Emergency Medicine Literature of Note
Musings on Emergency Medicine, Clinical Informatics, & High-Value Care.
Another tiny bit of self-promotion – a new publication published today. Stems essentially from a literature review I did after clawing through ECASS-III and noting that 12 of the 14 investigators were paid, sponsored, or employed by the manufacturers of alteplase – which muddied my estimation of the reliability of the conclusions. Turns out, ECASS-III wasn’t the only one….
…although the authors of this study draw the opposite conclusion.
In an effort to decrease the administration of TPA to stroke mimics and TIAs, some institutions are moving to the use of CT angiographic and perfusion studies after the initial non-contrast scan. Previous studies have suggested an association between iodinated contrast administration and ICH after TPA.
These authors beg to differ. In their study cohort, they retrospectively evaluate 319 patients receiving TPA for acute stroke, 69 of whom receive contrast and 243 who do not. Depending on whether the ECASS or SITS-MOST definition of symptomatic ICH is used:
ECASS – 4 of 69 (5.8%) with contrast, 12 of 243 (4.9%) without contrast
SITS-MOST: 3 of 69 (4.4%) with contrast, 9 of 243 (3.7%) without contrast
…and that small absolute difference does not reach statistical significance because their numbers are so small. This does not prevent the authors from stating “we found no association of either IV contrast administration or contrast dose with SICH in our series of patients treated with IV rtPA.” They’re not wrong – but they barely address how underpowered their study is, or how every baseline characteristic (age, stroke severity, comorbid conditions) favored their contrast group, yet they still trended towards increased ICH.
Does the author of every TPA article live in a distortion field that blinds them to reasonable consideration of safety issues and study limitations?
“Iodinated Contrast Media and Cerebral Hemorrhage After Intravenous Thrombolysis”
http://stroke.ahajournals.org/content/42/8/2170.short?rss=1
…but they almost all do well! Only 5.1% of patients without stroke who receive TPA end up with intracerebral hemorrhage – so it’s OK that we give TPA to a ton of patients without a confirmed diagnosis of stroke, right?
This is a retrospective Finnish registry study of 1,104 consecutive TPA patients enrolled in a prospective cohort. Of these, 119 had basilar artery occlusion, which is angiographically proven prior to treatment, and are excluded from their analysis, and a couple others were excluded for other reasons. This left 985 patients who were initially diagnosed with ischemic stroke, and, eventually, 14 of those patients were diagnosed as a stroke mimic such as migrane, epilepsy, or a demyelinating disorder. The authors then go on to say that stroke mimics such as these accounted for a mere 1.4% of all TPA patients, and none of them had ICH.
But, this isn’t exactly a true reading of their data. The authors also state that 275 of their patients had “neuroimaging negative ischemic stroke”, which is to say, their follow-up MRI detected no sign of infarct. Now, there is a false-negative rate on DWI MRI for stroke, but it’s in the range of 5% for acute infarcts, and generally involves small lacunar, small cortical, and some posterior circulation strokes. Not only that, it’s reasonable to suggest that around 40% of TIAs actually have DWI or FLAIR sequence abnormalities as well.
So, some of their “neuroimaging negative ischemic stroke” group probably does have ischemic stroke with false negative MRI – but not 30% of the study population. And, some of their neuroimaging positive group is likely false positive from TIA as well. These numbers for stroke mimics are also far below other reported case series, which have estimated 10-30% incidence, depending on whether TIAs are included.
I absolutely cannot fathom this line of reasoning and distortion Neurology is developing in justify recklessly pushing TPA onto a larger population.
“Stroke Mimics and Intravenous Thrombolysis”
http://www.ncbi.nlm.nih.gov/pubmed/22000770
Somewhere in the rush to but up billboards and focus the medical establishment on experimental revascularization interventions for acute stroke (e.g., time is brain), we’ve overlooked what truly matters – follow-up care after the ischemic event. This is a lovely study that reminds us of what we probably knew once, but have forgotten – that even in the absence of acute therapy, simple protocols to prevent fever, prevent hyperglycemia, and prevent aspiration pneumonia lead to profound differences in the number of patients with zero or minimal disability after stroke.
This is a prospective interventional study in which acute stroke units in New South Wales Australia were randomized to either no protocolized intervention, or an intervention with nursing protocols named above. At the end of the three-year intervention period, 42% of the control group had mRS 0 or 1 at 90 days, and 58% of the intervention group had mRS 0 or 1 at 90 days. There were small differences in the type of stroke, education level, and prior ability to work that probably favored the intervention group, but the differences at baseline were far smaller than the magnitude of the treatment effect. In short, a basic nursing protocol intervention improved outcomes more than any other intervention for acute stroke.
“Implementation of evidence-based treatment protocols to manage fever, hyperglycemia, and swallowing dysfunction in acute stroke (QASC): a cluster randomised controlled trial.”
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)61485-2/fulltext
The problem – the most difficult clinical situations are the ones where we need a handy decision tool – and the hardest to come up with an effective one. Syncope rules, PE prediction rules, ACS prediction rules, and now TIA evaluation.
The most important number to come out of this paper is probably 1.8% – the number of patients with a TIA who went on to have a stroke in the next seven days. That’s 38 out of their 2056 patients enrolled. The next number is 2.7%, which is the 56 patients who had another TIA within 7 days. So somehow a rule has to magically pick out that tiny proportion of patients who are going to have bad outcomes without excessively testing the remaining supermajority.
Nearly everyone had a CT of the head, nearly everyone had an EKG, very few (15% with an ABCD2 score ≤ 5 and 22.% with a score > 5) had consultation with a neurologist, and even fewer were admitted. The specificity for stroke within 7 days with a score >2 – the AHA definition of “high risk” – is only 12.5%. Not only that, but there was significant disagreement between enrolling physicians and the study center regarding the correct ABCD2 score for a patient.
So, in the end, ABCD2 is difficult to apply and only minimally useful. You’re going to miss half the strokes at 7 days if you apply it in a situation where the specificity is >50% – so, sure, a sky-high score tells you they’re in trouble, but that still doesn’t help you discharge the majority of your TIAs safely for outpatient follow-up.
“Prospective validation of the ABCD2 score for patients in the emergency department with transient ischemic attack.”
www.ncbi.nlm.nih.gov/pubmed/21646462
Catheter-based endovascular treatment of acute ischemic stroke has been around for several years – this is a nice, concise review of the published literature regarding their use.
The abstract sounds a little more favorably skewed than the actual content of the article – their discussion is appropriately skeptical regarding the efficacy and applicability of this particular treatment modality. It is certainly true that restoring flow to affected regions in stroke is advantageous, and the theory behind the use of these devices is to mechanically ensure open vessels in situations where systemic thrombolysis may not be efficacious and the disability is likely to be profound.
The problem is, there really isn’t any “evidence” in this article. The published literature on this topic is primarily retrospective cohort/case-reports by industry-affiliated inventors of these devices and, even despite this bias, that literature tends to report unacceptable levels of procedural complications while trying desperately to show benefit.
Regardless, as the authors mention, there are many studies of MERCI and Penumbra ongoing – slowly chasing that inexorable statistical probability of finally performing enough studies that, by chance, one of them will be favorable enough upon which to base widespread marketing efforts.
“Neurothrombectomy devices for the treatment of acute ischemic stroke: state of the evidence”
http://www.ncbi.nlm.nih.gov/pubmed/21242342