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Critically ill people need some form of feeding to give them protein and energy. The NIHR funded this multicentre trial to compare the costs and effects of early intravenous nutritional support with enteral feeding, feeding by tube into the stomach or the intestine. Death rates and other important outcomes were similar when using either route. The intravenous route was associated with lower rates of stomach overfilling, diarrhoea and low blood sugar, but the benefits gained were not great enough to justify the higher costs.

The findings support current practice across NHS critical care units where delivery of early nutritional support is predominantly given via stomach tube.

Why was this study needed?

Malnutrition is a common problem for critically ill patients who cannot feed themselves, estimated to affect about 40%. The consequences of malnutrition include susceptibility to complications such as infection which can lead to delays in recovery.

Early nutritional support is recommended to address nutritional deficiencies and prevent metabolic problems. It is unknown whether the intravenous or enteral route is better, particularly during the first few days in critical care. Though enteral feeding is most commonly used, it is associated with gastrointestinal intolerance and other side effects.

What did this study do?

The NIHR funded this randomised controlled trial to compare the costs and effectiveness of the two routes in 2,400 adult patients admitted to 33 NHS critical care units in the UK.

It compared five days of early intravenous feeding with enteral feeding.

The main outcomes were mortality at one month and cost-effectiveness at one year. Other outcomes studied included rates of infection and other complications, duration of organ support, and length of stay in critical care and in hospital. Cost-effectiveness was assessed and based on a willingness-to-pay threshold of £20,000 per quality-adjusted life-year, a measure of disease burden that considers both quality and quantity of life.

What did it find?

  • Mortality rates at one month were similar for adults in both groups – 393 deaths (33%) in the intravenous group compared to 409 deaths (34%) in the enteral group (relative risk 0.97, 95% confidence interval [CI] 0.86 to 1.08). Adjustments for age, degree of malnutrition, illness severity or treatment did not affect the results.
  • There were no significant differences between the groups for infectious complications, duration of organ support or for length of stay in the critical care unit or hospital.
  • Vomiting and hypoglycaemia were almost twice as common in the enteral feeding group. Vomiting occurred in 100 adults (8.4%) in the intravenous group compared to 194 (16.2%) in the enteral group (absolute risk reduction 7.81%, 95% CI 5.2 to 10.43). Hypoglycaemia occurred in 44 adults (3.7%) in the intravenous group compared to 74 (6.2%) in the enteral group (absolute risk reduction 2.49%, 95% CI 0.75 to 4.22).
  • At one year the overall costs were of £28,354 per patient for intravenous feeding and £26,775 per patient for enteral feeding. The incremental net benefit for the intravenous route was negative at -£1,320 (95% CI -£3,709 to £1,069). Given a willingness-to-pay threshold of £20,000, the likelihood that early nutritional support given intravenously is more cost-effective than enteral feeding is less than 20%.

What does current guidance say on this issue?

NICE 2006 nutritional support guidance provides recommendations for use of enteral and intravenous feeding for people who are malnourished, at risk of malnutrition or who have inadequate or unsafe oral intake. Critical care patients are usually provided with nutritional support via the stomach unless there is gastrointestinal dysfunction or intolerance.

NICE recommended that intravenous feeding is introduced gradually (starting with no more than 50% of estimated needs in the first 24 to 48 hours), and withdrawn once feeding is adequate via the enteral route or by mouth.

What are the implications?

This large multicentre trial found no difference in death rates of adults in critical care units when provided with early intravenous feeding compared to enteral feeding.

Though the intravenous route was associated with lower rates of gastrointestinal intolerance and low blood sugar, the benefits gained were not great enough to justify the higher costs. There may still be a place for intravenous feeding for sub groups of patients, with a risk of low blood sugar, for example. The trial suggests that where intravenous feeding is used it is safe.

The findings support the continuation of current practice in NHS critical care units where early nutritional support is predominantly delivered via the stomach or jejunum.


Citation and Funding

Harvey SE, Parrott F, Harrison DA, Sadique MZ, Grieve RD, Canter RR, et. al. A multicentre randomised controlled trial comparing the clinical effectiveness of early nutritional support via the parenteral versus the enteral route in critically ill patients (CALORIES). Health Technol Assess. 2016; 20(28):1-144.

This project was funded by the National Institute for Health Research Health Technology Assessment programme (project number 07/52/03).



NICE. Nutrition support for adults: oral nutrition support, enteral tube feeding and parenteral nutrition. CG32. London: National Institute for Health and Care Excellence; 2006.

Seron-Arbeloa C, Zamora-Elson M, Labarta-Monzon L et al. Enteral nutrition in critical care. J Clin Med Res. 2013:5(1);1-11.

Produced by the University of Southampton and Bazian on behalf of NIHR through the NIHR Dissemination Centre


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Enteral tube feeding is the delivery of a nutritionally complete feed into the gut, via a tube placed through the nose or mouth, or going through the abdominal skin (a “PEG”). It is the mainstay of nutritional support in critical care but requires an intact gastrointestinal tract and is frequently associated with gastrointestinal intolerance and underfeeding.

Intravenous or parenteral feeding is the delivery of a nutritionally balanced feed into the bloodstream. It is more invasive and expensive but may be used when enteral feeding is inadequate or when the gastrointestinal tract is compromised. It has previously been associated with more complications such as infections but these can be minimised by care in the delivery, formulation and monitoring of the feeding.



Expert commentary

The CALORIES trial provides much needed robust evidence for the choice of route of feeding in critically ill patients able to be fed enterally. Parenteral nutrition was not associated with increased risks, and resulted in fewer episodes of vomiting and hypoglycaemia. Although more expensive, this trial allays fears about the safety of feeding critically ill patients parenterally.

Dr Rob Mac Sweeney, Intensivist, Royal Victoria Hospital, Belfast

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