Higher Mortality Rate in Ventilated COVID-19 Patients in Large Sample

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APRIL 13, 2020 -- Mortality could be as high as two thirds among patients with COVID-19 who require ventilation, new data from the United Kingdom's Intensive Care National Audit and Research Center (ICNARC) show.

Some clinicians are asking whether other techniques, such as extracorporeal membrane oxygenation (ECMO), could improve outcomes, but the data are unclear.

The ICNARC data, posted online April 10, include data from 3883 patients with confirmed COVID-19 who were admitted to intensive care units (ICUs) in England, Wales, or Northern Ireland and for whom data on the first 24 hours of ICU care are available.

Of those, 871 patients died, 818 patients survived to ICU discharge, and 2194 patients were still receiving ICU care.

Among patients whose ICU outcome is known, 66.3% of the 1053 patients who required mechanical ventilated died, compared with 19.4% of the 444 patients who required basic respiratory support.

Importantly, mortality among patients with COVID-19 who require mechanical ventilation appears higher than that for patients with other types of viral pneumonia. Specifically, the ICNARC report shows a mortality rate of 35.1% among patients who were treated in the ICU for viral pneumonia and who required mechanical ventilation from 2017 to 2019.

The new ICNARC findings are consistent with previous reports of smaller case series. For example, a single-center case series of 52 patients treated in Wuhan, China, showed that 37 (71%) required mechanical ventilation and 32 (61.5%) died within 28 days of ICU admission. Morality was higher among those who required mechanical ventilation than among those who did not (94% vs 35%).

Similarly, a case series of 24 patients with COVID-19 who were treated in ICUs in the Seattle area indicated that 20 (75%) required mechanical ventilation. With a minimum follow-up of 14 days, four of the 20 patients had been discharged home, four remained hospitalized but were no longer in the ICU, nine had died, and three continued on ventilation in the ICU.

Time to Change Ventilator Strategies?

Results such as these have some physicians asking whether standard respiratory therapy protocols for typical acute respiratory distress syndrome (ARDS) might need to be adjusted for this novel pneumonia. As one critical care physician recently wrote in Britain's the Spectator, because of the threat of ventilator-induced lung injury, "putting patients on ventilators for COVID-19 pneumonia could be a bridge to nowhere.

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"Ventilation itself, though, may not be the problem. Rather, ventilator protocols may need adjusting, according to Luciano Gattinoni, MD, of the Medical University of Göttingen in Germany. "Ventilated COVID-19 patients are not more likely to die if they are properly treated," Gattinoni told Medscape Medical News in an email.

Gattinoni and colleagues have argued that some COVID-19 patients might need gentler positive end-expiratory pressure because they present with an atypical form of ARDS, similar to that seen with high-altitude pulmonary edema. They also emphasize that COVID-19 patients need to be treated according to individual pathophysiologic characteristics of their disease and not with a one-size-fits-all approach.

But not everyone agrees. Some say there is no solid evidence to support changing protocols for COVID-19 patients. "We don't have data to say these patients need to be managed differently. We do have data showing that standard procedures work," said Pavan K. Bhatraju, MD, a critical care physician at the University of Washington Medicine in Seattle, who is first author of the Seattle case series.

Kenneth Lyn-Kew, MD, a pulmonologist at Jewish National Health in Denver, Colorado, says the 50% mortality rate for ventilated coronavirus patients in the Seattle series is fairly comparable to that for ARDS patients. "We can't say if COVID-19 disease is killing ventilated people at a higher rate or whether it's just that more people are on ventilators because of it, " he told Medscape Medical News.

But pulmonologist and critical care specialist Angela Rogers, MD, MPH, paints a somewhat bleaker picture. As one who each winter treats severe ARDS, which has a mortality rate of 30% to 40%, Rogers says COVID-10 outcomes appear to be poorer, and the data from the United Kingdom, China, and Europe, as well as early experience in the United States, suggest that mortality is higher than with ARDS.

"There are important differences in the clinical course of COVID-19, and patients tend to be intubated quite a bit longer," Rogers, an assistant professor of medicine at Stanford University in California, told Medscape Medical News. In addition, COVID-19 patients don't present as early with other organ dysfunction, such as kidney problems. "It's all about lung failure at first, although heart problems often develop later. It seems that people are dying of their lung disease in a way that's not always the case with ARDS," Rogers said.

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"Here in the Bay area, we do see COVID-19 patients come off the ventilator and move on, but since mortality rate is a lagging indicator, we won't have a good sense of the mortality rate for another few weeks," she said.

Can ECMO Help COVID-19 Patients?

Regarding alternate methods of advanced respiratory support, some are suggesting the use of ECMO, which oxygenates blood outside of the body, similar to a heart-lung bypass machine, thereby causing less stress to the lungs. In Gattonini's view, however, ECMO remains a special intervention for those for whom standard therapy fails. "Given the number of COVID-19 patients needing support, it is not a practical alternative," he said.

Lyn-Kew agrees that widespread ECMO therapy is not realistic. "ECMO showed some benefit in severe ARDS, as was seen in the EOLIA trial, but the issue is availability. Our center uses ECMO, but not all centers have the machines, and those that do have to pull people from other jobs to run them," he said. "[O]ne respiratory therapist can run five to eight [ventilatilator] units, depending on how complex the patients are. If the same therapist is running an ECMO machine, they're taking care of one patient."

For COVID-19 patients, ECMO remains a rescue maneuver, not an everyday alternative. "It's expensive and has associated complications, such as bleeding, stroke, and infection," she said. "And data coming out of China showed a high mortality rate in patients on ECMO, so you have to ask whether it's really saving anyone."

recent small case series of eight Chinese ECMO-treated patient reported a 50% mortality rate.

Another option might be to relax somewhat the established ventilation protocols. The lungs of COVID-19 patients tend to be more elastic and compliant than those of ARDS patients, despite their very poor oxygenation, Rogers explained. "So we might be able to allow patients to take slightly bigger breaths with a bit more tidal volume in each breath and allow them to be less sedated, more awake, and more in sync with the ventilator," she said. "They may be able to be extubated earlier and be able to cough up their phlegm sooner than with strict tidal volumes."

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