IV intermittent chemotherapy in rural areas

SM
4 April
Sovetskaya medicina - 79
(soviet medicine - 79)
Body of the Ministry of Health Care of the RSSR
Monthly Research and Practice Journal
Editorial Board:
Editor in chief: I. I. Sivkov
Y. N. ARTEMYEV, N. N. VVULINA, L.G. YEROKHINA, Y. A. ILYINSKIY, B. D. KOMAROV, I. M. KOROCHKIN, I. Y. KOCHNOVA, M. K. KUZMIN, I. A. MANUILOVA, Y. I. MAROVA, V.N. NIKIFOROV, V. P. OKHOTSKIY, Y. M. PANTSYREV, B. E. PETERSON, V. S. POMELOV (executive secretary), V. P. POMERANTSEV (Deputy Editor in Chief), Y.A. PYTEL, V. B. RUMYANTSEV, A. M. SAZONOV (Deputy Editor in Chief), E. Y. SEVEROVA, M. Y. SEMENDYAEVA (executive secretary)
Founded in june 1937
“Medicina” publishing house
Moscow – 1979
Prof. I. G. Ursov, F. N. Volokitin, doctoral candidate of medical sciences V. G. Kononenko

Outpatient and inpatient intravenos intermittent chemotherapy for tuberculosis patients in rural areas

Novosibirsk Research Institute for Tuberculosis, Ministry of Health Care of the USSR 
Submitted 12/XII 1978

The issue of increasing the treatment effectiveness for pulmonary tuberculosis patients is particularly pressing in rural areas, where the results of therapeutic measures are lower compared to urban areas. It is necessary to use the most effective treatment methods and to improve the organization of the treatment process, particularly in terms of outpatient controlled intermittent chemotherapy (S. P. Burenkov, F. B. Shebanov).

It is known that intravenous administration of streptomycin, isoniazid and PASA is the most effective of the widely used tuberculostatic therapy methods. The effectiveness of this method is increased when combined with brief collapse therapy and early operative treatment. However, the available published data had been acquired in clinics and large inpatient hospitals in cities. Only a few works have been dedicated to application of intravenous chemotherapy in tuberculosis patients in rural antituberculosis facilities (V. P. Malko-Skroz). As for outpatient intermittent intravenous therapy, no published works whatsoever are available. At the same time, there is a real opportunity to improve the treatment results of first-diagnosed tuberculosis patients as well as to shorten the duration of inpatient treatment for the majority of patients with open tuberculosis forms to 2.5-3.5 months, while the use of outpatient intravenous chemotherapy (3 times weekly) would allow the patients to return to their families and jobs relatively quickly. There are undisputable advantages in avoiding disruptions that are caused by months of inpatient care and prolonged absence of patients from their families and work colleagues. Furthermore, on the days when the patients are free of intravenous infusions, they should be involved in productive labor, therefore considerably decreasing the costs of sick leave.

The antituberculosis department of the Ordynskoe central district hospital (Novosibirk region) has been using intravenous drop infusion of streptomycin, isoniazid and PASA on an intermittent basis (3 times weekly) for treatment of pulmonary tuberculosis patients since 1972. During this period, 144 patients received prolonged intravenous chemotherapy, of which 75 completed the infusion course in inpatient care, and 69 continued it in outpatient conditions.

110 of the patients were male, 34 female; the patients were aged 18 to 63, average age was 34. 41 patients had the focal tuberculosis form, 48 infiltrative tuberculosis, 20 disseminated, 7 had tuberculoma, 24 fibrous-cavernous tuberculosis, and 4 exudative pleuritis.

115 patients were first-diagnosed with tuberculosis, while the remaining 29 had already received a prolonged chemotherapy course and were registered for treatment due to a relapse or aggravation of a chronic destructive process.

Before intravenous chemotherapy was prescribed, the prevailing majority of patients had intoxication symptoms. Almost half of the patients suffered from a noticeable lack of body mass; 4/5 reported malaise, low appetite, weakness and moist cough; three-quarters reported subfebrile or febrile body temperature in the evening; 122 patients displayed various deviations in the blood picture (frequent cases of increased ESR, moderate leukocytosis, left blood shift and lymphopenia). Analysis of phlegm and washwater from the bronchi and the stomach by plain bacterioscopy, flotation or plating showed tuberculosis mycobacteria in 96 (66.7%) patients, including 74 (64.3%) of the 115 first-diagnosed ones.

Radiography showed cavities and caverns in 66 (45.8%) of 144 patients, including 51 (44.3%) of the 115 first-diagnosed ones.

Therefore, process acuteness and distribution, bacterial excretion and pulmonary tissue cavitation were considered indications for intravenous chemotherapy.

The medicinal mixture consisted of 400 ml 3% PASA solution in rongalite, 6-9 ml of 10% isoniazid solution (0.6 – 0.9 g of dry substance) and 1 g streptomycin. The two latter drugs were added to the sterile PASA solution immediately before infusion. Drop infusions were prescribed every other day. The duration of the procedure was initially 2-2.5 hours; if they were well-tolerated by the patient during 1 month, the infusion time was decreased to 1 hour or 40-45 minutes, depending on the individual capabilities of the patient.

During 3.5 to 9 months, the patients received 30 to 120 infusions (52 on average). The average number of infusions for patients receiving only inpatient intravenous therapy was 44, and for patients continuing intravenous chemotherapy in outpatient conditions – 61. As a rule, patients with focal tuberculosis, infiltrative tuberculosis without cavitation, and patients with exudative pleuritis did not require prolonged intravenous administration of streptomycin, isoniazid and PASA. Within 1 to 3 months, the general condition of the patients would be improved, their blood picture normalized, and the exudate, infiltrations and disseminations dispersed. Such patients were switched over to traditional tuberculostatic treatment regimens. For patients with bacterial excretion and cavitation, intermittent intravenous chemotherapy was continued until stable abacillation was achieved, the attack reliably suppressed, the cavities eliminated, or the patient prepared for operative treatment.

For patients with first-diagnosed destructive pulmonary tuberculosis, the intravenous treatment course was on average 6 to 6.5 months; each of them received 78-84 g streptomycin, 47-51 g isoniazid and 700-750 g PASA. Had the therapy been administered daily, the total medicinal load on the body would've been 2-2.5 times higher over the same term of 180-195 days. This also makes obvious the advantage of intermittent intravenous chemotherapy over the traditional daily one. It is a form of therapy that is more sparing for the patient, completely opposite to the treatment under which maximal tolerated doses of isoniazid are prescribed, and a patient with the body mass of 70 kg receives up to 315-375 g of the drug, or even more, therefore testing the capabilities of the body to adapt to medicinal overloads; furthermore, suppressing the toxic effect of isoniazid requires high doses of pyridoxine, which serves as an antidote.

Patients with chronic destructive pulmonary tuberculosis and relapses, in addition to the above intermittent intravenous therapy also received oral ethionamide (protionamide) or ethambutol – therefore, polychemotherapy was used to overcome the frequent cases of medicinal resistance of the mycobacteria to tuberculostatic drugs. In such cases, streptomycin in the medicinal solution was replaced by kanamycin or florimycin. Sometimes isoniazid was replaced by saluzide solution in ampoules (20 ml 5% solution or 10 ml 10% solution).

Abacillation was achieved in 92 (95.8%) out of 96 patients with bacterial excretion; in 73 (98.6%) of 74 first-diagnosed patients that displayed bacterial excretion before the start of intravenous tuberculosis mycobacteria chemotherapy, the bacterial excretion was stopped after 2 months on average. Among the patients with bacterial excretions and chronic destructive processes, and patients with relapses, abacillation was achieved in 19 out of 22 patients.

Out of 66 patients with lung cavities prior to the intravenous chemotherapy, cavities were closed in 49 (74.2%) patients, out of which 14 received operative treatment. Out of 15 patients with chronic destructive processes receiving prolonged tuberculostatic therapy or with relapses, cavities only closed in 6 patients. Cavern closing was achieved in 43 (84.5%) out of 51 first-diagnosed patients, on average after 4.6 months.

Among 72 first-diagnosed tuberculosis patients that had worked prior to the disease, 64 were restored to full labor capacity and 8 were temporarily incapacitated due to surgery.

During outpatient intermittent intravenous therapy, 15 patients were employed; their total duration of treatment was 224 days, while during 448 days, they worked in light conditions, and returned to normal work on average after 2 months. Even though the specifics of rural areas complicate controlled chemotherapy, because the residences of some patients are remote from the antituberculosis facility, and make rational employment more difficult, proper effort of the district phthisiologist should be enough to overcome these issues.

Therefore, intermittent intravenous therapy with streptomycin, isoniazid and PASA is a sparing, well-tolerated, highly effective, cost-effective and perfectly controllable method that allows decreasing the duration of inpatient care for tuberculosis patients (down to 2.5-3.5 months), not only for patients in the infiltration stage, but also for ones with destructive processes and tuberculosis mycobacteria. This method allows continuing intravenous therapy effectively in outpatient conditions, therefore relatively quickly returning the patients to their families and jobs and using their residual working capacity. In rural areas, implementing the above tactic during 6-8 months allowed to achieve abacillation in practically all of first-diagnosed patients during 1 to 3 months and eliminate cavitation in 80-90% patients during 4-5 months, including early operative treatment. The organizational issues of using the patients' residual working capacity during intermittent intravenous outpatient polychemotherapy require further study.

References

Burenkov S.P. – "Probl. Tub." (Issues of Tuberculosis), 1978, N 1, p. 6-11
Malko-Skroz V.P. – same, 1970, N 4, p. 87-88
Shebanov F. V. – "Vsesoyuzniy Syezd Ftiziatrov 8. Trudy" (Union Phthisiologists Convention N8. Proceedings).  Kishinev, 1976, p. 76-78.