Purpose This article presents a summary of recent advances, including tools and interventions, that are designed to improve drug safety for patients in critical care settings, particularly those undergoing anesthesia and surgery. Principal findings Medication error remains a leading cause of adverse events among patients undergoing anesthesia. Misidentification of ampoules, vials, and syringes is a common source of error. Systems are now being engineered to reduce the likelihood of medication misidentification through approaches such as revision of standards for labelling of drug ampoules and vials and the development of bar code systems that allow ''double checking'' or drug verification in the operating room. Also, efforts are being made to improve medication reconciliation, a process for accurately communicating a patient's medication information during transitions from one healthcare setting to another. Finally, the opportunity exists for anesthesiologists to increase awareness about the rising problem of opioid addiction in patients for whom typical doses are initially prescribed for appropriate indications such as postoperative pain. Conclusions There is a need to improve drug delivery systems in complex critical care environments, particularly the operating room. Anesthesiologists must continue to play a leading role in promoting drug safety in these environments.

In five of six epileptic children who were taking 18 to 49 mg/kg/day valproic acid (VPA), the steady-state serum free fractions of VPA rose from 12% to 43% when antipyretic doses of aspirin were also taken. Mean total VPA half-life (t1/2) rose from 10.4 +/- 2.7 to 12.9 +/- 1.8 hr and mean free VPA t1/2 rose from 6.7 +/- to 2.1 to 8.9 +2- 3.0 hr when salicylate was present in the serum. The in vitro albumin binding association constant (ka) for VPA was decreased by salicylate, but the in vivo ka value was not affected. The 12-hr (trough) concentrations of both free and total VPA were higher in the presence of serum salicylate in five of six patients. Renal excretion of unchanged VPA decreased in five of six patients, but the VPA carboxyl conjugate metabolite-excretion patterns were not consistently affected. Salicylate appeared to displace VPA from serum albumin in vivo, but the increased VPA t1/2 and changes in VPA elimination patterns suggest that serum salicylate also altered VPA metabolism.

Cimetidine is an inhibitor of drug metabolism. We studied the effects of cimetidine (1,200 mg/d) on steady-state serum concentrations of carbamazepine and phenytoin in 11 epileptic volunteers. The mean serum carbamazepine concentration was unchanged after 7 days of cimetidine treatment. Five subjects were taking phenytoin concurrently; their mean serum phenytoin concentration was significantly increased after 7 and 10 days of cimetidine treatment and returned to baseline 2 weeks after cimetidine was discontinued. Cimetidine apparently inhibits the clearance of phenytoin but not of carbamazepine in adults on chronic therapy.

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