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Noxious stimulus :Is one that is painfuland potentially damagnormal tissues
Stimuli that are painful can be thermal,mechanical or chemical
Encyclopedia of Pain.G.F. Gebhart , Robert F. Schmidt . Springer; 2nd ed. 2013 edition
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"armful stimuli activate the peripheral endings ofprimary
a#erent neurons, also called nociceptors
$heir cell bodies lie in the dorsal root ganglia %DRthe trigeminal ganglia
Encyclopedia of Pain.G.F. Gebhart , Robert F. Schmidt . Springer; 2nd ed. 201
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Noxious stimuli ! Nociception :
() Neurogenic in*ammation %S+ &R+'
-) Descending modulatory input %i.e.,serotonin,N/+, 0)aminobutyric acid, en1eph
2)Impulses pass to the ventral and ventrolahorns %%spinal' re*ex responses'
3) Spinothalamic and spinoreticular tracts
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ontinuous release of in*ammatory mediators:Sensitization of peripheral nociceptors may occurmar4ed by
Decreased threshold for activation
Increased rate of discharge ith activation
Increased rate of basal %spontaneous' discharge
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Intense noxious input from the periphery may alsin central
sensitizationand hyperexcitability
entral sensitization:
+ersistent post in5ury changes in the NS that respain hypersensitivity
"yperexcitability:
/xaggerated and prolonged responsiveness of nenormal a#erent input after tissue damage
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67$8RS for
+++
+reoperativeIntraoperative
+ostoperative
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+S+ is relatively common after :
limb amputation %29 to ;2'
$horacotomy %-- to
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+reventive 7nalgesia
$his de@nition broadly includes any reggiven at any time during the perioperaperiod that is able to control pain)indusensitization
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Maximal clinical bene@tis observed hen complemultisegmental bloc4ade of noxious stimuli occurextension of this e#ect into the postoperative per
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$he analgesic bene@ts of contropostoperative pain are generallmaximized hen a multimodal
strategy to facilitate the patientconvalescence is implemented
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SBS$/MI 7N7C&/SI $/"NI
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8+I8IDS
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F8pium
piate!
"arcotic
8pioid
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$he modern ord GopiumH is derived from the &reord opion %Gpoppy 5uiceH'
Drugs derived from opium are referred to as opiat%morphine is the best)4non opiate'
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$he term narcoticis derived from the &ree4 ordstupor and traditionally has been used to refer to
morphine)li4e analgesics ith the potential to pro
physical dependence
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$he development of synthetic drugs ith morphinproperties has led to the use of the term opioidtoall exogenous substances, natural and synthetic, produceat least some agonist %morphine)li4e' e#
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8+I8IDS
8pioid analgesics are one of the cornerstone optithe treatment of postoperative pain
$hey generally exert their analgesic e#ects throureceptors in the NS, although opioids may also a
peripheral opioid receptors
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8pioids act as agonists at speci@c opioid receptorpresynaptic and postsynaptic sites in the central system %mainly the brainstem and spinal cord' as
in the periphery
8+I8ID R//+$8RS 6EN$I8N F
$hese opioid receptorsnormally are activated by endogenous peptide opioid receptor ligands 4noen$ephalin!, endorphin!, and dynorphin!%8pioidsthe actions of these endogenous ligands'
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Is analgesic ceiling for opioids F
7 theoretical advantage of opioid analgesics is th
there is no analgesic ceiling
Realistically, the analgesic eJcacy of opioids istypically limited by
Development of tolerance
8pioid)related side e#ects such asNausea, vomiting
Sedation
Respiratory depressionDr Mehran Rezvani pain felloship anesthesiologist
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>ecause analgesicand ventilatorye#ects of opoccur by similar mechanisms, it is assumed thaequianalgesic doses of all opioids ill producedegree of ventilatory depression and reversaventilator depression ith an opioid antagonis
involves some reversal of analgesia
Stoelting#! handboo$ of pharmacology and phy!iology in ane!thetic practice. %olter! &l201*
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Most common routes of postoperativesystemic opioidanalgesic administratiooral and intravenous
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In general, opioids are administeredparenterally %intravenously orintramuscularly' for the treatment ofmoderate to severe postoperative pain
part because these routes provide a mrapid and reliable onset of analgesic acthantheoral route does
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8ral opioids %typically formulated as paa combination product that includes anad5uvant such as acetaminophen' aregenerally prescribed on an as)needed
basis postoperatively
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7lthough the traditional form %passive' of transdefentanylis notindicated for the routine treatmentacute postoperative pain, a neer version involvipatient)activated electrically facilitated delivery otransdermal fentanyl has been developed for use hospitalized adult patients
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7 single dose ofsufentanil
, 9.( to 9.3 mgK4g IL,produces a longerperiod of analgesiaand lessdepression of ventilation than does a comparaboffentanyl %( to 3 mgK4g IL'
Eniue advantage of alfentanilcompared ith feand sufentanil is the more rapid onset of action
Stoelting#! handboo$ of pharmacology and phy!iology in ane!thetic practice&l'(er )ealth 201*
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Alfentanil,compared ith euipotent doses of feand sufentanil, is associated ith a lower incidepostoperative nausea and vomitingin outpat
$he advantageof remifentanil possessing a sho
recovery period may be considered a disadvanthe infusion is stopped suddenly
Stoelting#! handboo$ of pharmacology and phy!iology in ane!thetic practice&l'(er )ealth 201*
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ontext)sensitive half)time for remifentanil isindependent of the duration of infusion and estimated to be about 4 minutes %rapid clearesponsible for the lac4 of accumulation even durprolonged periods of infusion'
Stoelting#! handboo$ of pharmacology and phy!iology in ane!thetic practice&l'(er )ealth 201*
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+ne!the!iology.2003;-312/3
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+7$S+atient)
7ctivated$ransdermal
SystemDr Mehran Rezvani pain felloship anesthesiologist
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+7$S is a compact, needle)freeanalgesic deliveryrecently approved by the E.S. 6ood and Drug
7dministration
$he device is preprogrammed to iontophoreticallyadminister a 39)mcg dose of fentanyl %over a (9)mperiod' upon patient activation
$he self)contained device is applied ith adhesivepatientAs upper arm or chest for analgesic delive
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$he patient activates the system by pressing therecessed dosing button tice ithin 2 seconds
7dditional dosing reuests are preventedby the sduring drug delivery
$hus patients may self)administer up to < doses p
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$he fentanyl I$S operates for up to -3 hours or amaximum of ;9 doses %hichever occurs @rst', afhich it automatically shuts don.
$he system may then be removed and discarded,
ne system may be applied to a di#erent s4in sitadditional analgesia is reuired
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Med Devices (Auckl). 2008; 1: 4957Dr Mehran Rezvani pain felloship anesthesiologist
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&alia ", "ai$ +, Garri!on , G'y R). 200. ontophoretic dr'g deli4ery. +d4 5r'g 5eli4 Re4,*-. 7opyright 8 200 El!e4ier Dr Mehran Rezvani pain felloship anesthesiologist
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8pioid induced hyperalges%8I"'
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$he opioid)induced hyperalgesia resultedspinal sensitization to glutamate andsubstance +
holecysto4ininand the NMD7nitric oxidsystem and spinal serotonin activity are
responsible for the development of acutetolerance to opioids
9iller - chp 31
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8pioid)induced hyperalgesia and subseueacute opioid tolerance can be prevented by4etamine
Methadone is uniue in possessing both )oand NMD7)antagonist properties
9iller - chp 31 Dr Mehran Rezvani pain felloship anesthesiologist! acupuncturist
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8pioid)induced hyperalgesia resultfrom the presence of l)methadone opioid agonist' in the racemate anantagonized by the presence of d)
methadone %NMD7 antagonist'
9iller - chp 31
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N-8is an e#ective NMD7 antagonist
Intraoperatively, =9 N-8 administratsigni@cantly reduced postoperative op
induced hyperalgesia in one study
9iller - chp 31
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"yperalgesia after 29)minute
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"yperalgesia after 29)minuteintravenous infusion of remifent
%9.( gK4gKminute' could bepreventedby the administraof parecoxib, before remifentainfusion
suggesting the involvement of - in opioid)induced hyperalgesi
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+ostoperative hyperalgesia induby intraoperative remifentanilinfusion as signi@cant ithsevo*urane anesthesia but not
apparent ith propofol anesthes
9iller - chp 31
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In mice
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In mice
+revetion for 8I" as done ith :
Selective P-)adrenergic receptor antagonis
butoxamine
Systemic or intrathecal in5ection of theondansetron
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7 potential connection beteen 8I" +++ has been recently suggested as is a dose)dependent relationship betintraoperative remifentaniluse and +
after thoracic surgery
4an G'li$ :, +hler! S , 4an de Garde E9, et al. Remifentanil d'ring cardiac !'rgera!!ociated (ith chronic thoracic pain 1 yr after !ternotomy. r +nae!th 2013; 10
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Decreasing the opioid dose %39 to ?9' aadding ad5uvants or a lo dose of methadonbe used to treat opioid)induced hyperalgesi
S. %aldman P+" 9+"+GE9E">., El!e4ire 2011
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Indirectly, in comparison to general anesthesuse of intraoperative neuraxial anesthesia rethe ris4 of severe +++ at one year after total 4nee replacement a bene@t partly attributed opioid)sparing e#ect of the analgesic techni
:i' SS. + cro!!?!ectional !'r4ey on pre4alence and ri!$ factor! for per!i!tent popain 1 year after total hip and $nee replacement. Reg +ne!th Pain 9ed 2012; 3
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$hereby, the concept of opioid-spanesthesia %even more, Gopioid)franesthesiaH' may be a ma5or stepprevention of ++S+
:i' SS. + cro!!?!ectional !'r4ey on pre4alence and ri!$ factor! for per!i!tent pain 1 year after total hip and $nee replacement. Reg +ne!th Pain 9ed 2012
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Intravenous
+atient)ontroll7nalgesiaDr Mehran Rezvani pain felloship anesthesiologist
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+7 is based on the premise that a negative)feed
loop existsQ hen pain is experienced, analgesicmedication is self)administered, and hen pain isreduced, there are no further demands
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Stoelting#! handboo$ of pharmacology and phy!iology in ane!thetic practice&l'(er )ealth 201*
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Stoelting#! handboo$ of pharmacology and phy!iology in ane!thetic practic&l'(er )ealth 201* Dr Mehran Rezvani pain felloship anesthesiologist
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7lthough some euipment)related malfunctions c
occur, the +7
device itself is relatively free of problems, and moproblems
related to +7 use result from user or operator er
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7 +7 device can be programmed for several vari
Demand %bolus' dose
Coc4out interval
>ac4ground infusion
Dr Mehran Rezvani pain felloship anesthesiologist! acupuncturist
7lthough the optimal demand %bolus' dose is unc
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g pthe data available suggest that the optimal demais
( mg for morphine and 39 g for fentanyl in opioipatientsQ hoever, the actual dose for fentanyl %(g' is often less in clinical practice%bolus'
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$he loc4out interval is a safety feature of intraven
+7, and although the optimal loc4out interval isun4non, most intervals range from ? to (9 minudepending on the medication in the +7 pump
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Initially,routine use of a bac4groundinfusion predictedcertain advantages,including improved analgesia, especiaduring sleepQ hoever, analgesic bene
a bac4ground infusion have not beensuccessful in opioid)nave patients
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7 bac4ground infusion only increasesthe analges
dosage used and the incidence of adverse respiraevents in the postoperative period especially in asub5ects
6urthermore, use of a nighttime bac4ground infusdoes not improve postoperative sleep patterns,analgesia, or recovery pro@les
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7 bac4ground infusion in opioid)tolor pediatric patients may be e#ect
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Stoelting#! handboo$ of pharmacology and phy!iology in ane!thetic practice. %olter! &l'(er
Dr Mehran Rezvani pain felloship anesthesiologist! acupuncturist
Meperidine F
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Meperidine F
$he clinical use of meperidine has declined greatl
recent years +7 ith meperidine cannot berecommended because of possible
normeperidine toxicity
Large doses of meperidine result in decreasesinmyocardial contractility, hich, among opioidsunique for this drug
Stoelting#! handboo$ of pharmacology and phy!iology in ane!thetic practice
&l'(er )ealth 201*
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Then compared ith traditional +RN analgesic re
Intravenous +7 provides superior postoperativeanalgesia
and improves patient satisfaction, but it is uncleahether
intravenous +7 can provide any economic bene@
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+atientsusually preferintravenous +7intravenously, intramuscularly, orsubcutaneously administered +RN opio
Dr Mehran Rezvani pain felloship anesthesiologist! acupuncturist
hronic Methadone $herapy F
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hronic Methadone $herapy F
+atients on chronic methadone therapy should be re
on their oral methadone dose as soon as possible afsurgery to meet basal pain needsQ any additionalpostoperative analgesic reuirements can be met vi
+atients often reuire high doses and can usually re
them safely due to individualized opioid tolerance
Perioperati4e Pain 9anagement. Arman Bford Ani4er!ity Pre!! 2013
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$he incidence of opioid)related adverse events from
intravenous
+7 does not seem to di#er signi@cantly from that opioids administered intravenously, intramuscularlsubcutaneously
$he rate of respiratory depression associated ithintravenous +7 is lo (.? and does not appear higher than that ith +RN systemic or neuraxial op
Dr Mehran Rezvani pain felloship anesthesiologist! acupuncturist
6actors for respiratory depression ith opioid
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Ese of a bac4ground infusion
7dvanced age
oncomitant administration of sedative or hypnotic age
oexisting pulmonary disease such as sleep apnea
/rrors in programming or administration %i.e., operator e
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NS7IDS
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7cetaminophen
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7cetaminophen %paracetamol' is an antipyretic as
an analgesic that acts centrally by inhibitingprostaglandin synthesis
In a placebo)controlled study, patients receivingparacetamol reported no di#erence in their pain compared ith placebo only in the @rst < hours afsurgery, but the pain intensity as diminishedin paracetamol group from (- to -3 hours
Dr Mehran Rezvani pain felloship anesthesiologist! acupuncturist
$he lac4 of cardiovascular and hemorrhagic
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complications
ma4es it an alluring option
It may be bene@cialin reducing oral opiate reuirin patients susceptible to respiratory complicationopiates:
8bstructive sleep apneaIncreased intracranial pressure
Morbidly obese patients
+ediatric and elderly populationsDr Mehran Rezvani pain felloship anesthesiologist
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7dult oral acetaminophen,
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7cetaminophen should be used cautiously in patie
ith alcoholism, chronic malnutrition, severehypovolemia, or severe renal impairment
+atients ith severe renal impairment %creatinineclearance UrlV W 29 mCKmin' reuire longer dosintervals and a reduced total daily doseofacetaminophen
Perioperati4e Pain 9anagement. Arman Bford Ani4er!ity Pre!! 2013Dr Mehran Rezvani pain felloship anesthesiologist! acupuncturist
IL7 may mas4 fever in patients treated for postsurgical p
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IL7 may mas4 fever in patients treated for postsurgical pto its antipyretice#ect and conseuently may mas4 the postoperative infection and sepsis
7cetaminophen has produced transient hypotension in cpatients ith fever
$he hypotension is usually mild to moderate but transien
(? to 29 minutes after the beginning of an infusion, and maximal hypotension occurring beteen ( and - hours adosingPerioperati4e Pain 9anagement. Arman Bford Ani4er!ity Pre!! 2013
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Dr Mehran Rezvani pain felloship anesthesiologist! acupuncturist
Nonsteroidal 7nti)in*ammatory7gents
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7gents
$he primary mechanism by hich NS7IDs exert th
analgesic e#ect is through inhibition of cyclooxyg%8O'and synthesis of prostaglandins, hich areimportant mediators of peripheral sensitization anhyperalgesia
NS7IDs can also exert their analgesic e#ects throinhibition of spinal 8O
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$he discovery of at least to 8O isoforms
8O)( is constitutive and 8O)- is inducibledi#erent functions %i.e., 8O)( participates platelet aggregation, hemostasis, and gastrmucosal protection, hereas 8O)- particip
pain, in*ammation, and fever' has led to thdevelopment of selective 8O)- inhibitors
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$he discovery of a 8O)2 variant may represent a
primary central mechanismby hich acetaminopother antipyretics decrease pain and fever
Esed as a sole agent, NS7IDs generally provide eanalgesia for mild to moderate pain
NS7IDs are also traditionally considered a useful ato opioidsfor the treatment of moderate to sever
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"ichola! . ). 5a4ie! . :eeC! Synop!i! of +nae!the!ia, 13e 200*
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Several meta)analyses have examined the analge
eJcacy of NS7IDs %including 8O)- inhibitors' anacetaminophenhen added to intravenous +7 opioids
NS7IDs, not acetaminophen, resulted statistically signi@cantreduction in paiscores
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NS7IDs are particularly useful as
components of a multimodal analgregimen by producing analgesiathrough a di#erent mechanism tha
that of opioids or local anesthetics
Dr Mehran Rezvani pain felloship anesthesiologist! acupuncturist
+erioperative use of NS7IDs is associatith b f id # t
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ith a number of side e#ects:
Decreased hemostasisRenal dysfunction
&astrointestinal hemorrhage
Deleterious e#ects on bone healing a
osteogenesisF
Dr Mehran Rezvani pain felloship anesthesiologist! acupuncturist
7spirinand
diclofenacare the
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mostpotentially
hepatotoxicNS7IDs,
and shouldbe avoidedin patients
ithpreexistinghepaticfailure
).)emming!, P)+R9+7:G +"5 P)S:G FR +"ES>)ES+, E:SEDDr Mehran Rezvani pain felloship anesthesiologist! acupuncturist
NS7IDs cause signi@cant lengthening%by about 29'bleeding time, but usually still ithin the normal rang
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$his can last for days ith aspirin %(9)(3 D' but 5ust f
ith non)aspirin NS7IDs
Single 299 to X99 mg dose of ibuprofencan inhibit plaggregation for - hours after administration, and thelargely dissipated by -3 hours
1?%+:: +"5 9E:+7S >E>& F P+".2013
2?).)emming!, P)+R9+7:G +"5 P)S:G FR +"ES>)ES+, E:S
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$orecent systematic revies indicated that he
examining the highest)uality there as no increris4 of nonunion ith NS7ID
ertainly, a short)term NS7ID regimen can be usetreatment of postfracturepain ithout signi@cant
increasing the ris4 of disrupted
healing
Dr Mehran Rezvani pain felloship anesthesiologist! acupuncturist
7 brief %Y(3 days' exposure to normal)dose NS7I4etorolacY(-9 mgKday' as safe after spinal fusihoever use of large dose 4etorolac %Z(-9 mgKd
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hoever, use of large)dose 4etorolac %Z(-9 mgKdincreased the ris4 of nonunion, suggesting a
dose)dependent e#ect of perioperative NS7IDs onfusion healing
Spine surgeons ill more refuse to have postopespine fusion patients receive NS7IDs
Dr Mehran Rezvani pain felloship anesthesiologist! acupuncturist
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+erioperative NS7ID)induced renal in high)ris4pat
"ypovolemia
7bnormal renal function
7bnormal serum electrolyte
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NS7IDs may cause a clinically unimpor
transient reduction in renal function inearly postoperative period in patientsnormal preoperative renal function
Dr Mehran Rezvani pain felloship anesthesiologist! acupuncturist
$here does notappear to be a bene@t in usin- i hibit i t d f t diti l l ti
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- inhibitors instead of traditional nonselectivNS7IDs in reducing the incidence of renal
complications %miller@=
+reliminary evidence suggests that 8O)- inmay be an alternative hen attempting to av
the detrimentale#ects of nonselective NS7IDbone
"ealing %miller@=
Dr Mehran Rezvani pain felloship anesthesiologist! acupuncturist
>ronchospasm may be induced by NS7
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>ronchospasm may be induced by NS7%including aspirin' or acetaminophen
$here may be cross)sensitivity ithacetaminophen in aspirin sensitive
asthmatic sub5ects
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+c'te pain management , >aylor Franci! Gro'p. 7R7 pre!! 201*Dr Mehran Rezvani pain felloship anesthesiologist! acupuncturist
8O)- inhibitors are associated ith a loerincidgastrointestinal complications and exhibit minima
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platelet inhibition, even hen administered insupratherapeutic doses
Cong)term use of 8O)- inhibitors has been associth excess cardiovascular ris4 such that rofecoxi
ithdran from the mar4et
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7lthough cardiovascular toxicity appears to be a c
e#ect of all 8O)- inhibitors, the cardiovascular ri8O)- inhibitors appear to be heterogeneousandin*uenced by many factors such as the speci@cmedication, dosage, and patient characteristics
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$he use of parecoxib and valdecoxiba
7>&as associated ith an increaseincidence of cardiovascular events, thearousing serious concern about the usethese drugs in such circumstances
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Subseuent randomized controlled trial
investigating the safety and eJcacy ofparecoxib and valdecoxib after ma5ornoncardiac surgery found that patients received the 8O)- inhibitors had similar
freuencies of prede@ned adverse eventscompared ith those ho
received placeboDr Mehran Rezvani pain felloship anesthesiologist
! acupuncturist
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R.9ende!,.. Selecti4e inhibition of cyclooBygena!e?2 ri!$! and beneHt!, Re4. 4ol.*2 no.* SIo Pa'lo Sept.Jct. 2012
Dr Mehran Rezvani pain felloship anesthesiologist! acupuncturist
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+arecoxib, the only in5ectable coxib, is
particularly suitable for acute painmanagementas it can be given as anintramuscular in5ection
It provides rapid onset of e#ective anaithin (9(? minutes and lasts (--3
Dr Mehran Rezvani pain felloship anesthesiologist! acupuncturist
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1etorolac, until recently, as the only parenteral NS7ID avthe Enited States and as therefore used uite extensivel
perioperative period
7 standard dose %29 mg' of 4etorolac provides analgesia eto < to (- mg of morphine but has a longer duration of acto ; hours and lac4s the respiratory depressant e#ect of m
Perioperati4e Pain 9anagement. Arman Bford Ani4er!ity Pre!! 2013
+harmacology and physiology for anesthesia : foundations and clinical application, elsevi
Dr Mehran Rezvani pain felloship anesthesiologist! acupuncturist
1etorolac
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&astrointestinal bleeding and operative site bleedin
have also been reported and are mostly associated
7dvanced patient age
Duration of therapy beyond ? days
"igher dosing regimens
+harmacology and physiology for anesthesia : foundations and clinical applicatioelsevire -9(2
Dr Mehran Rezvani pain felloship anesthesiologist! acupuncturist
1etorolac
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6or a single dose :
29 mg IL(? mg if patient ageis greater than
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&abapentanoids
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&abapentin and pregabalin, antiepileptic drugs alin the treatment of neuropathic pain
8ral pregabalin is absorbed more rapidly and hasabsolute bioavailability%[X9 versus Y
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consumption and opioid)related side e#ects, but n
di#erence in pain intensity
7nother meta)analysis :
+erioperative administration of pregabalin may proadditional analgesia in the short term but also resuan increasein side e#ects such asdizzinessKlightheadednessor visual disturbances
Dr Mehran Rezvani pain felloship anesthesiologist! acupuncturist
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+erioperative administration of
gabapentin and pregabalin may rethe incidence of +S+
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NMD7 receptor antagonis
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Tind)Ep +henomenon
Dr Mehran Rezvani pain felloship anesthesiologist! acupuncturist
Repetitive stimulation of unmyelinated Cbers canprolonged discharge of dorsal horn cells, termed Gi
GTind upH is a short lived process hoever repetiti
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Tindup is a short)lived process, hoever, repetiti
/pisodes may precipitate long)term potentiation %C$+hich involves a long lasting increase in the eJcacy
synaptic transmissionand thus alters synaptic plasti
>oth GindupH and C$+ are believed to be important
components of central sensitization.Encyclopedia of Pain.G.F. Gebhart , Robert F. Schmidt . Springer; 2nd ed. 2013 ed
Dr Mehran Rezvani pain felloship anesthesiologist! acupuncturist
http://www.amazon.com/s/ref=dp_byline_sr_book_1?ie=UTF8&text=G.F.+Gebhart&search-alias=books&field-author=G.F.+Gebhart&sort=relevancerank7/25/2019 Acute Postoperative Pain 2015 part 2.pptx
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NeuroplasticityF
Dr Mehran Rezvani pain felloship anesthesiologist! acupuncturist
Neuroplasticity is a general term referring to per
changes in neural activity or function
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7 neuroplastic change is caused by freuent usa
neuron or a
neuronal connection , hich stays for a longer petime after the end of the neuronal activity that stathe change
Memory processes and the transition from acutechronic pain are examples of neuroplastic chang
Dr Mehran Rezvani pain felloship anesthesiologist! acupuncturist
Surgery or trauma leading to tissue damage andsubseuentin*ammatoryresponses causes nocicestimuli to be carried along peripheral sensory nerv
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stimuli to be carried along peripheral sensory nervthe spinal cord
$he NS responds to this persistent input from tperiphery ith adaptive processes commonly descas neuroplasticity
$his leads to the development of spinal cordhyperexcitability, a process referred to as centralsensitization
Dr Mehran Rezvani pain felloship anesthesiologist! acupuncturist
$he increased excitability is primarily the
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increased excitatory amino acid %/77' rele
particular glutamate
It is mediated by glutamate activation of "methyl)Daspartate %NMD7' receptors in th
horn neurons of the spinal cord
+c'te pain management , >aylor Franci! Gro'p. 7R7 pre!! 201*Dr Mehran Rezvani pain felloship anesthesiologist
! acupuncturist
$hese changes happen in all patients after acute
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$hese changes happen in all patients after acute and therefore central sensitization contributessigni@cantly to the pain experience after trauma osurgery
In most patients central sensitization lessensas
in5ury heals and acute pain resolves
+c'te pain management , >aylor Franci! Gro'p. 7R7 pre!! 201*
Dr Mehran Rezvani pain felloship anesthesiologist! acupuncturist
In some patients, central sensitization persists behealing and can then contribute to persistent pain
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g p p
8f note is that the mechanismsunderlythe development of tolerance to opioidsopioid)induced hyperalgesia are similar
central sensitization+c'te pain management , >aylor Franci! Gro'p. 7R7 pre!! 201*
Dr Mehran Rezvani pain felloship anesthesiologist! acupuncturist
Medications that either :Reducethedevelopme
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Decrease /77 release
%gabapentin andpregabalin'
or
7ct as antagonists at
NMD7receptors
+c'te pain management , >aylor Franci! Gro' . 7R7 re!! 201*
developmeindupansensitizatiodonregulhyperexcitsensitizatiota4en plac
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1/$7MIN/
Dr Mehran Rezvani pain felloship anesthesiologist! acupuncturist
Ese of lo)dose 4etamine for postoperative analg
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p p gdeveloped
NMD7)antagonisticproperties, may be important attenuating central sensitization and opioid tolera
Racemicmixtures of 4etamine have been found toneurotoxic,and therefore the use of neuraxial 4etis discouraged
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+erioperative4etamine reduced -3)hour +7 mor
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pconsumptionand postoperative nausea or vomitin
lo)dose 4etamine infusion does not appear to cahallucinations orcognitive impairment, and the inof side e#ects, such as dizziness, itching, nausea,
vomiting donAt change
Dr Mehran Rezvani pain felloship anesthesiologist! acupuncturist
%Low-dose& pain setting use'etamine
%(igher-dos
setting use
+revention of central sensitizationand reduction of developed centralsensitization 7ttenuation of tolerance and
$reatment +rocedural p emergency de
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1etaminepain setting
uses
sensitization 7ttenuation of tolerance and
hyperalgesia
+reventive analgesia in patients atincreased ris4 of developing persistentpaino 7fter nerve in)ury %surgical, traumatic, or other
cause
+rehospital s
7nesthet$reatment of poorly opioid)responsive pain "europathicpain *schemicpain +ain in opioid-tolerantpatients
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$ramadol is a synthetic opioid that exhibits ea4i i i d i hibi 4 f i
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agonist activity and inhibits reupta4e of serotonin
norepinephrine
7lthough tramadol exerts its analgesic e#ects pri
throughcentral mechanisms, it may have peripheral localanesthetic properties
Dr Mehran Rezvani pain felloship anesthesiologist! acupuncturist
$ramadol is e#ective in treating moderate
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postoperative
+ain
omparable in analgesic eJcacy to aspirin
mg' ith codeine %
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is 4non to improve the eJcacy of tramadol in relievin
$ramadol is metabolised to 8)desmethyltramadol, hicmore potent opioid
$he addition of acetaminophen to tramadol %versus tra
alone' may decrease the incidence of tramadolAs side eithout
reducing its analgesic eJcacy
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Regional 7nalgesic
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Regional 7nalgesic$echniues
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7dministration of a single dose of opioid may beeJcacious as a sole or ad5uvant analgesic agent
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e cac ous as a so e o ad5u a a a ges c age
administered intrathecally or epidurally
Cipophilicity or "ydrophilicity FFF
Dr Mehran Rezvani pain felloship anesthesiologist! acupuncturist
"ydrophilic opioids %i.e., morphine andhydromorphone' tend to remain ithinS6 and produce a delayed but longerduration of analgesia along ith a gen
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duration of analgesia, along ith a gen
higher incidence of side e#ects becausthe cephalic or supraspinal spread of tcompounds
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Ese of a single)dose hydrophilic opioidbe especially helpful in providingpostoperative epidural analgesia hen
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epidural catheterAs location is not congith the surgical incision %e.g., lumbarepidural catheter for thoracic surgery'
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7n extended)release formulation of %single)dose'
morphine encapsulated ithin liposomes that res
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morphine encapsulated ithin liposomes that res
up to3;
hours of analgesia has recently been introduced
oncurrentadministration of liposomal extended)
morphineand local anesthetics may increase peaconcentrationsof morphine
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/pidural infusion of local anesthetic alone is less e
in controlling pain %in compare to local anesthetic
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epidural analgesic combinations'
$he precise location of action of local anesthetics epidural space is not clear, and potential sitesinc
spinal nerve roots, dorsal root ganglion, or spinal itself
Dr Mehran Rezvani pain felloship anesthesiologist! acupuncturist
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$he soleuse of local anesthetics is lesscommon than the use of a local anesth
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opioid combination because of a signi@failure rate %from regression of sensorybloc4ade and inadeuate analgesia' anrelatively high incidence of motor blochypotension
Dr Mehran Rezvani pain felloship anesthesiologist! acupuncturist
8pioids for /pidural Infusio
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$he analgesic site of action for continuhydrophilic opioid infusion is primarily
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Ese of a continuous infusion rather thaintermittent boluses of epidural morph
may result in superior analgesia ith feside e#ects
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oncentrations used for postoperativeepidural analgesia %^9.(-? bupivac
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or levobupivacaine or ^9.- ropivacaare loer than those used forintraoperative anesthesia
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clonidine %? to -9 gKhr'
Ris4s:
"ypotension %dose dependent'
>radycardia %%dose dependent'
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Sedation
+ther drugs
/pinephrine %- to ? gKml'
1etamine F
Dr Mehran Rezvani pain felloship anesthesiologist! acupuncturist
Cocation of atheter Insert
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Dr Mehran Rezvani pain felloship anesthesiologist! acupuncturist
Insertion of the epidural catheter congruent to theincisional dermatome :
8ptimal postoperative epidural analgesia
Mi i i i id # t % l t it
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Minimizing side e#ects %e.g., loer extremity moand urinary retention'
Decreasing morbidity
Coer drug reuirements
Decreased medication)related side e#ects
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Ese of thoracic epidural analgesiafor abdominal othoracic surgery may result in a relatively lo inc
of urinary Retention
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of urinary Retention
+lacement of thoracic epidural catheters appearsrelatively
safe, and there is no evidence of a higher incidenneurologic complications ith placement of a tho%versus lumbar' epidural catheter
Dr Mehran Rezvani pain felloship anesthesiologist! acupuncturist
R/8MM/ND/D 7$"/$/R INS/R$I8N SI$/S 68R S
+R8/DER/SCocation of Incision /xamples of Surgical +rocedures /pid
+lac
$horacic Cung reduction,Radical mastectomy, thoracotomy, thymectomy
$3);
Epper abdominal holecystectomy, esophagectomy, gastrectomy,
hepatic resection Thipple procedure
$
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hepatic resection, Thipple procedure
Middle abdominal ystoprostatectomy, nephrectomy $=)(
Coer abdominal 7bdominal aortic aneurysm repair, colectomyRadical prostatectomy,$otal abdominal hysterectomy
$;)
Coer extremity 6emoral)popliteal bypass, total hip or total 4neereplacement
C()3
Dr Mehran Rezvani pain felloship anesthesiologist! acupuncturist
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"ypotension
Incidence of postoperative hypotension ithpostoperative epidural analgesia may be as high the average may be 9.= to 2
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oDecreasing the overall dose of local anestheticadministered
oInfusing an opioid epidural alone
o$reating the underlying cause of the decrease inpressure
Dr Mehran Rezvani pain felloship anesthesiologist! acupuncturist
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Motor >loc4
Motor bloc4 resolves in most cases after stoppinepidural infusion for approximately - hours
+ersistent or increasing motor bloc4 should be
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+ersistent or increasing motor bloc4 should beevaluated promptly:
Spinal hematoma
Spinal abscess
Intrathecal catheter migration
Dr Mehran Rezvani pain felloship anesthesiologist! acupuncturist
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Nausea and Lomiting
$reatment:
Naloxone
Droperidol
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Droperidol Metoclopramide
Dexamethasone
8ndansetron
$ransdermal scopolamine
Dr Mehran Rezvani pain felloship anesthesiologist! acupuncturist
ruritus+ruritus is one of the most common side#ects of epidural or intrathecaladministration of opioids, ith an incide
of approximately
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of approximately
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Intravenous naloxone Naltrexone
Nalbuphine
Droperidol
Dr Mehran Rezvani pain felloship anesthesiologist! acupuncturist
Respiratory Depression
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Dr Mehran Rezvani pain felloship anesthesiologist! acupuncturist
Neuraxial opioids used in appropriate doses are nassociated ith a higher incidence of respiratorydepression than that seen ith systemic opioids
I id f N i l i id 9 ( t 9 X
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Incidence for Neuraxial opioids W 9.( to 9.X
Neuraxial lipophilic opioids are thought to causedelayed respiratory depression thanhydrophilic
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Ris4s factors
Increasing dose
Increasing age
concomitant use of systemic opioids or sedative
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concomitant use of systemic opioids or sedative +ossibly prolongedor extensive surgery
$he presence of comorbid conditions %e.g., obstructiapnea'
$horacic surgery
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Erinary Retention
Erinary retention associated ith the neuraxialadministration of opioids is the result of an interith opioid receptors in the spinal cord that decr
the detrusor muscleAs strength of contraction
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the detrusor muscle s strength of contraction
Erinary retention does not appear to depend on opioid dose and
Ese of lo)dose naloxone, though at the ris4 ofreversing the analgesic e#ect may be useful
Dr Mehran Rezvani pain felloship anesthesiologist! acupuncturist
Erinary Retention
/pidural administration of local anesthetics is alsoassociated ith urinary retention, ith a reportedapproximately (9 to 29
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"igher epidural infusion rates of local anestheticsgreater extent of sensory bloc4 and a higher incidmotor bloc4' may be associated ith a higher inc
of urinary retention
Dr Mehran Rezvani pain felloship anesthesiologist! acupuncturist
67I7C S1IN 7N/S$"/S
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Supraorbital and Supratroch
Nerves
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Nerves
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>loc4ade of the mental nerve as it exits the mentforamen provides
anesthesia to the loer lip and chin
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$he foramen is palpated in the mandible, and a -gauge, 2)cm needle is inserted inferomedially. In@of - to 3 mC of solution after
elicitation of a paresthesia or in the region of the results
in anesthesia of the mental nerveDr Mehran Rezvani pain felloship anesthesiologist
! acupuncturist
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Stellate &anglion >loc
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7 --) gauge, 3)cm short)beveled needle ith a (-syringe attached is inserted in a perpendicular diruntil the tip contacts the < transverse process
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$he needle is then ithdran 2 mm and @xed. 7ftcareful aspiration, ; to (- mC of local anesthetic sis in5ected
Dr Mehran Rezvani pain felloship anesthesiologist! acupuncturist
Signs of a successful stellate ganglion bloc4 :
"ornerAs syndrome
7nhidrosisIn5ection of the con5unctiva
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In5ection of the con5unctiva
Nasal stuJness
Lasodilation
Increased s4in temperature
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Dr Mehran Rezvani pain felloship anesthesiologist! acupuncturist
Side /#ects and omplications
>loc4 of the brachial plexus
>loc4 of recurrent laryngeal nerves
"ematoma formation
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"ematoma formation
Intravascular In5ection resulting in convulsions
/pidural and subarachnoid in5ection
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+atient)ontrolled /pidura7nalgesia
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6or +/7as /I, addition of an opioid to the localanesthetic can provide analgesia superior to that either agent alone
li hili i id i ll h b i
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7 lipophilic opioid is usually chosen because its raanalgesic e#ect and shorter duration of action mamore suitable for use ith +/7
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Dr Mehran Rezvani pain felloship anesthesiologist! acupuncturist