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.

Cardiology, Improving Outcomes, Mythbusting, Neurology

Chronic viral infection & Coronary disease.

Are you openly ignoring a cardiac risk factor that is in the ballpark of smoking or early family history?   Even after controlling for numerous factors, well controlled HIV has a significantly higher cardiovascular MORTALITY rate – with an adjusted rate ratio of 1.53, while poorly controlled patients even moreso, with an adjusted rate ratio of 3.53, according to this paper.  It should be noted that this is one of several papers looking into HIV as a risk factor for early cardiac disease and death.

It is important to realize the limitations of our tools that we have at our disposal.  For instance, PERC and HEART are not validated in an HIV population.

I suspect many if not all chronic viral infections will portray a similar trend. It is already seen in HepC, albeit to a lesser extent. It will be interesting to see if the new age HepC drugs decrease the known risk of increased coronary artery disease and cerebrovascular disease after treatment.

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, Neurology, Pediatrics

CDRs- good for you, patients, and lawyers!

One of my favorite tweets ever is the following from Jeff Kline:

Screen Shot 2015-11-23 at 3.42.40 PM

This paper from Academic Emergency Medicine continues to drive home Kline’s point – evidence based medicine is protective – both for the provider medicolegally, and for the patient to be saved from harm’s way of overtesting.

The author’s reviewed WestlawNext (from what I can tell, the closest thing law has to PubMed), for all cases, jury verdicts, settlements, and arbitrations from 1973 (when CT first was used clinically) until January 2014 for all instances of head injuries in which head CT was NOT performed. After trudging through about 1,000 cases in their initial search, the authors eventually found (only) 60 cases in which a head CT was not performed and a provider was sued because of it. Two abstractors independently determined which clinical decision rules applied to that specific case (PECARN, NEXUS, Canadian CT head rule, etc), and if imaging was warranted. Inter-rater agreement was 99.2% for determining tge presence or absence of decision rule indications for CT in a given case, and 98.3% for which specific decision rule applied to a particular case.

The Results: Only 8 out of the 60 cases involved patients under age 18. Among all patients, isolated subdurals were most common (58% of cases), 32/60 died from their injury, while the rest sustained permanent neurologic deficits. Time from when a CT should have been ordered to deterioration or death was <6 hours in 39% of cases, 6-24 hrs in 36% of cases, and >24 hrs in 25% of cases.

The juicy stuff: in all ten cases in which the provider was found negligent, a CT was indicated. Providers settled in 10/11 cases in which a CT was indicated. In the ONE case in which a CT was not clearly indicated involved an MVC with multiple facial fractures and experienced left sided numbness and was scheduled for CT the following day. For all 8 pediatric patients, CT was indicated.

So, if a CT was indicated, and you didn’t do it, good luck.

What about the other cases? Well, The authors do not go into much detail about the necessity of CT for these remaining cases except saying that there were 27 cases which found the provider not liable. This also leaves a few cases outcomes unaccounted for.

All in all, since 1973, there has been a grand total of 60 cases in which a head CT was not done that evolved into a lawsuit.  Many of these cases occurred before the publication of recommended guidelines. In some ways, that is not quite fair – I’d hate to be brought to court for not doing ECMO on a patient because ECMO found its way into standard practice in 10 years.  Regardless, I take this study as a step in the trend of discussing with decision rules with the patient and their family family & documenting clinical decision rule recommendations to minimize the swinging pendulum of both the over and underwork up of patients.

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, Neurology, Twelve Trials of Christmas!

Day Ten of Christmas: Keppra Post-Arrest.

Welcome to the Twelve Trials of Christmas series on EMinFocus! This is the tenth of twelve posts in a series where I ramble on various topics for which I would love to see an EM study done. I’ve taken morsels of prior studies (case series, small trials, etc) and highlight reasons on why I believe this study would benefit EM. Some may pan out, some may not. All of them I would be highly interested in assisting with in any way possible to continue to advance our fine specialty.

Even after a successful initial resuscitation of a cardiopulmonary arrest, there is then significant concern for the patients neurological outcome.  Sure, there is the  hypothermia protocol, but is there any other neuroprotective drugs that we may be able to trial post arrest to try and improve neuro outcomes?

Let’s first say this: we’re talking about mouse studies, so it’s a leap of faith.  However, levetiracetam is quite safe, and really, what harm, post arrest, could a few doses of Keppra for the first 72 hours really do?  In mouse models, its been shown to have neuroprotective effects in experimental stroke, ICH, and neurotrauma.  ( 1 , 2 )

There was a study published in March 2014 in regards to anti-epileptics (phenytoin, levetiracetam, valproate, clonazepam, propofol, midazolam), which showed no measurable difference when administered to patients post-arrest.  However, in this study, patients were already placed in the ICU and the requirement was to be placed on continuous EEG monitoring within 12 hours of hospital presentation.  If the EEG was positive, they were enrolled in the study, and initiated on some anti-epileptic (being on propofol post intubation, apparently allowed them into the protocol under the propofol group).  Essentially, this study is useless to the ED and should not stray us from doing a good study to begin Levetiracetam as early as possible in cardiac arrests.  We know that the later we attempt to reverse status epilepticus, the more difficult a time we will have(and here, they didn’t attempt for HOURS!), so why not make a good attempt at giving arrests the best possible outcome with an easy study?  Hang a bag of Levetiracetam vs a bag of saline on all arrests, those that survive, compare neurologic outcomes.  This is an easy one to pass through the IRB – cant hurt, may do a world of help.

Improving Outcomes, Neurology, Pediatrics

Friday Night Lights: The Zurich Protocol

I practiced in an area where High School football was idolized.  Ask an EM provider what the guidelines are for returning to practice, and I think most respond, “until cleared by neurology.”  A recent study evaluated how frequently patients were given concussion specific discharge instructions and clear indications as to when to return to physical activity.  Frankly, the results are embarrassing.  Only 31% of patients received concussion specific instructions  and only 62% were given activity restrictions.

Here is a copy of my discharge instructions for the concussed, adapted from the Zurich protocol:

The Zurich protocol emphasizes both physical AND MENTAL rest. Physical rest means: no sports practice, no training of any sort, no exercise, no weight lifting, beware of exertion with activities of daily living (ie, household chores, walking up stairs, etc). Bottom line – keep your heart rate down. Brain rest means no television, no extensive reading, no video games, no computer games or social media, stay off the phone – no texting!, minimize daytime sleep, and consider taking time off from school and delay test taking if at all possible.

The graduated protocol is as follows:

Step 1: No activity- no physical activity (see above), and brain rest (again, see above)

Step 2: light aerobic exercise- walking, swimming, biking < 70% of maximum HR. no resistance training.

Step 3: sport specific exercise- ie, skating drills in hockey, running drills in soccer, NO HEAD IMPACT ACTIVITIES. Resume normal brain activities.

Step 4: non-contact training drills- progression to more complex training. ie, passing drills in football & hockey. May start progressive resistance training.

Step 5: Full contact practice: Following medical clearance may participate in normal training (must have PMD or neurology clearance to begin step 5).

Step 6: return to normal activity



All steps should last for 24 hours. If symptoms recur, go back a step for 24 hours. About 90% of patients are resolved within 7-10 days. Again, it is important to follow up with either neurology or your primary care provider within the week. Not doing so may result in a chronic or permanent injury, pain, and/or disability. If there is any problem keeping or making an appointment, you must call back to this facility for assistance. Tylenol is the only recommended medication in these scenarios. No ibuprofen, motrin, aleve, aspirin, or other NSAIDs. It is recommended AGAINST taking sleeping aids as it may mask or prolong symptoms.

Likewise, before the start of the school year, it may not be a bad idea to feel out PMDs & neurology to see how soon they could see these patients for follow up.




PMID: 24365726