Parenteral anesthetics

Parenteral anesthetic agents as prescribed by veterinary surgeon (see Note 4 Hypnorm + Hypnovel). 

Parenteral anesthetic agents are preferable to gaseous ones as the size of the mouse creates problems when using standard anesthetic machines. 

The two principal parenteral anesthetic drugs used clinically are thiopental (an old prototype) and propofol (a relatively new drug). Thiopental is a derivative of barbituric acid, while propofol is a substituted propylphenol. Onset and duration of anesthetic effect for the two drugs are similar. However, recovery is more rapid following infusion with propofol (a desirable feature). The relatively rapid clearance of propofol explains its less severe hangover in patients compared to thiopental and may allow for a more accelerated discharge from the recovery room. 

Ketamine typically is administered intravenonsly bnt also is effective by intramnscnlar, oral, and rectal rontes. The indnc-tion doses are 0.5 to 1.5 mg/kg IV, 4 to 6 mg/kg IM, and 8 to 10 mg/ml. Onset of action after an intravenous dose is similar to that of the other parenteral anesthetics, but the duration of anesthesia of a single dose is longer. For anesthetic maintenance, ketamine occasionally is continued as an infusion (25 to 100 (tg/kg per minute). Ketamine does not elicit pain on injection or true excitatory behavior as described for methohexital, although involuntary movements prodnced by ketamine can be mistaken for anesthetic excitement. 

The onset and duration of an induction dose of ketamine are determined by the same distribution/redistribntion mechanism operant for all the other parenteral anesthetics. 

Ketamine is hepatically metabolized to norketamine, which has reduced CNS activity norketamine is fnrther metabolized and excreted in urine and bile. Ketamine has a large volume of distribution and rapid clearance that make it snitable for continuous infusion withont the drastic lengthening in duration of action seen with thiopental. Protein binding is much lower with ketamine than with the other parenteral anesthetics. 

Ketamine has indirect sympathomimetic activity. Ketamine s behavioral effects are distinct from those of other anesthetics. The ketamine-induced cataleptic state is accompanied by nystagmus with pupillary dilation, salivation, lacrimation, and spontaneous limb movements with increased overall mnscle tone. Although ketamine does not prodnce the classic anesthetic state, patients are amnestic and nnresponsive to painful stimuli. Ketamine produces profound analgesia, a distinct advantage over other parenteral anesthetics. 

DOSAGES AND CLINICAL USE Recommended intravenous dosing for parenteral anesthetics in a healthy young adult is given in Table 13-2. 

PHARMACOKINETICS AND METABOLISM Pharmacokinetic parameters for parenteral anesthetics are given in Table 13-2. As discussed above, the principal mechanism limiting anesthetic dnration after single doses is redistribution of these hydrophobic drugs from the brain to other tissues. However, after multiple doses or infusions, the duration of action of the barbiturates varies considerably depending on their clearances. 

Short-term administration of barbiturates has no clinically significant effect on the hepatic, renal, or endocrine systems. A single induction dose of thiopental does not alter tone of the gravid uterus, but may produce mild transient depression of newborn activity. Drug-induced histamine release is occasionally seen. Barbiturates can induce fatal attacks of porphyria in patients with acute intermittent or variegate porphyria and are contraindicated in such patients. Unlike inhala-tional anesthetics and succinylcholine, barbiturates and all other parenteral anesthetics apparently do not trigger malignant hyperthermia. 

Propofol (diprnan Figure 13—1) is the most commonly used parenteral anesthetic in the U.S. The drug is insoluble in aqueous solutions and is formulated only for IV administration as a 1% (10 mg/mL) emulsion in 10% soybean oil, 2.25% glycerol, and 1.2% purified egg phosphatide. Significant bacterial contamination of open containers has been associated with serious patient infection propofol should be either administered or discarded shortly after removal from sterile packaging. 

Unlike other parenteral anesthetics, ketamine increases cerebral blood flow and ICP with minimal alteration of cerebral metabolism. These effects can be attenuated by concurrent administration of thiopental and/or benzodiazepines along with hyperventilation. However, given that other anesthetics actually reduce ICP and cerebral metabohsm, ketamine is relatively contraindicated for patients with increased ICP or those at risk for cerebral ischemia. The effects of ketamine on seizure activity are mixed. Emergence dehrium characterized by hallucinations is a frequent comphcation of ketamine that can result in serious patient dissatisfaction and can complicate postoperative management. Delirium is most frequent in the first hour after emergence and appear to occur less frequently in children benzodiazepines reduce the incidence of emergence delirium. 

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