Primum non nocere

Two hospitalists muse on the current pandemic.

For centuries, humankind has been threatened by pandemics. The 1918 influenza pandemic was one of the most aggressive. Physicians searched desperately for a cure and used different empiric treatment modalities, including aspirin and quinine, mostly with no significant clinical improvement and little documentation of any adverse effects. The U.S. Surgeon General at the time, Rupert Blue, MD, emphasized good hygiene, avoidance of overcrowding, and covering coughs and sneezes as key tools to fight the virus.

Dr Auron
Dr. Auron

Just over 100 years later, a novel coronavirus was identified. This new pandemic has once again showcased our frailty and vulnerability, as well as our determination to control and treat an unknown disease, even with unproven therapeutic interventions.

The CDC, the World Health Organization, and national and international medical societies, including ACP, have developed educational materials and platforms to provide information about SARS-CoV-2 and COVID-19, and hospitals in all countries developed structured approaches to these patients, from triage to inpatient and critical care (many of which were very similar thanks to the academic sharing of protocols).

Dr Gracia-Ramos
Dr. Gracia-Ramos

However, at the same time, as knowledge about the disease and its manifestations grew, more than 20 different potential and experimental treatments were proposed. The anxiety that this pandemic has caused, and the need to “do something,” triggered the release of an insurmountable amount of publications, many of them pre-print, a quantity of information that exceeded physicians' ability to carefully analyze it. As of July 2020, there were 35,666 articles on the topic listed in PubMed.

In addition to the overwhelming quantity of literature, wider use of clinical prediction models originally intended for specific populations has led to unreliable data and decision making. Physicians have also struggled with cognitive biases such as availability and confirmation and reliance on unverified communications between colleagues. All this has led to the implementation of unproven therapeutic interventions, some of which have since been found to be unhelpful and even harmful. We've seen use of treatments that have not been applied before in a similar clinical context based on subjective judgment of the risk-benefit ratio. Some of them have strong potential for harm, such as cardiotoxicity with the use of azithromycin and hydroxychloroquine.

Clinicians must always maintain a healthy skepticism and perform critical appraisal of literature. The practice of evidence-based medicine is an essential safeguard against pseudoscience and potentially harmful assessment and treatment methods, because even interventions that appear to be plausible can be ineffective or dangerous. For COVID-19 and many other diseases, the basics of medical care should prevail—providing supportive care; ensuring proper nutrition, hydration, oxygenation, and elimination (airway secretions, etc.); enhancing mobility and functional status; and treating fever.

This supportive care is “medicine” and a very strong and powerful component of any therapeutic intervention. Several elements of supportive care have scientific evidence demonstrating benefit in reducing morbidity and mortality and are being evaluated in patients with COVID-19, with good early results, as described by Larson and colleagues in a study published May 30 by Clinical Infectious Diseases. Common factors in the areas where more patients have survived COVID-19 have included early isolation, but also early medical care and good supportive care. The evidence on treatments is controversial and there is a paucity of definitive data. Medications have toxicity, and despite our desperation to treat, it is important to be careful and use treatments judiciously within the context of clinical trials.

It is interesting how the conversations in the hallway and virtual “doctor's lounges” have shifted over the past several months. We have been immersed in an ocean of information, opinions, ideas, and personal professional experiences. Both disagreement and consensus have happened. Emotional and passionate discussions about potential treatments have taken place; evidence has been consistent only in its absence. Empiric treatments are favored based on patients who have survived or died, most likely not due to the treatments themselves.

Now more than ever the use of evidence-based medicine is necessary, because it's the gold standard to guide clinical decisions, improve medical practice, and limit variability and errors. COVID-19 is a disease that reminds us of our vulnerability, teaches us humility, and allows us to gain insight into the true therapeutic value of supportive care and evidence-based medicine. We must follow the teaching said to be derived from Hippocrates' writings 2,400 years ago: “Primum non nocere.”