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ORGAN AND SYSTEM DYSFUNCTIONS IN PATIENTS WITH ACUTE RESPIRATORY DISTRESS SYNDROME
Girsh A.O., Mishchenko S.V., Stepanov S.S., Klementyev A.V., Leyderman I.N., Stukanov M.M., Chernenko S.V., Malyuk A.I., Chumakov P.A.
Omsk State Medical University, Omsk, Russia
Acute respiratory distress syndrome (ARDS) is not only
an integral component of multiple organ failure in critically ill patients, but
also its catalyst throughout the entire period of its existence [1–7]. Arterial
hypoxemia arising from ARDS becomes responsible not only for the occurrence of
hypoxic damage to organs and systems [2], but also for significant
deterioration of metabolic processes in body cells, contributing to their
unprogrammed apoptosis, which form cascade damage to the structure of organs
and tissues, causing further deterioration of their functions. [8, 9].
It is the negative progressive reformation of the
structure and function of organs and systems, in particular the lungs, that
determines the unrestrained evolution of multiple organ failure [2, 3, 10, 11,
12]. This pathological process not only supports, but also independently
induces systemic inflammation [1, 5], which contributes to the onset of
hypermetabolism syndrome [8, 9] and the development of severe protein-energy
deficiency [13], which contribute to the existing multiple organ failure and
determine its progress [ 2, 4]. In turn, the resulting metabolic dysfunction
further aggravates the negative reformation of the structure and function of
organs and systems, thereby closing the vicious circles of the pathogenesis of
multiple organ failure [8, 9, 13].
Since in ARDS in the lungs, which have a uniquely
complex structure and numerous non-gas exchange functions [14], acute diffuse
inflammatory foci in their parenchyma cause disturbances in the structure of
the lung tissue and a decrease in its aerated mass, resulting in negative
metabolic, functional and structural changes in organs and organs and their
systems [2], it will be significant to identify the order of origin of their
insufficiency in these patients. This is due to the fact that to date, in
patients with ARDS of varying severity, the composition of organ-systemic
disorders induced directly by this pathology for targeted and personalized
maneuvering with the strategy and tactics of syndromic intensive treatment has
not been disclosed.
Taking into account all of
the above, the objective of the ongoing study was to establish the structure of
systemic organ failure and hypermetabolism syndrome in patients with acute respiratory
distress syndrome of varying severity.
MATERIALS AND METHODS
The study, which was of an open clinical and prospective nature, involved 209 patients with ARDS, which was formed as a result of traumatic shock of II and III severity, and were treated in the intensive care unit (ICU) of City Clinical Hospital of Emergency Care No. 1 and Kabanov City Clinical Hospital No. 1 from 2016 to 2021. All patients, whose average age was 31.2 (21; 38) years, were ranked into three groups depending on the severity of ARDS (Table 1). The conditions for participation in the study were: 1) patients aged 18 to 40 years; 2) the presence in patients of ARDS of varying severity, classified and differentiated using the oxygenation index (OI) after 39 ± 6 hours; 3) providing all patients with mild, moderate and severe ARDS in the ICU with appropriate (but taking into account individual characteristics) intensive care (including respiratory support), based on the clinical recommendations of the All-Russian public organization "Federation of Anesthesiologists and Resuscitators". The exclusion criteria from the study were: 1) persistent acute cardiovascular failure in patients requiring intravenous use of ά1- and β2-agonists in the treatment program; 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. Distribution of patients into groups, taking into account the severity of ARDS
|
Groups of patients (n; %) |
Severity of ARDS |
|
Group I |
Mild ARDS (200 mm Hg < OI ≤ 300 mm Hg) |
|
Group II |
Moderate ARDS (100 mm Hg < OI ≤ 200 mm Hg) |
|
Group III |
Severe ARDS (OI ≤ 100 mm Hg) |
|
Total |
|
The formation of multiple organ failure syndrome (MOFS)
in patients was determined on the 3rd, 4th and 5th days using SOFA scale
(points), and the specific insufficiency of organs and systems was determined
based on its components, namely the cardiovascular system, creatinine,
bilirubin, platelet count, OI, Glasgow Coma Scale with their subsequent
individual scoring. For this purpose, the Hitachi 902 analyzer (Roche Diagnostics,
Switzerland) identified the content of creatinine (mmol/l) and bilirubin
(mmol/l) in the venous blood plasma, and the number of platelets (109/l).
The severity of the degree of ARDS in patients was argued by OI (c.u.) [2]. Dysfunction
of the central nervous system (CNS) of patients was assessed according to Glasgow
Coma Scale (GCS, points). Taking into account that all the studied patients
received artificial respiratory support and various degrees of pharmacological
(intravenous administration of narcotic and/or sedative drugs as a bolus or
with the help of syringe perfusors) correction to prevent excessive
neuroendocrine and autonomic reactions, the rating of consciousness was formed
only when it was suspended. Identification of MAP (mm Hg), as well as
determination of the energy consumption necessary to ascertain the
disorganization of metabolism and confirm its dysfunction in patients, was
carried out using the MPR 6-03 device (Triton Electronics, Russia).
Statistical analysis of the obtained data was carried
out taking into account the requirements for the use of methods of paired and
multiple comparison of variational series [15]. The nature of the distribution
was checked using the Kolmogorov-Smirnov test and the graphical method.
Quantitative data are presented by median (Q2) and interquartile range (lower
and upper quartiles - Q1; Q3). The Wilcoxon test was used for pairwise
comparison of dependent variables (by time), and Friedman and Kruskal-Wallis
ANOVA was used for multiple comparisons. The use of non-parametric statistics
methods is due to relatively small groups (n = 20) and non-normal distribution
of variable values. The null hypothesis was rejected taking into account the
correction for the multiplicity of comparisons at the level of statistical
significance p < 0.01 [15].
The study was conducted on
the basis of the permission of the local bioethical committees of City Clinical
Hospital of Emergency Care No. 1 and Kabanov City Clinical Hospital No. 1, as
well as all its participants (based on voluntary informed consent) and complied
with ethical standards developed on the basis of the Declaration of Helsinki of
the World Medical Association - Ethical principles for conducting scientific medical
research involving humans as amended in 2013 and Rules of Clinical Practice in
the Russian Federation, approved by order of the Ministry of Health of the
Russian Federation dated June 19, 2003 No. 266.
RESULTS
Comparison of the studied criteria in patients of groups I, II and III with respect to time periods demonstrated their true disproportion (Table 2), which stated an absolute difference between the severity of ARDS. This was axiomatic in relation to the fact that the definition of dysfunctions of organs and systems in patients is correct only when they are ranked according to the severity of ARDS.
Table 2. Comparison of the studied criteria for patients in groups I, II and III with respect to time periods
|
Criteria |
Time intervals |
||
|
day 3 |
day 4 |
day 5 |
|
|
Energy requirement, kcal |
H = 48.6; p = 0.0000 |
H = 50.0; p = 0.0000 |
H = 52.1; p = 0.0000 |
|
SOFA, points |
H = 53,3; p = 0.0000 |
H = 53.4; p = 0.0000 |
H = 52.8; p = 0.0000 |
|
OI, c.u. |
H = 52.5; p = 0.0000 |
H = 52.5; p = 0.0000 |
H = 52.5; p = 0.0000 |
|
Glasgow Coma Scale, points |
H = 52.1; p = 0.0000 |
H = 53.0; p = 0.0000 |
H = 55.2; p = 0.0000 |
|
Creatinine, mmol/l |
H = 40.1; p = 0.0000 |
H = 52.5; p = 0.0000 |
H = 52.5; p = 0.0000 |
Note: here in the table, the differences between the groups are statistically significant (ANOVA Kruskal-Wallis test: df = 2) at p < 0.05.
In patients of group I, MODS was observed on the 3rd day due to the inferior functioning of the lungs, kidneys, and central nervous system (Table 3). Also, during this time period, patients showed increased energy consumption (Table 3). On the 4th day, MODS reduction was registered in patients due to a true regression of the inferiority of the kidneys and partially lungs, against the background of a continuing CNS deficiency and abnormal energy consumption (Table 3). On the 5th day, the patients were found to have no MODS due to elimination of the CNS deficiency (Table 3). At the moment, in patients of group I, only monoorganic dysfunction was identified, due to persistent, but already regressing lung pathology (Table 3). During this period, the patients retained excessive energy consumption, despite the positive difference with the previous time periods according to the identical criterion (Table 3).
Table 3. Kinetics of energy consumption, SOFA and its criteria in patients of group I, Q2 (Q1; Q3)
|
Criteria |
Time intervals |
||
|
day 3 |
day 4 |
day 5 |
|
|
Energy
requirement, kcal |
3106.5 |
3082 |
3020 (2961; 3054) |
|
SOFA, points |
4 |
3
(2; 4) |
2
(1; 2) |
|
OI, c. u. |
253 |
274.5 |
294 (285; 302,5) |
|
Platelets, 109/l |
> 180 |
> 180 |
> 180 |
|
Bilirubin, mmol/l |
< 20 |
< 20 |
< 20 |
|
Mean arterial pressure, mm Hg |
> 70 |
> 70 |
> 70 |
|
Glasgow Coma Scale, points. Friedman's ANOVA: |
13 |
13 |
15 (15; 15) |
|
Creatinine, mmol/l. Friedman's ANOVA: |
118 |
105,5
(100; 109.5) |
95
(88.5; 97.5) |
Note: here and
in Tables 3 and 4, multiple comparisons of three terms in the group (Friedman's
ANOVA), pairwise comparisons between terms in the group (Wilcoxon test). The
null hypothesis was rejected in all cases at p < 0.05. Q2 (Q1; Q3) –
median (upper and lower quartiles).
In patients of group II, on the 3rd day, MODS was established based on the inadequacy of the activity of the lungs, kidneys, liver, and central nervous system (Table 4). In parallel, patients showed increased energy consumption (Table 4). On the 4th day, despite the positively significant OI kinetics, the patients had the same level of MODS (Table 4). In addition, a significant increase in energy consumption was recorded in patients (Table 4). On the 5th day, patients showed a true decrease in the severity of MODS due to complete stagnation of liver inadequacy and partial in relation to the deficiency of lung, kidney and central nervous system activity (Table 4). A real decrease in energy consumption was recorded synchronously (Table 4).
Table 4. Kinetics of energy consumption, SOFA and its criteria in patients of group II, Q2 (Q1; Q3)
|
Criteria |
Time intervals |
||
|
day 3 |
day 4 |
day 5 |
|
|
Energy requirement,
kcal. Friedman's
ANOVA: |
3264.5 |
3360 |
3332.5 |
|
SOFA, points. Friedman's ANOVA: |
8 (7; 8) |
8 (7; 8) |
6 (6; 6) |
|
OI, c.u., Friedman's ANOVA: |
149.5 |
168.5 |
201.5 |
|
Platelets, 109/l |
> 180 |
> 180 |
> 180 |
|
Bilirubin, mmol/l. Friedman's ANOVA: |
23.5 |
26.5 |
19 (17.5;
20) |
|
Mean arterial pressure, mm Hg |
> 70 |
> 70 |
> 70 |
|
Glasgow Coma Scale, points. Friedman's ANOVA: |
9 (8; 9) |
9 (8; 9) |
9 (8; 9) |
|
Creatinine, mmol/l. Friedman's ANOVA: |
122.5 |
132 |
120.5 |
In patients of group III,
MODS was identified on the 3rd day, due to deprivation of the lungs, kidneys,
liver, and central nervous system (Table 5). Coherently, patients showed a
significant increase in energy consumption (Table 5). On the 4th day, patients
showed a true increase in the severity of MODS due to the actually increasing
inferiority of the lungs, kidneys, liver and central nervous system, as well as
the emerging evolution of a genuine platelet deficiency (Table 5). Also at this
stage, the patients had a high energy demand (Table 5). On the 5th day, a
reliable evolution of MODS was recorded in patients due to further negative
reformation of the functioning of the lungs, kidneys, liver, central nervous
system, platelet count, and the formation of stable insufficiency of the
cardiovascular system (Table 5). At the same time, patients recorded a
significant increase in energy demand (Table 5).
Table 5. Kinetics of energy consumption, SOFA and its criteria in patients of group III, Q2 (Q1; Q3)
|
Criteria |
Time intervals |
||
|
day 3 |
day 4 |
day 5 |
|
|
Energy requirement,
kcal. Friedman's
ANOVA: |
3514 |
3529 |
3589 |
|
SOFA, points. Friedman's ANOVA: |
12.5 |
13 |
15 (15; 15) |
|
OI, c.u., Friedman's ANOVA: |
91.5 |
86 |
83.5 (80;
88) |
|
Platelets, 109/l. Friedman's ANOVA: |
180 |
153.5 |
140.5 |
|
Bilirubin, mmol/l. Friedman's ANOVA: |
35.5 |
45 |
53.5 (48;
56) |
|
Mean arterial pressure, mm Hg / inotropic and vascular support (µg/kg per min) |
66.5 |
65.5 |
i.v.
dobutamine |
|
Glasgow Coma Scale, points. Friedman's ANOVA: |
6.5 |
7 (7; 7) |
7 (7; 7) |
|
Creatinine, mmol/l. Friedman's ANOVA: |
180 |
213 |
311.5 |
DISCUSSION
ARDS that occurred in the
studied patients was caused by indirect alteration, namely, shockogenic injury
of varying severity, which contributes to the disorganization of the
functioning of the vascular endothelium and the initiation of the evolution of
systemic inflammation, which are responsible for the formation of heterogeneous
severity of arterial hypoxemia [1–7], which, in turn, hampered tissue
oxygenation and generally disrupted aerobic metabolism in the cells of organs
and tissues [9]. It was also indisputable that in patients of groups I, II and
III, the registered manifestations of arterial hypoxemia and increased energy
demand, as well as the identified damage to systems and organs, including their
depth of alteration, depended directly on its severity. Therefore, the recorded
composition of MODS in patients of groups I, II and III was heterogeneous. It
was arterial hypoxemia, which turned out to be the main damaging factor [1–4],
that triggered the process of hypoxic alteration of the lungs, kidneys, liver,
CNS, and subsequently hemostasis and the cardiovascular system, which resulted
in the formation of their dysfunction and the formation of multiple organ
failure [8]. The process of hypoxic alteration of systems and organs
contributed to the evolution of unplanned death of their cells [14]. This, in
turn, formed cascade damage to the structure of organs and tissues, and
progressively reformed their functions, causing the unrestrained evolution of
MODS [8].
In patients of groups I, II, and III, the lungs acted
both as a damaged organ and as the main initiator and catalyst of MODS [2]. In
addition, the intensity of initiation and catalysis of MODS by the lungs
depended on the severity of their direct damage [1, 4] in the studied patients.
Moreover, the volume of lung alteration and their inadequacy of functioning,
combined with the activity of generalized inflammation and insufficiency of
organs and systems, were much stronger in patients of group III than in
patients of groups I and II, both initially and in dynamics against the
background of intensive therapy. It is these components, as well as their
severity, that contributed to the evolution of all types of metabolic disorders
and the materialization of impressive energy consumption and, as a result, the
development of metabolic dysfunction of varying severity in the studied
patients.
Undoubtedly, the energy demand of patients in group
III was significantly higher compared to the energy demand of patients in
groups I and II. Obviously, metabolic dysfunction in patients of groups I, II,
and III increased the deficit in lung activity, which, in turn, initiated and
formed organ-systemic deprivation [8, 13]. The formation of MODS in patients of
groups I, II, and III put an additional burden on the gas exchange function of
compromised lungs and progressively provoked an increase in metabolic
dysfunction [8, 9, 13].
Based on the above mentioned
facts, it becomes undeniable that the strategy and tactics of intensive care
for patients with ARDS should be carried out not only taking into account the
existing organ-systemic deficiencies [2, 4-7], but also nutritional regulation
of increased metabolism and its final stage - protein-energy insufficiency. [8,
9, 13].
CONCLUSIONS
1. The composition of MODS in patients with mild ARDS
- pulmonary, cerebral and renal, with moderate ARDS - pulmonary, cerebral,
renal and hepatic, with severe ARDS - pulmonary, cerebral, renal, hepatic,
cardiovascular and hemostasiological.
2. In patients with mild,
moderate and severe ARDS, from the moment of its onset, metabolic dysfunction
of varying severity is present, depending on its severity and manifested by an
increased need for energy.
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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