Case 68 - acute pain mgmt Flashcards
methadone characteristics
methadone
- long acting opioid
- half life 72-96 hrs
- bioavail 98%
- QT prolongation - obtain EKGs
tolerance vs dependence vs addiction
tolerance
- repeated exposure of medication with diminished clinical effect
Dependence
- abrupt cessation causes withdrawl symptoms - HTN, tachycardia, insomnia, craving sensation
Addiction
- compulsive use despite harm or craving
what are the mech of action of NSAID and gabapentin in terms of pain relief
NSAID
- inhibit prostaglandins and inflammatory cytokines in the periphery
Gabapentin
- inhibition of presynaptic glutamate secretion in substantia gelatinosa via inhibition of Ca2+ gated channels
- glutamate –> neurotrans involved with pain transmission
what are some of the clinical implications of inadequate postop analgesia?
- effects every system
- pain causes intense catecholamine surge
1) cards
- tachy = increase o2 consumption, MI
- vasoconstrict = cardiac dysrhythmias, MI
2) endo
- increased cortisol level =dec inflammatory response
- increase glucose = poor wound healing
3) heme
- pain and stress = hypercoaguable state = DVT, PE
- decreased immunity - postop infection
4) Resp
* splinting -> atelectasis & pneumonia
5) GI
* Ileus
6) discharge
* delayed mobility, prolong hospilization, delayed rehab, stress for patient and family, poor satisfaction
how is pain classified?
Pain classification
1) somatic
- superficial anatomic structure (skin, muscle, ligament)
- stabbing, achy, able to pinpoint area
- Alpha-delta fibers
2) Visceral
- deeper structures like organs
- diffuse, vague, poorly defined
- C fibers
somatic and visceral pain
- further divided into neuropathic pain or non-neuropathic pain
- non-neuropathic pain divided into sympathetic mediated or non-sympathetic mediated
- sympathetic mediated - assoc with allodynia (pain to nonnoxious stimuli), hypereshtesia (inc sensitivity to nonoxious stimuli)
briefly, what is the pain transmission form peripheray to central?
- nociceptors (mechano, electrical, chemical) sense an insult and release mediators (prostaglandin, cytokine, Interulekin)
- generates chemical transmission to DRG via alpha-delta and C fibers
- pain crosses over in spine to lateral spinothalamic tract and goes to higher central levels.
what is the role for NMDA receptors in central sensitizatoin?
NMDA receptor activation plays a role in maintaining impusles from peripheray by keeping their postsynpatic channels open for long periods
ketamine and methadone - play a role reducing postop pain in pts who have tolerance or depndent on high doses of preop opioid
which agents could be used intraop to diminish postop opioid use?
Tylenol
- 650mg - 1g shown to decrease opiod use in major ortho surgery
Toradol
- 30 mg equivalent to 10mg of morphine IV
- bleeding 2/2 inhibit plt aggregration, renal failure
Ketamine
- NMDA receptor antagonist
- 0.5 mg/kg/hr infusion intraop and continued 1-2 days post-op (monitored setting)
Methadone
- NMDA receptor antagnoist
- 5 to 10mg IV, long acting opioid, 95% bioavail
- analgesic level compared to 10mg of morphine within first 60 min
What are the advantages of neuraxial technique when compared to parenteral opioids?
Neuraxial advantages
- less total opioid consumption
- use of LA and clonidine
- enhance analgesia while decreasing use of opioid via neuraxial and parenteral route
- decreaes opioid-induced side effects
- resp depression, pruritus, n/v, constipation
- possible improved rates of satisfaction
Overall, what are the advantages of performing neuraxial analagesia?
1) efficacious level of analgesia
* decrease splinting –> dec atelectasis and infection
2) vasodilation of LA
- reduce afterload
- decrease myocardial workload –> dec risk of adverse cardiac events
3) increase unopposed vagal output to GI tract
* promotes gastric emptying time (reduces ileus)
4) decrease opioid use
- decrease bladder urinary retention
- decrease urinary tract infections
5) decrease stress response to surgery
* decrease incidence of thromboembolic events (stress causes hypercoaguable state)
what is the main mechanism by which opioids produce analgesia in epidural space?
- neuraxial opioids activate mu receptors in the substantia gelatinosa of the spinal cord dorsal horn
- when given thru spinal, there will be direct contact
- when given thru epidural, opioid has to transfer through the dura matter
- rate of dura transfer deneds on lipophilicity and dose of opioid administered
Which epidural opioids produce a fast onset of action, which opioids produce a delayed onset of action?
- epidural opioid actions involve transfer across dura matter to substantia gelatinosa of spinal cord
-
lipophilic opioids = fentanyl, sufentanil
- quicker onset of action
-
less lipophilic opioids = hydromorphone and morphine
- delayed onset of action, cephalad migratoin with concern of delayed onset of adverse effects (resp depression)
- need monitoring for at least 24 hours post-op
Morphine
- due to less lipophilicity, onset of epidural analgesia is 30-60 min
-
less lipophilic molecules travel cephalad in epidural and intrathecal space
- can get delayed supraspinal analagesia and risk for respiratory depression
briefly describe the mechanism of action of Local Anesthetics in the epidural space
Local Anes
- added to epidural opiod infusino to achieve higher dermatomal level of analgesia and anesthesia + decrease opioid dose
- inhibit Na+ gated channels along the nerve –> increase threshold for membrane depolarizatoin
- small myelinated A-delta and unmyelinated C fibers (nociception fibers) are blocked first before large myelinated A fibers (senosory, motor)
what is onset of action of LA determined by?
1) concentration
2) lipid solubility
* more lipid soluble LA leads to faster onset of action
3) pKa of LA
- most LA are weak bases
- when placed in blood (physiologic pH 7.4), there is higher proportion of ionized form
- non-ionized form - actually crosses nerve membrane
- ionized form - actually binds and inhibits Na+ channel intra-cellularly. Needs to get through nerve membrane first via non-ionized form
- closer the pKa is to physiologic pH (7.4), greater the proportion of nonionized molecules = faster onset
How can the addition of bicarbonate speed the onset of action? Does it work for all LA?
LA properities
- Almost all LA are weak bases, pKa ranging from 7.9-9
- hydrochloride salts are added to LA for molecular stability (particulary for LA esters and LA with epinephrine added to it).
- hydrochloride salts are mildly acidic, therefore the solution itself is acidic.
- LA mixed within an acidic solutoin results in higher proportion of ionized form
- Bicarb added to alkalize the LA solution so that the pH of the solution is closer to pKa of LA –> increase of non-ionized form of LA –> faster onset of action
Remember - bicarb added to LA solution can cause the drug to precipitate.
