Effect of Immunonutrition supplementation on Post-operative outcome after major Gastrointestinal surgery for Malignancy

 

Saraswathy Sivaprasadan1, Anju Kochupurackal Paul2, Sudhindran Surendran3, Uma Devi Padma2*

1Department of Pharmacy Practice, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham,

Kochi - 682041, Kerala, India.

2Department of Pharmacology, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham,

Kochi - 682041, Kerala, India.

3Department of Gastrointestinal Surgery, Amrita Institute of Medical Sciences and Research Centre,

Amrita Vishwa Vidyapeetham, Kochi - 682041, Kerala, India.

*Corresponding Author E-mail: umadevip@aims.amrita.edu, umadeviaims@gmail.com

 

ABSTRACT:

This prospective, pilot study evaluated the effect of immunonutrition supplementation using Pentasure Immunomax® on recovery after major gastrointestinal (GI) surgery for malignancy. It included two groups of patients (n = 25 each) who underwent major GI surgery for malignancy in two units, one of which routinely gave Pentasure Immunomax® (L – arginine, omega 3 fatty acids and ribonucleic acids) for two weeks following surgery (Group 1) while the other did not (Group 2). The pre-operative nutritional status of the patients were assessed using Subjective Global Assessment (SGA) scale. Post-operatively the following parameters were compared between the two groups: complications (using Clavien Dindo scale), calorie intake, length of intensive care unit (ICU) and hospital stay using SPSS software, version 20.0. Based on the SGA score, 66% of the entire study population was moderately malnourished, while 6% were severely malnourished. On assessing the body mass index, 26 (52%) patients were found to be overweight or obese, out of which 16 patients were found to be moderately malnourished. The mean caloric intake in Group 1 was significantly more than in Group 2 (1112.7± 51.6 versus 874.8±56.7; p = 0.0032). There was, however, no significant difference between the two groups in complications, ICU or hospital stay. The incidence of malnutrition in patients undergoing major GI surgery for malignancy is high even amongst those who are overweight/obese. Use of immunonutrition may help in better attainment of adequate calorie in post-operative period.

 

KEYWORDS: Gastrointestinal surgery, Immunonutrition, Malignancy, Malnutrition.

 

 


1. INTRODUCTION:

Patients undergoing major gastrointestinal (GI) surgery for malignancy are at high risk of malnutrition due to the hypercatabolism, decreased intestinal absorption and inadequate nutritional intake (secondary to nausea, vomiting, anorexia or mechanical obstruction) induced by the malignancy.1,2 Malnutrition can adversely affect the recovery of GI function, increase the risk for post-operative complications, and thereby prolong hospitalization.3,4

 

Following any major surgery, a biphasic metabolic response is usually seen: an initial hyperinflammatory state followed by a compensatory immune suppression that can increase the risk of morbidity and mortality.5 Immunonutrition (an intervention with specific nutrients to modulate the activity of the immune system) has been reported to positively modulate postsurgical immunosuppression and inflammatory responses.6,7 The European Society for Parenteral and Enteral Nutrition (ESPEN) guidelines, recommends an immunonutrient enriched formula comprising of arginine, nucleotides and omega 3 fatty acids, especially in malnourished patients undergoing major GI surgery for malignancy.8 Thus, the need for early nutritional support after surgery, in particular those performed for GI malignancy, cannot be overemphasized.

To evaluate the need for nutritional management in surgical patients, the present study aimed to assess the effect of immunonutrition supplementation using Pentasure Immunomax® on recovery after major GI surgery for malignancy.

 

MATERIALS AND METHODS:

This was a prospective pilot study conducted in the GI surgery department of our hospital between September 2018 and February 2019. Eligible patients included those undergoing major (lasting for more than four hours) abdominal visceral surgery for malignant indications. Patients undergoing liver transplantation for hepatocellular carcinoma, emergency surgery, stoma closure, patients with renal failure on hemodialysis and those referred from other hospitals with surgical complications were excluded. Written informed consent was taken from all patients after the details of the study were explained to them. The study was approved by the Institutional Ethical Committee (IEC-AIMS-2018-PHARM-173).

 

The data of the patients was collected in a standard data collection form through the institutional Health Information System and direct examination of patients’ medical records. Prior to the patient’s surgery, the following data were collected: patient’s age, gender, body mass index (BMI), medical diagnosis and nutritional status. The nutritional status of the patients were assessed using Subjective Global Assessment (SGA) scale, a validated and widely accepted tool. Subsequent to the patient’s surgery, the following details were collected: calorie intake, complications, length of intensive care unit (ICU) and hospital stay. Complications were assessed based on Clavien Dindo scale.

 

We selected two units in our hospital which had identical protocolized peri-operative management except for one parameter, one group of consultant preferred to give immunonutrition in the form of Pentasure immunomax® (Group 1) while the other group of consultant did not (Group 2). Pentasure immunomax® is a specifically designed formula for critically ill patients whose immune response is depressed due to stress, trauma and sepsis. It is enriched with immunonutrients such as L arginine, omega 3 fatty acids and ribonucleic acids (1 sachet: 61g; 250Kcal) [composition: carbohydrates 32.9g, protein 14g, fat 7.05g, L-arginine 3.11g, ribonucleic acid sodium salt 0.38g, omega 3 fatty acid 0.861g, vitamins and minerals]. Two teaspoons of the powder dissolved in water or milk was given three times in a day for two weeks following surgery (30g daily equivalent to 125 Kcal). Both groups received nutrition according to the nutrition protocol followed in the hospital. The minimum calorie recommendation for all study subjects was as follows, for a person with normal weight 30 Kcal per kg, for underweight 35 Kcal per kg and for overweight 25 Kcal per kg. Initially, clear liquids were given, tolerance was checked and subsequently rice porridge or oats meal was given. For tube feeding, blenderized formula feed were given. The difference in the use of immunomax between consultants gave us an opportunity to perform analysis on the effect of immunonutrition on recovery after major GI surgery for malignancy (Group 1 versus Group 2).

 

All the statistical analyses were performed using the IBM SPSS 20 window software. All the continuous variables are presented as mean ± standard error of mean. All categorical variables are presented as number and percentage. Independent sample t test was used to compare the continuous parameters between two groups. Mann Whitney U test was used to compare the categorical variables between two groups. Two-sided p value <0.05 was considered as statistically significant difference.

 

RESULTS:

The trial profile is given in Figure 1. During the study period, 50 patients meeting the eligibility criteria were evaluated. The mean age of the sample population was 59.7 years (range 29 to 80 years) with majority of the patients being in the age group of 61-80 years (54%). Based on the SGA score of the patient, nearly 66% of the population was moderately malnourished, while 6% were severely malnourished. On assessing BMI, 26 patients were found to be overweight or obese, out of which 16 patients were found to be moderately malnourished and only 10 were normal.

 

Figure 1: Trial profile

 

The two groups (Group 1 and 2) were similar with respect to the baseline characteristics. The mean caloric intake in Group 1 was significantly more than in Group 2 (1112.7±51.6 versus 874.8±56.7; p = 0.0032). The average hospital stay of patients with and without immunonutrition was 12.5 and 12.8 days, respectively. Five patients in Group 1 [wound infections (n = 2), tachycardia (n = 1), atrial fibrillation (n = 1) and elevated creatinine (n = 1)] and four patients in Group 2 [wound infections (n = 3) and bile leakage (n = 1)] had complications. There was no significant difference in complication rate, hospital and ICU stay when comparing the two groups (Table 1). No patient died during hospitalization.

 

Table 1: Effect of immunonutrition on post-operative outcomes

Characteristics

Group 1

(n = 25)

Group 2

 (n = 25)

p value

Age (years)

58.6 ± 2.8

60.8 ± 2.2

0.544

Gender

 

 

 

Male

11 (44)

10 (40)

 

BMI (kg/m2)

25.3 ± 0.8

23.5 ± 0.8

0.120

Diagnosis

 

 

 

Rectum

8 (32)

6 (24)

 

Pancreas

5 (20)

1 (4)

 

Bile duct

4 (16)

0

 

Liver

4 (16)

2 (8)

 

Stomach

3 (12)

2 (8)

 

Colon

1 (4)

7 (28)

 

Intestine

0

6 (24)

 

Gall bladder

0

1 (4)

 

Nutritional status

 

 

 

Normal nutrition

7 (28)

7 (28)

0.109

Moderate malnutrition

18 (72)

15 (60)

 

Severe malnutrition

0

3 (12)

 

Type of feeding

 

 

 

Oral

23 (92)

20 (80)

 

FJ + Oral

2 (8)

2 (8)

 

FJ only

0

2 (8)

 

TPN

0

1 (4)

 

Complications

5 (20)

4 (16)

1.00

Mean calorie intake (Kcal)

1112.7 ± 51.6

874.8 ± 56.7

0.0032

ICU stay (days)

4.3 ± 0.4

4.3 ± 0.4

1.00

Hospital stay (days)

12.5 ± 0.9

12.8 ± 1.1

0.825

Group 1 - Immunonutrition with Pentasure immunomax®; Group 2 - No immunonutrition; BMI – Body mass index; FJ – Feeding jejunostomy; ICU – Intensive care unit; TPN – Total parenteral nutrition

 

In the present study, six out of 50 patients required nutritional supplementation through feeding jejunostomy. None of these patients had any tube related complications. Only one patient required total parenteral nutrition (Group 2).

 

We also assessed the effect of malnutrition on post-operative outcomes by comparing malnourished patients (n = 36) with remaining 14 patients who had normal nutrition as indicated by SGA. There was no significant difference between these two groups in complications, ICU stay or hospital stay (Table 2).

 

Table 2: Effect of malnutrition on post-operative outcomes

Characteristics

Normal nutrition

(n = 14)

Malnutrition

(n = 36)

p value

Age (years)

61.2 ± 2.9

59.1 ± 2.2

0.591

Gender

 

 

 

Male

6 (43)

15 (42)

 

BMI (kg/m2)

26.1 ± 1

23.8 ± 0.7

0.077

< 18.5

0

6 (17)

 

18.5-24.9

4 (29)

14 (39)

 

25-29.9

8 (57)

13 (36)

 

30-34.9

2 (14)

3 (8)

 

Diagnosis

 

 

 

Rectum

7 (50)

7 (19)

 

Colon

2 (14)

6 (17)

 

Liver

2 (14)

4 (11)

 

Bile duct

1 (7)

3 (8)

 

Pancreas

1 (7)

5 (14)

 

Stomach

1 (7)

4 (11)

 

Intestine

0

6 (17)

 

Gall bladder

0

1 (3)

 

Type of feeding

 

 

 

Oral

12 (86)

31 (86)

 

FJ + Oral

1 (7)

3 (8)

 

FJ only

1 (7)

1 (3)

 

TPN

0

1 (3)

 

Complications

2 (14)

7 (19)

1.00

Mean calorie intake (Kcal)

1008.0 ± 62.8

988.2 ± 52.8

 0.8331

ICU stay (days)

4.1 ± 0.6

4.4 ± 0.3

0.710

Hospital stay (days)

11.9 ± 0.8

13.0 ± 0.9

0.366

BMI – Body mass index; FJ – Feeding jejunostomy; ICU – Intensive care unit; TPN – Total parenteral nutrition

 

DISCUSSION:

In the present study, based on the SGA score of the patient, nearly 72% of the population was malnourished (66% moderately and 6% severely). In other reports, the percentage of malnutrition in patients with GI cancer has varied from 40% to 85%, depending on the index used for assessing malnutrition.4,9 Interestingly, 26 patients of the present sample were found to be overweight or obese. Nevertheless, 16 of them were malnourished and 10 of them had normal nutrition. This suggests that obesity was probably a form of sarcopenic obesity. However, as we had not estimated sarcopenic index objectively, by assessing psoas muscle diameter on cross sectional imaging, this statement does require more clarification. In any case, this suggests that BMI alone will not suffice as a pre-operative nutritional index. The use of objective index such as SGA in pre-operative setting cannot be overemphasized.

 

The most salient finding in our study was that the mean caloric intake in Group 1 was significantly more than in Group 2 (1112.7±51.6 versus 874.8±56.7; p = 0.0032). Pentasure Immunomax® itself supplied only 125 Kcal daily by its carbohydrate, protein, fatty acid contents. Whether the immunonutrition in Pentasure Immunomax® resulted in faster recovery and hastened normal oral nourishment merits further investigation. This enhanced calorie intake in any case did not however translate into a shorter ICU or hospital stay or lesser morbidity. Perhaps this is not surprising, given that our sample size was small.

 

Although immunonutrition has been reported to positively modulate postsurgical immunosuppression and inflammatory responses6,7, we did not find any significant difference between both groups in infections, complications, ICU or hospital stay. However, there are conflicting reports in literature regarding the role of post-operative immunonutrition in patients undergoing surgery for GI malignancy. A study by Daly et al (1992)10 suggested that post-operative enteral nutrition with supplemental arginine, RNA, and omega 3 fatty acids in patients with upper GI malignancies reduced infectious complications and shortened the hospital stay. A study by Heslin et al (1997)11 reported no beneficial effect of enteral feeding with immune enhancing formula. A recent meta-analysis had considered enteral immunonutrition to improve the cellular immunity and modulate inflammatory reaction. However, the incidence of pulmonary infection, length of hospital stay and other clinical outcomes were not improved.12

 

A study by Garth et al (2010)4 showed that there is an association between pre-operative malnutrition and adverse post-operative outcomes (significantly longer hospital stay and a trend towards a greater risk of complications) for patients with upper GI and colorectal cancer. In our study, when we compared the group with malnutrition against those with normal nutrition, we did not find any significant difference in post-operative complication rate and ICU/hospital stay. This is probably because our sample size may have been inadequate leading to a type 2 statistical error.

 

The strength of our study is its prospective nature and well defined end points. Of course, there are several limitations as well. That it was not a randomized study is a major drawback. Secondly, we did not assess the effect of individual immunonutrients in supplement and whether its calorie advantage itself leads to better calorie attainment requires further study. Thirdly, the sample size and study duration were limited. More valid results can be obtained if the study is conducted with large sample size and longer follow up period.

 

CONCLUSION:

The incidence of malnutrition in patients undergoing major GI surgery for malignancy is high even amongst those who are overweight/ obese. Use of immunonutrition may help in better attainment of adequate calorie in post-operative period.

 

CONFLICTS OF INTEREST:

The authors declare that there is no conflict of interest.

 

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9.     Shpata V, et al. Malnutrition at the time of surgery affects negatively the clinical outcome of critically ill patients with gastrointestinal cancer. Medical Archives. 2014; 68(4): 263-267.

10.  Daly JM, et al. Enteral nutrition with supplemental arginine, RNA, and omega-3 fatty acids in patients after operation: immunologic, metabolic, and clinical outcome. Surgery. 1992; 112(1): 56-67.

11.  Heslin MJ, et al. A prospective, randomized trial of early enteral feeding after resection of upper gastrointestinal malignancy. Annals of Surgery. 1997; 226(4): 567-577; discussion 577-580.

12.  Cheng Y, et al. Enteral immunonutrition versus enteral nutrition for gastric cancer patients undergoing a total gastrectomy: a systematic review and meta-analysis. BMC Gastroenterology. 2018; 18: 11.

 

 

 

Received on 27.04.2020            Modified on 24.05.2020

Accepted on 28.06.2020         © RJPT All right reserved

Research J. Pharm. and Tech. 2021; 14(4):2258-2261.

DOI: 10.52711/0974-360X.2021.00399