Buffalo Chest

The American Bison is one of my favorite mammals, so it is no surprise that I found this interesting and a good teaching point last year while working along with the V.A. thoracic surgery service: http://www.nejm.org/doi/full/10.1056/NEJMicm010281#t=article — This article presents a case which illustrates a concept known as a “buffalo chest”, or absence of anatomical separation of the two hemithoraxes, secondary to genetics, trauma, or iatrogenesis. I saw these in patients who had undergone median sternotomies for various cardiothoracic procedures. It’s also a physiology seen in trauma patients, patients with cancer who have had resections, people with various kinds of primary pulmonary disease, or just randomly by genetic bad luck (I imagine, though the article doesn’t list this as a specific cause). This is known as a buffalo chest because the American Bison (or at least according to the article, some) has a single, contiguous pleural space. While I would never use the word “easy” to describe the hunting of buffalo, particularly with bows from horseback, this facilitated the killing of them for food (or sick entertainment in the case of some poor buffalo shot by settlers off a train), as a GSW or penetrating arrow would to their broad sides could lead to a tension physiology.

Consider this possibility in the crashing patient with tension pneumothorax that doesn’t resolve with a unilateral chest tube, especially if any of the risk factors described. I agree with something described (and criticized by some)  in the FOAMed trauma world — nobody should die of traumatic arrest without decompression of the bilateral chests. I think this supports the empiric decompression of the contralateral chest in the positive pressure-ventilated patient in undifferentiated cardiac arrest where pneumothorax is wanting to be ruled out, and would really like to see more research on better ways to manage it in the acute setting.

Faking it: How to detect malingered psychosis

This was an amusing and interesting article shown to me by one of our consulting psychiatry faculty — in it, the authors Drs. Resnick and Knoll lay out their approach to determining whether someone might be feigning madness for secondary gain. This is, sadly, something we see very frequently in the emergency department — not so much specifically the faking of psychosis, but more often things like suicidality, which some patients (whose unfortunate lives are such that they would prefer being stuck in the emergency department on an “involuntary” hold to being out in the streets, or often those who were just arrested and are now on their way to jail) will endorse knowing that it results in a cascade of CYA consultations that result in a longer LOS and often a sandwich / sometimes psychotropic medications, or alcohol withdrawal. In the case of arrested patients, sometimes they can avoid a trip to jail by diverting to the hospital which will lead the officer to write them a ticket instead of arrest them. Sometimes this population also endorses psychotic symptoms such as command hallucinations, and the subjective nature of these complaints makes them very difficult to determine as being organic or not.

Malingering, defined by the authors as “the intentional production of false or grossly exaggerated physical or psychological symptoms, motivated by external incentives” is obviously a diagnosis of exclusion, particularly in our most vulnerable populations such as the homeless or incarcerated. However, one must also consider the patients whose care is being delayed by beds occupied by those without true illness, and the resources allocated to sussing out those actually at risk from those who are angling for secondary gain. There is also a very strong “Peter and the Wolf” phenomenon that can result from dealing with the same patients every day who come in claiming suicidality, only to recant after they sober up, or who are found to have conditional suicidality that hinges on things like being fed, housed, or given controlled substances such as pain medications or benzodiazepines — meaning, there is a risk that it could both degrade one’s index of concern for true suicidal ideation, and one’s empathy for other patients presenting with concern that they are a danger to self.

So what do they recommend? Some highlights:

Asking about improbable symptoms, which are rarely seen even in the most severely disabled patients, e.g. “When people talk to you, do you see the words they speak spelled out?” or (my personal favorite) “Have you ever believed that automobiles are members of an organized religion?”

Focusing on incongruities between the way they are presenting or endorsing symptoms and the circumstances they were in before arrival, or the way they behave when the examiner is not present, e.g. endorsing having active auditory and visual hallucinations yet showing no evidence of being distracted or attending to internal stimuli.

Critically evaluate reported hallucinations, particularly visual ones which are less often seen in true psychosis than reported in malingering. True visual hallucinations also are usually of “normalized people” and seen in color, rather than dramatic or atypical things such as giant monsters or devils, or flashes of light/color, which is more associated with neurologic disease or drug intoxication than psychosis.

They close by advising clinicians to “avoid direct accusations of lying, and give the suspected malingerer every opportunity to save face. For example, it is preferable to say, ‘You haven’t told me the whole truth'”, rather than directly confront them as malingering or lying.

All in all, this was an interesting diversion regarding a very difficult population and a sad phenomenon seen in the ED. Worth the 10 minutes it takes you to read, even if it doesn’t ultimately stop you from consulting psychiatry.

 

Transient Hypotension in the Emergency Department

An interesting technicality in the use of the PERC rule to rule out pulmonary embolism is the tachycardia component — it asks not whether the patient is tachycardic at the time of the application of the rule, or whether tachycardia was sustained throughout the emergency department stay, but instead whether the patient had (as described by Jeff Kline in his great review article on PE diagnosis and risk stratification): “3. Pulse <100 beats/min during entire stay in ED”.  Meaning, even transient tachycardia may suggest a life-threatening diagnosis, even if it resolves while the patient is in the emergency department, and we’re probably PERCing out a whole bunch of patients inappropriately, at least according to Kline (who, notably, testifies a whole bunch as an expert witness in cases of missed pulmonary emboli).

I recently had a handful of patients in whom concerning blood pressures were measured and documented, which then resolved when vital signs were re-checked or after a small quantity of fluid or repositioning. I was wondering whether anyone had looked at the prognostic significance of ED hypotension, and whether these momentary dips in blood pressure should be something that concerns me. I did a quick search and found two studies that addressed this question in two different populations:

First we have, from the Rick Bukata school of title writing: “Emergency department hypotension predicts sudden unexpected in-hospital mortality: A prospective cohort study.”  This study, by Alan Jones and Jeff Kline out of (and formerly out of) Carolinas, prospectively enrolled 4,790 adult ED patients admitted to the hospital for reasons other than trauma. Patients were divided into those with and without systolic BPs below 100 mmHg at any time during their ED visit and followed through their hospitalization for the primary outcome of in-hospital mortality. Secondary outcomes included “sudden and unexpected death”, the relationship between the degree and the duration of hypotension measured and mortality, and the test characteristics of hypotension as a test for predicting in-hospital mortality.

Their conclusions are illustrated well in this graph:

hypotension

As they concisely summarize in the article’s conclusion:

Patients exposed to hypotension had a threefold increased risk of in-hospital death and a 10-fold increased risk of sudden, unexpected in-hospital death. Patients with any one SBP < 80 mm Hg had a sixfold-increased incidence of in-hospital death, and patients with a SBP < 100 mm Hg for > 60 min had almost a threefold-increased incidence of in-hospital death.

The second article from the same group echoes this conclusion in a different population of patients. This article, “The significance of non-sustained hypotension in emergency department patients with sepsis” is a secondary analysis of the above data set which looks specifically at the prognostic value of non-sustained hypotension defined as one or more occurrence of SBP < 100 mmHg in patients with sepsis as defined by the receipt of antibiotics in the ED + at least two SIRS criteria.

774 patients met their inclusion criteria for sepsis, and after 74 were excluded for “overt shock” (sustained hypotension or use of pressors). They examined the remaining patients for a primary outcome of in-hospital death.  They found, as one might expect, that hypotension predicts worse outcomes in this sub-population of patients — including when patients had non-sustained hypotension. Again, there seemed to be a “dose-dependent” relationship, with an inverse relationship between the nadir of the ED SBP and the frequency of in-hospital death, as shown here:

sepsishypotension

Another important finding (though taken in context of a fairly small sample) was the statistically similar incidence of the primary outcome in both the groups with transient and sustained hypotension. Both groups of patients had a 2.5-3x higher risk of in-hospital mortality when compared to patients without any hypotension.

Without belaboring the point, these two studies underscore the prognostic significance of even transient hypotension in the undifferentiated emergency department patient, and (as is better known to have implications in terms of severity) in patients diagnosed with sepsis. Like the previous post regarding lactate, or the well-known pearl about tachycardia at discharge, this is a number that should get your attention and which demands evaluation and possible intervention / escalation of care.

References

Marchick MR1, Kline JA, Jones AE. The significance of non-sustained hypotension in emergency department patients with sepsis. Intensive Care Med. 2009 Jul;35(7):1261-4. PMID: 19238354. [PubMed] [Read by QxMD]
Holler JG1, Bech CN1, Henriksen DP2, Mikkelsen S3, Pedersen C4, Lassen AT1. Nontraumatic hypotension and shock in the emergency department and the prehospital setting, prevalence, etiology, and mortality: a systematic review. PLoS One. 2015 Mar 19;10(3):e0119331. PMID: 25789927. [PubMed] [Read by QxMD]

Hyperlactatemia in the Emergency Department

Much has been made over measurement of serum lactate over the last several years– primarily focusing on whether we should be measuring it in the first place, and what the significance (and etiology) of elevations in serum lactate is, and what role it should play in diagnosis and risk stratification. Back in 2010, Scott Weingert was organizing the New York Sepsis Collaborative, and produced this podcast covering the basics of lactate measurement, with a particular bent towards sepsis. He did a great job covering the essential take-home of the data that existed thus far, and addressed a lot of points of confusion many people have about lactate — namely, the idea that it results from hypoxia/hypoxemia or anaerobic respiration, and covers some of the alternative etiologies of hyperlactatemia, i.e. any beta agonist, whether endogenous catecholamines or exogenous, such as albuterol or epinephrine being used as a vasopressor. The takeaway from this, echoed in sepsis care guidelines issued by many other organizations since and in the policies and protocols in many hospitals and emergency departments, is that elevated lactate is a marker of increased mortality, and may be an early alarm that someone is in septic shock or headed towards it.

I wanted to cover two studies — one by Shapiro et al. (a big name in sepsis research), and the other by del Portal et al– that looked at this question in the ED. These were prospective and retrospective cohort studies respectively, and both looked at over 1,000 emergency department patients and evaluated the prognostic significance of elevated venous lactate measurements. In the first study by Shapiro et al, they evaluated all patients admitted to the hospital with an infection-related diagnosis. In the second study, they looked at older adults admitted to the hospital with any diagnosis, though a very large proportion of patients were excluded. Reasons for exclusion (they excluded >14,000 of 16,886 total admissions , so I think this really affects the robustness of this paper) were things like being a sick trauma patient, transfers out, LWBS or leaving AMA — those are all reasonable, but they also excluded all patients in whom a lactate was not drawn in the ED. Without providing the numbers to break this down, it’s tough to say how generalizable these conclusions are, or if lactates were only obtained in patients that the providers thought were sick/potentially septic in the first place (which was the protocol at the hospital conducting the study by Shapiro et al.).

As one might expect, both studies found that hyperlactatemia correlates with badness in the form of increased mortality. The relationship is linear, and statistically significant. The authors also stratified the mortality by time — in Shapiro et al. by 28d in-hospital v. death within 3 days (top graph), and in del Portal’s study by in-hospital, 30 day and 60 day mortality (bottom):

lactateshapirolactatedelcar

Note the similar trend and the steep upward trajectory of the relationship — these results have been paralleled in the critical care literature, and have led to the commonly-accepted idea that a lactate > 4.0 is a threshold above which one should be concerned for hypoperfusion or shock, even in the absence of hypotension. These studies do not, and no studies have, established a causal relationship between lactate elevation and increased mortality– nor have they shown that trying to “clear” lactate will lead to better outcomes than trending alternative markers of perfusion (though several studies have looked at this question, without any definite conclusions). They also did not establish that one need only be worried about lactate > 4.0 — multiple studies including this one have shown that infected patients with lactate in the 2.0–3.9 mmol ⁄ L range have a risk of mortality that is approximately twice that of patients with a lactate level of < 2.0 mmol ⁄ L. They also have not established that we need not be worried about patients without hyperlactatemia — so-called “occult” sepsis.

More recent studies have questioned the relationship between hyperlactatemia and hypoperfusion per se by looking at changes in microcirculation, but I think it’s safe to say that an elevated lactate in a patient with suspected infection should still ring alarm bells in your head. Having these mortality “buckets” in mind when mentally risk stratifying patients or prioritizing them for workup or interventions can also help — particularly when these patients might otherwise look well and thereby fly under the radar.

In my mind, an elevated serum lactate must be explained — sometimes, the explanation is that they just got a nebulizer treatment, are in alcoholic ketoacidosis (which along with the production of ketones, leads to an accumulation in reduced nicotinamide adenine dinucleotide (NADH), which then results in impaired conversion of lactate to pyruvate or preferential conversion of pyruvate to lactate, both resulting in increased lactic acid level), or seized. But these are diagnoses of exclusion, and one must assume until proven otherwise that this represents their body’s sympathetic accelerator pedal being pushed to the floor and that they are needing resuscitation and provision of care with the mentality that this is a sick patient.

 

References

Shapiro NI1, Howell MD, Talmor D, Nathanson LA, Lisbon A, Wolfe RE, Weiss JW. Serum lactate as a predictor of mortality in emergency department patients with infection. Ann Emerg Med. 2005 May;45(5):524-8. PMID: 15855951. [PubMed] [Read by QxMD]
del Portal DA1, Shofer F, Mikkelsen ME, Dorsey PJ Jr, Gaieski DF, Goyal M, Synnestvedt M, Weiner MG, Pines JM. Emergency department lactate is associated with mortality in older adults admitted with and without infections. Acad Emerg Med. 2010 Mar;17(3):260-8. PMID: 20370758. [PubMed] [Read by QxMD]

D-Dimers & Dissection

A recent patient I saw in the emergency department was a fifties year-old woman with a family history of aortic dissections presenting with “chest pain” per the triage note. On my history and exam, she more endorsed vague neck and epigastric discomfort (which had now resolved), and had no other classic findings for a dissection (e.g. hemodynamic instability, asymmetric pulses or blood pressures, abnormal neurologic findings, etc.). She also had a a normal chest x-ray and a negative initial workup for ACS, including a normal ECG and undetectable troponin. In terms of other life-threatening diagnoses, she did not PERC out, and had a Wells score that suggested the D-Dimer would be an appropriate test to rule out pulmonary embolism.

When I discussed with her the potential utility of getting a CT scan of her chest to evaluate for an aortic dissection — she asked me about how much radiation exposure this involved, and shared her (valid and very appropriate) concerns about getting too much radiation. She had many CT scans for various reasons over the years she felt, and did not want any additional unnecessary radiation.

I talked to her more about this and tried to start some shared decision making by sharing a favorite infographic of mine about radiation amounts in diagnostic imaging, and (to myself) pondered a clinical question: If the D-dimer test was low, did that along with the low-ish pretest probability, safely decrease the likelihood of dissection enough to forego a CT scan? There is an emerging literature on the use of dimer testing to rule out aortic dissections, but how good is it? Do you use the same cut-off as in pulmonary embolism? Should that cutoff be age adjusted? And what are the test characteristics in this context? I had no idea, so that’s what today’s post-didactics reading was about.

I read through “A Systematic Review and Meta-analysis of D-dimer as a Rule-out Test for Suspected Acute Aortic Dissection” by Asha et al., which reviews the work of 30 studies and combines the data for 4 studies using a standard cutoff of 0.50 μg/mL to estimate sensitivity, specificity, and positive and negative likelihood ratios of a D-dimer. As the abstract conclusion reads:

“Overall, sensitivity and negative likelihood ratio were 98.0% (95% confidence interval [CI] 96.3% to 99.1%) and 0.05 (95% CI 0.03 to 0.09), respectively. These measurements had little statistical heterogeneity. Specificity (41.9%; 95% CI 39.0% to 44.9%) and positive likelihood ratio (2.11; 95% CI 1.46 to 3.05) showed significant statistical heterogeneity. When applied to a low-risk population as defined by the American Heart Association (prevalence 6%), the posttest probability for acute aortic dissection was 0.3%.”

So there you have it. Obviously, there’s more to it, and the actual paper is worth reading — it discusses some of the drawbacks of the included studies, specifically unanswered questions about bias and the generalizability to ED populations given the high prevalence of disease in the included cohorts. Limitations aside, basic conclusion that was in low risk patients, a negative D-dimer confers an even lower risk of acute aortic dissection, and it may be reasonable (don’t you love that phrase?) to consider using this result to inform your decision-making regarding the utility of imaging. Of course, one must also consider the rate of false positives, and the potential harms of resultant downstream testing as has been discussed regarding testing for PE.

I think that one of the more important (and potentially easily-overlooked, as when it comes to all clinical decision tools or supports, or anything that serves as a Bayesian modifier) points I took away from this review is that while this is a potentially useful test in this context, pretest probability matters. As the abstracts of some of the included studies say: “When applied to a low-risk population…”, “…in patients with low likelihood of the disease”,  “…the presence of ADD risk score 0 or ≤ 1 combined with a…” and so on. You should only really hang your hat on a negative dimer assay when you think the probability is low in the first place. Another question to consider though, is how low is the pre-test probability to suggest you *shouldn’t* order a dimer to r/o dissection? And how many people with potential dissections that might be caught and thereby managed earlier PERC’d out of receiving a test that might reveal this diagnosis (though might also subject them to an unnecessary scan for PE)?

As the full text of the article states:

It would be pertinent to comment on the many case reports of patients with confirmed acute aortic dissection but a negative D-dimer result. It should first be recognized that these cases did not have a risk-stratification applied and also that no test, no matter how good, including the reference standards for the disease, has 100% accuracy. These cases mostly represent a subgroup of patients with a thrombosed false lumen or an intramural hematoma who seem particularly likely to have a lower or negative D-dimer result. The studies in this meta-analysis included such patients, which means that the high sensitivity and excellent negative likelihood ratio were achieved with the inclusion of these problematic cases.

It is always worth remembering that rare diseases are rare, and that in a patient with a low pretest-probability of having a disease, any test can be construed as to have a high sensitivity when applied to the wrong population. For instance, I can figure out who is low risk for aortic dissection in most chest pain patients with the “Bryan” rule — I just ask if their name is Bryan, spelled with a y. If negative, they are extremely unlikely to have an aortic dissection. Of course, if they do, my test will likely miss them but the point remains. In the patient described above, even though the D-dimer was negative, this patient was not low risk by the fairly-conservative AHA acute aortic dissection risk score (pictured below), and therefore the sensitivities and specificities cited in the articles presented in this meta-analysis don’t apply to their case.

1-s2.0-S0196064415001183-gr3

In cases where acute aortic dissection is suspected as a likely potential diagnosis, a D-dimer is probably not an appropriate test to replace definitive diagnostic imaging of the aorta–  specifically, as stated by previous guidelines from the AHA: computed tomography (CT), magnetic resonance imaging (MRI), or transesophageal echocardiography. Let this inform your discussions of shared decision making in the emergency department, and document accordingly, and hopefully you’ll be able to adopt a strategy to help everyone sleep better at night.

References

Nazerian P1, Morello F2, Vanni S1, Bono A3, Castelli M1, Forno D3, Gigli C1, Soardo F3, Carbone F3, Lupia E3, Grifoni S1. Combined use of aortic dissection detection risk score and D-dimer in the diagnostic workup of suspected acute aortic dissection. Int J Cardiol. 2014 Jul 15;175(1):78-82. PMID: 24838058. [PubMed] [Read by QxMD]

Evaluation of Cervical Spine Clearance by Computed Tomographic Scan Alone in Intoxicated Patients With Blunt Trauma

One common and vexing problem I’ve run into thus far in residency is the intoxicated patient, found down, brought in by EMS in a rigid cervical collar placed because of the presumption of possible trauma leading to an unstable cervical injury. The efficacy and necessity of cervical collars has been debated elsewhere, and I’m not looking to discuss that here — what I’m more interested is, if these patients have a negative CT scan (for better and for worse, fairly common practice in those unable to give a reliable exam, especially if they have any sign of trauma on them), can we safely remove their collar?

This study, by the “Pacific Coast Surgery Association” and published in JAMA Surgery, prospectively evaluated 1668 intoxicated adults with blunt trauma who underwent cervical spine CT scans over one year at a single Level I trauma center. Intoxication was defined based on the results of urine and blood testing, and the outcome of interest was clinically-significant cervical spine injuries that required cervical immobilization (not necessarily surgical fixation).

The authors wanted to evaluate the negative predictive value of a normal CT scan in the intoxicated patient to determine whether this would allow safe removal of their cervical collar– it is well-known that some injuries (e.g. unstable ligamentous injuries or spinal cord injuries without fractures of the vertebrae) may not be identifiable on a CT scan, and in the patient who is altered, it may be difficult to elicit exam findings that would tip a practitioner off to the presence of these injuries.

So what did they find? In intoxicated patients, the negative predictive values of a CT scan read as negative for acute injury were 99.2% for all injuries and 99.8% for unstable injuries.  There were five false-negative CTs, with 4 central cord syndromes without associated fracture. There was also one false-negative for a potentially unstable injury identified in a drug-intoxicated patient who presented with clear quadriplegia on examination. All of these were detected on MR imaging. About half of the intoxicated patients with the negative CT went on to be admitted with their cervical collar left on. None of these intoxicated patients went on to have an injury identified later, or to have any neurologic deficit, leading to a conclusion of a NPV of 100% in that cohort.

My takeaway from this paper: while there are some weaknesses, e.g. the lack of protocol-based care and the significant heterogeneity in terms of “intoxication”, it seems reasonable to take away from this that a negative CT scan done on a modern scanner and read by an experienced trauma radiologist or neuroradiologist does allow you to safely clear the collar of an intoxicated patient who does not have any gross neurologic deficits. This data lends further support to the 2015 recommendations from the Eastern Association for the Surgery of Trauma who in a systematic review and meta-analysis “found the negative predictive value for identifying unstable CSIs to be 100% and thus have made a conditional recommendation for cervical collar removal based on a normal high-quality CT scan”. Adopting this practice could help minimize unnecessary testing (including expensive MRIs that are more likely to show false positives than to identify clinically-significant injuries) , allow for earlier disposition of patients from the emergency department, increase patient comfort, and decrease the emotional and cognitive burden placed on providers who otherwise often have to continuously struggle to keep patients adherent to immobilization practices.

References

Bush L1, Brookshire R1, Roche B1, Johnson A1, Cole F1, Karmy-Jones R1, Long W1, Martin MJ2. Evaluation of Cervical Spine Clearance by Computed Tomographic Scan Alone in Intoxicated Patients With Blunt Trauma. JAMA Surg. 2016 Jun 15. PMID: 27305663. [PubMed] [Read by QxMD]

Thrombolytic treatment of cardiac arrest or periarrest due to suspected pulmonary embolism

I recently saw a case in the department that led to me thinking about the role of thrombolytics in cardiac arrest patients — particularly for the purpose of trying to treat arrest from suspected PE. Thrombolytics in out-of-hospital cardiac arrest patients is something I’ve seen considerable inter-attending variability on in practice, and heard conflicting things about from the things that I’ve read and heard in podcasts. So, naturally when there are no podcasts readily accessible on the matter, I turned to PubMed and came across an excellent review article on the subject from Logan et al., “Evidence-based diagnosis and thrombolytic treatment of cardiac arrest or periarrest due to suspected pulmonary embolism”, published four years ago in AJEM.

As they write in the introduction, “This article discusses clinical features consistent with the presumptive diagnosis of PE, provides an overview of thrombolytic agents, and presents a detailed review of the literature supporting the use of thrombolysis as a treatment option for patients in cardiac arrest or periarrest due to suspected PE.” The authors do an excellent job summarizing the available (as of 2014, at least, or 2012 — this being the latest publication included) evidence and discuss strategies for considering whether to push lyrics in the cardiac arrest patient you think might have a pulmonary embolism. Note that this is a different question from lytics in patients with cardiac arrest due to coronary occlusion — though it is likely that many of those showed up in the reviewed trials of lytics in undifferentiated cardiac arrest, or PEA arrest that wasn’t necessarily thought to be secondary to an MI.

What does it boil down to?

“The above literature review shows that unstable or arresting patients experiencing massive PE will likely benefit from thrombolytic therapy. Studies with a retrospective design generally demonstrated the best outcomes, as was expected, due to the patient population having a known or high risk for PE, and possibly publication bias of positive results. Trials with a prospective design had more variation because these trials generally included a heterogeneous patient population in cardiac arrest and illustrates the potential difficulty of applying this intervention in real-time clinical practice. Analysis of the subgroup population of patients with PE in the prospective trials showed possible improved outcome after thrombolytic therapy, although these studies were not powered to look specifically at this group. This disparity emphasizes the importance of patient selection when evaluating for the efficacy of thrombolytic therapy.”

They said it best, so I won’t try to restate their conclusions — one thing I did find particularly interesting was a clinical decision making rule evaluated  in both a retrospective and a prospective trial which found the following triad to be associated with cardiac arrest secondary to massive PE: witnessed cardiac arrest, age less than 65 to 70 years, and PEA as the initial rhythm. This study found that 50% of the (admittedly fairly small n of 48) patients with this triad had a PE, which improved the diagnostic likelihood of PE when compared with the previously discussed sensitivity of 36% when only assessing for PEA rhythm in unexplained cardiac arrest.

There are robust data supporting the use of lytics in patients with hemodynamic compromise in the setting of diagnosed pulmonary embolism. Do these same data, or the data presented in this review and since support the use of it in all undifferentiated cardiac arrest patients, or in any subset of cardiac arrests? I agree with the authors — the data suggests that if the arrest is due to massive PE, lytics may benefit them and are probably worth trying, especially early on if your suspicion is high. But in the undifferentiated cardiac arrest patient, even one in PEA, I think there are many other things to consider like bedside ultrasound, duration of arrest, initial  rhythm, witnessed/unwitnessed, and cormorbid conditions / premorbid quality of life to consider before using an expensive, non-FDA-approved (for this indication) medication that has significant risks.

My next question that I still don’t have a good answer for yet, is whether someone can and should go to the cath lab after ROSC in the setting of the use of thrombolytics? And does this answer hinge on whether the lytics were given for a high suspicion of pulmonary embolism as the precipitating event? Is there ever a role for lytics in cardiac arrest where your suspicion isn’t high for PE as the etiology, but the patient is “too unstable” to go to catheterization? As I said in the last post, definitely more to come.

References

Logan JK1, Pantle H2, Huiras P3, Bessman E2, Bright L4. Evidence-based diagnosis and thrombolytic treatment of cardiac arrest or periarrest due to suspected pulmonary embolism. Am J Emerg Med. 2014 Jul;32(7):789-96. PMID: 24856738. [PubMed] [Read by QxMD]

Post-Arrest Prognostication

While I want to focus this blog on things relevant to practice in the Emergency Department, I have an academic interest (and maybe a career interest long-term) in critical care. I also feel that cardiac arrest is a particular area in critical care should be something that EPs are expert in — it’s also an area in which there is considerable nihilism which may lead in sub-optimal patient care, or early withdrawal of efforts before such withdrawal is justifiable.

What do I mean by nihilism? I mean that we in the ED rarely see good outcomes in out-of-hospital cardiac arrest (OOHCA) patients (and when we do, they’re often comatose and whisked away to the ICU, which means that even if they *do* have a good clinical outcome we do not see it happen and rarely even hear about it), and this leads to a sentiment that any cardiac arrest patient is bound for either death or a meaningless life due to neurologic injury.

Everyone in in the department, from patient care assistants and techs and medical students to the attendings, puts a lot of energy and effort into running codes and trying to resuscitate these patients. People care a lot and do some of their best work in these stressful contexts. But at the same time, I sometimes wonder whether we would focus more on improving our process and quality of care– and perhaps thereby do even better– if we had a better sense that our interventions translated into patients who could again be alive and well because of them. This sense is difficult to come by if many of the patients that you successfully attain ROSC on have features that many people associate with a very low likelihood of meaningful recovery.

This pair of recent review articles focused on prognostication in post-cardiac arrest patients — findings on clinical exam, imaging, and other methods to try to suss out who will go onto do well and who is unlikely to ever regain meaningful neurologic function. As ICU bed availability dwindles and the incidence of cardiac arrest and survival thereof continues to increase, this will be of increasing relevance to ED docs, intensivists, and those working with these patients.

So what is a “good outcome”? As the article says, “Experts in coma prognositication defined outcome by cerebral performance categories (CPCs; CPC 1 back to baseline, CPC 2 moderate impairment, CPC 3 severe impairment, CPC 4 vegetative or comatose, CPC 5: dead).” They bifurcate these into either a good (CPC 1 or 2) or poor (CPC 3-5) outcome. Obviously the difference between “moderate” and “severe” impairment is somewhat subjective, but there are additional tools used to help with this distinction.

The old standard was clinical assessment of brainstem reflexes, the response to pain, and the absence or presence of myoclonus during the first 72 hours post-arrest. In the TTM era, this becomes trickier because temperature management and the required sedation can alter these features, though the bedside exam still has significant prognostic significance. Absence of pupillary reflexes at 72 hours is the best bedside predictor of a bad outcome, with a false positive rate (FPR) of only 0.5% — presence of pupillary reflexes however, does not confer a good outcome, given that it only has a PPV of 61% (95% CI 50-71).

What about earlier? In the first 24 hours post-arrest, particularly in hypothermic patients, ~ 8% of patients without pupillary reflexes will go on to have a good recovery — so don’t count them out. In terms of corneal reflexes, the reliability is less than that of pupillary reflexes but their absence still correlates with a poor prognosis, with an FPR of 5%.

Motor response is the most affected by sedatives, opiates, and neuromuscular blockade — all common in patients undergoing TTM, and absent or extensor responses to painful stimuli at 72 hours had a FPR of 24%. To reliably utilize this for prognostication, you need exclusion of residual effects of sedation, which can be extended beyond when the drips are simply turned off secondary to the effects of TTM and also the effects of reduced clearance due to shock liver, renal dysfunction, or both.

In terms of myoclonus, which is classically associated with poor outcomes, ~ 9% of patients with myoclonus may survive, according to the data presented here. As the article states, myoclonus is somewhat of a nebulously defined entity — “Not all so-called twitches have the same prognostic implication, rather their usefulness in predicting prognosis depends on semiology, duration, and associated EEG findings.”

I’ll skip EEG and ERPs because this is already too long, but suffice to say they’re useful after hypothermia and for ruling out sub-clinical status epilepticus, which is something we really want to avoid happening in our post-arrest patients, but is very common. More to come on this, which I feel is of particular relevance to us in the ED. Same goes for biomarkers such as neuron specific enolase and Serum S-100B, which can both be measured and trended as the “troponins of the brain”, so to speak.

In terms of imaging — CT scan of the head is recommended in patients in whom there is not another obvious cause of cardiac arrest, to evaluate for a bleed or ischemic stroke. Evaluation of gray:white ratios can predict poor outcomes, but is less reliable than clinical exam and EEG, and this is true for MRI as well, though again MRI does not add very much prognostic capability beyond what can be achieved with bedside tests and the logistics and cost associated with MRI scans of every comatose survivor of cardiac arrest make this somewhat limited in utility.
PPV for Neuro Findings

So what’s the takeaway from all this? Basically, reliable prognostication after cardiac arrest is hard, but at the same time, it isn’t– don’t do it right away, and if you do, it shouldn’t necessarily be based on your bedside neurologic exam. There are tools that can give us useful information, but rarely certainty, to guide conversations with family. And the reality is that none of them are accurate enough inside the first 48-72 hours, especially in patients who are being cooled. There is a very powerful desire to be able to give families hope, or to caution against hope in a way that changes outcomes before they’ve happened — in my very early-in-development opinion, all you can really tell them is something I heard one of my mentors say to families whose children were in the Pediatric ICU: “Prepare for the worst, and hope for the best.”

I also take away from this that nihilism is an un-useful form of prognsotication in these patients — I have seen patients myself who had unreactive pupils or myoclonic jerks, who went onto walk out of the hospital, fairly neurologically intact. This is even more true if the arrest was witnessed, was a shockable rhythm such as VT or VF, and if the patient received high-quality chest compressions and early defibrillation, preventing lengthy low/no-flow states to the brain.

The message not to take away from this post that I believe in any sense that there is no ability to meaningfully make predictions about the likely outcome of cardiac arrest patients, whether or not you’ve gotten ROSC — there are many other variables not considered in the above article  that predict do reliably predict outcomes such as comorbidities, age of the patient, how long they were down for, the initial rhythm, and an often-overlooked variable in the literature (because it’s tough to quantify): consideration of their quality of life before they suffered a cardiac arrest. I also think that the pragmatic realities of cardiac arrest care — an emotionally charged event where patients are often teetering along a line between life and death, and where decisions have real and immediate impacts on that outcome– may require a sense of somewhat-morbid realism when the outcomes are often so dismal. I just hope that when people are making decisions about termination of efforts (or withdrawal of care post-ROSC) they’re considering all of these things and more, beyond just what their clinical gestalt is.

More to come, I’m sure — I’m especially interested in what happens moving forward in terms of biomarkers, cerebral oximetry, and near-infrared brain imaging to try to determine cerebral oxygenation and metabolism without having to move patients out of the ICU.

References

Rossetti AO1, Rabinstein AA2, Oddo M3. Neurological prognostication of outcome in patients in coma after cardiac arrest. Lancet Neurol. 2016 Mar 23. PMID: 27017468. [PubMed] [Read by QxMD]
Sivaraju A1, Gilmore EJ, Wira CR, Stevens A, Rampal N, Moeller JJ, Greer DM, Hirsch LJ, Gaspard N. Prognostication of post-cardiac arrest coma: early clinical and electroencephalographic predictors of outcome. Intensive Care Med. 2015 Jul;41(7):1264-72. PMID: 25940963. [PubMed] [Read by QxMD]

Pulmonary Embolism in Pregnancy

The diagnosis of pulmonary embolism in pregnant patients is one made difficult by many factors, including a normal elevation in serum d-dimer levels (see below) as well as the additional concern regarding exposure of a developing fetus to the high levels of radiation and contrast associated with CT pulmonary angiography. It is well-known that exogenous estrogen is a risk factor for thromboembolic disease, and while it seems from the data discussed below that pregnancy is not as scarily-high-risk for PE as we might think, we certainly know that pregnancy is a time when homones are running high Add to this the fact that in pregnancy, women are both tachypnic and tachycardic due to normal changes in cardiovascular and respiratory physiology — making a clinical diagnosis that much more difficult.

In these sequentially-published review articles by the PE guru Jeff Kline et al., the authors review the diagnostic dilemma presented by these patients and present the following algorithm:

Microsoft Word - jem_10231_JEM10231.edt

Note the inclusion of the trimester-stratified quantitative d-dimer for patients without a high pretest probability who are PERC negative — this goes against the conventional wisdom that the d-dimer is a worthless test in pregnant women due to the normal elevation found intrapartum. Similar to the way we have begun “age-adjusting” the threshold value of the quantitative d-dimer in non-pregnant patients, they propose that the threshold be “adjusted according to the trimester of pregnancy, as follows: first trimester, 750 ng/mL; second trimester, 1000 ng/mL; third trimester, 1250 ng/mL (assuming a standard cutoff of 500 ng/mL). If the patient has a non-high-pretest probability, has no high-risk features, is PERC negative, and the bilateral ultrasound is negative, and the D-dimer is below the trimester-adjusted values, PE can be ruled out to a reasonable degree of medical certainty.”

They acknowledge the limitations of this approach, including that it hasn’t been prospectively validated, and they do not present any data showing its performance as they’ve been using it, but in cases like this expert opinion is the best we have (so far). He discussed this approach on an episode of ER Cast, and explains it a little bit more in terms of the integration into clinical practice, as well as the role that gestalt can play in risk stratification. 

What I found interesting about this was the idea that the post-partum period is the most risky period of time for women in terms of pulmonary embolism — this echoes what we know about cardiovascular disease in the post-partum period, i.e. when women are autotransfused and their cardiopulmonary physiology is rapidly and massively altered, this presents the highest risk in terms of women with heart failure, valvular abnormalities, or disease entities like peripartum cardiomyopathy. According to the data presented by Kline et al, while the risk increases throughout a pregnancy, 70% of all peripartum PEs occur post partum, and the risk during pregnancy is low (OR 0.4-0.8, depending on trimester) — though, as the authors note, this may not actually reflect that pregnancy is protective against PE but instead suggest that we overtest women for pulmonary embolism during pregnancy, perhaps because of the clinical changes described above. The also cite a large meta-analysis of 23 epidemiologic studies that found PE occuring in only 3 of 10,000 pregnancies.

Another thing that stood out to me while reviewing this article was that for a patient to PERC out of these algorithms, their vital signs must be normal throughout their entire ED stay — normalization of vital signs during an ED visit does not lower the risk of PE, as specifically stated by the authors.

 

References

Kovac M1, Mikovic Z, Rakicevic L, Srzentic S, Mandic V, Djordjevic V, Radojkovic D, Elezovic I. The use of D-dimer with new cutoff can be useful in diagnosis of venous thromboembolism in pregnancy. Eur J Obstet Gynecol Reprod Biol. 2010 Jan;148(1):27-30. PMID: 19804940. [PubMed] [Read by QxMD]
Kline JA1, Williams GW, Hernandez-Nino J. D-dimer concentrations in normal pregnancy: new diagnostic thresholds are needed. Clin Chem. 2005 May;51(5):825-9. PMID: 15764641. [PubMed] [Read by QxMD]

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.

References

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]