ARDS

Question 1

What is respiratory failure?

Answer 1

Syndrome of inadequate gas exchange due to dysfunction in 1 or more components of the respiratory system

Question 2

What are the components of the respiratory system that could contribute to respiratory failure?

Answer 2

1. nervous system (CNS/brainstem, PNS, neuro-muscular junction)
2. respiratory muscles (diaphragm & thoracic muscles, extra-thoracic muscles)
3. pulmonary (airway disease, alveolar-capillary, circulation)

Question 3

What is the biggest risk factor for men, and for women for chronic respiratory disease?

Answer 3

For men smoking. For women household air pollution from solid fuels

Question 4

How do people present with ARDS, what is mortality from ARDS and what increases it?

Answer 4

Heterogenous presentation (present differently). Mortality 30-40%. Severity and age increase mortality.

Question 5

What are the ARDS berlin criteria?

Answer 5

1. timing - within 1 week of known clinical insult or new/worsening respiratory symptoms
2. imaging shows bilateral opacities not fully explained by effusions, lung collapse or nodules
3. origin - respiratory failure not fully explained by cardiac failure or fluid overload (need objective assessment eg ECHO to exclude hydrostatic oedema if no risk factor present)
4. oxygenation: mild P/F ratio 200-300mmHg with PEEP or CPAP >5cmH20. moderate: P/F ratio 100-200 mmHg. Severe P/F ratio <100

Question 6

what are acute causes of respiratory failure?

Answer 6

1. pulmonary - infection, aspiration, primary graft dysfunction after lung transplant
2. extra-pulmonary: trauma, pancreatitis, sepsis
3. neuro-muscular: myasthenia gravis / GBS

Question 7

What are chronic causes of respiratory failure?

Answer 7

1. pulmonary: COPD, lung fibrosis, CF, lobectomy

2. neuromuscular: muscular dystrophy

Question 8

What are acute on chronic causes of respiratory failure?

Answer 8

Infective exacerbation of COPD/CF, myasthenia gravis crisis, post-operative

Question 9

What is type I respiratory failure? What are potential causes? What is seen?

Answer 9

• Hypoxaemic respiratory failure PaO2 <60. failure of oxygen exchange.
• Causes: collapse of lobe, aspiration, pulmonary oedema, fibrosis, pulmonary embolism, pulmonary hypertension.
• There is increased shunt fraction (QS/QT) - amount of blood pumped by heart not completely oxygenated due to alveolar flooding in heart failure patients.
• Hypoxaemia refractory to supplemental oxygen

Question 10

What is type II respiratory failure? What are potential causes? What is seen?

Answer 10

• Hypercapnic PaCO2 >45. failure to remove/exchange CO2. decreased alveolar minute ventilation, dead space ventilation.
• Due to nervous system, neuromuscular diseases (weak muscles cant drive good tidal volumes) or airway obstructive diseases like COPD or chest wall deformities (severe scoliosis) and ageing (thorax cant open as efficiently) leading to hypoventilation

Question 11

What is type III respiratory failure? What are causes? What is seen?

Answer 11

• Peri-operative.
• Increased atelectasis due to low functional residual capacity FRC (can cause lung collapse) with abnormal abdominal wall mechanics (can be due to collapse of airways).
• Can have hypoxaemia or hypercapnea.
• Prevent by good positioning when extubating, anaesthetic or operative technique, incentive spirometry, analgesia, attempt to lower intra-abdominal pressure.

Question 12

What is type IV respiratory failure? What happens? what is impact on ventilation on heart?

Answer 12

• In those who are intubated/ventilated during shock (septic/cardiogenic/neurologic).
• Poor perfusion of lung, cant transfer oxygen, get peripheral pooling of blood and need intubation (positive pressure).
• Optimise ventilation to improve gas exchange & unload respiratory muscles lowering their oxygen consumption.
• Good for LV because reduces afterload (amount of work it needs to do). Bad for RV because increased pre-load (increased pressure in thorax so much harder to fill with blood and contractility affected)

Question 13

What are acute risk factors for respiratory failure?

Answer 13

Infection (viral, bacterial), aspiration, trauma, pancreatitis, transfusion

Question 14

What are chronic risk factors for respiratory failure?

Answer 14

COPD, pollution, recurrent pneumonia, CF, pulmonary fibrosis, neuro-muscular diseases

Question 15

What are pulmonary and extra-pulmonary causes of acute respiratory failure?

Answer 15

1. pulmonary: aspiration, trauma, burns - inhalation, surgery, drug toxicity, infection
2. extra-pulmonary: trauma, pancreatitis, burns, transfusion, surgery, BM transplant, drug toxicity, infection

Question 16

What is the pathophysiology of an acute lung injury in ARDS?

Answer 16

• Lung injury to interstitium causes resident macrophages & type 2 pneumocytes to release cytokines IL-6, IL-7, TNF-a.
• the inflammation makes capillaries leaky and we get protein rich pulmonary oedema and alveolar fluid build up.
• Damage to type 2 pneumocytes so inactivation/degradation of surfactant causes less efficient expanding.
• Migration of neutrophils causes damage, secrete proteases that damage and cause build up of fluid.
• More oedema, more diffusion distance, less efficient gas exchange.
• Systemic infection can cause bactaraemia

Question 17

What is in vivo evidence of molecules in ARDS? What is implicated?

Answer 17

• TNF signalling is implicated (KO animal TNFR-1 causes reduced injury).
• Alveolar macrophage activation & neutrophil lung migration.
• DAMP (damage associated molecular patterns) release HMGB-1 and RAGE.
• Cytokines released are IL-6, IL-8, IL-1B, IFN-γ.
• Cell death shown by necrosis in lung biopsies and apoptotic mediators -FAS, FAS-I, BCI-2

Question 18

What pharmacological interventions have been trialled and have had success?

Answer 18

Steroids, surfactant (more promising in kids), N-acetylcysteine (reduces viscosity of secretions so easier to ventilate), neutrophil esterase inhibitor, salbutamol (no real response), statins

Question 19

What therapies are we trialling and why?

Answer 19

Mesenchymal stem cells (ex-vivo benefit), keratinocyte growth factor (to reduce fibrotic response), micro-vesicles, high dose VItC, thiamine, steroids, ECCOO2R (not really efficient for oxygenation)

Question 20

What types of endo-types have been identified in ARDS?

Answer 20

Hyper and hypo-inflammatory endotypes.

Question 21

What is upregulated in hyper-inflammatory endotype?

Answer 21

Epithelial and vascular DAMPS upregulated in inflammatory endotype

Question 22

How can vascular DAMPS be used to discriminate between 2 diseases?

Answer 22

Discriminate between influenza & and COVID ARDS ECMO cohorts.

Question 23

Why is it important to identify driving mechanism in ARDS?

Answer 23

it is heterogenous

Question 24

What are the 3 keys to therapeutic intervention of ARDS?

Answer 24

1. treat underlying disease 2. respiratory support 3. multiple organ support

Question 25

How do you treat the underlying cause in ARDS? What drugs can be used?

Answer 25

If underlying neuromuscular disease (pyridostigmine or steroids), if vasculitic (steroids, plasma exchange), bronchodilators, pulmonary vasodilators, steroids, antibiotics, anti-virals, IVIG, rituximab

Question 26

How do you offer respiratory support in ARDS? What can be given?

Answer 26

Physiotherapy, oxygen, nebulisers (salbutamol, ipatropium bromide, hypertonic saline/mucocysteine to loosen up secretions), high flow oxygen (nasal cannulae/face masks up to 70L & 100% oxygen if airway patent), mechanical ventilation (intubation), for facial trauma/epistaxis non-invasive ventilation with tight fitted mask or air stent to open alveoli & let in oxygen in Type I or add booster assistant breath support to clear CO2, ECMO (extra-corpeal support)

Question 27

Why not give liberal oxygen to COPD patients or with chronic type II respiratory failure?

Answer 27

Supplemental O2 removes a copd patient's hypoxic respiratory drive causing hypoventilation which causes higher carbon dioxide levels, apnea and respiratory failure

Question 28

How do you offer multiple organ support in ARDS?

Answer 28

- CV: fluids, vasopressors, inotropes, pulmonary vasodilators. - Renal: hemofiltration, haemodialysis. - Immune: plasma exchange, convalescent plasma

Question 29

How does ARDS lead to other things (sequalae)?

Answer 29

Poor gas exchange, infection (sepsis), inflammation, systemic effects (stress on liver, CV, renal system can cause multi-organ dysfunction)

Question 30

What is positive pressure ventilation? How does it work? What types exist?

Answer 30

- Blows air into lungs with positive pressure. - Peak pressure to drive into lung & underlying base pressure to keep airways open. - Too much pressure can be damaging. - Types: volume controlled, pressure controlled, assistant breathing modes (to drive pressure using sensor) , advanced ventilatory modes

Question 31

Why is compliance reduced in lung injury?

Answer 31

Amount of lung that opens for amount of pressure used reduced because lung much thicker.

Question 32

What is upper inflection point and lower inflection point?

Answer 32

- Upper inflection point UIP - above this pressure additional alveolar recruitment requires too much pressure to point it would damage lung. - Lower inflection point LIP - minimum baseline pressure PEEP needed for optimal alveolar recruitment. If you drop below this you get lung collapse

Question 33

How do you manage ventilation in patients with COPD and why? What can be the consequences of too low or too high pressures?

Answer 33

- COPD have normally high CO2 and don’t exhale completely. On ventilator hard to manage because airways constricted so hard to get pressure right. - Air stays in lung (trapping) so increased lung pressure cant efficiently ventilate. 1. set time for exhalation to be long enough for gas to leave lung 2. don’t use too much pressure to drive air in because we wont be able to get air out 3. because they have intrinsic level of peak (chest held open) if we use lower pressure have to work much harder - tires muscles, trapping of air makes chest fuller. SO keep driving pressure (difference between peak and static pressure) to reduce ventilator induced lung injury

Question 34

How can a lung recruitment CT be used? What can it show?

Answer 34

- Lung recruitment CT to see if we can open up lung, see if it is recruitable by increasing distension of lung to see if can get some alveolar units to ventilate patients. - Too high pressure can over-distend lung trapping more gas in chest and reducing perfusion and causing RV dysfunction.

Question 35

How can a lung ultrasound be used? What can it show?

Answer 35

See how well expanded lung is - bedside - can see fluid in lung. Doesn’t pick up as much as CT but can pick up fluid (can drain)

Question 36

How do you guide escalation of therapy in ARDS? What are the parameters?

Answer 36

Murray score (average score of 4 parameters): 1. PF ratio 2. CXR (1 point per quadrant infiltrated) 3. PEEP 4. compliance. 0=normal, 1-2.5 moderate, 2.5 severe, 3 ECMO

Question 37

What is the P/F ratio? What indicates ards?

Answer 37

P/F ratio is PaO2/FiO2. | -assesses severity of hypoxameia - less than 300 indicates ARDS

Question 38

What are ECMO inclusion criteria?

Answer 38

1. Severe respiratory failure (non cardiac cause), 2. murray score 3 or more, 3. positive pressure ventilation not appropriate (eg trachael injury)

Question 39

What are ECMO exclusion criteria?

Answer 39

1. Contraindication to continuation of active treatment, 2. significant co-morbidity (depend on ECMO support/no prospect of recovery), 3. significant life-limiting comorbidity (better for those with reversible disease & not prolonged disability)

Question 40

What else needs to be considered when choosing ecmo?

Answer 40

Aetiology - eg patients with flu recover well

Question 41

How is ECMO done?

Answer 41

- Pass large cannula usually via groin (femoral vein) sit it bellow right atrium, withdraw blood with tubing - run it across artificial membrane that oxygenated and removes Co2 from blood and pass it through patient. - Either femoral-femoral axis or femoral-jugular axis

Question 42

How efficient is ECMO?

Answer 42

Good survival rate 79%. Case selection important

Question 43

What are issues with ECMO?

Answer 43

Time to access, referral system has geographical inequity, referral consideration, expensive, technical requires expertise, perfusionists in short supply, need blood thinning (heparin/anticoagulant) because increased risk of clotting/bleeding