Key messages
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Coronavirus disease 2019 (COVID-19) is the third coronavirus infection in two decades that was originally described in Asia, after severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS).
As the COVID-19 pandemic spreads around the world, intensive care unit (ICU) professionals, hospital administrators, governments, policymakers, and researchers must prepare for a surge of critical patients.
In this review, the authors have drawn on the experience of Asian ICU professionals in a variety of settings, and on the available literature on the management of critically ill patients with COVID-19 and related conditions, to provide an overview of the challenges facing the UCI community, its challenges and recommendations.
Epidemiology and clinical characteristics of critically ill patients
The number of people diagnosed with COVID-19 worldwide crossed the one million mark on April 2, 2020; The case fatality rate in 204 countries and territories was 5.2%.
In a review by the WHO-China Joint Mission of 55,924 laboratory-confirmed cases in China, 6.1% were classified as critical (respiratory failure, shock, and multiple organ dysfunction or failure) and 13.8% as severe (dyspnea). , RR ≥30 breaths per minute, oxygen saturation ≤93%, partial pressure of arterial oxygen to fraction of inspired oxygen [PaO2/FiO2] ratio <300 mm Hg, and increase in pulmonary infiltrates >50% within 24- 48 hours).
Critically ill patients with COVID-19 are older and have more comorbidities, including hypertension and diabetes, than non-critically ill patients. The most common symptoms are nonspecific: fever, cough, fatigue and dyspnea. The median time from symptom onset to development of pneumonia is approximately 5 days, and the median time from symptom onset to severe hypoxemia and ICU admission is approximately 7 to 12 days.
Most patients have bilateral opacities on chest x-ray and CT. Common CT findings are ground-glass opacities and consolidation .
Acute hypoxemic respiratory failure ( sometimes with severe hypercapnia) due to acute respiratory distress syndrome (ARDS) is the most common complication (in 60-70% of patients admitted to the ICU), followed by shock (30%), myocardial dysfunction (20–30%) and acute kidney injury (10–30%). Elderly patients may develop hypoxemia without respiratory distress . In one study, arrhythmia was observed in 44% of ICU patients.
Mortality is associated with older age, comorbidities (including hypertension, diabetes, cardiovascular disease, chronic lung diseases, and cancer), respiratory failure, higher concentrations of D-dimer and C-reactive protein, lower lymphocyte counts, and secondary infections .
The median time from symptom onset to death is 2 to 8 weeks, while the median time from symptom onset to clinical recovery is 6 to 8 weeks.
Diagnosis
Nonspecific clinical features do not easily distinguish severe COVID-19 from other causes of severe community-acquired pneumonia. The WHO suggests that COVID-19 be suspected in patients with acute respiratory illness and fever, in addition to traveling or residing in a place with community transmission, or contacting a confirmed or probable COVID-19 case in the 14 days before the onset of the symptoms; and in patients with severe acute respiratory illness requiring hospitalization without an alternative diagnosis that fully explains the clinical presentation.
Given the exponential increase in the number of areas with community transmission worldwide, ICU professionals must increasingly have a high index of suspicion and a low threshold for diagnostic testing for any patient with severe acute respiratory infection, when available.
The diagnosis is based on RT-PCR assays for SARS-CoV-2. Patients with pneumonia may have false-negative upper respiratory tract samples.
Although the WHO recommends sampling the lower respiratory tract, such as with sputum and endotracheal aspirates, these procedures potentially generate aerosols and should be performed with strict precautions. Repeat sampling may be required when initial tests are negative despite suspicious clinical features.
Management of acute respiratory failure
Current recommendations are based on existing evidence from other viral respiratory infections and general intensive care management. Reports suggest that non-invasive ventilation (NIV) and high-flow nasal cannula (HFNC) were used in one-third to two-thirds of critically ill COVID-19 patients in China.
Epidemiological data suggest that NIV was associated with nosocomial transmission of SARS; however, human laboratory data suggest that NIV does not generate aerosols. Although NIV could reduce intubation and mortality in mild ARDS, it is associated with increased mortality in moderate to severe ARDS, and a high risk of failure in MERS.
Although weak evidence suggests that high-flow nasal cannula (HFNC) could reduce intubation rates without affecting mortality in unselected patients with acute hypoxemic respiratory failure, delayed intubation as a consequence of its use may increase mortality.
Therefore, NIV and HFNC should be reserved for patients with mild ARDS until more data are available.
Intubation of patients with COVID-19 also presents a risk of viral transmission to healthcare workers, and intubation drills are crucial . The most trained operator available should perform the task with full personal protective equipment (PPE) and necessary preparation for difficult airways. The number of attendees should be limited to reduce exposure. Bag mask ventilation, which generates aerosols, should be minimized by prolonged pre-oxygenation.
A primary focus of mechanical ventilation for COVID-19 is to prevent ventilator-induced lung injury while facilitating gas exchange through lung protective ventilation.
The prone position of the patient should be adopted early, given its association with reduced mortality in other causes of severe ARDS. The tendency of SARS-CoV-2 to affect the peripheral and dorsal areas of the lungs provides ideal conditions for a positive oxygenation response in the prone position.
Venous-venous extracorporeal membrane oxygenation ( ECMO) is reserved for the most severe ARDS patients in light of evidence that it could improve survival.
Other intensive care treatments
Patients with COVID-19 may have hypovolemia due to anorexia, vomiting, and diarrhea. However, fluids should be administered with caution , given the high incidence of myocardial dysfunction in COVID-19. This incidence could be due to a strong binding affinity of the SARS-CoV-2 spike protein to human angiotensin-converting enzyme 2 (ACE2), a membrane receptor crucial for entry into the host cell that is expressed in the heart and lungs.
Most COVID-19 patients in China received empiric broad-spectrum antibiotics, and many received oseltamivir , because laboratory diagnosis of COVID-19 takes time, and it is often difficult to distinguish the disease from other bacterial and viral pneumonias.
Chinese reports also show that systemic corticosteroids were administered to about half of COVID-19 patients with severe or critical illness. A retrospective study of 84 patients with ARDS associated with COVID-19 found lower mortality in those treated with methylprednisolone, but the results are limited by the study’s observational design, small sample size, and potential confounders.
Because COVID-19 could be associated with a cytokine storm like that seen in other viral infections, immunosuppression has been proposed as an approach that could be beneficial for patients with signs of hyperinflammation, such as increased concentrations of ferritin. The benefits of immunosuppression are unproven and the role of corticosteroids in COVID-19 remains unclear, so until more data are available, routine use of corticosteroids in severe acute respiratory viral infections is not recommended. including COVID-19.
Rapid exit from invasive mechanical ventilation to reduce the incidence of ventilator-associated pneumonia and build ICU capacity must be balanced against the risks of premature extubation and subsequent re-intubation (and the concomitant risks) of viral transmission to healthcare workers. health).
Transferring patients out of the ICU for studies such as CT scans risks spreading SARS-CoV-2 and can be minimized with alternatives such as point-of-care ultrasound.
Finally, the median ICU stay for COVID-19 was 8 days in a Chinese report; However, larger studies are needed to better understand the course of COVID-19 after ICU admission.
The WHO recommends that isolation of patients requires clinical recovery and two negative RT-PCR tests performed 24 h apart. Viral shedding in the upper respiratory tract continues more than 10 days after symptom onset in severe COVID-19. This fact has significant implications for the use of isolation facilities.
Reused and experimental therapies
There is no proven therapy for COVID-19, but several candidates, some previously used against SARS-CoV and MERS-CoV, have been used empirically and are being investigated: remdesivir, lopinavir-ritonavir, chloroquine, hydroxychloroquine, intravenous immunoglobulin, convalescent plasma , tocilizumab, favipiravir and traditional Chinese medicines.
It is true that therapies for which efficacy is not supported by strong evidence, neither in COVID-19, nor even in SARS and MERS, are administered in the hope of improving outcomes, before or in parallel with clinical studies. Although guidance can be sought from experts in local or international societies, patients treated with experimental therapies should enroll in a clinical study when possible.
Infection prevention
COVID-19 is extremely transmissible, with each case seeding more than two secondary cases.
In the WHO-China Joint Mission report, 2,055 healthcare workers accounted for 3.7% of laboratory-confirmed COVID-19 cases in China. WHO recommends that personal protective equipment (PPE) for healthcare workers providing direct care to COVID-19 patients include medical masks, gowns, gloves, and eye protection with goggles or face shields. For aerosol -generating procedures (tracheal intubation, NIV, tracheostomy, cardiopulmonary resuscitation, mask ventilation, and bronchoscopy), masks should be N95 or FFP2 equivalent respirators , and gowns or aprons should be impermeable.
There are several difficulties related to PPE. Close attention needs to be paid to the supply chain given the global shortage of masks and respirators. Reusable non-N95 masks with high-efficiency particulate air (HEPA) filters may be considered. Although healthcare workers often focus on putting on PPE, data suggest a substantial risk of self-contamination when removing PPE . Training on the specific steps for wearing and removing PPE, along with hand cleaning, is crucial.
Surface decontamination is also key to infection prevention. SARS-CoV-2 persists on inanimate surfaces such as plastic and stainless steel for up to 72 hours.
Because more than a third of healthcare workers’ mobile phones could be contaminated with common viral pathogens, they should be cleaned regularly or wrapped in bags that are discarded after contact with patients or daily.
ICU visits should be restricted or prohibited to prevent further transmission, except perhaps for imminent death. Wherever possible, video conferencing via mobile phones or other interfaces can be used for communication between family members and patients or healthcare workers.
ICU infrastructure
To protect other patients and healthcare workers, critically ill patients with suspected or confirmed COVID-19 should ideally be admitted to a respiratory isolation room that is at negative pressure relative to surrounding areas, with accessible sinks and alcohol dispensers. in gel, especially if procedures with aerosol generation are performed.
Alternatively, patients can be placed in individual rooms with adequate ventilation and with doors closed, as recommended by the WHO.
When individual ICU rooms are not available, cohorting cases in shared rooms with dedicated staff is an alternative, with separate beds.
Although current evidence points to droplet rather than airborne transmission of COVID-19, concerns of nosocomial transmission in shared rooms persist, especially when aerosol-generating procedures are performed. Oxygen masks with HEPA filters may provide some protection for non-intubated patients.
ICU capacity
Controlling the community spread of COVID-19 is difficult but possible, and crucial to preserving ICU capacity. Most countries cannot match China’s feat of quickly building new hospitals and ICUs during the COVID-19 outbreak in Wuhan. The increase in the number of critically ill COVID-19 patients may occur rapidly.
Therefore, ICU professionals, hospital administrators, governments, and policymakers must plan ahead for a substantial increase in critical care bed capacity.
Adding beds in a pre-existing ICU is a possibility, but space limitations and nosocomial transmission due to overcrowding limit this option.
A substantial increase in ICU capacity implies an increase not only in the number of beds, but also in equipment (e.g., ventilators), disposable supplies, pharmaceuticals, and staff. To reduce strain on ICUs, elective surgeries should be postponed, and mild patients from other areas should be discharged.
ICU staff
High ICU-to-staff workload ratios are associated with increased patient mortality.
It may be necessary to augment staff with colleagues from other intensive care units (ICUs) or even non-ICU areas. Training these external staff in general intensive care management and specific COVID-19 protocols is crucial.
ICU staffing should take into account the risk of healthcare workers becoming infected with SARS-CoV-2. Minimizing the risk of infection is essential, not only because of the direct loss of workforce, but also because of the potentially devastating effect of infection on staff morale, which can lead to absenteeism. Physical distancing of staff, including eating separately, is important.
Healthcare workers in ICUs are especially vulnerable to mental health issues , including depression and anxiety, during outbreaks like COVID-19, due to constant fear of being infected and workload. Measures to prevent such problems include a focus on infection prevention to reassure staff, clear communication from hospital and ICU leadership, limiting shift hours and providing rest areas where feasible, and support mental health through multidisciplinary teams, including psychiatrists and psychologists.
Triage in ICU
Critical care triage may be required that prioritizes patients for intensive care and rations scarce resources. This applies to patients with and without COVID-19, because both groups will be competing for the same ICU resources.
Critical care triage is ethically complex and can be emotionally draining.
Although generic physiological outcome prediction scores may not accurately predict disease course, older adults with comorbidities, higher concentrations of D-dimer and C-reactive protein, and low lymphocyte counts worsen.
Resource rationing also involves the withholding and withdrawal of life-sustaining treatments for existing ICU patients. To this end, it is noteworthy that a quarter of the patients who died early in the Wuhan outbreak did not receive invasive ventilation.
Research questions and methodology
A search of the WHO International Clinical Trials Registry Platform on March 31, 2020 revealed 667 registered trials in COVID-19. Although many are trials of repurposed or experimental therapeutic agents, other more basic questions that are equally crucial must be addressed through research.
Data on the effectiveness of NIV and HFNC, and the associated risk of viral transmission, remain scarce. The risk of nosocomial transmission in shared ICU rooms should be studied. More data are needed on cardiac involvement and myocardial dysfunction. The role of ECMO is unclear. Indications for corticosteroids must be crystallized, while considering interactions between different therapies.
There are multiple challenges for research during pandemics.
First, disease escalation often overwhelms traditional steps for research, including protocol design, funding acquisition, and ethics approval, all in the midst of busy clinical work. Pre-approved adaptive plans drawn up before an outbreak are helpful.
Second, many ongoing COVID-19 studies are single-center and underpowered to detect significant differences in outcomes. To this end, pandemics provide a great opportunity for collaboration. Platforms such as the International Acute and Emerging Respiratory Infections Consortium (ISARIC) and the International Forum of Acute Care Trialists (InFACT), formed during the 2009 H1N1 pandemic, allow large research networks to share common goals and standardize data collection Worldwide. China’s rapid sharing of the SARS-CoV-2 genetic code had an immediate impact on case identification, isolation, and spread of the virus.
Conclusion
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