eLFH - Inhaled Anaesthetic Agents and Oxygen Toxicity Flashcards
Mechanism of oxygen toxicity
Note complex and not fully understood
Hyperoxia produces highly oxidative, partially reduced active metabolites
Radicals interfere with basic metabolic pathways and enzyme systems - especially those containing sulphydryl groups
Examples of highly oxidative, partially reduced active metabolites produced in hyperoxia
Hydrogen peroxide
Hydroxyl radicals
Oxygen free radicals - e.g. Superoxide
Types of oxygen toxicity triggers
Normobaric oxygen
Hyperbaric oxygen
Effects on pulmonary function exerted by hyperoxia in normobaric conditions
Range from atelectasis to tracheobronchitis to severe alveolar injury
Direct dose dependent and time dependent effect
Process of hyperoxia leading to impaired pulmonary function
Hyperoxia
Endothelial neutrophil and macrophage recruitment
Release of inflammatory mediators
Reduction in surfactant production
Interstitial oedema
ARDS
Impaired gas exchange + Hypoxia
Pulmonary fibrosis at 1 week
Normobaric oxygen at different FiO2 and time before detectable changes to pulmonary function
FiO2 1.0 = 12 hours
FiO2 0.8 = 24 hours
FiO2 0.6 = 36 hours
FiO2 0.5 = indefinitely
Effect of high FiO2 on lung volumes
Absorption atelectasis
May be responsible for reduced vital capacity and increased shunt fraction
Results by 2 mechanisms
Mechanism 1 for absorption atelectasis
Seen in dependent areas of lung
Airway occlusion forms trapped gas pockets - no longer ventilated
Initial pressure in these pockets is atmospheric, but as gas exchange occurs total partial pressure becomes sub-atmospheric
Continued gas exchange down partial pressure gradients results in collapse of these pockets and absorption atelectasis occurs
Mechanism 2 for absorption atelectasis
Inspired gas ventilates alveolar units and alveolar uptake removes this gas into blood
Alveolar volume is balance between alveolar ventilation and alveolar uptake
If alveolar uptake falls below a critical value, the alveolus will collapse
How does high FiO2 promote absorption atelectasis
On air, arterial PO2 is ~13 kPa
Extraction of 4.5 ml/dL of O2 by metabolically active tissue results in venous PO2 ~ 6.5 kPa
On FiO2 1.0, arterial PO2 is much higher ~ 89 kPa
Due to sigmoid shape of O2 dissociation curve, venous PO2 only increases by a fraction to ~7kPa
Therefore greater alveolar to mixed venous PO2 gradient created - stimulates more rapid O2 uptake and therefore faster alveolar collapse by mechanism 1 and 2
Special considerations for neonates younger than 44 weeks post conception age
Avoid concentrations of O2 greater than 10.6 kPa for more than 3 hours
Therefore saturations kept around 90%
Reason for lower oxygen concentrations and saturations in neonates younger than 44 weeks
Hyperoxia in these neonates associated with:
- Retinopathy
- Necrotising enterocolitis
- Bronchopulmonary dysplasia
- Intracranial haemorrhage
Reason for maintaining normoxia post cardiac arrest or traumatic head injury
Initial hyperoxia is associated with worse outcomes
The Bert effect
Effect of hyperoxia on the CNS under hyperbaric conditions
The Bert effect at 2 atmospheres
Paraesthesia
Nausea
Facial twitching
Myopia
The Bert effect at above 2 atmospheres
Convulsions may predominate
The Smith effect
Pulmonary changes seen from hyperoxia under hyperbaric conditions
Similar picture to pulmonary changes seen under normobaric conditions but are accelerated
Inhalation anaesthetic agents compartment model
Inhaled anaesthetic agents conform to a multi-compartment pharmacokinetic model
Lungs considered as additional compartment in series from which central compartment is dosed
At equilibrium:
Agent partial pressure in alveoli = Partial pressure in central compartment (arterial) = Partial pressure at effect site (brain)
Factors which affect inhalation agent distribution from central compartment (i.e. arterial compartment)
Peripheral compartment blood supply
Compartment capacity (tissue : gas coefficient)
Factors which determine uptake of inhalation agent from lungs to central (arterial) compartment
Alveolar fractional concentration
Blood : gas coefficient
Cardiac output
Alveolar : venous gradient
Concentration effect and Second gas effect
Determinants of alveolar fractional concentration (FA)
Alveolar ventilation - increases FA
Fi - increases FA
FRC - decreases FA (acts as reservoir which prolongs filling time and reduces rate of FA rise)
Effect of alveolar fractional concentration on inhalation agent anaesthesia time
Alveolar fractional concentration provides driving force for diffusion of agent into blood
Higher FA reduces time for onset / equilibrium
Blood : gas coefficient definition
Ratio of amount of anaesthetic agent in the blood to that in gas when the 2 phases are of equal volume and pressure in equilibrium at 37 degrees Celsius
Effect of Blood : gas coefficient on speed on inhalation agent onset
Lower blood : gas coefficient have greater speed of action
Lower solubility results in more rapid build in arterial and effect site partial pressure of agent
Partial pressure of agent determines effect
