|
ANALGESIC
CONSTANT RATE INFUSIONS
Dr. Robert Stein, Dr. David
Thompson, & the VIN Gang
January
2004
A constant rate infusion (CRI)
of analgesic drugs is a simple and effective means of improving patient
comfort. Various formulations can be used as a constant rate infusion; the
protocol chosen depends on the patient and the degree of pain experienced
or anticipated. Some of the commonly used drugs include the following:
1)
KETAMINE -- NMDA
(N-methyl-D-aspartate) receptors are present in the dorsal horn of the
spinal cord and certain areas within the brain. Intense and/or chronic
noxious input to the dorsal horn cells (mediated principally by C-fibers)
results in the removal of magnesium from the NMDA receptors and their
activation by glutamate. This causes prolonged depolarization of spinal
neurons (an increase in the magnitude and duration of neuron firing),
which leads to an “amplification” of the pain response. This is a
significant part of the process of central sensitization (an increase in
the excitability of spinal neurons) and may result in hyperalgesia (an
excessive response to a painful stimulus) and allodynia ( a painful
response to a normally non-painful stimulus).
It
is readily apparent that blocking (antagonizing) the NMDA receptors will
help to minimize excessively painful responses. Additionally, studies
suggest that antagonizing these receptors improves opioid receptor
sensitivity, reduces opioid tolerance and minimizes the development of
rebound hyperalgesia (the phenomenon of markedly increased pain when
opioids are withdrawn).
Ketamine
is the most commonly used antagonist of NMDA receptors in veterinary
medicine. While its effects as a dissociative anesthetic at standard doses
are well known, a new realm of activity occurs when it is delivered at
sub-anesthetic doses. At constant rate infusion doses, ketamine blocks
receptor activity without causing any dissociative or other adverse
effects.
It
should be noted that a microdose ketamine CRI should not be used as a sole
means of analgesia. It is intended to augment other pain relievers, and
should always be used in conjunction with opioids or other analgesics.
2)
MORPHINE -- When
combined with ketamine in a constant rate infusion, significant analgesia
is achieved. The steady-state levels of morphine help to avoid some of the
“peak and valley” effects seen with prn administration of opioids.
Additionally, its use intraoperatively (as a “piggyback” onto
anesthetic maintenance fluids) serves to reduce the amount of anesthetic
gas required, which can be useful in decreasing the risk of hypotension.
It
can be used in cats at the low end of the dosing spectrum (higher rates
may induce significant dysphoria and excitation).
While
other opiods can be substituted for morphine, we have elected to only
include information for one other mu agonist, fentanyl, in the dosing
information section. This reference is not intended to be an exhaustive
review of all CRI options but to serve as a solid but basic reference for
those adding CRI analgesia to their practice.
3)
LIDOCAINE -- The
addition of lidocaine has several benefits. For intractable/very severe
pain, it adds to the analgesia and sedation. Lidocaine is reported to have
some cytoprotective effects, such as weak calcium channel inhibition
(which may be helpful in preventing reperfusion injury), and reduced
neutrophil chemotaxis and platelet aggregation (which could help
significantly in cases with the potential for DIC or SIRS, including
GDV’s and splenectomies). Also, lidocaine has some activity in
preventing ileus (potentially useful for enterotomies).
Various
dosage rates of lidocaine have been advocated. In dogs, rates as low as 10
ug/kg/minute (0.6 mg/kg/hour) provide analgesia, though it may take up to
50 ug/kg/minute (3 mg/kg/hour) for the full cytoprotective and anti-ileus
effects. Until further data is available, lidocaine’s use in cats
cannot be recommended, due to the potential for toxicity, usually
manifested as seizures and severe bradycardia.
CRI
DOSING INFORMATION
KETAMINE
(100 mg/ml) - 2 to 20 ug/kg/minute (0.12 to 1.2 mg/kg/hr).
·
An
initial 0.25 to 0.50 mg/kg IV bolus is given to rapidly achieve initial
therapeutic blood levels of the drug (while the CRI is intended to
maintain, or very slowly, increase blood levels). Failure to administer
this "loading" dose will result in an excessive delay in the
drug reaching therapeutic levels.
·
Ket/val
inductions and telazol inductions both provide adequate loading doses (tiletamine
provides the same NMDA antagonism as ketamine).
·
2
to 20 ug/kg/min = 0.002 to 0.020 mg/kg/min.
MORPHINE
(15 mg/ml) - 2 to 6 ug/kg/minute (0.12 to 0.36 mg/kg/hr).
·
If
no previous mu agonist has been given, administer 0.5 mg/kg of Morphine IM
(or very slowly IV) to rapidly achieve initial therapeutic blood levels.
·
Morphine
is light sensitive. Make sure
the syringe or IV bag is covered to protect the morphine from light when
using long-term morphine CRIs.
·
2
to 6 ug/kg/min = 0.002 to 0.006 mg/kg/min.
LIDOCAINE
(20 mg/ml) - 10 to 50 ug/kg/minute (0.6 to 3.0 mg/kg/hr).
·
An
initial 1 mg/kg IV bolus is given to rapidly achieve initial therapeutic
blood levels.
·
Given
the volume of 2% lidocaine this is, a similar volume of the diluent should
be removed BEFORE any other drugs are added.
·
Lidocaine
is light sensitive too. Make sure the syringe or IV bag is covered to
protect the lidocaine from light when using long-term lidocaine CRIs.
·
10
to 50 ug/kg/min = 0.010 to 0.050 mg/kg/min.
GENERAL
INFORMATION
·
All
three drugs are used routinely in dogs and in any combination.
·
Cats
- the routine use of morphine CRIs in cats is not common. But it
can be an effective option if the feline patient is monitored closely for
dysphoric trends. Always start at the low end of the opiod CRI dose range.
·
Cats
- until more data is obtained, lidocaine’s use in cats cannot be
recommended due to potential toxicity issues. If it is used in cats,
do not exceed 10 ug/kg/minute, and monitor carefully for seizure activity
and cardiac abnormalities (bradycardia). 10 ug/kg/min = 0.010 mg/kg/min.
·
It
is common to use a ketamine only CRI bag over several patients, switching
IV extension lines between patients. When morphine is added to the CRI,
the bag is dedicated to that single patient. The amount of morphine drawn
up and the amount unused is carefully recorded in the controlled drug
logs.
·
Ketamine/morphine/saline solutions have
been shown to be stable for at least 4 days.
·
D5W
as well as other fluids are acceptable diluents.
EXAMPLE
FELINE OR CANINE KETAMINE RECIPE
This simple recipe is based on
routine supportive fluid rates of 10 to 20 ml/kg/hr.
This is the recommended starting
recipe for those new to CRI analgesics.
The following recipe can be used
in dogs and cats.
KETAMINE:
Add 60 mg ketamine (0.6 ml) to 1000 ml fluids
·
Deliver
at normal anesthesia supportive fluid rate of 10 ml/kg/hr = 10 ug/kg/min
or 0.6 mg/kg/hr.
· This
recipe assumes that the ketamine concentration is 100 mg/ml
GENERAL INFORMATION
·
Rate
can be doubled to 20 ml/kg/hr to deliver 20 ug/kg/min or 1.2 mg/kg/hr.
·
If
higher fluid rates are needed, add a second fluid line to meet the
patient’s need.
·
Remember
the loading dose requirement detailed above.
EXAMPLE
FELINE OR CANINE MK RECIPE
This simple recipe is based on a 1
ml of the final dilution/kg/hr fluid rate.
The following recipe can be used
in dogs and cats.
KETAMINE:
60 mg/500 ml = 0.6 ml/500 ml diluent = 1.2 ml/1000 ml diluent
·
Deliver at 1ml/kg/hr fluid rate = 2 ug/kg/min
or 0.12 mg/kg/hr
· This
recipe assumes that the ketamine concentration is 100 mg/ml
MORPHINE:
60 mg/500 ml = 4 ml/500ml = 8 ml/1000 ml
·
Deliver at 1ml/kg/hr fluid rate = 2 ug/kg/min
or 0.12 mg/kg/hr
· This
recipe assumes that the morphine concentration is 15 mg/ml
GENERAL
INFORMATION
·
It’s easy then to just enter the
patient's wt (in kg) in the infusion pump for the proper initial fluid
rate.
·
Dogs – fluid rates can be increased
up to 3 ml/kg/hr without exceeding the dosage guidelines for either of the
drugs.
·
Cats – fluid rates can be increased
up to 3 ml/kg/hr but may cause unwanted dysphoria in awake feline
patients. Monitor closely and reduce rate if dysphoria occurs.
·
To
substitute fentanyl for morphine at a dose equipotent to the morphine dose
above add:
§
FENTANYL
(0.05 mg/ml):
0.6 mg/500 ml = 12 ml/500 ml diluent = 24 ml/1000 ml diluent.
¨
Deliver
at 1ml/kg/hr fluid rate = 0.02 ug/kg/min or 0.0012 mg/kg/hr
§
Given
the volume of fentanyl this is, a similar volume of the diluent should be
removed before any other drugs are added.
§
For
dogs, the fluid rate can be increased up to 3 ml/kg/hr as
noted above.
·
Remember
the loading dose requirements detailed above.
EXAMPLE
CANINE MLK RECIPE
This simple recipe is based on a 1
ml of the final dilution/kg/hr fluid rate.
The following three drugs can be
used in any combination for dogs.
For
Excel CRI Calculators see Support Material
KETAMINE:
60 mg/500 ml = 0.6 ml/500 ml diluent = 1.2 ml/1000 ml diluent
·
Deliver at 1ml/kg/hr fluid rate = 2 ug/kg/min
or 0.12 mg/kg/hr
· This
recipe assumes that the ketamine concentration is 100 mg/ml
MORPHINE:
60 mg/500 ml = 4 ml/500ml diluent = 8 ml/1000 ml
diluent
·
Deliver at 1ml/kg/hr fluid rate = 2 ug/kg/min
or 0.12 mg/kg/hr
· This
recipe assumes that the morphine concentration is 15 mg/ml
LIDOCAINE:
500 mg/500 ml = 25 ml/500 ml diluent = 50 ml/1000 ml diluent
·
Deliver at 1ml/kg/hr fluid rate = 17 ug/kg/min
or 1.0 mg/kg/hr
· This
recipe assumes that the lidocaine concentration is 20 mg/ml
GENERAL
INFORMATION
·
Just enter the patient's weight (in kg)
in the infusion pump for the proper initial fluid rate.
·
Don’t forget to remove a volume equal
to the lidocaine volume from the diluent bag before adding
any of the drugs planned for the CRI.
·
Remember
the loading dose requirements detailed above.
·
Dogs – fluid rates can be increased
up to 3 ml/kg/hr without exceeding the dosage guidelines for any of the
drugs (irrespective of the drug combinations).
·
Cats
- until more data is obtained, lidocaine’s use in cats cannot be
recommended due to potential toxicity issues. If it is used in cats, do
not exceed 10 ug/kg/minute, and monitor carefully for seizure activity and
cardiac abnormalities (bradycardia).
§
LIDOCAINE
(20 mg/ml):
300 mg/500 ml diluent = 15 ml/500 ml diluent = 30 ml/1000 ml diluent
¨
Deliver
at 1ml/kg/hr fluid rate = 10 ug/kg/min or 0.6 mg/kg/hr
·
To
substitute fentanyl for morphine at a dose equipotent to the morphine dose
above add:
§
FENTANYL
(0.05 mg/ml):
0.6 mg/500 ml = 12 ml/500 ml diluent = 24 ml/1000 ml diluent.
¨
Deliver
at 1ml/kg/hr fluid rate = 0.02 ug/kg/min or 0.0012 mg/kg/hr
§
Given
the volume of fentanyl this is, a similar volume of the diluent should be
removed before any other drugs are added.
§
For
dogs, the fluid rate can be increased up to 3 ml/kg/hr as
noted above.
ADDITIONAL
CRI DRUGS AND DOSES
FENTANYL
– 0.02 to 0.06 ug/kg/minute (0.0012 to 0.0036 mg/kg/hr).
·
Fentanyl’s
duration of effect is
only about 30 minutes. Undesirable effects will not linger as long as when
morphine, hydromorphone, or oxymorphone are used
·
If
no previous mu agonist has been given, administer 0.003 mg/kg of Fentanyl
IM or IV to rapidly achieve initial therapeutic blood levels.
·
Given
the volume of fentanyl this is, a similar volume of the diluent should be
removed before any other drugs are added.
·
0.02
to 0. 06 ug/kg/min = 0.00002 to 0.00006 mg/kg/min.
|
