Podcast #3 - The REACT-2 Trial

You have waited long enough!  It is time for some real information and that has come in the form of a paper I find very important.  The REACT-2 study was published online with The Lancet on June 28, 2016.  I started looking at it right away but did not get the chance to actually post about the topic until now.  Listen to the podcast, read the blog, but do not forget to read the original paper, too!

As a side note, the amazing picture above is of a CT scanner for children at Ann & Robert H Lurie Children's Hospital of Chicago.  It helps remind us that we need to do more for children and to keep improving on ways to be out there for them.  However, as you will read below, our study is focused on adults.  Let us begin then!

This is podcast #3.  Now I must apologize again. You may have noticed in the last podcast that I said it had been almost a month.  If you have been looking closely, it has actually been a little over a month.  I’m still trying to figure out this podcasting and it took longer than I imagined which is our reason for the discrepancy is on the posting dates.  However, we will be trying to get content out regularly now. 
 
Title: Immediate total-body CT scanning versus conventional imaging and selective CT scanning in patients with severe trauma (REACT-2): a randomized controlled trial
 
Case: A 36 y/o male arrives via EMS for a rollover MVA with multiple injuries.  He denies LOC or headache but does have neck pain along with pain over the lower abdomen.  He has signs of bruising from his seatbelt and red marks to the face from where airbag deployed.  Patient also reports some difficulty breathing but says it started with the deflating airbag. 
 
Background: Previous studies that have not been randomized controlled trials have looked at the implementation of total body (pan-scan) CTs. 
 
Clinical Question: Does diagnosing patients with an immediate total-body CT scan reduce in-hospital mortality compared with the standard radiological work-up?
 
Reference:

• Population: All non-pregnant trauma patients 18 years of age or older having life threatening conditions with compromising vital parameters, clinical suspicion of life-threatening injuries, or severe injury. 
  • Life-threatening vital signs:
    • Respiratory rate greater than or equal to 30/minute or less than or equal to 10/minute
    • Pulse greater than or equal to 120
    • Systolic blood pressure less than or equal to 100 mm/Hg
    • Estimated exterior blood loss greater than or equal to 500ml
    • Glasgow Coma Scale less than or equal to 13/15
    • Abnormal pupillary reaction onsite
  • Patients with one of the following clinically suspicious diagnoses:
    • Flail chest, open chest, or multiple rib fractures
    • Severe abdominal injury
    • Pelvic fracture
    • Unstable vertebral fractures/spinal cord compression
    • Fractures from at least two long bones
  • Patients with one of the following mechanisms of injury:
    • Fall from height (>3meters or >10 feet)
    • Ejection from the vehicle
    • Death of occupant in the same vehicle
    • Severely injured patient in the same vehicle
    • Wedge or trapped chest/abdomen
  • Exclusion Criteria: Known age less than 18 years old, known pregnancy, referred from another hospital, clearly low-energy trauma with blunt injury mechanism, penetrating injury in 1 body region (except gunshot wounds) as the clearly isolated injury, or any patient judged to be too unstable to undergo a CT scan and requires (cardiopulmonary) resuscitation or immediate operation because death is imminent according to the trauma leader in mutual agreement with the other leading caregivers. 
• Intervention: Immediate total-body CT from head to pelvis; no FAST exam or conventional radiography of the torso.
• Comparison: Conventional trauma protocol with selective CT scanning.
• Outcome: In-hospital mortality.

 
Author’s Conclusions: Diagnosing patient with an immediate total-body CT scan does not reduce in-hospital mortality compared with the standard radiological work-up.  Because of the increased radiation dose, future research should focus on the selection of patients who will benefit from immediate total-body CT.
 
Quality Checklist for Randomized Clinical Trials:

1. The study population included or focused on those in the ED. Yes
2. The patients were adequately randomized. Yes
3. The randomization process was concealed. No, not possible with this design
4. The patients were analyzed in the groups to which they were randomized. No, patients who crossed over were removed from the trial and those who declined participation or there was a language barrier were also excluded
5. The study patients were recruited consecutively (i.e. no selection bias). Unsure, but based on design would seem consecutive
6. The patients in both groups were similar with respect to prognostic factors. No, more patients in the total-body CT group had polytrauma but this will be discussed further separately
7. All participants (patients, clinicians, outcome assessors) were unaware of group allocation. No
8. All groups were treated equally except for the intervention. Unsure
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. Yes

 
Key Results: In-hospital mortality did not differ between the two groups with total-body CT having 86 deaths out of 541 patients (16%) and standard work-up having 85 deaths out of 542 patients (16%) with a p=0.92 on analysis.  Mortality also did not differ between groups in subgroup analyses in patients with polytrauma (total-body CT 81 [22%] of 362 versus standard work-up 82[25%] of 331; p=0.46) and traumatic brain injury (68 [38%] of 178 versus 66 [44%] of 151; p=0.31).  Three serious adverse events were reported in patients in the total-body CT group (1%), one in the standard work-up group (<1%), and one in a patient who was excluded after random allocation.  All five patients died.
 
Key Points of Debate:

• 46% of patients in the standard work-up group underwent sequential segmental CT scans of all body regions
  • Almost half of all patients in the control arm eventually had a total-body CT which could potentially lead to bias as mortality rates may have been affected with this approach.
  • It is worth noting that this approach is pragmatic since protocols were not changed for the purposes of the study
  • However, keep in mind that this much crossover could potentially dilute results even if it was a pragmatic design.
• Total body scanning practices may have changed over the time of the study due to experience.
  • Authors attribute this to providers having developed more experience in trauma care over the course of the trial.
  • Again, they wanted to point out that this makes the study design more pragmatic since they did not force new protocols in place.
• Calculations of direct medical costs were done only in the Dutch hospitals.
  • Costs may be very different in other locations such as the United States where there is large variability.
  • Also, cost in the way this study was designed implies that it is not only the initial visit but also related expenses over the next six months.  We do not know what factors played in many of these cases.
• This was an unmasked randomization procedure.
  • Although others claim that selection bias was not possible, the team and its patients were aware of the randomization.  What is worth remembering is that some of the inclusion criteria had subjectivity.
  • One example of subjectivity the authors gave is in relation to high or low energy mechanism as this is a subjective measure. 
  • This in turn led to multiple exclusions later for inappropriate enrollment.
  • In the same sense, there were also a number of protocol violations with the use of total-body CT scanning which the authors attribute to experience leading to decreased violations. 
• There was a disproportional amount of polytrauma in the total-body CT group versus the standard work-up group.
  • At face value, this may seem like the total-body group would have been a sicker population, but this may not necessarily be true.
  • The findings are based on the injury severity score (ISS) which is a bit of a tricky system. Scoring is based on injuries that are discovered.
  • A patient receiving a pan-scan could inadvertently have more injuries discovered in scanning that are incidental and could in turn inflate the score.  Since the score is based on findings, this could lead to an artificial increase.
  • This is further supported by the fact that the deaths were essentially identical in the two groups despite the variation with in-hospital mortality, 24 hour mortality, and 30 day mortality (the three time frames measured).
• Time is probably not all that important.
  • Yes, technically there was a statistically significant difference in multiple times, but look at their differences.
  • Median time to end of imaging was decreased in the total-body group to the standard work-up group with 30 minutes (IQR 24-40) versus 37 minutes (IQR 28-52) with a p-value of <0.0001
  • There was also a time to diagnosis of 50 minutes (IQR 38-68) versus 58 minutes (IQR 42-78) with a p-value of 0.001
  • Also there was “weak evidence” of a decrease in median time spent in the trauma room of 63 minutes (IQR 47-102) versus 72 minutes (IQR 50-109) with a p-value of 0.067
  • The reason why this seems weak although technically a statistical difference is that it has limited clinical significance.  The time differences are less than 10 minutes when it comes to median times.  Without having a difference in mortality, does this justify pan-scan if it is meant to “speed up” a process less than 10 minutes?
  • It is possible that this could be more of a provider-oriented outcome as it shows that it speeds up the time to disposition, but keep in mind that patients did receive a statistically significant difference in the amount of radiation they received both in the resuscitation room and during the hospital stay with less radiation in the standard work-up group (except for polytrauma throughout their stay which received slightly more in the standard work-up group)

 
Comparing Conclusions:
We agree with the conclusions made by the study group that total-body CT scanning does not reduce in-hospital mortality compared to standard radiology work-up.  We also agree to their recommendation that future research should focus on the selection of who will benefit from immediate total-body CT. 
 
The Bottom Line:
We agree that total body CT scanning does not reduce in-hospital mortality compared to standard radiology work-up. 
 
Case Resolution:
After a thorough history and physical, you discussed with the patient options for management.  You explain how a new study shows that total-body CT scanning does not necessarily appear to reduce his risk of in-hospital mortality and would expose him to more radiation.  Using rule-out criteria, you clear his head and c-spine clinically.  An eFAST exam is done along with other basic radiological imaging.  With shared decision making, you both agree that CT scanning could be limited to the abdomen and pelvis with the exam being unremarkable.  He is discharged and in a month he follows up with you to thank you for the work that was done and limiting his exposure to radiation.
 
Clinical Application:
Although pan-scan CT may still be beneficial in certain patients, the empiric use of this technique may not be appropriate in many trauma patients.  Careful selection of who would be appropriate should be considered prior to application. Keep in mind that there are rule-out criteria for different regions of the body and that these can still be employed if used correctly. 
 
What do I tell my patient?
We have a new paper that demonstrates no decrease in mortality over your hospital stay, the next 24 hours, or the next 30 days if we CT your whole body versus limiting it to the areas of concern.  However, if on exam we find that there are concerns in any regions, we will still consider scanning them, especially after an informed discussion.  

Conclusion:
Thank you for listening to the podcast and reading the blog.  Please let me know if there is anything I need to change or improve.  We really want to do whatever we can to make this the best project.  Please e-mail us at [email protected] or see us at Twitter or Facebook.  We hope to talk to you soon.  Until then, continue to provide total care everywhere.

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