Clinical practice guidelines for the management of pain, agitation, and delirium in adult patients in the intensive care unit

OBJECTIVE: To revise the "Clinical Practice Guidelines for the Sustained Use of Sedatives and Analgesics in the Critically Ill Adult" published in Critical Care Medicine in 2002. METHODS: The American College of Critical Care Medicine assembled a 20-person, multidisciplinary, multi-institutional task force with expertise in guideline development, pain, agitation and sedation, delirium management, and associated outcomes in adult critically ill patients. The task force, divided into four subcommittees, collaborated over 6 yr in person, via teleconferences, and via electronic communication. Subcommittees were responsible for developing relevant clinical questions, using the Grading of Recommendations Assessment, Development and Evaluation method (http://www.gradeworkinggroup.org) to review, evaluate, and summarize the literature, and to develop clinical statements (descriptive) and recommendations (actionable). With the help of a professional librarian and Refworks database software, they developed a Web-based electronic database of over 19,000 references extracted from eight clinical search engines, related to pain and analgesia, agitation and sedation, delirium, and related clinical outcomes in adult ICU patients. The group also used psychometric analyses to evaluate and compare pain, agitation/sedation, and delirium assessment tools. All task force members were allowed to review the literature supporting each statement and recommendation and provided feedback to the subcommittees. Group consensus was achieved for all statements and recommendations using the nominal group technique and the modified Delphi method, with anonymous voting by all task force members using E-Survey (http://www.esurvey.com). All voting was completed in December 2010. Relevant studies published after this date and prior to publication of these guidelines were referenced in the text. The quality of evidence for each statement and recommendation was ranked as high (A), moderate (B), or low/very low (C). The strength of recommendations was ranked as strong (1) or weak (2), and either in favor of (+) or against (-) an intervention. A strong recommendation (either for or against) indicated that the intervention's desirable effects either clearly outweighed its undesirable effects (risks, burdens, and costs) or it did not. For all strong recommendations, the phrase "We recommend …" is used throughout. A weak recommendation, either for or against an intervention, indicated that the trade-off between desirable and undesirable effects was less clear. For all weak recommendations, the phrase "We suggest …" is used throughout. In the absence of sufficient evidence, or when group consensus could not be achieved, no recommendation (0) was made. Consensus based on expert opinion was not used as a substitute for a lack of evidence. A consistent method for addressing potential conflict of interest was followed if task force members were coauthors of related research. The development of this guideline was independent of any industry funding. CONCLUSION: These guidelines provide a roadmap for developing integrated, evidence-based, and patient-centered protocols for preventing and treating pain, agitation, and delirium in critically ill patients.

Comparison of the enteral and intravenous lansoprazole pharmacodynamic responses in critically ill patients.

BACKGROUND: While proton pump inhibitors are frequently administered in the intensive care unit, the pharmacodynamic response of acid suppression between the enteral and intravenous (IV) route is unknown. AIM: To compare the pharmacodynamic response between enteral and IV lansoprazole in intensive care unit patients requiring stress ulcer prophylaxis therapy. METHODS: Adult mechanically ventilated patients were randomized to receive 72 h of daily enteral [lansoprazole oral disintegrating tablet (LODT) 30 mg mixed in 10 mL of water via a nasal gastric tube] or IV lansoprazole (30 mg over 30 min) therapy. Serial blood samples were collected after the first and third dose and analysed for pharmacokinetic parameters. Pharmacodynamic determination of intragastric pHmetry began prior to the first dose and continued for 72 h using a single channel pH microelectrode. RESULTS: Nineteen intensive care unit patients were randomized [LODT (n = 10); IV-L (n = 9)]. LODT bioavailability was 76%. LODT maintained gastric pH > 4 longer than IV-L at both 24 h (7.4 vs. 5.9 h; P = 0.039) and 72 h (10.4 and 8.9 h; P = 0.046) and resulted in a greater average pH over the first 24 h (3.67 vs. 2.89; P = 0.03). CONCLUSION: Despite a lower bioavailability, enteral lansoprazole suppresses acid in intensive care unit patients to a greater extent than IV lansoprazole.

An in vitro comparison of different providers to deliver four proton pump inhibitor products through a feeding tube.

BACKGROUND: It is unclear how delivery through a feeding tube compares between esomeprazole in water, lansoprazole oral disintegrating tablet in water, omeprazole/NaHCO(3) in water and simplified lansoprazole suspension. AIM: This in vitro study compared delivery through a narrow calibre (8F) feeding tube among four proton pump inhibitors when given by skilled [nurse; (n = 8)] or unskilled [lay; (n = 8)] providers. METHODS: Following standard instruction, subjects were observed delivering each proton pump inhibitor in a sequential, but random, fashion to evaluate administration quality and time. Delivery was quantified using high-performance liquid chromatography methods and subject preferences were evaluated. RESULTS: Delivery (%), similar between lansoprazole oral disintegrating tablet (95.7 +/- 3.2) and omeprazole/NaHCO(3) (96.1 +/- 3.0), was both greater for lansoprazole oral disintegrating tablet than esomeprazole in water (88.9 +/- 8.6; P = 0.006) or simplified lansoprazole suspension (86.1 +/- 9.5; P = 0.0001) and omeprazole/NaHCO(3) than esomeprazole in water (P = 0.004) or simplified lansoprazole suspension (P < 0.001), and was not affected by prior subject experience. Quality was higher with both omeprazole/NaHCO(3) and lansoprazole oral disintegrating tablet than simplified lansoprazole suspension. Administration was quicker for lansoprazole oral disintegrating tablet than esomeprazole in water. Subjects preferred lansoprazole oral disintegrating tablet and omeprazole/NaHCO(3). CONCLUSIONS: When given through an in vitro feeding tube, omeprazole/NaHCO(3) and lansoprazole oral disintegrating tablet lead to greater drug delivery, improved administration quality and higher user satisfaction, than either esomeprazole in water or simplified lansoprazole suspension.

Temporal assessment of Candida risk factors in the surgical intensive care unit.

HYPOTHESIS: Risk factors for Candida infection in surgical intensive care units (SICUs) change over time. Risk factor progression may influence Candida colonization and infection. DESIGN: Multicenter cohort survey. SETTING: Three urban teaching institutions. PATIENTS: A total of 301 consecutively admitted patients in SICUs for 5 or more days. MAIN OUTCOME MEASURES: Assessment of patients on SICU days 1, 3, 4, 6, and 8 and SICU discharge for risk factors, Candida colonization, and antifungal use. Candida colonization status was categorized as noncolonized (NC), locally colonized (LC) if 1 site was involved, and disseminated infection (DI) if 2 or more sites or candidemia were involved. RESULTS: The most frequent risk factors in the 301 patients enrolled were presence of peripheral and central intravenous catheters, bladder catheters, mechanical ventilation, and lack of enteral or intravenous nutrition. Early risk factors included total parenteral nutrition or central catheter at SICU day 1 and previous SICU admissions or surgical procedures. Peak number of risk factors (mean +/- SD) were as follows: 7.2 +/- 2.6 in NC (n = 229), 9.2 +/- 2.3 in LC (n = 45), and 9.2 +/- 2.6 in DI (n = 27). These numbers were reached at day 8 in the NC and LC groups and day 4 in the DI group. The LC and DI groups had more risk factors on each SICU day than the NC group and longer median SICU length of stay (28 days in the DI group vs 11 and 19 days in the NC and LC groups, respectively). Antifungal therapy, while used most frequently in the DI group, was initiated later for this group than in NC and LC groups. CONCLUSIONS: Risk factors for Candida infection in SICU patients change over time. Patients with DI demonstrate a greater number of and more rapid increase in risk factors than patients in the LC and NC groups. Presence of early risk factors at the time of SICU admission, a high incidence of risk factors, or a rapid increase in risk factors should prompt clinicians to obtain surveillance fungal cultures and consider empirical antifungal therapy.

Recombinant human activated protein C, drotrecogin alfa (activated): a novel therapy for severe sepsis.

Sepsis remains a major cause of death in hospitalized patients. Despite a massive research effort over the past 2 decades to identify innovative therapies for sepsis, current treatment strategies consist primarily of antiinfective agents and a variety of supportive measures. Activated protein C, an endogenous protein that inhibits thrombosis and inflammation while promoting fibrinolysis, plays an important role in the pathogenesis of sepsis. Recombinant human activated protein C, drotrecogin alfa (activated), when compared with placebo in a randomized, double-blind study of 1690 patients with severe sepsis (Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis [PROWESS] trial), decreased the relative risk of death at 28 days by 19.4% (95% confidence interval 6.6-30.5%, p=0.005), although there was a trend for more serious bleeding (3.5% vs 2.0%, p=0.06) with its use. Drotrecogin alfa is the first antisepsis drug found to have a mortality benefit. It should be administered only to patients with severe sepsis who meet the PROWESS study inclusion criteria and should be avoided when risk factors for bleeding are present. Ongoing research will help determine the cost-effectiveness of drotrecogin alfa, as well as its role in critically ill populations not studied in the PROWESS trial.

Implementation and evaluation of guidelines for use of enoxaparin as deep vein thrombosis prophylaxis after major trauma.

Although enoxaparin is more efficacious than many other deep vein thrombosis (DVT) prevention strategies after trauma, its routine use in trauma patients at low risk for venous thrombosis is unlikely to be cost-effective and may be deleterious if risk factors for bleeding are present. By way of consensus of opinion of trauma surgeons and pharmacists, enoxaparin DVT prophylaxis guidelines were developed, implemented, and evaluated. Fifty patients with major orthopedic or spinal trauma were followed throughout hospitalization. Enoxaparin use and frequency of DVT, pulmonary embolism (PE), thrombocytopenia, and enoxaparin-related major bleeding (overt bleeding associated with a hemoglobin decrease > or = 2 g/dl, need for > or = 2 units of packed red blood cells, or need for surgery) were recorded. All pharmacist interventions pertaining to enoxaparin prophylaxis were collected. Average patient age was 45.6+/-19.5 years, average Injury Severity Score was 19.0+/-11.2, and average length of hospitalization was 14.3+/-10.0 days. Most injuries were related to motor vehicles (52%) and falls (30%). Sites of injury were femur or tibia (52%), pelvis or acetabulum (32%), hip (20%), and spinal cord (12%). Two-thirds (72%) of patients received enoxaparin during part of their hospital stay (on average, for 53% of the duration of hospitalization). Sequential compression devices and vena caval filters were used in 86% and 10% of patients, respectively. Duplex-proven DVT occurred in two patients, and angiography-proven PE developed in one patient. Enoxaparin-related major bleeding and thrombocytopenia occurred in three and one patient(s), respectively. Pharmacists recommended enoxaparin initiation in nine (18%) patients and discontinuation of the agent in seven (14%) patients (one for bleeding; six for lack of indication). Most recommendations (78%) were accepted. Data from the 50 patients in this study showed fewer thrombotic complications but more bleeding than the frequencies found in controlled studies. It is unclear whether the large number of days that patients did not receive enoxaparin was due to fears of enoxaparin-related bleeding or other factors.

Sedation assessment in critically ill adults.

OBJECTIVE: To review methods for assessing sedation in critically ill adults, discuss their impact on patient outcomes, and provide recommendations for implementing these methods into clinical practice in the intensive care unit (ICU). DATA SOURCES: A computerized search of MEDLINE from 1980 through June 2000 and a manual search of abstracts presented at recent critical care meetings were performed. STUDY SELECTION AND DATA EXTRACTION: Sedation assessment tools that have been used to titrate therapy in adult, critically ill patients were identified. Special emphasis was placed on sedation assessment instruments that have been prospectively validated. Objective methods that have been used to assess sedation therapy were also identified. DATA SYNTHESIS: Twenty-three adult sedation assessment instruments were identified. Few scales have been prospectively evaluated for validity (n = 6) or reliability (n = 7). Other methods of sedation assessment were identified (e.g., bispectral index monitor); however, most of these methods have only been studied in small subsets of critically ill patients. CONCLUSIONS: Incorporation of sedation assessment into ICU clinical practice may improve patient care. These sedation assessment instruments must be further evaluated to determine their impact on quality of care and ICU length of stay.

Nimodipine-induced acute hypoxemia: case report.

OBJECTIVE AND IMPORTANCE: Nimodipine is commonly used to improve neurological outcomes after subarachnoid hemorrhage. Although nimodipine reportedly has high specificity for the cerebral vasculature, adverse systemic effects such as hypotension have been described. This case report describes a patient with traumatic subarachnoid hemorrhage who experienced two episodes of previously undescribed, life-threatening hypoxemia that was directly related to nimodipine therapy. CLINICAL PRESENTATION: The patient experienced acute hypoxemia (partial pressures of oxygen of 32.9 and 58.7 mm Hg), on two separate occasions (3 d apart), that was temporally related to single doses of nimodipine therapy for traumatic subarachnoid hemorrhage. Other disease- and medication-related causes did not explain these episodes. INTERVENTION: After the inspired oxygen concentration was increased to 100% (both episodes) and the positive end expiratory pressure was increased to 7.5 mm Hg (first episode), the arterial oxygen saturation of the patient returned to baseline levels (>99%) within 40 minutes in each instance. Nimodipine therapy was discontinued after each episode. CONCLUSION: It is hypothesized that, in the presence of concomitant adult respiratory distress syndrome, nimodipine increased ventilation/perfusion ratio mismatch, through its direct vasodilatory effects on the pulmonary artery, and possibly interfered with the reflex hypoxic pulmonary vasoconstriction necessary to maintain adequate oxygenation for this patient. Clinicians should carefully monitor the oxygenation status of patients when nimodipine therapy is initiated.

Single versus multiple doses of acetazolamide for metabolic alkalosis in critically ill medical patients: a randomized, double-blind trial.

OBJECTIVE: To compare two dosing regimens of acetazolamide for the reversal of metabolic alkalosis in mechanically ventilated patients with asthma or chronic obstructive pulmonary disease. DESIGN: A randomized, double-blind, placebo-controlled trial. SETTING: A 35-bed medical intensive care unit in a tertiary care teaching hospital. PATIENTS: Forty mechanically ventilated patients with a metabolic alkalosis (arterial pH > or = 7.48 and serum bicarbonate concentration > or = 26 mEq/L) resistant to fluid or potassium therapy (serum potassium concentration, > or = 4 mEq/L) not receiving acetazolamide or sodium bicarbonate in the previous 72 hrs. INTERVENTIONS: Stratified by previous diuretic use and randomized to receive intravenous administration of acetazolamide, one dose of 500 mg or 250 mg every 6 hrs for a total of four doses. MEASUREMENTS AND MAIN RESULTS: Serum bicarbonate and potassium concentrations were drawn every 6 hrs for 72 hrs, arterial blood gases were drawn every 12 hrs for 72 hrs, and both urine chloride and pH were drawn at hours 0, 6, 12, 18, 24, 48, and 72. By using generalized estimating equation techniques, no difference was found between the two dosing regimens at any point over the study period for serum bicarbonate, serum potassium, or urine chloride end points. Results did not differ between diuretic- and nondiuretic-treated patients. Serum bicarbonate concentrations remained significantly decreased in both treatment groups 72 hrs after administration of the first acetazolamide dose (31.8 +/- 4.9-25.3 +/- 3.8 mEq/L, p < .0001 [250 mg x 4]; 31.9 +/- 25.4-25.4 +/- 3.6 mEq/L, p < .0001 [500 mg x 1]). CONCLUSIONS: We conclude that a single 500-mg dose of acetazolamide reverses nonchloride responsive metabolic alkaloses in medical intensive care unit patients as effectively as multiple doses of 250 mg. Studies to examine the prolonged duration of action of acetazolamide observed in this study as well as the effect of acetazolamide on clinical end points, such as duration of mechanical ventilation, are warranted.

Motor Activity Assessment Scale: a valid and reliable sedation scale for use with mechanically ventilated patients in an adult surgical intensive care unit.

OBJECTIVE: To establish the validity and reliability of a new sedation scale, the Motor Activity Assessment Scale (MAAS). DESIGN: Prospective, psychometric evaluation. SETTING: Sixteen-bed surgical intensive care unit (SICU) of a 937-bed tertiary care, university-affiliated teaching hospital. PATIENTS: Twenty-five randomly selected, adult, mechanically ventilated, nonneurosurgical patients who were admitted to the SICU > or = 12 hrs after surgery and were not receiving neuromuscular blockers. INTERVENTION: Four hundred assessments (eight per patient) were completed consecutively but independently, in pairs, at standardized times (both day and night) by two nurses who were preselected for each assessment from a pool of 32 pretrained SICU nurses. MEASUREMENTS AND MAIN RESULTS: To estimate validity, paired assessments (four/patient) compared the MAAS result with the subjective assessment using a 10-cm visual analog sedation scale, the percent change in blood pressure and heart rate from the previous 4-hr baselines, and the number of recent agitation-related sequelae. To estimate reliability, paired assessments (four/patient) measured correlation between assessments of the same type (e.g., MAAS-MAAS). Generalized estimating equations, which accounted for the four repeated measures in each patient, supported MAAS validity by finding a linear trend between MAAS and the visual analog scale (p < .001), blood pressure (p < .001), heart rate (p < .001), and agitation-related sequelae (p < .001) end points. The MAAS (kappa = 0.83 [95% confidence interval, 0.72 to 0.94]) was found to be more reliable than subjective assessment using the visual analog scale (intraclass correlation coefficient = 0.32 [95% confidence interval, 0.05 to 0.55]). CONCLUSIONS: The MAAS is a valid and reliable sedation scale for use with mechanically ventilated patients in the SICU. Further studies are warranted regarding the effect of MAAS implementation in our SICU on patient outcomes, such as quality of sedation and length of mechanical ventilation, as well as the use of the MAAS in other patient populations (e.g., medical).

Impact of trauma stress ulcer prophylaxis guidelines on drug cost and frequency of major gastrointestinal bleeding.

Trauma patients are routinely prescribed stress ulcer prophylaxis despite evidence suggesting such therapy be limited to patients with identifiable risk factors for bleeding. With surgeons' consensus, we developed and implemented trauma stress ulcer prophylaxis guidelines, and measured the impact of clinical pharmacists on implementing the guidelines and the effect of the guidelines on drug cost and frequency of major gastrointestinal bleeding. Two groups of 150 consecutive patients admitted with multiple trauma were evaluated before and after guideline implementation and stratified by Injury Severity Score (ISS) to minor (ISS < 9) or moderate to severe (ISS > or = 9) trauma groups. The number of patients prescribed stress ulcer prophylaxis, length and cost of this therapy, and number of patients experiencing major gastrointestinal bleeding (decrease in consecutive hemoglobin > or = 2 g/dl in conjunction with coffee-ground emesis, hematemesis, melena, or hematochezia) were measured. All pharmacist interventions pertaining to stress prophylaxis were collected. Fewer patients were prescribed stress ulcer prophylaxis after guideline implementation (105/150, 70% vs 39/150, 26%, p<0.0001), leading to a decrease in total drug cost of $4558. Use decreased more in patients with minor (40/54, 74% vs 9/59, 15%, p<0.0001) than moderate to severe (65/96, 68% vs 30/91, 33%, p<0.0001) trauma. Neither length of therapy nor agent of choice (> 95% cimetidine) differed between groups. Fifteen (38%) of 38 postguideline prophylaxis orders were determined by the pharmacist not to meet guideline criteria. Recommendations to discontinue therapy were accepted in 9 (60%) of 15 instances. The frequency of major gastrointestinal bleeding remained unchanged between groups (1/150 vs 0/150, p=1.0). Implementation of trauma stress ulcer prophylaxis guidelines limiting therapy to patients with risk factors for bleeding led to a 80% decrease in drug cost and did not affect the frequency of major gastrointestinal bleeding.

Cost-effectiveness of enoxaparin versus low-dose heparin for prophylaxis against venous thrombosis after major trauma.

We attempted to determine health and economic outcomes from the perspective of an integrated health system of administering enoxaparin 30 mg twice/day versus heparin 5000 U twice/day for prophylaxis against venous thrombosis after major trauma. A decision-analytic model was developed from best literature evidence, institutional data, and expert opinion. We assumed that 40% of proximal deep vein thromboses (DVTs) and 5% of distal DVTs are diagnosed and confirmed with initial or repeat duplex scanning; 50% of undiagnosed proximal DVTs result in pulmonary embolism; 2% and 1% of undiagnosed proximal DVTs will lead to readmission for DVT and pulmonary embolism, respectively, and pulmonary embolism-related mortality rates range from 8-30%. Length of hospital stay data and 1996 institutional drug use and acquisition cost data were used to estimate the cost of enoxaparin and heparin therapy. Diagnosis and treatment costs for DVT and pulmonary embolism were derived from institutional charge data using cost:charge ratios. A second analysis of patients with lower extremity fractures was completed. One-way and multiway sensitivity analyses were performed. For 1000 mixed trauma patients receiving enoxaparin versus heparin, our model showed that 62.2 (95% CI -113 to -12) DVTs or pulmonary emboli would be avoided, resulting in 67.6 (8 to 130) life-years saved at a net cost increase of $104,764 (-$329,300 to $159,600). Enoxaparin versus heparin resulted in a cost of $1684 (-$3600 to $9800) for each DVT or pulmonary embolus avoided and a discounted cost/life-year saved of $2303 (-$8100 to $19,000). For 1000 patients with lower extremity fractures, enoxaparin versus heparin resulted in a cost of $751 (-$4200 to $3300) for each DVT or pulmonary embolus avoided and a discounted cost/life-year saved of $1017 (-$10,200 to $6300). Although enoxaparin increases overall health care costs, it is associated with a cost/additional life-year saved of only $2300, which is generally lower than the commonly used hurdle rate of $30,000/life-year saved. The cost-effectiveness ratio is more favorable in patients with lower extremity fractures than in the general mixed trauma population.

Stress ulcer prophylaxis in medical ICU patients: annual utilization in relation to the incidence of endoscopically proven stress ulceration.

OBJECTIVE: To measure changes in the proportion of medical intensive care unit (MICU) patients prescribed pharmacologic stress ulcer prophylaxis therapy over a 4-year period in relation to the incidence of stress-related ulceration detected by endoscopy at our institution. DESIGN: Retrospective 4-year review of pharmacy and endoscopy databases. SETTING: A 35-bed MICU. PATIENTS: Patients (n = 2941) admitted to the MICU for longer than 24 hours, between January 1, 1993, and December 31, 1996, without acute gastrointestinal hemorrhage on admission. METHODS: Records were reviewed to identify patients prescribed pharmacologic stress ulcer prophylaxis (> 24 h of sucralfate or a histamine2-receptor antagonist [H2RA]), and patients with evidence of stress ulceration during endoscopy. RESULTS: The number of patients per year receiving stress ulcer prophylaxis significantly (p < 0.001) decreased between 1993 and 1996: 1993, 492/693 (71%); 1994, 478/798 (60%); 1995, 295/670 (44%); 1996, 164/780 (21%). There was no difference between years in the median duration of stress ulcer prophylaxis therapy or the proportion of patients receiving sucralfate versus H2RA therapy. There was no difference (p = 0.91) between years in the annual incidence of definite or possible stress-related ulceration: 1993, 6/693 (0.87%); 1994, 5/798 (0.63%); 1995, 6/670 (0.90%); 1996, 5/780 (0.64%). CONCLUSIONS: The incidence of endoscopically proven stress-related ulceration has remained unchanged over the past 4 years in our MICU despite significantly fewer patients receiving pharmacologic stress ulcer prophylaxis therapy.

The effect of ICU sedation guidelines and pharmacist interventions on clinical outcomes and drug cost.

OBJECTIVE: To measure the effect of evidence-based intensive care unit (ICU) sedation guidelines and interventions by a pharmacist to promote these guidelines on the weaning time from mechanical ventilation and sedation drug cost. DESIGN: Before-after study. SETTING: A 15-bed medical-surgical ICU at a tertiary-care teaching hospital. PATIENTS: 100 patients (2 groups of 50 consecutive patients) on mechanical ventilation (assist or pressure control mode for > or = 6 h) who were successfully discharged from the ICU. METHODS: ICU sedation guidelines were developed through physician, nursing, and pharmacy consensus using a physician survey and literature overview as points of reference and were implemented into practice. Prospectively, data on the time required to wean patients from mechanical ventilation (successful trial of T-piece, pressure support, or intermittent mandatory ventilation leading to extubation) and total drug costs for sedation were measured and compared between groups. All prospective ICU pharmacist interventions pertaining to sedation were documented. RESULTS: New sedation guidelines promoted lorazepam use in preference to midazolam and suggested propofol for patients not successfully sedated with high-dose lorazepam, haloperidol, or morphine. Over the 2-month collection periods, there was no difference in the median weaning time between the pre- (16 h, range 2-607) and post- (18 h, range 1-284) guideline groups. Total sedation drug costs decreased from $4515 to $1152 ($US) (p = 0.081). Median sedation drug costs decreased from $11.27 (range $0-1340) to $3.55 (range $0-250), with the amount (mg) of midazolam and propofol used decreasing by 86% and 100%, respectively. The ICU pharmacist successfully recommended a change from midazolam to lorazepam in 12 of 50 patients, 5 of whom had received midazolam for more than 24 hours. CONCLUSIONS: High compliance with ICU sedation guidelines promoting lorazepam rather than midazolam or propofol in mechanically ventilated patients led to a 75% decrease in sedation drug costs and did not adversely affect the clinicians' ability to wean patients from mechanical ventilation.

Observations and effects of educational consults on allopurinol prescribing.

Allopurinol has been used in the management of hyperuricemic states for several years. Despite its efficacy for these indications, recent concerns have been raised regarding the unnecessary morbidity and mortality occasionally associated with its inappropriate use. In an effort to assess the utilization of allopurinol, a concurrent drug utilization review was undertaken. Fifty patients who were prescribed allopurinol were entered into the study and underwent health record review and patient interview, to determine appropriateness of therapy and the need for educational intervention. A number of inconsistencies with regard to established guidelines were identified. As well, 11 of 50 patients (22%) required intervention because of either lack of indication or excessive dose. Fifty-five percent of the educational interventions, performed by the pharmacist, were accepted as written. The current utilization of allopurinol at our facility differs substantially from guidelines developed for optimal utilization of allopurinol. Further, a pharmacy based intervention program can improve prescribing practices of allopurinol.