Rectal administration of drugs. Fundamentals and applications in anesthesia]

Rectal administration of drugs has become a standard procedure in clinical anesthesia, most notably for anorectal induction in children. Limitations of this method include low bioavailability, a wide scatter of pharmacokinetic and pharmacological results, and poor predictability of the clinical effect in any particular patient. Historically, the rectal route has been used for the administration of smoke ("fumigation") for resuscitation and various other purposes. An ether boiler for rectal application was developed by Pirogoff as early as 1847. The pharmacokinetics of rectally administered drugs are determined by the anatomical properties of the rectum and, owing to interindividual variance, this adds to the inconsistency of absorption. Aspects that can be better controlled include the drug preparation and the vehicle, with hydrophilic solutions resulting in improved absorption. Larger volumes such as are associated with lower concentrations increase the bioavailability by enlarging the mucosal surface in contact with the drug. In contrast to the hypothetical assumption that hepatic circulation may be circumvented--thus avoiding first-pass metabolism--by direct venous drainage from the rectum into the systemic circulation via the vena cava, it has been shown that hepatic clearance is the main factor affecting bioavailability. This may be due to blood flow through anastomoses interconnecting the superior, medium and inferior rectal venous systems. Resorption from the rectum is also determined by physicochemical properties of drugs. According to the pH-partition hypothesis, only the non-ionized moiety of a compound will be available for transmucosal diffusion. The degree of ionization is a function of the local (or microclimate) milieu pH and pKa of the drug; the former is close to neutral in adults but alkaline in most children. Adsorption of feces, intraluminal degradation by microorganisms, metabolism within the mucosal cell, and lymphatic drainage do not significantly affect the fate of rectally administered drugs. In clinical practice, the rectal administration of methohexital and midazolam is an established method of premedication or induction of anesthesia in children; so far, midazolam appears to be associated with fewer complications. Ketamine has been shown to be as effective and as quick-acting as methohexital, but at least in one study its use as sole induction agent was associated with respiratory distress in some cases. However, painful diagnostic or therapeutic procedures in children may be indications for the rectal administration of ketamine. Early trials with rectally administered etomidate have been abandoned since its implication in suppression of cortisol synthesis. Narcotic analgesics in a hydrogel vehicle are effective in adult pain management.(ABSTRACT TRUNCATED AT 400 WORDS)