March 2024

Clinical Question What’s dose of dexamethasone should we give patients with migraine? Title of Paper Randomized Trial Comparing Low- vs High-Dose IV Dexamethasone for Patients With Moderate to Severe Migraine Journal and Year Neurology. 2023. Lead Author Benjamin Friedman Background

• Steroids have been shown in several studies to be beneficial for the prevention of migraine recurrence following discharge from the ED
• Andy did an NNT review of this back in 2011 - Andy has officially been a migraine geek longer than me and is at least partly responsible for creating this monster
• The studies out there really vary on dosing of dexamethasone, anywhere up to 24mg, and there hasn’t really been a definitive consensus on the most appropriate dose yet

Study Design

• Randomised, double-blind, comparative efficacy study

Patients Studied

• Adults presenting to ED for treatment of headache fulfilling International Classification of Headache Disorders criteria for migraine without aura
  • Only required to have experienced one similar headache previously
  • Did not exclude headache >72 hours
• Headache moderate to severe intensity

Intervention

• 10mg IV metoclopramide + 4mg dexamethasone (lowest previously tested)

OR

• 10mg IV metoclopramide + 16mg dexamethasone (mean dose used in previous trials)

Dexamethasone was given in 50ml bag of normal saline over 15 minutes - which will stop that patients getting that burning/itching to the bum that Dex is notorious for as a push. Outcomes

• Primary outcome: sustained headache relief for 48h
  • That’s a headache rated as “none” or “mild” within 2hours of medication administration and staying there, without further meds, for the 48 hour follow up period.
• They powered to detect a 15% absolute difference, needing n 360

Summary of Results

• They started their enrolment in December 2019 - possibly the worst time to start a trial really and their recruitment was paused from March - June 2020
• Following a pre-planned interim analysis, they stopped recruitment early, n 209

Primary: Sustained headache relief 48h

• 4mg group: 34%
• 16mg group: 41%
• 7% absolute difference [CI -6 - 20%]

Adverse events:

• A 23 year old was do with cerebellar stroke within a week of enrolment and someone had high BSLs - both were in the 4mg group

Authors Conclusion IV doses of dexamethasone greater than 4mg are unlikely to benefit patients in the ED with migraine when added to metoclopramide 10mg IV. Clinical Bottom Line I think that conclusion is a little strong. This study wasn’t able to show a significant benefit of larger doses of dexamethasone, as they say right before their conclusion “because the study was halted early, we do not know the true magnitude of the absolute differences; there remains a possible 20% absolute benefit for the higher dose. Unfortunately, I don’t feel we’re much further on after this study. Before reading it, I would plumb for around 10-12mg depending on which dose I plucked from the air that day (among other factors, I’m sure), and now I’m probably in the same position as I think the higher dose probably does have some benefit, and there wasn’t any signal of harm from this paper. Other #FOAMed Resources / References: Andy’s NNT review

www.rcr.ac.uk

Clinical Question

Should we be lowering our cut off for transfusing anemic patients with MI, just like we do for everyone else?

Title of Paper

Restrictive or Liberal Transfusion Strategy in Myocardial Infarction and Anemia

Journal and Year

NEJM 2023.

Lead Author

J.L.Carson

Background

• Recommendations for transfusion in patients with IHD is that the target Hb should be 100 (10 in old money)
• This means, however, giving blood products more frequently, and an increased amount of (potentially inflammatory) fluid to patients with less than perfect tickers.
• Some trails have shown non-inferiority with more restrictive approaches to transfusion targets for prevention of cardiac events at 30 days, and have shown a significant decrease in blood product use without differences in morbidity/mortality.

Study Design

• Open-label, randomised trial
• 144 sites in US, Canada, France, Brazil, New-Zealand and Australia.

Patients Studied

• Adults
• STEMI or NSTEMI (ACS type 1, 2, 4b, 4c in new money)
• Anemia (Hb <100)
• Excluded: uncontrolled active haemorrhage (fair enough), palliative, scheduled cardiac surgery during admission, if declined transfusion

Intervention

• Restrictive transfusion strategy:
  • transfusion permitted but not required when Hb <80
  • recommended when Hb <70 or anginal symptoms not controlled with other meds

Comparison

• Liberal transfusion strategy:
  • One unit PRBCs transfused to maintain Hb ≥ 100

Outcomes

• Composite primary outcome: MI or death (any cause) up to 30 days
• Secondary outcomes:
  • MI and death individually
  • and another composite of death, MI, ischaemia driven unscheduled revascularisation or readmission to hospital for cardiac ischaemia within 30 days

Power

• 3500 patients for 80% power, 20% relative between group difference

Summary of Results

• n=3504; some details:
  • Groups similar
  • 81% NSTEMIs
  • 42% Type 1
  • 56% Type 2
  • Mean Hb: Restrictive stayed <90 | Liberal stayed >100
  • Mean PRBCs: Restrictive 0.7 units | Liberal 2.5 units
  • 2.6% abandoned restrictive strategy. Around half has clinical reasons recorded like surgery or bleeding
  • 13.7% abandoned liberal strategy. Clinical reasons given for around 1/3 including fluid overload, adverse effects, dialysis, transfusion reactions
• Primary outcome (death or MI 30d): no difference between strategies
  • Restrictive 16.9% | Liberal 14.5%
    • Adjusted risk ratio 1.15 [0.99-1.34; p0.07]
    • Adjusted for baseline prognostic factors risk ratio 1.16 [1.00-1.36]
• Individual: (Restrictive v Liberal)
  • Death: 9.9% vs 8.3%
    • risk ratio 1.19 [0.96-1.47]
  • MI: 8.5% vs 7.2%
    • risk ratio 1.19 [0.94-1.49]
  • Type 1 MI, benefit: risk ratio 1.32 [1.04-1.67]
  • Type 2 MI, no benefit: risk ratio 1.05 [0.85-1.29]
• Cardiac death more common in restrictive group (5.5 vs 3.2%; risk ratio 1.74 [1.26-2.40]

Authors Conclusion

Our results show that in patients with acute MI and anemia, a liberal transfusion strategy did not significantly reduce the risk of recurrent MI or death at 30 days. Trial end points suggest some benefit of a liberal strategy over a restrictive strategy, but additional studies would be needed to confirm that conclusion.

Clinical Bottom Line

They were looking for 20% relative difference and found ~15%. All of their end points (as they say) did look like there was some benefit in the liberal group (Figure Four below) and the risk of transfusion seemed low.

Where does this leave us? We have to decide our risk/resource/benefit for our practice but given the number of little black squares resting on the “liberal” side for benefit, and that it is already our accepted practice, I’ll probably not rush to change by practice based on this study. At least we can see that whatever benefit there may be, its <20% and we can take that into account in our risk/benefit decision making.

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