PhilSPEN Online Journal of Parenteral and Enteral Nutrition

(Article 19 | POJ_0011) February 2012 - December 2014

Original Clinical Investigation

The effect of immuno-nutrition among mechanically ventilated patients due to severe Community Acquired Pneumonia: A double-blind, randomized, controlled trial

Abstract | Introduction | Methodology | Results | Discussion | Conclusion | References | Back to Total Names Codes

Submitted: December 12, 2009 | Posted: July 16, 2014


Reza K. Tanuwihardja, MD (1); Danilo C. Del Rosario, MD (2); Ruby G. Frane, RND (2); Celeste Mae L. Campomanes, MD, FPCCP (1); Ricardo C. Zotomayor, MD, FPCCP (1); Ma. Janeth T. Samson, MD, FPCCP (1); Luisito O. Llido, MD, FPCS (2)


  1. Institute of Pulmonary Medicine, St. Luke’s Medical Center, Quezon City, Metro-Manila, Philippines
  2. Clinical Nutrition Service, St. Luke’s Medical Center, Metro-Manila, Philippines


Background: Immuno-nutrition may decrease mortality among patients who are mechanically ventilated due to severe Community Acquired Pneumonia (CAP).

Objective: To compare the effects of an immuno-nutrition formula versus standard feeding on the 30 day mortality among mechanically ventilated patients due to severe pneumonia in St. Luke’s Medical Center.

Methodology: Mechanically ventilated patients due to severe pneumonia were randomized and double blinded to receive either an immuno-nutrition formula (Supportan, SP) or standard feeding formula (SF). 30-day mortality, mean ventilator days, ICU stay, as well as clinical parameter (Clinical Pneumonia Infection Score (CPIS) and PaO2/FiO2 ratio from Arterial Blood Gas) were measured. Follow-up was done on day 1, 4 and 7 on CPIS and PaO2/FiO2 ratio.

Results: Mortality: no significant difference noted between the two groups, 3 (7.89%) on SF group and 2 (5.26%) on SP group (p=0.64; 95% CI: -0.18 to 0.28). The 30 day mortality on 32 patients revealed 2 patients on SF (12.5%) and 1 patient on SP (6.25%) died; (p=0.52; 95% CI: -0.14 to 0.28). Mean ventilator days on the SF group was 7.44 days and in SP group 5.47 days (p=0.15; 95% CI: -0.75 to 4.69). Mean ICU stay in the SP group was shorter (7.05 days) than in the SF group (10.84 days) (p=0.04; 95% CI: 0.19 to 7.48). The CPIS and PaO2/FiO2 ratio: Day 1, mean PaO2/FiO2 ratio was higher on the SP group (p=0.0001; 95% CI: -93.54 to -36.79); mean CPIS was the same with baseline (p=0.43; 95% CI: -0.58 to 1.32). On day 4, no difference was noted (p=0.63; 95% CI: -109.85 to 66.87 and p=0.46; 95% CI: -1.26 to 2.18, respectively), up to day 7 (p=0.47; 95% CI: -81.71 to 168.05 and p=0.47; 95% CI: -2.07 to 4.67, respectively).

Conclusion: There was no difference in mortality between study (SP) and control group (SF). However, there is a trend towards earlier extubation and shorter ICU stay in patients who received immuno-nutrition (SP group)


KEYWORDS: immuno-nutrition, mechanical ventilated, pneumonia, mortality, ICU, elderly



Malnutrition is a major problem for patients admitted to Intensive Care Units (ICU). There are several reasons for this. First, the development of aggressive surgical and medical interventions, and the increasingly ageing population have resulted in higher levels of malnutrition and hospitalization. Secondly, advancements in intensive care may ensure the prolonged survival of severely ill patients, but this also results in malnutrition [1].

Current studies and guidelines favor enteral nutrition via tube feeding for the critically ill patient and it is also an important means of counteracting the catabolic state [2,3]. Giner et al. found that malnutrition is prevalent in ICU patients, has been reported as being as high as 40%, and is associated with increased morbidity and mortality, especially in mechanically ventilated patients [4]. In the last 15 years, immunonutrient substrates such as eicosapentaenoic acid (EPA), docasahexanenoic acid (DHA), glutamine, arginine, and antioxidants (Vit. A, C, E, ß-carotene and selenium) have been shown to improve immune function and these have been combined to develop an immune-enhancing enteral formula in the hope of improving outcomes in critically ill patients [5 - 8]. Its usage has been recommended in several guidelines and recommendation [9 - 12].

Several studies in animal model and humans have proved that enteral nutrition enriched with EPA, DHA and antioxidants can improve outcome in critically ill patients due to sepsis, trauma, and gastro-Intestinal (GI) surgery [13 - 17]. Galban et al. looked at the effects of immune modulating nutrition in septic patients in the ICU and found reduction in the number of bacteremias and lower mortality rate in the treatment group [13]. Gadek et al. did a study on clinical effect of EPA, linolenic acid and antioxidants in Acute Respiratory Distress Syndrome (ARDS) patients and found that patients with immunonutrition feeding have shorter ventilator days and ICU stays [14]. These benefits could be extended to patients suffering from an Acute Respiratory Failure (ARF) due to severe Community Acquired Pneumonia (CAP).

In view of the promising results of immuno-nutrition and the need to identify which patients and products are associated with clinical benefit, a study was designed to investigate the possible benefit of enterally fed immunonutrition on mechanically ventilated patients due to ARF secondary to CAP.



The study is prospective, randomized, double-blinded, and controlled. Inclusion criteria are: Adult (age ≥18 years); Mechanically ventilated patients secondary to severe CAP, as defined by CURB-65 criteria score ≥3 and/or Pneumonia Severity Index (PSI) class IV or V (see below).




The Exclusion criteria are: ARF caused by illness/disease other than CAP; Pregnancy; Malignancy; Congestive heart failure (CHF) NYHA class IV; Immunosuppressed (post transplant, long term glucocorticoid therapy); Hematologic disorder; Known food allergy against any ingredients of the investigational products.

This is the sample size computation:


This is the procedure:

  • All qualified patients were randomized to receive either immuno-nutrition enteral feed containing fish oil (omega-3 and omega-6 fatty acid; EPA and DHA), α-Linolenic acid and antioxidants (Supportan ®, produced by Fresenius Kabi – see Appendix A for details); or isonitrogenic, isocaloric standard enteral feed in our hospital
  • This study was conducted with support from the Clinical Nutrition Division, which randomized and gave the assigned feeding to all samples.
  • Randomization was done using an online computer generated program (

These are the outcome variables: a) Primary Outcome: Mortality (in-hospital mortality and 30-day mortality); b) Secondary Outcome: Ventilator days, ICU stays, PaO2/FiO2 ratio from Arterial Blood Gas and Clinical Pulmonary Infection Score (CPIS) (checked on day 1, 4 and 7)

Data was collected then analyzed using t-test comparing treatment and control group. Continuous variables were summarized using measures of central tendency (mean and standard deviation). Percentage-frequency distribution was constructed for all discrete categorical variables.




38 patients who were mechanically ventilated due to severe CAP met the eligibility criteria. Their baseline characteristics are shown in Table 1. The two groups were comparable and no difference was noted. The mean age in the Standard Feeding (SF) group was slightly older than in the Supportan (SP) group, but not statistically significant (SF: 74.8 years, SP: 72.3 years; p=0.54). Majority of patients were male in both groups (SF: 53% male; SP: 58% male).


Initial CURB-65 score, PSI score, CPIS and PaO2/FiO2 ratio from Arterial Blood Gas, were all taken when the patient was intubated and mechanically ventilated. The mean CURB-65 score was 3.42 in SF group and 3.31 in SP group (p=0.64). The mean PSI score showed an equal score in both SF and SP groups, 4.84 (p=1). The mean CPIS was noted to be slightly higher in SF group (6.05) than in SP group (5.68), but not statistically significant (p=0.43). The mean PaO2/FiO2 ratio was significantly higher in SP group (214.36) than in SF group (136.15) (p=0.0006), which can be explained by the hypercarbic respiratory failure noted on some patients in the SP group, while the rest of the patients in the study had hypoxemic respiratory failure.  


There were a total of 5 patients died out of 38 patients (13.16%), 3 (7.89%) on SF group and 2 (5.26%) on SP group. Three patients (60%), 2 on SF group and 1 on SP group, died due to infection-related cause (progression of severe CAP into SIRS and/or ARDS; or occurrence of other infection), while 2 patients (40%), 1 patient on each group, died due to acute cardiac cause, on top of the severe CAP. No significant difference noted between the two groups (p=0.64).


The 30-day mortality upon follow up on 33 patients revealed 3 mortalities (9.37%), with 2 patients (12.5%) originally assigned in the SF group and 1 patient (6.25%) in the SP group (p = 0.52). Unfortunately the cause of death was only known for 1 SF patient (cardiac cause), while the other two were undetermined/unknown to the informant.


Table 3, Figure 1:
The mean ventilator days in the SF group was 7.44 days and in the SP group 5.47 days respectively (p=0.15), although not statistically significant it showed a trend towards earlier extubation on the SP group. Please take note that the total number of patients that were successfully extubated in the SF group was 16 and in the SP group was 17 (2 patients died on each group and 1 patient on SF group was tracheostomized on day 22 of hospitalization, hence they were excluded from this data analysis).



Table 4, Figure 2:
We also looked at the number of mechanically ventilated patients during follow up on day 1, 4 and 7, as shown on Table 4 and Figure 2 (Please also note that 1 patient on SP group died on day 3 of hospitalization and 1 patient on SF group died on day 6). All patients were still mechanically ventilated on day 1. On the day 4, while no extubation yet done on the SF group, 6 patients (33.33%) were extubated already on the SP group (out of 18 patients), which was statistically significant (p=0.013). On day 7, out of 18 patients on the SF group, 10 patients (55.56%) were still being mechanically ventilated, while only 5 patients, out of 18 patients (27.78%) on the SP group; however this was not statistically significant (p=0.09).




Table 5, Figure 3:
On the ICU stay, from the total of 38 patients, 1 patient from the SP group was not included in the analysis because the said patient was transferred out from ICU while still being mechanically ventilated, per request of the family. The mean ICU stay in the SP group was noted to be significantly shorter (7.05 days) than in the SF group (10.84 days) (p=0.04).




Tables 6-8, Figures 4-5:

The CPIS and PaO2/FiO2 ratio was taken on day 1, 4 and 7 among mechanically ventilated patients on both groups. On day 1, the mean PaO2/FiO2 ratio was still significantly different between the two groups, similarly with the baseline value (p=0.0001); while the mean CPIS was still the same with baseline on both groups (p=0.43).


Upon follow-up on day 4, there was no longer difference on the mean PaO2/FiO2 ratio between the two groups (p=0.63), as well as the mean CPIS (p=0.46), probably because patients on the SF group was already improving with all the medical management being given.


Similarly, no significant difference was noted on day 7 among the mean PaO2/FiO2 ratio and CPIS between the two groups (p=0.47 and p=0.42, respectively).





This study tried to look beyond the study that was done by Gadek et al. [14] which used immuno-nutrition on ARDS patients. We looked further into a subset of patients who were mechanically ventilated due to severe CAP, using a commercially available immuno-nutrition product, to see its effect in clinical setting. The disadvantage of this study is the mean age of study population which is more than 70 year-old, a great risk factor in increasing morbidity.

Nevertheless, the result of this study confirms the previous result, which suggested that immuno-nutrition may enhance recovery of critically-ill patients, thus promoting earlier extubation and significantly shorter ICU stay. The result however has shown that the mortality outcome in this study did not differ between the two groups. Recent meta-analysis regarding immuno-nutrition [18] showed better results in terms of mortality, ventilator days and ICU stay; hence supporting its usage in critically ill patients. This study used a commercially available immuno-nutrition product: Supportan from Fresenius Kabi, which contains all the recommended ingredients (EPA, DHA, omega-3, omega-6, antioxidants and α-Linolenic acid).

The limitation of this study is the small number of population. Very little is known about the exact mechanism of immuno-nutrition and its effect in various clinical setting. Its cost implication also needs to be addressed in the future. Hence improvements are still open for further study regarding this field.

In summary, this is the first study in this institution comparing immuno-nutrition with standard feeding in mechanically ventilated patients due to severe CAP, despite no difference noted on the mortality in this study (whether in-hospital mortality or 30-day mortality), however a trend in terms of earlier extubation and significant shorter ICU stay in the Supportan fed group  is evident.


There was no difference in mortality between study (SP) and control group (SF). However, there is a trend towards earlier extubation and shorter ICU stay in patients who received immuno-nutrition (SP group)


This study received a product donation of Supportan from Fresenius Kabi, however the said sponsor did not involve nor place any restrictions with regards to any statements made in this final paper. The authors would like to thank all investigators who participated in this study including Fresenius Kabi.



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Nutritional Information of Supportan® (500ml per preparation)
Average content per 100 ml:

  • Caloric value: 630 kJ (= 150 kcal)
  • Protein: 10.0 g
  • Nitrogen: 0.9 g
  • Carbohydrates: 12.4 g
    • of which sugars: 6.1 g
    • of which lactose: ≤ 0.5 g
  • Mono- and Disaccharides: 0.5g
    • of which lactose: ≤0.5
    • of which fructose: 0.05
  • Fibers: 1.2g
  • Fat: 6.7 g
    • of which saturated fatty acids: 3.3 g
    • of which MCT: 2.3 g
    • of which monounsaturated fatty acids: 1.5 g
    • of which polyunsaturated fatty acids: 1.9 g
    • of which EPA: 0.4 g
    • of which DHA: 0.2 g
    • of which cholesterol: ≤ 20.0 mg
    • of which linoleic acid: 0.95g
    • of which α-linolenic acid: 0.02g
  • Water: 76 ml
  • Osmolarity: 340 mosmol/l
  • Osmolality: 435 mosmol/kg H2O
  • Vitamins and other nutrients
    • Vit. A: 150 μg
    • β-Carotene: 375 μg
    • Vit. D3: 2.5 μg
    • Vit. E: 3.75 mg
    • Vit. K1: 21 μg
    • Vit. B1: 0.3 mg
    • Vit. B2: 0.4 mg
    • Niacin: 3.75 mg
    • Vit. B6: 0.43 mg
    • Vit. B12: 0.75 μg
    • Pantothenic acid: 1.5 mg
    • Biotin: 9.4 μg
    • Folic acid: 62.5 μg
    • Vit. C: 18.8 mg
    • Choline: 2.5 mg
  • Minerals and trace elements
    • Sodium: 47.5 mg
    • Potassium: 128 mg
    • Chloride: 50 mg
    • Calcium: 203 mg
    • Magnesium: 26 mg
    • Phosphorus: 120 mg
    • Iron: 2.5 mg
    • Zinc: 2 mg
    • Copper: 375 μg
    • Manganese: 0.5 mg
    • Iodide: 37.5 μg
    • Fluoride: 0.25 mg
    • Chromium: 12.5 μg
    • Molybdenum: 18.8 μg
    • Selenium: 13.5 μg
  • Caloric distribution (energy%)
    • Protein: 27 %, fat: 40 %, carbohydrates: 33%

Abstract | Introduction | Methodology | Results | Discussion | References |