Anesthesia for trauma.

Results of investigations with vertebrates have implicated neuroactive steroids and in particular 5alpha-reduced metabolites of progesterone such as 3alpha-hydroxy-5alpha-pregnan-20-one (3alpha,5alpha-THP/3A5P and originally allopregnanolone) in the rapid modulation of diverse functions including that of nociceptive sensitivity. These effects have been indicated to involve modulation of GABA receptors. Results of recent phylogenetic studies have revealed the presence of GABA receptors in invertebrates that may also be subject to modulation by steroids and neuroactive steroids. The present study examined the effects of the neuroactive steroid, 3alpha-hydroxy-5alpha-pregnan-20-one, as well as progesterone on aversive thermal (nociceptive) responses in a mollusc, the land snail, Cepaea nemoralis. 3alpha-Hydroxy-5alpha-pregnan-20-one had significant dose-related (0.01-1.0 microg) antinociceptive effects in Cepaea increasing the latency of response to a 40 degrees C surface, with maximum effects being evident 15-30 min after administration. These effects of 3alpha-hydroxy-5alpha-pregnan-20-one were stereospecific, with the stereoisomer 3beta-hydroxy-5alpha-pregnan-20-one (3B5P) failing to affect nociceptive responses. Progesterone also had significant dose-related (0.10-10 microg) antinociceptive effects that, however, were delayed in onset and relatively prolonged (60-120 min), suggestive of the formation of active metabolites. The presence of endogenous progesterone (12.36+/-0.17 ng/g tissue) was ascertained by a radioimmunoassay further supporting a functional role for steroids in Cepaea. The antinociceptive effects of 3alpha-hydroxy-5alpha-pregnan-20-one and progesterone were blocked by the GABA antagonists, bicuculline and picrotoxin, while being relatively insensitive to opioid and N-methyl-D-aspartate antagonists. These results suggest an early evolutionary development and phylogenetic continuity of neuroactive steroid and GABA involvement in the mediation of nociception.

Anesthetics↗

PubMed2000

[Auditing of drug use practices in anesthesia].

OBJECTIVES: Internal pharmaceutical practice guidelines were produced in a department of anaesthesia of a University hospital in 1995, after a preliminary evaluation showing controversial and expensive practices. After approval, these recommendations were circulated to all members of the department. Phase I of this study was started 18 months later, to evaluate the compliance of anaesthetists with these guidelines. STUDY DESIGN: Prospective survey. METHOD: An audit was performed by a research assistant pharmacist, previously trained, who compared anaesthetic agents and fresh gas flows used during anaesthetics with those recommended in the internal guidelines. RESULTS: Implementation of guidelines was observed in more than 90% of cases for all agents studied, except for non-depolarizing neuromuscular relaxants. Relaxants of intermediate duration were used in 52% of cases with an expected surgery duration of more than 90 min, in opposition to the guidelines stating that pancuronium should have been administered in such circumstances. These results were presented and discussed. Slight changes in the guidelines (especially concerning monitoring of neuromuscular blockade) were made and evaluated again, using the same method (Phase II). A small but significant improvement was seen with induction agents (use of propofol in non-approved situations: 5 versus 0%, P = 0.03), while a non significant trend toward better implementation of guidelines was seen with non-depolarizing agents (use of pancuronium in surgery of expected duration > 90 min: phase I vs phase II = 47 vs 52%, NS; use of pancuronium in surgery of expected duration < 90 min: phase I vs phase II = 3.5 vs 0%, NS). CONCLUSION: This study suggests that implementation of internal guidelines is easy when clinical indications of the agents are not controversial.

Anesthetics↗