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Tuesday, April 7, 2020

Noninvasive Ventilatory Support in COVID-19: Friend or Foe?

With intensive care units (ICUs) in numerous countries overwhelmed in the face of the COVID-19 pandemic, many hospitals have turned to noninvasive ventilation (NIV) to stave off severe respiratory failure and ease the pressure on scarce resources.
This practice is seen as controversial by some US clinicians, but has been widely employed in China and is gaining traction in Europe, with the European Society of Intensive Care Medicine (ESICM) now recommending it.
And there is debate as to whether NIV devices — such as continuous positive airway pressure (CPAP), ordinarily used to treat conditions such as sleep apnea — should be the first port of call, or rather oxygen delivered by high-flow nasal cannula (HFNC).
Another concern is whether the benefits of using such interventions outweigh the risks of possible aerosolization of the virus, which could increase the risk of nosocomial infection. This issue may be especially pertinent when personal protective equipment for medical staff is in short supply
In some places, most notably Italy, helmet devices that cover the patient’s head entirely — as opposed to the face masks typically used with other NIV — have been employed, which may help limit aerosolization.

CPAP or HFNC to Slow Disease Progression?

NIV is defined as a ventilation modality that supports breathing by delivering mechanically assisted breaths without the need for intubation or surgical airway. There are two main types: negative-pressure ventilation and noninvasive positive-pressure ventilation (NIPPV).
The latter is further subdivided into several subtypes, including CPAP and bilevel positive airway pressure (BiPAP).
NIV devices reduce the effort of breathing and help maintain inflation of the alveoli, thus increasing oxygenation.
Detailing the Italian experience of the COVID-19 pandemic, one expert observed that CPAP could be beneficial not only to reduce ICU admissions and the number of patients requiring intubation but also because nurses can administer it.
However, are CPAP and similar NIV devices the best choice?
ESICM issued one of the first international guidelines on the management of critically ill patients with COVID-19 in intensive care on March 23, as reported by Medscape Medical News.
ESICM suggests using oxygen delivered by HFNC as first-line therapy for patients with COVID-19 and acute hypoxemic respiratory failure in preference to NIPPV/CPAP, although the latter could be used “with close monitoring and short-interval assessment for worsening respiratory failure.”
However, these are not recommendations, just suggestions, only supported by low-quality evidence, the society notes.
And in a study from China, HFNC was the most common ventilation support. Of patients experiencing severe acute respiratory failure because of COVID-19, 63% were treated with HFNC as first-line therapy and 33% were treated with NIV.
In contrast, the National Health Service in England has gone the other way; it recommends CPAP over HFNC, saying the latter is “not advocated in COVID-19 patients, based on lack of efficacy, oxygen use, and infection spread.”

“We Don’t Know the Effect of These Interventions on Patient Outcome”

Lead author of the ESICM guidelines Waleed Alhazzani, MD, McMaster University, Hamilton, Ontario, Canada, acknowledges that the discussion around NIV “is based on indirect evidence, communication with colleagues who treated a large number of COVID-19 patients, and common sense.”
He told Medscape Medical News that in China and Italy “many COVID-19 patients received HFNC and NIPPV, but we don’t know what the effect of these interventions on patient outcomes was.”
And this is what most concerns Angela Rogers, MD, MPH, Division of Pulmonary and Critical Care, Stanford University, California.
She told Medscape Medical News: “My impression is that the majority of US institutions are not using NIPPV, but there is even tremendous controversy around HFNC.”
This is “not only because of the risk of aerosolizing…but also because of concerns that patients can suddenly get much worse and that to intubate early may be the safest thing for patient care,” she explained.
“[HFNC] is the topic that was most controversial for us here at Stanford, with people disagreeing strongly in both directions. Many great institutions [in the United States] are using [HFNC], many other great institutions are not,” she said.

Risk of Infection From Aerosolization

What about the risk of infection from aerosolization?
In developing recommendations based on their frontline experience treating COVID-19, Massimiliano Sorbello, MD, AOU Policlinico San Marco University Hospital, Catania, Italy, and colleagues, recently writing in Anaesthesia, found that “all oxygen administration strategies in the spontaneous ventilating patient carry risks of aerosolization and disease transmission.”
This was underlined by Lili Guan, MD, PhD, National Clinical Research Center for Respiratory Disease, Guangzhou, China, and colleagues, who reported on their experience in the European Respiratory Journal.
“The majority of patients are still receiving respiratory support through nasal catheter or common mask in general wards or emergency departments with limited medical resources,” they said, noting that nosocomial rates of infection with COVID-19 in Chinese hospitals have been estimated at around 40%.
“Exhaled air dispersion during noninvasive respiratory support may increase the risk of coronavirus transmission and requires more attention from medical personnel,” they note.
Alhazzani said that, although it is known “that NIPPV/CPAP is an aerosolizing procedure with increased risk of disease transmission,” it may well be the same for HFNC.
“We don’t know, as there are no good studies that looked at this,” he told Medscape Medical News.
Editorialists writing about the ESICM guidelines in JAMA, agree: “Given the potential risks of inadvertent viral aerosolization using high-flow open circuits such as HFNC, more thorough examination of this potential source for disease transmission may be warranted.”
“Currently, clinicians and decision-makers who are trying to contain the outbreak may be uncomfortable with the liberal use of HFNC and NIPPV, especially if prolonged, in crowded emergency departments or on hospital wards,” they conclude.

Rushing Through New Machines and the Helmet Hope

Perhaps anticipating such use, however, the FDA has, in-line with other countries, announced urgent guidance on modifying respiratory devices, as long as they do not “create an undue risk.”
“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,” the guidance states.
This includes the use of devices for sleep apnea to treat respiratory insufficiency “provided that appropriate design mitigations are in place to minimize aerosolization,” such as filters, it notes.
There is also hope that helmet-based ventilation may help reduce the risk of nosocomial infection — in this instance, a helmet replaces a facemask as the mode of delivery of oxygen.
The helmet consists of a plastic bell that fits over the head and attaches to a rubber collar neck seal, reminiscent of Victorian diving helmets. Their potential in the current pandemic was demonstrated in striking footage from Sky News showing a room full of Italian COVID-19 patients wearing the devices on an emergency ward.
The Italian version is more advanced than those available elsewhere — it was designed with a virus filter to prevent aerosolization and is more user friendly, with extra ports for medical staff to use.
However, the Italian helmet is not approved by the US Food and Drug Administration (FDA), although helmet devices have been trialed by the US National Institutes of Health (NIH) as a treatment for acute respiratory distress syndrome.
In any case, the Italian government has banned the export of helmet devices while it tackles its own COVID-19 crisis.
US hospitals are consequently turning to locally produced helmet devices, with companies seeing huge increases in orders.
Nevertheless, there are some notes of caution on the issue of helmets.
The ESICM guidelines describe them as an “attractive option” because they have “been shown to reduce exhaled air dispersion,” but the authors emphasize that they are “not certain” about their safety or efficacy in COVID-19, and they were therefore “not able to make a recommendation regarding the use of helmet NIPPV compared with mask NIPPV.”
Lorenzo Berra, MD, medical director of respiratory care at Massachusetts General Hospital, Boston, went a step further.
He told the Wall Street Journal that although the helmet device “could buy some time” for patients, he is “skeptical of using it for a huge number of patients, unless there are no ventilators.”
Rogers has served as an advisor for Merck antibiotic trials (received no money) and has received research grants from the NIH and National Heart, Lung, and Blood Institute.
Intensive Care Med. Published online March 28, 2020. Full text
https://www.medscape.com/viewarticle/928259#vp_1

Is Protocol-Driven COVID-19 Ventilation Doing More Harm Than Good?

Physicians in the COVID-19 trenches are beginning to question whether standard respiratory therapy protocols for Acute Respiratory Distress Syndrome (ARDS) are the best approach for treating patients with COVID-19 pneumonia.
At issue is the standard use of ventilators for a virus whose presentation has not followed the standard for ARDS, but is looking more like high-altitude pulmonary edema (HAPE) in some patients.
In a letter to the editor published in the American Journal of Respiratory and Critical Care Medicine on March 30, and in an editorial accepted for publication in Intensive Care Medicine, Luciano Gattinoni, MD, of the Medical University of Göttingen in Germany, and his colleagues make the case that protocol-driven ventilator use for patients with COVID-19 could be doing more harm than good.
Dr. Gattinoni noted that COVID-19 patients in intensive care units in northern Italy had an atypical ARDS presentation with severe hypoxemia and well-preserved lung gas volume. He and his colleagues suggested that instead of high positive end-expiratory pressure (PEEP), physicians should consider the lowest possible PEEP and gentle ventilation-practicing patience to “buy time with minimum additional damage.”
Similar observations were made by Cameron Kyle-Sidell, MD, a critical care physician working in New York City, who has been speaking out about this issue on Twitter and who shared his own experiences in this video interview with WebMD chief medical officer John Whyte, MD.
The bottom line, as Dr. Kyle-Sidell and Dr. Gattinoni agree, is that protocol-driven ventilator use may be causing lung injury in COVID-19 patients.

Consider Disease Phenotype

In the editorial, Dr. Gattinoni and his colleagues explained further that ventilator settings should be based on physiological findings — with different respiratory treatment based on disease phenotype rather than using standard protocols.
“This, of course, is a conceptual model, but based on the observations we have this far, I don’t know of any model which is better,” he said in an interview.
Anecdotal evidence is increasingly demonstrating that this proposed physiological approach is associated with much lower mortality rates among COVID-19 patients, he said.
While not willing to name the hospitals at this time, he said that one center in Europe has had a 0% mortality rate among COVID-19 patients in the intensive care unit when using this approach, compared with a 60% mortality rate at a nearby hospital using a protocol-driven approach.
“Given this conceptual model, it follows that the respiratory treatment offered to Type L and Type H patients must be different,” Dr. Gattinoni said.
Patients may transition between phenotypes as their disease evolves. “If you start with the wrong protocol, at the end they become similar,” he said.
Rather, it is important to identify the phenotype at presentation to understand the pathophysiology and treat accordingly, he advised.
The phenotypes are best identified by computed tomography scan, but signs implicit in each of the phenotypes, including respiratory system elastance and recruitability, can be used as surrogates if CT is unavailable, he noted.
“This is a kind of disease in which you don’t have to follow the protocol – you have to follow the physiology,” he said. “Unfortunately, many, many doctors around the world cannot think outside the protocol.”
In his interview with Dr. Whyte, Dr. Kyle-Sidell stressed that doctors must begin to consider other approaches. “We are desperate now, in the sense that everything we are doing does not seem to be working,” Dr. Kyle-Sidell said, noting that the first step toward improving outcomes is admitting that “this is something new.”
“I think it all starts from there, and I think we have the kind of scientific technology and the human capital in this country to solve this or at least have a very good shot at it,” he said.

Proposed Treatment Model

Dr. Gattinoni and his colleagues offered a proposed treatment model based on their conceptualization:
1. Reverse hypoxemia through an increase in FiO2 to a level at which the Type L patient responds well, particularly for Type L patients who are not experiencing dyspnea.
2. In Type L patients with dyspnea, try noninvasive options such as high-flow nasal cannula, continuous positive airway pressure, or noninvasive ventilation, and be sure to measure inspiratory esophageal pressure using esophageal manometry or surrogate measures. In intubated patients, determine P0.1 and P occlusion. High PEEP may decrease pleural pressure swings “and stop the vicious cycle that exacerbates lung injury,” but may be associated with high failure rates and delayed intubation.
3. Intubate as soon as possible for esophageal pressure swings that increase from 5-10 cmH2O to above 15 cmH2O, which marks a transition from Type L to Type H phenotype and represents the level at which lung injury risk increases.
4. For intubated and deeply sedated Type L patients who are hypercapnic, ventilate with volumes greater than 6 mL/kg up to 8-9 mL/kg as this high compliance results in tolerable strain without risk of ventilator-associated lung injury. Prone positioning should be used only as a rescue maneuver. Reduce PEEP to 8-10 cmH2O, given that the recruitability is low and the risk of hemodynamic failure increases at higher levels. Early intubation may avert the transition to Type H phenotype.
5. Treat Type H phenotype like severe ARDS, including with higher PEEP if compatible with hemodynamics, and with prone positioning and extracorporeal support.
Dr. Gattinoni reports having no financial disclosures.
https://www.medscape.com/viewarticle/928236#vp_1

Covid-19 forces a new way of thinking for Quil, Comcast’s health tech startup

When telecom giant Comcast and health insurer Independence Blue Cross teamed up to found Quil in 2018, the health tech company’s goal was clear: give people simple, step-by-step guidance to help them navigate big health events, from pregnancies to hip replacements.
But today, the joint venture finds itself in a very different place, as the coronavirus pandemic has forced physicians to put off routine appointments and postpone elective surgeries. Everyday health care is, in some ways, being put on hold — and startups like Quil are racing to adapt.
The company uses people’s laptops, phones, and home TVs as health care hubs. Users can log into the online Quil portal on any of those devices and fill in information about their upcoming health procedures. Quil creates a customized “journey” that maps out checkpoints and offers guidance sourced from clinical best practices and peer-reviewed research. Now, with so many procedures delayed, the company now working to arm people with information on the virus. Quil launched a new coronavirus-specific tool last week, pointing people to trusted data sources, providing helpful tips on how to safely grocery shop and work from home, and doling out advice on caring for at-risk loved ones and preventing the spread of the virus.
It’s a new way of thinking for Quil, which up until now has focused on well-understood and well-defined experiences in health care. But the playbook for Covid-19 is being written in real time, and Quil’s tool has to change constantly to keep up.
C_Edwards Headshot
Quil CEO Carina Edwards Quil
STAT spoke with Carina Edwards, Quil’s CEO, to get a sense of how the company is grappling with the new reality the pandemic has imposed on its users and to learn how its coronavirus offering might help. This interview has been edited and condensed for length and clarity.
You recently launched what you’re calling a Covid preparedness tool. Why did you do that?
This is something no one’s ever seen before. To take a step back, we’re focused on helping people navigate their health life, or what we see as health care journeys. Traditionally, those journeys have a start, a middle, and an end. Think about pregnancy — that’s a journey. Or a hip replacement — another journey. You start, you consider what’s coming, you prepare and make a plan, you know your plan. The information you need along the way doesn’t really change every day. For the most part, there are known care pathways, and everything is prescribed by the case manager working with you.
This is different. With Covid, over just the past 19 days, there’s been new information and there have been new innovations and new testing. But there’s been no grounding of evidence-based best practice. So for us, it’s: “Why are you in [the Quil] app today? Are you a caregiver looking for information about how to care for someone at risk? Are you someone who’s now in a child care situation [because of social distancing]? Something else?” Our tool provides an action plan for adjusting to this new life reality. This is ongoing.
How often are you updating your tool to keep pace with what’s going on? 
We got this tool up and running in five days. This is truly a breaking-news kind of scenario where you need to be mindful of constant, daily updates. At the same time, we think that in general, what’s happening with Covid is information overload. So we didn’t try to do something like reinvent the symptom checker. That tool is available on the Centers for Disease Control, and we direct people to that through our tool.
What we’ve heard is that the information in the tool is calming. You’re not getting anxiety from just reading it. The app is very much: “Here’s what you need to do, it’s OK to breathe.”
Five days is a short time to put something like this together. What motivated you?
For the team, it was a call to purpose. Our clients’ needs for the tool pivoted. They had patients going through elective surgeries, and suddenly those surgeries were cancelled. So the team thought, “We have this scale, what can we do?” They scoured all the sources and came up with this toolkit.
What do you do for the people whose elective surgeries have been postponed? What’s the plan for them now?
We’re doubling down on in-home exercises they can do before surgery to prepare, things they can do for pain mitigation that are prescribed by their doctor, so we’re keeping them engaged in those.
There’s a long tail that’s going to result from the coronavirus that we can see now. How do we think through that longer tail to make sure patients have resources they need?
How many people are using this new tool? 
We’ve seen an uptick of use. This is scaling beyond our current user base.
What kind of feedback are you getting from users?
In the early days, people were mainly trying to get information about Covid: “What is this? What do I need to know about it?” Now, we’re seeing a transition — especially of people who’ve been on the app a bit longer — where people are going to the self-care part of the app and trying to navigate just being at home.
What’s your timeline for this tool? How long will you have it up? How long will you keep updating it?
I don’t know. No one knows. We want to be relevant throughout the journey. I think we can plan for when people are allowed to go back to work and when people are allowed to travel again. So we’re focused on curating that content in the ever-evolving situation that Covid presents.
The Covid-19 pandemic forces a new way of thinking for Quil, Comcast’s health tech startup

UnitedHealth accelerates ~$2B in payments, support to health providers

Aimed at easing short-term financial pressures caused by the COVID-19 pandemic, UnitedHealth Group (NYSE:UNH) is accelerating payments and other financial support to front-line healthcare providers.
It has also suspended prior authorization requirements to a post-acute care setting and when a member transfers to a new provider.
Other measures include extending timely filing deadlines for Medicare Advantage, Medicaid and Individual and Group Market health plans and implementing provisional credentialing to make it easier for out-of-network licensed clinicians to participate in UNH networks.
https://seekingalpha.com/news/3559164-unitedhealth-group-accelerates-2b-in-payments-support-to-healthcare-providers

COVID-19 demand stoked Q1 growth for Perrigo

On a preliminary basis, Perrigo (NYSE:PRGO) expects Q1 revenue of ~$1.3B, up 14% from a year ago and in line with consensus.
Reported operating income should be $140M – 145M (versus $102M a year ago) while non-GAAP operating income should be $220M – 225M (versus $203M a year ago).
The company experienced a dramatic surge in demand in March due to COVID-19 that the company was largely able to meet.
Global consumer sales were ~$1.1B, up 16%.
Management will release final Q1 results during the last week of the month.
Shares up 4% after hours.
https://seekingalpha.com/news/3559168-covidminus-19-demand-stoked-q1-growth-for-perrigo

Amazon confirms virus cases in Ohio, Kentucky

Amazon (NASDAQ:AMZN) confirms two positive coronavirus cases near Cleveland, Ohio, and one in Lexington, Kentucky.
The Kentucky worker and one of the Ohio employees worked at fulfillment centers, while the third person was at a delivery station.
Amazon’s response to coronavirus cases at its facilities led to strikes last week in Staten Island and near Detroit.
The tech giant recently announced plans to hire 100,000 additional workers, including warehouse employees and delivery drivers.
https://seekingalpha.com/news/3559093-amazon-confirms-virus-cases-in-ohio-kentucky

Integra LifeSciences sees drop in Q1 revenue amid COVID-1

On a preliminary basis, Integra LifeSciences Holdings (NASDAQ:IART) expects Q1 revenue of $352M – 354M, down almost 2% from a year ago on a reported basis and shy of consensus of $367M.
Q2 will be worse due to COVID-19 disruptions.
Management will update investors on May 7 during its Q1 earnings call.
https://seekingalpha.com/news/3559115-integra-lifesciences-sees-drop-in-q1-revenue-amid-covidminus-19