Pulmonary Medicine

Pleurodesis and Use of Long-term Pleural Catheters

General description of procedure, equipment, technique

Malignant pleural effusions (MPE) are common complications of advanced malignancy, usually resulting in significant dyspnea, chest tightness, or cough. The approach to the management of malignant pleural disease has evolved considerably in the past few years, with several options now available to our patients.

Traditional treatment methods that aim to fuse the pleural space with a sclerosing agent continue to represent the standard of care in many institutions, but with the introduction of long-term indwelling pleural catheters (IPCs), IPCs have become a mainstream option for palliation MPE. Pleurodesis approaches offer a limited course of treatment in pursuit of long-term control of the effusion, while IPCs offer minimally invasive long-term drainage with a lower chance of pleurodesis.

Indications and patient selection

Patients with symptomatic recurrent MPE should be considered for definite treatment of their effusion. Given the palliative nature of interventions, asymptomatic patients should usually be observed without invasive treatment.

Therapeutic thoracentesis should be considered at the time of initial presentation with a symptomatic effusion in the setting of malignancy. Therapeutic thoracentesis allows for rapid short-term improvement in dyspnea, confirmation that the effusion is, in fact, the cause of the symptoms, and diagnostic testing of the fluid to confirm its malignant nature and rule out other conditions, such as infection.

In patients with known advanced malignancy, the finding of an exudative effusion without alternative explanation is adequate to proceed with treatment, regardless of cytology results. In patients with no history of malignancy or in those whose pleural disease is the only site of advanced disease, with associated prognostic and treatment implications, additional diagnostic tests are required.

Repeated therapeutic thoracentesis should be avoided as a management strategy for symptomatic MPE. This approach is incompatible with good symptom control - given the short-lived nature of improvement and the symptom-prompted nature of the intervention. In addition, increasing difficulty with drainage may occur over time because of loculation of the fluid and development of a trapped lung.

These complications may also hinder the application of other definitive treatments. As such, therapeutic thoracentesis should be considered only in patients who have a very short life expectancy, in those expected to experience a rapid response following initiation of oncologic treatment (e.g., lymphoma or small-cell lung cancer), and in the occasional patient with a very slowly reaccumulating effusion. Following the initial thoracentesis, all other patients should have a management plan instituted with the expectation that fluid will recur in the short term.

Contraindications

Lack of improvement following therapeutic thoracentesis - Consider trapped lung or central airway obstruction if the lung does not re-expand, and other etiologies for dyspnea, such as COPD, pulmonary embolus, lymphangitic carcinomatosis, and pericardial disease.

Anticipated survival or very poor performance status (WHO >2) - Consider therapeutic thoracentesis in these patients, although a TPC may still be a reasonable option.

Uncontrolled coagulopathy or anticoagulation

Trapped lung - Incomplete re-expansion of the lung predicts failure of pleurodesis. Patients with partial symptom relief following thoracentesis and partially trapped lung can still be considered for a TPC.

High anesthetic risk (for thoracoscopic procedures), hemodynamic instability or respiratory failure

Chylothorax (a relative contraindication to TPC)

Extensive skin involvement with malignancy or infection over the TPC insertion site

Details of how the procedure is performed

Management of symptomatic malignant pleural effusions is best performed in consultation with specialists in chest diseases. Therapeutic options for treatment include placement of an indwelling pleural catheter and chemical pleurodesis via chest tube or thoracoscopy.

IPC placement

IPC placement can take place in an adequately equipped procedure room on an outpatient basis. A chest radiograph is reviewed prior to placement, as are prior CT scans, if available. Intravenous access and sedation is not required in the vast majority of subjects. Baseline and post-procedure measurement of vital signs is performed, but continuous monitoring is not required.

The patient is positioned in a semi-recumbent position on a stretcher or a procedure bed. When a posterior approach is selected (see below), the patient is placed in a sitting position, leaning on a table for support, as is commonly done for thoracentesis.

Use of pleural ultrasonography is recommended for all cases. It is particularly useful in patients with recently drained effusions, obesity, diseased skin, elevated hemidiaphragms/ascites, or loculated effusions. The preferred approach is to insert the catheter at the base of the effusion along the anterior axillary line, with tunneling of the catheter distally and medially over the abdomen. In patients with diseased skin or larger breasts, insertion along the posterior axillary line can be considered.

A sterile insertion technique is used with full barrier precaution, cleansing of the insertion site with chlorhexidine and application of a fenestrated sterile drape.

The skin at the insertion site and chest wall are anesthetized with 5-10ml of 1 percent lidocaine until the pleural space is entered and fluid aspirated. An introducer needle is then advanced into the pleural space, followed by insertion of a guidewire. An additional 5-10 ml of 1 percent lidocaine is used to infiltrate the skin and subcutaneous tissue along the 5-10 cm track where the catheter will be tunneled.

Two small incisions, the first adjacent to the guidewire and the second at the desired catheter exit site, are made. A tunneler device is then used to advance the catheter from the exit site to the guidewire incision until the tissue cuff of the catheter is in a subcutaneous position. A dilator and peel-away introducer sheath is then advanced over the guidewire and into the pleural space. The dilator and wire are removed and the distal end of the catheter advanced through the sheath into the pleural space. The peel-away sheath is broken and removed, leaving the catheter in position. Two simple interrupted sutures are placed over the pleural insertion site, and a simple interrupted suture with two long ends wrapped around the catheter is used at the distal incision to secure the catheter in place.

The catheter can then be drained immediately post-procedure, a dressing applied, and a chest x-ray obtained. The catheter can then be drained on an outpatient basis with 550 mL plastic vacuum drainage bottles every other day or on a Monday/Wednesday/Friday schedule. If additional drainage is needed, 1 L bottles can be used and/or drainage frequency increased to a daily regimen.

Placement of this catheter is only a small part of this overall treatment approach. IPC placement requires a combination of patient and caregiver education, home care support, arrangements to ensure adequate supply of drainage equipment for the patient, and availability of the treatment team to deal with problems and complications and to perform routine follow-up.

Catheter removal: Once fluid drainage decreases to less than 50ml in three consecutive drainage attempts without evidence of fluid re-accumulation in the x-ray, the catheter can be removed. After cleansing the exit site, 5mL of 1 percent lidocaine can be infiltrated around the tissue cuff, followed by application of a firm, constant rotary pulling of the catheter to dislodge the cuff. In some cases, small, curved forceps can be used to help dislodge the cuff. Once the cuff is freed, the rest of the catheter should follow without significant resistance. Steri-strips and a dry dressing can then be applied to the incision.

Bedside pleurodesis

Bedside pleurodesis can be performed on an inpatient basis in a regular medical or surgical ward. Small case series have described outpatient protocols, but these have not been widely adopted. A standard chest tube is inserted and placed at the base of the effusion. Standard surgical tubes can be utilized, although small-bore 14 French drains can also be used and may be better tolerated. The pleural space is then drained into an appropriate collection chamber and a chest x-ray performed to document complete lung re-expansion.

Once the lung has re-expanded, the pleurodesis procedure can be performed, regardless of the amount of ongoing fluid drainage, although patients with higher amounts of fluid output may have higher rates of failure rates. If there is incomplete lung re-expansion, the chances that the pleurodesis procedure will succeed is decreased, and alternatives should be considered.

A variety of sclerosing agents can be used for bedside pleurodesis (see below). The selected agent is suspended or diluted in approximately 50 mL of saline, followed by injection through the chest tube. An additional 50 mL of saline is used to flush the catheter. An intravenous line should be in place to administer analgesia, as acute pain can develop suddenly. Consideration should be given to intrapleural anesthetic administration (e.g., bupivacaine 0.5% solution with epinephrine, 20 mL intrapleurally) or systemic opioids prior to administering the sclerosing agent. A sterile technique should be maintained when preparing the sclerosing agent and accessing the chest tube.

Once the sclerosing agent is administered, the chest drain is clamped for two hours. There appears to be no benefit to various positioning maneuvers aimed at improving distribution of the agent in the pleural space. The drain is unclamped after two hours and connected to suction (-20cmH2O), and drainage is maintained until tube removal. The optimal time for tube removal is unclear, but it can be based on a specific time (e.g., 24 or 48 hours post-pleurodesis) or the amount of pleural fluid drained (e.g., less than 100-150 mL per day).

Sclerosing agents for bedside pleurodesis

A dose of 4-5g of sterile asbestos-free talc, which has been associated with the highest success rates, can be used for pleurodesis. Talc is not water-soluble, and it must be suspended in saline ("talc slurry") to be administered. Consideration regarding the source and calibration of talc particles may be important. (See the section on complications.)

The standard dose for doxycycline administration is 500 mg, using the sterile intravenous solution diluted in 50 mL of saline.

Silver nitrate has been used at various doses in the pleural space. Most commonly reported is 20 mL of a 0.5 percent solution.

While perhaps the most expensive and least effective agent, doses of 60 I.U. of Bleomycin can be used for bedside pleurodesis.

Thoracoscopy/talc poudrage

Specific description of thoracoscopic pleurodesis is beyond the scope of this chapter. Performance of this procedure requires specific training and expertise.

Thoracoscopic approaches to pleurodesis in malignant pleural disease range from a full video-assisted thoracoscopic surgery (VATS) technique under general anesthesia and single lung ventilation to single port, flexi-rigid medical pleuroscopy under conscious sedation and local anesthesia.

Drainage of the effusion is performed intraoperatively, and lysis of adhesions is possible. If needed, cytopathological samples can also be obtained, making this procedure ideal in cases of undiagnosed pleural effusions.

Once adequate lung expansion has been demonstrated, 4-5 g of talc is aerosolyzed or sprayed throughout the pleural space. A chest drain is then inserted and air is evacuated from the pleural space. Pleural drainage is maintained postoperatively, and tubes are removed as for bedside pleurodesis.

Interpretation of Results

Not applicable.

Outcomes

A variety of outcome measures have been used to assess the impact of treatments for malignant pleural disease. Given the palliative nature of the intervention, symptom control and quality-of-life measures would seem to be most important, but information on these measures are limited.

Selection on the most appropriate treatment approach will depend on the clinical characteristics of a given patient, local resources and expertise as well as patient preference. Ideally such patient should be assessed by chest physicians experienced in the management of pleural diseases.

Pleurodesis rates

Pleurodesis has long been considered the primary endpoint for treatment of malignant pleural disease. A variety of definitions have been used, but a thirty-day radiological outcome measure is usually used.

Pleurodesis is not in itself a goal of treatment with indwelling pleural catheters. Nevertheless, nearly half of all treated patients achieve a "spontaneous pleurodesis" with this treatment 30-60 days after insertion. Spontaneous pleurodesis appears more likely (70%) in patients with good short-term survival and absence of trapped lung than in other patients.

Pleurodesis rates following talc pleurodesis have been documented to be as high as 90 percent, but these results are not typically based on intention-to-treat analysis so substantial numbers of potential candidates for the procedure who, for various reasons, do not receive talc are excluded. In addition, many studies exclude subjects who do not survive to thirty days and/or ignore recurrences beyond thirty days. A Cochrane review of the literature suggests that talc is the most effective agent, although some randomized trials suggest equally effective results with silver nitrate.

Despite the common suggestion that thoracoscopic approaches are superior to bedside pleurodesis, four randomized controlled trials have failed to demonstrate improved outcomes of one technique over the other.

Symptom control and quality of life

Significant improvements in dyspnea as well as overall health status have been documented to occur following both pleurodesis procedures and IPC insertion. A prospective randomized trial of bedside talc pleurodesis vs. IPC noted similar improvement in dyspnea scores and overall quality of life measures in both groups.

Fluid reaccumulation and the need for repeat procedures

Since pleurodesis rates cannot be easily compared between IPC and pleurodesis procedures, the need for additional pleural procedures during the patient's lifetime can be used as an additional outcome measure for the success of a therapy. Additional procedures are rarely required following placement of an IPC; fewer than 10 percent of patients require an additional invasive procedure once an IPC is placed.

Delayed recurrence of pleural fluid has been noted to occur in 6-38 percent of patients treated with talc, although how many of these patients need additional procedures is unclear.

Several studies, including a randomized trial suggest that the need for further pleural interventions is lower in IPC-treated individuals than following pleurodesis procedures.

Hospitalization, costs, and burden of care

The mean length of hospital stay for pleurodesis techniques has been reported to be 5-7 days, while IPC are typically inserted on an outpatient basis. The trade-off for avoiding hospitalization associated with IPC treatment is a requirement for long-term repeated drainage of the device and catheter care.

Costs associated with these approaches appear similar based on modeling exercises as well as on actual cost analysis of a randomized trial. Retrospective analysis suggest that cost-analysis favours an IPC approach in patients with shorter survival time while a pleurodesis approach may be more cost-effective in those with longer survival time.

Alternative and/or additional procedures to consider

None.

Complications and their management

Complications have been associated with the treatment of MPE. The incidence and type of complications vary widely from study to study, likely because of study design, patient selection criteria, definition, approach, and the type, dose, and supply of sclerosing agent. Overall, it appears that IPCs may have a better safety profile, particularly with regard to severe complications. Empyema appears to occur at similar rates with the various techniques.

Complications associated with bedside pleurodesis

Fever and pain, which are common complications of pleurodesis procedures, occur in a quarter to a third of patients. Fever can be managed conservatively with antipyretics, while pain can be approached prophylactically or post-procedure with systemic opioids. (See the section on bedside pleurodesis.) These symptoms are usually limited to forty-eight hours post-procedure.

Cases of acute respiratory failure/ARDS that have been reported with intrapleural talc administration may relate to higher doses and to smaller-particle talc. The use of large-particle talc ("French talc," mined at Luzenac, France) has been found to be safe but is not universally available. Other suppliers offer "calibrated" talc of large particle size, but large trials are not available that document the safety of the various preparations.

In a large trial, complications appeared lower with talc slurry than with VATS poudrage, with lower rates of pneumonia, respiratory failure, and venous thromboembolism.

Procedure-related mortality was found to be 2.9 percent in a large trial of talc slurry with thirty-day mortality of 20 percent.

Complications associated with thoracoscopic poudrage

Several other complications associated with thoracoscopy for treatment of MPE beyond those associated with a sclerosing agent likely relate to the surgical nature of the intervention. Such complications include empyema, bronchopleural fistula, thromboembolic disease, arrhythmia, myocardial infarction, pneumonia, and respiratory failure. The incidence of these complications varies widely among studies.

Procedure-related mortality was found to be 3.7 percent in a large trial of VATS talc pleurodesis with thirty-day mortality of 14 percent. Another large, single-arm study of talc poudrage via medical pleuroscopy saw better short-term outcomes, with a 2 percent thirty--day mortality rate.

Complications associated with IPC treatment

Cellulitis

Occurs in approximately 3 percent of cases, typically in the first two weeks post-placement. Cellulitis can be managed with oral antibiotics directed toward skin flora without removing the catheter.

Empyema

Occurs in approximately 3 percent of cases, but its onset is usually delayed. Treatment follows the usual principles of empyema care, including hospitalization, intravenous antibiotics tailored to culture results (with staph. Aureus the most common), continuous drainage of the pleural space via the IPC, and use of CT imaging to define the fluid collection. Loculated effusion can be treated with intrapleural thrombolitic drugs/DNAse and/or placement of additional pleural drains. The IPC can be removed once adequate pleural drainage has been achieved, preferably prior to discontinuation of antibiotics. Surgical drainage is rarely considered or required.

In empyema in the setting of trapped lung, complete drainage and sterilization of the pleural space is challenging. Surgical decortication could be considered in patients with very good performance status, but in most cases, chronic drainage of the effusion is performed with the IPC, along with long-term use of antibiotics. Occasionally, the space organizes and allows removal of the IPC.

The problems of loculated fluid/blocked or poorly draining catheter can occur in 10 percent of patients. It is important to differentiate the impact of the poor drainage on the patient's symptoms; if a poorly draining catheter is not associated with increased dyspnea or increased fluid re-accumulation on x-ray, the clinician should consider removing the IPC after a period of observation.

In patients with worsening symptoms or increasing fluid on x-ray, differentiating a blocked catheter from a multi-loculated or septated effusion may be difficult. The catheter can initially be flushed with sterile saline and the pleural space can be examined with ultrasound to define the problem. If drainage does not resume after catheter flushing, rTPA 6-10mg in 20ml sterile water (flushed with an additional 20ml sterile water) can be administered through the IPC. The catheter valve can be accessed with a plastic 16-gauge intravenous cannula, followed by drainage of the IPC two to four hours later. If the problem persists or recurs, pleural thrombolytics can be repeated and thoracentesis can be performed, followed by insertion of a new IPC if thoracentesis is successful.

Catheter dislodgement may occur in 2 percent of cases, typically in the first two weeks post-placement in patients with poor wound healing, edema, or local infection. If the catheter tissue cuff is no longer in a subcutaneous position, the catheter should be removed. Preventative measures include ensuring that the distal skin incision made at the time of insertion is only large enough for the cuff to fit through--it should require a reasonable amount of tension to pass--and placement of a suture securing the catheter in place for ten to fourteen days post-placement to allow healing and scarring to occur around the tissue cuff.

It is not uncommon for a small amount of air to enter the pleural space during IPC insertion (pneumothorax), but this is of no consequence. Occasionally, particularly in patients with trapped lung, a hydropneumothorax forms following initial drainage or during routine drainage procedures. This condition is not usually associated with worsening symptoms, and it is usually managed with ongoing intermittent home drainage. In rare cases (<=1%), a significant broncho-pleural fistula may occur (with increased dyspnea, collapse of the lung, or development of subcutaneous emphysema). Such complications warrant hospital admission, connection of the IPC to a continuous drainage system, and insertion of additional chest drains as needed.

Tumor seeding of the catheter track is a rare event (<=1%). If symptomatic, it can be treated with external beam radiation.

Mild pain in the post-procedure period can usually be managed with over-the-counter analgesics, codeine, or a patient's current medications. Persistent pain beyond forty-eight hours is rare, but it occasionally requires catheter removal. In patients with trapped lung, care must be taken not to drain the pleural space too aggressively, as this will lead to significant decreased pleural pressures and associated pain and chest tightness.

No specific procedure-related mortality has been reported with IPC treatment, but one study reported an overall 12.8 percent thirty-day mortality. No difference in median survival was noted in two randomized trials that compared IPC and pleurodesis.

Selecting the best approach for your patient

Specific clinical scenarios

Chemoresponsive disease

Patients who are imminently starting oncologic treatment for a malignancy that is expected to respond rapidly to treatment may best be managed by repeated thoracentesis. These patients include those who are starting first-line chemotherapy for small-cell lung cancer or lymphoma. While patients who are starting first-line treatment for advanced breast cancer may have a good response rate, control of the effusion may not be achieved in the short term, so alternative options, such as an IPC, can be used as a bridge until chemotherapy response occurs.

Suspected malignant effusions

In cases of suspected malignant effusion in which pleural fluid analysis (+/- closed pleural biopsy) remain non-diagnostic, and without other evidence of metastatic disease, thoracoscopic techniques can be favored as a combined diagnostic and therapeutic procedure.

Hospitalized patient with chest drain

Patients may present with a large effusion, and a chest drain is inserted even if the nature of the effusion is unknown. When malignancy is confirmed and adequate lung re-expansion is achieved, a bedside pleurodesis technique via the chest drain already in place may be the most expedient method to manage the effusion.

Trapped lung

An IPC is the best treatment approach for patients who experience at least partial symptom relief following thoracentesis but in whom full lung re-expansion is not possible.

Poor performance status/short life expectancy

Patients with poor performance status (WHO >2) may be best suited to IPC treatment.

Outpatients with good performance status

These patients can likely be treated with inpatient bedside pleurodesis, thoracoscopy, or IPC, depending on local expertise and availability. In addition to considerations related to effectiveness and complication discussed above, the patient preference factor often relates to the outpatient vs. inpatient nature of the different modalities, as well as to the short-term vs. long-term course of treatment.

What’s the evidence?

Roberts, ME, Neville, E, Berrisford, RG, Antunes, G, Ali, NJ. "BTS Pleural Disease Guideline Group. Management of a malignant pleural effusion: British Thoracic Society Pleural Disease Guideline 2010". Thorax. vol. 65. 2010. pp. ii32-40.

(These are recent international guidelines on the management of MPE.)

Janssen, JP, Collier, G, Astoul, P, Tassi, GF, Noppen, M, Rodriguez-Panadero, F. "Safety of pleurodesis with talc poudrage in malignant pleural effusion: a prospective cohort study". Lancet. vol. 369. 2007. pp. 1535-9.

(A large prospective study documenting the safety of large-particle talc poudrage via medical thoracoscopy for treatment of malignant pleural effusion.)

Davies, HE, Mishra, EK, Kahan, BC, Wrightson, JM. "Effect of an Indwelling Pleural Catheter vs Chest Tube and Talc Pleurodesis for Relieving Dyspnea in Patients With Malignant Pleural Effusion: The TIME2 Randomized Controlled Trial". JAMA.. vol. 307. 2012. pp. 2383-2389 .

(A randomized prospective trial of talc slurry vs. IPC for the treatment of malignant pleural effusion which demonstrated no difference in dyspnea relief between approaches.)

Dresler, CM, Olak, J, Herndon, JE, Richards, WG, Scalzetti, E, Fleishman, SB. "Phase III intergroup study of talc poudrage vs. talc slurry sclerosis for malignant pleural effusion". Chest. vol. 127. 2005. pp. 909-15.

(A large RCT of VATS pleurodesis vs. slurry, which did not demonstrate an advantage of one approach over the other. Significant complications were noted in both groups.)

Chee, A, Tremblay, A. "The use of tunneled pleural catheters in the treatment of pleural effusions. Curr Opin Pulm Med". 2011.

(A recent review detailing use and experience with IPC for malignant (and other) pleural diseases.)

Shaw, P, Agarwal, R. "Pleurodesis for malignant pleural effusions". Cochrane Database Syst Rev. 2004. pp. CD002916.

(Although somewhat dated, this extensive systematic review summarizes the literature with regard to the differences among the various approaches and drugs used for pleurodesis. Missing are more recent large prospective trials and comparisons to IPCs. An update is planned for release in 2015.)

Casal, RF, Eapen, GA, Morice, RC, Jimenez, CA. "Medical thoracoscopy". Curr Opin Pulm Med.. vol. 15. 2009. pp. 313-20.

(A comprehensive review of medical thoracoscopy techniques and their application in malignant pleural disease.)
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