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Guidelines for
Use of Pentobarbital

Pentobarbital is one of the most common injectable general anesthetic agents used in rodents. Pentobarbital is one of the drugs belonging to the class of anesthetics known as barbiturates. All barbiturates are derived from barbituric acid which, structurally, has had appropriate side-chain substitutions that result in central nervous system (CNS) depressant activity that varies in potency and duration with carbon chain length, branching, and saturation. The barbiturates have been classified into four groups according to duration of action (i.e. long, intermediate, short, and ultrashort). Those used for general anesthesia fall in the intermediate to short or ultrashort category whereas those used for sedation or control of convulsions are of long and intermediate duration. The principal effect of a barbiturate is depression of the CNS by interference with passage of impulses to the cerebral cortex. Barbiturates act directly on CNS neurons in a manner similar to that of the inhibitory transmitter GABA. Barbiturate anesthesia is thought to be produced by the combined effect of enhanced inhibition and diminished excitation. The distinction between an anesthetic and an anticonvulsant barbiturate depends on the concentration at which amino acids modulation and GABA-mimicking activities occur.

Pentobarbital sodium occurs as white powder or crystalline granules that are freely soluble in water or alcohol to form a clear, colorless solution. The wide use of pentobarbital in rodents stems from its generalized availability, modest cost, widely available database for its use, rapid anesthetic onset, nonirritant nature, and ease of intraperitoneal injection to rodents of varying ages and body weights. Pentobarbital is a relatively poor analgesic. Higher doses are necessary to provide a surgical plane of anesthesia.

A mild excitement phase, during both anesthetic induction and recovery, is often observed with pentobarbital anesthesia. Pentobarbital causes respiratory depression which may result in hypercapnia with decreased tidal volume, minute volume, and respiratory rate. Reduced blood pressure, stroke volume, pulse pressure, and central venous pressure are common findings in pentobarbital-anesthetized animals. In prolonged anesthesia, the drug has also been shown to cause impaired myocardial contractility. Other reported effects include progressive decrease in core body temperature, decreased renal blood flow, reduced glomerular filtration rate, decreased intraocular pressure, and decreased urine output. Successful general anesthesia, using pentobarbital, is very dependent on good "support" (i.e. maintaining body temperature, maintaining hydration, etc.) during the anesthesia period. Pentobarbital freely crosses the placental barrier and enters the fetus. Environmental variables such as diet, environmental temperature, and type of bedding material the rodents are exposed to, can also affect the duration of pentobarbital-induced anesthesia. The effect of overdose of pentobarbital resembles the clinical signs produced by shock.