WHO REGIONAL OFFICE FOR AFRICA COVID-19 RAPID POLICY BRIEF SERIES

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WHO REGIONAL OFFICE FOR AFRICA COVID-19 RAPID POLICY BRIEF SERIES

SERIES 2: COVID-19 CASE MANAGEMENT - INTERVENTION MEASURES

NUMBER 002-02: Management of Severe/Critical cases of COVID-19 with non-invasive or mechanical ventilation

Based on information as at 1^st June 2020

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Number 002-02: Management of Severe/Critical cases of COVID-19 with non-invasive or mechanical ventilation

WHO/AF/ARD/DAK/07/2020

© WHO Regional Office for Africa 2020

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RAPID POLICY BRIEF

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NUMBER: 002-02

RESEARCH DOMAIN: COVID-19 Case management - intervention measures

TITLE: Management of Severe/Critical cases of COVID-19 with non-invasive or mechanicalventilation

RAPID POLICY BRIEF NUMBER: 002-02

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RAPID POLICY BRIEF NUMBER: 002-02

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RESEARCH DOMAIN: COVID-19 Case management - intervention measures

3 TITLE: Management of Severe/Critical cases of COVID-19 with non-invasive or mechanical ventilation

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DATE OF PUBLICATION: 08/06/2020

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BACKGROUND

The COVID-19 pandemic has been unprecedented in the effects that it has had on the world today.

Over 6,799,713 cases have been recorded globally with about 131, 324 of those cases recorded in the WHO African Region [1].

The pandemic has brought to the fore, an exponential increase in the demand of highly specialized intensive care interventions, as even in mildly symptomatic patients, it is characterized by oxygen desaturation[2]. The use of invasive and non-invasive ventilation to provide respiratory support to patients with severe/critical disease who often suffer acute hypoxemic respiratory failure has been commonplace across many countries where the incidence of severe and critical disease is high [3].

This policy brief seeks to summarize the existing evidence on the use of ventilation in management of severe and critical cases of COVID-19.

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SEARCH STRATEGY / RESEARCH METHODS

Three databases were searched: PUBMED, WHO COVID-19 and IRIS (WHO Institutional Repository for Information Sharing) employing search terms:

• ((((ventilators) OR (mechanical ventilation)) AND (covid-19)) AND (management)) AND (critical)

• ((case management) AND (ventilator)) AND (covid-19)

We further identified relevant papers from the reference lists of key publications. We reviewed papers published from 1st December 2019 to 1 June 2020. The initial search yielded 103 papers, 88 were excluded based on the review of titles and abstracts as these did not focus on our research area as well as the unavailability of the full text. Sixteen publications were retained, and full texts were reviewed to produce this Rapid Policy Brief (RPB). No publication related to the African Region was identified.

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SUMMARY OF GLOBALLY PUBLISHED LITERATURE RELATED TO THE SUBJECT

Severe and critical infection of SARS-CoV-2 is characterized by Acute Respiratory Distress Syndrome. The use of ventilators (non-invasive and mechanical), to deliver oxygen in cases of severe and critical COVID-19 has been championed, as the mainstay of treatment for severe and critical cases of COVID-19 though its use remains controversial. Thus far, among the 5% of COVID-19 patients who require treatment in an ICU [4], about 88% of them have been placed on mechanical ventilation due to the occurrence of severe hypoxemia[5] that progresses into acute hypoxemic respiratory failure (ARDS).

Current evidence suggests that once ARDS develops in COVID-19 patients, the prognosis is far worse than ARDS due to other causes, with a fatality rate greater even than ARDS due to sudden acute respiratory syndrome (SARS) or Middle East Respiratory Syndrome (MERS) [2].

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As a result, evidence supporting the use of non-invasive positive pressure ventilation (NIPPV) and mechanical ventilation and its effectiveness in improving mortality outcomes among severe and critical cases of COVID-19 remains inconclusive and mixed.

The risks associated with invasive ventilation and intubation of severe/critical cases of COVID-19 who suffer from ARDS include the risk of having minimal to no respiratory reserve, and an exhaustion of their physiological compensatory mechanisms for breathing. Second, due to strict infection control and the urgency of intubation, a careful airway evaluation is frequently not possible. Third, the personal protective equipment mandated, complexifies the performance of invasive mechanical ventilation, which may easily compromise the intubation process [6,7].

Emerging recommendations against the use of ventilation (invasive and non-invasive) are driven by two factors- the generation of virus aerosols (associated with risk of nosocomial infection among health personnel) [2,6,8,9] and the risk of lung injury and organ failure which leads to higher outcomes of mortality in severe and critical cases [6,8,10,11].

This observation of nosocomial infection was learned from the 2003 SARS outbreak where, a systematic review showed that compared with healthcare workers who did not perform aerosol -generating procedures, those who performed tracheal intubation had an increased risk of contracting the 2003 SARS OR(95%CI) (odds ratio, 6.6 (2.3, 18.9)), as were those who performed non-invasive ventilation (odds ratio, 3.1 (1.4, 6.8)), tracheotomy (odds ratio, 4.2 (1.5, 11.5)), and manual ventilation before intubation (odds ratio, 2.8 (1.3, 6.4)) [12].

With respect to lung injury and adverse outcomes, a case series by Wali et. al which documents the occurrence of pneumomediastinum and surgical emphysema in severe and critical COVID-19 patients (with ARDS) who received mechanical ventilation, suggests that the intervention, causes increased risk of alveolar damage and tracheobronchial injury as a result of the use of larger bore tracheal tubes and higher ventilation pressures, which leads to the development pneumomediastinum [13].

Receipt of ventilation, along with chronic pre-existing conditions, older age, lower body mass index and vasopressors have been reported to be significantly associated with the mortality rates among adults with critical cases of COVID-19 [10]. Evidence from two studies have shown high mortality outcomes in patients on ventilation for COVID-19 and related coronavirus associated diseases. Among 191 patients who were followed in a study by Zhou et al., in-hospital mortality was very high among the 33 patients requiring invasive mechanical ventilation, of whom 32 (97%) died [14]. Similarly, a retrospective case series from Yang et al. reported mortality of 62% among critically ill patients with COVID-19 and 81% (31/37 patients) among those requiring mechanical ventilation [15]. The study from Yang et al. also reported 72% of COVID- 19 patients given NIPPV died. Outcomes from use of non-invasive ventilation in treating acute hypoxemic respiratory failure remain mixed, with some studies reporting up to 85% failure and others observing an increased ICU mortality from NIV failure compared to invasive mechanical ventilation[16].

Conversely, another study suggests that, timely, but not pre-mature ventilation support may be superior to high-flow oxygen therapy in boosting transpulmonary pressure, opening collapsed alveoli, improving oxygenation, decreasing oxygen debt, and offering a better chance for the lungs to heal. However, the study documents the risk of procedure-related mishaps including lung injury and the risk of cross-infection of healthcare providers, which they emphasize should influence the consideration of this interv ention.

Despite mixed evidence of the success of ventilation, documentation of the adverse outcomes of pre- mature and early intubation suggest that use of ventilation for care of for treatment of ARDS patients, can

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only be effective, and unlikely to cause significant harm, if timing of intubation procedure in the course of infection, is appropriate; ensuring that it is used more as a proactive intervention vis à vis a salvaging mechanism [2,6].

The importance of this timeliness, Meng et al. report, reduces the risk of adverse outcomes that emergency intubation carries, and reduces the rate of mortality caused by “silent hypoxemia” which is the presence of increasing oxygen debt in asymptomatic patients. They attribute adversely delayed intubation to the results of a recent report that showed that, among the 22 ICU patients who were intubated, 19 (86%) of them died. The study is however unable to ascertain if early intervention would h ave altered these observed trends of mortality [6].

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SUMMARY OF AFRICA-SPECIFIC LITERATURE ON THE SUBJECT

None

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POLICY FINDINGS

Policy direction on the use of ventilation (invasive and non-invasive) across various patient populations and contexts remains mixed. Given the varying perspectives of care providers on the use of ventilators in management of severe/critical infection of SARS-CoV-2, a case-by case approach is proposed in determining its use [8].

Initial guidance on lung-protective, low tidal volume ventilation approaches for patients who suffer from ARDS emphasize [5,6,8] :

(1) Tidal volume less than or equal to 6ml/ kg predicted body weight- The precise tidal volume for an individual patient should be adjusted according to the patient’s plateau pressure;

(2) A respiratory rate less than or equal to 35 breaths/min;

(3) A plateau airway pressure less than or equal to 30 cm H2O; and (4) a positive end-expiratory pressure (PEEP) greater than or equal to 5 cm H2O. The tidal volume can be started at 8ml/kg and then lowered with an ultimate goal of 6ml/kg.

(4) Incremental combinations of fraction of inspired oxygen FiO2 and PEEP to achieve PaO2 of 5–80 mm Hg or SpO2 88%–95%. When patient is placed on high PEEP, the fraction of inspired oxygen (FiO2) should be reduced quickly once they are clinically stable. PEEP down-titration needs to be very slow, as there is a high risk of derecruitment in these patients

(5) Where NIPPV is opted for, placement in prone position vis à vis supine positioning, to optimize respiratory support [17].

To reduce the risk of nosocomial infection from these aerosol generating interventions, caregivers should keep the following in mind:

(1) Minimize unnecessary disconnection of the endotracheal tube to avoid unnecessary release of the virus aerosols into the environment.

(2) Adhere to personal protective equipment protocols and keep ventilator fittings tight.

(3) Ensure that ventilator and intravenous line monitors are placed outside the room to allow frequent ventilator adjustments while simultaneously decreasing the risk of exposure.

(4) Provide other general supportive ICU care, and enforce strict IPC measures.

Given the unclear outcomes and mixed reviews on the effectiveness of this intervention, increasing procurement of high-cost ventilators, in poor and resource constrained settings, where the opportunity cost is high, may not be prioritized. Rather, low-cost measures to reduce the speed and spread of the

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virus, including containment measures and antiviral treatment which could lead to better clinical outcomes in all cases of infection, beyond severe and critical illness[2].

Although the outcomes of ventilator use remain mixed and inconclusive, it is important to note that ventilator use during this pandemic has largely been limited to severe/critical cases, where chronic comorbidities are high and contribute to adverse outcomes or mortality. WHO-AFRO therefore

recommends a case-by-case approach to management of severe/critical COVID-19, adhering to current protocol for lung-protective ventilation management.

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ONGOING RESEARCH IN THE AFRICAN REGION

None identified

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AFRO RECOMMENDATIONS FOR FURTHER RESEARCH

• WHO AFRO encourages researchers to scientifically document case reports from Intensive Care Units in tertiary hospitals across the Region, where ventilation has been used in the treatment of severe/critical COVID-19. Emphasis should be placed on mortality outcomes, and documentation of observed proximal complications in ARDS (including organ failures, septic shock, lung injury etc.)

• Researchers are encouraged to accelerate surveillance of outcomes (both positive and adverse reactions) of ventilation in the Region, across various patient populations and contexts, to

support in the concretization of evidence on outcomes of ventilator use among severe and critical cases of COVID-19

• Research using prospective randomized control trials into more low-risk interventions, where there exists emerging evidence of reduced mortality amongst critically ill patients are

encouraged. Of particular importance currently, is evidence on the use of prone positioning in the optimization of respiratory support

• Researchers are encouraged to investigate the effectiveness of low-cost containment interventions that have been used thus far in treatment for severe/critical disease, as an alternative where ventilation was unavailable.

• Development of training manuals, contextualized to the Africa Region, to urgently scale -up capacity among the health workforce in ventilator management of severe/critical cases of COVID- 19, and increase the availability of highly trained staff who can apply the ARDSNet

recommendations for ventilator management[18], where the intervention is critically needed.

• To this end, WHO AFRO invites all COVID-19 response committees to make optimal use of their scientific committees and extend collaboration to academic institutions and other related partners to be able and undertake robust scientific studies on the topic

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REFERENCES

1 Coronavirus disease (COVID-19) Situation Report – 139. World Health Organization

https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200607-covid-19-sitrep- 139.pdf?sfvrsn=79dc6d08_2

2 Zareifopoulos N, Lagadinou M, Karela A, et al. Management of COVID-19: the risks associated with treatment are clear, but the benefits remain uncertain. Monaldi Archives for Chest Disease 2020;90.

doi:10.4081/monaldi.2020.1342

3 Grasselli G, Zangrillo A, Zanella A, et al. Baseline Characteristics and Outcomes of 1591 Patients Infected With SARS-CoV-2 Admitted to ICUs of the Lombardy Region, Italy. JAMA 2020;323:1574.

doi:10.1001/jama.2020.5394

4 Bein B, Bachmann M, Huggett S, et al. [SARS CoV-2/COVID-19: Evidence-Based Recommendation on Diagnosis and Therapy]. Anasthesiol Intensivmed Notfallmed Schmerzther 2020;55:257–65. doi:10.1055/a-1146-8674 5 Vashisht R, Duggal A. Respiratory failure in patients infected with SARS-CoV-2. Cleve Clin J Med Published

Online First: 14 May 2020. doi:10.3949/ccjm.87a.ccc025

6 Meng L, Qiu H, Wan L, et al. Intubation and Ventilation amid the COVID-19 Outbreak: Wuhan’s Experience.

Anesthesiology 2020;132:1317–32. doi:10.1097/ALN.0000000000003296

7 Yu Y, Xu D, Fu S, et al. Patients with COVID-19 in 19 ICUs in Wuhan, China: a cross -sectional study. Crit Care 2020;24:219. doi:10.1186/s13054-020-02939-x

8 Wilcox SR. Management of respiratory failure due to covid-19. BMJ 2020;369. doi:10.1136/bmj.m1786 9 Barker J, Oyefeso O, Koeckerling D, et al. COVID-19: community CPAP and NIV should be stopped unless

medically necessary to support life. Thorax 2020;75:367. doi:10.1136/thoraxjnl-2020-214890

10 Auld SC, Caridi-Scheible M, Blum JM, et al. ICU and Ventilator Mortality Among Critically Ill Adults With Coronavirus Disease 2019. Critical Care Medicine 2020;Online First. doi:10.1097/CCM.0000000000004457 11 Hirsch JS, Ng JH, Ross DW, et al. Acute kidney injury in patients hospitalized with COVID-19. Kidney International

2020;0. doi:10.1016/j.kint.2020.05.006

12 Tran K, Cimon K, Severn M, et al. Aerosol Generating Procedures and Risk of Transmission of Acute Respiratory Infections to Healthcare Workers: A Systematic Review. PLoS One 2012;7. doi:10.1371/journal.pone.0035797 13 Wali A, Rizzo V, Bille A, et al. Pneumomediastinum following intubation in COVID-19 patients: a case series.

Anaesthesia Published Online First: 6 May 2020. doi:10.1111/anae.15113

14 Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. The Lancet 2020;395:1054–62. doi:10.1016/S0140-6736(20)30566- 3

15 Yang X, Yu Y, Xu J, et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. The Lancet Respiratory Medicine 2020;8:475–81. doi:10.1016/S2213-2600(20)30079-5

16 Arabi YM, Fowler R, Hayden FG. Critical care management of adults with community-acquired severe respiratory viral infection. Intensive Care Med 2020;46:315–28. doi:10.1007/s00134-020-05943-5

17 Sztajnbok J, Maselli-Schoueri JH, Cunha de Resende Brasil LM, et al. Prone positioning to improve oxygenation and relieve respiratory symptoms in awake, spontaneously breathing non-intubated patients with COVID-19 pneumonia. Respir Med Case Rep 2020;30:101096. doi :10.1016/j.rmcr.2020.101096

18 NIH NHLBI ARDS Clinical Network Mechanical Ventilation Protocol Summary. ARDSNET http://www.ardsnet.org/files/ventilator_protocol_2008-07.pdf

BRIEF PRODUCED BY: Regina Titi-Ofei, Humphrey Karamagi, Kwami Dadji, Aminata Binetou-Wahebine Seydi, Jean Claude Nshimirimana, Pascal Mouhouelo, Juliet Nabyonga, Hillary Kipruto, James Asamani, John Adabie Appiah, Jean-Baptiste Nikiema, Prosper Tumusiime, and Felicitas Zawaira.