Comparative pharmacokinetics and anesthetic effects of methohexital, pentobarbital, thiamylal, and thiopental in Greyhound dogs and non-Greyhound, mixed-breed dogs

Pharmacokinetics and duration of anesthesia of methohexital, pentobarbital, thiamylal, and thiopental in Greyhound and non-Greyhound, mixed-breed dogs were compared. In all dogs evaluated, pentobarbital induced the longest duration of anesthesia and methohexital induced the shortest duration. Pharmacokinetics of pentobarbital and methohexital were similar in both groups of dogs. Thiobarbiturates induced longer anesthetic effects in Greyhound dogs than in mixed-breed dogs. Plasma thiobarbiturate concentrations remained above normal longer in Greyhound dogs than in mixed-breed dogs. Disposition of thiobarbiturates in Greyhound dogs was characterized by nonlinearity from 45 minutes to 8 hours after dosing.     

Mortality of purebred and mixed-breed dogs in Denmark

Causes of death and age at death of 2928 dogs are reported from a questionnaire study among members of the Danish Kennel Club (DKC) in 1997. The dogs represented 20 breeds, 15 breed-groups and a group of mixed-breed dogs. The median age at death for all dogs in the study was 10.0 years. Mixed-breed dogs had a higher median age at death (11.0 years) than the entire population, but breeds like Shetland Sheepdog, Poodle and Dachshund exceeded this age (12 years). The Bernese Mountaindog, the group of Molossian types and the Sighthounds had the shortest life span with a median age at death of 7.0 years. Old age was the most frequent reported cause of death (20.8%) followed by cancer (14.5%), behavioural problems (6.4%) accidents (6.1%), hip dysplasia (4.6%), heart diseases (4.6%) and spinal diseases (3.9%). Breed-specific proportional mortalities with 95% confidence limits are given for the six most prevalent specific causes of death.     

Hepatic copper concentrations in purebred and mixed-breed dogs

Histomorphologic, histochemical, and atomic absorption analysis studies were performed on liver tissue from 623 clinically normal purebred and mixed-breed dogs to assess the range of hepatic copper concentrations, the histologic distribution of copper, and the histomorphologic changes associated with the various copper concentrations that were found. Atomic absorption analysis revealed a continuous numerical spectrum ranging from less than 100 parts per million on a dry weight basis (ppm dw) to more than 2,000. No decisive numerical criterion was found that could be used to separate normal from abnormal copper concentrations because of this continuous array. The threshold for histochemical demonstration of copper-containing granules using rhodanine or rubeanic acid staining was 400 ppm dw. At this concentration the copper-containing granules were located in the centrilobular hepatocytes (zone 3 of Rappaport). Copper-containing granules were found in the midzonal and periportal hepatocytes (zones 2 and 1 of Rappaport) in livers with 1,000 ppm dw and higher copper concentrations. The majority of the 623 livers were normal histomorphologically. Multifocal hepatitis characterized by mixed inflammatory cell accumulation and centrilobular distribution was found to be associated with copper concentrations in the range of 2,000 ppm dw or higher. An appropriate upper limit for normal hepatic copper concentration in the dog was not determined based on the present study.     

A comparison of cardiopulmonary and anesthetic effects of an induction dose of alfaxalone or propofol in dogs

ObjectiveTo compare the physiological parameters, arterial blood gas values, induction quality, and recovery quality after IV injection of alfaxalone or propofol in dogs.Study designProspective, randomized, blinded crossover.AnimalsEight random-source adult female mixed-breed dogs weighing 18.7 ± 4.5 kg.MethodsDogs were assigned to receive up to 8 mg kg^?1 propofol or 4 mg kg^?1 alfaxalone, administered to effect, at 10% of the calculated dose every 10 seconds. They then received the alternate drug after a 6-day washout. Temperature, pulse rate, respiratory rate, direct blood pressure, and arterial blood gases were measured before induction, immediately post-induction, and at 5-minute intervals until extubation. Quality of induction, recovery, and ataxia were scored by a single blinded investigator. Duration of anesthesia and recovery, and adverse events were recorded.ResultsThe mean doses required for induction were 2.6 ± 0.4 mg kg^?1 alfaxalone and 5.2 ± 0.8 mg kg^?1 propofol. After alfaxalone, temperature, respiration, and pH were significantly lower, and PaCO₂ significantly higher post-induction compared to baseline (p < 0.03). After propofol, pH, PaO₂, and SaO₂ were significantly lower, and PaCO₂, HCO₃, and PA-aO₂ gradient significantly higher post-induction compared to baseline (p < 0.03). Post-induction and 5-minute physiologic and blood gas values were not significantly different between alfaxalone and propofol. Alfaxalone resulted in significantly longer times to achieve sternal recumbency (p = 0.0003) and standing (p = 0.0004) compared to propofol. Subjective scores for induction, recovery, and ataxia were not significantly different between treatments; however, dogs undergoing alfaxalone anesthesia were more likely to have ≥1 adverse event (p = 0.041). There were no serious adverse events in either treatment.Conclusions and clinical relevanceThere were no clinically significant differences in cardiopulmonary effects between propofol and alfaxalone. A single bolus of propofol resulted in shorter recovery times and fewer adverse events than a single bolus of alfaxalone.     

Dose and cardiopulmonary effects of propofol alone or with midazolam for induction of anesthesia in critically ill dogs

ObjectiveTo determine the dose and cardiopulmonary effects of propofol alone or with midazolam for induction of anesthesia in American Society of Anesthesiologists status ≥III dogs requiring emergency abdominal surgery.Study designProspective, randomized, blinded, clinical trial.AnimalsA total of 19 client-owned dogs.MethodsDogs were sedated with fentanyl (2 μg kg^–1) intravenously (IV) for instrumentation for measurement of heart rate, arterial blood pressure, cardiac index, systemic vascular resistance index, arterial blood gases, respiratory rate and rectal temperature. After additional IV fentanyl (3 μg kg^–1), the quality of sedation was scored and cardiopulmonary variables recorded. Induction of anesthesia was with IV propofol (1 mg kg^–1) and saline (0.06 mL kg^–1; group PS; nine dogs) or midazolam (0.3 mg kg^–1; group PM; 10 dogs), with additional propofol (0.25 mg kg^–1) IV every 6 seconds until endotracheal intubation. Induction/intubation quality was scored, and anesthesia was maintained with isoflurane. Variables were recorded for 5 minutes with the dog in lateral recumbency, breathing spontaneously, and then in dorsal recumbency with mechanical ventilation for the next 15 minutes. A general linear mixed model was used with post hoc analysis for multiple comparisons between groups (p < 0.05).ResultsThere were no differences in group demographics, temperature and cardiopulmonary variables between groups or within groups before or after induction. The propofol doses for induction of anesthesia were significantly different between groups, 1.9 ± 0.5 and 1.1 ± 0.5 mg kg^–1 for groups PS and PM, respectively, and the induction/intubation score was significantly better for group PM.Conclusions and clinical relevanceMidazolam co-induction reduced the propofol induction dose and improved the quality of induction in critically ill dogs without an improvement in cardiopulmonary variables, when compared with a higher dose of propofol alone.     

The effects of ketoconazole and cimetidine on the pharmacokinetics of oral tramadol in greyhound dogs

Tramadol is administered to dogs for analgesia but has variability in its extent of absorption, which may hinder its efficacy. Additionally, the active opioid metabolite (M1) occurs in low concentrations. The purpose of this study was to determine if administration of oral tramadol with suspected metabolism inhibitors (ketoconazole, cimetidine) would lead to improved bioavailability of tramadol and M1. Six healthy Greyhounds were included. They were administered tramadol orally and intravenously, M1 intravenously, oral tramadol with oral ketoconazole and oral tramadol with oral cimetidine. Oral tramadol bioavailability was low (2.6%). Ketoconazole and cimetidine significantly increased tramadol bioavailability to 18.2% and 20.3%, respectively. The mean maximum plasma concentration of tramadol alone was 22.9 ng/ml, and increased to 109.9 and 143.2 ng/ml with ketoconazole and cimetidine, respectively. However, measured tramadol plasma concentrations were below the minimum concentration considered effective in humans (228 μg/ml). In all treatment groups, measured M1 concentrations (<7 μg/ml) were below concentrations associated with efficacy in humans. To conclude, tramadol and M1 concentrations were low and variable in dogs after oral dosing of tramadol, even in combination with cimetidine or ketoconazole, but effective concentrations in dogs have not been defined.     

Cardiopulmonary and anesthetic effects of ketamine and its enantiomers in dogs

Dogs were used to determine cardiopulmonary and chemical restraining effects of racemic ketamine and its enantiomers. Levorotatory ketamine induced the shortest duration of unconsciousness and recumbency when compared with effects of dextrorotatory and racemic ketamine. Administration of racemic ketamine or either of its enantiomers (30 mg/kg of body weight, IV) to dogs recovering from isoflurane anesthesia induced transient, but significant (P less than 0.05), decreases in arterial blood pressure, left ventricular contractility, cardiac output, and total peripheral vascular resistance. Arterial blood pressure and left ventricular contractility significantly (P less than 0.05) increased at later times after ketamine administration. Arterial pH and the PO2 values decreased after IV administration of racemic ketamine or its enantiomers. Significant differences in cardiopulmonary variables were not observed between groups given ketamine or its enantiomers.     

Characterization of urinary metabolites of testosterone, methyltestosterone, mibolerone and boldebone in greyhound dogs

Androgenic steroids are used in female greyhound dogs to prevent the onset of estrus; moreover, these steroids also have potent anabolic activity. As anabolic steroids increase muscle mass and aggression in animals, the excessive use of these agents in racing greyhounds gives an unfair performance advantage to treated dogs. The biotransformation of most anabolic steroids has not been determined in greyhound dogs. The objective of the present study was to identify the urinary metabolites of testosterone, methyltestosterone, mibolerone, and boldenone in greyhound dogs. These steroids were administered orally (1 mg/kg) to either male or female greyhound dogs and urine samples were collected pre-administration and at 2, 4, 8, 12, 24, 72, and 96 h post-administration. Urine extracts were analyzed by high-performance liquid chromatography/mass spectrometry (HPLC/MS) to identify major metabolites and to determine their urinary excretion profiles. Major urinary metabolites, primarily glucuronide, conjugated and free, were detected for the selected steroids. Sulfate conjugation did not appear to be a major pathway for steroid metabolism and excretion in the greyhound dog. Phase I biotransformation was also evaluated using greyhound dog liver microsomes from untreated dogs. The identification of several in vivo steroid metabolites generated in this study will be useful in detecting these steroids in urine samples submitted for drug screening.     

A comparison of the effects of propofol and etomidate on the induction of anesthesia and on cardiopulmonary parameters in dogs

ObjectiveTo determine the effects of propofol or etomidate on induction quality, arterial blood pressure, blood gases, and recovery quality in normal dogs.Study designRandomized, blinded trial.AnimalsEighteen purpose-bred adult Beagles.MethodsDogs were randomly assigned to receive propofol at 8 mg kg⁻¹ or etomidate at 4 mg kg⁻¹ intravenously (IV) administered to effect. Midazolam was administered at 0.3 mg kg⁻¹ IV as pre-medication at least 1 minute prior to induction. Direct arterial blood pressure, arterial blood gases, and heart rate were obtained at baseline, before induction, after induction, and for every 5 minutes afterwards until the dog began to swallow and the trachea was extubated. The dogs were allowed to breathe room air with the endotracheal tube in place.ResultsThe systolic arterial pressure (SAP) was higher in the etomidate group compared with the propofol group after induction. The SAP and mean arterial pressure (MAP) were higher in the etomidate group compared with the propofol group at 5 minutes. The recovery quality and ataxia score were worse in the etomidate group compared with the propofol group. Time from extubation to sternal recumbency and sternal recumbency to standing was longer in the etomidate group compared with the propofol group. The heart rate, PaCO₂, and HCO₃ were higher in the propofol group compared with the etomidate group after induction. The PaO₂ and SaO₂ were lower in the propofol group compared with the etomidate group after induction. The SAP and MAP were lower in the propofol group at 5 minutes compared with baseline.Conclusion and clinical relevancePropofol caused a decrease in SAP and MAP which was not observed with etomidate. Etomidate caused longer and poorer recoveries than propofol.     

Comparison of anesthetic and cardiorespiratory effects of tiletamine-zolazepam-butorphanol and tiletamine-zolazepam-butorphanol-medetomidine in dogs

This study compared anesthetic and cardiorespiratory effects of tiletamine-zolazepam-butorphanol (TT), tiletamine-zolazepam-butorphanol-medetomidine (TTD), and tiletamine-zolazepam-butorphanol-medetomidine with atipamezole reversal 1 hour after TTD administration in dogs. All dogs received glycopyrrolate. All drug combinations effectively induced anesthesia within 5 minutes after IM injection. Duration of analgesia was 40 to 60 minutes. Recovery was smooth, but the overall quality of recovery was poorer in the TT group. Hypoxia occurred with some dogs in the TTD group at 5 minutes. TTD provided better analgesia with longer duration and better recovery quality compared with TT. Reversal of TTD with atipamezole was not effective in shortening recovery time.     

Scoping review of quality of anesthetic induction and recovery scales used for dogs

ObjectiveTo compare, describe and assess the level of validation of all instruments measuring quality of induction and recovery from anesthesia in dogs.Databases usedA search was performed using the electronic database PubMed to find articles containing an induction quality scale, a recovery quality scale or both in dogs. Articles not directly accessible through PubMed were obtained through the Auburn University Library website and Google Scholar. The phrases ‘induction scoring systems dogs’, ‘recovery scoring systems dogs’, ‘anesthetic induction score dogs’, and ‘anesthetic recovery score dogs’ were used for searches using the ‘best match search’ function. The time frame searched was from 1980 to May 2020. The search was conducted from March 2020 to May 2020.ConclusionsA thoroughly tested and validated scale for measuring the quality of induction and recovery does not exist in the current veterinary literature. A large disagreement exists between studies on the use of induction and recovery scales, and many have reported inconsistent results with current instruments. It is recommended that an induction and recovery scale intended for wide-scale use be constructed and tested extensively for psychometric validation and reliability.     

Plasma and urine pharmacokinetics of intravenously administered flunixin in greyhound dogs

Medication control in greyhound racing requires information from administration studies that measure drug levels in the urine as well as plasma, with time points that extend into the terminal phase of excretion. To characterize the plasma and the urinary pharmacokinetics of flunixin and enable regulatory advice for greyhound racing in respect of both medication and residue control limits, flunixin meglumine was administered intravenously on one occasion to six different greyhounds at the label dose of 1 mg/kg and the levels of flunixin were measured in plasma for up to 96 hr and in urine for up to 120 hr. Using the standard methodology for medication control, the irrelevant plasma concentration was determined as 1 ng/ml and the irrelevant urine concentration was determined as 30 ng/ml. This information can be used by regulators to determine a screening limit, detection time and a residue limit. The greyhounds with the highest average urine pH had far greater flunixin exposure compared with the greyhounds that had the lowest. This is entirely consistent with the extent of ionization predicted by the Henderson–Hasselbalch equation. This variability in the urine pharmacokinetics reduces with time, and at 72 hr postadministration, in the terminal phase, the variability in urine and plasma flunixin concentrations are similar and should not affect medication control.     

Comparative pharmacokinetics of intravenous fentanyl and buprenorphine in healthy greyhound dogs

The purpose of this study was to compare the pharmacokinetics of two highly protein‐bound, lipophilic opioid drugs. Fentanyl (10 μg/kg) and buprenorphine (20 μg/kg) were administered intravenously (IV) to six healthy greyhound dogs (three males and three females). The doses were based on clinically administered doses for dogs. Plasma drug concentrations were determined using liquid chromatography with mass spectrometry, and noncompartmental pharmacokinetics were estimated with computer software. The volume of distribution (area) was larger for fentanyl (7.42 L/kg) compared to buprenorphine (3.54 L/kg). The plasma clearance of fentanyl (38.6 mL·min/kg) was faster than buprenorphine (10.3 mL·min/kg). The terminal half‐life of fentanyl (2.22 h) was shorter than buprenorphine (3.96 h). Despite similar physicochemical properties including octanol–water partition coefficient and pKa, the pharmacokinetics of fentanyl and buprenorphine were not similar. Both fentanyl (84%) and buprenorphine (95–98%) are considered highly protein bound, but the differences in protein binding may contribute to the lack of similarity of pharmacokinetics in healthy dogs.