Category: Intubation

Update to Start 2024

A brief post collating a few bits of my various work published across the interwebs ….

The Annals of Emergency Medicine Podcast continues to summarise the meatiest articles from each month, featuring a cycle of new co-hosts, as well:

Naturally, there are continuing Journal Club features, covering the following articles:

I should also point out a couple additional new publications with two very different and amazing teams:

Lastly, in ACEPNow, we have:

Enjoy!

The Great Prehospital Airway Debate

… is over! With another 12,000 patients included in two prospective, randomized trials, we’ve finally arrived at unassailable conclusions regarding optimal airway management in the context of out-of-hospital cardiac arrest.

Or, as usual, not.

These two trials, AIRWAYS-2 from the United Kingdom and PART from the United States, randomized paramedics and emergency medical services agencies to routinely providing either endotracheal intubation or a supraglottic airway. The details of both trials are a little bit different, but they are both effectively pragmatic approaches directing the first attempt at airway management in patients deemed eligible in non-traumatic OHCA.

AIRWAYS-2 enrolled over 9,000 patients while PART enrolled over 3,000, and their results were similar, but not precisely the same. The primary outcome for AIRWAYS-2 was “good outcome” (0-3) on the modified Rankin Scale at 30 days, which was achieved by the ETI cohort in 6.8% versus 6.4% with SGA. The primary outcome for PART was 72-hour survival, which was 15.4% in their ETI cohort versus 18.3% with SGA. For rough comparison’s sake, PART also recorded mRS at hospital discharge, which was 5.0% with ETI and 7.1% with SGA.

These are both incredibly messy trials with regard to delivery of the intervention. Substantial fractions of both cohorts in the AIRWAYS-2 trial did not ultimately receive an attempt at an advanced airway, including over a quarter of those randomized to ETI. Then, the success rate for ETI in PART was only 51%, as compared with 90% with SGA. It is an imposing task to parse through their flow diagrams of randomization, patient interventions, and outcomes in both the main body of the articles and in the supplemental material.

Ultimately, while these can be argued back-and-forth due to substantial underlying uncertainty, there is little evidence to suggest ETI should be favored over SGA. This ought not be terribly surprising, as we’ve already seen a trial of ETI versus bag-valve mask ventilation which was unable to conclusively support one method over the other. While these findings probably could be used to substantially affect paramedic training and procedures with respect to ETI, the better, remaining question is whether any advanced airway should be routinely attempted at all.

“Effect of a Strategy of a Supraglottic Airway Device vs Tracheal Intubation During Out-of-Hospital Cardiac Arrest on Functional Outcome: The AIRWAYS-2 Randomized Clinical Trial”

https://jamanetwork.com/journals/jama/fullarticle/2698493

“Effect of a Strategy of Initial Laryngeal Tube Insertion vs Endotracheal Intubation on 72-Hour Survival in Adults With Out-of-Hospital Cardiac Arrest: A Randomized Clinical Trial”

https://jamanetwork.com/journals/jama/fullarticle/2698491

Roc Vs. Sux, Settled

Short answer: rocuronium, just because.

Better answer: it really doesn’t matter, please stop devoting neurons and pages to the debate.

This is a result from the National Emergency Airway Registry, a prospective database of ED airway procedures. In the sample analyzed, there were 4,275 intubations, roughly split evenly between succinylcholine and rocuronium. Generally, the cohorts were well-matched on baseline and operator characteristics.

The winner, and still champion is: they tied. First-pass success, a surrogate for effectiveness as a paralytic, was effectively identical between agents at ~87%. Adverse events, patient-oriented outcomes relating to procedural harms, were likewise effectively identical at ~15%.

This is not a randomized controlled trial, so it’s not possible to fully exclude a selection bias in which patient-level characteristics influenced the choice of agent. However, these are consistent with a Bayesian pretest likelihood of clinical equivalency. Frankly, I don’t think the cost of an RCT adds much value over these observational data sets, and any dogmatic attachment to one agent over another should be expunged. Certain clinical situations may make one agent more preferable than another, but, generally speaking, they are both excellent and effective tools.

“Emergency Department Intubation Success With Succinylcholine Versus Rocuronium: A National Emergency Airway Registry Study”
https://www.annemergmed.com/article/S0196-0644(18)30318-4/fulltext

More Futility: Apneic Oxygenation?

Here’s another pendulum swing to throw into the gears of medicine – an apparent failure of apneic oxygenation to prevent hypoxemia during intubation in the Emergency Department. Apneic oxygenation – passive oxygenation during periods of periprocedural apnea – seems reasonable in theory, and several observational studies support its use. However, in a randomized, controlled ICU setting – the FELLOW trial – no difference in hypoxemia was detected.

This is the ENDAO trial, in which patients were randomized during ED intubation, with a primary outcome of mean lowest oxygen saturation during or immediately following. These authors prospectively enrolled 206 patients of 262 possible candidates, with 100 in each group ultimately qualifying for their analysis. The two groups were similar with regard to initial oxygen levels, pre-oxygenation levels, and apnea time. Then, regardless of their statistical power calculations and methods, it is fairly clear at basic inspection their outcomes are virtually identical – in mean hypoxemia, SpO2 below 90%, SpO2 below 80%, or with regard to short-term or in-hospital mortality. In the setting in which this trial was performed, there is no evidence to suggest a benefit to apneic oxygenation.

It is reasonable to note all patients included in this study required a pre-oxygenation period of 3 minutes by 100% FiO2 – and that oxygen could be delivered by bag-vale mask, BIPAP, or non-rebreather with flush rate oxygen. These are not necessarily equivalent methods of pre-oxygenation, but, at the least, the techniques were not different between groups (>80% NRB). It is reasonable to suggest passive oxygenation may be more beneficial in those without an adequate pre-oxygenation period, but it would certain be difficult to prospectively test and difficult to anticipate a clinically important effect size.

Adding complexity to any procedure – whether with additional monitoring and alarms or interventions of limited efficacy – adds to the cognitive burden of the healthcare team, and probably has deleterious effects on the most critical aspects of the procedure. It is not clear that apneic oxygenation reliably improves patient-oriented outcomes, and does not represent a mandatory element of rapid-sequence intubation.

“EmergeNcy Department use of Apneic Oxygenation versus usual care during rapid sequence intubation: A randomized controlled trial”
http://onlinelibrary.wiley.com/doi/10.1111/acem.13274/full

Icatibant … Can’t?

In a small, problematic, Phase 2 trial, icatibant – a selective bradykinin B2 receptor antagonist – seemed promisingly efficacious for the treatment of angiotensin-converting enzyme inhibitor-induced angioedema. Considering the catastrophic and potentially fatal complications relating to airway angioedema, the prospect of having an effective rescue medication is of substantial clinical importance.

Sadly, and first picked up by Bryan Hayes, the phase 3 trial was a wash. Published with great fanfare in the Journal of Allergy and Clinical Immunology: In Practice, this multi-center study enrolled 121 patients with presumed, and at least moderately severe, ACE-I-induced angioedema. The primary efficacy endpoint was the subjective “time to meeting discharge criteria”, which was guided by a scoring system consisting of difficulty breathing, difficulty swallowing, voice change, and tongue swelling. Secondary endpoints included time to onset of symptom relief, rescue therapy, and other safety considerations.

Almost all patients received some “conventional” therapy prior to randomization, with most (>80%) receiving antihistamines or corticosteroids and approximately one-fifth receiving epinephrine. The median time to doses of conventional therapy were ~3.5 hours, and enrolled patients received either icatibant or placebo ~3.3 hours afterwards.

The picture is worth all the words:

No difference.

Laudably – although this ought to be the default, without special recognition – the sponsor and these COI-afflicted authors unabashedly published these neutral findings with little sugarcoating. I will defer, then, to their closing sentence:

In conclusion, icatibant was no more effective than placebo in treating at least moderately severe ACE-Ieinduced angioedema in this phase III trial.

“Randomized Trial of Icatibant for Angiotensin-Converting Enzyme Inhibitor Induced Upper Airway Angioedema”
http://www.sciencedirect.com/science/article/pii/S2213219817301721

Still Meandering Towards Apneic Oxygenation

The use of apneic oxygenation – so-called NODESAT – has been gaining rapidly in popularity.  Curiously enough, however, its continued promotion occurs in the absence of high-quality evidence for benefit.

This most recent study is a prospective, observational evaluation of two years’ worth of intubation procedural outcomes.  Patients receiving passive oxygenation during intubation were compared with those who did not, with the primary outcome being hypoxia (O2 saturation <90%) on the first-pass of intubation.  During this time period, the use of apneic oxygenation was explicitly encouraged as a quality improvement initiative.  Of the 1,140 intubations during this time period, 635 patients were included for analysis; 380 utilized apneic oxygenation and 255 did not.  The apneic oxygenation cohort had a 17.9% incidence of hypoxia on the first intubation attempt, compared with 31.0% without.  The authors conclude their observational data favors apnea oxygenation, and may improve safety.

This is a reasonable conclusion, to be certain.  There were, of course, massive confounders regarding the two cohorts – and the largest predictor of hypoxia was not apneic oxygenation or technical factors, but simply whether the baseline oxygen saturation was >93%.  An observational study, particularly one excluding 20% of potentially eligible patients due to incomplete data, simply continues to serve as hypothesis-generating for definitive evaluation.

I am not opposed to the use of apneic oxygenation, but it is reasonable to be realistic about the underlying evidence and not to behave dogmatically regarding its use.  There are probably a few acute procedural delays associated with its use, but any patient-oriented harms or benefits would seem to be rather difficult to detect.

Other notes:

  • LITFL publishes a lovely synopsis on the topic here.
  • Yes, I’m about four months late to the party on this article – having missed the electronic publication back in February!

“First Pass Success Without Hypoxemia Is Increased With the Use of Apneic Oxygenation During Rapid Sequence Intubation in the Emergency Department”
http://www.ncbi.nlm.nih.gov/pubmed/26836712

Is NODESAT Overhyped?

In the last few years, we’ve had a little bit of a sea-change in oxygenation during intubation.  We’ve stopped relying solely on pre-oxygenation to bridge our patients through apnea, and started providing passive oxygenation during intubation.  Usually supplied by high-flow nasal cannula, this takes advantage of physiology and diffusion to distribute oxygen into circulation.

But, as these authors state, the evidence for this practice is spotty – mostly observational evidence from controlled intubation settings.  Our critically-ill patients hardly have the same physiology as those undergoing elective airway procedures, and are generally less responsive to oxygenation adjuncts.  So, this is the FELLOW trial, a pragmatic, open-label randomized trial comparing apneic oxygenation vs. “usual care” – which was none.

With 150 patients in their intention-to-treat analysis, this cartoon sums up the results sufficiently:

Not much difference!

Their two groups were relatively well-balanced in terms of physiology and airway comorbidities.  The intubating operators were reasonably experienced (median >50 intubations), and 2/3rds of the patients were intubated on the first attempt.  There were probably no important differences in pre-oxygenation or procedural factors.

But, it is quite a small trial.  There are small differences here favoring the apneic oxygenation arm that simply might not reach statistical significance.  The exclusion criteria included “if the treating clinicians felt a specific approach to intra-procedural oxygenation or a specific laryngoscopy device was mandated for the safe performance of the procedure”, which could have introduced a selection bias.  The open-label effects may or may not be confounding.  The ICU environment and exclusion criteria also affect generalizability to the Emergency Department.

In the end, the answer is: apneic oxygenation still probably helps, particularly considering the pre-study evidence favored the intervention, and this one study does not move the needle much.  However, the observation here of a clinically unimportant effect size is not unreasonable.  If the effect size is small, the cost of an intervention becomes important.  However, in this case, the cost is fairly minimal – a small addition to set-up time and procedural complexity.  Considering the low cost and the post-test odds still favoring the intervention, it would be erroneous to stop providing apneic oxygenation based on this trial, and further study is indicated.

“Randomized Trial of Apneic Oxygenation during Endotracheal Intubation of the Critically Ill”
http://www.ncbi.nlm.nih.gov/pubmed/26426458

A Little Intubation Checklist Magic

In the interests of patient safety, many have turned to peri-procedural checklists.  Rather than,
essentially, “winging it”, a standardized protocol is followed each time, reducing the chance of an important omission.

These authors describe a checklist intervention for, as they describe, the high-risk procedure of endotracheal intubation in the setting of trauma.  The checklist involves, generally, assignment of roles, explicit back-up airway planning, and adequate patient positioning.  The authors used a before-and-after design using video review of all intubation events to compare steps performed.

In the six-month pre-checklist period, 7 of 76 intubation events resulted in complications – 6 desaturations, 2 emesis, and 2 hypotension.  In the post-intervention period, using the checklist, events were reduced to a single episode of desaturation in 65 events.  So, success?

As with every before-and-after study, it is hard to separate the use of the checklist to the educational diffusion associated with checklist exposure.  Would another, less intrusive, intervention been just successful?  Will the checklist lose effectiveness over time as it is superseded by newer safety initiatives?  And, most importantly, what did operators actually do differently after checklist implementation?

Only 4 of 15 checklist elements differed from the pre-checklist period: verbalization of backup intubation technique (61.8% vs. 90.8%), pre-oxygenation (47.3% vs. 75.4%), team member roles verbalized (76.4% vs. 98.5%), and optimal patient positioning (80.3% vs. 100%).  If only four behaviors were substantially changed, are they responsible for the outcomes difference – which, technically, is solely episodes of hypoxia?

Their intervention seems reasonable, and the procedure is likely high-risk enough to warrant a checklist.  However, I probably would not implement their specific checklist, as some refinement to the highest-yield items would probably be of benefit.

“A Preprocedural Checklist Improves the Safety of Emergency Department Intubation of Trauma Patients”
http://www.ncbi.nlm.nih.gov/pubmed/26194607

The Shock Index is a Shockingly Poor Predictor of Peri-Intubation Arrest

A guest post by Rory Spiegel (@CaptainBasilEM) who blogs on nihilism and the art of doing nothing at emnerd.com.
This retrospective analysis of 410 patients undergoing RSI is a helpful reminder of how a statistically significant association does not implicitly translate into a clinically useful one.

The authors of this paper attempted to identify factors that would predict peri-intubation cardiac arrest using a cohort of patients requiring emergent intubation in a large urban emergency department. Specifically does the Shock Index accurately predict those who will suffer post-intubation cardiac arrest? The Shock Index (HR/systolic BP) is essentially an attempt to quantify a patient’s volume status and cardiac reserve into simple ratio. These same authors have examined this score’s ability to predict peri-intubation hypotension in the past and found similar predictive capabilities.

Given the pedigree of the authors (Dr. Alan Jones and company) it is no surprise their chart review methods were next to flawless. Using standardized data collection forms, a single trained extractor identified patients who underwent ED intubations over a one year period. To ensure inter-observer reliability, 10% of this data was randomly audited by a second extractor blinded to the trials hypothesis. Backwards stepwise regression was utilized to determine what factors were independently associated with peri-intubation cardiac arrest (defined as cardiac arrest up to 60 minutes after intubation).

In this cohort, the rate of cardiac arrest after intubation was 4.2%, or 17 patients. 10 out of these 17 events occurred within 10 minutes of the intubation and, in 15 of the 17 events the initial arresting rhythm was PEA.  As one would expect, patients who experienced peri-intubation cardiac arrest had faster a heart rate, lower blood pressure and more frequent incidence of pre-RSI hypotension. The only two metrics that were found to be independently associated with cardiac arrest were the patient’s body weight and pre-intubation Shock Index. The Shock index was found to have an odds ratio of 1.16 with a confidence interval ranging from 1.003 to 1.3. Put in another manner, it was found to have an AOC of 0.73, rendering it essentially clinically useless.

Given these test characteristics, if we were to use a Shock Index of 0.88 (as suggested by the authors) to determine who is at risk for peri-intubation arrest than we would be left unprepared for an unacceptable quantity of patient who will decompensate during the procedure. This should be inherently obvious, as a formula that incorporates only heart rate and systolic blood pressure is incapable of encapsulating all the many reasons a patient may code peri-intubation. Not to mention that this study does not tell us whether the patients whom the Shock Index identifies as “at risk” will actually benefit from our added vigilance and pre-intubation hemodynamic optimization. Or does the Shock Index merely highlights a spectrum of the more critically ill patients who will inevitably deteriorate despite our clairvoyant best efforts?

Tachycardic, hypotensive patients are at increased peril for peri-intubation arrest. Sicker patients, older patients, and patients with poor cardiac reserve are all at higher risk. Most importantly, the Shock Index does not accurately predict who will and will not arrest after intubation. Similar to tools meant to predict difficult airways (not accurate enough to depend on clinically), we must be prepared for peri-intubation arrest in the majority of the patients requiring emergent intubation. Once a patient reaches the critical juncture of requiring intubation, we should be aware of all the perils this procedure involves and plan accordingly.

“Incidence and Factors Associated with Cardiac Arrest Complicating Emergency Airway Management”
www.ncbi.nlm.nih.gov/pubmed/23911630

Etomidate, Safe for Sepsis?

Sadly, the jury is still out.  Just months after Critical Care Medicine published the systematic review demonstrating an association between use of etomidate and mortality in sepsis, now they’re back with a retrospective data-mining expedition that draws the opposite conclusion.

This is a multi-center prospective registry of critically ill patients entered into a research database who were retrospectively data-mined for septic, intubated patients.  Of the 42,000 patients in the database, approximately 2,000 met this definition, and about half were identified as receiving etomidate as their induction agent.  In their cohort, there was no in-hospital mortality difference between the patients who received etomidate and the patients who received a different induction agent for intubation.

Unfortunately, as an observational, retrospective study of imperfectly matched cohorts, there are far too many uncontrolled confounders to base clinical practice on these findings.  Studies such as these, even robust, prospective cohorts, are capable of doing little more than suggesting a hypothesis contrary to the findings of prior work.

If you believe etomidate has a chance to harm patients in sepsis, this doesn’t change your practice.

“Single-Dose Etomidate Is Not Associated With Increased Mortality in ICU Patients With Sepsis: Analysis of a Large Electronic ICU Database”
www.ncbi.nlm.nih.gov/pubmed/23318491