Editorial Type: Anesthesiology
 | 
Online Publication Date: 01 Jan 2006

Effects of Intravenous Diazepam or Microdose Medetomidine on Propofol-Induced Sedation in Dogs

DVM, MS, Diplomate ACVA,
PhD,
DVM,
DVM, MS, and
DVM
Article Category: Research Article
Page Range: 18 – 27
DOI: 10.5326/0420018
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This crossover study tested the hypothesis that both diazepam and microdose medetomidine would comparably reduce the amount of propofol required to induce sedation. Four different medications, namely high-dose diazepam (0.4 mg/kg intravenously [IV]), low-dose diazepam (0.2 mg/kg IV), medetomidine (1 μg/kg IV), and placebo (0.5 mL physiological saline IV) were followed by propofol (8 mg/kg IV) titrated to a point where intubation could be performed. The effects of medetomidine were comparable to the effects of high-dose diazepam and significantly better than the effects of low-dose diazepam or placebo. Dogs in all treatment groups had transient hypoxemia, and induction and recovery qualities were similar.

Introduction

Propofol is an intravenous (IV) anesthetic induction agent approved for use in dogs and cats. Premedication with medetomidine has been shown to reduce the total dose of propofol needed for endotracheal intubation.1–4 Premedication with midazolam (0.1 mg/kg IV) reduced the dose of propofol required to obtain loss of the pedal reflex by 37% when compared to a control group.5 In another study, a very small dose (termed “microdose”) of medetomidine (5 μg/kg IV) given before diazepam and ketamine significantly extended the duration of lateral recumbency and analgesia without affecting the recovery quality in dogs when compared to the effects of diazepam and ketamine alone.6

The IV premedication effect of microdose medetomidine on propofol-induced sedation prior to inhalant anesthesia in dogs has not been evaluated. Clinical experience indicates that doses of medetomidine as low as 1 μg/kg IV administered 45 to 60 seconds prior to propofol are capable of reducing the total propofol dose required for endotracheal intubation. Similar observations have also been made when premedicating with IV diazepam. However, clinical observations have not determined whether a higher dose of diazepam reduces the requirement for propofol more than a lower dose of diazepam or a microdose of medetomidine.

It was hypothesized that microdose medetomidine (1 μg/kg IV) would reduce the dosage of propofol required for endotracheal intubation more than low-dose diazepam when administered in the same fashion. It was also hypothesized that high-dose diazepam would have comparable effects to microdose medetomidine while having a superior propofol sparing effect when compared to low-dose diazepam. The objectives of this study were to evaluate and compare the anesthetic and cardiorespiratory effects of two premedication doses of diazepam and a microdose of medetomidine administered IV immediately prior to propofol induction in dogs to be maintained on inhalant anesthesia. No attempts were made to assess analgesia or the use of these drugs under surgical conditions.

Materials and Methods

Eight, 1-year-old, female, mixed-breed hound-type dogs were used in this crossover study. Body weights ranged from 18 to 23 kg (mean ± standard deviation was 21±2 kg). The dogs were randomly assigned to four treatment groups: high-dose diazepama (0.4 mg/kg), low-dose diazepam (0.2 mg/kg), microdose medetomidineb (1 μg/kg), or placebo (0.5 mL physiological saline). The diazepam, medetomidine, and placebo were given as single IV boluses 45 seconds prior to propofol administration through a preplaced cephalic vein IV catheter.c The catheter was then immediately flushed with heparinized saline. Propofold was administered slowly IV (at a rate of approximately 8 mg/kg per 1.5 minute) until endotracheal intubation could be performed or until a maximum dose (8 mg/kg) of propofol was infused. The administration of propofol was stopped for 6 seconds after half of the propofol dose was administered, to allow time for propofol to reach the brain and to check the jaw tone of the dog. If the dog was unable to be intubated, half of the remaining propofol was administered, and the jaw tone was assessed again. If the dog still could not be intubated, then all of the propofol was administered followed by intubation.

Dogs received one of the four medications in a random order at 7-day intervals until each dog had received all four solutions. The investigator administering the propofol and performing the observations was blinded to the content of each test solution.

All dogs were connected to an electrocardiograph prior to any drug administration, and a lead-II electrocardiogram (ECG) was monitored for arrhythmias throughout the experiment. Baseline (immediately prior to treatment) heart rate (HR) and respiratory rate (RR) were measured via auscultation. Auscultated HR was also validated against the HR obtained from the ECG. An oscillometric arterial blood pressure monitore was used to record systolic, diastolic, and mean arterial blood pressures (MAP) 5 minutes prior to the first drug administration. After starting one of the four treatments, cardiorespiratory data were recorded at 2-minute intervals until the dogs recovered. The dogs were monitored for changes in RR, HR, the onset of arrhythmias, and for visible signs of drug effect (e.g., excitation, depression, salivation, or vocalization).

The total dose of propofol used for endotracheal intubation was recorded and compared among treatment groups. The percent reduction in propofol dose was calculated as:

\(1\ {-}\ (\frac{mean\ propofol\ dose\ from\ each\ treatment\ group}{mean\ propofol\ dose\ from\ the\ placebo\ group}\ )\ {\times}\ 100\)

Following endotracheal intubation, each dog was allowed to breathe room air. A 3.5-French (1.2 mm), red rubber urinary-type catheterf was inserted into the trachea via the endotracheal tube, such that the tip of the catheter rested at approximately the position of the thoracic inlet in order to measure alveolar gases. In anesthetic research, it is believed that a catheter this small placed in the lumen of the endotracheal tube does not affect the ventilation efficiency.6–9 The proximal end of the catheter was connected to side-stream capnographyg tubing for monitoring end-tidal carbon dioxide (etCO2) and RR. The etCO2 was monitored until the dog was extubated. A pulse oximeter with a lingual probeh was placed on the lip to monitor hemoglobin oxygen saturation (SpO2). The probe was placed on the lip instead of the tongue to maintain consistency in the pulse oximeter readings. As each dog was recovering, the tongue would often move or withdraw into the oral cavity, precluding the use of the lingual probe on the tongue during recovery. Three minutes after endotracheal intubation, an arterial blood sample was taken from the femoral artery and immediately submitted for a body temperature-corrected blood gas analysis.i

The duration of intubation and lateral recumbency and the total duration from intubation to standing were recorded. The qualities of induction and recovery were subjectively evaluated according to preset criteria [Table 1]. The quality of recovery was continuously observed and evaluated between extubation and when the dog was able to stand. The overall recovery quality was assigned a subjective score using the criteria outlined in Table 1.

The cardiorespiratory variables HR, RR, systolic and diastolic blood pressures, and MAP were measured at baseline (time 0), 1 minute after achieving endotracheal intubation with propofol induction, and at 2-minute intervals thereafter until the dog recovered to a standing position. The etCO2 and SpO2 were measured at 1 minute after endotracheal intubation and at 2-minute intervals throughout recovery.

Statistical Analysis

Analysis of variance (ANOVA) was used to assess treatment differences.j Dog was considered a blocking factor (i.e., means were adjusted for dog-to-dog variations), and the mean dosages for each treatment group were calculated and compared. When a significant difference (P ≤ 0.05) was detected, a protected Fisher’s least significant difference test was used to compare differences among the treatment groups. All results are reported as mean ± standard deviation.

Results

The body weights of the dogs did not significantly (P>0.05) differ over the course of the study [Table 2]. When compared with the placebo, all premedicants reduced the dose of propofol required for endotracheal intubation [Table 2]. This reduction was statistically significant (P=0.003) for the high-dose diazepam and medetomidine groups, where the percent reductions in propofol dose were 36% and 38%, respectively. While the percent reduction in propofol dose was 21% for the low-dose diazepam group, it was not statistically significant.

The mean duration of intubation and the mean time from intubation to walking are shown in Table 2. Induction and recovery qualities were similar among all treatment groups [Table 2]; however, there was a tendency for induction and recovery qualities to be poorer for dogs in the low-dose diazepam group. Severe salivation was observed after high-dose diazepam in one dog. In the low-dose diazepam group, three dogs exhibited excitement immediately after administration, and this excitement subsided with propofol induction. Severe paddling during recovery was observed in one dog given high-dose diazepam and in one dog given placebo. Muscle twitching was occasionally observed in all groups.

In both the high- and low-dose diazepam treatment groups, HR was significantly (P=0.03) increased at 1 minute after induction. For dogs in the high-dose diazepam group, HRs remained elevated until 5 minutes after endotracheal intubation, and for dogs in the low-dose diazepam group, HRs returned to baseline within 3 minutes of propofol administration [Figure 1]. In the medetomidine treatment group, the mean HR was significantly (P=0.01) decreased 5 minutes after endotracheal intubation and remained lower than baseline until the end of the recording period (17 minutes after endotracheal intubation). The lowest individual HR observed was 54 beats per minute, which occurred in a medetomidine-medicated dog 9 minutes after endotracheal intubation. The dogs in the medetomidine group had significantly (P=0.0001) lower mean HRs than dogs in the other treatment groups at 5, 7, 9, and 11 minutes after endotracheal intubation. No significant changes in mean HR were observed in the placebo group. Sinus arrhythmias were commonly observed in all treatment groups. No other arrhythmias were detected during the study.

The dogs in the medetomidine group had significantly (P=0.012) lower mean RRs than dogs in the other treatment groups at 1, 5, 7, 9, and 11 minutes after endotracheal intubation [Figure 2]. In all of the treatment groups, RRs significantly (P<0.05) decreased from baseline values at some point during the study. This decrease occurred at 3 minutes in the high-dose diazepam group; at 1, 3, and 5 minutes in the low-dose diazepam group; at all time points (1, 3, 5, 7, 9, 11, 13, 15, and 17 minutes) in the medetomidine group; and at 1, 3, 5, and 7 minutes after endotracheal intubation in the placebo group.

End-tidal CO2 became significantly (P<0.001) elevated in the high- and low-dose diazepam groups [Figure 3]. This elevation was observed 1 to 3 minutes after propofol administration and peaked at 3 minutes. However, the etCO2 did not exceed 51 mm Hg in any group. Although the mean RR of the medetomidine treatment group was significantly lower than the other treatment groups, etCO2 in the medetomidine group did not change significantly over time.

Mean SpO2 was significantly (P=0.02) lower in the medetomidine and placebo groups when compared to the high- and low-dose diazepam groups [Figure 4] at 3 minutes after endotracheal intubation. At 5 minutes after intubation, the placebo group had significantly lower mean SpO2 values than the other treatment groups. The lowest individual value (77%) was detected in the placebo group 5 minutes after propofol administration.

In the placebo group, MAP was significantly (P=0.01) lower than all other treatment groups at 1 minute after endotracheal intubation [Figure 5]. The lowest individual MAP recorded was 53 mm Hg in a dog receiving the placebo.

Arterial blood gases measured 3 minutes after endotracheal intubation were not significantly different among treatment groups [Table 3]. Arterial blood gas analyses, however, did confirm that dogs in all treatment groups experienced hypoxemia. The SpO2 values demonstrated that the hypoxemia was transient.

Discussion

The results of this study supported the hypothesis that the administration of microdose medetomidine 45 seconds prior to propofol administration would significantly reduce the dose of propofol required for induction when compared with low-dose diazepam. Results of the study also showed that high-dose diazepam was comparable to microdose medetomidine in reducing the required propofol dose. The use of 1 μg/kg medetomidine was based on clinical experience as well as the anticipation that this dose may not induce the profound bradycardia seen with higher doses of medetomidine. However, bradycardia still occurred in some of the medetomidine-treated dogs, and the mean HR was significantly lower in this group when compared to the other treatment groups.

A previous study showed that, when compared to the control group, midazolam (0.1 mg/kg IV) reduced by 37% the dose of propofol required to obtain loss of the pedal reflex.5 In the study reported here, 0.2 mg/kg diazepam decreased the propofol dose requirement by 21%, whereas 0.4 mg/kg diazepam decreased the propofol induction dose by 36%. These differences between midazolam and diazepam might be related to the higher potency of midazolam as well as to variations in study designs and methods.

Diazepam (0.5 mg/kg IV) has been shown to induce excessive excitement in healthy dogs.10 In an attempt to minimize this side effect, the interval between diazepam and propofol administration was shortened to 45 seconds in the present study. Despite this approach, the IV bolus administration of low-dose diazepam still induced excitement in three of the eight dogs. Once the propofol was administered, the excitement subsided in these dogs. None of the dogs experienced excitement in the other treatment groups, including the high-dose diazepam group. It is unknown why the high dose of diazepam did not cause excitement, yet the low dose did. Propofol has the potential to induce muscle twitching, but premedication with sedatives typically reduces such twitching.11 In this study, none of the premedications completely abolished the myoclonic twitching, which occurred in all treatment groups. However, the twitching was not considered clinically significant.

Haskin et al. reported increases in HR following IV injection of diazepam, but the reason for this increase was unknown.10 In the study reported here, a significant increase in mean HR was noticed after administration of both low-and high-dose diazepam. High-dose diazepam appeared to have a longer effect on HR than low-dose diazepam. In contrast to diazepam, the microdose medetomidine did not significantly change mean HR until 5 minutes after endotracheal intubation. Once the HR decreased in the medetomidine group, it remained lower than baseline until the end of the study. This reduction in HR with medetomidine was not considered clinically important, because the blood pressure was well maintained in these dogs.

A previous study demonstrated that propofol has a significant respiratory depressive effect in dogs.12 In the current study, respiratory depression occurred in the dogs of all the treatment groups, as indicated by the significant decrease in mean RRs and the elevations in mean etCO2. These changes indicated that although diazepam or medetomidine reduced the total induction dose of propofol, premedication did not ameliorate the respiratory depressive effects of propofol. A certain degree of the respiratory depressive effect may also have occurred from pretreatment with diazepam or medetomidine in these dogs.

Blood pressures were well maintained in dogs from the diazepam and medetomidine treatment groups, with MAPs remaining >60 mm Hg. Blood pressures were lowest in dogs of the placebo group 1 minute after endotracheal intubation, which may have reflected the effect of propofol on systemic vascular resistance (i.e., vasodilatation).13 The addition of diazepam or medetomidine 45 seconds prior to propofol administration may have ameliorated this vasodilatation either by reducing the amount of propofol administered or by offsetting propofol’s hemodynamic action on the vasculature or on cardiac output. Medetomidine increases systemic vascular resistance in dogs.2,13 When medetomidine and propofol were used together, the vascular effect of each drug appeared to be weaker, which may have resulted in the higher blood pressures seen in this study.

Clinically, dogs induced with propofol are frequently maintained on an inhalant anesthetic in 100% oxygen. In the present study, the dogs were purposefully allowed to breathe room air and were not given oxygen in order to monitor for hypoxia. An episode of hypoxemia occurred in each dog of every treatment group, with the lowest SpO2 (77%) observed in the placebo group 5 minutes after endotracheal intubation. It was possible that diazepam and medetomidine had different onset-of-action times, since SpO2 decreased to the lowest value at 3 minutes in the medetomidine group and did not reach a nadir until 5 minutes after induction in the diazepam groups. The presence of hypoxemia in all groups was confirmed with blood gas analyses at 3 minutes. Since propofol was common to all groups and the placebo group had significantly lower SpO2 than any other treatment group (at 5 minutes after endotracheal intubation), it was likely that propofol caused the hypoxemia and that the addition of diazepam or medetomidine did not ameliorate the problem. Since dogs in all treatment groups demonstrated transient hypoxemia during the course of propofol sedation while breathing room air, it is recommended that 100% oxygen be administered whenever propofol is administered alone or in combination with diazepam or medetomidine.

It is important to emphasize that the drug combinations used in this study produced little or no analgesia and were only intended for anesthetic induction prior to inhalant anesthesia. If surgery is to be performed, other analgesic or general anesthetic agents must be used.

Conclusion

This study demonstrated that IV premedication with high-dose diazepam or microdose medetomidine significantly reduced the propofol induction dose required for endotracheal intubation. While both drugs reduced the dose requirement of propofol, medetomidine had some advantages over diazepam, such as a longer anesthetic effect without altering the quality of recovery and the avoidance of using a controlled substance.

a

Diazepam; Abbott Laboratories, North Chicago, IL 60064

b

Domitor; Pfizer Animal Health, Exton, PA 19341

c

BD-Angiocath; The Medical Supply Company, Inc., Bethpage, NY 11714

d

PropoFlo; Abbott Laboratories, North Chicago, IL 60064

e

Cardell BP monitor, Model 9301 V; Sharn, Tampa, FL 33601

f

Sovereign; Kendall feeding tube and urethral catheter, St. Louis, MO 63143

g

Datascope-Gas Module II; Paramus, NJ 07652

h

Nellcor, N-20 PA; Puritan Bennett, Pleasanton, CA 94588

i

i-STAT blood gas analyzer; Heska Corp., Fort Collins, CO 80525

j

PROC MIXED in SAS, Version 8.2; SAS Institute, Cary, NC 27511

Table 1 Scoring System Used to Assess the Quality of Induction and Recovery in Dogs Given Four Premedication Solutions Followed by Propofol
Table 1
Table 2 Variables in Eight Dogs Given Four Premedications Followed by Propofol
Table 2
Table 3 Mean ± Standard Deviation Values for Arterial Blood Gases Measured 3 Minutes After Endotracheal Intubation in Eight Dogs Given Four Premedications Followed by Propofol
Table 3
Figure 1—. Mean (± standard deviation) heart rate in dogs following high-dose diazepam (HD, 0.4 mg/kg), low-dose diazepam (LD, 0.2 mg/kg), microdose medetomidine (M, 1 μg/kg), or placebo (P, 0.5 mL physiological saline) administered intravenously 45 seconds prior to propofol induction. Time 0 indicates baseline values prior to any drug administration. Other time intervals indicate minutes after endotracheal intubation. The letter "a" indicates values that are significantly different from values with the letter "b." The asterisks (*) indicate values that are significantly different from baseline values within the same treatment group.Figure 1—. Mean (± standard deviation) heart rate in dogs following high-dose diazepam (HD, 0.4 mg/kg), low-dose diazepam (LD, 0.2 mg/kg), microdose medetomidine (M, 1 μg/kg), or placebo (P, 0.5 mL physiological saline) administered intravenously 45 seconds prior to propofol induction. Time 0 indicates baseline values prior to any drug administration. Other time intervals indicate minutes after endotracheal intubation. The letter "a" indicates values that are significantly different from values with the letter "b." The asterisks (*) indicate values that are significantly different from baseline values within the same treatment group.Figure 1—. Mean (± standard deviation) heart rate in dogs following high-dose diazepam (HD, 0.4 mg/kg), low-dose diazepam (LD, 0.2 mg/kg), microdose medetomidine (M, 1 μg/kg), or placebo (P, 0.5 mL physiological saline) administered intravenously 45 seconds prior to propofol induction. Time 0 indicates baseline values prior to any drug administration. Other time intervals indicate minutes after endotracheal intubation. The letter "a" indicates values that are significantly different from values with the letter "b." The asterisks (*) indicate values that are significantly different from baseline values within the same treatment group.
Figure 1 — Mean (± standard deviation) heart rate in dogs following high-dose diazepam (HD, 0.4 mg/kg), low-dose diazepam (LD, 0.2 mg/kg), microdose medetomidine (M, 1 μg/kg), or placebo (P, 0.5 mL physiological saline) administered intravenously 45 seconds prior to propofol induction. Time 0 indicates baseline values prior to any drug administration. Other time intervals indicate minutes after endotracheal intubation. The letter "a" indicates values that are significantly different from values with the letter "b." The asterisks (*) indicate values that are significantly different from baseline values within the same treatment group.

Citation: Journal of the American Animal Hospital Association 42, 1; 10.5326/0420018

Figure 2—. Mean (± standard deviation) respiratory rate in dogs following high-dose diazepam (HD), low-dose diazepam (LD), microdose medetomidine (M), or placebo (P) administered intravenously 45 seconds prior to propofol induction. Time 0 indicates baseline values prior to any drug administration. Other time intervals indicate minutes after endotracheal intubation. The letter "a" indicates values that are significantly different from values with the letter "b." Values designated with "ab" are not different from the values labeled "a" or "b." The asterisks (*) indicate values that are significantly different from baseline values within the same treatment group.Figure 2—. Mean (± standard deviation) respiratory rate in dogs following high-dose diazepam (HD), low-dose diazepam (LD), microdose medetomidine (M), or placebo (P) administered intravenously 45 seconds prior to propofol induction. Time 0 indicates baseline values prior to any drug administration. Other time intervals indicate minutes after endotracheal intubation. The letter "a" indicates values that are significantly different from values with the letter "b." Values designated with "ab" are not different from the values labeled "a" or "b." The asterisks (*) indicate values that are significantly different from baseline values within the same treatment group.Figure 2—. Mean (± standard deviation) respiratory rate in dogs following high-dose diazepam (HD), low-dose diazepam (LD), microdose medetomidine (M), or placebo (P) administered intravenously 45 seconds prior to propofol induction. Time 0 indicates baseline values prior to any drug administration. Other time intervals indicate minutes after endotracheal intubation. The letter "a" indicates values that are significantly different from values with the letter "b." Values designated with "ab" are not different from the values labeled "a" or "b." The asterisks (*) indicate values that are significantly different from baseline values within the same treatment group.
Figure 2 — Mean (± standard deviation) respiratory rate in dogs following high-dose diazepam (HD), low-dose diazepam (LD), microdose medetomidine (M), or placebo (P) administered intravenously 45 seconds prior to propofol induction. Time 0 indicates baseline values prior to any drug administration. Other time intervals indicate minutes after endotracheal intubation. The letter "a" indicates values that are significantly different from values with the letter "b." Values designated with "ab" are not different from the values labeled "a" or "b." The asterisks (*) indicate values that are significantly different from baseline values within the same treatment group.

Citation: Journal of the American Animal Hospital Association 42, 1; 10.5326/0420018

Figure 3—. Mean (± standard deviation) end-tidal carbon dioxide (etCO2) in dogs following high-dose diazepam (HD), low-dose diazepam (LD), microdose medetomidine (M), or placebo (P) administered intravenously 45 seconds prior to propofol induction. The time intervals indicate minutes after endotracheal intubation. The asterisks (*) indicate values that are significantly different from the 1-minute values for the same treatment group.Figure 3—. Mean (± standard deviation) end-tidal carbon dioxide (etCO2) in dogs following high-dose diazepam (HD), low-dose diazepam (LD), microdose medetomidine (M), or placebo (P) administered intravenously 45 seconds prior to propofol induction. The time intervals indicate minutes after endotracheal intubation. The asterisks (*) indicate values that are significantly different from the 1-minute values for the same treatment group.Figure 3—. Mean (± standard deviation) end-tidal carbon dioxide (etCO2) in dogs following high-dose diazepam (HD), low-dose diazepam (LD), microdose medetomidine (M), or placebo (P) administered intravenously 45 seconds prior to propofol induction. The time intervals indicate minutes after endotracheal intubation. The asterisks (*) indicate values that are significantly different from the 1-minute values for the same treatment group.
Figure 3 — Mean (± standard deviation) end-tidal carbon dioxide (etCO2) in dogs following high-dose diazepam (HD), low-dose diazepam (LD), microdose medetomidine (M), or placebo (P) administered intravenously 45 seconds prior to propofol induction. The time intervals indicate minutes after endotracheal intubation. The asterisks (*) indicate values that are significantly different from the 1-minute values for the same treatment group.

Citation: Journal of the American Animal Hospital Association 42, 1; 10.5326/0420018

Figure 4—. Mean (± standard deviation) hemoglobin oxygen saturation (SpO2) in dogs following high-dose diazepam (HD), low-dose diazepam (LD), microdose medetomidine (M), or placebo (P) administered intravenously 45 seconds prior to propofol induction. The time intervals indicate minutes after endotracheal intubation. The letter "a" indicates values that are significantly different from values with the letter "b." The asterisks (*) indicate values that are significantly different from the 1-minute values for the same treatment group.Figure 4—. Mean (± standard deviation) hemoglobin oxygen saturation (SpO2) in dogs following high-dose diazepam (HD), low-dose diazepam (LD), microdose medetomidine (M), or placebo (P) administered intravenously 45 seconds prior to propofol induction. The time intervals indicate minutes after endotracheal intubation. The letter "a" indicates values that are significantly different from values with the letter "b." The asterisks (*) indicate values that are significantly different from the 1-minute values for the same treatment group.Figure 4—. Mean (± standard deviation) hemoglobin oxygen saturation (SpO2) in dogs following high-dose diazepam (HD), low-dose diazepam (LD), microdose medetomidine (M), or placebo (P) administered intravenously 45 seconds prior to propofol induction. The time intervals indicate minutes after endotracheal intubation. The letter "a" indicates values that are significantly different from values with the letter "b." The asterisks (*) indicate values that are significantly different from the 1-minute values for the same treatment group.
Figure 4 — Mean (± standard deviation) hemoglobin oxygen saturation (SpO2) in dogs following high-dose diazepam (HD), low-dose diazepam (LD), microdose medetomidine (M), or placebo (P) administered intravenously 45 seconds prior to propofol induction. The time intervals indicate minutes after endotracheal intubation. The letter "a" indicates values that are significantly different from values with the letter "b." The asterisks (*) indicate values that are significantly different from the 1-minute values for the same treatment group.

Citation: Journal of the American Animal Hospital Association 42, 1; 10.5326/0420018

Figure 5—. Mean (± standard deviation) blood pressures in dogs following high-dose diazepam (HD), low-dose diazepam (LD), microdose medetomidine (M), or placebo (P) administered intravenously 45 seconds prior to propofol induction. Time 0 indicates baseline values prior to any drug administration. Other time intervals indicate minutes after endotracheal intubation. The letter "a" indicates values that are significantly different from values with the letter "b." The asterisks (*) indicate values that are significantly different from baseline values within the same treatment group.Figure 5—. Mean (± standard deviation) blood pressures in dogs following high-dose diazepam (HD), low-dose diazepam (LD), microdose medetomidine (M), or placebo (P) administered intravenously 45 seconds prior to propofol induction. Time 0 indicates baseline values prior to any drug administration. Other time intervals indicate minutes after endotracheal intubation. The letter "a" indicates values that are significantly different from values with the letter "b." The asterisks (*) indicate values that are significantly different from baseline values within the same treatment group.Figure 5—. Mean (± standard deviation) blood pressures in dogs following high-dose diazepam (HD), low-dose diazepam (LD), microdose medetomidine (M), or placebo (P) administered intravenously 45 seconds prior to propofol induction. Time 0 indicates baseline values prior to any drug administration. Other time intervals indicate minutes after endotracheal intubation. The letter "a" indicates values that are significantly different from values with the letter "b." The asterisks (*) indicate values that are significantly different from baseline values within the same treatment group.
Figure 5 — Mean (± standard deviation) blood pressures in dogs following high-dose diazepam (HD), low-dose diazepam (LD), microdose medetomidine (M), or placebo (P) administered intravenously 45 seconds prior to propofol induction. Time 0 indicates baseline values prior to any drug administration. Other time intervals indicate minutes after endotracheal intubation. The letter "a" indicates values that are significantly different from values with the letter "b." The asterisks (*) indicate values that are significantly different from baseline values within the same treatment group.

Citation: Journal of the American Animal Hospital Association 42, 1; 10.5326/0420018

Footnotes

    Doctor Ko’s current address is the Department of Clinical Sciences, School of Veterinary Medicine, Purdue University, West Lafayette, Indiana 47907. This study was funded by the Center for Veterinary Health Sciences, Oklahoma State University and a NIH summer training grant: Short-term training for the health professional, T35 RR07061-08.

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Copyright: Copyright 2006 by The American Animal Hospital Association 2006
<bold> <italic toggle="yes">Figure 1</italic> </bold> —
Figure 1 —

Mean (± standard deviation) heart rate in dogs following high-dose diazepam (HD, 0.4 mg/kg), low-dose diazepam (LD, 0.2 mg/kg), microdose medetomidine (M, 1 μg/kg), or placebo (P, 0.5 mL physiological saline) administered intravenously 45 seconds prior to propofol induction. Time 0 indicates baseline values prior to any drug administration. Other time intervals indicate minutes after endotracheal intubation. The letter "a" indicates values that are significantly different from values with the letter "b." The asterisks (*) indicate values that are significantly different from baseline values within the same treatment group.

<bold> <italic toggle="yes">Figure 2</italic> </bold> —
Figure 2 —

Mean (± standard deviation) respiratory rate in dogs following high-dose diazepam (HD), low-dose diazepam (LD), microdose medetomidine (M), or placebo (P) administered intravenously 45 seconds prior to propofol induction. Time 0 indicates baseline values prior to any drug administration. Other time intervals indicate minutes after endotracheal intubation. The letter "a" indicates values that are significantly different from values with the letter "b." Values designated with "ab" are not different from the values labeled "a" or "b." The asterisks (*) indicate values that are significantly different from baseline values within the same treatment group.

<bold> <italic toggle="yes">Figure 3</italic> </bold> —
Figure 3 —

Mean (± standard deviation) end-tidal carbon dioxide (etCO2) in dogs following high-dose diazepam (HD), low-dose diazepam (LD), microdose medetomidine (M), or placebo (P) administered intravenously 45 seconds prior to propofol induction. The time intervals indicate minutes after endotracheal intubation. The asterisks (*) indicate values that are significantly different from the 1-minute values for the same treatment group.

<bold> <italic toggle="yes">Figure 4</italic> </bold> —
Figure 4 —

Mean (± standard deviation) hemoglobin oxygen saturation (SpO2) in dogs following high-dose diazepam (HD), low-dose diazepam (LD), microdose medetomidine (M), or placebo (P) administered intravenously 45 seconds prior to propofol induction. The time intervals indicate minutes after endotracheal intubation. The letter "a" indicates values that are significantly different from values with the letter "b." The asterisks (*) indicate values that are significantly different from the 1-minute values for the same treatment group.

<bold> <italic toggle="yes">Figure 5</italic> </bold> —
Figure 5 —

Mean (± standard deviation) blood pressures in dogs following high-dose diazepam (HD), low-dose diazepam (LD), microdose medetomidine (M), or placebo (P) administered intravenously 45 seconds prior to propofol induction. Time 0 indicates baseline values prior to any drug administration. Other time intervals indicate minutes after endotracheal intubation. The letter "a" indicates values that are significantly different from values with the letter "b." The asterisks (*) indicate values that are significantly different from baseline values within the same treatment group.

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