Respiratory Failure Flashcards
What is respiratory failure?
Syndrome of inadequate gas exchange due to dysfunction of one or more components of the respiratory system
What are the signs and symptoms of respiratory failure?
Shortness of breath - predominant feature Breathlessness Increased RR Cyanosis Wheezing Coughing Chornic Cough Reduced exercise tolerance Fatigue
Dysfunction is which parts of the respiratory system can lead to respiratory failure?
- Nervous system:
CNS/Brainstem - e.g. respiratory system that lies within the ventro-lateral medulla
Peripheral nervous system
Neuro-muscular junction - e.g. myasthenia gravis - Respiratory muscle:
Diaphragm and thoracic muscles
Extra-thoracic muscles
(often seen in muscular underlying diseases) - Pulmonary (most frequent):
Airway disease - e.g. asthma, COPD
Alveolar-capillary - e.g. damage due to fibrosis
Circulation
What is the epidemiology of respiratory failure?
Chronic respiratory diseases are the third biggest cause of mortality across the world (after cardiovascular disease, neoplastic disease)
Since 1990 til now, increase in respiratory diseases in Northern Europe and Northern America
In 1990 and now, there is a lack of chronic respiratory disease in Sub-Saharan Africe and South-East Asia
39.8% rise in chronic respiratory diseases since 1990
From 1990 to 2017, the prevalence, mortality, and DALY rates per 100k dropped by 14·3%, 42·6%, and 38·2% which suggests that treatment is getting more effective
Why is chronic respiratory disease the 3rd leading cause of death in the UK?
What are the risk factors?
Men - predisposed due to smoking
Women - predisposed due to air pollution from solid fuels
What is the epidemiology of acute respiratory failure (AKA acute respiratory distress syndrome - ARDS)
More difficult to assess as patients present very differently and it’s a heterogeneous disease
It could be down to pneumonia or an effective exacerbation, COPD worsening pulmonary hypertension, cystic fibrosis, infective exacerbation, lots of different ways people may present
Of ADRS -
Prevalence: 6-7 per 100,000 = 6-700 people/yr in UK
30 to 40% Mortality (ALIEN/Esteban)
35, 40 and 46% (Severity dependent. Bellani)
Severity and advance age –> increase mortality
What criteria is used to classify acute respiratory distress syndrome (ARDS)?
To classify, ARDS, the acute respiratory distress syndrome, we use a Berlin definition and for this, we look at:
Timing - within 1 week of a known clinical insult / new symptom / worsening repiratory symptom
Chest imaging - unexplained bilateral opacities not fully explained by effusions or lobar collapse
Origin of oedema - unexplained by cardiac failure or fluid overload
Oxygenation -
Mild (200mmHg < PO2/FiO2)
Moderate (100 mmHg < PO2/FiO2)
Severe (PO2/FiO2 < 100mmHg)
FiO2 (the fraction of inspired oxygen)
What increases mortality rates in those with ARDS?
Severity and advance age
What are the 3 classifications of acute respiratory failure?
- Acute
- Chronic
- Acute on Chronic
What are the causes of acute respiratory failure?
Pulmonary: infection, aspiration, primary graft dysfunction (result of a lung transplant)
Extra-pulmonary: trauma, pancreatitis, sepsis,
Neuro-muscular: myasthenia / GBS
What are the causes of chronic respiratory failure?
Pulmonary/Airways: COPD, lung fibrosis, cystic fibrosis (CF), post lobectomy
Musculoskeletal: muscular dystrophy
What are the causes of acute on chronic respiratory failure?
Infective exacerbation of chornic disease - worsening chronic condition e.g. COPD, CF
Myasthenic crises
Post operative - from underlying respiratory disease
What are the different respiratory failure classifications?
Physiological classifications:
Type I - failure of oxygen exchange
Type II - failure to exchange / remove CO2
Type III - perioperative respiratory failure (collapse of airways from low functional residual capacity)
Type IV - shock
What is the difference between Type I and Type II respiratory failure?
Type I (hypoxemic) = failure of oxygen exchange (low PO2) - may be due to collapsed lung, aspiration, pulomnary oedema fibrosis, pulmonary embolism, pulmonary hypertension, increased shunt fraction in heart failure, alveolar flooding
Type II (hypercapnic) = failure to exchange or remove carbon dioxide - may be due to dead space ventilation, decreased alveolar ventilation, nervous system disease, neuromuscular diseases, muscle failure, airway obstruction, chest wall deformity
What is Type III and Type IV respiratory failure?
Type III (preioperative respiratory failure) = collapse of the airways due to low functional residual capacity with abnormal abdominal wall mechanics - can lead to hypoxaemia or hypercapnoea
Type IV (shock) = patients who are intubated and ventilated during shock leads to poor perfusion of the lung (cardiogenic, septic or neurologic shock)
How can Type III respiratory failure be prevented?
Good anaesthetic or operative technique, good posture, incentive spirometry, analgesia, attempts to lower intra-abdominal pressure
How can Type IV respiratory failure be treated?
Optimise ventilation to improve gas exchange and to unload respiratory muscles, which lowers their O2 consumpction
What are the effects of ventilators on the left and right sides of the heart?
Ventilator gives positive pressure
Good for left ventricles (LV) = reduced afterload on the heart (as postive pressure from ventilator = increased pressure in the chest)
Bad for right ventricle (RV) = increased preload (increased positive pressure in thorac makes RV work harder)
What are the chornic risk factors for respiratory failure?
COPD Pollution Recurrent pneumonia Cystic fibrosis Pulmonary fibrosis Neuro-muscular diseases
What are the acute risk factors for respiratory failure?
Infection: viral, bacterial Aspiration - aspirate acidic gastric contents into lungs which induces a response Trauma Pancreatitis Transfusion
What are the 5 origins for shortness of breath in acute respiratory failure?
Explore the history of the shortness of the breath
- Lower respiratory tract infection - viral or bacterial
- Viral e.g. flu, covid, MERS
- Bacterial e.g. streptoccocal pneumonia, staph pneumonia, pseudomonas
These induce acute lung injury and potential respiratory failure - Aspiration - gastric contents
- Trauma
- Pulmonary vascular disease - pulmonary embolus, haemoptysis
- Extrapulmonary - pancreatitis, new medications
What are the causes of ARDS?
Pulmonary causes: Aspiration Trauma Burns Inhalation Surgery Drug toxicity Infection
Extra-pulomnary causes: Trauma Pancreatitis Burns Transfusion Surgery Bone marrow transplant Drug toxicity Infection
Mechanisms unknown
What are the different components that make up the lung unit?
Alveolus
Interstitium
Vascular supply - microvascular lung vessel
What occurs in acute lung injury?
Injury in lung leads to damage of interstitium which is the area surrounding the alveoli
And within the alveolus itself, you have resident alveolar macrophages and when they’re activated by an infection or inflammation, will release further cytokines like IL-6, IL-8 and TNF Alpha
There are also type II pneumocytes within the alveolus alongside the macrophages that differentiate down to Type I when activated by an infection
And in response to this inflammatory setup, you often get alveolar fluid build-up or protein-rich oedema forming within the lung
You can get a degradation of surfactant (alveolus becomes less efficient at expanding) which can cause alveolar collapse
And when you have inflammation of the alveolus you often get tracking or migration of leukocytes out of the blood vessels such as neutrophils squeezing through into the interstitium where they can cause damage before getting into alvelous there they secrete proteases and other inflammatory mediators, which can cause some damage and build up a fluid within all of these tissues
In the diseased version of the alveolus, there is a greater distance between alveolus and blood vessel due to oedema which makes gas exchange less efficient
So what are the key mechanisms in an interplay that contribute to respiratory failure?
The lung Leucocytes Inflammation Infection Immune response
These cause acute lung injury –> leads yo inefficient gas echange and respiratory failure –> may lead to dependence on respiratory support
What has been discovered in the in vivo experimental models about respiratory failure?
TNF signalling has been identified as very important - studies show you can reduce the alveolar lung injury by using knock outs of TNFR-1 or blocking the TNFR-1 signalling pathway with domain antibodies
There is macrophage activation in the alveolar space ad neutrophil lung migration - mechanisms to try and block either of these in animal models have been promising, but have not yet translated into human treatment
Looked at downstream particles ot predict who is going to get a worse injury - AKA thing released from the lung e.g. :
DAMP (damage associated molecular patterns) - HMGB-1 (high motility group box - 1) is very common, and RAGE (receptor for advanced glycation end products)
Cytokine release - IL6, IL8, IL1B, 1FN-y
Cell death - necrotic tissue in lung biopsies, may be apoptotic cells due to apoptotic mediators (FAS, FAS-I, BCI-2)
What therapies have been trialed in ARDS?
Steroids - e.g. dexamethasone
Salbutamol - does not translate to significant response
Surfactant - perhaps more promising in children than adults
N-Acetylcysteine - reduces viscosity of secretions
Neutrophil esterase inhibtitor
GM-CSF - promising in models but not yet trialed on humans
Statins - good in hyper-inflammatory response
What are some therapies that are trialling for ARDS?
Mesenchymal stem cells - ex-vivo benefit
Keratinocyte growth factor - important in repair factor in limiting fibrotic response
Microvesicles
High dose Vitamin C, thiamine, steroids - studies refuting this
ECCO2R (removes CO2)
Why is evidence in ARDS limited?
Because it is a very heterogeneous, severe disease
What is the underlying biological process in ARDS?
Pulmonary vascular endothelialitis = poor perfusion in vast areas of the lung
Leads to worsening ventilation perfusion mismatch
What is the HARP-2 ARDS study and how does it show that ARDS is a pro-inflammatory disease?
The HARP2 ARDS clinical study provided a unique opportunity to investigate necroptosis activation
This cohort has been described with 2 different inflammatory endotypes
Necroptosis is best described via TNFR-1 signalling and the HARP-2 inflammatory endotypes
Separated out by the soluble factors TNFR-1 and IL-6, not respiratory physiology per se
These endotypes provided an opportunity to identify if necroptosis activation underpins hyper-inflammation in ARDS
Secondarily to evaluate if necroptosis activation sustains inflammation
We confirmed the inflammatory endotypes ourselves within this cohort - we found two different groups consistent with the original analysis
Next we looked downstream at cell death ligands
The inflammatory signalling is differentiated by TNFR-1, we also see significant IL-8 release confirming downstream activation of complex I
How did Dr Handslip build on the HARP-2 ARDS study and what has he found?
We confirmed the inflammatory endotypes reported in the HARP-2 study
Marked differences in IL-6, 8 and TNFR-1 at baseline
In keeping with expected inflammation
Hyper-inflamed endotype demonstrate elevated DAMPs most markedly Epithelial predominant RAGE, Ang-2 and VEGF-D
Indicating significant induction of inflammation in this cohort - there is a more pronounced difference with RAGE
IL-18 is a necro-inflammatory mediator constitutively expressed in the airway.29 Circulating IL-18 is increased in COVID ARDS, hyper-inflammatory and ECMO ARDS cohorts. IL-18 initiates pro-inflammatory NF-kB signalling, and is pivotal to T cell differentiation and IFN-γ production. 30,31 IL-18 also induces airway hyperresponsiveness and macrophage activation, common features associated to ARDS.32,33,34 IL-18 and IFN-γ are enhanced in COVID and non-COVID ECMO cohorts, in keeping with viral infection. The IFN-γ response is protective in early defence against IAV & SARS but prolongs damaging IFN-γ cytokine responses and diminished antibacterial protection
What is the therapeutic intervention for respiratory failure?
Treatment of the underlying disease:
Respiratory support
Multiple Organ support
What can be used to treat the underlying disease?
Inhaled therapies - Bronchodilators - Pulmonary vasodilators Steroids - e.g. methylpredinisolone for vascular presentation Antibiotics Anti-virals Drugs - Pyridostigmine - for underlying muscular disease - Plasma exchange - IViG - Rituximab
What can be used for respiratory support?
Physiotherapy
Oxygen - can exacerbate Type II resp failure
Nebulisers - e.g. salbutamol, ipratropium bromide
Hypertonic saline - try to reduce mucus load
High flow oxygen - face maks, cannulae
Non invasive ventilation - for those with those with epitaxis or facial trauma injury = tight fitting face mask with single pressure
Mechanical ventilation
Extra-corporeal support
What can be used for multiple organ support?
Cardiovascular support - Fluids - Vasopressors - e.g. noradrenaline, norepinephrine - Inotropes - Pulmonary vasodilators (NO) Renal support - Haemofiltration - Haemodialysis Immune therapies - Plasma exchange - Convalescent plasma
What are the different types of respiratory support?
Non- rebreathe face mask Non-invasive ventilation Intubation Proning ECMO cannulation
What does poor gas exchange in ARDS lead to?
Inadequate oxygenation
Poor perfusion - stress on the cardiovascular, renal and liver systems AKA the highly metabolic systems
- May lead to multi-organ dysfunction as a result
Hypercapnoea
What does infection in ARDS lead to?
Sepsis
What does inflammation in ARDS lead to?
Inflammatory response
What are some specific interventions for ARDS?
Respiratory support
Intubation and ventilation
ARDS necessitates mechanical intervention
Types of Ventilation
- Volume controlled
- Pressure controlled - this is usually what is controlled, as pressure can be damaging so we can turn down pressure once we know there is adequate volume
- Assisted breathing modes
- Advanced ventilatory modes
It’s important to use high positive end-expiratory pressure, or PEEP to keep alveoli open even after expiration
Give a low tidal volume which doesn’t over-distend the fragile alveoli
Procedures to support ventilation
What is the aim for the tidal volume on ventilation?
6ml per kilo
What is meant by the terms: Compliance (C) Upper inflection point (UIP) Lower inflection point (LIP) on a pressure volume loop?
Compliance = the amount of lung that opens for the pressure used
- Compliance is markedly reduced in injured lungs
Upper Infection Point (UIP) = due to stiffness of the ARDS lung, it is important to not supply to high pressure as the lung damage presents a few days after (instead of immediately)
- Above this pressure, additional alveolar recruitment requires disproportionate imcreases in applied airway pressure (i.e. increasing the pressure above UIP serves little benefit in more alveolar recruitment)
Lower inflection point (LIP) = minimum baseline pressure (PEEP) needed for optimal alveolar recruitment
- If the pressure is dropped too low, it can cause alveolar collapse
What are the pitfalls of ventilation?
Minute ventilation
- PaCO2 control
Alveolar recruitment
- Positive end exspiratory pressure (PEEP)
V/Q mismatch
- Ventilation without gas exchange vice-versa
Ventilator induced lung injury
- due to driving pressure
What is it difficult to manage patients with COPD/ asthma?
Can be difficult to manage patients with COPD/ asthma because they don’t breath out properly so a lot of air remains in the lungs
Barrel chest so they do not completely exhale in normal life, so when they are on a ventilator due to their constricted airways, it is difficult to get the pressure right into the lungs AND pull the air back out of the lung
What is trapping during ventilation?
What is breath stacking?
E.g. in COPD/asthma patients, poor exhalation means air remains in the lung
Overtime, the amount of air left within the lungs builds up = breath stacking
Leads ultimately to increased pressure and volume = lack of efficient ventilation
So it becomes more and more difficult to manage their hypercapnoea (high CO2 levels)
How can trapping be solved during ventilation?
Set the time for the exhalation of breath to be long enough so that most of the gas can leave the lung
What is an intrinsic level of peak? How does this relate to COPD/Asthma patients?
COPD / asthma patients have an intrinsic level of peak as their chests are always held open by their underlying lung disease
So they always have a lower pressure
Hence using a lower pressure in a ventilator means they need to work harder - may tire out the muscles of the patient
What is a Lung recruitment CT?
High pressure ventilatory strategy with low driving pressure - to see if the lung can be opened up
We can try and “recruit” parts of the lungs – try and open alveolar units by applying pressure but when you go to very high pressure, you may at over distend the lung which traps more air within the chest
What is the use of a lung ultrasound scan (USS)?
Can also do a bedside US which has no radiation
Used ot evaluate how expanded a person’s lung is
Allows us to see fluid in the lungs - this can be drained using a chest drain
What are the guidelines to escalate the therapy (treatment) when the current treatment is not working?
Use the Murray score to determine therapy / treatment Murray score involves 4 parameters: - pO2 / FiO2 - CXR - PEEP - Compliance
As these parameters get worse you get a higher Murray score
0 = normal 1-2.5 = mild 2.5 = severe 3 = ECMO
What is ECMO?
Extracorporeal membrane oxygenation - ECMO machine is very similar to a heart–lung machine. An artificial lung (the membrane) oxygenates the blood outside the body (extracorporeally)
Last resort, if other ventilation options fail - online / telephone referral system for:
Murray score > 3
pH < 7.2
Done at 5 centres across the UK:
- Wythenshawe
- Glenfield
- Papworth
- GSTT
- Royal Brompton
What is the criteria for treatment with ECMO?
Inclusion Criteria:
Severe respiratory failure:
- Non-cardiac cause (i.e. Murray Lung Injury score 3.0 or above)
Positive pressure ventilation is not appropriate (e.g. significant tracheal injury)
Patients with a REVERSIBLE disease process that is unlikely to lead to prolonged disability
Eclusion Criteria:
Contraindication to continuation of active treatment;
Significant co-morbidity –> dependency to ECMO support
Significant life limiting co-morbidity
How does treatment of SARS (covid) VS flu differ from ECMO treatment?
SARS:
Data collection still on-going
Flu:
Patients with flu develop severe ARDS
Good recovery when they are placed on ECMO
How does ECMO work?
Significant, invasive thing to do
Pass a very large cannula up through the groin through the femoral vein or the jugular vein and it goes into the IVC or SVC
Withdraw blood through the tubing, which runs into a pump
This runs the blood across an artificial membrane
So the blood will be pumped through a section and gases are flowed over the top layer at the membrane - allows to remove the carbon dioxide and input of oxygen
And that oxygenated red blood then passes straight back into the patient that
What is the evidence for ECMO?
First major trial - EOLIA:
- Stopped early for futility
- Statistically no significant difference found as it was stopped too early
What is the general course mortality for ECMO?
30-40% generally
Royal Brompton Hospital has 79% survival
So case selection is very important
What are the issues with ECMO?
A very invasive and expensive procedure - carries many risks
Issues:
- Timing to acess the referral system
Geogrpahical inequality - need to be aware of ECMO in order to request / refer to it
What are the technical difficulties of ECMO?
Obtaining access via:
- internal jugular
- subclavian
- femoral
- Managing a circuit
- Haemodynamics
- Clotting / bleeding - ECMO requires blood thinners e.g. heparin, anticoagulation
Why do patients on ECMO have large shifts of blood flow within the brain?
Due to high carbon dioxide levels
