What are eventual and adverse effects of untreated pain?
What is the neural gateway for all our pain sensations that gets afferent and efferent input?
What are two chemicals released by our cells in response to injury that are precursors to eventual pain signal transduction?
Arachidonic acid (after modification by phospholipase A2)
In the spinal cord, where do pain signal transduction occur?
They run through the dorsal root ganglia which eventually congregate at the dorsal horns (carries signals up to the sensory cortex)
Describe the axonal tracts of neurons involved in pain signal transmission in the spinal cord.
Nociceptive-specific and WDR (wide dynamic-range) neurons send their axons up the dorsal horn and ant-lat spinothalamic tract.
These tracts synapse on 3rd order neurons in the contralateral thalamus (opposite side).
3rd order neurons project to the somatosensory Cx.
Note: 1st order neuron = initial pain signal, 2nd order neuron = the nociceptive-specific and WDR neurons aforementioned
3 classes of NT cmds integral to pain transmission
List and give examples.
Excitatory amino acids (glutamate, aspartate)
Excitatory neuropeptides (substance P, neurokinin A)
Inhibitory amino acids (glycine,GABA)
Are NMDA receptors involved in pain transmission?
Yes. This is why ketamine has analgesic properties.
What are traits of dynamic pain?
Pt can move
Relief provides improved outcome
What are the characteristics that describe pain (general)?
List 3 non-opioid systemic analgesics.
What is the analgesia ceiling effect?
Dose at which analgesia is maximized.
Beyond that, side effects increase (greater toxicity) without any additional benefits to the patient.
What is the does for adults and childre for acetaminophen?
Adults: 1 g QID
Children: 10-15 mg/kg
Studies of COX inhibitors have demonstrated improved post-op analgesia with up to X percent reduction in opioid analgesia requirements. What number(s) = X?
What are anesthetic benefits of NSAID as shown by research?
Reduced pain with movement
Reduced bladder spasm pain
Opioid sparing (up to 40%)
Earlier recovery of GI function
Describe the dosing of Ketorolac.
>50 kg: 30 mg IV q6
<50 kg: 15 mg IV q6
Children: 0.5 mg/kg q6
Limit dosing to < 5 consecutive days
What are complications of NSAIDs? Is there a special age group we need to worry about?
Operative site bleeding (bigger issue for cranial and ENT procedures)
Acute renal failure
**These risks are shown to be much more significant in pts > 75 y/o
Describe the mechanism of current NSAIDs.
They inhibit COX activation of prostaglandins.
COX = cyclo-oxygenase (comes from arachidonic acid)
Prostaglandins support renal and platelet functions, protect gastric mucosa, and lead to inflammation + pain.
Why were COX 2 inhibitors developed?
COX 1 (constitutive) was known to mediate effects on GI, renal, and plt systems.
COX 2 (inducible) was known to mediate effects on inflammatory sites.
Therefore, inhibition of COX 2 would theoretically avoid all the negative effects of non-selective COX inhibitors.
Describe what research has found out about our current COX 2 selective inhibitors.
-Similar analgesic effects to non-selective COX inhibitors
-Improved GI safety
-No plt effects
-Renal side effects still present
-Possible adverse CV and neuro effects with long-term use
What is a commonly seen COX-2 inhibitor? Describe dosing.
100-200 mg PO q12
No need to withold. Dose pre-op or immediately post-op
Does tolerance, physiologic dependence, and withdrawal from opioids indicate addiction?
Characteristics of opioid agonists include...
Full mu-receptor binding
No analgesic ceiling
Equianalgesic doses = equivalant efficacy
Similar side effects profiles
Different metabolites and elimination profiles
Effects on pain are highly patient variable!
Traits of opioid agonist-antagonist combinations include...
-Kappa agonism + partial/full mu antagonism
-Respiratory depression ceiling (although this ceiling is pretty high [~20 mg morphine], so still a concern)
-Acute withdrawal with mu-agonists
-Psychomimetic side effects
Approximate differences between peak-plasma levels and time-to-peak levels between IV and IM opioids are.. (give me a multiple)
Compared to IV opioids, IM opioids:
Peak plasma levels: 2-5 x lower
Time to peak: 3-7 fold higher
*Peaks and troughs in plasma levels rather than a steady plasma peak as in IV opioids
Note: HIGHLY patient variable
Are IM opioids safe?
Not really. Erratic absorption means severe respiratory depression can occur spontaneously.
No advantage over oral route* (more erratic)
Describe the elimination of Morphine. (Active metabolites, excretion)
Active metabolite = M6G
90% renal excreted
Any contraindications to morphine that we commonly see? What's a good long-acting alternative opioid we commonly give?
Yes: renal dysfunction due to active metabolite and predominantly renal excretion
Hydromorphone: 6x as potent as morphine; good alternative
What is the best opioid agent to use in pts with renal dysfunction?
Describe this drugs relative potency, onset, and duration to morphine.
80-100x more potent than morphine
Compare meperidine with morphine.
When is this opioid usually used?
Its 1/10th as potent as morphine
Has active metabolites (normeperidine) that provide no analgesic properties like M6G.
Contraindicated in renal dysfxn, siezures, MAOIs
Its pretty much used only if pt is intolerant to all other opioid agonists.
Give me the equianalgesic doses with 10 mg morphine for Dilaudid and fentanyl.
10 mg morphine = 1.5 mg hydromorphone = 100 mcg fentanyl
Is opioid consumption for pain correlated better with weight or age?
Very little correlation with weight (shallow slope)
Whhat very negative adverse effects can acute reversal of opioids cause?
Due to acute reversal of analgesia, reversing opioids too rapidly with Naloxone can cause acute MI, seizures, or pulmonary edema!
How should Naloxine be dosed?
Titrate 40 mcg q2-3 min to RR > 12/min
Infusion (due to spinals or IM overdose): hourly rate = load/3
For full respiratory arrest: 0.2 mg increments
Note: at MHTMC and most other places, comes in 0.4 mg bottles (titrate into a 10 cc syringe)
Risk factors for respiratory depression with PCA include..
Advanced pulmonary disease
Concurrent administration of sedatives/hypnotics (avoid benzos)
When should you use PCA with a basal/background infusion of more opioids?
If used, what limit should be placed on the rate of basal infusions?
Opioid tolerant patients
Children 5-12 y/o
Extreme extreme pain
Keep BI < 50% of total consumption possible that hour (titrate)
What is the dose of morphine for intrathecal/spinal and epidural analgesia?
Intrathecal = 0.1-0.5 mg
Epidural = 2-5 mg
Compare the use of bupi with ropi in epidurals (general pain mngmt)
Bupi causes differential sensory blockade
Ropi causes less motor blockade (lumbar)
When we give epidural opioids, where's the site of action we hope they get to exert their effects most?
Dorsal horn of the spinal cord to block pain signals presynaptically
What are hydrophilic opioids? Lipophilic opioids?
What difference does it make in spinals?
Hydrophilic = morphine, Dilaudid
Lipophilic = fentanyl, sufentanil, etc.
Hydrophilic = slow onset, long duration, extensive CSF spread, more side effects, delayed respiratory depression
Lipophilic = fast onset, short duration, minimal CSF spread, lower side effects profile
What are advantages of epidurals/spinals?
Superior pain relief
Decreased DVT and graft occlusions
Earlier return of bowel function
Less pulmonary complications
Unlike lipophilic opioids, the administration of hydrophilic opioids can cause two (rather than one) phases of respiratory depression.
Why do these two phases occur?
FIrst phase is an acute phase due to systemic absorption (equivalent to same dose given IM)
Second dose is due to cephalad CSF spread (lipophilics don't spread as much or last as long)
This second phase peaks in 8-10 hours and plateaus for >18 hours. Occurs in 0.1-0.6% pts.
Treat with naloxone load + infusion.
What are some common analgesic adjuncts?
Hydroxyzine (first gen anti-histamine with multiple antagonistic effects, not well studied)
Clonidine (or other alpha 2 agonists)
What is Gabapentin used for?
Used as an antisiezure drug.
Effective in treating neuropathic pain, comeplx regional pain syndrom
Can block development of hyperalgesia
Due to ability to effect nociceptive processes involving central sensitization
What kind of surgeries have been implicated to be the most likely predictor of chronic pain outcome?
(Followed by thoracotomies and breast surgeries)
What are some predictive factors for chronic pain?
Pre-op: repeat surgery, psychologic vulnerability, worker's comp (lol)
Intraop: nerve damage risk in surgery
Post-op: radiation Rx, chemo Rx, depression, psychologic vulnerability, anxiety, neuroticism