PATHOGENESIS OF ACUTE PNEUMONIA IN CHILDREN AS INDICATION IN TREATMENT
Igor Klepikov, MD
Keywords: acute pneumonia in children, pulmonary-pleural complications, pneumonia experimental model, pathogenesis, treatment, ABP
* Materials in this article were received and published during author’s work in the former Soviet Union and have no direct relationship to his current workplace.
SUMMARY
The article represents an abstract review of the author’s research (published in Russia from 1977 to 1993). The analyzed scientific material included 994 children with different forms of Acute Bronchial Pneumonia (ABP). Experiments conducted on 44 animals simulated the ABP model and its pulmonary-pleural complications. Fifty-six lung specimens affected by ABP underwent X-ray contrasting research.
A summary of the results allowed identifying certain components of the disease’s pathogenesis and substantiating the principles of targeted medical treatment. A pathogenically-justified approach treating ABP patients significantly improved the final results by decreasing forms with complications, shortened the treatment period by three-fold and avoided lethality completely.
INTRODUCTION
"In developing countries the incidence of bacterial pneumonia and its complications is much more frequent than in developed countries. By contrast, the majority of publications about pleural effusion come from developed countries. It is, therefore, important to encourage studies in developing countries." - H.T. Mocelin, G.B. Fischer "Epidemiology, presentation and treatment of pleural effusion." - Paediatric respiratory reviews, vol. 3, Iss. 4,Dec 2002, pp. 292-297
Acute Bronchogenic Pneumonias (ABP) are linked to climate, ecology, social and other factors. Lately, there have been numerous reports of an increase of complicated forms of ABP from the medical centers in North America and Europe. (5,10,12,18,19,49,56,58,67,68). Such increase is particularly alarming because it occurs in a high standard-of-living environment with directions to more aggressive methods of treatment (1-3,6,9,11,13-16,29,30,51,54,55,57,59,62-65,69-72).
The author previously practiced in Siberia where ABP in children was marked by an aggressive course of disease with a quick development of complications and lethality rate of 10% or more. This situation forced to find effective ways to help the ABP patients. Unfortunately, the resulting studies were published exclusively in former Soviet Union publications. Therefore, this article and information contained therein may be of interest to doctors dealing with ABP problems.
MATERIALS AND METHODS
General Description
Analyzed: 994 children aged from 4 months to 14 years, observed and treated at the Children’s Clinic of Novokuznetsk State Institute for Advanced Training of Doctors from 1976 to 1985 (34). The majority of observed patients (59.1%, 587 children) were in the 1 to 3 year old age group. This group contained only patients whose inflammatory process in a lung was considered a result of transbronchial infection of parenchyma. Septic or hematogenic pneumonia, lung inflammations due to a lung being pressured by extended formations of mediastinium or thorax, contact pleural empyema as a result of pussy mediastinitis or osteomyelitis of ribs, as well as thoraic injuries were excluded from this group because we believe these lung-pleural processes have different mechanisms of development warranting different treatment tactics (18,19,20,24).
Our clinic served as a specialized medical center for an ecologically unfavorable region of Southern Kuzbass (population 2.5 million), including a large industrial city, Novokuznetsk (population 600 thousands). The problem of having many patients with heavy pulmonary pathology and no specialized children’s medical centers in the region found a nonstandard organizational solution: patients with severe and rapid development of ABP were hospitalized into children’s surgical clinic when only intensive therapy and monitoring were required (4,23,24,28,35,40). Particular severity of this group of patients was confirmed by the fact that 1.1% of the patients with rapid ABP development had lung gangrene not observed in other regions (32).
Methods of the Patient Survey.
Patient survey included collection of anamnesis and physical examinations. Double-position chest radiographs, clinical analysis of blood and urine, central and peripheral hemoglobin and hematocrit for clarification of their gradients (HRD-hb and HRD-ht accordingly), volume of circulatory blood with dye T-1824 (61 patient; 6.1%), venous (407 patient; 40.9%) and arterial (54 patient; 5.4%) blood gases were dynamically performed.
Electrocardiography was performed on 447 people (45.0%). 112 people underwent a measurement of the central venous pressure (CVP) using a direct method (11.3%). A registration of comparative rheopulmonography (RPG) was administered before and immediately after some medical procedures to 36 patients (3.6%) aged 3.5 to 14 years old.
Experimental Research.
To reproduce the model of ABP and clarify some regularities of its development and complicated course, we performed four series of experiments on 44 rabbits. Among these, only two series (1st and 4th) are of an interest for this article.
In the first experimental series (11 animals), a lung tissue with an additional disruption of a bronchial passage was infected. A polyvinyl chloride catheter was inserted by means of a puncture of a cervical part of trachea. The distal end of the catheter (0.6 millimeter in diameter) moved up to the small bronchial branches in one of the lungs. The liquid blend contained 1 billion of microbial bodies of one-day culture Staphylococcus epidermidis and Escherichia coli and 1 сс of sterile sunflower oil; it was instilled through the catheter into the bronchial tree. After instillation, the catheter was immediately removed. On a second and third day of experiment, seven animals underwent slow jet-like intravenous infusions of rheomacrodex (30 cc/kg body mass). All animals were euthanized on a fourth day.
In fourth experimental series (15 animals), rabbits were given 5 cc normal horse serum (subcutis) seven days before a principal part of the experiment. Afterwards, using the method described above, the blend was instilled endobronchially containing 0,05 cc normal horse serum and aforementioned ingredients (bacterial cultures and sunflower oil). Seven animals did not go through additional procedures, while the remaining 8 animals received (3-4 hours after endobronchial procedures) intravenous jet-like slow infusions of rheomacrodex and 0.9% sodium chloride (30 cc/kg body mass). These infusions were repeated once a day. Six of the animals in the last group of eight had a dyestuff (2 cc of methylene blue) added into a solution for the intravenous infusions. All animals were euthanized on a fourth day after the endobronchial instillations.
Anatomo-roentgenological and Histological Research.
The lung roentgenograms with contrast were conducted on 56 specimens taken from children who died from ABP. The bronchial tree was contrasted in nine cases. In the remaining 47 specimens, the contrast substance was injected through arteries or veins.
The histological investigations were performed on the internal organs of 68 children (aged 7 months to 3 years) who died as a result of progressive ABP, parts of lung after resections in acute period of disease in connection with gangrene collected from 7 children, and lung specimens of experimental animals.
Statistical Evaluation of the Received Data.
A statistical evaluation of the research was performed by the successive plans of trials as well as by a method of controlling the mean variance in pairs. (Sachs L. "Statistische Auswertungsmethoden”. Springer Verlag. Berlin, Heidelberg, New-York, 1972).
RESULTS
Local Transformations
Anamnesis studies showed that in 983 cases (98.9%) the development of ABP was preceded by appearances of respiratory syndrome, which was mainly conditioned by viral infections and cold factor (36). Evident bronchial blockade in inflammatory zone, as a result of aspiration of foreign body, was found and solved by means of bronchoscopy only in 11 children (1.1%).
Bronchial passing disruption in pulmonary inflammatory zone was confirmed both during roentgeno-anatomic investigations of lung specimens with filling the bronchial tree with contrast substance (6 researches) and during contrast instillation of bronchi in ABP patients while performing microtracheostomy (44 observations). However, for reproduction of ABP model in experiment, the disruption of bronchial passing with parallel infection of pulmonary parenchyma was found insufficient. For example, in one experimental series, atelectasis picture without acute inflammatory signs was received.
Preliminary sensitization of organism and entry of a start doze of an allergen and infection into pulmonary parts with disrupted ventilation and drainage triggered the development of acute inflammatory process in the lungs. Adherence to aforementioned conditions allowed receiving a stable typical ABP picture in the fourth experimental series. In this connection, high pollution of the aerial basin with different admixtures can be viewed as a source of increased sensitization and more serious course of ABP among local residents.
Increased inflammatory infiltration first led to compression of more pliant venous vessels, impeding blood return from affected zone, with preserved (in initial stages of process) arterial afflux. Progress of these circulatory disruptions stopped the blood afflux toward inflammatory zone being the basic reason for the irreversible destructive alterations. Sequential transformation of angio-architectonics in the center of ABP was noted in 14 arteriograms and 21 venograms, performed on pulmonary specimens (31,36).
Pathological vessel transformation in the center of ABP created (in initial stages of the disease) “vessel trap” conditions, in which increased blood afflux toward inflammatory zone as a result of intravenous infusion contributed to rapid increase of alterations in pneumonic focus. This peculiarity of ABP progress with developing pleural complications was noticed in a clinical practice (see Figures 1 and 2). This hypothesis was experimentally supported. (36,46-48). In 4-b experimental series, all animals had acute lung inflammation accompanied by parapneumonic pleuritis. At the same time, destructive focuses in pulmonary tissue were formed in six cases, out of which two cases had a breach into pleural cavity. A dyestuff used in a solution for infusions colored the lung tissue on circumference of inflammatory zone identifying the areas where the inflammatory infiltration had spread (see Figure 3).
Microbiological analysis of the material taken from the morbid area at the time of admitting 542 children did not show a predominance of any particular sort of agents. Pathogenic varieties of Staphylococcus were in 32.7% cases. In 34% of the cases, microflora was not determined. 33.3% of the cases showed the growth of other trivial organisms (Pneumococcus, Escherichia coli, Proteus, Streptococcus et al.), frequency of which was in 1.5% to 12.7% range.
While the excess of secretory exudate in inflammatory zone depended on developmental intensity of the process, disruption of equilibrium between its production and resorption caused the development of a secondary ABP feature - accompanying pleuritis. Aggregation of pleural fluid led to the compression of infected lung and increased intrathoracic pressure. These factors additionally disrupted hemodynamics and ventilation. The results of a visual-laboratory research of pleural exudate reflected the degree of lung inflammation, which was a prognostic sign of disease. The most negative sign was suppurative-hemorrhagic pleuritis corresponding to a vast necrotic area in the lung.
General anomalies in patient's organism.
The development of ABP focus was accompanied by tachypnea and tachycardia, declining their proportion to 1:3 and even to 1:2 (8.7%). The initial data recorded by summary RPG also indicated the increase of the correlation coefficient between ventilation and perfusion indices (1.28 +/- 0.06). The analysis of arterial blood gases in initial ABP stages indicated the excessive pulmonary ventilation (85.2% +/-1.6%).
A stimulus for increasing the ventilation along with its massaging influence on blood and lymph circulation in lungs was the serious alterations of blood flow in pulmonary vessels as a result of reflecting influence of inflammatory focus. The decrease of the flow was manifested in decompensate conditions by signs of right heart sections overload, based on ECG, or increased CVP measure. An additional evidence of critical redistribution of the blood flow in lungs in ABP patients was the discovery of shunting vessels on periphery of the non-afflicted parts received on 2 venograms of lung's specimens (see Figure 4).
A direct anatomical-functional correlation between two blood circulation circles (great and lesser) - under the conditions of significant changes in lung’s blood flow - was observed on the level of peripheral microcirculatory layer. The extent of reconstruction of the systemic microcirculation toward blood redistribution as well as unloading of pulmonary vessels depended on the speed of ABP focus growth and the stage of the disease. Depth and characteristics of the changes in systemic perfusion transformation, along with registering of diuresis in patients and evaluating the biochemical indices, BVC, and AAC, were determined by the results of HRD-ht and HRD-hb. The results of the aforementioned indices showed a strong correlation with the seriousness of the patient’s condition. (25,36,41). The findings of the dynamic patient's examinations allowed highlighting three distinct stages of homeostasis damage which featured compensatory-adaptive character during the initial stages and did not require a special correction. ABP-accompanied transformation of central hemo-dynamics with progressive disturbance of perfusion on periphery was very similar in transformation in capillary channel to other etiological versions of the shock. The development speed of these disorders, which determine the seriousness of the patients’ conditions and represent the immediate danger to patients’ well-being when progressed, allowed determining these indicators of the disease as pulmonary shock (23-25,33,34,36,41). Such a formulation, which points to the cause of graveness of ABP clinical symptoms, obligates providing anti-shock measures.
Pathogenetic validation of approaches for ABP treatment.
The volume of medical procedures for the ABP patients was based on the common classical principles of patient care for the patients with inflammatory-originating diseases of any localization: (a) Actions toward the inflammatory focus; (b) Actions toward the cause of the disease; (c) Common methods to influence patient's organism.
A cervical procaine vagosympathetic blockade on the infected side was the method of first medical aid in action toward the inflammatory focus. We received an objective evaluation of the curative effect of these blockades during ABP using the records comparing RPG done before and immediately after the procedure. (24, 28, 36, 44). The results of the study conclusively showed a decrease of (P > 0.001) after a one-minute ventilation volume, lowering a breath frequency, blood flow and simultaneous correlation balancing between ventilation and perfusion in lungs. Given results as well as subjective improvement of the patients were probably caused by pharmacological vegetative isolation of inflammatory focus and adaptive influence on pulmonary-heart apparatus. In some cases, this procedure was repeated after 12-24 hours.
Action toward the inflammatory focus continued by performing the procedures for restoration of bronchial permeability and lung re-aeration. For the liquefaction of a firm bronchial secretion, along with medications reducing its density, we used steam inhalations 6 (or more) times a day with a help of our patented inhaler (36,38,39,42,50). We used permanent oropharingeal sputum suctions by a soft catheter to evacuate sputum and stimulate a natural protective mechanism such as a cough. In most serious cases (373 observations, 37.5%), in order to accelerate the endo-bronchial assanation, we utilized the tracheobronchial lavage through microtracheostomy according to Keown (24,27,28,36). The strongest effect of this procedure was achieved when positioning a distal catheter’s end in a zone of tracheal bifurcation.
A cervical vagosympathetic blockade and active restoration of bronchial permeability and aeration of lung parenchyma created favorable conditions for successful antibiotic therapy. The application of antibiotics in patients with ABP accounted for poly-etiology of the disease, while the range of medications applied encompassed the possible participants in inflammatory process - both Gram’s positive and Gram’s negative agent strains.
The change of medical approach during the initial stage of so-called “toxic” forms of ABP (use of vagosympathetic blockades, escalation of bronchial drainage processes and complete abandonment of intravenous infusions) highlighted the fact that once compared with an equivalent group, which had the first-aid approach based on intravenous detoxication therapy, the number of pleuro-pulmonary complications had reliably decreased (t=8,65; P 0,001), the hospital stay declined three-fold, and there were no lethal cases. (36). To illustrate, we included roentgenograms from one of ours patients (see Figures 5 and 6).
A majority of the observed patients (755 people; 80%) was transferred to the surgical clinic after the preliminary treatment in pediatric wards because of progressive deterioration of their conditions, therapy inefficiency, and/or addition of pulmonary and pleuro-pulmonary complications. In this category of patients, the treatment approach depended on the character of general and localized deviations. Symptoms of hemodynamics decompensation with decrease of BVC and peripheral microcirculation in combination with extensive metabolic and electrolythic deviations justified a reasonable corrective infusion therapy up to hemotransfusion.
A presence of effusion in a pleural cavity dictated the mandatory administration of the pleural paracentesis with both the diagnostic and healing goals. The accumulation of the pleural effusion by decreasing the useful volume of the pleural cavity and pressuring the ill lung further disturbed its aeration. Therefore, elimination of this additional cause of developing a damaging process was one of the most important conditions of eliminating a pulmonary inflammation. In the presence of serous or serofibrinous fluid, the local medical therapy was limited to pleural paracentesis (recurring if necessary). Pyo- and pyopneumothorax were considered absolute indications for insertion of a chest tube. In 7 cases (0.7 %) where the clinical roentgenological picture corresponded to extensive lung gangrene (total damage of a lobe), urgent thoracotomy with lobectomy was performed.
DISCUSSION
Acute nonspecific inflammations (ANSI), including ABP, have always been considered serious but far from being always fatal processes. Centuries of experience in treating these patients allowed a development of the certain medical treatments, which for a long time were a foundation for ABP elimination. For example, more than two thousand years ago, Hippocrates substantiated the advantages of drainage in patients with empyema in pleural cavity. (1).
Modern views of ANSI continue to be based on classical symptoms described hundreds years ago by Сelsus (rubor, tumor, calor, dolor) and Galen (functio lesae). Practicing doctors know very well that complexity and distinctiveness of ABP clinical manifestations are determined, first and foremost, by the last symptom (functio lesae) which dictates the need of applying specific therapeutic measures.
The introduction of antibiotics into clinical medicine in the middle of last century cardinally changed the methods applied during ABP. The success which followed the initial use of antibiotics for ABP treatment - an almost immediate cessation of inflammatory processes after injecting the first dose - created the impression that the universal cure had finally been found for this category of patients, requiring no supplementary therapeutic efforts. During the next several decades this theoretical illusion played a dominant role in the views and approaches to ABP problem. Therefore, the historical experience in ABP treatment which existed prior to the era of antibiotics is forgotten and uncalled-for. Current initial ABP treatment is limited in most cases to “antibiotics alone.” (6,14,16,19 30 49 54,57,61,65,66,70). For many ABP patients who have inflammatory process in a lung not characterized by rapid development such narrow-focused etiotrpic help is sufficient for successful treatment even outside of the hospital. Acute ABP progress with developing signs of so-called “intoxication” generally requires urgent admission to the hospital where a patient, according to the logic of contemporary ABP concepts, is getting infusion detoxication. If clinical signs of ABP get more severe, the intensity of the aforementioned help increases up to aggressive resuscitation with intravenous fluids. (55).
The published results of the recent studies of ABP force us at least to think about the outcomes of ABP treatments - "parapneumonic effusions develop in 40% to 60% of patients with pneumonia.” (16,52,53). These summarized results demonstrate that every other patient with ABP may need to undergo more invasive supplementary manipulations - due to pleural cavity involvement in the process. (60). Scientific explanation of such a high percentage of complicated ABP forms is generally based on attempts to connect this phenomenon with etiological factor of the disease. At the same time, such fact as progress of clinical and roentgenologic signs of the disease even under complete suppression of mircoflora in inflammatory zone is not considered. (3,14,57,59,63,72). In this connection, it should be noted that experimental ABP model was received by infecting lung with microflora, which under the clinical conditions is generally not viewed as etiological ABP factor. Absence of other points of view regarding the nature of ABP and ways of prophylaxis of its complicated forms is the reason for a long debate concerning advantages or disadvantages of additional, aggressive methods if pleural complications develop. (1-3,6,9,11,13-16,19,30,49,51,55,57,62-67,69-72).
Unfortunately, causation in inflammatory process dynamics of ABP is rarely examined. Although G.Cheng and J.R.E.Vintch (7) correctly point out "primary diagnosis of "pneumonia" and the secondary diagnosis of "pleural effusion"(7) while analyzing pleural empyema observations, they do not recommend any changes to the existing treatment strategy. Therefore, considering the treatment results of pleural empyema as a separate pathology unrelated to the main focus of inflammation in the lung cannot produce accurate conclusions. Pneumonia, even complicated by pleural empyema, should not belong to fatal or overly complicated medical cases - a comprehensive action toward the focus of the infection in a lung, along with an early, adequate drainage of pleural cavity produces wonderful results.
An acute inflammation is one of the most dynamic biological processes and the success of its treatment is determined in which development stage it was diagnosed, stopped, and reversed. This is especially important with rapidly progressive ABP forms (“croupous pneumonia” by old classifications). As our experience shows, early action towards the vascular reaction in the focus of inflammation by use of vagosympathetic blockade, decrease of blood flow to this area by eliminating intravenous infusions during early stages of the disease, intensive restoration of bronchial permeability, and adequate use of antibiotics give the optimal result. After starting the treatment, the progress of disease with inclination to complicated or prolonged course should be viewed as a serious reason for critical analysis of adequacy of undertaken therapy.
In recent years, fibrinolytic therapy and video-assisted thoracoscopic surgery (VATS) became additional methods of treating ABP with pleural empyema. The use of ferments is not an independent method of treating pleural empyema and fibrinopurulent pleuritis; it may be viewed as a supplemental method that reinforces the effect of pleural paracentesis and chest tube’s application. The use of VATS for these patients, however, requires a more thorough approach. Thoracic surgery successfully performed in non-emergency patients should not be automatically used in patients with fundamentally different initial conditions. On one hand, the most popular recommendation is the application of thoracoscopic sanitation of pleura limited by the second stage of pleural empyema, i.e., up to 10 - 14 days since the beginning of this process (51,55); lately, even the earlier stages are considered optimal for this procedure. (49,65).
On the other hand, during this period of the disease, the original focus of the infection of the pleural fabric is not reaching its resolution even during the best case scenario. Administering thoracoscopic manipulations at this stage of the disease assumes a compulsory adherence to the following conditions:
1. Absolute pulmonary collapse of the affected lung with the whole spectrum of the atelectasis-related changes in the organ during the whole surgical procedure.
2. Transfer of the negative intra-pleural pressure into the sharply positive (tension pneumothorax) and the support of this extreme patho-physiologic situation within the timeline of the surgery as a whole.
3. Unavoidable physical movement of the lung tissue which has inflammatory changes remaining.
Any one of the aforementioned reasons during ABP could worsen the course of the disease. However, dangers and complications of new technical methods in treating complicated ABP cases have not been receiving due attention in the press. At the same time, today VATS is the method of choice not only for treating pleaural empyema, but also fibrinous pleuritis. (1,7,9,14,15,16,49,51,54,55,63,64,65,66,71).
In light of the discussion above, any attempts to surgically resolve a purely pulmonary problem are rather puzzling. As experience shows, surgical involvement with ABP patients is a forced measure when the disease has not been timely diagnosed or initial treatment has not prevented the complications. ABP patients are originally not surgical, and a timely pathogenically treatment should not leave a surgeon any chance to practice his or her surgical skills.
CONCLUSION
Prophylaxis of complications of any disease has its indisputable advantages over methods of their eradication. Therefore, the solution of the problem of complicated ABP cases only by improving the treating methods of their complications is only a palliative measure. Contemporary therapeutic strategy in ABP cases requires expert revision and new approaches based not only on the ideas about etiology of inflammatory process, but also about its pathogenesis. It is obvious that initial “antibiotics alone” therapy does not adequately help the patients with rapidly progressive, toxic forms of disease. It is about time to re-examine the indications for routine infusion therapy, especially in early stages of inflammatory development in lungs.
Diagnostic equipment allows today to objectively monitor patients during their treatment. This in turn broadens the conception about dynamics of local and general dysfunctions in ABP cases and objectively proves the influence of different therapeutic methods on such dynamics. The consequence of pathogenically-justified immediate action toward the developing inflammation in lungs should be substantially improved results of treating this group of patients and minimization of surgeons’ involvement.
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Appendix B: Description of the Figures.
Figure 1. X-ray photograph of 2 y.o. girl 12 hours after the first signs of ABP with abdominal pain syndrome were discovered. There is homogeneous shading in a middle-right pulmonary field.
Figure 2. X-ray photograph of the same patient (see Figure 1), 36 hours after starting the inpatient care (antibiotic therapy, intravenous infusion therapy with detoxification). There is an intensive homogenous shading of almost the whole right hemithorax with mediastinum, dislocation to the left, and a cavity with a fluid level in upper pulmonary field.
Figure 3. Macro-preparation of the lung, experiment, series 4b. Massive focus of the inflammation in a pulmonary surface (red arrow), surrounded by the additional sections of infiltration with blue shading (blue arrows).
Figure 4. Venogram of lung’s preparation with a massive focus of the inflammation in the upper portion (histology which followed, did not show the features of the necrosis in inflammation’s focus). Sharp depletion of the venous picture in the upper portion of the lung. Lower portion shows relatively large vascular formations of a half-ring shape with a well-contrasted venous vessels in the background.
Figure 5. X-ray photograph of a 22 month old patient, 24 hours after starting ABP clinic. Intensive homogenous shading in basal sections of both lungs with moderate thickening of pleura in the left lung.
Figure 6. X-ray photograph of the same patient (see Figure 5) five days following the clinical treatment (vagosympathetic blockades, antibiotic therapy, bronchus-draining therapy, including lavages through micro-tracheostoma.) Full recovery of airiness in both lungs.
Appendix C: Figures.
Figure 1:
Figure 2:
Figure 3:
Figure 4:
Figure 5:
Figure 6:
