IP Fellows Reading List

https://pubmed.ncbi.nlm.nih.gov/27333122/

Case Series 

Reference: Majid A, Kheir F, Folch A, et al. Concurrent intrapleural instillation of tissue plasminogen activator and DNase for pleural infection. Ann Am Thorac Soc 2016; 13:1512–1518.

Summary: This study evaluated the efficacy and safety of concurrent instillation of tPA and DNase for the treatment of pleural infection. The study evaluated 73 patients that received concurrent tPA/DNase for pleural infection. The total number of doses was determined by pleural fluid drainage, clinical response and radiographic findings. Treatment was successful in 90.4% of patients and 80.8% of patients required fewer than six doses of therapy. Complications included non-fatal pleural bleeding (5.4%), chest pain (15.1%) and death related to pleural infection (2.7%). This study showed early, concurrent administration of tPA/DNase is relatively safe and effective for the treatment of pleural infection. It also showed that decisions regarding number of doses may be feasible based on clinical and radiographic response.

 Intrapleural use of tissue plasminogen activator and DNase in pleural infection

https://www.ncbi.nlm.nih.gov/pubmed/21830966

Landmark Article 

Reference: Rahman NM, Maskell NA, West A, et al. Intrapleural use of tissue plasminogen activator and DNase in pleural infection. N Engl J Med. 2011;365(6):518-26.

Background: Efficient treatment of pleural infections is crucial to improved outcomes in these patients. This study sought to evaluate intrapleural medication regimens for the management of pleural infection.

PICO:

Populations:

• Adult patients with pleural infection determined by clinical evidence of infection and either:
• Macroscopically purulent pleural fluid
• Positive fluid culture or gram stain
• Pleural fluid with a pH <7.2
• Excluded patients with: previous intrapleural fibrinolytic agents or DNase, stroke, major hemorrhage, surgery or trauma, previous pneumonectomy, pregnancy or lactation, expected survival less than 3 months

Intervention:

• Intrapleural tissue plasminogen activator (t-PA) and DNase

Comparison:

• t-PA and placebo
• DNase and placebo
• Double placebo

Outcome:

• Primary outcome: Significant difference between the two groups (tPA-DNase vs. Placebo), with the tPA-DNase group experiencing more improvement
• Change in pleural opacity, measured as the percentage of the hemithorax occupied by effusion, on chest radiography on day 7 as compared with day 1
• Secondary outcomes:
• Referral for surgery – Frequency of surgical referral at 3 months was significantly lower in tPA-DNase group when compared to placebo
• Duration of hospital stay – Post-hoc analysis revealed LOS was significantly lower in tPA-DNase group when compared to placebo
• Adverse events – No significant difference in other serious and non-serious adverse events between all groups

Take Home: This study showed intrapleural tPA-DNase therapy improved pleural fluid drainage in patients with pleural infection better than the other evaluated regimens. These patients required less surgery and had shorter hospital lengths of stay when compared to other evaluated groups.

The relationship between chest tube size and clinical outcome in pleural infection

Reference: Kheir F, Thakore S, Mehta H, et al. Intrapleural fibrinolytic therapy versus early medical thoracoscopy for treatment of pleural infection. Randomized controlled clinical trial. Ann Am Thorac Soc. 2020;17(8):958-964.

Background: Medical thoracoscopy can be used to treat pleural space infections by mechanically lysing adhesions, improving drainage, and directing chest tube placement. This is a multicenter randomized controlled trial evaluating outcomes of empyema/multiloculated pleural infection management with either early medical thoracoscopy versus intrapleural fibrinolytic therapy.

PICO:

• Adult patients with empyema or multiloculated pleural space infection (n=32)

• Early medical thoracoscopy (n=16)

• Intrapleural fibrinolytic therapy (n=16)

• The primary outcome was hospital length of stay. The median length of stay was two days for patients undergoing medical thoracoscopy versus four days in the intrapleural fibrinolytic therapy group (p = 0.026)
• There were no differences in treatment failure, adverse events or mortality between the groups.

Reference: Chaddha U, Agrawal A, Feller-Kopman D, et al. Use of fibrinolytics and deoxyribonuclease in adult patients with pleural empyema: a consensus statement. Lancet Respir Med. 2021;9(9):1050-1064.

Summary: This is a consensus statement derived from an international expert panel regarding the use of intrapleural fibrinolytic and deoxyribonuclease therapy in adult patients with bacterial empyema. This position paper includes seven graded and four ungraded recommendations. This consensus statement addresses the following for fibrinolytic or deoxyribonuclease therapy: mono- or combination therapy, dosage, sequence, duration of chest tube clamping, number of doses, use in those with coagulopathy or on antiplatelet/anticoagulant therapy, use as initial or subsequent therapy, cost, and role of normal saline irrigation.