IACUCGuideline

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.


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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


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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


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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


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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


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RODENTANESTHESIA&ANALGESIAFORMULARY
Naloxone
hydrochloride

Rodents

20

IP

REFERENCES

Gaertner,DJ,TMHallman,FCHankenson,MABatchelder.2008.Anesthesiaand
AnalgesiainRodents.AnesthesiaandAnalgesiainLaboratoryAnimals.SecondEdition,
AcademicPress,CA.

ApprovedMay27,2008