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 hospital- ised medical and surgical patients had some evidence of nutritional deficiencies. One interpretation of their findings was that up to 50% of the patients were ‘mal- nourished’ 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 insti- tute nutritional support or not have been reviewed by several authors [4,6].
Once the decision has been made to institute nutri- tional support, it can be provided by the enteral or par- enteral 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 re- search efforts towards optimising its efficacy. Our over- all aims have been firstly to increase our understanding of the basic physiology of nutrient assimilation in nor- mal 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 nutri- tion 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 sup- port, 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 avail- able 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, exo- crine 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 men- tioned, 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 gastro- intestinal 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 con- taining 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 hydro- lysates 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-
64 TOWARDS THE OPTIMIZATION OF ENTERAL NUTRITION
gen source in predigested chemically defined ‘elemen- tal’ 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 com- pared 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 compo- sition.
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 pre- digested 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 in- creased colonic influx of water and electrolytes. As a
CLINICAL NUTRITION 65
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 col- onic 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, oligo- peptides 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 gastro- intestinal 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
66 TOWARDS THE OPTIMIZATION OF ENTERAL NUTRITION
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 evi- dence 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 pre- digested 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 ab- sence 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
CLINICAL NUTRITION 67
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 continu- ous 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
68 TOWARDS THE OPTIMIZATION OF ENTERAL NUTRITION
administration techniques than by altering diet formu- lation. 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 pro- gramme, difficulties arose when attempting to aspi- ration from side ports, particularly when multiple ports
were employed. Moreover, difficulties with diet infu- sion 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 in- advertent 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 sig- nificant 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 contami- nation 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-
CLINICAL NUTRITION 69
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 poly- meric 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 contamina- tion. 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 contain- ing 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 duo- denum does not depend on the product of diet osmo- lality 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 re- duce 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 naso- enteral 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 obser- vations).
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
70 TOWARDS THE OPTIMIZATION OF ENTERAL NUTRITION
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 prospec- tive 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 sig- nificantly greater in the patients receiving full strength diet from the outset, the net result of this being signifi- cantly 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 rela- tively 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 con- sequence 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 cur- rently 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, bio- chemically 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 pos- sible 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, pro- viding at all times stimulatory and helpful ideas, which have permitted a fruitful and ongoing collaboration between indus- try and our unit.
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Submission date: 4 February 1987