The use of pharmaceutical care practices that ensure

Transcription

1 reports from the field efficiency Cost-Effective Medication Use in Critical Care: Capital Health System s Experience in VHA s MUSIC Program Liza Barbarello-Andrews, PharmD, BCPS, Greg Susla, PharmD, Vivien Ng, RPh, CCP, Douglas St. John, PharmD, RPh, and Chester Lau, MS, RPh Abstract Objective: To describe a team-based approach to optimizing medication use in the critical care setting. Methods: Ten hospitals participated in a collaborative program developed and supported by VHA, Inc. and VHA East Coast called Medication Usage Strategies in Critical Care (MUSIC). Hospital MUSIC teams worked to identify therapeutic target areas for improvement, assess usage patterns of target agents, develop strategies to influence prescribing habits, evaluate outcomes, and implement plans to sustain success. Capital Health System (Trenton, NJ) focused on agents used in stress ulcer prophylaxis, continuous sedation, anemia of critical illness, and hypoalbuminemia of critical illness. They implemented a variety of methods, including educational communication forms, pharmacist-physician discussions, and policy revisions, to influence prescribing practices. A VHA Web-based platform allowed teams to share strategies and knowledge during the program. Results: Policy changes and educational tools initiated by the MUSIC program positively influenced prescribing habits, resulting in refinement of use of the target agents. Dollar savings were realized through reduced inappropriate use of select targeted agents and reduced rates of ventilator-associated pneumonia and hospital length of stay that were attributed to changes in the sedation protocol. Conclusion: Pharmacist involvement and implementation of efficient and evidence-based medication use policies in critical care units can improve outcomes and reduce costs. The use of pharmaceutical care practices that ensure the best possible outcomes at the lowest cost is an important goal of the health care system. Hospitals have a mandate to improve their overall medication management systems. Best practices are expected to be associated with improvements in patient outcomes and increased efficiency and cost-effectiveness of medical care. VHA, Inc. is a health care provider alliance of more than 2400 not-for-profit, community-based health care organizations whose mission is to improve members clinical and economic performance. In 2004, VHA introduced a collaborative program developed and supported jointly by VHA, Inc. and VHA East Coast regional office that focused on optimizing medication use in the critical care setting. Termed the Medication Usage Strategies in Critical Care (MUSIC) program, it involved 10 VHA member hospitals that targeted a number of different therapeutic areas. The goals of the MUSIC program were to improve current practice while enabling pharmacy departments of member hospitals to deliver intensive care pharmacy services according to the standard of care set forth by the American College of Critical Care Medicine and to provide cost-effective care based on guidelines developed by the American Thoracic Society. With the support of VHA faculty, each participating hospital developed institution-specific, evidence-based approaches. Capital Health System, in Trenton, New Jersey, participated in the collaborative and achieved the greatest degree of change during the program. In this paper, we describe the program, with a focus on Capital Health s approach in changing their pharmaceutical care culture. Program Overview Ten VHA member hospitals in New Jersey and Pennsylvania volunteered to participate in the MUSIC program after a presentation at VHA East Coast's regional Pharmacy Council meeting, attended by the directors of pharmacy at member hospitals. Each participating institution established a multidisciplinary team that included pharmacists, nurses, physicians, and professionals in quality resource management. From the Department of Pharmacy Practice and Administration, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ (Dr. Barbarello-Andrews); VHA, Inc., Irving, TX (Dr. Susla); VHA East Coast, Trevose, PA (Ms. Ng); and Capital Health System, Trenton, NJ (Dr. St. John and Mr. Lau). Vol. 13, No. 11 November 2006 JCOM 615

2 medication use in critical care Table 1. Agents Evaluated by MUSIC Teams Antimicrobials (broad-spectrum and antifungal medications) Anticoagulants (enoxaparin, heparin) Agents used for stress ulcer prophylaxis (famotidine, lansoprazole, pantoprazole, sucralfate) Continuous sedatives (lorazepam, midazolam, propofol) Albumin 5% and albumin 25% Drotrecogin alfa Erythropoietin Nesiritide During the 12-month collaborative period, January through December 2005, each team worked to identify therapeutic target areas for improvement in critical care, assess usage patterns of target agents, develop strategies to influence prescribing habits, evaluate outcomes of their strategies, and implement plans to sustain successes. In the first stage of the collaborative, facilities collected data on their drug usage patterns in an effort to identify the areas in which interventions would be most effective. Data collected included number of doses used in the critical care areas for various agents (Table 1). In addition, the total dollar expenditure for these agents was calculated. Next, MUSIC teams convened for a 1-day workshop to review and discuss comparative data. The teams focused on identifying drug class projects at their facilities that would reduce cost and maintain quality. Presentations on evidencebased use of the agents in question as well as recommendations on appropriate and efficient use were made by VHA. The meeting also included instruction on methods to implement work plan strategies and influence prescribing at their institutions, lectures from nationally known clinical experts, and peer learning and networking opportunities. Each team identified targets and developed strategies for instituting change. Two onsite visits to each MUSIC site were made by VHA faculty during the collaborative, at Month 2 and Month 7. The first visit supported team building as well as development of target areas and implementation strategies. At the second visit, faculty assessed implementation and progress and offered recommendations for further development. Teams reported their progress to the VHA program director on a regular basis via teleconference. VHA s Web-based Share and Learn platform allowed participating teams to share their strategies for implementing change, problem solving, enhancing buy-in, and solidifying improvement. The Share and Learn Web site is a dynamic, online member-to-member exchange site that enables users to share ideas and knowledge with colleagues facing similar challenges. Information available to each facility included used-in-practice tools, techniques, and templates from each organization s improvement experience. Downloadable presentations, guidelines, patient education materials, protocols, and policies that peer health care organizations have already tried and tested were also available to each facility via Share and Learn. Capital Health System Capital Health System is an inner-city, 2-hospital system. The Fuld campus is a Level 2 trauma center containing newly renovated, state-of-the-art critical care units (CCUs), including a 9-bed CCU composed of mixed medical and cardiac beds and a 9-bed mixed medical-surgical intensive care unit (ICU). The Mercer campus has an 8-bed CCU with a cardiac focus and an 8-bed ICU with a mixed medicalsurgical patient population. Intensive care focused pharmacy services on the Fuld campus include a decentralized pharmacy satellite during weekdays and an academic-based clinical pharmacist dedicated to critical care. Through these services, pharmacists participate in medical rounds; partner with nurses, respiratory therapists, and other professionals providing patient care; teach pharmacy and nursing students; and provide overall cognitive services. The Mercer campus employs a hospital-based clinical pharmacist who provides support to all areas of the hospital including critical care areas. Therapeutic areas targeted by the Capital teams (Fuld campus [Team 1] and Mercer campus [Team 2]) were agents used in stress ulcer prophylaxis, continuous sedation, anemia of critical illness, and hypoalbuminemia of critical illness (Table 2). Rationale for Target Selections Use of Propofol as First-line Agent for Continuous Sedation Oversedation has been associated with unnecessary prolongation of intubation [1 3], which places the patient at risk for secondary complications such as ventilator-associated pneumonia (VAP). This is particularly problematic with benzodiazepines such as midazolam due to their lipophilicity, accumulation of active metabolites in prolonged or high-dose use, and variable kinetic parameters [4,5]. Propofol became popular for sedation of mechanically ventilated patients in the early 1990s. Multiple comparative studies have shown that the time to weaning and extubation is significantly shorter with propofol and that it may be more cost-effective compared with midazolam [6 9]. Kress et al demonstrated that interrupting sedation daily until patients awaken provides a means to ensure the use of the minimum effective amount of medication, which correlates to a reduction in ventilator use by 2.4 days and a reduction of length of stay by 3.5 days [1]. Since daily wake-ups are a standard 616 JCOM November 2006 Vol. 13, No. 11

3 reports from the field efficiency Table 2. Key Targets for Capital Health System Agent Rationale Strategy/Tools Results* Albumin 25% Erythropoietin Pantoprazole Propofol Lack of efficacy and potential mortality increase for anemia of critical illness Anemia does not always relate to a deficiency in erythropoietin. It can take several weeks to see a clinical response to erythropoietin PPIs provide no clinical advantage in regard to efficacy or safety for SUP but are more costly Characteristics (quick onset, short duration) facilitate the daily wake-up process, which has been demonstrated to reduce LOS and complications such as VAP Communication form (Figure 2) Patient-specific physician discussions Communication form (Figure 1) Revision of the continuous sedation policy, establishing a protocol for propofol as the first-line agent Team 1: 50 vials vs. 10 vials Team 2: 6 vials vs. 0 vials Team 1: 83% use reduction Team 2: 75% use reduction Team 1: 43% (IV) and 40% (oral) reduction in pantoprazole; 586% increase in famotidine IV Team 2: 25% (IV) and 18% (oral) reduction in pantoprazole; 172% increase in famotidine IV Increased drug acquisition cost offset by savings associated with LOS and VAP reductions LOS = length of stay; PPIs = proton pump inhibitors; SUP = stress ulcer prophylaxis; VAP = ventilator-associated pneumonia. *Baseline compared with last month of data collection. of practice, many clinicians have theorized based upon the pharmacologic properties of the available agents that propofol would best meet this goal due to it characteristic quick on, quick off properties. Carson et al demonstrated this point in a trial comparing intermittent lorazepam and propofol in mechanically ventilated medical ICU patients that revealed fewer ventilator days (8.4 vs. 5.8 days; p = 0.04) associated with propofol [10]. Although there is a significant difference in acquisition costs for propofol as compared with lorazepam or midazolam, the expected reduction in secondary complications with propofol due to fewer ventilator days should lead to savings that offset the higher acquisition cost. Preferential Use of Famotidine Over Pantoprazole for Stress Ulcer Prophylaxis Stress ulcer prophylaxis is required for multiple critically ill patient populations, including patients receiving mechanical ventilation for more than 48 hours, septic patients with coagulopathies not induced by therapeutic anticoagulation regimens, and patients with multiple traumas [11,12] (Table 1). Multiple trials have evaluated available agents that elevate the gastric ph to greater than 4 for this indication. Sucralfate is less effective than H 2 -receptor antagonists (H 2 RAs) such as famotidine and ranitidine. Several studies have shown that H 2 RAs significantly lower the rate of clinically important gastrointestinal bleeding compared with antacids and sucralfate [13,14], supporting the clinical efficacy of H 2 RAs for stress ulcer prophylaxis [15,16]. While several studies have compared the efficacy of histamine antagonists with proton pump inhibitors (PPIs) [17 20], no data have demonstrated a clinical advantage of one over the other. The majority of studies evaluating the effectiveness of PPIs for preventing stress gastritis were open-label, noncomparative, nonrandomized trials with small sample sizes and varying numbers of risk factors [13,14,19,21 26]. The fact that researchers monitored gastric ph after oral administration of a solution of the agents (which for PPIs includes sodium bicarbonate) limits the interpretation of these trials [19,20]. One study attempted to assess the cost-effectiveness of oral PPIs compared with H 2 RAs for stress ulcer prophylaxis, but no definitive conclusions could be drawn [27]. The only available clinical guidelines on stress ulcer prophylaxis recommend H 2 RAs as the preferred agent in appropriate candidates [11]. Appropriate Indications and Concentrations for Albumin Administration Many critically ill patients develop hypoalbuminemia with significant decreases in albumin levels over 3 to 5 days; this reduction is multifactorial and is due in part to decreased albumin synthesis as a response to stress, vascular leakage in septic patients, redistribution, and catabolic processes [28]. Studies have correlated these decreases to mortality, and large study by Reinhardt et al found a 30-day mortality rate of 62% for those with albumin levels less than 2 g/dl [29]. Despite this, research has not demonstrated the efficacy of exogenous albumin administration for curbing this mortality incurrence; in fact, exogenous albumin administration might actually increase mortality, as shown in some metaanalyses [28,30 33]. Vol. 13, No. 11 November 2006 JCOM 617

4 medication use in critical care Appropriate Use of Erythropoietin Anemia of critical illness develops in part due to decreases in endogenous erythropoietin production [34,35] and can result from iatrogenic blood loss as well. While some patients may benefit from exogenous erythropoietin administration, health care providers must consider the onset of action of this agent in concert with the expected duration of stay in the critical care area. While some studies showed no difference in hemoglobin levels when comparing patients who received erythropoietin to those who did not [36], other studies have demonstrated some benefit when administering erythropoietin to certain subsets of patients [37]. Therefore, not all patients with anemia of critical illness should have erythropoietin administered. Implementation The Capital teams implemented a variety of methods, including educational communication forms, storyboards, patientspecific physician-pharmacist discussions, and policy revisions, to influence positive change in prescribing practices. The teams developed standardized assessment forms for pantoprazole and albumin and presented these to the critical care and pharmacy committees for endorsement. Pharmacists prospectively evaluated these agents using these assessment forms (Figure 1 and Figure 2), which also provide educational material for the prescriber and a communication mechanism for attending physicians not readily available at the time of the pharmacist s assessment. The forms provide the evidence-based rationale for the request to change to an alternative agent or discontinue therapy. If therapy is inappropriate according to these criteria, the pharmacist communicates with the prescriber by placing the completed evaluation form in the progress notes section of the medical record. The form allows the prescriber to respond with additional information that might not be apparent from the chart but that would justify the use of the agent. The continuous sedation policy was revised through Capital s established committee structure. The revised protocol designates propofol as the first-line agent for continuous sedation during the first 72 hours of mechanical ventilation. To monitor and ensure safety, the revised protocol also includes measuring triglyceride levels between 48 and 72 hours if propofol use is likely to continue beyond 72 hours. Unless otherwise stated on a patient-specific basis, the protocol defines the following standard clinical endpoints: a Modified Ramsey Score of 2 to 3 or a Bispectral Index score of 40 to 60. To standardize the approach to the daily wake-up process, each nurse received guidelines regarding the procedures for wake-up and reinitiation. These guidelines permit the administration of a 1-mg bolus dose of lorazepam during the wake-up process to ensure that nurses could resedate patients per protocol if they became anxious to avoid the delay associated with acquiring a physician order. The policy further provided recommendations for conversion to benzodiazepines in patients expected to require prolonged sedation and ventilation. The policy was implemented after committee approval following education to all health care professionals. The pharmacist evaluates erythropoietin use prospectively on a per-patient basis. If the indication for use is inappropriate or the dose prescribed is not optimal, the pharmacist discusses the case with the physician. The erythropoietin and sedation policy changes were instituted by Month 2. Teams implemented the pantoprazole and albumin communication forms after education in Month 4 of the collaborative. Educational posters were displayed in the critical care nursing and physician areas starting in Month 6, showing outcomes to date. Each poster provided education regarding identified areas of noncompliance with evidence-based prescribing and areas often discussed when the pharmacist reviewed cases with physicians. Results Pantoprazole and Stress Ulcer Prophylaxis The use of intravenous and oral pantoprazole decreased and the use of famotidine increased. For Team 1 (Fuld), the use of intravenous pantoprazole decreased by 43%, from 233 doses per month at baseline to 133 doses per month during the last month of data collection. Similarly, pantoprazole use decreased 40%, from 121 doses per month to 72 doses per month. Intravenous famotidine use increased 319%, from 58 to 240 doses per month. Oral famotidine use increased from 2 to 122 doses per month. For Team 2 (Mercer), the use of intravenous pantoprazole decreased by 25%, from 130 doses per month at baseline to 98 doses per month in the last month of data collection. Oral pantoprazole use decreased 18%, from 76 doses per month to 63 doses per month. Intravenous famotidine use increased 72%, from 29 to 50 doses per month. Oral famotidine use increased 105%, from 22 to 45 doses per month. Albumin The inappropriate use of 25% albumin decreased throughout the program period. Team 1 used 50 vials at baseline as compared with 10 vials in the final month. Team 2 used 6 vials at baseline and 0 vials in the last month. Erythropoietin The use of erythropoietin for anemia of critical illness decreased throughout the program period. Team 1 reduced use of erythropoietin (40,000-U doses) by 83%, from 28 doses during the baseline month to 5 doses in the final month. Team 2 demonstrated a 75% reduction in erythropoietin use, from 12 doses in the baseline month to 3 doses in the final month. 618 JCOM November 2006 Vol. 13, No. 11

5 reports from the field efficiency Pantoprazole Communication Form and Worksheet Medication Use Strategies in Critical Care (MUSIC) COMMUNICATION FORM: NOT A PART OF THE PERMANENT RECORD Unit Secretaries: Please leave this communication form in the Physician Orders. Pharmacy will retrieve it upon completion of the communication. Patient: Medical Record No: DEAR DR Drug Regimen Evaluated: Pantoprazole IV/PO 40 mg daily Per our evaluation below, we recommend converting pantoprazole IV/PO 40 mg daily to famotidine 20 mg IV/PO for the indication of stress ulcer prophylaxis for the following evidence-based reasons: No published studies demonstrate superiority of proton pump inhibitors (omeprazole and lansoprazole) to histamine antagonists for stress ulcer prophylaxis (SUP). Pantoprazole has not been evaluated. Pantoprazole 40 mg IV costs 5 to 10 times as much as famotidine with no additional benefit for this indication. Pantoprazole is approximately $4 per dose and famotidine 20 mg IV is $0.40 per dose for a total of $0.40 to $0.80 per day depending on the dosing interval. If you have any questions, please do not hesitate to contact me at. Thank you., RPh (Date/Time) Physician Response. Please check your response and provide the requested information. I accept the recommendation above and will therefore write an order for famotidine as recommended. I decline the recommendation above because Pantoprazole for Stress Ulcer Prophylaxis Worksheet Pharmacist Evaluation Criteria: Assess the following for the patient and check all that apply. If the following apply, pantoprazole is being used therapeutically and not for PUD prophylaxis. Regimen is appropriate and no intervention is required. Patient DOES have a history of PUD or GERD per the (circle one) History & Physical or Progress Notes or and patient is on (list regimen) as an outpatient. Patient has recently had a GI bleed confirmed by (circle one) endoscopy or GI consult. Date of bleed: Patient was previously on famotidine and developed thrombocytopenia (platelets < 150,000 or a 50% decrease in 24 hours). Current platelet count: If pantoprazole is being prescribed exclusively for PUD prophylaxis, recommend conversion to famotidine 20 mg IV/PO BID or famotidine 20 mg IV/PO daily for CrCl < 50 ml/m if: Platelets > 150,000 Patient has an indication for PUD prophylaxis: Educational reference for pharmacists: According to ASHP (AJHP Feb 1999;56(4): ), appropriate indications for GI prophylaxis include the following Coagulopathies Platelets < 50,000 INR > 2 PTT > 2 times the normal limit Mechanical ventilation > 48 hours History of gastrointestinal bleeding within one year of current admission Or critical care patients with any of the following special criteria: GCS < 10 or inability to follow simple commands (A GCS can be found on the nursing critical care form until the neurological examination) Thermal injuries > 35% BSA Partial hepatectomy Multiple traumas (consistent with a Injury Severity Score 16) Hepatic failure Spinal cord injury Figure 1. Pantoprazole communication form and worksheet. Vol. 13, No. 11 November 2006 JCOM 619

6 medication use in critical care Pantoprazole Communication Form and Worksheet Medication Use Strategies in Critical Care (MUSIC) COMMUNICATION FORM: NOT A PART OF THE PERMANENT RECORD Unit Secretaries: Please leave this communication form in the Physician Orders. Pharmacy will retrieve it upon completion of the communication. Patient: Medical Record No: DEAR DR Drug Evaluated: Albumin Per our evaluation below, we recommend discontinuation of albumin therapy for the following evidence-based reasons: No evidence supports a mortality benefit with albumin therapy for the treatment of hypoalbuminemia associated with critical illness in adults (Haynes 2003). To the contrary a meta-analysis of 30 randomized, controlled trials (n = 1419) suggested that it increases mortality by 6% (Anon, 1998). Albumin therapy for hypoproteinemia associated with malnutrition is not associated with improved outcomes. Increases in serum albumin levels are transient. (Moss 1982, Vermeulen 1995, Koretz 1995). If you have any questions, please do not hesitate to contact me at. Thank you., RPh (Date/Time) Physician Response. Please check your response and provide the requested information. I accept the recommendation above and will therefore write an order to discontinue albumin therapy.. I decline the recommendation above because Albumin Worksheet Pharmacist Evaluation Criteria: Assess the following for the patient and check all that apply. If the following apply, the use of albumin is appropriate in an adult and no intervention is required. Use is appropriate if albumin is being used for: (Haynes 2003) Colloidal fluid resuscitation for sepsis. Paracentesis or management of ascites (Wilkinson 1998) If any of the above indications are associated with orders of higher doses or longer durations than expected, please recommend a clarification for the appropriate regimen. If albumin is being prescribed for the following, recommendation for discontinuation is warranted: (Moss 1982, Marik 1993, Koretz 1995, Rubin 1997, Cochrane Injuries Group Albumin Reviewers 1998, Haynes 2003) Hypoalbuminemia secondary to critical illness Nutritional support for malnutrition Figure 2. Albumin communication form and worksheet. Sedation Protocol To evaluate the effect of the changes in the sedation protocol, teams looked at several indicators, including the number of vials of propofol (100-mL equivalents) dispensed per month, average length of stay in the critical care areas, absolute rates of VAP and average ventilator days. Propofol use increased throughout the program period, from 29 to 121 vials for Team 1 and from 94 to 194 vials for Team 2. In comparing the first 5-month period of the collaborative (excluding the baseline month) to the second 5-month period, average length of stay in the critical care areas decreased by 11% (Team 1) and 18% (Team 2). Absolute number of VAP cases decreased 64%, or from 11 to 4 cases (Team 1) and by 100%, or from 4 to 0 cases (Team 2). Average ventilator days decreased 21% (Team 1) and 22% (Team 2). As expected, the increased use of propofol resulted in a $58,740 increase in spending for Team 1 and a $63,852 increase for Team 2. This cost increase correlated with a projected annualized financial improvement associated with the reduction of length of stay in the critical care areas of $965,000 for Team 1 and $1.27 million for Team 2 based on bed cost. The literature reports of costs associated with an incident of VAP range from $12,000 [38] to $57,000 [39]. A recent publication from the Institute for Health Improvement s 10,000 Lives Campaign estimated that VAP costs $40,000 per incident [40]. Based on this estimate, the collaborative 620 JCOM November 2006 Vol. 13, No. 11

7 reports from the field efficiency achieved a cost avoidance of $241,500 with the reduction of 7 cases of VAP for Team 1 and a cost avoidance of $138,000 for the reduction by 4 cases of VAP for Team 2. Change in monthly expenditures for target agents is shown in Table 3. Discussion Evidence-based medicine assures the application of therapies demonstrating clinical benefit, but there is also a need for clinicians to apply cost-effective strategies. As in the sedation example, daily wake-ups from continuous sedation have been associated with both shorter intubation times and shorter length of stay. Upon initiation of the sedation protocol, each facility incorporated mandatory wake-ups into the standard daily ventilator care plan. The use of propofol as a sedative agent facilitated compliance with the care plan. Although propofol has a higher acquisition cost than lorazepam or midazolam, our experience suggests that health systems can realize overall system-wide cost savings with this agent as a result of the associated shorter lengths of stay and reduced VAP rates. In the 6 months following the conclusion of this project, VAP rates have continued to remain low, with no VAP cases for Team 2 and 4 VAP-free months for Team 1. There were limitations to our data collection process, as we did not collect demographic data on individual patients. However, sustained success in the 6 months following the conclusion of the collaborative program suggests that the results attained are not due to differences in patient acuity or changes in the number of admissions. Nonetheless, further study into this area could be beneficial. Our program experience suggests that the educational strategies employed were efficacious and underscores the importance of the presence of a pharmacist in critical care areas. Education, reinforcement, and pharmacist discussions with physicians on a case-by-case basis can facilitate a cultural change in prescribing habits for sedation, stress ulcer prophylaxis, and other conditions associated with critical illness. Corresponding author: Liza Barbarello-Andrews, PharmD, BCPS, Department of Pharmacy Practice and Administration, Ernest Mario School of Pharmacy, William Levine Hall, Busch Campus, 160 Frelinghuysen Rd., Piscataway, NJ 08854, lbarbare@rci.rutgers.edu. References 1. Kress JP, Pohlman AS, O Connor MF, Hall JB. Daily interruption of sedative infusions in critically ill patients undergoing mechanical ventilation. N Engl J Med 2000;342: Wittbrodt ET. Daily interruption of continuous sedation. Pharmacotherapy 2005;25(5 Pt 2):3S 7S. 3. Riker RR, Fraser GL. Adverse events associated with sedatives, analgesics, and other drugs that provide patient comfort in the intensive care unit. Pharmacotherapy 2005;25(5 Pt 2): 8S 18S. Table 3. Monthly Expenditure on Target Agents Medication Baseline End of Program Pantoprazole $1411 $901 Famotidine $42 $175 Erythropoietin $16,215 $3243 Albumin $896 $ Reilly CS, Nimmo WS. New intravenous anaesthetics and neuromuscular blocking drugs. A review of their properties and clinical use. Drugs 1987;34: Shelly MP, Sultan MA, Bodenham A, Park GR. Midazolam infusions in critically ill patients. Eur J Anaesthesiol 1991; 8: Barrientos-Vega R, Mar Sanchez-Soria M, et al. Prolonged sedation of critically ill patients with midazolam or propofol: impact on weaning and costs. Crit Care Med 1997;25: Carrasco G, Molina R, Costa J, et al. Propofol vs midazolam in short-, medium-, and long-term sedation of critically ill patients. A cost-benefit analysis. Chest 1993;103: Chamorro C, de Latorre FJ, Montero A, et al. Comparative study of propofol versus midazolam in the sedation of critically ill patients: results of a prospective, randomized, multicenter trial. Crit Care Med 1996;24: Hall RI, Sandham D, Cardinal P, et al. Propofol vs midazolam for ICU sedation: a Canadian multicenter randomized trial. Chest 2001;119: Carson SS, Kress JP, Rodgers JE, et al. A randomized trial of intermittent lorazepam versus propofol with daily interruption in mechanically ventilated patients. Crit Care Med 2006;34: ASHP therapeutic guidelines on stress ulcer prophylaxis. ASHP Commission on Therapeutics. Approved by the ASHP Board of Directors on 14 Nov Am J Health Syst Pharm 1999;56: Tryba M, Cook D. Current guidelines on stress ulcer prophylaxis. Drugs 1997;54: Cook D, Guyatt G, Marshall J, et al. A comparison of sucralfate and ranitidine for the prevention of upper gastrointestinal bleeding in patients requiring mechanical ventilation. Canadian Critical Care Trials Group. N Engl J Med 1998;338: Cook D, Heyland D, Griffith L, et al. Risk factors for clinically important upper gastrointestinal bleeding in patients requiring mechanical ventilation. Canadian Critical Care Trials Group. Crit Care Med 1999;27: Cook DJ, Reeve BK, Guyatt GH, et al. Stress ulcer prophylaxis in critically ill patients. Resolving discordant metaanalyses. JAMA 1996;275: Shuman RB, Schuster DP, Zuckerman GR. Prophylactic therapy for stress ulcer bleeding: a reappraisal. Ann Intern Med 1987;106: Conrad SA, Gabrielli A, Margolis B, et al. Randomized, double-blind comparison of immediate-release omeprazole Vol. 13, No. 11 November 2006 JCOM 621

8 medication use in critical care oral suspension versus intravenous cimetidine for the prevention of upper gastrointestinal bleeding in critically ill patients. Crit Care Med 2005;33: Levy MJ, Seelig CB, Robinson NJ, Ranney JE. Comparison of omeprazole and ranitidine for stress ulcer prophylaxis. Dig Dis Sci 1997;42: Phillips JO, Metzler MH, Palmieri MT, et al. A prospective study of simplified omeprazole suspension for the prophylaxis of stress-related mucosal damage. Crit Care Med 1996; 24: Song JC, Quercia RA, Fan C, et al. Pharmacokinetic comparison of omeprazole capsules and a simplified omeprazole suspension. Am J Health Syst Pharm 2001;58: Balaban DH, Duckworth CW, Peura DA. Nasogastric omeprazole: effects on gastric ph in critically ill patients. Am J Gastroenterol 1997;92: Lasky MR, Metzler MH, Phillips JO. A prospective study of omeprazole suspension to prevent clinically significant gastrointestinal bleeding from stress ulcers in mechanically ventilated trauma patients. J Trauma 1998;44: Laterre PF, Horsmans Y. Intravenous omeprazole in critically ill patients: a randomized, crossover study comparing 40 with 80 mg plus 8 mg/hour on intragastric ph. Crit Care Med 2001;29: Otani Y, Kitajima M, Sugiyama M, et al. Inhibitory effects of intravenous lansoprazole on gastric acid hypersecretion in patients with postoperative stress. J Clin Gastroenterol 1995;20 Suppl 2:S Phillips JO, Olsen KM, Rebuck JA, et al. A randomized, pharmacokinetic and pharmacodynamic, cross-over study of duodenal or jejunal administration compared to nasogastric administration of omeprazole suspension in patients at risk for stress ulcers [published erratum appears in Am J Gastroenterol 2001;96:2528]. Am J Gastroenterol 2001;96: Tsai WL, Poon SK, Yu HK, et al. Nasogastric lansoprazole is effective in suppressing gastric acid secretion in critically ill patients. Aliment Pharmacol Ther 2000;14: Schupp KN, Schrand LM, Mutnick AH. A cost-effectiveness analysis of stress ulcer prophylaxis. Ann Pharmacother 2003; 37: Guthrie RD Jr, Hines C Jr. Use of intravenous albumin in the critically ill patient. Am J Gastroenterol 1991;86: Reinhardt GF, Myscofski JW, Wilkens DB, et al. Incidence and mortality of hypoalbuminemic patients in hospitalized veterans. JPEN J Parenter Enteral Nutr 1980;4: Human albumin administration in critically ill patients: systematic review of randomised controlled trials. Cochrane Injuries Group Albumin Reviewers. BMJ 1998;317: Haynes GR, Navickis RJ, Wilkes MM. Albumin administration what is the evidence of clinical benefit? A systematic review of randomized controlled trials. Eur J Anaesthesiol 2003;20: Koretz RL. Intravenous albumin and nutrition support: going for the quick fix. JPEN J Parenter Enteral Nutr 1995;19: Marik PE. The treatment of hypoalbuminemia in the critically ill patient. Heart Lung 1993;22: Gabriel A, Kozek S, Chiari A, et al. High-dose recombinant human erythropoietin stimulates reticulocyte production in patients with multiple organ dysfunction syndrome. J Trauma 1998;44: Rogiers P, Zhang H, Leeman M, et al. Erythropoietin response is blunted in critically ill patients. Intensive Care Med 1997;23: van Iperen CE, Gaillard CA, Kraaijenhagen RJ, et al. Response of erythropoiesis and iron metabolism to recombinant human erythropoietin in intensive care unit patients. Crit Care Med 2000;28: Corwin HL, Gettinger A, Pearl RG, et al. Efficacy of recombinant human erythropoietin in critically ill patients: a randomized controlled trial. JAMA 2002;288: Warren DK, Shukla SJ, Olsen MA, et al. Outcome and attributable cost of ventilator-associated pneumonia among intensive care unit patients in a suburban medical center. Crit Care Med 2003;31: Institute for Healthcare Improvement. Getting started kit: prevent ventilator-associated pneumonia. How-to guide. Available at Accessed 26 Oct Cocanour CS, Ostrosky-Zeichner L, Peninger M, et al. Cost of a ventilator-associated pneumonia in a shock trauma intensive care unit. Surg Infect (Larchmt) 2005;6: Copyright 2006 by Turner White Communications Inc., Wayne, PA. All rights reserved. 622 JCOM November 2006 Vol. 13, No. 11