Delayed epidural catheter removal: the impact of postoperative coagulopathy.

A retrospective analysis of 413 patients who received postoperative epidural analgesia under a standardized protocol found that 84 (20%) had a duration of epidural catheterization of greater than four days. The most common reasons were significant pain (n=64, 15%) and coagulopathy (n=26, 6%). Risk factor analysis for coagulopathy showed an odds ratio of 10.1 (95% confidence interval 4.2-24.5) for prolonged epidural catheterization among patients undergoing hepatectomy. Magnetic resonance imaging, performed in four patients with clinical signs suggestive of epidural haematoma, was negative for a space-occupying lesion in all cases. Eleven patients developed fever and clinical signs suggestive of epidural catheter-related infection, necessitating early catheter removal. Sixteen patients had persistent lower limb weakness at 24 hours after catheter removal. The signs soon resolved in all except two, one of whom had neuropathy related to intraoperative positioning and the other preoperative weakness. Accidental epidural catheter dislodgement occurred in 29 patients (7%) and is potentially hazardous if coagulopathy is unresolved. The risk-benefit ratio and factors complicating catheter removal, especially coagulopathy, should be considered when deciding whether to use epidural techniques.

Miltirone, a central benzodiazepine receptor partial agonist from a Chinese medicinal herb Salvia miltiorrhiza.

Ten diterpene quinones, which inhibited the binding of [3H]flunitrazepam to central benzodiazepine receptors with IC50s ranging from 0.3 to 36.2 microM, were isolated from the ethereal extract of the roots of Salvia miltiorrhiza. Among these natural products, miltirone has the highest potency (IC50 = 0.3 microM). It was orally active in an animal model used to predict clinical tranquilizing effects. Unlike diazepam, miltirone behaved as a partial agonist in the central benzodiazepine receptor binding and behavioural tests. Moreover, it produced no acute muscle relaxant effect and did not induce drug dependence and withdrawal reactions after chronic administration in mice.

Structure-activity relationship of miltirone, an active central benzodiazepine receptor ligand isolated from Salvia miltiorrhiza Bunge (Danshen).

Twenty one o-quinonoid-type compounds and one coumarin-type compound related to miltirone (1) have been synthesized with the aim to identify the key structural elements involved in miltirone's interaction with the central benzodiazepine receptor. On the basis of their inhibition of [3H]flunitrazepam binding to bovine cerebral cortex membranes, it is apparent that ring A of miltirone is essential for affinity. Although increasing the size of ring A from six-membered to seven- and eight-membered is well-tolerated, the introduction of polar hydroxyl groups greatly reduces binding affinity. The presence of 1,1-dimethyl groups on ring A is, however, not essential. On the other hand, the isopropyl group on ring C appears to be critical for binding as its removal decreases affinity by more than 30-fold. It can, however, be replaced with a methyl group with minimal reduction in affinity. Finally, linking ring A and B with a -CH2CH2- bridge results in analogue 89, which is 6 times more potent than miltirone at the central benzodiazepine receptor (IC50 = 0.05 microM).