Like so many other ventilator providers in recent days, Resmed Inc. has committed to ramping up production. It aims to triple its ventilator output and multiply its ventilation mask production by 10. But the San Diego-based company’s specialty is not mechanical ventilation that requires intubation, which is most commonly used in the intensive care unit (ICU), although it does produce some of those.
It focuses, rather, on noninvasive ventilators that are used in the ICU, hospitals and at home. Resmed already has experience helping to manage COVID-19 patients in China – and is exploring the extent to which noninvasive ventilators, which are much more commonly available and use a mask or mouthpiece instead of intubation, can be useful to support them.
Noninvasive FDA guidance
While some have explored splitting the capabilities of a single, standard ICU ventilator to serve multiple patients, in a March 22 guidance FDA also noted that in the absence of conventional ventilators, patients may be treated at home or in a health care facility with noninvasive ventilators, even including the commonly available home CPAP and BiPAP machines that are indicated to treat sleep apnea.
The agency also encouraged manufacturers to modify ventilation equipment as needed to more closely achieve the functionality of a standard ICU ventilator without an FDA submission, so long as it does not create undue risk. It did require that companies specify the FDA-cleared and the non FDA-cleared indications, however.
Finally, the FDA also pointed to several alternative devices beyond the standard, invasive ventilators typically used in the ICU. These include using ventilators designated for home use in the medical setting; emergency transport ventilators for prolonged use in the medical setting; adapted anesthesia gas machines; noninvasive ventilators; as well as CPAP and BiPAP machines typically indicated for sleep apnea.
“If the number of ventilators in your facility is running low, consider alternative devices capable of delivering breaths or pressure support to satisfy medically necessary treatment practices for patients requiring such ventilatory support,” said the FDA guidance.
There are millions of noninvasive CPAP (continuous positive airway pressure) and the newer BiPAP (bilevel positive airway pressure) machines that already exist in the U.S. An estimated 30 million Americans have obstructive sleep apnea (OSA), with the bulk of them remaining undiagnosed. Roughly five million patients were using CPAP support in 2016, according to a report commissioned by the American Academy of Sleep Medicine.
Sleep apnea – and associated CPAP/BiPAP use – is most common amongst precisely the population that is most severely afflicted by COVID-19: older, overweight or obese men, many of whom have associated chronic diseases.
Compliance with routine CPAP/BiPAP use is very poor despite some major health benefits, because the device itself is typically quite cumbersome and can interfere with patient comfort and sleep. So, that could mean that there are millions of unused or rarely used machines that could be made available.
Treatment and transmission?
It remains unclear, however, how useful noninvasive ventilation – or even invasive ventilation – is for severe COVID-19 patients. A March 5 Lancet Respiratory Medicine study in a Wuhan ICU found that some patients can be treated successfully with noninvasive ventilation. Of COVID-19 ICU patients studied, 29 were given noninvasive ventilation at ICU admission. Of these, 22 went on to require intubated ventilation. The mortality rate was 79% (23 out of 29) for the noninvasive only group and 86% (19 out of 22) for the invasive, mechanical ventilation group.
The researchers did not recommend noninvasive ventilation for patients until after viral clearance or for patients with pneumonia. That could prove a problem in practice as some Italian COVID-19 patients are reportedly being treated seated in hospital hallways with noninvasive ventilation, according to a March 18 article in the New England Journal of Medicine.
An observational study at a Milan hospital is slated to evaluate the usefulness of CPAP to treat COVID-19 patients with acute respiratory distress syndrome (ARDS), including assessing the mortality rate; the investigators were unavailable for comment.
FDA advised caution when using noninvasive ventilation, as some types could distribute pathogens into the air thereby increasing infection risk. The agency said, “Ventilating patients with communicable diseases using devices that are single limb or noninvasive without a filtered seal from the atmosphere may contaminate the room air and increase risk of transmission. This risk may be exacerbated by high-flow nasal cannula systems or CPAP machines.”
Noninvasive ventilator specialist Resmed is also cautious about potential disease spread with its products, but it argued that these mask or mouthpiece-based devices may be no worse than a coughing or sneezing person, distributing droplets rather than the more tiny and long-lasting airborne aerosols, within only about one meter.
When it comes to CPAP and BiPAP, Resmed expects that BiPAP might prove more useful for COVID-19 patients. “Our Aircurve 10 bilevel devices, which look like our CPAP devices, can provide support to some COVID-19 patients,” the company said in a COVID-19-related product Q&A.
BiPAP was developed in the 1990s as an alternative for sleep apnea patients who weren’t doing well on CPAP. The former alternates a higher pressure level during an inhale and lower pressure during an exhale, while the latter delivers a constant flow of air.
Still, Resmed does observe that CPAP devices could be made to function as a ventilator, but “would require significant rework” to do so.
“The FDA guidance does not suggest that CPAPs can be used as is today to treat the respiratory symptoms of COVID-19. The FDA still requires the modifications to be made in a manner that is consistent with existing safety, quality and manufacturing standards,” Resmed CEO Mick Farrell told BioWorld. “Resmed is currently exploring options for achieving this. However, converting in-market CPAPs to support more advanced modes of ventilation requires careful assessment to ensure risk is acceptable, and must meet labeling requirements set forth by FDA.”
He noted that in China’s Hubei province, the initial epicenter of the coronavirus outbreak, Resmed helped to set up thousands of COVID-19 patients with the company’s ventilators and masks. In mid-March, more than 100 Resmed employees in Malaysia volunteered to relocate to a Resmed Singapore ventilator and mask manufacturing plant to keep it running after Malaysia closed its borders.
“While we are exploring our options, we are also converting the manufacturing resources typically used for PAP devices to support manufacturing bilevel and noninvasive ventilation devices that are more suited to the care of COVID-19 patients, and today are ramping up production of invasive-capable and noninvasive ventilators to double normal levels, while working closely with the U.S. government and other government agencies to assess their needs,” he concluded.