Effect of Respiratory exercise in decreasing the fluid in the chest because of cancer.

Not yet recruiting

Conditions: Adult patients with diagnosed cancer of any site, having malignant pleural effusion and requiring pleurodesis will be recruited for the study

Registration Number: CTRI/2015/07/006005

Lead Sponsor: All India Institute of Medical Sciences

Brief Summary: **Title of theproject:** Toassess the role of respiratory physiotherapy in the effectiveness ofpleurodesis in adult patients with malignant pleural effusion.

**Background**:

Certain primary or metastatic cancercauses pleural effusions and causes severe respiratory symptoms. Malignancy is the major cause of both exudative pleural effusionsand massive recurrent pleural effusions.[1] Theseeffusions tend to recur in more than 90% of patients.[1] A confirmed malignant pleuraleffusion requires palliative treatment aimed mainly at alleviating the dyspneacaused by the tendency of the effusion to recur.In view of the limited life span in patients with malignant pleural effusion, the goal of management is aimed at sustained symptom relief,shortening the length of hospitalization, improvement of quality of life andminimizing the number of invasive procedures. A number of treatment strategies for the pleuraleffusion are available. The mostcost-effective method of controlling a malignant pleural effusion is chest tubeor catheter drainage and intrapleural instillation of a chemical agent. [1,2]

Pleurodesisis an accepted palliative management for patients with symptomatic or recurrentmalignant pleural effusion.[3] Pleurodesis involves instilling an irritant intothe pleural space to cause inflammatory changes that result in bridgingfibrosis between the visceral and parietal pleural surfaces, effectivelyobliterating the potential pleural space.

Simple small bore drainage cathetershave been used effectively for drainage of pleural fluid. There are emerging data on theuse of small-bore tubes for chemical pleurodesis.[2,4,5]. Pigtail catheter isconsidered a safe, easy, tolerable and effective alternative method incomparison to the traditional intercostal tubes in pleurodesis of malignantpleural effusions.[2]

Before a sclerosing agent isinjected, the ability of the lung to reexpand should be confirmed. Also, increase duration of chest tube drainage isassociated with increased hospital stay and increase risk of potentialinfection. So, it is warranted to decrease the duration of pleural fluiddrainage prior to pleurodesis. The physiotherapy intervention has been reportedto enhance the pleural fluid drainage. It also helps in lung reexpansion andthis aids in faster pleural fluid drainage and resolution of symptom ofdspnoea.[6] Physiotherapy is an important intervention that prevent and reducesthe negative effects of prolonged bed rest during hospitalization and improvesthe respiratory function in patients with pleural effusion. Some authors haveproposed treatment of pleural effusion with physiotherapy, however nodefinitive conclusion could be drawn about the success of this treatment onmalignanat pleural effusion and pleurodesis.[6,7]

**Lacunae in existing Knowledge:**

Â·        Though physiotherapy interventionhas been well described for lung expansion after surgical intervention but it is not known whether such intervention can producesimilar kind of re-expansion in subjects with unilateral malignant pleuraleffusion. Since lung expansion is paramount for the effectiveness ofpleurodesis, there exists a need to compare the effectiveness of respiratoryphysiotherapy intervention with deep breathing exercises, purse lip breathingand incentive spirometry on the chest expansion in patients with unilateralpleural effusion and thus the effectiveness of pleurodesis.

Research Question:Â·        Dorespiratory physiotherapy increases the effectiveness of pleurodesis formalignant pleural effusion in adult patients?

Aim of the study: Â·        Toevaluate the effect of the respiratory physiotherapy on effectiveness of pleurodesis in adult patientswith malignant pleural effusion.

Hypothesis: Â·        Respiratory physiotherapy in adult patients withmalignant pleural effusion improves the effectiveness of pleurodesis.  Study designand methodology: ***Study design*** â€“ Prospectiverandomized study

***Method***: After ethical approval, this prospective randomized study willbe carried at Pain and Palliative Care Clinic, Dr BRA Institute Rotary CancerHospital, AIIMS, New Delhi, India. Adult patients with diagnosed cancer of anysite, having malignant pleural effusion [confirmed by pleural fluid cytology and/oreither computed tomography (CT)-guided biopsy or tissue biopsy] and requiring pleurodesis will be recruited for the study. Thediagnosis of pleural effusion will be based on the presence of consistentradiological findings in posteroanterior (PA) and lateral chest (ipsilateral) radiographsin addition to the clinical presentation (dyspnea, pleuritic chest pain). Informed consent formwill be signed prior to participation and â€˜patient informationâ€™ sheet will be providedand explained to all participants. Visualanalog scale score (VAS) (0-no pain to 10-worst pain) for assessment of pain willbe explained to the patient.

***Inclusion criteria:***

Â·        Recurrent andsymptomatic malignant pleural effusion

Â·        Age morethan 18 years

Â·        Lifeexpectancy> 3 months

***Exclusion criteria:***

- Atelectasis due to endobronchial obstruction

- Previous pleural procedures (except for thoracocentesis and/or pleural biopsy).

- Cognitive impairments or comprehension deficits.

- Coagulopathies (PT INR>1.5, and/or thrombocytopenia (platelet count <80000/mm3).

- Active pleural or systemic infection.

- Unstable cardiovascular status i.e. hemodynamic instability requiring inotropes/vasopressors, recent myocardial infarction < 5 days or uncontrolled arrythmias

- Refusals.

The patients will be randomized toone of the two groups by computer generated random number concealed in opaquesealed envelope:

Â·        Group A (control group): Patients willreceive standard therapy (thoracocentasis using pigtail catheter andpleurodesis using Bleomycin)

Â·        Group B (Intervention group): Patientswill receive respiratory physiotherapy (deepbreathing exercises, purse lip breathing and incentive spirometry) inaddition to standard therapy (thoracocentasis using pigtail catheter andpleurodesis using Bleomycin)

**Procedures inthe two groups:**

***Thoracocentasisand catheter placement*****:** The patients will be made in asitting position on the edge of the bed, leaning forward with the patientâ€™sarms resting on a bedside table. When the patient is not able to be placed in asitting position, the lateral decubitus orsemidecubitus position will be used. Preprocedural ultrasound evaluationwill be done to localize the pleural fluid pocket and skin entry site at theposterior intercostal space. After cleaning and draping, the skin entry sitewill be infiltrated with 2% lidocaine with adrenaline (3-5 mL). After making a small skin incision, an 12 Fpigtail catheter will be inserted by single puncture trocar technique underultrasound guidance. Once the needle tip ispositioned inside the fluid pocket, the outer soft sheath will be advanced overthe metal stylet needle, which will be later removed. A three-way stopcockwill be connected to the hub, which in turn will be connected tounderwater seal for drainage of pleural effusion. The serial chest x-ray willbe done once daily to evaluate the lung expansion and drainage of pleuralfluid. The amount of pleural fluid will be noted and when the chest drainoutput is less than 100 mL over 24 hours, chest x-ray will be repeated to noteexpansion of the lung.

***Pleurodesis*****:**Once theexpansion of lung is ensured, sclerosing agent (Bleomycin) (1 IU/kg, maximally60 units) along with 2 mg/kg of lidocaine diluted in total of 50 mL of normalsaline will be injected through the catheter into the pleural space. Thecatheter will be clamped for 12 hours and then released for any residualpleural fluid. If during next 24 hours drain output will be less than 150mL,pigtail catheter will be removed and dressing will be done using tinctureiodine. Repeat chest x-ray will be done before discharge.

**Intervention:**

Physiotherapytreatment: Thetrained physiotherapist will explain the physiotherapy intervention to allpatients. Patients in intervention group will be instructed to performthe following intervention 4 times per day:

Â·        Deepbreathing exercises [8,9]:The deep breathing will be performed in four sets offive repetitions of deep breaths, from tidal expiration to maximum inspiration(ie from functional residual capacity to total lung capacity), with a 3-secondinspiratory hold followed by relaxed expiration. The physiotherapist will trainthe patient by providing proprioceptive feedback by placing his handsbilaterally on the patientâ€™s lower ribs. These exercises will be completed withthe patient sitting on a chair or on a bed with the head end raised. Normalbreathing will be encouraged between the repetitions of deep breathingexercises.

Â·        Pursedlip breathing [10]: The purse lip breathing will be done in four sets of fiverepetitions each waking hour. The patients will be instructed to make a normal tidalvolume nasal inspiration followed by expiratory blowing against partiallyclosed lips avoiding forceful exhalation.

Â·        Incentivespirometer [11]: This will be performed by patients using a volume-orientedincentive spirometer, which has coloured piston for indicating volume andrattle indicator for indicating flow. After a quiet expiration, patient will beencouraged to take slow maximal inspirations through the mouthpiece of thedevice and to hold each breath for as long as possible. While maintaining therattle indicator in smiley face zone (flow indicator). The patients will beencouraged to use the device for 10 breaths per hour.

            Pigtailcatheter insertion, and pleurodesis will be performed by a trained PalliativeCare physician in association with Interventional Radiologist. Thephysiotherapy interventions will be trained and supervised by thephysiotherapist. The assessment of pleurodesissuccess in the follow up period will be performed by an investigator blinded toallocation.

The duration from insertion ofpigtail catheter and time of pleurodesis and duration from time of pleurodesisand time of removal of pigtail catheter will be noted. The total length ofhospital stay i.e. from day of admission for pleurodesis and till date ofdischarge from the hospital will also be noted. Patients will be considered ’pleurodesis fit for discharge’the day the chest tube is removed.

Theroutine follow up in such patients is done at Pain and Palliative Care clinicat Dr BRAIRCH, AIIMS, New Delhi. The chest x-ray (posteroanteriorand lateral chest radiographs) will be done at baseline, at dischargeand repeated at 1, 3 and 6 months in follow up. The baseline pain, pain induced during procedure includingpleurodesis, at discharge and follow up at 1, 3 and 6 months will be recorded as per VAS score and controlled withstandard management including NSAIDS, Paracetamol and opioids to keep theVisual analog scale score (VAS) <4. The severity of dyspnoea will beassessed and recorded as per ModifiedMedical Research Council Dyspnea Scale (MMRC) [12] at baseline, afterpigtail catheter drainage, atdischarge and during follow up at 1, 3, and 6 months..

            Any complications like fever, bleeding, air-leaks/pneumothorax inperiprocedural period will be noted. **Primary OutcomeVariable**:

Â·        The effectiveness of pleurodesis as assessed by reaccumulation ofpleural fluid on chest radiographs on follow up at 1, 3 and 6 months - Revised to follow up at 1 month.

**Secondary OutcomeVariable**:

Â·        Lengthof hospital stay for pleurodesis.

ResearchvariablesÂ·        **Chestradiographs grading of size of malignant pleural effusion [13]****:**It will begraded into three groups:

o   ***small-to-moderate*** malignant pleural effusion willbe defined as occupying less than one-quarter of the hemithorax;

o   ***moderate-to-large*** malignant pleural effusion willbe defined as occupying greater than onequarter, but less than the entirehemithorax; and

o  ***massive*** malignant pleural effusion will be defined as those effusionsoccupying the entire hemithorax

Â·        **The effectiveness of pleurodesis willbe assessed as [14,15,16]:**

o   **Completeresponse:** ifthere will be no reaccumulation of pleural fluid in the chest radiograph in thesame hemithorax, after catheter removal, during the follow up period.

o   **Partialresponse**: Smallamount of fluid re-accumulation in the chest radiograph after catheter removalbut not causing symptoms and not requiring repeated thoracocentesis or tubedrainage.

o   **Failureof pleurodesis**:It will be considered if there will be difficulty to remove the catheter,because the pleural fluid drained through it is more than 250 mL/24 h (primaryfailure) or there was fluid reaccumulation after tube removal, that caused symptoms to the patient ornecessitated repeated thoracocentesis or intercostal tube drainage, during thefollow up period (secondary failure).

Â·        **Grading of Dyspnoea:** Garding of Dyspnoea ie shortness of breath will be doneas per Modified Medical ResearchCouncil Dyspnea Scale (MMRC) [12]:

| | |

| --- | --- |

|

|**Grade**

**Degree of dyspnea**

|0

no dyspnea except with strenuous exercise

|1

dyspnea when walking up an incline or hurrying on the level

|2

walks slower than most on the level, or stops after 15 minutes of walking on the level

|3

stops after a few minutes of walking on the level

|4

with minimal activity such as getting dressed, too dyspneic to leave the house

**Sample Size andStatistics**:

Â·                    Sample Size: The success rate of pleurodesis with bleomycinalone at one month documented in other studies ranges from 60-75 % [14,15,16].However, no study has tried to combine the respiratory physiotherapy with standardtherapy (thoracocentasis using pigtail catheter and pleurodesis usingBleomycin) to observe the effectiveness of respiratory physiotherapy on pleurodesis.However, if presume that physiotherapy might results in increase in success ofpleurodesis at one month by 15% (i.e. from 65% to 80%), than for one sidedtest, considering 95% confidence interval and power of 80%, a minimum of 65patients in each arm will be required. Also, to best of our knowledge, as perreview of literature, there is no evidence available through randomizedcontrolled trial on the added effectiveness of respiratory physiotherapy along with standardtherapy (thoracocentasis using pigtail catheter and pleurodesis usingBleomycin) on pleurodesis. Hence, it was not feasible to formally explore therequired sample size for the study. However keeping in view of past experiencea total of 50-60 patients/year are expected to be available who fulfillinclusion criteria to be part of the study. Accordingly this study proposed for2 years is expected to cover a total of about 130 patients which will besufficient to generate preliminary finding in this study.

Datacollected will be collated and analyzed statistically using SPSS version 20.0software.

**References**:

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Detailed Description: Not available

Recruitment & Eligibility

Status: Not Yet Recruiting

Sex: All

Target Recruitment: 130

Inclusion Criteria

â€¢Recurrent and symptomatic malignant pleural effusion â€¢Age more than 18 years â€¢Life expectancy> 3 months.

Exclusion Criteria

â€¢Atelectasis due to endobronchial obstruction â€¢Previous pleural procedures (except for thoracocentesis and/or pleural biopsy).
â€¢Cognitive impairments or comprehension deficits.
â€¢Coagulopathies (PT INR>1.5, and/or thrombocytopenia (platelet count <80000/mm3).
â€¢Active pleural or systemic infection.
â€¢Unstable cardiovascular status i.e. hemodynamic instability requiring inotropes/vasopressors, recent myocardial infarction < 5 days or uncontrolled arrythmias â€¢Refusals.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
â€¢The effectiveness of pleurodesis as assessed by reaccumulation of pleural fluid on chest radiographs on follow up at 1 month.	1 month follow up.
Grade	Degree of dyspnea
0	no dyspnea except with strenuous exercise
1	dyspnea when walking up an incline or hurrying on the level
2	walks slower than most on the level, or stops after 15 minutes of walking on the level
3	stops after a few minutes of walking on the level
4	with minimal activity such as getting dressed, too dyspneic to leave the house

Secondary Outcome Measures

Name	Time	Method
â€¢Length of hospital stay for pleurodesis.	After intevrntion and till discharge.

Trial Locations

Locations (1): AIIMS New Delhi
🇮🇳
South, DELHI, India
AIIMS New Delhi
🇮🇳South, DELHI, India
DR RAKESH GARG
Principal investigator
9810394950
drrgarg@hotmail.com