2010A03 Discuss the adverse effects that may occur with administration of desflurane.

 

List:

·     CVS

·     Resp

·     CNS

·     Other physiology

·     CO2 absorber

 

Cardiovascular system:

Direct actions

·    Mechanisms:

o ↑GABA/glycine -> ↓SNS output from medulla

o ↓L-Ca2+ channel activity

o ↑NO release

·    Effects:

o Venodilation -> ↓preload

o ↓Heart rate, contractility

o ↓SVR, ↓afterload

o ↓cardiac output

o ↓mAP

o ↓Renal blood flow, ↓urine output

Baroreceptor reflex

·    Preserved

·    Reflex ↑HR common

SNS stimulation

·    If sudden ↑[desflurane], especially MAC >1.5

·    ? Airway irritation ? systemic (since occurs on cardiopulmonary bypass)

 

Respiratory system:

Respiratory depression

·    Mechanisms:

o ↓Chemoreceptor function

o ↓Respiratory centre function: ↑GABA, ↑glycine

o ↓Spinal cord a-motor neuron output

o Presynaptic ↓L-Ca2+-> ↓ACh release

o Post-synaptic inhibition of nAChR

·    Effects:

o ↓TV but ↑RR

o ↓↓Response to PaO2 (~50% at 0.1MAC, ~0% at 1MAC)

o ↓Response to ↑PaCO2 (~50mmHg at 1MAC without stimulation)

Irritation/smell

·    Laryngospasm, cough, breath hold, secretion

·    Bronchospasm -> ↑airway resistance

·    More likely in smokers

·    Gas induction contra-indicated

Airway obstruction

·    ↓Pharyngeal dilator tone

·    ↑Risk of existing OSA

Bronchodilatation

·    ↓L-Ca2+

·    ↓Airway resistance, ↓work of breathing

·    ↑Anatomical dead space (not significant)

Ciliary dysfunction

·    ↑?Risk pneumonia

Pulmonary vasodilatation

·    ↓L-Ca2+, ↑NO, ↓SNS

·    ↓HPV -> ↑shunt -> ↓PaO2

 

Central nervous system:

Cerebral vasodilatation

·    <1MAC: ↓CBF (↓CMRO2 predominates)

·    >1MAC: ↑CBF (vasodilatation predominates - ↓L-Ca2+, ↑NO)

·    Desflurane causes the least ↑CBF of all the volatile agents

Emetogenesis

·    ↑5-HT activity

Antalgesia

·    At low partial pressure

Post-op delirium

·    ? Cause

·    ↑Risk if elderly

 

Other physiology:

Uterine relaxation

·    L-Ca2+ inhibition, ↑NO release

·    ↑Bleeding during GA Caesarean

Hepatotoxicity

·    Metabolism by CYP2E1 -> inorganic and organic fluorides, trifluoroacetic acid

·    Toxicity rare

Malignant hyperthermia

·    Life-threatening hypermetabolic reaction

·    Idiosyncratic; all other features listed are dose-dependent

·    Mutation in RYR1 gene encoding skeletal muscle ryanodine receptor

·    ↑↑Ca2+ release on excitation -> rigidity

CO2 absorber:

Carbon monoxide

·    CHF2 group + CO2 absorber -> carbon monoxide

·    ↑HbCO (up to 35%) -> anaemic hypoxia

·    ↑Risk if:

o  Isoflurane/enflurane > desflurane

o  Baralyme

o  Absorber hot and dry (e.g. machine used all weekend)