Ban on Use of Ether

Ban on Use of Ether

Ether and chloroform are obsolete anesthetic agents that are no longer used in human or companion animal medicine. Superior inhalant agents (such as halothane, isoflurane, and methoxyflurane) or suitable parenteral agents are recommended for use in research animals. Chloroform is a severe cardiovascular depressant and a potent hepatotoxin. For the past 5 years, the IACUC has avidly discouraged the use of ether as an anesthetic agent for two reasons:

  • Ether is highly explosive and presents a hazard even when stored and used properly. One research institution in Boston has incurred expenses in excess of $35,000 for incidents of ether can removal that required Bomb Squad intervention.
  • Ether is highly irritating to mucous membranes throughout the airways. Administration of ether is stressful to animals and stimulates catecholamine release*. Clinical problems caused by secretion of fluid in the lungs and bronchial passages may be fatal in small rodents.
  • Effective immediately, the use of ether or chloroform for animal anesthesia or euthanasia will not be approved on any IACUC protocol submitted for review. See enclosed list of approved alternative agents.

    The IACUC is dedicated to ensuring human safety as well as optimal animal care at Boston University Medical Center. Your cooperation in this effort is appreciated. Please call the IACUC office at 617-638-4263 if you require additional information or have any concerns.


    * Some reports also indicated stimulation of the pituitary-adrenal axis during anesthetic induction using ether in rats.

    Anesthetic and Euthanasia Agents* to Replace Ether

    Inhalant anesthetic agents; suitable for all rodent species; For your safety, all volatile agents must be used only with an active exhaust flow (chemical fume hood or gas scavenging system) to remove vapors from the room and discharge them to the outdoors.

    Isoflurane (Forane®, AErrane®) -volatile agent -requires active exhaust system

    • administer via precision vaporizer
    • 3-4% for induction, 1.5-2.5% for maintenance
    • purchase from Animal Facility or Schein, Inc., ph. 800-872-4346

    Halothane (Fluothane®) volatile agent-requires active exhaust system

    • administer via precision vaporizer
    • 2-4% for induction, 0.9-1.5% for maintenance
    • purchase from Animal Facility or Schein, Inc., ph. 800-872-4346

    Carbon Dioxide:Oxygen Mixture

    • for short duration (<5 min.) minor or terminal procedures only
    • induction in approx. 1 minute, rapid recovery upon removal from gas mixture
    • recommended ratios vary from CO2:O2 of 50:50 to 70:30;if CO2 too low, slow induction; if CO2 too high, pain and distress on inhalation;
    • do not exceed 70% CO2
    • purchase pre-mixed in gas cylinder

    Parenteral anesthetic agents

    Mouse

    pentobarbital 40-85 mg/kg IP;
    xylazine 5-10 mg/kg IP plus ketamine 50-80 mg/kg IP;
    tribromoethanol (Avertin) 240 mg/kg IP (= 1.25% solution dosed at 0.2 ml/10 g IP);
    pentobarbital 30 mg/kg IP plus ketamine 30 mg/kg IP.

    Rat

    pentobarbital 40-65 mg/kg IP;
    xylazine 5 mg/kg IP plus ketamine 40-60 mg/kg IP;
    Guinea pig
    pentobarbital 30-40 mg/kg IP;
    xylazine 5 mg/kg SC followed in 5-10 minutes by ketamine 30-40 mg/kg IM;
    Euthanasia agents – Acceptable methods of euthanasia for mice, rats, and guinea pigs are:
    carbon dioxide inhalation; or
    pentobarbital overdose (120 mg/kg IP); or
    general anesthesia followed by vital tissue removal.
    Cervical dislocation, decapitation, or other methods are not allowed on unanesthetized animals unless approved by the Institutional Animal Care and Use Committee on the basis of scientific justification provided by the investigator.

    *Alternatives to the anesthetic and euthanasia agents listed above may be approved by the Animal Research Committee on the basis of scientific justification provided by the investigator. The duration and invasiveness of the proposed surgical procedure need to be considered in the selection of an anesthetic regimen for any animal.

    Additional information on animal anesthesia is available from the Committee office-call 638-4263. The generic name, dose (mg/kg), route, and frequency of administration of any agent(s) that will be used for animals must be specified in the protocol that is reviewed by the Committee.

    Comparison of Inhalant Anesthetic Agents to Replace Ether

    Agent VP Max. % Useable range Solubility a Rodent MAC% (b)
    Ether 450 59 % 0-15 % 15 c 3.2
    Halothane 243 33 % 0-4 % 2.3 0.92 – 1.1
    Methoxyflurane* 23 3 % 0-3 % 12.0 0.22
    Isoflurane 250 31 % 0-5 % 1.4 1.4
    * No longer manufactured as of March 1999.
    VP= Vapor pressure at 20C
    Max%= maximum percentage in room air
    Solubility = blood-gas solubility at 37 C

  • Ratio of the concentration of the agent in blood divided by the concentration of the agent in alveolar spaces (lung) at equilibrium. This ratio is also known as the partition coefficient. The blood-gas coefficient is a useful indicator of the speed of anesthetic induction (the lower the coefficient, the faster the induction).
  • Minimum alveolar concentration (MAC) is that anesthetic concentration required to prevent gross muscular movement in response to a painful stimulus in 50% of a tested population. It is a useful standard for comparing the potency of inhalation anesthetics. The MAC may be considered the effective dose-50% (ED50). The alveolar concentration of an anesthetic needed to achieve surgical anesthesia must be equal to or greater than MAC.
  • Observations of rapid induction with ether are not supported by the blood-gas coefficient (15) for this compound. There are other possible explanations for rapid onset of unconsciousness in animals exposed to ether. Breath-holding, which has been well documented during anesthetic induction with ether, may cause unconsciousness in animals due to hypoxia. When ether is inhaled at high concentrations (i.e., in an open drop system), paralysis of the respiratory centers may also cause hypoxia and unconsciousness.