Anesthesia in experimental animal surgery

U. Windberger, DVM, BSc Department Biomedical Research MedUni Wien

Basically:

n  Sedation n  Analgesia n  Relaxation

Basically:

n  Volatile Anesthetics n  TIVA n  Combinations

What else? n  Artificial ventilation (O2 vs. CO2) n  Intravenous infusion regime n  Acid-base balance n  Temperature (not > Δ1°C) n  Hemodynamics

Ventilation n  Supporting spontanous breath:

n  CPAP/PEEP (FRC increased) n  SIMV (Seufzer)

n  Substituting spontanous breath: n  Controlled ventilation

•  Volume controlled •  Pressure controlled

n  High Frequency Ventilation, HFV (ARDS, at high CO2) n  Mixed forms of ventilation

n  Biphasic positive airway pressure, BIPAP

Fluid balance (1)

Fluid input n  Ringer´s solution,

saline n  HES, Dextrane n  Blood transfusion n  Diverse short infusions

Fluid output n  Urine n  Bleeding n  Drain n  Blood samples n  Breathing n  Saliva (ruminants)

Basis: 10 mL/kg/h Ringer´s -lactate + potassium, starting with 15 mL/kg/h Restoration of volume (slowly), Dextran, Hämaccel, HES warmed

Fluid balance (2)

Blood n  Slowly, warmed blood, catheter with big lumen (not via venflon) n  (20 mval Ca++ per 500 mL blood!!)

•  Autologous whole blood, max 3 weeks, coll storage (post transfusion lung, -hepatitis)

•  Autologous blood from Cell-Saver •  Homologous blood (twins, sheep, rodents, rabbits) •  Frozen autologous plasma •  Humane albumine

n  Transfusion reaction: treatment •  Volume •  Oxygen, controlled ventilation •  corticosteroids •  Stabilize blood pressure •  NaHCO3 •  Heparine •  Diuretics

n  Avoid bleeding during surgery n  Training n  Controlled hypotension n  Acute normovolämic hemodilution

Acid-base balance n  BGA (0,7 ml blood / 0.2 ml blood in capillary) n  Metabolic acidosis: BE x kgBW/4 mval NaHCO3

n  Metabolic alkalosis: BE x kgKG/4 mval Lysin.HCl n  Respiratory acidosis: elevate tidal volume n  Respiratory alkalosis: decrease tidal volume

Necessary preparations n  Fasting depends on species and experiment n  Always water ad lib. n  Bedding for thermoregulation n  preOP und postOP individual housing with contact to other

animals n  Shaving, cleaning of skin, fur, claws

n  Conditioning on specific manipulations postOP (personal, measuring instruments, treadmill)

Premedication (1) n  Premedication is species

specific n  Depends on animal

type and temperament, feasibility of venous cannulation in the conscious animal

Premedication (2) n  Benzodiazepines

•  Midazolam •  Diazepam

n  Barbiturates •  Thiopentone

n  Neuroleptics •  Promazin •  Butyrophenone

n  Dissoziative anesthetics •  Ketamine in combination with Xylazin

n  Analgetics •  Opiates not alone for premedication

n  Anticholinergics •  Atropine only for ruminants (saliva)

Start n  Measure body weight n  Premedication i.m. or s.c. n  Animal on the table n  Ear vein cannulation n  Application of pharmacon until loss of consciousness n  Orotracheal intubation n  Eye ointment n  Fixation n  Gastric tube, bladder catheter, rectal temperature probe n  ECG n  Thermoregulation n  Preparation of skin for surgery

Intubation rat

Intubation rat

Rat ventilated

Rat, tail vein

Rat preOP

Intravenous anesthesia n  TIVA: each species

(except mice) n  pro: good adjustment

(Propofol), use of Ketamine to avoid hypotension

n  contra: in rodents cannulation of a vein might be problematical

or volatile anesthesia

n  Useful for each species n  1-2 Vol% (closed system)

n  pro: good adjustment n  contra: decrease of

blood pressure n  Problematic during

electrophysiologic measurements

Anesthetics (1) n  Benzodiazepines: premedication and TIVA n  Opiates: always n  Ketamine, Xylazin: premedication and TIVA n  Propofol: TIVA n  Barbiturates: premedication n  Relaxants: if needed n  Volatile: Isoflurane

Anesthetics (2) n  Benzodiazepines

•  Not alone for surgery! •  Anticonvulsant, anxiolytic, paradox reaction •  Minor respiratory depression when given alone •  Respiratory depression when given with opiates •  No major influence on cardiovascular system

n  Opiate •  Respiratory depression •  Brain perfusion decreases •  Anti-stress •  Hypotension, venous pooling •  Histamine release •  Take care of drug half-life in case of antagonisation

Anesthetics (3) n  Ketamine

•  Analgesia, amnestic (catalepsy) •  Increase of brain pressure! •  Emergency drug (limited respiratory depression) •  Increase of blood pressure (systemic and pulmonal) •  Pos. chronotropic – sympathomimetic •  Pos. inotropic – cardiac output increases •  Cardiac work load increases

n  Xylazine (α2-agonist) •  Sedating, hypnotic, relaxant •  Potentiates Ketamine

Anesthetics (4) n  Barbiturates

•  Take care of respiratory depression •  Decreases brain pressure •  Neg. inotropic •  Decreases blood pressure and preload •  Reflectory tachycardia, VPCs

n  Propofol •  No analgesia •  Decreases brain perfusion and O2-consumption in brain •  Neg. inotropic •  Decreases blood pressure •  Brady- or tachycardia

Volatile anesthetics n  Isoflurane

•  brain •  Spasms (ton.-clon.), O2-consumption decreased,

dilates brain vessels (metabol. coupling deranged, ischemic regions?), brain pressure relatively stable

•  Cardiovascular system •  VPCs, neg. inotropic, cardiac filling pressures increase,

coronary dilatation (shunt, steal) •  Direct action on vascular wall + autonomic NS,

hypotension, •  Lung

•  FRC decreases, death space increases, HPV diminished (shunt)

•  Kidney •  GFR decreases, nephrotoxicity (fluoride),

•  Splanchnic compartment •  Liver perfusion decreases, hepatotoxicity of Halothane

Typical combinations

n  Ruminants n  Atropine (1mg i.m.) n  Thiopentone 15 mg/kg i.v. bolus n  Fentanyl 0.1 mg/kg i.v. bolus n  Fentanylbypass: 0.01 mg/kg/h n  Propofolbypass: 10 mg/kg/h

Typical combinations n  Pig

n  No atropine!!! n  20 mg/kg Ketamine + 1.76 mg/kg Acepromazin i.m. n  Thiopentone 15 mg/kg i.v. bolus n  Fentanyl 0.1 mg/kg i.v. bolus n  Fentanylbypass: 0.016 mg/kg/h n  Propofolbypass: 10 mg/kg/h

Pig intubated

Pig: ear artery for pressure monitoring and blood gas

Typical combinations n  Rabbit

n  25 mg/kg Ketamine + 2 mg/kg Xylazin i.m. n  50 mg Ketamine + 2 mg Xylazin ad 5 ml NaCl n  Ketaminebypass: 60 mg/kg/h n  Fentanylbypass: 0.15 mg/kg/h; Fentanylbolus: 0.025 mg n  Or: Xylazinbypass: 2 mg/kg/h n  If necessary Isoflurane

Rabbit: ear vein and ear artery

Rabbit intubation

Typical combinations n  Rat

n  100 mg/kg Ketamine + 5 mg/kg Xylazin i.p. n  0.6-1 Vol% Isoflurane

n  50 mg/kg Thiopentone i.p.

Typical combinations n  Mouse

n  100 mg/kg Ketamine + 10 mg/kg Xylazin i.p. •  1 ml Ketamin® + 0.1 ml Rompun® ad 10 ml saline: give

0.1 ml per 10 g mouse. •  Re-dosing is done using a forth of the dose to effect

Monitoring during anesthesia n  Minimum requirement (except mouse)

n  ECG n  ETCO2 n  Inspiratory pressure n  Body temperature n  Clinical examination!

n  Long-term surgery n  Arterial blood pressure (invasive)

n  If necessary n  CVP, PAP, PCWP, CO

Monitoring during anesthesia

n  Blood gas n  arterial: paCO2, pH,

HCO3, O2-sat, paO2

n  venous: O2-sat, pH, BE n  Electrolytes

n  K, Na, Ca, n  Substrates

n  glucose, lactate

Anticoagulation n  Heparin i.v. (low MW)

•  Total anticoagulation (HLM): 300 IE/kgBW i.v. postOP anticoagulation: 30 IE/kgBW i.v. every 8-12 hrs.

n  Lovenox s.c. (large animals) •  40 mg twice daily

n  Protamin: to antagonize heparin •  Take care of blood pressure decrease! Same

amounts of units as heparin. Start with half of dosis

End of anesthesia n  Stop bypasses and volatile anesthetics n  Criteria for extubation

n  Spontaneous breaths against 10 mmHg n  SaO2 >95% at FiO2 0.3; paO2 >70 mmHg n  paCO2 <45 mmHg

n  Warm up (Bair-Hugger) n  Suction from intratracheal tube n  Silence n  Eyelid reflexe positive n  Start postoperative therapy against pain n  Start postoperative management against stress in pigs to

prevent overheating

Postoperative therapy n  i.v.-infusions n  Oxygen via mask n  Warm up or cool down (pigs) n  Antibiotics (start preOP, follow 3 days) n  Smooth bed made of bedding material n  Personal care!!!

Postoperative analgesia n  Cave: respiratory depression

n  Sufficient spontanous breaths n  Start as early as possible n  Control the animal

•  Animals does not eat •  Animal has buckled back •  Respiration is accelerated •  Pulse/heart frequency is accelerated • movements •  Loss of body weight (chronic pain/distress)

Postoperative analgesia n  Opiates

n  Bolus s.c. oder i.m. (during the night!) •  Buprenorphin each 4-8 hrs. •  Piritramid each 6-8 hrs.

n  Via drinking water (rodents) •  Piritramid ad lib.

n  Ketamine n  i.v. bypass

n  Nonsteroid antiphlogistics •  Metamizol each 8 hrs.

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