Complex Febrile Seizure & The Utility of Doing Something(s)

A complex febrile seizure — AKA one occurring with focality, duration > 15 minutes or recurrence within 24 hours, or associated with persistent AMS or post-ictal state — demands a greater amount of testing than a simple one. But to what extent? Which children benefit from neuroimaging, lumbar puncture, EEG testing, and which of these children go onto either have a bad outcome or have something diagnosed on one of those tests?

A group of authors studied 526 patients presenting with their first complex febrile seizure. In two separate papers, 64% received an LP and 50% received emergency head imaging. Of these, 3 patients (0.9%) were found to have acute bacterial meningitis — two of these grew out Strep pneumoniae by CSF culture. Among those with Strep pneumo in the CSF, one was non responsive at presentation and the other had a bulging fontanelle and apnea — the third child was well-appearing at presentation, and had a culture that grew out Strep Pneumo from the blood but the LP was unsuccessful. None of the patients who did not undergo lumbar puncture returned to the hospital with a ABM presentation.

In terms of imaging, 4 of the 526 patients had significant finding — two of these patients had ICH, one had ADEM (acute disseminated encephalomyelitis), and one had focal cerebral edema. Of these patients, 3/4 had obvious findings — nystagmus, emesis, AMS, hemiparesis, and bruising suggestive of NAT.

A second, more recent study performed in a Californian emergency department reported outcomes in 193 patients presenting with new-onset CFS, of which 136 received LP (showing the significant variability that exists between practice environments in terms of this practice). Of these, 14 had CSF pleocytosis, and one (0.5%) went on to be diagnosed with ABM. In a subset of these patients who had a second brief febrile seizure within 24 hours and who received LPs, none were found to have ABM or other serious neurologic disease. Again, this supports the suggestion that in patients without other concerning findings on exam, LP may be deferred — it also suggests (though this is a small patient series) that more than one seizure occurring within 24 hours may be protective in terms of risk stratification for ABM or other serious neurologic illnesses.

Takeaway? Tough to say. It seems that the majority of patients presenting with a complex febrile seizure without “obvious” (always easy to write in retrospect) signs of intra-axial badness go on to do very well, or at least go onto have normal findings on LPs and emergent head imaging. This seems to support the idea that LP and neuroimaging should be selectively added to the workup of a complex febrile seizure, rather than be thought of as necessarily indicated in this patient cohort. That said, guidelines are yet to be published by any leading groups such as ACEP or the AAP in terms of workup for complex febrile seizure, so guidance and support for a “standard of care” is yet to exist — tread carefully, and document thoroughly.


Teng D1, Dayan P, Tyler S, Hauser WA, Chan S, Leary L, Hesdorffer D. Risk of intracranial pathologic conditions requiring emergency intervention after a first complex febrile seizure episode among children. Pediatrics. 2006 Feb;117(2):304-8. PMID: 16452347. [PubMed] [Read by QxMD]
Kimia AA1, Ben-Joseph E, Prabhu S, Rudloe T, Capraro A, Sarco D, Hummel D, Harper M. Yield of emergent neuroimaging among children presenting with a first complex febrile seizure. Pediatr Emerg Care. 2012 Apr;28(4):316-21. PMID: 22453723. [PubMed] [Read by QxMD]

More Low-Risk Chest Pain!

In this article published in JAMA Internal Medicine in July of last year, a group of emergency physicians reviewed 11,230 records of patients hospitalized for chest pain with 2 negative troponin tests, nonconcerning initial ED vital signs, and nonischemic, interpretable electrocardiographic findings to determine the incidence of patient-centered adverse events in the short term.

What is interesting and unique about this study is the shift from using MACE (which, as I have discussed before, includes somewhat-nebulously-patient-centered bad outcomes such as need for cardiac revascularization — this is an intervention, not a harm that occurred to a patient due to a lack of intervention) from using their more  “clinically relevant adverse cardiac events” (of course requiring a new catchy acronym, CRACE): (1) life-threatening arrhythmia (ventricular fibrillation, sustained ventricular tachycardia requiring treatment, symptomatic bradycardia or bradyasystole requiring emergent intervention, and any tachydysrhythmia treated with cardioversion); (2) inpatient STEMI; (3) cardiac or respiratory arrest; and (4) death.

Another unique aspect of this study was the enrollment of patients who were sick who met their criteria discussed above– many other studies only considered “low risk patients” to be those without significant comorbidities or CV disease histories (e.g. history of CABG, multiple stents, diabetes, hypertension, etc) . They did exclude patients with LBBB or pacemaker rhythms on EKGs, which would have made identification of ischemia perhaps more difficult.

What did they find? Only four patients out of 7266 meeting the above criteria went on to have any of the primary endpoints. Of these, two were non-cardiac and two were possibly iatrogenic. This is a rate of 0.06% (95% CI 0.02-0.14%), which is much lower than many people would likely guess, and can help inform the discussion we can have with patients when arriving at a disposition. If I am practicing in a community such as the authors’, where short-term follow up with a cardiologist can be arranged, and a patient is reliable, I feel that this data can help me feel more comfortable discharging them with that plan rather than admitting to the hospital, if the patient is comfortable with this.

As Ryan Radecki wrote, the applicability of this hinges on tightly integrated follow up, and we cannot practice “catch and release” medicine. This is also only one data set, and requires prospective validation, and we need to acknowledge that this is not a zero-miss strategy (just like any strategy). That said, there are many potential downsides associated with admission, from costs and downstream sequelae of unnecessary invasive testing to iatrogenic harms, and this study will help better inform our conversation with patients about all of these issues.


Weinstock MB1, Weingart S2, Orth F3, VanFossen D4, Kaide C5, Anderson J6, Newman DH7. Risk for Clinically Relevant Adverse Cardiac Events in Patients With Chest Pain at Hospital Admission. JAMA Intern Med. 2015 Jul;175(7):1207-12. PMID: 25985100. [PubMed] [Read by QxMD]

Age-Adjusted D-Dimer

Pulmonary embolism is a commonly-investigated diagnosis in the world of emergency department risk stratification — the presentation of these patients is varied, the ultimate impact on patients of the disease entity itself is questionable when it comes to the less sick end of the spectrum, and the tools we have for diagnosis are associated with significant amounts of radiation and contrast. However, in a practice environment with a low tolerance for missed diagnoses (however questionable the risk:benefit balance of the intervention that would have been performed), we continue to strive to balance the risks and costs of diagnostic testing with the very real risk of progressive disease.

The D-Dimer level is a test used in patients with a low to moderate pretest probability of DVT or PE (and possibly aortic dissection?) — if negative, it will virtually rule out PE, and can help you avoid further testing with CT pulmonary angiography. If positive, further testing is required. So why do emergency physicians hate the D-Dimer? Because while elevation in D-Dimer levels is sensitive for pulmonary embolism or DVT, it is not specific — particularly with cutoff levels of ~ 500 ng/dL, which is the conventional cutoff for a positive test. Elevated D-Dimer levels occur for a multitude of reasons, including liver disease, inflammation, malignancy, trauma, pregnancy, and– most complicating of all– advanced age.

The first of the studies I read this weekend, the ADJUST-PE study, a group of authors had previously retrospectively derived and valid the value of a progressive D-Dimer cutoff adjusted to age in 1712 patients — the optimal age-adjusted cutoff was defined as patient’s age multiplied by 10 in patients 50 years or older. The ADJUST-PE study represented their attempt to prospectively validate the adjustment and to assess its impact on patients in real life. In this multi-center study which enrolled 3324 patients, the age adjusted D-Dimer cut off did very well — only one patient who had a D-Dimer between 500 ng/dL and their age-adjusted cutoff (in other words, someone who would have gotten scanned if they weren’t using the new tool) was found at three month follow up to have a PE, and this was non-fatal. The age adjusted level allowed for safe discharge of patients that might otherwise have been exposed to the costs/potential harms associated with CTPA or treatment of non-hemodynamically significant emboli.

The second study takes the same approach and retrospectively applies the cutoff to 31,094 suspected pulmonary embolism patients presenting to an emergency department in the community. They report data for all ED visits for Kaiser Permanente Southern California members older than 50 years, from 2008 to 2013, who received a D-dimer test after presenting with a chief complaint related to possible PE such as chest pain or dyspnea (due to their focus on PE rather than DVT). The authors excluded patients who underwent ultrasound imaging for DVT for the same reason. What they found was a sensitivity of 92.9% and a specificity of 63.9% for the age-adjusted D-Dimer threshold applied to this population — this compares to 98.0% and 54.4% for the traditional threshold of 500 ng/dL. This is not unsurprising — what I thought was interesting about the second paper was its expansion of the discussion of this testing strategy to include estimates for other harms beyond symptomatic PE that might be missed — specifically, they discuss the incidence of contrast-induced nephropathy, and how changes in testing strategies translate into potential benefits there that may outweigh the harms done by missing clots. These are statistical models, and need to be taken with a grain of salt, but they predict that  “using an age-adjusted D-dimer threshold would miss or delay diagnosis of 26 more pulmonary embolisms than the current standard, but it would prevent 322 cases of contrast- induced nephropathy, 29 cases of severe renal failure, and 19 deaths related to contrast-induced nephropathy in this sample.”

So what will I do with this information? Probably try for better shared decision making and try to avoid CTPA in patients with D-Dimers below the age-adjusted cutoff. I think sharing these numbers with our patients in a comprehensible way, and talking to them about the potential harms associated with testing is the best way forward– this will require further work in terms of identifying the best way to communicate these risks and odds to patients, and as always, trying to balance advocacy for patients, and our ultimate goal of keeping them safe, alive and functional, with the fear of missing a diagnosis or sending someone home with a nebulous non-diagnosis and the possibility of clinical deterioration.


Righini M1, Van Es J2, Den Exter PL3, Roy PM4, Verschuren F5, Ghuysen A6, Rutschmann OT7, Sanchez O8, Jaffrelot M9, Trinh-Duc A10, Le Gall C11, Moustafa F12, Principe A13, Van Houten AA14, Ten Wolde M15, Douma RA2, Hazelaar G16, Erkens PM17, Van Kralingen KW18, Grootenboers MJ19, Durian MF20, Cheung YW15, Meyer G8, Bounameaux H1, Huisman MV3, Kamphuisen PW21, Le Gal G22. Age-adjusted D-dimer cutoff levels to rule out pulmonary embolism: the ADJUST-PE study. JAMA. 2014 Mar 19;311(11):1117-24. PMID: 24643601. [PubMed] [Read by QxMD]

Duration of symptoms of respiratory tract infections in children

From the BMJ, we have a very interesting systematic review evaluating the duration of symptoms in children seen in the ED (or A&E, if you will) for fairly minor complaints: otitis media, acute cough, sore throat, and common cold. In my time in the pediatric ED, I’ve noticed that a not-insignificant number of visits are repeat visits for persistent symptoms in well-appearing children who were seen and discharged from the ED within the last week or so. The parents are often concerned that the cough has still not gone away, or that the child’s breathing at night still sounds funny to them — these are not different symptoms than the child was originally evaluated for, but I thought it was possible that better anticipatory guidance in terms of the duration of symptoms parents could expect might result in fewer of these “bounce

So what did the authors at BMJ find? In 90% of children, earache was resolved by seven to eight days, sore throat between two and seven days, croup by two days, bronchiolitis by 21 days, acute cough by 25 days, common cold by 15 days, and non-specific respiratory tract infections symptoms by 16 days.

21 days of cough for bronchiolitis and 25 days for non-bronchiolitis URIs? That is way longer than what I hear when parents are being discharged — I am no less guilty of underselling the duration of symptoms than others. It’s a tough question to answer, right? “How much longer will this last?” — Prognostication is always the hardest part of medicine, whether you’re talking to the dying cancer patient or to the parents of the child with the perpetually stuffy nose and inflamed upper airways. Well, I personally intend to try to provide parents with a more evidence-based answer for the rest of this season– something along these lines: “Longer than you can possibly imagine. Most kids will have a cough for three weeks or more, and many will seem like they go the entire winter without getting better. But as long as they’re eating, drinking, pooping, peeing, moving about and more or less acting like a slightly-more-congested-and-therefore-irritable version of themselves, that’s okay!”

It’s a tough balance. You wouldn’t want to dissuade parents from seeking medical attention (ideally from their PMD) if the child doesn’t get better in a reasonable amount of time, but it’s very difficult knowing what that time is for them. Moral of the story: encourage that follow up visit with the PMD, and make sure to give thorough and explicit return precautions accounting for the myriad reasons we *do* need to see these patients back ASAP.


Thompson M1, Vodicka TA, Blair PS, Buckley DI, Heneghan C, Hay AD; TARGET Programme Team. Duration of symptoms of respiratory tract infections in children: systematic review. BMJ. 2013 Dec 11;347:f7027. PMID: 24335668. [PubMed] [Read by QxMD]

ALTE Badness – Who to Admit?

Kaji et al. bring us “Apparent life-threatening event: multicenter prospective cohort study to develop a clinical decision rule for admission to the hospital”, which is pretty much what it sounds like. What did it leave us with? The study looked at 832 kids presenting w/ ALTE to four different sites and identified three variables (obvious need for admission, significant medical history, >1 apparent life-threatening event in 24 hours) that identified most (but not all!) infants with apparent life-threatening events necessitating admission. I’ll just put that here again, in case you missed it: one of the conclusions was that obvious need for admission was a variable that predicted need for admission. Huh.

That point aside (and really, it’s a more interesting conclusion than it sounds like — meaning, that the ALTE kids who look sick when they get there tend to go on to have bad outcomes (hypoxia, apnea, bradycardia that is not self-resolving, or serious bacterial infection) discovered while in-hospital or receive some sort of “significant intervention” during their hospitalization that, retrospectively, necessitated admission. To be fair, the variable “obvious need for admission” was defined in the paper as occurring “if the child needed supplemental oxygen for non–self-resolving hypoxia, intubation, ventilation, cardiopulmonary resuscitation (CPR), intravenous antibiotics for a confirmed serious bacterial infection, or antiepileptic drugs (for status epilepticus); had hemodynamic instability warranting continuous intravenous fluids or vasopressors; or had a positive test result for respiratory syncytial virus or pertussis in the setting of an apparent life-threatening event.”

It would be difficult to argue against admitting any patient in one of these contexts (with the possible exception of non-self-solving hypoxia, which in the bronchiolitic child who is otherwise well-appearing should probably not serve in isolation as a reason to admit), and I imagine that such events occurring in the context of an ALTE are even more clear-cut indications for continued observation and management. Still, this is a nice body of literature showing that even with 84% of patients appearing well at time of ED presentation, 23% go onto need serious interventions once hospitalized — which is to say, being well-appearing at presentation does not protect against the need for escalation of care or therapeutic interventions soon thereafter.


Kaji AH1, Claudius I, Santillanes G, Mittal MK, Hayes K, Lee J, Gausche-Hill M. Apparent life-threatening event: multicenter prospective cohort study to develop a clinical decision rule for admission to the hospital. Ann Emerg Med. 2013 Apr;61(4):379-387. PMID: 23026786. [PubMed] [Read by QxMD]

Bronchiolitis and the Risk of Apneic Events – Risk Stratification Tool?

Walsh et al. published “Derivation of Candidate Clinical Decision Rules to Identify Infants at Risk for Central Apnea.” in Pediatrics in November, which attempted to derive several CDRs and compare them for identifying risk of central apnea in pediatric patients with respiratory illness. Of course, for an outcome as rare as central apnea in a population that usually does very well, almost any set of criteria you apply to patients will leave you with a rule that has a very high NPV — so what did they find?

The group analyzed 990 ED visits for 892 infants. Central apnea subsequently occurred in the hospital in 41 (5%) patients. Three candidate CDRs were generated by different techniques, and the results were analyzed and yielded the following risk factors: Parental report of apnea, previous history of apnea, congenital heart disease, birth weight ≤2.5 kg, lower weight, and age ≤6 weeks all identified a group at high risk for subsequent central apnea. All CDRs and RFs were 100% sensitive (95% confidence interval [CI] 91%-100%) and had a negative predictive value of 100% (95% CI 99%-100%) for the subsequent apnea.

Candidate clinical decision rules from Walsh et al.

Candidate clinical decision rules from Walsh et al.

The third tool, not shown above, is a computationally-intensive algorithm that used a Random Forest method to generate a risk stratification. Much like the recently-published work on sepsis using Big Data strategies, this had a better AOC than either of the above two, which are much simpler and can by applied by clinicians. This rule and others like it may have a future in the form of electronic heath record-embedded decision support, but are less amenable to being remembered and applied by the physician at the point of care when making a disposition decision.

It is important to note some caveats about this and the results — particularly the prevalence of apnea in this population, which accepted parental reports of apneic events as part of the numerator (i.e. not just monitored and captured events), but it still underscores the idea that parental concern should be your concern until proven otherwise.

Anyway, all this to say, bronchiolitis-related apnea is a terrible outcome but a very rare outcome. Admission for observation may be considered in high-risk patients, and should be discussed with parents. If a hospital doesn’t have apnea monitoring, is it still reasonable to admit these kids for observation? That’s not really germane to the studies published here, but came up recently on one of my rotations — I guess if a respiratory arrest happened, it would be better to be in a setting where a response could occur swiftly and with full capabilities, but I don’t know that such an admission is better than sending the kid home with parents who will likely be steadfast bedside observers of the child’s respiratory status throughout the night. That question will have to wait for another study, I suppose.


Walsh P1, Cunningham P2, Merchant S3, Walker N3, Heffner J3, Shanholtzer L3, Rothenberg SJ4. Derivation of Candidate Clinical Decision Rules to Identify Infants at Risk for Central Apnea. Pediatrics. 2015 Nov;136(5):e1228-36. PMID: 26482666. [PubMed] [Read by QxMD]

Upper Extremity DVTs

After recently seeing a patient who came in with upper extremity swelling in the setting of chronic HD with an A/V fistula in the same arm, and a negative U/S for DVT in the upper extremity, I was wondering about two questions — 1.) What is the sensitivity of U/S for DVT of the upper extremity, and more proximal central veins, and 2.) What is the risk profile of these thrombii when found? How many will lead to badness we worry about, e.g. pulmonary embolism?

Here’s what I found:

In terms of upper extremity DVT:

– Hingorani et al published comparative rates of PE in UE DVT v. LE, finding a prevalence rate of pulmonary embolism of 17% from UEDVT compared with 8% from lower extremity deep venous thrombosis. Another paper combining data from nine studies reported a 13% PE rate (Kommareddy A et al. Semin Thromb Hemost 2002; 28:89–99).
Our patient was found to *not* have an upper extremity DVT per the initial U/S, but as we discussed, it seemed more likely that (especially given his neck and facial swelling, which is almost universally found in these patients) that any thrombosis he had would be more proximal as it had been in the past, so ultrasonography may not have been the best first imaging test — according to a J. Ultrasound Medicine paper regarding UE DVT screening, “centrally situated veins, including the medial segment of the subclavian vein, the brachiocephalic vein, and their confluence with the superior vena cava, may be difficult to visualize” — and perhaps would be better evaluated with MR Venography or contrast venography.
So for more central clots, e.g. SVC or brachiocephalic veins, what are the associated risks?
– Otten et al. state in a 2003 Chest article, “Thromboembolic Disease Involving the Superior Vena Cava and Brachiocephalic Veins”: “The frequency of isolated thrombosis of the SVC or brachiocephalic veins that we report probably grossly underestimates the true incidence, because the test that is usually performed in symptomatic patients, color duplex Doppler ultrasonography, cannot image the SVC and proximal segment of the brachiocephalic veins.”
– In this article, they report an 8.7% rate of PE from SVC/brachiocephalic DVTs. A larger series of 33 patients with thromboembolic disease involving the BC or SVC reported 36% of these patients as having symptomatic PE, with four of these being fatal.
Lastly, but probably most importantly, Shennib et al. reported in May of this year a patient who suffered an UE DVT after aggressively utilizing a “popular modified, oscillating dumbbell”, more commonly known as a Shake Weight. So please consider screening for Shake Weight usage as a risk factor in any patients being assessed for UE DVT.
What I found interesting about this was the incredible variability in reported incidence of serious complications, and conclusions in terms of what the risk of complication was — vascular surgery literature tended to minimize these complications relative to hematology literature. I’m not sure if this reflects just different patient populations the two specialties are exposed to, or the fact that these problems are often found in the setting of prior vascular interventions, but it’s interesting to think about the implications of widely-disparate risk estimates coming out of different bodies of literature.


Rosa-Salazar V, Trujillo-Santos J, Díaz Peromingo JA, Apollonio A, Sanz O, Malý R, Muñoz-Rodriguez FJ, Serrano JC, Soler S, Monreal M; RIETE Investigators. A prognostic score to identify low-risk outpatients with acute deep vein thrombosis in the upper extremity. J Thromb Haemost. 2015 Jul;13(7):1274-8. PMID: 25980766. [PubMed] [Read by QxMD]
Oymak FS1, Buyukoglan H, Tokgoz B, Ozkan M, Tasdemir K, Mavili E, Gulmez I, Demir R, Ozesmi M. Prevalence of thromboembolic disease including superior vena cava and brachiocephalic veins. Clin Appl Thromb Hemost. 2005 Apr;11(2):183-9. PMID: 15821824. [PubMed] [Read by QxMD]
Chin EE1, Zimmerman PT, Grant EG. Sonographic evaluation of upper extremity deep venous thrombosis. J Ultrasound Med. 2005 Jun;24(6):829-38; quiz 839-40. PMID: 15914687. [PubMed] [Read by QxMD]
Hingorani A1, Ascher E, Hanson J, Scheinman M, Yorkovich W, Lorenson E, DePippo P, Salles-Cunha S. Upper extremity versus lower extremity deep venous thrombosis. Am J Surg. 1997 Aug;174(2):214-7. PMID: 9293848. [PubMed] [Read by QxMD]
Otten TR1, Stein PD, Patel KC, Mustafa S, Silbergleit A. Thromboembolic disease involving the superior vena cava and brachiocephalic veins. Chest. 2003 Mar;123(3):809-12. PMID: 12628882. [PubMed] [Read by QxMD]
Oymak FS1, Buyukoglan H, Tokgoz B, Ozkan M, Tasdemir K, Mavili E, Gulmez I, Demir R, Ozesmi M. Prevalence of thromboembolic disease including superior vena cava and brachiocephalic veins. Clin Appl Thromb Hemost. 2005 Apr;11(2):183-9. PMID: 15821824. [PubMed] [Read by QxMD]

“The Overdose” – Story of an overdose at my new home institution

One of my favorite non-medical websites to visit when I’m looking for something to occupy my internet time with is It’s a blog that collects and publicizes links to what it considers the best of “longform journalism”, AKA literary non-fiction AKA a mix of essays, reporting, and occasionally short stories. I think perhaps it’s the pace with which they publish things, and the resultant quality and consistency, that makes this better in many ways than other aggregators of content, but your mileage may vary.

Anyway, the article describes over its five parts how a pediatric patient with a chronic metabolic disease, through a series of oversights and mistakes (I’ll avoid using the term “accident” here, without implying that this was intentional or grossly negligent), received a whopping dose of almost 6.5 grams of Bactrim DS, or 38.5 times the dose that the patient should have received. This mistake originated when the requirement for weight-based dosing in pediatric patients met some built-in alarm systems that notify pharmacy and then require manual entry from the ordering provider when the rounded dose (taking into account the actual dosing given pill contents) differs from the ordered dose by > 5%. When the pharmacist contacted the resident and asked that she modify the order, the requested dose of 160 mg was entered as 160 mg/kg. A robot in the pharmacy pulled the meds and dispensed them into a baggie that was bar-coded and labeled, and a pharmacist missed the opportunity to recognize the overdose before the bar-coded baggie was sent to a nurse. When asked later on, the nurse said she had a weird feeling about giving so many pills to a child, but assumed that since it was ordered, dispensed by the robot and the pharmacy, and it was unquestionably for the right patient (barcodes ensured this) she gave it anyway.

The patient, a teenager, very quickly thereafter became symptomatic of his overdose and seized, followed by a brief period of apnea. There was a rapid response and a transfer to the PICU and ultimately he was okay. So no harm, no foul, right? Sort of. Obviously, mistakes were made here– it should be incumbent on ordering providers to make sure the details of each order they sign are correct, especially in terms of the dose. But there were so many systemic contributing factors in play, that the the changes required to avoid this happening again were more institutional than individual. In emergency medicine particularly, where orders are entered quickly and under pressure, it is interesting to consider how failsafe mechanisms and provider order entry-assistance tools can both prevent and enable medication errors and other patient safety hazards. As medicine becomes increasingly interwoven with computers and providers off-load more and more cognitive work onto the computer systems they work with, telling these stories and learning from them will be evermore important.

“How Technology Led a Hospital To Give a Patient 38 Times His Dosage” –

View story at

Have a HEART! And some low-risk chest pain risk stratification, while you’re at it!

Chest pain is tricky. And scary. The combination of these two things makes it one of the chief complaints that seems to be difficult to work up in a thoughtful way, which minimizes risk to the patient (and provider) while also not overreaching in one’s diagnostic testing and thereby adding additional harms.

In medical school, we learned about the TIMI score as the best way for evaluating chest pain in our patients– however, this score was developed for inpatients on the cardiology service admitted with NSTEMI/UA, not ED patients presenting with chest pain, and has only really been validated in high-risk ED patients. The GRACE score is another one that seems to slightly outperform the TIMI in terms of predicting certain adverse events, but again was not designed for risk stratification of ED patients with chest pain.

So now we have (and have had for a while, this isn’t exactly new – I am more reviewing it for my own benefit) the HEART score, designed to “identify both low and high risk patients for an acute coronary syndrome” in the emergency department. It was not derived from a database, but from “clinical experience and medical literature”, and was then prospectively validated in 2440 patients at 10 sites. When compared to TIMI and GRACE, the c-statistic (or area under the receiver-operator curve) was 0.83 v. 0.75 and 0.70 respectively, showing that it did a better job discriminating patients with higher risk for major adverse cardiac events (MACE) in these patients. Pertinently for the ED physician, it also did a better job ruling *out* badness, with a lower percentage of “low-risk” scorers having an adverse event. With all this in mind, I plan to try to use the HEART score in my discussions with attendings when presented with chest pain patients, and hope that I will not only catch more (and rule out more) badness, but may also help reduce invasive imaging and stress testing in these low-risk patients.

In a recent single-center study, Mahler et al. looked back at patients who had HEART scores of 0-3 (low risk) admitted to an ED-based observation unit (keep the population in mind) and evaluated the impact of this score on their receipt of further diagnostic testing down the line, as well as the incidence of adverse events in this group. They found, unsurprisingly, that these patients were in fact at low-risk for ACS — only 0.5% of patients in this group had an adverse event in the next 30 days (though to be thorough, they had a LTFU rate of 30% which is pretty significant). The surprising, and meaningful to me finding was that they reduced the rate of further testing by 83%, no doubt saving these patients from unnecessary stress and anxiety, potential harms or complications, and costs to both them and the health care system.

This is a very incomplete treatment of chest pain risk stratification, I know, but I hope to add more as I learn and read more about these scoring systems and others, and grow in my understanding of critical appraisal of the literature.


Antman EM1, Cohen M, Bernink PJ, McCabe CH, Horacek T, Papuchis G, Mautner B, Corbalan R, Radley D, Braunwald E. The TIMI risk score for unstable angina/non-ST elevation MI: A method for prognostication and therapeutic decision making. JAMA. 2000 Aug 16;284(7):835-42. PMID: 10938172. [PubMed] [Read by QxMD]
Mahler SA1, Hiestand BC, Goff DC Jr, Hoekstra JW, Miller CD. Can the HEART score safely reduce stress testing and cardiac imaging in patients at low risk for major adverse cardiac events? Crit Pathw Cardiol. 2011 Sep;10(3):128-33. PMID: 21989033. [PubMed] [Read by QxMD]
Backus BE1, Six AJ, Kelder JC, Bosschaert MA, Mast EG, Mosterd A, Veldkamp RF, Wardeh AJ, Tio R, Braam R, Monnink SH, van Tooren R, Mast TP, van den Akker F, Cramer MJ, Poldervaart JM, Hoes AW, Doevendans PA. A prospective validation of the HEART score for chest pain patients at the emergency department. Int J Cardiol. 2013 Oct 3;168(3):2153-8. PMID: 23465250. [PubMed] [Read by QxMD]

β-Blockade for the treatment of recurrent VF arrest

Maybe! In this post, I’ll be looking back at a couple papers that I came across over the last year. One of the more interesting developments in medicine over the last decade in my eyes has been the increasing focus on vagal tone in treating various diseases such as epilepsy and treatment-refractory depression, mostly via the use of implantable devices such as the vagal nerve stimulator (VNS). The mechanisms of action of the VNS in these somewhat-nebulous and poorly-understood pathologies is a murky thing, but the simplified way that I understand it is that you’re calming the body down– putting the foot on the sympathetic nervous system’s proverbial brake, in other words, and this has some beneficial effect. On my ICU rotation, I decided to look into work that has been done on the use of beta-blockade in septic shock patients (coming soon), and during that same month, a few clinicians I had worked with on my away rotation in emergency medicine published a chart review showing the use of beta-blockade in refractory VF cardiac arrest.

The paper on cardiac arrest comes out of Hennepin Co. medical center, and is the work of their new research director, a really cool and smart doc named Brian Driver and some of his colleagues who are very well-known in the emergency cardiology field. They present a retrospective review of 25 patients with refractory VF arrest, all of whom received at least 300 mg of amiodarone and 3 mg of epinephrine and three or more defibrillation attempts (why these numbers?)

Shortcomings of this include the retrospective nature, the sample size, which was small and therefore makes comparisons between these groups useful primarily for hypothesis generation (which is what the authors state), and the use of only one reviewer (presumably unblinded, but this was not addressed). That said, the question itself is a creative one to ask and the neurologic outcomes in the admittedly-small intervention group were excellent– very unusual for something with as high of associated morbidity/mortality as RVF.

Interestingly, the authors provide some historical information reflecting the use of beta blockade to treat cardiac arrest as early as in the 1960s, when the use of propanolol was a second-line agent after lidocaine or procainamide. They also discuss the use of beta-blockade in septic shock patients (as mentioned above– check back in the next couple days for a discussion of those papers) and the idea that dampening the non-beneficial hyperadrenergic state that exists in many critical illnesses may be the reason these studies have shown possible benefit. If any institution is equipped to do this study, it’s Hennepin, and I hope to see more from them regarding this soon.