N O V E M B E R 2 0 0 6 • VO L . 1 3 • 3 5 3H O S P I TA L P H A R M AC I S T

For personal use only. Not to be reproduced without permission of the editor(permissions@pharmj.org.uk)

Malnutrition is a common butfrequently ignored problemin hospital patients. Symp-toms of malnutrition may go

unnoticed or may be mistaken for those ofthe patient’s main illness. Furthermore,nutritional status is frequently unrecorded inthe patient’s medical notes. However, if apatient is malnourished and no attention ispaid to nutritional intake, disease prognosisis likely to be poor, hospital stay lengthenedand the patient may be less able to respondto surgical and medical procedures, includ-ing medication, thus increasing the risk oftherapeutic failure and adverse effects.

In addition, hospital malnutrition coststhe NHS a considerable sum of money. Ofthe total cost of treating malnutrition in theUK, which is in excess of £7.3 billion (andmore than double the projected £3.5 billioncost of obesity), more than half arises fromthe treatment of malnourished patients inhospital (approximately £3.8 billion) and inlong-term care facilities (approximately£2.6 billion).1 The National Institute forHealth and Clinical Excellence (NICE) andthe National Collaborating Centre forAcute Care have produced a clinical guide-line on treatment of malnutrition.2

Although pharmacists are not usuallyinvolved in nutritional assessment, theyshould be aware of the high incidence of

malnutrition in hospitals and of the contri-bution they can make to the detection andmanagement of this important public healthproblem.

What is malnutrition?Malnutrition can be defined as a state ofnutrition in which a deficiency or excess (orimbalance) of energy, protein, and othernutrients causes measurable adverse effectson tissue/body form and function, and clini-cal outcome. Malnutrition therefore refersto both obesity and undernutrition. Thisarticle focuses on undernutrition.

Practically, undernutrition is defined by abody mass index (BMI) of less than 18.5(kg/m2); unintentional weight loss greaterthan 10 per cent within the previous three tosix months; or a BMI of less than 20 andunintentional weight loss greater than 5 percent within the previous three to six months.2

Undernutrition in hospitalUndernutrition is a significant public healthproblem in both hospitals and the community.In terms of absolute numbers of patients,mostundernutrition exists in the community, butthe incidence is greater in hospital and nursinghomes. In addition, the passage of patientsthrough hospitals is considerable. Althoughonly about 0.4 per cent of the UK populationis in hospital at any one time,about 12 millionpeople are admitted to hospitals in Englandeach year, including day cases.

Studies investigating the incidence ofundernutrition in patients in hospital havereported widely variable results (see Panel 1,p354).A pioneer study published in the USin 1974 found a 50 per cent incidence ofmalnutrition in surgical patients.25 Two yearslater, the same author detected a 44 per centmalnutrition rate in both surgical and med-ical patients.26 A year after that, a Britishstudy reported a 50 per cent incidence ofmalnutrition in surgical patients.21 Sincethese early publications, a large number ofclinical studies conducted in several coun-tries have shown that the risk ofundernutrition in patients in hospital rangesfrom 6 to 55 per cent, depending on thecountry, the hospital sector and the measuresof undernutrition used in the study.

When BMI is used as an indicator of nutri-tional status, the prevalence of undernutritionin adult patients admitted to UK hospitals hasbeen found to be between 10 and 40 per cent(undernutrition was defined in this study asBMI < 20).22 However,use of BMI alone willlead to underestimates of undernutritionbecause many people who have unintention-ally lost more than 10 per cent of their bodyweight in the preceding six months will be atrisk of undernutrition even though theirBMI may remain above 20. Furthermore,most undernourished patients admitted tohospital lose more weight during their stay,22

and are at risk of worsening nutritional sta-tus.14,19,31 They are therefore discharged backinto the community in a worse nutritionalstate than when they were admitted.

Malnutrition refers to both undernutrition

and obesity. Pharmacists should be aware

of the high incidence of undernutrition in

hospital patients and how they can

contribute to detecting this problem. This

article describes the relationship between

undernutrition and medicines

Undernutrition in hospital— causes and consequences

Pamela Mason is a freelance pharmaceuticaljournalist

Special features

By Pamela Mason, PhD, MRPharmS

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Causes of undernutritionUndernutrition has many causes, which arerelated to both physical issues and psychoso-cial issues such as poverty, education, socialisolation etc.The main causes of undernutri-tion can be classified as follows:

Impaired intake Impaired intake can becaused by poor appetite, illness, pain or nau-sea when eating, medication, dysphagia,depression, confusion, weakness, arthritis inthe hands or arms, painful mouth, poor den-tition, surgery to the head, jaw or neck, lackof food, poverty, homelessness, alcoholabuse, idiosyncratic diets, inability or lack ofmotivation to shop and cook, poor qualitydiet or poor food presentation at home, incare homes or hospital.

Impaired digestion or absorptionImpaired digestion and/or absorption canbe caused by medical or surgical problemsaffecting the stomach, intestine, liver or pan-creas.

Increased nutrient requirements Illness,surgery, treatment and organ dysfunctioncan all increase nutritional demands.

Excess nutritional losses Vomiting, diar-rhoea, fistulae, stomas, skin exudates fromburns and losses from nasogastric tubes andother drains can lead to excessive nutritionallosses.

Undernutrition and diseaseAlmost any moderate or severe chronic dis-ease or recovery from a severe acute diseaseincreases the risk of undernutrition. Olderpeople and those on multiple medicines orrequiring prolonged hospital stay are at par-ticular risk. Any condition causing muscleweakness (respiratory or peripheral), pain,poor co-ordination, gastrointestinal symp-toms, chewing or swallowing problems andimpaired appetite, taste, sight or smell can have deleterious consequences fornutrition.

Examples of diseases where undernutri-tion can occur include:

● Cancer● Stroke● Chronic neurological disease (eg,motor

neurone disease,multiple sclerosis,Parkinson’s disease)

● Chronic gastrointestinal disease (eg,Crohn’s disease, ulcerative colitis)

● Chronic obstructive pulmonary disease● AIDS● Dementia● Severe chronic arthritis● Anorexia nervosa and bulimia nervosa

Undernutrition can also occur in pre- andpost-operative patients.

MedicinesThe use of medicines, particularly whenthree or more drugs are used, usually indi-cates the presence of severe disease ormultiple physical and psychosocial problemsand, for those reasons among others, is asso-ciated with an increased risk ofundernutrition.

More specifically, medication can increasethe risk of undernutrition by:

● Reducing appetite (eg, amantadine,digoxin, fluoxetine, levodopa, lithium,metformin, penicillamine)

● Changing taste (eg,ACE inhibitors,allopurinol, amiodarone)

● Suppressing saliva production and causing dry mouth (eg, antihistamines,tricyclics, benzatropine, orphenadrine,oxybutinin, procyclidine, propantheline,trihexyphenidyl hydrochloride,selegeline)

● Causing confusion and/or depression.Any drug with a sedative effect couldincrease the possibility of reduced foodconsumption.

● Causing gastrointestinal adverse effectssuch as those listed in Panel 2 (p357).

Use of medicines is also associated withreduction in the bioavailability of specificnutrients.Anti-epileptic therapy is associatedwith reduced folic acid and raised homocys-teine levels, and also with an increased risk offracture, for which calcium and vitamin Dsupplementation should be considered. Pro-ton pump inhibitors and H2-receptorantagonists may reduce vitamin B12 absorp-tion. However, this effect has been seenmainly in patients taking these medicines forprolonged periods (eg, for more than fouryears). Colchicine and metformin are alsoassociated with reduced bioavailability ofvitamin B12. Probably the most well knownexamples of drugs reducing nutrient absorp-tion are tetracyclines, quinolones andpenicillamine which form insoluble com-plexes with minerals and trace elements, andliquid paraffin,which can reduce the absorp-tion of fat-soluble vitamins.

Consequences Undernutrition can manifest itself in a vari-ety of ways and affects every system in thebody, producing adverse effects on physicaland social well-being, including the following:2

Panel 1: Prevalence of undernutrition in patients in hospital

Country/region

Argentina3

Australia4

Australia5

Brazil6

Cuba7

Denmark8

France9

Germany10

Iran11

Latin America12

Lebanon13

Netherlands14

New Zealand15

Norway16

Poland17

Singapore18

Spain19

Spain20

UK21

UK22

UK23

UK24

US25

US26

US27

US28

US29

US30

Number ofpatients

1,00084

8194,0001,905

750324

803156

9,348100155—

2443,310

307201

Inpatient population105500850219131251134288

Inpatient population

837

Percentage ofpatients malnourished

471436484122

30 (men)41 (women)

226

5053454239104931135040201350444838

25 (acute)27 (chronic)

29

Number of hospitals/ department/ward

38 hospitalsSurgicalTwo hospitalsMulti-centreTwo hospitalsThree hospitalsMedical

Multiple departmentsNine wardsMulti-centreSurgeryMedicalHip fracture patientsSurgery12 hospitalsSurgeryStroke patientsTertiary careSurgicalMultiple departmentsMultiple departmentsMedical, surgicalSurgeryGeneral medicineGeneral medicineGeneral medicineTertiary care

Sub-acute care centre

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● Impaired immune response,predisposing to infection and delayedrecovery when infection occurs.

● Impaired wound healing,which canlead to prolonged recovery from illnessand increased length of hospital stay.

● Reduced muscle strength and fatigue,contributing to inactivity, inability towork, poor self-care and predispositionto falls.

● Reduced respiratory muscle strength,predisposing to delayed recovery fromchest infections and difficulty in comingoff a ventilator.

● Inactivity, particularly in bed boundpatients, leading to pressure sores andthromboembolism.

● Impaired thermoregulation, leading tohypothermia,particularly in older people.

● Menstrual irregularities,with the potential for infertility and osteoporosis.

● Vitamin and mineral deficiencies (eg,scurvy,B vitamin deficiencies in alcoholism, iron deficiency anaemia,trace element deficiencies).

● Water and electrolyte disturbances, suchas potassium,phosphate and magnesiumdepletion and overload in sodium andwater.

● Psychosocial effects, including apathy,depression, self-neglect, lack of interestin food, poor motivation for compliancewith therapy.

Nutritional assessmentIn hospital, it would not normally be the roleof a pharmacist to perform a nutritionalassessment. However, it is important to beaware that undernutrition is often unrecog-nised and not treated in hospital and othercare settings. The pharmacist’s role in thedetection of undernutrition is outlined inPanel 3.A study in Glasgow24 found that 70per cent of patients admitted to hospital werenot recognised as having protein energy mal-nutrition,while a US hospital study32 showedthat malnutrition went unrecognised in 62per cent of patients. Studies of hospital out-patients suggest that 45–100 per cent of casesof undernutrition go undetected.33

Failure to recognise malnutrition occursbecause of general lack of awareness of thisissue, arising from lack of training of healthprofessionals in nutrition.While health pro-fessionals may understand the nutritionalimplications of conditions such as diabetesmellitus, cardiovascular disease and obesity,the most fundamental nutritional disorder,ie, undernutrition, is often overlooked.Thesymptoms of malnutrition are often mistak-en for those of the disease itself, resulting in anegative impact on the patient’s condition,which in turn worsens the malnutrition.Lit-tle attention may also be paid to the fact

that, when ill, patients’ nutritional require-ments are likely to increase because of theillness,metabolic changes or the treatment.

Early detection of nutritional risk is thebest way of diagnosing malnutrition.Variousscreening tools are available for this purpose,including the Malnutrition Universal Screen-ing Tool (MUST),34 which can be used toscreen both undernutrition and obesity.

The NICE guideline on treatment ofmalnutrition recommends that all hospitalinpatients on admission and all outpatientson their first clinic appointment should bescreened (weighed, measured and BMI cal-culated). Screening should be conductedweekly for inpatients and when there is clin-ical concern for outpatients.2

Management Management of undernutrition involvestackling the underlying causes. Nutritionsupport should be considered for any patientunable to consume enough food and fluid tomeet their requirements. Oral optionsinclude dietary counselling to facilitate theaddition of ingredients high in energy and/orprotein, adopting a pattern of three meals aday with snacks in between, the inclusion ofnourishing fluids, and the use of proprietaryoral supplements. If oral intake is limited,

The following gastrointestinal adverse effects, which can be caused by the medicines indicated, increase the risk of undernutrition.

■ Oesophagitis and oesophageal obstruction (can be caused by doxycycline, ferrous sul-phate,modified release potassium chloride, tetracycline and slow-release formulationsof other drugs

■ Pancreatitis (azathioprine, oestrogens, furosemide, opiates or valproate)■ Dyspepsia, bleeding and ulceration (non-steroidal anti-inflammatory drugs)■ Pseudomembranous colitis (antibiotics)■ Diarrhoea (magnesium salts)■ Nausea and vomiting (chemotherapy)■ Constipation (anticholinergics)

Panel 2:Gastrointestinal adverse effects

■ Consider the possibility of undernutrition when conducting medication reviews atany point in the patient’s health care journey

■ Consider the possibility of the patient’s medication as a risk factor for undernutrition■ Consider the possibility of undernutrition as a risk factor for adverse drug reactions■ Ask questions about the patient’s pre-admission eating habits, appetite, problems

around preparing and eating food, social isolation, changes in the fitting of clothes,recent unintentional weight loss.

■ Check the patient’s notes to see if nutritional status is being assessed and documented■ Check (on ward visits) whether the patient is eating during the hospital stay

Panel 3:The pharmacist’s role in detecting undernutrition

Panel 4:Nutritional factors that influence cytochrome P activity35–37

Nutritional factor

Energy restrictionProtein deficiencyProtein and calorierestriction

Starvation

Iron deficiencyThiamine deficiency Vitamin A deficiencyVitamin C deficiency

Species

RatHumanRat

Rat

RatRatRatGuinea pig

Tissue

LiverWhole bodyLiver

Liver

IntestineLiverLiverLiver

CYP activity

↑CYP3A4↑CYP1A2↓CYP1A2↓CYP2A1↓CYP2C11↓CYP2E1↓CYP3A1/A2↓CYP1A↓CYP2C11↑CYP2B↑CYP 2E1↑CYP3A↓Total CYP↑CYP2E1↓CYP2C1 ↓CYP1A2

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enteral tube feeding or parenteral nutritionmay be required (see p362). Detailed guid-ance on the appropriate use of nutritionalsupport is covered in the NICE guideline.2

Altered drug handling Malnutrition is associated with variable butpotentially important effects on the bioavail-ability, binding, metabolism and renalclearance of drugs. It is important to note thatmuch of the research in this area to date hasbeen conducted either in animals, or in chil-dren with protein energy malnutrition(PEM) in developing countries.Although thisresearch cannot readily be translated to theUK hospital situation, pharmacists should beaware that differences in drug response couldoccur in malnourished patients in the UK.

Restriction of protein and energy and vit-amin and mineral deficiencies can influencethe activity of the cytochrome-P (CYP)enzymes in the liver and other tissues (seePanel 4, p357). Effects on other hepatic drugmetabolising enzymes have also beennoted.35 As a result of these effects, drugmetabolism and disposition can be altered.

Severe malnutrition may lead to lowerplasma protein concentrations. For highlyplasma protein bound drugs this can increasethe amount of free drug able to exert itstherapeutic effects and its adverse effects.Reduction in adipose tissue can lead toincreased plasma concentrations of fat-soluble drugs. Glomerular filtration ratemay also be reduced in severely malnour-ished individuals, potentially increasingplasma concentrations of parent drug oractive metabolites. Half-lives of drugs,including sulphonamides, chloramphenicol,isoniazid, penicillin G and metronidazolehave been shown to be longer in malnour-ished than in healthy children. Studies in ratswith PEM have shown that clearance ofmethotrexate, 5-fluouracil and paracetamolis reduced while clearance of salicylates isincreased with variable effects for otherdrugs, including diuretics and antibiotics.

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