towards the optimization of enteral nutrition

CLINICAL NUTRITION (1987) 6:61-74

THE ARVID WRETLIND LECTURE 1986

Towards the optimization of enteral nutrition

D. B. A. Silk Department of Gastroenterology &Nutrition, Central Middlesex Hospital, Acton Lane, London NW10 7NS, UK.

INTRODUCTION

It is 10 years since Bistrian and colleagues published their papers [ 1, 21 showing that up to 50% of hospitalised medical and surgical patients had some evidence of nutritional deficiencies. One interpretation of their findings was that up to 50% of the patients were ‘malnourished’ and therefore in need of nutritional support. Subsequently it has become clear that it is difficult to agree on what actually represents clinically significant malnutrition [3]. Moreover, even if agreement is reached, it may not be clear that outcome will be prejudiced by providing nutritional support. This is so because in the hospitalised patient malnutrition often arises as a consequence of the underlying disease pro- cess which may often not be amenable to correction. In the light of these comments it is not surprising that it is frequently not possible to clearly define the indications for instituting nutritional support. The problems involved in reaching a decision as to whether to institute nutritional support or not have been reviewed by several authors [4,6].

Once the decision has been made to institute nutritional support, it can be provided by the enteral or parenteral route. Clinical experience during the last decade has confirmed that enteral nutrition is an efficient way of providing nutritional care to patients with normal or near normal gastrointestinal function, and two surveys carried out in our own unit during the last 7 years have shown that over three quarters of all patients receiving nutritional support have been fed enterally.

It is because enteral nutrition has found such wide application that we have directed a good deal of our research efforts towards optimising its efficacy. Our overall aims have been firstly to increase our understanding of the basic physiology of nutrient assimilation in normal and disease states in order to apply principles gained to the formulation of enteral diets. In addition, clinical research has been directed towards improving the techniques involved in administering enteral nutrition to patients.

The term enteral nutrition commonly refers to the infusion of a formulated enteral diet with or without the use of a peristaltic pump via per nasal fme bore feeding tubes, positioned in the stomachor small intestine [7].

One of the most vexing problems facing investigators has been how to monitor the efficacy of nutritional support, and in this regard enteral nutrition is no excep- tion. Since we have found it practically and technically possible to calculate nitrogen balance on a regular basis we have used this parameter as a judge of efficacy. We would not, however, necessarily advocate that this is the best or only method available and in this regard the recent work on the effects of parenteral nutrition on muscle function is of considerable interest [8].

Table 1 Nitrogen balance during enteral feeding

Values are mean f SE Duration of Nitrogen

feeding balance Diet n (days) g/24 h

-] Vivonex’b HN 25 16.0 f 1.6 a 1 Clinifeedg

+0.6 f 0.8 21 20.3 f 2.8 +2.6 f 0.6

i

Clinifeedn 400 30 10.9 f 8.7 -1.2 f 0.4 b Clinifeed@ 400 29 9.9 f 8.9 +0.4 f 0.3

Expresssm EFl 27 7.9 f 5.9 +Z.8 f 1.1

(a) Data from Jones et al [9], (b) Data from Keohane et al [IO].

Table 1 summarises the nitrogen balance data observed in two of our controlled clinical trials [Q, lo]. It can be seen that the results are far from impressive and up to 400/b of individual patients entered in to the two trials remained in overall negative nitrogen balance despite continuous 24 h enteral feeding. It is now clear that in traumatised and septic hypermetabolic patients even on adequate intake of nitrogen and calories may not overcome the primary neuroendocrinological re- sponses [l l] and at least in the early phases these patients will remain in overall negative nitrogen balance. In other patients, however, negative nitrogen balance is more likely to persist on account of inude- quate intakes.

We have identified a number of factors that are likely to result in inadequate nutritional intake in enterally fed patients. Summarised in Table 2, these include the choice of the wrong type of enteral diet, the use of an inadequately formulated diet, the poor performance of

61

62 TOWARDS THE OPTIMIZATION OF ENTERAL NUTRITION

Table 2 Factors leading to inadequate nutritional intake during enteral nutrition

1. Incorrect choice of enteral diet 2. Inappropriate diet formulation 3. Poor performance of enteral feeding tubes 4. Use of small volume diet containers 5. Inappropriate route of administration 6. Routine use of ‘starter regimens’ 7. Slowing of infusion rates to counteract gastrointestinal side

effects and aspiration

enteral feeding tubes, the use of small volume diet con-

tainers, the wrong route of administration, and the

routine use of ‘starter’ regimes. The ensuing article dis-

cusses some of our experiences which have led us to

believe that there are simple methods available whereby

nutritional intake can be increased thereby improving

the efficacy of enteral nutrition.

Enteral diets

Table 3 summarises the different categories of enteral

diets available. Until recently controversy has existed as to whether enteral feeds formulated and prepared in the

hospital dietetic department should be used in prefer-

ence to their commercially prepared counterparts.

Problems with infection have now been well docu-

mented with ‘home brew’ diets [12] and there is now

controlled data to show that the incidence of diarrhoea is higher when ‘home brew’ rather than commercial

diets are used for enteral feeding [ 131. We therefore still

recommend the routine use of the commercially available diets. Knowledge gained about the processes

involved in the physiology of nutrient absorption and

subsequent metabolism both in normal and disease

states continues to influence the formulation of enteral diets, and recent advances in these areas that are influencing diet formulation are discussed.

Table 3 Classification of enteral diets

Fat absorption

There has been little research that has actually in-

fluenced diet formulation in the last 2 years. The im-

portance of preventing essential fatty acid deficiency needs emphasising, particularly since it may occur in

situations where gut function is particularly impaired

and long chain triglycerides are poorly assimilated [ 141.

This author continues to point out [15] that medium

chain triglycerides (MCTs) are probably not as well

assimilated in the presence of bile salt deficiency, exocrine pancreatic insufficiency and intestinal resection as

many would believe [16] and at least in the latter two

situations pancreatic supplements will greatly enhance

energy assimilation from MCTs and reduce steator-

rhoea [ 171.

Carbohydrate

The physiology of digestion and absorption of dietary carbohydrate in relationship to formulation of enteral

diets has been reviewed [ 181. Although the early chemi-

cally defined ‘elemental’ diets administered to man con-

tained glucose as the sole carbohydrate energy source

[19, 201, the glucose content was soon replaced in part

by sucrose [21], and later by glucose polymer mixtures

derived from the hydrolysis of starch by cc-amylase

[ 181. Although the potential carbohydrate forms used

in enteral diets have been categorised [22], Jones and

colleagues [23] have characterised in detail the compo-

sition of starch hydrolysates commonly used as the

carbohydrate energy source of enteral diets. Using gel

permeation chromatography they found that most con- sist of a very heterogenous mixture of glucose polymers

approximately 50yb of the glucose content being present as polymers containing more than 10 glucose

molecules, the remaining glucose content being present as shorter chain polymers containing less than 10 glu-

cose molecules [23]. Intestinal perfusion studies per-

Type

Polymeric

Comments

Protein nitrogen source. For use in patients with normal or near normal gastrointestinal function

Predigested ‘chemically defined Free amino acid or oligopeptide nitrogen source. Small quantities of long chain triglycerides. elemental’ For use in patients with severe gastrointestinal disease

‘Disease specific diets’

Portosystemic encephalopathy Free amino acid nitrogen source. High branched chain amino acid content, low aromatic ammo acid content. Indications still under discussion [ 1031

Stress Branched chain amino acid enriched. Indications still under discussion [90]

Renal failure Enteral nutrition in renal failure discussed elsewhere [ 1041

Respiratory and cardiac failure Protein nitrogen source. Reductions in carbohydrate component of energy source [ 1051

CLINICAL NUTRITION 63

formed in normal human volunteers in the absence of

luminal cc -amylase activity showed a differential hand-

ling of the glucose polymers by the jejunum. The

higher MW glucose polymers (containing > 10 glucose

molecules) were assimilated slower than the lower MW glucose polymers. It seemed that the latter could be

conferring a kinetic advantage on glucose transport [23]. This was confirmed in a further study [24] in

which purified high and low MW polymer fractions

were perfused. Although the oz -amylase hydrolysate of

the low MW glucose polymer fraction (< 10 glucose

molecules) conferred the expected kinetic advantage on glucose transport, the high MW fraction (osmolality 2

of the starting material) was surprisingly well absorbed

even in the absence of x-amylase [24]. The authors

concluded that the energy content of enteral diets could

be increased at the same time as lowering diet osmo-

lality by substituting the commonly used heterogenous starch hydrolysates with purified high MW fractions.

To date in only one diet (Vivonex TEN”, Norwich

Pharmaceuticals Inc) has this concept been utilised, with a subsequent lowering of osmolality from 830-630

mosmol/kg.

Lactose

Lactose deficiency is common in certain racial and

ethnic groups, particularly those of African descent,

Asians and Jews, with an incidence‘as high as 60-1009,

[25]. On account of this it is perhaps hardly surprising

that it is now considered commercially wise to minimise the lactose content of new enteral products. Walike &

Walike [26] were the first to suggest that the lactose

content of blenderised formulae was the cause of diar-

rhoea that occurred during enteral feeding. Certainly the recent study of O’Keefe and colleagues [27] demon-

strated that if patients with biochemically proven lactose malabsorption are bolus fed with lactose con-

taining enteral diets, then diarrhoea will occur with

stool volumes in excess of 1 L/24 h. It must be mentioned, however, that it is far from proven that it is the

lactose content that causes gastrointestinal symptoms

when milk is ingested by normal subjects with bio-

chemically proven lactose intolerance. Two studies have failed to show that the ingestion of

480 ml lactose containing milk by healthy normal sub-

jects with biochemically proven lactose malabsorption results in a significantly higher incidence of gastrointestinal side effects as compared with when the same subjects ingested the same quantity of lactose free milk [28,29]. In the recent study of Keohane and colleagues [lo], enterally fed patients with biochemically proven lactose malabsorption did not have a higher incidence of gastrointestinal side effects when fed a lactose containing enteral diet (20.9 f 5.3 g lactose/24 h) as com-

pared to a lactose free formulation. What then is the ex-

planation for the discrepancy in these findings? The

answer lies in the load (concentration x rate) of lactose

that is administered to lactose-‘intolerant’ patients.

Lactase, or fi-galactosidase, is a brush broder hydrolase whose specific activity is reduced but not absent in

patients and subjects with lactose malabsorption. If 2-

3 L lactose containing diet is infused constantly over 24 h, then the load of lactose administered per unit time

is low, and symptoms, as demonstrated by Keohane

and colleagues [lo] will not occur. Symptoms will de-

velop, however, as demonstrated by O’Keefe and col-

leagues [27] if high loads of lactose are administered by

the bolus technique. The commercial pressures are now

such, that it is unlikely that any of the new enteral diets

will contain appreciable quantities of lactose.

Sucrose

In patients with a very short small intestine, the factors.

that will limit uptake of glucose from glucose polymer

mixtures will usually include intraluminal and brush

border saccharide hydrolysis and in a few instances

when these are not rate limiting the capacity of the

membrane carrier to mediate uptake of the released

monosaccharide. Jejunal perfusion studies have shown

that if glucose transport from glucose polymers is satur-

ated, sugar absorption can be enhanced if the disacchar-

ide sucrose is added [30]. This is so because sucrose is

hydrolysed by the sucrase moiety of the hybrid brush

border hydrolase sucrose-isomaltase [31] to glucose and

fructose, fructose absorption then being mediated by a

carrier that is distinct from that utilised during glucose uptake [32].

Protein absorption

The digestion and absorption of dietary protein in re-

lationship to the formulation of enteral diets has been

recently reviewed [33]. While it remains clear that patients with normal gastrointestinal function should

be fed diets containing whole protein as the nitrogen

source, controversy still exists as to whether the nitro-

gen source of enteral diets for use in patients with

severly impaired gastrointestinal function should con- sist of free amino acids or oligopeptides, and if the latter, what was the most rational formulation should be. Intestinal perfusion studies in our laboratory have consistently shown more efficient absorption of X- amino acid nitrogen from partial enzymatic hydrolysates of whole protein than equivalent equimolar free amino acid mixtures [34]. On the basis of these physio- logical studies we have proposed theoretical reasons for using peptides rather than free amino acids as the nitro-


gen source in predigested chemically defined ‘elemental’ diets [4]. Other benefits which include effects on osmolality, cost and palatability have also been pointed

out [4, 331. We have been struck by the variability in

handling of the different partial enzymic hydrolysates

of whole protein studied [34] and in recent studies have

elucidated the influences that starter protein compo-

sition, hydrolysis method [35] and peptide chain length

[36] have an absorption profile of partial enzymic

hydrolysates of whole protein.

One of the most interesting observations has been the

finding that subtle increases in peptide chain length

from 2-3 to 3-5 amino acid residues have a significantly

deleterious effect on x-amino acid nitrogen absorption [37]. If a peptide based nitrogen source is considered

desirable, evidence now points to the fact that mixtures

of di- and tripeptides rather than higher peptides will

result in the most efficacious rates of a-amino acid

nitrogen absorption per unit length of intestine.

Amino acid versus peptides-clinical studies

There have appeared recently three studies [38-40] that

have compared the efficacy of Vivonex HNa,, whose

nitrogen source is composed of free amino acids, and

Criticare HN” whose nitrogen source is composed of

partially hydrolysed protein (peptides and amino

acids). In the first Smith and colleagues [38] demon-

strated higher blood urea nitrogen and urinary urea excretion values in patients with inflammatory bowel

disease fed Vivonex HN K. In the second, similarly in-

creased blood urea nitrogen values were observed in

patients with pancreatic insufficiency fed with the two

diets [39]. A significant weight gain was seen only in the

patients fed Criticare HN” [39]. In malnourished

patients with head and neck cancer significantly greater

weight gains, higher serum albumins and lower rises in blood urea nitrogen were seen in the patients fed with

Criticare HNH [40]. Contrary to some unpublished

suggestions, the differences noted in these three trials

do not indicate a superiority of peptides over amino

acids. The quantitative differences of the amino acid com-

position of the two diets is marked [40], particularly in respect of glutamine an amino acid known to directly stimulate the urea cycle [40]. Ureagenesis with resul- tant increases in excretion of urinary urea nitrogen and impairment of nitrogen balance would thus be expected to occur with Vivonex HNx as compared to Criticare HNH. In our unit, we have also noted higher urinary urea excretion values in patients fed Vivonex’h, as compared with Clinifeed 40012, a whole protein containing polymeric diet [9]. The question as to whether peptides have a specific nutritional advantage over free amino acids can only be answered if patients with severely im-

paired gastro-intestinal function are fed peptide and free amino acid diets of identical amino acid composition.

The preliminary results of such a study performed in

our unit are now available. No significant differences in

protein turnover rates were observed in patients with

inadequate short bowel syndrome [41] fed a peptide as

compared to a free amino acid containing diet.

Unfortunately chromatographic analysis of peptide

chain lengths in the former diet showed that significant

quantities of peptides containing four or more amino

acid residues were present. Hydrolysis of these by

brush border peptidases limits the rate of amino acid

nitrogen absorption [37] so that the study will have to

be repeated using a defined di- and tri-peptide contain-

ing diet before final conclusions about the possible

nutritional superiority of peptide containing predigested diets can be drawn.

Vitamin and trace elements

The mineral, trace element and vitamin contents of

enteral diets have traditionally been based on recom-

mended dietary allowances (RDA) which are the levels

judged by the various National Boards as well as WHO

on the basis of available scientific knowledge to be ade-

quate to meet nutritional needs of practically all healthy

persons. As has been pointed out [42], the RDA do not

cover therapeutic nutritional needs, so that vitamin and

trace element requirements as affected by disease or

pharmaceutical preparations may not be met in all

enteral feeds [42]. As far as vitamin requirements are

concerned, the subject has been comprehensively reviewed [42]. Of the trace elements, zinc has received

the most attention and in 2-3 times the RDA is recom-

mended for hypermetabolic patients [43]. Require- ments of other trace elements for hypermetabolic

patients are unknown, and deficiencies of magnesium,

copper, chromium and selenium have all been reported

in patients receiving parenteral nutrition [44-46].

Recently Bunker & Clayton [47] have reported dis-

crepancies between levels of zinc, copper, iron and manganese in enteral diets stated by the manufacturers and those found on analysis. Several diets were actually found to contain less than the United States RDA [47].

Electrolytes

Despite the fact that nearly 9 L of water and in excess of 1000 mmol sodium is ingested, secreted and absorbed, little emphasis has been placed, until recently, on water and electrolyte absorption during enteral feeding. Small intestinal disease or resection results in an increased colonic influx of water and electrolytes. As a


consequence of the large absorptive capacity of the colon [48], however, severe diarrhoea and depletion of

water and electrolytes usually only occurs in the pres-

ence of co-existing colonic disease or resection. It

follows that the ‘diarrhoea’ that occurs in enterally fed patients with normal or near normal gastrointestinal

function in up to 2494 of cases [9], is either due to a hor-

monally induced colonic secretion of water and electro-

lytes, a hypothesis currently unsubstantiated [49], or to

other causes such as a synergistic action between enteral

feeding and concomitant antibiotic therapy [50]. In

patients with the short bowel syndrome, however, the

situation is quite different. Here one is faced with the

situation where large segments of small bowel are dis-

eased or have been resected, often with co-existing colonic disease or resection. In the absence of the reserve

absorptive capacity of the colon [48], it becomes im- perative that fluid and electrolyte absorption from

residual small gut is maximised during enteral feeding.

We were disturbed to find, therefore, that a net secre-

tion of fluid and electrolyte was observed during in vivo

steady state perfusion of segments of normal jejunum

with isotonic Vivonex” [39]. Further studies have been

performed using a range of solutions containing the

amino acid and glucose polymer components of

VivonexH [51]. Results showed that for all the nine

nutrient solutions studies there was a linear correlation

between initial sodium concentration and net sodium absorption so that if the initial concentration exceeded

90mmol/l net sodium absorption occurred, while at

concentration below this, net secretion of sodium was

observed. Water absorption was linearly related to net

absorption of osmotically active particles, a substantial

proportion of which was accounted for by the move-

ment of sodium and its anions. Net sodium secretion observed during perfusion of Vivonex” [30] is not a

unique feature of this diet, but will occur during jejunal

perfusion of any low sodium containing diet. The sodium content of four widely used predigested chemi-

cally defined ‘elemental diets’, Vivonex b, Vivonex

HN”, Nutranel* and Flexical” is 39.2, 36.3, 20.1 and

30.1 mmol/l respectively, values substantially lower than would be required to promote net sodium and

water absorption. There are thus proven experimental

grounds for suggesting that the sodium concentration of the predigested diets, when used in the management of the inadequate short bowel syndrome should be raised to 90 mmol/l.

Choice of enteral diets’

Patients with normal or near normal gastrointestinal function

In a carefully performed study, Moriarty and col-

leagues [52] showed that no significant differences

occurred in nitrogen balance when patients with normal

gastrointestinal function were fed three enteral diets of

similar composition excepting the nitrogen source

which was composed either of whole protein, oligopeptides or free amino acids. There would thus seem to

be no advantage in feeding patients with normal gastro-

intestinal function with a predigested chemically

defined diet. That these patients should receive a poly-

meric diet is further supported by the results of two

controlled clinical trials [9,53]. As mentioned above the

formulation of these diets is based on our knowledge of the physiology of nutrient absorption and what is

known about nutrient requirements in health and dis-

ease. The composition of two polymeric diets is sum-

marised in Table 4. Until recently we have

recommended the routine use of a polymeric diet of

energy density 1 kcal/ml for non hypermatabolic

patients [4]. It has been a clinical observation in our

unit that it is difficult to actually administer more than

2-2.5 L of enteral diet per day to the routinely word fed

patient [9, 10, 501. In the light of this we have recently

tested a hypothesis that nitrogen balance in routinely

ward fed patients with normal or near normal gastro-

intestinal function can be improved by administering

an energy and nitrogen dense polymeric diet. In a double blind randomised controlled clinical trial [53]

significantly better nitrogen balance was seen when an energy nitrogen dense diet (1.5 kcal/ml; 9.4g N/l) was administered as compared to either an energy dense

(1.5 kcal/ml; 7.8g N/l) or a standard (1 kcal/ml; 6.3g

H/l) polymeric diet. As a result of these findings we

believe that a radical rethinking about polymeric diet

formulation is required. We are now using energy and

nitrogen dense diets for routine enteral feeding as they

appear to be well tolerated [53], and lead to a greater efficacy of enteral nutrition at least as far as nitrogen

balance is concerned.

It can be seen from Table 4 that the osmolality of the

energy and nitrogen dense diet is higher than the stan-

dard 1.0 kcal/ml diet. However, if the carbohydrate energy moiety was rationalised according to the con-

cepts of purified high MW glucose polymer mixtures

proposed by Jones and colleagues [24], the osmolality could be lowered.

For very hypermetabolic patients, for example those with burns and multiple trauma with normal gastrointestinal function, polymeric diets are available with an energy density of 2.0 kcal/ml and nitrogen contents of up to 14g N/l. These are hypertonic diets and we have no personal experience of their uses. It should be borne in mind that there may be a real risk of infusing excess carbohydrate to those patients, some of whom already have insulin resistance. Furthermore, excessive carbohydrate loads could also have a deleterious effect


Table 4 Choice and formulation of enteral diets

Polymeric diets for patients with normal or near normal gastrointestinal function

Nitrogen source (g/l)

Carbohydrate

Non-hypermetabolic to moderately Predigested diets for hypermetabolic patients with severely

impaired gastro- Current Proposed Hypermetabolic intestinal function

Protein Protein Protein Purified low molecular weight peptide mixtures

(5-7) P-10) (11-13) (5-10)

Glucose polymers Glucose polymers Purified glucose Glucose polymers f sucrose polymers (now > 10

glucose molecules) f sucrose

Fat source Long chain Long chain Long chain Medium chain tri- triglycerides triglycerides triglycerides glycerides linoleic

acid Energy (9,) 32-36 32-36 34-41 ?

Kcal/ml 1.0 1.5 2.0 1.0 Electrolytes (mmol/l)

Sodium 30-70 30-70 30-70 7c-90 Potassium 30-70 30-70 30-70 30-70 Chlorine 30-70 30-70 30-70 70-90

Minerals (fraction BDA) 1.0 l-l.5 1.5-2.0 1.0-l 5 Vitamins (fraction BDA) 1.0 l-l.5 1.5-2.0 1 O-l.5 Osmolality (mosmol/kg) 300-400 up to 500 Up to 600 450-650

Table 4 is reproduced from Silk D B A. Diet formation and choice of enteral diet. Gut 1986,27: 4H6, by kind permission of the publishers.

on respiratory function [54]. Modular formulae, sults in the maximal absorption in normal subjects. The

whereby the composition of a diet is formulated in the suggested formulation of such a diet is summarised in

diet kitchen according to the needs of the individual Table 4 and is based on discussions of the physiology of

patient, has been proposed for these difficult patients nutrient absorption outlined at the beginning of this

1551. paper.

Patients with impairedgastrointestinalfunction

In those clinical situations where the rate of nutrient

absorption is limited by impaired iuminal hydrolysis, or reductions in mucosal absorption or hydrolytic capa-

city, the use of enteral diets containing predigested nutrients will result in more efficient nutrient repletion that the polymeric diets discussed above. Strictly speaking, these criteria for using the predigested or so called chemically defined elemental diets, will usually occur only in patients with severe exocrine pancreatic insufficiency and patients with an inadequate or short bowel syndrome. Although other indications for using predigested chemically defined elemental diets have been proposed [56], there is very little controlled evidence to support the majority of the claims [57].

When nutrient assimilation is severely impaired,

there are theoretical reasons for believing that nutrients should be presented to the mucosa in the form that re-

In practical terms, it may often be difficult to decide

whether a polymeric or predigested diet should be used. In the author’s opinion, the assimilatory capacity of the human gastrointestinal tract for nutrients is often under

estimated. For example, there is no evidence that there

is any clinically significant impairment of exocrine pan-

creatic secretion or intestinal absorptive capacity in the post-operative period. Moreover, there is no clinical evidence to support a contention that the use of predigested diets in jejunostomy feeding results in more efficient nutrient repletion than polymeric diets [58].

Little attention has been directed towards enteral feeding in patients with cholestatic jaundice. In the absence of other co-existing gastrointestinal disease these patients will be able to assimilate all the major classes of nutrients except fat and fat soluble vitamins. Diets for

those patients should not contain LCTs, so most of the currently available diets are not indicated. A modular formula based on whole protein, glucose polymers, MCTs, linoleic acid (in the hope of preventing essential


fatty acid deficiency), electrolytes, minerals and water more, these findings also suggest that the ratio of

and fat soluble vitamins would be most appropriate. carbohydrate to fat should be decreased in enteral diets

MCT assimilation by the jaundiced patient will depend administered to patients with respiratory failure. A new

on a number of factors, including the degree of jaun- diet (Pulmocare,” Ross) has been formulated on these

dice, and the presence of co-existing gastrointestinal lines.

pathology. Although there is no data to support it, MCTs should probably not contribute to more than

20”, of the total energy content of these formulations. Stress

There has been much interest in the role of BCAA’s in

Chronic portal systemic encephalopathy

Patients with chronic portal-systemic encephalopathy (PSE) are faced with a nutritional dilemma. They re-

quire dietary protein to maintain the nitrogen balance,

but the ingestion of protein often precipitates encepha-

lopathy. Despite treatment with lactulose, lactitol or

neomycin, many cirrhotic patients are unable to tolerate

sufficient protein to prevent long standing negative

nitrogen balance. As the plasma amino acid profiles of

these patients are characterised by decreased levels of

branched chain amino acids (BCAA’s) and increased levels of aromatic amino acids (AAA’s) {phenylalanine,

tyrosine, free tryptophan and methionine) [59] investi-

gators have administered mixtures of amino acids rich

in BCAA’s and deficient in AAA’s [60]. Overall, it has

not been easy to draw conclusions from the published

data since the controlled trials evaluated different types

and degrees of encephalopathy using different mixtures

of BCAA’s administered in different ways, using differ-

ent end points and finding different results. As far as

enteral nutrition is concerned, one trial [61] clearly shows that a BCAA enriched enteral diet low in AAA’s

induced positive nitrogen balance in protein intolerant

cirrhotic patients all of whom had had chronic PSE, to approximately the same degree as an equivalent amount

of dietary protein without inducing encephalopathy as

frequently. This interesting topic is discussed in more

detail elsewhere [62,63].

Respiratory and cardiac failure

In an important study, respiratory, cardiovascular and

metabolic changes were monitored during balance studies in undernourished patients receiving continuous feeding [54]. At increasing energy infusion rates 0, consumption, CO, production, minute ventilation, heat production, heat release and heart rate increased on

the management of the stressed patient. The plasma

concentrations and catabolism of the BCAA’s change

under stress [60] and as in vitro incubations of isolated

muscle indicate that leucine specifically increases the

rate of protein synthesis and decreases the rate of pro-

tein degradation [64, 681, a special role for BCAA’s as

anticatabolic amino acids in stressed patients has been

proposed. It can be argued, however, that the in vitro studies

were grossly unphysiological as all preparations were in negative nitrogen balance (degradation > synthesis). In

vivo leucine has no effect on muscle protein synthesis,

even at greatly increased concentrations [69] and it is thus hard to justify the use of BCAA enriched formula-

tions in enteral nutrition. Although Cerra and col-

leagues [70] showed that enriched parenteral solutions

seemed to give a more rapid return to a positive nitro-

gen balance than standard solutions after abdominal

surgery, the cumulative nitrogen balances measured

over 6 days were the same. In their most recent study

[71], BCAA enriched enteral diets resulted in better

nitrogen balance after feeding for 5 and 7 days than

standard diets in moderately high ICU stresss ( < 10 g

urinary nitrogen/day). Any potential clinical benefits

were not reported. The remaining controlled trials

published recently were disappointing. Of the seven

studies, one has shown greater nitrogen loss with high

BCAA’s [72] and six have shown no difference in pro-

tein metabolism and nitrogen balance [73-781.

The current vogue for using BCAA enriched formu-

lations for stressed or catabolic patients is therefore probably misconceived for two reasons. Firstly, the

metabolic rationale for high concentrations of BCAA’s

and a specific role for leucine are questionable,

Secondly, there has been no convincing proof over the past few years of a definite clinical benefit from these solutions.

both a high carbohydrate and high fat diet. Rather dis- turbingly increases in CO, production and minute ven-

Techniques ofadministration

_- tilation were greater for the high carbohydrate relative The practical aspects of administration techniques used to the high fat formula. In the clinical setting, care must during exiteral feeding are important. In reality, we be taken not to precipitate heart failure during continu- believe we have increased the efficacy of enteral nutri- ous enteral feeding in compromised patients. Further- tion to a greater extent by modifying and improving our


administration techniques than by altering diet formulation. Put very simply, there seems little point in advo-

cating a change in diet formulation which results in a 5-

loo,; increase in nutrient assimilation if the administra-

tion technique being used results in the administration of only 60° u of prescribed diet [lo].

Feeding tube design and performance

As Bastow has pointed out [79] when wide bore tubes of

the Ryle type are used for nasogastric feeding, the size

and rigidity of the tubes tend to produce irritation and

inflammation of the oesophagus with subsequent

haemorrhage and stricture formation. Such side effects

are not seen with the newer softer and narrower bore

tubes now available. We developed a special interest in

enteral feeding tube design and performance when our first retrospective survey [80] highlighted the limi-

tations and drawbacks of the simple open ended

unweighted polyvinyl chloride nasogastric feeding

tubes that we had used in 200 patients. On average 2.5 tubes were used per course of enteral nutrition and the

mean duration of tube use was only 5.8 days. The non

elective removal rate was high at 61.876. Although

claims had been made that 3.5 g weights incorporated

into the tip of nasogastric tubes act to keep the tube in

the stomach and thus inhibit inadvertent displacement

[81, 821, we could not confirm this is one retrospective

and two subsequent controlled trials [80, 83, 841. The

reasons for the high inadvertent removal rates have not

been defined and to date we have not confimed as-

sertions [85] that inappropriate removal is confined to

forceful removal of tubes soon after placement by men-

tally confused patients [83]. Disappointed with the overall performance of the

weighted and unweighted nasogastric tubes investi- gated in the first two of our studies [80, 831, a design

programme was initiated which has resulted in the de-

velopment of a new generation of polyurethane feeding

tubes [84]. Polyurethane was preferred to PVC, silicone

or latex because our clinical experience showed that ‘kink resistance’ could be maintained despite using thinner tubing. Thus while the outside diameter of the new tubes is the same as that of the PVC tubes, the in-

ternal diameter is 24.5% larger with a 54qb increase in flow area, providing, therefore, less resistance to infu-

sion of the relatively more viscous energy dense feeds. The interior wall, as well as the outside of the tip of the feeding tube, is impregnated with a water activated lubricant, which eases tube insertion through the naso- pharynx and facilitates the removal of the introducer wire. In the early phase of our tube development programme, difficulties arose when attempting to aspiration from side ports, particularly when multiple ports

were employed. Moreover, difficulties with diet infusion also arose when mucus and/or curdled diet accu- mulated in the tube distal to the side port or ports. In

retrospect we realised that resistance to outflow could

occur when too small a side port was employed, and that the shape was important, outflow seeming to be re-

stricted if the edges of the port were rightangled. In the

final design of the outflow ports of the new tubes, there-

fore, attempts were made to mimic as far as possible the flow characteristics of the open ended PVC tubes. Thus

the tubes contain, a long, single, wide-necked, smooth and curved edged outflow port and there is no ‘dead

space’ distal to outflow port to trap mucus or curdled

diet.

The performance of the new tubes has been investi-

gated under prospective controlled trial condition and

has been found to be superior to that of the previously

used PVC tubes used as a control [84], in regard to duration of tube use, ease of intubation and in the abil-

ity to aspirate gastric contents after tube insertion. The

delay that occurs before reintubating patients once inadvertent tube removal has occurred [83] leads to

inevitable reductions in nutrient intake which in turn

impairs the efficacy of enteral nutrition. Thus while we

consider that the new polyurethane nasogastric feeding

tubes (Corpak Co, Wheeling, IL, USA) represent a significant advance, further research is clearly needed to

develop a masogastric tube that maintains its position for longer in the stomach of both conscious and uncon-

scious enterally fed patients.

Diet containers

Concern has been expressed over the possible role of nasogastric feeds as potential sources of infection and

cross infection, especially in patients in intensive care units [86], and the whole subject of microbial contamination of enteral feeds has now been reconsidered [87].

The concern about diet contamination led to the

widespread use of 500 ml diet containers that required changing at least every 6 h. Bastow and colleagues [88] have shown that if sterile commercial feeds are carefully emptied into diet containers on the ward they remain sterile, whereas if a diet is blended with additives in the diet kitchen it is likely to become contaminated and

subsequent bacterial multiplication occurs ( 109*0 organisms/ml after 24 h exposure to ward temperature (21-24°C)). As a consequence of this, it is clear that if enteral feeds are to be prepared in the diet kitchen then 500ml diet containers must be used. If pre-sterilised enteral diets are used without blending, then 1.5-2 L containers can be used. We have recently shown in two separate controlled clinical trials [ 10, 891 an added and important advantage of using large volume diet con-


tainers. Thus significant greater proportions of the

daily prescribed diet were actually administered to the

patient from a single 2 L container than from four 0.5 L

or two l.OL containers [lo, 891. The single 2 L con-

tainers used were pre-packaged with presterilised polymeric diet and were preferred by the nursing and

dietetic staff as they took less time to prepare [893. A word of caution is required, however, as one of 648 2 L

containers used in the second study [89] was found to be contaminated before use, and two of 26 containers from which aliquots were cultured during use, showed

significant (> lo* organism/ml) bacterial contamination. More stringent nursing procedures are probably

required during the setting up of the infusion system,

and possibly further thought needs to be given to the

type of material used to manufacture the 2L pre-

packaged diet containers before this type of system finds widespread clinical usage.

As far as cost effectiveness is concerned, it must be

remembered that it is the water component of enteral

diets that is the most expensive to transport, and the

most bulky component to store. As mentioned pre-

viously [90] we believe that the most efficient system in

the future may be the distribution of 2 L bags containing pre-sterilised powder which is then reconstituted

with water just prior to use. Such a system is currently being evaluated in our unit.

Routes of administration

Nasogastric zj nasoenteral tube feeding

The main disadvantage of nasoduodenal or nasojejunal

feeding is that the pylorus is bypassed. Gastric empty-

ing is mediated by the action of the pylorus, and the

mechanisms underlying the ‘duodenal braking effect’, whereby the rate of gastric emptying is governed by

entry of gastric contents into the duodenum, have been

analysed recently by Spiller [91]. The importance of the

‘duodenal brake’ is often ignored in enteral nutrition, and the point that needs emphasising for the future is

that the osmotic load of nutrients presented to the duodenum does not depend on the product of diet osmolality and rate of diet infusion, but on the product of

gastric effluent osmolality and rate of gastric emptying.

The cramping, distension, and diarrhoea that occur during nasoenteric feeding is probably related, at least in part to the rapid secretion of fluid and electrolytes in response to the high osmotic load of nutrients entering the upper small bowel. The ‘duodenal brake’ will reduce these symptoms if enteral feeds are infused intra- gastrically. In our experience, using the nasogastric rather than the nasoenteral route reduces the necessity of slowing infusion rate to counteract the development of gastrointestinal side effects. In turn this has the effect

of optimising nutrient intake and thus efficacy of enteral

feeding. Although there have been no controlled clinical trials

to support the theory, it does seem likely that regurgi-

tation and aspiration of feed occur more commonly in nasogastrically than nasoenterically fed neurological

patients. Particularly at risk, it is said, are the aged,

debilitated, demented and stuperous patients; those

with poor gag reflexes and neuromotor deglutition dis-

orders; and neurosurgical patients in the immediate

postoperative phase [92].

A case then, therefore, can be made to feed this sub- group of patients nasoenterally. Despite the fact that at

least 30”+, of our enterally fed patients have underlying

neurological or neurosurgical disease, our documented

incidence of aspiration (nine cases out of 781 patients

enterally fed over 8536 days [83]) is lower than that of others [93]. Since we believe that greater nutritional in-

takes can be achieved via the nasogastric than nasoenteral route we usually resort to nasoenteral feeding in

only the very difficult cases.

Routes for long term enteral feeding

It is possible that as physicians my group has a propen- sity for advocating long term enteral feeding via the

nasogastric route rather than via a surgically created gastrostomy or jejunostomy. Bearing in mind the limi-

tations of nasograstric feeding tubes discussed above it seems possible that the efficacy of long term enteral

feeding could on occasions be improved by resorting to

the surgical creation of a more permanent route of ad-

ministration. The techniquess of surgically creating

tube enterostomy feeding routes have been eloquently

summarised by Rombeau and colleagues [94]. With re-

spect to gastrostomy feeding, a new advance in the sur-

gical technique has been described by Sriram and

colleagues [95]. Based on the construction of a perma-

nent mucosal-lined gastrostomy using a stapling device,

the gastronomy is essentially ‘continent’, that is the

feeding tube can be removed in between feeding with

no leak of gastric contents. This in turn leads to a lower incidence of skin excoriation, a well recorded complica- tion of traditional gastrostomies [96]. Tubes used for

enterostomy feeding are well known to have their limi-

tations. Ongoing research is in progress to redesign these tubes in the hopes of improving performance. As with the nasogastric tubes, the current prototypes are manufactured with polyurethane and have similarly designed exit ports (D. Quinn, unpublished observations).

As an alternative to routes of administration created by formal surgical techniques, a number of percu- taneous endoscopic techniques of fashioning a tube feeding gastrostomy have recently been described, and


recent experiences with these techniques have been reviewed [97]. Although increasing experience is being

gained with this type of technique in America, we have only a very limited and rather unsuccessful experience

ourselves. Nevertheless such approaches are likely to

gain a much wider application in the future, particu-

larly when enterostomy feeding tube design has been

improved. In difficult cases where aspiration of enteral

diet is almost inevitable and in patients requiring long

term enteral feeding, nutritional intake is likely to be

enhanced using this technique, in turn leading to im-

proved efficacy of enteral feeding.

Starter regimes

Gastrointestinal side effects that occur during enteral

nutrition include nausea, abdominal bloating and pain

as well as diarrhoea. Diarrhoea, defined as the passage of too loose and frequent stools to be of discomfort to

the patient or the nursing staff, occurs in up to a quarter of patients receiving enteral nutrition [9]. Tradition-

ally, it has been believed that the incidence of these side

effects, particularly diarrhoea can be minimised by

gradually introducing full strength feeding over a 3-

4day period at the outset of feeding-the so called

‘starter regimen’ technique. On the basis of this think-

ing one presumed that the onset of side effects, particu-

larly the diarrhoea, was related to initial intolerance of

the high osmotic loads presented to the upper small

intestine during enteral feeding. Unimpressed by such

thinking Keohane and colleagues, undertook a prospective randomised controlled clinical trial to examine the

relationship between the onset of gastrointestinal side

effects and diet osmolality [50]. Patients with normal

gastrointestinal function requiring constant 24 h naso-

gastric infusion of a polymeric diet were randomised to

receive either undiluted, ‘full strength diet’ from the outset, the same diet but using a ‘starter regimen’

whereby 4 days were taken to gradually introduce full

strength feeding, or an isotonic diet. The incidence of

gastrointestinal side effects was somewhat lower rather than higher in the first group of patients receiving full strength diet from the outset. While nitrogen losses were similar in all three groups, nitrogen intake was significantly greater in the patients receiving full strength diet from the outset, the net result of this being significantly better nitrogen balance in this group of patients. It was entirely clear from these data that the efficacy of enteral feeding could be improved by not using starter regimens and since completion of the above trial [50] the routine use of starter regimens in our unit has been abandoned. Further studies have shown that the relatively hyperosmolar predigested ‘chemically defined elemental’ diets can also be routinely administered to

patients with acute exacerbations of inflammatory

bowel disease without ‘starter regimes’ [98].

Complications of enteral nutrition

In our experience the efficacy of enteral nutrition can be maintained even in the event of many of the known side

effects developing. This is so because once an under-

standing is gained of the factors involved in their patho-

genesis, the necessary steps can be taken to deal with

the problem, often without reducing the rate of diet

infusion. It is necessary to stop enteral feeding on

account of the onset of side effects only very rarely.

The common complications of enteral nutrition are

summarised in Table 5. Probably the commonest is diarrhoea, occurring as mentioned above in up to a

quarter of patients [9]. A number of factors have been

implicated in its pathogenesis [4]. These include the use

of infected feeds, lactose intolerance, intolerance of

high osmotic loads administered, inappropriate release

of gastrointestinal polypeptide hormones, concomitant

antibiotic therapy, and ingestion of laxatives. If an unexpected outbreak of diarrhoea occurs, infec-

tion of water used for diet dilution or reconstitution or

powder should be suspected and water cultured [9].

The relevance of lactose intolerance has been discussed

above, as has the question of diet osmolality. Animal

studies performed in our laboratory have not confirmed

that the onset of diarrhoea is related to an inappropriate

release of gastrointestinal polypeptide hormones [49].

We have identified laxatives as a cause of diarrhoea in some patients [9]. In the majority of patients, diarrhoea

occurs in association with concomitant antibiotic

therapy administered either by the oral or parenteral

route [50]. It seems that there is a curious synergistic

effect of enteral feeding and antibiotic therapy. Intesti- nal perfusion studies performed in our unit suggest that

certain antibiotics have a deleterious effect on fluid and electrolytes assimilation in the human small intestine

[99], which might have relevance to this problem. We

have speculated that in at least some patients the diar-

rhoea may have a colonic basis. Short chain fatty acids (SCFAs), normally produced in the colon as a consequence of the bacterial metabolism of unabsorbed carbohydrate and fibre, act as a powerful stimulant to colonic water and electrolyte absorption [ 100, lOl]. In our unit we have developed an ‘artificial colon system’ whereby we are able to assess the effect of normal human faecal bacterial metabolism in vitro [ 1021. Cer- tain antibioticss inhibit SCFA production (RC Spiller & DBA Silk, unpublished observations). Enteral diets have a very low fibre content and investigations are currently in progress in our laboratory to assess the com- pleteness of small intestinal carbohydrate assimilation during enteral feeding. We are therefore currently test-

CLINICAL NUTRITION 7 1

Table 5 Complications of enteral nutrition

Type Comment Remedy

Feeding tube related Oesophageal inflammation haemorrhage or stricture formation

Tube misplacement

Oesophageal, nasopharyngeal or gastric perforation

Nausea Abdominal bloating Abdominal pain I

Diarrhoea

Biochemical hyperglycaemia

hypokalaemia

hypophosphataemia

vitamin, mineral, trace elements, essential fatty acid deficiencies

Abnormal liver function tests

Rare with new ‘fine bore’ PVC or polyurethane tubes

Most commonly occurs in unconscious patients

Rare

Occurs transiently in 5-15% of patients; not usually severe. Probably due to gastric stasis and high osmotic loads of nutrients administered

See text

Usually related to insulin resistance

Related to nitrogen losses or occurs in anabolic phase

Insulin

Supplements required

Related to nitrogen losses Supplements required

Rare. Monitor clinically and biochemically Supplements required

Causes multifactorial and related to underlying disease or malnutrition. May in part be due to continuous 24 h infusion of diet

Prophylactic treatment with H, receptor antagonists if wide bore Ryle type tubes have to be used for more than 4-5 days

Check position by X-ray

Can be treated conservatively

Usually settle spontaneously. Occasional need to reduce rate of diet infusion

If possible stop antibiotics treat with imodium or codeine phosphate

In our experience seldom clinically significant. In patients without liver disease, LFTS return to normal after cessation of feeding

ing a hypothesis that there is a colonic basis to enteral

feeding related diarrhoea which in turn is related to de-

creased colonic SCFA production, consequent upon a combination of a reduction in colonic carbohydrate and

fibre substrates and inhibition of bacterial fermentation

by antibiotics.

Conclusions

This article has attempted to summarise the progress

we had made towards optimising enteral nutrition. In

the light of our experiences we would recommend that

patients with normal or near normal gastrointestinal

function should receive 2-2.5 L correctly formulated

polymeric diet (1.5 kcal/ml, 9 g N/L) via continuous 24 h infusion (without a starter regimen) from 1-2L containers using unweighted fine bore polyurethane feeding tubes incorporating an anti-clog tip situated wherever possible in the stomach. The same techniques should be used to infuse correctly formulated pre-

digested chemically defined elemental diets to patients with severely impaired gastrointestinal function. Patients should be carefully monitored, clinically, biochemically and haematologically in order to identify

side effects early, most of which can be dealt with early,

without prejudicing the efficacy of enteral feeding.

ACKNOWLEDGEMENTS

None of the work described in this paper would have been possible without the scholarly efforts and hard work on the part of my past and present research fellows. My grateful thanks are due to Dr B. J. M. Jones, Dr P. P. Keohane, Dr R. C. Spiller, Dr D. H. Patil and Dr R. G. Rees. The analytic laboratory in my unit is run by Dr G. K. Grimble. His innovative work and efforts are also gratefully acknowledged. Miss Helen Attrill, Nutrition Sister, has played a major role in the organisation and performance of the clinical trials. Her efforts have been much appreciated. My secretary, Miss Tina Carrick, has made a major contribution throughout and we are all very grateful to her. Finally, the financial contributions received from the nutrition industry have enabled our work to proceed. All those who have contributed have done so in a most helpful way, providing at all times stimulatory and helpful ideas, which have permitted a fruitful and ongoing collaboration between industry and our unit.

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Rees R G I’, Ryan J, Attrill H A, Silk D B A Clinical evaluation of 2 L pre-packaged enteral diet delivery system-A controlled trial. (submitted to JPEN)

Silk D B A 1986 Enteral nutrition: The future. Journal of Clinical Nutrition and Gastroenterology 1: 91-96

Spiller R C 1985 The influence of fat on human small bowel motility. Cambridge: University of Cambridge. (Thesis)

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Rees R G P, Keohane P P, Grimble G K, Frost P G, Attrill H, Silk D B A (1985) Tolerance of an elemental diet administered without starter regimen. British Medical Journal 290: 1869-1879

Spiller R C, Higgins B E, Frost P G, Silk D B A 1984 Inhibition of jejunal water and electrolyte absorption by therapeutic doses of clindamycin in man. Clinical Science 67: 117-120

McNeil N I, Cummings J H, James W P T 1978 Short chain fatty acid absorption by the human large intestine. Gut 19: 819-822 Ruppin H, Barr-Meir S, Soergel K H, Wood C M, Schmitt M G 1980 Absorption of short chain fatty acids in the colon. Gastroenterology 78: 1500-1507 Patil D H, Westaby D, Mahida Y R, Palmer K R, Rees R G, Clark M L, Dawson A M, Silk D B A Comparative modes of action of lactitol and lactulose in the treatment of hepatic encephalopathy. Gut (in press)

Submission date: 4 February 1987

towards the optimization of enteral nutrition

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