "normal" caloric targets in most critically ill patients.

As stated above, caloric goals are theoretical and controversial, and were developed without outcomes-based evidence. In patients who were previously adequately nourished, providing minimal calories (trophic feedings) enterally for up to 7 days led to equivalent outcomes to more aggressive feeding, in mechanically ventilated critically ill patients (EDEN). A 2011 randomized trial suggested feeding critically ill patients below caloric goals might improve survival.

In a 2015 trial of 890 patients, targeting ~50% of "normal" caloric goals also resulted in no differences in outcomes, compared to patients targeted to receive a full healthy day's calories.

These findings were bolstered by the huge TARGET trial (2018), showing no improvement in clinical outcomes among mechanically ventilated patients receiving ~1,800 kcal/day compared to ~1,200 kcal/day. The patients receiving more calories required more insulin, vomited more, and had higher gastric residuals treated with promotility agents.

If you can’t feed the gut, wait before starting TPN.

Many critically ill patients have reduced gut motility and fail to tolerate enteral feedings in the amounts calculated to meet their theoretical caloric needs. For these patients, there appears to be no benefit to starting total parenteral nutrition in the first week after impaired gut motility occurs, and doing so may increase the risk for nosocomial infection. Providing no nutritional support or dextrose infusions are as good or better than early TPN for critically ill patients who can’t tolerate tube feedings. That being said, early parenteral nutrition has never been shown to increase mortality from critical illness.

The CALORIES trial showed no difference in mortality, infections, or any other clinically significant outcome between patients treated with early enteral vs total parenteral nutrition. However, the TPN arm in this pragmatic trial did not receive any more calories than the enteral feeding group, raising the question of whether it adequately tested TPN's potential risks at full doses.

Gastric residual volumes, prokinetics and postpyloric feeding might not matter.

Although enteral feedings are often interrupted in patients with high residual volumes to avoid precipitating aspiration events, this fear may be unfounded. In the NUTRIREA 1 randomized trial of 449 patients, not checking gastric volumes at all did not increase risk for aspiration or poor outcomes. (The increased enteral feedings and calories the unchecked arm received did not seem to improve their outcomes, either.) Another trial, REGANE, suggests residual volumes up to 500 mL are safely tolerated by patients.

Prokinetic agents (erythromycin and metoclopramide) have not been shown to improve outcomes, and neither has postpyloric placement of feeding tubes.

Vitamins and Minerals (Micronutrients)?

Vitamins E, C, beta carotene, thiamine, and trace elements like selenium, zinc, iron, copper, and manganese (in addition to electrolytes like potassium, magnesium and phosphate) are essential to life. Deficits of these micronutrients (mainly phosphate) are implicated in the refeeding syndrome, in which food intake after starvation results in insulin-mediated phosphate uptake, with resultant myocardial collapse and death due to hypophosphatemia.

A meta-analysis suggested giving micronutrients to critically ill patients could improve survival, but a large and well-conducted multicenter randomized trial showed no benefit of micronutrient supplementation. It also showed that glutamine supplementation was harmful. Nevertheless, some experts recommend micronutrient supplementation during the acute phase of critical illness, to prevent refeeding syndrome.

Enteral Nutrition (Tube Feedings) Preferable During Critical Illness

Enteral nutrition within 48 hours in critically ill patients might reduce the risk of hospital-acquired infection (nosocomial infection), compared to providing no nutrition or delaying enteral nutrition. This conclusion comes from a meta-analysis of 15 randomized trials showing an approximately 50% reduced risk for infection among those receiving early enteral nutrition. Another meta-analysis suggested early enteral nutrition reduced mortality risk by 50% as well, but fell just short of statistical significance.

These data are fairly old and from heterogeneous trial designs; some have argued these findings might be due to publication bias or other biases. Also, most of the included patients in these randomized trials were surgical (burns, trauma, etc.) and not medical patients (who have mainly been studied in observational trials).

Enteral nutrition is preferable to total parenteral nutrition, which is associated with nosocomial infections. A meta-analysis of 6 randomized trials (n=498) comparing enteral with parenteral nutrition suggested TPN almost doubled the infection rate compared to tube feedings. However, another meta-analysis of 12 randomized trials (n=748) did not show TPN worsened mortality, as compared to enteral feedings.

Starting Parenteral Nutrition Early May Be Harmful

For patients who cannot tolerate enteral feedings in sufficient quantities to meet their theoretical nutritional requirements, parenteral nutrition ("TPN") is often begun. However, evidence suggests it may be better to forego nutrition entirely rather than to receive parenteral nutrition in the first week after gut motility falls. Those receiving early TPN have experienced a 4-5% increase in nosocomial infections compared to those treated more conservatively:

Notably, the European critical care nutritional guidelines advise starting parenteral nutrition within 2 days, despite the above data, while the U.S. and Canadian guidelines advise waiting 7 days (see below for links to critical care society guidelines).

Most clinical trials studying nutrition in critical illness have excluded malnourished patients, so less is known about this patient population. Some experts advise use of the same nutritional support principles for malnourished patients as for adequately nourished patients. A study is underway testing the use of TPN in malnourished patients.

During recovery from critical illness, the body rebuilds muscle and fat (anabolism) and replenishes other energy stores (fat and glycogen). Nutritional supplementation should often continue after acute critical illness to support this process.

Obese Patients May be Malnourished, Too

Obesity appears to be protective during critical illness, but this effect is poorly understood. Obese people who eat nutrient-poor diets may have protein malnutrition, and limited evidence suggests malnourished obese people are at increased risk for death during critical illness compared to healthy-weight people. Nutrition should not be withheld from obese people during critical illness under the premise that they have "adequate reserves."

See also:

McClave SA et al. Feeding the critically ill patient. Crit Care Med. 2014 Dec;42(12):2600-10.

Nutrition in the Acute Phase of Critical Illness. NEJM 2014; 370:1227-36.

Nutrition in the ICU: An Evidence-Based Approach. Chest. 2014;145(5):1148-1157. doi:10.1378/chest.13-1158

Canadian clinical practice guidelines for nutrition support in mechanically ventilated, critically ill adult patients. JPEN J Parenter Enteral Nutr. 2003 Sep-Oct;27(5):355-73.

Guidelines for the Provision and Assessment of Nutrition Support Therapy in the Adult Critically Ill Patient: Society of Critical Care Medicine (SCCM) and American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.). JPEN J Parenter Enteral Nutr. 2009;33(3):277-316.

ESPEN Guidelines on Parenteral Nutrition: intensive care. Clin Nutr. 2009 Aug;28(4):387-400. doi: 10.1016/j.clnu.2009.04.024. Epub 2009 Jun 7.

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