BJA Education, 19(3): 90e95 (2019)

doi: 10.1016/j.bjae.2018.11.007
Advance Access Publication Date: 26 January 2019

Matrix codes: 1A02,

2C01, 3C00

Nutrition in critical care

R. Chowdhury1,2 and S. Lobaz2,3,*
1
Sheffield Teaching Hospitals, Sheffield, UK, 2University of Sheffield, Sheffield, UK and 3Barnsley NHS
Foundation Trust, Barnsley, UK
*Corresponding author: [email protected]

Learning objectives Key points

By reading this article, you should be able to:
Nutritional status should be assessed clinically

Describe how to assess the nutritional risk of the for all patients on admission to ICU, though the
critically ill patient. value of scoring tools remains controversial.

Discuss the risks and benefits of starting enteral
If haemodynamically stable, enteral nutrition
nutrition (EN) in critical illness. (EN) is recommended as first-line and should be

Recall the indications for supplemental or total started within 48 h of admission.
parenteral nutrition (PN).
Where EN is contraindicated or insufficient,
parenteral (PN) should be used for supplementa-
tion or replacement.
The optimal approach to nutrition in critical illness is un-
New evidence suggests PN may be no riskier than
known despite numerous RCTs over the past decade. This EN.
article is an update on previous articles in this journal on
Most studies of supplementation with micro-
nutrition (2007) and parenteral nutrition (2013).1,2 nutrients or using specific nutrient blends have
shown either no benefit or harm, except in spe-
So why feed? cific subgroups.

The aim of nutritional support is to attenuate the detrimental

effects of critical illness on nutritional state, such as increased and regular reassessment of adult nutritional intake, using a
energy deficit and catabolism; it may favourably influence validated tool such as the Malnutrition Universal Screening
outcomes and prevent or reverse malnutrition,3,4 Currently, it Tool (MUST).5 A five-step tool, MUST identifies adults who are
is unknown how long starvation in critical illness can last obese, malnourished, or at nutritional risk. MUST uses BMI,
without harmful consequences, but most guidance agrees weight loss, and an acute disease effect score to give an overall
that nutritional therapy should be started as soon as possible malnutrition risk.
and certainly within the first week of critical illness. In 2016, the American Society of Parenteral and Enteral
Nutrition (ASPEN) and Society of Critical Care Medicine
Nutritional assessment (SCCM) guidelines recommended that if high risk (score 2)
and where insufficient oral intake is anticipated, a dietician or
The UK’s National Institute for Health and Care Excellence
nutrition team perform a formal nutritional risk assessment,
(NICE) recommends the screening on admission to hospital
using a scoring system such as the Nutritional Risk Screening
(NRS-2002) or Nutrition Risk in the Critically Ill (NUTRIC)
Rajin Chowdhury PGDip (Medical Education) is a specialty trainee score.3 NUTRIC stratifies patients as low (score 0e4) or high
in anaesthesia and intensive care at Sheffield Teaching Hospitals and (score 5e9) risk, based on comorbidities and clinical condition
an honorary clinical teacher at The University of Sheffield. to help individualise nutrition to current circumstances and
disease state.3
Steven Lobaz BMedSci FRCA FFICM is a consultant in anaesthesia However, the most recent European Society for Clinical
and intensive care, and is also clinical lead for fluids management Nutrition and Metabolism (ESPEN) guidelines contest this.4
and acute kidney injury at Barnsley NHS Foundation Trust. He is an MUST and NRS-2002 are not specific for critical illness and
honorary senior lecturer at the University of Sheffield.

Accepted: 30 November 2018

© 2019 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.
For Permissions, please email: [email protected]

90
 Nutrition in Critical Care

although NUTRIC was designed for such patients, NUTRIC has caloric requirement) with similar protein intake targets
not been validated in the ICU and does not improve mortal- (1.2e1.5 g kg1 day1). There was no difference in 90 day
ity,4,6 ESPEN recommends a general clinical assessment mortality or other outcomes, regardless of nutritional risk.6
(looking for a history of and examination, pre-ICU weight loss The Initial Trophic vs Full Enteral Feeding in Patients With
or a decline in physical performance decline before admission Acute Lung Injury trial (EDEN) recruited 1000 predominantly
to ICU, and examination of, muscle mass, body composition medical patients with acute lung injury (ALI) to either trophic
and strength); and that patients admitted to ICU for >48 h (400 kcal day1) or full (1300 kcal day1) EN. Trophic EN for up
should be considered at high risk for malnutrition.4 to 6 days did not improve ventilator-free days, 60-day mor-
During acute illness, the aim is to meet patient energy tality, or infectious complications, but was associated with
expenditure (EE), thus decreasing negative energy balance. less gastrointestinal intolerance.10
Ideally, EE should be determined using indirect calorimetry First-line, EN should be delivered to the stomach via a
(IC), which measures oxygen consumption (VO _ 2) and carbon nasogastric tube. There is no evidence that post-pyloric
dioxide production (VCO_ 2 ). ESPEN recommends that if IC is feeding is superior to nasogastric feeding.3 In addition, post-
_
unavailable, VCO _
2 only (derived from the ventilator) or VO2 pyloric feeding is more complex and requires input from the
only (derived from a pulmonary artery [PA] catheter) will radiology or gastroenterology teams. However, in patients at
estimate EE more accurately than feeding equations.4 How- high risk of pulmonary aspiration, switching from bolus to
ever, obtaining such values routinely in UK practice may be continuous feeding may be safer; and post-pyloric feeding
difficult, particularly with the declining use of the PA may be indicated should this fail.3 Administration of proki-
catheter. netic drugs early in those at risk may improve tolerance and
If unavailable, feeding equations (e.g. Harris-Benedict, reduce the incidence of aspiration further3: erythromycin is
Schofield)dusing sex, weight, height, age, and activity lev- recommended as the first-line agent, with metoclopramide a
eldapproximate EE but vary up to 60%.4 Failing these as- second-line addition or alternative.4
sessments, patients should receive 25 kcal kg1 day1 of feed, Gastric residual volumes (GRVs) of <500 ml do not correlate
increasing to target over 2e3 days.3 The Tight Calorie Control with the risk of aspiration.3 One study suggests GRV moni-
Study (TICACOS) compared nutrition guided by resting EE toring makes no difference to the incidence of ventilator-
(intervention) with a weight-based regimen (control: 25 kcal associated pneumonia. EN should not be stopped because of
kg1 day1) during critical illness. The results were slightly diarrhoea unless no other aetiology for the diarrhoea is found,
conflicting, with longer durations of ICU stay and artificial and the rate should only be reduced if GRVs exceed 500 ml.3
ventilation but lower mortality in the intervention group.7 During haemodynamic instability, timing is problematic.
In the Early Goal-Directed Nutrition in ICU Patients (EAT- Ideally, patients should be fully resuscitated and vasopressors
ICU) study, early-goal directed nutrition (EGDN) (with enteral stopped before EN is commenced. However, where prolonged
nutrition [EN] and supplemental parenteral nutrition [PN]) vasopressor therapy is anticipated, EN should be started with
and using measurements from IC and 24 h urinary urea cautious monitoring for signs of intolerance.3
excretion was compared with standard care (EN within 24 h
and supplemental PN after 7 days if less than a 25 kcal kg1
Parenteral nutrition
day1 target was achieved) in a single-centre RCT.8 EGDN
resulted in greater energy and protein delivery with more The optimal timing for starting PN timing in critical illness
episodes of hyperglycaemia episodes (blood glucose 15 remains unknown. ESPEN recommends starting PN after 3e7
mmol L1), greater use of insulin, and increased plasma urea. days if the patient cannot tolerate EN.4 However, early PN has
There was, however, no increase in renal replacement ther- not been found to alter mortality or other critical care out-
apy (RRT) need and no differences found in any clinical comes. ESPEN recommends exhausting all EN strategies
outcome at 6 months. before considering supplemental PN, case by case. Compared
Certain disease subgroups (e.g. patients with extensive with PN, no nutritional therapy for 14 days from ICU admis-
burns patients) may have greater nutritional requirements sion is associated with greater mortality (21 vs 2%, P<0.05) and
than in health. Though a one-size approach to energy and longer hospital stay (36.3 vs 23.4 days, P<0.05).11
nutritional replacement probably does not fit all, individu- The Early vs Late Parenteral Nutrition in Critically Ill Adults
alised EE targets appear to confer no additional benefit. (EPaNIC) trial compared early (day 3) and late (day 8) PN
initiation in those at risk of malnutrition.12 Late initiation was
associated with improved ICU survival, shorter mechanical
When to start feeding? ventilation duration, and less need to RRT. The EPaNIC trial
showed no benefits from additional PN in patients who could
Enteral nutrition receive EN. The early PN group had higher infection rates and
ESPEN and ASPEN both recommend that EN should start healthcare costs.12
within 48 h of ICU admission, preferably once haemodynamic The Early PN Trial compared early PN in critically ill adults
stability is achieved.3,9 The trials we have reviewed defined with relative contraindications to early EN with a standard
‘early’ as starting feed as soon as feasible, at most within 48 h. regimen of EN, PN, or no early feeding, and found no differ-
There are two approaches: trophic (increasing from 10 to 20 ml ence in 60 day mortality or ICU infection rates.13
h1, 1 kcal ml1) or full feeding. Trophic feeding has been
found to be safe, with fewer gastrointestinal complications
and is recommended up to 6 days from admission to ICU.3
Enteral vs parenteral nutrition
The Permissive Underfeeding or Standard Enteral Feeding The Trial of the Route of Early Nutritional Support in Critically
in High- and Low-Nutritional-Risk Critically Ill Adults Trial Ill Adults (CALORIES) aimed to answer whether EN was su-
(PERMIT) randomised 894 patients to permissive underfeeding perior to PN.14 It randomised 2388 adults within 36 h of un-
(40e60% of caloric requirement) or standard feeding (70e100% planned ICU admission to EN or PN. Early PN was found to be

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Nutrition in Critical Care

neither harmful nor beneficial compared with EN. EN was 40% of non-protein calories), carbohydrate/glucose (60% of
found to increase episodes of vomiting and hypoglycaemia non-protein calories), amino acids, electrolytes, vitamins,
(but without evidence of harm), infectious complications, and minerals, and trace elements. Basal requirements for nutri-
30 day mortality (33.15% PN vs 34.2% EN, P¼0.57). One criticism ents are summarised in Table 1.5,16 The exact compositions
was most patients in both groups did not achieve the 25 kcal and infusion rates can be tailored to the patient’s needs. PN
kg1 day1 target. should be delivered via a dedicated central venous catheter
The Enteral vs Parenteral Early Nutrition in Ventilated (CVC) or peripherally inserted central catheter (PICC) lumen.
Adults with Shock trial (NUTRIREA-2) found neither early PN lasting fewer than 3 months does not require a tunnelled
(within 24 h) isocaloric (20e25 kcal kg1 day1) EN nor PN line (e.g. Hickman); PICCs are equally safe.17
improved mortality or secondary infection risk.15 Early EN was
associated with more severe gastrointestinal complications
and a four-times increase in bowel ischaemia. Both Table 1 Basal nutritional requirements in critical illness.3,5
NUTRIREA-2 and CALORIES found no benefit of EN over PN Note that these are basal requirement and may need to be
and reveal EN is not as harmless as previously thought. increased in certain patients such as those with burns. Please
see text for more details
EN remains recommended as the first-line strategy in
critical illness, with total or supplemental PN considered
Nutritional requirement Per day
where EN is contraindicated, complications develop, or energy
(maintenance)
targets are unmet. Early EN during haemodynamic instability
may not be beneficial and may cause harm. Early nutritional Water 30 ml kg1
support (EN or PN) does not appear to improve ICU mortality. Sodium (Naþ), Chloride (Cle) 1e2 mmol kg1
An aid to nutritional support in critical illness can be found in Potassium (Kþ) 0.8e1.2 mmol kg1
Fig. 1. Calcium (Ca2þ), Magnesium 0.1 mmol kg1
(Mg2þ)
Phosphate 0.2e0.5 mmol kg1
Energy 25 kcal kg1
PN prescription and formulation Carbohydrate 2 g kg1
Protein 0.8e1.2 g kg1
PN must be prescribed by those trained in its use. Standard PN
Fat 1 g kg1
formulations are now available in preformulated combination
bags with an admixture of solutions containing lipid (about

Fig 1 Aid to decision-making for nutritional support during critical illness. This should be used as a guide and specific decisions regarding nutrition should be
made on an individual basis. CVS, cardiovascular system.

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 Nutrition in Critical Care

Carbohydrate Different fatty acids, their blend, and administration

Glucose is the main carbohydrate in PN with concentrations of route (e.g. EN vs PN) can influence many physiological, im-
40%, 50%, and 70%. ESPEN recommends <5 mg kg1 min1.4 mune, and metabolic processes. The ideal lipid emulsion (LE)
blend and route has yet to be determined, but should be
tailored to type of patient, critical illness severity and overall
Protein
nutritional needs. Many different LEs are now available,
Optimal protein intake during critical illness is unknown,
including vegetable soybean oil (SO; rich in both n-6 PUFA
although ESPEN recommends 1.3 g kg1 day1 delivered pro-
and LA), MCTs (usually from coconut oil), olive oil (OO; con-
gressively.4 The Timing of PROTein INtake and clinical out-
taining oleic acid), and fish oils (FO; which contain EPA and
comes of adult critically ill patients on prolonged mechanical
DHA). ESPEN recommends that immune-modulating EN
VENTilation (PROTINVENT) study demonstrated a time-
formulae be enriched with arginine and omega-3 fatty acids.
dependent association between protein intake and ICU mor-
Nucleotides may be superior to standard EN formulations in
tality.18 A low protein intake (<0.8 g kg1 day1) before day 3
only certain subgroups (e.g. surgery and trauma).9 In severe
combined with a high protein intake (>0.8 g kg1 day1) after
sepsis, immune-modulating EN may be harmful and is not
day 3 was associated with lower 6 month mortality (adjusted
recommended.
hazard ratio [HR], 0.609; 95% confidence interval [CI],
Omega-3-polyunsaturated fatty acids have many anti-
0.480e0.772, P<0.001) compared with patients with overall low
inflammatory properties. However, despite this the Enteral
(<0.8 g kg1 day1) or high protein intake (>1.2 g kg1 day1).
Omega-3 Fatty Acid, a-Linolenic Acid, and the Antioxidant
PN must provide all essential amino acids, for example histi-
Supplementation in Acute Lung Injury (OMEGA) trial found
dine, isoleucine, leucine, lysine, methionine, phenylalanine,
patients given omega-3 fatty acids had fewer ventilator-free
threonine, tryptophan, and valine.
days and longer ICU stays.19 In 2014, a multicentre trial per-
In critical illness, synthesis of certain amino acids may be
formed by Koekkoek and colleagues18 compared standard
insufficient through increased demand. These are ‘condi-
high-protein EN with standard high-protein EN enriched with
tional’ amino acids: arginine, cysteine, glutamine, tyrosine,
glutamine, omega-3 PUFAs, selenium, and anti-oxidants with
glycine, ornithine, proline, and serine. It is unclear whether
no effect on clinical endpoints. On subgroup analysis, medical
these should be replaced.
ICU patients had a higher 6 month mortality.19
Glutamine facilitates nitrogen transport and may reduce
ESPEN recommends lipids as an essential part of PN but in
protein catabolism. Low plasma glutamine is associated with
doses not exceeding 1.5 kg1 day1.4 PN with pure SO may
poorer outcomes. One small trial (n¼45) reviewed by ASPEN
worsen surgical-related stress and inflammatory response.
suggested some benefit of glutamine supplementation in
ASPEN recommends SO-based PN be withheld in the week
burns although insufficient to justify a recommendation.
after PN initiation or limited to 100 g week1 if there are
Other trials have shown either harm or no benefit; one found
concerns over fatty acid deficiency with other groups recom-
early glutamine administration in critical illness with multi-
mending against pure SO-based PN.3,19 OO-based LEs appear
organ failure increased in-hospital and 6 month mortality.3
safe and well tolerated in critical illness, although there is no
Routine glutamine supplementation is not recommended.
consistent evidence they are superior to SO-based LEs. The
Only one trial has examined the effects of arginine sup-
combination of mixed SO/MCT-based LEs instead of pure SO
plementation. In patients with severe sepsis and APACHE
may be better than SO alone. FO-enriched EN and PN (with
(acute physiology and chronic health evaluation) II scores
EPA and DHA) seems well tolerated and confers further ben-
between 10 and 15, arginine supplementation reduced bac-
efits (e.g. reduced complications and shorter ICU and hospital
teraemia and nosocomial infection incidence. However, sup-
stay) in surgical ICU patients.19 Research on FO-enriched
plementation made no difference to mortality in other groups
nutrition in medical ICUs is inconclusive, and further trials
when administered alongside other immune-modulating
are needed.
formulas. Routine arginine supplementation is not
recommended.3
Vitamins and trace elements
Non-essential amino acids which are produced in the body
Micronutrients (trace elements and vitamins) appear to
include alanine, asparagine, aspartic acid, and glutamic acid.
modulate the immune and inflammatory response (‘immu-
nonutrition’) and need consideration during nutritional sup-
Lipids port. Many micronutrients are antioxidants. PN does not
The high calorific content of lipids makes them fundamental contain trace elements or vitamins because of instability. It
in nutritional support. They also provide essential fatty acids requires separate prescribing and adding under controlled
such as linoleic acid (LA), omega-6 (n-6) polyunsaturated fatty aseptic pharmaceutical conditions. Micronutrients are often
acid (PUFA), and omega-3 (n-3) PUFA a-linolenic acid (ALA) omitted in more than half of ICU patients. Trace elements and
and their derivatives have important biological functions. LA vitamins include: thiamine (B1), ascorbic acid/vitamin C,
is the metabolic precursor of arachidonic acid (ARA) and ALA vitamin B12, folate, fat-soluble vitamins (vitamins A, D, E, and
is the precursor of eicosapentaenoic acid (EPA) and docosa- K), copper, selenium, zinc, chromium, cobalt, fluoride, iron,
hexaenoic acid (DHA).19 iodine, manganese, molybdenum, and vanadium. Several
Lipids are essential for cell membrane synthesis and assist trials have examined micronutrient supplementation beyond
delivery of fat-soluble vitamins (i.e. A, D, E, K). Lipids for minimum requirements.
nutritional support tend to be delivered as triglycerides. These Selenium supplementation in the Randomised Trial of
may be as medium-chain fatty acids (medium-chain tri- Glutamine and Selenium Supplemented Parenteral Nutrition
glycerides [MCTs]; e.g. capric, caprylic, myristic, or lauric for Critically Ill Patients (SIGNET) demonstrated no benefits in
acids), long-chain (long-chain triglycerides [LCTs]; e.g. a- terms of infectious complications or mortality.3
linolenic, linoleic, oleic, and palmitic acids), or very long-chain Although vitamin D deficiency is associated with poorer
fatty acids (e.g. DHA and EPA). patient outcomes, the Effect of High-Dose Vitamin D3 on

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Nutrition in Critical Care

Hospital Length of Stay in Critically Ill Patients With Vitamin D Summary

Deficiency (VITdAL-ICU) study in 2014, found routine supple-
Overall, providing nutrition within a week of admission ap-
mentation with high-dose vitamin D did not improve hospital
pears to convey benefit for patients in ICU. When there is
length of stay or 6 month mortality; however, patients with
cardiovascular stability, nutrition should be started as soon as
severe deficiency may benefit. ESPEN recommends single
possible and ideally within 48 h of admission. If the patient is
high-dose vitamin D3 administration (500 000 IU) within a
haemodynamically unstable, there is no clear answer to the
week of admission where 25-hydroxy-vitamin D plasma
timing of feeding; the risks of starvation must be weighed
concentrations <12.5 ng ml1.4
against the risk of adverse effects.
Overall, despite evidence showing certain nutrients
Feeds should be increased to target over 2e3 days (slower if
modulate inflammatory and immune responses, routine
at refeeding risk) and GRVs <500 ml should not be used to
supplementation is mostly associated with harm.
assess tolerance to feeding. Although EN remains first-line,
the CALORIES and NUTRIREA-2 studies have shown that PN
Complications of PN may be less risky than previously thought; if monitored and
Although the CALORIES and NUTRIREA-2 trials concluded that administered correctly, PN is safe as an alternative to EN.
complications from PN with good CVC care may be less With few exceptions, most attempts at modulating stan-
problematic than previously thought,14,15 they are still sig- dard formulations have been of no benefit or harmful. In
nificant. The incidence of CVC-associated infection (bacterial/ general, first-line nutritional support in ICU should be stan-
fungal) was higher in patients who receive PN compared with dard formulation EN within 48 h of admission with PN
those who did not. Infection is also higher when hygiene is replacement where necessary. Supplemental PN should be
poor, with emergency CVC insertion, increasing illness considered on a case-by-case basis.
severity and duration of CVC use. Metabolic complications of
PN include hyperglycaemia, electrolyte abnormalities, Wer-
nicke’s encephalopathy, nutrient excess or deficiency, liver Declaration of interest
dysfunction, and refeeding syndrome. Although these are The authors declare that they have no conflicts of interest.
rare, routine monitoring of glucose, fluids, and electrolytes is
warranted.
Acknowledgements
The authors thank Dr Simon Gabe, president of the British
Special groups of patients Association for Parenteral and Enteral Nutrition (BAPEN), for
ASPEN’s most recent guidelines make specific recommenda- helpful contributions to the early drafts of this article.
tions for certain groups of patients. These include patients
with: acute respiratory distress (ARDS), acute kidney injury MCQs
(AKI), hepatic failure, acute pancreatitis, sepsis, trauma,
The associated MCQs (to support CME/CPD activity) will be
traumatic brain injury (TBI), spinal cord injury, open
accessible at www.bjaed.org/cme/home by subscribers to BJA
abdomen, burns, postoperative major surgery, critical illness
Education.
recovery, and those who have chronic critical illness, obesity,
and those at the end of life.3 Detailed discussion of each
subgroup is beyond the scope of this article. However, some References
are briefly discussed below.
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