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against COVID-19: a story of a mid-sized city in Brazil.
A clinicians personal experience - reported by cardiologist Fernando Luiz de Melo Bernardi, M.D.
Fernando Bernardi 11.07.2020
A Game-changing Triad against COVID-19: a story of a mid-sized city in Brazil
The COVID-19 Pandemic has been haunting the World for more than six months now. The death toll is unparalleled for modern medicine, so it is the physical and psychological morbidity that the virus will leave in millions across the globe. But what has been most striking is the incapacity of medicine to find an effective consensual treatment, even after nearly 8 million confirmed cases and an unprecedented number of studies in such a short time.
COVID-19 has caught the attention of not just infectologists and intensivists, but all physicians regardless of their specialty. As a young interventional cardiologist who still praises much of his Internal Medicine background, I was no different. Three months ago, when an outbreak struck some meat processing plants in our region, the locomotive of our economy, the first cases being admitted in our hospital quickly grew exponentially. As I was still an active member of our general ICU, I found myself soon engulfed in COVID-19 matters, participating in the protocol's design.
At first, considering ourselves a non-expressive health facility, we followed recommendations from renowned national and international institutions. The instructions were clear, early intubation for severe pneumonic cases followed by supportive care in ICU. So we did it. But soon, we realized how complex treating these intubated patients were. The death rates reported from highly experienced ICUs were high, above 25%. Moreover, the intubation process per se was extremely stressful. My first experience intubating a COVID-19 patient was a 43-year-old man. The technique was not to pre-ventilate to avoid aerosolization of respiratory secretion, which could put myself and the whole team at risk. Despite being successful in my very first attempt, the patient's pulse oximetry dropped to below 60%. And that occurred with most patients that needed an endotracheal tube, with some terrifying cases.
That left me to wonder how many lives were potentially being lost around the World during the intubation process. On top of that, we began staring at the risk of running out of ICU beds and mechanical ventilators. A local tragedy seemed inevitable unless we found a solution based on our reality and limitations. We could not wait anymore for randomized clinical trials, and one thing was crystal clear: we had to minimize invasive mechanical ventilation. Thankfully, we were successful as we saw the number of deaths and the need for intubation quickly plunge, with the situation now under control.
In the process, we found what I called our game-changing triad against COVID-19.
COVID-19 pneumonia is a virus-triggered inflammatory disease. Utilizing a potent anti-inflammatory drug has always been a potential target. Still, there was the fear of reducing the capacity of our immune system to eliminate this deadly pathogen with a potent anti-inflammatory drug. Furthermore, there were dismay results from several studies with corticosteroids in severe cases of H1N1, another respiratory virus infection with similar clinical presentation2. This was not H1N1, though. Early in the crisis, a colleague reported the fantastic improvement after administering IV dexamethasone in a patient with severe COVID-19 pneumonia and bronchospasm (@Laísa Bonzanini). Several other similar reports started popping up from all over the World, not only with corticosteroids but also with other potent anti-inflammatory drugs, such as the interleukin inhibitors. That encouraged us to try giving corticosteroids in our first patient on April 12th, a 40-year-old man that had been on mechanical ventilation for 24 hours. After initiation of IV methylprednisolone 1 mg/kg t.i.d., his condition improved progressively, and we were able to extubate him within six days. Since then, the use of Methylprednisolone in a dose of 2-3 mg/kg/day for 5-7 days was incorporated into our protocol for all patients with moderate or severe pneumonia based on CT scan. In mild cases, the drug was initiated if there was a progression of pulmonary lesions in a 48-72-hour control CT regardless of the day of symptom onset. The amelioration we observed was remarkable within 48 hours in most patients. Many with horrendous images on CT and severe hypoxemia were certainly spared from intubation. It made sense; it was plausible. Corticosteroid therapy was undoubtedly a game-changer.
COVID-19 is not just an inflammatory disease; it is also a thrombotic one. Innumerous cases of thrombotic phenomena were being reported.
Many institutions were already considering implementing anticoagulation therapy in their protocol early on the Pandemic. In mid-April 2020, preliminary results from an autopsy study in Italy hinted at a pro-thrombotic state of the lung circulation. When our first cases show up, this thrombotic nature was soon noted, as very often patients presented with extremely high D-dimer levels, sometimes up to 50.000 ng/mL. In some individuals, pulmonary embolism was observed on angio-CT, a finding latter pointed in up to 23% of patients in one series.
Thus, enoxaparin 40 mg SC b.i.d was implemented for all patients. However, despite this doubled dose of thromboprophylaxis, in some patients, the D-dimer levels continue rising within the first days along with clinical deterioration even though they were already on a Methylprednisolone and antibiotics scheme. Thrombotic progression seemed the most plausible explanation.
Enoxaparin 1 mg/Kg b.i.d was then added to the protocol for all patients with severe hypoxemia or D-dimer above 3.000 ng/mL. Bleeding concerns were present. As an interventional cardiologist, I knew quite well there were risks with full heparinization, but I also knew how safe a short course of these drugs is. Regularly, cardiologists anticoagulate patients for short periods on top of dual antiplatelet therapy for acute coronary syndromes with low bleeding rates.
Considering the high lethality of COVID-19 pneumonia, the hemorrhagic risk seemed very acceptable. Fortunately, we had zero major complications, and not long after, a large study with renkwon authors showing an association of anticoagulation with lower mortality backed our conduct. Anticoagulation appeared to be another game-changer.
3. Non-invasive mechanical ventilation (NIMV):
The information coming from overseas early in the Pandemic was clear, NIMV must be avoided because it aerosolized the virus, endangering the health professionals. Therefore, early intubation was the norm, so the lungs of the patients affected by severe pneumonia could gradually heal, a process that could take weeks. And the whole World followed.
Not long after, hospitals started running out of ICU beds and mechanical ventilators. However, COVID-19 patients are the perfect candidates for NIMV. Patients retain a good level of consciousness even in a hypoxemic state, there is no airway secretion, and the lungs maintain good complacence in this early stage of the disease.
Although we were seeing most of the severe patients escaping intubation with the methylprednisolone/enoxaparin therapy, some were arriving in such an advanced respiratory condition that placing them in mechanical ventilation was inevitable. But what if we hold these patients on NIMV for 48-72h to give them time for our combination therapy to act?
It worked. In our most extreme case, a 70-year-old obese lady with a 90% pulmonary compromise on CT, whose pulse oximetry dropped to 60% while moving her to the ICU bed, was on oxygen through nasal cannula within four days. Had we followed the early intubation rule, her odds of surviving would have been very low. NIMV was a game-changer for this lady.
For mitigating professional exposure, some actions can be taken, such as:
limiting the number of patients on NIMV,
isolating them in separated rooms with open windows or negative pressure,
minimizing the professionals entering in, and, if available,
appointing immunized staff members for caring of those patients.
Besides, we realized having patients two to three days on NIMV was probably less risky for the staff than having them on mechanical ventilation for two to three weeks. Our game-changing triad undoubtedly worked.
Being the only high-complex reference hospital for a population of nearly 150 thousand, facing an outbreak of this deadly virus, with over 2,000 confirmed cases within three months. Yet, we have had only twelve deaths among 220 severe patients that required hospital admission.
Of note, this report was never intended to be a scientific study. Even if we wish it to be, there would be so many cofounders and potential biases that, in the end, it would have been discredited as bad science.
This is merely a good-faith report of well-thought-out medicine on a deadly disease showing plausible treatments and results worth sharing.
Unfortunately, thousands are still dying daily due to COVID-19. I look with awe on how medical societies have progressed so little with their treatment recommendations because, of course, there is no robust scientific evidence. In the era of evidence-based medicine, no expert would dare to recommend an unproven therapy in an official statement. As a consequence, many hospitals are still struggling, intubating their patients precociously. Although evidence-based medicine has been fundamental for the advances seen in modern medicine, the COVID-19 unveiled its weakness. Not only could it not give us a quick answer to a deadly Pandemic, as it also locked us, physicians, in a state of clinical inertia. The art of medicine must be bigger than just that."
Fernando Luiz de Melo Bernardi, M.D. OBS: esse texto foi escrito no inicio de Junho de 2020. Desde então mais estudos científicos foram publicados confirmando o benefício dos tratamentos acima descritos nos doentes críticos com COVID-19.
In an earlier stage of the pandemic, on April 08, when
was heavily promoted by populist politicians as the
warned of the serious, lethal side effects.
His conclusion as a specialist in internal medicine and cardiologist - I do consider them a good example on how to adapt local clinical routine, even under the pressure of a growing epidemic, to growing knoledge sticking to the rules of medicine in resource constrained settings:
start with what you have!
keep up to date of literature
monitor and evaluate regularely.
[Traducao nao-oficial: Dr. Pitt Reitmaier]
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