an overview of ards in the icu - university of kwazulu-natal

02 October 2020 No. 15

An overview of ARDS in the ICU

K Jadhunandan

Moderator: S Verwey

School of Clinical Medicine Discipline of Anaesthesiology and Critical Care

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CONTENTS INTRODUCTION ........................................................................................................................ 3

Epidemiology ............................................................................................................................. 3 Pathophysiology ........................................................................................................................ 3 Risk Factors ............................................................................................................................... 5

Definition .................................................................................................................................... 6 Issues with the Berlin definition ............................................................................................ 6

Differential Diagnosis ................................................................................................................ 7 Diagnostic Evaluation................................................................................................................ 7 Imaging findings in ARDS ......................................................................................................... 8 TREATMENT ............................................................................................................................. 10

VENTILATORY ...................................................................................................................... 10 VENTILATORY ADJUNCTS .................................................................................................. 13 NON-VENTILATORY STRATEGIES ..................................................................................... 14

COVID-19 PNEUMONIA ............................................................................................................ 16

CONCLUSION ........................................................................................................................... 19 REFERENCES .......................................................................................................................... 20

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INTRODUCTION 1,2,3

Acute Respiratory Distress Syndrome (ARDS) is an inflammatory lung condition that may occur following local or systemic insult by a variety of conditions including severe pneumonia, aspiration, sepsis and trauma. ARDS is characterized by intractable hypoxaemia due to increased permeability of pulmonary capillaries and pulmonary oedema. It was first described by Ashbaugh in 1967 as an “acute onset of tachypnoea, hypoxaemia and loss of compliance after a variety of stimuli”. ARDS is commonly seen in the ICU population. However, after over 50 years since its first description, mortality still remains high upto 45%. Epidemiology 4

A substantial amount of our knowledge regarding the epidemiology of ARDS has been acquired from the LUNG SAFE study, an international, multicentre, prospective study of over 29 000 patients from 459 ICUs in 50 countries. The LUNG SAFE study revealed that 10.4% of all ICU admissions fulfilled ARDS criteria, as classified by the Berlin definition. It also found that ARDS criteria were met in 23% of patients requiring mechanical ventilation. ARDS was mild in 30% of cases, moderate in 46.6%and severe in 23.4% of cases. Hospital mortality ranged from 34.9% for patients with mild ARDS, to 46.1% for patients with severe ARDS. Pathophysiology 3,5,6

ARDS is characterized by an acute inflammatory response following pulmonary or extrapulmonary insult. ARDS progresses through three overlapping phases: an acute exudative phase, followed by a subacute proliferative phase, and then either a chronic fibrotic stage or resolution. Initial exudative phase: This phase occurs within the first 7 days. Alveolar macrophages release inflammatory cytokines, which stimulate neutrophil migration to the lung. Neutrophils accumulate in alveoli and become activated, releasing pro-inflammatory mediators, which lead to damage to the alveolar-capillary barrier, increased vascular permeability and damage to pneumocytes. This leads to the accumulation of protein-rich inflammatory exudate in alveoli (pulmonary oedema), as well as loss of surfactant resulting in alveolar collapse and shunting, and hyaline membrane formation in alveoli, leading to decreased pulmonary compliance and impaired gas exchange.

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Normal alveolus on left. Injured alveolus in the exudative phase of ARDS on right.

Proliferative phase: This occurs between 7-14 days, and is characterized by a process of lung repair, deactivation of neutrophils, reabsorption of oedema, proliferation of Type II alveolar cells and the beginning of restoration of the epithelial and endothelial linings. Fibrotic phase or resolution: Some patients show clinical improvement and resolution, whilst others progress to a chronic fibrotic phase in which there is persistent inflammation and oedema, membrane damage and marked fibrosis. Figure 2: Mechanisms of resolution of ARDS 7

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Proliferative phase of ARDS on left. Fibrosis or resolution on right.

Risk Factors 4

There are a number of potential precipitating conditions, and these may be classified as pulmonary or extra-pulmonary. The following are potential precipitating conditions for ARDS and associated percentages from the LUNG SAFE study.

Pulmonary Extrapulmonary

Pneumonia (59.4%) Sepsis (16%)

Aspiration (14.2%) No obvious risk factor (8.3%)

Pulmonary contusion (3.2%) Noncardiogenic shock (7.5%)

Inhalation injury (2.3%) Blood transfusion (3.9%)

Pulmonary vasculitis (1.4%) Trauma (4.2%)

Drowning (0.1%) Other risk factors (2.7%)

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Definition 8 In 1994 the “American-European Consensus Conference (AECC) defined ARDS as acute respiratory failure, bilateral infiltrates on chest xray, hypoxaemia (PaO2/FiO2 ratio ≤200mmHg), and the absence of left atrial hypertension”. The term Acute Lung Injury (ALI) was also used to describe less severe respiratory failure, “defined by a PaO2/FiO2 ratio >200 and ≤300mmHg”. There were numerous issues identified including low specificity, substantial inter-observer variability of chest xray interpretation, and hypoxaemia affected by patient’s ventilator settings and PEEP level used. In 2011 the European society of Intensive Care medicine created the currently used definition of ARDS, the Berlin definition. Figure 3: ARDS Berlin Definition 8

Issues with the Berlin definition 4, 9

• The results of the LUNG SAFE study revealed that despite application of the new Berlin definition, ARDS continues to be under-recognized and under-treated. This study showed that 40% of all cases of ARDS were not being diagnosed, and the clinician recognition rate was less than 80% in severe ARDS.

• Chest xray findings are still included in this new definition, which still depends on inter-observer variability in interpreting chest xrays. The definition recognizes that opacities seen on CT scan could be a substitute. CT findings may be more reliable, however CT abnormalities were not included as a central part of the definition due to feasibility, cost and lack of availability at all centres.

• The new definition does not specify the type of ventilatory support and does not include a prognostic index.

• Biomarkers may serve as an early indicator of ARDS or lung injury in the Intensive care. Levels of biomarkers such as Clara cell secretory protein (CCSP, CC16), and Pulmonary surfactant-associated protein D (SP-D) appear to correlate with mortality rate as well as length of hospital stay. SP-D appears to increase in the early stages of ARDS and may assist with early diagnosis. Inflammatory markers such as Inteleukin 8 may predict ARDS caused by infection. Laboratory tests including biomarker studies should perhaps be incorporated in the definition to assist in early identification of ARDS.

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Differential Diagnosis 5,10

The presenting symptoms of ARDS may overlap with other conditions, and the clinician must consider other aetiologies including respiratory, cardiac and infectious causes. Differential diagnoses may include congestive cardiac failure, pneumonia, diffuse alveolar haemorrhage inflammatory or auto-immune conditions and exacerbation of interstitial lung disease. ARDS commonly needs to be differentiated from congestive cardiac failure and pneumonia. Patients with congestive cardiac failure are fluid overloaded, and may present with an elevated jugular venous pressure, lower limb oedema, a third heart sound and a raised Brain natriuretic peptide (BNP). They may also respond to diuretics. Pneumonia is a leading cause of ARDS, but may be present as an uncomplicated pneumonia. These patients may have hypoxia which should respond to oxygen, and do not meet the criteria for ARDS. Diagnostic Evaluation The diagnostic workup is focused on identifying ARDS and its precipitating aetiology. An Arterial blood gas and chest xray are essential for the diagnosis of ARDS. The use of CT scans has been increasing, and appears to be more accurate than CXR in identifying the underlying aetiology and possible complications of ARDS. Lung ultrasonography has also been used to detect pleural effusion, alveolar consolidations and alveolar interstitial syndrome (considered to be suggestive of pulmonary oedema) in ARDS. It can also be used to monitor recruitment efficacy and exclude pneumothorax.

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Imaging findings in ARDS 11

Acute (Exudative) phase: first 7 days In the first 2 days after the initial insult, CXR may appear normal. It may demonstrate an original lesion in the case of a pneumonia. In the following 2-3 days there is a quick deterioration with the development of bilateral patchy alveolar opacities which progresses to widespread consolidation. In severe ARDS there may be a “white lung” appearance. Air bronchograms may be detected and lung volumes appear reduced. Figure 4: Radiological changes over the first week in ARDS 11

CXR findings during the acute phase of ARDS. a) No pathological changes noted on initial CXR. b) From Day 2 pulmonary consolidations noted in the lower lobes. c,d) Rapid deterioration noted over the following days. Increasing consolidations with diffuse alveolar involvement, the “white lung” appearance.

During this phase, CT scan demonstrates a lack of homogeneity and a gravitational gradient with dense consolidation in the dependent (dorsal) regions. There is a diffuse ground-glass appearance of opacities. The ventro-dorsal gradient of opacification is due to posterior compressive atelectasis.

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Figure 5: CT Scan during Acute phase of ARDS 12

Typical features of Acute phase of ARDS: non-homogenous distribution of infiltrates, with more consolidation in dependent regions (gradient). Widespread ground-glass opacities noted.

Proliferative phase (7-14 days): CXR demonstrates persisting alveolar opacities, and a super-imposed pneumonia may develop. CT may show early fibrosis and signs of increased mortality (opacities>80% of lung fields, bronchiectasis and features of pulmonary hypertension). Fibrotic phase or resolution (after 2 weeks): Radiological findings may show either a normal looking lung, or reticular opacities with decreased lung volume. CT usually shows a continuing ground-glass opacification as well as air cysts and bullae. These a predominantly situated in the ventral areas of the lung.

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TREATMENT Treatment of ARDS is usually supportive and may be divided into ventilatory and non-ventilatory strategies. General measures such as prevention of stress ulcers, venous thromboembolism and nutritional support while identifying and treating the underlying aetiology, are also important. VENTILATORY 5,13

Ventilation focuses on decreasing the shunt fraction, improving oxygen delivery, reducing oxygen consumption and avoiding further lung injury. Measures must be taken to prevent barotrauma (limiting plateau pressures), volutrauma (limiting tidal volumes) and atelectrauma. A lung protective ventilation strategy is recommended, to decrease mechanical stress on the lung, which can result in ventilator induced lung injury (VILI). The ARDS Clinical Network Mechanical Ventilation protocol suggests the following:

• Tidal volume 4-8ml/kg of predicted body weight

• Respiratory rate not > 35 bpm

• PaO2 55-80 mmHg or SpO2 88-95%

• Plateau pressure ≤ 30 cmH2O

• pH goal 7.30-7.45

• I:E ratio: duration of inspiration≤ expiration

Lower Tidal-volume ventilation 3,14

Excessive distention or stretch of the aerated lung may result in the release of pro-inflammatory cytokines which may contribute to lung injury and multiple system organ failure. The ARMA trial pioneered by the ARDS Network in 2000 showed that lower tidal volumes in ARDS patients significantly decreased in-hospital mortality and the number of ventilated days. Positive End-Expiratory Pressure (PEEP) 15,16

Cyclical opening and closing of small airways and alveolar units may cause lung injury. Numerous clinical trials have been conducted to determine if higher PEEP limits atelectrauma in ARDS patients. A meta-analysis of trials from 1996-2010 showed that there was no difference in mortality in high vs low PEEP levels in patients with mild ARDS. However, in patients with severe ARDS (P/F ratio<100) there was a benefit from increased levels of PEEP. The guidelines by the Faculty of Intensive Care Medicine (FICM) and the Intensive Care Society (ICS) suggest the use of high PEEP strategies for patients with moderate or severe ARDS. The ARDS Network recommend a minimum PEEP of 5cm H2O and to consider the use of incremental FiO2/PEEP combinations to achieve the PaO2 or SpO2 goals stated above. Recruitment manoeuvres 17,18

The rationale of recruitment manoeuvres (RMs) is to use transient increase in ventilatory pressure to open up collapsed alveoli. This helps to reverse the atelectasis seen in ARDS and improve gaseous exchange. This does appear to have short-term physiological benefits, such as reduced intra-pulmonary shunt and improved pulmonary compliance. However it can result in haemodynamic instability and barotrauma. The American Thoracic Society (ATS) guidelines give a conditional recommendation for the use of RMs after evaluating 6 RCT which demonstrated lower mortality, higher oxygenation at 24hrs (improved P/F ratio), and a decreased need for rescue therapy, following the use of RMs. However, since these recommendations in 2017, the ATS conducted the “Alveolar Recruitment for Acute Respiratory Distress Syndrome Trial”, which demonstrated an increased mortality with their strategy of RM and PEEP titration. The use of RMs is thus currently unclear and should probably be used with caution. Driving Pressure 19,20

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Driving pressure (∆P), calculated as the difference between Plateau pressure and PEEP, reflects dynamic lung stress and lung injury risk. Decreases in driving pressure secondary to changes in ventilator settings have been shown to be strongly associated with increased survival. Figure 6: Pressures measured in mechanical ventilation. Calculation of driving pressure.21

Novel ventilatory strategies have been invented to improve oxygenation. These include airway pressure release ventilation (APRV) and High-frequency oscillation ventilation (HFOV). APRV 22,23

APRV was first described in 1987. Its aim is lung protection by constant recruitment of alveoli and attempts to decrease VILI. It combines high levels of continuous positive airway pressure for an extended period of time, with time cycled ‘releases’ at a lower pressure. It allows spontaneous breathing which may allow reduced sedation requirements, shorter duration of mechanical ventilation and improved cardiac performance. It is also known as ‘inverse ratio ventilation’ as the majority of the respiratory cycle is spent at high pressure with a brief drop to lower pressure to allow expiration. It has a marked inverse inspiratory:expiratory ratio of approximately 8:1-10:1.

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Figure 7: Mechanism of APRV demonstrating long inspiratory time with release phase from P High to P Low. 22

The rationale behind APRV is that the higher airway pressure recruites alveoli and holds them open. This constant alveolar recruitment improves oxygenation. This is known as the “open lung” concept. By maintaining spontaneous ventilation it allows greater displacement of the lower diaphragm and alveolar recruitment and ventilation of the more dependent, better perfused areas, thus improving V/Q matching. It may reduce the risk of VILI by avoiding repeated opening and closing of alveoli. APRV appears to be a tempting mode of ventilation within the concept of open lung ventilation. Some studies have shown improved gas exchange and more ventilator free days in the APRV groups, however the ICS guidelines have not offered an opinion on the use of APRV. It is possible that further studies are required. APRV can possibly be reserved as rescue therapy in patients with moderate to severe ARDS, after failure of deep sedation, paralysis, or proning, to improve hypoxaemia. High-Frequency Oscillatory Ventilation (HFOV) 16,24,25 HFOV involves generating high ventilatory frequency (100-900 bpm), holding the lungs open at a high mean airway pressure (25-30 cmH2O) and small tidal volumes of 1-3ml/kg. Theoretically it reduces VILI by avoiding cyclical collapse of alveoli and overdistention. However trials have suggested against the use of HFOV. The OSCAR trial demonstrated no difference in mortality with the use of HFOV, and the OSCILLATE trial showed increased mortality with oscillation. ICS Guidelines therefore recommend strongly against the use of HFOV.

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VENTILATORY ADJUNCTS

PRONING 17,26,27

Prone positioning results in improved oxygenation by ameliorating the ventro-dorsal transpulmonary pressure difference, improving lung perfusion and decreasing dorsal lung compression. Prone position reduces the difference between dorsal and ventral transpulmonary pressure, which makes ventilation more homogenous. This results in a decrease in ventral alveolar hyperinflation and dorsal alveolar atelectasis. This limits VILI by homogenizing the effects of stress and strain in the lung. Proning also results in reduced lung compression. In the supine position lung compresses the medial posterior lung parenchyma and the diaphragm compresses the posterior lower lung parenchyma. In prone ventilation the heart rests on the sternum and the diaphragm is displaced caudally. Proning may result in improved perfusion: V/Q mismatch improves as the previously dependent lung still receives most of the blood flow and ventilation to this area improves. The dominant dorsal lung perfusion in supine patients does not change to a dominant ventral lung perfusion in prone patients. Lung perfusion is more uniformly distributed in prone patients. The landmark PROSEVA trial looked at proning in severe ARDS, and revealed that prone position significantly reduced 28-day mortality and 90-day mortality. Prone patients were also successfully extubated at higher rates and needed fewer days of ventilation when compared with supine patients. However, there are obvious technical difficulties with proning patients, including needing trained nursing staff, as well as risk of endotracheal tube obstruction, difficult access to endotracheal tubes, disconnection of invasive lines and pressure sores. The PROSEVA trial demonstrated mortality benefit when using prone position for more than 12 hours in severe ARDS patients only. The ATS strongly recommend that adult patients with severe ARDS receive prone positioning for more than 12 hours per day. Extracorporeal Membrane Oxygenation (ECMO)16,17,28,29

ECMO may be performed veno-venously, whereby large-bore central venous catheter access is used to remove blood, pass it through a gas exchanger that removes CO2 and oxygenates the blood, and returns it into a large central vein. It is a highly effective method of oxygenation, however it is invasive, expensive and is associated with many complications including complications related to vascular access, anticoagulation and serious bleeding. The CESAR trial (2009), showed a mortality benefit of patients assigned to the ECMO group. However, the study was criticized as of the 90 patients in the ECMO group, only 68 actually received ECMO. More recently in 2018, the EOLIA trial, showed an 11% reduction in mortality in the ECMO group, which unfortunately failed to reach statistical significance. This study was terminated after 67 months due to futility. It was underpowered and complicated by the fact that 35 patients in the control group required emergency cross-over to ECMO. The ATS suggest that more evidence is required to make a definitive recommendation regarding ECMO in severe ARDS. The ICS guidelines do not recommend the routine use of ECMO for all patients with ARDS, and suggest ECMO with lung protective ventilation only in a select group of patients with severe ARDS.

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NON-VENTILATORY STRATEGIES

Corticosteroids 16,30,31

Considering that ARDS has a significant inflammatory component, it would appear that steroids would have a role. There are several small studies regarding the use of steroids in ARDS, but most were low quality and were performed prior to the lung protection strategy era. The largest trial carried out by the ARDS Network- the LaSRS Trial- a multicentre RCT compared methylprednisolone vs placebo for 21 days in patients with moderate to severe ARDS. Patients receiving methylprednisolone had more ventilator-free, shock-free and ICU-free days by day 28. However no survival benefit was shown. This study as well as other studies showed an increased mortality when patients were commenced on steroids 2 weeks after the onset of ARDS. Potential harms from steroids include higher risk of hospital-acquired infections, neuromyopathy and delirium. The role of steroids remains controversial. The Society of Critical Care Medicine and the European Society of Intensive Care Medicine’s (ESICM) steroid guideline moderately recommends the use of methylprednisolone 1mg/kg/day in moderate to severe ARDS. The FICM/ICS recommend further research, and state that a large, multicentre study on steroids in ARDS is currently planned. Neuromuscular Blockade 16,32,33,34

Neuromuscular blocking agents (NMBA) have been suggested for moderate to severe ARDS to improve oxygenation and reduce patient ventilatory dysynchrony. Earlier studies demonstrated that NMBAs may improve oxygenation by reducing VILI and inhibiting inflammatory cytokines. However, the use of NMBA could result in ICU weakness and increased sedative requirements. The ACURASYS trial (2010) evaluated the outcomes of patients with severe ARDS placed on cisatracurium for 48 hours. This study found that in patients with severe ARDS, administering a NMBA early in the course of the disease improved their 90day survival as well as ventilator-free days. It did not appear to increase muscle weakness. The more recent ROSE trial was the largest RCT on NMBA in early ARDS, also examined the effects of early continuous NMBA in patients with moderate-to-severe ARDS. In contrast to the ACURASYS trial, they used lighter sedation in the control group to be more consistent with current recommendations. Patients in the experimental arm received 48 hours of continuous cisatracurium with deep sedation. The study was stopped due to futility. It found that early continuous neuromuscular blockade with cisatracurium with concomitant deep sedation did not reduce mortality, as apposed to the usual mechanical ventilation with lighter sedation. The rates of ICU weakness were not different in the two groups. More cardiovascular adverse events were reported in the intervention group including hypotension and bradycardia. A recent meta-analysis of RCTs evaluating 28 day mortality in ARDS patients treated with NMBA for 48hrs, aimed to shed light on the effects of NMBA on patient survival, oxygenation and adverse events. This study demonstrated that NMBA improved oxygenation but only after 48hrs in moderate or severe ARDS patients. The positive impact on oxygenation could be due to the decrease in VILI due to barotrauma. This study showed that NMBA had a lower barotrauma risk without affecting ICU weakness. NMBA also had an anti-inflammatory action and decreased muscle oxygen consumption. However NMBA did not improve mortality, or reduce ventilator free days. The ICS has a weak recommendation of cisatracurium infusion for 48 hours in patients with early moderate or severe ARDS.

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Fluid Management 16,35,36

Considering that ARDS is associated with noncardiogenic pulmonary oedema, conservative fluid management has been considered. The FACTT trial in 2006 compared conservative and liberal fluid strategies and showed no difference in mortality, but showed an improvement in ventilator-free and ICU-free days. A recent systemic review with meta-analysis looked at optimal fluid strategy in ARDS. This review included patients with ARDS, sepsis and SIRS. It found that a conservative or deresuscitative fluid strategy improved the number of ventilator-free days and reduced ICU stay compared to a liberal fluid strategy. However, no difference in mortality was shown. The results of these trials are however hampered by substantial clinical heterogeneity. Acute Kidney Injury (AKI) and the requirement of renal replacement therapy (RRT) were questioned as potential harms of a conservative fluid strategy. However the FACTT trial showed decreased requirement for RRT with a conservative strategy, and a post hoc analysis of this trial suggested a decrease in AKI with a conservative fluid strategy. The ICS guidelines weakly recommend using a conservative fluid strategy in patients with ARDS. Based on the results from the FACTT trial, the ICS states that conservative fluid management may be beneficial without harm, and suggest a conservative fluid strategy that includes fluid restriction, diuretics and possible hyperoncotic albumin to avoid a positive fluid balance. Inhaled Vasodilators 37

The role of inhaled vasodilators (inhaled Nitric oxide) in ARDS has been assessed by multiple RCTs. An updated Cochrane review showed that inhaled nitric oxide results in a transient improvement in oxygenation but does not decrease mortality and can infact result in harm as it appears to increase renal impairment. The ICS guidelines weakly recommend against using inhaled Nitric oxide in patients with ARDS.

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COVID-19 PNEUMONIA Can we apply what we know about the management of ARDS to save lives in COVID-19 patients? 38,39,40,41,42

COVID-19 is a novel disease, and are many unanswered questions regarding its management. ARDS however is a syndrome much more well known to us, and which has decades of research-based guidelines to guide our management. Severe COVID-19 may lead to ARDS (CARDS). ARDS develops in 42% of patients with COVID-19, and develops in 61-81% of patients requiring ICU. CARDS seems to have worse outcomes when compared to ARDS from other causes. Mortality in ICU and hospital from ARDS are 35.3% and 40.0%. However in CARDS mortality in ICU is up to 61.5%, and up to 94% for mechanically ventilated patients. In order to save lives of patients with CARDS, the clinical features and clinical course of CARDS has been observed, including its heterogeneity. This has resulted in the proposal of different phenotypes and different managements based on these phenotypes. Gattinoni proposes two types of COVID-19 patients: the ‘non-ARDS’ type 1 patient and the ARDS type 2. Type 1 and 2 patients may be distinguished by CT scan. Type L: Near normal pulmonary compliance

• Low elastance: There is near-normal compliance > 50ml/cmH20.

• Low ventilation-to-perfusion (VA/Q) ratio: Gas volume is near normal. A possible reason for severe hypoxaemia despite good lung compliance is due to loss of hypoxic pulmonary vasoconstriction. There is significant hyperperfusion of gasless tissue.

• Low lung weight: Ground-glass intensities on CT scan.

• Low lung recruitability: The gas volume is high, there is minimal non-aerated tissue, and hence recruitability is low. CT confirms that there are no areas to recruit.

Unlike patients with ARDS from other causes, in these patients, high levels of PEEP or utilizing a prone positioning does not improve oxygenation by improving recruitment as these patients have poorly recruitable lungs. These measures may improve oxygenation by redistributing perfusion and improving V/Q mismatch. Figure 8: CT scan: Type L CARDS 38,40

CT demonstrates lower lung weight. Gas volume is near normal, with well aerated compartments.

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Transitioning from Type L to Type H The progression of the disease is determined by the severity of the disease as well as a concept called patient self-inflicted lung injury (P-SILI). P-SILI occurs when these severely hypoxaemic patients have very high respiratory drives, and high inspiratory efforts. This results in negative inspiratory intrathoracic pressure resulting in inflammation, increased vascular permeability and lung oedema. The Type H phenotype then progressively develops. Hence, early intubation in these distressed patients is advised to avoid P-SILI and limit the transition to Type H. Type H: Decreased pulmonary compliance

• High elastance: Increased pulmonary oedema accounts for increased lung elastance or poor compliance <40ml/cmH20, in keeping with ARDS.

• High right-to-left shunt: Tissue in dependent lung regions is non-aerated due to oedema and pressure. Perfusion of this tissue results in a right to left shunt.

• High lung weight: On CT there is increase in lung weight which is in keeping with severe ARDS.

• High lung recruitability: As in severe ARDS there is much non-aerated tissue, and hence increased recruitability.

Figure 9: Type H CARDS 38,40

CT demonstrates increased non-aerated compartments. Increased lung weight. Non-aerated tissue in

dependent regions. Importantly, these two types are the extremes of the range of features of CARDS, and characteristics may overlap in patients in intermediate phases. Another important feature is coagulation dysfunction with diffuse micro and macrovascular thromboses in the lungs and other organs. This may account for the atypical manifestation of dilated pulmonary blood vessels on CT. This is usually not seen in typical ARDS. Given these proposed phenotypes of the COVID-19 patient, it is clear that different respiratory management needs to be applied to each type.

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Respiratory management of COVID-19 patients Based on the observed pathology, the following management of COVID-19 Respiratory distress and CARDS has been suggested. ARDS management principles of low tidal volume, higher PEEP, and proning may be applied in the following ways. Type L CARDS -Tidal volume: Due to their increased compliance, if hypercapnic they can be ventilated with volumes > 6ml/kg (up to 8-9 ml/kg) without the risk of VILI. -PEEP: Due to the lack of recruitability, PEEP should limited to 8-10 cmH2O, as high PEEP in normal compliance may impair right heart function -Proning: Proning should only be used as a rescue manoeuvre in these patients to redistribute pulmonary blood flow, rather than opening collapsed alveoli as in typical ARDS. -Respiratory rate should not be greater than 20 bpm Type H CARDS: Should be treated as severe ARDS -Tidal volume: Lower tidal volume of 4ml/kg -PEEP: Due to the higher recruitability, increased lung weight and oedema, higher PEEP may be beneficial for gas exchange. -Proning: As in severe ARDS prone positioning may be used as a long-term treatment. -ECMO may also be considered in these patients. Figure 10: “Treatment approach to ventilation for patients with CARDS” 39

Until new data surfaces, it is suggested that we should continue to manage CARDS patients with our current ARDS evidence-based practices as well beside physiology.

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CONCLUSION Despite advances in critical care, ARDS remains a life-threatening form of respiratory failure, with a high mortality rate. Supportive therapies represent the mainstay of treatment, and focus is on preventing further lung damage. The ATS guidelines and the more recent FICM/ICS guidelines do provide evidence based recommendations to assist in our management of these patients. However, there appears to be room for further research in ARDS and evolution of the definition of ARDS and its treatment options. Our knowledge of ARDS may assist in the current COVID-19 pandemic. ARDS appears to develop in a significant number of patients affected by COVID-19, and our evidence based management of ARDS may possibly be applied to assist in managing patients with COVID that develop CARDS.

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