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Transcript
Nonhuman Primate Anesthesia and Analgesia Guidelines
I. PURPOSE
This document has been designed by the ULAM veterinary staff as a guideline for tranquilization, anesthesia
and analgesia of laboratory nonhuman primates. This is not intended to be an inclusive tutorial on all possible
drug combinations that can be used in nonhuman primates. The following guidelines are also general
recommendations and consequently have not factored in specific research-associated concerns.
If you have questions about the use of anesthetics or analgesics for your particular situation or if you have
questions or comments about this document, please contact the ULAM veterinary staff at [email protected]
or (734) 936-1696. The ULAM Training Core at [email protected] or (734) 763-8039 can be
contacted to provide training in these techniques at no charge.
II. DEFINITIONS
A. Special Concerns in Primate Anesthesia
1. Pre-anesthetic evaluation:
a. All subjects should be in good health prior to the administration of general anesthesia. If an
animal has any pre-existing medical conditions or diseases (anemia, high blood pressure,
diabetes, kidney problems, etc.), please consult the ULAM veterinarians prior to the
administration of any drugs.
2. Handling & Restraint:
a. Keep in mind that nonhuman primates, regardless of origin, are still wild animals and will
resist restraint. Direct contact with nonhuman primates without the use of chemical restraint is
not recommended. Personal protective equipment should always be worn when handling
nonhuman primates to help prevent the transmission of zoonotic diseases (such as herpes B) to
the handler or the spread of tuberculosis (TB) to the nonhuman primate. The amount of restraint
(generally chemical) and its duration should be kept to the minimum necessary to complete the
procedure. All necessary equipment and reagents for the procedure should be ready prior to
restraint. The use of pre-anesthetic sedatives/tranquilizers will help reduce anxiety and the
subsequent doses of other agents.
3. Pre-anesthetic fasting:
a. Nonhuman primates can vomit and aspirate stomach contents while under general anesthesia. To
help prevent this, animals should be fasted for 12 hours prior to general anesthesia. Juveniles or
small species such as marmosets, squirrel monkeys and tamarins should only be fasted 4-6 hours
to help avoid hypoglycemia. Do not withhold water prior to anesthesia. In the event of an
emergency, when pre-anesthetic fasting is not an option, the primate should be intubated and
placed in lateral recumbency (with its body and head lying on its side).
Approved: 10/18/2012, Version: 2
Nonhuman Primate Anesthesia and Analgesia Guidelines
III. PROCEDURES
A. Vascular access:
1. Placement of an intravenous catheter allows for easy and rapid administration of fluids and drugs
during the procedure. This may be a lifesaving factor if an emergency arises. For major surgery or
long procedures (> 30 min.), an intravenous catheter should be placed. The cephalic or saphenous
veins are most commonly employed for vascular access. For arterial sampling or direct blood
pressure monitoring, the femoral artery is most commonly employed. Intramuscular injections are
generally given in the thigh or back muscles (parallel to the spine). The smallest possible injection
volume should be employed.
B. Fluids:
1. Fluid support should be provided for major surgery or procedures lasting longer than 30 minutes.
Intravenous fluids should be given at an initial rate of 5- 10ml/kg/hr for most procedures. Blood loss
should be replaced with a three-fold volume of fluids (e.g.100ml blood lost is replaced with 300ml of
IV fluids). Accurate administration of fluid volume is important especially for patients less than or
equal to 5 kg. Use of a fluid pump and mini-drip (administration set that delivers 60 drops/ml) is
recommended for these individuals. Choice of fluid should be made on case-by-case bases under
veterinary consultation.
C. Hypothermia:
1. Primates are prone to hypothermia during anesthesia. Animals that weigh less than 5kg, those
undergoing long procedures and those given Telazol® are most at risk. Hypothermia can cause
bradycardia, low cardiac output, and delay recovery from anesthesia. Serial evaluations of body
temperature during anesthesia and recovery should be performed. Please refer to the Anesthesia
and Sedation Monitoring Guidelines for recommendations on maintaining body temperature under
anesthesia.
D. Endotracheal intubation:
1. Airway control via endotracheal intubation is highly desirable during anesthesia and required in some
situations where controlled ventilation is mandatory (e.g. thoracotomies). Administration of inhalation
anesthetics is best accomplished via an endotracheal tube. Intubation of nonhuman primates
requires some skill and practice and is best accomplished using a laryngoscope. Prior to attempting
endotracheal intubation, training should be obtained through ULAM.
IV. MONITORING AND RECOVERY
A. Intraoperative and postoperative monitoring is of vital importance for proper patient management during
anesthesia and recovery. The goals of intraoperative monitoring are to maintain adequate anesthetic
depth while preserving the normal function of organ systems. Anesthetic depth may be ascertained by
evaluating palpebral and corneal reflexes, jaw tone, and the absence of movement in response to
painful stimuli. Reduction and/or loss of these reflexes and responses are associated with an adequate
surgical depth of anesthesia. Increased respiratory rate in response to surgical stimuli is a sensitive
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Nonhuman Primate Anesthesia and Analgesia Guidelines
indication of inadequate depth of anesthesia. Increases in heart rate may be due to pain perception or
from increased blood level of carbon dioxide, hypoxia, or hypotension.
1. Cardiovascular (CV) monitoring:
a. Heart rate and rhythm, pulse quality, and capillary refill time should be evaluated at regular
intervals to assess cardiovascular status. The use of an esophageal stethoscope, ECG, and blood
pressure monitor can help facilitate CV monitoring.
2. Respiratory monitoring:
a. Proper monitoring of the respiratory system involves quantitation of oxygenation and ventilation.
For evaluating oxygenation, mucus membrane color is most commonly used, however it is a very
insensitive technique. Patients may become dangerously hypoxic by the time a change in mucus
membrane color (pink to blue) is noted. Increases in respiratory rate may also indicate low blood
oxygen levels; however, this parameter is primarily regulated by blood levels of carbon dioxide.
Normal vital signs for nonhuman primates can be found in Appendix 1.
b. Pulse oximetry is a non-invasive method for continuous measurement of oxygen saturation and
heart rate. However, serial arterial blood gas sampling is the gold standard for evaluating blood
oxygenation. End-tidal CO2 monitors can also be used as a non-invasive measure of ventilation.
V. AGENTS USED PREOPERATIVELY AND FOR CHEMICAL RESTRAINT
A. The recommended dosages for all of the recommended agents are listed according to species
in Tables I – IV.
1. Sedatives:
a. Acepromazine
•
Acepromazine is a tranquilizer/sedative. Acepromazine is used as a preanesthetic and an
anesthetic adjunct. It is often used in conjunction with ketamine. It can cause vasodilation
and hypotension due to blockade of alpha-receptors on smooth muscle. Acepromazine
should not be given with drugs that can lower the seizure threshold.
b. Dexmedetomidine (Dexdomitor)
•
Dexmedetomidine is an alpha agonists that is used as a sedative, anesthetic and
analgesics. It is similar in activity to medetomidine, but dexmedetomidine has twice the
potency with the same pharmacological activity and equivalent analgesic and sedative
effects. Alpha-receptor selectivity is nearly 1000 times that of xylazine. Due to its
antagonism of alpha-receptors, these drugs can cause initial bradycardia, followed by
hypertension. This is followed by hypotension. Lower respiratory rate and body temperature
can also occur when using these drugs. If adverse reaction is observed, the effects can be
reversed with atipamezole.
c. Ketamine (Ketanest®, Ketaset®, Ketalar®)
•
Ketamine is the most common agent used for chemical restraint of nonhuman primates.
It has a wide margin of safety and can be used alone or in combination with other drugs.
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Nonhuman Primate Anesthesia and Analgesia Guidelines
When used alone it produces immobility and some analgesia along with varying degrees of
muscle contraction, tremors, and salivation. Ketamine is the agent of choice for restraint in
order to safely perform clinical exams, short procedures, and diagnostic tests (TB test,
phlebotomy etc.). Laryngeal, pharyngeal and corneal reflexes are preserved. Ketamine
given alone is insufficient for endotracheal intubation, complete immobilization or for
performing surgical procedures. When given at high doses or in susceptible individuals,
seizures may occur.
d. Ketamine-xylazine (Rompun®)
•
Ketamine-xylazine combinations provide complete immobilization, excellent muscle
relaxation, analgesia sufficient for minor surgical procedures and a longer duration of action
than ketamine alone. The use of these drugs together usually provides enough sedation and
relaxation to enable endotracheal intubation; however, animals may still salivate profusely.
Bradycardia and hypotension may occur, in particular at the high end of the xylazine dose.
e. Ketamine-dexmedetomidine
•
Ketamine-dexmedetomidine combinations provide complete immobilization, excellent
muscle relaxation, analgesia sufficient for minor surgical procedures and a longer duration
of action than ketamine alone. The use of these drugs together usually provides enough
sedation and relaxation to enable endotracheal intubation; however, animals may still
salivate profusely. Dexmedetomidine is of the same class of drug as xylazine with a higher
affinity for alpha 2 receptors, which lowers cardiovascular side effects. Bradycardia and
hypotension may occur still, in particular at the high end of the dexmedetomidine dose.
f. Tiletamine- zolazepam (Telazol®)
•
Telazol® is a combination of the dissociative anesthetic tiletamine and zolazepam, a
benzodiazepine. Telazol has the advantage of providing rapid onset of action with smooth
recovery. This drug is water-soluble and is given in smaller volumes than ketamine. Low
doses may be used for chemical restraint. High doses can be used for minor surgical
procedures and endotracheal intubation. Hypothermia may be a problem when this drug is
used to induce general anesthesia. Seizures are rarely seen after Telazol administration as
compared to ketamine.
g. Anticholinergics (Atropine, Glycopyrrolate)
•
Anticholinergics block the parasympathetic nerves. Atropine or glycopyrrolate can be used
as a pre-anesthetic to reduce salivation. Anticholinergics may also be used to prevent
abnormal heart rhythms and slowing of the heart rate. The use of anticholinergics to prevent
bradycardia in patients administered α-2 agonists such as xylazine and medetomidine is
controversial. Bradycardia in these patients is in response to initial hypertension and
decreased cardiac input, which is considered by many a normal physiologic response.
h. Neuromuscular Blocking Agents (Pancuronium, Vecuronium)
•
Neuromuscular blocking agents are used in conjunction with general anesthetics to achieve
greater control of muscle activity. Both drugs produce skeletal muscle relaxation and are
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Nonhuman Primate Anesthesia and Analgesia Guidelines
very useful when control of ventilation or muscle movement is needed (e.g. ophthalmic
surgery). These agents do not have any anesthetic or analgesic properties and should
only be used along with an anesthetic drug. Extreme care must be taken to ensure that
the patient is at a proper level of anesthesia when using these agents. Since the ability of
the animal to move is eliminated, parameters such as heart rate and blood pressure must be
used to monitor anesthetic depth. These agents paralyze the diaphragm and cause
respiratory arrest; therefore, the animal must be intubated and mechanically ventilated.
Pancuronium lasts longer than vecuronium and produces mild increases in blood pressure
and heart rate.
VI. PREFERRED GENERAL ANESTHETIC AGENTS
A. Inhalation Anesthesia:
1. Inhalation agents enable the anesthetist to precisely control the depth of anesthesia. They are the
drugs of choice for procedures lasting longer than 30 minutes or for major surgical procedures. They
can be delivered by mask or endotracheal tube, the latter being the safest and preferred method.
Inhalation agents also produce reliable anesthesia in all primates. Placement of an endotracheal
tube (intubation) requires the use of an injectable drug combination that produces greater degrees of
jaw relaxation than can be achieved with ketamine alone. Ketamine-xylazine, Ketaminemedetomidine or Telazol® may be used for this purpose and can be given intramuscular (IM).
Propofol may be used as well, but requires the placement of an intravenous catheter for delivery.
When using inhalation anesthesia in primates, use of a bacterial/viral filter will help avoid potential
contamination of the anesthesia machine.
2. Isoflurane (Forane®)
a. Isoflurane is the most commonly used inhalation agent for all species and is considered by many
to be the inhalation anesthetic of choice for nonhuman primates. Isoflurane's onset of action and
recovery times are much shorter than for other inhalation agents. Other advantages of this agent
are that it does not sensitize the heart to catecholamine induced arrhythmia’s and produces less
myocardial depression.
3. Sevoflurane (Ultane®)
a. Sevoflurane is an inhalational anesthetic similar to isoflurane.Sevoflurane has a very low
blood/gas partition coefficient (0.6) allowing very rapid anesthesia induction and recovery.
Because of the rapid recovery associated with sevoflurane use caution (and appropriate sedation)
during the recovery phase. Sevoflurane can react with carbon dioxide absorbents to produce
"compound A", a nephrotoxin, unless an oxygen flow rate of at least 1 liter per minute is used.
B. Injectable Anesthetics:
1. Propofol (Diprovan®, Rapinovet®, Propoflo®)
a. Propofol is a substituted phenolic drug (2,6,-diisopropylphenol) dissolved in a lipid vehicle giving
it a white opaque appearance. Propofol must be given by IV injection. It has a very rapid onset of
action and recoveries are very rapid and smooth. It provides good muscle relaxation for minor
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Nonhuman Primate Anesthesia and Analgesia Guidelines
procedures (suturing small wounds, catheter placement, MRI, CT scan, etc). It is also well suited
for induction and endotracheal intubation for gas anesthesia. When used alone, it must be given
by constant rate infusion or by repeated boluses if procedures longer than a few minutes are to
be performed. For major or painful procedures, it should only be used in combination with an
opioid. Apnea (cessation of breathing) is a common problem after IV bolus administration. This
can be minimized by using a slow rate of administration, however, it is generally recommended
that patients should be intubated along with its use. This drug can also produce profound
hypotension. The vehicle that the drug is emulsified in readily supports microbial growth, and the
entire contents of a vial must be used the same day it is opened.
2. Pentobarbital
a. Pentobarbital is an injectable general anesthetic agent that for the most part has been replaced
by the inhalation agents. It provides excellent muscle relaxation and analgesia sufficient for major
surgical procedures. Pentobarbital does have some significant drawbacks. Severe respiratory
depression occurs at high doses and depth of anesthesia is very difficult to control. Recovery
from pentobarbital anesthesia can be very long. This drug is useful for neurosurgical procedures,
imaging studies such as MRI, or non-survival procedures.
VII. LOCAL ANESTHETICS (Lidocaine, Bupivacaine)
A. Local Anesthetic Techniques
1. Local anesthesia fits the category of pre-emptive analgesia perfectly because it is usually
administered prior to surgery. The duration of blockade is determined by both the agent used and to
a lesser degree by the site of administration. Lidocaine has a fairly rapid onset (10-15 minutes) and
short duration of action (1 to 11⁄2 hours) whereas bupivacaine has a slow onset (20-30 minutes) but
longer duration of action (4 to 6 hours). The agents are often combined to provide rapid onset and
long duration of effect. Not only is intra- and post-op analgesia provided by local anesthesia, but the
anesthetic period is frequently stable because the lack of sensation prevents variable CNS
stimulation. Aspiration of the syringe to assure the needle is not in a vessel is very important,
as Lidocaine and Bupivacaine have adverse cardiovascular effects if administered
systemically. Intravenous injection can result in non- resuscitatable cardiac arrest and death, so
always aspirate prior to injection.
VIII. ANALGESICS
A. Signs of Pain: Signs of pain in nonhuman primates may include, but are not limited to, the following:
•
•
•
•
•
•
Persistent vocalizations
Restlessness
Lethargy
Inappetence
Ungroomed hair coat
Crouched posture
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Nonhuman Primate Anesthesia and Analgesia Guidelines
•
•
•
•
•
Glassy eyes
Social isolation
Abnormal aggression
Elevated respiratory rate
Reluctance to move
1. Any procedure known to produce pain in humans or other species should be assumed to cause pain
in nonhuman primates. In these instances analgesic drugs are indicated to decrease discomfort and
to reduce pain associated morbidity and mortality.
2. The two most common classes of analgesic drugs used for nonhuman primates are the non-steroidal
anti-inflammatory drugs (NSAIDs) and the opioids. NSAIDs are appropriate for treating mild pain or
can be used in combination with opioids. For moderately to very painful procedures (thoracic,
abdominal or orthopedic procedures), opioids are the analgesics of choice.
B. NSAIDS:
1. Ketorolac is a potent NSAID that is available in oral and injectable form. In certain cases, its
analgesic properties may be equal to or exceed those of the opiates. It has been used with good
results in macaques and baboons.
2. Carprofen (Rimadyl®)
a. Carprofen has overcome some of the limitations of traditional NSAIDS, and become a useful
adjunct in the treatment of acute and chronic pain. Carprofen differs from other NSAIDS in that it
is a weak inhibitor of cyclooxygenase activity and exerts only a weak influence on the formation of
prostaglandin E2. The minimal effect on prostaglandin synthesis suggests that a spinal or central
mechanism of action is responsible for carprofen's strong analgesic effects. Although it appears
that carprofen may be an important adjunct for the treatment of acute post-surgical pain, by itself
it is unlikely to provide adequate analgesia for moderately to severely painful animals and should
not be viewed as a sole analgesic. Carprofen is available in oral and injectable form.
3. Ketoprofen (Orudis®, Oruvail®)
a. Ketoprofen is a potent inhibitor of prostaglandin synthesis that is available in both injectable and
oral form. Ketoprofen may be administered IV, IM, or SQ postoperatively to nonhuman primates
as an alternative to carprofen. Ketoprofen should only be administered to animals with normal
renal function since it may decrease renal perfusion in the presence of hypotension.
4. Long-term use of NSAIDS: Long-term use of NSAIDS has been associated with gastric ulcers and
kidney disease. Consult with a ULAM veterinarian concerning repeated administration of these
agents.
5. Opioids:
a. Buprenorphine (Buprenex®)
•
Buprenorphine is an effective analgesic for mild to moderate pain. It has the advantage of a
long duration of action with almost no sedation and minimal effects on heart rate and
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Nonhuman Primate Anesthesia and Analgesia Guidelines
respiration. One disadvantage is that it is dispensed in single use vials and for the most part
can not be effectively reversed by naloxone.
b. Morphine
•
Morphine is an inexpensive and effective opioid for use in both Old World and New World
primates. It can be administered SQ, IM, by IV drip, and as an epidural. It will, however,
produce dose dependent sedation and decreases in heart rate and respiratory rate. These
effects may be more pronounced in New World monkeys.
c. Oxymorphone
•
Oxymorphone is an alternative to morphine and has a longer duration of action. It has been
reported to cause less respiratory depression than morphine. Some authors consider it to be
the opioid of choice for nonhuman primates. Oxymorphone will produce dose dependent
sedation and decreases in heart rate. It is also considerably more expensive than the other
opioids.
d. Tramadol (Ultram®, Ultram ER®)
•
Tramadol is a synthetic opoid which also inhibits serotonin and norepinephrine. Tramadol is
useful for mild to moderate pain and also can be used for cough. Tramadol is available only
in oral form in the United States.
e. Opioid use in marmosets
•
Anecdotal evidence suggests that opioid use may cause severe respiratory depression in
common marmosets (Callithrix jaccus). Avoid administration of opioids prior to or during
anesthesia or sedation. Post-operative administration of opioids following recovery of
spontaneous ventilation and voluntary movement is acceptable.
IX. REVERSAL AGENTS
A. Naloxone (Narcan®)
1. Naloxone is an opioid antagonist that is used to reverse the effects of morphine, oxymorphone, or
fentanyl. It rapidly and effectively reverses opioid sedation, respiratory depression, and bradycardia.
Naloxone can be given IV or IM. It should be noted that naloxone will also eliminate the analgesic
effects of opioids and its duration of action may be shorter than the opioid it is being used to reverse.
Careful monitoring and redosing may be needed if the animal begins to relapse as a result of this
difference in duration of action.
B. Yohimbine
1. Yohimbine is used to reverse the action of xylazine under similar circumstances as indicated for
naloxone. In general, only one dose of yohimbine (0.1 mg/kg) is need to treat xylazine related
problems.
C. Atipamezole(Antisedan®):
1. Atipamezole is 200 to 300 times more selective for both α 2 and α 1 sites than yohimbine. It is
superior to other clinically available compounds. Atipamezole can be used to reverse
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Nonhuman Primate Anesthesia and Analgesia Guidelines
dexmedetomidine and xylazine. Severe hypotension and tachycardia can occur following rapid IV
injection. This can be prevented by giving the agent IM or very slowly IV. Atipamezole is produced at
a strength that is more potent than dexmedetomidine, however the manufacturer has made it so that
you give the same milliliter dosage to reverse the effects of the agonist.
Example: If medetomidine is given IM 0.4mls, atipamezole 0.4mls IM reverses medetomidine.
D. Flumazenil
1. Flumazenil is a benzodiazepine receptor antagonist that can be used to reverse diazepam and
zolazepam. In general, only one dose of flumazenil is necessary to reverse benzodiazepine related
problems.
APPENDIX 1
Normal Vital Signs in Nonhuman Primates
Species
Rectal Temp (°F)
Respiratory Rate †
Heart Rate ‡
Callithrix jaccus
Common marmoset
97 – 102.5
20 - 50
240 - 350
Macaca fasicularis
Java/Cynomolgus
97 – 100.4
32 - 44
107 - 215
Macaca fuscata
Japanese/Snow
175 - 253
Macaca mulatta
Rhesus
98 - 102
10 - 25
150 - 220
Pan troglodytes
98 - 100
35 - 60
80 - 150
Pappio spp.
Baboon
98 - 102
29
80 - 200
Saimiri sciureus
Squirrel monkey
98 - 101
20 - 50
200 - 300
† 10 – 20% reduction in rates for anesthetized patients is acceptable
‡ low end of range is acceptable for anesthetized patients
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Nonhuman Primate Anesthesia and Analgesia Guidelines
Table I: Drugs & Doses for Macaca spp.
Drug
Anticholinergics
Atropine
Dose (mg/kg) & Route
Approximate Duration
0.02 – 0.04 IM, IV, SC
20 – 30 min
Glycopyrrolate
0.004 – 0.08 IM
45 – 60 min
Injectable Agents
Acepromazine
0.1 – 0.5 IV, IM
20 – 30 min
5 – 20 IM
10 – 20 min
4 IM
0.04 IM
20 – 30 min
Ketamine
Ketamine
+ Acepromazine
Ketamine
+ dexmedetomidine
5 – 20
0.005 – 0.0075 IM
30 – 120 min
Ketamine
7 IM
+ Xylazine
0.6 IM
30 – 120 min
2 – 6 IM
45 – 60 min
Propofol* (induction)
2 – 5 IV bolus slowly
5 – 10 min
Propofol* (CRI)
Loading dose: 2 – 5 IV
bolus slowly
Infusion: 0.3 – 0.4
mg/kg/min
Pentobarbital a
5 – 15 IV
Telazol ®
(Tiletamine/Zolazopam)
Neuromuscular blockers b
Pancuronium
Vecuronium
0.08 – 0.1 IV
0.04 – 0.06 IV
Inhalation Anesthestics a
Isoflurane
Sevoflurane
3 – 4% induction
1 – 3% maintenance
3 – 5% induction
1.5 – 3.5% maintenance
Approved: 10/18/2012, Version: 2
30 – 60 min
Nonhuman Primate Anesthesia and Analgesia Guidelines
Local Anesthetics
Lidocaine
≤0.4 – 0.8 local infusion
1 to 1 ½ hours
≤4 local infusion
4 – 6 hours
Ketorolac
15 – 30 IM
15 – 30mg/animal initially;
then 10 – 15mg/animal q8h
Carprofen
2 PO, SQ, IM
12 hours
Ketoprofen
2 IM, IV, SQ
24 hours
1 – 2 IM, SQ
2 – 4 hours
0.15 IM
4 – 6 hours
0.01 – 0.03 IM
6 – 8 hours
2 – 4 PO
12 hours
Bupivacaine
NSAIDs
Opioids
Morphine
Oxymorphone
Buprenorphine c
Tramadol
Reversal Agents
Atipamizole (Antisedan)
Dexmedetomidine reversal
Flumazenil
Diazapam/zolazopam reversal
0.15 – 0.3 mg/kg IM
(same volume as used
for dexmedetomidine)
0.02 mg/kg IV, IM
Opioid Antagonist
Nalaxone
0.1 – 0.2 IV, IM; PRN
Opioid reversal
a Intubation indicated when using this agent
1 -2 hours
b
Intubation and assisted ventilation mandatory when using this agent
c
Preemptive analgesia, particularly opiates like buprenorphine, can reduce the dose of anesthetics
required for surgical anesthesia and increase the respiratory depression associated with anesthetics.
When pre-emptive analgesia is used, consider reducing the dose of anesthetic (whether inhalant or
injectable) to the low end of the recommended range. Anesthetic depth must be carefully monitored
and drug doses may need to be titrated to maintain appropriate levels. With new projects, sexes,
strains or anesthetic analgesic combinations, assess a subset of animals before expanding to use in a
larger cohort.
PRN = as needed
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Nonhuman Primate Anesthesia and Analgesia Guidelines
Table II: Drugs & Doses for Papio spp.
Drug
Anticholinergics
Atropine
Dose (mg/kg) & Route
Approximate Duration
0.02 – 0.04 IM
20 – 30 min
Glycopyrrolate
0.005 – 0.01 IM
45 – 60 min
Injectable Agents
Ketamine
10 – 15 IM
15 – 30 min
Ketamine
+ Diazepam
7 – 10 IM
0.2 – 0.35 IM
Telazol ®
4 – 10 IM
Propofol a
2.0 – 4.0 IV bolus slowly
for induction
Continuous infusion
45 – 60 min
0.4 – 0.6 mg/kg/min
Neuromuscular blockers b
Pancuronium
0.08 – 0.1 IV
Vecuronium
0.04 – 0.06 IV
Inhalation Anesthestics a
Isoflurane
1 MAC = 1.28%
Analgesics
Ketorolac
Opioids
Morphine
15 – 30 IM
1 – 2 IM, SQ
2 -4 hours
Oxymorphone
0.15 IM
4 – 6 hours
Buprenorphine c
0.01 IM
6 – 8 hours
Opioid Antagonist
Nalaxone
0.1 – 0.2 IV, IM; PRN
a Intubation indicated when using this agent
1 – 2 hours
b
Intubation and assisted ventilation mandatory when using this agent
c
Preemptive analgesia, particularly opiates like buprenorphine, can reduce the dose of anesthetics
required for surgical anesthesia and increase the respiratory depression associated with anesthetics.
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Nonhuman Primate Anesthesia and Analgesia Guidelines
When pre-emptive analgesia is used, consider reducing the dose of anesthetic (whether inhalant or
injectable) to the low end of the recommended range. Anesthetic depth must be carefully monitored
and drug doses may need to be titrated to maintain appropriate levels. With new projects, sexes,
strains or anesthetic analgesic combinations, assess a subset of animals before expanding to use in a
larger cohort.
PRN = as needed
Table III: Drugs & Doses for Saimiri sciureus
Drug
Injectable Agents
Ketamine
Dose (mg/kg) & Route
Approximate Duration
10 – 30 IM
15 – 30 min
Ketamine
+ Xylazine
10 – 20 IM
0.5 – 1.0 IM
Telazol ®
5 – 10 IM
Inhalation Anesthestics
Isoflurane*
1 – 3%
Opioids
Morphine
1 – 2 IM, SQ
2–4
Oxymorphone
0.075 IM
4–6
Buprenorphine c
0.015 IM
6–8
Opioid Antagonist
Nalaxone
0.1 – 0.2 IV, IM
a Intubation indicated when using this agent
1 – 2 hours
b
Intubation and assisted ventilation mandatory when using this agent
c
Preemptive analgesia, particularly opiates like buprenorphine, can reduce the dose of anesthetics
required for surgical anesthesia and increase the respiratory depression associated with anesthetics.
When pre-emptive analgesia is used, consider reducing the dose of anesthetic (whether inhalant or
injectable) to the low end of the recommended range. Anesthetic depth must be carefully monitored
and drug doses may need to be titrated to maintain appropriate levels. With new projects, sexes,
strains or anesthetic analgesic combinations, assess a subset of animals before expanding to use in a
larger cohort.
PRN = as needed
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Nonhuman Primate Anesthesia and Analgesia Guidelines
Table IV: Drugs & Doses for Callithrix jacchus
Drug
Injectable Agents
Atropine
Dose (mg/kg) & Route
Approximate Duration
0.04 IM, SQ
Ketamine
15 – 20 IM
Ketamine
+ Xylazine
15 – 20 IM
1.0 – 1.5 IM
Telazol ®
5 IM
15 – 30 min
15 min
Inhalation Anesthestics
Isoflurane a
1 – 3%
Opioids b,c
Oxymorphone
0.075 IM
4 – 6 hours
Butorphanol
0.02 SQ
6 hours
0.005 – 0.1 IM
6 – 8 hours
Buprenorphine
Opioid Antagonist
a
Nalaxone
0.1 – 0.2 IV, PRN
Intubation indicated when using this agent
1 – 2 hours
b
Use caution in marmosets. May cause severe respiratory depression. See Section VII.B.5.e.
c
Preemptive analgesia, particularly opiates like buprenorphine, can reduce the dose of anesthetics
required for surgical anesthesia and increase the respiratory depression associated with anesthetics.
When pre-emptive analgesia is used, consider reducing the dose of anesthetic (whether inhalant or
injectable) to the low end of the recommended range. Anesthetic depth must be carefully monitored
and drug doses may need to be titrated to maintain appropriate levels. With new projects, sexes,
strains or anesthetic analgesic combinations, assess a subset of animals before expanding to use in a
larger cohort.
PRN = as needed.
X. EMERGENCY RESUSCITATION
A. In the event of cardiopulmonary arrest, contact the ULAM Veterinary staff at 936-1037 or 764-0277.
These instructions are provided as a guideline for emergency treatment prior to the arrival of ULAM
Veterinary staff. Follow the “ABCs” (airway, breathing, cardiovascular support, drugs) for basic CPR.
B. The most important procedure is to ventilate the patient. Establishing control of the airway and
breathing should be the first priority, do nothing else first!!!
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Nonhuman Primate Anesthesia and Analgesia Guidelines
1. If the patient is not already intubated place an endotracheal tube. If an endotracheal tube is not
available use a face mask to ventilate.
2. Ventilate with 100% O 2 at a rate of 1 breath every 5 seconds. If using inhalant agents make sure the
vaporizer is turned off.
3. After establishing control of ventilation, start regular strong chest compressions (at least 1 per
second). It is not necessary to coordinate compressions with ventilation. Rapid infusion of IV fluids
should be started to support perfusion.
4. If no heartbeat can be heard or no pulses felt, then epinephrine should be given IV (see chart
below). Reversal drugs should be given if opioids or xylazine have been used. Dopram® may be
given to stimulate respiration if spontaneous breathing is not noted (see chart below).
C. Have emergency drugs and instruments in the surgery suite ready for use.
Dose in Milliliters
Body Weight Kg
Drug
Concentration (Route)
2.5
5.0
7.5
10
12.5
14.0
Epinephrine
1:1000 (IV, IM, IT)
0.25
0.5
0.75
1.0
1.25
1.4
Atropine
0.54 mg/ml (IV, IM)
0.15
0.25
0.4
0.5
0.6
0.7
Naloxone
0.4 mg/ml (IV, IM)
0.6
1.25
2.0
2.5
3.0
3.5
Yohimbine
2 mg/ml (IV)
0.13
0.25
0.38
0.5
0.60
0.70
Dopram ®
20 mg/ml (IV)
.25
0.5
.75
1.0
1.25
1.4
XI. REFERENCES
•
APV Primate Formulary http://www.primatevets.org/Formulary.xls
•
Flecknell, P. (1996) Laboratory Animal Anesthesia, Second Edition, Academic Press, Ltd., London.
•
Flecknell PA and Waterman-Pearson A. Pain Management in Animals. W.B. Saunders, Philadelphia, PA.
2002.
•
Fox JG, Anderson LC, Loew FM, Quimby FW eds. Laboratory Animal Medicine 2nd Ed. Academic Press,
London England, 2002.
•
Gaynor J, Muir W, Handbook of Veterinary Pain Management, Mosby, St. Louis Missouri, 2002.
•
Hawk, C. et al. (2005) Formulary for Laboratory Animals, Third Edition, Blackwell Publishing, Ames,
Iowa.
•
Hrapkiewicz K, Medina L, Holmes D, Clinical Laboratory Animal Medicine 2nd ed. Iowa Sate University
Press, Ames, Iowa, 1998.
•
Plumb, DC. (2002). Veterinary Drug Handbook Iowa State University Press, Ames, Iowa.
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Nonhuman Primate Anesthesia and Analgesia Guidelines
•
Popilskis, S. Kohn, D. (1997). Anesthesia and Analgesia in Dogs and Nonhuman Primates. In
Anesthesia and Analgesia in Laboratory Animals (D.F. Kohn, S.K. Wixson, W.J. White, and G.J. Benson,
eds.), pp. 233-253. Academic Press, San Diego, California.
•
Primate Medicine Department, California National Primate Research Center, University of California,
Davis.
•
Swindle MM, Vogler GA, Fulton LK, Marini RP, Popilskis S. (2002). Preanesthesia, Anesthesia,
Analgesia, and Euthanasia. In Laboratory Animal Medicine 2nd Edition (JG
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