CLINICAL GUIDELINES: A Personal Perspective! Boon or Bane? The Good, The Bad and The Ugly!

 

THE GOOD: 

Guidelines have always been considered as the cornerstone with regard to treatment protocols for all healthcare providers and patients alike. The availability of guidelines is a godsend because it really makes treatment of diseases easier, more structured and everyone can rest assured that it is in keeping with the normally accepted standards.  It is based mostly on robust clinical evidence-based recommendations to help both patients and medical practitioners alike in having an informed decision regarding medical interventions. It is for these reasons that it has always been used as a gold standard to evaluate  good clinical practice for all doctors, medical trainees and training programs alike. In addition to helping medical professionals and patients, HMO's especially in the first world countries like US, use this as their barometer in their approval process to decide whether the recommended medical interventions and treatment protocols are justified.  

THE BAD:

     1. The Fallacy called " Expert Opinion" 

While published guidelines are mostly evidence-based, I must emphasize that there are exceptions to this rule for which many of us may not be aware of. While it is mostly based on solid foundation called evidence, there are limitations we physicians must be aware of. Where there is paucity of information & data, medical experts on special situation fill in their recommendations based on  "expert opinion" and therefore are incorporated despite insufficient evidence. As medical practitioners,  this is where it gets blurred and murky, we need to discern and know what is evidence-based and what is not.  

     2. Guidelines: A work in progress

Unbeknownst to many, clinical recommendations come from information gathered from studies of the past, as much as  5yrs old.  While updates come with the aura of being  fresh, they actually come from historical clinical data some of which may already be obsolete by the time they get published. It is for one of these reasons that we consider guidelines as merely guidelines and therefore should not  override critical thinking.  Guidelines will and should always be considered a work in progress. Despite these shortcomings, they are an integral part of medical practice now and in the foreseeable future. Based on my observations, it is unfortunate that many seems to subconsciously apply guidelines-based protocol as a "rule that should be followed" all the time.  It was meant to streamline and assist medical practitioners stay current but, it should  absolutely not to replace the use of good clinical judgement and our most important asset called common sense.  

    3. The Disconnect : Clear and present danger

We tend to  consider the fact that guidelines are basically generated from the first world countries like the US and EU.  There will always be some disconnect and that it is not one size fits all.  In the Philippines, we simply copy and paste what the first world countries would put out and label it as our own but, that is far from making it fit our local situation. For example, the original Mc Donalds in the US only serve chicken and fries which won't sell locally, so they adjust to our local demands and sell chicken with rice instead. As the saying goes, when in Rome, be a Roman.  In the same token, our guidelines must  be customized to fit our unique situation, especially on the disparity of our economic standards. We do not have any socialized medicine that is at par with that of the first world and we do not have adequate safety net on people  who are economically challenged. This is where our local guidelines fail miserably. Failure to see the light and adjust is our clear and present danger in the healthcare industry.  

    4. The Era of Reflex intervention 

Guidelines tend to spoon feed healthcare providers and it is becoming part of the problem. It makes us lose the art of thinking and analyzing disease processes based on pathophysiology,  the very foundation of teachings in medical school. It is very much like a wild animal being domesticated to the point they lose their innate instinct and ability to survive in the wild. If it is suddenly released without proper training, this wild animal may not be able to survive.  Guidelines are available for practically all conditions and doctors use them all the time and this process leaves us to forget the art and rationale of using our brain. After some time of repetitive action, medical intervention becomes a reflex rather than a thoughtful process largely devoid of meaningful understanding.

 THE UGLY: 

     1. Medical Practice as an Art

 Medical doctors study to human physiology and disease processes  from medical school.  This is followed by post graduate residency training that can take several years to achieve clinical competence. While guidelines make medical decisions simple and straight forward,  over dependence on  it inadvertently made many healthcare providers stop to cultivate and hone the art of critical thinking. We become too dependent on data-driven therapies that once data is not available, many would freeze and get paralyzed. Case in point, is the most recent covid pandemic that wreaked havoc around the world. The recent pandemic was truly a humbling experience to all healthcare providers, it reemphasized that the  practice of medicine is still very much an art and not a perfect science.

    2. Pitfalls: "Copy & Paste Strategy"

The Covid pandemic was the greatest equalizer, as it affected everyone regardless of gender and social status.  It leveled the playing field in the healthcare sector, as none of us  had any prior experience with regard to managing this disease.  The paucity of information added to the dire situation during the crisis. Doctors and researchers scrambled to understand the disease and whatever available information we had came out in trickles.  As the world waited with bated breath for additional information and understanding, the best that  doctors resorted to was what I call the  "Copy & Paste" approach. We copied treatment protocols regardless of proof of benefit from other countries. Despite our best efforts, many patients died with an unheard of proportion and yet despite the meager success we experienced on the sickest of the sick.  We continued to implement many of what we later realized as failed therapies simply because we had nothing much to hold on to. Every intervention was considered experimental and early treatment was literally a case of trial and error. The magnitude of the problem made some doctors stood frozen & resigned while many others continued  a valiant fight and did their best to understand.

3. Anecdotal Evidence: Testing the Hypothesis

Early on, I realized the need to go back and understand basic pathophysiology. The most significant breakthrough came out with  the concept called "Cytokine Storm".  It was a good first step in understanding the role of rising inflammatory plasma cytokines  that would eventually overwhelm the body's defenses. To test this hypothesis head on came the idea of doing plasmapheresis, a procedure used to treat certain autoimmune diseases. This procedure entails the removal of the patient's so called "dirty plasma" and then replace  it with fresh plasma much like doing an oil change in cars.  It is a very slow tedious process that could take as much as 12-24 hours to finish.  I noticed the dramatic effect with improvement on the patient's  oxygen saturation starting as early as the 2nd hour of therapy.  Almost all of  the patients treated with plasmapheresis required less oxygenation at the end of the treatment proving without a doubt  on the important role of cytokines.  The procedure hastened healing, aborted intubation and shortened intubation time on those who were already mechanically ventilated. I felt so certain of the benefit that I decided to share my experience with my colleagues in the hope that they too would  try to benefit others but, unfortunately it mostly  fell on deaf ears. 

The benefit on the pioneering patient, a 68 yo female, diabetic, hypertensive and  atrial fibrillation admitted on June 9, 2020 was extremely remarkable. Many gave her  a   zero chance at healing, but her 

subsequent recovery was very fast, short of being called a miracle.  She was intubated at the ER with ARDS and diffuse bilateral pulmonary infiltrates on  CXR. Her O2 saturation was in the 50's despite maximal O2 via nasal cannula. Despite the two days of delay in treatment  to get the necessary approvals (Emergency Hospital Approval and Patient Consent) for the planned experimental therapy,  she responded positively at an unprecedented speed once the treatment was commenced. She was extubated in less than a week and discharged after only 12 total days in the hospital. She was treated with a combination of plasmatherapy, aggressive anticoagulation and convalescent plasma transfusion (another pioneering therapy by giving passive immunity using harvested plasma from recovered covid patient). Despite the dramatic effect, I can still remember hearing comments that mine could simply be due to chance and the evidence considered anecdotal at best. This approach became my standard of therapy on all subsequent covid patients admitted under my watch. Over time and with many more experience with plasmatherapy  sometime in the year 2022, plasmatherapy was officially recognized as an acceptable and a recommended therapeutic adjunct for the severely sick covid. While data came late, it did support the benefit observed on this pioneering patient. 

     4. Treatment by Intuition

 As the saying goes, we learn more from the mistake we make than on those that we do right. Just like anything in medicine, we learn not only from patients who survived but, we also learn from those who died. Post mortem analysis gave us a glimpse with the  added understanding that diffuse clot formation was prevalent and could be responsible for the majority of the clinical manifestations of the disease. Diffuse clot formation can affect various organ systems like the lung circulation (poor oxygenation), kidney (Renal failure) or heart (myocardial infarction or heart attack). Recognizing the importance of hypercoagulability, led a world renowned cardiologist, Dr. Valentin Fuster of Mt. Sinai Hospital in New York to implement and later found benefit with the use of  anticoagulant called Enoxaparine. An approach he readily admitted as based solely on feel and intuition. A virtually unheard of strategy in a data-driven field of medicine done by force of circumstance. They estimated that it afforded at least 50% better survival rate on admitted patients given enoxaparine than those without. His protocol rapidly gained wide acceptance despite it being simply an observational study. The use of the anticoagulant enoxaparine became the default standard for all hospitalized covid patients around the world. 

    5. Pitfalls of Copy & Paste Approach

As beneficial as enoxaparine maybe, there were patients who would break thru it and continue to form clots unabated.  Enoxaparine is given at a  fix dose based on weight. While routine testing is not necessary, it is available by measuring Anti-Xa activity in select hospitals in the US and EU. It is the only known test to evaluate enoxaparine's  anticoagulant effect which was not available locally. Rising D-dimer (breakdown products of clot) suggests aggressive clot formation and if this occurs despite being on enoxaparine is a very bad sign. If clot formation is  left unabated, the patient's lung, heart and renal function  would start to deteriorate.  Since enoxaparine is excreted by the kidneys, once the renal function starts to deteriorate,  the natural reflex for us physicians was to reduce the dose in the hope of avoiding toxicity & subsequent bleeding. While seemingly a logical approach, to me it was  counterproductive because reducing enoxaparine would accelerate more clotting that would eventually lead to worsening renal function and dialysis. Recognizing this potential problem, I shifted and used another anticoagulant called heparin. A drug that we can readily measure its anticoagulant effect using a test called aPTT (Activated Partial Thromboplastin Time). 

    6. Back to Basic Pharmacology

Aside from our inability to measure adequate anticoagulation effect with enoxaparine, another potential problem that came to my mind was the unpredictable bioavailability on  those who are on vasopressor  support. Bioavailability, is the amount of drug that gets absorbed and be made available in the circulation to provide its anticoagulant effect. Enoxaparine is given subcutaneously and since patients who are on vasopressor support are so vasconstricted, it would potentially make absorption of the drug quite unpredictable.  The use of IV heparin would now address both issues on bioavailability and our ability measure the efficacy of anticoagulation.  It is tantamount to putting your headlights on during night driving so you know where you are going and avoid accidents. The only drawback for the aPTT test was the rather long turnaround time which can take several hours and covid patients did not have that luxury of time. To tackle this handicap, I reached out and used the cartridge type ACT (Activated Clotting Time) we normally use in the cardiac catheterization lab. This method affords us with an ACT result being available in minutes rather than hours. Now that all challenges have been addressed, I was assured of not only having a 100% bioavailability, know the degree of anticoagulation and most importantly with a very short ACT turnaround time to allow rapid heparin dose adjustments. I have seen so many patients improve and recover fully with this strategy during the pandemic.

    7. Keep an Open Mind: Bias vs Ego 

The benefit I saw on the patients were undeniable but, convincing colleagues to consider using it was another challenge of the tallest order. Many resisted and failed to take the time to  understand, much less recognize the benefit of this novel therapeutic option.  It was a huge challenge in convincing  colleagues who are stuck with what they thought was just as appropriate.  It was an understandable resistance because during that era of uncertainty, everyone's opinion is considered correct. It was not until the latter part of  the pandemic when clinical studies supported the seemingly aggressive approach I used. The trial was published in the NEJM (August 4, 2021N Engl J Med 2021;385:777-789)  which showed a remarkable benefit and superiority with full anticoagulation using IV heparin on severe covid patients vs the standard anticoagulation approach. Again and again, this strategy came out to be correct but, again, just like anything else in medicine evidence is always late.

All be told, healthcare providers get very dependent on guidelines making many  forget the true essence and  art of healing. Covid pandemic was  a humbling experience for everyone in the healthcare industry,  reminding us to always be vigilant and keep an open mind.  That there is so much value to be had if we go back to basic and use our God-given gift called common sense.