Wednesday 20 September 2017

Promising prognostic accuracy of Sepsis-3 criteria for in-hospital mortality among patients with suspected infection presenting to the emergency department

Thank goodness for the Third International Consensus Definition for Sepsis and Septic Shock! (Yes, this is an odd statement…) They have done away with the terrible SIRS criteria and put the sepsis back in sepsis.

Sepsis has reverted to “a life-threatening organ dysfunction caused by a dysregulated host response to infection.” This is always what we had thought it to be… not the young person with man-flu.

SIRS has been criticised for having poor test characteristics so now we have SOFA and the easier qSOFA

qSOFA is (0-3):

  • Hypotension (SBP less than 100)
  • Alterred mental status
  • Respiratory Rate >22

Yeeeeehaaaa... even I can remember 3 things!

The purpose of this study was to externally validate the qSOFA score among patients presenting to the ED and compare them to the old tools (SIRS, lactate, etc) to predict mortality.

This was a multicentre prospective cohort study mostly done in French ED’s that analysed 879 patients with sepsis. There was an overall 8% mortality rate.

How good was qSOFA?

Pretty darn good (if you believe this study to be valid).

If the qSOFA was less than 2, mortality was 2%. For 2 or greater it was 24%.

The area under the curve (AUC) is a plot of the true positives (sensitivity) on the y-axis and the false positives (1- specificity) on the x-axis. This is a great way to evaluate & compare diagnostic/prognostic tests that have continuous or ordinal values. An AUC of 0.5 would be a useless test (i.e. equal number of true to false positives). 1.0 would be perfect and of course does not exist.

What was the AUC for qSOFA?

0.80 (95%CI 0.74-0.85). This AUC would be considered excellent but certainly not perfect.

This was much better than SIRS which was marginal 0.65 (95% CI 0.59-0.70)

Of course, no study is without problems. This study used the worst qSOFA measurement during the patient's ED stay which increased the sensitivity. In the end, I doubt this tool is really that good.

Some aspects of qSOFA have face validity. I don’t need a decision instrument to tell me that patients with altered mental status and hypotension will do worse!

I also don’t know how this score will be in screening for sepsis. It strikes me as overly simplistic.

Sepsis is a complex and heterogeneous disease process. Clinical decision instruments have never been that useful in these circumstances. They often fail as no fancy regression analysis can account for all of the intricacies of complex disease and individual variability.

The good news is we can use experienced clinician judgement… go figure! In addition, you can incorporate aspects of SOFA in your decision making.  No doubt there will be more to come.

Tuesday 19 September 2017

Acupuncture for analgesia in the emergency department: Theatrical placebo vs. inadequate doses of analgesia



Was an RCT really done in multiple Australian ED’s investigating acupuncture for analgesia?

Why yes…

Anyway… This study aimed to assess analgesia from acupuncture alone or in combination with medications in ED patients with low back pain, migraine or ankle sprain. The primary outcome measure was pain at 1 hour.

There was no sham acupuncture arm and of course patients were not blinded to treatment allocation. 

Without going into too many details, they assessed 1964 patients and nothing seemed to work very well. Acupuncture was just as bad as pharmacotherapy. In addition, patients in the acupuncture group were almost twice as likely to require rescue analgesia.

Ok… perhaps I’m biased so I’ll quote “the implications” from the paper below

Acupuncture is safe, acceptable and has an analgesic effect comparable with that of pharmacotherapy, but none of the therapeutic strategies used provided optimal analgesia within one hour of presentation.

And a quote from the conclusion at the end of the manuscript

Our finding that acupuncture was safe and acceptable form of acute analgesia suggests it may be useful as an adjunct to pharmacotherapy or when pharmacotherapy is unsuitable.

There are no reputable high-quality studies of acupuncture show it is anything more than theatrical placebo. (The vast majority have small numbers, high risk of bias, and have conflicted researchers that want to prove it works.)When sham acupuncture and proper blinding is performed, it is no better than incantations, rain dances or Haitian Voodoo.

But this study was published in a highly regarded journal with a number of authors that are quite clever. So perhaps I’m wrong… and hopefully they don’t stab me with a voodoo doll.


Is it safe to routinely send patients home with topical tetracaine from the ED after corneal abrasion? A retrospective chart review

Simple corneal abrasions heal quickly but can be quite painful and irritating. Topical anaesthetics work like magic at relieving the pain. But tradition has told us sending patients home with this medication is a no-no. Your eyeballs will rot and fall out…

But recent literature has suggested this is probably all a myth. A New Zealand RCT performed by Waldman et al. in 2014 supported the safety of topical tetracaine.

Waldman et al. has been on a roll down in Invercargill. Their RCT changed local practice in the ED and they started discharging patients with simple corneal abrasions with a take home pack of tetracaine (3 plastic 0.5ml commercially available vials or approximately 50 drops. They could use it as often as every 30 minutes for 24 hours)

They did a retrospective medical records review to see if this practice was safe.

During the study period, tetracaine was used 459 times for corneal abrasion. How many serious complications did they find?


Sounds like a slam dunk. Send home patients with topical anaesthetic. Boy… that was easy.

Or maybe not…

To be fair, this is poor quality evidence. Retrospective record reviews suffer from poor quality data that was never collected with the intention to be included in a study. Much may be incomplete, missing or wrong.

In addition, the surrogate measures for “safety” are problematic. ED rechecks and ophthalmology clinic referrals were thought to suggest complications. But were they? We don’t know.

The authors conclusions and editors capsule summary are appropriately cautious. They mention wide confidence intervals, some increased risk for complicated corneal abrasions and large prospective studies are needed to confirm safety. Sure…

But it is probably true that no eyeballs went rotten or fell out… so I’m tempted to believe it. This may be poor quality evidence but it has face validity anyway. It also adds to an evolving body of literature that is pretty much telling us the same thing.

Send them home with topical anaesthetic… it’s ok.


Sunday 17 September 2017

Ketamine as an adjunct to opioids for acute pain in the ED: a peer review fail

Another ketamine for acute pain in the ED study…

Unfortunately there are numerous problems with the way in which this paper is presented that makes me genuinely concerned about the integrity of the data (I'll get to this... shame…)

Anyway… adult patients were eligible for enrollment if they reported pain greater than 6/10 and had a dose of intravenous opioid analgesia (about 5mg morphine I think… but half got hydromorphone).

Patients were randomized to 0.1mg/kg of ketamine vs. placebo. At 30 minute intervals they were asked their pain level and if they needed more pain medication.

The primary outcome was pain control over 120 minutes. (Really they claimed two primary outcomes which you can’t do in an RCT… did a power calculation then decided to do a different power calculation later… oh boy…)

In the end, they had 63 people in the placebo group and 53 in the ketamine group. (Block randomisation should have prevented substantially extra patients in one group so I’m not sure how they explain this. In addition, their CONSORT flow diagram shows 32 and 34 patients in each group, sloppy…)

I think most patients had abdominal or flank pain. (But it is really unclear as 20% of patients are unaccounted for in the descriptor of chief complaint on Table 2. Slop slop)

Without going into too many details, the authors claim that ketamine as an adjunct to opioid therapy was more effective at reducing pain.

If you look at the pain reduction over time, it looks like the ketamine worked best at 120 minutes; long after it should have worn off. I’m sure someone could come up with some biological plausibility for this, but it does seem odd.

50% of the ketamine group had patient reported side effect. But “no patient had side effects lasting longer than 6 minutes.” I find this very difficult to believe.

So in the end, a study claiming a low dose of ketamine 0.1mg/kg had quite an analgesic effect. This is of course discounting the low total dose of opioids given, changing research methods, numerous figures & tables that were wrong and some dispensing of belief. 

Opioids have been around for a long time. They are reasonably safe, predictable & effective with a reversal agent.

Researchers have been furiously looking how we can “spare opioids.” How about more research on how we can "spare ketamine!"

Ok... perhaps I've overstated things. There probably is a role for low dose ketamine when adequate doses of first line analgesia are contraindicated or not working. But unfortunately this paper does not really add much to our knowledge.