Respiratory distress syndrome

Respiratory distress syndrome (RDS) – acute lung injuries – rather frequent and severe complications of acute pneumonia and other diseases (acute inflammatory diseases of the chest and abdominal cavities, severe traumas, burns, eclampsia, sepsis and other). RDS is the major causes of unfavorable outcomes, despite the use of most modern medicaments.

Our previous experimental studies have demonstrated that endotoxicosis developed in animals since first minutes of acute pneumonia modeling.There are many pathogenous factors of endotoxicosis: bacterial endo- and exogenous toxins, inflammatory toxic metabolites, products of proteolisis, activation of lipid peroxydation and decrease of anti-oxidation protection, toxic middle molecular weight compounds (oligopeptides), lysosomal enzymes.

As a result arise some complications of endotoxicosis: increase vascular permeability (microvascular leaking), hypoproteinemia, hypooncotic hypovolemia,  low blood pressure, toxic pulmonary edema – respiratory distress syndrome, acute respiratory insufficience, disseminated intravascular coagulations syndrome and, as result – multiple organ failure. Endotoxicosis determined in many respects the scale and severity of lung parenchyma injury as the type of  toxic edema .

Of the same opinion and Conciliation Commission (Consensus) scientists involved in the issue of European and American countries in 1994, considering that the basis of acute respiratory distress syndrome is a toxic lesion of the lung parenchyma [1], but no recommendations for detoxifications in this document does not contain. Nothing new has been added and the last Consensus ‘Berlin definition” in the choice of treatment in 2012 [2].

Furthermore, it is not clear – why still “respiratory distress syndrome” called “acute” (ARDS) as if there are chronic form? So we being adhered more simplified name – “respiratory distress syndrome” (RDS), which can only be acute. 
The aim of this work is to analyze the effectiveness of various methods of detoxification for RDS.

DATA BASE INFORMATION
We analyzed the therapy of 153 RDS patients: 99 -  with moderate, 44 - with severe and 10 - with extremely severe degree of lung injury (table 1, 2).

67 patients received the conventional therapy only (antibiotics and other drugs, and in severe degree of RDS – mechanical lung ventilation).

76 patients received an additional detoxification therapy – hemadsorption or plasma exchange of 1.5-2.5 l of plasma with replacing of fresh frozen plasma, using an apparatus for membrane plasmapheresis.
10 patients with extremely severe RDS were underwent the extracorporeal membrane oxygenation of the blood (ECMO) 1.0-1.5 l/min lasting from 15 to 44 hours with passing 1-2 circulating blood volume throw the  sorption column every 6-10 hours to three session a day (hemoadsorption).
Table 1. Clinical and laboratory signs of RDS
Stage severity
RDS
Stages severity
Middle weight molecules РаО2 X-Rey
lung capacity
Respiration
I Moderate  350,0±22,5 68,2±1,8
(FiO2 0,4)
Low lung zones Spontaneous
II Severe 444,2±45,3 60,3±0,8
(FiO2 0,7)
Low and middle
zones
CPPB
PEEP
III Extremely
severe
680,1±52,6 44,7±0,9
(FiO2 1,0)
Total “hepatisation” PEEP
ECMO


Table 2. Severity stages of RDS and treatments methods
(n – patients)
Stage severity
RDS
Treatments methods
Conventional Detoxification
I Moderate 52 47 99
II Severe 15 29 44
III Extremely severe 10 10
67 86 153


Results.
           In moderate RDS group there were no lethal outcomes. The duration of hospital stay was significantly lower in patients underwent detoxification than in ones of control group (28,9±1,5 versus 40,3±3,3 days; p < 0,05), and there were no destructive processes in lungs.
            In patients with severe RDS and only conventional therapy the lethality level attained 73.33% while additional using of hemoadsorption or plasmapheresis allowed to decrease it to 31.03%. We failed to save just patients in which detoxification was performed in more late terms after the disease onset.

The extremely severe RDS degree was characterized by practically total injury of lung parenchyma and severe respiratory failure, which was not corrected with mechanical ventilation.
Using ECMO during from 15 to 44 hours with 3-4 hemoadsorption procedures allowed to save 7 of 10 these patients (table 3).
Table 3. Lethality rate in different severity stages of respiratory distress syndrome
and treatments methods
Stage severity
RDS
Treatment
Conventional Detoxification ECMO
+ detoxification
I Moderate 0 0
II Severe 73.33% 31.03%
III Extremely
severe
30%


DISCUSSION
As seen from the table 3, even with moderate stage severity of RDS detoxification quickly and reliable to stop acute lung injury, however more severe it is reflected on the overall outcome of the disease. It should be noted that the earlier methods were used to detoxify, the more pronounced was their effectiveness. Thus, as a rule, was sufficient only one session hemoadsorption or plasmapheresis to advance change in course of the disease in the future and at a lower level medical support for coping with the some complications.  In severe RDS often required repetition of two or three sessions to achieve detoxification stabilization and regression of lesions in the lungs, but their belated application is not able to save all patients.

When extremely severe RDS with almost total pulmonary parenchimal damage develop severe respiratory failure, not recoverable by any means artificial ventilation.  In these cases, ECMO provides a more rapid normalization of gas exchange, and in parallel pursued intensive detoxification (up to three session per day) contributed to the elimination of toxic edema of the lung parenchyma with the restoration of degree “airness” lung X-ray examination after 7-15 hours, and by the end of ECMO managed to recover quite satisfactory gas exchange function of the lungs.
Western European countries and US have used ECMO far more widespread and its efficiency in recent years has increased to 47-60% [3, 4], however to achieve stable gas exchange recovery typically requires from several days to two weeks duration of such treatments. And while no any detoxification methods are generally used. In our practice, when carried out in parallel hemoadsorption enough 20-24 hours ECMO [5].
   
Endotoxemia, which determines the severity of RDS and the degree of the defeat of the lung parenchyma, multicomponent enough.  It consist of bacterial endo- and exotoxins, mediators  of inflammation and tissue destruction, products of proteolysis and lipid peroxidation.  All of these toxins disrupt cell membrane permeability, including vascular endothelium, with a yield in the interstitium not only liquid but also proteins. Such toxic edema and underlies the development of RDS, but to the same extent and affects other organs and systems, leading to multiple organ failure [6]. It should be born in mind that during hemoadsorptoon occurs fairly complete elimination of many pathological products and even delay the fixation of both living and dead bacteria that, for example, when an infection caused by Pseudomonas aeruginosa, hemoadsorption was the only truly effective treatment due to inadequate antibiotic therapy [7].

However, only one detoxification  and achievable using hemosadsorption also insufficient for full therapeutic effect, as the body remains in a state of immunosuppression, which creates due at the time the possibility of developing this severe complication. More stable result gives plasmapheresis with replacement remote plasma of a patient with “incompetent” antibodies, immunoglobulins, complement, opsonins by native donor plasma above immune components which immediately begin to fight against pathogens and other pathological products.

It should be noted that this approach not only normalized the humoral and cellular immunity but, as happens without complement opsonization receptors of macrophages, without which it is impossible to capture and subsequent destruction of pathogens. This provides more reliable results, particularly when replacing a plasma in a volume approaching  circulating plasma volume of patient. At the same time, in fairness, it should be emphasized that it is actually not so much about plasmapheresis, but about plasma exchange. Indeed, in a hypoproteimemia can not remove even a small volume of plasma without immediately replacing it with a donor  plasma  at a ratio of 1 : 1. However, the return of donor plasma can be started but after completion of plasmapheresis and compensation hypoproteinemia can provide synchronous  intravenous infusion hydroethyl starch solutions (HES, Voluven 6-10% 500 ml). This makes it possible to successfully remove 2,5-3,0 liters of plasma, even with unstable systemic circulation supported sympathomimetics, because the filling  volume of our apparatus does not exceed 65-70 ml.  This allowed us to ensure the safety of plasmapheresis even infants. And in recent years, we almost completely switched to such tactics [8].

Accepted standard of treatment RDS now is the use of different modes of mechanical ventilation with maintaining high end-expiratory pressure (PEEP) in the airways. But hopes to use PEEP may not always justify itself as an increase in pressure in the pleural cavities complicates the lymphatic drainage of the lungs and may contribute to further accumulation of fluid in them [9].
Moreover, RDS is often accompanied by acute renal failure (ARF) up to anuria [9]. Such unfavorable prognosis in cases of ARF, of course, requires intensive care. However, as with RDS, when trying to treat respiratory failure through various methods of artificial ventilation, in cases of ARF the excretory function some tend corrected it through the removing the accumulating fluid by hemodialysis or various methods of hemofiltration [11, 12, 13, 14].

And in both cases, this approach was explained by the desire to eliminate the only visible disorders – breathing with RDS and diuresis in case of ARF. Such mechanistic thinking  determines the actually symptomatic therapy not affecting the essence of pathology – endotoxemia, which is the basis of these organ disorders.  And really – the mortality in these patients remained quite high – up to 50-70%, regardless of the choice of methods of "renal replacement therapy" – dialysis, intermittent or continuous veno-venous hemofiltration [15, 16, 17].

Using only hemofiltration we cannot remove macromolecular and no less toxic products, including fibrinogen, which causes the need to use plasmapheresis [18]. This confirms our belief that only such symptomatic therapy (removal of excess fluid) does not eliminate the problem of endotoxemia – a major factor of tanatogenesis. 

Furthermore, removing only the liquid is not capable to restore immune protection. In most of these cases the fact of progressing course of RDS indicates an initial lack of defense systems. The development of endotoxicosis aggravates this “secondary” immune deficiency with development of so-called immune distress syndrome. Only drug immune stimulation is also unable to restore suppressed mechanisms of immune defense. If the patient does not resist, no medicine will not be able to save him.

In our opinion, in such cases, you must not remove the excess liquid, but eliminate the reasons that caused the suppression of renal excretory function. Necessary to remove the “toxic press” of the kidneys. And really after hemoadsorption or plasmapheresis, the next day urine output was not less than 500-700 ml, which talked about restoring self-renal excretory function. And this required only 2-3 hours instead of 2-3 days hemofiltration.

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