Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

CHAPTER 14 OPIOID ANALGESICS
may achieve the desired effect, although in general the
level of sedation produced by standard clinical doses is
poor for most opioids when used as the sole agent. Apart
from providing increased sedation when used in combination
with a sedative or tranquilizer, opioids as part of
a premedication protocol can act in a pre-emptive
fashion, reducing both the intraoperative and postoperative
analgesic requirements. Controlling surgical pain in
animals before they fully recover from general anesthesia
is easier and requires less total drug to be administered
than waiting for the animals to show obvious signs of
pain and then administering an analgesic.
Opioids and anesthesia induction
Another preoperative application for some of the full
opioid agonists is as a component of the protocol for
induction of anesthesia. Selected opioid agents have
been used for anesthetic induction in a number of situations
because of the marked cardiovascular stability
they provide, aside from bradycardia. This technique is
most often reserved for very ill and moribund animals,
the very elderly or those with a pronounced degree of
cardiovascular compromise. In such cases, higher doses
of ultra-fast acting pure agonist µ-receptor opioids (fentanyl,
alfentanil) may be administered as part of a
coinduction (immediately prior to the induction agent).
As a result, the dose of induction agent will be significantly
reduced but other unwanted effects such as ventilatory
depression are minimized or, where seen, can
be quickly managed in the anesthetized patient with a
controlled airway. It is also recommended that where
possible, without stressing the patient, animals be preoxygenated
via facemask or oxygen chamber, prior to
induction of anesthesia.
The onset of anesthesia during an opioid induction is
much slower than that achieved with other intravenous
agents such as thiopental and propofol. Delay in onset
during induction relates to those factors that influence
the transfer across the blood–brain barrier: lipid solubility,
ionization and protein binding. Some opioids, fentanyl
in particular, make animals hyperresponsive to
sudden, loud sounds, which should therefore be avoided
during induction.
Intraoperative use of opioids
Many studies have demonstrated a reduced requirement
for inhalant anesthetic agents (reduction in the minimum
alveolar concentration – MAC) in animals that have
received opioid analgesics. This effect is dose dependent;
however, even at extremely high dose rates the MAC
reduction is still not 100%, which further indicates the
inability of opioids to act as true anesthetic agents.
Therefore opioid analgesics can be used to supplement
the main anesthetic agent, whether it be infused or
inhaled, and at the same time provide analgesia; this
combination of drugs is often referred to as ‘balanced
anesthesia’.
There are two commonly used approaches to the
delivery of intraoperative opioids: intermittent bolus
and continuous infusion.
Intermittent boluses
All µ-agonists, with the exception of the ultra-short
acting agent remifentanil, can be administered by intermittent
intravenous bolus, the important difference
between them being the dosing intervals, which need to
be greater for the longer-acting drugs. If such administration
is continued for a long surgical procedure, then
the dosing interval will often need to be increased as the
case progresses to avoid accumulation, which may only
become apparent during recovery. Signs of accumulation
observed during recovery include prolongation of
recovery, in particular delayed extubation, respiratory
depression and possibly excitatory behavior, including
thrashing and vocalization, which can be difficult to
distinguish from insufficient analgesia and an extreme
response to pain.
Continuous infusion
Shorter-acting µ-agonists are well suited to this technique
and more recently have been developed for this
purpose. As well as acting as supplements to inhalational
anesthesia, these drugs may also be used as part
of a total intravenous anesthesia (TIVA) protocol in
conjunction with a hypnotic agent such as propofol and
muscle relaxants. In some instances, all three classes of
drug may be administered as continuous infusions. By
selection of the appropriate agents and infusion rates,
this technique can provide precise control of anesthetic
depth and hence reduce recovery times. Fentanyl has
traditionally been the agent of choice for this indication
in veterinary anesthetic practice. The cumulative nature
of fentanyl when infused for more than 90 min and
the introduction of remifentanil means that fentanyl
is no longer the infusion opioid of choice in most
circumstances.
Extradural and intrathecal
administration of opioids
Other techniques for opioid administration perioperatively
are extradural (epidural) and intrathecal (subarachnoid,
spinal) placement of opioids alone or in
combination with local anesthetic agents. These techniques
can be used to supplement general anesthesia or
heavy sedation and provide highly effective analgesia
with MAC reduction of 30–60% and good cardiovascular
stability. Patient and procedure selection are very
important if these techniques are to be used without
general anesthesia but they can be extremely successful
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