Ministry of Health of the Ussr

MINISTRY OF HEALTH OF THE USSR

NOVOSIBIRSK STATE MEDICAL INSTITUTE

Printed as manuscript

UDC 616.24 – 002.5 – 085.2/3 : 616.25 – 003.219 – 021.6

KUZINA Lyudmila Nikolayevna

3-6 MONTH ARTIFICIAL PNEUMOTHORAX WITH INTERMITTENT

INTRAVENOUS CHEMOTHERAPY IN NEWLY DIAGNOSED PATIENTS WITH DESTRUCTIVE PULMONARY TUBERCULOSIS

(140026 - Phthisiology)

Author’s abstract of the

thesis for the degree of Candidate (Ph.D.) of Medical Sciences

Novosibirsk

1975

The work was performed at the Novosibirsk Scientific Research Institute of Tuberculosis (Director is the Honored Doctor of the RSFSR, Doctor of Medical Science I.G.Ursov) and Tomsk Oblast TB dispensary (the Chief Doctor is the Candidate (Ph.D.)of Medical Sciences O.E. Sharaburova).

Research supervisor:

Honored Doctor of the RSFSR, Doctor of Medical Sciences. I.G.Ursov

Official opponents:

E.I.Schutskaya, MD, Professor

G.M.Kagalovsky, MD, Professor

External review of the scientific and practical value of the thesis was obtained from the Tomsk State Medical Institute named after Order of Red Banner of Labor.

Abstract was sent on ______197

The defense of a thesis will be held on ______197

At the meeting of the Scientific Council on the clinical sciences of the Novosibirsk State Medical Institute (630091, Novosibirsk, 52 Krasny Prospect).

The thesis is available in the library of the institute.

The scientist, the Secretary of the Council

The Doctor of Medical Sciences, Professor Sidorova

Despite the great advances in the fight against tuberculosis, which became particularly evident in our country with the large-scale implementation of tuberculostatic therapy and phthisiological and surgical methods into practice, the cure of the destructive pulmonary tuberculosis is currently not achieved in 20-40 % of patients.

According to data, provided by A.L.Terlikbayev (1974), the caverns (tuberculous cavities) closed in 60.6% patients in Kazakhstan after 12-month supervision. As the experience gained in Ukraine shows (L.S.Mamolat et al., 1965), long-term hospitalization of patients with newly diagnosed destructive pulmonary tuberculosis in the basic hospitals, where the best staff of the phthisiologists works and all the opportunities are created for the adequate treatment and monitoring, does not result in cure of caverns in about one fifth of those of them who had been treated for more than 3 months.

The abovementioned conditions suggest that the new schemes and methods of treatment should be currently searched, as well as enable some researchers (Bondaryev I.M. et al., 1970, N.Ya.Batmanov et al., 1973, A .; A.Ye.Rabukhin, 1973; F.V.Shebanov, 1973) to raise the question of the intensification of destructive pulmonary tuberculosis chemotherapy fully reasonably. The resolution of VIII All-Union Congress of Phthisiologists (1973) suggests the same.

The ways of “tuberculostatic therapy”, which would significantly increase its efficacy as early as in the first months of treatment of patients with newly diagnosed destructive pulmonary tuberculosis, searched for in the Novosibirsk Scientific Research Institute of Tuberculosis over the recent years, resulted in the selection of intermittent (every second day) intravenous drop infusion of streptomycin solutions, tubazid (isoniazid) and paraaminosalicylic acid (PAS) (Serebrov, Kononenko, Sharapova) as the most reasonable method. It was shown that the efficacy of this method is not inferior to that of the daily drop infusions of the same drugs, but it is much better tolerated by the patients and causes fewer side effects. Moreover, it provides an opportunity to overcome drug intolerance, does not require monitoring of administration of these drug products to patients, it is organizationally more available to twice the number of patients, and therefore it is more cost efficient than a daily administration. Intermittent intravenous chemotherapy according to the abovementioned scheme does not exclude the possibility of addition of tuberculostatics of the second line, as well as pathogenetic treatments. Thus, being prescribed from the first days of patients’ hospitalization, intermittent intravenous chemotherapy is the way of intensification of therapeutic interventions. But as practice shows, using intravenous chemotherapy alone with three abovementioned tuberculostatics makes it possible to achieve the elimination of destructive changes in about four fifths of patients with newly diagnosed pulmonary tuberculosis.

In order to maximize the cure rate, the use of additional treatments is apparently required. As it is known, such means of the active influence on fresh cavernous changes include therapeutic pneumothorax, which was successfully prescribed by phthisiologists over several decades back in the pre-antibacterial era. With the development of tuberculostatics, the procedure of artificial pneumothorax management has significantly changed. It was continued for not more than 1-1.5 years, and in some cases even less than this period. The authors, who studied the effectiveness of short-term artificial pneumothorax (N.S.Pilipchuk, 1960; K.A.Harcheva, 1962,1972; L.A.Vinnik, 1964; L.S.Kartoziya, 1965, I.A.Kutkov, 1972; L.V.Sazonova, 1974), confirmed that it can result in the recovery of up to 95% of patients, when combined with chemotherapy. But no evidence of use of the short-term artificial pneumothorax combined with concomitant intravenous tuberculostatic therapy was found in the available literature.

Moreover, as was proven by the works of some authors, intravenous chemotherapy with streptomycin, PAS and isoniazid (tubazid) results in a much more rapid resolution of inflammatory infiltrative and focal changes than that observed with usual administration of the same tuberculostatics (Yu.M.Repin, 1964; F.V . Shebanov and Yu.G.Grigoryev, 1967; O.M.Ivanyuta, 1971, etc.). The faster cessation of abacillation (cessation of bacterial excretion in the sputum), as well as faster healing of destructions are observed.

Since all abovementioned is true, it has been suggested that the duration of artificial pneumothorax with intravenous chemotherapy may be reduced to 4-6 months, that is by 2-4 times, and is limited only by the period of the patient’s first hospital stay. Such a simplification allows us not only to resolve a number of organizational difficulties associated with the return to artificial pneumothorax in the outpatient practice, but also to avoid the risk of complications that had been observed in the past in case of long-term continuation of insufflations. In addition, one can expect to solve the problem of pre-term discharge from the hospital, since there is a higher probability of healing of the collapsed cavern with the use of artificial pneumothorax in this case as well. Therefore, the procedure of early application of artificial pneumothorax with the use of intermittent intravenous chemotherapy with the first-line drugs, would be, in our opinion, an optimal way of intensification of therapeutic interventions, as discussed above.

Thus, the purpose of this work was to study the possibilities of use of the 3-6-month therapeutic pneumothorax and intravenous drop infusions of streptomycin, tubazid and PAS 3 times per week (every second day) on the first - hospital step of treatment in adult patients with newly diagnosed destructive pulmonary tuberculosis.

Specifically, the following tasks were set to be resolved:

1) to evaluate the efficacy of the use of the early short-term artificial pneumothorax, in combination with intermittent intravenous chemotherapy;

2) to study the nature and frequency of any types of healing of caverns under the influence of such combination therapy;

3) to develop the indications and methodology of short-term artificial pneumothorax management at the present stage in treatment of patients with destructive forms of pulmonary tuberculosis.

The frequency and nature of the residual changes in the lungs as well as functional changes of external respiration and cardio-vascular system under the influence of short-term pneumothorax were studied in the study.

General and clinical characteristics of the patients.

Method of research

Our observations are related to the direct results of inpatient stay of 140 patients who were distributed into 2 groups. The first group included 68 persons who were treated only with intravenous infusions of streptomycin, tubazid and PAS every second day. The second group included 72 patients, in whom the artificial pneumothorax was used in addition to intermittent intravenous therapy.

The patients under observation included 93 males and 47 females; their average age was 31.7 ± 1.4 years. All the patients had the pulmonary tuberculosis diagnosed for the first time. According to the current classification, the analyzed groups had the patients with focal (12.2%), infiltrative (75.6%) and metastatic (12.2%) pulmonary tuberculosis. Mycobacteria were excreted by 84.2% of patients. Primary drug resistance of mycobacteria was found in 11.7% patients in the group I and 12.5% patients- in the second group. Monoresistant cultures prevailed among all the resistant cultures. The destruction was confirmed in all cases with the findings of radiological tomography. Tuberculous changes mainly occupied 1-2 lobes (91.4%). The right-side processes dominated. The destruction was most commonly localized in 1-2 segments (83.4%). Bilateral destructive process was observed in. 9.3% of cases. Specific changes in the bronchi were detected in 8.3% patients of the second group. Concomitant diseases were found in 5.9% patients in the first group and 11.1% of the patients in the second group (chronic cholecystitis, I-II st.hypertensive disease, gastritis).

Statistical processing showed that there were no significant differences between the analyzed groups of patients in terms of age or sex, objective symptoms or clinical forms. This gave us the right to consider them fully representative for evaluating the dynamics of the process and final outcomes of treatment according to the selected schemes.

From the first days of hospitalization, the patients in both groups were administered with intravenous drop infusions of streptomycin, tubazid and PAS three times a week (every second day) with no additional prescription of the same or other tuberculostatics in the intervals.

The drug mixture contained the following substances:

PAS 3% - 400-500 ml. on rongalite,

tubazid 10% - 6.0-10.0 ml

dihydrostreptomycin - 1.0

vitamins were alternated: vit. C 5% - 2,0; vit.B1 5% - 1.0; vit. B6 5% - 1.0.

When choosing the drugs, we sometimes replaced tubazid with saluzidum (5% - 20.0), dihydrostreptomycin – with streptomycin calcium chloride or streptomycin - sulfate.

The use of short-time artificial pneumothorax was preceded with intermittent intravenous therapy on average for 6-7 weeks. Therapeutic pneumothorax was used in 31 patients on the first month, in 25 patients on the 2nd month and in 16 patients – on the 3rd-4th months. Pneumothorax was used early almost in four fifths of patients, on the month 1-2 of antibacterial therapy. With limited processes without expressed intoxication, we considered it possible to use intravenous chemotherapy, preceding insufflations, for 2-3 weeks. In case of more disseminated processes with marked infiltration and bronchogenic colonization, the intravenous infusions were continued, mainly, for 1.5-2 months in order to resolve perifocal inflammatory changes. 73 pneumothoraxes were used in 72 patients. On average, thoracoscopy was performed in 54 (75%) patients 3-4 weeks after the date of the first insufflation. Of these, no adhesions were found in 6 of them. Non-burnable adhesions were found in 2 patients. Complete destruction of pleural adhesions was reached in 95.8%, according to the method developed by A.I.Borovinsky (1964). Thoracoscopy was not conducted in the remaining 18 patients due to the clinical effectiveness of pneumothorax from the first days of his use. Experience showed that the destruction of adhesions soon after the formation of the sufficient collapse leads to the rapid collapse of the cavern, i.e. creates the preconditions for their scarring.

Immediate outcomes of treatment in the compared groups of patients

Duration of therapeutic pneumothorax in 83.6% of patients was from 3 to 6 months, and it was not more than 4 months in half of the patients. The average duration of insufflations from the date of the first insufflation was 4.5 ± 0.2 months (Table 1).

Duration of artificial pneumothorax Table 1.

Number of pneumothoraxes / Duration of artificial pneumothorax (months)
Up to 2 / 3-4 / 5-6 / 7-8
73
100% / 6
8.2% / 31
42.5% / 30
41.1% / 6
8.2%

The criteria for the end of the therapeutic pneumothorax were as follows: stable clinical well-being, cessation of bacterial excretion (abacillation), established by the method of repeated cultures, radiological tomographic data in the dynamics, showing the healing of the cavity in one way or another.

The average duration of hospital stay of the patients treated with short-term artificial pneumothorax was not significantly different from that in patients treated only with the intermittent intravenous chemotherapy (7.0 and 6.4 months, respectively, p> 0.05), although the artificial pneumothorax was started, continued and ended successfully over this time. This fact should be emphasized, since the use of early pneumothorax during the short term does not extend the time of patient’s stay in a hospital, it does not separate him/her from his/her family and work for a long time. And, as it is known, prolonged isolation of patients negatively affects their mood and mental status, leading to more frequent noncompliance with their regime. Ability to perform all the steps of therapeutic pneumothorax in the hospital makes it possible to fully control each patient with such kind of collapse therapy.

As for the effects of intoxication, physical changes, changes in hemogram and erythrocyte sedimentation rate, etc., their favorable dynamics was observed synchronously within the same period in both groups; no significant differences were seen.

When considering one of the major criterion of the treatment effectiveness – abacillation (cessation of bacterial excretion) – it was found that this parameter was high in both analyzed groups (91.2 ± 3.5% and 98.4% ± 1.6%, respectively, p> 0.05). And the average periods, during which there was the negative reaction of sputum and bronchial epithelial lining fluid (2.7 ± 0.2 months), coincided (Table 2).

The frequency and periods of abacillation in both groups of patients

Table 2

Group of patients / The number of persons discharging bacilli / Of them, abacillated persons (percent)
Total / Including within terms(months)
1-3 / 4-6 / 7-8
The first / 57 / 91.2±3.5 / 73.7 / 14 / 3.5
The second / 61 / 98.4±1.6 / 85.2 / 8.3 / 4.9

But an assessment of the radiological dynamics fully proved the advantage of combined use of short-term artificial pneumothorax and intravenous chemotherapy, prior to use only infusion intermittent therapy with streptomycin, tubazid and PAS.

There was the distinct resolution of perifocal infiltration (85.7%), reduction in the size of the cavities (35.9%) in the patients of both groups as soon as within 1 month of treatment. Of the 68 patients, treated only with intravenous infusions every second day, the closure of cavities was achieved in 56 patients (82.3 ± 4.6%). The caverns closed by 2-4 months of treatment with intravenous intermittent infusions in almost half (47%) of them. The average closing time of destructions in the patients of this group was 4.6 ± 0.2 months. The different surgical means had to be used in 9 of 12 persons, in whom the destruction cavities had not closed. The other 3 persons flatly refused surgery.