Experimental animals: Six intact, adult beagle dogs (3
males and 3 females) that were 3 to 5 years of age [4.2 ± 1.0 (mean ± standard
deviation) years old] and that weighed 9.0 to 11.5 kg (10.1 ± 0.8 kg) were used in the
present study. All dogs were judged to be in good physical condition based upon a physical
examination. Food was withheld for at least 12 hr before drug administration, but the dogs
were allowed free access to water prior to each treatment. The dogs were cared for according
to the principles of the “Guide for the Care and Use of Laboratory Animals” prepared by
Rakuno Gakuen University. The Animal Care and Use Committee of Rakuno Gakuen University
approved this study (approved No. VH25B7).
Study design: The dogs received 3 IM doses each of 1% alfaxalone-HPCD
(Alfaxan, Jurox Pty. Ltd., Rutherford, NSW, Australia) at increasing dose rates of 5 mg/kg
(IM5), 7.5 mg/kg (IM7.5) and 10 mg/kg (IM10) every other day over a 5 day period. The IM
doses were injected slowly (i.e., approximately 10 ml/min) into the dorsal
lumbar muscle of the dog by using a syringe with a 23-gauge, 1-inch needle (TOP injection
needle, TOP Co., Ltd., Tokyo, Japan). The maximum volume of IM injection was set at 0.5
ml/kg per injection site. Therefore, the IM dose of alfaxalone-HPCD was
divided into 2 or 3 syringes and injected into 2 or 3 separate sites on the dorsal lumber
muscle when the dogs received the IM7.5 and IM10 treatments. The dogs breathed room air and
were endotracheally intubated with an endotracheal tube [Endotracheal tube with cuff (I.D.
7.5 mm), Fuji Systems Corp., Tokyo, Japan] when possible after the dog first moved into a
position of lateral recumbency. The endotracheal tube was removed when the dog regained its
laryngeal reflex. Anesthetic and cardiorespiratory effects of the IM alfaxalone-HPCD were
evaluated in the dogs before (baseline) and at 5, 10, 15, 20, 30, 45, 60, 90, 120 and 180
min after starting drug administration.
Evaluation of anesthetic effect: Anesthetic effect was evaluated by the
degree of neuro-depression, the quality of anesthetic induction including the ease of
tracheal intubation and the quality of recovery from anesthesia. The neuro-depression
produced with alfaxalone-HPCD was subjectively evaluated as a sedation score using a
composite measurement scoring system modified from a previous report in dogs [41 (link)]. The scoring system consisted of 5 categories:
spontaneous posture, placement on side, response to noise, jaw relaxation and general
attitude. These categories were rated with a score of 0 to 2 for jaw relaxation, 0 to 3 for
placement of side and general attitude and 0 to 4 for spontaneous posture and response to
noise based on the responsiveness expressed by the dogs (Table 1 Composite scoring system for evaluating neuro-depressive effects in dogs
categories (a maximum of 16). The qualities of anesthetic induction and recovery were
assessed using numerical scoring systems modified from one previously used in dogs [30 (link)] (Table
2 Scoring systems for evaluating the qualities of anesthetic induction and recovery<br/>in dogs
anesthetic effect of the treatments using these scoring systems mentioned above throughout
the present study. In addition, the time of onset of lateral recumbency, placement of the
endotracheal tube, the first appearance of spontaneous movement, head lift and unaided
standing after starting drug administration, and the durations of acceptance of endotracheal
intubation and maintenance of lateral recumbency were observed and recorded.
Measurements of cardiorespiratory valuables: Lead II electrocardiography
(ECG), heart rate (HR; beats/min) and rectal temperature (RT; °C) were recorded before and
after drug administration. Mean arterial blood pressure (MABP; mmHg), percutaneous oxygen
saturation of hemoglobin (SpO2; %) and partial pressure of end tidal
CO2 (PETCO2; mmHg) were measured when the dogs were intubated. An
SpO2 sensor was applied to the tongue and changed periodically.
PETCO2 was measured by using a mainstream capnometer. ECG, HR, SpO2and PETCO2 were recorded by a patient monitoring system (DS-7210, Fukuda Denshi
Co., Ltd., Tokyo, Japan). HR was also counted by thoracic auscultation. Respiratory rate
(RR; breaths/min) was counted by observing thoracic movements. RT was measured with a
digital thermometer (Thermo flex for animal, Astec Co., Ltd., Chiba, Japan). MABP was
indirectly measured by an oscillometric method (PetMAP, Ramsey Medical, Inc., Hudson, OH,
U.S.A.) using a blood pressure cuff with a width of approximately 40% of the circumference
of the measuring site placed around the clipped tail base of each dog. The arterial blood
pressure was measured three times at each assessment, and the average of these measurements
was defined as the arterial blood pressure.
Statistical analysis: The total sedation, induction and recovery scores
were reported as the median ± quartile deviation. The total sedation score was analyzed by
the Friedman test to assess changes from baseline values with time for each treatment.
Differences in the total sedation, induction and recovery scores among the treatments were
compared by Friedman test with the Scheff test for post hoc comparisons. Times related to
the anesthetic effects and cardiorespiratory variables were reported as the mean ± standard
deviation. The times were compared by paired t test or 1-way (treatment)
factorial ANOVA with the Bonferroni test for post hoc comparisons among treatments. The
cardiorespiratory variables were analyzed using 2-way (treatment and time) repeated measure
ANOVA followed by the Bonferroni test. Observations and/or perceived adverse effects related
to drug administration were compared between treatments by using the chi square test. The
level of significant was set at P<0.05.
males and 3 females) that were 3 to 5 years of age [4.2 ± 1.0 (mean ± standard
deviation) years old] and that weighed 9.0 to 11.5 kg (10.1 ± 0.8 kg) were used in the
present study. All dogs were judged to be in good physical condition based upon a physical
examination. Food was withheld for at least 12 hr before drug administration, but the dogs
were allowed free access to water prior to each treatment. The dogs were cared for according
to the principles of the “Guide for the Care and Use of Laboratory Animals” prepared by
Rakuno Gakuen University. The Animal Care and Use Committee of Rakuno Gakuen University
approved this study (approved No. VH25B7).
Study design: The dogs received 3 IM doses each of 1% alfaxalone-HPCD
(Alfaxan, Jurox Pty. Ltd., Rutherford, NSW, Australia) at increasing dose rates of 5 mg/kg
(IM5), 7.5 mg/kg (IM7.5) and 10 mg/kg (IM10) every other day over a 5 day period. The IM
doses were injected slowly (i.e., approximately 10 ml/min) into the dorsal
lumbar muscle of the dog by using a syringe with a 23-gauge, 1-inch needle (TOP injection
needle, TOP Co., Ltd., Tokyo, Japan). The maximum volume of IM injection was set at 0.5
ml/kg per injection site. Therefore, the IM dose of alfaxalone-HPCD was
divided into 2 or 3 syringes and injected into 2 or 3 separate sites on the dorsal lumber
muscle when the dogs received the IM7.5 and IM10 treatments. The dogs breathed room air and
were endotracheally intubated with an endotracheal tube [Endotracheal tube with cuff (I.D.
7.5 mm), Fuji Systems Corp., Tokyo, Japan] when possible after the dog first moved into a
position of lateral recumbency. The endotracheal tube was removed when the dog regained its
laryngeal reflex. Anesthetic and cardiorespiratory effects of the IM alfaxalone-HPCD were
evaluated in the dogs before (baseline) and at 5, 10, 15, 20, 30, 45, 60, 90, 120 and 180
min after starting drug administration.
Evaluation of anesthetic effect: Anesthetic effect was evaluated by the
degree of neuro-depression, the quality of anesthetic induction including the ease of
tracheal intubation and the quality of recovery from anesthesia. The neuro-depression
produced with alfaxalone-HPCD was subjectively evaluated as a sedation score using a
composite measurement scoring system modified from a previous report in dogs [41 (link)]. The scoring system consisted of 5 categories:
spontaneous posture, placement on side, response to noise, jaw relaxation and general
attitude. These categories were rated with a score of 0 to 2 for jaw relaxation, 0 to 3 for
placement of side and general attitude and 0 to 4 for spontaneous posture and response to
noise based on the responsiveness expressed by the dogs (
| Spontaneous posture | Score |
| Standing | 0 |
| Tired and standing | 1 |
| Lying but can rise | 2 |
| Lying with difficulty rising | 3 |
| Unable to rise | 4 |
| Placement on side | Score |
| Resists strongly | 0 |
| Modest resistance | 1 |
| Slight resistance | 2 |
| No resistance | 3 |
| Response to noise | Score |
| Jump | 0 |
| Hears and moves | 1 |
| Hears and twitches ear | 2 |
| Barely perceives | 3 |
| No response | 4 |
| Jaw relaxation | Score |
| Poor | 0 |
| Slight | 1 |
| Good | 2 |
| General attitude | Score |
| Excitable | 0 |
| Awake and normal | 1 |
| Tranquil | 2 |
| Stuporous | 3 |
| Total sedation score* | 0–16 |
This scoring system was modified from a previous report in dogs [41 (link)] and consisted of 5 categories (spontaneous
posture, placement on side, response to noise, jaw relaxation and general attitude).
These categories were rated from 0 to 2, 0 to 3 or 0 to 4 based on responsiveness
expressed by the dogs. *The total sedation score was calculated as the sum of the
scores for the 5 categories: spontaneous posture, placement on side, response to
noise, jaw relaxation and general attitude.
categories (a maximum of 16). The qualities of anesthetic induction and recovery were
assessed using numerical scoring systems modified from one previously used in dogs [30 (link)] (
2
| Categories | Conditions in dogs |
|---|---|
| Induction score | |
| 4 (Very smooth) | No swallowing, intubation at first attempt, no coughing, no struggling, no vocalization. |
| 3 (Quite smooth) | Some swallowing, intubation after 2–3 attempts, no coughing, some physical movement, no vocalization. |
| 2 (Moderately smooth) | Swallowing a lot, more than 3 attempts to intubate, coughing, vocalization and/or physical movement for more than half the induction time, some distress and excitement. |
| 1 (Poor) | Vocalization and physical movement during entire induction period, major distress aggression or excitement, additional induction agent needed for intubation. |
| Recovery score | |
| 4 (Very smooth) | No excitement. No paddling, vocalizing, trembling or vomiting. No convulsions. |
| 3 (Quite smooth) | A little excitement. Some head movement, possibly some shivering but no paddling, vocalizing, trembling or vomiting. No convulsions. |
| 2 (Moderately smooth) | Moderate excitement. Some paddling, vocalizing, trembling or vomiting. No convulsions. |
| 1 (Poor) | Extreme excitement observed, aggression, vocalizing, violent movements or convulsions. Rescue sedation or anticonvulsant drugs necessary. |
anesthetic effect of the treatments using these scoring systems mentioned above throughout
the present study. In addition, the time of onset of lateral recumbency, placement of the
endotracheal tube, the first appearance of spontaneous movement, head lift and unaided
standing after starting drug administration, and the durations of acceptance of endotracheal
intubation and maintenance of lateral recumbency were observed and recorded.
Measurements of cardiorespiratory valuables: Lead II electrocardiography
(ECG), heart rate (HR; beats/min) and rectal temperature (RT; °C) were recorded before and
after drug administration. Mean arterial blood pressure (MABP; mmHg), percutaneous oxygen
saturation of hemoglobin (SpO2; %) and partial pressure of end tidal
CO2 (PETCO2; mmHg) were measured when the dogs were intubated. An
SpO2 sensor was applied to the tongue and changed periodically.
PETCO2 was measured by using a mainstream capnometer. ECG, HR, SpO2and PETCO2 were recorded by a patient monitoring system (DS-7210, Fukuda Denshi
Co., Ltd., Tokyo, Japan). HR was also counted by thoracic auscultation. Respiratory rate
(RR; breaths/min) was counted by observing thoracic movements. RT was measured with a
digital thermometer (Thermo flex for animal, Astec Co., Ltd., Chiba, Japan). MABP was
indirectly measured by an oscillometric method (PetMAP, Ramsey Medical, Inc., Hudson, OH,
U.S.A.) using a blood pressure cuff with a width of approximately 40% of the circumference
of the measuring site placed around the clipped tail base of each dog. The arterial blood
pressure was measured three times at each assessment, and the average of these measurements
was defined as the arterial blood pressure.
Statistical analysis: The total sedation, induction and recovery scores
were reported as the median ± quartile deviation. The total sedation score was analyzed by
the Friedman test to assess changes from baseline values with time for each treatment.
Differences in the total sedation, induction and recovery scores among the treatments were
compared by Friedman test with the Scheff test for post hoc comparisons. Times related to
the anesthetic effects and cardiorespiratory variables were reported as the mean ± standard
deviation. The times were compared by paired t test or 1-way (treatment)
factorial ANOVA with the Bonferroni test for post hoc comparisons among treatments. The
cardiorespiratory variables were analyzed using 2-way (treatment and time) repeated measure
ANOVA followed by the Bonferroni test. Observations and/or perceived adverse effects related
to drug administration were compared between treatments by using the chi square test. The
level of significant was set at P<0.05.
