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Date: August 27th, 2020

Guest Skeptic: Dr. Malthaner is the Chair/Chief of the Division of Thoracic Surgery, Director of Thoracic Surgery Research and Simulation, and Professor in the Departments of Surgery, Oncology, and Epidemiology and Biostatistics at the Schulich School of Medicine and Dentistry and Western University. Rick is also the founder of Western University’s Department of Surgery Journal Club and runs The Skeptik Thoracik Journal Club.

Reference: Brown et al. Conservative versus Interventional Treatment for Spontaneous Pneumothorax. NEJM 2020

Case: A 49-year-old healthy male electrician presents to the emergency room with right chest pain and dyspnea. The work-up reveals a diagnosis of a right pneumothorax confirmed by chest x-ray (CXR). What do you do?

Background: A patient with a pneumothorax is a common presentation to the emergency department. Pneumothoraxes can be broken down into either primary or secondary. Primary pneumothorax occurs in healthy people. Secondary pneumothoraxes are associated with underlying lung disease.

There is considerable heterogeneity in the management of primary spontaneous pneumothoraxes, but the most common treatment is interventional drainage, sometimes progressing to surgical intervention.

However, the insertion of a chest tube is often painful and can cause organ injury, bleeding, and infection. An alternative approach is conservative management, with intervention reserved for patients for whom the pneumothorax becomes physiologically significant. I covered in the Skeptik Thoracik Journal Club which can be viewed on YouTube.

Clinical Question: Does everyone with a large first-time spontaneous pneumothorax need a chest tube?

Reference: Brown et al. Conservative versus Interventional Treatment for Spontaneous Pneumothorax. NEJM 2020

  • Population: Patients 14 to 50 years of age with a unilateral primary spontaneous pneumothorax of 32% or more on chest radiography according to the Collins method.

  • Exclusion:
    • Previous primary spontaneous pneumothorax on the same side
    • Secondary pneumothorax (defined as occurring in the setting of acute trauma or underlying lung disease including asthma with preventive medications or symptoms in the preceding two years)
    • Coexistent hemothorax
    • Bilateral pneumothorax
    • “Tension’ pneumothorax” (systolic BP <90 mmHg, mean arterial pressure <65 mmHg, or shock index HR/SBP ≥1)
    • Pregnancy at time of enrolment
    • Social circumstances (inadequate support after discharge to re-attend hospital if required or unlikely to present for study follow up)
    • Planned air travel within the following 12 weeks
  • Intervention: A small chest tube (≤12 French) was inserted and attached to an underwater seal, without suction and a CXR was obtained one hour later.
    • If the lung had re-expanded and the underwater drain no longer bubbled, the drain was closed with the use of a three-way stopcock. Four hours later, if the patient’s condition was stable and a repeat CXR showed that the pneumothorax had not recurred, the drain was removed, and the patient was discharged.
    • If the initial drain insertion did not result in resolution on CXR or if the pneumothorax recurred under observation, the stopcock was opened, the underwater seal drainage was recommenced, and the patient was admitted.
    • Subsequent interventions were at the discretion of the attending clinician.
  • Comparison: Patients were observed for a minimum of four hours before a repeat CXR was obtained.After observation, if patients did not receive supplementary oxygen and were walking comfortably, they were discharged with analgesia and written instructions.
    • Interventions were allowed in the conservative-management protocol under five conditions:
      1. Clinically significant symptoms persisted despite adequate analgesia;
      2. Chest pain or dyspnea prevented mobilization;
      3. Patient was unwilling to continue with conservative treatment;
      4. Patient’s condition became physiologically unstable (systolic blood pressure of <90 mm Hg, heart rate in beats per minute greater than or equal to systolic blood pressure in millimeters of mercury, respiratory rate of >30 breaths per minute,
      5. Spo2 of <90% while the patient was breathing ambient air or a repeat chest radiograph showed an enlarging pneumothorax along with physiological instability.
    • In these situations, subsequent interventions were at the discretion of the attending clinician.
  • Outcome:
    • Primary Outcome: Complete radiographic resolution of primary spontaneous pneumothorax (full lung re-expansion), as determined by the treating physician, within eight weeks after randomization.
    • Secondary Outcomes: Per-protocol analysis of the primary outcome. Time to radiographic resolution. Time to symptom resolution of symptoms. Pneumothorax recurrence 24 hours or later after chest tube removal. Adverse events. Length of stay (LOS) in the hospital in the first eight weeks. Number of invasive procedures. Number of radiologic investigations. Number of days off from work. Chest-tube drainage for equal to or greater than 72 hours. Patient satisfaction. Two sensitivity analyses of the primary outcome.

Authors’ Conclusions: “Although the primary outcome was not statistically robust to conservative assumptions about missing data, the trial provides modest evidence that conservative management of primary spontaneous pneumothorax was noninferior to interventional management, with a lower risk of serious adverse events.”

Quality Checklist for Randomized Clinical Trials:

  1. The study population included or focused on those in the emergency department. Yes
  2. The patients were adequately randomized. Yes
  3. The randomization process was concealed. Yes
  4. The patients were analyzed in the groups to which they were randomized. Yes
  5. The study patients were recruited consecutively (i.e. no selection bias). Unsure
  6. The patients in both groups were similar with respect to prognostic factors. Yes
  7. All participants (patients, clinicians, outcome assessors) were unaware of group allocation. No
  8. All groups were treated equally except for the intervention. No
  9. Follow-up was complete (i.e. at least 80% for both groups). Yes
  10. All patient-important outcomes were considered. Yes
  11. The treatment effect was large enough and precise enough to be clinically significant. Unsure

Key Results: The cohort of patients analyzed was 256 (154 intervention group and 162 conservative group). The mean age was 26 years and the mean pneumothorax size was about 65% based on the Collins formula.

Conservative management was shown to be non-inferior to placing a chest tube in a patient with a large first-time spontaneous pneumothorax.

  •  Primary Outcome: Re-Expansion within Eight Weeks
    • Intervention Group 98.5% vs. Conservative Group 94.4%
    • Risk Difference -4.1% (95% CI; -8.6% to 0.5%) p=0.02 which meets the pre-specified non-inferiority margin of -9%
  • Secondary Outcomes: 

  • Sensitivity Analysis: Worst Case
    • Intervention Group 93.5% vs. Conservative Group 82.5%
    • Risk Difference -11.0% (95% CI; -19.4% to -1.5%) which does not meet pre-specified non-inferiority margin of -9%

1. Missing Data: An important thing to look at when critically appraising a study is how did the authors manage missing data? In this study, what happened when the data on patients in whom the 8-week visit occurred after 56 days? Were treated as missing, unless a later CXR showed a persisting pneumothorax, thereby confirming treatment failure.

Two sensitivity analyses were undertaken in this trial. In one analysis, the 8-week window was extended to 63 days and data on patients in whom the 8-week visit occurred after 63 days were treated as missing, unless a later CXR showed a persisting pneumothorax, thereby confirming treatment failure. In the other analysis, data on patients in whom the 8-week clinic visit occurred after 56 days were imputed as failure (worst case scenario).

2. Per-Protocol vs. Intention-to-Treat (ITT) Analysis: Their primary outcome used an ITT analysis. It is better in non-inferiority trials to use a per-protocol analysis. This is because the ITT will bias towards finding non-inferiority while a per-protocol is a more conservative approach. Their secondary outcomes did include a per-protocolanalysis of the primary outcome (complete lung re-expansion within 8 weeks, as reviewed by two radiologists who were unaware of the trial-group assignments).

In the per-protocol analysis, 98.4% in the intervention group had resolution within 8 weeks as compared with 94.6% in the conservative group (RD, −3.8% [95% CI; −8.3 to 0.7]).

3. Satisfaction Scale: They used a 6- point Likert scale to assess patient satisfaction at eight weeks. While the scale has face validity, we are not aware that this specific instrument has been validated in this disease specific condition. I don’t think one exits and this may be a minor nerdy point.

4. Adaptive Biased-Coin Randomization: The urn randomization is the most widely known type of the adaptive biased-coin randomization. They are a compromise between designs that yield perfect balance in treatment assignments and complete randomization which addresses experimental bias. The urn design forces a small-sized trial to be balanced but approaches complete randomization as the size of the trial (n) increases (Wei and Lachin 1988).

In an adaptive biased-coin randomization the probability of being assigned to a group decreases if the group is overrepresented and increases if the group is underrepresented. This special less common method of randomization is thought to be less affected by selection bias than permuted-block randomization.

We talked about Cluster Randomization on SGEM#:247. Rather than randomizing the individual patients, it randomizes groups of patients to the intervention or control. There are strengths and weaknesses to any trial design.

5. Non-Inferiority Margin: How do you determine what is considered non-inferior? That authors stated in the methods there was not any previously established noninferiority margin. As such, the steering committee of respiratory and emergency physicians reasoned that a success rate of 90% in the conservative-management group as compared with an anticipated 99% success rate in the intervention group after 8 weeks would be acceptable to both doctors and patients. While I think this was a reasonable margin based their expert opinion and assumptions.

It would have been interesting to ask patients what they would consider “reasonable” for non-inferiority? Ultimately, the data showed their assumptions were pretty good with the success rate in the intervention group being 98.5% vs. 94.4% in the conservative group. This gave a difference of -4.1% (95% CI; -8.6% to 0.5%) p=0.02 which met the pre-specified non-inferiority margin of -9%.

Comment on Authors’ Conclusion Compared to SGEM Conclusion: We agree with the authors conclusions but are not sure if they apply to our patients. In Canada we don’t admit spontaneous pneumothoraxes with chest tubes. We send these patients home with Heimlich valves and follow-up in Thoracik clinic. I sleep better knowing they won’t develop the dreaded tension pneumothorax.

SGEM Bottom Line: It is reasonable to provide conservative management in a patient with large first-time spontaneous pneumothoraxes as long as you can ensure close follow-up.

Case Resolution: You enter a shared decision-making process with the patient on whether or not to place a chest tube. Part of that is to support whatever decision he chooses. He decides to go with conservative management and will follow-up in the clinic.

Clinical Application: This new evidence provides give us more confidence to our practice of treating some of these patients with patients with a first large spontaneous pneumothoraxes conservatively.

What Do I Tell My Patient?  You have a collapse of your lung. This can happen randomly is some people. It seems to be stable and not getting worse. We going to keep an eye on you and not put a tube in your chest. These tubes have been used before to let the lung re-inflate. While a chest tube is a very safe procedure there are always some risks. New research shows more than 90% of patients will be fine without a tube in their chest. If the repeat CXR in about four hours is ok, we will send you home with follow-up with your friendly Thoracik surgeon. You can come back to the emergency department at any time if you are feeling worse or are concerned. 

Keener Kontest: Last weeks’ winner was Claudia Martin a respiratory therapist, long time listener and multiple keener contest winner. She knew egophany comes from Greek word meaning “bleating of a goat”.

Listen to the SGEM podcast to hear this weeks’ question. Send your answer to TheSGEM@gmail.com with “keener” in the subject line. The first correct answer will receive a cool skeptical prize.

Other FOAMed: 

Remember to be skeptical of anything you learn, even if you heard it on the Skeptics’ Guide to Emergency Medicine.

References:

  • Wei and Lachin. Properties of the urn randomization in clinical trials. Control Clin Trials 1988.
  • Observer-expectancy effect. Wikipedia
  • Schulz and Grimes. Allocation concealment in randomised trials: defending against deciphering. The Lancet 2002.