respiratory failure Flashcards
what is respiratory failure?
Syndrome of inadequate gas exchange due to dysfunction of one or more components of the respiratory system
wha tare the signs and symptoms of respiratory failure?
basically shortness of breath
all other symptoms are the effects of inadequate gas exchange due to damage to any parts of the respiratory system: nervous system - CNS/Brainstem Peripheral nervous system Neuro-muscular junction
respiratory muscle - Diaphragm & thoracic muscles
Extra-thoracic muscles
pulmonary - Airway disease (copd, asthma)
Alveolar-capillary disease
Circulation
what is the epidemiology of chronic respiratory disease?
Chronic respiratory disease 3rd leading cause of death* (2017) 39.8% rise from 1990
worse in the more developed world
worse in females than males
getting worse over time
Costs: EU 380m Euro’s annually (2019) care for chronic respiratory disorders
Accounts for: Inpatient care, lost productivity
Despite extensive costs: limited granular data
biggest risk factors:
Males: Smoking
Women: Household air pollution from solid fuels
treatments are getting more effective as morbidity is dropping faster than prevalence
what is the epidemiology of acute respiratory failure?
Limited data:
Heterogenous disease presentation (pneumonia, pulmonary hypertension, CF)
Acute respiratory distress syndrome
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
how do we define ARDS?
Acute respiratory distress syndrome
we use the berlin definition to classify it:
timing - Within 1 week of a known clinical insult or new/worsening respiratory symptoms.
chest imaging - Bilateral opacities not fully explained by effusions. Lobar/lung collapse or nodules.
origin of oedema -
Respiratory failure not fully explained by cardiac failure or fluid overload.
Needs objective assessment (e.g. echocardiography) to exclude hydrostatic oedema if no risk factor present.
oxygenation - mild moderate severe PF ratio
what are the three different classifications of respiratory failure?
acute:
Pulmonary: Infection, aspiration, Primary graft dysfunction (Lung Tx)
Extra-pulmonary: Trauma, pancreatitis, sepsis
Neuro-muscular: Myasthenia/GBS
chronic:
Pulmonary/Airways: COPD, Lung fibrosis, CF, lobectomy
Musculoskeletal: Muscular dystrophy
acute on chronic: Infective exacerbation COPD, CF Myasthenic crises Post operative
how do we classify respiratory failure based on physiological measures?
Type I or Hypoxemic (PaO2 <60 at sea level)
Type II or Hypercapnic (PaCO2 >45)
Type III Respiratory Failure: Perioperative respiratory
Failure
Type IV Respiratory Failure: Shock
what is type I respiratory failure?
Failure of oxygen exchange
Increased shunt fraction (Q S /QT )
Due to alveolar flooding
Hypoxemia refractory to supplemental oxygen
eg. aspiration, pulmonary oedema, fibrosis, pulmonary embolism, pulmonary hypertension
what is type II respiratory failure?
Failure to
exchange or remove carbon dioxide
Decreased alveolar minute ventilation (V A )
Dead space ventilation
eg. nervous system, neuromuscular, muscle failure, airway obstruction, COPD
what is type III respiratory failure?
Increased atelectasis (collapse of the airways) due to low functional residual capacity
(FRC) with abnormal abdominal wall mechanics
n Hypoxaemia or hypercapnoea
n Prevention: anesthetic or operative technique, posture,
incentive spirometry, analgesia, attempts to lower intra- abdominal pressure
what is type IV respiratory failure?
Type IV Respiratory Failure: Shock
n Type IV describes patients who are intubated and ventilated
During shock (Septic/cardiogenic/neurologic)
n Optimise ventilation improve gas exchange and to unload the
respiratory muscles, lowering their oxygen consumption
Ventilatory effects on right and left heart
Reduced afterload (good for LV) Increased pre-load (bad for RV)
what are the risk factors for chronic respiratory failure?
COPD Pollution Recurrent pneumonia Cystic fibrosis Pulmonary fibrosis Neuro-muscular diseases
what are the risk factors for chronic (I think I meant acute) respiratory failure?
Infection Viral Bacterial Aspiration Trauma Pancreatitis Transfusion
what are the possible origins (causes) of shortness of breath in acute respiratory failure?
Lower respiratory tract infection:
viral
bacterial
aspiration (of gastric acid)
trauma:
transfusion
pulmonary vascular disease:
pulmonary embolus
haemoptysis
Extrapulmonary: pancreatitis, new medications
what are the causes of ARDS?
Pulmonary: Aspiration Trauma Burns: Inhalation Surgery Drug Toxicity infection! (effects airways down to the alveoli)
Extra-pulmonary: Trauma Pancreatitis Burns Transfusion Surgery BM transplant Drug Toxicity infection! (more systemic)
what biology drives acute lung injury in respiratory failure?
leukocytes and inflammatory cells in the lungs
macrophages produce cytokines like IL-6, IL-8, TNF-a
this causes alveolar oedema
and makes them less efficient at expanding as the surfactant round the lungs is degraded
this causes migration of immune cells like neutrophils to migrate out of the blood vessels
this causes more oedema
this increases the distance between the alveoli and the capillaries
making gas exchange less efficient
also angiogenesis
(leukocyte response, inflammatory response, governed by infection
what evidence has been discovered in in vivo experiments for respiratory failure biology?
TNF signalling implicated in vivo and in vitro:
Reduced injury in TNFR-1 animal KO
Leucocyte activation and migration:
Macrophage activation: alveolar
Neutrophil lung migration
DAMP release: HMGB-1 and RAGE
Cytokine release IL-6,8,IL-1B, IFN-y
Cell death:
Necrosis in lung biopsies
Apoptotic mediators: FAS, FAS-l, BCl-2
these molecules can be produced in the lungs and released into the systemic vasculature, to cause damage in other organs such as the kidneys, heart and liver
what pharmacological therapies have been tried to treat respiratory failure?
steroids salbutamol surfactant N-acetylcysteine neutrophil esterase inhibitor GM-CSF statins
trialling now: mesenchymal stem cells: ex vivo benefit keratinocye growth factor microvesicles high dose vitamin C ECCO2R
not much on either of these lists work in humans
what is evidence in ARDS like?
very limited
because it is a severe disease
and wildly heterogenous
ie. lower concentrations of oxygen work better
proning redices mortality
and reducing fluid administration reduces time on a ventilator
but all these studies are quite old
what are the three mechanisms of acute lung injury?
inflammation
infection
immune response
what are the three main categories of therapeutic intervention for respiratory failure?
treat the underlying disease
respiratory support
multiple organ support
how do you treat the underlying cause of respiratory failure?
Inhaled therapies
Bronchodilators
Pulmonary vasodilators
Steroids
Antibiotics
Anti-virals
Drugs Pyridostigmine Plasma exchange IViG Rituximab
what respiratory support can be given for respiratory failure?
Physiotherapy Oxygen Nebulisers High flow oxygen Non invasive ventilation Mechanical ventilation Extra-corporeal support
what multiple organ support can be given for respiratory failure?
Cardiovascular support Fluids Vasopressors Inotropes Pulmonary vasodilators
Renal support
Haemofiltration
Haemodialysis
Immune therapies
Plasma exchange
Convalescent plasma
