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RODENTANESTHESIA&ANALGESIAFORMULARY
Background
Thisguidelineisdesignedtoprovideasinglesourceofinformationforinvestigatorsthat
userodentsmodelsofbiomedicaldiseaseanddiscovery.Thefollowingtablesreference
contemporaryliteratureandareamodificationofasimilarpresentationofinformation
inarecentlyupdatedchapterfromAnesthesiaandAnalgesiainLaboratoryAnimals
(AcademicPress;Gaertneretal.2008).Investigatorsarealwaysstronglyencouragedto
consultwithULARveterinariansinthedesignoftheiranimalresearchprojects,including
theselectionofthemostefficaciousanestheticandanalgesicregimensfortheanimals
andthemodel.
(CS)=ControlledSubstance.Theseagentsarescheduledascontrolledsubstancesby
theDrugEnforcementAgency.Speciallicensingisrequiredinordertoprocureand
prescribeacontrolledsubstance.Applicationsforlicensuremaybecompletedonline.
INDUCTIONAGENTS
Someinductionagentsandpremedicationscalmtheanimal,smoothanesthetic
inductionandrecovery,andreducethedoseofanestheticagentneeded,butare
seldomusedpriortorodentanesthesiaduetotheadditionalstressofadministeringa
secondinjection.Preemptiveanalgesiashouldbeadministeredwiththeinduction
agents.
Anestheticinductionofarodentwithinhalantsoftenrequirescloserattentionthan
duringmaintenanceofanesthesiaduetotherelativelyhighdosesusedforandthe
rapidonsetofinduction.
Whendrugsaregivenbyinjection,thedosagecannotbereducedafterinduction.
Therefore,drugsateitheralowdoseorwithawidesafetymarginshouldbeused
forinjection.
Subcutaneous(SC)administrationofanestheticsisnotrecommendedbecausethe
inductionofanesthesiaisprolongedandvariableinonset.
Intravenousinjectionsinrodentscanbeperformedbymorehighlytrained
personnel.
Formostpurposes,generalanesthesiainrodentsispreferredtolocalizedanesthesia
becauseitisbelievedtoreducestresstotheanimalandincreasesafetyfor
personnel.
Smallmammalsrequireanalmostcontinuoussupplyoffoodandwater;accordingly
fastingandwaterdeprivationshouldbeminimizedpriortoanestheticinduction.
IACUCGuideline
RODENTANESTHESIA&ANALGESIAFORMULARY
Doserange
INDUCTIONAGENT
Isoflurane
Propofol
Species
(mg/kg,unless
otherwisespecified)
Routeof
Administration
Mice
4%
Inhaled
Neonatalmice
24%
Inhaled
Rats
5%
Inhaled
Mice
26
IV
Rats
10
IV
ANESTHETICS
Onemustadministerappropriateanesthesiatoanimalsundergoingproceduresthat
causemorethanmomentaryorslightpainordistress.Anestheticsrendertheanimal
unconsciouswithoutlossofvitalfunctions.Itisimportanttoprovideappropriateand
gentlerestraint,asufficientamountofanalgesiatodiminishpainsensationduringthe
procedure,andrelaxationofmuscletonetothedegreethatprocedurescanbe
performedquicklyandefficiently.
Inhalantanestheticsprovideasafe,reliable,reversible,andreproduciblemeansof
renderingrodentsunconsciousinordertoperformsurgeriesandotherintricateor
potentiallypainfulprocedures.
Inhalantanesthesiaofsmallrodentsisgenerallymaintainedutilizingfacemasksor
nosecones.Endotrachealintubationhasalsobecomeamorecommonpracticein
miceandratsandshouldbeconsideredwhereappropriate.
Injectableagentsmayallowmultipleanimalstobemaintainedunderanesthesiaat
thesametime.Longerperiodsofanesthesiacanbeaccomplishedbyrepeated
injectionsorbyconstantrateinfusions(CRI).
Whenusingparenteralanestheticsitisimportanttoconsideraccuratedosingwith
correctmultidruguseratios,storageconditions,andfeasibilityofimmediateuse
followingreconstitution.Itiscriticaltoweigheachanimalaccuratelypriorto
administrationofacalculateddoseofanesthesiatoavoideitheroveror
underdosing.
IACUCGuideline
RODENTANESTHESIA&ANALGESIAFORMULARY
Doserange
ANESTHETIC
Species
(mg/kg,unless
otherwisespecified)
Routeof
Administration
Rats
114ofa5%
solution
3165
Mice
60150
IM
Mice
60120
IP
Rats
1025
IV
Rats
2530
IP
Guineapigs
80%for60s
Inhaled
Mice
80%for120s
Inhaled
Rats
80%for60s
Inhaled
Mice
370400
IP
Rats
300450
IP
Rats
400600
SC
Mice
0.081.5%
Inhaled
Neonatalmice
0.252.5%
Inhaled
Rats
0.252.5%
Inhaled
Rats
2%I/5M
Inhaled,IP
Ketamine(CS)/
Diazepam(CS)
Mice
100K/5D
IP
Rats
40K/5D
IP
Ketamine(CS)/
Midazolam(CS)
Mice
5075K/110M
IP
Rats
60K/0.4M
IP
Ketamine(CS)/
Xylazine
Mice
90150K/7.516X
IP
Rats
4080K/510X
IM,IP
Ketamine(CS)/
Xylazine/
Acepromazine
Medetomidine/
Fentanyl(CS)
Medetomidine/
Sufentanil(CS)
Sevoflurane
Mice
100K/2.5X/2.5A
IM
Rats
40K/8.0X/4.0A
IM
Alphachloralose
Alphaxolone
alphadolone
Carbondioxide
Chloralhydrate
Isoflurane
Isoflurane/
Morphine(CS)
Mice
Rats
Rats
Rats
200300ug/kg/
300ug/kg
150ug/kg/40
50ug/kg
22.4%
IP
IP
IP
SC
Inhaled
IACUCGuideline
RODENTANESTHESIA&ANALGESIAFORMULARY
Sodium
pentobarbital(CS)
Mice
3090
IP
Rats
3060
IP
Tiletamine(CS)/
Zolazepam(CS)
Thiobarbital
(Inactin)(CS)
Tribromoethanol
(TBEorAvertin)
Rats
2040
IP
Mice
80
IP
Mice
125300
IP
Tribromoethanol/
Medetomidine
Rats
150/0.5(reversal
2.5mg/kg
atipamezole)
IP
ANALGESICS
Improvedpainmanagementforrodentsisanimportantgoalintheuseofexperimental
animals.Onemustadministeranalgesiatoanimalsundergoingproceduresthatcause
morethanmomentaryorslightpainordistress.Analgesicsreduceorrelievepain
withoutlossofconsciousness.Theavoidanceorminimizationofdiscomfort,distress
andpaininlaboratoryanimalsisamoralimperativeforallindividualswhoworkwith
thesespeciesinbiomedicalresearch.
Systemicand/orlocalanalgesicsmayalsoreducetheanestheticrequirements,and
haveapreemptiveeffectonpainperceptionwhichpersistsintotherecovery
period.
Notonlypreoperative,butalsoimmediatepostoperativeanalgesicadministration
isimportantforadequatepainreliefinpostsurgicalrodents.
Themostcommonlyusedanalgesicsinrodentsandotherlaboratoryanimalspecies
areopioidsandnonsteroidalantiinflammatorydrugs(NSAIDs).Theultimate
decisionforselectionofdrugmustbebasedupontheexperimentalmodelunder
studyandthespecifictypesofdatatobecollected.
Stress,pain,anddistresshaveaneffectontheimmunesystem.Severalviable
optionsexistforreliefofpaininchronicmodelsofinflammationandinfection.
Doserange
ANALGESICS
Species
(mg/kg,unless
otherwisespecified)
Route
Acetaminophen
(Tylenol)
Rats
50
SC,IP
Rats
100
PO
IACUCGuideline
RODENTANESTHESIA&ANALGESIAFORMULARY
Aspirin
Buprenorphine
(Buprenex)(CS)
Butorphanol(CS)
Carprofen
(Rimadyl)
Celecoxib
Clonidine
Clonidine/
Morphine(CS)
Diclofenac
Dipyrone
Dipyrone/
Morphine(CS)
Ethylcarbamate
Ethylcarbamate/
alphachloralose
Fentanyl(CS)
Flunixinmeglumine
(Banamine)
Rodents
110305
PO
Rodents
110305
IP
Rats
100
PO
Rodents
20
SC
Rodents
100120
IP
Mice
SC
Mice
1.1mMinDMSO
Topical
Rodents
0.0020.055
IV
Rodents
0.040.13
IP
Rats
0.050.5
SC,IP
Rats
0.4
PO
Mice
SC
Rats
SC
Rats
515
SC
Rats
1020
PO
Mice
0.250.5
PO
Mice
0.0010.1
IP
Rats
0.025C/0.5M
IP
Mice
9.028
IP
Rats
SC,IP,IV
Mice
50600
177600D/3.13.2
M
10001500
250400EC(30
minutespriorto
alphachloralose)
0.0250.6
Mice
0.032
SC
Rats
0.011.0
SC
Rats
2.04.0g/day
PO
Mice
4.011
IV
Rats
Rats
Rats
SC,IV
IP
IP
SC
IACUCGuideline
RODENTANESTHESIA&ANALGESIAFORMULARY
Ibuprofen(Advil),
Motrin,Nuprin)
Ibuprofen/
Hydrocodone(CS)
Ibuprofen/
Methadone(CS)
Ibuprofen/
Oxycodone(CS)
Ketoprofen
(Ketofen)
Lidocaine
(Xylocaine)
Lidocaine/
Buprenorphine(CS)
Meloxicam
(Metacam)
Mice
40
PO
Rats
200I/2.3H
SC
Rats
200I/1.7M
SC
Rats
200I/0.5O
SC
Rats
515
SC
Rats
IP
Mice
1020
0.671.3mg/kg/h
CRI
0.44mML/0.18
mMBinDMSO
1.010
Rats
1.04.0
SC,IP
Rats
Mice
SCpump
Topical
IP
Meloxicam/
Tizanidineor
Clonidine
Meperidine(CS)
Mice
0.5M/0.25T
PO
Mice
20
IP
Methadone(CS)
Rats
0.53
SC
Mice
10
SC
Mice
6.1mMinDMSO
Topical
Rats
2.010
SC
Rats
2.8
SCL
Rats
200N/1.3H
SC
Mice
SCL
Rats
0.03mg/kg/hCRI
IV
Rats
0.1
IV
Rats
1.21.6
SCL
Physostigmine
Rats
50200g/kg
SC
Tizanidine
Tizanidineor
Clonidine/
Nimesulide
Mice
0.251.0
PO
Mice
0.25T/1.0N
PO
Morphine(CS)
Naproxen/
Hydrocodone(CS)
Oxymorphone(CS)
IACUCGuideline
RODENTANESTHESIA&ANALGESIAFORMULARY
Tramadol
Mice
2040
IP
LOCALANDTOPICALANESTHETICS
Localanestheticssuchaslidocaine,bupivicaineandothersmaybeusedtoreducethe
perceptionofpainatthesurgicalsiteaslocalorregionalanesthetics.Inconjunction
withotheragents,theirusemayallowreducedlevelsofgeneralanesthetics,whichmay
speedrecoveryandminimizemortality.Whencarefullyused,directinjectionofalocal
anestheticcanbeausefuladjuncttoanesthesia.
LOCALORTOPICAL
ANESTHETICS
Bupivicaine
Lidocaine/
Morphine(CS)
Lidocaine/
prilocainecream
(EMLACream)
Doserange
Species
(mg/kg,unless
otherwisespecified)
Route
Rodents
Localinfiltration
0.85mM/1.7mM
inDMSO
SC
Mice
Rodents
Localapplication
Local
Topical
REVERSALAGENTS
Reversalleadstoearlyterminationofanesthesiawhichmayreducemortalityandallow
rapidreturnoftherodentstothehomecageenvironment.Reversalagentsalsoreverse
bradycardiaandbradypnea,butdonoteliminatethehypothermiceffects,thusthermal
supportremainsessential.Ifreversalagentsareused,boththeanestheticandanalgesic
propertiesofthedrugmaybeterminated,thusalternativesourcesofanalgesiamustbe
provided.
Doserange
REVERSALAGENTS
Atipamezole
(Antisedan)
Flumazenil
Levallorphan
tartrate
Species
(mg/kg,unless
otherwisespecified)
Route
Rats
0.5
SC
Rodents
10nmol
IP
Rodents
0.89
SC
IACUCGuideline
RODENTANESTHESIA&ANALGESIAFORMULARY
Naloxone
hydrochloride
Rodents
20
IP
REFERENCES
Gaertner,DJ,TMHallman,FCHankenson,MABatchelder.2008.Anesthesiaand
AnalgesiainRodents.AnesthesiaandAnalgesiainLaboratoryAnimals.SecondEdition,
AcademicPress,CA.
ApprovedMay27,2008