Sunday 16 February 2020

Conservative vs interventional Treatment for Spontaneous Pneumothorax: Don’t just do something… stand there!


This study in the New England Journal of Medicine is going to change how we treat spontaneous pneumothorax. If you haven’t read it, you should.

(Disclaimer: the lead author, Dr Simon Brown is a colleague of mine at the Royal Hobart Hospital. He is bigger than me and knows where I live. Hmmmm….)

By way of background, there are conflicting guidelines regarding the treatment of primary spontaneous pneumothorax. The Americans are quite aggressive with intervention, the British less so. Any time you see such variation, it usually means there is no high-quality evidence to inform practice.

Fortunately, we now have that evidence.

The Primary Spontaneous Pneumothorax (PSP) trial was a prospective randomised open-label non-inferiority study that enrolled 316 patients in 39 hospitals in Australia & New Zulund over 6 years.

They included stable patients between the ages of 14-50 with at least a 32% (sum of interpleural distance greater than 6cm) primary spontaneous pneumothorax.

Those randomised to intervention had a <12 French Seldinger style chest tube placed. They got a repeat chest x-ray in one hour. If the lung was re-expanded and there was no air leak, they clamped the tube. Another x-ray was taken 4 hours later. If all was fine, the tube was pulled and the patient discharged. If not, they got admitted.

The conservative” arm was observed for 4 hours and a repeat chest x-ray was taken. If they did not require oxygen and they were walking around comfortably, they could be discharged. However, intervention could be allowed for if the patient had clinically significant symptoms despite adequate analgesia, couldn’t walk, unwilling to continue, became unstable or if the chest x-ray was getting worse.

The primary outcome was full lung expansion by 8 weeks. There were lots of arguably more important secondary outcomes.

Results?

As expected, patients were generally young, male and thin. Half were smokers.

Mean pneumothorax size was 65%! Holy crap… that’s big.

For the primary outcome, 98% of the intervention arm had full lung re-expansion at 8 weeks vs. 94% in the conservative arm. This was within their prespecified non-inferiority margin of -9% as such, this is a positive study.

However, even more impressive are the secondary outcomes in favour of a conservative approach.

85% of patients randomised to conservative management got no intervention. The intervention arm had many more adverse events (26% vs. 8%) mostly related to the chest tube. Mean time to resolution of symptoms was 15 days in both groups. Recurrent pneumothorax was double in the intervention arm; 16% vs. 8%.

Median hospital length of stay was 3.8 days in the intervention group compared to 0.2 in the conservative arm!

All of this is quite a good argument for us to change our practice.

For what it is worth, the manuscript goes into length regarding the limitations of loss to follow-up. Even going so far as to perform an analysis assuming all of them were treatment failures making this study “fragile.” While perhaps technically correct, I think this was overzealous peer review that was ultimately biased.

A 26-year-old male, who got no treatment and feels fine is probably less likely to follow up as directed. However, patients in the intervention arm (who got painful tubes and spent 4 days in hospital) were more likely to return for the 8-week visit.

What’s the take home point?

Looks like we’ll be doing less chest tubes in stable patients with primary spontaneous pneumothorax.
 
Bummer… I like putting in chest tubes.


Covering:

Brown S.G.A, Ball E.L, Perrin K, Conservative versus Interventional Treatment for Spontaneous Pneumothorax. N Eng J Med. 2020;382:405-15. [link to article]





Diagnosis of PE with D-Dimer Adjusted to Clinical Probability- A game changer!


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Intern, “the D-dimer just came back at 0.6… what should I do?”

Me, “… faaaaaaaaaaaaaaaaaaaaaaaaarrrrrrrk!”

Fortunately, this study is probably a game changer.

These Canadian’s conducted a prospective study in which PE was considered to be ruled out if the pretest clinical suspicion was low (Well’s score0-4) and a D-dimer of less than 1.0mg/L or if the clinical suspicion was moderate (Well’s score 4.5-6) and D-dimer less than 0.5mg/L.

Just over two thousand patients were enrolled. Their overall rate of PE was 7.4%.

Of the 1325 patients with low or moderate clinical suspicion for PE and a negative D-dimer (as above), NONE (95%CI 0.0 to 0.29%) of them had venous thromboembolism during the 3-month follow up.   

This is amazing.

Once again, two-thirds of all patients were excluded from imaging and the diagnostic performance of this strategy was perfect.

Furthermore, this publication from the NEJM is one in line of papers supporting the notion of adjusting D-dimer thresholds. Consistency in the literature is reassuring.

Slam dunk?

Ok… no studies are perfect. What were the two major limitations?

The quality of a study looking at diagnostic performance of a test is only as good its gold standard. Unfortunately, patients that were ruled out by this strategy did not have definitive imaging. This study relied on 3-month follow up (sometimes by telephone) and may have led to the underdiagnosis of PE.

Secondly, there were 34 deaths during follow-up.

Yikes!

But they claim, “no deaths were attributed by the central adjudication committee to pulmonary embolism.” Table S5 in the supplementary appendix shows that most died of cancer or cardiovascular disease. I very much doubt many (if any) of the deaths had autopsy performed. We all know PE can be quite tricky to diagnose. I still wonder if some of these deaths were due to missed PE.

Despite these limitations, I still think adjusting D-dimer thresholds makes sense. And now it is supported by numerous studies published in high impact journals.

Intern, “the D-dimer just came back at 0.6… what should I do?”

Me, “Never order a D-dimer without asking me first!”

Oh… I meant, “send them home…” And hopefully they don’t die of “cancer.”


Covering:

Kearon C, de Wit, Parpia S, et al. Diagnosis of Pulmonary Embolism with D-dimer Adjusted to Clinical Probability. N Engl J Med 2019;381:2125-34. [link to article]



Saturday 15 February 2020

Roc vs. Sux for RSI… a storm in a teacup


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Far too much time and effort has been spent debating the winner of the rocuronium vs. succinylcholine contest. But it is a bit too hard to ignore this paper claiming to be the first RCT of these drugs in an emergency setting.

This was a multicenter, non-inferiority RCT of 1248 patients with out-of-hospital cardiac arrest in France. Tout bon!

Rocuronium dosed at 1.2m/kg was compared to succinylcholine at 1mg/kg. The authors note the patients were blinded to the assigned drugs. Yes… really… Patients with no health insurance were excluded. Yes… really…

About 90% of the intubations were conducted by a specialist emergency doctor. They only used direct laryngoscopy (no video) and half the time intubated in some pretty creative places… i.e. on the ground.

The primary outcome was first pass intubation success rate. Hardly a patient oriented outcome, but at least it is reasonably objective and measurable. They also looked at some secondary outcomes.

A non-inferiority margin of 7% was chosen.

Results?

It turns out that rocuronium was not non-inferior to succinylcholine!

Howzat…?

First pass success rate was 79% in the sux group vs. 74% in the roc group. The difference in the 95% confidence interval was up to 9%. This is greater than their non-inferiority margin.

Sux is the winner!

Not really.

There were more adverse events in the succinylcholine group.

Unfortunately, this study will not end the Sux vs. Roc debate. C'est la vie... But either way it doesn’t really matter.

Both drugs are fine. And in your practice, you can always use both.

Don’t forget some contraindications to giving sux (mostly hyperkalemia) and don’t forget to provide post intubation sedation after giving a proper dose of roc.




Covering:

Buihard B, Chollet-Xemard C, Lakhnati P, et al. Effect of Rocuronium vs Succinylcholine on Endotracheal Intubation Success Rate Among Patients Undergoing Out-of Hospital Rapid Sequence Intubation. JAMA 2019;322(23):2303-2312 [link to article]