Intrapleural quinacrine instillation for recurrent pneumothorax or persistent air leak

doi:10.1016/0003-4975(93)90999-X

The Annals of Thoracic Surgery

Volume 55, Issue 2, February 1993, Pages 368-371

https://doi.org/10.1016/0003-4975(93)90999-X Get rights and content

Abstract

From 1982 to 1990, 27 patients with recurrent pneumothorax or persistent air leak (28 episodes) underwent pleurodesis with intrapleural administration of quinacrine, according to a standardized scheme. A first evaluation was done about 1 month after the intervention. In August 1990, all patients were invited for a second check-up. In 4 patients quinacrine plasma concentrations were determined. There was one early failure. No late recurrences were observed. Neither serious nor late complications were seen with our low-dose regimen. Transient fever was the only constant side effect. In contrast to other chemicals proposed for pleurodesis, quinacrine did not cause major pain. Only very low quinacrine plasma concentrations (peak, <10 ng/mL) were found. In conclusion, chemical pleurodesis with quinacrine can be considered a safe and effective treatment. The number of administrations as well as the dosage are important to prevent morbidity and recurrence.

References (21)

K Granke et al.
The efficacy and timing of operative intervention for spontaneous pneumothorax
Ann Thorac Surg
(1986)
JE Harvey et al.
The difficult pneumothorax
Br J Dis Chest
(1987)
JE Heffner et al.
Tetracycline pleurodesis. Adios, farewell, adieu
Chest
(1992)
GH Almassi et al.
Chemical pleurodesis in the presence of persistent air leak
Ann Thorac Surg
(1989)
S Björkman et al.
Determination of quinacrine in plasma by high-performance liquid chromatography with fluorometric detection
J Chromatogr
(1987)
RO Ofoegbu
Pleurodesis for spontaneous pneumothorax. Experience with intrapleural olive oil in high risk patients
Am J Surg
(1980)
LW Stephenson
Treatment of pneumothorax with intrapleural tetracyline
Chest
(1985)
AJ Larrieu et al.
Intrapleural instillation of quinacrine for treatment of recurrent spontaneous pneumothorax
Ann Thorac Surg
(1978)
WG Smith et al.
Treatment of spontaneous pneumothorax
Thorax
(1962)
D Kaiser
Fibrin gluing in spontaneous pneumothorax
Pneumologie
(1989)

There are more references available in the full text version of this article.

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Quinacrine (4-N-(6-chloro-2-methoxyacridin-9-yl)-1-N,1-N-diethylpentane-1,4-diamine) is an acridine derivative available as quinacrine dihydrochloride for oral administration [3]. Quinacrine has also been used as an antimicrobial for giardiasis [4,5], an anti-inflammatory for systemic lupus erythematous and rheumatoid arthritis [6–10], and an intrapleural sclerosing agent for malignant pleural effusions and pneumothorax prophylaxis in patients with high risk of recurrence [11–16]. Furthermore, it is still used in some countries for female sterilization and is under clinical evaluation for Creutzfeldt-Jakob disease [17,18].
Quinacrine, also known as mepacrine, has originally been used as an antimalarial drug for close to a century, but was recently rediscovered as an anticancer agent. The mechanisms of anticancer effects of quinacrine are not well understood. The anticancer potential of quinacrine was discovered in a screen for small molecule activators of p53, and was specifically shown to inhibit NFκB suppression of p53. However, quinacrine can cause cell death in cells that lack p53 or have p53 mutations, which is a common occurrence in many malignant tumors including high grade serous ovarian cancer. Recent reports suggest quinacrine may inhibit cancer cell growth through multiple mechanisms including regulating autophagy, FACT (facilitates chromatin transcription) chromatin trapping, and the DNA repair process. Additional reports also suggest quinacrine is effective against chemoresistant gynecologic cancer. In this review, we discuss anticancer effects of quinacrine and potential mechanisms of action with a specific focus on gynecologic and breast cancer where treatment-refractory tumors are associated with increased mortality rates. Repurposing quinacrine as an anticancer agent appears to be a promising strategy based on its ability to target multiple pathways, its selectivity against cancer cells, and the synergistic cytotoxicity when combined with other anticancer agents with limited side effects and good tolerability profile.
Determination of quinacrine dihydrochloride dihydrate stability and characterization of its degradants
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The Food and Drug Administration has approved the use of QDD not only in the treatment of tapeworm infestation2 and resistant giadiasis3 but also in systemic lupus erythematosus.4 It has also been tested in diseases such as pneumothorax,5 asthma,6 and hepatitis.7 Moreover, QDD has been considered in the treatment of Creutzfeldt–Jacob disease8–10 and continues to be the subject of various research.10–12
Although quinacrine dihydrochloride dihydrate is a widely used drug substance, a comprehensive determination of its stability profile is lacking. In this work, an integrative approach is implemented to determine the drug stability both in the solid state and aqueous solutions, identify the impurities that can be found in the active pharmaceutical ingredient, and evaluate the associated toxicity risks. Thermal analyses pointed out a two‐step dehydration of the solid state. This phenomenon seems to be consistent with the organization of the water molecules in the crystal structure and results in the destruction of the lattice. Seven related compounds of quinacrine have been identified by liquid chromatography–ion trap mass spectrometry. The main thermal degradant both in the solid state and the solution corresponds to the N‐deethyl compound, whereas quinacrine tertiary amine oxyde appears to be a signal impurity of oxidative stress in solution. Moreover, two photolytic impurities can be formed in solution either by aromatic amine cleavage or via O‐demethylation. Additionally, using computational approaches, the analysis of the potential toxicity of the impurities compared with the parent compound one shows that ketone and O‐demethyl derivatives may exhibit specific toxicity profiles. © 2011 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 100:3223–3232, 2011
Postoperative Strategies to Treat Permanent Air Leaks
2010, Thoracic Surgery Clinics
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If the residual lung is fully expanded, pleurodesis might be a suitable option to facilitate sealing of the visceral pleura. Tetracycline, quinacrine, talcum, and silver nitrate have been employed successfully in selected cases.32–36 All these chemical agents have been able to favor pleural inflammation with encouraging results; however, none contributed to definitively solve the problem in all patients.
Pleurodesis with an autologous blood patch to prevent persistent air leaks after lobectomy
2007, Journal of Thoracic and Cardiovascular Surgery
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However, notwithstanding these well-known methods, some patients still have this complication; when it occurs, a number of procedures may be used to solve the problem. Conservative approaches include a longer period of drainage; physiotherapy; pleurodesis with tetracycline, quinacrine, talcum, or silver nitrate; pneumoperitoneum; and the use of a Heimlich valve.1-7 These methods have produced encouraging results in selected settings, but none have definitively solved the problem.
Air leakage after pulmonary lobectomy is a well-known problem often contributing to extended hospitalization. Many techniques have been proposed to prevent and treat air leakage, but none have been proved incontrovertibly effective. We evaluated the role of an autologous blood patch after pulmonary lobectomy.
Twenty-five patients with air leaks on the sixth postoperative day after lobectomy were enrolled in this study. They were randomly assigned to 2 groups: group A (12 patients), with 50 mL of autologous blood infused in the pleural cavity; and group B (13 patients), with 100 mL of blood infused. These 2 groups were retrospectively compared with the last 15 patients showing the presence of air leaks for at least 6 days (group C) (in this group the duration of leakage after the sixth postoperative day was compared). We recorded the duration of posttreatment air leaks and hospitalization.
Air leaks stopped 2.3 ± 0.6 days after the procedure in group A, 1.5 ± 0.6 days after the procedure in group B, and after 6.3 ± 3.7 days in group C. The air leakage disappeared within 72 hours in all patients in groups A and B. There was a statistically significant difference in the duration of drainage between groups A and B (P = .005), groups A and C (P = .0009), and groups B and C (P = .0001), showing the effectiveness of an autologous blood patch, particularly with 100 mL of blood.
Management of air leaks after lobectomy with an autologous blood patch is easy, safe, and effective, and does not add costs. It may become the gold standard treatment early in the postoperative course.
Management of malignant pleural effusions and pneumothorax
2000, Radiologic Clinics of North America
Citation Excerpt :
Residual pneumothoraces may also be seen after catheter placement if the air leak is large, wherein insertion of a second catheter or large thoracostomy tube may be required for successful treatment. Patients with a persistent pneumothorax may also benefit from chemical pleurodesis using sclerosing agents, such doxycycline, talc, or bleomycin.2,33,53,66 Complications of percutaneous placement of small-bore drainage catheters for the treatment of pneumothorax are rare.
Acute mental status changes following intrapleural instillation of quinacrine for traumatic pneumothorax
1996, Psychosomatics

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Original articleIntrapleural quinacrine instillation for recurrent pneumothorax or persistent air leak

Abstract

Ann Thorac Surg

Br J Dis Chest

Chest

Ann Thorac Surg

J Chromatogr

Am J Surg

Chest

Intrapleural instillation of quinacrine for treatment of recurrent spontaneous pneumothorax

Ann Thorac Surg

Treatment of spontaneous pneumothorax

Thorax

Fibrin gluing in spontaneous pneumothorax

Pneumologie

Original article
Intrapleural quinacrine instillation for recurrent pneumothorax or persistent air leak