"Prophylactic" NIPPV for Extubation in Obese Patients? The De Jong study, Lancet Resp Med, 2023

I got interested in this topic after seeing a pulmccm.org post on 4 studies of the matter this morning. "They" are trying to convince me that I should be applying NIPPV to obese patients to prevent....well, to prevent what?

We begin with the French study by De Jong et al, Lancet Resp Med, 2023. The primary outcome was a composite of: 1. reintubation; 2. switch to the other therapy (HFNC); 3. "premature discontinuation of study treatment", basically meaning you dropped out of the trial, refusing to continue to participate. 

Which three of those outcomes mean anything? Only reintubation. I actually went into the weeds of the trial because I wanted to know what were the criteria for reintubation. If you have some harebrained protocol for reintubation that is triggered by blood gas values or even physiological variables (respiratory rate), it could be that NIPPV just protects you from hitting one of the triggers for reintubation. You didn't "need" to be reintubated, your PaCO2 which changed almost imperceptibly (3mmHg) triggered a reintubation. These triggers for intubation are witless - they don't consider the pre-test probability of recrudescent respiratory failure, and this kind of mindless approach to intubation gets countless hapless patients unnecessarily intubated every day. Alas, the authors don't even report how the decision to reintubate was made in these patients.

But it doesn't matter. Prophylactic NIPPV doesn't prevent reintubation:

As you can see in this table, the entire difference in the composite outcome is driven by more people being "switched to the other study treatment". Why were they "switched?" We're left to guess. And being a non-blinded study, there is a severe risk that treating physicians knew the study hypothesis, believed in NIPPV, and were on a hair trigger to do "the switch". 

But it doesn't matter. This table shows you that you can start off on HFNC, if you look at the doctors cross-eyed and tachypneic, they can switch you from HFNC to NIPPV and voile! You needn't worry about being reintubated at a higher rate than had you received NIPPV from the first.

Look also at the reintubation rates: ~10%. They're not extubating people fast enough! Threshold is too high.

So we have yet another study where doing something to everyone now saves them from the situation where a fraction of them would have had it done to them later. Like the 2002 Konstantinidis study of early TPA for what we now call intermediate risk PE. In that study, you can give 100 people TPA up front, or just give it to the 3% that crumps - no difference in mortality.

I won't do it. Because people are relieved to be extubated and it's a buzz kill to immediately strap a tight-fitting mask to them. 

Regarding the Thille studies (this one and this one): I'm already familiar with the original study of NIPPV plus HFNC vs HFNC alone directly after extubation in patients at "high risk" of reintubation. The results were statistically significant in favor of NPPV with 18% reintubated vs 12%. And, they did a pretty good job of defining the reasons for reintubation - as well as anybody could. But these patients were all over 65 and had heart and/or lung diseases of the variety that are already primary indications for NIPPV. And the post-hoc subgroup analysis (second study linked above, a reanalysis of the first) focusing on obese patients shows the same effect as the entire cohort in the original study, with perhaps a bigger effect in overweight and obese patients. But recall, these patients have known indications for NIPPV, and we've known for 20 years that if you extubate everybody "high risk" to NIPPV, you have fewer reintubations. (The De Jong study, to their credit, excluded people with other indications for NIPPV in that study, e.g., OHS.) The question is whether you want an ICU full of people on NIPPV for 48 hours (or more) post-extubation with routine adoption of this method, or whether you wanna use it selectively. 

Now would be a good time to mention the caveat I've obeyed for over 20 years. That's the Esteban 2004 NEJM study showing if you're trying to use NIPPV as "rescue therapy" for somebody already in post-extubation respiratory failure, they are more likely to die, probably because of delay of necessary reintubation and higher complication rates stemming therefrom.

Now, whenever I can get access to the Hernandez 2025 AJRCCM study, which is firewalled by ATS for this university professor (who is no longer an ATS member, having rejected the political ideology that suffused the society), I will do a new post or add to this one.

Once Bitten, Twice Try: Failed Trials of Extubation

“When a distinguished but elderly scientist states that something is possible, he is almost certainly right. When he states that something is impossible, he is very probably wrong.”                                                                                   – Clark’s First Law

It is only fair to follow up my provocative post about a “trial of extubation” by chronicling a case or two that didn’t go as I had hoped.  Reader comments from the prior post described very low re-intubation rates.  As I alluded in that post, decisions regarding extubation represent the classic trade-off between sensitivity and specificity.  If your test for “can breathe spontaneously” has high specificity, you will almost never re-intubate a patient.  But unless the criteria used have correspondingly high sensitivity, patients who can breathe spontaneously will be left on the vent for an extra day or two.  Which you (and your patients) favor, high sensitivity or high specificity (assuming you can’t have both) depends upon the values you ascribe to the various outcomes.  Though these are many, it really comes down to this:  what do you think is worse (or more fearsome), prolonged mechanical ventilation, or reintubation?

What we fear today we may not seem so fearsome in the future.  Surgeons classically struggled with the sensitivity and specificity trade-off in the decision to operate for suspected appendicitis.  “If you never have a negative laparotomy, you’re not operating enough” was the heuristic.  But this was based on the notion that failure to operate on a true appendicitis would lead to serious untoward outcomes.  More recent data suggest that this may not be so, and many of those inflamed appendices could have been treated with antibiotics in lieu of surgery.  This is what I’m suggesting with reintubation.  I don’t think the Epstein odds ratio (~4) of mortality for reintubation from 1996 applies today, at least not in my practice.

Bite the Bullet and Pull It: The NIKE approach to extubation.

I was very pleased to see McConville and Kress' Review article in the NEJM this week (December 6, 2012 issue) regarding weaning patients from the ventilator. I have long been a fan of the University of Chicago crew as well as their textbook and their pioneering study of sedation interruption a decade ago.

In their article, they provide a useful review of the evidence relating to the discontinuation of mechanical ventilation (aka weaning , liberation, and various other buzz words used to describe this process.) Yet at the end of the article, in describing their approach to discontinuation of mechanical ventilation, they provide a look into the crystal ball that I think and hope shows what the future may hold in this area. In a nutshell, they push the envelope and try to extubate patients as quickly as they can, ignoring inconvenient conventional parameters that may impede this approach in select instances.

Much of the research in this field has been dedicated to trying to predict the result of extubating a patient. (In the case of the most widely cited study, by Yang and Tobin, the research involves predicting the result of a predictor of the ultimate result of interest. This reminds me of Cervantes' Quijote - a story within a story within a story....but I digress.) And this is a curious state of affairs. What other endeavor do we undertake in critical care medicine where we wring our hands and so helplessly and wantonly try to predict what is going to happen? Don't we usually just do something and see what happens, making corrections along the way, in silent acknowledgment that predicting the future is often a fool's errand? What makes extubation so different? Why the preoccupation with prediction when it comes to extubation? Why not "Just Do It" and see what happens?