ANALGESIA, ANESTHESIA AND POST-OPERATIVE CARE IN LABORATORY ANIMALS Thiago Vignoli, PhD Médico Veterinário CRMV SP 20615 Initial Considerations • Procedures involving pain or discomfort to the animals, included euthanasia • Essential knowledge: physical restraint/handling, routes of administration, appropriate equipment, vital parameters • Anti-inflammatories, antibiotics, sedatives, tranquillizers, analgesics and anesthetics • Copy or know that you are using! Choice of Technique Species-responses to agents Temperament and physical condition of the animal Familiarity with the animal Degree of invasiveness and duration of the procedure Prior experience with certain anesthetics Availability of equipment and drugs, as well as staff training Factors Influencing Anesthesia • Fasting* • Usual medication • Age • Species/Animal strain • Nutrition • Body and environmental temperature • Stress • Gestation • PAM • Invasive procedures, duration, etc. Surgical Procedure Steps • Preparation laboratory: surgical field, anesthetics and solutions • Animal Care: housing, handling, drug administration (Respect!) • Environmental Care: Asepsis, noise, movement of people, light and odors PRE-ANESTHETIC MEDICATION • Reduce stress of handling, aggressiveness and fear • Facilitates the preparation for surgery and other procedures • Reduces anesthetic dose and their undesirable effects PRE-ANESTHETIC MEDICATION 1) ANTICHOLINERGICS - Parasympatholytic action; reduction of bronchial and salivary secretions (Flecknell et al., 1990; Harrison et al., 2006) Atropine 0,04 mg/Kg (SC, IP, IM) 2) TRANQUILLIZERS - Produce calming effect, drowsiness, reduced fear / anxiety, hypnotic, anticonvulsant (Pieri, 1981; Amrein, 1990) Neuroleptics: Acepromazine Benzodiazepines: Dizepan, Midazolan PRE-ANESTHETIC MEDICATION 3) SEDATIVES - Produce sedation, hypnosis, muscle relaxation, ataxia, analgesia * (Murrell and Hellebrekers, 2005; Kastner, 2008) Alpha-2-adrenergic agonist: Xylazine, Medetomidine 4) OPIOIDS ANALGESICS - Produce moderate sedation and profound analgesia, without loss of consciousness (Breivik, 1994; Grape and Tramer, 2007) Fentanyl* (30 min), Tramadol (4-5h), Meperidine (1-2h), Sufentanyl (100x) NSAIDs: Preemptive analgesia ANESTHETIC INDUCTION AND MAINTENANCE 1) INJECTABLE ANESTHETICS - Produce unconsciousness (narcosis), neurovegetative protection, muscle relaxation, mild analgesia (Glen and Hunter, 1984; Murayama et al., 2005) Ketamine / Tiletamine (dissociative) Barbiturates (peritonitis), Propofol (without cumulative effect / exclusive IV) 2) INHALATIONAL ANESTHETICS - Globally depress the CNS (no analgesia) - Great advantages! - Orotracheal intubation (cannulae or scalpe PE) or mask - Vaporizer: Induction 5% and Maintenance 1-3% Halothane*, Isoflurane, Sevoflurane ANESTHETICS AGENTS IN ASSOCIATION • Ketamine (60 a 80 mg/Kg) + Xylazine (10 a 30 mg/Kg) Diazepan (2 mg/Kg) ou • Ketamine (40 a 60 mg/Kg) + Xylazine (10 a 15 mg/Kg) Acepromazine (1 mg/Kg) ou Tramadol (2 mg/Kg) Flecknell, 2009; Unifesp, 2005 • Physiological Monitoring • Ophthalmic ointment or liquid tears to prevent damage to the cornea • Responses to Painful Stimuli: pedal withdrawal reflex! BZP, NLT GENERAL ANESTHETICS XYLAZINE VDI VAP OPIOIDS KETAMINE POST-SURGICAL: PAIN 1) NON-STEROIDAL ANTI-INFLAMMATORY: • Dipirone (10-20mg/Kg, VO, SC / BID or TID) and Acetominophen (200-300 mg/Kg, VO / BID or TID) • Ketoprofen (2-5 mg/Kg, VO, SC / SID) • Carprofen (5 mg/Kg, VO / BID) Hawk and Leary, 2005 ; Unifesp, 2005 POST-SURGICAL: PAIN 1) NON-STEROIDAL ANTI-INFLAMMATORY: • Meloxicam (1-5 mg/Kg, VO, SC, IM / BID) • Flunixin Meglumin (1 - 2,5 mg/Kg, VO, SC / SID) 2) OPIOIDS ANALGESICS : • Tramadol (5 mg/Kg, VO, SC, IM / SID or BID) Hawk and Leary, 2005 ; Unifesp, 2005 POST-SURGICAL: INFECTION 3) ANTIBIOTICS: • Enrofloxacin (5-10 mg/Kg, VO, SC / BID) • Ampicillin (100-150 mg/Kg, VO, SC / BID) • Sulfamethoxazole/Trimethoprim (15-30 mg/Kg, VO, SC / BID) Hawk and Leary, 2005 ; Unifesp, 2005 POST-SURGICAL: INFECTION 3) ANTIBIOTICS: Pregnancy and Lactation • Penicillin (100.000 UI/Kg, SC, IM / SID) • Cephalexin (60 mg/Kg, VO / BID) Hawk and Leary, 2005 ; Unifesp, 2005 • House them separately after surgery (blood / cages) • Low light, noise and manipulations • Temperature: 27-30°C adults and 35-37°C neonates until restore parameters (mice!) • Administration of SC or IP fluids • Evaluate the parameters of pain and stress!!! EVALUATIN OF GENERAL ACTIVITY Unrest Movement reduction EVALUATION OF SURGICAL SITE Abdominal writhe PHYSIOLOGICAL CHANGES Edema RR/ HR Licked Body temperature Points CHANGE IN EATING BEHAVIOR PARAMETERS OF EVALUATION PAIN/STRESS APPEARANCE Piloerection Porphyrin Food and water comsuption Back arch Weight loss Urine/Faeces BEHAVIOR VOCALIZATION Aggression Social interaction reduced Stasiak, et al., 2003 Facial Expression of Pain (Grimace Scale) Dr Mary Lynch (president of the Canadian Pain Society), Nature 2010; Sotocinal, et al., 2010, 2011 Orbital tightening Cheek flattening Nose shape Whisker position Ear position (Keating, 2012; Flecknell, et al, 2012) Piloerection Porphyrin “All species, including humans, feel pain with the same quality and intensity” TODAY IT’S A MORAL AND ETHICAL DUTY OF MAN TO MINIMIZE ANIMAL SUFFERING (WHO, 2006) Thiago Vignoli, MV, PhD thiagovignoli@alesco.ind.br Tel: (11) 99715-5508 If you were to ask any of the monkeys why they were knocking other monkeys that tryed to pick up bananas, maybe the answer would be: “I do not know, things have always been so here!” The conformism and inertia make human being limited by choice. “The mind that opens to a new idea never returns to its original size.” ALBERT EINSTEIN REFERENCES • Manual de Terapêutica Veterinária (3° ed), Silvia Franco Andrade, 2008 • Anestesiologia Veterinária – Farmacologia e Técnicas (6° ed), Flávio Massone, 2011 • Princípios Éticos e Práticos do uso de Animais de Experimentação, Universidade Federal de São Paulo, 2005 • Laboratory Animal Anaesthesia (3rd edition), Paul Flecknell, 2009 • Formulary for Laboratory Animals (3rd edition), C. Terrance Hawk and Steven L. Leary, 2005 • Canadian Council on Animal Care (CCAC)