JOURNAL OF THE Vol. 40, No.

6
WORLD AQUACULTURE SOCIETY December, 2009

Sedation by Orally Administered Ketamine in Goldfish, Carassius

auratus; Hybrid Striped Bass, Morone hybrid saxatilis ×
M. chrysops; and Ocellated River Stingray, Potamotrygon motoro
Janis A. Raines1,2
The Dallas World Aquarium, 1801 North Griffin Street, Dallas, TX 75202 USA

Meredith M. Clancy
The Dallas World Aquarium, 1801 North Griffin Street, Dallas, Texas 75202 USA, and Texas
A & M University, P.O. Box 6013, College Station, Texas 77844 USA

Abstract
With the continued popularity of pet aquaculture and concurrent demands for advances in veteri-
nary medicine of fish species, a need exists for a reliable, safe, and environmentally noncontaminating
method of sedation. With appropriate sedation, fish can be more safely transported or handled for
veterinary care. Sedation can minimize stress or physical damage caused by handling and cap-
ture, and prepare fish for the deeper planes of anesthesia necessary for more extensive handling,
longer transport, or invasive procedures. This study assessed the efficacy of ketamine as a sedative
when administered orally to three species of fish: common goldfish, Carassius auratus, ocellated river
stingray, Potamotrygon motoro, and hybrid striped bass, Morone saxatilis × Morone chrysops. A prac-
tical application opportunity that became available at the end of the study demonstrated the use of
oral ketamine in the transport of a single arapaima, Arapaima gigas.

Typically, fish have been anesthetized
through inhalation by chemical baths using
tricaine methanesulfonate (Finquel, Argent
Chemical Labs, Inc., Redmond, WA, USA)
or, more recently in companion fish medicine,
eugenol (clove oil) (Ross and Ross 1999;
Sladky et al. 2001; Stoskopf, 1995; Thurmon,
1996). While this method is characterized by
rapid induction, ease of recovery, and wide
margin of safety, it requires that the fish be spa-
tially restricted (Lewbart and Harms 1999) to
achieve effective concentrations of the sedative.
For larger display aquaria with many individu-
als, difficulties are encountered with confining
the fish or the sedative to the specific individual
without affecting tankmates. To overcome this
problem, some veterinarians have attempted
direct approach to the target fish by spray of
a concentrated bolus of the bath agent (Stet-
ter, 2000). This method requires a stationary
or extremely malleable fish, and still produces
contamination of the exhibit. When the housing
1
Corresponding author.
2 Present address: Dallas Zoo and Dallas Aquarium
at Fair Park, Dallas, Texas 75203 USA.
© Copyright by the World Aquaculture Society 2009
of aquatic species is often augmented by the
inclusion of invertebrates to provide a more
realistic environment, the acidity of these water-
borne sedatives can be detrimental to the health
of these non-fish species housed in the sys-
tem (Noga, 1996). Additionally, many of these
water-borne anesthetic agents must be buffered
to prevent substantial damage to the gill fila-
ments of the target fish species (Harms, 1999;
Stoskopf, 1993).
A second sedation technique for approach-
able fish is intramuscular injection. (Muir et al.
1995; Soto and Burhanuddin 1995; Chong et al.
2006) Although an individual administration,
this method is more stressful to the patient, and
for the larger carnivorous species in which it
is most applicable, could also be stressful to
the anesthetist. These challenges lead to lim-
ited options for the veterinarian needing to
anesthetize the freely roaming, schooling, eas-
ily stressed or large fish patient. Currently, no
sedation regimen is available that guarantees
efficacy for only the chosen fish while reducing
environmental contamination. For this reason,
oral sedation has potential benefits. It would
allow the veterinarian to apply the anesthetic

788
 SEDATION BY ORALLY ADMINISTERED KETAMINE
agent in the fish’s typical diet, minimizing con-
tamination of both the environment and other
fish by directing it to the specific individual.
Although this route may produce a variable
induction period, defining appropriate doses
would facilitate use of this technique in clinical
veterinary medicine.
Successful studies of oral anesthesia in fish
have been very rarely attempted or published,
and so little confirmed knowledge exists in
the field. By placing the drug in food, a cap-
sule or by gavage, different chemical agents
have been orally administered. In 1979, Ameri-
can shad, Alosa sapidissima, were offered food
that contained diazepam (Abbott Laboratories,
North Chicago, IL, USA) to ameliorate trans-
port stress, and resulted in a slow induction
as the drug was absorbed through the gastro-
intestinal tract (Muir et al. 1995). Tiletamine-
zolazepam (Fort Dodge Animal Health, Fort
Dodge, IA, USA) was encapsulated in pow-
der form and fed via prey items to yellow-
tail jacks, Seriola lalandi (Steers and Sherrill
2001). Because of difficulties in assessing the
dosages and identifying individual fish, four of
fourteen yellowtail jacks died during sedation,
but a successful sedation and transportation was
completed for the others.
The gastro-intestinal tracts of fish vary
greatly from the complex digestive tracts of
bony fish (teleost) (Bond 1979) carnivores to
the simpler systems of herbivores. For the anes-
thetic agent to have effect via a food vehicle,
some digestion must occur to release the drug
for absorption; so species anatomic variability
must be considered. In primitive teleost fish,
such as goldfish Carassius auratus, the short
esophagus empties directly into the intestine
with no stomach (Bond 1979). In contrast, car-
tilaginous fish (elasmobranchs, such as skates,
rays, and sharks) have highly evolved diges-
tive tracts with extensive absorption adapta-
tions. Hybrid striped bass have distinctly folded
intestines and pyloric cecum but no stom-
ach, placing their digestive physiology between
goldfish and stingrays (Bond 1979).
Ketamine (Fort Dodge Animal Health, Fort
Dodge, IA, USA) produces dissociative anes-
789
thesia with profound amnesia, superficial anal-
gesia, and catalepsy (Muir, 1995). This state
of altered consciousness will allow for heavy
sedation with supplemental dosing inducing
full anesthesia. Oral, ocular, and swallowing
reflexes remain, as does skeletal muscle tone,
but the induced patient should be sedentary and
malleable. When parenterally administered to
an animal, ketamine provides quick induction
and sedation of moderate duration; can be eas-
ily administered orally with excellent mucosal
absorption (Grove and Ramsay 2000; Pulley
et al. 2004; Chong et al. 2006); has a wide mar-
gin of safety; is water-soluble and effective in a
working solution for more than 24 h (Lewbart
and Harms 1999).
With both practical need and limited infor-
mation on oral sedation in fish, this study was
designed to evaluate oral ketamine as a poten-
tial sedative agent. The initial phase of the study
with goldfish as the study model used gav-
age for administration of ketamine followed by
placement of ketamine within a gel diet using
three methods. Once these doses were estab-
lished, the study was applied to the ocellated
river stingray, Potamotrygon motoro, with a
short gavage trial before the food trial using live
prey (earthworms). Finally, the goldfish proto-
col was repeated on hybrid striped bass, Morone
saxatilis x M. chrysops, using the same live
prey as in the stingrays. The gavage portion
of the experimental design was not used in this
last species as it tolerates stress very poorly in
an unsedated state.
Materials and Methods
Goldfish
Twenty juvenile goldfish were obtained from
an aquatic wholesaler. These fish ranged in
weight from 3 to 20 g. They were acclimated
for 14 days to a 40-gallon bare-bottomed glass
aquarium with an external filter to provide fil-
tration. This tank was filled with reverse osmo-
sis water maintained at a pH of 7.0–7.2 at a
temperature of 70–73 F. The goldfish were con-
verted from a flake food to a gel diet during this
acclimation period.
790 RAINES AND CLANCY
Freshwater Stingrays
Four stingrays, which had a weight range
of 93–100 g, were acquired through a captive
breeding program at the investigating facility.
The stingrays were maintained at a pH of
6.7–7.0 and a temperature of 75–78 F in a
200-gallon system. These animals were fed an
earthworm diet.
Hybrid Striped Bass
Six juvenile hybrid striped bass, acquired
from a hatchery, ranged in size from 13 to
31 g. These fish were maintained at the same
parameters as the goldfish in a 40-gallon tank.
However, as these fish had been raised on live
food, attempts to convert the hybrid striped bass
to gel diet during this time were unsuccessful.
Over the course of acclimation, the fish were
converted to a diced earthworm diet similar to
the stingrays for purposes of the study.
Arapaima
This fish was housed in a 27,000-gallon
freshwater, flow-through aquarium for 5 years
with multiple South American fish species and
aquatic turtles, being fed a gel diet made of
gelatin, beef heart, and a vitamin premix. This
particular fish’s favorite food item was fresh-
frozen, thawed trout, which was selected as the
medication vehicle. The water pH was basic
for this species of fish (7.8 and above) with
a temperature of 68–74 F because the source
of the water was an artesian spring that filtered
through limestone.
Determination of Effective Dose
The trial began with gavages of increasing
dosages (50, 67, 100, 200 mg/kg) of ketamine
to determine an effective oral dose with goldfish
as experimental models. Each individual was
weighed and the appropriate ketamine dose cal-
culated, beginning at 50 mg/kg. Baseline res-
piratory rates were obtained on all individuals
prior to initiating the experiment.
The fish were observed continuously from
the moment of administration until 60 min
postadministration. Their opercular rates, a
visual indicator of respiration in fish, were
recorded every minute during the observation
period. As catching individual fish for gav-
aging is not an effective clinical dosing regimen
for aquaria, the next portion of the experiment
evaluated diet for drug delivery. Aquatic Omni-
vore Gel (Mazuri Test Diet, St. Louis, MO,
USA) was formulated as per recommended
label instructions. The experimental subjects
were then acclimated to this diet. Once the fish
were taking the food readily, three presentations
of the ketamine dose in small cubes (1 mm3 )
of food were provided to assess compliance:
steeped, injected (using fine gauge needles), or
gel diet reconstituted using ketamine as the liq-
uid component. This was determined by taking
the manufacturer’s suggested fluid-to-powder
ratio and adjusting the volume to formulate the
proper consistency using the ketamine. Steep-
ing involved soaking the cubes of gel diet in the
calculated amount of ketamine needed until all
fluid was absorbed (approximately 5–10 min).
Use of Ketamine as an Oral Anesthetic
in Elasmobranchs
This phylogenetic group has shown effec-
tive responsiveness to ketamine when admin-
istered parenterally (Stoskopf 1993); so, for
the purposes of this experiment, a return to
the original 50 mg/kg protocol was indicated.
Attempts were made to offer a more protein-
based gel diet but it was refused. Therefore, live
earthworms were chopped into 2 mm sections
and then injected with the appropriate dose
of ketamine and fed. In these species respira-
tory rate was easily measured through spiracle
movement.
Hybrid Striped Bass
The administration was challenging because
of difficulty in converting these very active
pelagic (midlevel, open water swimming) fish
to a gel diet. This problem was overcome by
their tendency to ingest rapidly moving items
and so food items were administered in a com-
paratively deep tank to permit consumption.
Offering varying doses of ketamine (125, 300,
500 mg/kg) injected into pieces of earthworm
 SEDATION BY ORALLY ADMINISTERED KETAMINE 791

proved to be a successful vehicle. Again oper- Stingray

cular movement was the means through which
respirations were evaluated.
Results
Goldfish
An observable decrease in opercular rate
shortly after initial gavage administration of the
ketamine was noted. Over the course of 30 min,
the goldfish given a 50 mg/kg dose demon-
strated a 40% reduction of average respiratory
rate from baseline at reaching a maximum seda-
tion level of Stage III. The stages of anesthe-
sia most often seen were stages I, II, and III
(Table 1), of which stage III would be ideal for
most transport and short diagnostic procedures
(i.e., gill clips or skin scrapes). (Smith 2002)
These results were consistent in this species
even with a marked increase in the ketamine
dose offered and vehicle of administration.
A ketamine dose of 50 mg/kg did not pro-
duce sedation when combined with gel diet in
any form. The dose was increased until a plane
of sedation was achieved; however, the results
did not reach those of direct gavage. At a dose
of 100 mg/kg injected in gel diet, changes in
opercular rate occurred, but no sedation was
observed. A single fish was tested at a dose
of 200 mg/kg to ensure that it was not a dose-
dependent issue. Overall, the sedative effects
were varied and largely unsuccessful.
Table 1. Stages of Anesthesia Results in Goldfish.
Time elapsed Average
since ingestion respiratory
Dose administered (min) rate (bpm)
Even with the lower dose of ketamine
ingested, 20 mg/kg, the stingray results were
very similar to those noted with the hybrid
striped bass (Tables 2 and 3). After ingestion
and allowing time (15 min) for gastric absorp-
tion, the stingray could easily be netted and
placed into dorsal recumbency.
Hybrid Striped Bass
When compared to goldfish, the hybrid
striped bass, after ingesting 300 mg/kg of
ketamine, demonstrated very similar decrease
in average opercular rate (Table 3). However,
even with a decrease of up to 50% of rest-
ing respiratory rate after ingestion of ketamine,
the hybrid striped bass acquired only a Stage II
level of sedation. Variation in dosage strength
equates to relative sedation planes: 125 mg/kg
resulting in light sedation, and 300 mg/kg
induced a deeper stage of anesthesia.
Arapaima–A Practical Application
A 7-ft arapaima (136 kg) housed in a 27,000
gallon aquarium was scheduled for transport
to a new facility 35 miles distant. A chemi-
cal bath would have contaminated the entire
aquarium and affected the other fish and rep-
tiles housed with this fish. This fish species
could not be approached for injection of the
anesthetic agent intramuscularly because of its
interlocking armor-like scales and extremely
skittish behavior when approached. However,
as a favorite prey item (whole trout) could
be fed to this carnivore, a dose of 10 mg/kg

Goldfish, 0 100 Table 2. Stages of Anesthesia Results in Striped Bass.

C. auratus 10 70—Stage II Time elapsed Average
50 mg/kg 20 80 since ingestion respiratory
(gavage); n = 20 30 60—Stage III Dose administered (min) rate (bpm)
60 84
Goldfish 0 90 Stingray, P. motoro 0 65
67 mg/kg (gavage) 10 50—Stage III 20 mg/kg 10 43
15 20 30 45—Stage II
60 60 60 80
Goldfish 0 110 Stingray 0 90
200 mg/kg (in gel 10 80—Stage II 50 mg/kg 10 40—Stage II
diet) 60 85 30 60
792 RAINES AND CLANCY

Table 3. Stages of Anesthesia Results in Freshwater due to difficulty in determining dosages within
Stingray. the gel and apparent problems with the efficacy
Time elapsed Average of the ketamine when prepared in combination
since ingestion respiratory with gel diet potentially binding to components
Dose administered (min) rate (bpm) within the gel. Some fish were unable to con-
Hybrid striped 0 70
sume medicated gel diet as a single piece. The
bass, Morone sp. 10 45—Stage I fish had been fasted for the typical 24 h prior to
125 mg/kg 30 50 trial, and larger boluses of gel diet were prob-
60 80 lematic for complete consumption of the food
Hybrid striped bass 0 75 by smaller specimens, meaning they did not
300 mg/kg 10 45—Stage II
ingest all of the dosage. This refusal permit-
30 55
60 78
ted ketamine to disperse into the water, possibly
Hybrid striped bass 0 85 causing some of the delayed reactions observed.
500 mg/kg 10 44—Stage II Regurgitation can often be a complication of
30 50 oral administration of ketamine in higher ver-
60 60 tebrates; this complication also occurred in the
goldfish that subsequently reingested the food
which complicated induction.
ketamine was offered to the fish after a 12-h
Although the final method of presenting
fast. In 27 min, the fish was sedated sufficiently
the ketamine by using it as the liquid recon-
for calm transport. However, a delay in the
stituent of the gel diet permitted the ability to
transport container occurred that allowed suf-
present much smaller pieces resulting in com-
ficient time (∼30–40 min) for the arapaima
plete ingestion of the dose, the gel consistency
to partially recover. The fish was reluctant to
was much looser than that made with water and
take a food item at this point due to all the
caused quick dispersal in the water. This water
increased activity in the tank; so in order to
contamination with ketamine may account for
increase sedation plane for transport, smaller
the prolonged effects in some fish. The hyperac-
doses of ketamine were successfully injected
tive and inactive swings were concluded to be a
into the less-armored gular area using a Telin-
result of the variable concentrations of ketamine
ject (Telinject USA, Inc., Agua Dulce, CA,
presented and within the water environment,
USA) dart underwater as the fish was malleable
causing the fishes to be variably affected but
with sedative. Despite the delay, ketamine per
not anesthetized. The ineffectiveness of this gel
os permitted the fish to be placed in a plas-
presentation, coupled with the danger for con-
tic sling for isolation and transported. After
tamination of the water in a clinical situation,
a 45-min drive, the arapaima could be safely
prompted the return to injection of the dosage
moved into the new enclosure but the fish was
into the gel diet.
alert enough to navigate safely.
Diet injection was tested again at 100 mg/kg
on six goldfish. Although sharp increases and
Discussion
decreases were seen in respiratory rates, the
Direct gavage trials were conducted with goldfish still did not show deep enough effects
ketamine to establish a baseline for this drug of sedation, much less anesthesia. A final evalu-
in three fish species. Since the most profound ation at 200 mg/kg in one goldfish showed less
effect was observed at 50 mg/kg in goldfish, signs of anesthesia (Table 4) than fish from the
that dosage was set as the starting point for the previous trial. This last observation suggests
food vehicle trials. apparent resistance to the route of food drug
From these studies, it appeared that the delivery in this species.
ketamine administered in the gel diet was less The conclusion drawn from these experi-
effective than a similar dose that was gav- ments was that a confounding problem existed
aged. These results were potentially obscured with absorption of ketamine from the digestive
 SEDATION BY ORALLY ADMINISTERED KETAMINE
Table 4. Stages of anesthesia in fish as defined for this
study.a
Stage I Erratic swimming, some loss of
equilibrium, increased respiration,
can have an excitatory period
during this phase
Stage II Loss of equilibrium, very slow
swimming, decreased operculum
movement, loss of muscle tone
Stage III Stops swimming, no response to
stimuli, optimal stage for invasive
procedures (i.e., gill biopsy)
Stage IV Very shallow operculum
movements—typically considered
the surgical plane of anesthesia.
Stage V Critical stage, spasmodic operculum
distension. May result in death
a
Whitaker (1999).
tract of the goldfish rather than the dose of the
ketamine. Goldfish, as they have neither a dis-
tinct stomach nor a pyloric cecum, appeared
unable to absorb enough ketamine from a food
vehicle to induce sedation from a per os dose.
In contrast, freshwater stingrays showed
the expected response to the ketamine. With
50 mg/kg in food, a stingray could be easily
netted and placed in dorsal recumbency; this
sedation plane would be very useful for a vet-
erinary procedure or transport. As the stingrays
never fully reached surgical anesthesia with res-
piratory rates increasing after stimuli, they did
not have sufficient duration or depth to be con-
sidered truly anesthetized.
Hybrid striped bass proved to be good
experimental models for teleosts. They showed
light sedation at ketamine doses of 125 mg/kg,
although with fluctuating respiratory rates.
Doses were increased with concurrent improve-
ment in sedation plane with the fish becom-
ing gradually recumbent at 300 mg/kg within
13 min with much slower purposeful move-
ments and breathing rates as compared to
unanesthetized conspecifics housed in the same
tank. The sedated fish could have been eas-
ily netted for transport or other minor pro-
cedures, and if a deeper plane of anesthesia
was needed, supplemental anesthetics could be
administered without much impact to an eas-
ily stressed patient. A hybrid striped bass was
given 500 mg/kg of ketamine that fully induced
793
the fish during the trial. This fish could have,
too, been easily restrained because of its state
of hypnosis. The hybrid striped bass trial con-
firmed that the ketamine could be effectively
used to orally sedate, or induce, teleost fish.
The success further supported that the apparent
resistance of the goldfish is likely to have been
absorption dependent. Only with further repe-
tition will the precise dosage be calculated for
the average teleost fish, but with this experiment
one can ascertain that fish can be orally anes-
thetized using ketamine for minor procedures
and transport.
Conclusion
Aquatic medicine is a currently evolving field
and methods of managing fish are developing
rapidly. As evidenced in this study, even though
the physiology and anatomy of fish is varied, it
is possible to extrapolate techniques of mam-
malian species to their care. Ketamine has been
shown in felids and nonhuman primates to have
excellent penetration and effect when adminis-
tered transmucosally. This route can be utilized
similarly to specifically induce a desired fish to
permit isolate to complete induction. Ketamine
can be safely administered orally and in food up
to at least 500 mg/kg in less primitive teleost
fish and 50 mg/kg in elasmobranchs to induce
a hypnotic sedation plane.
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