Abstract

The COVID-19 outbreak has led to 80,409 diagnosed cases and 3,012 deaths in mainland China based on the data released on March 4, 2020. Approximately 3.2% of patients with COVID-19 required intubation and invasive ventilation at some point in the disease course. Providing best practices regarding intubation and ventilation for an overwhelming number of patients with COVID-19 amid an enhanced risk of cross-infection is a daunting undertaking. The authors presented the experience of caring for the critically ill patients with COVID-19 in Wuhan. It is extremely important to follow strict self-protection precautions. Timely, but not premature, intubation is crucial to counter a progressively enlarging oxygen debt despite high-flow oxygen therapy and bilevel positive airway pressure ventilation. Thorough preparation, satisfactory preoxygenation, modified rapid sequence induction, and rapid intubation using a video laryngoscope are widely used intubation strategies in Wuhan. Lung-protective ventilation, prone position ventilation, and adequate sedation and analgesia are essential components of ventilation management.

The outbreak of the “Coronavirus Disease 2019” (COVID-19) started in December 2019 and quickly became a sweeping and unprecedented challenge to different stakeholders in mainland China.1  Although the epidemic of COVID-19 is not yet over, it has already outpaced the previous severe acute respiratory syndrome (SARS) in 2003 and Middle East respiratory syndrome (MERS) in 2012 in nearly every respect, except for the mortality rate (table 1). As of March 4, 2019, a total of 80,409 patients were diagnosed with COVID-19, and a total of 3,012 patients among those confirmed cases died, corresponding to a mortality rate of 3.7% (http://www.nhc.gov.cn/; accessed March 5, 2020). At the writing of this article on March 5, 2020, it appears that the momentum of the epidemic in mainland China, especially that in the epicenter of Wuhan, Hubei Province, China, has slowed down. However, the disease is gaining momentum outside of China, and it could ultimately become very severe (https://www.who.int/emergencies/diseases/novel-coronavirus-2019/events-as-they-happen; accessed March 5, 2020). The concern is whether the COVID-19 epidemic could become a once-in-a-century pandemic.2 

It did not take more than a few days before the healthcare system and providers in the epicenter of Wuhan were stunned by the COVID-19 outbreak’s scale, speed, severity, and serious threat to healthcare providers themselves. Many patients developed serious symptoms, with some of them becoming critically ill.1  The hospitals were quickly overwhelmed, forcing the administration to lock down the city of Wuhan, reactivate the workforce a few days ahead of the most popular holiday in China, Lunar New Year, reorganize the case flow, convert noninfectious floors and hospitals into infectious ones, build two new hospitals from ground zero, and open 16 Fang Cang hospitals using the big sport, conference, exhibition, and performance buildings (fig. 1; http://wjw.wuhan.gov.cn/; accessed March 1, 2020). The most common and severe complication in patients with COVID-19 is acute hypoxemic respiratory failure or acute respiratory distress syndrome (ARDS), requiring oxygen and ventilation therapies.3  Some of these critically ill patients required intubation and invasive ventilation.3,4  Moreover, although elective surgeries were largely cancelled, emergency surgeries for patients with confirmed or suspected COVID-19 were permitted to proceed. Some of these surgeries were performed under general anesthesia with endotracheal intubation. Intubating and ventilating patients with COVID-19 who are critically ill or require emergent surgical procedures present some unique challenges to providers.

The healthcare system and providers need to be prepared in and outside of China for the COVID-19 outbreak now and for any outbreaks in the future. Preparedness is a pressing issue considering that many places and countries in the world are under-resourced, and at the time of writing this article, COVID-19 is quickly unfolding and evolving outside of mainland China. Healthcare providers, who are tasked with taking care of critically ill patients, need to perform the best practices of intubation and ventilation tailored explicitly to the victims of this sweeping COVID-19 outbreak and, at the same time, adhere to strict self-protection precautions. Wuhan’s experience needs to be highlighted and quickly communicated throughout the world. In February 2020, we conducted four webinars specifically discussing the issues related to preparedness, airway management, lung-protective ventilation, the goal of oxygenation, and extracorporeal membrane oxygenation (fig. 2). We summarize the results of these discussions, which were based on firsthand experience with treating critically ill patients in Wuhan.

Demand of Intubation and Invasive Ventilation amid the COVID-19 Outbreak

COVID-19 has a wide spectrum of clinical severity, ranging from asymptomatic to critically ill, and ultimately death.1,5,6  A common and prominent complication of advanced COVID-19 is acute hypoxemic respiratory insufficiency or failure requiring oxygen and ventilation therapies (fig. 3).3,4  A recent report showed that 14% of patients developed dyspnea, tachypnea with a respiratory rate greater than or equal to 30 per minute, desaturation with peripheral oxygen saturation (Spo2) less than or equal to 93%, poor oxygenation with a ratio of partial pressure of arterial oxygen (Pao2) to fraction of inspired oxygen (Fio2) less than 300 mmHg, or lung infiltrates greater than 50% within 48 h.1  ARDS occurred in 20% of the 138 patients hospitalized and in 61% of the 36 patients admitted to the intensive care unit (ICU) in Zhongnan Hospital in Wuhan.4  Organ dysfunction, injury, or failure, excluding the lungs, is common. Cardiac injury occurred in 23%, liver injury in 29%, and acute kidney injury in 29% of critically ill patients.3  Neurocognitive impairments occurred in more than one third of patients with advanced COVID-19.7 

Invasive ventilation via an endotracheal tube is common amid this outbreak. It was performed in 2.3% of the 1,099 patients with confirmed COVID-19 based on the patient cohort from 552 hospitals in 30 provinces, autonomous regions, and municipalities in mainland China,1  in 47% of the 36 patients admitted to the ICU in Zhongnan Hospital in Wuhan,4  and in 42% of the 52 patients admitted to the ICU in Jin Yin Tan Hospital in Wuhan.3 

Although elective surgeries were cancelled in the epicenter of Wuhan, emergent surgeries were permitted amid this outbreak. As of February 29, 2020, a total of 105 emergent surgical procedures, including 90 cesarean sections (classified as emergent surgery amid this outbreak; fig. 4), were performed in patients with confirmed or suspected COVID-19 in Tongji Hospital in Wuhan (data from Dr. Wan). Some of these procedures were performed under general anesthesia with endotracheal intubation. The anesthesiologists from the Department of Anesthesiology at Tongji Hospital in Wuhan performed approximately 200 nonoperating room intubations in patients with confirmed COVID-19 as of February 29, 2020. This is just a snapshot of the anesthetic practice in the epicenter of Wuhan amid this outbreak.

Currently, we do not have data detailing the total number of patients with COVID-19 who received intubation and invasive ventilation or details about the outcomes associated with and after these invasive interventions. Nonetheless, we can attempt to estimate this based on the available data. As of February 29, 2020, a total of 2,870 patients with confirmed COVID-19 have died (http://www.nhc.gov.cn/; accessed March 1, 2020). It is assumed that all of these patients died in ICUs, as most, if not all, of them should have been admitted to the ICU before their death. We estimate that, if using a mortality rate of 50% among patients who were admitted to the ICU, a total of 5,740 patients would have been admitted to the ICU (2,870 × 2 = 5,740) as of February 29, 2020. One recent report showed a mortality rate of 61.5% in patients who were admitted to the ICU.3  The other report showed a mortality rate of 49% among critically ill patients.8  We used a mortality rate of 50% in our estimate. Based on the data reporting an invasive ventilation rate of approximately 45% in patients who were admitted to the ICU,3,4  we estimate that approximately 2,583 patients with COVID-19 received intubation and invasive ventilation, accounting for approximately 3.2% (2,583 of 79,824) of all confirmed COVID-19 cases, as of February 29, 2020, in mainland China.

Intubation Criteria

The decision to intubate can be obvious and require little deliberation, as for patients with cardiopulmonary arrest or a lost or jeopardized airway. It can also be a decision that lacks quality evidence for guidance and, thus, is a decision made at the discretion of the treating physician. In patients with acute hypoxemic respiratory failure due to COVID-19, it can be challenging when deciding whether to proceed with intubation and invasive ventilation. The Chinese Society of Anesthesiology Task Force on Airway Management released a fast-track publication with the recommendation to proceed with endotracheal intubation for patients showing no improvement in respiratory distress, tachypnea (respiratory rate greater than 30 per minute), and poor oxygenation (Pao2 to Fio2 ratio less than 150 mmHg) after 2-h high-flow oxygen therapy or noninvasive ventilation.9 

These criteria should be regarded as empirical as there is no robust supporting evidence. The frontline physicians taking care of critically ill patients in Wuhan suggest that intubation and invasive ventilation may have been adversely delayed in some patients. They are concerned that, amid this particular outbreak, intubation is more often used as a salvage therapy than a proactive means of supporting patients whose oxygenation is progressively declining and oxygen debt keeps increasing. The most recent report showed that, among the 22 ICU patients who were intubated, 19 (86%) of them died.3  Although most frontline physicians believe the decision of intubation in some critically ill patients with COVID-19 had been adversely delayed, we do not know at this time if early intubation could save more lives. We do know, based on the work performed 30 yr ago by Shoemaker et al., that there is a close association between the oxygen debt accumulated over 48 h and the chance of survival in patients undergoing high-risk surgery and ICU admission afterward.10  Shoemaker et al.’s work highlights the importance of timely stopping an enlarging oxygen debt using effective oxygenation and ventilation therapies.

The decision-making process for nonoperating room intubation used in Wuhan is summarized in figure 5. Timely, not premature, intubation is the keyword in decision-making. We added liberal criteria, including Spo2 less than 93% in room air and a Pao2 to Fio2 ratio less than 300 mmHg, to facilitate preparedness for intubation based on the experience of taking care of critically ill patients in Wuhan. This proposal is justified as unprepared emergent intubation carries more risks, including cross-infection. It is also justified by the observation that some patients are relatively asymptomatic although they have a good degree of hypoxemia for inexplicable reasons (referred to as “silent hypoxemia” in Wuhan).11  Silent hypoxemia may be responsible for the quick deterioration in some patients because it gives a false sense of well-being when the oxygen debt has been actually and asymptomatically increasing. This algorithm emphasizes vigilance by asking two questions for patients with respiratory distress or hypoxemia. One is whether the condition has been progressively deteriorating or if it is expected to get worse; if the answer is yes, the next question is whether 2-h high-flow oxygen therapy or noninvasive ventilation is effective.

Enhanced Risks and Protective Mandate during Intubation and Ventilation

Both patients and healthcare workers have to endure enhanced, but distinctive, risks during intubation and ventilation management amid the COVID-19 outbreak. The enhanced risks to patients will be discussed in the coming sections of this article. The enhanced risk to healthcare workers is cross-infection.

Of the 138 hospitalized patients with confirmed COVID-19 in Zhongnan Hospital in Wuhan, 40 (29%) patients were healthcare workers with hospital-associated transmission suspected as the mechanism of infection.4  Five anesthesia providers working in Tongji Hospital in Wuhan were diagnosed with COVID-19. Two providers likely contracted the infection when taking care of patients with COVID-19 in December 2019 when the self-protection mandate had not yet been established. The other three providers likely contracted the infection from family members. All five providers have recovered. Since the establishment of the self-protection mandate in January 2020, no anesthesia providers in Tongji Hospital have contracted the infection. Dr. Shanglong Yao, a well-known anesthesiologist and former vice president of the Union Hospital in Wuhan, was diagnosed with COVID-19, with the infection likely transmitted from his daughter. Dr. Yao was hospitalized for a prolonged 4 weeks for close observation of the new-onset atrial fibrillation and poorly controlled hypertension. He eventually recovered and was discharged home (fig. 6). These are just some examples of the situations related to the healthcare providers who were infected.

It was estimated that, as of February 11, 2020, a total of 1,716 health workers had confirmed COVID-19 and five had died (0.3%) in mainland China.12  The total number of cases of healthcare worker infections could be much more than this estimate. It was an observation that most of these infections occurred at the early stage of this outbreak when the self-protection mandate had not been established and reinforced. The mechanisms of transmission responsible for these infections are unknown; some cases may be nosocomial infections while the remainder may not be work related. We also do not know how many nosocomial infections are attributable to the intubation process or ventilation management.

The lesson we learned from the 2003 SARS outbreak is that, compared with healthcare workers who do not perform intubation or ventilation management, those who perform these tasks have a higher risk of contracting the infection. A systematic review showed that compared with healthcare workers who did not perform aerosol-generating procedures, those who performed tracheal intubation had an increased risk of contracting the 2003 SARS (odds ratio, 6.6), as were those who performed noninvasive ventilation (odds ratio, 3.1), tracheotomy (odds ratio, 4.2), and manual ventilation before intubation (odds ratio, 2.8).13  A separate study found that the protection guidelines failed to thoroughly prevent the transmission of 2003 SARS to healthcare workers and that 9% of the interviewed healthcare workers who had intubated patients contracted SARS.14  However, the cause-effect relationship between infection and intubation in these healthcare workers who contracted SARS was unknown.14 

Despite the enhanced risk to healthcare workers, the potential harm of withholding intubation may outweigh the potential risk of cross-infection in patients who would benefit from invasive ventilation support.15  Whenever intubation and invasive ventilation are needed, they should be timely and effectively provided. The healthcare workers who are involved in caring for patients with known or suspected COVID-19 should strictly adhere to the self-protection mandate (table 2).

The self-protection mandate for healthcare workers was quickly established and reinforced throughout different hospitals in Wuhan after the recognition of human-to-human transmission of COVID-19 toward the end of January 2020. Extensive and efficient education and training were provided to all healthcare workers. At the same time, personal protective equipment that was most needed was delivered to Wuhan and the rest of the country where the epidemic was quickly evolving. The contact and airborne precautions, with components of personal protective equipment, are presented in table 2. The different levels of precautions were scaled per the settings of patient care in Wuhan and the rest of China (table 3). Full precaution (level III) is mandatory for any care that involves direct patient contact, including intubation and ventilation management.

In China, it is mandatory to strictly follow the personal protective equipment donning process for high-risk exposure in the following order: disposable hair cover, fit-tested N95 respirator or equivalent, fluid-resistant gown, two layers of gloves, goggle and face shield, and fluid-resistant shoe covers.9  Before entering an isolation area, an experienced nurse or assistant is responsible for checking the donning process (fig. 7). It is crucial to make sure the personal protective equipment is donned in the manner that will not interfere with procedures. It is also mandatory to strictly follow the personal protective equipment doffing process after high-risk exposure in the followingorder: hand hygiene, face shield and goggle removal, fluid-resistant gown removal, outer glove removal, shoe cover removal, inner glove removal, hand hygiene, N95 respirator or equivalent removal, and hair cover removal.9  The doffing process should also be supervised, but not facilitated, to reduce the chance of contamination. It is mandatory to report any inadvertent contamination of the skin or mucosa to the hospital infection control office to assess the need for quarantine. A shower and the use of oral, nasal, and external auditory canal disinfectants are recommended after the removal of personal protective equipment.

Intubation and Extubation

Patients with confirmed or suspected COVID-19 should be regarded as having an augmented risk of presenting potentially difficult and complicated intubation for the following reasons. First, when a patient requires intubation for acute hypoxemic respiratory failure, they have minimal to no respiratory reserve, and their compensatory mechanisms have already been exhausted. It is common to see a patient who starts with a dangerously low Spo2 quickly decline after loss of spontaneous breathing, followed by a slow recovery with manual facemask ventilation. Second, due to strict infection control and the urgency of intubation, a careful airway evaluation is frequently not possible. Third, the personal protective equipment mandated by the level III scaled precaution makes the performance of the procedure clumsy, which may easily compromise the intubation process. Fourth, strict infection and traffic control restrict backup supplies and helpers from being readily available when they are needed. Fifth, the psychological pressure related to concerns of cross-infection challenges the providers, which may make an otherwise easy intubation complicated.

Preparedness minimizes the chance of cross-infection and improves the chance of smooth intubation. The proposed approach to prepare for intubation for patients with confirmed or suspected COVID-19 is summarized in table 4. We recommend using the acronym OH–MS. MAID—Oxygen, Helper, Monitor, Suction, Machine, Airway supplies, Intravenous access, and Drugs—to facilitate the preparation process for intubation. In Wuhan, all portable supplies, needed or potentially needed, are packed in one package. One-time use disposable supplies are preferred. Equipment that has to be reused is dedicated for patients with confirmed or suspected COVID-19. No glitch or imperfection is minor when there is an associated risk. Preparedness is even more crucial amid the COVID-19 outbreak, as the chance of contamination may be readily enhanced during the process of a complicated intubation when all attention is devoted to saving a patient’s life. An experienced practitioner, instead of students or junior personnel, should be assigned to this job. A careful and efficient airway evaluation, whenever possible, should be performed ahead of intubation.

Equipment that is used for more than one patient should be cleaned and disinfected before and after each use. The mixture of ethanol and chlorhexidine is recommended as the disinfecting solution for the breathing circuit in China. Two single-use filters (PALL BB50T Breathing Circuit Filter, Pall Corp., USA), placed in the inhalation and exhalation breathing circuits, are used for infection control in Wuhan. This breathing circuit filter appears capable of preventing the spread of influenza A (H1N1) virus from intubated patients,16  and thus is implicated to be equally capable of preventing the spread of the 2019 novel coronavirus.

In Wuhan, most of the patients were on either high-flow oxygen therapy or bilevel positive airway pressure ventilation when the intubation was called. If the patient is on high-flow oxygen therapy, consider using a bag valve mask or a tightly fitting facemask connected to the already prepared ventilator for preoxygenation. If the patient is on a bilevel positive airway pressure machine, continue bilevel positive airway pressure ventilation for preoxygenation (Supplemental Digital Content, http://links.lww.com/ALN/C348). Increase oxygen flow and use 100% Fio2 to maximize oxygenation. Make sure the airway is patent. It is well advised to apply an oral or nasal airway at the first sign of difficult masking. Consider manual positive pressure ventilation using a bag valve mask if preoxygenation fails to improve oxygenation.

It was shown that noninvasive ventilation applied for 3 min before tracheal intubation resulted in better oxygenation than a nonrebreather bag valve mask.17  However, a multicenter randomized trial based on the evaluation of 100% Fio2 administered with noninvasive ventilation versus that with a facemask for 3 min before tracheal intubation failed to demonstrate any benefits of using noninvasive ventilation as a preoxygenation method to reduce organ dysfunction in hypoxemic, critically ill patients.18  Clearly, there is a gap between improved oxygenation and unchanged outcomes. Although the aerosol-generating potential of noninvasive ventilation is a potential concern to some providers,19  the bilevel positive airway pressure machine is widely used amid this outbreak for patients with acute hypoxemic respiratory failure in Wuhan and the rest of China. We would not recommend using bilevel positive airway pressure for preoxygenation in patients who are not on bilevel positive airway pressure ventilation; however, bilevel positive airway pressure ventilation should be continued if it is already in use.

After satisfactory preoxygenation, modified rapid sequence induction is the recommended technique for anesthesia induction.9  Midazolam 1 to 2 mg may be considered for extremely anxious patients. Intravenous lidocaine, 1.5 mg/kg or more, is effective in suppressing coughing during endotracheal intubation.20  Use a small dose of etomidate (0.2 to 0.3 mg/kg) for patients with hemodynamic instability or propofol (1 to 1.5 mg/kg) for patients with stable hemodynamics for induction.9  Some providers may opt to avoid etomidate due to concerns of adrenal suppression. Rocuronium 1 mg/kg or succinylcholine 1 mg/kg is administered immediately after loss of consciousness. Fentanyl 50 to 100 mcg, sufentanil 10 to 20 mcg, or remifentanil 2.5 mcg/kg21  may be used to suppress laryngeal reflexes and optimize the intubation condition. Because opioids have the potential to cause coughing,22  some providers prefer to give opioids after the accomplishment of satisfactory muscle relaxation. The choice and dose of anesthetics should be determined on a case-by-case basis, with the patient’s hemodynamic stability, severity of illness, and mental status taken into consideration. Vasoactive drugs should be readily available to treat extreme cardiovascular reactions. Ventilation through a patent airway and using a small tidal volume should be continued throughout the induction process until the patient is intubated. The goal is to have the patient intubated within 60 s after administration of muscle relaxants.9  The rationale behind modified rapid sequence induction in China is to shorten the period of potentially ineffective ventilation, from the moment of losing consciousness to the moment of successful endotracheal intubation, in critically ill patients with minimal to no oxygen reserve due to COVID-19.

The approach of using modified rapid sequence induction in this patient population may be criticized, as some providers may prefer to proceed with slow and controlled induction if there is no immediate aspiration risk. They may argue that maximizing oxygen reserve, immediately after anesthetic induction but before endotracheal intubation, is warranted in patients with acute hypoxemic respiratory failure. They may also argue that immediately administering muscle relaxants after anesthesia induction, without testing the effectiveness of bag valve mask ventilation, is not well advised. We recognize this potential difference in approaches and leave it open for further discussion.

Patient coughing during intubation can generate aerosols and should be avoided. Gentle airway manipulation is warranted. It is prudent to use video laryngoscopy rather than direct laryngoscopy for intubation because the former increases the distance between the healthcare worker’s face and the patient’s face, which may minimize the risk of contamination (fig. 8). Videoscopes also allow assistants to visualize the airway so that they can better facilitate the procedure. In Wuhan, chest auscultation after intubation is not recommended, unless absolutely needed, due to concerns of contamination. Capnography, fogging inside of the endotracheal tube, chest movement, Spo2, the color of the patient’s skin and mucous membrane, and vigilance are used to differentiate between a failed and successful intubation.

The same precautions should be considered during extubation. Measures to prevent patient agitation, coughing, and bucking should be applied. Appropriate levels of sedation, such as dexmedetomidine (0.4 mcg · kg-1 · h-1)23  or remifentanil (1 to 4 ng/ml target organ concentration)24  infusion, should be considered. Intravenous lidocaine (1 to 1.5 mg/kg) is effective for cough reduction.25,26  Alfentanil (15 mcg/kg) is also effective in decreasing coughing and agitation during anesthesia emergence.27 

Ventilation Management

Mechanical ventilation, though vital in supporting respiratory function in patients with acute hypoxemic respiratory failure or ARDS, may promote lung damage, a phenomenon known as ventilator-induced lung injury.28  Currently, we lack any guidelines or evidence to help us manage invasive mechanical ventilation in critically ill patients with COVID-19. It is well advised to adopt the guidelines established for patients with ARDS,29,30  with appropriate modifications based on the firsthand patient care experience in Wuhan (table 5). This is justified as 67% of the ICU patients developed ARDS based on the recent report.3 

The ARDS lung-protective ventilation guidelines emphasize: (1) a tidal volume less than or equal to 6 ml/kg predicted body weight; (2) a respiratory rate less than or equal to 35 breaths/min; (3) a plateau airway pressure less than or equal to 30 cm H2O; and (4) a positive end-expiratory pressure (PEEP) greater than or equal to 5 cm H2O.31,32  The tidal volume can be started at 8 ml/kg and then lowered with an ultimate goal of 6 ml/kg. Some clinicians believe that, as long as the plateau pressure can be maintained at less than or equal to 30 cm H2O, it may be safe to ventilate the patient with tidal volumes greater than 6 ml/kg predicted body weight.33  The precise tidal volume for an individual patient should be adjusted according to the patient’s plateau pressure, selected PEEP, thoracoabdominal compliance, and breathing effort.29  It is advantageous to have a driving pressure (plateau pressure minus PEEP) below 12 to 15 cm H2O via tidal volume and PEEP adjustments in patients who are not spontaneously breathing.34 

In Wuhan, patients with acute hypoxemic respiratory failure due to COVID-19 have a poor tolerance to high PEEP, likely as the result of the direct and severe lung damage by the virus and inflammatory reactions. The plateau pressure reaches 40 to 50 cm H2O when the PEEP is set at 18 cm H2O, Fio2 at 100%, and the tidal volume at 6 ml/kg according to the Fio2 and PEEP table.32  The widely used practice in Wuhan, after lung recruitment maneuvers, is to set PEEP at 20 cm H2O and titrate down in a decrement of 2 to 3 cm H2O each time until the goals of oxygenation, plateau pressure, and compliance are all achieved. The commonly used PEEP in this patient population is less than 10 cm H2O.

No mode of ventilation has been suggested to be superior to others.35  There is literature suggesting that high-frequency oscillatory ventilation may be an option for viral-induced lung injury.36  However, it may be best to avoid high-frequency oscillatory ventilation in patients with COVID-19 due to concerns of aerosol generation.19,37,38  High-frequency oscillatory ventilation has not been used amid this outbreak in Wuhan. Pressure-regulated volume control ventilation, although increasingly popular in the perioperative arena, has not gained momentum in ICUs due to the lack of evidence for its outcome benefits. In patients with acute lung injury or ARDS, the tidal volume can markedly exceed the lung-protective ventilation target during pressure-regulated volume control ventilation,39  which is not desirable. Pressure-regulated volume control is not the preferred mode of ventilation in Wuhan.

Ventilation in the prone position improves lung mechanics and gas exchange and is currently recommended by the guidelines.29,30  The prone position, if planned, should not be a desperate final attempt but should be considered in the early stages of the disease,40  as the evidence suggests that the early application of prolonged ventilation in the prone position decreases 28- and 90-day mortality in patients with severe ARDS.41  Prone position ventilation is currently widely used for critically ill patients in Wuhan (fig. 9). Lung recruitment maneuvers, via transient elevations in airway pressure applied during mechanical ventilation, can open collapsed alveoli and thus increase the number of alveoli available for gas exchange. Lung recruitment maneuvers do not significantly reduce mortality but may improve oxygenation and shorten the length of hospital stay in ARDS patients.42  Overall, recruitment maneuvers are not supported by high-quality evidence,43  and caution should be exercised when using it because it can be irritating, incite coughing, and generate aerosols.

Adjunct therapies can be considered. Many patients with acute hypoxemic respiratory failure due to COVID-19 have breathing overdrive. Appropriate sedation and analgesia, such as dexmedetomidine, propofol and remifentanil infusion, are warranted. The outcome evidence related to the use of muscle relaxants has been controversial.44,45  A recent meta-analysis concluded that muscle relaxants improve oxygenation after 48 h, but do not reduce mortality in moderate and severe ARDS patients.46  Nonetheless, muscle relaxation should be considered in cases of breathing overdrive, patient–ventilator dyssynchrony, and inability to achieve the targeted tidal volume and plateau pressure. It is appropriate to be conservative with intravenous fluids in patients with severe lung injury if there are no signs of tissue hypoperfusion.29  Conservative fluid therapy is the strategy used in Wuhan. It is important to avoid corticosteroid treatment, given that this treatment has been shown to increase mortality and hospital-acquired infections in patients with severe influenza.47–49  However, the most recent study suggested that early dexamethasone administration may reduce overall mortality and mechanical ventilation duration in ARDS patients.50  Corticosteroid treatment is currently used in selected patients with severe inflammatory lung injury in Wuhan. Disconnecting the patient from the ventilator results in loss of PEEP and atelectasis, and it should be avoided. In-line catheters for airway suctioning and endotracheal tube clamping are recommended before disconnecting breathing circuits.

Extracorporeal membrane oxygenation was successfully used in patients with severe influenza51  and may play an important role in select patients. A recent review concluded that the potential of extracorporeal membrane oxygenation in reducing mortality in patients with ARDS due to H1N1 infection was apparent and that extracorporeal membrane oxygenation should be used as a salvage option in severely hypoxemic ARDS patients.52  The Conventional Ventilation or ECMO for Severe Adult Respiratory Failure (CESAR) trial showed that there is a potential role for extracorporeal membrane oxygenation–based management protocols in patients with severe but potentially reversible respiratory failure, and these protocols may improve survival without causing severe disabilities.53  The ECMO to Rescue Lung Injury in Severe ARDS (EOLIA) trial showed that extracorporeal membrane oxygenation was not able to significantly reduce 60-day mortality in patients with very severe ARDS;54  however, the post hoc Bayesian analysis suggested a potential mortality benefit under a broad set of assumptions.55  Extracorporeal membrane oxygenation has been used in some critically ill patients with COVID-19 in Wuhan. More than 40 extracorporeal membrane oxygenation cases (combined) have been treated in Zhongnan Hospital, Jin Yin Tan Hospital, and Lung Hospital in Wuhan. The outcomes of these patients remain to be analyzed.

Summary

The COVID-19 outbreak is a sweeping and unprecedented challenge in China. Its impacts are currently rapidly unfolding outside of China. As of March 4, 2020, COVID-19 was confirmed in 80,409 patients and led to 3,012 deaths in mainland China. Approximately 3.2% of patients with COVID-19 received intubation and invasive ventilation support. How to provide the best practices of intubation and ventilation amid this mass medical emergency is a real but unprecedented question. In this article, we summarize the firsthand experience pertinent to intubation and ventilation management from the physicians who are taking care of the critically ill patients with COVID-19 in Wuhan. In patients with acute refractory hypoxemic respiratory failure, timely, but not premature, intubation and invasive ventilation support may be superior to high-flow oxygen therapy and bilevel positive airway pressure ventilation in boosting transpulmonary pressure, opening collapsed alveoli, improving oxygenation, decreasing oxygen debt, and offering a better chance for the lungs to heal. The invasive nature of intubation and ventilation exposes patients to an augmented risk of procedure-related mishaps. At the same time, these procedures present healthcare providers with an enhanced risk of cross-infection; thus, strict self-protection precautions are mandatory.

Acknowledgments

This article was made possible by the generous sharing of firsthand experience from the physicians who had participated in the webinars held in February 2020. The authors thank Dr. Lize Xiong (Shanghai Fourth People’s Hospital, Shanghai, China), Drs. Yuhang Ai, Qulian Guo, and Jie Meng (Central South University Xiangya Hospital, Changsha, China), Dr. Zhanggang Xue (Fudan University Zhongshan Hospital, Shanghai, China), Drs. Chunchun Zhai, Qianqian Qiao, and Wenfang Xia (Renmin Hospital of Wuhan University, Wuhan, China), Dr. Chuanyao Tong (Wake Forest University, Winston-Salem, North Carolina), and Dr. Hong Liu (University of California Davis Medical Center, Sacramento, California) for their participation in the first webinar held on February 8, 2020, discussing the preparedness of anesthesiologists and intensivists amid the COVID-19 outbreak. The authors also thank Dr. Lize Xiong (Shanghai Fourth People’s Hospital, Shanghai, China), Dr. Dan Liu (West China Hospital, Chengdu, China), Dr. Zhanggang Xue (Fudan University Zhongshan Hospital, Shanghai, China), Dr. Mingzhang Zuo (Beijing Hospital, Beijing, China), Dr. Wuhua Ma (The First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, Guangzhou, China), Dr. Hongfei Zhang (Guangzhou Zhujiang Hospital, Guangzhou, China), Dr. Huafeng Wei (University of Pennsylvania, Philadelphia, Pennsylvania), Dr. Liming Zhang (University of Pittsburgh, Pittsburgh, Pennsylvania), and Drs. Chunchun Zhai and Qianqian Qiao (Renmin Hospital of Wuhan University, Wuhan, China) for their participation in the second webinar held on February 15, 2020, discussing airway management amid the COVID-19 outbreak. The authors also thank Dr. Shanglong Yao (Wuhan Union Hospital, Wuhan, China), Drs. Haibo Qiu and Yi Yang (Southeast University Zhongda Hospital, Nanjing, China), Dr. Hongliang Wang (Harbin Medical University Affiliated Second Hospital, Harbin, China), Dr. Wei Fang (The Affiliated Hospital of Qingdao University, Qingdao, China), Dr. Xiuling Shang (Fujian Provincial Hospital, Fuzhou, China), Dr. Lina Zhang (Central South University Xiangya Hospital, Changsha, China), Dr. Dongxin Wang (Peking University First Hospital, Beijing, China), Dr. Zhanggang Xue (Fudan University Zhongshan Hospital, Shanghai, China), and Dr. Chuanyao Tong (Wake Forest University, Winston-Salem, North Carolina) for their participation in the third webinar held on February 22, 2020, discussing lung-protective ventilation and the goal of oxygenation amid the COVID-19 outbreak. The authors also thank Dr. Zhaohui Tong and Dr. Xuyan Li (Beijing Chaoyang Hospital, Beijing, China), Dr. Xiaotong Hou (Beijing Anzhen Hospital, Beijing China), Dr. Ming Hu (Wuhan Pulmonary Hospital, Wuhan, China), Dr. Bo Hu (Wuhan Zhongnan Hospital, Wuhan, China), Dr. Ming Zhong (Fudan University Zhongshan Hospital, Shanghai, China), Dr. Ruiqiang Zheng (Su Bei People’s Hoispital, Yangzhou, China), Drs. Haibo Qiu, Chun Pan, and Jianfeng Xie (Southeast University Zhongda Hospital, Nanjing, China), and Dr. Hong Liu (University of California David Medical Center, Sacramento, California) for their participation in the fourth webinar held on February 29, 2020, discussing extracorporeal membrane oxygenation amid the COVID-19 outbreak. All these four webinars were organized by Dr. Lingzhong Meng (Yale University School of Medicine, New Haven, Connecticut). Most of these physicians are currently working at the epicenter, Wuhan, China. We thank Dr. Xu Zhao (Xiangya Medical School, Central South University, Changsha, China) for his assistance with the literature search, data analysis, and manuscript preparation.

Research Support

This work was supported, in part, by research grant No. 2020YFC0843700 from the Ministry of Science and Technology of the People’s Republic of China (Beijing, China; to Dr. Haibo Qiu). It was also supported by institutional and departmental sources with which the authors are affiliated.

Competing Interests

The authors declare no competing interests.

References

References
1.
Guan
WJ
,
Ni
ZY
,
Hu
Y
,
Liang
WH
,
Ou
CQ
,
He
JX
,
Liu
L
,
Shan
H
,
Lei
CL
,
Hui
DSC
,
Du
B
,
Li
LJ
,
Zeng
G
,
Yuen
KY
,
Chen
RC
,
Tang
CL
,
Wang
T
,
Chen
PY
,
Xiang
J
,
Li
SY
,
Wang
JL
,
Liang
ZJ
,
Peng
YX
,
Wei
L
,
Liu
Y
,
Hu
YH
,
Peng
P
,
Wang
JM
,
Liu
JY
,
Chen
Z
,
Li
G
,
Zheng
ZJ
,
Qiu
SQ
,
Luo
J
,
Ye
CJ
,
Zhu
SY
,
Zhong
NS
: .
Clinical characteristics of coronavirus disease 2019 in China.
N Engl J Med
.
2020
.
[Epub ahead of print]. DOI: 10.1056/NEJMoa2002032
2.
Gates
B
: .
Responding to COVID-19—A once-in-a-century pandemic?
N Engl J Med
.
2020
.
[Epub ahead of print]. DOI: 10.1056/NEJMp2003762
3.
Yang
X
,
Yu
Y
,
Xu
J
,
Shu
H
,
Xia
J
,
Liu
H
,
Wu
Y
,
Zhang
L
,
Yu
Z
,
Fang
M
,
Yu
T
,
Wang
Y
,
Pan
S
,
Zou
X
,
Yuan
S
,
Shang
Y
: .
Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: A single-centered, retrospective, observational study.
[Epub ahead of print].
Lancet Respir Med
.
2020
.
DOI: 10.1016/S2213-2600(20)30079-5
4.
Wang
D
,
Hu
B
,
Hu
C
,
Zhu
F
,
Liu
X
,
Zhang
J
,
Wang
B
,
Xiang
H
,
Cheng
Z
,
Xiong
Y
,
Zhao
Y
,
Li
Y
,
Wang
X
,
Peng
Z
: .
Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus–infected pneumonia in Wuhan, China.
[Epub ahead of print].
JAMA
.
2020
.
DOI:10.1001/jama.2020.1585
5.
Huang
C
,
Wang
Y
,
Li
X
,
Ren
L
,
Zhao
J
,
Hu
Y
,
Zhang
L
,
Fan
G
,
Xu
J
,
Gu
X
,
Cheng
Z
,
Yu
T
,
Xia
J
,
Wei
Y
,
Wu
W
,
Xie
X
,
Yin
W
,
Li
H
,
Liu
M
,
Xiao
Y
,
Gao
H
,
Guo
L
,
Xie
J
,
Wang
G
,
Jiang
R
,
Gao
Z
,
Jin
Q
,
Wang
J
,
Cao
B
: .
Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China.
Lancet
.
2020
;
395
:
497
506
6.
Chen
N
,
Zhou
M
,
Dong
X
,
Qu
J
,
Gong
F
,
Han
Y
,
Qiu
Y
,
Wang
J
,
Liu
Y
,
Wei
Y
,
Xia
J
,
Yu
T
,
Zhang
X
,
Zhang
L
: .
Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: A descriptive study.
Lancet
.
2020
;
395
:
507
13
7.
Mao
L
,
Wang
M
,
Chen
S
,
He
Q
,
Chang
J
,
Hong
C
,
Zhou
Y
,
Wang
D
,
Li
Y
,
Jin
H
,
Hu
B
: .
Neurological manifestations of hospitalized patients with COVID-19 in Wuhan, China: A retrospective case series study.
[Epub ahead of print].
medRxiv
.
2020
.
DOI: 10.1101/2020.02.22.20026500
8.
Wu
Z
,
McGoogan
JM
: .
Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: Summary of a report of 72 314 cases from the Chinese Center for Disease Control and Prevention.
JAMA
.
2020
.
[Epub ahead of print]. DOI: 10.1001/jama.2020.2648
9.
Zuo
MZ
,
Huang
YG
,
Ma
WH
,
Xue
ZG
,
Zhang
JQ
,
Gong
YH
,
Che
L
;
Chinese Society of Anesthesiology Task Force on Airway Management
: .
Expert recommendations for tracheal intubation in critically ill patients with noval coronavirus disease 2019.
[Epub ahead of print].
Chin Med Sci J
.
2020
.
DOI: 10.24920/003724
10.
Shoemaker
WC
,
Appel
PL
,
Kram
HB
: .
Role of oxygen debt in the development of organ failure sepsis, and death in high-risk surgical patients.
Chest
.
1992
;
102
:
208
15
11.
Xie
J
,
Tong
Z
,
Guan
X
,
Du
B
,
Qiu
H
,
Slutsky
AS
: .
Critical care crisis and some recommendations during the COVID-19 epidemic in China.
Intensive Care Medicine
.
2020
.
[Epub ahead of print]. DOI: 10.1007/s00134-020-05979-7
12.
Novel Coronavirus Pneumonia Emergency Response Epidemiology Team:
: .
[The epidemiological characteristics of an outbreak of 2019 novel coronavirus diseases (COVID-19) in China].
Zhonghua Liu Xing Bing Xue Za Zhi
.
2020
;
41
:
145
51
13.
Tran
K
,
Cimon
K
,
Severn
M
,
Pessoa-Silva
CL
,
Conly
J
: .
Aerosol generating procedures and risk of transmission of acute respiratory infections to healthcare workers: A systematic review.
PLoS One
.
2012
;
7
:
e35797
14.
Caputo
KM
,
Byrick
R
,
Chapman
MG
,
Orser
BJ
,
Orser
BA
: .
Intubation of SARS patients: Infection and perspectives of healthcare workers.
Can J Anaesth
.
2006
;
53
:
122
9
15.
McCracken
J
: .
Should noninvasive ventilation be considered a high-risk procedure during an epidemic?
CMAJ
.
2009
;
181
:
663
4
16.
Heuer
JF
,
Crozier
TA
,
Howard
G
,
Quintel
M
: .
Can breathing circuit filters help prevent the spread of influenza A (H1N1) virus from intubated patients?
GMS Hyg Infect Control
.
2013
;
8
:
Doc09
17.
Baillard
C
,
Fosse
JP
,
Sebbane
M
,
Chanques
G
,
Vincent
F
,
Courouble
P
,
Cohen
Y
,
Eledjam
JJ
,
Adnet
F
,
Jaber
S
: .
Noninvasive ventilation improves preoxygenation before intubation of hypoxic patients.
Am J Respir Crit Care Med
.
2006
;
174
:
171
7
18.
Baillard
C
,
Prat
G
,
Jung
B
,
Futier
E
,
Lefrant
JY
,
Vincent
F
,
Hamdi
A
,
Vicaut
E
,
Jaber
S
: .
Effect of preoxygenation using non-invasive ventilation before intubation on subsequent organ failures in hypoxaemic patients: A randomised clinical trial.
Br J Anaesth
.
2018
;
120
:
361
7
19.
Al-Dorzi
HM
,
Alsolamy
S
,
Arabi
YM
: .
Critically ill patients with Middle East respiratory syndrome coronavirus infection.
Crit Care
.
2016
;
20
:
65
20.
Yukioka
H
,
Hayashi
M
,
Terai
T
,
Fujimori
M
: .
Intravenous lidocaine as a suppressant of coughing during tracheal intubation in elderly patients.
Anesth Analg
.
1993
;
77
:
309
12
21.
Demirkaya
M
,
Kelsaka
E
,
Sarihasan
B
,
Bek
Y
,
Üstün
E
: .
The optimal dose of remifentanil for acceptable intubating conditions during propofol induction without neuromuscular blockade.
J Clin Anesth
.
2012
;
24
:
392
7
22.
Böhrer
H
,
Fleischer
F
,
Werning
P
: .
Tussive effect of a fentanyl bolus administered through a central venous catheter.
Anaesthesia
.
1990
;
45
:
18
21
23.
Kim
SY
,
Kim
JM
,
Lee
JH
,
Song
BM
,
Koo
BN
: .
Efficacy of intraoperative dexmedetomidine infusion on emergence agitation and quality of recovery after nasal surgery.
Br J Anaesth
.
2013
;
111
:
222
8
24.
Nho
JS
,
Lee
SY
,
Kang
JM
,
Kim
MC
,
Choi
YK
,
Shin
OY
,
Kim
DS
,
Kwon
MI
: .
Effects of maintaining a remifentanil infusion on the recovery profiles during emergence from anaesthesia and tracheal extubation.
Br J Anaesth
.
2009
;
103
:
817
21
25.
Bidwai
AV
,
Bidwai
VA
,
Rogers
CR
,
Stanley
TH
: .
Blood-pressure and pulse-rate responses to endotracheal extubation with and without prior injection of lidocaine.
Anesthesiology
.
1979
;
51
:
171
3
26.
Venkatesan
T
,
Korula
G
: .
A comparative study between the effects of 4% endotracheal tube cuff lignocaine and 1.5 mg/kg intravenous lignocaine on coughing and hemodynamics during extubation in neurosurgical patients: A randomized controlled double-blind trial.
J Neurosurg Anesthesiol
.
2006
;
18
:
230
4
27.
Mendel
P
,
Fredman
B
,
White
PF
: .
Alfentanil suppresses coughing and agitation during emergence from isoflurane anesthesia.
J Clin Anesth
.
1995
;
7
:
114
8
28.
Parker
JC
,
Hernandez
LA
,
Peevy
KJ
: .
Mechanisms of ventilator-induced lung injury.
Crit Care Med
.
1993
;
21
:
131
43
29.
Rhodes
A
,
Evans
LE
,
Alhazzani
W
,
Levy
MM
,
Antonelli
M
,
Ferrer
R
,
Kumar
A
,
Sevransky
JE
,
Sprung
CL
,
Nunnally
ME
,
Rochwerg
B
,
Rubenfeld
GD
,
Angus
DC
,
Annane
D
,
Beale
RJ
,
Bellinghan
GJ
,
Bernard
GR
,
Chiche
JD
,
Coopersmith
C
,
De Backer
DP
,
French
CJ
,
Fujishima
S
,
Gerlach
H
,
Hidalgo
JL
,
Hollenberg
SM
,
Jones
AE
,
Karnad
DR
,
Kleinpell
RM
,
Koh
Y
,
Lisboa
TC
,
Machado
FR
,
Marini
JJ
,
Marshall
JC
,
Mazuski
JE
,
McIntyre
LA
,
McLean
AS
,
Mehta
S
,
Moreno
RP
,
Myburgh
J
,
Navalesi
P
,
Nishida
O
,
Osborn
TM
,
Perner
A
,
Plunkett
CM
,
Ranieri
M
,
Schorr
CA
,
Seckel
MA
,
Seymour
CW
,
Shieh
L
,
Shukri
KA
,
Simpson
SQ
,
Singer
M
,
Thompson
BT
,
Townsend
SR
,
Van der Poll
T
,
Vincent
JL
,
Wiersinga
WJ
,
Zimmerman
JL
,
Dellinger
RP
: .
Surviving sepsis campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016.
Intensive Care Med
.
2017
;
43
:
304
77
30.
Fan
E
,
Del Sorbo
L
,
Goligher
EC
,
Hodgson
CL
,
Munshi
L
,
Walkey
AJ
,
Adhikari
NKJ
,
Amato
MBP
,
Branson
R
,
Brower
RG
,
Ferguson
ND
,
Gajic
O
,
Gattinoni
L
,
Hess
D
,
Mancebo
J
,
Meade
MO
,
McAuley
DF
,
Pesenti
A
,
Ranieri
VM
,
Rubenfeld
GD
,
Rubin
E
,
Seckel
M
,
Slutsky
AS
,
Talmor
D
,
Thompson
BT
,
Wunsch
H
,
Uleryk
E
,
Brozek
J
,
Brochard
LJ
;
American Thoracic Society, European Society of Intensive Care Medicine, and Society of Critical Care Medicine
: .
An official American Thoracic Society/European Society of Intensive Care Medicine/Society of Critical Care Medicine Clinical Practice guideline: Mechanical ventilation in adult patients with acute respiratory distress syndrome.
Am J Respir Crit Care Med
.
2017
;
195
:
1253
63
31.
Petrucci
N
,
De Feo
C
: .
Lung protective ventilation strategy for the acute respiratory distress syndrome.
Cochrane Database Syst Rev
.
2013
, pp
Cd003844
32.
Brower
RG
,
Matthay
MA
,
Morris
A
,
Schoenfeld
D
,
Thompson
BT
,
Wheeler
A
: .
Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome.
N Engl J Med
.
2000
;
342
:
1301
8
33.
Marini
JJ
,
Gattinoni
L
: .
Ventilatory management of acute respiratory distress syndrome: A consensus of two.
Crit Care Med
.
2004
;
32
:
250
5
34.
Amato
MB
,
Meade
MO
,
Slutsky
AS
,
Brochard
L
,
Costa
EL
,
Schoenfeld
DA
,
Stewart
TE
,
Briel
M
,
Talmor
D
,
Mercat
A
,
Richard
JC
,
Carvalho
CR
,
Brower
RG
: .
Driving pressure and survival in the acute respiratory distress syndrome.
N Engl J Med
.
2015
;
372
:
747
55
35.
Chacko
B
,
Peter
JV
,
Tharyan
P
,
John
G
,
Jeyaseelan
L
: .
Pressure-controlled versus volume-controlled ventilation for acute respiratory failure due to acute lung injury (ALI) or acute respiratory distress syndrome (ARDS).
Cochrane Database Syst Rev
.
2015
;
1
:
Cd008807
36.
Ramsey
CD
,
Funk
D
,
Miller
RR
3rd
,
Kumar
A
: .
Ventilator management for hypoxemic respiratory failure attributable to H1N1 novel swine origin influenza virus.
Crit Care Med
.
2010
;
38
(
4 Suppl
):
e58
65
37.
Sud
S
,
Sud
M
,
Friedrich
JO
,
Wunsch
H
,
Meade
MO
,
Ferguson
ND
,
Adhikari
NK
: .
High-frequency oscillatory ventilation versus conventional ventilation for acute respiratory distress syndrome.
Cochrane Database Syst Rev
.
2016
;
4
:
CD004085
38.
Sweeney
AM
,
Lyle
J
,
Ferguson
ND
: .
Nursing and infection-control issues during high-frequency oscillatory ventilation.
Crit Care Med
.
2005
;
33
(
3 Suppl
):
S204
8
39.
Kallet
RH
,
Campbell
AR
,
Dicker
RA
,
Katz
JA
,
Mackersie
RC
: .
Work of breathing during lung-protective ventilation in patients with acute lung injury and acute respiratory distress syndrome: A comparison between volume and pressure-regulated breathing modes.
Respir Care
.
2005
;
50
:
1623
31
40.
Xie
H
,
Zhou
ZG
,
Jin
W
,
Yuan
CB
,
Du
J
,
Lu
J
,
Wang
RL
: .
Ventilator management for acute respiratory distress syndrome associated with avian influenza A (H7N9) virus infection: A case series.
World J Emerg Med
.
2018
;
9
:
118
24
41.
Guérin
C
,
Reignier
J
,
Richard
JC
,
Beuret
P
,
Gacouin
A
,
Boulain
T
,
Mercier
E
,
Badet
M
,
Mercat
A
,
Baudin
O
,
Clavel
M
,
Chatellier
D
,
Jaber
S
,
Rosselli
S
,
Mancebo
J
,
Sirodot
M
,
Hilbert
G
,
Bengler
C
,
Richecoeur
J
,
Gainnier
M
,
Bayle
F
,
Bourdin
G
,
Leray
V
,
Girard
R
,
Baboi
L
,
Ayzac
L
;
PROSEVA Study Group
: .
Prone positioning in severe acute respiratory distress syndrome.
N Engl J Med
.
2013
;
368
:
2159
68
42.
Cui
Y
,
Cao
R
,
Wang
Y
,
Li
G
: .
Lung recruitment maneuvers for ARDS patients: A systematic review and meta-analysis.
Respiration
.
2019
, pp
1
13
43.
Hodgson
C
,
Goligher
EC
,
Young
ME
,
Keating
JL
,
Holland
AE
,
Romero
L
,
Bradley
SJ
,
Tuxen
D
: .
Recruitment manoeuvres for adults with acute respiratory distress syndrome receiving mechanical ventilation.
Cochrane Database Syst Rev
.
2016
;
11
:
CD006667
44.
Papazian
L
,
Forel
JM
,
Gacouin
A
,
Penot-Ragon
C
,
Perrin
G
,
Loundou
A
,
Jaber
S
,
Arnal
JM
,
Perez
D
,
Seghboyan
JM
,
Constantin
JM
,
Courant
P
,
Lefrant
JY
,
Guérin
C
,
Prat
G
,
Morange
S
,
Roch
A
;
ACURASYS Study Investigators
: .
Neuromuscular blockers in early acute respiratory distress syndrome.
N Engl J Med
.
2010
;
363
:
1107
16
45.
Moss
M
,
Huang
DT
,
Brower
RG
,
Ferguson
ND
,
Ginde
AA
,
Gong
MN
,
Grissom
CK
,
Gundel
S
,
Hayden
D
,
Hite
RD
,
Hou
PC
,
Hough
CL
,
Iwashyna
TJ
,
Khan
A
,
Liu
KD
,
Talmor
D
,
Thompson
BT
,
Ulysse
CA
,
Yealy
DM
,
Angus
DC
: .
Early neuromuscular blockade in the acute respiratory distress syndrome.
N Engl J Med
.
2019
;
380
:
1997
2008
46.
Ho
ATN
,
Patolia
S
,
Guervilly
C
: .
Neuromuscular blockade in acute respiratory distress syndrome: A systematic review and meta-analysis of randomized controlled trials.
J Intensive Care
.
2020
;
8
:
12
47.
Martin-Loeches
I
,
Lisboa
T
,
Rhodes
A
,
Moreno
RP
,
Silva
E
,
Sprung
C
,
Chiche
JD
,
Barahona
D
,
Villabon
M
,
Balasini
C
,
Pearse
RM
,
Matos
R
,
Rello
J
;
ESICM H1N1 Registry Contributors
: .
Use of early corticosteroid therapy on ICU admission in patients affected by severe pandemic (H1N1) v influenza A infection.
Intensive Care Med
.
2011
;
37
:
272
83
48.
Rodrigo
C
,
Leonardi-Bee
J
,
Nguyen-Van-Tam
J
,
Lim
WS
: .
Corticosteroids as adjunctive therapy in the treatment of influenza.
Cochrane Database Syst Rev
.
2016
;
3
:
CD010406
49.
Lansbury
LE
,
Rodrigo
C
,
Leonardi-Bee
J
,
Nguyen-Van-Tam
J
,
Shen Lim
W
: .
Corticosteroids as adjunctive therapy in the treatment of influenza: An updated Cochrane systematic review and meta-analysis.
Crit Care Med
.
2020
;
48
:
e98
e106
50.
Villar
J
,
Ferrando
C
,
Martínez
D
,
Ambrós
A
,
Muñoz
T
,
Soler
JA
,
Aguilar
G
,
Alba
F
,
González-Higueras
E
,
Conesa
LA
,
Martín-Rodríguez
C
,
Díaz-Domínguez
FJ
,
Serna-Grande
P
,
Rivas
R
,
Ferreres
J
,
Belda
J
,
Capilla
L
,
Tallet
A
,
Añón
JM
,
Fernández
RL
,
González-Martín
JM
;
dexamethasone in ARDS network
: .
Dexamethasone treatment for the acute respiratory distress syndrome: A multicentre, randomised controlled trial.
Lancet Respir Med
.
2020
;
8
:
267
76
51.
Davies
A
,
Jones
D
,
Bailey
M
,
Beca
J
,
Bellomo
R
,
Blackwell
N
,
Forrest
P
,
Gattas
D
,
Granger
E
,
Herkes
R
,
Jackson
A
,
McGuinness
S
,
Nair
P
,
Pellegrino
V
,
Pettila
V
,
Plunkett
B
,
Pye
R
,
Torzillo
P
,
Webb
S
,
Wilson
M
,
Ziegenfuss
M
: .
Extracorporeal membrane oxygenation for 2009 influenza A(H1N1) acute respiratory distress syndrome.
Jama
.
2009
;
302
:
1888
95
52.
Aretha
D
,
Fligou
F
,
Kiekkas
P
,
Karamouzos
V
,
Voyagis
G
: .
Extracorporeal life support: The next step in moderate to severe ARDS-A review and meta-analysis of the literature.
Biomed Res Int
.
2019
;
2019
:
1035730
53.
Peek
GJ
,
Mugford
M
,
Tiruvoipati
R
,
Wilson
A
,
Allen
E
,
Thalanany
MM
,
Hibbert
CL
,
Truesdale
A
,
Clemens
F
,
Cooper
N
,
Firmin
RK
,
Elbourne
D
;
CESAR trial collaboration
: .
Efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR): A multicentre randomised controlled trial.
Lancet
.
2009
;
374
:
1351
63
54.
Combes
A
,
Hajage
D
,
Capellier
G
,
Demoule
A
,
Lavoué
S
,
Guervilly
C
,
Da Silva
D
,
Zafrani
L
,
Tirot
P
,
Veber
B
,
Maury
E
,
Levy
B
,
Cohen
Y
,
Richard
C
,
Kalfon
P
,
Bouadma
L
,
Mehdaoui
H
,
Beduneau
G
,
Lebreton
G
,
Brochard
L
,
Ferguson
ND
,
Fan
E
,
Slutsky
AS
,
Brodie
D
,
Mercat
A
;
EOLIA Trial Group, REVA, and ECMONet
: .
Extracorporeal membrane oxygenation for severe acute respiratory distress syndrome.
N Engl J Med
.
2018
;
378
:
1965
75
55.
Goligher
EC
,
Tomlinson
G
,
Hajage
D
,
Wijeysundera
DN
,
Fan
E
,
Jüni
P
,
Brodie
D
,
Slutsky
AS
,
Combes
A
: .
Extracorporeal membrane oxygenation for severe acute respiratory distress syndrome and posterior probability of mortality benefit in a post hoc Bayesian analysis of a randomized clinical trial.
JAMA
.
2018
;
320
:
2251
9
56.
Wang
C
,
Horby
PW
,
Hayden
FG
,
Gao
GF
: .
A novel coronavirus outbreak of global health concern.
Lancet
.
2020
;
395
:
470
3
57.
Kilinc
FS
: .
A review of isolation gowns in healthcare: Fabric and gown properties.
J Eng Fiber Fabr
.
2015
;
10
:
180
90
58.
Munshi
L
,
Del Sorbo
L
,
Adhikari
NKJ
,
Hodgson
CL
,
Wunsch
H
,
Meade
MO
,
Uleryk
E
,
Mancebo
J
,
Pesenti
A
,
Ranieri
VM
,
Fan
E
: .
Prone position for acute respiratory distress syndrome. A systematic review and meta-analysis.
Ann Am Thorac Soc
.
2017
;
14
(
Supplement_4
):
280
8
59.
Taccone
P
,
Pesenti
A
,
Latini
R
,
Polli
F
,
Vagginelli
F
,
Mietto
C
,
Caspani
L
,
Raimondi
F
,
Bordone
G
,
Iapichino
G
,
Mancebo
J
,
Guérin
C
,
Ayzac
L
,
Blanch
L
,
Fumagalli
R
,
Tognoni
G
,
Gattinoni
L
;
Prone-Supine II Study Group
: .
Prone positioning in patients with moderate and severe acute respiratory distress syndrome: A randomized controlled trial.
JAMA
.
2009
;
302
:
1977
84
60.
Bloomfield
R
,
Noble
DW
,
Sudlow
A
: .
Prone position for acute respiratory failure in adults.
Cochrane Database Syst Rev
.
2015
, pp
Cd008095
61.
Wang
L
,
Li
X
,
Yang
Z
,
Tang
X
,
Yuan
Q
,
Deng
L
,
Sun
X
: .
Semi-recumbent position versus supine position for the prevention of ventilator-associated pneumonia in adults requiring mechanical ventilation.
Cochrane Database Syst Rev
.
2016
, pp
Cd009946
62.
Guery
B
,
Poissy
J
,
el Mansouf
L
,
Séjourné
C
,
Ettahar
N
,
Lemaire
X
,
Vuotto
F
,
Goffard
A
,
Behillil
S
,
Enouf
V
,
Caro
V
,
Mailles
A
,
Che
D
,
Manuguerra
JC
,
Mathieu
D
,
Fontanet
A
,
van der Werf
S
;
MERS-CoV study group
: .
Clinical features and viral diagnosis of two cases of infection with Middle East respiratory syndrome coronavirus: A report of nosocomial transmission.
Lancet
.
2013
;
381
:
2265
72