key: cord-1024840-apw1q940
authors: Sundaram, Manu; Ravikumar, Namita; Bansal, Arun; Nallasamy, Karthi; Basavaraja, G. V.; Lodha, Rakesh; Gupta, Dhiren; Odena, Marti Pons; Ram, Ashwath; Jayashree, Muralidharan
title: Novel Coronavirus 2019 (2019-nCoV) Infection: Part II - Respiratory Support in the Pediatric Intensive Care Unit in Resource-limited Settings
date: 2020-03-29
journal: Indian Pediatr
DOI: 10.1007/s13312-020-1786-x
sha: 967f4957bd4dd15955a22f8b644770397e04c407
doc_id: 1024840
cord_uid: apw1q940

The 2019-novel coronavirus predominantly affects the respiratory system with manifestations ranging from upper respiratory symptoms to full blown acute respiratory distress syndrome (ARDS). It is important to recognize the risk factors, categorize severity and provide early treatment. Use of high flow devices and non-invasive ventilation has been discouraged due to high chances of aerosol generation. Early intubation and mechanical ventilation areessential to prevent complications and worsening, especially in resource-limited settings with very few centers having expertise to manage critical cases. Hydrophobic viral filter in the ventilator circuit minimizes chances of transmission of virus. Strategies to manage ARDS in COVID-19 include low tidal volume ventilation with liberal sedation-analgesia. At the same time, prevention of transmission of the virus to healthcare workers is extremely important in the intensive care setting dealing with severe cases and requiring procedures generating aerosol. We, herein, provide guidance on non-invasive respiratory support, intubation and management of ARDS in a child with COVID-19.

N ovel coronavirus 2019 (2019-nCoV) infection has been declared a pandemic by the World Health Organization (WHO). We elaborated the epidemiology, preparedness of intensive care units, clinical course, intensive care needs and complication of patients with Coronavirus disease in a previous article [1] . In this write-up, we will focus on the respiratory manifestations, progression and intensive care management of respiratory complications of COVID-19. As we learn more about the 2019-nCoV (novel coronavirus) and the impact this has had on the patients and health care workers (HCW) globally, the focus has shifted to safety of the HCW so that the patients can be treated appropriately and kept safe. This is based on the lessons learned from previous epidemics and mitigating steps to reduce risks to HCW. Most of the following suggestions are based on expert opinionon providing safe care in these challenging times.

The most common presentation is short history of prodrome with myalgias, malaise, cough and low-grade fever. As per the case series from China, only 40-70% of the pediatric patients have fever as an initial presentation [2] [3] [4] . During the second week of illness, progression of the disease gradually leads to difficulty in breathing. Reports from China have suggested that it takes an average of 8 days for the development of dyspnea and 9 days for the onset of pneumonia/pneumonitis [5] .

CDC does not currently recommend chest radiography (CXR) or computed tomography (CT) to diagnose COVID-19 [6] . Viral testing remains the only specific method of diagnosis and has been discussed in detail in part-I [1] . Confirmation with the viral test is required, even if radiologic findings are suggestive of COVID-19 on CXR or CT scan [7] .

The clinical presentation and findings on chest imaging in COVID-19 are not specific.The clinical presentation of COVID-19 overlaps with other infections like influenza, respiratory syncytial virus (RSV), adenovirus, human

The 2019-novel coronavirus predominantly affects the respiratory system with manifestations ranging from upper respiratory symptoms to full blown acute respiratory distress syndrome (ARDS). It is important to recognize the risk factors, categorize severity and provide early treatment. Use of high flow devices and non-invasive ventilation has been discouraged due to high chances of aerosol generation. Early intubation and mechanical ventilation areessential to prevent complications and worsening, especially in resource-limited settings with very few centers having expertise to manage critical cases. Hydrophobic viral filter in the ventilator circuit minimizes chances of transmission of virus. Strategies to manage ARDS in COVID-19 include low tidal volume ventilation with liberal sedation-analgesia. At the same time, prevention of transmission of the virus to healthcare workers is extremely important in the intensive care setting dealing with severe cases and requiring procedures generating aerosol. We, herein, provide guidance on non-invasive respiratory support, intubation and management of ARDS in a child with COVID-19. R R  R R T  T T  T T I  I I  I I C  C C  C C L  L L  L L E  E E  E E  VOLUME 57 __ APRIL 15, 2020 SUNDARAM, ET AL. COVID-19: RESPIRATORY MANAGEMENT IN PICU meta-pneumovirus, non COVID-19 coronavirus, atypical organisms (mycoplasma, chlamydia) and bacterial infections. It is not possible to differentiate COVID-19 from these infections clinically or through routine laboratory tests. In the context of pandemic and local transmission setting in, the travel history will become irrelevant. There are some radiological and hematological findings that may help indicate COVID-19, even though they are not very specific [1] .

Severity of illness is based on the presenting symptoms and has been discussed previously [1] . Patients can shed RNA from 1-4 weeks after symptom resolution, but it is unknown if the presence of RNA equals presence of infectious virus. As per current guidelines, COVID-19 patients are "cleared" of isolation once they have 2 consecutive negative RNA tests collected >24 hours apart. This practice may not be clinically possible in our setting due to various constraints. Therefore, keeping them in isolation for longer duration is the key.

One of the key considerations during management is mitigating risk to health care workers. Hypoxemia can be present due to impaired respiratory functions in COVID-19. Oxygen supplementation treatment can correct hypoxemia and relieve secondary organ damage caused by hypoxemia [8] . The management of children with Severe acute respiratory illness (SARI) in COVID is similar to any other viral pneumonia with ARDS but with strict precautions to reduce risk of transmission [9] .

All aerosol generating procedures/events require donning of personal protective equipment which includes N95 mask, goggles or face shield, cap, full sleeve gown and shoe cover ( Table I ) [10] . Where possible, a nebulizer may be replaced with an MDI and spacer for administration of bronchodilators. NIV generates droplets >10 µm in size and most fall on local surfaces within 1-meter distance. Learning from droplet dispersion studies, HCWs who are providing NIV, chest physiotherapy or working within 1 meter of an infected patient should have a high level of respiratory protection [11] [12] [13] .

Oxygen therapy is necessary for patients with oxygen saturation (SpO 2 ) less than 90% and/or with signs of respiratory distress. It has been noted that many elderly patients with severe hypoxemia may not have obvious symptoms of respiratory distress [14] . It is pertinent that the evaluation of all children with respiratory symptoms should include pulse oximetry. Low flow oxygen devices are recommended as high flow devices have the potential for risk of spread through aerosol generation. Nasal cannula at flows of 2-4 L/min is a good choice for milder forms of SARI. A triple layer mask should be used to cover the mouth and nose of the patient over the nasal cannula, especially during transport, unless the child does not tolerate [15] .

HFNC therapy can be useful in special situations for hypoxia. A flow of 2-3 mL/kg with FiO 2 targeted to SpO 2 is used. However, it is necessary that when patient is on HFNC interface, HCW are wearing optimal airborne PPE and child is managed in negative pressure rooms,if available [16] . In infants, while HFNC is being given they can be placed in an oxygen hood to minimize dispersion. Surviving Sepsis Guidelines recommend HFNC in milder cases of adult SARI [17] . However, no such guidelines are there for children. HFNC should be tried for a maximum of 1-2 hours. Signs of improvement are decrease in heart rate and respiratory rate by 10-20%, decrease in FiO 2 requirement to less than 50% and improvement in oxygen saturations.

Patients with worsening hypercapnia, acidemia, respiratory fatigue, hemodynamic instability or those with altered mental status should be considered for early invasive mechanical ventilation.

Over the last two decades, the use of non-invasive ventilation (NIV) is increasing in children with viral illness and the rates of intubation are reducing. At the same time there is paucity of literature regarding the use of NIV in respiratory pandemics. In a Chinese observational study in adults of the SARS outbreak, it was shown that NIV was effective in preventing the use of endotracheal intubation in 70% of patients because of early initiation of NIV. In this study, none of the HCW acquired SARS from the patients. This was attributed to NIV being applied in a negativepressure environment with strict PPE regime and close monitoring of the HCW involved [18] . In another study from Toronto during SARS, the use of NIV was discouraged after clinicians contracted the disease when a patient was intubated following NIV failure [19] . Therefore, some clinicians consider NIV is contra-indicated for acute respiratory failure due to airborne respiratory diseases unless it is used in a negative-pressure isolation room and strict precautions are taken [19] .

After the two viral pandemics, most of the professional societies including the European Respiratory Society, European Society of Intensive Care Medicine, and American Association for Respiratory Care have recommended against NIV use to treat acute respiratory failure due to H1N1 influenza, particularly in severely ill patients. Thus, NIV is accepted as a high-risk procedure that should be used cautiously because of possible spread of infection [20] [21] [22] [23] .

Routine use of NIV is not recommended in COVID-19. It should be used only in selected patients with hypoxemic respiratory failure. Ideally, negative pressure single rooms are preferable for patients on NIV. However, in an outbreak of such a magnitude, some professional societies recommend keeping a distance of at least two meters between two beds. Due to the high percentage of failure with NIV and the rapid progression of the hypoxemic failure due to COVID-19, all patients receiving NIV need a clear plan for treatment failure.

Selection of interface is the key for success and protection of the HCWs. Preferred interfaces are helmet, total face mask and oro-nasal non-vented masks.Risks of NIV include delayed intubation, large tidal volumes and injurious trans-pulmonary pressures. Limited data suggest a high failure rate in patients with other similar viral infections such as MERS-CoV [24] . PaO 2 /FiO 2 is a sensitive and accurate indicator of oxygenation function on NIV and can be used to define the severity of ARDS once the patient has been on a PEEP of 5 cm for a minimum of 30 minutes. Invasive ventilation must be considered if PaO 2 /FiO 2 ratio is below 300. In the absence of an ability to do an arterial blood gas, the SpO 2 /FiO 2 can also be used to identify oxygenation failure as long as the FiO 2 has been titrated to get saturations between 92%-97%.

The most recent World Health Organization (WHO) interim guidance on management of the novel-CoV has also recommended the use of NIV for mild cases of ARDS without hemodynamic instability [8] .

Conventional ventilators with NIV option having double lumen tubing is a safer option than NIV ventilator with single lumen tubing requiring exhalation port to washout the CO 2 . Antiviral/Antibacterial filters should be attached to the exhalation limb of the circuit to reduce environmental contamination. Alternatively, when these options are not available, home ventilators with built-in oxygen blender or transport ventilators can provide adequate mechanical ventilation.

In situations where both non-invasive and invasive mechanical ventilation are not available, bubble nasal CPAP (commercial or indigenous) may be used for newborns and children with severe hypoxemia as these are readily available alternative in resource-limited settings.To minimize environmental contamination the infant could be placed in an oxygen hood to reduce droplets.

These patients should be on continuous monitoring and cared for by experienced personnel capable of performing endotracheal intubation in case the patient acutely deteriorates or does not improve after a short trial (about 2 hours).

Patients with known contraindications for NIV like moderate/severe ARDS with PaO 2 /FiO 2 ratio below 200, hemodynamic instability, multi-organ failure, or abnormal mental status should receive invasive ventilation from the very beginning.

During the previous SARS epidemics in China and Singapore, infection rates were higher in doctors and nurses carrying out endotracheal intubation [relative risk (95% CI)-13.3 (2.99-54.04)] [20] . In an observational study of influenza-A and influenza-B in exhaled breath, viral RNA was seen in one-third of infected patients and 99% of particles had a diameter of <5 µm when sampled during tidal breathing [25] . Studies have demonstrated that particles <10 µm in diameter are more likely to cause infection in the lower respiratory tract [9, 10] . Coronavirus virions (or 'particles') are spherical particles with diameters of approximately 125 nm (0.125 µm) [26] .

Tracheal intubation should be performed as early as possible for patients with aPaO 2 /FiO 2 ratio <300, worsening trend of the SpO 2 /FiO 2 ratio <200, worsening respiratory distress, high concentration (>60%) of oxygen on HFNC or multiple organ dysfunction. VOLUME 57 __ APRIL 15, 2020 SUNDARAM, ET AL.

Preparation : Prepare the plan, ready the equipment and set-up the ventilator prior to intubation (Table II) . At least three personnel are needednamely, airway operator, airway assist and a nurse for medication. The most experienced person should intubate to ensure minimum number of attempts to decrease aerosol generation. Wherever possible, usedisposable equipment. Video laryngoscopy is ideal to protect the intubating HCW from operating too close to the airway (Fig.2) . If equipment or expertise isnot available, take measures to reduce droplets during the procedure using a plastic sheet (Fig. 1) .

Pre-medication: Use benzodiazepine (midazolam 0.1-0.2 mg/kg) with opioid (fentanyl 2-3 µg/kg) combination for sedation and analgesia. Short acting neuromuscular blockers like rocuronium is preferred (if unavailable, use a higher dose of vecuronium or atracurium as per availability).

Pre-oxygenation: After a quick assessment for anatomically difficult airway, pre-oxygenation is carried out with non-rebreathing mask (NRM) or tight-fitting face mask attached to a self-inflating ambu-bag with 100% oxygen for 5 minutes. A hydrophobic viral filter between the mask and ambu-bag is recommended and some units cover the head, neck and chest with transparent plastic apron/sheet to prevent aerosol contamination (Fig.1) . Avoid bag and mask ventilation (BMV) to limit aerosol and if needed, use low tidal volume with lesser breaths.

Intubation: Cuffed endotracheal tubes (ETT) must be used in all ages and cuff needs to be inflated immediately following intubation. Disposable ventilator circuit with a viral filter attached at the expiratory limb (between circuit and machine) is used. Heat moisture exchanger (HME) is preferred for humidification. Ventilator should be in 'stand-by' mode and only to be turned on after connected to the patient. Prior to connecting to ventilator, the ETT can be clamped or attached to a viral filter. Closed suction (inline suction catheters) is preferred to prevent aerosol generation. If not available, open suction may be performed with aerosol precautions and after administering a dose of short acting neuromuscular blocking agent.

Lung protective mechanical ventilation (MV) is recommended strategy for management of acute hypoxemic respiratory failure. SSC guidelines in adults recommend low tidal volume strategy (4-8mL/kg), limiting plateau pressures to <30 cmH 2 O and using higher PEEP (>10 mm Hg) [17] . Permissive hypercapnia is well tolerated and may reduce volu-trauma. Viral filters should be utilized, and circuits should be maintained for as long as allowable (as opposed to routine changes) ( Table III) .

Prone ventilation is a recommended strategy in adults with PaO 2 /FiO 2 <150 to improve lung mechanics and oxygenation.Patient is usually kept prone for12-16 hours. Prone ventilation can be ceased once PaO 2 /FiO 2 is > 150 for more than 4 hours in the supine position. However, in children and resource-limited setting, due to limited availability of HCWs and PPEs, it may not be possible to prone the child and may unnecessarily increase the risk of infection to the healthcare workers.

To reduce pulmonary exudation and improve oxygenation, the fluid balance should be strictly controlled while ensuring adequate end-organ perfusion. Fluid restriction to 70-80% maintenance is necessary to prevent fluid overload. 

VAP bundled strategies should be strictly implemented as per recommendations [27] .

Once the patient's PaO 2 /FiO 2 is more than 300 the neuromuscular blockade and sedatives must be weaned and discontinued. Extubation should be performed if the patient is considered ready for extubating to nasal O2 as post-extubation NIV is avoided where possible.Aerosol precautions are essential during extubation. Few units practice extubating using a plastic bag over the face with a tight seal after inflating with oxygen ( Fig. 4) or some units use a transparent large plastic sheet over the face and chest to capture droplets from coughing and suctioning. Post-extubation, the need for HFNC or NIV can be assessed while reducing monitoring.

Various professional bodies have given their recommendations for respiratory support in pediatrics and adult [8, 15, 17, 28] and these are summarized in Table IV 

SARI is the most common presentation of COVID-19 and requires intensive care support. Low flow oxygen devices are preferred to high flow devices to prevent aerosol generation. Early intubation and mechanical ventilation are recommended to delay progression and need for emergent intubation, which poses significantly higher risk of transmission of infection to HCW. Use of HFNC and NIV is to be avoided routinely and if necessary, a full PPE with aerosol precautions is a must. Management of ARDS includes lung protective ventilation with liberal sedation-analgesia and avoidance of steroids.

Contributors: MS, NR, AB, KN: substantial contribution to the conception and design of the work, anddrafting the work; GVB, RL, DG, MPO, ARRN, MJ: substantial contributions to the acquisition and interpretation of data for the work,and revising it critically for important intellectual content.All authors gave final approval of the version to be published, and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Funding: None; Competing interest: None stated.

et al for the Intensive Care Chapter of Indian Academy of Pediatrics. Novel coronavirus 2019 (2019-nCoV) infection: Part I -Preparedness and management in the pediatric intensive care unit in resource-limited settings

Clinical and CT features in pediatric patients with COVID 19 infection: Different points from adults

Coronavirus Disease-19 Among Children outside Wuhan, China (Internet)

Preliminary epidemiological analysis on children and adolescents with novel coronavirus disease 2019 outside Hubei Province, China: an observational study utilizing crowdsourced data (preprint)

Clinical features of patients infected with 2019 novel coronavirus in Wuhan

org/Advocacy-and-Economics/ACR-Position Statements/Recommendations-for-Chest-Radiographyand-CT-for-Suspected-COVID19-Infection

Interim Guidelines for Collecting, Handling, and Testing Clinical Specimens from Persons Under Investigation (PUIs) for Coronavirus Disease

Clinical management of severe acute respiratory infection (SARI) when COVID-19 disease is suspected: Interim guidance

Care for critically ill patients with COVID-19

Consensus statement: Safe airway society principles of airway management and tracheal intubation specific to the COVID-19 adult patient group

Evaluation of droplet dispersion during non-invasive ventilation, oxygen therapy, nebuliser treatment and chest physiotherapy in clinical practice: Implications for management of pandemic influenza and other airborne infections

Transmission of influenza: Implications for control in health care settings

The airborne transmission of infection in hospital buildings: Fact or fiction?

Critical care crisis and some recommendations during the COVID-19 epidemic in China

Australian and New Zealand Intensive Care Society. ANZICS COVID-19 Guidelines. Melbourne; 2020

for the China Novel Coronavirus Investigating and Research Team. A novel coronavirus from patients with pneumonia in China

Surviving sepsis campaign: Guidelines on the management of critically Ill adults with coronavirus disease 2019 (COVID-19)

Effectiveness of noninvasive positive pressure ventilation in the treatment of acute respiratory failure in severe acute respiratory syndrome

Identification of severe acute respiratory syndrome in Canada

Transmission of severe acute respiratory syndrome during intubation and mechanical ventilation

Infection and control of epidemic-and pandemic-prone acute respiratory diseases in health care. WHO interim guidelines. World Health Organization

Noninvasive ventilation for patients with acute lung injury or acute respiratory distress syndrome

Clinical characteristics and outcomes of patients with 2009 influenza A (H1N1) virus infection with respiratory failure requiring mechanical ventilation

COVID-19: RESPIRATORY MANAGEMENT IN PICU

Clinical course and outcomes of critically ill patients with Middle East respiratory syndrome coronavirus infection

Influenza virus in human exhaled breath: an observational study

A novel coronavirus from patients with pneumonia in China

The Intensive Care Society recommended bundle of interventions for the prevention of ventilator-associated pneumonia

Updated PICS guidance on management of critically ill children with Covid-19 infection