Author: Dr Dilip Gude
MBBS(Osmania), MPH (USA) | MD, DNB, MNAMS (Internal Med), Fellowship in Diabetology (All India Gold-medalist), Fellowship in Critical Care Medicine, Masters in Diabetology and Endocrinology (Royal College of Physicians, UK)download Article
COVID-19 pandemic spread globally has created a challenge for the health care fraternity. The deployment of various measures for smooth management of infected patients is crucially required. The improved infection prevention methods, rapid diagnosis, functional isolation wards and skilled professionals are also critically important, not only for patients but also for healthcare workers and other patient who are at risk of contracting nosocomial transmission. Along with these the hospital administration, governments and policy makers also are important for handling of infrastructure, staff management and critical supplies adequately on time. Collaboration of agencies at different local, national and international levels offer improved outcome from this chaotic scenario.
COVID-19 is coronavirus pandemic which has spread globally, causing mass infection and creating a surge in critically ill patients.  Therefore, it is necessary for the ICU, medical facility, hospital management and researchers to be ready for this chaotic scenario. Hence it is must to focus on the cumulative experiences gained up till now on the management of COVID-19 patients and associated conditions. This provides us with the overview of upcoming challenges and the recommendations to deal with them.
The cases diagnosed positive for COVID-19 crossed a million mark in April 2020, all across 204 countries, causing fatality rate of 5.2%.  These rates vary across different regions, do not account for patients having mild symptoms or are not diagnosed.
As per the status on July 31, 2020 the total number of registered cases globally reaches 17,303,253 causing 673,284 deaths leading to 3.89% fatality rate. In India, the total cases reached to 1,638,321 causing 35,743 deaths leading to a fatality rate of 2.18%. 
Most of the cases diagnosed as critical include the clinical features of respiratory failure, shock and multiple organ dysfunction or failure. Whereas, clinical features of severe cases include dyspnoea, respiratory rate ≥30 breaths per min, oxygen saturation ≤93%, partial pressure of arterial oxygen to fraction of inspired oxygen [PaO2/FiO2] ratio <300 mm Hg, and increase in lung infiltrates >50% within 24–48 h.  All the critical and severe cases require ICU admission, but the actual scenario depends on the capacity and availability of beds. The most critically ill patients diagnosed with COVID-19 infection were older and had other comorbidities, such as diabetes, hypertension, cardio-vascular disease, chronic lung disease, cancer and others.
The most common symptoms affecting COVID-19 patients are dry cough, fever, difficulty breathing and fatigue.  The approximate time for development of pneumonia from the onset of symptoms is 5 days, whereas to development of severe hypoxemia and ICU admission is approximately 7-12 days.  The most common complication is acute hypoxemic respiratory failure (sometimes with severe hypercapnia) from acute respiratory distress syndrome (ARDS), followed by shock, myocardial dysfunction and acute kidney injury.  older patients are associated with a number of fatal cases and the median time of death accounted from the onset of symptoms is approximately 2-8 weeks.
The initial approach by ICU practitioners towards COVID-19 patients should be taken with caution, as some of the non-clinical feature of covid-19 is not easily distinguishable from other respiratory symptoms.  Besides the presence of symptoms, diagnosis for clinical presentation as suggested by WHO are  –
Current diagnostic tests for coronavirus include reverse-transcription polymerase chain reaction (RT-PCR), real-time RT-PCR (rRT‐PCR), and reverse transcription loop‐mediated isothermal amplification (RT‐LAMP).  The samples are collected through swab from upper and lower respiratory tract. Upper respiratory tract samples at times give false-negative results, therefore, WHO recommends testing lower respiratory tract sample such as sputum and endotracheal aspirates.  The sample collection procedure generates aerosol, and should be carried out under strict precautionary measures. 
The sensitivity for detection of COVID-19 sample RT-PCR is low, therefore repeated samples must be tested besides the negative results of initial sample, if affirmative clinical features are observed. 
The data for supportive ICU care is based on the existing available evidences from other types of respiratory viral infections and general intensive care management. Generally, it is suggestive to use non-invasive ventilation (NIV) and high-flow nasal cannula (HFNC) for critically ill COVID-19 patients.  There are controversies related to nosocomial transmission of infection associated with use of NIV, as epidemiological data suggests its transmission, whereas human laboratory data disapproves this.  Moreover, NIV is known to reduce intubation and mortality in mild cases of ARDS, but are associated with high mortality in moderate-to-severe cases of ARDS. Therefore, the patients need close monitoring with airborne precautions and use of single rooms is to be taken into account. 
The intubation of patients with COVID-19 infection possess the risk to health care workers also, therefore, a full PPE should be worn up by the skilled professionals prior to procedure. While using the equipment which may generate aerosol, a viral filter can be placed between exhalation valve and mask as a precautionary measure;  and also use of muscle relaxant can reduce coughing.
Prone positioning is related to the reduced mortality rate and must be applied during early phases. The SARS-CoV-2 has a tendency to affect peripheral and dorsal regions of lungs, this provides ideal conditions for a positive oxygenation response to prone positioning. Veno-venous extracorporeal membrane oxygenation (ECMO) in some cases, is known to improve survival rate in severe ARDS patients, therefore must be reserved for emergency. However, decision to provide very advanced care for some patients should be based on number and severity of cases. 
The condition of hypervolemia due to vomiting, anorexia and diarrhea is known to occur in COVID-19 patients, therefore administration of fluids should be done cautiously. SARS-CoV-2 spike protein has high affinity to human angiotensin converting enzyme 2 (ACE2), which is crucial to virus for host cell entry. This membrane-bound receptor is expressed in lung, heart and other organs, therefore might be responsible for high incidence of myocardial dysfunction in COVID-19.  Hence a conservative fluid strategy must be deployed and also early use of vasopressors and inotropes are recommended (figure 1).
As the laboratory diagnosis of COVID-19 takes time, and the symptoms are hard to be differentiated from the other bacterial and viral pneumonia, so early administration of empirical broad-spectrum antibiotics are common.  but the therapy should be de-escalated with the conformation of positive results.
The retrieving from invasive mechanical ventilation must be considered to reduce the chances of ventilator-associated pneumonia, but must be balanced with the risk of premature extubation and subsequent increased chances of re-intubation. As per the reports, the average ICU stay of COVID-19 patients are approximately 8 days.  However, WHO recommends the discharge of patients requires clinical recovery and negative result of the two tests done 24 hours apart. 
COVID-19 is known to be associated with cytokine storm, as also observed with other kinds of viral infection. Therefore, it is proposed that immunosuppression as an approach might be beneficial to patients with hyper-inflammation.  Few reports show the use of systemic corticosteroid for the severe or critical COVID-19 patients.  But this role is not clearly to be beneficial in these cases. Moreover, a systemic review of an observational study of corticosteroid for SARS is associated with possible harm, such as avascular necrosis, psychosis, diabetes, and delayed viral clearance.  Therefore it is not recommended to use corticosteroid in viral severe acute respiratory infections, including COVID-19, until further confirmation supporting research is available.
Cytokine storm not only overwhelms the immune system, but also contribute to significant systemic inflammatory reaction which is destructive to kidney and other vital organs. Patients admitted to ICU with COVID-19 infections are also observed to suffers from other ailment such as, ARDS, trauma, kidney failure, acute heart damage, and secondary bacterial infection. [8, 22] The common complications in these ailments are usually cytokine storm, further deteriorating the condition of patients. Cytokine filtration may be a proposed way to mitigate such situation. These filters do not destroy or remove virus, but act like a sponge to absorb and capture cytokines; along with uremic toxins filtered by kidneys and endotoxins released by bacteria which induces cytokine gush. The use of cytokine filters helps in reverse the shock, control severe inflammation, proper function of heart and improve breathing; mitigating few of the primary reasons patients suffer during COVID-19 infection. 
Figure 1: Clinical management of critically ill patients with COVID-19.  [ARDS: acute respiratory distress syndrome; COVID-19: coronavirus disease 2019; ECMO: extracorporeal membrane oxygenation; HFNC: high-flow nasal cannula; NIV: non-invasive ventilation; PaO2/FiO2: partial pressure of arterial oxygen to fraction of inspired oxygen; PPE: personal protective equipment]
Still the cure or proven therapy is not available for COVID-19, however, some therapy used for earlier kinds of coronavirus infections are been used empirically and are under investigation.  Of them the more prominent ones are – remdesivir, faviparavir, lopinavir–ritonavir, chloroquine, hydroxychloroquine, tocilizumab, convalescent plasma, IV immunoglobulin and other traditional herbal medicines. 
There are other therapies as well, whose results are not proven, but are being administered in the hope of improved outcomes. However, trying of new therapies must be balanced by ethical consent and scientifically supporting data for safe conduct. During the Ebola outbreak, WHO experts concluded that due to “exceptional circumstances”, it was “ethically acceptable to offer unproven interventions that have shown promising results in the laboratory and in animal models but have not yet been evaluated for safety and efficacy in humans as potential treatment or prevention”.  However still the expert guidance is required, and the patient treated must be enrolled in clinical studies as per the rules and guidelines.
With the rapid transmission, every case seeding more than two secondary cases.  As many as healthcare workers including MBBS student, resident doctors, nurses and mess workers, have tested positive for COVID-19. WHO recommends that use of Personal Protective Equipment (PPE) should be made compulsory by hospitals for every health worker to wear it while treating patients. PPE should include medical masks, gowns, gloves, and eye protection with goggles or face shields.  For aerosol-generating procedures, masks should be N95 or FFP2-equivalent respirators, and gowns or aprons should be fluid resistant.
Health-care workers often focus on donning PPE, however data suggests, there is a significant risk of self-contamination when doffing PPE.  Specific steps of wearing and removing PPE, together with hand cleansing, is crucial to be followed.  Encouraging staff to build a safety culture and point out protocol errors are useful to reduce nosocomial SARS transmission. 
For infection prevention, surface decontamination plays an important role as viable SARS-CoV-2 persists up to 72 h on inanimate surfaces such as plastic and stainless steel.  Health-care
workers should clean their mobile phones regularly or wrapped with specimen bags that are discarded after contact with patients as they might be contaminated with common viral pathogens.  In Singapore, Environmental contamination by SARS-CoV-2 was detected on furniture and equipment within a patient’s room and toilet.  Viable Coronavirus was detected on doorknobs, bed guardrails, air exhaust dampers, and elevators during the MERS outbreak in South Korea.  SARS-CoV-2 might be transmitted faecally, proper disposal of soiled objects is also permitted. [31, 33]
To prevent further transmission, visits to the ICU should be restricted,  and interfaces likewise video conferencing via mobile phones can be used for communication between family members and patients or health-care workers where feasible.
Suspected or confirmed COVID-19 should ideally be admitted to an airborne infection isolation room (AIIR) that is at negative pressure relative to surrounding areas, with accessible sinks and alcohol hand gel dispensers (figure 2), especially if aerosol-generating procedures are done.  This protocol protects other patients and health-care workers. In case, If AIIRs are not available, critically ill patients can be placed in adequately ventilated single rooms with the doors closed, as recommended by WHO. 
One of the Asian survey depicts that only 37% of ICU rooms were single rooms, and 13% of ICUs had no single rooms.  Generally the number of single rooms and AIIRs were lowest in low-income countries. In case if single ICU rooms are not available, cohorting of cases in shared rooms with dedicated staff is an alternative, with beds spaced apart. 
PPE should be considered for patients in shared rooms as there remains a concern of nosocomial transmission, especially when aerosol-generating procedures are performed. For non-intubated patients, oxygen masks with HEPA filters might provide some protection. 
Figure 2: Initial approach to critically ill patients with suspected COVID-19.  [COVID-19: coronavirus disease 2019; ICU: intensive care unit; PPE: personal protective equipment]
Though controlling the community spread of COVID-19 is difficult but possible,  and is crucial for the preservation of ICU capacity. Modelling of needs for intensive care is crucial at national and regional level. 
There might be a shortage of ICU beds in many countries at the first place, let alone isolation or single rooms. The median number of critical care beds per 100,000 population was 2.3 in ten low-income and lower-middle-income countries, 4.6 in five upper middle-income countries, and 12.3 in eight high-income countries in Asia in one analysis,  and 9.6 in 28 high-income countries in Europe in a 2012 report.  China, an upper-middle-income country, has 3.6 critical care beds per 100,000 population,  and Wuhan was initially overwhelmed by COVID-19. Italy, a high-income country with 12.5 critical care beds per 100,000 population,  continues to struggle with the outbreak. By contrast, a low-income country such as Uganda has only 0.1 critical care bed per 100,000 population. [40, 42] This raises serious concerns about the ability of resource-limited settings to manage critically ill patients with COVID-19.
Surges in the number of critically ill patients with COVID-19 can occur rapidly.  Thus, governments, hospital administrators, ICU practitioners, and policymakers must plan in advance for a substantial increase in critical care bed capacity. [26,43] In pre-existing ICU, beds can be added, but space constraints and nosocomial transmission from crowding limit this option. Other options are the provision of intensive care outside ICUs, which are in high-dependency units, remodeled general wards, post-anesthesia care units, emergency departments, or deployable field units (Figure 2). 
ICU capacity involves not only in bed numbers but also in equipment (eg, ventilators), consumables, pharmaceuticals, and staffing. [26,43] To avoid the short supply of equipment’s, there should be focus on availability of necessary equipment, not only on bed numbers. To reduce strain on ICUs, elective surgeries should be postponed, and lower-acuity patients discharged to other areas.
Increase in patient mortality is associated with high ICU workload-to-staffing ratios.  Acquisition of staff with colleagues from other ICUs or even non-ICU areas might be required. Likewise, in Wuhan, more than 40 000 health-care workers were deployed from other parts of China to Wuhan.  Training and Basic course for external staff, such as mobile app for access to course material while caring for patients, on general intensive care management and specific COVID-19 protocols is crucial. 
Staffing of ICUs must take into account the risk that health-care workers might become infected with SARS-CoV-2. To minimize the risk of infection, rostering of staff should consider segregation of teams to limit unprotected exposure of all team members to infected patients or colleagues, and the resultant loss of staff to illness, medical leave, or quarantine. Physical distancing of staff, including having meals separately, is also important.
The constant fear of being infected and the demanding workload have added stress on Health-care workers. They are vulnerable to mental health problems, including depression and anxiety.  Staff who worked in high-risk SARS units continued to suffer from post-traumatic stress disorder years later. Necessary measures need to be taken to prevent such problems which includes a focus on infection prevention to reassure staff, clear communication from hospital and ICU leadership, limitation of shift hours and provision of rest areas where feasible, and mental health support through multidisciplinary teams, including counsellors, psychiatry, psychologists, and. 
Critical care triage should ideally be coordinated at a regional or national health-care systems level, and by following the guidelines for COVID-19.  Prioritize patient care and allocate resources in accordance with generally accepted ethical principles is required.
For Inclusion criteria, identify patients who may benefit from admission to critical care and primarily focus on respiratory failure, since the provision of ventilator support is what fundamentally differentiates the ICU from other acute care areas. For exclusion criteria identify patients who are not candidates for ICU admission including patients such as with a poor prognosis despite care in an ICU, requiring resources that cannot be provided, whose underlying illness has a poor prognosis with a high likelihood of death and who are too well. 
A triage policy, complemented by clinical decision support systems, implemented by clinicians might identify patients with such a low probability of survival that they are unlikely to benefit from ICU care.  However generic physiological outcome prediction scores might not accurately predict the course of illness, older adults with comorbidities, higher d-dimer and C-reactive protein concentrations and lower lymphocyte counts do worse. [4,49] Apportioning of resources likewise involves the retention and withdrawal of life-supporting medicines for existing ICU patients.
World must get ready for the likelihood that containment and mitigation measures may come up short, all nations should increase efforts to prevent the spread of COVID-19. Regardless of whether SARS-CoV-2 infects a little extent of the 7·8 billion people on earth, a large number will become critically ill and require ICU care. The ICU practitioners must prepare itself for this possibly surge of patients and streamline workflow, ahead of time, for rapid diagnosis and isolation, clinical administration, and infection prevention. All essential bodies such as hospital administrators, governments, and policy makers must join hands with ICU practitioners to get ready for a significant increment in basic consideration bed limit protect of health-care workers from nosocomial transmission, physical fatigue, and mental well-being issues. Some questions need to be addressed by researchers concerning what remains an inadequately understood disease. To this end, pandemics provide a great opportunity for collaboration at the local, regional, national, and international level. Platforms such as the International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) and the International Forum for Acute Care Trialists (InFACT)—formed during the 2009 H1N1 pandemic—enable large research networks to share common goals and standardize data collection globally will be key to the success of these efforts.