The drug application site is of importance on ratites and birds in general, due to the presence of the renal portal system, directing part of the venous blood from the hind limbs and general posterior region of the animal’s body through the kidneys before reaching the general circulation. This system may interfere directly with plasmatic concentration of drugs administered on this parts of the animal’s body . However, ensuing data in ostriches (Struthio camelus) reports similar and satisfactory results with drugs administered on the fore limbs and hind limbs .
The maintenance of heart and respiratory rate stability inside normal parameters for the species was also observed in ostriches [5, 19] using dissociative anesthetic agents coupled with benzodiazepines and α-2 agonists in conventional doses. In emus (Dromaius novaehollandiae), an increase in HR was reported using dissociative drugs, but this results were connected by the authors to the use of atropine as a pre-anesthetic drug . By utilizing dissociative anesthetic agents through allometric scaled doses in domestic dogs , oncillas  (Leopardus tigrinus) and the giant anteater  (Myrmecophaga tridactyla), the same HR and RR stability was reported. The tiletamine has notable cardiovascular activity by central nervous system activation, while the zolazepam, as most benzodiazepines, have little effect on cardiorespiratory rates .
No studies referenced reported assessment of defense reflexes, like palpebral and pedal withdrawal reflexes. However, all reported sedation without deep analgesia, compatible with the use of tiletamine/zolazepam in chemical restraint or initial anaesthesia induction.
The use of dissociative anesthetic agents, coupled with xylazine, acepromazine and atropine, in conventional doses in ostriches and emus, resulted in observations very similar to this manuscript regarding muscle relaxation, sedation times and adequate recovery [5, 20]. The use of xylazine specially is common coupled with dissociative anesthetics, usually inducing greater cardiac depression and muscle relaxation.
Bradycardia and bradypnea were reported in the use of tiletamine/zolazepam in small doses (5 mg/kg) associated with dexmedetomidine and thiafentanil, respectively a α-2 agonist and an opioid narcotic, in greater rheas . These observations were most likely related to the drugs associated to tiletamine/zolazepam, instead of tiletamine/zolazepam itself. The authors call for the use of α-2 agonists or other drugs combined with tiletamine/zolazepam, citing better anesthesia and lower volume injected. However, cost of drug acquisition must be considered, as well as risks associated with the use of narcotic drugs.
Different results were obtained in induction time in ostriches using xylazine and acepromazine associated to tiletamine/zolazepam. Induction times, characterized by the authors as time from drug administration to loss of postural reflex, varied from 6 to 40 minutes, averaging around 20 minutes . The methods, similar to the present manuscript, were hardly responsible for this difference. However, physiological characteristics, like body temperature and nutritional condition, may significantly affect metabolism of anesthetic drugs . Specific differences between ostriches and rheas may also be considered. In emus, however, reported induction times with tiletamine/zolazepam/atropine were 40 to 60 seconds, and anesthesia time of 20 to 25 minutes, similar to this manuscript .
Agitated recovery after the use of tiletamine and zolazepam has been previously reported, highlighting sudden head and neck movements and with animals needing assistance to avoid self-trauma on the animals, similarly to what we report in this manuscript . Such behavior cannot be considered completely abnormal in the use of dissociative agents , justifying its use associated with muscle relaxing drugs and tranquilizers, to avoid such effects [5, 6, 11]. The plasmatic half-life of zolazepam, however, may be smaller than that of tiletamine, explaining the excess of excitatory effects during the later stages of recovery .
A behavior of walking with open wings, with short-winded breathing and bristling feathers was observed in all animals a few minutes before and during initial stages of spontaneous ambulation. These reflexes may aim to regulate body temperature, coordinated mainly by the brain staff, beginning after partial recovery from sedation. Dissociative anesthetic agents partially or completely inhibit the nervous system’s control of main body functions, relating these observations with initial stages of recovery from anesthesia [6, 12, 14, 19].
The interspecific allometric scaling method of dose extrapolation has been used successfully in several wildlife animal species, like gray monkey saki (Pithecia irrorata), the kinkajou (Potos flavus), the southern two-toed sloth (Choloepus didactylus), the pygmy anteater (Cyclopes didactylus) and the southern tamandua (Tamandua tetradactyla), with reported results ranging from regular to excellent . A comparison of allometric scaling extrapolation with the linear extrapolation of human doses on the use of ketamine in brown howling monkeys (Alouatta guariba clamitans) showed superior results by the allometric method, with superior anesthesia time and muscle relaxation .
The choice of the model animal is important in allometric scaling extrapolation. Ideally, it should be as taxonomically close as possible to the target animal, and with a similar body mass, as extrapolating from animals too far apart may lead to inadequate results. However, there are no birds among the standard model animals, and the most common domestic animal used as a model is the dog, since the most important trait of the target animal is a very well-defined protocol for the drug used [18, 27]. The body mass of model animals is standardized, with the method using a 10 kg body mass for the domestic dog. So, it is important when determining the drug dose for the model animal to use a dose applicable to a 10 kg dog .
Allometric scaling extrapolation is based on mathematical models that aim to estimate and predict physiological, anatomical and biochemical parameters between different species and taxa, on the basis that several of these variables exhibit power-law relationship with body size. Through those relationships, pharmacological and physiological variables can be extrapolated from a model animal to a target animal, based on their body mass and taxonomical group [8, 27].
Some factors, however, are neglected by allometric scaling and must be considered when designing protocols with this method. Protein binding, toxicity, idiopathic adverse effects and drug sensibility, for example, are independent of body size and related to the species and drug used and, when extrapolating across species, and should be handled outside of allometric scaling [18, 27].
Allometric scaling extrapolation cannot claim to, on a short equation, completely adjust anatomical and physiological differences between completely different animals, and this create an error-proof protocol. As veterinary medicine and pharmacology covers hundreds of species of different size and physiology, merging these animals into large and somewhat heterogenic groups becomes a necessity, despite decreasing the accuracy of the method. It does, however, provide a reference point, a guideline to assist the veterinary physician, especially in wildlife medicine .