Caballero B. (ed.) Encyclopaedia of Food Science, Food Technology and Nutrition. Ten-Volume Set

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Oocysts are highly resistant to chlorination but are

sensitive to heat and prolonged freezing. Diagnosis is

by microscopic detection of oocysts in fecal speci-

mens stained by the acid-fast technique or immuno-

fluorescence, as well as by antigen detection assays.

Giardia intestinalis

0030 G. intestinalis has a worldwide distribution and

is responsible for the most frequently reported human

protozoal infection. Giardias is an intestinal infection

associated with poor socioeconomic conditions. In-

fection is acquired by ingestion of food or water

contaminated with feces. Cysts are the infective stage

excreted in feces of humans and other animals.

Asymptomatic carriage and excretion are frequent.

Cysts can be found in water, sewage, vegetables,

fruits, and other food. They resist chlorination but

are killed by heat and by prolonged freezing. Diagno-

sis is by microscopic identification of cysts in fecal

specimens. Trophozoites may sometimes be detected

in feces from patients with diarrhea.

Toxoplasma gondii

0031 Toxoplasmosis is a worldwide zoonosis. Prevalence

of human infection increases with age and is generally

30–70%. Infection is acquired by ingestion of infect-

ive oocysts from cat fecal contamination or by inges-

tion of improperly cooked meat from animals serving

as intermediate hosts, e.g., pork, mutton, and beef.

Oocysts need a period of maturation outside the

cat bowel. Cysts in meat are killed by heating, by

smoking or curing, and by prolonged freezing at

20



C. Diagnosis is by demonstration of specific

immunoglobulin (IgM) antibodies or increasing IgG

antibody titers in blood by immunological tests.

These tests are not satisfactory in immunocomprom-

ised patients with latent or reactivated infections.

Ascaris lumbricoides

0032 A. lumbricoides has a worldwide distribution but is

more prevalent in areas of poor sanitation, with 25%

of the world’s population estimated to be infected. It is

the most common helminthic parasite causing human

infection. No animal reservoir is known. Infection is

acquired by ingestion of water or food contaminated

with embryonated eggs from human feces. A. lumbri-

coides eggs need a maturation period outside the gut

and can remain infectious for months. Diagnosis is

by microscopic detection of eggs in fecal specimens.

Occasionally, adult worms are eliminated in feces.

Taenia solium

0033 Ta. solium is prevalent in Africa, South-east Asia,

Central and South America, eastern Europe, Spain,

and Portugal. The human is the definitive host and

the pig the intermediate host. Human intestinal infec-

tion is acquired by ingestion of undercooked pork

containing a larval stage called the cysticercus.

0034Humans can also harbor the larval stage of Ta.

solium in tissues. This potentially severe disease,

called cysticercosis, occurs after ingestion of water

or foods contaminated with Ta. solium eggs (from

human feces) or by autoinfection when eggs from

adult worms hatch in the intestine, producing a larval

form that penetrates the intestinal wall and enters the

circulation to reach structures such as muscle, brain,

lungs, and eyes. Diagnosis is by macroscopic detec-

tion of segments of the adult worm (proglottids) or by

microscopic detection of eggs in fecal specimens.

Cysticercosis may be diagnosed by radiological or

scanning examinations and by detection of rising

titers of specific antibodies. Sometimes, identification

of cysts after surgery may be the only means of defini-

tive diagnosis.

Trichinella spiralis

0035Trichinosis, the infection due to Tr. spiralis,isa

disease of carnivorous animals which accidentally

occurs in humans. It has a worldwide distribution

but is more prevalent in temperate regions. Human

infection is acquired by ingestion of raw or poorly

cooked pork or pork products containing encysted

larvae. Laboratory diagnosis is confirmed by the de-

tection of spiral larvae in biopsy muscle tissue from

the patient, sometimes after trypsin digestion of

muscle fibers. Demonstration of rising titers of

specific antibodies is also available for diagnosis.

See also: HIV Disease and Nutrition; Immunoassays:

Principles; Radioimmunoassay and Enzyme

Immunoassay; Shellfish: Contamination and Spoilage of

Molluscs and Crustaceans

Further Reading

Casemore DP (1990) Foodborne protozoal infection.

Lancet 336: 1427–1432.

Gamble HR and Murrell KD (1998) Detection of parasites

in food. Parasitology 117 (supplement): S97–S111.

Herwaldt BL (2000) Cyclospora cayetanensis: a review,

focusing on the outbreaks of cyclosporiasis in the

1990s. Clinical Infectious Diseases 31(4): 1040–1057.

Smith HV (1998) Detection of parasites in the environment.

Parasitology 117 (supplement): S113–S141.

Todd EC (1997) Epidemiology of foodborne diseases: a

worldwide review. World Health Statistics Quarterly

50(1–2): 30–50.

PARASITES/Occurrence and Detection 4355

Illness and Treatment

J Botas (formerly of) and J Melo-Cristino, Hospital

de Santo Maria, Lisboa, Portugal

This article is reproduced from Encyclopaedia of Food Science,

Protozoal Infections

Illness

0001 Protozoa are a major cause of morbidity and mortal-

ity worldwide, either in developing or in western

countries. Some of those able to infect humans by

the oral route have long been known to cause disease,

but others are only now being increasingly recognized

as pathogenic in immunocompromised hosts, espe-

cially in patients with acquired immune deficiency

syndrome (AIDS). They are very diverse in epidemi-

ology, symptomatology, treatment, and preventive

measures.

0002 In immunocompetent hosts most infections are

asymptomatic, but overt local or systemic symptoms

may be present, which may be severe in some cases.

However, protozoal infections are particularly

troublesome, sometimes life-threatening, in immuno-

compromised patients.

0003 Acute, self-limited diarrhea is the most common

symptom caused by protozoa listed in Table 1, but

sometimes more intense manifestations do occur,

including abdominal cramps, flatulence, anorexia,

vomiting, malabsorption, weight loss, and fever. In

AIDS patients, insuperable chronic watery diarrhea

with malabsorption and, eventually, wasting syn-

drome may be due to some of these parasites.

0004 Blood, pus, and mucus in stools are the result of

invasion of the intestinal wall and common only in

intestinal infection by Entamoeba histolytica, which

is also able to cause systemic infection, especially liver

abscesses, manifested by fever, weight loss, abdom-

inal pain, and hepatomegaly.

0005Humans may be either intermediate or definitive

hosts for Sarcocystis spp. and, while intestinal infec-

tion is thought to be asymptomatic, parasites in

muscle may cause swelling and pain. Microsporidia

have only recently been recognized as human patho-

gens in AIDS and very few cases have been reported in

non-AIDS patients. Pleistophora spp. has been found

in muscle biopsy, Encephalitozoon spp. in liver and

the central nervous system and Nosema spp. in dis-

seminated infection. (See HIV Disease and Nutrition.)

Treatment

0006Susceptibility of protozoa to chemotherapy correlates

roughly with metabolism and, accordingly, with

species. Several drugs are active against different

protozoa. For some of them, e.g., diloxanide furoate,

the exact mechanism of action is still uncertain.

Others, e.g., metronidazole, are broad-spectrum

antibiotics, interfering with the DNA of susceptible

infectious agents.

0007Some antibiotics are active directly against proto-

zoa, but others exert their effect on enteric bacteria

necessary for proliferation of protozoa, e.g., Enta-

moeba histolytica. Most of these drugs are contra-

indicated in pregnancy and treatment of pregnant

women often must be delayed until after delivery.

0008Metronidazole is effective against most flagellates

and amoebae and is an alternative choice in the treat-

ment of Balantidium coli. Other nitroimidazoles

(tinidazole and ornidazole) have similar activity and

less untoward side-effects, including headache, metal-

lic taste, nausea, vomiting, and diarrhea.

0009Emetine and dehydroemetine have considerable

side-effects, gastrointestinal and systemic, and are

tbl0001 Table 1 Foodborne and waterborne protozoa causing human infection

Amoebae Flagellates Ciliates Coccidia Microsporidia

Intestinal infection Endolimax nana

Chilomastix mesnili

Balantidium coli Cryptosporidium spp.

Enterocytozoon spp.

Entamoeba coli

Dientamoeba fragilis Isospora belli

Entamoeba hartmanii

Enteromonas hominis

Sarcocystis spp.

Entamoeba histolytica Giardia intestinalis

Iodamoeba b

tschlii

Retortamonas intestinalis

Blastocystis hominis Trichomonas hominis

Trichomonas tenax

Systemic infection Entamoeba histolytica Cryptosporidium spp.

Encephalitozoon spp.

Toxo p l a sma gon d ii

Nosema spp.

Sarcocystis spp. Pleistophora spp.

Nonpathogenic for immunocompetent humans.

Infection often serious in immunocompromised patients. Infection usually with C. par vum : avian species of doubtful significance.

Importance as human pathogens, particularly in patients with acquired immune deficiency syndrome (AIDS), has only recently been recognized.

4356 PARASITES/Illness and Treatment

reserved only for extraintestinal amoebiasis. They are

not active against E. histolytica in the bowel and

diloxanide furoate, tetracycline, paramomycin, or

iodoquinol must be added in order to treat simultan-

eous intestinal infection.

0010 Iodoquinol is also effective against Dientamoeba

fragilis (sensitive also to paramomycin and tetracyc-

line) and is used as an alternative drug against Balan-

tidium coli. Infections due to Giardia intestinalis may

be treated with quinacrine, metronidazole, or furazo-

lidine. Tetracycline is the drug of choice against B.

coli and D. fragilis. Iodoquinol must be used with

great caution, as it may cause myelitis and optic

atrophy. This is the reason why it is no longer avail-

able in most developed countries.

0011 Treatment of protozoal diseases in AIDS patients is

far from satisfactory. There is no effective specific

therapy for microsporidia or Cryptosporidium spp.,

perhaps the most common agent of infection of the

bowel in AIDS. Isospora belli and Sarcocystis spp.

respond poorly, if at all, to antifolates, which include

co-trimoxazole, sulfadiazine, and pyrimethamine.

Prevention

0012 Despite high prevalence and easy fecal–oral transmis-

sion of protozoa, foodborne and waterborne infec-

tions, although surely underestimated, seem rare.

Good sanitary conditions and personal hygiene are

keystones in preventing these infections. Protozoal

cysts and oocysts differ in sensitivity to adverse con-

ditions (heat, desiccation, freezing, chlorination) and

some are amazingly resistant.

0013 In countries with poor sanitary conditions, water

should be boiled and uncooked vegetables and un-

peeled fruits avoided, as they may have been washed

with contaminated water. Flies and other arthropods

may also be vehicles for fecal contamination of food.

But even when a visitor takes every possible precau-

tion to avoid these infections, a local food handler,

even in the best hotel, may be a cyst passer not aware

of the elementary rules of personal hygiene.

0014For some species there are several possible animal

reservoirs, which lessens the effectiveness of prevent-

ive measures. Even for these species with humans as

the only hosts, patients in some institutions, espe-

cially those who are mentally handicapped, are a

difficult group to control. The occurrence of sexual

transmission of some protozoa by oral–anal and oral–

genital sex is also considered important and is diffi-

cult to control.

Helminthic Infections

Illness

0015Helminths are probably the most common infectious

agents of humans. Two of those transmitted orally,

Ascaris lumbricoides and Trichuris trichiura, are each

thought to cause 1000 million infections worldwide.

Humans may be, for different helminths, definitive or

intermediate hosts and clinical manifestations, when

present, depend on localization and worm burden.

Unlike protozoa, helminths are not generally con-

sidered opportunistic pathogens in immunocom-

promised hosts.

0016Most intestinal infections caused by helminths

listed in Table 2 are asymptomatic. Gastrointestinal

symptoms are related to the number of worms in the

bowel. Diarrhea and abdominal pain are the most

common complaints, but malabsorption and weight

loss may occur and, if untreated, infection may even

be fatal, e.g., Capillaria philippinensis. Enterobius

vermicularis is frequently responsible for anal

pruritus, especially nocturnal, and restless sleep in

children.

0017Some parasites compete for absorption of spe-

cific nutrients, with symptoms resulting from their

deficiency, e.g., Diphyllobothrium latum causes

tbl0002 Table 2 Foodborne and waterborne helminths causing human infection

Nematodes Trematodes Cestodes

Intestinal infection Anisakis spp. Fasciolopsis buski Diphyllobothrium spp.

Ascaris lumbricoides Heterophyes heterophyes Dipylidium caninum

Capillaria philippinensis Metagonimus yokogawai Hymenolepis diminuta

Enterobius vermicularis Hymenolepis nana

Trichuris trichiura Taenia saginata

Taenia solium

Systemic infection Angiostrongylus spp. Clonorchis sinensis Echinococcus granulosus

Bayliascaris procyonis Fasciola hepatica Echinococcus multilocularis

Capillaria hepatica Opistorchis spp. Hymenolepis nana

Dracunculus medinensis Paragonimus westermani Multiceps multiceps

Toxocara spp. Taenia solium

Trichinella spiralis Spirometra spp.

PARASITES/Illness and Treatment 4357

deficiency of vitamin B

and consequently megalo-

blastic anemia and neurological symptoms. (See

Cobalamins: Physiology.)

0018 Systemic infections, although sometimes asymp-

tomatic, are more commonly associated with symp-

toms which depend on localization of the parasite.

Liver and biliary tract are targets for some helminths,

e.g., Capillaria hepatica, Clonorchis sinensis, Fasciola

hepatica, and Opistorchis spp., and symptoms of

hepatitis and cholangitis may occur. Furthermore,

increased incidence of cholangiocarcinoma seems to

be associated with these infections.

0019 Spirometra spp. and Dracunculus medinensis are

present in subcutaneous tissue, causing pain and

swelling or chronic ulcers with protrusion of worms.

Lung is infected by Paragonimus westermani, with

resulting bronchopulmonary symptomatology, in-

cluding cough, hemoptysis, bronchitis, or lung

abscesses.

0020 Infections by Angiostrongylus spp., Bayliascaris

procyonis,orMulticeps multiceps, when symptom-

atic, cause central nervous system disease, especially

seizures. Visceral larva migrans syndrome (fever, hep-

atomegaly, and eosinophilia) is caused principally by

Toxocara spp., but may also be due to Angiostrongy-

lus spp., Anisakis spp., and Capillaria spp.

0021 Larvae of Trichinella spiralis may be responsible

for fever, edema, myositis and, rarely, encephalitis,

pneumonia, or myocarditis. Larvae may encyst in

different tissues, resulting in space-occupying lesions

when they are big enough. Cysts of Echinococcus

granulosus are found more frequently in liver and

lung and are often multiple, but cysts of E. multi-

locularis have an unlimited germinal membrane and

spread either locally or to distant sites like neoplastic

metastases.

Treatment

0022 Susceptibility of helminths to chemotherapeutic

agents correlates with species even more closely than

is the case with protozoa. Some drugs are preferred

because they act in the bowel, expelling adult worms,

while others must be absorbed and act systemically,

in order to kill parasites in tissues. For most of them,

the exact biochemical mechanism of action is still

unknown. Some cause spastic paralysis of adult

worms, e.g., pyrantel pamoate, while others cause

flaccid paralysis, e.g., piperazine, with resulting

expulsion of worms by peristalsis.

0023 Mebendazole is the drug of choice for intestinal

nematodes and replaced thiabendazole, which is

much more toxic. In higher doses it is also used in

the treatment of infections by T. spiralis, E. granulo-

sus and E. multilocularis. Liver and bone marrow

toxicity are not uncommon with high doses.

0024Other benzimidazole drugs (albendazole and flu-

bendazole) are new alternatives which are perhaps

less toxic. Pyrantel pamoate, pyrvinium pamoate

and piperazine offer no pharmacological advantages

over mebendazole. Mebendazole is also the drug of

choice in systemic infections by nematodes, but is

much less effective. Removal of worms is the best

treatment for Anisakis spp. and D. medinensis.

0025Praziquantel is effective against most trematodes

and cestodes. It is the drug of choice for either intes-

tinal or systemic infections due to these parasites and

failures have only been reported in F. hepatica (bithio-

nol is the preferred drug for fascioliasis). Untoward

side-effects, including nausea, abdominal pain, and

headache, although not uncommon, are mild and

transient.

0026Niclosamide is equally effective against intestinal

cestodes, is less expensive, and has fewer untoward

side-effects than praziquantel. Although imidazoles

might be tried, surgery is still the best treatment for

M. multiceps and Spirometra spp. and should be

considered in echinococcosis, in which it is the only

treatment when the cyst is calcified.

0027Although drugs now available to treat helminthic

infections are less toxic than before, some authors still

prefer, particularly in intestinal infections, treating

only heavy infections, or using low doses of drugs to

reduce the number of parasites in order to avoid

undesirable side-effects. In contrast, reinfection with

Enterobius vermicularis is so easy that some authors

prefer to treat all household contacts. As with proto-

zoal therapy, treatment of pregnant women is better

delayed until delivery.

Prevention

0028Foodborne and waterborne infections are common

with both helminths and protozoa, although direct

person-to-person, fecal–oral contamination is also

responsible for transmitting some infections. Good

personal hygiene and sanitary conditions are thus

mandatory for prevention and control of these infec-

tions. Flies and other arthropods may transmit eggs

from feces to food and water. Vegetables may be

contaminated either by encysted larvae (aquatic vege-

tables) or after contact with contaminated water.

0029Veterinary inspection of meat is very important in

parasites which are infectious by macroscopic cysts

or larvae. Raw meat or fish may transmit several

helminths and should be avoided. Larvae and eggs

may be extremely resistant to adverse conditions

and remain viable for prolonged periods of time in

salted, smoked, or undercooked meat and fish, as well

as in chlorinated water. Snails, crayfish, crabs, and

prawns may harbor larvae and so should be properly

cooked. (See Fish: Spoilage of Seafood; Shellfish:

4358 PARASITES/Illness and Treatment

Contamination and Spoilage of Molluscs and

Crustaceans.)

Specific Examples

Cryptosporidium

spp.

0030 Cryptosporidium spp. were recently recognized as an

important cause of diarrhea in humans. Infection is

frequently symptomatic and in immunocompetent

hosts symptoms include mild acute self-limited

watery diarrhea, sometimes with abdominal cramps,

flatulence, nausea, anorexia, and weight loss. In im-

munocompromised patients, especially AIDS, chronic

diarrhea and profound weight loss may occur and are

an important cause of morbidity and mortality.

0031 Spiramicin has been used for treatment with doubt-

ful efficacy; no effective therapy is available. Nonspe-

cific symptomatic therapy is important to avoid fluid

and electrolyte imbalance, as in acute diarrhea of

other etiology. Prevention may be difficult, as oocysts

are extremely resistant and fully infectious when

passed in stools. Good sanitary conditions and per-

sonal hygiene are of utmost importance. Precautions

with stools in hospitals and other institutions should

be taken in order to avoid outbreaks.

Giardia intestinalis

0032 Giardiasis is now the most commonly reported proto-

zoal infection worldwide. About 20–50% of infected

people present symptoms, usually self-limited acute

diarrhea, but chronic diarrhea with malabsorption

may follow. Treatment with quinacrine has a high

degree of efficacy, but the drug is poorly tolerated

(vomiting, abdominal pain). Metronidazole and

other nitroimidazoles are equally effective and better

tolerated. Furazolidine has no advantages over quina-

crine, either in efficacy or in untoward gastrointest-

inal side-effects. Good water control is the most

important way of prevention. When necessary, water

should be filtered or boiled. Chemical treatment is of

doubtful efficacy.

Toxoplasma gondii

0033 Toxoplasmosis in immunocompetent people is gener-

ally asymptomatic or may resemble an infectious

mononucleosis. Tissue cysts, however, remain viable

for life. In immunocompromised patients, such as

AIDS patients, transplant recipients and patients sub-

mitted to immunosuppressive therapy, either acute or

reactivation of latent infection, may be responsible

for severe or fatal toxoplasmosis, mostly of the cen-

tral nervous system. Congenital toxoplasmosis may

present several clinical manifestations, some severe

(encephalitis, retinitis), depending on the time of

pregnancy when infection was acquired.

0034The combination of pyrimethamine plus sulfadia-

zine is the most effective therapy for toxoplasmosis

and has been the choice in immunocompromised pa-

tients. To avoid relapses, it must be maintained for life

in AIDS patients and as long as immunodeficiency

persists in other cases. Bone marrow toxicity and

skin rash are frequent with this combination and

may cause replacement of sulfadiazine by clindamy-

cin. Acute toxoplasmic infection in immunocompe-

tent hosts is only to be treated when symptoms are

severe or persistent.

0035Infection in pregnant women, either with or with-

out symptoms, must be treated. Spiramycin can be

used throughout pregnancy and after the first trimes-

ter, pyrimethamine plus sulfadiazine can be used.

None of the available drugs is active on cysts, but

only on vegetative forms. Oocysts are present in cat

feces in large numbers and so contacts must be

avoided by seronegative pregnant women and im-

munodeficient patients. In meat, cysts do not resist

prolonged freezing (20



C), heating (66



C),

smoking, or curing.

Ascaris lumbricoides

0036Clinical manifestations of A. lumbricoides infection

are diverse, being related to worm burden. Broncho-

pulmonary complaints may be present, due to migra-

tion of larvae through the lungs. If infection is slight,

adult worms cause no symptoms, but heavy infections

may be responsible for malabsorption or even intes-

tinal obstruction. Other rare manifestations may be

due to abnormal worm migration. Mebendazole is

the treatment of choice. Pyrantel pamoate or pipera-

zine are effective alternatives. Good sanitary condi-

tions are keystones in prevention. Infection is also

avoided by hand washing after contact with soil.

Taenia solium

0037Human intestinal infection by Taenia solium is gener-

ally asymptomatic. Symptoms due to cysticercosis

depend on organ involvement, the central nervous

system being the system most commonly affected

(by seizures), followed by orbit, muscle, liver, and

lungs. Niclosamide is widely used in the treatment

of intestinal taeniasis. It is effective and has few unto-

ward side-effects, but is not active against larvae.

Praziquantel is highly active against adults and

larvae, and should be preferred. Calcified cysts will

not respond to drugs and may justify surgery. Symp-

tomatic treatment of seizures may also be necessary.

The most effective prevention is by good sanitary

conditions, avoiding contamination of animal and

human food and water by human feces. Veterinary

PARASITES/Illness and Treatment 4359

inspection of meat decreases the risk of ingestion of

cysticercus, as does thorough cooking of pork.

Trichinella spiralis

0038 Most intestinal and tissue infections by Trichinella

spiralis are subclinical, symptoms depending mostly

on the number of viable larvae and their localization.

Diarrhea is the most common symptom due to adult

worms in the gut, but abdominal discomfort and

vomiting may also occur. Systemic invasion by larvae

is more often symptomatic, with fever, myalgia,

periorbital edema, and headache. Occasionally,

myocarditis, pneumonitis, or encephalitis may occur.

Mebendazole and thiabendazole are the drugs of

choice for treatment, along with salicylates and bed

rest. The most effective method of prevention is

thorough cooking of pork.

See also: Cobalamins: Physiology; Fish: Spoilage of

Seafood; HIV Disease and Nutrition; Shellfish:

Contamination and Spoilage of Molluscs and Crustaceans

Further Reading

Casemore DP (1990) Foodborne protozoal infection.

Lancet 336: 1427–1432.

Mandel GL, Douglas RG Jr and Bennett JE (eds) (1990)

Principles and Practice of Infectious Diseases, 3rd edn.

New York: Churchill Livingstone.

Mehlhorn H (ed.) (1988) Parasitology in Focus. Berlin:

Springer-Verlag.

Strickland GT (2000) Hunter’s Textbook of Tropical Medi-

cine. Philadelphia: WB Saunders & Co.

Thompson JH Jr (1990) Parasitology. In: Murray PR, Drew

WL, Kobayashi GS and Thompson JH Jr (eds) Medical

Microbiology, pp. 349–436. London: Wolfe.

PARENTERAL NUTRITION

C C Ashley and L Howard, Albany Medical College,

Albany, NY, USA

Definition and History

0001 The development of central venous catheters in the

1960s provided for the safe infusion of hypertonic

nutritive solutions. As placement of these catheters

became more widespread, so did the use of parenteral

nutrition (PN). In the early 1970s, this also became an

available therapy for patients with chronic intestinal

insufficiency living at home. Today, a variety of

vascular access options are available to patients, and

portable pumps can be used to infuse outside of

the home/hospital setting. PN is sometimes called

total parenteral nutrition (TPN), but this is an

overstatement because several hard-to-solubilize but

important nutrients are left out. Another term,

‘hyperalimentation,’ has also gone out of vogue, as

we learn the downside of overproviding substrate,

especially in a stressed patient.

Indications for Therapy

0002 Wide availability does not necessarily imply broad

applicability. Only recently has the evidence for and

against the use of parenteral nutrition in a variety of

clinical settings become better defined. Enteral routes

of nutritional support are generally cheaper, safer,

and equally efficacious. PN is indicated in those

patients where delivery of nourishment via the gut

is either unsafe or not possible. Candidates for PN

should be carefully selected because the therapy is

costly, cumbersome, and risky. A systematic approach

to choosing candidates for PN is detailed in Figure 1.

0003The first step in the process requires the clinician to

form a clinical judgement about whether the severity

and nature of the patient’s illness will lead to nutri-

tional impairment. Initial considerations are whether

a lengthy course of chemotherapy will provoke

nausea and reduce oral intake to negligible levels;

whether severe intestinal ileus will make it impossible

to use the gut; and whether a planned surgery is likely

to significantly reduce the patient’s absorptive sur-

face. The second step is to assess whether the patient

is at increased risk for malnutrition because of limited

nutritional reserves. The physician must determine

whether the patient is an alcoholic. Are they already

on catabolic drugs such as steroids? Are they vulner-

able by virtue of age or chronic illness such as dia-

betes? The third step is to determine whether the

patient is already malnourished. Loss of more than

20% of lean body mass, serum albumin depression

signs of vitamin or mineral deficiency independently

indicate a high-risk nutritional status. The fourth step

is the most critical. The physician must decide

whether the quality of life and prognosis can be posi-

tively effected by the provision of specialized nutri-

tional support and therefore whether this therapy

should be recommended to the patient. The

4360 PARENTERAL NUTRITION

remaining steps are concerned with choosing the

route of delivery for the indicated specialized nutri-

tional support. A summary of common clinical

scenarios, where provision of PN is considered, is

shown in Table 1.

Evidence Base for PN

0004 Insufficient evidence exists to assess the utility of PN

in many specific clinical settings, but there are several

broad areas where prospective randomized controlled

studies support the use of PN.

Perioperative

0005 Strong evidence exists to support the use of PN in the

perioperative setting when the patient has severe

protein–calorie malnutrition. The benefit is a modest

(several studies found 10%) reduction in postopera-

tive complications.

Critical Illness

0006In critical illness, there is support for the use of PN

in patients with severe protein–calorie malnutrition

using modest calories. Complication rates are lower

when lipids are not infused as a part of this

specialized nutritional support. Excessive exogenous

carbohydrate enhances hypermetabolism and lipo-

genesis, leading to increased carbon dioxide produc-

tion; this makes ventilatory weaning more difficult.

Wasting Syndromes

0007Cancer Like noncancer patients, cancer patients

suffering from severe protein–calorie malnutrition

benefit from perioperative PN when undergoing

cancer surgery. There are some data to suggest that

bone-marrow-transplant patients benefit from PN

supplemented with glutamine and that PN during

the cytoreductive phase enhances long-term survival.

0008HIV HIV patients appear to benefit from special-

ized nutrition support if their wasting reflects poor

intake or malabsorption; they do not benefit if their

weight loss is principally cytokine-related wasting.

The route of nutrition support is more controversial.

In one well-controlled study, PN was not superior to

enteral nutrition in repleting lean body mass, but it

did add more weight as water and fat. One small

study showed a longer survival in PN HIV patients

compared to those who received diet counseling

alone.

Chronic Renal Failure

0009PN improves survival in acute renal failure. A solu-

tion using just essential amino acids is not superior

to the usual essential–nonessential combination. In

Risks > Benefits

Yes

Step 1

Step 2

Step 3

Step 4

Step 5

Risks > Benefits

Is the patient malnourished

or at high risk for

malnutrition?

Is the disease process

likely to cause nutritional

impairment?

Would treating/preventing

malnutrition improve

prognosis or

QOL (quality of life)?

What are the fluid, energy,

vitamin and mineral

requirements and can

these be adequately

supplied by the enteral

route?

Can only PN safely meet

the patient's requirements?

Request placement of

central venous access

device and start PN

Use EN with

supplemental PN

Use EN as sole

source of nutrition

fig0001 Figure 1 Systematic approach to assessing candidacy for total

parenteral nutrition. Adapted from Howard L (1998) Parenteral

and enteral nutrition. In: Fauci AS, Braunwald E, Isselbacher KJ

and Wilson JD (eds) Harrison’s Principles of Internal Medicine, 14th

edn., chapter 78, figure 78-1, p. 473. New York: McGraw-Hill, with

permission.

tbl0001Table 1 Various indications for parenteral nutrition

Obstruction

Anatomical (congenital malformation, strictures, adhesions)

Functional (prolonged postoperative ileus, intestinal

dysmotility)

Hypermetabolic state/wasting syndromes

Critical illness

Multisystem organ failure and bowel ischemia

Severe pancreatitis

Burns

Cancer

Bone-marrow transplantation

HIV

Malabsorption/mucosal disease

Insufficient surface area from short bowel syndrome

Proximal enteric fistula

Severe inflammatory bowel disease

Severe chemotherapy related mucositis

Radiation enteritis

PARENTERAL NUTRITION 4361

chronic renal failure requiring dialysis, 15% of

patients become significantly malnourished. PN may

be indicated if there is severe bowel dysmotility asso-

ciated with autonomic neuropathy, as may occur with

diabetes. Routine use of intradialytic PN has not been

shown by randomized studies to clearly alter survival.

Pancreatitis

0010 In pancreatitis, PN can decrease mortality rate and

reduce rates of infectious complications when it is

used early in the management of the most severe

cases.

Short Bowel Syndrome

0011 The prognosis of acute short bowel syndrome has

been dramatically improved by PN, so much so that

a randomized study of PN vs. enternal nutrition (EN)

would be unethical. In the adaptive phase, an open

study purported to show that supplementation with

growth hormone and glutamine improved bowel

adaption, but this was not confirmed in a more rigor-

ous controlled trial.

Inflammatory Bowel Disease

0012 In inflammatory bowel disease, Crohn’s disease, or

ulcerative colitis, specialized nutritional support

(SNS) is often necessary for severe disease associated

with protein calorie malnutrition, but there are no

clear data that show any advantages of PN over EN.

SNS alone is not superior to steroids in reducing

remission or preventing relapse; however, it may be

the preferred approach in a growing child.

Technical Details

Route

0013 Peripheral PN PN can be delivered via peripheral

intravenous access, but this route is appropriate only

for formulations of modest osmolarity (e.g., less than

900 mOsm or 10 g of dextrose per 100 ml), since

small veins quickly sclerose and become useless for

further infusion. Peripheral PN is best used in a sup-

portive role for patients with inadequate oral intake.

Patients who are unable to meet their fluid and elec-

trolyte needs can be supported in this way without

exposure to the complications of central venous

access. However, peripheral PN is not a long-term

solution.

0014 Central PN Central access is a prerequisite when

infusing formulations of PN that are more complex

and more hyperosmolar. The catheter used to deliver

PN should be a dedicated line used for nothing else in

order to minimize the risk of infection. If additional

intravenous therapy is needed, additional access sites

should be arranged. Sometimes, multilumen catheters

are used, but studies have shown higher infection

rates in multilumen catheters versus single lumen

catheters.

0015Conventional central venous line In the setting of

an acute requirement for parenteral therapy or as a

bridge to the placement of a longer-lasting device, an

externalized central venous line (CVL) inserted by the

conventional Seldinger technique in the subclavian or

internal jugular vein is acceptable for the delivery of

PN. This catheter may be placed at the bedside as

long as full aseptic precautions are taken. This can

be a considerable advantage over other devices that

may take several days to arrange.

0016Peripherally inserted central venous catheter The

peripherally inserted central venous catheter (PICC)

can be placed at the bedside in the antecubital fossa

by specially trained personnel. PICCs placed at the

antecubital fossa are subject to mechanical stress

from flexion and extension of the elbow. They are a

short-term option. For long-term use, especially in

patients going home on PN, PICC lines are best

placed to the upper arm (brachial vein) under ultra-

sound and fluoroscopic guidance. Such lines are not

subject to the same level of mechanical stress. One

disadvantage common to all PICCs is that they are

more difficult for home patients to care for without

nursing support, because the patient has only one free

hand.

0017Tunneled catheter The chief advantage of tunneled

catheters is that an exit site low on the chest wall

permits a patient at home to see their catheter site

and manipulate the catheter with both hands. This

considerably simplifies the act of catheter access and

improves patient independence. Tunneled catheters

have a dacron cuff just under the skin which aids

catheter fixation and prevents bacteria from accessing

the blood stream through the tunnel. Patients with an

externalized catheter are usually advised to cover

their access devices with an adhesive/occlusive dress-

ing before showering or bathing in order to keep it

dry. Swimming is not recommended.

0018Subcutaneous port Subcutaneous ports are often

preferred by long-term patients, who have active life-

styles and want to swim. Subcutaneous ports are less

obtrusive and therefore cause less disturbance to body

image. The disadvantage of these catheters is that

they require a needle stick for accessing, but this

uncomfortable procedure is made easier by the use

of topical anesthetics. Also, it is rarely possible to

4362 PARENTERAL NUTRITION

clear an infected part and hence removal is necessary.

For this reason they are not wise in patients with a

history of frequent line sepsis.

Infusion Method

0019 Continuous Once a route is decided upon and avail-

able, a method of delivery must be selected. Most

patients begin PN as a continuous infusion. Continu-

ous infusion is the least complicated method of

delivering PN, since a metabolic steady state is quickly

achieved and maintained. This is the method of choice

in patients who are critically ill, hemodynamically

compromised, have marginal renal function, or are

brittle diabetics. However, continuous infusions are

not optimal from the perspective of most patients.

Long-term patients frequently seek some freedom

from their parenteral infusion. If a long-term continu-

ous infusion is necessary, portable pumps are available

that allow patients to perform most activities of daily

living without needing to disconnect.

0020 Cycled TPN infusions can usually be compressed to

a period between 10 and 12 h, depending upon the

volume and calories needing to be infused. Most

home patients opt to infuse during night time hours.

This leaves the patient free for a period of between 12

and 14 h a day to be more active. When the infusion is

cycled on and off daily, the risk for dehydration rises

especially toward the end of the infusion-free period

and in patients with significant gastrointestinal (GI)

losses. The risk of both hyper- and hypoglycemia is

increased at the start and conclusion of the daily

infusion. Swings in serum glucose levels demonstrate

the impact of carbohydrate delivered directly to the

systemic rather than the portal circulation.

0021 Intermittent In patients requiring less PN support, it

may be possible to provide PN every second or third

day. The complication of such a regimen is making

sure that mineral and vitamin requirements are met.

Establishing a Nutrient Formula

0022 Once the need for parenteral support is established

and the route and method of delivery are decided on,

the formulation can be determined. The first step is to

estimate the total nutritional requirement of the

individual patient. The requirement of an individual

patient may vary from day to day, depending upon

abnormal Gl losses. Over time, bowel adaption

occurs, so fluid and nutrient requirements may

significantly decrease.

0023 Fluid requirements

Basal The normal daily fluid requirement is 25–

35 ml kg

1

(for adults) and 120 ml kg

1

(for infants).

In a 70-kg man, normal losses are 1600 ml of urine

daily, 800 ml of insensible losses, 100 ml of stool

losses and 350 ml per degree Celsius per day of

fever.

0024Extraordinary fluid losses Fluid losses can vary con-

siderably in patients who require TPN, often because

of excessive loss from the GI tract. In the example

shown in Table 2, the patient requires twice the usual

volume of fluid because of extraordinary losses

through his jejunostomy. All fluid losses must be

meticulously reviewed in order to ensure adequate

replacement. Commonly excessive losses from the

GI tract will precipitate a greater oral intake.

0025Calorie requirement The total amount of calories

required is determined by weight and the patient’s

level of stress. Between 20 and 40 kcal kg

1

day

1

is usually provided to adults and 80–110 kcal

1

day

1

to infants. In patients who are simply

starved but not stressed, 35–40 kcal kg

1

day

1

(100–

110 kcal kg

1

day

1

for infants) can be effectively util-

ized. In patients who are moderately stressed and mal-

nourished, slightly lower amounts are provided, e.g.,

30–35 kcal kg

1

(80–100 kcal kg

1

day

1

in infants).

In patients who are severely stressed, calories are kept

modest (< 25 kcal kg

1

), since the stress induces a cata-

bolic state that prevents efficient utilization of high

levels of calories. Excessive calories precipitate hepatic

steatosis and retention of carbon dioxide.

0026Carbohydrate content Glucose provides 3.4 kcal

1

because it is glucose monohydrate. The carbohy-

drate content of the formulation varies from 4 to

7gkg

1

day

1

and usually accounts for 50–60% of

total calories.

tbl0002Table 2 Daily fluid requirements

Normal man (70 kg)

35 ml day

1

70 kg ¼2.5 l

In: 1.2 l of fluid Out: 1.6 l of urine

1.0 l of water in food 0.8 l insensible losses

0.3 l of water from

metabolism of food

0.1 l stool

Same patient status post high jejunostomy

In: 2.2 l of fluid Out: 1.6 l of urine

1.0 l of water in food 0.8 l of insensible losses

0.3 l of water from

metabolism of food

4.1 l of jejunostomy losses

3.0 l TPN

The patient needs to have enough parenteral fluid to maintain an adequate

urine output. Short-bowel patients have an increased risk of kidney stones.

Adapted from Howard L (1998) Parenteral and enteral nutrition. In: Fauci

AS, Braunwald E, Isselbacher KJ and Wilson JD (eds) Harrison’s Principles

of Internal Medicine, 14th edn., chapter 78, figure 78-4, p. 476. New York:

McCraw-Hill.

PARENTERAL NUTRITION 4363

0027 Fat content Fat solutions provide 10 kcal g

1

rather

than the expected 9 kcal g

1

because the lipid is made

iso-osmolar with glycerol. The fat content of the for-

mulation varies from 0.5 to 1.0 g kg

1

day

1

and

usually accounts for 30% of total calories.

0028 Protein content Amino acids provide 4 kcal g

1

The protein content of the formulation varies from

0.8 g kg

1

for a nonstressed patient to 1.5 g kg

1

for a

severely catabolic patient. Amino acids generally ac-

count for 10–15% of total calories. A patient whose

protein requirements are adequately met will be in

nitrogen balance based upon the following formula:

Nitrogen balance ¼ nitrogen intake  nitrogen loss

(nitrogen intake is 14% of all protein or amino acid

intake in g per 24 h; nitrogen loss is urine urea nitro-

gen in g per 24 h þ4 (a constant for other losses) ).

In the long term, protein balance can be assessed by

wound healing, resumption of growth, and/or restor-

ation of body composition.

0029 Electrolytes and minerals PN solutions are based on

a standard physiologic preparation of electrolytes.

The content of specific electrolytes can be varied to

replace patient losses or avoid excessive levels in pa-

tients with impaired renal or hepatic excretion. Extra-

ordinary losses of alkali and chloride salts are more

the rule than the exception in patients with large

volumes of GI fluid loss. Serum chemistries must be

intensively monitored until a state of equilibrium is

established, after which, periodic assessment remains

necessary. The necessary electrolyte replacement can

be based on the composition of the abnormal fluid

losses (see Table 3).

0030Vitamins and trace elements Parenteral provision

of vitamins and trace elements is complicated by

systemic infusion and altered enterohepatic cycles.

In addition, some micronutrients may adhere to for-

mula bags and delivery tubing or be destroyed by

exposure to light (vitamin A). Some nutrients (diva-

lent cations and fat-soluble vitamins) are especially at

risk for deficiency in patients with bowel disease and

steatorrhea. Others, cleared by the liver, may accu-

mulate in toxic amounts in patients with liver dys-

function and in that setting should be supplied only in

reduced amounts (Cu, Mn). Still others are at risk for

toxic levels of accumulation in the setting of chronic

renal failure (Se, Mb, l). The daily parenteral require-

ments for essential fatty acids, minerals and vitamins

are summarized in Table 4.

0031Medications and other additives Daily central

venous infusions create an opportunity for delivery

of a variety of medications by the intravenous route.

Any admixing must take into account compatibility

with the PN formulation and any cycling of PN

delivery that may create an unsafe or inefficacious

situation for an added medication (see Table 5).

Complications

Catheter Failure

0032Infection Catheter-related infection heads the list of

serious complications, since it is both common and

potentially devastating. More serious than any

individual infection is a pattern of infections that

increases the risk of endovascular colonization. The

incidence of infection is higher in children. Mortality

from these infections is low, but the dangers are real,

tbl0003 Table 3 Enteric fluid volumes and their sodium, potassium, chloride and bicarbonate contents

lday

1b

Na (meq l

1

(meq l

1

)Cl(meql

1

)HCO

(meq l

1

)

Oral intake 2–3

Enteric secretions

Saliva 1–2 10 30 10 30

Gastric 2 60 9 90 0

Bile 2–3 150 10 90 70

Small bowel 1 100 5 100 20

Colon Variable 40 100 15 60

Enteric secretions are also rich in divalent cations (Ca, Mg, Zn, Cu), and their loss is increased by steatorrhea, a high bowel fistula, or prolonged gastric

suction.

Of the total oral and enteric fluid presented to the upper small bowel, normally 50% is absorbed in the jejunum, 40% in the ileum, and 10% in the colon.

In short-bowel patients, the colon may absorb greater amounts, up to 3 l day

1

Potassium losses are small except in secretions distal to the ileocecal valve. The colon ion exchange is partly controlled by aldosterone, and therefore,

Na depletion increases K loss in the stools.

Bicarbonate losses must be replaced in parenteral solutions as acetate or lactate because of potential precipitation of bicarbonate with ingredients such

as calcium.

From Howard L (1998) Parenteral and enteral nutrition. In: Fauci AS, Braunwald E, Isselbacher KJ and Wilson JD (eds) Harrison’s Principles of Internal

Medicine, 14th edn., chapter 78, figure 78-5, p. 477. New York: McGraw-Hill.

4364 PARENTERAL NUTRITION