I recently attended my son’s elementary school holiday event. Besides all of the merriment associated with the upcoming season, the school’s chorus sang “We are the World.” Many of you, like me, probably have not thought about or heard this song in a long time. Listening to the children sing brought back many emotions associated with the song and the message it conveyed.

To refresh your memories, this song was written and produced in 1985 with the goal of raising awareness and funds for African famine relief.

 Some of the most popular artists of the day sang together, with the release of the single being one of the best selling to date. It was great to watch the video again and listen to the lyrics 27 years later.

One of the first lines of the song is “the world must come together as one.” I had the privilege of attending the 100th anniversary of the International Pharmaceutical Federation (FIP) in Amsterdam, the Netherlands, last October. I have participated in this international meeting in the past few years and have thoroughly enjoyed leaning about hospital practice around the world and meeting many people who practice in these settings. I am always impressed by everyone’s commitment to the profession of pharmacy and how friendships and collaborations can transcend country-specific politics.

During a special ceremony, a representative of each of FIP’s 127 member organizations signed the Centennial Declaration. It begins with the following statement:

 Pharmacists and Pharmaceutical scientists accept responsibility and accountability for improving global health and patient health outcomes by closing gaps in the development, distribution, and responsible use of medicines. Society can contribute to these objectives by supporting the advancement of pharmacy practice and the pharmaceutical sciences.

 The words “responsibility” and “accountability” demonstrate the explicit roles pharmacists have toward patients and the integrity of the drug product. Unfortunately, not all countries have systems that allow practice in accord with this mandate.

Even though the role of the pharmacist varies by setting and nation, there are some countries where pharmacists do not need to be licensed or trained to dispense medications. They are free to open a community pharmacy in their village, dispensing medications and providing advice to patients. In some countries, hospitals operate without pharmacist oversight for medication preparation. Continuing education is not an expectation for maintenance of licensure. These are things we take for granted in the United States.

In other countries, the desired workplace is the pharmaceutical industry or academia, not patient care. The best graduates flock to these research positions because of their prestige or better salary. Some nations have limited educational opportunities and institutions and are not able to train the number of pharmacists needed to support the health care infrastructure demanded by society.

With limited numbers of trained pharmacists, the ownership of the medication distribution system cannot exist to the desired level in these nations. This establishes opportunities for counterfeit medications to be introduced—making the care system dangerous to the patient. Of course, there are also differences in health care infrastructure and economics on what can be afforded. All of these forces create variations in pharmacy practice that are observed across the world.

Having the endorsement of such a collaborative document in the form of the FIP Centennial Declaration will provide strategic planning and focus to governmental agencies, academic institutions, and professional pharmacy organizations to steer the activities of pharmacists toward being accountable and responsible for patient care.

We have an obligation to “come together as one” in advancing the patient-centered practice of pharmacy.

Stephen F. Eckel, PharmD, MHA, BCPS, FASHP, FAPhA, is assistant director of pharmacy, University of North Carolina Hospitals and clinical assistant professor, University of North Carolina Eshelman School of Pharmacy.

1. We are the world. Wikipedia website. http://en.wikipedia.org/wiki/We_Are_the_World. Accessed December 1, 2012.

2. Improving global health by closing gaps in the development, distribution, and responsible use of medicines. International Pharmaceutical Federation website. http://fip.org/www/uploads/database_file.php?id=339&table_id=. Accessed December 1, 2012.

Articles

Editor’s Note

We Are the World

More than 6.5 million adults in the United States have heart failure, the prevalence of which is expected to increase by 25% by the year 2030.

 Admission rates for heart failure remain high, and hospitalizations account for the majority of the direct costs associated with its management.

 Among patients hospitalized with heart failure, nearly 1 in 4 are readmitted within 30 days.

Managing these patients in the inpatient setting often involves careful titration of intravenous (IV) and oral therapies with complex hemodynamic effects. It is important for pharmacists to have a basic understanding of these management strategies in order to help facilitate and monitor appropriate therapy and improve outcomes.

Patients presenting with fluid overload may experience dyspnea at rest or on exertion, paroxysmal nocturnal dyspnea, orthopnea, peripheral edema, abdominal swelling, rales, elevated jugular venous pressure, or nausea and vomiting, all often accompanied by weight gain. Signs of low cardiac output and hypoperfusion include worsening renal function, altered mental status, fatigue, and hypotension.

In addition to addressing the reversible and treatable causes of heart failure, management of acutely decompensated patients is focused on improving symptoms, improving hemodynamic parameters, and ultimately optimizing chronic medications known to improve outcomes. On discharge and during follow-up, medication management and titration are paramount to improving these outcomes.

Much as the diagnosis of heart failure is based upon the presenting signs and symptoms, these signs and symptoms help guide therapy. For patients presenting with fluid overload, there are several approaches to help facilitate diuresis.In addition to sodium and fluid restriction, converting to an IV loop diuretic (furosemide or bumetanide), typically done in tandem with increasing the loop diuretic dose, is a common initial strategy. IV diuretic administration can facilitate more rapid onset of diuresis as well as avoid potential absorption concerns with orally administered diuretics (eg, furosemide).

For patients in whom diuresis remains difficult, the addition of a thiazide diuretic (typically metolazone or IV chlorothiazide) may be beneficial.

 Close electrolyte monitoring is important, particularly in the setting of aggressive diuresis. In addition, monitoring should include urine output, fluid intake, renal function, vital signs, and daily weights to assess progress.

Continuous infusion of a loop diuretic is noted as an option by both the Heart Failure Society of America and American College of Cardiology/American Heart Association Practice Guidelines for diuretic resistance.

 Although concerns have been raised over the potential effects of high bolus doses, a recent trial examining the utility of continuous infusion loop diuretics found no differences between intermittent and continuous infusion with respect to effects on renal function.

The DOSE trial examined whether high-dose loop diuretic (given intravenously at 2.5 times the patient’s home dose) versus low dose and whether continuous infusion versus intermittent boluses doses led to greater improvements in global symptom assessment or change in serum creatinine at 72 hours in patients admitted with an acute decompensation. Analysis of secondary end points suggested greater net fluid loss and greater improvements in selfreported dyspnea in patients randomized to high-dose diuretics. Continuous infusion of loop diuretics remains an option, but the advantages of continuous infusion compared with bolus dosing remains unclear.

Ultrafiltration is another option for patients with diuretic resistance. The UNLOAD study demonstrated greater net fluid and weight loss at 48 hours and a reduction in hospitalization for heart failure at 90 days in patients with heart failure and signs of fluid overload randomized to ultrafiltration versus standard therapy.

 No differences in chan-ges in renal function were noted between groups. In contrast, the CARRESS-HF study found that a stepped pharmacologic therapy algorithm (goal 3 to 5 liters negative per day) was superior to ultrafiltration with respect to preservation of renal function in patients admitted with heart failure with signs of fluid overload and worsening renal function.

Weight loss was similar between groups. In the inpatient setting, barriers to ultrafiltration include the need for more frequent monitoring and a higher level of nursing care, anticoagulation (eg, heparin) to prevent filter clotting, and the high cost of filter replacement. In light of the results of the CARRESSHF trial, ultrafiltration in patients with acutely decompensated heart failure and worsening renal function should be avoided. Ultrafiltration remains a potential strategy for patients with diuretic resistance and fluid overload in the absence of renal dysfunction.

Vasodilators are generally used as an adjunct to diuretic therapy in patients with continued signs of congestion despite diuretics, or in patients with acute pulmonary edema or severe hypertension.

 They can also be used to lower afterload in patients with low cardiac output with the goal of improving forward flow. Oral vasodilators including angiotensin-converting enzyme (ACE) inhibitors can be used to manage stable patients, although titration is generally slower due to the longer relative half-lives of oral medications.

For more acutely ill patients, IV vasodilators may be warranted. The immediate goals of vasodilator therapy vary based on patient presentation, but include relief of congestion, improved diuresis, and improved cardiac output and end-organ perfusion. Hypotension is common, and patients should have frequent blood pressure monitoring while receiving IV vasodilators.

Nitroglycerin reduces congestion primarily through venodilation, although decreases in afterload can be seen with high doses. The use of nitroglycerin is limited by tachyphylaxis and adverse effects, generally hypotension and headache.

In contrast to nitroglycerin, nitroprusside has both arterial and venodilating properties and can be advantageous in patients with elevated filling pressures, low cardiac output, and adequate blood pressure.

Hemodynamic monitoring is important, particularly with nitroprusside, due to the potential for profound decreases in blood pressure. Thiocyanate toxicity is rare but can occur with high doses or renal dysfunction.

 Data evaluating the use of nitroprusside and nitroglycerin in the acute decompensated heart failure population are limited.

Nesiritide is a B-type natriuretic peptide with preload and afterload lowering and other potential beneficial effects.

 Initial clinical studies showed rapid improvements in pulmonary capillary wedge pressure compared with placebo.

Subsequently, 2 meta-analyses were published suggesting an association between nesiritide and renal failure and increased mortality.

 More recently, a randomized controlled trial (ASCEND-HF) found no difference in patient-reported symptoms of dyspnea at 6 or 24 hours, nor did it find differences in mortality or hospitalization for heart failure at 30 days in patients randomized to nesiritide versus placebo.

 The ultimate benefit of nesiritide in acute decompensated heart failure remains unclear. Table 1 summarizes the vasodilators used in acute decompensated heart failure.

Patients for whom IV vasodilator therapy is deemed necessary should be monitored closely for hypotension, changes in renal function, and signs of improvement in diuresis and cardiac output. Due to the inherent limitations of continued IV therapy, transition to oral medications should occur when the patient is clinically stable. ACE inhibitors and hydralazine are used commonly when weaning IV vasodilators, though frequent monitoring remains necessary until the IV agents have been weaned successfully.

Inotropes are typically reserved for patients with low left ventricular ejection fraction presenting with signs and symptoms of low cardiac output and hypoperfusion. Inotropes are also used as palliative therapy in patients with end-stage disease, or as a bridge to advanced therapies including left ventricular assist device or heart transplantation. In patients with symptomatic hypotension who are unable to tolerate vasodilators, inotropes may be indicated. However, the use of inotropes in patients without signs of hypoperfusion is not recommend due to the high incidence of adverse effects without demonstrated benefits.

Dobutamine and milrinone are the most frequently encountered agents in patients with acute decompensated heart failure requiring inotropes. Milrinone has both peripheral and pulmonary vasodilating effects in addition to inotropic effects. Although some vasodilation may occur with dobutamine through beta

 receptor stimulation, milrinone has greater vasodilatory effects and should be used cautiously in patients with low systemic vascular resistance.

Dopamine can be used to supplement inotropic support, although increases in systemic vascular resistance can become problematic with dose escalation in patients with compromised cardiac output.

The choice of inotrope depends on patient-specific parameters and must be weighed closely. In patients with normal or elevated systemic vascular resistance, milrinone may be warranted due to more pronounced effects on systemic vascular resistance than dobutamine. In patients with renal dysfunction, milrinone clearance may be prolonged. Patients must be monitored closely for hemodynamic changes and signs of improvement. Table 2 summarizes the inotropes that are commonly used.

Inotropes are not without adverse effects. In the ADHERE registry, inotropes were associated with higher in-hospital mortality than vasodilators in patients presenting with acute decompensated heart failure.

 In the OPTIME-CHF study, patients randomized to milrinone experienced more sustained hypotension and atrial arrhythmias than the placebo group.

 Patients should be monitored closely for tacharrhythmias. Current practice guidelines recommend vasodilators be considered over inotropes in patients with acute decompensated heart failure and adequate blood pressure.

Management of acute decompensated heart failure in the inpatient setting can be challenging. Pharmacists can play a critical role in managing these patients by providing recommendations on drug titration and monitoring, dose adjustments based on patient-specific parameters, and providing assistance with optimizing oral therapy. Pharmacists in both the inpatient and outpatient settings have the opportunity to ensure appropriate transition of care from one setting to another. Through patient and provider education and assessment of appropriate therapy, the pharmacist can help to ensure optimal outcomes and improve overall care.

John E. MacKay, PharmD, BCPS, graduated from Oregon State University College of Pharmacy and completed both his pharmacy practice and cardiology specialty residencies at the University of North Carolina Hospitals and Clinics in Chapel Hill, North Carolina. He currently works as a clinical pharmacist in advanced heart failure at Oregon Health and Science University.

1. Heidenrech PA, Trogdon JG, Khavjou OA, Butler J, Dracup K, Ezekowitz MD, et al. Forecasting the future of cardiovascular disease in the United States. 

2. Ross JS, Chen J, Lin Z, Bueno H, Curtis JP, Keenan PS, et al. Recent national trends in readmission rates after heart failure hospitalization. 

3. Dunlay SM, Shah ND, Shi Q, Morlan B, VanHouten H, Long KH, et al. Lifetime costs of medical care after heart failure diagnosis. 

4. Hunt SA, Abraham WF, Chin MC, Feldman AM, Francis GS, Ganiats TG, et al. 2009 focused updated incorporated into the ACC/AHA 2005 guidelines for the diagnosis and management of heart failure in adults: A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines: Developed in collaboration with the International Society for Heart and Lung Transplantation. 

5. Lindenfeld J, Albert NM, Boehmer JP, et al, and the Heart Failure Society of America. HFSA 2010 Comprehensive Heart Failure Practice Guideline. 

6. Felker GM, Lee KL, Bull DA, Redfield MM, Stevenson LW, Goldsmith SR, et al.  Diuretic strategies in patients with acute decompensated heart failure. 

7. Costanzo MR, Guglin ME, Saltzberg MT, Jessup ML, Bart BA, Teerlink JR, et al. Ultrafiltration versus intravenous diuretics for patients hospitalized for acute decompensated heart failure. 

8. Bart BA, Goldsmith SR, Lee KL, Givertz MM, O’Connor CM, Bull DA, et al. Ultrafiltration in decompensated heart failure with cardiorenal syndrome. 

9. Parker JD. Counterregulatory responses: sustained-release isosorbide-5-mononitrate versus transdermal nitroglycerin. 

10. Mullens W, Abrahams Z, Francis GS, Skouri HN, Starling RC, Young, JB, et al. Sodium nitroprusside for advanced low-output heart failure. 

11.  Mills RM, LeJemtel TH, Morton DP, Liang C, Lang R, Silver MA, et al. Sustained hemodynamic effects of an infusion of nesiritide (human b-type natriuretic peptide) in heart failure: a randomized, double-blind, placebo-controlled clinical trial. 

12. Publication Committee for the VMAC investigators. Intravenous nesiritide versus nitroglycerin for treatment of decompensated heart failure: a randomized controlled trial. 

13. Sackner-Bernsetin JD, Skopicko HA, Aaronson KD. Risk of worsening renal function with nesiritide in patients with acutely decompensated heart failure. 

14. Sackner-Bernsetin JD, Kowalski M, Fox M, Aaronson K. Short-term risk of death after treatment with nesiritide for decompensated heart failure: a pooled analysis of randomized controlled trials. 

15. O’Connor CM, Starling RC, Hernandez AF, Armstrong PW, Dickstein K, Hasselblad V, et al. Effect of nesiritide in patients with acute decompensated heart failure. 

16. Abraham WT, Adams KF, Fonarow GC, Costanzo MR, Berkowitz RL, LeJemtel TH, et al. In-hospital mortality in patients with acute decompensated heart failure requiring intravenous vasoactive medications. 

17. Cuffe MS, Califf RM, Adams KF, Benza R, Bourge R, Colucci WS, et al. Short-term intravenous milrinone for acute exacerbation of chronic heart failure. A randomized controlled trial. 

Chronic Care Focus

Acute Decompensated Heart Failure Management Strategies

J H is a 45-year-old woman scheduled to undergo an exploratory laparotomy with liver laceration repair and splenectomy following a motor vehicle collision. She has been taking 20 mg prednisone daily for the past 5 years for rheumatoid arthritis, and the surgical team inquires about the need for supplemental perioperative steroids.

Patients undergoing a surgical procedure or responding to stress, trauma, or an acute illness will exhibit an increase in adrenal cortisol production up to 6-fold normal levels. However, in patients on chronic exogenous steroid therapy, atrophy of the hypothalamicpituitary-adrenal (HPA) axis may occur through feedback inhibition, leading to an inability to respond to stress. It has historically been believed that patients receiving long-term corticosteroids require supplemental, perioperative doses, and that failure to provide such coverage in secondary adrenal insufficiency may lead to an adrenal crisis characterized by hypotension and cardiovascular collapse. Currently, however, minimal evidence exists regarding optimal type, dose, and duration of supplemental steroids, if any, that should be recommended perioperatively. Given the known detrimental side effects of corticosteroids, including hyperglycemia, delayed wound healing, water retention, hypertension, and neuropsychiatric complications, use of the lowest possible doses is warranted.

Consideration of the need for supplemental doses depends not only on the magnitude of the surgical procedure performed, but also on the patient’s current steroid regimen. Normal cortisol production on average is 15 to 20 mg/day, which can increase to 50 mg/day in response to minor procedures and 75 to 150 mg/ day for moderate/major surgery. The onset of adrenal suppression can occur as early as 1 week after commencing therapy, and usually requires doses of 10 mg of prednisone equivalent or greater.

Therefore, patients receiving “physiologic replacement” doses (<10 mg/ day) do not need additional steroids perioperatively beyond their standard regimen. Patients receiving doses exceeding the normal expected stress response for their surgery (>150 mg/ day of hydrocortisone equivalent for moderate/major surgery, or >50 mg/ day of hydrocortisone equivalent for minor surgery) also do not need additional coverage beyond their current therapy, because acute immunosuppressive doses are more than sufficient to maintain cardiovascular stability during the operation.

For the remaining group of patients, current evidence in the literature, although scant, suggests that the combination of the patient’s regimen, along with endogenous cortisol production around the time of surgery, is sufficient to preclude additional coverage. However, if supplemental steroids are warranted, the combination of the patient’s usual dose with the additional corticosteroid should not exceed the maximum expected cortisol production for the severity of that particular surgical procedure. For patients unable to take oral steroids perioperatively, divided doses of hydrocortisone every 6 to 8 hours is appropriate.

Generally, cortisol levels return to baseline within 48 to 72 hours following the procedure. Thus, in patients receiving supplemental dosing, an additional postoperative 24 hours of coverage for moderate surgery and 48 to 72 hours for major surgery may be reasonable. Recovery of normal adrenal function following steroid discontinuation has been documented to require as short as a few days up to 9 months, with the time course of recovery a function of the dose and duration of prior therapy. It has been suggested that patients who discontinued their steroids within 3 months of surgery should be assumed to have adrenal suppression, and be treated as such, whereas the remaining patients should simply have additional monitoring for hemodynamic compromise.

In the case of JH, a reasonable recommendation would be either administering only her home prednisone dose of 20 mg/day, or if supplementation is needed, hydrocortisone 50 mg IV q8h could be used instead, and continued for 48 to 72 hours, at which point her home regimen could be resumed.

Roxana Dumitru, PharmD, BCPS, is a clinical specialist-trauma/surgery at the Harborview Medical Center in Seattle, Washington.

Pharmacist Rounds

Perioperative Management of the Surgical Patient on Chronic Steroid Therapy

AN is a 3-year-old male with a past medical history of pica and developmental speech delay. The patient presented to the emergency department following a routine blood lead level (BLL) obtained at his pediatrician’s office, which was 109 mcg/dL; a repeat level was 131 mcg/ dL. AN began to experience abdominal pain, vomiting, and constipation 2 days prior to presentation. Abdominal imaging demonstrated the presence of foreign bodies, possibly lead paint chips, throughout the colon. A complete blood count revealed the following values: hemoglobin 9.8 g/dL, hematocrit 30.2%, MCV 75 fL. The patient’s zinc protoporphyrin level was 714 mcg/dL and G6PD deficiency was ruled out. The clinical pharmacist was consulted regarding the most effective treatment option.

Lead toxicity (plumbism) most commonly occurs in pediatric patients following exposure to lead paint chips or dust. Children are at increased risk of lead toxicity due to greater absorption of ingested lead, mobilization of lead deposits in soft tissue, an immature blood brain barrier, and developing organ systems.

 Lead levels ≥10 mcg/ dL are known to cause IQ reduction.

 Recent studies, however, have demonstrated even greater rates of cognitive impairment with lead levels <10 mcg/ dL, including those as low as 1 mcg/ dL.

 In January 2012, the Centers for Disease Control and Prevention modified their recommendations to encourage additional monitoring of children with a BLL ≥5 mcg/dL, as adverse neurologic effects may occur at any lead level.

Children with elevated blood lead levels are often asymptomatic. Patients with a BLL ≥60 mcg/dL may experience headaches, abdominal pain, constipation, agitation, and somnolence. Encephalopathy and seizures may occur with a BLL ≥100 mcg/dL.

 When a patient’s BLL exceeds 45 mcg/ dL, a complete blood count, iron studies, and zinc protoporphyrin (ZPP) or free erythrocyte protoporphyrin (FEP) should be obtained. Lead disrupts heme synthesis, of which erythrocyte protoporphyrin is a precursor, resulting in microcytic, hypochromic anemia. An elevated ZPP or FEP level indicates chronic lead exposure.

Chelation therapy is indicated for patients with a BLL ≥45 mcg/dL.

 Calcium disodium EDTA is utilized for patients with a BLL ≥70 mcg/dL and may be administered intravenously at a dose of 50 mg/kg/day or 1000 to 1500 mg/m2 /day as a continuous infusion over 8 to 24 hours for a total duration of 5 days. Calcium disodium EDTA mobilizes lead from bones and forms lead complexes that may induce encephalopathy and seizures. Due to the neurologic risks of calcium disodium EDTA monotherapy in patients with a BLL ≥70 mcg/dL, it must be used in combination with and initiated 4 hours after the first dose of dimercaprol.

Among patients with a BLL ≥100 mcg/ dL, concurrent use of calcium disodium EDTA and dimercaprol reduces lead levels more rapidly than calcium disodium EDTA alone.

 /day divided every 4 hours is administered intramuscularly for a minimum of 3 days and may be discontinued when the BLL is below 50 mcg/dL. Dimercaprol is contraindicated in patients with glucose-6-phosphate deficiency.

 Following initial chelation therapy, lead redistributes from bones, necessitating further BLL monitoring. A repeat lead level of 45 to 69 mcg/ dL may be treated with oral chelators (succimer or penicillamine) or calcium disodium EDTA monotherapy. If the BLL exceeds 70 mcg/dL, dimercaprol and calcium disodium EDTA therapy should be repeated, with a minimum of 2 days between treatment courses, until the BLL is below 45 mcg/dL.

 AN was successfully treated with a 5-day course of calcium disodium EDTA and dimercaprol, after which his BLL was 26 mcg/dL.

Two weeks later, AN’s lead level was 52 mcg/dL, requiring further outpatient treatment with succimer. Daily iron supplementation was also initiated following completion of chelation therapy, as iron decreases absorption of ingested lead.

Michelle Rychalsky, PharmD, is a pediatric clinical pharmacist at Yale-New Haven Hospital in New Haven, Connecticut, where she works as a neonatal intensive care unit pharmacist and is involved in establishing protocols and preparing for an upcoming pharmacy information system upgrade.

Lead Toxicity in a Pediatric Patient

Liposomal bupivacaine (Exparel), manufactured by Pacira Pharmaceuticals, is a long-acting, local anesthetic FDA approved for single-dose infiltration into the surgical site to produce postsurgical analgesia. Efficacy of immediate-release bupivacaine HCl for acute postsurgical pain when administered via wound infiltration is well established; however, Exparel offers the advantage of a longer-acting local formulation that can be administered as a single dose.

The formulation of Exparel allows for a longer duration of action and a slower absorption into systemic circulation, avoiding high plasma concentrations. Local infiltration can result in significant liposomal bupivacaine systemic plasma concentrations for up to 96 hours; however, significant levels are not correlated with local efficacy. The peak plasma concentration (Cmax) of liposomal bupivacaine occurs at 2 hours for a bunionectomy and 30 minutes for a hemorrhoidectomy. After bupivacaine has been released from Exparel and is absorbed systemically, distribution is expected to be the same as for any bupivacaine HCl. The mean elimination half-life of local administration of 106 mg for a bunionectomy is approximately 34 hours and approximately 24 hours for a 266-mg single dose for a hemorrhoidectomy.

Liposomal bupivacaine is intended for single-dose infiltration only. The recommended dose is based on the surgical site and the volume required to cover the area. The maximum dose of liposomal bupivacaine should not exceed 266 mg. Exparel should be injected slowly into soft tissues of the surgical site with frequent aspiration to check for blood and minimize the risk of intravascular injection. The administration of Exparel should be delayed by at least 20 minutes following nonbupivacaine local anesthetics (eg, lidocaine), as they may cause an immediate release of bupivacaine from Exparel.

Dasta et al published a pooled analysis of 9 studies evaluating the effect of liposomal bupivacaine on pain intensity scores and opioid consumption. The 9 studies included in the analysis represented a total of 5 surgical procedures and compared liposomal bupivacaine with bupivacaine HCl. In the studies, a single dose of liposomal bupivacaine was administered to the surgical site. A total of 503 patients who received liposomal bupivacaine at doses up to 266 mg were compared with 409 patients who received bupivacaine HCl doses up to 200 mg.

In all 9 studies, patients who received liposomal bupivacaine reported significantly less pain over 72 hours compared with patients who received bupivacaine HCl. In addition, patients who received liposomal bupivacaine consumed an average of 12.2 mg of opioids compared with 19 mg in the bupivacaine HCl group (P <.001). Regarding safety data, 50% of patients in the liposomal bupivacaine group reported adverse effects, compared with 74% of patients in the HCl group. The authors concluded that a decreased need for opioids in the post-operative setting, may lead to better patient outcomes and lower costs.

Several safety considerations exist for the liposomal formulation of bupivacaine. The Institute of Safe Medication Practices classifies liposomal bupivacaine as a high-alert medication due to its similar appearance to propofol. If liposomal bupivacaine were administered intravenously as if it were propofol, adverse cardiac effects may result. Unlike bupivacaine HCl, liposomal bupivacaine is not intended for systemic use and should not be administered via the intrathecal, intravenous, or epidural routes. 

Liposomal bupivacaine is available as a 13.3 mg/mL (1.3%) solution in a 20-mL single-use vial. Liposomal bupivacaine should be refrigerated but may be stored at room temperature for up to 30 days in sealed, unopened vials. Vials should not be re-refrigerated. Liposomal bupivacaine can be administered undiluted or diluted up to 0.89 mg/mL with preservative-free normal (0.9%) saline for injection. Exparel vials should be inverted multiple times to re-suspend particles immediately prior to withdrawal from the vial, and diluted suspensions should be used within 4 hours of preparation in a syringe.

The average wholesale price (AWP) of a 20-mL vial is $285. Exparel is significantly more expensive per vial than bupivacaine HCl (AWP $1 to $3 per vial.)

Ashley N. Lewis, PharmD, BCPS, is a drug information specialist at University of North Carolina Hospitals (UNCH). She completed her pharmacy training at Virginia Commonwealth University and went on to complete a general pharmacy practice residency followed by a drug information specialty at the Medical University of South Carolina. She is currently the pharmacy and therapeutics secretary at UNCH and manages the day-to-day operations of the Drug Information Center and serves as a clinical assistant professor at the UNC Eshelman School of Pharmacy.

1. Exparel [package insert].  Pacira Pharmaceuticals, Inc: San Diego, CA. October 2011.

2. Bupivacaine, liposomal (Drug Evaluation). In: DRUGDEX® System [Internet database]. Greenwood Village, Colo: Thomson Reuters (Healthcare) Inc. Updated periodically.

3. Bergese SD, Ramamoorthy S, Patou G, Bramlett K, Gorfine SR, Candiotti KA. Efficacy profile of liposome bupivacaine, a novel formulation of bupivacaine for postusurgical analgesia. 

4. Dasta J, Ramamoorthy S, Patou G, Sinatra R. Bupivacaine liposome injectable suspension compared with bupivacaine HCl for the reduction of opioid burden in the postsurgical setting. 

Formulary Drug Review

Liposomal Bupivacaine (Exparel)

The role of information technology in pharmacy practice is dynamic and not likely to lose relevance in the coming years. To some degree, pharmacists are interested in information technology because we can envision it increasing efficiency in our daily tasks and improving our access to vital information. However, federal legislation is also driving adoption of Health Information Technology (HIT) for its potential impact on patient safety. This is not a new concept, as the role of HIT in reducing medical errors has been discussed on the national stage since 

What is new is our profession’s most recent initiative to evaluate our practice model. The American Society of Health-System Pharmacists’ (ASHP’s) Pharmacy Practice Model Initiative (PPMI) presents a unique opportunity to evaluate the delivery of pharmaceutical care in such a way that incorporates safe and effective adoption of HIT.

 It is pertinent at this time to consider evidence supporting PPMI recommendations related to HIT as well as barriers to successful implementation and utilization of HIT to support innovative pharmacy practice models.

According to the Office of the National Coordinator, HIT is defined as the application of information processing involving both computer hardware and software that deals with the storage, retrieval, sharing, and use of health care information, data, and knowledge for communication and decision making.

 The first of 2 reports from the Institute of Medicine (IOM), 

, suggests that if implemented appropriately, HIT should:

Use constraints, forcing functions, protocols, and checklists

This report, among other things, encouraged careful consideration of information technology as a means of improving patient safety. Specifically, the IOM report promotes adoption of a proactive approach by examining processes of care for threats to safety and redesigning them before accidents occur, inclusive of HIT processes. Ancker et al describe the “Triangle Model” for evaluating the effect of HIT on quality and safety.

 This model acknowledges the interactions between technology, providers, and an organization to influence quality and safety outcomes, with patients at the center of the model.

, which was broader in scope than the first report, recommended that HIT be used to improve access to clinical information and support clinical decision-making. The report also recommended a national health information infrastructure. This infrastructure would not be some sort of centralized government database, as may be a common misconception. Rather, it could be described as “rules for the road.” 

 defines the infrastructure as a set of technologies, standards, applications, systems, values, and laws that support all facets of individual health, health care, and public health. This standardization would support communication across the continuum of care and improve access to health information.

In keeping with the theme of standardization, the legislative response to these 2 reports, starting with the 

Medicare Prescription Drug Improvement and Modernization Act 

of 2003, aimed to increase interoperability and standardization by requiring Medicare Part D programs to support electronic prescribing.

 This prompted the creation of technical communication standards. Following in 2004, the 

Health Information Technology Adoption Initiative

, an executive order, established the position of National Heath Information Technology Coordinator within the Department of Health and Human Services.

		Ensures that needed information is available at the time and place of care

Improves health care quality, reduces medical errors, and advances the delivery of appropriate, evidence-based medical care

Reduces health care costs resulting from inefficiency, medical errors, inappropriate care, and incomplete information

Promotes more effective health care marketplace through widely available, accurate health information

Improves the coordination across the continuum of care

Ensures that patients’ individually identifiable health information is secure and protected

Health Information Technology for Economic and Clinical Health (HITECH) Act

 of 2009 that legislative efforts gained “teeth” in the form of requirements for incentive payments and reimbursement.

 This act empowered the national coordinator, established standards and certifications, encouraged protection and privacy for health information, and established 

Stage 1 of meaningful use involves optional participation with incentive payments beginning in 2011. Institutions adhere to 20 “core” requirements, and choose 5 out of 10 “menu” items. In 2015, Medicaid and Medicare reimbursement adjustments are made in lieu of incentive payments. Stages 2 and 3 begin in 2013 and 2015, respectively, and each builds upon the previous stage in terms of requirements. Not all measures for each stage have been decided at this point, but each is meant to ensure that health care providers are making meaningful use of health information technology.

Overriding themes from the IOM reports and legislative response include human factors engineering, health information infrastructure, meaningful use of HIT, improved access to health information for decision making, and protection of health information (Table 1).

Unfortunately, the rate of implementation of HIT, specifically those aspects that affect the practice of pharmacy, is still less than ideal. As of 2007, some HIT has been widely adopted. Greater than 80% of institutions surveyed had adopted automated dispensing cabinets and repackaging automation.

 However, implementation of pharmacy information systems that interface with other HIT was only 51% and use of bar-code medication administration or electronic medication administration record was only 46%. Perhaps most alarming, as of 2010, only 14% of institutions surveyed utilized inpatient computerized provider order entry with decision support. Since 2007 and 2010, implementation has improved as described in the ASHP 2011 survey, but this information was not available prior to the PPMI summit.

In 2011, Siska and Tribble described challenges related to HIT and performed a gap analysis based on the ideal future state of pharmacy HIT adoption.

 Barriers identified include cost, adverse effects, resistance to change, insufficient staffing, interoperability issues, and privacy concerns. Although some of these are only perceived barriers, most are real and significant. However, many can be overcome or mitigated through proper evaluation and careful implementation, which are supported by the evidence reviewed thus far in this article. The gap analysis describes a future state laden with terms such as continuum of care, standardization, interoperability, track, audit, and evaluation. These concepts are supported by the IOM reports and legislative response, but how do PPMI recommendations match up?

PPMI recommendations are displayed in Table 2, and have been displayed in 2 different groups for the purposes of discussion. The first are recommendations related to specific HIT. Although the use of these technologies is supported by the reports and legislation reviewed here, the overriding themes and the future state described in the HIT gap analysis focus less on specific technologies and more on the general approach to HIT implementation and utilization.

Each of these technology solutions is part of a larger recommendation simply stating that they enable the advancement of practice models. All other recommendations are very much in line with the concepts discussed here. Not only do PPMI recommendations address human factors engineering, HIT design, and patient safety, but they also add to the discussion by addressing the concept of training pharmacy students, residents, and practicing pharmacists on the proper use of HIT.

In conclusion, it would seem that technology-related PPMI recommendations are in line with patient safety efforts as evidenced by the IOM reports and federal regulation. As pharmacists, we are fortunate to be evaluating our practice model at a time when legislation is requiring health care providers to make meaningful use of HIT to care for patients in a safe and financially responsible way. It is encouraging that we have reached consensus in such an important time in a way that is supported by other best practice statements as well as legislative initiatives.

Jacob Holler, PharmD, MS, BCPS, is a pharmacy specialist at the pharmacistdirected anticoagulation service at the Henry Ford Hospital Department of Pharmacy Services in Detroit, Michigan.

		Institute of Medicine: To Err Is Human: Building a Safer Health Care System. Washington, DC: National Academy Press, 2000.

		American Society of Health-System Pharmacists. The consensus of the Pharmacy Practice Model Summit. 

		Health IT terms glossary. HealthIT.gov website. http://healthit.hhs.gov/portal/server.pt/community/health_it_hhs_gov__glossary/1256. Accessed December 7, 2012.

		Ancker JS, Kern LM, Abramson E, Kaushal R. The Triangle Model for evaluating the effect of health information technology on healthcare quality and safety. 

		Medicare prescription drug improvement and modernization act. US Government Printing Office website. www.gpo.gov/fdsys/pkg/PLAW-108publ173/pdf/PLAW-108publ173.pdf. Accessed December 7, 2012.

		Executive order 13335: Incentives for the use of health information technology and establishing the position of the National Health Information Coordinator. US Government Printing Office website. www.gpo.gov/fdsys/pkg/FR-2004-04-30/pdf/04-10024.pdf. Accessed December 8, 2012.

		Health information technology for economic and clinical health act. Department of Health and Human Services website. www.hhs.gov/ocr/privacy/hipaa/understanding/coveredentities/hitechact.pdf. Accessed December 8, 2012.

		Pedersen CA, Schneider PJ, Scheckelhoff DJ. ASHP national survey of pharmacy practice in hospital settings: dispensing and administration. 

		Siska MH and Tribble DA. Opportunities and challenges related to technology in supporting optimal pharmacy practice models in hospitals and health systems. 

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