Abstract
OBJECTIVE
To compare IV doses of alfaxalone and ketamine needed to facilitate orotracheal intubation and assess effects of each treatment on selected physiologic variables in goats undergoing orthopedic surgery with isoflurane anesthesia.
ANIMALS
18 healthy adult goats.
PROCEDURES
Behavior was assessed before and after sedation with midazolam (0.1 mg/kg, IV) for IV catheter placement. Anesthesia was induced with additional midazolam (0.1 mg/kg, IV) and alfaxalone (n = 9) or ketamine (9) at 2 mg/kg, IV, over 30 seconds. An additional dose of alfaxalone or ketamine (1 mg/kg) was given IV if needed for intubation; anesthesia was maintained with isoflurane in oxygen and IV fluids with ketamine (0.5 to 1 mg/kg/h). Direct systolic (SAP), diastolic (DAP), and mean (MAP) arterial blood pressures; heart rate; and respiratory rate were recorded before induction, immediately after intubation, and during surgery. Qualitative anesthetic induction and recovery characteristics were assessed. Variables were compared within and between groups by statistical methods.
RESULTS
No preinduction variables differed significantly between groups. Postintubation and 30-minute intraoperative SAP, DAP, and MAP were higher for the ketamine group than for the alfaxalone group; within the alfaxalone group, postintubation SAP, MAP, and respiratory rate prior to mechanical ventilation were lower than respective preinduction values. All alfaxalone-group goats were intubated after 1 dose of the induction agent; 5 of 9 ketamine-group goats required an additional (1-mg/kg) dose. Postoperative recovery was good to excellent for all animals.
CONCLUSIONS AND CLINICAL RELEVANCE
Both drugs were suitable for induction of anesthesia after sedation with midazolam, but most goats required higher doses of ketamine to allow intubation. For situations in which alfaxalone administration is appropriate, the potential for decreased arterial blood pressures and respiratory rate should be considered.
Goats are gaining popularity as companion animals and are increasingly used in investigative studies, so the need to anesthetize these animals to facilitate surgical treatment or research is increasing. Only a few reports1–3 describe induction of anesthesia in goats, but ketamine continues to be a mainstay in the anesthetic management of small ruminants because of its reasonable cost and wide margin of safety.4 However, challenges with intubation owing to large amounts of salivary and oral secretions, maintenance of reflexes, and inadequate muscle relaxation combined with the anatomic challenges of a small oral cavity opening and long soft palate are reported.5 For these reasons, large or repeated doses may be necessary to provide adequate conditions for intubation in this species.1,6 A delay in intubation or multiple unsuccessful attempts can predispose a patient to potential complications such as regurgitation and aspiration.1,6 In goats, as with other species, ketamine is therefore frequently combined with either propofol or a benzodiazepine in an effort to improve intubation conditions and reduce the required dose of ketamine.4,6,7
Alfaxalone, a neuroactive steroid anesthetic induction agent, has recently become available in the United States. It has been used to induce anesthesia in many veterinary species, including cats, dogs, sheep, horses, and pigs.8–12 Intravenous doses of 2 and 5 mg of alfaxalone/kg have resulted in anesthesia of unpremedicated dogs and cats, respectively.8,9 Results from a study3 of 6 mixed-breed goats indicate the anesthetic induction dose of alfaxalone is between 2 and 3 mg/kg, depending on the degree of sedation following preanesthetic medication. In that study,3 alfaxalone was administered at a dosage of 1.5 mg/kg, IV, over 30 seconds, followed by additional alfaxalone boluses of 0.5 mg/kg, IV, every 15 seconds as needed until swallowing reflexes were diminished and jaw tone was relaxed enough to allow for orotracheal intubation. The use of alfaxalone as a maintenance anesthetic in a population of indigenous African goats is also described.3,13,14 The purpose of the study reported here was to build on this limited prior information in a different population of goats and directly compare the traditional anesthetic agent ketamine with the newer anesthetic agent alfaxalone for induction of anesthesia in premedicated goats. The null hypothesis was that no differences in measured variables would be observed between goats that received ketamine and those that received alfaxalone.
Materials and Methods
Animals and study design
A convenience sample of 18 adult female Boer-cross goats concurrently enrolled in an orthopedic research study (unpublished at the time of the present study) were assigned to receive 1 of 2 anesthetic induction treatments (alfaxalone or ketamine) in a prospective, randomized, blinded investigation. Orotracheal intubation was designated as the main study end point, and selected behavioral, cardiovascular, and respiratory variables were assessed at predetermined time points. Assignment of alfaxalone or ketamine as treatment was determined by a coin toss. Group assignment was performed by means of a random number generator.a Nine animals received each treatment. All goats were weighed (mean ± SD, 58.5 ± 8.7 kg) ≤ 4 days before the start of the study, and in addition to daily observations of behavior and appetite during this period, a physical examination was performed by a veterinarian the evening prior to the day of the study to ensure animals were healthy. The study was approved by the Animal Care and Use Committee at Colorado State University (protocol No. 14-5998A).
Procedures
Food was withheld for a minimum of 12 hours prior to the study, but water remained available at all times. A presedation behavior score (Supplementary Appendix S1, available at http://avmajournals.avma.org/doi/suppl/10.2460/ajvr.80.9.819) was assigned to each goat on the first attempt to catch the animal in the pen and again during placement of an IV catheter. The behavior assessments were made by 1 investigator (KTB). Both behavior scales were created by the authors for study purposes and ranged from 1 to 4, where 1 represented the greatest resistance and 4 represented the least resistance to the described procedures. The same investigator performed all behavioral assessments throughout the study. All goats had hair over the caudal auricular vein clipped and the site aseptically prepared for IV catheter placement prior to sedation with midazolamb (0.1 mg/kg, IV). Following midazolam administration, the ipsilateral caudal auricular artery was aseptically prepared for placement of an arterial catheter to facilitate measurement of blood pressure with a direct arterial blood pressure transducerc that was zeroed to atmospheric pressure. The external zero reference point at which the transducer was placed for all readings was the point of the shoulder. The zeroing was verified following positioning of the goat on the surgical table. Calibration of the transducer was also verified against a mercury manometer over the working range of blood pressures. After allowing time for the goat to calm following arterial catheter placement (as determined by observation of behavior), the level of sedation was assessed and scored from 1 (no sedation) to 4 (profound sedation) for all goats (Supplementary Appendix S1).
Oxygen was administered to all goats (via a loose-fitting face mask with oxygen delivery set at 5 L/min and a standard small-animal circle breathing circuit) for 2 to 4 minutes prior to induction of anesthesia, and during this time, preinduction cardiorespiratory variables (HR, DAP, SAP, and MAP) were observed over a period of 1 minute by use of the arterial catheter waveform and recorded. Respiratory rate was obtained by visually counting chest wall excursions over 15 seconds and multiplying by 4. Immediately prior to induction of anesthesia, all goats were given an additional IV dose of midazolam (0.1 mg/kg). Alfaxalone group goats were administered alfaxaloned (2 mg/kg, IV), and ketamine group goats were administered ketamine hydrochloridee (2 mg/kg, IV). The doses used were selected on the basis of previous studies3,4,13 and supporting clinical evidence suggesting that, when used with premedicants, 2 mg of alfaxalone/kg and 2 mg of ketamine/kg are equivalent for anesthetic induction and intubation in goats. To facilitate blinding, ketamine was diluted to a concentration of 10 mg/mL in sterile saline (0.9% NaCl) solution to provide a volume equivalent to that for alfaxalone.
A certified veterinary technician (LMM) who was experienced and proficient at small ruminant intubation and was blinded to the treatment group assignment administered the induction drugs over 30 seconds. Intubation was attempted after an additional 30 seconds (approx time required to position the goat) elapsed. If the first intubation attempt was unsuccessful, an additional dose (1 mg/kg) of the assigned drug was administered as a bolus, and intubation was reat-tempted after an additional 30 seconds. Qualitative induction characteristics were subjectively assessed by the same individual (LMM). Time to intubation from initial drug administration and immediate postintubation variables (HR, DAP, SAP, MAP, and RR prior to mechanical ventilation) were recorded as previously described. After induction and intubation, all goats were positioned on the surgical table in dorsal recumbency and monitored and managed similarly, regardless of the induction agent received. The initial vaporizer setting was recorded following connection to a standard small-animal circle breathing circuit with an oxygen flow rate of 1.5 L/min. The anesthetist (LMM), who was blinded to the treatment group, set the vaporizer dial on the basis of physiologic variable (HR, SAP, DAP, and MAP) measurements and clinical assessment of anesthetic depth (eye position, jaw tone, and degree of muscle relaxation during patient positioning on the surgical table).
All animals were mechanically ventilated, and end-tidal carbon dioxide concentrations were maintained within a range of 35 to 45 mm Hg. Heart rate, RR (ie, mechanical ventilation rate), SAP, DAP, MAP, oxygen saturation as measured by pulse oximetry, end-tidal carbon dioxide concentration, esophageal temperature, and isofluranef vaporizer setting were observed continuously and recorded at 10-minute intervals during maintenance of anesthesia. Blood pressures (SAP, DAP, and MAP), HR, and RR were recorded at 9 time points throughout the procedure (including before and immediately after induction of anesthesia), and remaining physiologic variables were recorded beginning 10 minutes after induction for a total of 7 time points. All goats were administered an isotonic electrolyte solutiong at a rate of approximately 3 to 5 mL/kg/h, with ketamine added at a dose of 0.5 to 1.0 mg/kg/h in accordance with the standard animal care and use committee-approved protocol for orthopedic procedures that were part of the preclinical surgical research project being performed concurrently with our investigation. The time of skin incision (as measured from the time of intubation) and duration of anesthesia (as measured from the time of intubation to the time of discontinuation of inhalation anesthetic) were noted. Goats were weaned from the ventilator, and oxygen delivery through the anesthetic circuit was maintained until extubation. The animals were monitored throughout recovery, and times from discontinuation of the anesthetic gas to sternal recumbency (as defined by the goat's ability to hold its head up), extubation, and standing were recorded. Recovery quality was scored for each animal by a designated investigator (KTB) from poor to excellent (Supplementary Appendix S1).
Statistical analysis
Behavioral and physiologic data except for RR were found to be normally distributed on the basis of visual inspection of diagnostic plots, and continuous data were summarized as mean ± SD. A repeated-measures ANOVA was performed for each response variable separately with statistical software.h Specifically, treatment (alfaxalone or ketamine) and time (7 or 9 time points, depending on the variable) and the treatment-by-time interaction were treated as fixed effects. To account for repeated measures across time, animal was included in the model as a random effect. For each time point, comparisons were also made between treatments with a repeated-measures ANOVA. For each treatment, comparisons between downstream time points and the preinduction values for HR, SAP, DAP, and MAP were performed by the Dunnett method. The proportion of goats with apnea was compared between groups by use of a Fisher exact test. For RR, the assumption of normality did not hold (primarily because of the use of mechanical ventilation following intubation), and nonparametric analyses were used for this variable. Specifically, a Wilcoxon rank sum test was used to test for RR differences between groups at each time point, and a Wilcoxon signed rank test was used to test for differences between preinduction and downstream time points for each group. Bonferroni-adjusted P values were used to compare measurements for downstream time points with the preinduction values. Behavioral and recovery score data were also analyzed for differences between groups with a Wilcoxon rank sum test and were reported as median and range (with recovery scores ranked from 1 [poor] to 4 [excellent] for analysis purposes). Values of P < 0.05 were considered significant for all comparisons.
Results
Physical examination findings on the day prior to the study were similar between treatment groups. No significant intergroup differences were detected in behavior scores during the preanesthetic period. Median scores for goats being caught in the pen were 3 (range, 2 to 4) for the alfaxalone group and 2 (range, 1 to 4) for the ketamine group (P = 0.227), and median scores during placement of the IV catheter were 3 (range, 2 to 4) for the alfaxalone group and 3 (range, 1 to 4) for the ketamine group (P = 0.984). After midazolam administration and arterial catheter placement, median post-sedation behavior scores were 2 (range, 1 to 3) and 2 (range, 2 to 3) for the alfaxalone and ketamine groups, respectively (P = 1.0). All goats in the alfaxalone group were successfully intubated following administration of the initial 2-mg/kg dose, whereas a mean dose of 2.6 mg/kg was needed for animals in the ketamine group; 5 of 9 goats in the ketamine group required 1 additional dose (1 mg/kg) of ketamine to facilitate intubation. All goats in the ketamine group were intubated approximately 2 minutes from the start of administration of the first ketamine dose. All goats in the alfaxalone group were intubated on the first attempt, approximately 1 minute after the start of alfaxalone administration.
No significant intergroup differences were identified for preinduction HR (P = 0.174) or immediate postintubation HR (P = 0.640) or for preinduction SAP (P = 0.502), DAP (P = 0.187), or MAP (P = 0.495; Table 1). Significant differences in immediate postintubation SAP (P = 0.005), DAP (P = 0.012), and MAP (P = 0.010) were identified. Preinduction and immediate postintubation RR did not differ significantly (P = 0.619 and 0.068, respectively) between groups, and similar proportions of animals developed apnea immediately after intubation and prior to mechanical ventilation (5/9 vs 3/9 for the alfaxalone and ketamine groups, respectively; P = 0.637).
Preinduction and immediate postintubation cardiorespiratory variables for 18 healthy adult Boer-cross does in a study to compare IV doses of alfaxalone and ketamine needed to facilitate orotracheal intubation and assess the effects of each treatment on selected physiologic variables in goats undergoing surgery with isoflurane anesthesia.
| Variable | Alfaxalone (n = 9) | Ketamine (n = 9) |
|---|---|---|
| HR (beats/min) | ||
| Preinduction | 86.1 ± 17.7 | 95.9 ± 22.6 |
| Postintubation | 104.8 ± 18.6* | 108.1 ± 9.5 |
| SAP (mm Hg) | ||
| Preinduction | 134.1 ± 8.9 | 139.3 ± 20.1 |
| Postintubation | 115.2 ± 12.5* | 138.0 ± 23.5† |
| DAP (mm Hg) | ||
| Preinduction | 108.1 ± 7.1 | 117.9 ± 17.1 |
| Postintubation | 95.1 ± 12.2 | 114.0 ± 21.4† |
| MAP (mm Hg) | ||
| Preinduction | 122.1 ± 6.2 | 127.2 ± 18.8 |
| Postintubation | 104.0 ± 12.1* | 123.7 ± 22.6† |
| RR (breaths/min) | ||
| Preinduction | 60 (20–88) | 60 (36–148) |
| Postintubation | 0 (0–12)* | 28 (0–52)* |
Preinduction measurements were obtained after sedation with midazolam (0.1 mg/kg, IV) and prior to induction of anesthesia with additional midazolam (0.1 mg/kg, IV) and either study drug (2 mg/kg, IV, with an additional I-mg/kg dose administered if required to facilitate intubation). The mean dose of alfaxalone was 2 mg/kg, and that for ketamine was 2.6 mg/kg. Postintubation measurements were obtained immediately after placement of the endotracheal tube (prior to mechanical ventilation for orthopedic surgery with inhalation isoflurane anesthesia and IV fluids that included ketamine [0.5 to 1.0 mg/kg/h] in a concurrently performed study). Data represent mean ± SD or median (range) for the indicated group.
Within a column, the result for a given variable differs significantly (P < 0.05) from the preinduction value for the same group.
Within a row, the result is significantly (P < 0.05) different from that for the alfaxalone group.
In the alfaxalone group, there were significant differences between preinduction and postintubation HR (P = 0.004), SAP (P = 0.016), and MAP (P = 0.022) but not DAP (P = 0.186), whereas differences for all of these values were nonsignificant in the ketamine group (P = 0.129, 0.999, 0.995, and 0.991, respectively; Table 1). Differences between preinduction and immediate postintubation RR were noted in both groups (P = 0.031 for both comparisons).
There was a significant (P = 0.04) difference in the initial vaporizer setting between the alfaxalone (mean ± SD, 2.4 ± 0.17%) and ketamine (3.1 ± 0.82%) groups. Although goats were not subjectively assessed to be at different planes of anesthesia, significant differences were observed between the alfaxalone and ketamine groups at the 30-minute time point for SAP (95.8 ± 11.6 mm Hg and 112.6 ± 25.8 mm Hg, respectively; P = 0.034), DAP (77.9 ± 14.2 mm Hg and 94.7 ± 26.7 mm Hg, respectively; P = 0.025), and MAP (86.7 ± 13.1 mm Hg and 102.9 ± 25.2 mm Hg, respectively; P = 0.033; Figure 1) and at the 20-minute time point for HR (95.4 ± 17.4 beats/min and 79.1 ± 9.5 beats/min, respectively; P = 0.025). No additional differences in these cardiorespiratory variables were noted between groups during the anesthesia maintenance period. Additionally, no differences were found between groups for the duration of anesthesia (mean ± SD, 56.9 ± 7.9 minutes for the alfaxalone group and 56.7 ± 7.1 minutes for the ketamine group; P = 0.951) or time to skin incision (mean ± SD, 28 ± 4 minutes for the alfaxalone group and 26 ± 3 minutes for the ketamine group.)
Mean SAP (dotted line), DAP (solid line), and MAP (dashed line) values for 18 healthy adult Boer-cross does in a study to compare IV doses of alfaxalone and ketamine needed to facilitate orotracheal intubation and assess the effects of each treatment on selected physiologic variables in goats undergoing surgery with isoflurane anesthesia. Goats were randomly assigned to the alfaxalone (n = 9; circles) and ketamine (9; triangles) induction treatment groups. After sedation with midazolam (0.1 mg/kg, IV) for IV catheter placement, anesthesia was induced with additional midazolam (I mg/kg, IV) and alfaxalone or ketamine (2 mg/kg, IV, with an additional I -mg/kg dose of the same drug if needed for intubation). Arterial blood pressures were recorded at I0-minute intervals during anesthesia. For a concurrent study, all goats underwent orthopedic surgery during which general anesthesia was maintained with isoflurane in oxygen and received IV fluids including ketamine (0.5 to 1.0 mg/kg/h). Surgery start times were 28 and 26 minutes from the time of intubation (time 0) for the alfaxalone and ketamine groups, respectively. *Within a time point, values for all 3 variables differ significantly (P < 0.05) between groups.
Citation: American Journal of Veterinary Research 80, 9; 10.2460/ajvr.80.9.819
Recovery quality did not differ significantly (P = 0.335) between groups; all goats were assigned a rating of good or excellent (median score of 3 [range, 3 to 4] for the alfaxalone group and median score of 4 [range, 3 to 4] for the ketamine group). Time to extubation was also similar between groups (mean ± SD, 13.2 ± 4.82 minutes for the alfaxalone group and 11.9 ± 3.89 minutes for the ketamine group; P = 0.528). Time to sternal recumbency (mean ± SD, 15.8 ± 4.99 minutes for the alfaxalone group and 14.1 ± 6.25 minutes for the ketamine group; P = 0.541) and time to standing (mean ± SD, 36.3 ± 9.30 minutes for the alfaxalone group and 45.7 ± 20.19 minutes for the ketamine group; P = 0.233) were also similar between groups.
Subjectively, goats in the alfaxalone group appeared less responsive to the mouth gag and laryngoscope used during the intubation process than did goats in the ketamine group. The goats in the alfaxalone group generally had variable eye position, whereas those in the ketamine group maintained a fixed, forward gaze along with gagging, chewing, and swallowing behaviors. However, muscular movements were noted in 7 of 9 goats in the alfaxalone group and were described as focal (blinking or facial twitching) or generalized (limb paddling or muscle tremors). These were transient and of short duration and seemed unassociated with anesthetic depth.
Discussion
In the present study, a plane of anesthesia that enabled intubation was achieved with IV administration of alfaxalone or ketamine in healthy goats premedicated with midazolam. However, after receiving the initial 2-mg/kg dose, 5 of 9 goats of the ketamine group required an additional dose of the drug (predetermined as another 1 mg/kg) to achieve this, whereas goats of the alfaxalone group could all be intubated after receiving a single 2-mg/kg dose. This finding suggested that the 2 drugs, when administered over 30 seconds, are not equivalent following midazolam pre-medication in goats as we had hypothesized on the basis of previous reports.3,4,13 The ability to accomplish intubation with a dose of alfaxalone < 2 mg/kg was not evaluated. The speed of drug administration was a potential factor in the final drug dose needed for intubation, but to the authors' knowledge, there are no studies evaluating the pharmacokinetics of alfaxalone or ketamine following IV administration and the time course of peak concentration of drug in the brain for goats. It is interesting that results of a study15 indicate the concentration of ketamine in the CNS of sheep is nearly identical to the plasma concentration of the drug 1 minute after IV administration. Similar information was not found for alfaxalone, but all animals that received alfaxalone in the present study were intubated approximately 1 minute after IV administration of the drug, which suggested rapid equilibration.
Subjective assessment of qualitative induction characteristics by the blinded evaluator indicated greater muscle tone and reflexive activity in goats of the ketamine group than in the those of the alfaxalone group when placing the mouth gag and laryngoscope to view the larynx. Subtle differences in reflexive activity between groups were also noted, including blinking, twitching, and changes in eye position (alfaxalone) and maintenance of jaw tone, gagging, and swallowing (ketamine). Whereas intubation was designated as the main end point in this study, drug-specific reflexive activity may influence assessment of anesthetic depth and should be considered. The maintenance of reflex activity and muscle tone has been previously reported in veterinary patients after anesthetic induction with ketamine, but this is usually mitigated with the use of benzodiazepines at doses similar to those in this study.4,6,7
On the basis of a subjective difference in the reflexive activity and need for a higher initial vaporizer setting, despite the ability to intubate all animals, it seems possible that goats of the ketamine group were at a lighter plane of anesthesia. While not considered clinically meaningful, direct arterial blood pressure values were also higher following induction with ketamine, compared with those after induction with alfaxalone. Although these results could have been at least partially explained by the increase in sympathetic activity reported for various species following ketamine administration,4,6,16–18 differences in the initial anesthetic plane may have played an additional role. The differences noted at the 30-minute time point likely corresponded to the skin incision, which occurred just prior to this reading for all goats. Goats were not subjectively assessed to be at different anesthetic planes at this time point, and although a difference in physiologic responses was noted, the values remained within acceptable ranges.
Although differences between groups were not significant, we considered that the apparently higher median postintubation RR of the ketamine group might have also reflected a lighter plane of anesthesia. Unlike alfaxalone, ketamine is not typically considered to cause significant respiratory depression after IV administration.4,6,18 The speed of drug administration may have further influenced this difference in inherent drug properties, as at least 1 report19 suggests that respiratory depression is less likely with slower administration of alfaxalone. Slower administration may also result in administration of lower doses but could increase the time to intubation, which is not desirable in a species predisposed to regurgitation.5,6 If slower administration is elected, this potential consequence should be considered.
The finding that significant arterial blood pressure decreases from preinduction values in the alfaxalone group still resulted in clinically acceptable values suggested that perhaps the more clinically relevant effect of alfaxalone administered in this manner for induction is respiratory depression. The duration and magnitude of respiratory depression were not evaluated in this study because mechanical ventilation was instituted after induction of anesthesia according to the standard of practice in this laboratory. Similarly, the assessment of blood gases was beyond the scope of this study. However, in other species, the duration of respiratory depression or apnea following intubation after alfaxalone administration is dose dependent, and apnea has been noted in dogs 30 seconds and 1 minute after administration of 2 mg/kg, IV, and 6 mg/kg, IV, respectively.8,9 Despite the inability to assess the magnitude and duration of respiratory depression in this study, the immediate postintubation decrease in RR suggested that this effect is worthy of attention when administering alfaxalone.
Given the primary assignment of the study goats to a single surgical procedure, a crossover design was not feasible. Likewise, the number of animals used was determined by availability and presumed appropriate on the basis of information in prior studies of horses.20,21 Additionally, all goats were of similar breeds (Boer cross), and only females were represented. Despite frequent handling, the goats were not acclimatized to the study environment. This likely influenced variables measured prior to induction, as is supported by data from conscious goats for which reported values of HR, RR, SAP, DAP, and MAP were 73 to 90 beats/min, 24 to 27 breaths/min, 105 mm Hg, 70 mm Hg, and 86 mm Hg, respectively.6 This was also a small sample of healthy animals, and the results may not extrapolate to effects in compromised animals.
Our results suggested that alfaxalone could reasonably be considered as an alternative anesthetic induction agent in healthy goats, if circumstances exist in which it is preferred (eg, changes in drug regulation, availability, or cost). However, the potential for a decrease in arterial blood pressures and clinically relevant decrease in RR immediately after IV administration as performed in this study should be considered. Furthermore, it should be noted that alfaxalone is currently not licensed for use in caprine species in the United States.
Acknowledgments
No third-party funding or support was received in connection with this study or with the writing or publication of the manuscript. The authors declare that there were no conflicts of interest.
Published in abstract form in the Proceedings of the American College of Veterinary Anesthesia and Analgesia Annual Meeting, New Orleans, September 2018.
ABBREVIATIONS
| DAP | Diastolic arterial blood pressure |
| HR | Heart rate |
| MAP | Mean arterial blood pressure |
| RR | Respiratory rate |
| SAP | Systolic arterial blood pressure |
Footnotes
Random integer generator. Randomness and Integrity Services Ltd, Dublin, Ireland. Available at: www.random.org/integers/. Accessed Dec 16, 2017.
West-Ward Pharmaceutical Corp, Eatontown, NJ.
Deltran, Utah Medical Products Inc, Midvale, Utah.
Alfaxan, Jurox Inc, Kansas City, Mo.
VetaKet, Akorn Animal Health, Lake Forest, Ill.
Piramal Critical Care Inc, Bethlehem, Pa.
Normosol R, Hospira Inc, Lake Forest, Ill.
SAS Proc Mixed, version 9.4, SAS Institute Inc, Cary, NC.
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