Improving Outcomes, Mythbusting, Neurology

Early vs late meningitis diagnosis: capturing the needle in the haystack

Needle in the haystack, infectious pathway, take 6.

This is a retrospective study looking at early vs late diagnosis of bacterial meningitis from three hospitals in Denmark (one looking at data from 1998-2014; the other two from 2003-2014). To be eligible, patients had to be >15 years of age, and, obviously, had to be hospitalized with a clinical presentation consistent with possible community acquired meningitis (any combination of headache, neck stiffness, fever, altered mental status, petechiae) with no alternative diagnoses made during or after admission. Furthermore, all patients also had to have a proven bacterial etiology by either: positive CSF culture, positive blood culture and CSF with >10 wbcs, bacteria seen on CSF gram stain, or bacteria in CSF by PCR or antigen analysis.

So what is early and what is late diagnosis? They define “early diagnosis” as being recognized in the ED (1.3 hours to antibiotics median), and “late diagnosis” as, well, not diagnosed in the ED (ie, diagnosed on the wards- 13 hours to antibiotics median). Over roughly 15 years, they saw 358 cases of bacterial meningitis, (~8 cases per year per institute – seems a bit high? They do not mention total number of annual ED visits), with 32% being classified as diagnosed “late.” … so, probably 2-3 cases a year of “late” diagnosis – a true needle in the haystack.

Why the late diagnosis? They tended to be older (65 years of age vs 56), less likely presenting with headache (58% vs 82%), less likely with neck stiffness (36% vs 78%), less likely with fever (59% vs 78%), with the classic triage of AMS, fever, and neck stiffness was only present 20% of the time in the late diagnosis group vs 50% in the early diagnosis…. So, it wasn’t an easy catch.

Why does this matter?  Welp, with early antibiotics having a positive effect on mortality (18% vs 36%) as well as unfavourable outcome (which they do not actually define, 37% vs 66%, in favor of early antibiotics).  This is a HUGE difference in mortality and unfavourable outcomes if you do not catch it early!  … Then again, do we do more harm by giving 1-2g of ceftriaxone to everyone who is a bit altered?  Would the risk of cdiff then outweigh the 2-3 annual misses? I’m not so sure.  What about the recurrent headaches and repeat visits for post-LP headaches?

If you really want to tease out the data a bit, 53% of late diagnosis patients vs 26% or earlier diagnosis patients had a head CT before the LP. 72% of “late diagnosis” patients tentatively had a non-infectious etiology- so let’s explore some of the tentative diagnoses:

loss of consciousness (19 patients)

stroke (12 patients)

intracranial / subarachnoid hemorrhage (7 patients)

impaired mental status (6 patients)

headache (5 patients)

back pain (5 patients)

seizures (5 patients)

loss of vision (2 patients)

(among others)


What I’m seeing here is a a trend towards a neurologic issue (a CT scan, a diagnosis of syncope / seizures, AMS, etc) – which may indicate that the thought of meningitis (or even endocarditis) may not have been entertained. Cant make the diagnosis if you dont think about it. In a similar vein, this diagnosis is rare and runs across a spectrum – on one end, the febrile, meningeal and altered, on the other, the vaguely unwell.  And that, surprisingly, even a 12 hour delay to antibiotics can wreck havoc on the patient.

The take home points?  Be vigilant, entertain the spectrum of disease for meningitis, but remember that every decision you make has consequences, including the decision to, and not to, perform an LP, not to mention the decision to indiscriminately give antibiotics for those “altered”.  Choose wisely, and remember there is no such thing as zero risk.

Improving Outcomes, Improving Throughput, Neurology

Opiates beget Opiates – Headache edition.

This is a study comparing 3 EDs in my homeland of CT and their (mis)use of opiates for headaches over a 14 month period. This compared an academic tertiary care center with an approximate 110,000 annual patient volume; an urban hospital with an approximate 85,000 patient annual volume, and a community ED that sees approximately 19,000 patients annually. A total of 1,222 visits were included for final analysis.

Results? Opiates, are not good, mmmmkay?

Patients given opioids as first line treatment had a 37.7% increase in visits over the study period compared to those who were not given opioids. If you were given opioids as first line, 36.0% required rescue treatment compared to 25.1% in those who were not given opioids. Strangely, female patients were significantly more likely to have opioids ordered than male patients (38.2% vs 24.2%).

Need more reason not to give opiates? Patients not given opioids had a 30.3% reduction in length of stay.

I’m surprised these numbers are so high.  As a community EM AP, I’m embarrassed at these numbers – A shocking 58% of headaches in a community setting were given opiates as first line compared to 6.9% of those at the academic center). Then again, opiates beget opiates.  Opiates lead to repeat visits, more rescue meds, and an increased length of stay, without an improvement in patient satisfaction with opiates.  I question how often those in the community ED just gave opiates to avoid conflict.

Just.  Stop.  Giving.  Opiates.  For.  Headaches.  NOW.

Critical Care, Improving Outcomes, Mythbusting, Neurology

Compazine… for infectious disease?

Today’s article’s (1, 23 ) are a break from the usual trials that are typically discussed and a bit more “benchside medicine” than bedside medicine.  In fact, let’s look at this as an early request for one of the 12 trials of Christmas.

Phenothiazines have demonstrated in vitro (as well as some in vivo) activity for gram positive cocci, mycobacteria, amoeba (4; 5), and some gram negative rods.

It should be noted that Klebsiellae, pseudomonads and acenetobacters were highly resistant to almost all of these drugs.

The MIC for phenothiazines are usually not reached with conventionally used doses, but these compounds do enhance the activity of various antibiotics to which various bacteria are susceptible (including vancomycin), and even decrease the MIC of resistant organisms.

So where am I going with all of this? For starters, lets look at some common causes of meningitis, in no specific order:

Strep pneumo (gram positive); group B strep (gram positive); staph aureus (gram positive); Listeria (gram positive); Neisseria meningitidis (gram neg diplococci); H flu (gram neg)

All things phenothiazines are thought to have activity against.

You’re likely to be giving patients with potential meningitis something for pain (I hope?), so why not go with compazine?  Likewise, patients whom you may suspect bacteremia from a cellulitis, why not give compazine to, ummm, “counteract the nausea” associated with the opiates you gave for pain control?

I think this falls into the unlikely to harm, might help category, and is seemingly a ripe area for research.  Is this practice changing?  Nope, not at all.  Food for thought, but until compazine is proven unsafe in an infectious process, I will continue my love affair with compazine for headaches, nausea, and vomiting (regardless of suspected etiology).

Improving Outcomes, Pediatrics

Peds Concussions last a looong time

Little Billy is a star hockey player at 13 years old.  So much so, that he is pushing the envelop and playing with the 14-16 year old class.  Billy gets checked into the glass one day and visits your ED, clearly concussed.  He’s dizzy, easily irritated by family, nauseated, and, of course, has a headache.  How long will these symptoms last? 

The Zurich Protocol suggests that most symptoms are resolved within 10 days, with 5-10% having prolonged symptoms.

However, this is the second study I’ve seen that suggests a prolonged duration in pediatrics.  This prospective cohort study of patients aged 13-18 years of age with an ED diagnosis of concussion were referred to one of 3 hospital-affilated sports medicine clinics.  The patients were evaluated using a variety of methods (neurological exam, computerized neurocognitive testing, post concussion symptom score), with duration of symptoms the main outcome.  Mean symptom duration was 44.5 days, with 48% of patients having symptoms beyond 28 days, and 13% of patients having symptoms persisting beyond 90 days (!).  Essentially, the less physically mature the patient, the longer it took for symptoms to resolve – 54.5 days vs 33.4 days to complete recovery.

Given the high likelihood that Billy will have prolonged symptoms, it would behoove those of us on the frontline to educate parents about this, and set up family expectations accordingly.

Critical Care, Improving Outcomes, Mythbusting

No benefit for Keppra in Status Epilepticus?

This was a prehospital, randomized, double blind, placebo controlled trial of adults with convulsions lasting >5minutes comparing 2.5g (!) of levetiracetam (Keppra) or placebo in combination 1mg of clonazepam. If convulsions lasted another 5 minutes, another 1mg of clonazepam was given. The primary outcome was cessation of convulsions within 15 minutes of initial drug injection. The trial was stopped early due to no evidence of a treatment difference after an interim analysis showed no difference (68 patients in intent-to-treat analysis per arm). Convulsions were stopped at 15 minutes in 57/68 (84%) patients receiving clonazepam vs 50/68 (74%) of patients receiving levetiracetam.

This study was funded by UCB, who manufactures Keppra.

As someone who embraces aggressive treatment of status epilepticus (escalating benzos + early dilantin / keppra followed by early intubation if needed) – particularly with Keppra since it can be given relatively quickly – this makes me go back to the literature rethink my treatment algorithm.

Improving Outcomes, Improving Throughput, Mythbusting, Neurology, Neurology, Radiology, Radiology

Community EM rejoice- CT within 6 hours safe for SAH rule out.

There is yet another paper to further elucidate who should get the CT / LP work up for subarachnoids. The authors looked at six EDs over 5 years, and encompassed 2,248 patients – of which 1898 had suitable LPs for analysis (insufficient sample, exposed to light [?], blood contamination, incorrect storage or transport [?], or they just plain lost the sample). CT reads were done by on-call radiologists in training (I imagine that means residents), or by board-certified radiologists. Images were then reviewed by a board-certified neuro-radiologist OR by a board-certified general radiologist for a final report. There was no “time limit” from onset of headache for exclusion (ie, patients did not need to be scanned within six hours).

92 patients of the 1898 patients were positive for blood via spectrophotometry – 4.8%. Nine of these positives ended up having a subarachnoid hemorrhage (9.8% of their LPs, or 0.47% of patients). What do these nine patients generally have in common? Six of them had a headache for a week or longer. One had a previously coiled embolism. One had a negative CT performed within 3 hours of onset.  All of these nine patients got coiled or clipped.

So, what do we make of these? If you present within 6 hours with a negative CT (or, dare I say, less than a week!), you have a 0.053% of having a subarachnoid. If you still do the LP in those <6hours from onset (or, <1 week from onset), the baseline risk of a false positive is 10% vs 1.1% chance of true SAH.

Time for some well-informed shared decision making, and perhaps a higher threshold for those that present with a prolonged headache.  Further good news to take away from this study- it does not seem as neuro-radiologists need to make the call and that the <6 hour proposal can be safely extended to the community setting at this point.


(First link is to free text of article.  Pubmed did not have a working link to the paper at time of post.  If the first link does not work, try here)

Critical Care, Improving Outcomes, Improving Throughput, Mythbusting, Neurology, Radiology, Radiology

Patient Backstabbing in the Age of SDM

11 non-academic hospitals reviewed 760 consecutive patients who had a brain CT for an acute headache that was followed by an LP 12 hrs from the onset of headache from January 2007 to January 2013.  These 11 centers diagnosis roughly 250 subarachnoid bleeds annually.  In this study, the patients presented within 6 hours from onset of the headache, and all had a negative CT read by staff radiologists, and were independently reviewed by two neuroradiologists and one stroke neurologist.  At these 11 centers, of the 760 patients with a negative CT read by staff radiologists, 52 patients had CSF positive for bilirubin (7%).  Of these 52 patients, there was one patient identified to have a non-aneurysmal perimesencephalic SAH on repeat review of the images.  This one patient had a benign outcome.  There were 8 others who had an aneurysm on CTA, DSA, or MRA  (3 of which had been previously coiled).  All of them were deemed as having rupture unlikely for various reasons (RBC <100, no bilirubin on spectrophotometry, etc).

So, with a negative CT read at a non-academic center by non-neuro radiologists, at the high end, we have a 1 in 760 miss rate if we *only* miss perimesencephalic bleeds on CT.  These types of bleeds account for about 5% of SAH, so, potentially, at the low end, we are looking at a miss rate of 1 in 15,200.  Essentially, the lumbar puncture is not a very useful test to diagnose SAH – with a posttest probability of 1.9% in cases with a positive CSF spectrophotometric result (a previous study reported about 8% PPV for xanthochromia)

Unfortunately, it is not mentioned how SAH was diagnosed throughout the study period.  It would be nice to know if they were made via CT in the ED, as that would help solidify the author’s suggestion that CT/LP is a dinosaur in the age of shared decision making.  Speaking of which…

I’ve had a few colleagues who have said, “show them the needle” as a somewhat subversive way to have patients either sign AMA or a refusal to consent for an LP for a subarachnoid hemorrhage.  Few, if any, have actually said, “tell them the evidence.”

What sounds better to you for well informed shared decision making?

A) “You could die from this. You need a spinal tap. If you don’t do it, you could die.”

B) “Ultimately, I think your risk of a bleed is low, but I want you to understand that there is significant consequences to a subarachnoid and over half of those diagnosed may die.  With that said, studies show that with a normal CT scan, your risk of having this condition is well below 2%.  “Normal” spinal tap results performed 12 hours from the onset of your headache helps to further reduce your risk, but also comes with a significant number of false positives.  While an abnormal spinal tap is concerning for a subarachnoid, it is not specific, and you will likely require admission for further testing if your spinal tap is abnormal.”


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