Range of sizes

The domestic dog has been manipulated by selective breeding into a bewildering variety of shapes and sizes, originally with some functional purpose, but more recently with appearance as a major driving force of breed standards. This has led to an array of adult dog weights ranging from < 1 kg (e.g., teacup Yorkshire terrier) to > 100 kg (e.g., St. Bernard). Clinical experience suggests that smaller dogs generally require larger doses, on a mg/kg basis, of many drugs used in the perioperative period compared with large dogs. However, there is no scientific basis for calculating these relative dose rates. One common approach to this issue is to use an exponent based on metabolic activity. Within a species, this is usually thought to be two‐thirds, and a common formula used for calculation of body surface area (BSA) based on body mass (BM) is as follows: BSA (m²) = 0.101 × (BM in kg)^2/3. This formula has been criticized and a number of other multipliers and exponents have been proposed [1]. The use of BSA is historical; BSA happens to also vary as a function of BM^2/3, so BSA started being used to index various functions. While its exact calculation has been, and still is, debated, it is actually irrelevant to allometric scaling, including scaling of drug dose. The relevant information is the slope of the relationship between size (i.e., BM) and the variable to be corrected (e.g., dose); this slope is determined by the exponent, and therefore scaling to BM^0.67 instead of BSA would be as effective (provided that dose actually varies with that function of body size) and would avoid the criticism that exact BSA may not be known. Nevertheless, use of BSA to adjust dose has been used extensively with chemotherapeutic agents but this does not reduce the toxic side effects of these drugs, as smaller dogs seem to be more likely to suffer from adverse effects [2]. The inclusion of a body length factor may help to reduce the variability associated with different breeds and a recent study using computerized tomography (CT) scanning included this in their final model to calculate BSA [3]. The manufacturers of medetomidine and dexmedetomidine decided to use BSA and the product monograph for the dog provides doses in mg/m². Using their recommendation, a 1 kg dog would receive 37 μg/kg and an 80 kg dog would get 9 μg/kg of dexmedetomidine administered intravenously (IV). In clinical practice, many people have found that the dose for the bigger dogs is inadequate, suggesting that BM^0.67 may not be the correct function of BM for these drugs. Most drugs used for anesthesia and sedation are targeting the central nervous system and are metabolized in the liver. When we use drugs IV, they are distributed to the body by the cardiac output and when we use inhalants, they are taken up through the lungs. Accordingly, should drug dose be scaled to brain mass, hepatic metabolism, cardiac output, lung capacity, or some complex interaction of these body attributes that also accounts for the lipid solubility or hydrophobicity of the drug, assuming the latter would affect uptake by many of the tissues mentioned [1]? Table 50.1 shows how the dose might be affected by scaling it to some of these different tissues and attributes. Perhaps a more rational approach would be to base it on pharmacokinetics using virtual parameters to define the passage and distribution of a drug throughout the body. While the “central compartment,” as defined in a pharmacokinetic analysis, is likely to include the blood volume and some of the vessel‐rich tissues (e.g., brain, kidney, and heart), empirical pharmacokinetic models do not try to relate compartment volumes to actual, physical volumes in the body, and use changes in plasma concentration to describe the movement of the drug in the body. Initial distribution of a drug is into this central compartment and that appears to generally scale to body weight [4]. Because at least some drugs used in anesthesia, in particular the induction agents, but possibly also some of the analgesics, produce an effect with a rapid onset and short duration, concentrations immediately after administration (i.e., after dilution in the central compartment) are likely highly relevant to the effect [5]. Based on these considerations, it would appear that, at least for these drugs, calculation of the dose based on body weight is most appropriate. The relationship between dose and body size, and between dosing interval and body size is more complicated, as other pharmacokinetic parameters, such as clearance, appear to scale to a range of functions (exponents) of body weight, depending on the drug [4].

A further complication for both canine and feline patients is the current increase in pet obesity with estimates that over 50% of cats and dogs are overweight or obese [6–8]. This presents a challenge for the anesthetist because the brain of the animal is still the same size as that of the lean animal but there are no simple techniques available to estimate what that lean weight would be. Although adipose tissue has a low blood supply, it will obviously begin to affect the volume of distribution of a drug if there is a large amount in the body and it is likely that the blood volume of the animal may have increased as well [9]. Experience in humans indicates that the dose of induction drugs is greater than the dose expected for the predicted lean body weight but not as high as the dose required for the actual body weight of the patient. For example, in a study of propofol dose in obese and non‐obese children, the total dose for the obese children was only 7% greater, even though the average weight of the obese children was 170% of the non‐obese children [10]. In dogs, propofol was infused at 2.5 mg/kg/min and the dose at loss of consciousness was compared between a control group (Body Condition Score [BCS] 4–5 on a nine‐point scale) and an obese group (BCS 8–9). The total dose was 19% higher in the obese group when these animals weighed 170% of the non‐obese dogs [11]. The dose of propofol adjusted to an estimate of lean BM was not statistically different from the control group. This study was performed in dogs less than 10 kg so the data may not apply to larger obese dogs. Such relative changes in dose can be accounted for, in clinical practice, by titrating the drug to the desired effect. Obesity has many other medical implications for our patients that need to be addressed before and during anesthesia [12,13].

Sighthounds

These are dogs that hunt based on being able to see their prey rather than using scent. Phenotypically these dogs are deep‐chested and have long legs and relatively narrow bodies. The muscles on the pelvic limbs are well developed and powerful to provide the thrust required to attain the high speeds necessary to outrun their prey. As hunters, they are also very lean animals. In an article on anesthesia in sighthounds, the Afghan, Borzoi, Saluki, Greyhound, Italian Greyhound, Whippet, Irish Wolfhound, Scottish Deerhound, Ibizan hound, Basenji, and Rhodesian Ridgeback, as well as a number of other rarer breeds were included [18]. However, it is now clear, on the basis of genetic analysis, that these breeds do not all share the same lineage [19]. In the most recent analysis, the sighthounds can be split into two groups. The first group includes the Greyhound, Italian Greyhound, Whippet, Borzoi, Deerhound, and Irish Wolfhound, while the Saluki, Afghan Hound, Ibizan Hound, and Pharoah Hound comprise a distinctly different genetic group. Published studies related to the topic of anesthesia and sighthounds relate specifically to the Greyhound and show that these dogs have a longer recovery from thiobarbiturates than other breeds [20,21]. There are also data showing slightly longer recoveries following both propofol and alfaxalone in Greyhounds [22,23]. This was initially ascribed to the phenotype of these dogs with regard to their large muscle mass and minimal adipose tissue and hence the generalization to all sighthounds. However, more recent data have suggested that the Greyhound may have some relative deficiencies in hepatic metabolism. One study examined the pharmacokinetics of thiopental in Greyhounds and showed that the plasma concentrations plateaued after an initial distribution phase. The Greyhounds were then administered phenobarbital in order to increase hepatic microsomal enzymes and then given thiopental again. The plasma concentrations of thiopental decreased at rates similar to those of mixed‐breed dogs after this treatment [24]. These data do not prove that there is a hepatic deficiency in this breed, they merely show that if the rate of hepatic metabolism is increased, it will lead to a more rapid recovery. However, it has now been shown that Greyhounds have polymorphisms in their CYP2B11 cytochrome gene (H2, H3) that lead to slower metabolism of substrates for this enzyme. This polymorphism has been shown to be highest in the American Kennel Club‐registered Greyhounds but is present in sighthounds in the first group above, but not the second group. This implies that this delayed recovery is less likely to affect the second group despite their lean body type. There are no published reports of significantly delayed anesthetic recoveries in sighthounds other than Greyhounds, although there are many anecdotes regarding such events. With this in mind, and until we have better information, it is probably best to avoid the use of thiobarbiturates in group one sighthounds and expect slightly longer recoveries from other anesthetic induction agents. Some drugs have been used to inhibit CYP2B11 in order to prolong the activity of known substrates for this enzyme. An example of this is the inclusion of fluconazole with methadone, which can increase the peak plasma concentration of methadone 17‐ to 30‐fold and prolong its duration of action from minutes to hours [25].

Other breed sensitivities to anesthesia

Information obtained from the World Wide Web suggests that many purebred dogs have increased “sensitivity” to anesthetics. This is a subject that is constantly referred to by clients in veterinary practice who have been advised by a breeder or have looked up information themselves [26]. The origin of these “sensitivities” is unclear and very few of them have been consistently reported in any particular breed. An abnormal response to an anesthetic could be related to an individual strain within a breed whereby a particular breeder or group of breeders have produced animals that have a characteristic that they want to promote at the expense of alterations in response to anesthetics. Such a trait may not be present in all members of the breed, but the breed may earn that reputation. An abnormal response could also be related to a genetic trait that has been promoted over time and has become more generalized. The multidrug resistance (MDR)‐1 or ABCB1 gene polymorphism has been found in a number of herding breeds and some others (http://prime.vetmed.wsu.edu/2021/10/19/breeds‐commonly‐affected‐by‐mdr1‐mutation/). This gene controls the production of P‐glycoprotein, which is an intracellular transporter protein that removes substances from the inside of the cell. This is a member of the adenosine‐5′‐triphosphate (ATP) binding cassette (ABC) family of proteins and so is one of several proteins that perform this function [27]. These proteins are found in many areas of the body but their presence in the intestine and the blood–brain barrier are most important for the anesthetist. Some drugs inhibit the action of P‐glycoprotein and so may be associated with increased uptake of other drugs, others are removed from the cell by P‐glycoprotein and so an animal with minimal production of this protein may show increased sensitivity to that drug. Acepromazine is a P‐glycoprotein inhibitor, so even under normal circumstances, it may enhance the uptake of other drugs into the brain or through the intestine following oral administration. It is also suggested that it will cause more profound sedation in dogs with the ABCB1 (MDR1) mutation. Many of the opioids interact with P‐glycoprotein and so their uptake into the brain is increased in ABCB1‐deficient dogs. From experiments in ABCB1‐deficient mice, there is about a 25% increase in the uptake of morphine and fentanyl and more than a twofold increase in the uptake of methadone [28,29]. Meperidine does not appear to interact with P‐glycoprotein [30]. In vitro data would suggest that sufentanil, alfentanil, oxymorphone, and butorphanol [29,31] do not have significant interactions with P‐glycoprotein, although it has been suggested that butorphanol may have some increased effect in ABCB1‐deficient dogs. Buprenorphine appears to have minimal interaction with P‐glycoprotein but its metabolite, norbuprenorphine, is ejected from the brain by this transporter. Norbuprenorphine is a potent respiratory depressant and so repeated administration of buprenorphine to ABCB1‐deficient dogs may increase the risk of this adverse event [32]. The drugs used for the induction and maintenance of anesthesia do not appear to interact with P‐glycoprotein.

Other breed “sensitivities” may have more to do with prevalent pathology in that breed rather than something inherent in the breed as a whole. Boxers appear to be sensitive to the effects of acepromazine, something that has been “well known” without any documented information (it is often quoted as being restricted to British Boxers but these authors have seen problems in North American Boxers too). This sensitivity tends to take the form of collapse following acepromazine and has been associated with profound bradycardia (authors’ observations) but it is not known if this is related to the prevalence of arrhythmogenic right ventricular cardiomyopathy in this breed or an enhancement of a vagal response to the drug, as reported in a number of brachycephalic breeds [33]. The authors have also observed greater than expected sedation in Boxers administered acepromazine. Given the plethora of other drugs available for premedication, it seems unnecessary to use acepromazine in this breed or, if used, it seems prudent to administer very low doses (0.01–0.03 mg/kg) in combination with an anticholinergic (to prevent bradycardia) and monitor the animal carefully after administration.

The sense from the internet is that most breeds are “sensitive” to anesthetics yet very few anesthesiologists recognize such differences in purebred animals. However, a number of breeds have emerged from morbidity/mortality studies as having higher risks based on univariate analysis. These effects did not appear to survive a multivariate analysis indicating that other factors may have more strongly influenced the observed complication rate (e.g., a greater incidence of complications in small breed dogs) [34,35]. In one study, the “pastoral” or herding dogs were found to have a high mortality rate and it is possible that this is related to the ABCB1 (MDR1) gene polymorphism mentioned above [34]. Obviously, breeds that have a predisposition to cardiac disease may have greater risks for anesthesia. Despite the unreliability of internet reports of breed sensitivities, it is incumbent on the anesthetist to investigate specific concerns that are presented by an owner. If the last two of the owner’s same‐breed dogs died under anesthesia, it would be foolhardy to dismiss this without obtaining more details of the circumstances.

Histamine release

This appears to be greater in dogs than in other species, but the specific mechanism is unclear. The most notorious example of this was the spectacular release of histamine following the administration of alfaxalone–alfadolone in its original Cremophor base. This resulted in the deaths of a number of dogs [36] before pretreatment with antihistamines was advocated [37]. The drug in this formulation was never licensed for use in dogs, although many practitioners continued to use it in conjunction with antihistamines [38]. Morphine and meperidine are two opioids known to release histamine and, although it is difficult to make direct comparisons between species, the plasma concentrations of histamine in dogs appear to be considerably higher than those found in humans [39–41]. Of note in one experiment in humans is that the hemodynamic effects of the histamine release were not entirely blocked by administration of H₁ or H₂ blockers but were abolished when both were co‐administered [41]. Cetirizine appears to be more effective than diphenhydramine at preventing the effect of histamine in a skin wheal but this was after a 6‐day course of the drug so it is not known if this would be true with a single dose [42]. Recently, a study tested the histamine release in dogs with mast cell tumors (MCT) administered 0.5 mg/kg morphine intramuscular (IM) and in two MCT cell lines [43]. Unsurprisingly, there was no statistical difference in histamine release, but the authors concluded that morphine administration would be “safe” in dogs with MCT. However, their study only included 10 animals and they did not include the route of administration in this statement. This is an unfortunate overstatement of their results.

Brachycephalic breeds

Of the breeds in this class, there are various degrees of the manifestation of the typical brachycephalic obstructive airway syndrome (BOAS) – stenotic nares, elongated soft palate, everted lateral ventricles, hypoplastic trachea, and bronchial collapse [44]. The addition of conchal shortening to these anatomical abnormalities, with effects on both rostral and caudal obstruction of the nasal passages, has been described [45]. This constellation of anatomic changes leads to a higher‐than‐normal potential for airway obstruction, especially if the animal is not fully conscious and it is likely that these dogs suffer from something similar to sleep apnea in humans. Brachycephalic dogs have been shown to have higher PaCO₂ and lower PaO₂ values than meso‐ or dolicocephalic dogs [46]. Important considerations for the anesthetist are summarized in Box 50.1.

These authors’ preference is that any brachycephalic dog that is to be anesthetized should have its upper airway examined immediately after induction and surgical correction performed if deemed necessary. Ideally, this should be done before any other procedure so that any bleeding has stopped by the time the animal is recovering. This reduces the risk of postoperative airway obstruction by removing some of the contributing factors.

Tracheal collapse

Some breeds such as Yorkshire Terriers are well known for this, and it can be very difficult to manage. Clinical signs include coughing, honking, hacking, wheezing, and dyspnea, although some dogs can have a degree of collapse with no clinical signs other than exercise intolerance. Tracheal collapse is also commonly associated with collapse in the lower airways making it even more difficult to manage perioperatively [47]. In theory, an extrathoracic tracheal collapse should be associated with increased inspiratory effort while an intrathoracic collapse is associated with an increased expiratory effort, but clinically, this is often not that distinct. Although, traditionally, radiographs have been used as part of the diagnostic workup for these cases, it has been shown that this is a relatively insensitive test compared with bronchoscopy [47]. Tidal breathing flow–volume loops are also a useful diagnostic tool and can be used to separate those dogs with and without tracheal collapse and those with severe collapse compared with mild/moderate disease. The variables used in this diagnosis are (1) the expiratory time divided by the inspiratory time, (2) the inspiratory time divided by the total respiratory time, and (3) the expiratory flow at end‐tidal volume plus 75% end‐tidal volume divided by the same inspiratory variable [48].

Medical management of these patients is often possible with the use of antibiotics to treat respiratory infections, weight loss, antisecretory agents, antitussives, and diuretics [49]. Anabolic steroids such as stanozolol may also improve the airway of these animals and could be used as a preoperative treatment to decrease the risk to these patients [50]. However, mean survival times have been much greater with the addition of a stent than with medical management alone [51].

The anesthetic management of these patients is, in many ways, similar to that used for brachycephalic breeds. In setting up for these animals, it is important to have endotracheal tubes (ETTs) available that are long enough to reach the carina if there is expected to be intrathoracic tracheal collapse. Once an airway has been secured and the tracheal collapse bypassed the patient may breathe spontaneously or be put on positive‐pressure ventilation with or without continuous positive airway pressure (CPAP)/positive end‐expiratory pressure (PEEP) if there is bronchomalacia involved. Recovery is the most dangerous period if the airway has not been stented, as collapse may reoccur and cause airway obstruction. It is therefore important to try to provide a calm recovery with a slow return to consciousness so that there are no sudden increases in activity that require increased respiratory effort or that will stimulate coughing. Antitussives, acepromazine, and α₂‐adrenergic receptor agonists can be extremely helpful if administered close to the time of extubation. In order to reduce the risk of coughing, it may be prudent to remove the ETT earlier than normal. A technique for applying CPAP via facemask has been described, which may prove useful for these patients [52].

Many extra‐ or intra‐luminal stents have been inserted in dogs with tracheal collapse [53]. With the placement of extraluminal stents, the anesthetic management is as above. For intraluminal stents, the dog must be intubated initially for tracheal size measurement. This is achieved by placing an ETT just past the larynx and inflating the lungs to 20 cm H₂O. The relevant tracheal diameter is then measured using known measurement markers in the image (e.g., fluoroscopy with image capture). In small patients, it is not possible to deploy the stent through the ETT so anesthesia must be maintained using injectable anesthetics such as propofol or alfaxalone and oxygen supplemented by insufflation or jet ventilation during placement.

Red blood cell potassium

Dogs are unusual in having low potassium concentrations in their erythrocytes. Concentrations around 5–6 mmol/L are usually found in most canine erythrocytes but there are a number of breeds, including the Akita, Shiba Inu, and some other Japanese breeds, that may have high potassium concentrations. This only becomes a concern when blood is stored. In citrate‐phosphate‐dextrose‐adenine (CPDA‐1) stored canine blood, plasma potassium increased to over 8 mmol/L after 30 days of storage but in human stored red cells (where the erythrocytes contain higher concentrations of potassium), the plasma potassium increased to 30 mmol/L at 3 weeks and to 44 mmol/L by 6 weeks [54,55]. Even with these higher concentrations of potassium, it is unlikely to significantly raise plasma potassium during a single unit transfusion in humans but when multiple units are used, it can result in hyperkalemia [56].

Handling and behavior

Recommendations for feline‐friendly handling have been developed by the American Association of Feline Practitioners and the International Society of Feline Medicine and endorsed by the American Animal Hospital Association [57,58]. In particular, handling a fearful or aggressive cat may be challenging. Recommendations for managing these cats include training prior to the visit to get them used to the cat carrier and being in the vehicle. A number of drugs have been used to calm animals prior to transportation and these include gabapentin, trazodone, α₂‐adrenergic receptor agonists, acepromazine, alprazolam, and melatonin [59,60] (Table 50.2). Gabapentin has been examined in a number of studies and has been shown to reduce the stress of transport, sedate the cat, and facilitate handling at the clinic [61–63]. The pharmacokinetics of the drug are significantly altered in cats with chronic kidney disease, suggesting that lower doses should be used in these animals [64]. Presedating a cat with gabapentin does not appear to alter acute antinociception [65]. Gabapentin administered IV to cats did not appear to affect inhalant anesthetic minimum alveolar concentration (MAC), but oral administration resulted in a 32% reduction in MAC [66,67]. These different results may be simply due to dose, although this is deemed unlikely. The highest plasma concentration in the IV study maintained the peak plasma concentration expected after approximately 25 mg/kg orally for the duration of MAC determination. Although the oral study used 30 mg/kg, the plasma concentration would be expected to gradually decrease below its peak over time, likely resulting in limited differences between the IV and oral studies at the time of MAC measurement [66]. A dose of 10–20 mg/kg can be used as a starting point and it has been suggested that it be given the night before and on the day of the visit, ideally 2–3 h before travel. Trazodone can also decrease anxiety associated with transportation and entering the clinic and it may ensure that the cat is easier to manage in the clinic [68]. A number of behavioral side effects are reported with trazodone, including vomiting, diarrhea, hypersalivation, excitation, and ataxia. Dexmedetomidine, in the form of Sileo^® gel for mucosal application, which is licensed in dogs to treat fear of loud noises, has been used off‐label in cats. Use of the injectable solution of dexmedetomidine for buccal administration has also been examined [69]. As with any α₂‐adrenergic receptor agonist, it can produce profound sedation and may induce vomiting. Alprazolam is a benzodiazepine but there are no studies in cats showing its value in this setting. Although it is classified as an anxiolytic, excitation has been reported with the use of two other benzodiazepines in cats (midazolam and diazepam), so it may not be the most reliable drug to use for this purpose [70]. Acepromazine is usually criticized by behaviorists as not being an anxiolytic, but it is an ataractic that tends to decrease the animal’s awareness of its surroundings. It is best to use the injectable solution for buccal administration, which facilitates administration by the owner. Although the sedation with acepromazine in cats is rarely profound, it may decrease the animal’s reactiveness to transportation and examination, but there are no studies supporting this application. Acepromazine may decrease the dose of drug needed for induction and maintenance of anesthesia [71]. Melatonin has been shown to have a calming effect in some cats [72]. One group has been using a combination of gabapentin and melatonin for preoperative sedation and has anecdotally reported positive effects with this combination [59].

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Tags: Veterinary Anesthesia and Analgesia

May 1, 2025 | Posted by admin in SUGERY, ORTHOPEDICS & ANESTHESIA | Comments Off on Comparative Anesthesia and Analgesia – Dogs and Cats

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Medication	Form and concentration	Feline dose and route	Onset	Duration	Adverse effects
Dexmedetomidine