Critical Care of Patients with COVID-19: What Cardiologists Should Know

Cardiologists at Massachusetts General Hospital and elsewhere may be called on to care for critically ill patients with COVID-19. At a virtual Mass General Cardiology Grand Rounds conference on March 25, 2020, David M. Dudzinski, MD, director of the Cardiac Intensive Care Unit at Mass General, reviewed what cardiologists should know about Mass General's guidance for critical care of patients with COVID-19.

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The Mass General protocols, which are subject to continuous revision, were developed in collaboration with physicians across the hospital, and with input from the experiences of multiple frontline clinicians in China, Italy, New York and Washington state.

Presentation of Severe COVID-19

Patients with severe COVID-19 generally present to the hospital with dyspnea, tachypnea and/or hypoxemia. Lung failure is now well understood to be the primary cause of death, but cardiologists should keep alert to the potential for cardiac deterioration, as well as septic shock, coagulopathy, acute kidney injury, venous thromboembolism and secondary infection.

The Mass General emergency department is working with specialists in palliative care to help patients discuss the goals of care early in the illness.

According to a multivariable analysis of 191 patients treated in China and published in The Lancet, poor prognostic factors at initial presentation of COVID-19 are older age, higher Sequential Organ Failure Assessment score and admission D-dimer >1 mcg/mL. A bivariate analysis of 201 patients in China, published in JAMA Internal Medicine, determined that risk factors for acute respiratory distress syndrome (ARDS)—and for progression of ARDS to death—were older age, neutrophilia, higher lactate dehydrogenase and higher D-dimer. Analogous data on 416 patients hospitalized in Wuhan was published in JAMA Cardiology, identifying cardiac injury, defined as elevated high sensitivity troponin I, as strongly associated with in-hospital mortality in COVID-19 patients. Other risk factors are based on underlying comorbidities and derangements in presenting vital signs.

With few exceptions, Mass General is not offering noninvasive positive-pressure ventilation or high-flow nasal cannula oxygen to patients in respiratory distress during the pandemic. Aerosolization increases the risk of viral transmission to health care workers and other patients. There is also concern among Mass General intensivists that noninvasive positive-pressure ventilation or high-flow nasal cannula oxygen may allow spontaneously-breathed large tidal volumes, which may contribute to high transpulmonary pressure and exacerbate lung injury in ARDS. It is worth noting that the Society of Critical Care Medicine offers a weak recommendation to trial noninvasive positive-pressure ventilation or high-flow nasal cannula oxygen modalities. Other hospitals have varying recommendations, as a hospital's recommendation may be dynamic, reflecting the available supply of mechanical ventilators.

Background on ARDS

SARS-CoV-2 appears to cause respiratory failure in the setting of the ARDS. ARDS is a syndrome defined by the Berlin criteria:

• Onset within seven days of a known clinical insult (or new or worsening respiratory symptoms)
• Bilateral opacities on pulmonary imaging
• Noncardiogenic etiology
• Marked hypoxemia

Oxygenation is quantified as the ratio of partial pressure of arterial oxygen to the fraction of inspired oxygen (PaO2:FiO2). A normal value is 400 to 500 mm Hg, but in patients with COVID-19 on admission the ratio is often in the 100s or low 200s.

ARDS as a syndrome involves inflammation, alveolar dysfunction and collapse, ventilation-perfusion mismatching and disruption of the alveolar–capillary boundaries; at this boundary, intravascular capillary fluid can infiltrate into the lung extravascular space. This further impairs ability to deliver oxygen to the blood. To minimize this interstitial edema, it is crucial to be conservative with fluid administration, and consider judicious diuresis.

Early Intubation

In ARDS, as the airways become clogged with edema and mucus, total available lung volume increases and overall lung compliance decreases. Patients with ARDS need exogenous pressure applied throughout the respiratory cycle so the small airways and alveoli remain open.

Mass General recommends early intubation for patients with marked hypoxemia so the procedure can be done in a controlled and organized manner. The goal is to avoid a situation where health care staff must urgently respond to cardiopulmonary deterioration. Rather best practice is to anticipate and respond to these deteriorations, so that there is sufficient time for all staff to don protective equipment and possibly move the patient to a negative pressure room; such practices should reduce the risk of viral transmission. This dictum applies even to a true medical emergency situation – hard lessons learned from the Ebola crisis mandate that before rendering any care, the first step of all health care workers must be to don personal protective equipment.

There is no one specific marker or trigger about when to intubate patients with COVID-19; the decision depends on the clinical gestalt and the patient's trajectory. "If you have the thought that the patient is going to need intubation later, think whether they need intubation now," Dr. Dudzinski said, reflecting experiences from front-line practitioners across the globe. "Of course, we are also seeing how precious of a resource that ventilators are and trying to carefully balance benefits from saving of ventilator-days in our units. Mass General has carefully planned for surges in the need for its ICUs, and trained intensivists will be available in all existing and newly created ICUs to consult minute-by-minute on patient management."

The Basics of Ventilation

Mechanical ventilation is a methodology to support a patient's oxygenation when they cannot. Unfortunately, mechanical ventilation does not alter the biology or course of ARDS. When we mechanically ventilate a patient, our goal besides supporting oxygenation is to minimize ventilator-associated harms.

On a basic level, variables that can be input on a ventilator (in volume controlled ventilation mode, which will be the primary mode for initial ARDS treatment) fall into two categories:

Related to clearing CO2 — tidal volume and respiratory rate. The product of those variables is called minute ventilation. Patients with COVID-19 don't generally appear to have significant problems clearing CO2; what's needed is to maintain minute ventilation without repeatedly overextending the alveolus and letting it collapse. Based on a robust body of clinical evidence, including studies published in the New England Journal of Medicine, a tidal volume of around 6 cc per kilogram of patient body weight is the general standard of care for patients with ARDS as part of "lung-protective" ventilation.

Related to oxygenation — FiO2 and positive end-expiratory pressure (PEEP). The value of FiO2 available from the atmosphere for a person breathing on their own is 0.21 (21%). In ARDS, we may need to temporarily increase FiO2 value higher, to 1.0 (100%). Mass General recommends that PEEP start at about 10 cmH2O and to judiciously adjust and individualize PEEP; individualization is based on key metrics in ARDS, including the plateau pressure and the driving pressure. Some COVID-19 ARDS patients may need higher PEEP, e.g. about 14 cmH2O, and the Society of Critical Care Medicine guidelines weakly recommend a higher PEEP strategy. All clinicians must be attentive to possible risks of PEEP, including barotrauma and adverse impacts on the right ventricle and venous return.

Adjunctive Management of ARDS at Mass General

• Prone positioning of ventilated patients improves lung mechanics, reduces regional lung compression and optimizes ventilation-perfusion matching. Mass General is recommending prone ventilation early for COVID-19 patients who have profound hypoxemia. Mass General is also investigating protocols for prone positioning of non-ventilated patients
• Inhaled nitric oxide is a potent and rapidly inhaled vasodilator, and therefore may improve ventilation-perfusion mismatch for COVID-19 patients hypoxemic despite PEEP titration and prone ventilation. As a nebulized agent, epoprostenol is avoided because it risks aerosol generation
• Corticosteroids will not be administered routinely to patients with severe COVID-19 ARDS, as discussed in a prior grand rounds conference. Other adjunct medications including anti-viral and anti-inflammatory medications were also discussed in a prior Cardiac Grand Rounds
• Neuromuscular blockade — may be useful for reducing ventilator dyssynchrony, however paralytic agents increase the risk of critical-illness myopathies, and there are concerns about impending medication shortages
• Veno-venous extracorporeal membrane oxygenation — this is a rescue therapy only for truly refractory hypoxemia. This modality was rarely reported in the Chinese and Italian experiences. At Mass General, a central committee will evaluate the need daily for all ICU patients and collaborate in decision-making with bedside teams

Summing up, Dr. Dudzinski urged attendees to think about the theme of protection in everything they do, being cognizant of the theme of "lung-protection" for the patient, as well as protection of themselves and other health care personnel. The pandemic has forced an about-face in medicine: clinicians ordinarily center risk-benefit decisions on the patient in front of them, but now we must consciously consider the direct impacts to our peer workers, the hospital and health care enterprise and the rest of society by protecting the health of our clinical workforce and appropriate stewardship of all resources.

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