Aortic Aneurysm Mimicking Recurrent Achalasia after Mediastinitis Complicating Botulinum Toxin Injections.......for Achalasia

In this case report, the authors describe a case of a young woman with achalasia who got repeated episodes of mediastinitis complicating botulinum toxin injection. Later she presented with "pseudoachalasia" or presumed recurrence of achalasia, but imaging showed that, lo and behold, she had developed a complication of her mediastinitis, viz an aortic arch aneurysm that required surgical repair. The authors claim that Ockham's razor suggested recurrent achalasia, whereas Hickam's dictum prevailed because the patient had more than one disease. They would have benefited from reading our paper elaborating and operationalizing both clinical saws. The case is easily synthesized into a unifying diagnosis -- a unifying causal pathway -- which obviates invoking multiple diagnoses. The symptoms representing the aortic aneurysm did so because they are in the same anatomic location as the mediastinitis causing them, which was in turn caused by the botulinum injections treating the original achalasia. A coauthor and I wrote a letter to the editor, which was not published, but is pasted below. While this critique may seem punctilious or pedantic, there are tangible consequences of this failure of synthesis: the patient went unnecessary testing for Marfan's syndrome and other genetic conditions of the vasculature, and case reports of this very condition (aneurysm after botulism injection induced mediastinitis) were apparently ignored, an omission that may have compromised surgical planning.

Goodrich et al¹ present an interesting case of a young woman with achalasia who developed pseudoachalasia mimicking recurrence of achalasia. The pseudoachalasia was caused by an aneurysm of the posterior aortic arch, and Hickam’s dictum is invoked to remind readers that new symptoms ought not to be reflexively attributed to recurrences of known diseases, an approach they suggest is encouraged by Ockham’s razor. A recent paper operationalized the application of Hickam’s dictum and Ockham’s razor to the problem of multiple diagnoses². According to this framework, multiple diagnoses are almost always due to a primary diagnosis that explains the chief complaint and one or more of: incidentalomas, known pre-existing diseases, or phenomena causally connected to the primary diagnosis. This latter category comprises Occam’s razor which, rather than suggesting a simple or single diagnosis, is better understood as favoring a single causal pathway that links findings together into a unifying diagnosis. When viewed through this lens, the posterior aortic aneurysm was caused by mediastinitis episodes that in turn were caused by treatment of achalasia -- a single, unifying diagnosis. While patients indeed may “have as many diseases as they damn well please” it is prudent to first try to link phenomena into a unifying causal pathway. Such an approach would have led to multiple case reports of aortic aneurysms associated with botulinum toxin injection for achalsaia,^3-5 informed operative planning (e.g., presaging adhesions), and obviated searches for unlikely genetic diseases (e.g., Marfan’s syndrome) in a patient without other features of these conditions.

1.           Goodrich HWF, Muniraj T, Masoud AE. Pseudoachalasia in an Achalasia Patient: A Ticking Time Bomb. ACG Case Rep J. Dec 2025;12(12):e01927. doi:10.14309/crj.0000000000001927

2.           Aberegg SK, Poole BR, Locke BW. Hickam's Dictum: An Analysis of Multiple Diagnoses. J Gen Intern Med. Oct 28 2024;doi:10.1007/s11606-024-09120-y

3.           Berman SS, Sabat JS. Mycotic aneurysm of the distal thoracic aorta after botulinum toxin injection for esophageal dysmotility. J Vasc Surg Cases Innov Tech. Sep 2020;6(3):388-391. doi:10.1016/j.jvscit.2020.04.005

4.           Chao CY, Raj A, Saad N, Hourigan L, Holtmann G. Esophageal perforation, inflammatory mediastinitis and pseudoaneurysm of the thoracic aorta as potential complications of botulinum toxin injection for achalasia. Dig Endosc. Jul 2015;27(5):618-21. doi:10.1111/den.12392

5.           Tan MZ, Whitgift J, Warren H. Mediastinitis, pseudo-aneurysm formation, aortic bleed, and death from endoscopic botulinum toxin injection. Endoscopy. 2016;48 Suppl 1:E186-7. doi:10.1055/s-0042-107074

Hickam Tricked 'em with the 'ol Red Herring Ruse

One of my favorite Charlie Munger quotes goes something like this:

"Warren, over the years you and I have appreciated the great value in learning from mistakes; Another thing we realized is that it's a lot more pleasurable to learn from other people's mistakes."

In light of that sage advice, here's another recent case report invoking Hickam's dictum. In this case, a 38-year-old man from Pakistan who has sex with men presents with uveitis and a rash on his palms and soles. He has a positive interferon-gamma release assay. This caused diagnostic confusion which resulted in the unnecessary invocation of Hickam's dictum. There is, after all, a simple explanation for the two findings, as I explicated in an online comment:

"This is an interesting case. Neither Ockham's razor, nor Hickam's dictum, nor Crabtree’s bludgeon need be invoked to sort it out.

The annual incidence of syphilis in men who have sex with men in the USA is a whopping 309 cases per 100,000 persons per year - almost as common as community acquired pneumonia in unselected adults. Compare that to 2.9 syphilis cases/100,000 person-years in men who have sex only with women. A risk factor that increases the incidence of disease over 100-fold should point even the novice diagnostician straight to the diagnosis. Combined with a rash on the palms and soles? The diagnosis is all but made. Positive RPR? We’re finished here! For guidance on using incidence/disease frequency as a surrogate for disease probability, see: https://pubmed.ncbi.nlm.nih.gov/34854514/

Next, IGRA (e.g., quantiferon Gold) is NOT a diagnostic test for active tuberculosis infection (indeed, active infection is a cause of false negative IGRA), it is used clinically as a marker of prior tuberculosis exposure. In Pakistan, the annual incidence of tuberculosis is 230 cases per 100,000 persons per year, so it is hardly surprising that this patient has a positive quantiferon-gold. This is a red herring rather than an instantiation of Hickam’s dictum. Likewise, the dermatologist consultation was a false negative test for secondary syphilis. It is unbelievable that they attributed this rash to psoriasis, but this highlights that we should not put too much credence into any single piece of data or consultation if it flies in the face of the totality of the evidence. Similarly, angiotensin converting enzyme (ACE) levels are notoriously both insensitive and non-specific.

In the end, there is a simple unifying (and unsurprising) diagnosis in this case: syphilitic rash and uveitis in a man who has sex with men. For an explication of Ockhams razor and Hickams dictum (and the limits of their inferential powers), see: https://pubmed.ncbi.nlm.nih.gov/39467949/

Interestingly, Hickam started in the Boston hospital system, went to Emory, then to Duke, and finally to Indiana. Though not formally specialty trained, he did pioneering work in ophthalmology research, as well as cardiopulmonary research. An entire edition of the Archives of Internal medicine was dedicated to him after his death by reprinting seven of his original papers – the entire issue of the journal."

Hickam's Victim: The Unwary Diagnostician

In this case report, the authors describe a woman, some 82 years of age who had immigrated from Korea 30 years prior to presenting with syncope and dehydration, which was soon discovered to be Salmonella enterica subspecies typhi. Despite urine culture growing gram negative rods, 

"CT of chest, abdomen, and pelvis without contrast was ordered to better characterize the source of her sepsis."

Ignoring that we already have a source for her sepsis (indeed the most common source: urosepsis), and that gram negative sepsis almost never originates from the chest, we will move on after noting that they found multiple cavitary lesions in the upper lobes of the lungs. The authors state that they tried to link the cavitary lung disease with the urinary tract infection (staghorn calculi were found too!) and Salmonella bacteremia, because of an inclination towards Ockham's razor, but alas learned that the chest disease was tuberculosis (who knew!?) so they invoke Hickam's dictum. I rather think that this is a case of Crabtree's bludgeon which states that:

"No set of mutually inconsistent observations can exist for which some human intellect canno t conceive a coherent explanation, however complicated."

Alas, much about the epidemiology and natural history of both Salmonella and tuberculosis in this case report was neglected, so I penned this letter to the editor, below. I did not receive confirmation of my submission, and this journal's website is a bit inchoate, so I assume my letter was lost....

Added on 10/6/2025: Actually, my letter was not lost, as I received an acceptance letter today, but only after the invoice charging me $1530.00 USD as a publication fee for a letter to the editor! But let me tell you, the reviews, wherever they came from, were over the moon with my "clinical acumen" and "insightful analysis".

I replied saying nevermind, I can't afford that charge to publish a *letter* They replied saying "how much can you afford?" I offered $200 and it was immediately accepted. Never overlook the value of flattery, or the cold hard dollar. 

So I will link the letter, after it is published. In the meantime, comment below if you have your own insights about the case.

Added 10/21/2025: Published letter linked here. Text below:

Letter to the Editor: Guo and Liu reported an interesting case of a woman who presented with Salmonella enterica serovar typhi bacteremia and was also concurrently diagnosed with pulmonary tuberculosis [1]. Readers of this report may appreciate two additional perspectives beyond those discussed by the authors. First, humans are the only reservoir for S. enterica serotype typhi; all disease results from human shedding of the bacterium and it is not endemic in the U.S [2]. Because the patient was a Korean resident 30 years ago when it was endemic there [3], it is most likely that she acquired the infection prior to immigration to the U.S., and the reported infection arose from a chronic carrier state. The source of carriage is usually the gallbladder, which was not mentioned in the report, but could have been the source of seeding the urinary tract. Second, as was recently reported [4], the juxtaposition of Hickam’s dictum and Ockham’s razor as conflicting clinical maxims oversimplifies their application to the diagnostic process. Multiple diseases in the same patient are commonplace, and concurrent diagnosis must consider timing of symptoms, probability, and causal connections between diseases in addition to the much rarer situation where two independent diseases present with nearly simultaneous symptoms [4]. The only plausible causal connection between Salmonella and tuberculosis in the case reported is that they were probably both acquired in Korea – a common cause that would seem to satisfy Ockham’s razor. But because the symptoms the patient sought care for are directly attributable to Salmonella bacteremia, the tuberculosis infection likely represents a chronic infection, or an incidentaloma, albeit a consequential one. Within a framework that considers symptom timing as a non-arbitrary marker of disease onset, physicians are alerted to the omnipresent possibility of discovering asymptomatic diseases such as incidentalomas if causal connections between two diseases discovered concurrently cannot be made. This framework obviates the impossible task of discerning which of two allegedly conflicting clinical axioms – Hickam’s dictum or Ockham’s razor – applies in a given case, since diagnosticians can never know, a priori, which one to invoke. In the final analysis, this patient had chronic, asymptomatic tuberculosis reactivation, which was accidentally discovered during her acute illness with Salmonella, both of which were acquired remotely in Korea.

1. Guo S, Liu M. A rare concurrent presentation of typhoid fever with bacteremia and pulmonary tuberculosis. Arch Clin Biomed Res 9 (2025): 226-228. 

2. Tagg KA, Kim JY, Henderson B, et al. Azithromycin-resistantpositive Salmonella enterica serovar Typhi in the United States. J Glob Antimicrob Resist 39 (2024): 69-72. 

3. Yoo S, Pai H, Byeon JH, et al. Epidemiology of Salmonella enterica serotype Typhi infections in Korea for recent 9 years: trends of antimicrobial resistance. J Korean Med Sci 19 (2004): 15-20.

4. Aberegg SK, Poole BR, Locke BW. Hickam’s dictum: an analysis of multiple diagnoses. J Gen Intern Med 39 (2024): 1-4.

Epistemic Arrogance. Case Records of the Massachusetts General Hospital. Diagnosis is Stochastic, NOT Deterministic

This post was spurred by my reading the July 24^th NEJM case records, “A Man with Cough, Dyspnea, and Hypoxemia.”  When I was still using twitter, I mused that the discussants have too high a rate of getting the right diagnosis. This implies that there is no stochastic or aleatory uncertainty in diagnosis; that if you have the requisite information and reasoning process, you can connect the dots, every single time, to the final diagnosis. In this view, there is no randomness to diagnosis, no inherent and irreducible probabilistic (or stochastic, or aleatory) uncertainty. Of course, this is pure codswallop: stochastic uncertainty is what makes diagnosis so hard.

You cannot say that the result in any case was not possible with the information presented, but with a population of cases you can make inferences about whether the percentage of correct discussant diagnoses is improbable. The fact that the discussant gets the right diagnosis almost 100% of the time (I have tabulated the % correct for over 10 years of these cases – it rounds to 100%) in the CRMGH (Case Records of the Massachusetts General Hospital) is like finding too little variability in a research study (or  studies; or Bernie Madoff’s annual returns) and concluding that the results (returns) were manipulated. We use our well-justified first principles assumption of stochasticity, find that there is not enough variability, and conclude that something is being manipulated to remove the aleatory uncertainty. (I use stochastic, aleatory, and probabilistic herein as interchangeable adjectives for uncertainty.) And so must it be in the CRMGH. How the aleatory uncertainty is being removed is anybody’s guess and any insider’s knowledge, I suppose. Possibilities include both implicit and explicit cues. An implicit cue may be the selection of, say, a specialist in heritable cardiomyopathies as the discussant in a case where the final diagnosis is a genetic cardiomyopathy. Explicit cues may be that somebody tells the discussant the final diagnosis at the outset or tells them to revise their discussion if they get it wrong in draft. Hospitals are not closed systems either. People hear if there was a case of Creutzfeld-Jacob diagnosed recently, and the director of the microbiology lab knows if a particular rare species was recently cultured. Tales of rare diagnoses spread, as they are the currency of clinical acumen. I can’t say that any of these mechanisms -- from subtle queueing to explicit cheating -- are occurring. I only know that the near 100% hit rate means that randomness has been removed from an inherently random process.

A Foolish Consistency: Policy, Practice, and Rationality in Medical Decision Making

"A foolish consistency is the hobgoblin of little minds, adored by little statesmen and philosophers and divines" - Ralph Waldo Emerson

As I was making coffee this morning, I grabbed a filter and realized that two may be stuck together. I faced a common dilemma: do I bother to separate them so as to not waste a filter? A trivial example, I will use it as an analogy for decisions we face every day in life and medicine.

Folks approach this kind of decision (or the decision to brush one's teeth, or wear a seatbelt) in various ways. Paul may have a "Paulicy" of never wasting anything, and separates them; doesn't-give-a-damn Sam would never bother; Sometimes Suzie separates them when she has time, and doesn't when she's in a hurry.

The decision hinges on the value of a filter in terms of cost, waste, etc. The value of a single filter is a rounding error, but clearly a lifetime of wasting filters can add up to a lot of filters magnified by the number of people wasting them. Why not go to great lengths to save every filter possible?

In this kind of situation, a rational agent may decide to institute a policy of doing things in a certain way, but accept deviation from that policy under special circumstances. My favorite example of this situation is in medicine with central lines. A left-sided line is not supposed to come at a 45-degree angle to the wall of the SVC; rare cases are reported where, over time, it can erode through the great veins and cause fatal hemorrhagic mediastinum. But what is the probability of that? Something on the order of one instance per 10,000 lines. Supposing you have just placed a left internal jugular hemodialysis catheter and the tip is at the proscribed 45-degree angle. You can't retract that catheter, and you can't advance it either. Do you replace it with a longer one? What if your right internal jugular 20 cm catheter is "too deep" into the right atrium; do you retract it and use the little clamp, knowing that often the line slides in it, increasing risk for infection? What if the upper great veins are suboptimal targets, but you've read the Parienti paper in NEJM and know that the risk of infectious and thrombotic complications doubles (but increases only a percent or so, absolute) with femoral vein catheters? Should the femoral vein be verboten?

In cases such as this and many more analogous ones, a rational agent may employ a general policy of always trying a priori to avoid the 45-degree angle; select the appropriate length catheter; and favor the upper access sites, but to allow exceptions whenever the probability of an untoward outcome in an individual case is low, and the costs of avoiding it are higher. In the case of the 45-degree dialysis catheter, the risks of infectious and mechanical complications of repositioning or replacing it exceed the benefits, especially if it is going to be in place for a short period of time. Reluctance to use the femoral site which has but a 1% increase in adverse events compared to the jugular can lead to far greater complications from forcing patients to lie flat for prolonged periods, or from failed attempts under more difficult operating conditions with non-collaborator patients (delirious, thrashing). The policy to default to a preferred standard becomes irrational when, in a specific case the preferred standard doesn't deserve its status.

The same situation is true with many policies. Studies have shown that a policy of routine use of right heart catheters in sepsis or ARDS does not benefit patients (it also does little harm). So, we have policy of NOT doing routine Swan-Ganz catheters. But that hardly means that in specific circumstances we should not do them. The same holds true for so much of what we do in medicine. Part of the problem is that physicians memorize the policy and the direction of harm/benefit ("there's an increased risk of DVT with femoral lines!"), but they don't know the magnitude of the effect.

So, to be a rational agent, you should establish a policy of what is best, under optimal conditions, for all-comers. But when you have more information a posteriori (because the line went into the wrong place; or you forgot your helmet; or your kid fell asleep in the car seat), default to the policy only if a cost-benefit analysis justifies it. Also, be on the lookout for situations where the all-comer policy does not apply. Like the 90-year-old patient with a small (250cc) complicated parapneumonic effusion. Policy says drain. Rational practice says hold tight; it's a small target, risk of complication or failed drainage higher, benefits of avoiding a small fibrothorax (losing 250cc of vital capacity) in someone with reduced life expectancy and limited mobility are small.

I was not in a hurry, so I separated the filters. Had I been running late or the kids were screaming, I may not have.

Edit to add later in the day: it occurred to me that I do a lot of anal-retentive things in my home, many concerned for the environment or recycling. Example: we don't use paper towels, or disposable plates/silverware. 

The consequence is when we have a get-together, guests can be out of sorts with my "environmental policies." Even though our family, as a routine policy, is (I hope) happy to adapt to these well-intentioned standards, the social costs of this routine policy are off-putting to my guests. So, I keep things in perspective: this is just one gathering, a roll of paper towels here and there is no big deal to avoid the off-putting social costs. So we use disposable stuff on occasion when the convenience in a specific instance overrides the general routine policy goals. Same would be true if you had a general policy of "no shoes in the house" that you let lapse when you invited guests into your home.

Many doctors would do well to make such exceptions to their general policies, in the name of building (or not spending) "social capital."

Bayesian Implications for Factitious Disorder

The next time you encounter a patient with an odd constellation of rare or poorly defined diseases (POTS and MCAS is a common duo), especially if a psychogenic one is on the list (e.g., PNES - not, I presume, intended to be sounded out, as it was proposed as a less offensive alternative to pseudoseizures), do yourself a favor and read one of Mark Feldman's excellent books on factitious disorder, such as the most recent, Dying to Be Ill.

These patients are wellsprings of iatrogenesis, but it is a special variety because the patients actively deceive physicians into unwittingly fostering complications through well-intentioned attempts to diagnose and treat disease. Several biases in medical decision making are exploited by patients with factitious disorder (and its close sibling, malingering, where the reward for the sick role is external - e.g., relief from work, military service or thwarting criminal justice proceedings - rather than internal), and I address some of them in this post.

Numeracy in Medicine: Clinical Wagers to Estimate Probability in Diagnosis

As has become my custom, I offered a wager on rounds the other day. An nonagenarian had gastrointestinal hemorrhage. He presented with syncope and gross (red) blood per rectum. History was significant for Apixaban for atrial fibrillation, and NSAID use. My questions to the team were: what are the possible etiologies of the bleeding; and which among are most likely? After the diagnostic possibilities were enumerated, I offered my wager: a $10 stake that it is peptic ulcer disease (PUD) at 4:1 odds. If the patient has PUD, a taker of my wager owes me $10. If the patient does not have PUD, I owe the taker the $10 stake multiplied by the odds: $40.

There are several pedagogical and practical reasons I engage my team in these games, most of them pedagogical. First, making a wager about clinical outcomes gives you skin in the game. It is remarkable how, when I assign a stake and odds, the interest level goes up and my would-be wager-takers become carefully attuned to the differential diagnosis and other pieces of data that until then had been glossed over or wholly neglected. Recently, when making a wager about results of a pending echocardiogram, the resident did a much deeper chart dive than had previously been done and found a remote echo which bore on the probabilities for the current wager. I had to reassign the odds in light of this new information. Related to this deeper search for available information about the case, there can be a search for information about the diseases under consideration. It would be folly to try to make a bet about the probability of a disease that you understand incompletely, or not at all. Skin in the game will likely lead you to www.uptodate.com where you can ascertain knowledge about the considered diseases to apply it to the wager.

Cheating in Medical School? A Personal Tale in the Wake of the Dartmouth Scandal

A recent NYT article about cheating at Dartmouth reminded me of some hermetic knowledge of cheating in medical school that I have kept mostly secret for almost a quarter century. Without commenting on the Dartmouth case, I will relate this tale to demonstrate that cheating in medical school is real, and my experience is the opposite that of Dartmouth - administrators turned a blind eye to cheating, denying its existence until confronted by direct evidence of it.

In 1996, the "final exam" after an 8-week internal medicine rotation was a so-called "shelf board" exam, which I have always understood as meaning a copy of some prior year's board examination, or a preparation test for it. In medical school in late August 1996, I had the top score on this examination during the first "rotation" of 8 blocks that we did during the third year. I was pleased by this and considered it vindication of my method of not "studying to the test" but instead reading Harrison's Principles of Internal Medicine (13th edition) cover to cover during the second and third years of medical school. I later noted that the top score crept up as the year went on, and I was bemused. Were others reading Harrison's Principles of Internal Medicine? Doubtful. There were rumors of a "question bank" that previous takers of the exam compiled as the year went on, and shared with one another. If the "shelf exam" was only changed each year this would make sense. Alternatively, the kids were just getting smarter as the year progressed.

Applying Applied Physiology to COVID: Silent Hypoxia and The Work of Breathing

Enough time has passed and enough clinical experience with the behavior of COVID gained that we can now apply some applied physiology to our understanding of this aweful illness.  I don't have the answers any more than the next person, but I do know that whatever the behavior of COIVD, it can be viewed through the lens of what we do know about applied lung physiology, and some inferences can be made.  This post will be about that physiology and those inferences, using the frameworks in these lectures about applied physiology.

One of the striking early observations about patients presenting with COVID was their apparent lack of distress despite very low oxygen saturations.  This was termed "silent hypoxia" at some point, and I leave it to internet sleuths to trace its origins.  It led to a policy of early intubation of some COVID patients:

“Never in my life have I had to ask a patient to get off the telephone because it was time to put in a breathing tube,” said Dr. Richard Levitan, who recently spent 10 days at Bellevue Hospital Center in Manhattan.

There are two simple explanations for the observed phenomenon of silent hypoxia: first is that hypoxia is not nearly as potent a stimulus of respiration as is hypercarbia, as I took great pains to explain in the Applied Physiology lectures, using the example of shallow water breath hold divers who do not pre-oxygenate and emerge with sats on the order of 50%, the same as climbers on Mt Everest.  (See also this post on the boy in the wheel well, unpressurized, from California to Hawaii.)  I thank Matt Wong (@EM_phile on Twitter) for pointing me to this video which provides a striking illustration of lack of dyspnea with sudden and severe hypoxemia.  This video is compulsory viewing:

Dyspnea is driven far more by ventilation demands and the work of breathing than it is by hypoxia alone.  This is underrecognized.  I wager this stems in part from the fact that in most diseases that cause hypoxia, there is significantly elevated work of breathing because of parenchymal disease/infiltration (elastic loads) and airway secretions (resistive loads), combined with minute ventilation loads from high CO2 production, dead space ventilation (Vd/Vt) and metabolic acidosis.  If COVID does not have all of those loads, patients may not experience substantial subjective dyspnea despite low oxygen.

Are the "Vent Protocols" causing harm in COVID?

Here is a response to Deborah Mayo's excellent blog post posing this question.  I encourage you to first read her post.  Here, I explicate my view of the problems that are raised in that post.  I don't have time for a lot of hot links and stuff, so post your specific comments below.

There is a lot correct here, and @learnfromerror has done a far better job of summarizing it than I could ever explain a normal distribution. But there is a lot missing, because the commentators have not gotten to the crux, and have made slogans for their points that are distracting and misguided if not totallly incorrect.

First, and this is very very important, is that *there are NO protocols for intubation* as the NYC ER doctor suggests. I talk about that on my other blog a lot. ARDS trials enroll patients who are *already intubated* and the criteria for that intubation are absent from the study protocols. It is assumed in an ARDS study that if you are intubated, you were appropriately intubated. Therefore, there is no “problem with the protocols” for ventilators, there is a glaring and longstanding problem with the criteria (or the absence of criteria) for intubating patients. Is it blood gas values, or vital signs, or physical examination signs, or subjective distress or some combination? There is ZERO standardization in this area. COVID has brought this underappreciated problem to the fore.

Why is this just coming out now? Ah, that’s another crux of the problem and a reason that COVID has become a perfect storm for ventilator management. Usually, if you intubate a little old lady with influenza, even if you do it for shaky reasons, she can be extubated (tube removed) in a couple of days or a week with little harm done (or with a level of harm that we take for granted, probably mistakenly). Not so with COVID. The natural history of the disease has 2 important features that make the decision to intubate likely to culminate in a massive therapeutic misadventure: 1.) the duration of the illness is protracted, two to perhaps as long as four weeks; and 2.) the level of sedation needed to counteract the massive air hunger these patients have, for the duration they need it, is through the roof.  This problem is compounded by the mandate to use small tidal volumes which are poorly tolerated in the face of massive air hunger. So, 2 weeks after intubation, they are veritable zombies, cannot be weaned from sedatives (a prerequisite from being weaned from the ventilator), and are stuck on the vent, assuming that before this stage other complications have not set in and/or death ensued.

Another facet of the perfect storm, which I think is also the Rosetta Stone, and a key to untangling this giant mess we find ourselves in, is that this normal lung compliance that people are talking about is *the reason why* there is this so-called “silent hypoxemia” of the type mentioned by the ER doc in Mayo’s post. Failure to recognize this connection betrays a common misunderstanding of respiratory physiology (my attempt to disabuse people of these errors can be found here: https://pulmccm.org/ards-review/great-lecture-applied-respiratory-physiology/). Dyspnea is not driven by hypoxemia as much as it is by hypercarbia, which can be compensated for by hyperventilation which these patients are doing! To a person who has a firm grasp on applied respiratory physiology, this is no surprise – the patients have compliant lungs, so they don’t have workload imbalance and can sustain ventilation in the face of significant hypoxemia (which is a MINOR driver of dyspnea) very well. In sum, I am not surprised by these clinical presentations, nor am I surprised that this quagmire has allowed problems with the understanding of applied respiratory physiology to surface.

This disease is very difficult for these and many other reasons. When the choice is let a hypoxemic person who is defending her CO2 - like the little old lady the ER doc talks about - ride it out (which she can probably do for a very long time, see my tweets about sustaining very high Ve indefinitely [50% of the 15-second MVV]), versus intubating her for a marginal gain in gas exchange accompanied by a massive cost in sedation and paralysis, the choice is clear, let them ride it out, don't incur that cost.

The problem is not with the “vent protocols” the problem lies in a widespread lack of understanding of applied respiratory physiology which leads to questionable calls regarding intubation which are usually, in non-pandemic times, lost in the signal and noise of the fray. Not so with COVID – premature or unnecessary intubations precipitate a cascade of status iatrogenicus.

"I'm Not Comfortable With"....Analyzing Decisions Involving Risk

A woman with upper gastrointestinal bleeding is admitted to the ICU with significant hemoglobin drop from baseline several months before.  The INR was >10 on admission, presumably reflecting sphlanchnic hypoperfusion during the bleeding episode (decreasing clearance or increasing effect of warfarin) in addition to consumption of clotting factors during bleeding.  The INR is reversed with vitamin K, and an EGD is performed showing a nonbleeding vessel which was clipped.  The following day, the patient is up and walking around and eating a full liquid diet with no further evidence of bleeding.  MAPs are in the mid to low 60s, and she is "called out" for a transfer to the regular medical ward.  The resident is reportedly "not comfortable with" having the patient on the floor with the low mean arterial pressures.  How best to analyze the situation?

(I will only briefly note that the expression of discomfort describes an emotional reaction that may or may not be concordant with a logical and factual analysis of the situation at hand.  In this case I suspect it has something to do with the availability heuristic, where dramatic events [gushing blood] are estimated to have higher probabilities than they warrant.)

The discomfort seems to stem from a concern that the patient will deteriorate on the regular medical ward and require interventions that are not available there, prompting readmission to the ICU and incurring the risk of a missed opportunity to provide necessary care during any delays in executing the transfer.  Factors that may raise that concern are marginal hemoglobin values (7-8) especially considering a baseline of almost twice that several months before, the size of the GIB and the resulting hemodynamic instability, the marginal MAPs at the time of transfer.  Mitigating factors are the absence of ongoing bleeding, the inference that any marginal MAPs must be from a residual volume deficit (she does not have coincident sepsis), that the vessel was successfully clipped, and the patient is up and walking about in spite of the measured MAPs.  But how are we to integrate this into an estimate of the risk that may be incurred from transfer?

The Bermuda Triangle of Guidewires: Do They Just Fly Away Never to Be Seen Again?

In last week's NEJM, author Matt Bivens reports an extraordinary experience: while inserting a venous catheter, he let go of the guidewire and moments later looked and saw it migrating into the patient's jugular vein, on its own.  He grabbed it as it was running away, just before it escaped from him.  While I can imagine, as he did, how it may have happened, it is an exceptional claim.  Some aspect of the venous circulation or respiratory motion must have been pulling the wire downstream into the patient, if this story is true.  I say "if" because it is truly extraordinary.  Not only must the venous circulatory flow have been "grabbing" the wire, carrying it downstream, it had to do so with enough force to overcome the friction of the wire as it traversed the tissues of the neck.  (Not mentioned is the size of the patient's neck or whether this happened pre- or post-dilation, or whether the patient was in Trendelenberg - if so the catheter had to be pulled up hill!)

I have never seen or felt a guidewire move in such a way, over 20 years and thousands of lines.  However, I did turn my back on an intern circa 2000 and that intern pushed and/or flushed the guidewire into the patient.  So I was interested in the 4 references in the article purporting to show that guidewires have wings or feet or that the venous circulation can pull them and overcome the tissue resistance and mass of the wire.  Here is a summary:

The Truth Doesn't Always Need A Test: Thresholds for Medical Decisions

Jason Carr, MD didn't need a test to know what this is

Kassirer (and Pauker) got the idea for the Threshold Approach to Medical Decisions in part (as he tells it in his memoir Unanticipated Outcomes) because he had observed a pattern of irrational behavior among nephrologists (he was one) in the 1960s.  Evaluating a patient with nephrotic syndrome and knowing the diagnosis was very likely to be membranous glomerulonephritis, most nephrologists still insisted on a biopsy prior to starting corticosteroids.  Pauker and Kassirer realized that we never get to 100% certainty in medicine and that tests only modify the pre-test probability of disease.  They reasoned that there ought to be a threshold of pre-test probability of disease that is high enough to justify treatment without testing.  That is, sometimes, the pre-test probability of disease is so high as that it obviates testing, and we can just skip to treatment and avoid risky and invasive testing like a kidney biopsy.  Only if the disease fails to respond to therapy (thereby reducing the clinical pre-test probability below the treatment threshold) should we resort to the biopsy.

Almost 40 years after the publication of their article, we still are not consistently following the axioms of the threshold approach.  Here are several recent examples:

A 20-something black woman presents with cough, weight loss, massive hilar and mediastinal lymphadenopathy and interstitial parenchymal changes.  She is scheduled for a bronchoscopy and EBUS to confirm the diagnosis of sarcoidosis prior to initiating corticosteroids.

The Test is Not the Truth: One Week in the Lonely Life of a Bayesian Clinician

DAH from GPA or CPE/ESRD?

If there is one thing you should remember about clinical decision making it is this:  the test is not the truth.  A diagnostic test raises or decreases the prior or pre-test probability (PTP) of the disease under consideration.  The amount of increase or decrease in probability with a positive or negative test depends on the starting probability and the likelihood ratio of the test.  (LR+ = sensitivity/1-specificity; LR- = 1-sensitivity/specificity).  If we don't attend to the PTP of disease, serious diagnostic errors and therapeutic misadventures may result.  This is especially true when a low PTP disease is diagnosed on the basis of a test with poor sensitivity and specificity (and a LR not much greater than 1 or 2 or even 4 or 5).  Several examples of this came up a while back.

A woman presented with thunderclap headache and had recurrent seizures during initial evaluation.  A differential diagnosis was formulated and it included PRES (posterior reversible encephalopathy syndrome) with a PTP of about 20%.  Subarachnoid hemorrhage was excluded with CT and LP and the PTP of PRES rose to about 40% (since it occupied some of the probability space previously occupied by SAH once the latter was excluded.)  The subsequent MRI images were consistent with PRES.  Nonetheless, a vascular MRI was ordered to "exclude the possibility of cerebral vasculitis".  The problems are twofold.  First, the probability of PRES is now on the order of 70% if the sensitivity and specificity of MRI are on the order of 80%, and it is 85% if sensitivity and specificity are each 90%.  (Go ahead and plug some numbers into the calculator on the sidebar of the blog.)  This probability meets or exceeds the probability threshold to both consider the diagnosis made, and to take action based on it.  In this case inaction and supportive care are indicated.  Even if a vascular MRI were consistent with cerebral vasculitis, which has a PTP an order of magnitude or more less than PRES, the diagnosis is still PRES.  The truth is not in the test, the truth is in the rationally considered diagnostic process of which the test is one part.

Pitfalls of Protocols: Pushing the Limits of Extubation

A recent post described extubating an asthmatic patient with very bad weaning parameters, and I promised to provide a followup telling whether he "flew" or not.

He flew.

It was a nail-biting experience and for the first hour it was unclear if he was going to make it.  His respiratory rate settled down into the teens which was reassuring, but he did not gain lucidity for quite a while and was intermittently midly "combative" and uncooperative.  He was on HFNC with oxygen saturations in the high 80s and low 90s, and he remained tachycardic and was wheezing.  His wife and the nurse were continuously in the room reassuring him, as were several doctors during the first hour or two.  During the course of several hours, he was able to be weaned to simple face mask and then nasal cannula and the next day he was discharged from the ICU.

If we had followed some sort of "weaning protocol" with blind faith, I don't know how long it would have been before he would have "passed" the protocol's tests and been extubated.  At some point, somebody would have said, "Hey, we better stray here, or we'll never get him extubated."

Limits of the Possible: Clinical Reasoning of a Harrowing Extubation

"The only way of discovering the limits of the possible is to venture a little way past them into the impossible."  -  Clark's Second Law

In prior posts here and on the Medical Evidence Blog (here, here, here, and here), I have outlined my position that the only way you can really know if a patient can breathe on their own is to let them try - a "trial of extubation".  Prediction equations get you published, but their signal to noise ratio is often poor and ignored, to patients' peril.  Indeed the reason I'm obsessed with extubation is because I think being intubated unnecessarily is one of the worst things a patient can endure, and the best thing I can do as an intensivist is identify the earliest moment when a patient can breathe on his own and extubate him.

I faced a very harrowing extubation decision recently, and I admitted to the medical students that it was the most nail-biting of my career.  But I think analyzing it, both before and after the fact can be very instructive.

Speed Matters: Landmark Guided Left Subclavian Vein Central Venous Catheter Insertion & the "Deep Spot"

Recently, I got permission from a patient to video a subclavian line insertion.  This patient was absolutely terrified of any line insertion as he had had many in the past and a lot of them had been traumatic, prolonged, and painful.  I offered a bedside subclavian as an alternative to a PICC line or a right internal jugular in Interventional Radiology, promising that the entire procedure could be done in under 10 minutes.  It took just over 2 minutes, excluding prepping, draping, locally anesthetizing, and suturing.  These aspects would have added about another 3-4 minutes to the task.  Before the video started, I had infiltrated the area generously with 2% lidocaine, after prepping and draping in the usual careful fashion.

Before you watch the video, I should describe the essence of subclavian landmarking and several mandates of the procedure.  The key anatomical landmark is a spot seen in the photo accompanying this post that I call "the deep spot."  This is a spot along the inferior border of the clavicle, about 4 inches from the suprasternal notch (SSN).  It is important because it is the spot where soft tissue adjacent to the inferior border of the clavicle can be depressed the deepest, allowing the needle the easiest access to the subclavian region while being inserted "FLAT, FLAT, FLAT, FLAT, FLAT" under the clavicle with respect to the ground, i.e., parallel to the ground.  Entering the subclavicular region in this spot and remaining flat/parallel to the ground are keys to both success and avoidance of the oh-so-feared (but rare!) pneumothorax.

This spot can be found by making the middle finger and the thumb of the non-dominant hand into a comfortable "C" shape as seen in the photo.  The middle finger and thumb will be parallel to each other when in the "C" shape and will be about 4-5 inches apart depending on your fingers and the patient's anatomy.  With the middle finger in the SSN, the thumb finds the spot along the inferior border of the clavicle where the skin can be depressed the deepest.  If you're too medial, you will be atop ribs and "too high not deep enough" and if you're too lateral from the SSN, you will start climbing up the humeral head and deltoid and be "too high, not deep enough".  If you are too close to the clavicle or atop it, you will not be in the "deep spot" (it is a finger breadth or so inferior) and if you go too inferior from the clavicle, you will climb atop the pectoralis/breast and not be in the deepest spot.  Find the "deep spot"!  Again, the point (no pun intended) is to find the spot where the tissues near the clavicle can be depressed the deepest to facilitate the insertion of the needle under the clavicle and parallel to the ground.  This cannot be overemphasized, and you can feel for that spot on yourself or a willing companion for practice.

Once this spot is located, you anesthetize and then use the needle to confidently identify the clavicle and by advancing the needle towards the SSN, you can press down with your thumb on the needle (even the part under the skin) to depress it so that when advanced, it is parallel to the ground towards the SSN and it goes easily under the clavicle.  You should never "dive" to try to get under the clavicle, or use the clavicle as a fulcrum, bending the needle downward.  Watch the video carefully to see how I'm using several tactile inputs to determine where the clavicle is as I guide the needle under it.  You will see that the first several "pokes" or short advancements of the needle hit the clavicle (it happens fast, watch carefully!) which is a very important tactile confirmation of where you are, and then I push the inserted needle down with the left thumb to allow the advancement to proceed below the clavicle.

As seen in the video, the SCV is often entered when the needle is maximally inserted ("hubbed") with the skin invaginating, or upon withdrawal.  Notice too in the video that the flash was subtle at first and too rapid a withdrawal might have missed it.  Also in the video, the flash was highly positional, and the exact optimal position had to be found by iterative advancement and withdrawal and then maintained by carefully pinching the hub of the needle with the hand referenced to the patient's chest to allow the wire to be fed without inadvertent and unrecognized migration of the needle out of the vessel.

The voice overlay of the video gives several other useful tips and I hope you enjoy watching it.  The SCV central line is one of the final remaining procedures where use of ultrasound guidance (USG) confers minimal, if any benefit, and USG markedly prolongs this (and all) procedures.  Over my career during the past 20 years, I estimate I have done 500 or more SCV catheters all guided by landmark, most in critically ill patients.  I had *one* pneumothorax (PTX), in 2011 in a patient with severe COPD.  (I also supervised a resident once where there was a PTX, and to this day I don't understand how it happened.)  In properly trained hands, this procedure is incredibly safe, is the preferred location for a central venous catheter in terms of patient comfort, and infection and thrombosis risks, can be performed with a very high success rate using landmarks alone, and can be done very speedily.  Speed is the final frontier: Safety, Success, Speed.

Here is the NEJM.org video, for comparison:  https://www.youtube.com/watch?v=braNvVl8-QU

And here is a Right Internal Jugular HD Catheter insertion using landmarks by The Phlegmfighter (yours truly).

Activated Charcoal and Beta Blocker Overdose: Clinical Decision Making and the Risks of Dichotomization

This very nice case report in the current issue of the Annals of the ATS is an opportunity to discuss rational clinical decision making.  The authors did almost everything that I would have done in this case and it is a lovely discussion of this toxidrome and its treatment.  There is just one simple and apparently inconsequential decision that I disagree with and I intend to use it as a springboard to discuss rational clinical decision making.

The young woman had a multidrug overdose including metoprolol succinate, extended release.  She presented in shock.  The authors state "Gastrointestinal decontamination was not performed because her ingestion was suspected to have occurred several hours before admission" [emphasis mine].  I have already in an early post on this blog, discussed the inadequacy of the existing data and experimental models on the timing of charcoal administration, which interested readers can read about here.

Studies of the timing of Activated Charcoal (AC) administration use normal volunteers taking therapeutic doses of drugs (for ethical reasons).  We have inadequate data on the speed of absorption of drugs in people who are shocked or who take very large doses of drugs, or extended release drugs.  To dichotomize the efficacy of AC by a bright line of 30 or 60 or even 120 minutes is a gross oversimplification of reality that belies overconfidence in the existing data and experimental models.  This patient took a large dose of a sustained release medication and at some point became shocked presumably causing splanchnic vasoconstriction.  She also took Tramadol and other medications which may slow gut motility via anticholinergic or other effects.  And there may be other unknowns - other medications she took that slowed absorption of the sustained release metoprolol that we don't even know about.