|Year : 2020 | Volume
| Issue : 7 | Page : 65-71
Published guidelines on COVID-19: Which to follow?
Manu Sundaram1, Rohit Saxena2, Marti Pons Odena3, Giovanna Chidini4, Mohammed Salameh5, RN Ashwath Ram6, Utpal Bhalala5
1 Division of critical care, Sidra Medicine and Weill Cornell Medicine, Doha, Qatar
2 Department of Cardiac Intensive Care, Great Ormond Street Hospital for Children NHS Foundation Trust and University College, London, United Kingdom
3 Department of Pediatric Intensive Care and Intermediate Care, Sant Joan de Déu University Hospital, Barcelona, Spain
4 Department of Anesthesia and Intensive Care, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy
5 Department of Pediatric Intensive Care, Baylor College of Medicine, The Children's Hospital of San Antonio, San Antoni, TX, USA
6 Department of Pediatrics Intensive Care, Manipal Hospital, Bengaluru, Karnataka, India
|Date of Submission||24-Apr-2020|
|Date of Decision||29-Apr-2020|
|Date of Acceptance||03-May-2020|
|Date of Web Publication||29-May-2020|
Dr. Manu Sundaram
Division of Critical Care, Weil Cornell Medicine, Doha
Source of Support: None, Conflict of Interest: None
The novel coronavirus 19 (COVID-19) pandemic has brought the world to a halt and humans at existential risk from an unknown enemy. In view of a high reproductive number, the number of deaths and people affected by COVID-19 has been unprecedented. At the same time, the knowledge sharing by the medical community from social media, networking, and the large number of publications has brought new challenges. To review the literature and bring out the best practice summary, we have involved physicians from the COVID-19 hotspots and societies to share their knowledge, experience, and transferable skills learned from helping their adult intensive care unit colleagues and managing pediatric COVID-19 patients. This has been particularly challenging as the goal post has been shifting very quickly and will continue to evolve while high-quality evidence is obtained.
Keywords: COVID19, guidelines, international
|How to cite this article:|
Sundaram M, Saxena R, Odena MP, Chidini G, Salameh M, Ashwath Ram R N, Bhalala U. Published guidelines on COVID-19: Which to follow?. J Pediatr Crit Care 2020;7, Suppl S1:65-71
|How to cite this URL:|
Sundaram M, Saxena R, Odena MP, Chidini G, Salameh M, Ashwath Ram R N, Bhalala U. Published guidelines on COVID-19: Which to follow?. J Pediatr Crit Care [serial online] 2020 [cited 2020 Jul 9];7, Suppl S1:65-71. Available from: http://www.jpcc.org.in/text.asp?2020/7/7/65/285379
| Introduction|| |
The initial reports of respiratory tract infection caused by a newly emergent novel coronavirus (SARS-CoV-2) causing coronavirus disease (COVID-19) was first reported from Wuhan, China, in December 2019. This led to implementation of a widespread strict lockdown measures in China, while the rest of the world watched anxiously. There was also recognition of the paucity of experience regarding best possible management strategies for this novel disease, which we all knew little about. The initial management strategies were understandably based on the Chinese experience; however, they were mainly targeted toward adult disease. As the virus spread without boundaries, the World Health Organisation (WHO) declared COVID-19 as a pandemic. The various intensive care societies and professional bodies felt the need to publish management guidelines rather hastily, while evidence synthesis is still in progress [Figure 1].
Hereby, we bring in the best practice summary from intensive care physicians across the world who are directly involved in the management of these patients while learning continuously about the disease from the patients and by sharing experience and resources with each other. Apart from a narrative summary of available guidelines, the authors are also sharing their experience and opinion. However, as the process of evidence building continues, the recommendations may need rapid adaptation to align with the new findings.
| What Did We Learn From The “sars” Epidemics?|| |
The previous SARS epidemics in Southeast Asia and Middle East had showed that the virus is extremely contagious, particularly when there is close contact between people.
In case of the SARS-CoV-2, reproduction number (R0) estimates that on an average one person may infect three others. Most of the guidelines were initially based on the series from China and the experience of countries initially affected by the SARS epidemics. Figures from the China's National Health Commission show that more than 3300 health-care workers (HCWs) have been infected as of early March 2020. It is interesting to mention that the most important factors related to infection in HCWs in China were lack of personal protective equipment (PPE), inappropriate hand washing, and longer shifts. There is no mention of the respiratory support offered to the patients and the largest portion of infection of the HCWs happened unexpectedly between clinicians and patients with mild symptoms in the early phase in the outbreak. This also makes the work of HCWs very challenging. Twenty percent of responding HCWs were reported infected in Italy, great proportion of those who died where general practitioners older than 60 years.
The infection of the HCWs was attributed mainly to the aerosolization of the virus from the various respiratory support mechanism and interventions., It was found that the interventions such as high-flow nasal cannula (HFNC) or continuous positive airway pressure (CPAP) generated aerosols. Droplets which are >10 μm in size will fall on local surfaces within 1-m distance. This has an effect on treatment strategies due to selection of supportive respiratory devices which is continuously adapted in light of emerging evidence.
| How Are Covid-19 Infected Children Different From Adults?|| |
From the current reports and case series, children do not account for a large proportion of COVID-19 disease and have less severe illness than adults. In Italy, the pediatric COVID-19 disease represents a logistic more than a clinical emergency. Only few children are admitted nowadays to the Northern Italy pediatric intensive care units (PICU) with the need of respiratory support (1 on mechanical ventilation, 1 on noninvasive ventilation [NIV], and 3 on high flow oxygen therapy). In a large case series with 2143 affected children, more than 90% of all patients were asymptomatic, mild, or had moderate illness.
There have been various explanations for why the infection affects children less severely. It appears that the virus directly infects cells via the ACE2 receptor, which is expressed in various organs, including the lung. As the cells in children's lungs express this receptor less as compared to adult lungs, they seem to be affected less severely.,, Cytokine storm is a cascade process whereby the virus leads to increased levels of cytokines that cause direct tissue damage, recruitment of neutrophils to tissues, and other proinflammatory effects leading to acute respiratory distress syndrome (ARDS) in adults.
In summary, available data are indicative of milder disease in children with a very low number of admissions to the critical care unit.
| What Does the Literature and Experts Suggest About Covid-19 Preparedness?|| |
Planning and organization of the whole hospital is the key to successful management of this pandemic when resources and HCWs are stretched. These are the practice recommendations from experiences in China, Europe, and America.
This would require formation of task forces, committees, and subcommittees to plan for appropriate dissemination of locally developed policies and protocols as an important part of preparedness. Several options should be considered according to the resources available:
- Transfer pediatric patients to children's hospitals, to make beds available in general or community hospitals for adult COVID-19 patients
- Transfer stabilized adult patients through an established transport team from intensive care unit (ICU) to PICU when there is an urgent need for admission
- Recruit pediatric intensivists and PICU nurses and fellows to join adult teams.
Cohorting and testing
Cohort all suspected/confirmed COVID-19 cases to ICU areas, high dependency unit areas, and dedicated step down (ward) areas; divided into three zones: red zone (COVID +ve)/green zone (COVID −ve); amber zone acts as a holding place till laboratory results for the test are back.
It is recommended to test every patient admitted to PICU for SARS-CoV-2 if resources permit. Symptom profile is not limited to respiratory symptoms only. Children presenting with acute gastroenteritis or meningoencephalitis are strongly recommended for testing. Adults may demonstrate false negative on nasopharyngeal aspirate test, so if the case is highly suspicious (especially with other positive signs such as chest X-ray changes, lymphopenia, neutrophilia, and high inflammatory markers), retesting is advised. No clear guidelines exist for retesting and high index of clinical suspicion is the key here.
Nursing ratio will understandably fall as the demand for PICU beds increase and PICU staff sickness increases. Prepare for 1:3–1:4 nursing rather than usual standards. Avoid pairing patients under investigation (PUI)/COVID assignment with non-PUI/non COVID assignment. Engage and upskill other HCWs to help look after intensive care patients. Each trained nurse may supervise 3–4 HCW. In case of a surge, think out of the box and plan to involve non-ICU, multidisciplinary team members to help in ICU management. For example, use of surgical teams for proning, vascular access, or simulation for the use of PPE. Do not expose HCWs with risk factors such as age >60 years, hypertension, diabetes, obesity, and asthma to COVID-19 or PUIs.
Personal protective equipment
Follow national guidance as this is a scarce resource in every country. Invest in training and simulation to prepare staff for correct use of this equipment.
Plan dedicated teams for intubation (anesthetists), proning (anesthetists and surgical colleagues), and vascular access (vascular surgeons), so that PICU team can focus on a large number of cases requiring intensive care (depends on individual center case load). Organise bundle approach with procedures to minimize multiple team members being exposed and for resource preservation.
Staff well-being and mental health
This is an area often neglected during the peak of the action. Ensure there are arrangements in place for promoting and safeguarding staff well-being and mental health. We suspect there will be an increased incidence of posttraumatic stress disease among staff members after the peak infection rate has passed.
| What Do The Guidelines Tell Us About Managing The Covid-19 Patients?|| |
In addition to the work of breathing, the saturations and vital signs other parameters such as SpO2/FiO2(S/F) ratio, PaO2/FiO2(P/F) ratio, oxygenation saturation index (OSI), or the oxygenation index (OI) can be used for grading the severity as per the pediatric acute lung injury consensus conference recommendations.
The S/F ratio correlates well with the P/F ratio in nonintubated patients to grade the degree of severity of ARDS as long as the FiO2 is titrated to achieve saturation between 92 and 97%. Some experts underline the importance of monitoring the work of breathing more than focusing on oxygenation perse. With the self-inflicted lung injury being a major concern, clinicians should rapidly escalate the first-line treatment initiated if it is not relieving the patient's work of breathing.
[Table 1] gives a summary of the various guidelines on the PICU management of the COVID19 patients.
|Table 1: Summary of respiratory management of coronavirus disease 19 patients|
Click here to view
Low-flow oxygen therapy (LFOT) has been recommended to maintain SpO2>94% in patients with respiratory distress, hypoxemia, or shock., If there is no organ dysfunction, SpO2 of 90% can be tolerated. Some guidelines are against the use of LFOT in view of higher exhaled air dispersion. This is one of the main differences from adults with regard to the Paediatric Mechanical Ventilation Consensus Conference guidelines.
High-flow nasal cannula/continuous positive airway pressure
The European Society of Paediatric and Neonatal Intensive Care (ESPNIC) has given a structured recommendation for initiation of HFNC based on the SpO2/FiO2 ration >264. [Table 1] gives a summary of the recommendations from the various guidelines for the initiation of respiratory support. The various recommendations are based on the objective assessments and strength of recommendations based on the quality of the evidence. The Paediatric Intensive Care Society, UK, has recommended HFNC as first choice.
CPAP or bi-level NIV has been recommended as first-line approach by ESPNIC for patients with moderate severity (SpO2/FiO2>221 and <264), for recruitment of the airway with higher airway pressures. Strict PPE is necessary while managing suspected or confirmed COVID-19 on NIV. Based on the dispersion studies, helmet devices and nonvented full-face mask with a double-lumen circuit and appropriate bacterial/viral filters/high-efficiency particulate air filters have recommended to minimize aerosol generation. The Ministry of Health and Family Welfare, India, has recommended either HFNC or CPAP as the first choice.
HFNC could also be used to provide support if CPAP is unavailable for patients with SpO2/FiO2>264 (FiO2 <0.35–0.40). HFNC or NIV should be used only in selected patients with hypoxemic respiratory failure.,,, Patients treated with either HFNC or NIV should be closely monitored for clinical deterioration. In view of the concerns regarding aerosol generation by some types of HFNC devices, HCWs should have adequate PPE and the patient should be managed in a negative pressure rooms, if available.
The Society of Critical Care Medicine (SCCM) and the Australian and New Zealand Intensive Care Society (ANZICS) have published adult guidelines. They prefer HFNC for acute hypoxic respiratory failure in adults though the quality of evidence is weak. The ANZICS does not recommend CPAP in adults.
Intubation is recommended if there is no improvement in oxygenation (target SpO2 92%–97% and FiO2<0.6) within 60–90 min of trial of HFNC/NIV and the SpO2/FiO2<221.
Adult guidelines from the SCCM initially recommended early intubation of patients to reduce aerosol generation and mitigate risk to the HCW. The high mortality seen with this approach as reported by China, Italy, and UK has shifted this back to a more conservative approach with a trail of CPAP followed by intubation in deteriorating cases.
All the guidelines give similar recommendations regarding lung protective ventilation strategy, i.e., lower level of plateau pressure <28 cmH2O, driving pressure ≤15 cm H2O, tidal volumes adapted as per disease severity: 3–6 mL/kg predicted body weight (PBW) in the case of poor respiratory system compliance, and 5–8 mL/kg PBW with better preserved compliance.,
There is also a realization that COVID-19 pneumonia is not a classic ARDS. Recent paper from Gattinoni has highlighted that there are different phenotypes for the lung disease in the patients. The type 1 has near-normal pulmonary compliance with isolated viral pneumonia and needs a lower positive end expiratory pressure (PEEP) and prone position for rescue therapy while on NIV. The type 2 patients have a decreased pulmonary compliance because of natural progression of disease, reduced gas volume, increased lung weight and oedema. They require a higher PEEP (14-15 cms-H20) and prolonged periods of prone position while intubated. These two types can be differentiated to some extent on the basis of computed tomography (CT) scan. In addition, microthrombosis and ischemic events are common leading to ventilation perfusion mismatch., Avoid spontaneous respirations in the early phase of illness and keep those patients well sedated and paralyzed for 2–3 days before weaning paralysis.
The preferred method of intubation is rapid sequence intubation. However, if the patient's oxygen reserve is very poor with significant desaturations, ventilate with two hand bag and mask technique with a heat and moisture exchanger (HME) viral filter to reduce aerosols. Use a cuffed tube; video laryngoscope and an HME-Viral filter at the end of the endotracheal tube (ETT) to limit HCW exposure. Clamp the ETT if disconnection from the ventilator is required. Use closed in-line suctioning with minimal disconnection of the ventilator circuit.,
Initial recommendation was to use passive humidification with HME. As there was a need to change the HME every 24 h, active humidification was tried. However, this resulted in frequent blockage of end-tidal CO2 monitoring catheter. Hence, most centers are using passive humidification, with a process to clamp the ETT and turn off the ventilator while the HME is changed.
All guidelines and experience from the front-line physicians suggest early and prolonged (up to 16 h) prone positioning in moderate-to-severe ARDS (i.e., PaO2/FiO2<150; OI ≥12; OSI ≥10). Newer, rapidly emerging evidence suggest early, conscious proning in adults with hypoxemia who are on HFNC/NIV. Our expert panel recommends to prone all patients with respiratory distress when safe and feasible with or without low dose sedative for comfort.
The evidence for the use of steroids in COVID-19 pneumonia is weak, hence not recommended,, except in clinical trial or in short courses at low-to-moderate doses, for critically ill patients with COVID-19. Existing evidence is inconclusive, with no agreement even with systematic reviews and meta-analyses. Identification of children benefitting from this therapy beforehand is almost impossible.
High rate of re-intubation
The rate of reintubation is more than the usual with definite airway swelling/stridor. There is a high incidence of laryngeal edema in adult population so steroids are used as a pre-empt for extubation in some centers. To prevent reintubation, wait longer than usual and let the inflammatory markers come down prior to extubation. With the proper protection provided to HCWs, elective or rescue NIV may be cautiously used in risky patients with residual atelectasis, morbid obesity, etc.
Extracorporeal membrane oxygenation
Guidelines have suggested a trail of inhaled nitric oxide/inhaled prostacyclin in severely ill patients sliding toward indication for extracorporeal membrane oxygenation therapy.
Consider placing invasive lines such as central venous and arterial lines early during the ICU course especially soon after intubation (bundled procedures approach) anticipating a prolonged ICU stay.
Inotropes and vasopressors
There is a high incidence of myocardial involvement in adult population with bradycardia and raised troponin. Malignant arrhythmias are rare. An echocardiogram assessment and a 12-lead electrocardiogram are recommended if there is cardiovascular involvement to define treatment strategy and monitor progress.
In moderate-to-severe ARDS, the early use of neuromuscular blocking agents for 24–48 h has been recommended. Adult patients have been kept sedated and paralyzed for long time due to difficulty in ventilation. As a result, critical illness polyneuromyopathy is extremely common which may contribute towards extubation failure.
Some societies has suggested administration of empirical antibiotics,, within an hour of presentation. Bacterial infections are exceedingly common 5–8 days after admission.
Rebound increase in inflammatory markers or a rise in procalcitonin may be a good indicator to investigate and treat ventilator associated pneumonia.
Fluid management and nutrition
The initial recommendations were to aim for restrictive,, fluid balance, but now with understanding of the thrombotic phenomena, the higher insensible losses and parenchymal disease; patients are being kept on the euvolemic side unless visibly edematous. Adult studies have reported acute kidney injury and prolonged continuous venovenous hemofiltration (CVVH) runs. CVVH circuit clot is notably very common requiring aggressive anticoagulation strategies. Enteral nutrition is preferred wherever possible.
There is emerging evidence with COVID-19 adult population regarding pulmonary microangiopathy and clots; therefore, there is a role of preventive anticoagulation. Due to a high clot load, a CT-pulmonary angiogram is recommended to exclude pulmonary embolism especially in patients with persistent hypoxia despite high ventilator requirements and signs of right ventricular failure. Prior expert opinion recommended therapeutic heparin but reports of pulmonary hemorrhages have promoted a safer practice of low dose, continuous heparin (prophylactic dose).
Specific therapeutic options
There is no proven specific therapy as of now for treatment of this novel disease. Symptomatic and supportive management with strict infection control measures remains the corner stone for managing these patients.
Below is the summary of evidence for some commonly proposed options:
- Antiviral treatments such as hydroxychloroquine,, remdesivir,, HIV protease inhibitors (lopinavir and ritonavir) or immune-based therapies involving convalescent serum, interleukin (IL)-1 or IL-6 inhibitors (Anakinra and SariluMab, respectively), have insufficient data for routine recommendation and are predominantly prescribed as part of clinical trials
- Corticosteroids: There is some weak recommendation for its use in late stages of ARDS or refractory shock. Steroids should not be discontinued if the patient is receiving medication prior to COVID-19 diagnosis for another underlying condition, including inhaled steroids for asthma. Consider adjusting for steroid stress dosing in this situation
- Nonsteroidal anti-inflammatory drugs (NSAID): There were initial concerns regarding increased disease severity with the use of NSAID. At the current time, there is insufficient scientific evidence connecting the use of NSAIDs with worsening COVID-19 symptoms.,
Resuscitation in the intensive care unit
The United Kingdom Resuscitation Council and the American Heart Association have published specific recommendations for cardiopulmonary resuscitation (CPR). The main difference is that full PPE must be worn before commencing any CPR as CPR in itself is aerosol generating.
| Conclusion|| |
We are in the middle of an ongoing pandemic due to an organism we hardly understand. Every country and professional bodies will have to produce and adapt guidelines according to the disease pattern and available resources – “one size will not fit all” in this case. Moreover, these guidelines need to be constantly revised as the new evidence comes to light. Until robust evidence is being synthesized, management of COVID-19 will be driven mainly by learning from experiences from the front-line workers. No one is an expert on COVID-19 yet, some are just a little more experienced.
The recommendations for respiratory support based on S/F ratio can be easily applied even in resource-limited setting and is widely applicable. At the same time, experts are advocating a trial of noninvasive ventilation before proceeding with intubation as long as there is adequate PPE for the HCW in view of high aerosolization. Standard ICU practices such as lung protective ventilation targets based on the compliance of the lungs, prone position and euvolemic fluid balance in addition to standard ICU care have been recommended in all of these guidelines. Currently, there is no strong recommendation on the therapeutic options.
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Conflicts of interest
There are no conflicts of interest.
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