Neuraxial Opioids

Question 0

Describe neuraxial analgesia

Answer 0

• analgesia is dose related
• epidural dose is 5-10x Subarachnoid dose since it has to diffuse through dura mater

-specific for visceral (organ) pain rather than somatic (muscles, tendons, fascia, bone)

• doesn’t include sympathetic denervation, skeletal muscle weakness or loss of perception of pressure like with IV opioids or epidural or subarachnoid injection of local anesthetic
• good for laboring, doesn’t block motor

Question 1

Describe receptor distribution

Answer 1

• all three (Mu, kappa, delta) found in high concentrations in the dorsal horn of the spinal cord
• mainly Mu receptors present in the substantia gelatinosa

Question 2

What is the MOA of neuraxial opioids?

Answer 2

Opioids placed in the epidural space diffuse across the dura to affect the Mu receptors on the spinal cord AND are absorbed to produce the effects like IV opioids

• highly vascular space
• higher lipid soluble fentanyls cross dura rapidly and are absorbed more systemically (may have no advantage over IV admin)
• less lipid soluble morphine has slower onset and longer duration

Question 3

What determines how fast agents diffuse across the dura with an epidural dose?

How much of the dose actually enters the CSF?

Answer 3

The more lipid soluble, the faster the diffusion into the CSF

*sufentanil > fentanyl > morphine

Only 3% of epidural dose enters CSF
*with fentanyl and sufentanil, probably a less % @ peak concentration d/t vascular absorption

Question 4

How fast does fentanyl reach its CSF peak concentration with and epidural?

Answer 4

20 min

Question 5

How fast does sufentanil reach its CSF peak concentration with an epidural?

Answer 5

6 min

Question 6

How fast does morphine reach its CSF peak concentration with an epidural?

Answer 6

1-4 hrs

Question 7

How are epidural opioids absorbed into vascular system?

Answer 7

• rapidly absorbed via the extensive venous plexus in the epidural space
• absorption produces blood levels similar to an IM injection
• less morphine goes to the blood

Question 8

How fast does fentanyl reach its peak blood concentration through vascular absorption with an epidural?

Answer 8

5-10 min

Question 9

How fast does sufentanil reach its peak blood concentration through vascular absorption with an epidural?

Answer 9

< 5 min

Question 10

How fast does morphine reach its peak blood concentration through vascular absorption with an epidural?

Answer 10

10-15 min

Question 11

How can vascular absorption be decreased?

Answer 11

Add epinephrine to the solution to cause vasoconstriction

• if injected into the epidural space, does not affect diffusion across the dura
• if injected into the subarachnoid space, analgesia is enhanced with morphine
• causes prolonged duration since it is not taken up into circulation

Question 12

What is the duration of morphine epidural?

Answer 12

4-24 hrs

Question 13

What is the duration of fentanyl epidural?

Answer 13

1-3 hrs

Question 14

How do opioids move once in the CSF?

Answer 14

• lipid solubility affect degree of cephalad movement (towards head)
• higher lipid solubility limits movement as drug is taken up by spinal cord (travels higher up spinal cord)
• lower lipid soluble morphine longer time in CSF and movement cephalad

Question 15

What accelerates movement of opioid cephalad?

Answer 15

Coughing or straining

• *not body position
• consider timing of emergence when placing…extubated? Done coughing?

Question 16

What affects side effects of neuraxial opioids?

Answer 16

• either with opioids in CSF or systemic circulation
• dose dependent
• may be r/t opioid receptors but now always
• bigger the dose, more chance of side effects

Question 17

What are the four classic side effects of neuraxial opioids?

Answer 17

• severe pruritus (most common)
• nausea and vomiting
• urinary retention
• ventilatory depression

Question 18

What is pruritus likely due to?

Answer 18

Opioids in CSF moving up to interact with opioid receptors in the trigeminal nucleus

• more likely in OB pts d/t estrogen effect on opioid receptors
• itching may be confined to face, neck or upper thorax or could be generalized

Question 19

How can the pruritus be treated?

Answer 19

narcan 0.25 mcg/kg/hr

• more effective than antihistamines which cause sedation
• enough narcan to reverse itching but not reverse analgesia

Question 20

What is urinary retention caused by?

Answer 20

Interaction of opioid with opioid receptors of the sacral spinal cord

• inhibition of sacral parasympathetic outflow causing detrusor muscle relaxation, increasing bladder capacity, and increased sphincter tone not allowing excretion
• occurs within 15 min and last up to 16 hrs

Question 21

When is urinary retention more common?

Answer 21

• in young males
• with neuraxial opioids than IV or IM
• not related to dose size or systemic absorption

Question 22

How is urinary retention reversed?

Answer 22

Narcan

*usually won’t use with young children having urology procedures

Question 23

What is the most serious side effect?

Answer 23

Ventilation depression

*1% incidence (same as with IV or IM)

Question 24

What is the onset of ventilatory depression?

Answer 24

Unpredictable onset- may be within minutes or 6-12 hrs after neuraxial morphine * early onset (within 2 hrs) with fentanyl and sufentanil d/t systemic absorption and cephalad movement * delayed onset with morphine as opioid moves up to effect receptors in the ventral medulla where respiratory center is

Question 25

What are some risk factors for ventilatory depression?

Answer 25

- larger doses - geriatric * received other opioids or sedative systematically - prolonged or extensive surgery (increased risk regardless) - presence of co morbidities (pulmonary or cardiac history) - thoracic surgery (dura morph given more with thoracic surgery)

Question 26

What increases the risk of delayed ventilatory depression?

Answer 26

- patient also receiving IV opioid or sedative - patient coughing to move opioid cephalad in CSF *dont need to give neuraxial opioids to same day patient, need to be monitored for sudden respiratory depression

Question 27

What decreases risk of ventilatory depression?

Answer 27

-increased stimulation from progesterone in OB patients

Question 28

What is the most reliable sign of ventilatory depression?

Answer 28

Decreased level of consciousness (sleep) possibly caused by hypercarbia - hypercarbia is a sympathetic stimulation * tachycardia, HTN, dysrhythmias

Question 29

What is the treatment for ventilatory depression?

Answer 29

- narcan (infusion may help) | - supplemental oxygen (helps with oxygenation not ventilation)

Question 30

What is sedation related to with neuraxial opioids?

Answer 30

Dose related * most common with sufentanil * *be alert for ventilatory depression

Question 31

What may happen with patients with herpes virus when given epidural morphine?

Answer 31

Reactivation - occurs 2-5 days post epidural admin - same sensory innervation as primary infection (facial areas innervated by trigeminal nerve) * d/t cephalad movement and interaction of trigeminal nucleus *usually don't use morphine with laboring patients

Question 32

What may happens with neonates?

Answer 32

respiratory depression of neonate from admin to maternal patient * r/t systemic absorption (fentanyl more lipid soluble to cross placenta) - minimal opioid found in breast milk

Question 33

What are some other misc. side effects of neuraxial opioids?

Answer 33

- miosis nystagmus, vertigo (balance) * delayed gastric emptying (if coming to surgery from floor and been on opioids treat as "full stomach") * decreased body temp d/t inhibition of shivering (resets body temp) * water retention d/t release of vasopressin (caution with CHF) * *spinal cord injury r/t effects of toxic preservatives (must use preservative free)