“The Adventure of the Second Stain”

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Subarachnoid Hemorrhage (SAH) is one of the more angst-inducing pathologies an Emergency Physician faces on a daily basis. A disease for which we have a well established diagnostic pathway. The strategy of non-contrast CT followed by a lumbar puncture (LP) has been showed to effectively eliminate the risk of SAH (1). And yet there is great resistance to performing an LP on the large majority of patients suspected of SAH. In a paper by Perry et al published in CJEM, the authors demonstrated that only 27% of the patients who received a CT to rule out SAH had a subsequent LP. In the patients who did receive an LP the length of stay increased significantly(2). Because of this there have been various alterative strategies proposed to eliminate the need for a lumbar puncture in the Emergency Department. One of these strategies involves a non-contrast CT followed by a CT angiogram (CTA). The thought process is that if no blood is identified on the CT and no aneurysm can be seen on the CTA, then even if the patient does have a SAH it is not of aneurysmal origin and therefore requires no further management.

There are a number of problems with a CT/CTA protocol. The first and most obvious is that CTA is an anatomic test meant to identify the presence of an aneurysm. It does not tell you whether that aneurysm is the cause of the presenting headache. Given this, using CT/CTA as a diagnostic pathway to rule out SAH will inevitably lead to the frequent misclassification of incidental aneurysm in an otherwise benign headache. Studies have found the rate of asymptomatic unruptured cerebral aneurysms in the general population as high as 7%(3). In assuming all aneurysms discovered by CTA are the cause of the presenting headache,  we will transform people into patients, and cause unnecessary downstream testing and interventions.

In addition to this decrease in specificity, there is no evidence CT/CTA adds any diagnostic value to our current management of suspected SAH. Currently our knowledge of the diagnostic accuracy of CTA for SAH is based primarily off small cohorts trials comparing CTA to the gold standard of digital subtraction angiography (DSA) in patients who have already been diagnosed with SAH. In these trials CTA was utilized to identify an aneurysmal cause of a known SAH. Even in this population, the sensitivity of CTA ranges from 81% to 99% (4-7). In fact in some cases even the initial DSA can be falsely negative secondary to arteriospasm, and only appear positive after a delayed DSA 2-3 days later (11). The failure of logic occurs when attempting to apply this data to the undifferentiated headache patient in the Emergency Department. These studies do nothing to inform us how CTA performs when used in series with CT for the diagnosis of SAH in undiagnosed patients presenting with thunderclap headache. If one assumes independence of the two tests and applies the most optimistic test characteristics for CTA, then the post-test probability following a negative CT and CTA may be clinically useful. Unfortunately, given the current data we are unable to assume independence between these two tests.

Conditional Independence is the assumption that two diagnostic tests have different factors that determine the individual diagnostic accuracy of each test. People who argue for the CT/CTA strategy assume that since CT and CTA are looking for different findings (blood vs aneurysm), then their ability to identify SAH are independent and augmentative. On the other hand, if the aneurysmal bleeds that are missed by CTA are the same bleeds that are commonly read as negative on CT, then this protocol will add little to the sensitivity of CT alone. This concept is demonstrated nicely in a paper by McCormack et al, published in Academic Emergency Medicine (8). In this paper the authors calculate the post-test probability following a negative CT and CTA given 25, 50, and 75% dependence. In the case where the tests only have 25% dependence the post-test probability of a negative CT and CTA would be 0.29% (or 1 in 344 patients). On the other hand if you were to assume 75% dependence between the tests, then the post-test probability would be 0.86% (1in 116 patients),very close to the post-test probability of a negative CT alone.

This of course comes back to, what is an acceptable miss rate? At what threshold does the harm of over-testing, false positives, and needless interventions overcome the harm of a missed SAH? Perry et al’s data on the sensitivity of non-contrast CT alone performed within the first 6-hours of symptom onset demonstrates that a negative CT already stratifies these patients into a fairly low risk cohort(9). What to do after a negative CT is still up for debate. If you believe that a negative CT places a patient below the test threshold, and any further testing will do more harm than good, then there is reasonable data to support this decision(10). In the cases of the high risk patient in whom CT alone is not adequate to rule out SAH, the LP is the appropriate next step. Although LP has a high rate of false positive findings (a specificity of only 67%) (1) in its own right, it has  demonstrated a proven negative predictive value above CT alone (1).

Without formal investigations evaluating the performance of a CT/CTA in the diagnosis of SAH, we are incapable of knowing its true diagnostic utility. If CT followed by CTA strategy ends up having a significant degree of conditional dependence, not only will this protocol increase the rate of false positive findings by identifying incidental aneurysms, it will not add diagnostic capabilities above CT alone. It is clear this strategy provides very little immediate benefit and will surely lead to far more downstream harm.

Sources Cited:

1. Perry JJ, Spacek A, Forbes M, et al. Is the combination of negative computed tomography result and negative lumbar puncture result sufficient to rule out subarachnoid hemorrhage? Ann Emerg Med. 2008; 51:707–13.

2. Perry et al.. Diagnostic test utilization in the emergency department for alert headache patients with possible subarachnoid hemorrhage. CJEM 2002;4(5):333-337

3. Ming-Hua  et al Prevalence of Unruptured Cerebral Aneurysms in Chinese Adults Aged 35 to 75 Years A Cross-sectional Study. Annals of Internal Medicine. 2013 Oct;159(8): 514-521.

4. MaccKinnon et al. Acute Subarachnoid haemorrhage: Is a negative CT angiogram enough? Clinical Radiology, Vol. 68, Issue 3, 232-238

5. Ergun et al. Diagnostic Value of 64-slice CTA in Detection of Intracranial Aneurysm Patients with SAH and Camparison of the CTA

Results with 2D-DSA and Intraoperative Findings

6. Kokkinis et al. The Role of 3d-Computer Tomography Angiography (3D-CTA) in Investigation of Spontaneous Subarachnoid haemorrhage: Comparison with Digital Subtraction Angiography (DSA) and Surgical Finding. British Journal of Neurosurgery. Vol. 22:71-78

7. Westerlaan et al. Multislice CT Angiography in the Selection of Patients with Rupture Intracranial Aneurysms Suitable for Clipping or Coiling. Neuroradiology (2007) 49:997-1007

8. McCormack et al. Can Computed Tomography Angiography of the Brain Replace Lumbar Puncture in the Evaluation of Acute-onset Headache After a Negative Noncontrast Cranial Computed Tomography Scan? Volume  17, Issue 4, pages 444–451, April 201)

9. PerryJJ,StiellIG,SivilottiML,etal.Sensitivityof computed tomography performed within six hours of onset of headache for diagnosis of subarachnoid haemorrhage: prospective cohort study. BMJ. 2011;343:d4277.

10. LP for Subarachnoid Hemorrhage: The 700 Club DECEMBER EMERGENCY PHYSICIANS MONTHLY. 4TH, 2012http://www.epmonthly.com/features/current-features/lp-for-subarachnoid-hemorrhage-the-700-club/

11. Agid et al. Negative CT Angiographic Finds in Patients with Spontaneous Subarachnoid Hemorrhage: When is Digital Subtraction Angiography still Needed? Am J Neuroradiol 31:696-705, April 2010

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Med Apps per chi lavora in emergenza

In più occasioni e da più persone mi è stato chiesto di fare un post sulle applicazioni per smartphone e tablet utili a chi lavora nell’ambito della medicina d’emergenza. Personalmente credo che sia difficile dare consigli e che in questo ambito molto dipenda dalle abitudini e dai gusti personali, cerchero di limitare il discorso a […]

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Justin Bieber arrest refocuses spotlight on “sizzurp”

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[In the video above, the Today show's Jeff Rossen explains why "sizzurp" — a drug favored by some rap music and pop stars — is so dangerous.]

Reports describing the arrest of pop star Justin Bieber, 19,  this week for driving under the influence — after he was stopped while apparently drag racing his Lamborghini in Miami Beach — often mentioned that one of his favorite drinks is “sizzurp“, a potentially lethal mix of prescription cough syrup (codeine and promethazine), soda pop, and hard candy. TPR wrote about this concoction last year when rapper Lil’ Wayne was admitted to the ICU at Cedars-Sinai Hospital in Los Angeles, possibly after ingesting “sizzurp.”

I have also written about “sizzurp” in Emergency Medicine News. To read that column, click here.

 

INR overestimates coagulopathy in stable trauma and surgical patients

From OHSU, Portland, Oregon study came out in Journal of Trauma and Acute Care Surgery in Dec 2013.  The main idea was that INR should not guide to transfuse FFP in stable trauma patient. This was a prospective observational study with 106 patients enrolled. They checked all clotting factors, and as well TEG. The median TEG was in normal limits, with clotting factors  function remained adequate Pre and Post FFP transfusion. The conclusion is: “INR is not a predictor of coagulopathy and should not be used to guide coagulation factor replacement in stable trauma and surgical patients.”

 

Link to article