Intraocular pressure evaluation of equines anesthetized with romifidine, tiletamine/zolazepam, halothane and vecuronium

Avaliação da pressão intra-ocular de eqüinos anestesiados com romifidina, tiletamina/zolazepam, halotano e vecurônio

INTRAOCULAR PRESSURE EVALUATION OF EQUINES ANESTHETIZED WITH ROMIFIDINE, TILETAMINE/ZOLAZEPAM, HALOTHANE AND VECURONIUM¹

AVALIAÇÃO DA PRESSÃO INTRA-OCULAR DE EQÜINOS ANESTESIADOS COM ROMIFIDINA, TILETAMINA/ZOLAZEPAM, HALOTANO E VECURÔNIO

Juliana Noda Bechara² Paulo Sérgio de Moraes Barros³ Denise Tabacchi Fantoni⁴ Silvia Renata Gaido Cortopassi⁵ Luis Claudio Lopes Correa da Silva⁶

SUMMARY

The purpose of this study was to evaluate an anesthetic association with and without the use of a nondepolarizing muscle relaxant agent and its effect on intraocular pressure of horses, and also obtain an anesthetic technique free of adverse effects for ophthalmic surgeries in this specie. Sixteen horses were randomly divided in two groups of eight horses each. In group I, horses were pre-medicated with romifidine, anesthesia induced with tiletamine/zolazepam and maintained with halothane and vecuronium. Horses of group II received the same anesthetic association except for vecuronium. Intraocular pressure, arterial pressure and heart rate were evaluated in different moments during the experiment. The anesthetic association composed by romifidine, tiletamine/zolazepam and halothane with and without vecuronium did not promote statistically significant alterations in horses intraocular pressure and its use is practicable in ophthalmologic procedures.

Key words: intraocular pressure, anesthesia, horses, neuromuscular blocking agent.

RESUMO

O objetivo deste estudo foi o de avaliar uma associação anestésica com e sem a utilização de relaxante muscular não-despolarizante e seu efeito sobre a pressão intra-ocular de eqüinos. Também objetivou-se uma técnica anestésica sem efeitos adversos que possa ser utilizada em procedimentos e cirurgias oftálmicas nesta espécie animal. Para tanto, dezesseis eqüinos foram divididos aleatoriamente em dois grupos de oito animais cada. Os animais do grupo I foram pré-medicados com romifidina, induzidos com tiletamina/zolazepam e a anestesia foi mantida com halotano e vecurônio. Os animais do grupo II receberam a mesma associação anestésica, com exceção do vecurônio. No decorrer do experimento, a pressão intra-ocular, a pressão arterial e a freqüência cardíaca foram avaliadas em diferentes momentos. A associação anestésica composta pela romifidina, tiletamina/ zolazepam e halotano com e sem vecurônio não promoveu alterações estatisticamente significativas na pressão intra-ocular de eqüinos e o seu uso é exeqüível em procedimentos oftálmicos nesta espécie animal.

Palavras-chave: pressão intra-ocular, anestesia, eqüinos, bloqueador neuromuscular.

INTRODUCTION

In veterinary medicine few studies were conducted about different anesthetic associations that can be used in ophthalmic surgeries and procedures in horses with the intent to minimize the changes on intraocular pressure. Specialized literature shows contradictory opinions among several authors and few studies made in veterinary medicine in concern with the use of dissociative anesthetic agents in ophthalmic procedures. This study was conducted after a review about different anesthetic associations used in ophthalmic surgery in the last few years in veterinary and human medicine. The review made by MURPHY (1985) and CUNNINGHAM & BARRY (1986) on anesthesia and intraocular pressure (IOP) pointed out several improvements made in the highly specialized field of human intraocular surgery that surfaced in recent years and also defíned IOP as the pressure exerted by the contents of the eye against its containing wall (MURPHY, 1985).

Due to the development of new anesthetic agents and techniques, the anesthesiologist can improve the conditions for examination and for ophthalmic surgery. Apart from providing an immobile and uncongested field he can, by manipulating the factors at his disposal, decrease intraocular pressure and thus minimize the danger of expulsion of intraocular contents when the eye is opened (MURPHY, 1985). With the use of a nondepolarizing neuromuscular blocking agent an immovable operating camp is obtained and there is also the possibility of using fewer depressing inhalatory anesthetic agents.

It is believed that the action of romifidine on equine IOP is equal to that caused by xylazine, which means that probably romifïdine causes a decrease in IOP. IOP tends to decrease after intravenous administration of xylazine (MCCLURE et al., 1976; VAN DER WOERDT et al., 1995) and xylazine with ketamine in equines (TRIM et al., 1985).

The main problem caused by anesthesia on ophthalmic human surgery is the increase of IOP that occurs in the moment of endotracheal intubation when a depolarizing neuromuscular blocking agent is used to facilitate endotracheal intubation (WYNANDS & CROWELL, 1960; MACDIARMID & HOLLOWAY, 1976; COUCH et al., 1979). Succinylcholine chloride administered to horses anesthetized with halothane in oxygen and mechanically ventilated induced slight but insignifícant increases in IOP (BENSON, 1981).

Neuromuscular blocking agents are also used to promote centralization of the eye during surgery. In regard to the nondepolarizing agents, it is said that they do not increase the IOP significantiy. According to POLARZ et al. (1995), vecuronium preceded by thiopentone and alfentanil decreases IOP, and concluded that it can be given when increases in humans IOP have to be avoided.

In spite of the mention made by some authors that the use of the dissociative agent ketamine cause an increase of IOP (COUCH et al., 1979; FRAGEN & HAUCH, 1981; CALLA et al., 1987; MIRAKHUR et al., 1988), it is said that it can be used safely for pediatric ophthalmic examinations (YOSHIKAWA & MURAI, 1971; PEULER et al., 1975).

Although there is knowledge about the isolated effects of dissociative agents and it is known that in human beings it can cause no significam increase on IOP, the effect of the administration of a combination of drugs including a dissociative anesthetic drug in animals is not yet known.

In a study made by WATCHA et al. (1990) with children anesthetized with halothane and nitrous oxide, was concluded that IOP after induction remains constant over time and is not affected by end-tidal halothane concentrations up to 1.0% but is affected by tracheal intubation. In human patients with a low normal pre-operative IOP tended to show a rise in IOP during halothane anesthesia, and those with a high normal pre-operative IOP tended to show a fall (VAN DEN BERG et al., 1995).

The objective of this study was to evaluate the IOP of horses anesthetized with the association of romifidine, tiletamine/zolazepam and halothane with and without vecuronium.

MATERIAL AND METHODS

Animals

Sixteen horses of different breeds and ages, weighing between 300 and 500kg refereed to the University of São Paulo Veterinary Hospital were used. The horses underwent both clinical and ophthalmic examinations to rule out diseases that could interfere in IOP values. They were randomly assigned into two groups of eight horses each.

Anesthesia

Group 1: Romifidine^a (0.08mg/kg) was administered by intravenous route (IV) as the pre-anesthetic medication. After 15 minutes a combination of tiletamine/zolazepam^b (2.00mg/kg, IV) were administered. The animals gradually collapsed into a dog-sitting position and could be easily positioned in lateral recumbency. Endotracheal intubation was performed since the swallowing reflex was absent m all horses. Anesthesia was maintained on a closed circle system of a large animal anesthetic machine (Model 2800, Mallard Medical, Irvine, California) with halothane^c in 100% oxygen. Halothane concentration was enough to maintain the horses on a stable surgical anesthetic plane. Abolition of spontaneous ventilation was accomplished by the administration of vecuronium^d (0.1 mg/kg, IV). Once apnea was established controlled ventilation was started. Tidal volume (12ml/kg), respiratory rate (10breaths/min.) and I:E relation (1:2) were settled in the ventilation machine (Rachel, Model 2800, Mallard Medical, Irvine, California). At the end of the surgical procedure, in all animals the respiratory rate at the ventilator was gradually decreased. The intent was to increase the partial carbon dioxide pressure in order to promote stimulation of the respiratory center by the chemoreceptors. There was no necessity of the administration of neostigmine to reverse the neuromuscular blockade caused by vecuronium, because of its short acting time. In fact, after weaning the animals were able to maintain a normal tidal volume, which reinforced the no need of pharmacological antagonism.

Group 2: The same anesthetic protocol used in Group 1 was used in this group except for vecuronium, which was not administered. controlled ventilation was not required.

Assays

The parameters of: intraocular pressure, systolic and diastolic arterial pressure (SAP and DAP) and heart rate (HR) were evaluated at the moments M0 (before the pre-anesthetic medication), M1 (5 minutes after the pre-anesthetic medication), M2 (1 minute after induction), M3 (immediately after endotracheal intubation), M4 (15 minutes after the beginning of the inhalatory anesthesia), M5 (one minute after neuromuscular blockade) and M6 (three minutes after neuromuscular blockade). The IOP was measured with an applanation tonometer (TONOPEN, Biorad, California) after topical anesthesia with proximetacaine^e. Three measurements were taken for each moment probe. Arterial pressure was evaluated by indirect measurement using an aneroid manometer and mitt placed over the base of the animal tail and the auscultation of the bruits by the alignment of the extremity of a ultrasonic stethoscope (Imbracrios, São Paulo, SP) with gel over the coccigeal artery. Heart rate on non-anesthetized horses was measured with the auscultation of heart beats with the stethoscope over the cardiac area. Once the animal was anesthetized, heart rate was obtained with an oscilloscope (Ecafíx, São Paulo, SP).

Statistical methods

The results were compared statistically by parametric tests, with the ANOVA test (variance analysis) followed by the Tukey's test, for the comparison of different moments of observation of a same group, and the test of t-Student for the comparison of different moments of IOP observation within the two groups; p<0.05 was considered signifïcant.

RESULTS

The administration of romifidine, as well as the maintenance with halothane caused a signifïcant decrease of heart rate. In Group I, a decrease of HR was observed 5 minutes after the romifidine administration which returned to its normal value after induction, also a decrease of HR was observed 3 minutes after the vecuronium administration. In Group II, a decrease of HR was verified 5 minutes after the pre-anesthetic medication (Tables 1 and 2).

During inhalation anesthesia, a significant decrease of arterial blood pressure was verified in both groups. The administration of romifidine and the induction with tiletamine/zolazepam caused a initial increase of blood pressure (Tables 1 and 2).

No statistically signifïcant alteration occurred on IOP values in Groups I and II (Tables 1 and 2), and also when comparing the moments within the Groups.

DISCUSSION

It is believed that xylazine, an ∞-2 agonist pre-anesthetic agent, cause a decrease of horses IOP, what means that probably romifidine would have the same effect. In equines, IOP decreases after intravenous administration of xylazine (MCCLURE et al., 1976; VAN DER WOERDT et al., 1995) and xylazine with ketamine (TRIM et al., 1985). In this study romifidine administration did not cause any signifïcant alteration of IOP.

Almost all anesthetic agents commonly used for humans anesthetic induction decreases IOP, for example, thiopental, propofol and etomidate, with the probable exception of ketamine (COUCH et al., 1979; FRAGEN & HAUCH, 1981; CALLA et al., 1987; MIRAKHUR et al., 1988). Ketamine presents undesirable characteristics when used for anesthetic induction in ophthalmic surgery in humans, but it is commonly used as an anesthetic agent for pediatric ophthalmic examinations (YOSHIKAWA & MURAI, 1971; PEULER et al., 1975). Indeed, according to PEULER et al. (1975), there is a reduction in IOP after ketamine. The IOP reduction occurs 2 minutes after the administration of ketamine and normal values are obtained 2 minutes after the initial reduction. In the present study it was verified that the association tiletamine/zolazepam did not cause a significam increase of horses IOP.

The increase of IOP that is frequently verified during difficult orotracheal intubation in humans and/or when succinylcholine is administered is one of the problems that must be avoided during anesthesia for ophthalmic surgeries.

Endotracheal intubation was easily performed in all horses after induction with tiletamine/ zolazepam and no alterations on IOP immediately after endotracheal intubation were observed.

In human patients with spontaneous respiration halothane reduces IOP (MAGORA & COLLINS, 1961; MEHTA, 1962; TAMMISTO et al., 1975). Apparently all volatile agents causes a decrease of IOP that is dose dependent, but factors like PaCO₂ and posture may be an important factor that could change IOP in patients with spontaneous ventilation (MURPHY, 1985; CUNNINGHAM & BARRY, 1986). No statistically significant decrease of horses IOP values obtained 15 minutes after the beginning of the inhalatory anesthesia was observed in both groups.

Administration of vecuronium during steady state anesthesia was associated with a significant decrease on human IOP (MIRAKHUR et al., 1987). This experiment showed that vecuronium associated with tiletamine/ zolazepam and halothane did not cause a statistically significant alteration of horses IOP.

In both groups a decrease of heart rate was observed after romifidine administration what is in agreement with the results obtained by GÓMEZ-VILLAMANDOS (1995). There was a decrease of HR after the neuromuscular blockade. There was an increase of HR after the pre-anesthetic medication when the values where compared to those obtained after the induction and after the endotracheal intubation.

Continuous doses of halothane causes myocardial depression and vasodilatation that will provoke decrease of blood pressures (MILLER, 1989). A significant decrease of systolic and diastolic pressures was verified in this experiment after halothane administration when compared with the earlier moments. IOP was not directiy affected by the changes in arterial blood pressure, what confirms the results obtained by DEAR et al. (1987) in a study made in young children.

Vecuronium is a good neuromuscular blocking agent because it does not act in the autonomic ganglia and is almost all eliminated in bile, it also does not alter arterial pressure (MUIR et al., 1995), being suitable for ophthalmic procedures. In the present study it was verified that its administration was not associated with changes of systolic and diastolic arterial pressures.

Although, the induction with tiletamine/zolazepam caused an increase of heart rate and systolic and diastolic arterial pressure, it did not alter equines IOP.

It can be concluded with the present study that romifidine can be safely used in the pre-anesthetic medication of equines being submitted to ophthalmic procedures or surgeries once it caused a decrease of the IOP. Tiletamine/zolazepam association used for induction preceded by romifidine did not statistically alter equines IOP as well as endotracheal intubation did not promote sympathetic stimulation that would increase IOP. Halothane showed to be a good anesthetic agent for ophthalmic surgeries once it did not alter the equines IOP, vecuronium preceded by tiletamine/zolazepam and halothane did not alter equines IOP and it can be used to immobilize and centralize the ocular globe during the surgical procedure.

SOURCES AND MANUFACTURES

a - Sedivet©, Boehringer de Angeli, Itapecerica da Serra, SP.

b - Zoletil©, Virbac do Brasil, São Paulo, SP.

c - Halotano©, Cristália - Produtos Químicos Farmacêuticos Ltda, Itaparica, SP.

d - Norcuron©, Akso Ltda., Divisão Organon Teknika. São Paulo, SP.

e - Anestalcon© 0,5%. Alcon Laboratórios do Brasil Ltda. São Paulo. SP.

² Médico Veterinário, Pós-graduanda, Faculdade de Ciências Agrárias e Veterinárias da UNESP, Campus de Jaboticabal, SP. Endereço para correspondência: Av. Aristides Bellodi, 451, 14870-000, Jardim São Marcos, Jaboticabal, SP.

³ Médico Veterinário, Professor Titular, Faculdade de Medicina Veterinária e Zootecnia da Universidade de São Paulo (FMVZ-USP).

⁴ Médico Veterinário, Professor Doutor, FMVZ-USP.

⁵ Médico Veterinário, Professor Doutor, Faculdade de Medicina Veterinária, UNIP.

⁶ Médico Veterinário, Pós-graduando, FMVZ-USP.

Recebido para publicação em 13.06.97. Aprovado em 20.08.97

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¹

Financial support: Fundação de Apoio à Pesquisa do Estado de São Paulo.

Publication Dates

• Publication in this collection
  19 Oct 2007
• Date of issue
  Mar 1998

History

• Received
  13 June 1997
• Accepted
  20 Aug 1997