Malignant Effusions
L. Bressler
November, 1997
OBJECTIVES
1. Discuss, briefly, the factors responsible for the development of malignant effusions.
2. Discuss the treatments used in the management of malignant effusions.
REQUIRED READING
NONE
SUGGESTED READING
NONE
I. MALIGNANT PLEURAL EFFUSIONS
The pleural space normally contains about 5-20ml of fluid. Usually the concentration of protein in this fluid is <2gm/dl. Factors that promote increased collection of fluid in this space (ie. a pleural effusion) include: increased capillary permeability, increased hydrostatic pressure (eg. in CHF), increased negative intrapleural pressure (eg. atelectasis), decreased oncotic pressure (eg. hypoalbuminemia), or increased pleural fluid oncotic pressure (eg. with pleural tumor growth). Impaired pleural lymphatic drainage also leads to accumulation of pleural fluid.
The most important factors contributing to the development of MALIGNANT PLEURAL EFFUSIONS are INCREASED CAPILLARY PERMEABILITY (from inflammation or disruption of capillary endothelium) and IMPAIRED LYMPHATIC DRAINAGE due to obstruction by tumor. These factors most commonly result from direct invasion of the pleural space by primary or metastatic tumor.
The most common tumors causing malignant pleural effusions are: LUNG CANCER, BREAST CANCER and LYMPHOMAS.
SYMPTOMS associated with malignant pleural effusions include: DYSPNEA, COUGH and CHEST PAIN. Dyspnea is due to pleural compression. Cough is nonproductive. It is caused by compression of the bronchial walls by fluid. Inflammation of the parietal pleura results in pleuritic chest pain.
The severity of symptoms is related to the rapidity with which the fluid accumulates rather than to the amount of fluid. Most effusions have more than 500ml of fluid.
THORACENTESIS, the removal of the pleural fluid through a chest tube, is both diagnostic and therapeutic. The fluid is sent for analysis: cytology (to look for the presence of malignant cells), protein (>3gm/dl in malignant effusions), specific gravity (>1.025 in malignant effusions), pleural/serum LDH (>0.6 in malignant effusions). Symptoms will improve with thoracentesis, but fluid removal alone will not generally be successful in controlling the effusion (ie. the recurrence rate in people treated with thoracentesis alone and followed for one month is 97%, with the majority of recurrences seen in 1-3 days).
SCLEROSIS - This procedure produces fibrosis and obliterates small pleural blood vessels. It is done after the space occupied by the effusion is obliterated by thoracentesis followed by suction drainage. The purpose of sclerosis is to PREVENT REACCUMULATION.
The following agents have been used for sclerotherapy:
- QUINACRINE
- TALC
- NITROGEN MUSTARD
- THIOTEPA
- BLEOMYCIN
- DOXORUBICIN
- 5-FLUOROURACIL
- MITOXANTRONE
- DOXYCYCLINE
The cytotoxic drugs work by producing fibrosis, NOT BY EXERTING AN ANTINEOPLASTIC EFFECT. Systemic side effects (bone marrow suppression) can be seen with the intrapleural administration of cytotoxic drugs.
TETRACYCLINE was among the most commonly used agents for sclerotherapy until recently, when the only parenteral preparation was removed from the market by the manufacturer. A variety of other agents have been recommended in its place. The following represents some general information about the intrapleural administration of some of these agents. Individual procedures should be reviewed for each drug if needed.
- Patients are premedicated with opioid analgesics about 1/2 hour before treatment
- Bleomycin 60 units in 50ml D5W or NaCl, or doxycycline 500mg in 30ml NaCl, or mitoxantrone 30mg in 50-100ml NaCl, or nitrogen mustard (mechlorethamine) 20mg in 50-150ml NaCl, or thiotepa 30-45mg in NaCl is instilled through the chest tube.
- Lidocaine 100-300mg has been added to solutions to provide local anesthesia.
- The patient changes positions every 15 minutes for several hours (eg. lying flat, right side up, etc.).
- The chest tube clamp is removed and fluid drains, with suction, for about 24 hours.
- The chest tube drains by gravity, and when drainage is decreased (ie. to 50-100ml/day) and the lung remains re-expanded, the chest tube is removed.
Note: The above is intended as a general overview of the sequence of events commonly observed in the management of malignant effusions. It is not intended as a step-by-step guide.
TALC for pleurodesis is enjoying a resurgence in use in various centers. The procedure for insufflation is different than that described above, and is usually done in an operating room setting. The goals of sclerosis are the same.
II. MALIGNANT PERICARDIAL EFFUSIONS
Malignant pericardial effusions are most common in BREAST and LUNG CANCERS. Heart or pericardial involvement is also seen in leukemia, Hodgkins or non-Hodgkins lymphomas, melanoma, gastrointestinal cancers and sarcomas.
Fluid accumulates in the pericardial space as a result of OBSTRUCTION OF LYMPHATIC and VENOUS DRAINAGE OF THE HEART.
Symptoms of pericardial effusions include DYSPNEA, COUGH, CHEST PAIN, ORTHOPNEA, PALPITATIONS, WEAKNESS, FATIGUE and DIZZINESS. CARDIAC TAMPONADE is the most severe form of presentation. The occurrence of symptoms depends on how fast the fluid accumulates, how much fluid accumulates and underlying ventricular function.
TREATMENT of malignant pericardial effusions may involve PERICARDIOCENTESIS and SCLEROTHERAPY (eg. doxycycline, bleomycin, etc., similar to that discussed above for pleural effusions), or SURGERY.
III. MALIGNANT PERITONEAL EFFUSIONS
When drugs are used in the management of malignant peritoneal effusions, SCLEROTHERAPY may also be similar to that noted above.
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