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SGEM#134: Listen, to what the British Doctors Say about LPs post CT for SAH

SGEM#134: Listen, to what the British Doctors Say about LPs post CT for SAH

Podcast Link: SGEM134
Date: October 27th, 2015

Guest Skeptic: Dr. David Sayer is a physician completing his general practice training in the United Kingdom.

Case Scenario: A 34-year-old woman presents with acute onset of headache peaking in 30 minutes with no recent trauma, focal deficits and a normal neurologic examination.

Background: Headaches represent around 2% of all emergency department visits. Of these presentations 1-3% turn out to be a subarachnoid hemorrhage (SAH)  (EdlowVermeulenPerryMorgenstern).

About 5% of SAH are misdiagnosed on the first emergency department assessment (Vermeulen). This is partly because 50% of SAH present with no neurologic deficit (Weir).

Dr. Jeff Perry and his team have tried to create a clinical decision tool to rule out SAH for acute headaches (SGEM#48). The Ottawa SAH Tool contains six variables to decide if a CT scan is necessary.

Applying the tool could decrease the miss rate of SAH from about five percent down to almost zero with a slight increase in utilization. However, the tool needs further evaluation in implementation studies before it is ready for “prime time”.

Traditional methods of working up a SAH has been non-contrast CT followed by a lumbar puncture (LP). Dr. David Newman has questioned this dogma on his SMART-EM podcast. He suggested LPs are not always needed after a negative CT scan.

Dr. Newman calculated the number needed to LP to identify one SAH for which an intervention was indicated to be 700, prompting the question “are you part of the ‘700 Club’?” Should any of us be part of the 700 Club?


Clinical Question: In emergency department acute headache patients, how frequently does LP diagnose SAH after unremarkable CT scan?


Reference: Sayer et al. An Observational Study of 2248 Patients Presenting with Headache, Suggestive of Subarachnoid Hemorrhage, that Received a Lumbar Puncture Following a Normal CT Head.  Acad Emerg Med Nov 2015

  • Population: Adult patients (2248 total, >17 years old) presenting to one of six urban EDs in the United Kingdom with acute headache suspicious for subarachnoid hemorrhage, who had both a negative CT and a lumbar puncture performed.
  • Intervention: LP to achieve identification of CT-negative SAH patients
  • Comparison: None
  • Outcome: Incidence of positive LP (defined only by spectrophometric detection of bilirubin, not by any CSF RBC count) and proportion with cerebral aneurysm identified

Authors Conclusions: In patients presenting to the emergency department with acute, non-traumatic severe headache, LP to diagnose or exclude SAH after negative head CT has a very low diagnostic yield, due to low prevalence of the disease and uninterpretable or inconclusive samples. A clinical decision rule may improve diagnostic yield by selecting patients requiring further evaluation with LP following non-diagnostic or normal non-contrast CT brain imaging.

Quality Checklist for A Diagnostic Study:

  1. checklistThe clinical problem is well defined. YES. Headache represents 1-2% of all ED visits and SAH is one of the most devastating etiologies of headache, yet considerable controversy exists about whether an LP is essential to rule-out the diagnosis after a “negative” CT using contemporary high-resolution scanners.
  2. The study population represents the target population that would normally be tested for the condition (ie no spectrum bias). YES. Emergency department patients with concerning headaches.
  3. The study population included or focused on those in the ED. YES
  4. The study patients were recruited consecutively (ie no selection bias). NO.  Retrospective chart review.
  5. The diagnostic evaluation was sufficiently comprehensive and applied equally to all patients (ie no evidence of verification bias). NO. Although every patient had a CT and LP, neither of these tests is the gold standard for SAH, which would be CT angiogram, traditional cerebral angiogram, MRI/MRA, or 3-month follow-up.
  6. All diagnostic criteria were explicit, valid and reproducible (ie no incorporation bias). NO
  7. The reference standard was appropriate (i.e. no imperfect gold-standard bias). YES
  8. All undiagnosed patients underwent sufficiently long and comprehensive follow-up (i.e. no double gold-standard bias). NO
  9. The likelihood ratio(s) of the test(s) in question is presented or can be calculated from the information provided. NO  There was no 2×2 data provided.
  10. The precision of the measure of diagnostic performance is satisfactory. NO

Key Results: The population was 45% male with a mean age of 41 years. Using the authors’ spectrophotometric criteria for the total population evaluated (2,248 patients), the LP results broke down as follows:

  • 4% positive
  • 13% inconclusive
  • 16% un-interpretable
  • 67% negative

Of the 92 “positive” LP results, 9 were identified with an aneurysm (9/2248 = 0.4%), which equates to 250 LPs to identify one aneurysm.


Number Needed to Tap (NNTap) of 250 to diagnose one aneurysm not picked up on CT scan.


Screen Shot 2015-04-25 at 3.11.12 PMThis was a retrospective study including acute, non-traumatic adult headache patients with suspected SAH presenting to one of six urban training EDs in the UK between 2006 and 2011. Eligible subjects had a non-diagnostic head CT and had a lumbar puncture performed.

Dr. David Sayer

Dr. David Sayer

Five Limitations/Questions (listen to podcast for Dr. Sayers responses):

  1. Spectrophotometry to Evaluate CSF: The authors’ note using appropriate chart review methods and evaluated only spectrophotometric CSF analysis, not CSF RBC counts or visual xanthochromia. This outcome may be problematic since 99% of North American hospitals use visible xanthrochromia rather than spectrophotometry to evaluate for CSF bilirubin. Emergency department providers at centers that lack spectrophotometry would benefit from understanding the sensitivity, specificity, and likelihood ratios and interval likelihood ratios for CSF RBCs, although that becomes problematic with traumatic taps. However, traumatic LPs are a real-world problem and these authors had access to LP results that could have been analyzed as a secondary outcome.
  2. Differential Verification Bias (Double Gold Standard): This occurs when the test results influence the choice of the reference standard. So a positive index test get an immediate/gold standard test whereas the patients with a negative index test get clinical follow-up for disease. This can raise or lower sensitivity/specificity. Since only LP-positive patients routinely underwent additional neuroimaging (CTA or MRA), this study is at risk for differential verification bias that lowers estimates of sensitivity and specificity for disease processes that only become apparent during periods of follow-up (Understanding the Direction of Bias). Un-interpretable LPs were only evaluated at two (out of six) sites and only 5/28 (18%) and 17/56 (30%) had further imaging at those sites so unrecognized cerebral aneurysms probably occurred. Prospective studies would have the benefit of routine criterion standard testing for all patients or alternatively a period of follow-up to ensure that “negative” LP patients were not false-negatives with subsequent symptomatic SAH at a later date.
  3. Chart Review Methods: The authors’ reference chart review methods (Gilbert et al), but they do not describe them explicitly in their methods. Who abstracted the data from the medical records? How were these individuals trained and monitored? Were they blinded to the study hypothesis? Was a standardized abstraction form used? Was inter-rater reliability of chart abstraction assessed for key variables? Without understanding the authors’ specific chart abstraction methods, it is not possible to meaningfully evaluate the possibility of bias in this study.
  4. More Details on Time to CT and Time to LP: Since CT is less accurate for SAH beyond 12-hours after the onset of headaches, additional details about the average delay between headache and imaging is important to understand. Also, theoretically at least 12-hours must elapse between headache onset (sentinel bleed) and formation of CSF bilirubin, so the timing of headache onset and LP should also be reported.
  5. Temporal Bias: Diagnostic tests that rely upon evolving imaging technology are sometimes at risk for temporal bias in which improved ability to obtain high-quality images or finer anatomical cross-sections yield more accurate results (Evidence-Based Emergency Care: Diagnostic Testing and Clinical Decision Rules, 2nd Edition, 2013, pages 54- 64). Since CT technology was evolving between 2006 and 2011, readers should interpret these results conservatively in 2015 and beyond. In other words, when multi-slice CTs (64-slice, 128-slice) are used in your ED today they probably detect CSF blood with even higher resolution than in 2006, resulting in higher sensitivity of the initial CNS imaging, and an even higher number needed to LP than this study suggests.

Comment on authors conclusion compared to SGEM Conclusion: In the setting of acute, non-traumatic headache presenting to the ED, a multi-slice CT (16-64 slice) that does not demonstrate radiographic evidence of SAH is likely sufficient to rule-out a SAH in most patients. In fact, the number needed to tap (NNTap) to detect one aneurysm in this CT-negative population is 250 using a spectrophotometric definition of abnormal LP, which constitutes a significant amount of patient risk and discomfort, expense to healthcare payers, and delays in care for others awaiting treatment with no benefit for 249/250 patients.

Also, an additional 33% of CT-negative/LP equivocal patients with positive, inconclusive, or un-interpretable CSF results would still require additional imaging (CTA or MRA) to truly rule out SAH. Although an accurate, reliable, well-validated clinical decision instrument with a convincing impact analysis would be a useful adjunct to clinical gestalt, such an instrument does not currently exist and was not tested in this study.

Future studies that evaluate the role of LP in CT-negative headache patients with suspected SAH should prospectively assess outcomes similarly in all patients to avoid differential verification bias, while reporting on both visual/spectrophotometric CSF bilirubin and overall CSF RBC diagnostic accuracy (including likelihood ratios and interval likelihood ratios).


SGEM Bottom Line: In this study, one patient would be diagnosed with SAH out of every 250 patients receiving a LP who presented to the emergency department with a headache that did not have their bleed identified on CT scan.


Case Resolution: You are clinically concerned and get a non-contrast CT head that is negative. You discuss the risks and benefits of an LP with the patient. A shared decision is made with the patient not to do an LP. She is discharged home with appropriate analgesia. She is to return to the emergency department if she develops focal neurologic symptoms, pain increases, loss of consciousness, seizure or is otherwise worried.

Clinically Application: Contrary to classic teaching, LP in the setting of acute, non-traumatic headache of <12 hours duration concerning for SAH rarely yields the elusive cerebral aneurysm diagnosis and is often falsely positive or inconclusive.

What do I tell my patient? Sudden onset headaches are clinically concerning for SAH, which can have devastating long-term consequences if misdiagnosed. Unfortunately, migraine headaches outnumber SAH headaches 50:1 in ED settings and do not benefit from CT-imaging of your brain, evaluation of your cerebrospinal fluid, or surgery. Modern CT scanners are very good at identifying blood in your brain from a SAH, if the CT is obtained within 12-hours of when the headache began. Older research indicated that only 9/10 SAH were detected by a CT so evaluation of fluid around your brain (CSF) was recommended to be completely certain that SAH was not the cause of the headache. Newer research indicates that CT scans almost never miss the diagnosis of SAH and that 250 lumbar punctures (LP) are needed to identify one cerebral aneurysm that CT missed. LPs are not benign procedures and can cause post-LP headaches, infections, nerve damage, and bleeding around your spinal cord.

Keener Kontest: Last weeks winner was Gregory Rodgers. He knew that Willem Einthoven was the Dutch physician who designed the first practical ECG in 1903 and won the Nobel Prize in medicine in 1924 for the invention.Listen to the podcast for this week’s question. If you know the answer, then be the first person to email TheSGEM@gmail.com with “keener” in the subject line to win a cool skeptical prize.SGEM-HOP-SAEM-logo-227x300

 

SGEM-HOP Social Media Feedback: Respond early and often to this podcast for a chance to have your comments published. You can use the SGEM blog, Twitter, or Facebook, but you only have one-week to respond before this carriage turns into a pumpkin. At the end of 1-week, we’ll pick the Top Five Social Media comments to publish in a future edition of AEM.


Remember to be skeptical of anything you learn, even if you heard it on the Skeptics’ Guide to Emergency Medicine.


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  • Salim R. Rezaie

    Hey Ken,
    Great topic and an important one. Would have loved to have seen time to Head CT and time to LP as it is a well known fact that as time from headache progresses, CT becomes less sensitive for SAH. Also there appears to be a few windows worth mentioning in time to LP:

    6hr but 12hr:
    -LP with Pos RBCs & Neg Xanthochromia = Neg LP
    -LP with Pos RBCs & +Xanthochromia = Pos LP

    Would love to hear others thoughts on the above? Also I made a summary slide of the episode below…..

    Salim

    • SAEM EBM IG

      Salim:

      Nice synopsis and I agree that (if future studies are warranted to evaluate the role of post-CT LP to rule-out SAH — a rather large “IF” in my opinion), that prospective studies that explicitly assess the time from symptom onset to both CT and LP are essential. Five studies that I’m aware of have evaluated CT accuracy at any time after headache onset (http://pmid.us/7897421, http://pmid.us/15961003, http://pmid.us/16374977, http://pmid.us/21768192, http://pmid.us/22821609) with sufficient reporting to compute sensitivity and specificity, but only two have stratified that analysis by 6 hours (http://pmid.us/21768192, http://pmid.us/22821609). In addition to the delay between symptom onset and CT imaging, important details include the number of CT slices (generation of scanner) and experience of the CT interpreter.

      Additional key questions regarding the CSF analysis include
      1) How to define “abnormal” CSF (visual vs. spectrophotometric xanthochromia, number of RBC/mL in Tube 4, other)?
      2) How to define a traumatic LP (and whether a traumatic LP can be interpreted to rule-in or rule-out SAH)?
      3) The Number Needed to LP to identify alternative causes of headache (meningitis, pseudotumor cerebri) — one recent retrospective study reported that the NNLP to identify one CNS infection was 227 (http://pmid.us/23358626).
      4) Interval likelihood ratios for CSF RBC to diagnose SAH in non-traumatic LP.
      5) The etiologies and outcomes of “true positive” LPs in suspected SAH, remembering that not all blood in the arachnoid space results from a ruptured cerebral aneurysm — almost 15% result from perimesencephalic hemorrhage for which there is no intervention, only watchful waiting.

      Finally, it would be most helpful to have a synopsis of history and physical exam (and CDRs) for the diagnosis of SAH.

      SAH is a challenging diagnosis with an opportunity for EM to improve outcomes with timely diagnosis, but the issue is balancing potential benefits and harms on a case-by-case basis. Opinions against (http://epmonthly.com/article/lp-for-subarachnoid-hemorrhage-the-700-club/) and for (http://epmonthly.com/article/a-proud-member-of-the-700-club/) routine post-negative CT LP exist and will continue to be debated. What will you decide?

      Chris Carpenter

  • clostridium

    Great points by Salim, the time from HA to CT scan is a key missing piece of information. When you review the cases that LP caught and CT missed all except for 1 of them are > 6 hours and a good number are much longer.

    The other thing to consider is that you can get more than SAH yes/no from an LP. You can diagnose other problems like meningitis. How much value that has is of course outside the purview of this particular article but it is something to consider.

    Another thing to consider is that many US hospitals are looking at non-con CT + either LP or CTA head/neck if the patient is > 6-12 hours out from the headache. In that setting the LP is avoiding additional radiation and potentially also avoid finding the little aneurysms that you don’t quite know what to do with. The approach by the study authors is not the same but this is important to consider.

    In the end here’s how it breaks down for me: there is a small but non-zero chance of missing the SAH with non-con CT only. there is also a chance of discovering an alternative source for the headache with LP. I share the statistics with the patient and have a discussion with them about how to proceed now that they are informed and know what they are getting in to.

    We also know that there are the “classic” SAH stories like thunderclap headache out of nowhere vs. the less compelling stories we hear all the time. And we know that patients have different risk levels based on other factors. And we know that missing the sentinel bleed could mean a devastating outcome. So I work with the patient to ascertain what the risks really are and do some shared decision making including the chances we might find another headache etiology with the LP. It isn’t perfect but no one ever said clinical medicine was that way.

    Craig

    • tim harris

      Thank you for your interest and comments. We chose to put the time to CT in simple time categories as this is hard to abstract from notes with a high degree of accuracy. What is the time of booking ip – rival, assessment – key in the UK with the 4 hour target. Time to CT may be leaving ED or arrival in CT or time of scan – different units report different points. We used the time of the CT from the PAVCS record here. All patients who had an LP in this study did so at > 12 hours from headache peak severity. Our practice is now as described by Salim in the first post here.
      One issue we discovered when collecting data but not emphasised in the paper is what constitutes a ‘thunderclap’ headache with attending differing in their definition of this from < 5 mins to 30 mins from onset to peak intensity.
      re David's point above – We also noted that the history described by patients as regards this did differ at presentation to review in our CDU's the following day; indeed this is why some patients re admitted for LP but do not receive one. This was a 'pragmatic' study so observing how clinicians behaved as opposed to mandating a set approach.
      re Craigs point above – we actively try not to move to CT angiography as we are concerned about the detection of incidental aneurysms.
      The one case who presented at 3 hours certainly gave a good history but the scan upon review by attending neuroradiologists was normal.
      We have picked up one case of viral menningitis that presented with a history suggesting SAH.
      We apologise for not recording the morbidity of the LPs as this is key data.
      We are very grateful for the excellent critique offered here.
      with thanks
      Tim Harris

  • davidnewman44

    Another data set, flawed but interesting, that adds to mounting literature and cultural awareness suggesting that a routine approach of LP for severe or acute headaches is more harmful than helpful. The aneurysm rate here was, as the authors note, at or below what would be expected in an asymptomatic screening cohort. Other than ‘good story’ cases these appear to be mostly incidental. Clinical history, as is often the case, should rule the day, helping to determine the very few who undergo LP.

    What is badly needed is a reliable, published Test Threshold calculation for further testing after CT in such patients (stay tuned…).

    Nice review, gentlemen.

  • David Sayer

    Good question Salim,
    I will address the time to LP first.
    Although we didn’t specifically measure time to LP, the way that the service is set up in the UK is that we have to admit or discharge people from the ED within 4 hours. People on a ‘rule out Subarachnoid’ pathway generally get admitted to either the ED ward or under the medical team. The other factor is that as labs use spectrometry to analysie CSF this service is only available during working hours. The upshot of this is most people do not get a LP until the following working day. This practically will always be at least 12 hours after the headache onset. It is usually much longer – the joys of the NHS!
    Your second point re: time to CT. It would have been good to have recorded this, we didn’t do this due to the practical limitation of the study. We generated our data from people who had had LPs looking for SAH. Due to the numbers involved and time constraints we only exhaustively investigated those with ‘missed’ aneurysmal SAH. In the paper we listed the time frames involved from headache to CT. Most of the missed ones were actually quite late >1 week. There was only one in a short time frame.
    But you are absolutely right if we had this data for all 2248 LPs it would be really powerful. I suspect even if you extensively trawled the notes this wouldn’t be recorded well in a lot of cases.
    I hope this explains your questions.
    DAVID

  • Kirsty Challen

    Great podcast & topics, thanks all (keep going with the British takeover).

    #paperinapic for easy reference.
    Kirsty

    • TheSGem

      Thank you for taking the AEM paper and the #SGEMHOP episode and summarizing it in an info graphic. This will help cut the KT window down from over ten years to less than one month!

    • David Sayer

      Hi Kirsty,
      I love this graphic, makes the headline results much easier to interpret.
      DAVID

      • Kirsty Challen

        Welcome! I will be using it for shared decision making with the next patient I see with a negative CT :-)

        • David Sayer

          I think at the moment that is the key, there is no definitive answer and shared decision making is the key.

  • Thomas E Carter DO

    Cheng Y-C, Kuo K-H, Lai T-H. A common cause of sudden and thunderclap headaches: reversible cerebral vasoconstriction syndrome. J Headache Pain. 2014;15(1):13. http://www.biomedcentral.com/c…. Accessed November 2, 2015.

    Although not robust numbers, this article brings up many other good ideas and causes of Sudden Onset Headache, I agree we should fixate some on the highest morbidity one but I am often dissuaded from LP if the onset was during a well-described activity at onset.

    • TheSGem

      Thanks for joining the conversation Thomas and providing additional information.

  • TheSGem

    Do you usual do a LP post neg CT to rule out SAH (Yes or No)?
    Vote today on the Twitter Poll @TheSGEM

  • TheSGem

    Final results from the Twitter Poll…50/50 split on getting LP post negative CT to rule out SAH.

    • SAEM EBM IG

      Now that’s what I call clinical equipoise. Although a randomized controlled trial following non-diagnostic CT (LP vs. non-LP) would be tremendously challenging due to the infrequency of CT-LP+ SAH, I wonder if anything short of a RCT would sway the 50% who still routinely LP in this scenario?

  • TheSGem

    See what Dr. Ian Stiell (Clinical Decision Rule/Tool) guru says about getting a LP post negative CT to rule out SAH.

  • Tom

    Evening. As a fellow Brit I’m sorry to disagree but I think there’s a difference in practice that may not have crossed the Atlantic. Partly because CT is harder to come by over here, and partly baca use of a healthy respect for radiation, we tend to come at things the other way round- Q1 is there subarachnoid blood present? If visible on plain CT, proceed to CTA looking for aneurysm. If no blood on CT, LP and CSF analysis is the diagnostic test for subarachnoid blood.

    If you do CT arteriography before LP, and see an aneurysm, you still don’t know if it’s bled or not. The morbidity of coiling (certainly clipping) an aneurysm that has not bled will far outweigh the harm of an LP. On the other hand CT, LP, then back in the scanner for CTA answers all the questions you need to know.

    In my unit by the way the rate of CT neg, LP pos runs about 8-10% annually, of which about 2/3 aneurysmal.

    And to avoid the confusion Dr Rezaie mentions, just wait until 12h to LP anyone, since my biochemists assure me that sens/spec of xanthochromia from the lab (bilirubin absorbimetry) is better than visual xanthochromia, and avoids the confusion with traumatic taps, which are inevitable.

    Keep up the good work.

    Tom

  • David Sayer

    Hi Tom,
    I couldn’t agree more about CTA. We should not be doing a CTA unless we have proved there is blood in the subarachnoid space. There is a potential for great harm in uncovering incidental aneurysm that haven’t bled.
    I think one of the problems is how to handle the ct negative patients who have an inconclusive LP for one reason or another. Because you aren’t any further down the line. In these case I think it is all about history and clinical judgement about whether or not further imaging is necessary. In a reasonably low risk history which has presented in a timely manner I would be very loath to do a CTA precisely because of the danger of finding an incidental aneurysm.
    It is interesting that you have a reasonably high rate of positive LPs at your unit. Do you have a strict selection criteria for them e.g. consultant input on decision making? Because one of the ways round this problem is to develop a tool to select the higher risk headache patients who may benefit from a LP rather than just all patients who have had a sudden onset bad headache. I beleive Leicester are doing some work on this.

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  • TheSGem

    SGEM Hot Off the Press review published in Academic Emergency Medicine with top social media comments. http://onlinelibrary.wiley.com/doi/10.1111/acem.12919/abstract