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CONTEXT: Pharmacist review of medication orders in the intensive care unit (ICU) has been shown to prevent errors, and pharmacist consultation has reduced drug costs. However, whether pharmacist participation in the ICU at the time of drug prescribing reduces adverse events has not been studied. OBJECTIVE: To measure the effect of pharmacist participation on medical rounds in the ICU on the rate of preventable adverse drug events (ADEs) caused by ordering errors. DESIGN: Before-after comparison between phase 1 (baseline) and phase 2 (after intervention implemented) and phase 2 comparison with a control unit that did not receive the intervention. SETTING: A medical ICU (study unit) and a coronary care unit (control unit) in a large urban teaching hospital. PATIENTS: Seventy-five patients randomly selected from each of 3 groups: all admissions to the study unit from February 1, 1993, through July 31, 1993 (baseline) and all admissions to the study unit (postintervention) and control unit from October 1, 1994, through July 7, 1995. In addition, 50 patients were selected at random from the control unit during the baseline period. INTERVENTION: A senior pharmacist made rounds with the ICU team and remained in the ICU for consultation in the morning, and was available on call throughout the day. MAIN OUTCOME MEASURES: Preventable ADEs due to ordering (prescribing) errors and the number, type, and acceptance of interventions made by the pharmacist. Preventable ADEs were identified by review of medical records of the randomly selected patients during both preintervention and postintervention phases. Pharmacists recorded all recommendations, which were then analyzed by type and acceptance. RESULTS: The rate of preventable ordering ADEs decreased by 66% from 10.4 per 1000 patient-days (95% confidence interval [CI], 7-14) before the intervention to 3.5 (95% CI, 1-5; P<.001) after the intervention. In the control unit, the rate was essentially unchanged during the same time periods: 10.9 (95% CI, 6-16) and 12.4 (95% CI, 8-17) per 1000 patient-days. The pharmacist made 366 recommendations related to drug ordering, of which 362 (99%) were accepted by physicians. CONCLUSIONS: The presence of a pharmacist on rounds as a full member of the patient care team in a medical ICU was associated with a substantially lower rate of ADEs caused by prescribing errors. Nearly all the changes were readily accepted by physicians.

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OBJECTIVE: To identify and evaluate the systems failures that underlie errors causing adverse drug events (ADEs) and potential ADEs. DESIGN: Systems analysis of events from a prospective cohort study. PARTICIPANTS: All admissions to 11 medical and surgical units in two tertiary care hospitals over a 6-month period. MAIN OUTCOME MEASURES: Errors, proximal causes, and systems failures. METHODS: Errors were detected by interviews of those involved. Errors were classified according to proximal cause and underlying systems failure by multidisciplinary teams of physicians, nurses, pharmacists, and systems analysts. RESULTS: During this period, 334 errors were detected as the causes of 264 preventable ADEs and potential ADEs. Sixteen major systems failures were identified as the underlying causes of the errors. The most common systems failure was in the dissemination of drug knowledge, particularly to physicians, accounting for 29% of the 334 errors. Inadequate availability of patient information, such as the results of laboratory tests, was associated with 18% of errors. Seven systems failures accounted for 78% of the errors; all could be improved by better information systems. CONCLUSIONS: Hospital personnel willingly participated in the detection and investigation of drug use errors and were able to identify underlying systems failures. The most common defects were in systems to disseminate knowledge about drugs and to make drug and patient information readily accessible at the time it is needed. Systems changes to improve dissemination and display of drug and patient data should make errors in the use of drugs less likely.

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The acceptance of new and increasingly expensive technologies is a major component of the rising costs of health care. While the practice of anesthesia has been relatively immune from the effects of cost containment, it is inevitable that practitioners will have to justify costly practices. Available pharmacoeconomic methods can be applied to the use of all anesthetic drugs, particularly neuromuscular blocking drugs. Cost-effectiveness analysis allows the practicing anesthesiologist to prioritize the use of neuromuscular blocking drugs to maximize their benefit while reducing unnecessary costs.

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The feasibility of implementing a multiple-dose, multiple-flow-rate syringe pump system in a large teaching institution and a community hospital is described. The new syringe pump system was evaluated on medical and surgical wards in each hospital for a period of time sufficient to evaluate 40 courses of therapy in each hospital. At the time the new syringe pump system was implemented, the teaching hospital was using a gravity-dependent bottle and burette system and the community hospital was using a single-dose syringe pump system. At the end of the study period, the material costs of the existing i.v. infusion systems were compared with the material costs of the new syringe pump system, and the nurses involved in the study were questioned about their attitudes toward the new system. Use of the multiple-dose syringe pump system resulted in a savings of $934.81 in material costs compared with the bottle and burette system and $9.70 in material costs compared with the single-dose syringe pump system (based on 40 doses). When the cost of wasted drug was considered, the cost per day of the multiple-dose syringe pump system was substantially less (70%) than the cost per day of the bottle and burette system and approximately the same as the cost per day for the single-dose syringe pump system. The majority of nurses indicated that the new system was easier or no more difficult to use than the existing i.v. infusion system and were in favor of switching to the new system. Implementation of a multiple-dose, multiple-flow-rate syringe pump system may result in cost savings over a traditional bottle and burette system and could complement an existing single-dose syringe infusion system.

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5-Aminosalicylic acid (5-ASA), the presumed active moiety of sulfasalazine, has shown clinical efficacy when administered per rectum as initial therapy to patients with distal ulcerative colitis. We report the results of a randomized double-blind trial comparing nightly retention of a 4-g 5-ASA enema with continued administration of hydrocortisone enemas in 18 patients with persistent active distal ulcerative colitis after at least a 3-wk course of treatment with 100-mg hydrocortisone enemas with or without oral sulfasalazine. Continuation of hydrocortisone enemas rather than placebo was used in the control group to reflect the realistic alternative therapy likely to be employed in current practice. Response to therapy was assessed after 3 wk by comparing pretreatment and posttreatment point scores of clinical, sigmoidoscopic, and histological severity. Improvement in clinical score was achieved in seven of nine 5-ASA enema-treated patients versus one of nine hydrocortisone enema-treated patients (p less than 0.05). Sigmoidoscopic and histological improvement generally paralleled clinical improvement. We conclude that in patients with distal ulcerative colitis unresponsive to standard therapy, treatment with 5-ASA enemas results in significant short-term clinical and sigmoidoscopic improvement in a majority of cases. Moreover, a significantly greater number of refractory patients improve when switched to 5-ASA enemas than when continued on standard therapy.

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This article provides a detailed overview of the concept of intravenous drug delivery. Recognizing the limitations inherent in a gravity-controlled system and the new advantages achieved in the technology of microinfusion, defined here as the (controlled) delivery of small volumes of concentrated solutions of drugs, we have described the concepts and advantages associated with a microinfusion system. The clinical advantages to such a system are far reaching and include lower incidences of bacterial contamination, phlebitis, embolization, and fluid overload as well as more accurate delivery of drug. Since financial advantages are a prerequisite for any new system in this era of fiscal restraint, the financial considerations associated with the use of a microinfusion system are also delineated. These advantages, which range from decreases in supply costs to decreases in the overall cost of patient care, support the argument for increased utilization of microinfusion systems. Overall, it is our contention that microinfusion offers a more rational approach to the delivery of drugs in many patient populations, and expanded implementation of this challenging concept should be further explored.

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The variability of protein binding of phenytoin in epileptic patients was evaluated using a rapid ultrafiltration system. Thirty-one pairs of total and free (unbound) phenytoin plasma concentrations were reviewed. Filtered plasma for free phenytoin determination was obtained using an ultrafiltration membrane system. All samples were analyzed by an enzyme-multiplied immunoassay technique. A good correlation was obtained for total phenytoin concentration v free phenytoin concentration. Comparison of obtained and predicted free phenytoin values differed significantly. Of nine patients demonstrating toxic effects, six had total phenytoin concentrations within the accepted therapeutic range with free concentrations above the therapeutic range. The results of this study indicate a wide variation of phenytoin protein binding in chronic epileptic patients, implying that total phenytoin concentration must be interpreted cautiously, and use of free phenytoin concentration appears to be a more appropriate guide to therapy. The availability of a rapid method of ultrafiltration makes free phenytoin plasma levels readily available to the clinician.

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Amphotericin B, a systemic antifungal agent, has not been associated with clinical evidence of cardiac toxicity. We report the case of a 76-year-old patient who developed transient asystole with cardiovascular collapse on two occasions, which coincided with infusion of amphotericin B. The patient was semicomatose and had candida septicemia and renal failure. Serum potassium and digoxin levels were elevated, and serum calcium was low when these episodes occurred. Subsequent postmortem examination revealed no gross evidence of cardiac disease apart from fungal vegetations on the aortic valve. A clear causal relationship between amphotericin B and transient asystole is not demonstrated, but a temporal association, confirmed with rechallenge, is documented in this patient. No similar cases were found in a review of the literature.

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The degree of protein binding of carbamazepine was evaluated in 45 mentally retarded epileptic patients. Although the mean percent unbound carbamazepine agreed with that obtained elsewhere, a wide interpatient variability was noted. There was a good correlation between unbound carbamazepine and total carbamazepine serum concentrations. The results of this study indicate that the total carbamazepine serum concentration must be interpreted with caution, and the unbound fraction may be a more appropriate therapeutic measure.

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