2000A15 Describe the effects of opioids on the respiratory system.

 

List:

·      Respiratory depression

·      Airway reflex depression

·      Other

 

Respiratory depression:

Mechanism

·   MOP, DOP in resp centre in dorsal medulla

·   Much less effect on chemoreceptors?

·   ↓RR more than ↓VT; risk of apnoea

·   If also sedated: risk of airway obstruction -> death

·   ↓↓Response to ↑PaCO2 (↑apnoeic threshold and ↓gain; dose-dependent)

·   ↓Response to ↓PaO2 (dose-dependent)

 

Therapeutic index

·   Morphine 70

·   Fentanyl 400

·   Sufentanil 27,000

·   Remifentanil 33,000

·   (Note effects begin in the analgesic range (e.g. fentanyl 2-5ng/mL))

Risk factors

·   Other drugs:

o Benzodiazepines: synergistic depression

o Residual volatile anaesthetic -> ↓↓ responsiveness to ↓PaO2

·   Patient:

o Neonate: immature respiratory centre, immature BBB -> ↑morphine effect

o Elderly: ↑PD sensitivity

o Sleep -> ↓responsiveness to ↓PaO2 and ↑PaCO2

·   Pathology:

o Hypothermia -> ↑sensitivity

o Denervated carotid body -> no response to ↓PaO2

o Desensitised respiratory centre (OSA, OHS)

Protective factors

·   Pain

·   Chronic opioid use (note tolerance varies considerably)

Timing

·   Drug:

o ↑Lipid solubility, ↑%unionised -> faster peak effect (e.g alfentanil)

o ↓Lipid solubility, ↓% unionised -> slower peak effect (e.g. morphine)

o Partial agonist -> ↓risk respiratory depression (e.g. buprenorphine)

·   Route:

o IV -> highest peak effect

o IM/SC -> lower peak effect but risk of dose stacking if low skin/muscle blood flow

o Intrathecal: peak effect fentanyl 30mins (systemic absorption), morphine 6-12 hours (CSF circulation)

 

Airway reflex depression:

Receptor

·   MOP

Location

·   Medulla

Effects

·   ↑ETT tolerance

·   ↓Cough, ↓laryngospasm

·   ↓Risk laryngospasm

Use

(particularly remifentanil)

·   Intubation without paralysis (e.g. neuromuscular disorder, large intracranial aneurysm)

·   Extubation without coughing (e.g. neurosurgery)

 

Other:

Chest wall rigidity

·   Associated with remifentanil boluses

·   May herald uncconsciousness

·   Cause: MOP on GABA-ergic neurons in basal ganglia

·   Problem: unable to ventilate

·   Rx: paralyse

Bronchospasm

·   Morphine -> MOP on mast cells -> histamine release

Ciliary dysmotility

·   ? Mechanism

Antisialogogue

·   Especially pethidine: muscarinic ACh receptor antagonist

 

 

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