Mythbusting

Shocker! Parents may prefer PO to IV treatement.

FOR MENINGITIS!

One dogma that particularly sticks in my craw is that IV antibiotics are somehow mythically better than their PO counterparts. This is one that clinicians continue to perpetuate despite quite a bit of evidence to the contrary, and sometimes under the guise that “its what the patients want.”

Well, this paper from Brown University in Rhode Island (home of Del’s Lemonade and the Awful Awful) have sought to dispel.

For 3 months, the authors surveyed 102 consecutive parents of children who were not undergoing evaluation for potential Lyme disease and who were being seen in a pediatric ED. The reason for choosing Lyme disease as their hypothetical case is that the great state of Rhode Island is an are endemic to Lyme disease, and children with Lyme meningitis are often treated with intravenous ceftriaxone although oral doxycycline may be effective.

The parents were surveyed after observing a 9 minute video describing a hypothetical Lyme meningitis treatment trial (PO doxy vs IV ceftriaxone), and 84 of 102 parents (82%) would consent to their child participating (!). Even more impressive was that 37% of parents would accept 2 additional days of symptoms with oral meds even if intravenous treatment hastened symptom resolution (44% would accept one additional day symptoms). When told that there was likely equivalence, 47% would prefer doxycycline treatment, 24% thought it would be equivalent, and 29% still preferred IV treatments – with no differences in likelihood of choice based on age, ethnicity, education or knowledge of lyme disease. There was a weak correlation between perceived efficacy and tx preference, while there was a moderate correlation between perceived safety and treatment preference.

Basically, explain that about a third of patients have issues with IV antibiotics or PICCs (more diarrhea, allergic reactions, more DVTs, etc – not to mention bigger bills from VNS services, inpatient stays, etc), and you’ve got ~70% chance that the parents would be ok with outpatient treatment.

Understandably, as the authors put it, “the hypothetical nature of this study may overestimate the proportion of parents who would consent in an actual trial” – but it provides great food for thought to at least consider having the conversation with parents on your next shift when you as the clinician are on the fence of stay or go.

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Cardiology, Improving Throughput, Mythbusting

Yes, No, and Maybe – Magnesium for Afib RVR

I really, really, wanted this study to work.  Few things are more disheartening on an overnight observation shift than needing to place someone on a diltiazem drip after an inability to rate control. Ergo, I have been known to give a few grams of magnesium to try to decrease the likelihood of that happening. Therefore, on the surface, this study seems promising – it looks at standard of care for Atrial fibrillation with rapid ventricular response (dealer’s choice, metoprolol, diltiazem, or digoxin) given in combination with either one of 3 treatments: placebo, 4.5g of magnesium, or 9g of magnesium; with about 150 patients in each arm. This study took 5 years (!) over 3 academic centers in Tunisia, who’s ED’s service 90,000-110,000 patients per year. Patients needed to have a heart rate over 120 bpm, have a systolic BP >90 mmHg, and without: renal impairment, wide-complex tachycardia, decompensated CHF, acute myocardial infarction, or an impaired level of consciousness. All seems fair.

The results, at face value, seem great if you’re a magnesium believer: rate control at 24h of 83.3% for placebo, 97.9% for 4.5g MgSO4, and 94.1% for 9g of MgSO4. This is a great example of completely reading a paper before you start to fight about giving magnesium.

First, all groups used digoxin around 50% of the time for rate control.  This clearly does not mimic US practice. Nor does giving 4.5-9g of magnesium over 30 minutes.  Then the authors sneak this one in:

In a secondary analysis including only patients receiving beta blockers and calcium channel blockers, the obtained results were not significantly different compared to those found in the overall group.

This is sandwiched between mentions of adverse drug reactions (4% flushing in the 4.5g arm vs 12% in the 9g arm vs <1% in the placebo arm, and otherwise there was no significant difference between the 3 arms), and the discussion of 24h rate control. I am not 100% certain what they meant by this statement – were they referring to ADRs? Were they implying that there was no difference between metoprolol and diltiazem treated patients and placebo at 24 hours?  With only about 50% of patients per arm (~75 patients in total/arm) being treated with these agents, it would be hard to show a meaningful improvement.  Not to mention the fact that the actual data for this secondary analysis is nowhere to be found in this paper.  Nor have the authors responded to my email asking for it.

Then, of course, there are the prior trials with less than 60 patients / arm comparing diltiazem to metoprolol showing >90% efficacy with diltiazem.

And, of course, there is the next question, of are we doing any good?  Since rate control has not always shown to be in the patients best interest – a 6 fold higher rate of adverse events– and none of the ED AFib RVR magnesium studies look further out than 24 hours, perhaps we should cautiously, if at all, recommend magnesium, or even suggest waiting until long term outcomes are further elucidated.  Since this study took 5 years to complete, I do not see the desired study happening anytime soon.

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Improving Outcomes, Improving Throughput

POCUS guided Flexor Tenosynovitis

It feels good to be back! Now, fresh off the inaugural AAPA18 iScan ultrasound event, its only right that my next post is on two of my favorite things- POCUS and infectious disease.

This is a review of 73 patients presenting to an emergency hand clinic (!) over the course of 3.25 years with a pyogenic flexor tenosynovitis.  Yep, a whole 22 patients a year… at an emergency hand clinic.

All patients underwent a resident and attending surgeon eval as well as labs including CRP and films. 16 confirmed pyogenic flexor tenosynovitis patients were excluded (these were the slam dunk obvious ones)- while the remaining 57 underwent POCUS while pending labs. POCUS was done by either a resident with 2 years experience in MSK sono, an attending surgeon with sono training, or senior radiologist.  Suffice to say, that this isnt exactly us work-a-day EM providers.

Of the remaining 57 patients, there were 29 were ultrasound negative (non-thickened tendon sheath without hyperemia and no peritendonous effusion); all were given PO antibiotics and discharged with every other day follow up until symptom resolution; only one required OR intervention.

Of the 27 patients with positive ultrasound findings- 17 of these had either a positive OR culture or significant purulence seen at the time of OR washout.  While this results in a decreased PPV of 63%, and a decreased specificity of 74% – I maintain POCUS is actually much better; keep in mind these numbers do not include the 16 slam dunks on clinical exam.  It doesnt take into account the rapid sterilization after a single dose of antibiotics seen in CSF and ascites; nor the 30% negative OR-culture rate seen in other pyogenic flexor tenosynovitis studies.  Nor does it take into account that POCUS approaches MRI for sensitivity and specificity in prior studies.

Ultimately, it would be fantastic (and likely better medicine!) if, stateside, we could adopt an ultrasound first strategy (especially with a 97% NPV and 94% sensitivity!).  If POCUS negative, patients could get expedited follow up and oral antibiotics.  This is pretty much exactly what this group has done.  Presumably with this strategy, a small fraction of these more ugly “slam dunk” tenosynovitis cases may not require the OR (the group did not comment on positive OR-culture rates), and the patients in the middle ground could get expedited follow up or overnight observation and serial sonography.  It should be noted that “delayed” diagnoses which resulted in poor outcomes were >10 days out from the initiation of symptoms (!); so a day or two may not make much of a difference.  This study comes with the usual caveats- there are few MSK ultrasound courses in the USA (I contacted the Jefferson MSK fellowship, no dice for hand sonography!), different equipment than our usual sonosite machines, more training.  But that certainly does not mean we can not have something to aspire to.

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Mythbusting

Do Prehospital Antibiotics Matter?

In short, probably not, but still not completely disproven.

This randomised controlled open-label trial looked at giving 2 grams of IV ceftriaxone to patients that met SIRS criteria (save for WBC- testing unavailable to EMS) with suspected infectious illness. Patients were randomly assigned (1:1) to the intervention group or usual care group using block-randomisation with blocks of 4. This study took place across ten large regional ambulance services serving 34 secondary and tertiary care hospitals in the Netherlands over a 2 year period. They screened 3228 patients of which 2698 were eligible (pregnancy, beta-lactam or ceftriaxone allergy, suspected prosthetic joint infection, among others); 1150 in the usual care arm (IV fluids, supplemental oxygen prn), and 1548 in the intervention group (2g ceftriaxone plus usual care). 13 patients in each arm were excluded from final analysis or excluded due to withdrawn consent or being lost to follow up. The primary outcome was all-cause mortality at 28 days.

So, while they screened over 3,000 patients over 2 years (a massive undertaking!), unfortunately, only 37 (3.3%) patients in usual care and 66 (4.3%) patients in the early antibiotics group had septic shock. Perhaps you could make an argument that the intervention group was slightly sicker with 22% vs 17% having 2 or more qSOFA criteria. Despite a median time to antibiotics of 70 minutes in the ED (thus, probably close to 90+minutes faster in the intervention cohort), and with 14% having antibiotics >3hrs from presentation and 14% having none at all (suspected viral syndrome) – there was 8% mortality in both arms at 28 days and 12% at 90 days in both arms. No difference.

When you look at mortality for septic shock it was 27% (10/37) in the prehospital antibiotic cohort vs 28.8% (19/66). Again, not statistically significant. While prehospital antibiotics might make a difference in a larger cohort, its probably going to be very hard to ever do that study – this was a 2 year study looking at over 3,000 patients and they were barely able to accumulate over 100 septic shock patients.

While an American might argue “they only gave ceftriaxone, you need a real drug like Pip-tazo and vancomycin!” – slow down. The authors acknowledge that ceftriaxone may not have been appropriate because it was “a big gun” that they could all agree on and most patients were rapidly narrowed to receive, most commonly, amoxicillin–clavulanic acid with ciprofloxacin and ceftriaxone the second and third most common antibiotics given. They did not have culture reports back at time of publication, but having low mortality, and 9% of each cohort were not given antibiotics from the ED due to suspected viral illness makes me suspect that they do not have nearly the resistance problem (or concerns) that the Americans do, likely do to appropriate stewardship. Likewise, while one may be concerned about missed diagnosis due to premature closure, there was a miss rate of 1.4% in the intervention group vs 1.7% in the usual care group, also not statistically significant.

In the end, the authors provide a sensical view of the current state of prehospital antibiotics, “Studies showing that early antibiotic treatment is beneficial for reducing mortality found this positive association mainly in patients with more severe illness and a (time to antibiotic) of more than 5–6 hours… However, we currently do not advise antibiotic administration in the ambulance to patients with suspected sepsis.“

While it is certainly plausible that prehospital antibiotics may be beneficial for those with septic shock, it is a near certainty that, at least in the USA, sepsis hysteria would further ensue and the inertia of giving everyone a dose of broad spectrum antibiotics will likely occur – not to mention our continued fixation with iatrogenic salt-water drowning. The cost to the system – including other patients in the department – of responding to these prehospital alerts for those not in shock will likely be the hidden cost infrequently published or discussed by administrations.

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GI, Improving Outcomes, Mythbusting

NG tubes. just. wont. die.

My angst for the NGT has been explained in a previous post, and while this study adds to said angst, it sadly comes short of putting a nail in the coffin in the debate with surgical colleagues.
This is a retrospective single center study which enrolled 181 ED patients with SBO from September 2013 to Sept 2015, and essentially grouped patients according to whether or not a nasogastric tube was placed (49% of patients did not receive the dreaded NGT). Looking at a multitude of factors, they attempted to tease out items associated with nasogastric tube placement, and if there were any appreciable benefits to NGT placement.

Ultimately, if you are over age 70 (37% NGT+ vs 19% NGT-),  have a malignancy (30% NGT+ vs 17% NGT-), or had a prior SBO (56% NGT+ vs 32% NGT-) you’re more likely to have an NGT because, hey, one good NGT deserves another.  NGT+ patients were also less likely to have “likely / early SBO” (19% NGT+ vs 40% NGT-) on CT imaging as well.

All in all, while I’d love to point at the mean length of stays (7 days for NGT+ vs 4.2 days for NGT-; median 5 days vs 3 days), and non-statistically significant resection rates of 13% vs 9% as indications that the NGT is not needed…. well, we’re not exactly comparing apples to apples. The NGT+ patients were sicker- they were older, had higher malignancy rates, had a slightly higher surgical rate, and were more likely to have “definite SBO” on CT. Sadly, this is not the paper to put the NGT argument to rest.  We still need a larger study, preferably with matched controls, to fully put this dinosaur to rest.

 

Someone?  please? … anyone? please?

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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.

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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.

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