PK Talk for SMACC 2014

Here’s my PK talk for SMACC for 2014. The PK talks for those who can’t remember are short, snappy focused presentations on anything – the SMACC ones are of course focused on critical care.

I presented the same material at our  joint ICU/ED meeting a few days ago so I figured I may as well share it as a PK.

Genuinely intersted as to whether people are aiming for the higher MAPs in SCI. Was news to me and no one in our department was that impressed by it. The studies aren’t wonderful after all.

For those interested here’s last years PK too.

See you at SMACC Gold people!

Low yield from cardiac stress testing for ED patients

Title says it all. And it’s all been said before. David Newman is unsurprisingly involved in this paper and the SMART EM on this is well worth your time.

What they did:

  • prospective data on their chest pain unit with some chart review (with good but not fully described methods)
  • their routine was a 6 hour rule out then EST if possible or nuclear testing (which we don’t seem to do much of over here)

What they found:

  • mainly young patients (50) and mainly female and lots of hypertensives
  • about 80% were considered intermediate risk. Which is interesting in itself seeing as so many ended up discharged with negative tests
  • of the 4000 with stress tests ,470 had positive tests
  • ultimately about 130 got angios and only half of them had obstructive disease
  • only 28 got appropriate intervention as defined by cardiology guidelines. Lots of other people got stents but probably shouldn’t have.

Their discussion includes this phrase

While AHA guidelines suggest that provocative testing risk stratifies patients to a potentially near-zero short-term adverse event rate, there is increasing recognition that a negative result on serial bio-marker evaluation (typically a prerequisite for provocative testing) may also achieve this goal, making further risk stratification attempts redundant or inherently difficult.


Hermann, Luke K, David H Newman, W Andrew Pleasant, Dhanadol Rojanasarntikul, Daniel Lakoff, Scott A Goldberg, W Lane Duvall, and Milena J Henzlova. “Yield of Routine Provocative Cardiac Testing Among Patients in an Emergency Department-Based Chest Pain Unit: Yield of Stress Testing in Emergency Department Observation Units..” JAMA Internal Medicine (May 20, 2013): 1–6. PMID 23689690

Long term follow up on IST-3

I read this a few months back and forgot to post something on it. It’s not headline data the way IST 3 was but it’s worth knowing it’s out there. This is the long term (by which they mean 18 month) follow up on IST 3. The original trial has been written about and discussed fairly extensively on the FOAMed sites.

What they found:

  • they got around 2000 or so because only certain countries did follow up.
  • for those available they managed to follow up on the vast majority
  • the follow up was mainly phone and postal so not that great.
  • 30% knew which drug they got which they try to play down but given that the supposed benefit is so small then any recall may cause the difference
  • they do find about a 3.6% difference in alive and independent at 18 months favouring tPA (as pointed out by Brandon in the comments)
  • there’s a great Kaplan Meier curve showing early harm from TPA and then completely flat with placebo from then on. It’s behind the pay wall unfortunately but worth looking at
  • there was no difference in alive and independent at 18 months

“the unadjusted absolute difference in the number of patients alive and independent at 18 months was not significant”

So just to summarise that. A third of the patients knew which group they were in (nothing versus the fancy new drug) and ultimately there was no difference at 18 months.


“Effect of Thrombolysis with Alteplase Within 6 H of Acute Ischaemic Stroke on Long-Term Outcomes (the Third International Stroke Trial [IST-3]): 18-Month Follow-Up of a Randomised Controlled Trial.” The Lancet Neurology (June 2013). PMID 23791822

The 3MG Trial

Didn’t even know this trial was being done till Simon Carley posted on it. It came just too late to be added to be talk on the Crashing Asthmatic but there you go.

Here’s my two cents on the trial

Goodacre, Steve, Judith Cohen, Mike Bradburn, Alasdair Gray, Jonathan Benger, and Timothy Coats. “Intravenous or Nebulised Magnesium Sulphate Versus Standard Therapy for Severe Acute Asthma (3Mg Trial): a Double-Blind, Randomised Controlled Trial.” The Lancet Respiratory Medicine 1, no. 4 (June 2013): 293–300. doi:10.1016/S2213-2600(13)70070-5.


  • UK publicly funded
  • 34 EDs involved in the UK
  • acute severe asthma (remember it’s not that hard to get into that category)
  • specifically excluded those with life threatening features
  • centrally randomised and reasonable description of blinding
  • each pack had nebs and an infusion
  • IV Mag (2g) v 3 Mg Nebs v placebo
  • all dummys so it looked like everyone gets the same
  • treated as per SIGN and BTS guidelines, though I didn’t see details of how many salbutamol nebs they got etc…
  • two primary outcomes
    • hospital admission either at the time or within 7 days or
    • a change in breathlessness on a VAS


  • Big trial – 1000 folk, average age 35 or so. This is important as a trial this size is unlikely to be equaled.
  • about 75% admitted, no one died in the ED. 2 died overall (not sure why)
  • powered to detect a 10% difference in admission rates and there was only about an 6% difference favouring IV Mag. This didn’t reach stat significance of course.
  • Neb Mag didn’t seem to do much of anything
  • 7 of 1000 needed intubation emphasising how “severe” acute severe asthma is
  • Standard treatment with beta agonists and steroids was awesome as you can see in the placebo group.


  • to be honest this is hardly surprising. I’ve rarely, if ever, seen magnesium work like a magic drug. I’ve always given it cause it’s benign (which this trial reinforces) and there was some support for its use. That was enough for me. It’s hardly surprising that the trial was negative but I suspect the small improvement that is there is real but is just that – small. 
  • having never used nebulised Mag, I’m now not about to start.


I had some correspondence from the author of this paper [free full text] regarding the ‘atrial calming’ effect of magnesium. I certainly gave lots of IV magnesium for patients in fast AF. Usually not for the ‘lone AF’ patients, but the sickies with pneumonias and deranged electrolytes. I’d never considered that the supposed rate control effect of magnesium might be useful in the asthmatic to help control the slightly ridiculous tachycardia you get if you’re doing it right.

As mentioned, the paper is free and well worth a read.

Standing Test for Long-QT syndrome

This was all brand new to me. I was reviewing a syncope patient left over from the night shift before. The hand over was: recent change in anti-hypertensives, now feeling weak and dizzy about 1 week. Syncopal episode at dinner table last night.

She’d been in the department overnight, got some fluids, bloods and an ECG. The ECG was said to be normal.

I went and chatted to the patient and yes indeed it did sound all very like postural hypotension. I went back and looked at the ECG and did my usual syncope ECG review looking for the following:

  • Brugada
  • HOCM
  • WPW
  • intervals – QT and PR

And there it was – a nice big QTc of 550ms staring at me.

I still suspect that postural hypotension was the main cause of her symptoms but it would be a tad on the risky side to call it that in the context of a long QT. K+ and Mg++ were on the low side (3.5 and 0.6) so she got a bit of both and admitted for ECG monitoring.

The interesting bit came in the discussio with admitting doctor who was (for once) interested, enthusiastic and asked about the standing test for Long QT. This was all news to me but effcetively people with a long QT syndrome (LQTS) have an abnormal response in QTc with standing.

In healthy people on standing the heart rate goes up with corresponing shortening of the QT interval. Due to the fact that heart rate goes up more than the QT comes down, the QTc actually goes up slightly,

In LQTS the QTc often goes up substantially.

This paper addresses this concept and while it’s in now waty perfect (ie it examined it in people known to have LQTS which undermines its use as a diagnostic test in undiagnosed QT problems) it suggests that in healthy people an increase in QTc on standing of about 10-15ms is allowed but in LTQS is likely to be in the range of 90-100 ms.

Viskin, Sami, Pieter G Postema, Zahurul A Bhuiyan, Raphael Rosso, Jonathan M Kalman, Jitendra K Vohra, Milton E Guevara-Valdivia, et al. “The Response of the QT Interval to the Brief Tachycardia Provoked by Standing: a Bedside Test for Diagnosing Long QT Syndrome..” Journal of the American College of Cardiology 55, no. 18: 1955–1961. doi:10.1016/j.jacc.2009.12.015. PMID 20116193



  • the normal response to standing after lying is an increase in HR. This would normally be accompanied by a shortedned QT. In LQTS this apparently isn’t the case
  • The intervention was standing and recording QT changes.
  • they did this on high risk LQTS (lots of features but no diagnosis as yet) and those who actually had it genetically documented. The controls were healthy relatives of those pts or volunteers (the vast majority)
  • took them off Beta blockers for a day then lay them flat 10 mins and stood them up for 5 mins with telemetry.
  • blinded investigator performed the measurement had a set part of the trace. Bazzett’s  formula was the main one used.
  • excluded the obviously normal and obviously prolonged



  • 68 LQTS; 82 controls
  • the baseline QTs were 380 v 450 – not diagnositcially different but borderline
  • the QT went down in all the normals but less than the RR interval therefore the QTc goes up slightly.
  • the QT of those with LQTS didn’t change at all. In some it went up. Or put another way the QTc of the control group went up 13ms while the LQTS patients the QTc went up 89ms

Not something I’m going to be doing every day, but it’s a fairly nice, bedside test that we can apply in the ED.