IOP is determined by aqueous humour volume, choroidal blood volume, vitreous humour volume, scleral rigidity and elasticity, extraocular muscle tone, and external pressure. IOP is maintained by a balance between production and outflow of aqueous humour [8]. It is essential that the effects on ocular pressure are taken into consideration when choosing an anaesthetic protocol for ophthalmic surgery or examination. Sudden changes in IOP during the whole perianaesthetic period can have disastrous effects on patients with certain ocular pathologies, such as deep corneal ulcers or glaucoma [9].
Sedation may be of extreme value as an adjunct to manual restraint to ease the handling of veterinary patients, and also to reduce anxiety associated with ophthalmic examination. Ocular pain, when severe enough to prevent a thorough ophthalmic examination or when present due to ocular disease, should also be minimized with analgesics. For these reasons, the need for understanding the effects on intraocular pressure of opioids on behalf of animals suffering from ophthalmic diseases or animals undergoing intraocular surgery is of paramount importance.
Preanesthetic agents can be useful to reduce stress and anxiety, to facilitate restraint, decrease the dose requirement of potentially more dangerous drugs used in general anaesthesia, to smooth the induction phase, to enhance perioperative analgesia, and to reduce arrhythmogenic autonomic reflex activity [10]. Presently, one of the most common sedative/preanesthetic/analgesic agents’ categories are opioids. This class of drugs have very few negative effects on haemodynamics. The stimulation of the vagus nerve may cause a decrease in heart rate which can be managed by co-administration of an anticholinergic agent, if necessary [10]. Most opioids have minimal effects on cardiac output in dogs, except for methadone, which may produce more consistent decreases. The choice and dosage of the appropriate opioid depends upon the anticipated level of pain caused by the lesion and/or procedure and its duration [10].
The purpose of this study was to determine the effects of methadone on IOP values in dogs and cats, as a solo agent of sedation, analgesia or anaesthetic premedication.
The selection of this particular opioid was due to the fact that presently it is the most commonly used drug at our Hospital for sedation and pre-medication protocols and for being an effective analgesic agent both in dogs and cats, even superior to butorphanol in the latter species [11]. Methadone, when used alone, produces minimal sedation [10], but for ophthalmic diagnostic procedures such as electroretinographies, the authors still find the level of sedation appropriate. Its combination with acepromazine can provide a powerful sedation, similar to morphine in dogs [10]. Apart from methadone, no other drugs were administered before all IOP measurements were collected. However, in some dogs, acepromazine was administered after T30 due to the need of a more profound sedation [12].
According to our results, no significant changes in IOP values were detected after premedication with methadone in clinically normal dogs or cats. This could be due to the low administered dosage. The presence of opiate receptors has previously been documented in the iris of rabbits and man, and the intraocular injection of morphine was reported to induce a significant decrease in the pupillary size of conscious rabbits as well as a pupillary constriction after a morphine conjunctival instillation in man [13]. Drugs with sympathetic or parasympathetic actions may alter IOP due to their effects on aqueous humour formation, intraocular blood volume and vascular resistance and/or extraocular muscle tone The different drugs used to tranquilize, sedate and/or anaesthetize patients may affect IOP directly by influencing the dynamics of the aqueous humor, or indirectly if hypercapnia or hypoxemia occurs or if changes in extraocular muscle tone are caused. Sedatives, tranquilizers, and anesthetic drugs tend to cause lowered IOP readings, probably because of reduced extraocular and adnexal muscle tone, while ketamine may cause a slightly elevated IOP reading [7]. The mechanisms by which most opioids lower intraocular pressure or may increase aqueous outflow drainage are still unknown, but hypothesis such as changes in the permeability of iris vessels or the inhibition of aqueous humor production at the ciliary body are the ones considered.
IOP can be measured through paracentesis of the anterior chamber which, due to its invasiveness, is highly impractical in clinical practice [14]. All of the currently available tonometers do not actually measure IOP directly but evaluate physical properties of the cornea and use them to estimate true IOP [14]. Rebound tonometry was used in this study. The tonometer Tonovet® creates a magnetic field ejecting a small probe at a fixed distance from the cornea and, after it reaches the cornea surface, it returns to the instrument. The instrument assesses the probe deceleration (rebound), which allows for the conclusion that eyes with a higher IOP cause a more rapid deceleration of the probe and shorter return time of the instrument than those with a lower IOP [14].
An altered ocular surface tension as seen with the application of topical medications (including topical anesthesia) can affect the results obtained with rebound tonometry. For this reason, this technique should be performed before the application of such medications [7]. With the method described, it is extremely important to perform a careful restraint of the patient to prevent an IOP overestimation, avoiding an excessive compression both of the neck, where the jugular veins are located, or around the periocular area when retracting the eyelids [7]. It is also advisable to obtain more than one IOP measurement and, if possible, at different periods of the day. We obtained three different measurements for each eye and for each timepoint to decrease errors. We elected the morning period in order to re the values after patient admission for surgery and to decrease variability in IOP due to the circadian rhythm [15].
Comparison of IOP between both eyes of the same animal is always critical for achieving a correct diagnosis, and the variation should not exceed 20% [8]. A low or high IOP should not be the only diagnostic criteria for uveitis or glaucoma, respectively, the patient requiring assessment for other signs compatible with those diagnoses [7].
One study limitation is the fact that the sedative effects of opioids, in this case methadone, may differ significantly depending on the animal’s breed, character and level of excitement or aggressiveness. Another study limitation is the lack of higher dose studies and additional measurements latter in time, but the patients’ diagnostic or surgical procedures had to be performed while the patients were under the drug’s effect.