All posts by TheTraumaPro

Mainstem Intubation In Pediatric Patients: How Common?

Mainstem intubation in the pediatric patient is a common problem. There are two major issues: the trachea is shorter than in an adult, and the angles are different making intubation of the right mainstem bronchus much easier. Frequently, the intubator watches the balloon slide between the cords, then pushes the tube in “just a little further.”

Unfortunately, that “little bit” can vary significantly. An abstract from my hospital was presented at the Pediatric Trauma Society in 2016. Subjectively, we noticed that mainstem intubation was occurring with some regularity in our pediatric trauma patients.  It seemed as though insufficient attention was being paid to the depth of the tube.

A major difference between adult and pediatric intubations is that in adults, optimal tube depth is locked into a relatively narrow range. In children, the depth varies considerably based upon child age and size. And small variances in depth can have major implications for tube position.

We decided to implement a PI project to change our intubation policy. In order to focus the entire team on tube depth, a color coded card was attached to each size of endotracheal tube. This card listed the optimal depth for insertion. Once the provider inserted the tube, the final depth was called out for the team and documentation scribe to hear. This had the added advantage of allowing multiple team members confirm the appropriateness of tube depth. A chest x-ray was immediately obtained to confirm position.

We retrospectively reviewed our seven year experience with pediatric intubations, from 2009-2015. Here are the factoids:

  • Nearly 2,000 pediatric trauma patients were admitted during the study period
  • 94 patients (5%) required intubation in the ED
  • Prior to implementation of the new protocol, 6 of 68 patients (8.8%) had confirmed right mainstem intubation 
  • After the change, only one further mainstem intubation occurred in 26 procedures (3.8%)

Bottom line: Unfortunately, this series is too small to determine statistical significance. There is a definite trend toward fewer mainstem intubations. It appears that by calling more attention to the proper tube depth, fewer deep placements occur. Our numbers  have remained low since this change.

Are there other methods to ensure proper ET tube placement in small patients? In my next post, I’ll review a paper that compares three additional different techniques that can be used.

Reference: Eliminating the Preventable Occurrence of Right Mainstem Intubation in the Pediatric Trauma Patient: A Quality Performance Improvement (PI) Initiative. Pediatric Trauma Society Poster Abstract #1, 2016.

How To Predict Venous Thromboembolism In Pediatric Trauma

As with adults a decade ago, the incidence of venous thromboembolism (VTE) in children is now on the rise. Whereas adult VTE occurs in more than 20% of adult trauma patients without appropriate prophylaxis, it is only about 1% in kids, but increasing. There was a big push in the early 2000′s to develop screening criteria and appropriate methods to prevent VTE. But since the incidence in children was so low, there was no impetus to do the same for children.

The group at OHSU in Portland worked with a number of other US trauma centers, and created some logistic regression equations based on a large dataset from the NTDB. The authors developed and tested 5 different models, each more complex than the last. They ultimately selected a model that provided the best fit with the fewest number of variables.

The tool consists of a list of risk factors, each with an assigned point value. The total point value is then identified on a chart of the regression equation, which shows the risk of VTE in percent.

Here are the factors:

Note that the highest risk factors are age >= 13, ICU admission, and major surgery.

And here is the regression chart:

Bottom line: This is a nice tool, and it’s time for some clinical validation. So now all we have to do is figure out how much risk is too much, and determine which prophylactic tools to use at what level. The key to making this clinically usable is to have a readily available “VTE Risk Calculator” available at your fingertips to do the grunt work. Hmm, maybe I’ll chat with the authors and help develop one!

Reference: A Clinical Tool for the Prediction of Venous Thromboembolism in Pediatric Trauma Patients. JAMA Surg 151(1):50-57, 2016.

Reversing Direct Oral Anticoagulants With Andexxa

I just finished a summary of the Australian consensus paper regarding anticoagulants (and anti-platelet agents) in patients with hemorrhagic TBI. One of the issues addressed was reversal of these agents. Today I’m going to provide more specific information on one of the new reversal agents, Andexxa (recombinant Factor Xa, inactivated-zhzo).

First, maybe someone can help me here. What does zhzo mean? I’ve done a deep dive including a review of the FDA filings, and still can’t figure out what this is. I have a hard enough time with the thousands of something-umab monoclonal antibody products out there. Now we’re adding on a bunch of z’s to the end of drug names?

There are currently two classes of direct oral anticoagulant drugs (DOACs) available, direct thrombin inhibitors and Factor Xa inhibitors. Andexxa was designed to reverse the latter by providing a lookalike of Factor Xa to selectively bind to apixaban (Eliquis) and rivaroxaban (Xarelto).

The Austrian consensus paper I previously discussed recommended giving Andexxa in patients taking apixaban or rivaroxaban if it was not possible to show that the drugs were non-therapeutic. This means that if your lab could not measure anti-Factor Xa levels in a timely manner and the patient was known to be taking one of these agents, reversal should be considered.

Sounds cut and dried, right? Your patient is taking a Factor Xa inhibitor and they are bleeding, so give the reversal agent. Unfortunately, it’s much more complicated than that.

  • The half-life of Andexxa is much shorter than that of the drugs it reverses. The reversal effect of Andexxa begins to wear off two hours after administration, and is gone by four hours. On the other hand, the half life of rivaroxaban is 10+ hours in the elderly. The half-life of apixaban is even longer, 12 hours. This means that it is likely that multiple doses of Andexxa would be necessary to maintain reversal.
  • There are no studies comparing use of Andexxa with the current standard of care (prothrombin complex concentrate, PCC). The ANNEXA-4 study tried to do this. It was a single-arm observational study with 352 subjects. These patients were given Andexxa if major bleeding occurred within 18 hours of their DOAC dose. Two thirds of the patients had intracranial bleeding. All were given a bolus followed by a two hour drip. All showed dramatic drops in anti-Factor Xa levels, and 82% of patients had good or excellent control of hemorrhage. However, 15% died and 10% developed thrombotic complications.
  • The FDA clinical reviewers recommended against approval due to the lack of evidence for clinical efficacy. The director for the Office of Tissues and Advanced Therapies overruled the reviewers and allowed approval until such time a definitive study was completed. So far there have been no justifiable claims that Andexxa is superior to PCC.
  • To be fair, PCC has not been compared to placebo either. So we don’t really know how useful it is when treating bleeding after DOAC administration.
  • Andexxa is very expensive. Old literature showed a single dose price of $49,500 but this has been revised downward. Effective in October 2019, Medicare agreed to reimburse a hospital about $18,000 for Andexxa over and above the DRG for the patient’s care. Remember, due to the half life of the Factor Xa inhibitors, two doses may be needed. This comes to about $36,000, which is much higher than the cost for PCC (about $4,000).

Bottom line: Any hospital considering adding Andexxa to their formulary should pay attention to all of the factors listed above and do the math for themselves. Given the growing number of patients being placed on DOACs, the financial and clinical impact will continue to grow. Is the cost and risk of this therapy justified by the meager clinical efficacy data available?

References:

  1. Full Study Report of Andexanet Alfa for Bleeding Associated with Factor Xa Inhibitors. NEJM 380(14):1326-1335, 2019.
  2. Key Points to Consider When Evaluating Andexxa for Formulary Addition. Neurocrit Care epub ahead of print, 22 Oct 2019.

Best Practices For TBI Patients On Oral Anticoagulants: Part 5

Here is the fifth and final installment of my series summarizing the Austrian consensus paper on management of TBI patients with intracranial hemorrhage. The previous posts have run the gamut from diagnostic tests to detection of specific drugs to management. I’ve covered platelet inhibitors and Vitamin K antagonist reversal in previous posts, and today I’ll go over the panel’s reversal strategies for the direct oral anticoagulant drugs (DOACs).

Q1. Should idarucizumab (Praxbind) always be administered to patients with hemorrhagic TBI who are taking dabigatran (Pradaxa).

Answer: Only in cases where your laboratory is not capable of testing for thrombin time.

If thrombin time (TT) can be measured and is within the normal range, then the drug is not therapeutic and reversal should not be carried out. The consensus statement recommends giving this drug if the TT is prolonged or your lab cannot measure it. Keep in mind that there are very, very few papers on DOAC reversal in trauma patients. Most studies address the stroke population, and this may not translate well to trauma. And there are no studies yet that show that idarucizumab offers any survival benefit if given.

Q2. Should prothrombin complex concentrate (PCC) always be given to patients who are taking Factor Xa inhibitors?

Answer: Only in cases where your laboratory is not capable of testing for anti-Xa activity.

If anti-Xa activity can be measured (in a timely manner) and is low, then the drug is not therapeutic and PCC need not be given. If the level is high or your lab cannot test for it, then the group recommends administering PCC if the specific reversal agent (Andexxa) is not available.

As with dabigatran above, there is very little trauma literature to justify this recommendation. Furthermore, Andexxa is very expensive and, like idarucizumab, has not been shown to improve survival. Next week, I’ll write about why Andexxa is probably not worth the cost, in my opinion.

Q3. Should DOACs always be reversed in hemorrhagic TBI?

Answer: We don’t know.

As I just mentioned, there is little if any data showing that administration of a reversal agent is beneficial. And the decision to give it must be balanced with patient risk for thrombosis and consideration of any other agents they may be taking.  Expert opinion suggests that DOACs need not be reversed in TBI without blood on the CT scan, patients with unilateral, asymptomatic chronic subdural hematoma, and those with other wounds that do not appear to be bleeding excessively.

Hopefully, this series has helped shine some light on a confusing set of problems. Next week I’ll dig a bit deeper into the DOAC reversal agents Praxbind and Andexxa.

Reference: Diagnostic and therapeutic approach in adult patients with traumatic brain injury receiving oral anticoagulant therapy: an Austrian interdisciplinary consensus statement. Crit Care 23:62, 2019.