seen by death.

As a nurse, I have seen death on more occasions than I care to imagine.
Twice death has seen me.

Once, as a very young boy I was playing beside a pool when I slipped and fell in.
I could not swim, and I cannot recall if I even tried. But I do remember at some point a short time later, sinking downwards.

Laying on my back at the bottom of the pool, my perspective seemed to roll over, and instead of looking up at the surface, it was as if I was suspended in space, looking down at some vast, overexposed, silver lake.
The world I had left moments before now seemed to warp and writhe just out of reach below a mercury meniscus.

From what I remember, there was no struggling, no feeling of panic. Just this calm resignation, and this feeling of anticipation as to what might happen next. Perhaps, this is the way things are when you finally slot into the groove of death.
Perhaps, I am just really lazy.

I seem to recall some sort documentary of my life that spooled really quickly through my mind, just before I was pulled downwards… which was actually upwards…as my rescuer dragged me out.
I cant remember much more than that. Other than lots of coughing and vomiting.

I have probably never been as close to death as I was that day.

Except maybe the time, when I was much older, that I was out hiking with friends and I slipped on wet rocks whilst making a river crossing.

We had chosen to cross at this pinch-point. A place where this flood-fed river was all scrunched up between a sheer rise of overhanging cliffs.
Here, the river had picked up speed, and was foaming in boiling protest as it shot a step-down toss of papular rapids, before finally dropping downwards with all the might of a jade hammer between a gap you could easily jump across.
If you were committed.

My two companions made the jump without incident.

Loosing traction as I pushed off, my angle was all wrong and I landed all goofy and grasping amongst the slippery tufts of scrub along the steep bank.
Way not anywhere near the spot I had planned to land.
For a moment the tussock handholds of razor grass held my weight.
Until the soft stuttered tearing of roots seemed to drown out the entire river roar as they pulled loose from the soil.

Hanging there, I remember clearly thinking, of all things, about learning to ride a motorcycle. The instructor was telling us that if you dropped into a corner a little too fast, or a little too steep, you should always look over to where you wanted to be.
Never look down at the road, or over at that tree you don’t want to hit. Because you will.
Trust your body to take you where you want to be.

Despite this memory squirting up from my adrenals, I could not help but to stare down over my shoulder transfixed at the exact point I was going to fall into the abyss.
Not two meters on from my entry point, the whole world was swallowed as the river compressed with an unimaginable squishiness between a narrow tunnel of boulders.

My foothold slipped again. This was it.
Holding with a vice-like desperation onto the two clumps of grass that were themselves no longer attached to anything, there was nothing much left to do but fall sideways into empty space.
It was a beautiful sunny day. I could smell the wet grass. I could smell the water.

As every thing let go, I finally looked up at where I wanted to be.

Instead of the icy green envelopment that I expected, instead of the powerful rush downwards into an unimaginable something… or an abrupt end to everything… instead of all that, my body entangled me in the spiky safety of a gnarled old thorn bush that had somehow managed to sink its roots amongst the rocks and scree just above the water.
It held me. Just.
Until I could scramble under the urging directions of my friends from slippery foothold to macerating handhold.
And up. And out.

We all lay on our backs in the sun beside that river for quite some time that day. Breathing hard. Laughing and whooping off the adrenaline. Sucking in the deliciously thick soup of life.

And being my best friends and all, they did their best not to notice my seriously shaking hands.


References:

Featured image via: kia4067

International Normalised Ratio (INR).

Download this Thunderbox Paper:

International Normalised Ratio (INR)

 

A Thunderbox is Australian slang for an old style outside toilet that was little more than a drafty wooden shed over a hole in the ground.

They also used a wad of papers (usually out of a magazine or newspaper) stuck on an old piece of wire for toilet paper. Life was rough back then. Hardcore.

These pdf files are a one page overview of a particular topic that you can print out and stick on the door of your toilet (hence thunderbox).

  • They will always be only one page.
  • Sometimes it will be VERY short (just a few lines).

The trick is to make it ONE thing for you to remember before the next paper is published.

To make this work you must commit to posting on your toilet door (you could even consider posting on the toilet door at work) and taking a moment to read over each time you………well, you know. Business.

The goal is to commit each paper to your long-term memory before the end of the week. So repetition is essential (as is business regularity).

Print it, stick it, study it.

“The Case of the Uncertain Principle”

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Atoms or elementary particles themselves are not real; they form a world of potentialities or possibilities rather than one of things or facts.  -Werner Heisenberg

The uncertainty principle states, there is a limit to the precision with which the position and momentum of  any subatomic particle can be measured. Their location and velocity can only be described in degrees of probability, rather than with the certainties we are accustomed to. This nanoscopic world cannot be predicted by classical physics nor understood using the anecdotal experiences of everyday life. What, you may ask, does this have to do with the practice of Emergency Medicine? Although some would argue that Schrodinger and his cat would have made wonderful Emergency Physicians, until now Emergency Medicine and Quantum Mechanics have occupied their own mutually separate sectors of space. With the arrival of high-sensitivity troponin assays and the uncertainty that comes with interpreting their results, these independent circles may have come closer to intercepting then we ever would have anticipated.

Ideally during an acute myocardial infarction,  serum levels of cardiac-specific troponin rise incrementally. We utilize this predicted rise and its high specificity to confirm our suspicion of myocardial necrosis. More recently, as the troponin assays have become more sensitive they have been utilized to further risk stratify chest pain patients at low risk for ACS (9). Given the delayed fashion of troponin’s release into the blood stream, a single troponin is not sensitive enough to effectively rule out ACS (2), and thus emergency providers have taken to measuring troponin levels in a serial fashion. Traditional recommendations state providers should allow at least 3-6 hours between measurements to ensure identification of patients who are early in their presentation (6). The hope of those who are supporters of the high-sensitivity assays is that these tests will be able to identify patients earlier in their disease process and reduce time required between serial measurements leading to faster, more accurate dispositions.

The difficulty with the increasing sensitivity of troponin assay is two-fold. First, the newest generation of assays can now detect troponin levels in well over 50% of the general population (1). In fact, in an article published in NEJM in 2009 by Reichlin et al, the Roche high sensitivity troponin assay, at its limit of detection (LOD) found 87% of the cohort to have measurable troponin levels (2). This baseline troponinemia makes differentiating ACS from baseline noise a difficult proposition. The standard concept of utilizing the 99th percentile, or the troponin level below which 99% of a healthy cohort will fall, is only moderately more effective. In this same trial,  using the 99th percentile, Reichlin et al raised the specificity of the assay to 80% but at the cost of missing 5% of the acute myocardial infarctions (2). To better distinguish this baseline troponin levels from the disease state in question, a delta troponin approach has been proposed (4). The delta troponin strategy asserts that rather than using an absolute threshold from which to base your decisions on, trending the changes in the troponin level with serial troponin measurements may be a more accurate method of differentiating ACS from this baseline troponinemia. Given that the high-sensitivty assays are capable of measuring levels of troponin exponentially smaller than our standard assays, they seem to be the ideal tool for the delta strategy.

Unfortunately things are not so simple. The second concern with the use of the high-sensitivity troponin is the inherent imprecision of the assays themselves. All assays, both standard and high-sensitivity, will demonstrate a certain degree of test-retest variability. At high values of serum troponin, this variability is inconsequential but at the very low levels with which we are attempting to trend incremental changes, this imprecision becomes increasingly more important (7). The 10% coefficient of variation is a measurement attempting to quantify this variability. This is the serum troponin level below which the variability of the assay is greater than 10%. Simply put, it is the level at which the imprecision of the assay becomes clinically significant (6). The accuracy of assays in which the level of the 99th percentile is below that of the 10% coefficient of variation will suffer (2).Similarly as you attempt to measure smaller  absolute changes in troponin between serial measurements, this imprecision will undermine your efforts (3).

These flaws are illustrated nicely in an article published in Circulation in 2011, in which Reichlin et al attempt to validate the delta troponin strategy. The authors compare the absolute and relative changes of two troponin assays at 1 and 2 hours after presentation to the “gold standard of the diagnoses of myocardial infarction made by 2 cardiologists using standard troponin assays drawn at six and nine hours after presentation. Using an absolute change of 0.007 micrograms/L at 2 hours after presentation,  the hs-TnT assay had a sensitivity of 89% and a specificity of 93%. In the subgroup of patients who presented with initial troponin levels above the 99th percentile, the delta troponin methods produced a sensitivity and specificity of 90% and 87% respectively. In the subgroup who presented with an initial troponin level below the 99th percentile, the  delta troponin provided a negative predictive value of 100%. Unfortunately in this group a positive delta troponin meant very little, providing a positive predictive value of only 22%. Compared to the diagnostic characteristics of a single troponin measurement taken at presentation (sensitivity of 95% ,specificity of 80%, NPV of 99% and PPV of 50%), very little is gained from this delta troponin strategy (2).

Thus you are left in perpetual uncertainty. Unsure if the low level of troponin is the early rise associated with myocardial necrosis or a baseline troponinemia present in so many patients. Likewise you are equally uncertain if the change in levels at 2-hours is further confirmation of infarction or simply due to the random imprecision of the assay itself. In a recently published article by Pretorius et al, these authors have turned to statistical modeling in an attempt to resolve this ambiguity (5). The reference change value (RCV) is a mathematical concept contrived to combat this variability. It is a calculation that takes into account this analytical imprecision, the estimates of within-subject biological variation and calculates the amount of change above which is not likely to be due to chance alone (8). Pretorius et al have attempted to apply this concept to the delta troponin strategy (5).  Using the RCV the authors calculate a z-score and propose a threshold of 1.96 above which the delta troponin measurements should be considered positive. This is the level that corresponds to a p-value of 0.05 or a 5% probability that the change in troponin level was due to chance. This strategy of course speaks to the more nerdy among us but how well does it perform clinically?

Using a prospectively gathered cohort of Emergency Department chest pain patients, Pretorius et al retrospectively applied their z-score, comparing it’s performance to absolute and relative change of the 2-hour troponin assay levels. As a tool to rule in myocardial infarction the z-score method outperformed both the absolute and relative changes methods. Among the three high-sensitivity assays examined, the z-score’s specificity was found to be 94%, 97%, and 98% respectively, each one outperforming their absolute and relative change counterparts. Unfortunately when using the z-score, the sensitivities  of each assay (79%, 77%, and 69% respectively) suffered. Interestingly most of the AMI patients, which the z-score missed, had initial troponin levels well above the diagnostic threshold of the 99th percentile and would probably have not required a second troponin value to confirm the diagnosis. Of note, this was a retrospective application of this statistical method and it will have to be tested prospectively on a novel cohort before it can be applied clinically. In addition, its performance was evaluated in an undifferentiated chest pain population. Where the z-score may potentially provide benefit is in the clinically ambiguous patients.

The most obvious question is how clinically relevant is any of this? The major weakness of all these trials is that each of the various assays and techniques which were evaluated, were done so in a vacuum. What is important to the Emergency Physician is not how these high-sensitivity assays perform in isolation but how much they add to our clinically evaluation and EKG findings.  The majority of the ACS cases will be identified by clinical exam and EKG. When these factors are taken into consideration, the troponin assay provide very little additional diagnostic utility. Than et al utilized the strategy of clinical risk stratification in combination with EKG and serial troponin measurements in 2-hours increments (9).  In doing so, the authors identified 99.7% of 30-day major adverse cardiac events (MACEs). Taken together TIMI risk score and EKG identified 98.3% of these events without the help of the troponin assay. The added value of the standard assay was minimal. When a high-sensitivity troponin assay was applied to the same cohort it added no statistical or clinically relevant diagnostic utility (10).

Up to this point, the benefits that high-sensitivity assays provide has been abstract in nature. As far back as the publication of Dr. Hector Pope’s trial in NEJM, Emergency Physicians were accurately identifying the large majority of ACS patients. These physicians ultimately missed 19 out 10,689 patients (11). To improve on this performance would be a Herculean task. Increasing the sensitivity of our troponin assays does not seem to be the answer. Using minute changes in troponin values to guide our treatment is fraught with uncertainty. These changes are equally likely to be due to random chance as they are to be caused by true myocardial necrosis. Like the subatomic particle, discrete troponin values and their respective momentum can only by reported in varying degrees of uncertainty. After all, physicist Werner Heisenberg wrote when describing the uncertainty principle, In the sharp formulation of the law of causality– “if we know the present exactly, we can calculate the future”-it is not the conclusion that is wrong but the premise.

Sources Cited:

1. Lippi G, Cervellin G. Do we really need high-sensitivity troponin immunoassays in the emergency department? Maybe not. Clin Chem Lab Med. 2014 Feb 1;52(2):205-12.

2. Reichlin et al. et al. Early diagnosis of myocardial infarction with sensitive cardiac troponin assays. N Engl J Med. 2009;361(9): 858-867.

3. Mueller M, Biener M, Vafaie M, et al. Absolute and relative kinetic changes of high-sensitivity cardiac troponin T in acute coronary syndrome and in patients with increased troponin in the absence of acute coronary syndrome. Clin Chem 2012; 58: 209–218.

4. Reichlin et al. Utility of absolute and relative changes in cardiac troponin concentrations in the early diagnosis of acute myocardial infarction. Circulation. 2011 Jul 12;124(2):136-45.

5.Pretorius et al. Towards a consistent definition of a significant delta troponin with z-scores: a way out of chaos? Eur Heart J Acute Cardiovasc Care. 2013 Dec 17.

6. Thygesen K, Alpert JS, White HD. Joint ESC/ACCF/AHA/WHF Task Force for the Redefinition of Myocardial Infarction, Jaffe AS, Galvani M, Katus HA, Newby LK et al. Universal definition of myocardial infarction. Circulation. 2007;116:2634–2653

7. Panteghini et al. Evaluation of Imprecision for Cardiac Troponin Assays at Low-Range Concentrations.  Clinical Chemistry. February 2004 vol. 50 no. 2 327-332

8. Fraser, CG. Reference change values. Clin Chem Lab Med. 2011 Sep 30;50(5):807-12.

9. Than et al. 2-Hour accelerated diagnostic protocol to assess patients with chest pain symptoms using contemporary troponins as the only biomarker: the ADAPT trial. J Am Coll Cardiol. 2012 Jun 5;59(23):2091-8

10. Cullen et al. Validation of High-Sensitivity Troponin I in a 2-Hour Diagnostic Strategy to Assess 30-Day Outcomes in Emergency Department Patients With Possible Acute Coronary Syndrome. J Am Coll Cardiol, Volume 62, Issue 14, 1 October 2013, Pages 1242-1249

11. Pope et al. Missed Diagnoses of Acute Cardiac Ischemia in the Emergency Department. N Engl J Med 2000; 342:1163-1170 April 20, 2000

 

The post “The Case of the Uncertain Principle” appeared first on EM Nerd.

ACEP Practice Guideline on Procedural Sedation

ACEP published Clinical Policy on Procedural Sedation and Analgesia in the Emergency Department in Feb 2014. as usual critical questions and very useful answers. Let’s review them:

1. In patients undergoing procedural sedation and analgesia in the emergency department, does preprocedural fasting demonstrate a reduction in the risk of emesis or aspiration?

Level B recommendations. Do not delay procedural sedation in adults or pediatrics in the ED based on fasting time. Preprocedural fasting for any duration has not demonstrated a reduction in the risk of emesis or aspiration when administering procedural sedation and analgesia.

2. In patients undergoing procedural sedation and analgesia in the emergency department, does the routine use of capnography reduce the incidence of adverse respiratory events?

Level B recommendations. Capnography* may be used as an adjunct to pulse oximetry and clinical assessment to detect hypoventilation and apnea earlier than pulse oximetry and/or clinical assessment alone in patients undergoing procedural sedation and analgesia in the ED.

*Capnography includes all forms of quantitative exhaled carbon dioxide analysis.

3. In patients undergoing procedural sedation and analgesia in the emergency department, what is the minimum number of personnel necessary to manage complications?

Level C recommendations. During procedural sedation and analgesia, a nurse or other qualified individual should be present for continuous monitoring of the patient, in addition  to the provider performing the procedure. Physicians who are working or consulting in the ED should coordinate procedures requiring procedural sedation and analgesia with the ED staff.

4. In patients undergoing procedural sedation and analgesia in the emergency department, can ketamine, propofol, etomidate, dexmedetomidine, alfentanil, and remifentanil be safely administered?

Level A recommendations. Ketamine can be safely administered to children for procedural sedation and analgesia in the ED. Propofol can be safely administered to children and adults for procedural sedation and analgesia in the ED.

Level B recommendations. Etomidate can be safely administered to adults for procedural sedation and analgesia in the ED. A combination of propofol and ketamine can be safely administered to children and adults for procedural sedation and analgesia.

Level C recommendations. Ketamine can be safely administered to adults for procedural sedation and analgesia in the ED. Alfentanil can be safely administered to adults for procedural sedation and analgesia in the ED. Etomidate can be safely administered to children for procedural sedation and analgesia in the ED.

Link to Policy on ACEP website