Annals of the Royal College of Surgeons of England
(I979) vol 6i
Abnormal liver function during nutritional support in postoperative cancer patients F D Skidmore MD FRCS D E F Tweedle chM FRCSEd E N Gleave FRCS E Gowland PhD MRCPath D A Knass BscPharm MPS Departments of Surgery, Biochemistry, and Pharmacy, University Hospital of South Manchester
Summary Patients who receive total intravenous or nasogastric nutritional support after surgery for head and neck cancer show abnormalities of liver function. Twenty such patients were maintained in positive nitrogen balance. Serum alkaline phosphatase and aspartate aminotransferase values were increased in I5 and i8 cases respectively. Possible causes for the abnormalities are discussed and further investigations proposed.
Introduction Patients undergoing surgery for cancer of the head and neck are often malnourished because of facial pain, dysphagia, and chronic dental problems. TIhey require radical surgery and reconstruction with major regional flaps. When such treatment involves the oral cavity the patients require a nutritional intake which effectively bypasses the mouth and oropharynx for 3-6 weeks after surgery. The effectiveness of nasogastric tube feeding has been compared with that of intravenous feeding in 20 patients undergoing head and neck cancer surgery. One patient was studied twice; thus the effects of nasogastric feeding were studied on Iv) occasions and of intravenous feeding on 6 occasions.
weight. They received O.I7 g N/kg desirable body weight/24 h and 4I non-protein kcal/ kg/24 h. Thus a patient of 71-75 kg desirable weight would receive 3000 ml of fluid containing 3000 non-protein kcal and i2.6 g of nitrogen by either the intravenous or nasogastric route. The decision as to which regimen to use in a particular patient was based on the inindividual patient's requirements and certain contraindications: (i) Local factors-maxillary or nasopharyngeal tumour involvement precludes the use of a nasogastric tube; conversely, skin flaps in the jugular and deltopectoral area prevent the use of subclavian cannulation sites. (2) General factors-for example, a history of congestive cardiac failure precludes the use of intravenous feeding because of the risk of circulatory overload.
The details of the formulations administered are given in Tables I and II. The feeding regimens were started i -3 days before surgery, depending on the nutritional state of the patient. The following clinical and laboratory measurements were made daily for the duration of the regimen: (i) haemoglobin, packed cell volume, and white cell count; (2) serum and urine osmolality; (3) serum electrolytes; (4) biochemical profile-serum Method calcium, phosphorus, glucose, urate, urea, The nutritional intake that the patients re- cholesterol, total protein, albumin, bilirubin, ceived was calculated according to ideal body alkaline phosphatase (AP) and aspartate Requests for reprints should be addressed to FDS, University Hospital of South Manchester, Manchester M2o 8LR.
aminotransferase (AST); (5) 24-h urine electrolyte and nitrogen excretion; (6) body weight; (7) skin-fold thickness.
i84
F D Skidmore, D E F Tweedlle, E N Gleave, E Gowland, and D A Knass
TABLE I Fluid, non-protein energy, and nitrogen intake in relation to desirable body weight Desirable body weight Total volume Non-protein g N/24 h Non-protein (kg)
(ml/24 h)
41-45 46-50
I 800
kcal/24 h I800
5I-55
2000 2200
2000 2200
56-60 61-65
2400 2600
2400 2600
66-70
2800
2800
7I-75
3000 3200
3000 3200
3400 3600 3800 4000
3400
76-80 8 I-85 86-90 91 -95
96-i00
kcal/kg
3600 3800
4000
7.6
42.4
8.4
41.2
9.2 10.1
4I.1 41.0
I 0.9
41.0
i i.8 12.6 I 3.4 I 4.3 I 5.1 i 6.o i 6.8
41.0 41.0
41.0
41.0 41.0 41.0
4I.0
Results the infusion was discontinued. The patient Patients were fed intravenously for a mean of died of a portal vein thrombosis and cardiac 20.4 days and by the nasogastric route for a failure on the 28th postoperative day. mean of I5.8 days. The results will be fully A 70-year-old emaciated man had a carcireported elsewhere"2, but both regimens pro- noma of the alveolus resected and was manduced satisfactory homoeostasis over the aged on an i8oo-ml nasogastric feed. He was period of intravenous or nasogastric feeding. known to have peripheral vascular disease and on the gth postoperative day suffered CLINICAL Deaths during period of study A 66-year-old a thromboembolic occlusion of the left femoral artery, necessitating embolectomy. The followwoman had a carcinoma of the lip and cheek resected and was subsequently managed on an ing day he died of a pulmonary embolus and I8oo-ml iptravenous regimen. On the I 4th respiratory failure. postoperative day the AP level was I21 IU/l Late deaths Four patients died as a result of and that of AST 78 IU/I and these values recurrence and progress of their malignant rose until the 25th postoperative day, when disease 5, 7, 8, and 20 months after surgery. TABLE II Details of equivalent regimens administered to patients INTRAVENOUS FEED NASOGASTRIC FEED* Desirable Synthamin Electrolytesolution Intralipid Dextrose GastroBeef serum body weight io % 8.5 % At B§ 20% I0% 40% 5% Caloreen protein derivative (kg) (ml) (ml) (ml) (ml) (ml) (ml) (ml) (ml) (g) (g) i
41-45
450
46-50
500
5I-55
-
650
56-60
6o
250
250
500
250
100
250
250
500
350
I50
469 521
250
250
500
500
50
573
92.5
250
250
500
625
200
625
10I.5
750
IOO OO
677 729
109.95
150
78I
126.5
6I-65
500
250
250
500
66-70
700
250
250
500
71-75
750
500
350
750
76-80 8 I-85 86-go
850
250 500
250 250
I000 1000
500
91-95 96-ioo
950 IOOO
250
950
500
500
500
IOOO
500
500
I000
500
500
1000
-
500 -
-
500 500
76.5
84.5
II8.5
50
250
833
135.0
500 500 6o0
300
885 938
144.0 152.0
250
989 I04I
I6i.o
750
1OO 250
I69.0
*Nasogastric regimen gives weight of dry substance made up to volume as per Table I tElectrolyte solution A: 20 % w/v dextrose + C1- I08 mmol/l, Mg++ 28 mmol/l, Ca++ 26 mmol/l, Zn++ o.o8 mmol/l, Mn-F+ -0.4 mmol/I §Electrolyte solution B: 20 % w/v dextrose + K+ 6o mmol/l, P04'-- 6o mmol/l
Abnormal liver function during nutritional support in postoperative cancer patients BIOCHEMISTRY
Serum urea and electrolyte levels were maintained wvithin the normal range by both regimens and all patients were maintained in positive nitrogen balance. Patients receiving intravenous feeding had a mean nitrogen balance of + 1.21 g N/rn2 body surface/24 h. Patients on the nasogastric feed had a mean nitrogen balance of ±2.17 g N/m2/24 h. (Student's t test for unpaired data, P=O.OI9). These figures are comparable with those given in the reports of Allardyccb and Groves3 and Allardyce4. ABNORMAL LIVER FUNCTION TESTS
As discussed above, one patient receiving intravenous nutrition died of a portal vein thrombosis on the 28th postoperative day. Serum AST and AP values were elevated at this time. It was decided to discontinue intravenous feeding in subsequent cases if the liver enzyme levels became consistently elevated. Although serum concentrations of bilirubin and total protein showed little variation, raised serum levels of these enzymes were noted subsequently in patients on both types of regimen. A typical graph of enzyme changes is shown in the figure (Patient I4). Fifteen of 20 patients had abnormal AP levels and I8 of 20 patients had abnormal AST levels. These abnormalities were seen in patients fed nasogastrically as well as intravenously. However, in none of these patients was there any evidence of hepatic metastases or ascites. Minimum and maximum enzyme levels are shown in Tables III and IV.
I85
Discussion Possible causes for the abnormal serum levels of liver enzymes may be considered as follows. TOXIC FACTORS CAUSING HEPATIC DAMAGE
There have been previous reports of abnormal liver function tests in neonates receiving intravenous nutrition for respiratory distress syndrome5'-. Intrahepatic cholestasis and cirrhosis has been reported in other children on intravenous nutrition8. It has been suggested that these abnormal serum AST and AP levels are a reflection of the toxic effects of amino-acid metabolism in the immature liver.
Patients undergoing jejunoileal bypass for morbid obesity may also show abnormal liver function tests in their convalescent period9. In the majority of these cases the serum levels of AP and AST fell after 3-4 months, but in the occasional case the jejunoileal bypass had to be reversed because of toxic liver damage and 3 out of 4 patients with this serious complaint died. McGill"0 and Heimburger et al" have suggested that increased mobilisation of peripheral fat stores in protein-depleted patients who have undergone jejunoileal bypass may have an adverse effect on liver metabolism.
Evidence that tryptophan was unstable in commercially available amino-acid solutions led Grant et al'2 to study liver changes in rats receiving amino-acid mixtures. Where tryptophan breakdown products were present histological examination of the liver in the experi-
200
400
150
300
aI
LI) cc
(I979) vol 6i
Abnormal liver function during nutritional support in postoperative cancer patients F D Skidmore MD FRCS D E F Tweedle chM FRCSEd E N Gleave FRCS E Gowland PhD MRCPath D A Knass BscPharm MPS Departments of Surgery, Biochemistry, and Pharmacy, University Hospital of South Manchester
Summary Patients who receive total intravenous or nasogastric nutritional support after surgery for head and neck cancer show abnormalities of liver function. Twenty such patients were maintained in positive nitrogen balance. Serum alkaline phosphatase and aspartate aminotransferase values were increased in I5 and i8 cases respectively. Possible causes for the abnormalities are discussed and further investigations proposed.
Introduction Patients undergoing surgery for cancer of the head and neck are often malnourished because of facial pain, dysphagia, and chronic dental problems. TIhey require radical surgery and reconstruction with major regional flaps. When such treatment involves the oral cavity the patients require a nutritional intake which effectively bypasses the mouth and oropharynx for 3-6 weeks after surgery. The effectiveness of nasogastric tube feeding has been compared with that of intravenous feeding in 20 patients undergoing head and neck cancer surgery. One patient was studied twice; thus the effects of nasogastric feeding were studied on Iv) occasions and of intravenous feeding on 6 occasions.
weight. They received O.I7 g N/kg desirable body weight/24 h and 4I non-protein kcal/ kg/24 h. Thus a patient of 71-75 kg desirable weight would receive 3000 ml of fluid containing 3000 non-protein kcal and i2.6 g of nitrogen by either the intravenous or nasogastric route. The decision as to which regimen to use in a particular patient was based on the inindividual patient's requirements and certain contraindications: (i) Local factors-maxillary or nasopharyngeal tumour involvement precludes the use of a nasogastric tube; conversely, skin flaps in the jugular and deltopectoral area prevent the use of subclavian cannulation sites. (2) General factors-for example, a history of congestive cardiac failure precludes the use of intravenous feeding because of the risk of circulatory overload.
The details of the formulations administered are given in Tables I and II. The feeding regimens were started i -3 days before surgery, depending on the nutritional state of the patient. The following clinical and laboratory measurements were made daily for the duration of the regimen: (i) haemoglobin, packed cell volume, and white cell count; (2) serum and urine osmolality; (3) serum electrolytes; (4) biochemical profile-serum Method calcium, phosphorus, glucose, urate, urea, The nutritional intake that the patients re- cholesterol, total protein, albumin, bilirubin, ceived was calculated according to ideal body alkaline phosphatase (AP) and aspartate Requests for reprints should be addressed to FDS, University Hospital of South Manchester, Manchester M2o 8LR.
aminotransferase (AST); (5) 24-h urine electrolyte and nitrogen excretion; (6) body weight; (7) skin-fold thickness.
i84
F D Skidmore, D E F Tweedlle, E N Gleave, E Gowland, and D A Knass
TABLE I Fluid, non-protein energy, and nitrogen intake in relation to desirable body weight Desirable body weight Total volume Non-protein g N/24 h Non-protein (kg)
(ml/24 h)
41-45 46-50
I 800
kcal/24 h I800
5I-55
2000 2200
2000 2200
56-60 61-65
2400 2600
2400 2600
66-70
2800
2800
7I-75
3000 3200
3000 3200
3400 3600 3800 4000
3400
76-80 8 I-85 86-90 91 -95
96-i00
kcal/kg
3600 3800
4000
7.6
42.4
8.4
41.2
9.2 10.1
4I.1 41.0
I 0.9
41.0
i i.8 12.6 I 3.4 I 4.3 I 5.1 i 6.o i 6.8
41.0 41.0
41.0
41.0 41.0 41.0
4I.0
Results the infusion was discontinued. The patient Patients were fed intravenously for a mean of died of a portal vein thrombosis and cardiac 20.4 days and by the nasogastric route for a failure on the 28th postoperative day. mean of I5.8 days. The results will be fully A 70-year-old emaciated man had a carcireported elsewhere"2, but both regimens pro- noma of the alveolus resected and was manduced satisfactory homoeostasis over the aged on an i8oo-ml nasogastric feed. He was period of intravenous or nasogastric feeding. known to have peripheral vascular disease and on the gth postoperative day suffered CLINICAL Deaths during period of study A 66-year-old a thromboembolic occlusion of the left femoral artery, necessitating embolectomy. The followwoman had a carcinoma of the lip and cheek resected and was subsequently managed on an ing day he died of a pulmonary embolus and I8oo-ml iptravenous regimen. On the I 4th respiratory failure. postoperative day the AP level was I21 IU/l Late deaths Four patients died as a result of and that of AST 78 IU/I and these values recurrence and progress of their malignant rose until the 25th postoperative day, when disease 5, 7, 8, and 20 months after surgery. TABLE II Details of equivalent regimens administered to patients INTRAVENOUS FEED NASOGASTRIC FEED* Desirable Synthamin Electrolytesolution Intralipid Dextrose GastroBeef serum body weight io % 8.5 % At B§ 20% I0% 40% 5% Caloreen protein derivative (kg) (ml) (ml) (ml) (ml) (ml) (ml) (ml) (ml) (g) (g) i
41-45
450
46-50
500
5I-55
-
650
56-60
6o
250
250
500
250
100
250
250
500
350
I50
469 521
250
250
500
500
50
573
92.5
250
250
500
625
200
625
10I.5
750
IOO OO
677 729
109.95
150
78I
126.5
6I-65
500
250
250
500
66-70
700
250
250
500
71-75
750
500
350
750
76-80 8 I-85 86-go
850
250 500
250 250
I000 1000
500
91-95 96-ioo
950 IOOO
250
950
500
500
500
IOOO
500
500
I000
500
500
1000
-
500 -
-
500 500
76.5
84.5
II8.5
50
250
833
135.0
500 500 6o0
300
885 938
144.0 152.0
250
989 I04I
I6i.o
750
1OO 250
I69.0
*Nasogastric regimen gives weight of dry substance made up to volume as per Table I tElectrolyte solution A: 20 % w/v dextrose + C1- I08 mmol/l, Mg++ 28 mmol/l, Ca++ 26 mmol/l, Zn++ o.o8 mmol/l, Mn-F+ -0.4 mmol/I §Electrolyte solution B: 20 % w/v dextrose + K+ 6o mmol/l, P04'-- 6o mmol/l
Abnormal liver function during nutritional support in postoperative cancer patients BIOCHEMISTRY
Serum urea and electrolyte levels were maintained wvithin the normal range by both regimens and all patients were maintained in positive nitrogen balance. Patients receiving intravenous feeding had a mean nitrogen balance of + 1.21 g N/rn2 body surface/24 h. Patients on the nasogastric feed had a mean nitrogen balance of ±2.17 g N/m2/24 h. (Student's t test for unpaired data, P=O.OI9). These figures are comparable with those given in the reports of Allardyccb and Groves3 and Allardyce4. ABNORMAL LIVER FUNCTION TESTS
As discussed above, one patient receiving intravenous nutrition died of a portal vein thrombosis on the 28th postoperative day. Serum AST and AP values were elevated at this time. It was decided to discontinue intravenous feeding in subsequent cases if the liver enzyme levels became consistently elevated. Although serum concentrations of bilirubin and total protein showed little variation, raised serum levels of these enzymes were noted subsequently in patients on both types of regimen. A typical graph of enzyme changes is shown in the figure (Patient I4). Fifteen of 20 patients had abnormal AP levels and I8 of 20 patients had abnormal AST levels. These abnormalities were seen in patients fed nasogastrically as well as intravenously. However, in none of these patients was there any evidence of hepatic metastases or ascites. Minimum and maximum enzyme levels are shown in Tables III and IV.
I85
Discussion Possible causes for the abnormal serum levels of liver enzymes may be considered as follows. TOXIC FACTORS CAUSING HEPATIC DAMAGE
There have been previous reports of abnormal liver function tests in neonates receiving intravenous nutrition for respiratory distress syndrome5'-. Intrahepatic cholestasis and cirrhosis has been reported in other children on intravenous nutrition8. It has been suggested that these abnormal serum AST and AP levels are a reflection of the toxic effects of amino-acid metabolism in the immature liver.
Patients undergoing jejunoileal bypass for morbid obesity may also show abnormal liver function tests in their convalescent period9. In the majority of these cases the serum levels of AP and AST fell after 3-4 months, but in the occasional case the jejunoileal bypass had to be reversed because of toxic liver damage and 3 out of 4 patients with this serious complaint died. McGill"0 and Heimburger et al" have suggested that increased mobilisation of peripheral fat stores in protein-depleted patients who have undergone jejunoileal bypass may have an adverse effect on liver metabolism.
Evidence that tryptophan was unstable in commercially available amino-acid solutions led Grant et al'2 to study liver changes in rats receiving amino-acid mixtures. Where tryptophan breakdown products were present histological examination of the liver in the experi-
200
400
150
300
aI
LI) cc
