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VARIABILITY OF NUTRITIONAL IMPAIRMENT IN PATIENTS WITH ACUTE RESPIRATORY DISTRESS SYNDROME (REPORT 1)
Girsh A. O., Mishchenko S. V., Stepanov S. S., Klementyev A. V., Chernenko S. V.
Omsk State Medical University, Omsk, Russia
In patients with mild to moderate acute respiratory distress syndrome (ARDS), during the first three days after staying in the intensive care unit (ICU), severe nutritional deficiencies develop [1], which is not only one of the damaging factors directly for already compromised lungs [2], but also the evolution and progressive development of multiple organ dysfunction syndrome (MODS) [3]. This situation is extremely unfavorable for the general condition of patients, since progressive lung dysfunction initiates worsening of MODS, which, in turn, catalyzes further respiratory failure [2], which contributes to poor clinical outcomes [4]. Undoubtedly, nutritional therapy in patients with ARDS, which is necessary to eliminate nutritional deficiencies, should begin early [1], taking into account its severity [5, 6] and the activity of the gastrointestinal tract [7, 8]. Considering the above mentioned facts, the objective of the study was to reveal the variability of nutritional deficiencies in patients with mild to moderate acute respiratory distress syndrome in the implementation of heterogeneous nutritional therapy.
MATERIALS AND METHODS
This opened clinical prospective study included 396 patients with ARDS due to impact of an indirect alternating factor (shockogenic trauma of degree 2-3). The patients were treated at intensive care units of City Clinical Hospital of Emergency Medicine No. 1 and Kabanov City Clinical Hospital No. 1 in 2016-2022. The patients involved in the observation had the mean age of 31.2 (21; 38) years and were sorted into two groups according to the severity of ARDS, which, in turn, were ranked into six subgroups, each depending on the nutritional support option being implemented (Tables 1 and 2). The inclusion criteria were: 1) patients aged 18 to 40; 2) the presence of mild to moderate ARDS in patients, classified and delineated using the oxygenation index (OI) after 39 ± 6 hours; 3) realization of identical intensive care (with consideration of individual features) for all patients with mild and average ARDS, including respiratory support, on the basis of the clinical guidelines from All-Russian public organization – Federation of Anesthesiologists and Resuscitators. The exclusion criteria were: 1) acute persistent cardiovascular insufficiency requiring intravenous use of agonists in the treatment program for ά1 and β2 adrenomimetics; 2) the presence of clinical, laboratory and instrumental signs of traumatic shock in patients; 3) the presence of any concomitant pathology in patients.
Table 1. Options for nutritional support in patients of group I
|
Patients |
Nutritional support options and their energy value in patients |
|
Group I (patients (198; 100 %) with mild ARDS (200 mm Hg IO ≤ 300 mm Hg) |
|
|
subgroup 1 (34; 17.2 %) |
Enteral nutrition, carried out during the entire observation period, with a mixture of Nutricomp Diabetes Liquid (B. Braun, Germany) began with a volume of 500 ml (500 kcal) on the first day, followed by a daily increase in the volume of the injected mixture by 500 ml (500 kcal) and achievement of the maximum daily volume up to 2,000 ml (2000 kcal) on the 4th day |
|
subgroup 2 (38; 19.2 %) |
Enteral nutrition, carried out during the entire observation period, with a mixture of Nutricomp immune liquid (B. Braun, Germany) began with a volume of 500 ml (650 kcal) on the first day, followed by a daily increase in the volume of the injected mixture by 500 ml (500 kcal) and reaching the maximum daily volume up to 2000 ml (2,600 kcal) on the 4th day |
|
subgroup 3 (32; 16.2 %)
|
Parenteral nutrition using the "three in one" system Nutriflex 48/150 lipid (B. Braun, Germany) – 625 ml (632 kcal) was started on the 1st day and continued up to 4 days. From the 5th day, in parallel with parenteral nutrition, the enteral mixture Nutricomp immune liquid (B. Braun, Germany) – 500 ml (650 kcal) was administered, followed by a daily increase in the volume of the injected mixture by 500 ml (650 kcal) and the maximum daily volume was reached up to 2000 ml (2,600 kcal) on the 8th day and the abolition of parenteral nutrition at the same time |
|
subgroup 4 (36; 18.2 %) |
Parenteral nutrition using the "three in one" system Nutriflex 70/180 lipid (B. Braun, Germany) – 625 ml (740 kcal) was started from day 1 and continued up to day 4. From the 5th day, in parallel with parenteral nutrition, the enteral mixture Nutricomp immune liquid (B. Braun, Germany) – 500 ml (650 kcal) was administered, followed by a daily increase in the volume of the injected mixture by 500 ml (650 kcal) and the maximum daily volume was reached up to 2000 ml (2,600 kcal) on the 8th day and the abolition of parenteral nutrition at the same time |
|
subgroup 5 (30; 15.2 %) |
Mixed nutrition (parental nutrition using the "three in one" system Nutriflex 70/180 lipid (B. Braun, Germany) – 625 ml (740 kcal) + enteral nutrition with a mixture of Nutricomp diabetes liquid (B. Braun, Germany) – 500 ml (500 kcal) started from the 1st day, with a daily increase in the volume of the enteral mixture administered by 500 ml (650 kcal) and the achievement of a maximum daily volume of up to 2,000 ml (2,000 kcal) on the 4th day and the abolition of parenteral nutrition during this period |
|
subgroup 6 (28; 14 %) |
Mixed nutrition (parenteral nutrition using the "three in one" system Nutriflex 70/180 lipid (B. Braun, Germany) – 625 ml (740 kcal) + enteral mixture Nutricomp immune liquid (B. Braun, Germany) – 500 ml (650 kcal) started from the 1st day, with a daily increase in the volume of the enteral mixture administered by 500 ml (650 kcal) and the achievement of a maximum daily volume of up to 2,000 ml (2,600 kcal) on the 4th day and the abolition of parenteral nutrition during this period |
Table 2. Options for nutritional support in patients of group II
|
Patients |
Nutritional support options and their energy value |
|
Group II (patients (198; 100 %) with moderate ARDS (100 mm Hg < IO ≤ 200 mm Hg) |
|
|
subgroup 1 (34; 17.2 %) |
Enteral nutrition, carried out during the entire observation period, with a mixture of Nutricomp Diabetes Liquid (B. Braun, Germany) began with a volume of 500 ml (500 kcal) on the first day, followed by a daily increase in the volume of the injected mixture by 500 ml (500 kcal) and reaching the maximum daily volume up to 2000 ml (200 kcal) on the 4th day |
|
subgroup 2 (32; 16.2 %) |
Enteral nutrition, carried out during the entire observation period, with a mixture of Nutricomp immune liquid (B. Braun, Germany) began with a volume of 500 ml (650 kcal) on the first day, followed by a daily increase in the volume of the injected mixture by 500 ml (650 kcal) and reaching the maximum daily volume up to 2,000 ml (2,600 kcal) on the 4th day |
|
subgroup 3 |
Parenteral nutrition using the "three in one" system 48/150 lipid (B. Braun, Germany) – 625 ml (632 kcal) was started from the 1st day and continued up to the 5th day. From the 6th day, in parallel with parenteral nutrition, the enteral mixture Nutricomp immune liquid (B. Braun, Germany) – 500 ml (650 kcal) was administered, followed by a daily increase in the volume of the injected mixture by 500 ml (650 kcal) and the maximum daily volume was reached up to 2,000 ml (2,600 kcal) on the 9th day, as well as the abolition of parenteral nutrition at the same time |
|
subgroup 4 |
Parenteral nutrition using the "three in one" system Nutriflex 70/180 lipid (B. Braun, Germany) – 625 ml (740 kcal) was started from the 1st day and continued up to the 5th day. From the 6th day, in parallel with parenteral nutrition, the enteral mixture Nutricomp immune liquid (B. Braun, Germany) – 500 ml (650 kcal) was administered, followed by a daily increase in the volume of the injected mixture by 500 ml (650 kcal) and the maximum daily volume was reached up to 2,000 ml (2,600 kcal) on the 9th day, as well as the abolition of parenteral nutrition at the same time |
|
subgroup 5 |
Mixed nutrition (parental nutrition using the "three in one" system Nutriflex 70/180 lipid (B. Braun, Germany) – 625 ml (740 kcal) + enteral nutrition with a mixture of Nutricomp diabetes liquid (B. Braun, Germany) (B. Braun, Germany) – 500 ml (500 kcal) was started on the 1st day, with a daily increase in the volume of the administered enteral mixture by 500 ml (500 kcal) and the maximum daily volume was reached up to 2,000 ml (2,000 kcal) on the 4th day and the abolition of during the same period of parenteral nutrition |
|
subgroup 6 |
Mixed nutrition (parental nutrition using the "three in one" system Nutriflex 70/180 lipid (B. Braun, Germany) – 625 ml (740 kcal) + enteral nutrition with a mixture of Nutricomp immune liquid (B. Braun, Germany) – 500 ml (650 kcal) started on the 1st day, with a daily increase in the volume of the enteral mixture administered by 500 ml (650 kcal) and the achievement of a maximum daily volume of up to 2,000 ml (2,600 kcal) on the 4th day and the abolition of parenteral nutrition at the same time |
Hitachi
902 Roche Diagnostics (Switzerland) was used for measurement of the content of
albumin (g/l) and transferrin (g/l) in the venous blood plasma, and the
absolute number of lymphocytes (cells in ml3) in venous blood. Sysmex XT (USA)
4000i was used for measurement of absolute number of lymphocytes (cells in ml3)
in venous blood. The degree of nutritional deficiency in patients with ARDS was
determined based on the result in points of the simplified nutritional
deficiency assessment scale [6] after its unification (Table 3). The
unification of the malnutrition assessment scale was due to the fact that the
indicators used in it, such as body mass index (BMI, kg/m2),
thickness of the skin-fat fold over the triceps and arm circumference (AC),
have low diagnostic content in critically ill patients [7, 8, 9], including
patients with ARDS [10].
Significantly
greater diagnostic significance in relation to determining the degree of
nutritional deficiency in patients with ARDS is related to such criteria as
transferrin, albumin and the absolute number of lymphocytes [10]. Therefore,
for the correct diagnosis of the degree of nutritional deficiency in patients
with ARDS, a simplified and unified scale of its severity of nutritional
deficiency with a score was used (Table 3). The degree of malnutrition was established in patients
of group I on days 1, 3, 5, 7 and 9, and in group II - on days 1, 3, 5, 7, 9 and
11. This was due to the fact that the duration of respiratory support in
patients of group I was 6 (5; 7) days, and in group II - 8 (7; 9) days.
Table 3. Assessing the degree of malnutrition in patients with ARDS
|
Criteria |
Normal values |
Malnutrition |
||
|
Mild |
Average |
Severe |
||
|
Albumin, g/l |
≥ 35 |
34-30 |
29-25 |
< 25 |
|
Transferrin, g/l |
≥ 2 |
1.9-1.8 |
1.7-1.6 |
< 1.6 |
|
Lymphocytes, cells in ml3 |
> 1.8 |
1.8-1.5 |
1.4-0.9 |
< 0.9 |
|
Number of points for each criterion |
3 |
2 |
1 |
0 |
|
Sum of points |
9 |
8-6 |
5-3 |
< 3 |
Statistical
analysis was carried out using the Statistica 8.0 software package (StatSoft
Inc., USA). The nature of the distribution was assessed using the
Kolmogorov-Smirnov test and the construction of quantile graphs. Statistical
hypotheses were tested using non-parametric statistical methods: Wilcoxon test
- for dependent samples, Kruskal-Wallis ANOVA - for multiple comparison of
independent samples, Friedman ANOVA – for dependent samples. The multiple
comparison problem was solved by using Kruskal-Wallis ANOVA. Null hypotheses
were rejected taking into account the correction for the multiplicity of
comparisons at the level of statistical significance p < 0.01. Quantitative
data in the study tables are presented as median (Me – 50 % quartile, Q2) and interquartile
range (Q1-Q3 – 25-75 % quartile) [11].
The
study was conducted with approval from the local bioethical committees of City
Clinical Hospital of Emergency Medicine No. 1 and Kabanov City Clinical
Hospital No. 1, with written consent of all participants, and in compliance
with Helsinki Declare – Ethical Principles for Medical Research with Human Subjects
2013, and the Rules for clinical practice in the Russian Federation confirmed
by the Order of Health Ministry of RF on June 19, 2003, No. 266.
RESULTS
In patients of all subgroups of group I, the ongoing nutritional therapy contributed to a decrease in the severity of malnutrition, which was stated by a multiple comparative analysis performed between all periods of observation (Table 4). The effectiveness of the applied nutritional support schemes in reducing the degree of nutritional deficiencies in all patients of group I was confirmed by the implemented pairwise comparison in the studied subgroups with the previous period (Table 4). It was noteworthy that on the 5th day, with the same degree of malnutrition in patients of the 3rd and 4th subgroups, a significant difference was found in its scoring with patients of the 1st, 2nd, 5th and 6th subgroups (Table 4). However, on the 9th day, patients of all subgroups of group I had non-statistically significant identical (moderate) malnutrition (Table 4).
Table 4. The degree of malnutrition in patients of group I Me (QL; QH) – median (lower and upper quartiles)
|
Observation periods |
Scoring the degree of malnutrition |
|||||
|
Enteral nutrition (subgroups) |
Parenteral nutrition (subgroups) |
Mixed nutrition (subgroups) |
||||
|
1 |
2 |
3 |
4 |
5 |
6 |
|
|
day 1 |
0 (0; 0) |
0 (0; 0) |
0 (0; 0) |
0 (0; 0) |
0 (0; 0) |
0 (0; 0) |
|
day 3 |
0 (0; 0) |
0 (0; 0) |
0 (0; 0) |
0 (0; 0) |
0 (0; 0) |
0 (0; 0) |
|
day 5 # |
2 (2; 2) |
2 (2; 2) |
1
(1; 1) |
1
(1; 1) |
2 (2; 2) |
2 (2; 2) |
|
day 7 |
3 (3; 3) |
3
(3; 4) |
3 (3; 3) |
3
(3; 3) |
3 (3; 3) |
3
(4; 3) |
|
day 9 |
4 (4; 5) |
4
(4; 5) |
4
(4; 4) |
4
(4; 4) |
4
(4; 5) |
4
(4; 5) |
|
Friedman's ANOVA |
N = 35, df = 4; |
N = 38, df = 4; |
N = 34, df = 4; |
N = 35, df = 4; |
N = 30, df = 4; |
N = 28, df = 4; |
Note: here and in Table 5 * – differences in subgroups between all follow-up periods are statistically significant (Friedman's ANOVA, at p < 0.05); p = n-n – pairwise comparison in subgroups conducted with the previous term (Wilcoxon test, p < 0.05); # – comparison of subgroups by timing (Kruskal-Wallis ANOVA).
Implemented nutritional support in patients of all subgroups of group II contributed to a decrease in the degree of nutritional deficiencies, as evidenced by multiple comparative analyses in all periods of observation (Table 5). The effectiveness of the nutritional therapy programs used in reducing the severity of nutritional deficiencies in all patients of group II was evidence-based by a paired comparison with the previous term in the studied subgroups (Table 5). It was noteworthy that on the 7th day the scoring of the severity of nutritional deficiencies in patients of the 3rd and 4th subgroups was statistically significantly higher than in patients of the 1st, 2nd, 5th and 6th subgroups, despite its equal severity (Table 4). But at the same time, by the end of the observation period, all patients of group II had a moderate degree of malnutrition, which did not have a true difference (Table 5).
Table 5. The degree of malnutrition in patients of group II Me (QL; QH) – median (lower and upper quartiles)
|
Observation periods |
Scoring the degree of malnutrition |
|||||
|
Enteral nutrition (subgroups) |
Parenteral nutrition (subgroups) |
Mixed nutrition (subgroups) |
||||
|
1 |
2 |
3 |
4 |
5 |
6 |
|
|
day 1 |
0 (0; 0) |
0 (0; 0) |
0 (0; 0) |
0 (0; 0) |
0 (0; 0) |
0 (0; 0) |
|
day 3 |
0 (0; 0) |
0 (0; 0) |
0 (0; 0) |
0 (0; 0) |
0 (0; 0) |
0 (0; 0) |
|
day 5 |
0 (0; 0) |
0 (0; 0) |
0 (0; 0) |
0 (0; 0) |
0 (0; 0) |
0 (0; 0) |
|
day 7 # |
2 (2; 2) |
2 (2; 2) |
1
(1; 1) |
1
(1; 1) |
2 (2; 2) |
2 (2; 2) |
|
day 9 |
3 (3; 3) |
3
(3; 4) |
3 (3; 3) |
3
(3; 3) |
3 (3; 4) |
3
(3; 4) |
|
day 11 |
4 (4; 5) |
4
(4; 5) |
4
(4; 4) |
4
(4; 4) |
4
(4; 5) |
4
(4; 5) |
|
Friedman's ANOVA |
N = 35, df = 5; |
N = 33, df = 5; |
N = 28, df = 5; |
N = 30, df = 5; |
N = 38, df = 5; |
N = 37, df = 5; |
DISCUSSION
In
all patients suffering from ARDS of varying severity, severe nutritional
insufficiency was recorded already at its diagnosis, catalyzing the progression
of pulmonary dysfunction [1]. Arterial hypoxemia initiated organ-system damage
in patients of groups I and II [2] and, as a result, further progression of
systemic inflammation [3], which contributed to the development of protein-energy
insufficiency [1]. The formation of MODS in all patients of groups I and II put
an additional burden on the gas exchange function of compromised lungs and
contributed to the further evolution of systemic inflammation [6]. This caused
severe protein-energy deficiency in patients of all subgroups of group I for
two days, and in patients of all subgroups of group II for three days, despite
the implementation of heterogeneous nutritional support. Positive kinetics of
the severity of nutritional deficiency was recorded in patients of group I
starting from the fifth day, and in patients of group II - from the seventh
day. The different time duration in relation to the positive kinetics of the
severity of nutritional deficiency was due to the fact that patients of group
II, compared with patients of group I, had a large area of lung tissue damage
[2] and more significant gas exchange disorders [5]. It was noteworthy that in these
terms, the patients of the 3rd and 4th subgroups of groups I and II, compared
with other subgroups, had an actual difference in the scoring of malnutrition.
The lower efficiency of parenteral nutrition, compared with enteral and mixed
nutritional support, in patients of groups I and II was due to the fact that
these patients had impaired gas exchange (arterial and venous hypoxemia) [2]
and non-gas exchange functions (inadequate synthesis and desynthesis proteins
and fats) of the respiratory organ [1], which is also affected by local and
systemic inflammation [5].
This
situation contributed to the fact that fatty acids, which are synthesized by
the lungs from substrates delivered to them by the systemic circulation [6],
cannot be adequately formed even during parenteral nutrition due to functional
insufficiency of the respiratory organ [3]. This is a serious problem in
patients with ARDS, since at least 50 % of the total energy value should be
provided by lipid solutions [7], which must be quickly disposed of from the
bloodstream in order to prevent hyperlipidemia and increase the rate of
triglyceride utilization to increase the rate of energy production and protein
synthesis [6], while the rest of the energy demand is compensated by
carbohydrates [8]. Given
that patients with ARDS, due to their etiopathogenetic reasons, tolerate any
intravenous fluid administration extremely mediocrely [2], parenteral nutrition
should be implemented in them according to the methodology of low-volume
nutritional support [7]. This concept has its own characteristics, consisting
in the fact that the patient receives a smaller amount of energy and plastic
material, which, under conditions of increased metabolism, cannot contribute to
its effective regulation [6]. It was the addition of the enteral mixture to
parenteral nutrition from the fifth day that made it possible to increase the
caloric density and the amount of plastic material in patients of the 3rd and
4th subgroups of groups I and II, which contributed to the productivity of
eliminating nutritional deficiencies during the entire observation period. So, in
patients of the 3rd and 4th subgroups of group I on the seventh and ninth days
of the observation period, there was no difference in the dynamics of
regulation of nutritional deficiencies in relation to patients of the 1st, 2nd,
5th and 6th subgroups. A similar situation was recorded in patients of the 3rd
and 4th subgroups of group II: on the ninth and eleventh days of the
observation period, no differences were recorded in the kinetics of correction
of nutritional deficiencies in comparison with patients of the 1st, 2nd, 5th
and 6th subgroups.
CONCLUSION
1.
In patients with mild ARDS, severe nutritional malnutrition is recorded from
the first to the fifth day, and in patients with its moderate course, from the
first to the seventh day against the background of nutritional support.
2.
Implemented heterogeneous nutritional support reduced severe nutritional
malnutrition to a moderate degree in patients with mild ARDS on the 7th day,
and with moderate ARDS - on the 9th day.
3.
All used nutritional therapy programs contributed to the reduction of
malnutrition in patients with mild to moderate ARDS.
4.
After the cessation of artificial lung ventilation due to regression of
hypoxemic acute respiratory failure and subsequent transfer to spontaneous
breathing in patients with mild and moderate ARDS, there is a nutritional
deficiency of moderate severity, which justifies the continued use of
nutritional (enteral nutrition) therapy in the treatment program until its
transformation to a mild degree.
Funding and conflict of interest information
The
study was not sponsored.
The authors declare the absence of obvious and
potential conflicts of interest related to the publication of this article.
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