VT 215_Week6_Lecture_Mice+Rats Anesthesia+Analgesia1.pptx
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VT 215: Laboratory Animal Science Week 6 Lecture: Mice & Rats: Anesthesia & Analgesia Kati Marshall, CVT, RLATG, CMAR, BS Objectives Know where to find SLA Anesthesia Formularies Understand that (in labs) ALL procedures MUST be approved by IACUC List unique Sx & anesthesia needs as they pertain to...
VT 215: Laboratory Animal Science Week 6 Lecture: Mice & Rats: Anesthesia & Analgesia Kati Marshall, CVT, RLATG, CMAR, BS Objectives Know where to find SLA Anesthesia Formularies Understand that (in labs) ALL procedures MUST be approved by IACUC List unique Sx & anesthesia needs as they pertain to mice & rats Understand that Lab animal medicine has specific requirements Understand that lab animals MUST be treated for pain List pros and cons of both inhalant & injectable anesthesia Understand that No documentation = NEVER HAPPENED Surgery in Laboratory Animals Classification of surgery Major vs. minor Major – enters body cavity or impairs movement or physiological function Minor – does not enter body cavity or cause impairment Survival vs. non-survival Survival – animal wakes up Non-survival – euthanized while anesthetized Would you be able to explain the difference between a major vs minor surgery? Surgery in Laboratory Animals Implants Placement of IV access port, indwelling catheter Telemetry device Cannulae Animal Tumor as surgical model or tissue implants Study tumor response to treatment Reproductive studies (Hormone manipulation – ovex, orchiectomy) Clinical – same as pets Mice & Rats Anesthesia, Sedation, Analgesia U.S. Government Principle V Procedures with animals that may cause more than momentary or slight pain or distress should be performed with appropriate sedation, analgesia, Momentary or slight pain/distress = or anesthesia. blood collection, injection, similar level of invasion and time required to perform procedure When to use anesthesia, sedation or analgesia Surgery Certain laboratory procedures CSF tap Imaging When necessary to handle animal safely aka ‘chemical restraint’ To decrease stress during minimally invasive procedure Local anesthetics – aka Locals Nerve blocks: Sx, dental & diagnostic procedures and pain management Infiltration: for minor Sx procedures & dentals Lidocaine Bupivicaine Other -caines Nerve blocks Incision line infiltration Dilution required typically Analgesics – aka pain meds Opioids Buprenorphine Meloxicam BupSR Carprofen Ethique Fentanyl injectable Morphine NSAIDS Analgesics NSAIDS Meloxicam Carprofen Research Considerations: May interfere with research results Dilution typically required Or specialized preparations Analgesics Opioids Buprenorphine BupSR Ethique** Fentanyl injectable Morphine Dilution typically required Or specialized preparations Be able to list the PO methods Analgesia administration IP: Common for initial dose Sustained release formulations SQ: Depends on absorption, formulation Would PO be PO a good Drinking water Gel cups Chews Gavage option for malocclusio n? Mammals and N0n-Traditional species Finding Formularies Examples from ONPRC Mathing Drug Doses in Small Mammals and N0n-Traditional species Where do you get them? Textbooks Journal articles Formularies What if there isn’t a dose for the drug/species??? Pilot studies Direct studies Extrapolation ▪ May not account for basal metabolic differences Experience Advice from colleagues Resources: Formularies, Textbooks, Journals Drug dilution for small rodents Typically necessary for accurate dosing of mice Balance: Ability to accurately measure drugs Volume for injection site Ease of administration ▪ Consider needle hub for small volumes ▪ Comfort of animal ▪ Speed of administration ▪ pH & physical parameters of solution Use sterile saline for injection for dilution Discard single dose vials after 1 day Med Contains Diluted Oxytocin Common Usage Dosage Notes Dystocia 0.5mls SQ 2nd dose @ 30min Diluted Ketoprofen 1mg/ml (dilute 0.1ml 100mg/ml ketaprofen with 9.9mls sterile saline Analgesia .07mls/30gm NSAID analgesia Tetracycline (liquid) 250mg/ml Diarrhea 18mls/300ml water bottle SIDx7.Replace and repeat for another 7 days Remove 18mls of H20 Add the med Mix well Trimethoprim Sulfa (TMS) Sulfamethoxazol e and Trimethoprim (200mg/40mg per 5mls) General antibiotic .03ml PO Baytril Enrofloxacin 100mg/ml General antibiotic 1.9mls/250mls drinking water Replace weekly Online Calculator for weight dosage: http://reference.medscape.com/calculator/weight-dosing Selecting Anesthetics you list Selection of AnestheticsCan the pros and cons? Injectables Injectable Pros: ▪ No need for specialized equipment ▪ May provide analgesia ▪ Easy to administer ▪ IP most common: often longer duration of action compared to IV ▪ No exposure to WAGs ▪ Ideal when unencumbered access to head is needed Injectables: Cons: ▪ Titration is challenging ▪ Longer induction and recovery period ▪ Can also be a pro ▪ Increases risk of hypothermia ▪ Risk of peritonitis or bleeding with IP injections ▪ Higher rate of anesthetic complications/death ▪ Controlled substances Injectable Anesthesia/Sedation Common cocktails: Ketamine + acepromazine Ketamine + xylazine Ketamine + xylazine + acepromazine +/- Benzodiazepines as adjunctive agent Pentobarbital for specific projects Type of research and effects of anesthetic agents are key considerations Mouse Injectable Anesthesia https://animal.research.uiowa.edu/iacuc-guidelines- Selection of Anesthetics Inhalants Can you list the pros and cons? Pros: Rapid induction and recovery ▪ Can also be a con Rapid titration to effect Lower rate of anesthetic complications/de ath Cons: ▪ Specialized equipment required ▪ Potential exposure to WAGs ▪ Face mask may obstruct procedures around the head ▪ Some species (hedgehogs) hold their breath ▪ Some species have a lag in response & then are overly anesthetized (ferrets) Inhalant anesthesia Isoflurane most common Induction = Chamber Maintenance = Typically via mask/nosecone Rodents are obligate nose breathers Non-rebreather set-up Indications for intubation ▪ Surgery involving head ▪ Thoracotomy Inhalant anesthesia: Ind uction Inhalant anesthesia: Maintenance Inhalant anesthesia: Low flow Intubation of Small Rodents NOT ROUTINELY DONE DUE Poisseuille’s Law TO Intubation of small rodents Not routinely done Why? Can you describe what Poisseuiile’s Law is, and how it relates to mouse anesthesia? Poisseuille’s Law ▪ Fluid dynamics of laminar flow ▪ Small change in airway diameter leads to big changes in airway resistance ▪ 50% decrease in airway diameter = 16X increase in resistance Intubation of small rodents Rivard, et al, Journal of Investigative Surgery, 19:2676274, 2006 Intubated small rodents must be ventilated Ventilators for small mammals Necessary for intubated rodents These machines are Automatic Ventilators for rodents - you’ll want to remember that term Surgical Standards for Small Laboratory Rodents Brought to us by the letter “G”, for The Guide for the Care and Use of Laboratory Animals Pre-Operative Prep Anesthetic Depth Peri-Operative Monitoring & Support Post-Procedural Monitoring Surgical Standards The Guide for the Care & Use of Laboratory Animals Successful surgical outcomes require appropriate attention to: presurgical planning personnel training anesthesia aseptic and surgical technique assessment of animal well-being appropriate use of analgesics animal physiologic status during all phases of a protocol involving surgery and postoperative care Pre-operative Preparation Patient Preparation Remove hair Clippers Nair Sterile prep Povidone iodine Chlorhexidine Drapes Clear drapes are best for monitoring Pre-operative Preparation Equipment sterilization Autoclave Ethylene oxide Bead sterilizer Chemicals Povidone iodine Chlorhexidine Glutaraldehyde Anesthetic depth Which reflex is best for assessing mice? 1. Pedal reflex Most accurate reflex in rodents 2. 3. 4. 5. 6. Lack of purposeful movement Loss of righting reflex Respiratory rate and character Lack of response to external stimuli Pinnal response Most useful in rabbits 7. Ocular position Not useful in rodents 8. Palpebral reflex Not useful in rodents 9. Tail pinch – more useful with rats ASSESS MORE THAN ONE REFLEX! Stages of Anesthesia Stage 1 Excitatory Disorientation, vocalization, urination, defecation Stage 2 Loss of consciousness, +/- paddling/movement Loss of righting reflex (many other reflexes still intact) Rigidity, rapid irregular breathing Stage 3 Surgical stage of anesthesia Loss of reflexes Muscle relaxation, deep and rhythmic breathing Planes 1-4 (light to deep) Stage 4 : Not Desirable! Medullary paralysis with respiratory arrest Hypotension and imminent death CPR and reversal agents required or animal will die. Small mammal https://lafeber.com/vet/anesthetic-depth-in-exotic-animals-monitoring-the-degree-of-central-nervous-system-depre ssion/ Pollock CG, Nugent-Deal J. Anesthetic depth in exotic animals: monitoring the degree of central nervous system Large mammal Peri-operative Monitoring Specialized monitors required Temperature Respiratory rate Heart rate Pulse oximetry Capnography Blood pressure Can you list the #1 cause of perioperativ e death? Peri-operative Support Heat Warm water pad Right Temp pads Snuggle safe disc Hot Hands Baer hugger Must prevent hypothermia! ▪ #1 cause of perioperative death Fluids Subcutaneous Intraperitoneal Eye lubrication (why is this important?) Post-procedural monitoring REQUIRED by IACUC Pain Rx must be administered according to protocol Rx must be documented Distress Adverse reactions RECORD KEEPING!!! Monitoring Pain U.S. Government Principle IV Would you assume something that hurts you, would also hurt an animal? “Unless the contrary is established, investigators should consider that procedures that cause pain or distress in human beings may also cause pain or distress in other animals.” AALAS Position Paper: Alleviating Pain & Distress in Laboratory Animals https:// www.aalas.org/about-aalas/position-paper s/alleviating-pain-and-distress Read on your own; focus on: ▪ Humane Endpoints ▪ If signs of pain are the same across species Monitoring Pain Difficult in rodents Animals are often stoic ▪ Prey species Signs of pain are subtle Signs of pain are not apparent Pain Scoring Systems Objective criteria Weight, food intake, types of activities Behavior/absence of behavior ▪ Nest building ▪ Burrowing Consistent across multiple observers Specific to a particular species Rats different from mice Specific to the kind of pain Acute different from chronic Requires extensive training of observers Videotaping Pain in Rodents Hunched posture Lethargic Flinching Abdominal press Writhing Abdominal stretch Chewing at incision Grimace Scale Grimace Scale Data Collection Accurate pain scoring requires extensive, remote observation Assessment during active phase is most accurate Need baseline scoring for comparison ▪ Habituate to chamber first Videotaping ▪ Software frames and captures images of face ~ q 2-3 minutes ▪ Video for 30-45 minutes Still photographs ▪ Multiple images over defined time periods “Live” assessments are challenging. Why? Rat Grimace Scale 4 Criteria Assessed: 1. Orbital Tightening 2. Nose/Cheek Flattening 3. Ear Changes 4. Whisker Change Rats: Orbital Tightening 0 1 2 e: Closed eyes without orbital tightening is evidence of relaxation (not p Higher numbers = painful animal Rats: Nose/Cheek Flattening 0 1 2 Higher numbers = painful animal Rats: Ear Changes 0 1 2 Higher numbers = painful animal Rats: Whisker Change 0 1 2 Higher numbers = painful animal Mouse Grimace Scale 5 Criteria Assessed: 1.Orbital Tightening 2.Nose Bulge 3.Cheek Bulge 4.Ear Position 5.Whisker Changes Mouse: Orbital Tightening 0 1 2 Higher numbers = painful animal Mouse: Nose Bulge 0 1 2 Higher numbers = painful animal Mouse: Cheek Bulge 0 1 2 Higher numbers = painful animal Mouse: Ear Position 0 1 2 Higher numbers = painful animal Mouse: Whisker Changes 0 1 2 Higher numbers = painful animal Grimace Scale Scoring Per photo: Grimace scale score= Sum of each “action unit” ▪ Some scales use the average of the action unit sums ▪ Must also score baseline photos ▪ Baseline may not be zero ▪ Scorer must be blinded to condition (baseline v postprocedure) Pain score = (Post-procedure GS score) – (Baseline GC score) Establish a pain scoring chart ▪ Cut-offs for pain/possible pain/no pain ▪ When is treatment (or additional treatment) needed? ▪ In humans: Higher numbers = painful animal ▪ Change of 2 points from baseline is considered clinically important Wrap-Up All procedures MUST be approved by IACUC Mice & rats have unique Sx needs Lab animal medicine has specific requirements Animals MUST be treated for pain No documentation = NEVER HAPPENED Did we meet these objectives? Know where to find SLA Anesthesia Formularies Understand that (in labs) ALL procedures MUST be approved by IACUC List unique Sx & anesthesia needs as they pertain to mice & rats Understand that Lab animal medicine has specific requirements Understand that lab animals MUST be treated for pain List pros and cons of both inhalant & injectable anesthesia Understand that No documentation = NEVER HAPPENED Questions?
