Total Injectable Anesthesia of Dogs and Cats for Remote Island Veterinary Sterilization Clinic CURRENT STATUS: UNDER REVIEW

Background : Sterilization clinics may occur in remote places where anesthesia machines and compressed oxygen are unavailable. This study evaluated the efficacy of total injectable anesthesia in dogs and cats presented for sterilization on Isabela Island, Galápagos, Ecuador. Results: A total of 100 animals were sterilized; 26 female cats (FC), 22 male cats (MC), 28 female dogs (FD), and 24 male dogs (MD). FC were anesthetized with dexmedetomidine (20 mcg/kg), ketamine (8 mg/kg) and hydromorphone (0.1 mg/kg) IM. MC were anesthetized with dexmedetomidine (15 mcg/kg), ketamine (5 mg/kg) and hydromorphone (0.1 mg/kg) IM. Inadequate anesthesia in cats was treated with alfaxalone (1mg/kg) IM. All cats were administered meloxicam at 0.3mg/kg SQ. FD were anesthetized with dexmedetomidine (15 mcg/kg), ketamine (7-10 mg/kg) and hydromorphone (0.1 mg/kg) IM. MD were anesthetized with dexmedetomidine (15mcg/kg), ketamine (5 mg/kg) and hydromorphone (0.1 mg/kg) IM. All dogs had IV catheter and endotracheal tube placed. If SpO2<90%, dogs had assisted ventilation via Ambu bag. Inadequate anesthesia in dogs was treated with alfaxalone (1mg/kg) IV. All dogs were administered meloxicam at 0.2 mg/kg SQ. Following surgery, atipamezole (0.05-0.1mg/kg) IM was administered to any patient that did not have voluntary movement. All patients survived and were discharged. Less than 25% of cats and male dogs required supplemental anesthesia. Fifty seven percent of female dogs required supplemental anesthesia. More than 89% of patients (in any group) required atipamezole administration. One cat recovered with agitation and hyperthermia (41.1C/ 106F). Some dogs required ventilatory assistance


Introduction
Unwanted reproduction in dogs and cats negatively affects communities by contributing to: the spread of disease, aggression to humans, nuisance behavior (e.g. getting into garbage) and predation of other species (e.g. wild birds). Sterilization of both pet and feral dog and cats is often needed in remote or underdeveloped areas, where access to veterinary medicine is limited or absent. Spay-neuter programs are offered in a variety of styles in these locations via mobile clinics, but access to facilities and equipment is variable. The Association of Shelter Veterinarian has offered guidelines to assure consistent care to dogs and cats presented to these clinics(1) (2). Unfortunately, these guidelines assume access to equipment that might not be possible in some remote locations, such as compressed gasses (e.g. oxygen) or anesthesia machines(1) (2).
The Galapagos Islands are an archipelago off the coast of Ecuador. While renowned for their interesting and diverse wildlife, many of the islands have large populations of intact dogs and cats that predate indigenous and sometimes endangered wildlife species (e.g. birds, turtles, marine iguanas) (3)(4)(5)(6). Isabela Island is the largest of the Galapagos Islands, but has a population of only about 1800 people (7), and is accessible primarily by boat. While it is a permanent home to some, and a tourist destination for others, it does not have a human medical facility. Therefore, on islands such as this, getting all the equipment necessary for a sterilization clinic presents a significant logistical issue. From the planning stages, it was considered improbable to be able to transport an anesthesia machine and/or oxygen tanks (or the ability to refill them) to Isabela Island. Therefore, by necessity, the team was required to plan the clinic with use of injectable anesthetics only. While anesthesia in high volume, low cost spay/neuter clinics has been studied (8,9), the majority of those studies were done in non-remote places and in locations where resources are available if needed, even though not routinely used (e.g. anesthetic machines/oxygen). Conversely, there is a paucity of information regarding anesthesia management and complications in remote location spay/neuter clinics where rescue use of oxygen and or inhalant anesthetics are not available. The goal of this study was to document the anesthetic protocols used in a remote location spay neuter clinic as well as any complications that occurred. We hypothesized that it is possible to anesthetize dogs and cats in a remote location for OVH and neuter procedures with minimal morbidity.

Materials And Methods
In June of 2016 a team of 14 volunteers from the USA who all work within the veterinary community traveled to Isabela Island, Galapagos, to provide sterilization for any dog or cat (pet or feral). The team consisted of nine veterinarians, one licensed veterinary technician, two veterinary assistants, and two general assistants. Of the 14 members, one veterinarian and one general assistant were fluent in Spanish.
A local organization, the Intercultural Outreach Initiative, provided advertisement for the clinic as well as a building equipped with electricity and cold water. All equipment and supplies were transported by the volunteers via boat to the island.
Informed consent in writing was provided by the owners or guardians for all animals that were sterilized. At least one translator was present with each owner/guardian during the consent process.
Following admission, each patient has a physical examination by an attending veterinarian, who decided if the patient was healthy enough for anesthesia and sterilization. Each animal was weighed with a hanging luggage scale. Four anesthetic protocols were developed by a veterinary anesthesiologist (LPP) for each species and gender (Table 1). Dogs and cats were sterilized in order of arrival. All animals deemed healthy enough for surgery were sterilized within the hours of the clinic over one week. The total number of animals sterilized (100) was not chosen, but rather was the result of patients presented to the clinic and those deemed appropriate for surgery.  Table 2.  Table 3. * Rescue drugs were given when initial dosing was insufficient to maintain anesthesia.
The need for reversal with atipamezole, Reversal drug requirements, duration of recovery from reversal and recovery temperature are presented in Table 4. Antibiotic, anthelmintic, and TGH (to go home) analgesia were also provided for many patients of this project, but that data is outside the scope of this paper.

Discussion
The data presented here supports that anesthesia for spay/neuter clinics can be accomplished in remote locations where anesthesia machines and/or oxygen is not available. Furthermore, this study has evaluated anesthetic protocols that produced rapid unconsciousness, but allowed for reversal and rapid recovery of patients. This is important in many remote locations, as there are few if any recovery cages/ holding areas, some of the patients are feral, and the longer the patient remain in the clinic's care, the less patients that can be seen per day. Total patient time in the clinic was approximately 1 hr, with cat neuters requiring the shortest stay and dog OVH requiring the longest.
Surgery time ranged from 1 min to 1hr. This made estimation of IM drugs needed difficult. Not surprisingly, 1% of cats being neutered needed rescue anesthetics while 57% of dogs undergoing an OVH required additional anesthetics. In cats that were inadequately anesthetized during surgery, alfaxalone IM provided a rapid deepening of anesthesia. Intramuscular alfaxalone has been evaluated in cats for physiologic stability and PK/PD profiles (10,11). When administered to cats at 5 mg/kg IM, cats showed good physiologic stability, but recovery was considered behaviorally poor (10). In a different study, IM alfaxalone at the same dosage was shown to reach peak concentration (Tmax) iñ 22 min (11) The cats in this study did not show any unpleasant recovery characteristics, likely due to the smaller dosage used in this study (1 mg/kg IM). Intramuscular alfaxalone worked rapidly enough to be considered a good choice for rescue anesthesia during a surgical procedure in a cat.
Based on the Tmax of ~ 22 min, it was unexpected, but repeatable that the dose and route was sufficient. This was likely due to being used in combination with other CNS depressants. If a cat was considered too responsive to continue surgery, stimulation was stopped and IM alfaxalone was administered. Subjectively, IM alfaxalone appeared to work faster than IM dexmedetomidine + ketamine. For dogs too responsive for surgery, alfaxalone IV provided suitable conditions for canine OVH and neuter anesthetic maintenance. This agrees with data showing that following premedications, a constant rate infusion (CRI) of alfaxalone produced suitable anesthesia conditions for dogs undergoing OVH (12). However, in both the Suarez study and in this one, many of the dogs required assisted ventilation to remain normoxemic (12).
Due to the lack of boarding space, and the potential for patients to be unsupervised outside, any animal that was not able to walk was administered atipamezole. While the loss of analgesia was considered, there is evidence in cats that reversal with atipamezole did not affect post-operative analgesia in cats that also received an opioid and ketamine as was used in this study (13).
Additionally, all the animals received an NSAID to supplement analgesia. The vast majority of patients required reversal of dexmedetomidine with atipamezole (89-100% of groups). In the first three dogs that were neutered, the reversal resulted in an agitated/dysphoric recovery. Ketamine at anesthetic dosages are associated with a high incidence of agitation in the recovery period in humans and veterinary patients (14,15). Anesthesiologists often combine administration of ketamine with other CNS depressants such as benzodiazepines and alpha-2 adrenergic agonists to balance the risk of an agitated recovery from anesthesia (15). Thus, the most likely reason for the agitation following administration of atipamezole in those dogs (and in some cats) was loss of CNS depression from dexmedetomidine, which was balancing the behavioral effects of ketamine in the relatively shorter neuter procedures. Immediately following the three dysphoric dog neuter recoveries, the anesthesiologist decreased the dosage of ketamine from 7 mg/kg to 5 mg/kg and none of the subsequent neuters had dysphoric recoveries.  Table 4 showed that the majority of patients remained normothermic. This was likely due to the combination of a warm surgery /recovery environment, the lack of cold anesthetic gases, and the rapid time of surgery/ anesthesia. One cat did become significantly hyperthermic (106F, 41.1C). Hydromorphone has been implicated in post anesthesia hyperthermia in cats (16) (17), and it is has been implicated in causing seizures in a variety of veterinary species (15). Therefore it is possible that both dogs did have seizures following high dose ketamine administration. However, it is also possible that unbalanced absorption of ketamine and dexmedetomidine following IM administration might have resulted in an exaggerated Stage 2 plane of anesthesia (involuntary excitement) which appeared seizure-like and the loss of consciousness was due to anesthesia induction. Both of those dogs muscle movement stopped after IV alfaxalone administration and both dogs recovered uneventfully.
Based on pulse oximetry, all the dogs and cats remained normoxemic. However, many of the dogs required assisted ventilation with an Ambu bag and endotracheal tube to maintain normoxemia.
Placing and securing an endotracheal tube did not appreciably increase total patient time and proved important in patients where anesthesia was being maintained with injectable drugs, a situation that can result in hypoventilation or apnea. While all of the patients survived to discharge from the clinic, this project did not consistently assess of the physiologic variables that are important during anesthesia, such as ventilation, blood pressure, etc. Physiologic assessment of dogs and cats anesthetized and sterilized with these protocols needs to be done.
Although pain scoring was not recorded, all patients were evaluated at recovery and before discharge for pain/discomfort. Aside from the dysphoric recoveries, the remaining patients appeared comfortable at extubation and again at discharge.
Limitations of this study included: variability within each group in patient age and size, variability with four different surgeons, and varying health of patients. However, since this type of variability is expected in a remote-clinic setting, the overall success of the anesthetic plans with the variability is promising.

Conclusion
Total injectable anesthesia is feasible for remote location sterilization of dogs and cats with minimal morbidity.

Declarations
Ethics approval and consent to participate: This manuscript did not have an ethics panel approval, since it is a retrospective evaluation of veterinary clinical practice (commonly used drugs and commonly performed surgeries).

Consent for publication:
All authors have reviewed the manuscript and agree to consent for submission