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

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 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

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

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

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)