At this time, only MS-222 is registered for use on food fish in the U. S. However, many compounds have been evaluated experimentally and some are being used on nonfood fish and in research.
The substances described below have been extensively evaluated in the U. S. or other countries. Effective dosages of these drugs for different fish species are summarized in Table 2.
MS-222:
The chemical name for MS-222 is tricaine methanesulfonate. It is sold as Tricaine-S and Finquel. It comes as a white, crystalline powder that can be dissolved in water at up to an 11% solution. It lowers the pH of water, creating an acidic condition that can irritate fish and cause harmful side effects.
To prevent problems, the stock solution can be buffered with sodium bicarbonate (baking soda) to achieve a pH of 7. One of the major drawbacks of MS-222 is that even when fish are deeply anesthetized, handling still increases levels of plasma cortisol concentrations, an indicator of stress.
Induction is rapid and can take as little as 15 seconds. Salmonids are quickly anesthetized when immersed in 25 to 50 mg/L. Anesthesia can be maintained at 10 mg/L. Channel catfish (Ictalurus punctatus) require 25 to 50 mg/L for sedation and 100 to 250 mg/L for full anesthesia, with a 3-minute induction time.
Up to 100 mg/L is required for some species, including tilapia. Generally, concentrations greater than 100 mg/L should not be used for salmonids, and levels higher than 250 mg/L should not be used for warm-water fish.
Recovery is usually rapid and equilibrium can be expected to return after only a few minutes. A recovery time longer than 10 minutes suggests that too much anesthetic is being used or that the exposure time is too long. MS-222 has a good safety margin in fish.
In trout, for example, the effective concentration is 40 mg/L and the maximum safe concentration is 63 mg/L. The safety margin narrows as temperature rises and appears to be smaller for smaller fish. The drug is more potent in warm waters with low hardness.
MS-222 is excreted in fish urine within 24 hours and tissue levels decline to near zero in the same amount of time. It is approved for use on food fish in the U. S. and the United Kingdom, but was recently banned in Canada. The withdrawal time for MS-222 required by FDA is 21 days, which makes it impractical as an anesthetic for fish en route to market.
Benzocaine:
Benzocaine, or ethyl aminobenzoate, is a white crystal that is chemically similar to MS-222. However, benzocaine is almost totally insoluble in water and must first be dissolved in ethanol or acetone.
The standard approach is to prepare a stock solution in ethanol or acetone (usually 100 g/L) that will keep for more than a year when sealed in a dark bottle. In solution, benzocaine is neutral (pH 7) and therefore causes less hyperactivity and initial stress reaction than unbuffered MS-222. Benzocaine is effective at approximately the same doses as tricaine (25 to 100 mg/L).
Benzocaine has a fair margin of safety, although this appears to be reduced at higher temperatures. It is not safe for exposures longer than 15 minutes. Its efficacy is not affected by water hardness or pH. As with MS-222, it is fat-soluble and recovery times can be prolonged in older fish or gravid females. Benzocaine is not approved by FDA for use on food fish in the U. S.
Quinaldine:
Quinaldine is a yellowish, oily liquid with limited water solubility that must be dissolved in acetone or alcohol before it is mixed with water. While it is an effective anesthetic, it is an irritant to fish, has an unpleasant odor, and is a carcinogen.
The low cost of quinaldine has made it a popular tool for collecting tropical fish for the aquarium trade, as well as in the bait and sport fish industries. Quinaldine sulfonate is a pale yellow, water-soluble powder; it is more costly than quinaldine or MS-222.
Quinaldine solutions are acidic and are usually buffered with sodium bicarbonate. Induction takes 1 to 4 minutes and may cause mild muscle contractions. Recovery is usually rapid. The effective treatment concentration of quinaldine solutions varies with species, but is generally 15 to 60 mg/L. Grass carp (ctenopharyngodon idella) lose equilibrium within 5 minutes of exposure to 15 mg/L. However, quinaldine concentrations of 50 to 1,000 mg/L were required to completely anesthetize tilapia.
Quinaldine may not produce the deep anesthesia needed for surgery because some reflex responsiveness is usually retained. Higher doses (150 mg/L) have been used for surgical procedures, but quinaldine is not usually recommended for these procedures.
Fish under full quinaldine anesthesia normally do not stop their gill ventilation so are not as susceptible to asphyxia from respiratory arrest as they are with MS-222. In general, the potency of quinaldine is higher in hard water and warm water. Quinaldine is not approved by the FDA for use on food fish in the U. S.
2-Phenoxyethanol:
2-Phenoxyethanol is an opaque, oily liquid. This drug is moderately soluble in water but freely soluble in ethanol. The solution is bactericidal and fungicidal and is, therefore, useful during surgery.
It is relatively inexpensive and remains active in the diluted state for at least 3 days. 2-Phenoxyethanol has a relatively large margin of safety and has been reported to produce a range of effects from light sedation to surgical anesthesia at concentrations of 100 to 600 mg/L.
Concentrations of 300 to 400 mg/L are useful for short procedures, and lower concentrations of 100 to 200 mg/L are considered safe for prolonged sedation, such as during transport. 2-Phenoxyethanol is not approved by FDA for use on food fish in the U. S.
Metomidate:
Metomidate has been used extensively in human medicine. It anesthetizes fish without the usual stress of an elevated heart rate. Induction is rapid—1 to 2 minutes— and recovery is faster than with MS-222.
It anesthetizes salmonids at doses of only 2 to 6 mg/L; low doses are also effective in catfish. In salmonids, metomidate is reported to be more potent in larger, sea-water- adapted fish than in freshwater fingerlings or parr. With larval goldfish, Carassius auratus, and red drum, Sciaenops ocellatus, it has been reported to produce inadequate anesthesia with high mortalities.
Metomidate is not approved in the U. S. for use on food fish and is not widely used.
Clove oil:
Clove oil has been widely used as an anesthetic in human dentistry and as a food flavoring. The major constituent (70 to 90 percent by weight) is the oil eugenol, but clove oil contains a wide range of other compounds that impart its characteristic odor and flavor.
It is an effective anesthesia in carp (Cyprinus carpio) at 40 to 120 mg/L. In rainbow trout, Oncorhynchus mykiss, doses as low as 2 to 5 mg/L produced sedation sufficient to transport the fish, while doses of 40 to 60 mg/L for 3 to 6 minutes gave effective surgical anesthesia. Recovery time increases with higher doses and longer exposure time.
Clove oil is also an effective anesthetic for crustaceans at doses of 100 to 200 mg/L. Clove oil has a very high margin of safety; however, it also requires a relatively long recovery time compared to MS-222. The major advantage of clove oil is that it is inexpensive and not unpleasant to work with. Clove oil is not approved for use on food fish in the U. S.
Aqui-S:
Aqui-S is a relatively new anesthetic for fish developed by the Seafood Research Laboratory in New Zealand. This compound is approximately 50 percent isoeugenol and 50 percent polysorbate 80. A dosage of 20 mg/L is effective for most fish species and induction is described as “stress free” because the substance suppresses cortisol.
A recent study indicated that Aqui-S was an effective anesthetic on freshwater prawns, but only at much higher concentrations of 100 to 200 mg/L (S. Coyle and J. Tidwell, unpublished data).
Currently, Aqui-S is approved for use on food fish in Australia and New Zealand, with no withdrawal period. It is undergoing the New Animal Drug Approval process for use in the U. S., with no withdrawal time.
It is used primarily for the “rested harvest” of commercial fish species, where the low stress induction improves the color, texture and appearance of the product. If approved for use in the U. S. with the zero withdrawal time, Aqui-S would be a valuable tool to use when transporting live food fish to market.
Carbon dioxide:
Carbon dioxide, CO2 , has been used as an anesthetic for many years, especially during transport. It is extremely soluble in water and can simply be diffused into the water as CO2 gas.
However, it is somewhat difficult to control the final concentration of CO2 . Carbon dioxide anesthesia is effective in rainbow trout at 120 to 150 mg/L for fingerlings and 200 to 250 mg/L for adults. Hyperactivity and subsequent stress can be reduced by buffering the water with sodium bicarbonate.
Sodium bicarbonate (NaHCO3 ) and acetic acid have also been used to produce CO2 . When dissolved in water, sodium bicarbonate releases carbon dioxide if the pH is acidic. Peak (1998) compared the efficacy of sodium bicarbonate and acetic acid to produce anesthesia in smallmouth bass (Micropterus dolomieu), northern pike (Esox lucius), and lake stugeon (Acipencer fulvescens).
He found that for these cool-water species a 2.6-g/L NaHCO3 solution (30 L water, 80 g NaHCO3 , and 80 mL acetic acid) performed better than the 1.3-g/L NaHCO3 solution (30 L water, 40 g NaHCO3 , and 15 mL acetic acid) previously recommended for salmonids.
Durborow and Mayer (unpublished data) found that largemouth bass (Micropterus salmoides) reached stage 2 anesthesia after 6 minutes when exposed to a 0.67-g/L NaHCO3 solution (30 L water, 20 g NaHCO3 , and 7.5 mL acetic acid) at 6 °C, and recovered in 10 to 15 minutes after being anesthetized for 1 hour.
The inconvenience of adjusting and maintaining the required pH makes other methods more attractive for most procedures. Carbon dioxide requires a relatively long induction time—generally 5 minutes at concentrations of 120 to 640 mg/L.
The main advantage of carbon dioxide is that it is not a controlled substance in the U. S. and is recognized as a “Low Regulatory Priority,” unapproved drug by the FDA. This permits its use in food fish with no withdrawal time. At this time it is the only chemical method available for harvesting or transporting food fish to market.
Authors:
Shawn D. Coyle, Robert M. Durborow and James H. Tidwell
