NIHR Signal Intravenous nutrition is more costly than feeding by stomach tube, with few added benefits

Published on 28 June 2016

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.

Intravenous nutrition is more costly than feeding by stomach tube, with few added benefits

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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).

Bibliography

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.

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).

Bibliography

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.

A multicentre, randomised controlled trial comparing the clinical effectiveness and cost-effectiveness of early nutritional support via the parenteral versus the enteral route in critically ill patients (CALORIES)

Published on 1 April 2016

Harvey SE, Parrott F, Harrison DA, Sadique MZ, Grieve RD, Canter RR, McLennan BKP, Tan JCK, Bear DE, Segaran E, Beale R, Bellingan G, Leonard R, Mythen MG, Rowan KM.

Health Technology Assessment Volume 20 Issue 28 , 2016

Background Malnutrition is a common problem in critically ill patients in UK NHS critical care units. Early nutritional support is therefore recommended to address deficiencies in nutritional state and related disorders in metabolism. However, evidence is conflicting regarding the optimum route (parenteral or enteral) of delivery. Objectives To estimate the effect of early nutritional support via the parenteral route compared with the enteral route on mortality at 30 days and on incremental cost-effectiveness at 1 year. Secondary objectives were to compare the route of early nutritional support on duration of organ support; infectious and non-infectious complications; critical care unit and acute hospital length of stay; all-cause mortality at critical care unit and acute hospital discharge, at 90 days and 1 year; survival to 90 days and 1 year; nutritional and health-related quality of life, resource use and costs at 90 days and 1 year; and estimated lifetime incremental cost-effectiveness. Design A pragmatic, open, multicentre, parallel-group randomised controlled trial with an integrated economic evaluation. Setting Adult general critical care units in 33 NHS hospitals in England. Participants 2400 eligible patients. Interventions Five days of early nutritional support delivered via the parenteral (n = 1200) and enteral (n = 1200) route. Main outcome measures All-cause mortality at 30 days after randomisation and incremental net benefit (INB) (at £20,000 per quality-adjusted life-year) at 1 year. Results By 30 days, 393 of 1188 (33.1%) patients assigned to receive early nutritional support via the parenteral route and 409 of 1195 (34.2%) assigned to the enteral route had died [p = 0.57; absolute risk reduction 1.15%, 95% confidence interval (CI) −2.65 to 4.94; relative risk 0.97 (0.86 to 1.08)]. At 1 year, INB for the parenteral route compared with the enteral route was negative at −£1320 (95% CI −£3709 to £1069). The probability that early nutritional support via the parenteral route is more cost-effective – given the data – is < 20%. The proportion of patients in the parenteral group who experienced episodes of hypoglycaemia (p = 0.006) and of vomiting (p < 0.001) was significantly lower than in the enteral group. There were no significant differences in the 15 other secondary outcomes and no significant interactions with pre-specified subgroups. Limitations Blinding of nutritional support was deemed to be impractical and, although the primary outcome was objective, some secondary outcomes, although defined and objectively assessed, may have been more vulnerable to observer bias. Conclusions There was no significant difference in all-cause mortality at 30 days for early nutritional support via the parenteral route compared with the enteral route among adults admitted to critical care units in England. On average, costs were higher for the parenteral route, which, combined with similar survival and quality of life, resulted in negative INBs at 1 year. Future work Nutritional support is a complex combination of timing, dose, duration, delivery and type, all of which may affect outcomes and costs. Conflicting evidence remains regarding optimum provision to critically ill patients. There is a need to utilise rigorous consensus methods to establish future priorities for basic and clinical research in this area. Funding This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 20, No. 28. See the NIHR Journals Library website for further project information.

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