Chest Tubes and Empyema Management

Dose De-escalation of Intrapleural Tissue Plasminogen Activator Therapy for Pleural Infection. The Alteplase Dose Assessment for Pleural Infection Therapy Project

https://pubmed.ncbi.nlm.nih.gov/28324671/

Case Series 

Reference: Popowicz N, Bintcliffe O, De Fonseka D, et al. Dose de-escalation of intrapleural tissue plasminogen activator therapy for pleural infection. The alteplase dose assessment for pleural infection therapy project. Ann Am Thorac Soc 2017; 14:929–936.

Summary: This study evaluated the efficacy and safety of dose de-escalation for intrapleural tPA in the treatment of pleural infection. The study evaluated 61 patients with pleural infection treated at 4 centers in Australia, the UK and New Zealand. The patients were treated with 5mg of tPA and DNase twice daily instead of the regular regimen of 10mg tPA and 5mg DNase twice daily. Treatment success was defined by a clearance of pleural opacities on chest radiography, increase in pleural fluid drainage and decrease in blood CRP level. Seven of 61 patients had dose escalation of tPA to 10mg and three patients underwent surgery. This pilot study showed a dose de-escalation of 5mg tPA in combination with 5mg DNase twice daily may be safe and efficacious for the treatment of pleural infection.


 Concurrent Intrapleural Instillation of Tissue Plasminogen Activator and DNase for Pleural Infection. A Single-Center Experience

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.


 Management of pleural infection in adults: British Thoracic Society Pleural Disease Guideline 2010

https://www.ncbi.nlm.nih.gov/pubmed/20696693

Guideline 

Reference: Davies HE, Davies RJ, Davies CW. Management of pleural infection in adults: British Thoracic Society Pleural Disease Guideline 2010. Thorax. 2010;65 Suppl 2:ii41-53.

Summary: Pleural infection is a common clinical problem that requires prompt evaluation and intervention. This article reviews available literature and provides recommended guidelines regarding the management of pleural infections. It also provides a good algorithm for the evaluation and management of pleural infections.


 

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

https://pubmed.ncbi.nlm.nih.gov/19820073/

Clinical Trial 

Reference: Rahman NM, Maskell NA, Davies CWH, et al. The relationship between chest tube size and clinical outcome in pleural infection. CHEST 2010; 137:536-43.

Background: The optimal chest tube size for treatment of pleural infection was only evaluated in small cohort studies prior to this study. This publication describes information gained from patients enrolled in a study investigating the utility of fibrinolytic therapy for the treatment of pleural infection.

PICO:

Populations:

  • 405 adult patients with pleural infection were enrolled in the MIST1 trial at 52 centers in the UK
  • Included patients with: pleural fluid that was macroscopically purulent, positive for bacteria on Gram’s staining or culture, or a pH below 7.2 in a patient with clinical infection

Intervention:

  • Chest tube insertion (size and method determined by treating institution) and administration of intrapleural streptokinase or placebo

Comparison:

  • Various chest tube sizes

Outcome:.

  • Primary outcome: No significant difference in the frequency of death or thoracic surgery in patients receiving chest tubes of various sizes (ranging from <10F to >20F).
  • Secondary outcomes: No significant difference in hospital length of stay, change in chest radiograph or lung function at 3 months in patients receiving chest tubes of various sizes.
  • Pain scores were recorded in 128 patients and were found to be substantially higher in patients receiving larger tubes (primarily requiring blunt dissection insertion).

Take Home: Smaller, guide wire inserted chest tubes cause less pain for patients when compared to larger chest tubes that require blunt dissection for insertion. There does not appear to be any reduction in clinical efficacy for the treatment of pleural infection with a smaller diameter chest tube. Smaller chest tubes may be a reasonable alternative to large bore chest tubes in the treatment of pleural infection.


 U.K. Controlled trial of intrapleural streptokinase for pleural infection

https://pubmed.ncbi.nlm.nih.gov/15745977/

Clinical Trial 

Reference: Maskell N, Davies C, Nunn A, et al. U.K. Controlled Trial of Intrapleural Streptokinase for Pleural Infection: MIST1. N Engl J Med 2005; 352(9):865-874.

Background: This study formally evaluated the role of intrapleural streptokinase for the treatment of pleural infection as previous studies were small and unable to formally evaluate clinical safety and efficacy.

PICO:

Populations:

  • Randomized 427 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
  • Patients were enrolled at 52 centers in the UK

Intervention:

  • Chest tube insertion and administration of 250,000IU intrapleural streptokinase in 30mL saline every 12 hours for six doses

Comparison:

  • Chest tube insertion and administration of intrapleural placebo in 30mL saline every 12 hours for six doses

Outcome:

  • Primary outcome: No significant difference between the two groups in the proportion of patients requiring surgical drainage or who died in the three months after randomization
  • Secondary outcomes: No significant benefit of streptokinase in regards to mortality, rate of surgery, radiographic outcomes or length of hospital stay when compared to intrapleural placebo.
  • Serious adverse events were more common with streptokinase when compared to placebo (P=0.08)

Take Home: This study did not reveal any significant benefit of intrapleural streptokinase administration when compared to intrapleural placebo administration in the treatment of pleural infection and is therefore not recommended.