February 5, 2024

The Needle Vs. The Knife for Spontaneous Pneumothorax: A Closer Look at the EXPRED Study

Written by Bryan Tiernan, DO
REBEL EM
Medical Category: Thoracic and Respiratory

Background: The optimal management of primary, spontaneous pneumothorax (sPTX) remains an area of active debate. The British Thoracic Society recommends the least invasive approach possible. In contrast, the American College of Chest Physicians favors first-line chest tube drainage for any sPTX with an estimated volume of over 20%.(3) A Cochrane systematic review comparing simple aspiration with drainage for adult cases identified several randomized controlled trials of small, heterogeneous populations with first or recurrent pneumothorax. They concluded that more research of higher quality is needed to strengthen the evidence in favor of one technique over the other. The EXPRED (Exsufflation of Primary Spontaneous Pneumothorax versus Chest Tube Drainage) study aimed to strengthen the evidence that simple aspiration is non-inferior to chest tube placement during the first episode of complete primary pneumothorax.

Article: Marx T, Joly LM, Parmentier AL, et al. Simple Aspiration versus Drainage for Complete Pneumothorax: A Randomized Noninferiority Trial. Am J Respir Crit Care Med. 2023;207(11):1475-1485. PMID: 36693146

Clinical Question: In patients aged 18-50 years with primary and complete pneumothorax, is simple aspiration non-inferior to chest tube drainage for rates of pulmonary re-expansion within 24 hours?

What They Did:

Study Design: Investigators conducted a multicenter, prospective, open-label, randomized-controlled, non-inferiority trial.
Sites: Investigators recruited patients at 31 French emergency departments at university and nonuniversity hospitals
Duration: June 1, 2009 to March 31, 2015.
Funding: The Cardinal Health Laboratory provided Turkel thoracentesis kits to two hospitals
Trial Registry: Clinicaltrials.gov: NCT01008228.

Population:

Inclusion:

Patients between 18–50 years of age.
Symptomatic with chest pain and/or dyspnea for < 48 hours.
First episode of primary and complete pneumothorax.

Exclusion:

Tension pneumothorax (identified clinically or on radiographic images)
Traumatic pneumothorax
Recurrent pneumothorax
Primary pneumothorax associated with pleural effusion
Secondary pneumothorax with underlying lung disease
Pregnant or lactating women
Patients not available for follow-up
Unable to give consent or under trusteeship, guardianship, or judiciary protection

Intervention:

Simple aspiration using an 8-french polyurethane safety catheter (Turkel Thoracentesis Kit, Cardinal Health).
- Thoracentesis with free drainage for 15 minutes
- Drainage at -25cm H20 for 30 minutes
- Clamping and radiograph;
- If failed, 2nd aspiration at -25cm H20 for 30 minutes,
- Repeat clamping and radiograph.
- If it fails again, chest tube placement and continuous drainage.

Control:

Chest tube drainage with a 16-French or 20-French large chest tube.

Outcomes:

Primary Outcome:

Pulmonary expansion 24 hours after the procedure.
- Absence of residual pneumothorax or the presence of an apical residual pneumothorax smaller than 2 cm, based on chest radiography.

Secondary Outcomes:

Pulmonary expansion 7 days after the procedure.
Recurrence of pneumothorax within 1 year.
Tolerance of the techniques (pain, dyspnea, and anxiety) at 24 hours and 7 days.
Adverse events at 24 hours and 7 days, including major and minor complications.

Minor Complications:

Pain limiting breathing
Bleeding at the insertion site
Kinking of the device
Subcutaneous emphysema

Serious Adverse Events:

Hemothorax by laceration through the neurovascular bundle
Persistent bubbling or leakage at the insertion site
Accidental ablation of the device
Perforation of an organ
Local abscess
Reexpansion pulmonary edema

Results:

402 patients were enrolled across the 31 hospitals
- 200 assigned to the simple aspiration group
  - 11 excluded from the simple aspiration group
  - 189 were included in the intention-to-treat analysis.
  - A further eight were excluded, for a total of 181 included in the per-protocol analysis
- 202 assigned to the chest tube drainage group
  - 12 were excluded from the chest tube drainage
  - 190 included in the intention-to-treat analysis,
  - A further 12 were excluded, for a total of 178 were included in the per-protocol analysis.

Primary Outcome:

Per Protocol:
- Simple aspiration group failure: 29%
- Chest tube drainage group failure: 18%
- The difference in failure rate: 0.113 (95% CI 0.026-0.200) with a noninferiority margin of +0.205
Intention to treat
- Simple aspiration group failure: 29%
- Chest tube drainage group failure: 19%
- The difference in failure rate: 0.097 (95% CI 0.011-0.183) with a noninferiority margin of +0.201
Simple aspiration did not exceed the fixed absolute margin of 0.45, indicating statistical noninferiority as defined by their noninferiority margin.

Secondary Outcomes:

Treatment failure after 7 days: 16% for aspirations, 15% for drainages with a difference of rate 0.004 and 0.005 for per protocol and intention to treat with a noninferiority margin of 0.212.
Pneumothorax recurrence within 1 year: 20% for aspirations, 27% for chest tubes.
Tolerance: At 24 hours, Pain was rated lower in the aspiration group (2.2) than in the drainage group (3.6).
Adverse events: Similar rates of major complications in both groups.

Strengths:

The Investigators asked a clinically relevant research question; as such, the study may potentially affect practices related to the management of spontaneous pneumothorax.
A non-inferiority design was a sound methodologic choice because simple aspiration offers distinct advantages, such as reduced pain, and the skills required to perform simple aspiration are more widely available to various specialties compared to chest tube placement.
The multicenter study design increases generalizability and external validity by including a diverse population.
The randomized study design increases generalizability and external validity by limiting bias.
The study employed block randomization with sizes of 4 and 6, enhancing unpredictability in patient assignment while ensuring balanced group sizes and reducing selection bias.
The randomization was concealed and managed offsite through a dedicated hotline, minimizing bias and ensuring a rigorous study design.
The moderate sample size enhances the study’s statistical power, increasing the reliability of the results and their applicability to a broader population.
Registering the trial with clinicaltrials.gov promotes transparency and allows other researchers to replicate and validate the study more easily.
Blinding the outcome assessors to the initial assessment reduces the risk of measurement bias, enhancing the objectivity of the results.
The trial investigators conducted both per-protocol and intention-to-treat analyses, providing a thorough examination of the data and accounting for various patient adherence levels.

Limitations:

The study was only conducted in one country under one healthcare system, which limits its applicability to other regions due to the potential geographical differences.
The focus on patients with complete pneumothorax narrows its relevance to cases with smaller pneumothoraces.
Including only patients with primary pneumothorax excludes applicability to patients with secondary, traumatic, iatrogenic, and other pneumothorax types.
The patient demographic was predominantly young males, which may not represent the wider patient population, especially women and older adults.
Including only hospitals with extensive specialist networks may not reflect the conditions in less-resourced hospitals.
The open-label design, with both patients and physicians aware of treatment allocation, introduces bias. Moreover, clinicians performing the procedure also evaluated the outcomes.
Chest X-rays were reviewed centrally by experts blind to the initial assessment, but these experts could likely tell if the device was a chest tube or aspiration device, which introduces bias.
Recruitment from only emergency departments may not represent the broader clinical context.
The availability of study personnel limited enrollment to specific times, which introduces selection bias. This raises the question of whether the enrolled cohort is representative of the entire population of patients with pneumothorax.
The use of a single aspiration device and specific chest tube sizes (16 or 20 French) may not reflect the variety of medical practices and equipment.
The study’s focus on pulmonary re-expansion as the primary outcome may not fully address patient-oriented outcomes.
Many secondary outcomes were subjective, such as dyspnea, pain, and anxiety. Reliance on subjective data could affect the reliability of the results.
The non-inferiority margin set at 25% with an acceptable failure rate of 45% for aspiration may be too generous, potentially overestimating the effectiveness of the treatment.
Additional statistical analysis was required because the control group did not meet the historic failure rate of 30%, indicating possible deviations in patient characteristics or treatment efficacy.
Physician preference dictated chest tube placement, introducing variability in treatment application.
There was no information on length of stay and cost analysis, which may have provided additional evidence to support the use of either device.

Discussion:

Noninferiority:

Noninferiority trials attempt to prove a new treatment is NOT MUCH WORSE than an existing one. However, a key ethical concern is whether providing a treatment that might be less effective than the standard of care is acceptable. However, these trials may be justifiable when one therapy has evident benefits over another beyond efficacy. For instance, compared to more invasive procedures, simple aspiration could offer advantages like reduced pain and fewer complications. Additionally, its nonsurgical nature could make it more accessible to a broader range of healthcare providers.

The investigators determined that simple aspiration was statistically non-inferior to chest tube insertion. However, they set the noninferiority margin at a substantial 25%. A larger noninferiority margin makes it easier to show statistical noninferiority, which could influence the robustness of the trial’s conclusions.

Inside the Numbers:

The ITT analysis in this study shows that patients who underwent aspiration had a 39% higher likelihood of treatment failure. Moreover, the broad confidence interval (CI) ranging from 1.08 –2.15 amplifies the uncertainty. This wide CI suggests the true value for treatment failure rate with simple aspiration could be more than twice as high as that for chest tube insertion. Likewise, the per-protocol analysis presents a 48% relative risk of treatment failure, with a CI between 1.11–2.29, indicating that the risk of failure is even higher among those who adhered to the treatment protocol.

Practice Updates:

While published in 2023, the data from this trial were gathered between 2009 and 2015. Smaller-sized pigtail catheters, which are linked to reduced pain, fewer complications, and success rates comparable to surgical chest tubes, are now frequently used (Chang SH). Additionally, recent evidence suggests that observation of patients with moderate-sized pneumothoraces may be a viable approach. (6)

Considering these developments, the benefits of simple aspiration compared to chest tube drainage are less evident. A small pigtail catheter, inserted using the Seldinger technique, may offer the same benefits as simple aspiration with similar success rates. Moreover, it’s important to note that all patients in the study were hospitalized, and physicians needed to drain the chest in both treatment groups. Still, a failure in the simple aspiration group resulted in two procedures.

Author’s Conclusions: “In conclusion, the results of the EXPRED study are in line with a higher rate of failure of the simple aspiration as a first-line strategy than seen with chest tube drainage for achieving lung expansion in adults experiencing a first episode of complete primary spontaneous pneumothorax, but this strategy is better tolerated, less invasive, and safer. These results, therefore support the adoption of simple aspiration as the initial treatment for complete primary spontaneous pneumothorax.”

Our Conclusions:

Simple aspiration presents clear advantages compared to surgical chest tubes and is associated with fewer complications and less pain. However, the effectiveness of simple aspiration compared to more contemporary treatment options like smaller pigtail catheters is unclear and was not studied in this trial. Based on current evidence, small pigtail catheters share many of the same benefits as simple aspiration, such as fewer complications and decreased pain, but with similar success rates to chest tubes. Ultimately, a comparative study between simple aspiration and pigtail catheters would help inform future treatment decisions.

For More on This Topic Checkout:

References:

MacDuff A, Arnold A, Harvey JManagement of spontaneous pneumothorax: British Thoracic Society pleural disease guideline 2010Thorax 2010;65:ii18-ii31. PMID: 20696690
Baumann, M. H., Strange, C., Heffner, J. E., Light, R., Kirby, T. J., Klein, J., Luketich, J. D., Panacek, E. A., & Sahn, S. A. (2001). Management of spontaneous pneumothorax. Chest, 119(2), 590–602. Ashby M, Haug G, Mulcahy P, Ogden KJ, Jensen O, Walters JAE. Conservative versus interventional management for primary spontaneous pneumothorax in adults. Cochrane Database of Systematic Reviews 2014, Issue 12. Art. No.: CD010565. Accessed 12 September 2023. PMID: 25519778
Carson‐Chahhoud KV, Wakai A, van Agteren JEM, Smith BJ, McCabe G, Brinn MP, O’Sullivan R. Simple aspiration versus intercostal tube drainage for primary spontaneous pneumothorax in adults. Cochrane Database of Systematic Reviews 2017, Issue 9. Art. No.: CD004479. Accessed 12 September 2023. PMID: 28881006
Marx T, Joly LM, Parmentier AL, et al. Simple Aspiration versus Drainage for Complete Pneumothorax: A Randomized Noninferiority Trial. Am J Respir Crit Care Med. 2023;207(11):1475-1485. PMID: 36693146
Chang SH, Kang YN, Chiu HY, Chiu YH. A Systematic Review and Meta-Analysis Comparing Pigtail Catheter and Chest Tube as the Initial Treatment for Pneumothorax. Chest. 2018;153(5):1201-1212. PMID: 29452099
Brown SGA, Ball EL, Perrin K, et al. Conservative versus Interventional Treatment for Spontaneous Pneumothorax. N Engl J Med. 2020;382(5):405-415. PMID: 31995686

Guest Post By:

Bryan Tiernan, DO
PGY-1, Emergency Medicine Resident
Vassar Brothers Hospital, Poughkeepsie, New York
E-mail: Bryan.Tiernan@nuvancehealth.org

Marco Propersi, DO FAAEM
Vice-Chair, Emergency Medicine
Assistant Emergency Medicine Residency Program Director
Vassar Brothers Hospital, Poughkeepsie, New York
Twitter/X: @marco_propersi

Post Peer Reviewed By: Salim R. Rezaie, MD (Twitter/X: @srrezaie) and Anand Swaminathan, MD (Twiiter/X: @EMSwami)

Cite this article as: Bryan Tiernan, DO, "The Needle Vs. The Knife for Spontaneous Pneumothorax: A Closer Look at the EXPRED Study", REBEL EM blog, February 5, 2024. Available at: https://rebelem.com/the-needle-vs-the-knife-for-spontaneous-pneumothorax-a-closer-look-at-the-expred-study/.