Coagulopathy, Empyema, Pleural, Parapneumonic Effusion
Conditions
Keywords
VATS Decortication, Surgical Pleural Decortication, Fibrinolytic Therapy, Pneumonia, Thoracostomy
Brief summary
This study aims to standardize the treatment of pleural space (parapneumonic) infections by comparing the difference in outcomes between 2 methods of treatment: early VATS (Video Assisted Thorascopic Surgery) decortication versus fibrinolytic therapy. During treatment, the patient's coagulopathy status will also be evaluated.
Detailed description
The treatment of parapneumonic infections (infection in the pleural space) at the Denver Health Medical Center is not standardized, and timing for advanced interventions such as fibrinolytic therapy or surgical decortication remain unclear. The definitive treatment strategy in these patients may be sub-optimal, and lead to prolonged hospitalization and morbidity. This is concerning as the mortality rate of community acquired pneumonia triples in the presence of a parapneumonic process (5-15%) and can reach over 25% if it becomes bilateral(1). Prompt recognition of pleural space infections is essential for reducing morbidity and mortality. This is attributable to the progression of the disease from a simple fluid collection amenable to pleural space drainage, to necrotizing empyema requiring thoracotomy decortication and open drainage. The keys to management of parapneumonic effusions are early diagnosis, appropriate therapeutic intervention, and recognition of failure of conservative management. The investigators propose that a standardized pathway for identifying and treating parapneumonic effusions will be an important quality improvement. A key gap in the literature remains if patients with parapneumonic infections that cannot be drained with a chest tube should undergo a trial in intrapleural fibrinolytic therapy, or if they should go directly to video assisted thoracic surgery (VATS) for decortication of all infectious material.
Interventions
PROCEDUREVATS Decortication
Surgical procedure to unroof all located collections of the pleural space through a chest wall incision
Instillation of DNAse and tPA together through patient's chest tube already in placed to break down complex fluid collection in the pleural space. DNAse and tPA are are administered together only i.e. are not mutually exclusive.
Sponsors
Denver Health and Hospital Authority
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Prospective Randomized Clinical Trial
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 18 years old and older * Admitted with pleural effusion that undergoes thoracentesis by medical/pulmonary service * Pleural fluid pH \<7.3 * SICU placed chest tube * Subsequent transfer to SICU
Exclusion criteria
* Existing malignancy * Malignant cells from initial pleural fluid sample * End stage liver disease (Child's B or greater) * Coagulopathy * Unable to tolerate surgical procedure * Frank purulent drainage (needs OR regardless) * Recent surgery of abdomen or thorax precluding the use of tPA * Baseline neurologic impairment requiring a proxy for consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hospital Length of Stay | From patient's admission to hospital to their discharge, (excluding extended stay due to social work reasons) up to 28 days or discharge, which ever comes first. | How long the patient remains admitted in the hospital during their index hospitalization |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| ICU Free Days | From admission to discharge, or for 28 days, whichever comes first. | Admission days during index hospitalization that are of a lower acuity of care than intensive care |
| Chest Tube Days | From admission to discharge, or for 28 days, whichever comes first. | Days with chest tube in place after intervention |
| Cost of Admission and Treatment | From admission to discharge, or for 28 days, whichever comes first. | Cost of care for the patient after their intervention |
| Pain Score | From admission to discharge, or for 28 days, whichever comes first. | What the patient's level of pain is from 0 to 10; zero being no pain, 10 being the worst pain imaginable. score is categorical 0,1,2,3,4,5,6,7,8,9 or 10. |
| Chest Tube Drainage | From admission to discharge, or for 28 days, whichever comes first. | The amount and character of the drainage from the chest tube after intervention |
| Fever Days | From admission to discharge, or for 28 days, whichever comes first. | The amount of days it takes to resolve fever (temp \>100.4) |
| Supplemental Oxygen Days | From admission to discharge, or for 28 days, whichever comes first. | The amount of time the patient needs to warn off any supplemental oxygen |
| Days of Antibiotics | From admission to discharge, or for 28 days, whichever comes first. | The number of days antibiotics are required after intervention |
| Elevated White Blood Count Days | From admission to discharge, or for 28 days, whichever comes first. | The amount of days it takes to resolve a leukocytosis |
| Changed in Coagulopathic Status | From admission to discharge, or for 28 days, whichever comes first. | Changes in laboratory TEG values after intervention |
| Incentive Spirometry | Everyday for 5 days post study intervention, from admission to discharge, or for 28 days, whichever comes first. | To what volume the patient can inspire using an incentive spirometer |
Countries
United States
Participant flow
Recruitment details
Prospective randomized clinical trial of hospitalized patients identified to have complicated parapneumonic effusions with radiographic imaging. Denver Health and Hospital Authority.
Participants by arm
| Arm | Count |
|---|---|
| Operative VATS Decortication Operative group that will undergo early VATS decortication of complicated parapneumonic effusion/empyema
VATS Decortication: Surgical procedure to unroof all located collections of the pleural space through a chest wall incision | 5 |
| Non-operative Fibrinolytic Therapy Non-operative group that will undergo instillation of the drugs DNAse and tPA (tissue plasminogen activator) together i.e. 5mg DNAse and 10mg tPA twice a day for up to six doses, through chest tube as treatment of the patient's complicated parapneumonic effusion/empyema. Fibrinolytic therapy = DNAse + tPA; these medications are not mutually exclusive.
Fibrinolytic Therapy: Instillation of DNAse and tPA together through patient's chest tube already in placed to break down complex fluid collection in the pleural space. DNAse and tPA are are administered together only i.e. are not mutually exclusive. | 5 |
| Total | 10 |
Baseline characteristics
| Characteristic | Operative VATS Decortication | Non-operative Fibrinolytic Therapy | Total |
|---|---|---|---|
| Age, Continuous | 44 years STANDARD_DEVIATION 16.1 | 45.6 years STANDARD_DEVIATION 11.1 | 44.8 years STANDARD_DEVIATION 13.6 |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Sex: Female, Male Female | 1 Participants | 2 Participants | 3 Participants |
| Sex: Female, Male Male | 4 Participants | 3 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 5 | 1 / 5 |
| other Total, other adverse events | 2 / 5 | 1 / 5 |
| serious Total, serious adverse events | 0 / 5 | 2 / 5 |
Outcome results
Primary
Hospital Length of Stay
How long the patient remains admitted in the hospital during their index hospitalization
Time frame: From patient's admission to hospital to their discharge, (excluding extended stay due to social work reasons) up to 28 days or discharge, which ever comes first.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Operative VATS Decortication | Hospital Length of Stay | 12.4 days | Standard Deviation 16.7 |
| Non-operative Fibrinolytic Therapy | Hospital Length of Stay | 8.4 days | Standard Deviation 4.1 |
Secondary
Changed in Coagulopathic Status
Changes in laboratory TEG values after intervention
Time frame: From admission to discharge, or for 28 days, whichever comes first.
Population: No participants were analyzed on this measure in the final analysis, because the data were not collected.
Secondary
Chest Tube Days
Days with chest tube in place after intervention
Time frame: From admission to discharge, or for 28 days, whichever comes first.
Population: All 10 participants were analyzed on this data point and aggregate data is provided below for each treatment arm.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Operative VATS Decortication | Chest Tube Days | 7.4 Days | Standard Deviation 8.2 |
| Non-operative Fibrinolytic Therapy | Chest Tube Days | 8.2 Days | Standard Deviation 2.4 |
p-value: 0.84ANOVA
Secondary
Chest Tube Drainage
The amount and character of the drainage from the chest tube after intervention
Time frame: From admission to discharge, or for 28 days, whichever comes first.
Population: Incomplete analysis documented in records on this measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Operative VATS Decortication | Chest Tube Drainage | 60.1 mL | Standard Deviation 12.3 |
| Non-operative Fibrinolytic Therapy | Chest Tube Drainage | 713.2 mL | Standard Deviation 180.3 |
Secondary
Cost of Admission and Treatment
Cost of care for the patient after their intervention
Time frame: From admission to discharge, or for 28 days, whichever comes first.
Population: The data were not collected
Secondary
Days of Antibiotics
The number of days antibiotics are required after intervention
Time frame: From admission to discharge, or for 28 days, whichever comes first.
Population: All 10 participants were analyzed on this data point and aggregate data is provided below for each treatment arm.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Operative VATS Decortication | Days of Antibiotics | 17 Days | Standard Deviation 9.3 |
| Non-operative Fibrinolytic Therapy | Days of Antibiotics | 25.6 Days | Standard Deviation 24.6 |
p-value: 0.45ANOVA
Secondary
Elevated White Blood Count Days
The amount of days it takes to resolve a leukocytosis
Time frame: From admission to discharge, or for 28 days, whichever comes first.
Population: All 10 participants were analyzed on this data point and aggregate data is provided below for each treatment arm.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Operative VATS Decortication | Elevated White Blood Count Days | 5.6 Days | Standard Deviation 4 |
| Non-operative Fibrinolytic Therapy | Elevated White Blood Count Days | 6 Days | Standard Deviation 3.6 |
p-value: 0.87ANOVA
Secondary
Fever Days
The amount of days it takes to resolve fever (temp \>100.4)
Time frame: From admission to discharge, or for 28 days, whichever comes first.
Population: All 10 participants were analyzed on this data point and aggregate data is provided below for each treatment arm.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Operative VATS Decortication | Fever Days | 4.8 Days | Standard Deviation 5.3 |
| Non-operative Fibrinolytic Therapy | Fever Days | 0.8 Days | Standard Deviation 1.1 |
p-value: 0.25ANOVA
Secondary
ICU Free Days
Admission days during index hospitalization that are of a lower acuity of care than intensive care
Time frame: From admission to discharge, or for 28 days, whichever comes first.
Population: All 10 participants were analyzed on this data point and aggregate data is provided below for each treatment arm.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Operative VATS Decortication | ICU Free Days | 22.4 Days | Standard Deviation 8 |
| Non-operative Fibrinolytic Therapy | ICU Free Days | 20 Days | Standard Deviation 6.2 |
p-value: 0.61ANOVA
Secondary
Incentive Spirometry
To what volume the patient can inspire using an incentive spirometer
Time frame: Everyday for 5 days post study intervention, from admission to discharge, or for 28 days, whichever comes first.
Population: No participants were analyzed on this measure in the final analysis, because the data were not collected.
Secondary
Pain Score
What the patient's level of pain is from 0 to 10; zero being no pain, 10 being the worst pain imaginable. score is categorical 0,1,2,3,4,5,6,7,8,9 or 10.
Time frame: From admission to discharge, or for 28 days, whichever comes first.
Population: The pain score was provided at the discharge date or at 28 days of admission (whichever came first).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Operative VATS Decortication | Pain Score | 3.6 score on a scale | Standard Deviation 1 |
| Non-operative Fibrinolytic Therapy | Pain Score | 4.6 score on a scale | Standard Deviation 2 |
Secondary
Supplemental Oxygen Days
The amount of time the patient needs to warn off any supplemental oxygen
Time frame: From admission to discharge, or for 28 days, whichever comes first.
Population: All 10 participants were analyzed on this data point and aggregate data is provided below for each treatment arm.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Operative VATS Decortication | Supplemental Oxygen Days | 17.8 Days | Standard Deviation 24.5 |
| Non-operative Fibrinolytic Therapy | Supplemental Oxygen Days | 9.6 Days | Standard Deviation 2.3 |
p-value: 0.48ANOVA