Supplementary parenteral nutrition in patients with malignant disease
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Supplementary parenteral
nutrition in patients with
malignant disease
Guidelines to patient selection
Much of the morbidity and mortality of malig-
nant disease is due to the profound nutritional
depletion caused by the disease. This is particu-
Ralph DeMatteis, M.D.* larly true of gastrointestinal related malignancies.
Robert E. Hermann, M.D. Recentl? D u d r i c k , ; d e s c r i b e d . w e i S h t Sain\ in"
J
crease tn strength and activity, and positive
Department of General Surgery nitrogen balance in patients with malignancies
treated with supplementary parenteral nutrition.
Schwartz et al2 have also shown parenteral nutri-
tion to be of significant value when combined
simultaneously with chemotherapy in the treat-
ment of patients with disseminated carcinoma.
However, serious complications can occur which
preclude indiscriminate application of parenteral
nutrition, especially in patients weakened by
malignant disease. This paper reports results of
a prospective clinical study undertaken specifi-
cally to establish guidelines for the use of total
or supplemental parenteral nutrition as an ad-
junct to the treatment of cancer patients.
Clinical material and methods
Twenty-three patients are included in the
study. All patients had malignant disease and
* Fellow, Department of General received either supplemental or total parenteral
Surgery. nutrition during hospitalization at the Cleveland
139
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require permission.140 Cleveland Clinic Quarterly Vol. 40, No. 3
Table 1. Tumor site The 16 patients treated in the post-
operative period were treated with
Site No. patients
total parenteral nutrition.
Colon 7 The catabolic state induced by ma-
Stomach 6 lignant tumors, particularly gastro-
Pancreas 4 intestinal malignancies, is well known.
Cervix 4 It is also well known that sepsis and
Ovary 1
trauma produce significant, additional
Lung 1
loss of nitrogen. The patients in this
Total 23 study were divided into four groups
based on the extent of the malignancy
and the degree of sepsis: Group 1—
Table 2. Indications for nutritional depletion secondary to the
parenteral nutrition tumor manifested by severe weight
loss, without disseminated disease or
Indication No. patients
sepsis; Group II—nutritional deple-
Preoperative : weight loss, weak- 7 tion complicated by mild to moderate
ness, hypoalbuminemia sepsis; Group III—patients with severe
sepsis; and Group IV—patients with
Postoperative complications 16
Ileus, sepsis, poor wound heal- 3 disseminated malignancy.
ing Solutions for parenteral nutrition.
" H i g h o u t p u t " fistula and 4 Positive nitrogen and calorie balance
sepsis
was achieved with hypertonic paren-
Postoperative pancreatitis 2
" L o w output" fistula 2
teral solutions.3' 4 T o achieve this goal,
Disseminated carcinoma with 4 large amounts of carbohydrate calories
progressive weakness were given simultaneously with nitro-
Gastric outlet obstruction 1 gen to spare amino acids for utiliza-
tion in protein synthesis. A ratio of
100 to 150 carbohydrate calories to 1 g
Clinic or at St. Vincent Charity Hos-
nitrogen is required to achieve a posi-
pital, Cleveland, Ohio. Table 1 lists
tive nitrogen balance. In this study the
the patients according to site of
nitrogen source was protein hydro-
tumor. As indications for parenteral
lysate* or crystalline amino acid.-j-
nutrition all patients had (1) a
Dextrose was the sole source of carbo-
2 0 % weight loss from predisease
hydrate calories. The parenteral solu-
weight, with marked weakness or sig-
tion formulas are listed in Table 3.
nificant hypoalbuminemia; or (2) a
The schedule for administration of
prolonged postoperative course com-
parenteral fluids is listed in Table 4.
plicated by poor wound healing,
Blood glucose, serum osmolality, and
wound dehiscence, or fistula forma-
electrolyte determinations were ob-
tion ( T a b l e 2). An operative procedure
tained daily; reductions of urine excre-
confirmed the diagnosis of malignancy
in all 23 patients. The seven patients
* Hyprotigen 10%, McGaw Laboratories,
selected for treatment preoperatively
Glendale, California.
were given supplemental parenteral \ FreAmine 8.5%, McGaw Laboratories, Glen-
nutrition in addition to oral feedings. dale, California.
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Table 3. Hyperalimentation solution shaved and prepared with an iodine
compound. The patient is placed in a
Basic solution slight Trendelenberg position to dis-
1. 500 c c 10% Hyprotigen (6.7 g N ) or
tend the subclavian veins. A local anes-
8 . 5 % FreAmine (6.25 g N )
2 . 300 cc 5 0 % dextrose in water
thetic is injected into the area of the
3. 40 mEq NaCl middle third of the clavicle. A 14-
4. 25 mEq KC1 gauge needle is then directed toward
5. Sterile H 2 0 to 1,000 ml the suprasternal notch, hugging the
Additives
underneath border of the clavicle, and
1. Salt poor albumin 12.5 g to 25 g / l i t e r if
serum albumin is less than 2.5 g / 1 0 0 ml slight negative pressure is kept on the
2. Calcium 5 m E q / l i t e r syringe. The needle is never moved
3. Magnesium 0.5 g to 1 g / l i t e r , added as haphazardly once it is beneath the
indicated clavicle. If this approach fails, the
4. Dextroferon 3 mg to 6 m g / l i t e r as
needle must then be removed from
indicated
5. Vitamin B12 5 m E q / l i t e r added in cases beneath the clavicle, but this time it
of prolonged hyperalimentation should be aimed between the two
6. Folic acid 4 mg to 5 m g / l i t e r heads of the sternocleidomastoid mus-
7. K 2 P O I 5 mEq to 10 mEq added only cle.
when 8 . 5 % FreAmine is used
When the needle is in the subclavian
vein, the syringe is removed and a
finger is placed over the hub of the
Table 4. Ideal schedule for delivery of needle to prevent air embolus. An 18-
parenteral solutions gauge polyethylene catheter is in-
Carbo-
serted. The catheter is then fixed to
Day
Nitrogen
g
hydrate
calories
Volume
infused
the skin with no. 4-0 nylon suture. A
topical antibiotic, usually gentamicin,
First to second
S e c o n d to third
21
21
1,800
2,400
3 , 0 0 0 cc
3 , 0 0 0 cc
is applied to the catheter, and the
T h i r d to fourth 21 3,000 3 , 0 0 0 cc catheter is covered with a sterile dress-
ing. A chest x-ray film should be ob-
tained to check on placement of the
tion were monitored every 6 hours. catheter in the superior vena cava and
Most patients who had loss of protein to check for a pneumothorax.
from fistulas or severe malnutrition The amount of fluid infused was
causing low serum proteins and hypo- related to the patient's basic main-
albuminemia were given, in addition, tenance requirements or cardiac status.
serum albumin supplements intra- All solutions were administered by
venously. The ability of some patients intravenous drip; millipore filters and
to maintain serum albumin despite pump infusions were not used. The
losses by fistulas will be discussed later. infusion was maintained at a constant
Patients usually received from 12.5 to rate over a 24-hour period to insure
25 g salt-poor albumin added to each effective utilization. Blood transfusions
liter of parenteral fluid for 3 to 5 days. were given only in accordance with
Subclavian catheterization. An in- the patient's need for blood replace-
fraclavicular, subclavian approach was ment. The intravenous tubing was
used in all patients, with one excep- changed daily. The intravenous sys-
tion. The infraclavicular region is tem was maintained as a closed system
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require permission.142 Cleveland Clinic Quarterly Vol. 40, No. 3
to reduce the possibility of outside con- result of a relative glucose intolerance.
tamination. The three patients in Group III, all of
whom had severe sepsis, progressively
Results lost weight despite supplementary
parenteral nutrition. Hyperosmolality
The usefulness of parenteral nutri-
and glucose intolerance developed in
tion in patients with malignant dis-
all patients despite the addition of
ease was judged by: weight gain or
moderate amounts of added regular
loss, increase or decrease of serum
insulin. Cultures of the catheters in
albumin, glucose metabolism, healing
these patients revealed staphylococcus
of fistulas, improvement in general
coagulase positive infections and Can-
well-being, increased strength, and in-
dida albicans septicemia. The Candida
creased energy for activity. Nitrogen
albicans septicemia was associated
balance studies were not done in this
with severe hyperosmolality and glu-
study, but several investigators have
cose intolerance.
shown weight gain to reflect a positive
Patients in Group IV tolerated glu-
nitrogen balance, providing the blood
cose loads well. However, despite this,
urea nitrogen remains normal and
these patients either lost weight or
water retention is not present.5
gained weight which was complicated
Weight gain and glucose metabo-
by edema. Interestingly, patients with
lism. The weight response in various
large pancreatic tumors tolerated 3,000
groups is summarized in Table 5.
calories in 24 hours.
Weight gain was recorded in most of
Serum albumin. Eighteen patients
the patients in Groups I and II. This
had hypoalbuminemia, a serum albu-
indicates the ability of most patients
min of 2.5 g or less. Four patients
in Group II to overcome the increase
were dropped from the study because
in metabolic demand of mild to
they received parenteral nutrition for
moderate sepsis. Patients from both
only 5 days. Of the 14 remaining pa-
Group I and Group II showed less
tients, 12 had extra-body losses of
weight gain and less adequate glucose
serum protein. Most patients with
metabolism with advancing age. Other
extra-body losses of serum protein
investigators have noted similar limita-
were given from 25 g to 75 g of salt-
tions in parenteral nutrition with
poor albumin per day for 3 to 5 days
advancing age.1 The inability of older
to try to bring the serum albumin level
patients to regain weight is, in part, a
into the normal range, Patients who
could not maintain a serum albumin
Table 5. Weight response of Groups between 2.5 g to 3.0 g/100 ml after
I through IV 3 to 5 days of therapy were given addi-
Change in weight (lb)
tional supplements. Of the 14 patients
with hypoalbuminemia, 8 required
Aver- additional protein supplements to
Group Range age
maintain serum albumin levels. The
I (7 patients) +20 to - 1 0 +5 mean age of these eight patients was
II (6 patients) +20 to -7 +3 59.1 years; the mean length of paren-
III (3 patients) -8 to -5 -6
teral nutrition was 12.1 days. Two of
IV (6 patients) + 12 to - 1 2 0
the eight patients were in Group II,
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three were in Group III, and the re- Table 6. Complications of parenteral
maining three patients were in Group nutrition in 23 patients with
IV. malignant disease
Six patients improved or maintained
their serum albumin levels between 2.5 Complications No.
g and 3.0 g/100 ml without additional Hyperosmolality without c o m a 3
supplements. All but one of these six C a t h e t e r sepsis 1
patients had extra-body losses of pro- Candida albicans septicemia 1
tein. T h e mean age of this group of 1 0 % pneumothorax 1
Caval thrombosis 1
patients was 44.8 years; the mean dura-
tion of parenteral nutrition was 22.5
days. Two of these six patients were in with fulminating sepsis prior to the
Group I and the remaining four were start of parenteral nutrition. Candida
in Group II. albicans septicemia developed in an-
Fistula and wound healing. Eight other patient. Complications are listed
patients had fistulas and one had a in Table 6.
slowly granulating, open wound. In
four of the eight patients who were Discussion
receiving hyperalimentation the fis- The metabolic response of patients
tulas closed promptly. Of these four with malignancy to supplemental
in whom the fistulas closed, only one parenteral nutrition decreased progres-
had irradiation previously; of the four sively with increasing age. Younger
in whom the fistulas did not close, patients appeared to have a better
three had had irradiation previously. glucose tolerance, more energy re-
Wound healing problems were directly serve, and were better prepared to deal
related to prior tissue irradiation and with stress. They were generally able
not to an inability to handle paren- to gain weight, increase or maintain
teral nutrition. their serum albumin levels above 2.5
All patients in Group I and Group g/100 ml, and increase their levels of
II exhibited some increase in strength, activity. Older patients showed rela-
activity, and sense of well-being while tive glucose intolerances, had less
receiving parenteral nutrition. Group energy reserve, and were less prepared
I I I patients with profound sepsis were to deal with their catabolic states.
moderately to severely obtunded and The addition of sepsis to malignant
difficult to evaluate. Group IV patients disease apparently represents a pro-
noted little change in well-being and found metabolic expenditure. Mild to
most patients continued to deteriorate moderate sepsis did not significantly
gradually. increase this expenditure. Patients
Complications. Sepsis and hyper- with fulminating sepsis, however, ap-
osmolality were the most frequent pear to be limited by a significant
complications of supplementary paren- degree of glucose intolerance, not
teral nutrition. Catheters were cul- overcome by added insulin. T h e glu-
tured at least once, and often up to cose intolerance was especially severe
three times, in 19 of 23 patients. One in one patient with Candida albicans
catheter tip was positive (staphylo- septicemia. Other observers have also
coccus coagulase positive) in a patient noted the onset of glucose intolerance
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require permission.144 Cleveland Clinic Quarterly Vol. 40, No. 3
with the development of Candida septi- thrombosis has also been reported as
cemia.6 Some investigators have re- a complication of parenteral nutri-
lated Candida septicemia to prolonged tion.4 One death in this series was
use of intravenous catheterization.7 related to multiple, septic pulmonary
We agree that patients with chronic emboli from a thrombosis in the sub-
sepsis are more prone to complica- clavian vein extending into the supe-
tions; adherence to strict aseptic con- rior vena cava. Even subclavian vein
ditions should reduce the incidence of catheterization, which we prefer, does
infection secondary to parenteral nu- not guarantee against subclavian or
trition.8- 9 superior vena cava thrombosis.
Patients with widespread, dissemi-
nated malignancies did poorly on ad- Summary
junctive parenteral nutrition. These
A prospective study was undertaken
patients continued to deteriorate and
of 23 patients with malignant disease
lose weight. With one exception,
who were given supplementary paren-
weight gain was associated with water
teral nutrition while undergoing treat-
retention. There was no increase in
ment of malignancy. An effort was
strength or level of activity. In some
made to establish guidelines in select-
instances, it appeared that the rate of
ing patients for parenteraf nutrition.
growth of metastases actually increased
Results were based on the ability to
with improved nutrition. Animal
gain or sustain weight, to raise or
studies have demonstrated an increase
maintain serum albumin above 2.5
in the rate of growth of hepatic metas-
g/100 ml, to heal wounds and fistulas;
tases when protein intake is increased.
and on an increase in the sense of well-
Although some investigators have ob-
being and the level of activity.
served marked improvement in pa-
The best results were obtained in
tients with disseminated malignancy
relatively young patients without
when chemotherapy and adjunctive
severe sepsis or disseminated disease.
parenteral nutrition are given simulta-
Older patients, particularly those over
neously, we no longer have enthusiasm
age 70, and patients with severe sepsis
for supplementary parenteral nutri-
had a limited metabolic response, were
tion in this group of patients. We
unable to handle large glucose loads,
believe that adjunctive parenteral nu-
and were more susceptible to serum
trition has little advantage in patients
hyperosmolality. Patients with widely
with far advanced malignancy.
disseminated carcinoma progressively
Complications are an ever present
lost weight and showed no increase in
fact of parenteral nutrition. Proper
the level of activity. We believe that
sterile technique for catheter place-
supplementary parenteral nutrition is
ment, maintenance, and fluid prepara-
of limited value in the elderly patient,
tion is stressed. In our experience, the
seems to be poorly tolerated by the
elder-ly and the patient with sepsis are
patient with severe sepsis, and is of no
more prone to develop the problem of
value in patients with disseminated
hyperosmolality. By careful monitor-
disease. Sterile technique, subclavian
ing of serum osmolality, urine reduc-
catheterization, careful monitoring,
tions, and daily blood sugars, severe
and appropriate patient selection are
hyperosmolality can be avoided. Caval
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require permission.Fall 1973 Supplementary parenteral nutrition 145
all essential to avoid or minimize com- 4. Rush BF Jr, Richardson JD, Griffen W O
J r : Positive nitrogen balance immediately
plications of supplementary parenteral
after abdominal operations. Am J Surg
nutrition. 119: 70-75, 1970.
5. Freeman JB, MacLean LD: Intravenous
References hyperalimentation: a review. Can J Surg
1. Dudrick SJ: Intravenous feeding as an aid 14: 180-194, 1971.
to nutrition in disease. CA 20: 198-211, 6. Ashcraft KW, Leape LI: Candida sepsis
1970. complicating parenteral feeding. JAMA
2. Schwartz GF, Green HL, Bendon ML, et 212: 454-456, 1970.
al: Combined parenteral hyperalimenta- 7. Curry CR, Quie PG: Fungal septicemia in
tion and chemotherapy in the treatment of patients receiving parenteral hyperalimen-
disseminated solid tumors. Am J Surg 121: tation. N Engl J Med 285: 1221-1225, 1971.
169-173, 1971. 8. Fischer J E , Abbott WM, Abel RM: Fungal
3. Dudrick SJ, Wilmore DW, Vars HM, et al: septicaemia complicating intravenous hy-
Long-term total parenteral nutrition with peralimentation. Lancet I: 640, 1972.
growth, development, and positive nitro- 9. Shils ME: Guidelines for total parenteral
gen balance. Surgery 64: 134-142, 1968. nutrition. JAMA 220: 1721-1729, 1972.
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