Research and sepsis and biomarkers in practice oh my!


I didn’t forget about the blog…

However, as some might notice, my writing is a pretty good indicator of how busy I am. This last month was fairly busy without any payoff yet, but I am hoping that will come.

The month started off with me wrestling with all of the administrative paperwork of applying for a license to practice in another country which seems to really value useless bureaucracy even more so than Poland if that is possible. To their credit, the bureaucracy in Poland is mostly a formality and in my experience, more often than not, the paperwork catches up to what is happening, what happens is usually not waiting for papers. (though there are some exceptions as with all things in life)

But As if hunting down employers over the last 10 years and begging them to sign and mail paperwork to me was not keeping me busy enough, I have to take an English language proficiency test as a requirement. I have to admit I really have not been studying for it and hopefully it will be the last block in the road.

Of course, when it rains it pours, and I was sent an email that I was invited to submit an article in 30 days and to put together an original research article on diagnostic biomarkers in emergencies in a fairly respectable journal. I tried to rally just about every researcher I knew for usable data and unfortunately, came up short. So despite a fairly intense effort, publication number 10 will have to wait a bit.

But the medical topic I would like to write about today ties into the call for emergency biomarkers. That topic is sepsis. There are all kinds of efforts underway all around the world to identify and treat sepsis. The most prolific is the surviving sepsis campaign. I am working under the influence of the idea (and some coffee) that the whole point of the campaign was to get providers to think about sepsis, not really to be a great guide on how to treat it. Most of the treatment recommendations are after all fairly dated and more than a little vague.

But here is the rub with sepsis. Gross clinical signs of sepsis are late stage; in many cases well past the stage where treatment is effective. All of the non-intensive care providers I talk to are under the impression that SIRS precedes sepsis rather than being a pathological process of its own. Consequently, they are using SIRS criteria to attempt to diagnose sepsis, and not surprisingly, it usually turns out 1 of 2 ways. 1. They recognize clinical symptoms that are late in presentation like with sepsis. 2. They get some negative cultures back and then aren’t sure how to proceed.

The real trick to discovering sepsis before gross clinical symptoms are present is a high index of suspicion based on knowledge of the most likely culprits of sepsis. Like all occult conditions, you generally have to specifically look for them and rule them in or out. As we know, patients do not come with a multiple choice answer sheet on what their disease process is. Providers also have to understand disease progression, which doesn’t seem to be very popular today. Disease and diagnosis like emergency treatment should always pose the question “what happens next?” Here is my favorite example. Parents bring their kid (let’s say 6-8 years old) to the doctor for upper respiratory complaints. Most doctors, especially PCPs whom I have no love for, then decide since the child just presented, it is within the time period of a virus, so they diagnose virus, and suggest a bunch of over the counter medications, like they have mystically solved the puzzle. There is just one problem… In the year 2015, with this great invention called the “internet” and pharmacists who are more than willing and able to recommend the same “treatments”, parents don’t bring kids to the doctor the day they get sick. They usually show up a few days after the internet and the pharmacist already failed them. They show up after the school officials have deemed the kid too sick to attend, or after they have missed work taking care of the kid for a few days. This completely changes where in the course of the illness the child is and “what happens next.?”

This is where the emergency room comes into play. Because at 0’ dark 30, when the parents and kids cannot cope anymore, either EMS will be called, or they parents will drive to the emergency department (A&E for all the UK and common wealth folks). This is where we start discussing dehydration, pneumonia, IVs, breathing treatments, x-rays, admissions, and the potential of SIRS and subclinical sepsis. Now out comes some mantra of “early antibiotic” administration. Hmmm… Early antibiotics for sick people…Sounds sort of counter intuitive to many. After all, rumor has it that despite less than 16% of all world antibiotic usage being in humans, inappropriately giving them out might create some resistant pandemic. Pay no attention to what you learned about gene mutation being more common with each replication in general biology. Pay no attention to the idea that incomplete antibiotic therapy leads to resistance. Do not consider for a minute that autoimmune conversion of pharyngeal flora has the potential to cause chronic health problems like heart valve insufficiency in a decade or 2 like in the developing world, which will require cardiac surgery and valve replacement. (I didn’t forget about repair, but despite being taught how to do it, it doesn’t seem to work very often for the best cardiac surgeons and ends up being a replacement anyway.) It is much easier on a real human than on a pig heart though. The pig valves are really thin and being dead, they don’t retain form very well.

But I digress. The Surviving Sepsis campaign is recommending early antibiotic administration. There is actually a very good reason for this. As I described above, the clinical signs of sepsis are late in progression. So if you actually notice them, it is probably well past time for antibiotic therapy and the ICU folks will have a wonderful time playing mad scientist and trying to mix and match all sorts of coverage cocktails waiting for cultures and the bacteriograms.

Despite my falling short on the deadline for my original research in emergency biomarkers, I have published a couple of papers on early biomarkers in sepsis, and the bottom line is: There are no reliable ones. But in researching them, I discovered something. Actually, I didn’t discover it, I was taught in school and tested on it, but during the research I started actually practicing it regularly… You have to look for and identify common causes of infection. I don’t mean pneumonia or UTI. I mean the specific bacteria, incubation periods, vectors, the whole deal. You have to select antibiotic cocktails that specifically cover those.

The very key to successfully treating sepsis is subclinical detection. It is difficult, but like anything else in medicine, prevention is better than early treatment, which is better than late treatment. Prevention and early treatment means anticipating, not reacting.

This applies to more than just sepsis. It applies to every type of medical emergency; from massive hemorrhage, stroke, MI, to all the rest. That is why emergency providers are always asking history questions relevant to these conditions. But particularly in sepsis, providers need to start looking at “infection history.” Prior to sepsis, they need to prevent or treat early. Since there are no reliable biomarkers, the lactate measurements, etc. are imperfect tools, that suffer from multiple limitations. Is it SIRS or sepsis? Let the people who normally figure that out figure that out. In the meanwhile, give the damn antibiotics. It also wouldn’t hurt to look at “infection history”, specifically test for the common causes of sepsis, like pneumonia, urinary tract infections, etc. It also wouldn’t hurt to attempt to give directed antibiotic treatment to the likely causes and it may require a cocktail. The time for treating sepsis is not when it is so obvious you recognize it. The time for treating it is when you can’t see it.

Don’t pay lip-service to the mantra children are not adults. Children come in various developmental stages. They have different physiology in the different stages. I like to think of it as the diagrams of insect development I had to suffer through in biology class. (The same place I learned about DNA mutation funny enough.) In any class you take in pediatrics you will hear: “Children compensate really well, they may not even look like they are sick, but when they crash they crash hard.” We hear it. We say it. But we don’t think about it. How sick is a kid? You have to have a high index of suspicion, they compensate really well. Not just in life and death pathologies, but in all of them. Overt signs are not early signs. You have to search for occult pathology. The signs and symptoms and guidelines for things like infection in adults do not readily apply. After all, would you expect to see the same symptoms of a disease (or even the same diseases) in a caterpillar as a butterfly? Of course not. Are you using that basic biology knowledge in your medical practice or just trying to memorize and equate if:then statements? (You may find this hard to believe, but there is actually a valid reason you had to take basic courses like biology, chemistry, and physics, in order to become a doctor.) If you had poor teachers, they didn’t tell you why or how it applied. But now that I have told you, start applying it. If you want to more; I think my rates are reasonable, I am sure we can set something up.

In closing: Biomarkers, medical adjuncts like ultrasound, x-ray, labs, and on and on are just tools. They help differentiate between things you are knowledgeable about. Without knowledge, they will not help. Guidelines will not help. (or if they do it is by accident) Why on Earth would anyone go to a doctor, much less pay the doctor who sometimes accidentally finds the right diagnosis and treatment because (s)he simply does the same thing for everyone? That is historic medicine! Imbalance of Humors, tincture of arsenic type of practice.

Firearms enthusiasts would call such an approach “shot-gunning” or perhaps “spray and pray”. Nobody gets awards for that. If you want a trophy, you need precision and accuracy. Call it…”Medical sniping.” There’s no secret to it, it is not magic. Education, knowledge, technique, and practice.

This post sponsored by all the numerous people talking about sepsis I have listened to this week. (Much smarter people I must say that vaccine deniers and homeopaths)

PS: Grammar Nazis take note, according to word, all grammar and spelling is correct. Any errors are likely from the normal limitations of pasting word documents to WordPress.