Abstract
This study evaluated the safety and efficacy of propofol when used to deepen anesthesia and provide muscle relaxation in narcotic anesthetized non-domestic equids. Intramuscular carfentanil or etorphine was used either alone or in combination with sedatives to immobilize 23 non-domestic equids representing five species. Each animal received at least one intravenous bolus of propofol. Physiologic data collected during anesthesia included heart and respiratory rate, pulse oximetry, and rectal temperature at various time intervals. No significant difference (p<0.05) was noted in any parameter when each time interval was compared with the time 0 measurement (completion of propofol administration). Analysis of results indicate intravenous propofol given at 1–1.5 mg/kg over 1–2 min provided 8–10 min of relaxation in these animals without causing noteworthy changes in physiologic status. If given slowly and titrated to desired effect, intravenous propofol is a safe and effective method of increasing the quality of anesthesia in narcotic anesthetized non-domestic equids.
Introduction
Narcotics are considered the drug of choice for anesthesia in many non-domestic hoofstock species because of their potency, rapid onset of action and reversibility.8 Respiratory depression in the patient and accidental human narcotic exposure are noteworthy concerns. The safe use of narcotics and other anesthetic agents in non-domestic equids has grown over the past decade due to the appearance of safe and effective protocols in the literature.1-3,10,15,18
The need for supplemental drugs to achieve muscle relaxation in narcotic anesthetized equid species is common due to the muscle rigidity and fasciculation often seen during such immobilizations. Side effects of muscular rigidity may include hyperthermia and myopathy.21 Furthermore, if the patient is experiencing muscular rigidity or fasciculation it is difficult, if not impossible, to adequately monitor the animal’s clinical status. Vital patient information at risk include accurate auscultation of the rate, rhythm and character of the heart and lung sounds, electrocardiography, and oxygen saturation via pulse oximetry. Since narcotics are well-known respiratory depressants, it would be logical and prudent to include these devices for the safe monitoring of these patients.22
Propofol (Diprivan, Zeneca Pharmaceuticals, Wilmington, Delaware, USA) is a relatively new sedative-hypnotic intravenous induction anesthetic agent used in human7 and veterinary medicine5,16. This drug is also used to maintain or deepen anesthesia in man and is considered a choice agent for short outpatient surgical procedures.19 Its use and popularity has grown over the past few years in non-domestic species.4.6,9,11,21 Benefits of this drug include rapid metabolism and clearance, short duration of action, titratable effects, and safety in compromised patients. Reported undesirable aspects include dose dependent respiratory depression, cost, and storage requirements. The use of propofol is described in the domestic equid12-14,17 but there are no reports in non-domestic equid species.
Due to its purported benefits, the use of propofol as a supplemental anesthetic agent was investigated. The objective of this study was to improve the quality and/or safety of anesthesia in the narcotic anesthetized non-domestic equid by the administration of propofol.
Methods
Animals: Five species of non-domestic equids were anesthetized for routine procedures at the San Diego Wild Animal Park between 1993 and 1997: Przewalski’s horse (Equus przewalskii), Hartmann’s mountain zebra (Equus zebra hartmannae), kiang (Equus kiang holdereri), Grevy’s zebra (Equus grevyi), and Persian onager (Equus hemionus onager). Nineteen animals were used in this study of 23 anesthetic events. See Table 1 for a review of species, sex, age, and weights of animals.
Table 1. Species list and bio-data of 23 non-domestic equids in propofol study
|
Species
|
Number
(M/F)a
|
Age in yr
(range)
|
Weight in kg
(range)
|
|
Przewalski’s horse
|
9 (5 M, 4 F)
|
6.6
(1.2–26)
|
294.1
(226.4–367.3)
|
|
Przewalski’s horse, with pre-medb
|
3 (2 M,1 F)
|
11.3
(4.8–19)
|
405.9
(345.5–451.4)
|
|
Hartmann’s mountain zebra
|
6 (2 M, 4 F)
|
5.8
(0.75–20)
|
317.1
(212.7–371.4)
|
|
Eastern kiang
|
3 (3 M)
|
6.8
(3.5–9.3)
|
288.5
(278.2–300)
|
|
Persian onager
|
1 (1 F)
|
4.6
|
304.5
|
|
Grevy’s zebra
|
1 (1 F)
|
3.5
|
425.9
|
Data are reported as mean age and weight, (range)
a(Male/Female)
bSee Methods
To enter this study, all anesthetic events had to fulfill certain criteria. All animals were clinically normal and were anesthetized only by this author (JRZ) for routine procedures. Narcotic was used as the primary induction agent and all animals had satisfactory dart placement deep into the caudal thigh muscles. Body weight was obtained during the procedure for accurate drug dose calculation. Propofol was administered only if necessary to improve quality of anesthesia.
Induction of anesthesia: All animals received induction and premedication anesthetic agents via remote dart injection (Vario dart, Telinject USA, Saugus, California, USA). All procedures occurred “in the field” away from hospital facilities. See Table 2 for a review of narcotic induction agents used in this study.
Table 2. Dosage and administration rate of narcotic induction agent and propofol used in 23 non-domestic equids
|
Species
|
Induction agent
(mg/kg)a
|
Supplemental propofolb
|
|
Dosage
(mg/kg)
|
Duration of administration
(sec)
|
Administration rate
(mg/kg/sec)
|
|
Przewalski’s horse
|
0.0227 Carfc
(9)
|
1.53±0.64
(13)d
|
60.4±36.6
|
0.03±0.01
|
|
Przewalski’s horse, with pre-mede
|
0.0209 Carf
(3)
|
0.93±0.30
(4)
|
63.7±7.50
|
0.014±0.004
|
|
Hartmann’s mountain zebra
|
0.0133 Carf
(6)
|
1.03±0.22
(7)
|
100±34.6
|
0.013±0.01
|
|
Eastern kiang
|
0.0441 Carf
(3)
|
2.20±0.48
(3)
|
120±60.0
|
0.02±0.007
|
|
Persian onager
|
0.0525 Carf
(1)
|
1.64±0.0
(1)
|
30±0.0
|
0.05±0.0
|
|
Grevy’s zebra
|
0.0176 Etorf
(1)
|
0.76±0.42
(2)
|
150±42.4
|
0.005±0.001
|
aInduction agent data reported as mean dosage in mg/kg, (number of animals)
bAll propofol data represent mean±standard deviation
cCarf=carfentanil
dTotal number of supplemental propofol doses used in each species
eSee Methods
fEtor=etorphine
Twelve anesthetic events were recorded in 10 Przewalski’s horses. In nine of the 12 anesthetic events carfentanil (Wildlife Laboratories, Fort Collins, Colorado, USA) was used as the sole induction agent. The remaining three animals were premedicated with 10–15 mg intramuscular detomidine (Dormosedan, Pfizer, Inc., West Chester, Pennsylvania, USA) alone or combined with 10 mg intramuscular butorphanol (Torbugesic, Fort Dodge Laboratories, Fort Dodge, Iowa, USA) 15–20 min prior to carfentanil induction. Mild sedation was achieved in all cases.
A total of six anesthetic events in four Hartmann’s mountain zebras were recorded using only carfentanil for anesthetic induction. Three kiang and one Persian onager received carfentanil as the sole induction agent. One Grevy’s zebra received a combination of detomidine (10 mg) and etorphine (M99-Ten [10 mg/ml], Wildlife Laboratories, Fort Collins, Colorado, USA) in the same dart for induction.
Supplemental anesthesia: All 23 animals received at least one jugular vein infusion of propofol to deepen anesthesia, improve muscle relaxation and increase procedure safety. Prior to anesthesia an estimated weight was obtained on the patient which allowed us to have a pre-calculated amount of propofol ready for initial delivery if needed. The amount of propofol placed in the syringe was approximately 2 mg/kg. A total of 31 propofol events occurred during the 23 anesthetic events; eight animals received more than one dose of propofol. The initial dose of propofol served as time 0 in animals receiving more than one bolus of this drug. Each propofol event was critiqued for safety and efficacy. See Table 2 for a review of mean propofol dosage and administration rate.
Supportive pharmacologic agents: Four horses received intravenous doxapram (Dopram, Fort Dodge Laboratories, Fort Dodge, Iowa, USA) (200–300 mg total dose) 5–8 min following propofol administration for decreased respiratory rate, low oximetry readings and/or pale mucous membrane color. One horse received doxapram prior to the administration of propofol for poor respiratory rate.
Narcotic reversal: Narcotic agent was reversed by single administration of intravenous nalmefene (Anesta Corp., Salt Lake City, Utah, USA) or naltrexone (Trexonil, Wildlife Laboratories, Fort Collins, Colorado, USA) at 50 or 100 times the mg dose of induction narcotic. No renarcotizations were noted.
Patient monitoring: Physiologic parameters monitored included rectal temperature, respiratory rate, heart rate, and indirect oxygen saturation via pulse oximetry. Body weight was obtained during the procedure. Attempts were made to collect data within the following time intervals immediately after administration of propofol: 0–1, 2–3, 4–5, 6–7, 8–10, 11–13, 14–16, and 17–20 min (Table 3). Data were analyzed by one-way ANOVA; p<0.05 was considered statistically significant. Note that data were not available at certain time intervals so the total number (n) of animals may be different at each interval. All animals were maintained in lateral recumbency and received supplemental intranasal oxygen at 15 L/min.
Table 3. Cardiorespiratory and body temperature measurements in 23 narcotic anesthetized non-domestic equids following propofol administrationa
|
Time (min)
|
0–1
|
2–3
|
4–5
|
6–7
|
8–10
|
11–13
|
14–16
|
17–20
|
|
Respiratory rate
|
9.7±5.1
(22)
|
9.2±4.0
(19)
|
9.7±4.0
(21)
|
9.7±4.4
(16)
|
11.1±5.3
(21)
|
11.2±5.1
(18)
|
10.2±4.0
(13)
|
12.7±4.7
(6)
|
|
Heart rate
|
84.8±31
(23)
|
85.2±37
(18)
|
82.3±34.8
(20)
|
85.3±37.2
(16)
|
88.8±35.7
(22)
|
94.1±40.8
(18)
|
84.1±33.5
(13)
|
82.4±47.1
(7)
|
|
Oximetry
|
82.5±9.9
(12)
|
83.1±11.0
(10)
|
87.1±5.4
(9)
|
86.6±6.1
(9)
|
88.3±5.7
(10)
|
87.5±4.7
(11)
|
87.6±5.5
(6)
|
87.2±4.2
(5)
|
|
Temperature
|
102.4±2.0
(15)
|
102.4±2.3
(8)
|
103.0±2.8
(8)
|
103.5±2.3
(7)
|
102.8±2.2
(10)
|
101.7±3.1
(4)
|
102.6±1.7
(3)
|
104.0±1.6
(2)
|
All data represent mean±standard deviation, (number of animals).
Time intervals represent minutes following administration of propofol.
aNo statistical significance (p<0.05) was noted in any parameter when compared to initial measurement.
Anesthetic rating: Each anesthetic event received a subjective rating for quality of anesthesia, muscle relaxation and recovery. Quality of anesthesia was evaluated by the efficacy and safety of propofol administration by the following scoring system: 1=good, 2=satisfactory, and 3=poor. Muscle relaxation due to propofol was scored as 1=good, 2=slight, and 3=poor. Recovery was scored as 1=good with no instability, 2=satisfactory with slight instability, and 3=poor due to instability and potential danger to patient.
Results
Mean anesthesia time (dart to reversal) for the 23 animals was 28.1 min (±6.5). The mean time at which propofol was first administered was 12.0 min (±3.9).
Heart and respiratory rates, oximetry readings and rectal temperature did not change significantly over the anesthetic procedure. No animal became apneic due to the administration of propofol at the dosage and administration rate in this study. All animals had increased muscle relaxation by the end of propofol administration with a mean duration of action of 8.7 min (±2.9).
The mean rating score for quality of anesthesia was 1.4 (±0.5); for muscle relaxation 1.3 (±0.5); and for recovery 1.1 (±0.3).
Discussion
Propofol provided good muscle relaxation and increased quality of anesthesia in all 23 narcotic anesthetized non-domestic Equidae in this study. No statistically significant changes were noted in the four physiologic parameters measured in this study by comparing each time interval with the initial measurement at time 0 (completion of propofol administration). No individual animal appeared to react adversely to the amount of propofol administered in this study.
Propofol was administered based on pre-procedure estimated body weight and desired level of anesthesia to achieve muscle relaxation. The dose and rate of administration must be considered and titrated to effect to provide muscle relaxation while avoiding significant cardiorespiratory changes. Respiratory depression and apnea are important side effects of propofol but were not seen here likely due to the slow administration and low dose used in these animals. Four animals received doxapram to stimulate respiration following propofol administration; only two of four responded with a slight change in respiratory rate. Since narcotic induction agents cause respiratory depression this could explain the generally low respiratory rate and pulse oximetry readings when propofol was first administered. Respiratory rate and oximetry readings did not change significantly following the administration of propofol. Doxapram is routinely used, sometimes prophylactically, in our practice when equids are immobilized with narcotic agents alone.
Rectal temperature was not expected to change since procedure length was short, however, it has been reported to decrease temperature in dogs due to decreased skeletal muscle tone, vasodilation and impaired thermoregulatory mechanism.16 Pulse oximetry readings were low, but not significantly different over time, for all animals in this study reflecting the respiratory depressive effect of narcotic induction agents. Providing all narcotic anesthetized patients with supplemental oxygen, ideal positioning, respiratory stimulant drugs and short anesthetic times are techniques used to increase patient safety.
Propofol proved to be an effective and safe supplemental anesthetic agent in these study animals. This drug offers predictable results in a variety of other species as well. Many other equid, primate, carnivore, avian and exotic ungulate species have received intravenous propofol to increase quality of anesthesia without complication. This author (JRZ) now considers propofol a routine supplemental agent to improve muscle relaxation and deepen anesthesia in difficult anesthetic events such as rhinoceros’ immobilizations. This study only included healthy animals but our practice has used propofol safely in clinically ill animals needing to be anesthetized for diagnostic procedures or treatment with similar results. Paramount, of course, is the recognition and avoidance of the potential side effects of this drug by titrating to effect while diligently monitoring the physiologic status of the patient.
If considering the use of propofol to supplement narcotic anesthesia in non-domestic Equidae the author recommends preparing a precalculated dose of propofol, based on an educated estimation of patient body weight, ready for administration if needed. From this study, the slow bolus administration of propofol given over 1–2 min at 1.0–1.5 mg/kg provided 8–10 min of improved muscle relaxation and anesthesia in healthy non-domestic equids without causing obvious physiologic change in the patient.
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