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 Table of Contents  
GUIDELINE
Year : 2020  |  Volume : 4  |  Issue : 2  |  Page : 27-44

The saudi critical care society clinical practice guidelines on the management of COVID-19 patients in the intensive care unit


1 Department of Medicine; Department of Health Research Methods, McMaster University, Hamilton, Canada
2 Clinical Excellence Administration, Second Health Cluster in Central Region, Ministry of Health, Saudi Arabia, King Fahad Medical City, Second Health Cluster in Central Region, Ministry of Health, Riyadh, Saudi Arabia
3 Departments of Emergency Medicine and Critical Care, College of Medicine, King Saud University, Riyadh; Adult Critical Care Services, Ministry of Health, Saudi Arabia
4 Dr. Sulaiman Al Habib Medical Group, Riyadh, Saudi Arabia, Wollongong University, Australia
5 Departments of Medicine, and Intensive Care, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
6 Molecular Diagnostics Laboratory, Johns Hopkins Aramco Healthcare, Dhahran, Saudi Arabia
7 Critical Care Services Administration and Pulmonary Section, Department of Medicine, King Fahad Medical City, Dammam, Saudi Arabia
8 Critical Care Services Administration, King Fahad Medical City, Riyadh, Saudi Arabia
9 Prince Mohammed Bin Abdulaziz Hospital, 2nd Central Health Cluster, Riyadh, Saudi Arabia
10 Department of Emergency and Critical Care Medicine, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
11 Department of Pharmacology, Alfaisal University; Department of Infectious Diseases and Pharmacology, Dr. Sulaiman Alhabib Medical Group, Riyadh, Saudi Arabia
12 Pediatric Intensive Care, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
13 Pediatric Intensive Care, Prince Sultan Military Medical City, Riyadh, Saudi Arabia
14 Al Hammadi Hospital, Riyadh, Saudi Arabia
15 Respiratory Care Services, Prince Sultan Military Medical City, Riyadh, Saudi Arabia
16 King Saud Bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, Riyadh, Saudi Arabia
17 Pediatric Respiratory Care Services, Prince Sultan Military Medical City, Riyadh, Saudi Arabia
18 Saudi Patient Safety Centre, Riyadh, Saudi Arabia
19 Department of Health Research Methods, McMaster University, Hamilton, Canada; Department of Critical Care Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
20 Dr. Sulaiman Al Habib Medical Group, Riyadh, Saudi Arabia, Wollongong University, Australia; Department of Medicine, Alfaisal University, Riyadh, Saudi Arabia

Date of Submission08-Apr-2020
Date of Decision05-May-2020
Date of Acceptance14-May-2020
Date of Web Publication1-Jul-2020

Correspondence Address:
Waleed Alhazzani
Departments of Medicine, and Health Research Methods, Evidence, and Impact, McMaster University
Canada
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/sccj.sccj_15_20

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  Abstract 


Background: Although recent international guidelines have been published on the management of critically ill patients with the novel coronavirus disease 2019 (COVID-19), there is a vital need to develop clinical practice guidelines tailored to the context of Saudi Arabia. Methods: The Saudi Critical Care Society (SCCS) is the sponsor for this guideline. The expert panel consisted of 19 members. All members completed the World Health Organization Conflict of Interest Form. The expert panel formulated questions on the management of critically ill patients in the intensive care unit with COVID-19. Panel members identified relevant studies. The panel used the categories of Grading Recommendations, Assessment, Development, and Evaluation (GRADE) to assess the confidence in the evidence. Results: The SCCS expert panel issued 53 statements; of which 7 were strong recommendations, 9 were best practice statements, 32 were weak recommendations, and we were not able to issue recommendations in 5 instances. The statements covered different aspects of the critical illness in COVID-19 patients, including: infection control; therapeutic interventions; supportive care; and crisis management. Conclusion: The SCCS guidelines on the management of critically ill COVID-19 patients have been based on the best available evidence and tailored to the context of Saudi Arabia. These guidelines will be updated periodically to incorporate new evidence.

Keywords: ARDS, COV-2, COVID-19, Critical Care, Intensive Care Unit, Practice Guidelines, SARs


How to cite this article:
Alhazzani W, Al-Suwaidan FA, Al Aseri ZA, Al Mutair A, Alghamdi G, Rabaan AA, Algamdi M, Alohali AF, Asiri AY, Alshahrani MS, Al-Subaie MF, Alayed T, Bafaqih HA, Alkoraisi S, Alharthi SM, Alenezi FZ, Al Gahtani A, Amr AA, Shamsan A, Al Duhailib Z, Al-Omari A. The saudi critical care society clinical practice guidelines on the management of COVID-19 patients in the intensive care unit. Saudi Crit Care J 2020;4:27-44

How to cite this URL:
Alhazzani W, Al-Suwaidan FA, Al Aseri ZA, Al Mutair A, Alghamdi G, Rabaan AA, Algamdi M, Alohali AF, Asiri AY, Alshahrani MS, Al-Subaie MF, Alayed T, Bafaqih HA, Alkoraisi S, Alharthi SM, Alenezi FZ, Al Gahtani A, Amr AA, Shamsan A, Al Duhailib Z, Al-Omari A. The saudi critical care society clinical practice guidelines on the management of COVID-19 patients in the intensive care unit. Saudi Crit Care J [serial online] 2020 [cited 2020 Aug 6];4:27-44. Available from: http://www.sccj-sa.org/text.asp?2020/4/2/27/288728




  Introduction Top


The recent viral outbreak first identified in Wuhan, China has now crossed most borders and had spread into more than 224 countries.[1] The outbreak is caused by a virus that belongs to the Coronaviridae family of viruses. Coronaviruses are RNA viruses, having RNA as their genome.[1] The recent outbreak is caused by a novel strain of coronavirus which is very similar to the SARS-CoV that resulted in the SARS outbreak. Initially, it was named as 2019-nCoV. Recently it has been renamed by the International Committee on Taxonomy of Viruses (ICTV) as Severe Acute Respiratory Syndrome Corona Virus-2 (SARS-CoV-2).[2] The World Health Organization (WHO) has termed it coronavirus disease 2019 (COVID-19),[3] the WHO characterized the new COVID-19 as a pandemic, the first pandemic ever caused by a coronavirus.[4] According to the WHO, as of May 5th, 2020, there were over 3 million confirmed COVID-19 cases, causing over 100,000 deaths globally.

Saudi Arabia has commenced number of actions, including screening for travelers that were made to prevent an outbreak. The Ministry of Health and the Saudi Center for Disease Prevention and Control have published the Coronavirus Infection Guidelines along with other guidelines that should help to detect and prevent an epidemic. A decision was made to develop clinical practice guidelines for critically ill patients with COVID-19 in the intensive care unit (ICU) by the Saudi Critical Care Society, as the governing body of critical care practice in Saudi Arabia. The objectives of these guidelines were to provide guidance and recommendations to help hospitals in Saudi Arabia prepare for an outbreak of COVID-19 and standardize clinical management pathways for COVID-19 patients in the ICU.

Scope of Guidelines

The scope of the current guidelines is to provide recommendations to the critical care teams providing care to critically ill patients with COVID-19 in the ICU. The target users of this guideline are: intensivists; nurses; respiratory therapists; clinical psychologists, clinicians involved in the care of critically ill COVID-19 patients, and policymakers.

Panel Expertise

The Saudi Critical Care Society (SCCS) selected expert panel members in order to issue recommendations in a timely manner. The expert panel was instructed to develop the guidelines based on their expertise and evidence within a set length of time. The panel included experts in critical care, infection control, respiratory therapy, nursing, public health and clinical psychology.


  Methods Top


Data sources and evidence assessment

Each panelist was assigned one or more guideline questions. Panelists reviewed the recently published Surviving Sepsis Campaign guidelines to structure some of the guideline questions and identify relevant evidence. They performed their own searches to identify additional relevant evidence for each question.

We relied on direct COVID-19 evidence wherever available, but we relied on indirect evidence from acute respiratory distress syndrome, sepsis, and other coronaviruses when applicable. We did not perform a systematic appraisal or grading of the evidence.

Recommendation formulation

The guideline covered three major domains related to COVID-19. These were: 1) infection control, 2) therapeutic interventions, and 3) critical care managerial strategies. Each panelist reviewed the evidence on the assigned question, drafted a preliminary recommendation, and then presented the recommendation to the panel. Consensus was reached by discussion between panel members on teleconferences and electronically. We used “we recommend” for strong recommendations and “we suggest” for weak recommendations.

Infection control

The WHO and the United States Center for Disease Control and Prevention (CDC) have issued guidelines on infection control in hospital settings. Recently, the Surviving Sepsis Campaign COVID-19 guidelines issued recommendations related to infection control in the ICU.[5] In this section the panel addressed pertinent infection control questions and issued evidence-based recommendations.

Recommendations

Recommendation 1

For healthcare workers performing (or in proximity to) an aerosol generating procedure (AGP) on COVID-19 patients, we recommend using fitted N95 respirators or equivalent in addition to other personal protective equipment (PPE) (best practice statement).

When fitted N95 respirators are not available or a healthcare worker fails fit-testing, we recommend using a Powered Air-Purifying Respirator (PAPR).

Rationale

A recent report from Chinese CDC stated that, among laboratory-confirmed cases, 1,716 (3.8%) were healthcare workers; among them, 14.8% had severe or critical illness and, of them, 5 died.[6] In Italy, as of March 15, 2020, there were 2026 healthcare workers with confirmed COVID-19.[7] These observations indicate a great burden of infection among healthcare workers. Therefore, we recommend adhering to infection control measures in the ICUs. Respirator masks can block 95 to 99% of aerosol particles and, therefore, should always be used when performing an AGP. Surgical masks are deemed to block only large particles or droplets and are less efficient in blocking small aerosol particles (<5 micrometers).[8] Our recommendation is consistent with existing CDC, WHO, and other guidelines.

Recommendation 2

For healthcare workers performing non-aerosol generating procedures or providing care to COVID-19 patients; we suggest using surgical masks instead of respirator masks, in addition to other PPE (weak recommendation).

Rationale

A recent systematic review of 4 RCTs showed that N95 did not reduce the risks of laboratory-confirmed viral infection or clinical respiratory illness in healthcare workers, compared to surgical masks.[9] The results are indirect and do not apply to the context of AGP and, therefore, should be interpreted with great caution.

A study from South Korea showed that surgical masks did not effectively filter SARS–CoV-2 during coughing by infected patients.[10] Until more evidence is available and, given the global shortage of PPE, the panel felt that the use of surgical masks when caring for CPVOD-19 patients (who are not undergoing an AGP) in the ICU is an acceptable option.

Recommendation 3

For healthcare workers in the ICU, we suggest wearing a single surgical/medical mask when caring for known or suspected COVID-19 patients (weak recommendation).

Remarks: The masks must be changed if they become wet or contaminated. The masks are not allowed to be worn outside the clinical care areas, nor to be hung around the neck or kept in a pocket. Proper hand hygiene should be done before donning and doffing. A recent study reported the rationing of PPE to the medical staff in Singapore. They are given only 2 sets of PPE and are directed to use one set in the first half and the second set in the second half of their shift while masks are worn at all times and only changed when contaminated or at midway point in the shift.[11]

Rationale

This recommendation follows the guideline of universal masking released by Saudi CDC, Ministry of Health, Saudi Arabia. Surgical masks are recommended to provide protection to patients and healthcare workers from exposure to infection from asymptomatic healthcare workers with COVID-19. They are also intended to provide protection for the healthcare workers from undiagnosed asymptomatic patients and patients having mild COVID-19.

Recommendation 4

For healthcare workers using an N95 respirator or surgical/medical mask, we recommend using additional PPE including gloves, gown, and eye protection; i.e., face shield or safety goggles (best practice statement).

Rationale

This recommendation is in line with the WHO guidelines for the use of PPE in healthcare and community settings while dealing with COVID-19.[12]

Recommendation 5

For healthcare workers interacting with COVID-19 patients, we recommend maintaining hand hygiene (best practice statement).

Remark: Hands should be washed before putting on or removing masks.

Rationale

A recent report highlighted that healthcare workers are directed to use the restroom at the midpoint of their shift and use alcohol rub/gel prior to using or disposing of masks.[11] Hand hygiene is crucial to prevent the transmission of coronaviruses. A 2015 study found that people touch their faces on an average of 23 times an hour; therefore, hand hygiene may reduce virus transmission.[13] This recommendation is consistent with the WHO guidance.[14]

Recommendation 6

We suggest minimizing unnecessary interaction and maintaining physical distancing in ICUs (weak recommendation).

Rationale

A recent study in Singapore described how physicians were split into teams of 4, doing12 hour shifts alternately. These teams did not interact with each other. If a doctor in the team fell ill, the team covered him or her. Functional redundancy and rest periods are set to ensure that the physicians take enough rest.[11] There is insufficient indirect evidence on the effect of social distancing in healthcare workers.[15] However, due to the simplicity and lack of downsides for practicing physical distancing at work, we suggest maintaining physical distancing among healthcare workers.

Recommendation 7

We recommend performing AGPs on ICU COVID-19 patients in negative pressure rooms with at least 12 air-changes per hour and controlled direction of air flow (best practice statement).

Rationale

In negative pressure rooms, a negative pressure is created and maintained to avoid the accidental release of pathogens outside the room. Studies report that negative pressure rooms were useful in preventing cross-contamination during the SARS epidemic.[16] The WHO also recommends performing AGPs such as bronchoscopies and non-invasive ventilation, in negative pressure rooms[17],[18],[19]

Recommendation 8

We recommend limiting the number of healthcare workers in the room to the minimum required to provide care for COVID-19 patients (best practice statement).

Rationale

This approach was implemented during the MERS epidemic and was perceived to be effective in controlling the infection. Therefore, it can be implemented in COVID-19 prevention. This guideline is in accordance with the Saudi Center for Disease Management and Control.

Recommendation 9

For COVID-19 patients needing endotracheal intubation, we recommend that an experienced healthcare provider in airway management performs the endotracheal intubation to decrease the number of attempts and the risk of disease transmission (best practice statement).

Rationale

Endotracheal intubation is an AGP, and is associated with higher risk of disease transmission to healthcare workers.[20] Therefore, minimizing the number of attempts and the time spent during endotracheal intubation will help reduce exposure time and possible transmission risk.

Recommendation 10

We suggest providing clean scrubs for healthcare workers to use during working hours and access to changing rooms and showering facilities, if applicable (weak recommendation).

Rationale

This would result in avoidance of cross-contamination among healthcare workers.[19] This approach was supported by the CDC during the Ebola epidemic and by recent articles supporting healthcare workers during the COVID-19 pandemic to minimize contamination of personal clothing and disease transmission.[21],[22]

Recommendation 11

We suggest using disposable bronchoscopes when performing bronchoscopy or percutaneous tracheostomy on patients with COVID-19 (weak recommendation).

Rationale

Disposable bronchoscopes are available in Saudi Arabia and are commonly used when there are concerns about disease transmission. Although clinicians should minimize the number of AGPs on patients with COVID-19, if bronchoscopy is indicated and disposable bronchoscopes are available, clinicians may consider using them. Recent reports from Singapore showed that they used disposable bronchoscopes to perform the procedure when indicated.[19]


  Therapeutic Interventions Top


Antiviral therapy

Several ongoing clinical trials are investigating the potential therapeutic regimens for COVID-19. Antiviral therapy might improve clinical outcomes as critically ill patients has a prolonged detection of SARS-CoV-2 RNA in their respiratory tract and other sites. Currently, no direct-acting antiviral agents improve the outcomes of patients with COVID-19. Many drugs approved for other indications have been anticipated as a potential treatment of COVID-19 and are undergoing clinical trials in many countries. The drugs are used either alone or in combination. They include arbidol, chloroquine, hydroxychloroquine, favipravir, interferons, ivermectin, lopinavir/ritonavir, remdesivir, ribavirin, and traditional Chinese medicines. Our recommendations are based on published literature up to April 12, 2020 and will be updated as evidence evolves.

Recommendation 12

We recommend not using high-dose hydroxychloroquine or chloroquine in critically ill adults with COVID-19 (weak recommendation).

We make no recommendation on the use of usual-dosing hydroxychloroquine or chloroquine in critically ill adults with COVID-19 outside clinical trials.

Rationale

Early in vitro studies showed that chloroquine and hydroxychloroquine inhibit SARS CoV-2 replication.[23],[24] Chloroquine and hydroxychloroquine can impair the replication of several viruses by interacting with the endosome-mediated viral entry or the late stages of replication of enveloped viruses,[25] they increase the pH of intracellular vacuoles and alter protein degradation pathways through acidic hydrolases in the lysosomes, macromolecule synthesis in the endosomes, and post-translational protein modification in the Golgi apparatus.[25]

There are several ongoing RCTs investigating the efficacy of these agents in COVID19.[26] Currently, there are no clinical trials to support the use of chloroquine or hydroxychloroquine.

Recent news briefings from China on 10 trials that included more than 100 patients reported that “chloroquine phosphate is superior to the control treatment in inhibiting the exacerbation of pneumonia, improving lung imaging findings, promoting a virus negative conversion, and shortening the disease course”. However, the results have not yet been published.[27] An open-label non-randomized clinical trial conducted in France reported on 42 patients with COVID-19; among these, 16 patients received usual care and were classified as “controls”, and 26 patients were treated with hydroxychloroquine; of those, 20 patients completed the study, and 6 patients received azithromycin in addition to hydroxychloroquine. Azithromycin was given as a single dose of 500 mg, then followed by 250 mg for 4 days to prevent secondary bacterial infection. Patients' nasopharyngeal swabs were tested daily where the presence or absence of SARS CoV-2 on the 6th day was the primary end-point. Virologic clearance was achieved in all patients treated with hydroxychloroquine and azithromycin, compared with 57.1% in patients treated with hydroxychloroquine alone, and 12.5% patients in the control arm (P < 0.001).[28] Despite the small number of patients, this study has gained enormous attention worldwide. However, the study has many limitations. Unblinding and non-randomization of patients was subjected to bias as the patients were chosen to be either treated or serve as controls. In addition, the control group and treatment group were not balanced with regards to important baseline variables. Moreover, the patients in the control group were allocated at different centers to the treatment group; hence, the care was not standardized between thee centers. Lastly, six patients in the treatment group were excluded due to several reasons which could have introduced attrition bias.

A recent expert consensus in China recommended using chloroquine phosphate at 500 mg twice daily for 10 days (with a minimum of 5 days) for patients with COVID-19 pneumonia.[29] An in vitro study has shown hydroxychloroquine to be more potent than chloroquine against SARS-CoV-2, and based on pharmacokinetic models, hydroxychloroquine sulfate was recommended to be given orally in a loading dose of 400 mg twice daily, followed by a maintenance dose of 200 mg given twice daily for 4 days.[3] This can serve as an alternative to chloroquine in countries with a chloroquine shortage. The results of many clinical trials are still pending; therefore, a recommendation for or against the use of chloroquine and hydroxychloroquine therapy cannot be issued.

Recently, an RCT compared high dose hydroxychloroquine (600 mg twice daily) versus a lower dose (450 mg twice daily) was stopped early for increased risk of cardiac adverse effects in the high dose arm and possible increased risk of death.[30]

Recommendation 13

We suggest not using lopinavir/ritonavir for the treatment of critically ill adult patients with COVID-19 outside the context of clinical trials (weak recommendation).

Rationale

Lopinavir is an anti-retroviral protease inhibitor used for the treatment of human immunodeficiency virus infection, in combination with ritonavir to enhance lopinavir exposure.[31] Lopinavir/ritonavir are recorded as having in vitro activity against SARS-CoV-1[32] and MERS-CoV.[33] A recently published randomized open-label trial included 199 hospitalized patients with laboratory-confirmed SARS-CoV-2 infection in China. In this trial, 199 patients were assigned to the lopinavir/ritonavir group, and 100 patients to the standard care group. There was no statistical difference in 28-day mortality and time to clinical improvement between the two groups.[34] Even though this trial serves as the only available evidence for treatment of COVID-19 patients with lopinavir/ritonavir, it has several limitations. The trial was unblinded which could have introduced performance bias, and the results were imprecise due to the small number of patients. Therefore, the suggestion not to routinely use lopinavir/ritonavir in critically ill adult patients with COVID-19 disease is reasonable. Lopinavir/ritonavir is one of the arms in a core treatment study protocol planned by WHO for COVID-19 patients,[35] and in a trial to evaluate multiple treatment strategies for pneumonia in critically ill patients “REMAP-CAP (Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community-Acquired Pneumonia) trial (NCT02735707)”. The evidence on lopinavir/ritonavir is still evolving and will help in the precision of the recommendations.

Recommendation 14

We make no recommendation on the use of other antiviral agents outside the context of clinical trials.

Rationale

Remdesivir is an investigational drug (with a development code GS-5734), undergoing clinical trials and has not yet been approved or licensed. It is considered a potential treatment for COVID-19 and recommended by WHO for research prioritization of candidate therapeutic drugs.[35]

Remdesivir is an adenosine analog and monophosphoramidate prodrug. Remdesivir is metabolized into GS-441524, its active form, that blocks viral RNA polymerase, causing a decrease in viral RNA production.[36]In vitro studies have demonstrated remdesivir's antiviral activity against SARS-CoV, MERS-CoV, and SARS-CoV-2.[36] It was shown to be superior to lopinavir/ritonavir in animal models of MERS-CoV when combined with systemic IFN-β.[37],[38] Currently, there are several ongoing RCTs, intended to study the efficacy and safety of intravenous remdesivir versus placebo for severe COVID-19 (clinicaltrials.gov NCT04257656), and for mild/moderate COVID-19 (clinicaltrials.gov NCT04252664). Many Phase III trials to evaluate the safety and antiviral activity of remdesivir in COVID19 patient s are recruiting patients (clinicaltrials.gov NCT04292899, NCT04292730).

Another adaptive, randomized, double-blind, placebo-controlled trial to evaluate the safety and efficacy of novel therapeutic agents in hospitalized adults diagnosed with COVID-19 in the USA is sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), and its results are currently analyzed and are expected shortly (clinicaltrials.gov NCT04280705). Of note, on the basis of data available to them NIH issued emergency authorization for the use of this drug. Until clinical evidence is available we cannot, however, issue a recommendation for or against the use of remdesivir; we can only encourage its use in the context of clinical trials.

Recommendation 15

We make no recommendation on the use of recombinant interferons, they are better used in the context of clinical trials.

Rationale

Recombinant interferons have been investigated previously in many viral infections including SARS-CoV and MERS-CoV, mainly in combination with ribavirin or antiretroviral agents due to their in vitro activity against these viruses.[39],[40],[41],[42],[43] In a large multicenter observational study conducted in Saudi Arabia in critically ill patients with MERS-CoV, interferons in combination with ribavirin were not associated with reduction in 90-day mortality or viral clearance.[43] Another RCT in Saudi Arabia is currently recruiting patients to study the efficacy of recombinant interferon beta 1b in combination with lopinavir/ritonavir for the treatment of MERS-CoV.[44] Interferons might be a potential treatment option for COVID-19 as they have been prioritized for research. The current guidelines will be updated based on the development of new evidence.

Recommendation 16

There is insufficient evidence on the use of convalescent plasma; therefore, we make no recommendation on its use in critically ill patients with COVID-19.

Rationale

Transfusing plasma obtained from COVID-19 patients who recovered from their illness has been proposed as a potential therapeutic option. A systematic review of observational studies that reported on the use of convalescent plasma in other coronaviruses and influenzas showed an association with reduced odds of death (OR 0.25; 95% CI 0.14, 0.45).[45],[46],[47] Recent case series have showed that most patients with COVID-19 who received convalescent plasma had clinical and biochemical improvement.[48] However, these studies lacked a control arm, and many co-interventions were administered; therefore, we cannot make any strong inferences. Given the uncertainty about the effect of convalescent plasma on COVID-19 patients' outcomes, the panel elected not to issue a recommendation until more evidence is available. Multiple RCTs are ongoing.

Recommendation 17-18

For critically ill adults with COVID-19, we suggest measuring D-dimer level (weak recommendation).

For critically ill adults with elevated D-dimer levels and no contraindication for anticoagulation, we recommend using unfractionated or low molecular weight heparin at prophylactic doses (strong recommendation).

We make no recommendation on the use of systemic anticoagulation in the absence of venous thromboembolic disease in COVID-19 patients.

Rationale

Autopsy reports of deceased patients with COVID-19 showed evidence of microvascular thrombosis and pulmonary infarction.[49] Furthermore, several studies have shown that patients with elevated D-dimer level are at higher risk of death. It is not clear if the elevated d-dimer level is caused by thrombosis or inflammation. Nevertheless, observational studies have showed a higher risk of thrombosis in critically ill COVID-19 patients.[50] One observational study has showed that patients who received prophylactic dosing of heparin were at lower risk of death compared to those who did not: the results are hypothesis- generating and further high-quality studies are needed to determine the effect of anticoagulation in this population. However, because VTE prophylaxis is considered the standard of care for critically ill patients, we recommend using subcutaneous heparin, if no contraindication, at prophylactic doses.

Ventilatory support

Recommendations 19-23

We recommend starting supplemental oxygen for COVID-19 patients with SpO2 is <90% (strong recommendation),

We suggest targeting SpO2 of 92% to 96% when treating hypoxemic patients with COVID-19(weak recommendation).

Supplemental oxygen for up to of 5 L/minute can be given via nasal cannula or simple face mask, may use face mask with a reservoir bag (at 10-15 L/minute) if needed. Nasal prongs or a nasal cannula are preferred in young children.

If targeted SpO2 is not achieved despite conventional oxygen therapy, we suggest using high flow nasal cannula (HFNC) over conventional oxygen therapy for adults and pediatrics with COVID-19 (weak recommendation).

We recommend using HFNC in a negative pressure room, and that healthcare workers use airborne precautions when interacting with these patients (best practice statement).

For adults with COVID-19 on HFNC, we suggest using surgical masks to cover the patient's mouth and nose and minimize aerosolization (weak recommendation).

Rationale

In a Chinese study, the prevalence of hypoxemic respiratory failure in COVID-19 patients was about 19%. Most cases were mild 81%, whereas 14% were severe and 5% were critical with complications, such as respiratory failure, septic shock, and multi-organ failure.[6] The risk factors associated with respiratory failure requiring mechanical ventilation are not well-described. However, risk factors associated with critical illness and ICU admission were older age, male gender, and the present of pre-existing comorbidities.[6],[51]

Indirect RCTs have showed that a liberal oxygen strategy increases hospital mortality and that there was a linear association between higher SPO2 and mortality[52]. Furthermore, in the context of a pandemic, oxygen becomes a valuable resource that should only be used if needed. Our recommendations are consistent with those of the Surviving Sepsis Campaign COVID-19 guidelines.[5]

Close monitoring of patients on conventional oxygen therapy is essential for early recognition of respiratory failure and to ensure timely and safe initiation of respiratory support. In this case, HFNC can be considered over conventional oxygen therapy. Meta-analyses of RCTs in non-COVID patients showed that HFNC, compared to conventional oxygen, was associated with reduced intubation rate.[52],[53] The reduced need for intubation reported with the application of HFNC alone is very important, especially with increased demand for critical care during a pandemic.[5]

Practical consideration

Before applying HNFC, the patient must be moved to a negative pressure room. The air exiting a negative pressure room should be filtered with a high-efficiency particulate air (HEPA) filter. Entry to the patient's room while receiving HFNC oxygen therapy should be minimized. A surgical mask applied to the patient while receiving HFNC oxygen therapy may lower the health workers' exposure overall.

Recommendations 24 – 25

If HFNC is not available or fails to provide required support, and immediate endotracheal intubation is not indicated, we suggest a trial of non-invasive positive pressure ventilation (NIPPV), with close monitoring for clinical deterioration and the need for urgent intubation (weak recommendation).

We recommend using NIPPV in a negative pressure room, and that healthcare workers use airborne precautions and PPEs when interacting with these patients (best practice statement).

Remarks: the patient interface should be selected based on institutional guidelines and tailored to achieve patient comfort and minimal leak. Infection control measures should be taken due to aerosol generation from the leak port. Commercially available filters that can be fitted to the leak port could be used.

Rationale

Critically ill adult patients with COVID-19 commonly present with acute hypoxic respiratory failure and ARDS.[6],[51] An RCT showed that NIPPV has a higher mortality rate when compared with conventional oxygen therapy and HFNC[60]. NIPPV did not reduce mortality nor length of stay when compared with invasive mechanical ventilation[61]. The role of NIPPV in respiratory pandemics is not clear [1]. Possible complications associated with NIPPV are high transpulmonary pressure and tidal volumes leading to ventilator induced lung injury (VILI), and delay in initiating invasive ventilation.[54],[55] Moreover, NIPPV is an AGP which increases the risk of disease transmission.[20] Consequently, the routine use of NIPPV in critically ill adults with COVID-19 should be avoided, but when conventional oxygen therapy or HFNC fail to provide required support then, a trial NIPPV is not unreasonable [1]; this may avoid the need for intubation and mechanical ventilation, especially with limited resources during a pandemic [1,19]. When NIPPV is used, close patient monitoring especially within the first 1-2 hours should be continued; if no improvement, then intubation and invasive mechanical ventilation should be considered.

Practical considerations

Before using HNFC or NIPPV, the patient must be moved to a negative pressure room. The air exiting a negative pressure room should be filtered with a high-efficiency particulate air (HEPA) filter. Entry to the patient's room while receiving HFNC oxygen therapy should be minimized. HFNC or NIPPV should be used selectively after balancing the risks and benefits to the patient and the risk of exposure to healthcare workers. Younger patients with no comorbidities may tolerate HFNC or NIV better than older patients with comorbidities. Patients with abnormal mental status, hemodynamically instability, and/or multiorgan failure should generally not receive HFNC or NIPPV. Patients receiving HFNC or NIPPV should be closely monitored for clinical deterioration or lack of improvement, with availability of personnel capable of endotracheal intubation if required.

Recommendation 26-27 When initiating invasive mechanical ventilation for adults with COVID-19 and moderate to severe ARDS; We recommend: using volume or pressure control modes; targeting a tidal volume of 6 ml/kg (4-8 ml/kg) of predicted body weight (PBW); and maintaining plateau pressure <30 cm H2O (strong recommendation).

If plateau pressure is >30 cm H2O, we suggest decreasing the tidal volume by 1 ml/kg increments to a minimum of 4 ml/kg PBW (weak recommendation).

We suggest setting the positive end expiratory pressure (PEEP) at 5 cm H2O, then applying the PEEP/FiO2 table from ARDS Network Protocol to adjust to appropriate PEEP level for the patient (see exception in the next recommendations) (weak recommendation).

We suggest using a higher PEEP strategy (>10 cm H2O), over a lower PEEP strategy, only in patients with low lung compliance who are PEEP responsive (weak recommendation).

When applying a high PEEP strategy, patients should be monitored for barotrauma and worsening hemodynamics.

Rationale

Adults with COVID-19 requiring invasive ventilation due to acute respiratory failure are severely ill, and several pathology reports have showed diffuse alveolar damage and other findings commonly seen in ARDS.[56] Therefore, the AARC recommended the ARDS Network Protocol recommendations for the initiation and management of invasive ventilation for critical patients with COVID-19[62]. The SCCM Guideline recommendations and suggestions on invasive ventilation initiation and management were mostly based on the ARDS Network Protocol recommendations. There are no studies on mechanical ventilation strategies in patients with COVID-19 as of this time[1]. A lung protective approach should always be applied to prevent ventilator-associated lung injury which may lead to multiorgan failure in patients with ARDS[63].

There is insufficient evidence to confirm whether pressure-controlled ventilation (PCV) offers any advantage over volume-controlled ventilation (VCV) in acute lung injury or ARDS.[57] Therefore, either mode is considered reasonable.

Low tidal volume ventilation strategy minimizes VILI. A multicenter RCT (861 patients) showed a lower mortality rate and more ventilator-free days with low tidal volume ventilation.[58] A systematic review and meta-analysis of 9 RCTs (1,629 patients) showed that protocolized low tidal volume with high PEEP strategy reduced mortality.[59]

Plateau pressure that exceeds 30 cm H2O is associated with increased risk of VILI. A systematic review and meta-analysis of 9 RCTs (1,629 patients) showed lower risk of death with using protocolized low tidal volume, high PEEP strategy, and plateau pressure <30 cm H2O.[59] Several clinical practice guidelines have recommended using low tidal volume ventilation (4-8 ml/kg PBW) and maintaining plateau pressure <30 cm H2O in patient with ARDS.[5]

An individual patient-data meta-analysis (2,299 patients) showed that a higher PEEP strategy reduced ICU and in-hospital mortality and the need for rescue therapies in patients with ARDS, though at the expense of increased risk of pneumothorax.[60] Clinicians should monitor their patients closely for evidence of barotrauma after increasing PEEP levels and should use the ARDS Network Protocol strategies to determine optimal PEEP level.

Practical considerations:

For mechanically ventilated adults with COVID 19 and normal compliance and no/mild ARDS, we suggest using a lower PEEP strategy to mitigate the unwanted effects of a higher PEEP such as barotrauma and hemodynamic instability. Also, pulmonary hemorrhagic infarcts and micro-thrombosis formations have been reported in pathological biopsies of a critically ill patient with COVID 19, suggesting the importance of the meticulous use of PEEP in such patients.[61]

Recommendation 28 and 29

We recommend not using the staircase (incremental PEEP) recruitment maneuver (SRM) (strong recommendation).

In pediatric patients, careful recruitment maneuvers (RMs) are in the attempt to improve severe oxygenation failure by slow incremental and decremental PEEP steps.

Rationale

When RMs are used in moderate to severe ARDS, the transpulmonary pressure increases enhancing recruitment of atelectatic lungs, eventually improving oxygenation, yet it may cause transient hemodynamic instability and increase the risk of barotrauma. Varying RM strategies are described and tested in clinical trials [1]. A systematic review and meta-analysis of 6 RCTs (1423) showed that conventional RMs reduced mortality and rescue interventions,[62] but the use of incremental PEEP RM resulted in higher risk of death.

Recommendations 30-31

We recommend not routinely using inhaled nitric oxide (iNO) in adults or children with COVID-19 (strong recommendation).

In adults and children with COVID-19 and severe ARDS, we suggest using iNO only as a rescue therapy. If oxygenation does not rapidly improve, the patient should be weaned off the treatment (weak recommendation).

Rationale

The use of iNO in patients with ARDS may improve oxygenation, but does not reduce mortality, and may increase the risk of acute kidney injury (AKI).[63]

Prone ventilation

Prone ventilation is one of the few interventions that have shown a mortality benefit in mechanically ventilated patients with moderate to severe ARDS.[64] The prone position reduces lung compression, improves lung perfusion, and reduces the ventral-dorsal transpulmonary pressure difference, resulting in improved ventilation and oxygenation.[65],[66],[67],[68] Prone ventilation has recently been adopted by multiple international guidelines as a rescue management for patients with moderate to severe ARDS to reduce mortality.[69],[70]

Recommendation 32

In institutions with expertise in prone ventilation and adequate human resources, we suggest prone ventilation for at least 12 to 16 hours over no prone ventilation for mechanically ventilated adults with COVID 19 and moderate to severe ARDS (weak recommendation).

Rationale

In a large RCT of 466 patients with ARDS, prone ventilation reduced 28-day and 90-day mortality, compared with ventilation in supine position.[64] Several systematic reviews and meta-analyses showed that prone ventilation for 12-16 hours reduces mortality but increases the rates of endotracheal tube obstruction and pressure sores.[71],[72],[73]

The recently released WHO interim guidance was strongly in favor of prone ventilation for patients with severe ARDS associated with COVID-19 disease, as long as sufficient human resources and expertise are available.[74] Currently, no studies are evaluating the outcomes of prone ventilation in patients with COVID-19. Prone ventilation was utilized in 11.5% of 52 critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China[51] and in 27% of 875 critically ill COVID-19 patients in Lombardy, Italy.[75]

Practical considerations

Safe prone ventilation requires expertise and adequate human resources. Appropriately trained healthcare workers should take the necessary infection control precautions at the time of proning. Patients should be closely observed during prone ventilation for dislodgment of endotracheal tubes or vascular catheters, pressure sores, nerve compression, and crush injury.[72] Clinicians should be recognizing contraindications for prone ventilation such as spinal instability, anterior burns, unstable fractures, and active bleeding.

Institutions offering prone ventilation should use a protocol for proning and should provide the necessary training. A Protocol, including a practical video, is available.[64] (https://www.nejm.org/doi/full/10.1056/NEJMoa1214103).


  Supportive Care (Hemodynamic Support and Fluid Therapy) Management in Covid-19 Top


Myocarditis and Shock

Problem/issue: In patients with COVID-19, the presentation of myocarditis varies from mild chest pain and dyspnea to left ventricular failure, arrhythmia and cardiogenic shock.[76] Although the diagnosis is mainly clinical; nonspecific electrocardiogram (ECG) changes and high cardiac enzymes are common.[77] Infection is triggered by the binding of SARS-CoV-2 spike protein to angiotensin-converting enzyme 2 (ACE2), which is highly expressed in the heart and lungs[78] The severity of the symptoms might be associated with increased secretion of ACE2 in these patients compared with healthy individuals.[78]

In a retrospective study of 150 patients using the database of two hospitals in Wuhan, mortality was 45%, (68 patients). Among those, 5 (7%) of patients died with circulatory failure. Deaths were noticed mainly in elderly patients, especially more than 60 years old (P < 0.001); patients with cardiovascular disease have a high risk of death (P < 0.001).[79] The rate of myocardial injury and myocarditis is between 4.8-7.2%.[80],[81] Among 52 critically ill patients with COVID-19, 32 (61·5%) patients died at 28 days, and the median duration from ICU admission to death was 7 days. The APACHE II score and SOFA score at ICU admission were higher in non-survivors: 18 and 6 respectively, 23% with cardiac injury.[51]

Recommendation 33

We suggest using dynamic parameters over static parameters to assess fluid responsiveness in patients with COVID-19 and shock (weak recommendation).

Rationale

Currently there are no studies on the assessment of fluid responsiveness in COVID-19 patients with shock. Our recommendation is based on indirect evidence on critically ill patients. The surviving sepsis campaign recommends following the dynamic parameters to judge the fluid responsiveness.[82] A systematic review and meta-analysis including 13 RCTs found goal-directed fluid therapy based on dynamic assessment of fluid responsiveness to reduce mortality, ICU length of stay, and duration of mechanical ventilation.[83]

Recommendations 34-36

For adults with COVID-19 and shock:

We suggest using a conservative fluid strategy (weak recommendation).

Remarks: many critically ill patients with COVID-19 are hypovolemic and have high insensible losses from ongoing fever: careful and frequent volume status assessment is warranted.

We suggest using crystalloids over colloids (weak recommendation). When crystalloids are used, we suggest using balanced crystalloids over saline (weak recommendation).

We recommend against using hydroxyethyl starches (strong recommendation).

Rationale

No studies have examined fluid resuscitation in confirmed COVID-19 patient with septic shock. Our recommendation is based on available evidence on critically ill patients. A recent meta-analysis of 9 studies published after 2015 showed no statistically significant difference between lower versus higher fluid volumes in all-cause mortality.[84] We recommend a conservative fluid resuscitation strategy to avoid the fluid overload associated with liberal fluid.

Our recommendation is based on available evidence on critically ill patients. A meta-analysis of 14 studies, with a total of 18,916 patients, showed that patients with sepsis, resuscitation with crystalloids or albumin, compared with other fluids was associated with reduced mortality.[85] A meta-analysis published in 2018 included 69 studies of volume resuscitation in a total of 30,020 critically ill patients. It showed no difference in mortality when using starches, dextran, albumin, FFP and gelatins versus crystalloids.[86] Due to the availability and the low cost we recommend the use of crystalloid.

In a recent meta-analysis examining buffered intravenous fluids versus intravenous 0.9% saline in resuscitation or maintenance, a total of 21 RCTs, including 20,213 patients, adult and children in a critical care setting, showed no effect of buffered intravenous fluid on in-hospital mortality compared to 0.9% saline in critically ill patients. The effects of buffered intravenous fluids and 0.9% saline solutions on prevalence of acute kidney injury were similar.[87] The Surviving Sepsis Guidelines on the Management of Critically ill Adults with COVID-19, suggested buffered intravenous fluids, as the point estimates for both outcomes suggest a potential for benefit from buffered crystalloid solutions in the previously mentioned meta-analysis. We recommend using buffered intravenous fluid, with 0.9% saline remaining a reasonable alternative.

Our recommendation is based on the available evidence on critically ill patients. The previously mentioned 2018 meta-analysis showed no difference in mortality with using starches, versus crystalloids in 24 studies including 11,177 patients.[86] There were increased risk of blood transfusion and renal replacement therapy with starches. Given the risk of the side effects, and absence of benefit from the use of hydroxyethyl starches and cost, we recommend against its use for resuscitation of patients with COVID-19 and shock.

Renal Replacement Therapy

The incidence of acute kidney injury (AKI) in patients with COVID-19 ranges from 0.5% to 23% according to the most recent data.[80],[88],[89] According to the studies, AKI develops at a median of 7-15 days after admission.[90],[91] AKI in COVID-19 accompanies sepsis, multiorgan failure, and shock; therefore, acute tubular necrosis (ATN) appears to be the most likely cause.[92],[93] AKI is associated with worse outcomes in patients with COVID-19. The incidence of requiring renal replacement therapy (RRT) in COVID-19 ranges from 0.8% to 5%.[91],[92],[94],[95] The management of AKI in this disease is probably similar to other settings.

Recommendations 37-38

For adults with COVID-19 and AKI, we recommend starting RRT if life-threatening hyperkalemia, severe acidosis, pulmonary edema, or uremic complications are present (strong recommendation).

We suggest against the early initiation of RRT in the absence of known indications (weak recommendation).

Rationale

The timing of initiating RRT in ICU patients has been a subject of multiple recent studies. A single-center unblinded RCT randomized 231 critically ill patients with AKI into an early start after progressing to stage 2 AKI or a delayed start when an urgent indication is present. All-cause mortality at 90 days was 39.3% in the early arm compared with 54.7% in the delayed arm (P 0.03).[96] In contrast, a multicenter RCT randomized 619 critically ill patients with Stage 3 AKI without acute indications into an early arm starting RRT immediately or a delayed arm starting after developing emergent indications. All-cause mortality at 60 days did not differ between the two treatment arms. Furthermore, almost half of the patients in the delayed arm did not ever require any RRT.[97] A recently completed trial looked at 488 ICU patients with sepsis and AKI and randomized them into an early RRT or a delayed start after developing an indication. Ninety-day mortality was similar in both groups.[98] A recent meta-analysis and systematic review showed that early initiation of RRT compared with late was not associated with improved mortality (RR 0.98, 95% CI 0.85–1.13).[99]

Recommendations 39-40

When prescribing RRT, we recommend choosing the modality based on availability, expertise, resources, and associated cost (best practice statement).

For adults with COVID-19 and shock requiring RRT, we suggest using continuous renal replacement therapy (CRRT) as opposed to intermittent hemodialysis (IHD) (weak recommendation, expert opinion).

Rationale

Patients with AKI can be treated with different RRT modalities such as intermittent hemodialysis (IHD), CRRT, and “Hybrid” modalities like sustained low-efficiency dialysis (SLED). Evidence does not support one modality over the other. A meta-analysis comparing clinical outcomes of critically ill patients with AKI treated with IHD, CRRT, and SLED found no significant difference in hospital mortality or dialysis dependence.[100] Despite lack of high quality evidence, recent guidelines prefer using CRRT for hemodynamically unstable patients and, in COVID-19, critically ill patients with AKI.[101]

Recommendation 41

For COVID-19 patients on CRRT, we suggest using an effluent flow rate of 20 to 25 ml/kg/hour over a higher flow rate (weak recommendation).

Rationale

Multiple RCTs addressed the question of the CRRT dose. A study has randomized patients on continuous veno-venous hemodiafiltration (CVVHDF) to either an effluent dose of 25 ml/kg/hour or to a 40 ml/kg/hour.[102] Another RCT randomized patients on CVVHDF to an effluent dose of 20 ml/kg/hour or to 35 ml/kg/hour.[103] In both studies, intensive therapy did not improve survival or recovery of kidney function. A recent systematic review and meta-analysis found no significant difference in the 90-day mortality between high-dose and low-dose hemofiltration (OR 0.90, 95% CI 0.73, 1.11).[104] Current guidelines recommend a minimal effluent of more than 20 to 25 ml/kg/hour to be provided. In a context of pandemic and increased disease transmission to healthcare workers, minimizing patient contact is important, therefore, a lower dialysis dose adds the extra advantage of a lesser need to interact with the CRRT machine.

Recommendations 42-43

When using CRRT for patients with COVID-19 (without coagulopathy or contraindications to anticoagulation), we recommend using anticoagulation over no anticoagulation (strong recommendation).

For anticoagulation in CRRT, we suggest using either regional citrate anticoagulation or unfractionated heparin, depending on each institution's own practice and procedure (weak recommendation).

Rationale

There are several trials comparing different anticoagulants to maximize the lifespan of the CRRT circuit. In a multicenter RCT, 212 patients with a total of 857 circuits were randomized to citrate versus heparin anticoagulation. The median lifespan of the first filter was significantly longer in the citrate group (39.2 hours; 95% CI, 32.1 to 48.0), compared with heparin anticoagulation (22.8 hours; 95% CI, 13.3 to 48.0).[105] A subsequent meta-analysis of 14 RCTs found that regional citrate, compared to unfractionated heparin, prolongs the CRRT circuit lifespan by a mean 8.2 hours (IQR, 3.9–12.5).[106]

Veno-venous extracorporeal membrane oxygenation Problem: Extra-corporeal life support (ECLS) is used in mechanically ventilated patients with refractory hypoxemic respiratory failure where conventional measures and other rescue therapies and interventions fail to maintain adequate oxygenation. In experienced centers, the use of veno-venous extracorporeal membrane oxygenation (VV ECMO) may improve the outcomes of those patients.[107] There are no RCTs on the use of VV ECMO in COVID-19 patients. A recent retrospective observational study from Italy reported that 1% of the 1591 COVID-19 patients in the ICU received VV ECMO, but the outcomes of these patients were not reported.[75]

Recommendation 44

In mechanically ventilated adults with COVID-19 and refractory hypoxemia, despite optimizing ventilation, using rescue therapies, and proning, we suggest using VV ECMO if available, or referring the patient to an ECMO center (weak recommendation).

Rationale

The WHO interim guidelines for the management of suspected COVID-19 recommend VV ECMO for eligible patients with COVID-19 and ARDS in experienced centers.[74] A recent systematic review and meta-analysis included two RCTs that evaluated the use of VV ECMO in non-COVID patients with severe ARDS, and three observational studies. The use of ECMO was associated with lower risk of death (RR 0.73; 95% CI 0.58, 0.92).[71] During MERS-COV outbreak in Saudi Arabia, a before-after cohort study showed lower mortality with VV ECMO in patients with severe ARDS and MERS (65% versus 100%; P = 0.02).[108] Another matched pair analyses of 75 H1N1 patients who developed sever hypoxemic respiratory failure showed survival benefits when patients were transferred to experienced ECMO centers (52.5% versus 23.7%).[109] In the context of a pandemic, resources are valuable and healthcare systems are under continuous strain; therefore, the use of VV ECMO should only be reserved for patients who need it and are likely to survive or benefit if offered ECMO.

Timing for tracheostomy

Problem: Although trans-laryngeal intubation is the first choice for airway access in patients requiring invasive mechanical ventilation, prolonged endotracheal intubation can be associated with complications.[110] Therefore, tracheostomy is often considered for patients who are unable to wean from invasive mechanical ventilation or when the need for invasive mechanical ventilation is expected to be prolonged.

Recommendation 45

For intubated adults with COVID-19 who are ventilated for >10 days and are unable to wean from invasive mechanical ventilation, we suggest deferring tracheostomy until SARS CoV-2 testing is negative (weak recommendation).

Rationale

The appropriate timing for tracheostomy for patients who are unable to wean from invasive mechanical ventilation is unclear.[111],[112] There are no studies on the proper timing of tracheostomy for patients with COVID 19. However, several studies have evaluated early and late timing periods for tracheostomy in the ICU population.[113],[114],[115]

In an RCT of 1032 adult patients, tracheostomy within 4 days of ICU admission was not associated with an improvement in 30-day mortality compared with tracheostomy after 10 days.[116] Interestingly, only 45% of the patients assigned to late tracheostomy received a tracheostomy, suggesting that the ability of clinicians to predict which patients require extended ventilatory support is limited.[116]

A systematic review and meta-analysis of 9 studies, including 2040 patients, revealed that tracheostomy within 10 days of intubation did not significantly improve mortality compared with tracheostomy after 10 days of intubation (9 RCTs; RR = 0.88; 95% CI = 0.76-1.00; P = 0.06).[117] None of the other clinical outcomes were different, except for a reduction in the duration of sedation in the early tracheostomy group (3 RCTs; MD -5.99 days; 95% CI = -11.41 to -0.57 days). Another systematic review and meta-analysis of 14 RCTs (2406 patients) reached a similar conclusion.[118] Our recommendation for late tracheostomy places a high value on avoiding unnecessary procedures and high-risk exposure. Also, early tracheostomy is of unproven benefit and may prolong invasive ventilation in patients with COVID-19 that may otherwise be extubated.

Practical considerations

Tracheostomy is considered an AGP. Appropriate infection control measures should be taken during the procedure itself, during suctioning and care provision.


  Managerial Strategies Top


Preparation of intensive care for expected pandemic

Pandemics are usually associated with a limited resource because of the large number of admitted patients.[119] This should encourage heath care policy makers to start preparations early when the WHO declares phase IV. One of those measures is minimizing admissions and elective surgeries while increasing intensive care (ICU) beds by transferring non COVID-19 patients to other units.[119] At the level of hospital and intensive care, it is important to redesign the hospital and create special units with negative pressure rooms to accommodate those patients while maintaining the safety of non COVID-19 patients, protecting them from getting exposed to infectious disease.[120] Addressing the length of stay for existing ICU patients and goals-of-care discussion for patients with overall very poor prognosis helps free some ICU beds and.[120] We recommend using a published model that predict the course of pandemic to help in evaluating the capacity of intensive care unit (ICU) requirements over time, looking into alternative sites to provide ICU-l care within the hospital, such as operating rooms.[121],[122] These steps and planning were highlighted in recent recommendations to US hospitals to prepare for the COVID 19 pandemic.[122]

Recommendations 46–47

We suggest grouping all critically ill COVID-19 patients in one unit (weak recommendation).

We suggest dedicating ICUs with negative pressure rooms for confirmed and suspected COVID-19 cases (weak recommendation).

Rationale

Despite all preparations, the course of a pandemic can quickly get out of control and the demand often exceeds the current capacity of critical care and hospitals.[123] For these reasons, policy-makers should be prepared at the national level to deal with a pandemic and direct special attention toward intensive care and areas with limited resources.[123],[124]

Strategies for ICU surge capacity

During a pandemic, hospitals often make fundamental changes and reallocate resources to accommodate a large number of critically ill patients.[124] Planning should start before a disaster to be prepared and respond to surges at any time.[125] Surge capacity in mass critical care refers to the ICU's ability to rapidly expand and accommodate as many patients as possible in a disaster.[125] There are four necessary components of surge capacity: staff, supplies, space, and structure. In a pandemic, ICUs will certainly receive the sickest COVID-19 patients and will be directly affected by availability of resources and resource allocation.[125] Planned surge and crisis preparedness expose critically ill patients to high workload staffing ratios, which is associated with reduced odds of survival.[126]

Recommendation 48

When planning for critical care surge capacity:

We suggest adopting a phased and tiered response based on the worst-case scenarios of the COVID-19 pandemic (weak recommendation).

We suggest transferring non-acutely ill chronically ventilated patients to low-acuity ICUs (weak recommendation).

We suggest training non-ICU healthcare workers to manage critical patients outside of ICUs with supervision by ICU specialized healthcare workers (weak recommendation).

Rationale

As the demand for critical care grows, the gap between demand and supply of intensivists widens.[126] To handle dramatic increases in the demand for essential services, hospitals must develop a mass-casualty plan with clear and practical steps.[127] The severity of SARS-CoV-2 pneumonia poses a great strain on critical care resources.[51] Surge plans should be at a system level in order to provide the required care for a large cohort of patients.[125]

During a surge, the paradigm shifts away from universal and comprehensive care to providing good care on a population rather than an individual level, implementing strict ICU admission criteria, and utilizing a dynamic surge protocol.[125] The level of response should be based on the projected number of critically ill patients, taking into account the availability of essential resources.[125] In the context of a pandemic, all health care sectors and governmental entities should partner to maximize capacity and offer regional consistency of care.

Tele-critical care is another commonly used method to address the shortage of critical care providers that may improve care and reduce costs.[128],[129] A phased-response, based on the impact on the capacity of the ICU to meet daily operational needs, should be implemented.


  Patient Psychology and Staff Management Top


Psychological support for staff and patients is crucial during an epidemic. The fear of having and transmitting serious illness and being stigmatized by others can have a significant psychological impact.[130] The WHO recommends healthcare providers take care of their psychological well-being as well as their physical health.[130] During an epidemic, healthcare workers are at risk of developing severe anxiety, depression, delirium, and psychosis.[130],[131] Mental health services and psychological support during and after infectious diseases should not be ignored, and they are crucial for effective rehabilitation.[132]

Recommendation 49

We suggest creating a mental health support system for patients and healthcare workers (weak recommendation).

Rationale

During the SARS epidemic, healthcare providers were prone to develop high levels of anxiety and depression.[131] The prevalence of posttraumatic stress disorder (PTSD) after a traumatic event in the ICU is between 14 to 59%. Approximately a third of SARS-survivors developed symptoms of anxiety or depression or both within 1 month of discharge.[130] During the 2003 epidemic, one study reported on two groups of healthcare workers. The first group included high-risk healthcare workers, who practiced respiratory medicine. The second group included low-risk healthcare workers. At one year, the high-risk group's Perceived Stress Scale (PSS-10) score differed between the two groups (P < 0.05). The study concluded that healthcare workers who practiced respiratory medicine were at higher risk of depression, anxiety, and PTSD [185]. Applying the mental health support system may help to assess staff and patients' needs and support them through the pandemic and after, by identifying the stressors and normalizing them through a guideline.

Possible approaches to providing psychological support may include: 1) providing insurance, accommodation, and compensation for frontline healthcare workers and administration, 2) providing an ICU psychologist for patients, 3) a confidential mental health support phone line for staff and patients, 4) post-discharge follow up, 5) outpatient psychiatrists and clinical psychologists to support healthcare workers, patients and their families.

Ethical Framework for Critically Ill Patients

During pandemics the main objectives of medical care is to minimize mortality and morbidity.[133] But there are variables that should be taken into consideration: such as that human resources constraints and treatment options will change the nature of the ethical decisions that will be made, and this has to be adjusted continuously.[133],[134] According to assessment tools for the magnitude of the pandemic and surge capacity resilience, preset triggers with defined surge capacity levels under vigilant evaluation are crucial for justifying altered standards of care in pandemics.[135] A higher commanding center approval is essential to call for and end an altered care ethics.[136]

Recommendations 50-51

We recommend building ethical choices in the ICU, based on the utility and efficiency of interventions, fairness, and equity of resource distribution (weak recommendation).

We suggest using a scoring system such as Biddison's scoring system[134] or any other acceptable rapid prognostication score, to prioritize access to scarce life-support interventions in the ICU during failure of surge plans or extreme phases of surge (weak recommendation).

Rationale

It is very difficult to develop well-structured studies in disasters and pandemics addressing ethical considerations when demand on health-care resources overcomes availability of staff, space or utilities for patients.[134] The ethical principles used in normal situations are applicable in pandemics until the point that a health-care facility has exhausted all its surge capacity resources, leading to the likelihood of death or severe injury to patients either in the health-care facility, or coming to it. Proposed medical criteria for the patients that will benefit the most has been used, such as SOFA scoring[134] and the Clinical Frailty Scale,[137] honoring the “Save the greatest number of people” ethical criteria that directs us to give priority in allocation decisions to the category or categories of people that will result in the most lives saved. This usually involves allocating resources on the basis of a patient's prognosis and the amount of resources and/or personnel that will be required to sustain life.

Special Considerations for Pediatric Patients

Although COVID-19 primarily causes critical illness in adults, there have been some reports of critically ill children. All infection control recommendations are applicable to both adult and pediatric ICUs.

There are no trials on the use of chloroquine and hydroxychloroquine in critically -ill children with COVID-19 in the pediatric ICU. Therefore, its routine use should be avoided and decisions regarding its use should be individualized. Similarly, there are no trials on the use of antiviral agents in pediatric patients with severe COVID-19, therefore, we make no recommendations on the use of these agents in the pediatric population.

Illness among children appears to be mild, commonly presenting with cough, nasal congestion, rhinorrhea, sore throat, and gastrointestinal symptoms.[138],[139] As per the WHO guidance, conventional oxygen therapy should be administered only for hypoxic patients.[74] If children are hypoxic despite conventional oxygen therapy, then HFNC can be tried with close monitoring for any sign of increased work of breathing and respiratory distress. HFNC should not routinely be used as a method of reducing the work of breathing in children who are otherwise saturating adequately. A literature review of the 26 original clinical studies including children on HFNC beyond the new-born period concluded that “until more evidence from randomized studies is available, HFNC may be used as a supplementary form of respiratory support in children, but with a critical approach regarding effect and safety, particularly when operated outside of a pediatric intensive care unit”.[140]

When ventilating pediatric patients with COVID-19 and pediatric acute respiratory distress syndrome (PARDS), the panel issued the following recommendations:

We suggest: using volume or pressure control modes; targeting tidal volume of 6 ml/kg (4-8 ml/kg) of PBW; and maintaining plateau pressure <28 cm H2O (weak recommendation). If plateau pressure is >28 cm H2O, decrease tidal volume by 1 ml/kg increments to minimum of 4 ml/kg PBW. Tidal volume of (3 ml/kg ideal body weight) can be considered for patients with poor respiratory system compliance or may accept plateau pressure of up to 30 cm H2O.

We suggest setting the PEEP at 5 cm H2O and using a higher PEEP only in patients with clinical features of severe ARDS (weak recommendation).

Remarks: when applying a high PEEP strategy, patients should be monitored for signs of barotrauma, oxygen delivery, respiratory system compliance, and hemodynamics.

We suggest using High-Frequency Oscillatory Ventilation (HFOV) in severe pediatric PARDS and refractory hypoxemia (weak recommendation, expert opinion).

The above recommendations were developed based on the recommendations of the Pediatric Acute Lung Injury Consensus Conference.[141]

The recommendation on iNO use also applies to children with COVID-19. Prone position is usually used early and sometimes for a longer duration in paediatric patients with ARDS.

For pediatric COVID-19 patients who develop septic shock, readers can refer to the children surviving sepsis campaign guidelines.[142],[143] In addition, the children surviving sepsis campaign suggest using VV ECMO in sever PARDS and refractory hypoxia.

All recommendations on the preparation of intensive care for an expected pandemic, ICU surge capacity, psychological support, ethical framework, and training are also applicable to the pediatric context.

Financial support and sponsorship

The project was fully funded by the Saudi Critical Care Society.

Conflict of interest

All members complete the WHO COI forms. None declared any conflict of interest related to this guideline.


  Guideline Supplement Top


Supplement A: Respiratory Care Equipment and Supplies:

  • We suggest that the respiratory care team should quantify their current stock of respiratory care equipment and supplies with well-planned emergency chain of supply in case of increased demand. We recommend the following to be considered:
  • Identify manufacturers and suppliers capable of providing needed respiratory care equipment and supplies through the institutional emergency chain of supply.
  • Older but functional ventilators not presently in use, which can be operationalized by biomedical departments to be included in the equipment counts. Those ventilators should be checked and maintained to be ready for use at early stages of the pandemic.
  • The list of ventilators should include availability of built-in air compressor and intended use.
  • Bronchoscopy tower with its supplies and consumables should be maintained for use on COVID-19 patients.
  • Intubation kits/boxes should be prepared for emergency use inside patients' rooms, including difficult intubation equipment.
  • Other respiratory care consumables and disposables should be assessed for potential increased need and demand.


Staffing Handling COVID-19 Patients:

  • Respiratory care staffing plans should be developed and ready to implement when need during pandemic. Workforce shortage, additional workload, staff moral and wellbeing should be considered. In this regard we suggest the following:
  • Identify workforce capacity and assess additional workload consideration for pandemic specific requirements.


Screen respiratory care staff for:

  • Level of experience with critical ill patients
  • Level of experience with respiratory care equipment and modalities
  • Critical thinking and reasoning


Medical conditions and age, staff with comorbidities such as asthma, COPD, DM, heart diseases and older staff should not enter COVID-19 care areas and should be assigned for non-clinical supporting duties.

Develop respiratory care team for COVID-19 patients (COVID-19 Team), this team should only work in areas receiving COVID-19 patient and should be separated from other respiratory care staff (Clean Team) caring for other patients. A dedicated Rota to segregate “clean teams” from “COVID-19 teams”.

Develop backup staff list to increase staffing capacity when needed.

When unexperienced staff are needed, they should work under close supervision by more experienced staff or assigned to routine care, documentation or re-supply, storage and inventory of equipment.

Other considerations to address

  • Simplifying of administrative processes which limit staffing flexibility and recruitment.
  • Debriefing and psychological support; staff morale may be adversely affected due to the increased workload, anxiety over personal safety and the health of family members.
  • The cancellation of pre-arranged annual leave during a pandemic should only be considered if necessary.
  • Maintaining staff morale is imperative.
  • Other staff supporting measures
  • Clean scrubs available to change into before each shift
  • Showering facilities at the end of each shift.
  • Provision of meals and drinks for frontline staff
  • Medical support and screening
  • Ventilatory Support General Considerations
  • The American Association of Respiratory Care (AARC) recommend using the highest technology equipment for the most severely ill patients.
  • Distinct ventilators used for COVID-19 patients from other ventilators for use on other patients.
  • Identify ventilators with built-in air compressors, if available, should be placed on standby and only used when clinical areas lack compressed medical air outlets or when all other available ventilators are used.
  • Transport and home ventilators can be used for transitional periods with expiratory HEPA/antiviral filters. Due to their lack of some monitoring features, should be triaged to less critical patients.
  • Do not to repurpose CPAP machines designed for obstructive sleep apnea to be used as ventilators.
  • Bilevel/NIV machines can be used for invasive mechanical ventilation, in fact some, but not all, come with built-in invasive ventilation option. When needed the following concerns should be addressed:


    • Infection prevention and control measures should be taken due aerosol generation from the leak port, commercially available filters that can be fitted to the leak port.
    • The AARC recommend active humidification when a bilevel ventilator is used for invasive respiratory support. Alternatively, a heat-and-moister exchanger (HME) can be used. When an HME-filter is used, there is no need for a filter on the leak port.
    • In bilevel ventilators the tidal volume depends on the driving pressure (IPAP – EPAP). This difference is the level of pressure support or pressure control. The level of EPAP (PEEP) can be increased as needed to support hypoxemic respiratory failure, but it is important to remember that IPAP must be increased when EPAP is increased (and vice versa).
    • For some bilevel ventilators the oxygen (FiO2) can be set directly, others the oxygen is titrated into the system follow the manufacturer instructions (16).
    • For safety, alarms should be set appropriately when any bilevel ventilator is used.
    • The use of bilevel ventilators for invasive support should be triaged ideally, they can be used for patients who do not have COVID-19, if needed, thus freeing critical care ventilators for patients with COVID-19 hypoxemic respiratory failure (16).






     
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