Services on Demand
Print version ISSN 0034-7094
Rev. Bras. Anestesiol. vol.58 no.4 Campinas July/Aug. 2008
Standardization of anesthesia in swine for experimental cardiovascular surgeries*
Estandarización de la anestesia en cerdos para procedimientos quirúrgicos cardiovasculares experimentales
Glaucylara Reis GeovaniniI; Fábio R. PinnaII; Flávio A. P. PradoII; Wagner Tetsuji TamakiIII; Euclides MarquesIII
do Marcapasso - Incor/SP FMUSP
IIAcadêmicos do Quarto Ano da FMUSP
IIIMédicos do Incor - HC/FMUSP
OBJECTIVES: Although dogs are the animals used more often in Experimental
Surgeries, the use of sheep, bovine, and swine as models for scientific experiments
has been growing. Thus, further learning on the treatment and basic standardization
of more complex surgeries in swine are necessary. The objective of this study
was to evaluate sedation and analgesia, obtained by the intramuscular administration
of midazolam and ketamine, and local anesthetics with 2% lidocaine without vasoconstrictor,
in tracheostomy and dissection of femoral artery and vein.
METHODS: The heart rate and corneal-palpebral reflex were evaluated at the beginning of sedation, during the surgical procedures, and at the end of those procedures. Eight Large White swine, without prior treatment, weighing 35 to 42 kg were provided by local farms. They received intramuscular injections of 22 mg.kg-1 of ketamine and 0.3 mg.kg-1 of midazolam.
RESULTS: The anesthetic approach on those animals, who present both difficult intubation and access to deep vessels, proved to be safe for sedation and analgesia by the method chosen: intramuscular administration.
CONCLUSIONS: An adequate plane of anesthesia for the proposed procedure was achieved.
Key Words: ANALGESICS: ketamine; ANIMALS: pigs; HYPNOTICS, benzodiazepines: midazolam; SURGERY: experimental.
Y OBJETIVOS: Aunque los perros sean los animales más a menudo usados
en Cirugía Experimental, se nota un aumento en la utilización
de los ovinos, bovinos y porcinos como modelo para experimentación científica.
De esa forma, se hace necesario aprender más con su tratamiento y estandarizaciones
básicas para los procedimientos quirúrgicos más complejos
en porcinos. El objetivo fue evaluar la sedación y la analgesia obtenidas
por la inyección intramuscular de midazolán y la cetamina y anestesia
local con lidocaína a un 2% sin vasoconstrictor, en la realización
de traqueostomía, disección de arteria y vena femorales.
MÉTODO: La frecuencia cardíaca y el reflejo córneo-palpebral fueron evaluados inmediatamente al inicio de la sedación, durante los procedimientos quirúrgicos descritos y después en su conclusión. Se utilizaron ocho porcinos que fueron suministrados por haciendas de la región sin tratamiento previo de la raza Large White, con peso de 35 a 42 kilos que recibieron inyección intramuscular de 22 mg.kg-1 de cetamina y 0.3 mg.kg-1 de midazolán.
RESULTADOS: El abordaje anestésico en esos animales, de difícil intubación y acceso a los vasos profundos, demostró ser seguro para la sedación y analgesia a través del método utilizado: el acceso intramuscular.
CONCLUSIÓN: Se obtuvo un adecuado plan de anestesia para el procedimiento propuesto.
Since its beginning, Cardiac Surgery has based its advances and development on animal studies, and the dog is the species used more often; however, the use of bovine, sheep, and swine has been increasing 1,2. Dogs used in our field are stray dogs captured on the streets and released by the Health Department. Frequently, their race is undetermined, with different sizes, weights, ages, and poor health conditions. Inbred swine provided by local growers with standardized race, weight, age, gender, health conditions, and without seasonal variations, have been stimulating the use of those animals in experimental studies 2. However, further learning on their manipulation is necessary to avoid unnecessary animal suffering, associated with basic standards for more complex surgeries.
The objective of this study was to evaluate sedation and analgesia with the intramuscular administration of midazolam and ketamine associated with local anesthesia with 2% lidocaine without vasoconstrictor in tracheostomies and dissection of the femoral arteries and veins, using the heart rate and corneal-palpebral reflex as parameters.
Eight Large White swine, delivered by local farms, without previous treatment, were used; they were fasting since the night before the procedure. Animals received intramuscular ketamine chloride, 22 mg.kg-1, and midazolam, 0.3 mg.kg-1, and their weight was determined from the information given by the farmer. The animals were, then, weighed and transferred to the operating room. Monitoring included continuous surface electrocardiogram with a T5000 Gould polygraph and evaluation of the corneal-palpebral reflex before, during, and after the surgical dissections. Anesthesia was complemented with subcutaneous infiltration of 2% lidocaine in the areas of vascular dissection and tracheostomy. After the anesthesia, a median longitudinal incision 10-cm long extending cranially from the suprasternal notch (Figure 1) was made, exposing the trachea for the tracheostomy, an 8.5F tracheal cannula was introduced. Using the same incision, the right internal jugular vein and common carotid artery were identified, and an 8F Hemaque catheter was introduced in the right internal jugular vein (Figure 2). The femoral artery and vein were also dissected and catheterized. They were approached via a left inguinotomy; those deep vascular structures are covered by the adductor muscles, hindering their dissection (Figure 3). The heart rate and corneal-palpebral reflex, stimulated by touching the eye with a finger, were evaluated before, during, and after the surgery. Analysis of Variance by ranks (medians) was used for the statistical analysis and values of p < 0.05 were considered significant. The corneal-palpebral reflex could be either present or absent.
Table I shows the results and it is possible to see that the heart rate (HR) at the beginning and end of the procedure did not show significant changes. The interval between intramuscular sedation and the end of the procedures varied from 24 to 32 minutes. Animals in the study weighed between 35 and 42 kg (mean of 40.1 kg and standard deviation of 2.23). The corneal-palpebral reflex also did not show differences throughout the study, being absent at all times.
Despite the growing use of swine in several fields of Medicine, they have characteristics that hinder their handling, such as absence of superficial veins and difficult airways 3,4. In the absence of large caliber superficial veins, an intramuscular anesthetic alternative with fast induction of hypnosis and analgesia and with a high safety margin was sought 4.5. Tracheal intubation in pigs is difficult due to its depth, besides its glottis mobility and reduced caliber (Figure 4), which required the use of 20-cm laryngoscopic blades. Some authors have suggested directives for tracheostomy in those animals 6, but this is another matter for discussion. Tracheostomy facilitates cannula maintenance, and weaning off ventilatory assistance constitutes an additional advantage, since they are necessary in studies requiring survival of the animal in large surgeries such as cardiovascular surgeries. Using the same incision, it is possible to access the jugular veins and carotid arteries. However, with the knowledge on the anatomy of the inferior vena cava, central venous access by puncture became feasible 6,7.
The ideal anesthetic for the proposed study should have:
a) Good sedative, analgesic, and muscle relaxation properties without hemodynamic compromise;
b) A high safety margin;
c) Fast onset of action and recovery after the administration is discontinued;
d) A regular metabolism with good dose-effect correlation;
e) Easy administration;
f) Absence of toxic effects (immediate and late);
g) Compatibility with the study animal;
h) Correlation with drugs used in humans; and
i) Low cost, be easy to administer, and readily available.
The choice of the anesthetic in the present study also considered:
1) The procedure: type of surgery; its duration; severity of pain potentially induced during the surgery, and effects of the drugs on the parameters evaluated.
2) The animal: species, behavior, correlation with humans, animal weight-age and gender, metabolism, distribution of the anesthetic in the different body compartments, prior exposure to other drugs, specific tendency to toxicity, and concomitant studies.
Some inhalational anesthetics are associated with the development of malignant hyperthermia, like isoflurane 8. Although local anesthetics, like bupivacaine, provide adequate and lasting anesthesia, they predispose those animals to the development of fatal ventricular arrhythmias, while other anesthetics, such as medetomidine, may cause cardiovascular depression. Fentanyl is a phenylpiperidine 60 to 80 times more potent than morphine; it is highly liposoluble and is deposited in the adipose tissue; and it is metabolized in the liver 10. Despite its analgesic and sedative efficacy, it causes respiratory depression, precipitating mechanical ventilation in an animal with difficult airways 10,11, it requires intravenous administration and, in prior studies with swine, this drug showed a high consumption and it was necessary to associate other drugs such as benzodiazepines 12. Although they provide good sedation, benzodiazepines did not provide good analgesia and, therefore, it was difficult to handle the animal without associating another anesthetic. Propofol is an alkylphenol with hypnotic properties. Its clearance surpasses hepatic blood flow, suggesting and extra-hepatic metabolism or extra-renal elimination. It can reduce the blood pressure and heart rate. It is not a good analgesic and must be administered intravenously 12. Ketamine chloride produces dissociative anesthesia and after a short period of thirty to forty seconds unconsciousness sets in, which can last 15 minutes after a single dose, and also a deep analgesia that can last 40 minutes. Other effects of ketamine include an increase in muscle tonus with sudden involuntary contractions, decrease airways resistance, which almost abolishes the risk of bronchospasm, up to 25% increase in blood pressure associated with an increase in cardiac output and heart rate due to an increase in sympathetic activity 12,13. The association with midazolam, a fast-acting benzodiazepine, can maintain the animal unconscious during the entire procedure. The molecular structure of midazolam is that of a benzene ring fused with a 7-atoms diazepinic ring, one substituted 5-aryl, and a 1,4-diazepinic ring, besides an imidazole ring closed at radical 1. In cases of tachycardia, midazolam can reduce the cardiac output 12,13.
The association of ketamine and midazolam proved to be adequate for the surgery proposed, that is, to establish safe airways and proper venous and arterial accesses 1. Respiratory depression is not frequently observed with the usual doses of those drugs, and their association in the present study allowed the vessels to be dissected without triggering cardiac arrhythmias or loss of the anesthetic plane.
However, this study has a limitation, since it did not evaluate neither ventilatory volumes nor blood gases before and after sedation, because intubation and arterial and venous accesses were only done after the anesthesia, but, once the anesthetic, surgical, and ventilatory methods have been standardized, future studies could evaluate those parameters. Recent studies proved the benefits of ketamine with few hemodynamic effects during anesthesia of hypovolemic swine when compared with other anesthetic agents, such as lidocaine 14.
It was possible to conclude that anesthesia with ketamine and midazolam, complemented with local anesthesia with lidocaine, was effective and safe for the surgeries proposed.
01. Hughes HC - Swine in cardiovascular research. Lab Anim Sci, 1986;36:348-350. [ Links ]
02. Vainio OM, Bloor BC, Kim C - Cardiovascular effects of a ketamine-medetomidine combination that produces deep sedation in Yucatan mini swine. Lab Anim. Sci, 1992;42:582-587. [ Links ]
03. Swindle MM, Horneffer PJ, Gardner TJ et al. - Anatomic and anesthetic considerations in experimental cardiopulmonary surgery in swine. Lab Anim Sci, 1986;36:357-361. [ Links ]
04. White RG, DeShazer JA, Tressler CJ et al. - Vocalization and physiological response of pigs during castration with or without a local anesthetic. J Anim Sci, 1995;73:381-386. [ Links ]
05. Gilman AG et al. - Goodman and Gilman's the Pharmacological Basis of Therapeutics, 8th Ed, New York, McGraw-Hill,1996. [ Links ]
06. Tamaki, WT - Efeito da atriomioplastia no pico de fluxo e pressão média pulmonar em modelo experimental agudo: suas implicações na operação de Fontan. Tese de Doutorado - Faculdade de Medicina da Universidade de São Paulo - Departamento de Cardiopneumologia. Área de Concentração Cirurgia Torácica e Cardiovascular, São Paulo, 1998. [ Links ]
07. Freysz M, Timour Q, Bertrix L et al. - Enhancement by ischemia of the risk of cardiac disorders, especially fibrillation, in regional anesthesia with bupivacaine. Acta Anaesthesiol Scand, 1993; 37:350-356. [ Links ]
08. Claxton-Gill MS, Cornick-Seahorn JL, Gamboa JC et al. - Suspected malignant hyperthermia syndrome in a miniature pot-bellied pig anesthetized with isoflurane. J Am Vet Assoc, 1993; 203:1434-1436. [ Links ]
09. Nishimura R, Kim H, Matsunaga S et al. - Sedative effect induced by a combination of medetomidine and midazolam in pigs. J Vet Med Sci, 1993;55:717-722. [ Links ]
10. Stolf NAG, Jatene AD - Tratamento Cirúrgico da Insuficiência Coronária. São Paulo, Atheneu, 1998. [ Links ]
11. Storer TI, Usinger RL - Zoologia Geral. 2ª Ed, São Paulo, Editora Nacional, 1976. [ Links ]
12. Mitruka BM, Rawnsley HM - Clinical Biochemical and Hematological Reference Values in Normal Experimental Animals and Normal Humans. 2nd Ed, New York, Masson, 1981. [ Links ]
13. Sisson S, Grossman JD, Getty R - Anatomia dos Animais Domésticos. 5ª Ed, Rio de Janeiro, Guanabara Koogan, 1986. [ Links ]
14. Errando CL, Sifre C, Moliner S et al. - Utilización de ketamina para anestesia subaracnoidea durante hipovolemia. Estudio experimental preliminar em cerdos. Rev Esp Anestesiol Reanim, 2004;51:3-11. [ Links ]
Correspondence to: Submitted em 24
de abril de 2007 *
Received from Instituto do Coração (Incor) da Faculdade de Medicina
da Universidade de São Paulo (FMUSP), São Paulo, SP
Dra. Glaucylara Reis Geovanini
Rua Dr. Enéas de Carvalho, 25
05401-900 São Paulo, SP
Accepted para publicação em 8 de abril de 2008
Submitted em 24
de abril de 2007
* Received from Instituto do Coração (Incor) da Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, SP