Patient Safety Challenges in Treprostinil Therapy
Posted on: Wednesday, 30 April 2008, 03:00 CDT
By Roncesvalles, Agnes Lee, Fu Wen; Camamo, James; Priestley, Gail
Treprostinil (Remodulin(R)) is a new therapy for pulmonary hypertension. A multidisciplinary plan for safely managing the drug is described, and includes a flow chart to guide practice through high-risk issues. New therapies and medications are an exciting part of health care, bringing hope of improved quality of life for patients. However, innovations also present a challenge to a health care system when the therapy is complex and used infrequently. A quality improvement process conducted to assure safe and effective use of treprostinil (Remodulin?), a new medication for treating pulmonary hypertension, is described.
Background
Pulmonary hypertension is rare but considered to be one of the most serious and devastating chronic disorders of the pulmonary circulation, when pressure in the pulmonary artery rises above normal levels and has the potential to become life threatening. The American College of Chest Physicians (ACCP) revised the classification of pulmonary hypertension to describe more accurately the contemporary understanding of the disease (Rubin, 2004). Pulmonary arterial hypertension (PAH) is now classified as either idiopathic pulmonary arterial hypertension (IPAH), formally known as primary pulmonary hypertension, or familial pulmonary arterial hypertension (FPAH). Other categories for pulmonary hypertension are related to specific etiologies (see Table 1). Currently, hemodynamic criteria for defining PAH are not accepted uniformly; however, most clinicians use a mean pulmonary artery pressure greater than 25 mmHg with a pulmonary capillary pulmonary wedge pressure less than 15 mmHg (Rubin, 2004).
Although the exact pathophysiology of PAH is unknown, at least three factors appear to contribute to its development: vasoconstriction, vascular wall remodeling, and thrombosis in situ (Clavecilla & De Marco, 2003; Gain & Rubin, 1998). Together, these factors cause increased pressure in the pulmonary artery and result in right ventricular hypertrophy. Patients diagnosed with PAH typically experience fatigue, shortness of breath with minimal exertion, chest pain, syncope, bluish lips and skin, lower- extremity edema, and eventually right ventricular heart failure and death (Clavecilla & De Marco, 2003; Gain & Rubin, 1998). Exertional intolerance can be quantified using the World Heath Organization classification of functional status of patients with pulmonary hypertension (see Table 2) (Rubin, 2004). Treatment for PAH is aimed at reducing pulmonary pressure, removing edema, and preventing clot formation (Badesch et al., 2004). Patients typically are managed with vasodilators, diuretics, and anticoagulants. Supplemental oxygen, digoxin (Lanoxin?), and intravenous inotropes may be administered in certain situations (Badesch et al., 2004; Berkowitz & Coyne, 2003).
Epoprostenol (Flolan?) and treprostinil are prostacyclin analogues used to treat PAH. Both agents work by dilating the pulmonary and systemic vasculature and inhibiting platelet aggregation. Epoprostenol was the first of these agents to be approved by the U.S. Food and Drug Administration (FDA), and current ACCP guidelines recommend continu-ous infusions of intravenous epoprostenol for patients with PAH in functional class III and IV who do not respond to or are not candidates for calcium channel blocker therapy (Badesch et al., 2004). Although epoprostenol is effective at managing patients with PAH, several limitations with its use led to the development of treprostinil.
The FDA approved treprostinil in 2002 for subcutaneous use and in 2004 for intravenous use for treating PAH in patients with New York Heart Association (NYHA) (see Table 2) functional class II, III or IV symptoms (United Therapeutics Corporation, 2006). Treprostinil is recommended as an alternative for patients with PAH in NYHA functional class IV (Badesch et al., 2004). During clinical testing, treprostinil improved symptoms associated with PAH, including distances walked during the 6-minute walk test (Simonneau et al., 2002). Treprostinil possesses several advantages that make it an attractive alternative to intravenous epoprostenol (United Therapeutics Corporation, 2006):
1. Unlike epoprostenol, treprostinil can be administered subcutaneously and does not require central venous access; therefore, complications associated with the intravenous route of administration are avoided.
2. Treprostinil has a longer elimination half-life compared to epoprostenol (2-4 hours vs. <6 minutes). As a result, adverse events associated with abrupt discontinuation in treatment are minimized (for example, rebound pulmonary hypertension, cardiovascular collapse, and death).
3. Treprostinil is administered using a subcutaneous infusion pump that is significantly smaller than the intravenous pump required for epoprostenol administration. Administration therefore is more convenient for the patient.
4. Treprostinil is stable at room temperature, while epoprostenol must be kept cold using ice packs.
5. The subcutaneous infusion pump used for treprostinil is refilled every 72 hours. In contrast, the intravenous infusion pump for epoprostenol requires medication replacement every 24 hours. Therefore, treprostinil may be more convenient for patients and caregivers.
Despite these advantages, however, the use of treprostinil in the inpatient setting provides hospitals with additional challenges.
A Quality Improvement Effort: Designing a Safe Medication Administration Process
This project was conducted in a 350-bed university-affiliated medical center in the southwestern United States. Drawing on experience from the use of epoprostenol, staff involved in the care of patients with pulmonary hypertension anticipated potential care issues associated with treprostinil?s unique features. For example, treprostinil is available in multiple strengths, has unusual dosing (in nanograms), and is administered subcutaneously via a pump that would be new to the institution. In keeping with national patient safety initiatives, safe administration of the medication was a primary concern.
A task force was convened to identify problems and solutions and to develop guidelines for the care of patients receiving treprostinil. The task force included representatives from nursing, pharmacy, nursing administration, biomedical engineering, medical staff, and the hospital supply department. Table 3 summarizes the problems identified by the task force and possible solutions; a discussion of each issue follows.
Issue 1: Availability and Storage of Infusion Pumps and Supplies
The U.S. FDA had approved one infusion pump for subcutaneous administration of treprostinil, the MiniMed(R) 407C pump (Medtronic MiniMed, Northridge, CA) (see Figure 1). This pump is small, convenient for patients, and allows administration of extremely small volumes of medication via a 3.2 ml syringe. Upon initiation of therapy, patients are provided with two of their own pumps to assure that they always have a back up available in case of pump failure. The pumps are provided by the local home infusion company that supports this therapy.
More familiar in the outpatient setting, this type of pump was not owned by the hospital. The task force identified a need for the hospital to purchase pumps for several reasons:
1. Patients would be able to have therapy initiated immediately rather than wait for pumps to be delivered from the home infusion company.
2. Although patients are instructed to bring their back-up pumps when admitted to the hospital, this safety instruction could be overlooked in an emergency. In such a case, the hospital pump could be utilized.
3. When not in use for patients, the spare pumps would be available for staff education.
Two Mini-Med pumps were purchased by the hospital based on the recommendation of the task force.
Due to the pumps? small size (about the size of a pager), a reliable tracking system was required to prevent their loss. The pharmacy was selected to store the pumps because of its central location. To further secure these devices, the pumps would be kept in a locked cabinet along with the treprostinil vials. A logbook was created to doc-ument the required signatures of a pharmacist and nurse when the pumps are checked in and checked out. In addition, the MiniMed 407C pump requires special supplies that were not available in the hospital: specific tubing, syringes, subcutaneous needles, insertion devices, and batteries. The committee members obtained the specific product information and coordinated the acquisition and stocking of these supplies.
Issue 2: Low Volume of Infusion Pump Alarm
Initial experience with the pump revealed an unanticipated challenge the low volume of the pump alarm. The pump has three adjustable volume settings for the alarm. While the maximal volume is adequate to alert the patient, it could not be heard outside the patient?s room in the general care area. As noted by the Joint Commission (2004), audible alarms are an important safety issue.
An investigation of the pump alarm by the biomedical engineering member concluded that further increases in alarm volume were not possible. As a result, the committee was faced with the challenge of providing safe monitoring. The proposed solution was based on the 2- 4 hour half-life of the drug. Nurses conduct pump checks for proper function and alarm state every 2 hours. Should the pump fail or an alarm state not be heard outside the room, the 2-hour frequency is within the half-life of the drug. The team designed a flow chart that addresses all the safety issues of the drug administration (see Figure 2). Issue 3: Medication Issues
Treprostinil is available in multiple concentrations: 1 mg/ml, 2.5 mg/ml, 5 mg/ml, and 10 mg/ml (United Therapeutics Corporation, 2006). Because it is administered subcutaneously in very small volumes (e.g., 0.002 ml/hr), the variable concentrations allow for increasing dosage over time while limiting the volume of drug infused. For example, as a patient?s dose is increased gradually (requiring an increased volume of medication), a more concentrated solution of treprostinil can be used to reduce the volume infused. Because all concentrations of the drug would need to be available in the hospital, another potential error was identified in drug preparation and administration calculations. To eliminate this potential error, physicians were required to include drug concentration in their orders. Medication concentration also was included in the Remodulin Flow Chart.
Although treprostinil has a half-life of 2-4 hours, delays in drug availability must be avoided to prevent interruptions in drug administration and the potential for cardiopulmonary instability. A coordinated system was needed to avoid disruption of medication delivery. Treprostinil is also an expensive medication; avoiding unnecessary drug wastage is important to control costs.
The hospital pharmacy acquired stock supplies of all the concentrations of treprostinil as well as the special syringe used for the MiniMed 407 pump. Medications were prepared in the pharmacy and delivered to the nursing units in the special syringe. The nurse caring for the patient communicated with the pharmacist to ensure that new syringes were delivered on time. The flow chart, which is completed every 2 hours, addressed the amount of medication remaining in the syringe. Pharmacy was to be notified at least 3 hours before a new syringe would be needed.
The basis for treprostinil dose calculations is the patient?s weight (United Therapeutics Corp, 2006). By convention, practitioners identify a dosing weight (Accredo Therapeutics, 2008). The dosing weight is not changed over time as the patient?s actual weight fluctuates. Titration of the drug is based on symptoms and side effects, not changes in the patient?s actual weight. The dosing weight provides stability in drug calculations and prevents abrupt changes in the amount of drug delivered. For example, a patient may be readmitted to the hospital with severe peripheral edema. The patient?s weight at that time may be greater than the original dosing weight; diuresis over subsequent days would result in a dramatic decrease in the actual weight, but not a change in the dosing weight.
The concept of a dosing weight also is used for epoprostenol, but otherwise is uncommon. The concept needed to be clear to prescribers, pharmacists, and nurses to avoid errors in drug calculations and administration. In addition, the computerized charting system defaults to an admission weight for automated dose calculations for infusions. Treprostinil doses are ordered in nanograms/kilogram/minute, another potential source of error identified by the task force.
To reduce potential errors in the prescribing process, dosing weight and doses in ng/kg/min are required fields in the computerized physician order entry system. Confirmation of the patient?s dose, infusion rate, and drug concentration can be obtained from the home health agencies. Dosing weight is specified on the top of the flow chart and is used for all drug calculations during the hospitalization. Changes must be made manually in the computerized charting system to substitute the dosing weight for the automated admission weight. Two nurses double check all dose calculations and the infusion pump settings.
Issue 4: Nursing Care Issues And Education
As a vasodilator, treprostinil may cause hypotension (United Therapeutics Corporation, 2006). The drug is initiated at very low doses (e.g., 1.25 nanograms/kg/ minute) to minimize untoward effects. The dose is increased gradually as the patient tolerates to maximize the benefits of the drug. Positive effects of the drug therapy include decreased dyspnea, chest pain, fatigue, and improved symptoms of right ventricular failure.
Higher titration of the drug dose may be limited by side effects. Over-medication may result in hypotension (United Therapeutics Corporation, 2006). Other symptoms that may limit higher drug doses include flushing, headache, jaw pain, nausea, vomiting, and diarrhea. Although not life-threatening, these symptoms may be intolerable and require a decrease in the treprostinil dose. Over time, patients usually adjust to the dose, side effect symptoms subside, and they are able to tolerate increases in the medication. Nursing care includes frequent monitoring for these symptoms (see Table 4).
Additional unique management issues for treprostinil arise from the subcutaneous route for infusion. The drug may cause a local inflammatory tissue reaction (Badesch et al., 2004) in which the skin becomes red and swollen, resembling infection. Many patients also experience pain at the injection site. Initial management recommendations include site rotation every 3 days (Eells, 2004) to decrease pain. Site changes have been extended up to 28 days in practice, with the observation that pain typically decreases after 3 days (Lang et al., 2006). Topical ointments may be administered to alleviate the pain (Eells, 2004).
The needle insertion site must be inspected for signs and symptoms of infection. Site infections occur, but are not common (Lang et al., 2006). Purulent drainage, abscess, or new inflammation at a site that has improved (after 3 days) would be signs of infection. The injection site is rotated per physician order or as needed if there are signs of infection. Occasionally, patients are unable to tolerate the local site reactions and another drug or route of administration must be used.
The task force collected information related to drug administration, effects and side effects, pumps and supplies, and required observations to develop a comprehensive protocol. The protocol serves as a patient care guide and supports the education of new staff. The flow sheet guides daily observations and drug administration. The flow sheet was designed to:
1. Reduce adverse medication events by using a consistent drug infusion practice.
2. Outline the proper pump checks, frequencies, and elements in the drug calculations as well as provide a consistent format for documentation.
3. Serve as a communication tool for the many disciplines involved in the care of these patients.
4. Help nurses master the care process by reinforcing practice.
In addition to the patient name and medical record number, the dosing weight, current drug concentration, and dose are recorded on the top of the flow sheet. During the scheduled checks every 2 hours, verification of the dose, infusion rate, infusion site, and battery is documented.
Education Plan
Given the complexities and uncommon features of treprostinil, the task force concluded that a well-organized, comprehensive educational program for the staff would be essential. Because pulmonary hypertension is a relatively rare disease, administration of treprostinil was limited to two intensive care units and two general care units.
The multidisciplinary education plan was developed by physicians, the home health agency, committee members, and members of the nursing staff. The education program included a videotape of psychomotor skills, protocol, selflearning modules, and bedside folders with drug information and resources such as the drug Web site (www.remodulin.com).
Because patients and caregivers must manage the treprostinil administration at home, patient education is very important to assure safe therapy. Education is provided primarily by staff of the home infusion companies that distribute and support the therapy; their contact information is available on the Web site. Hospital staff nurses reinforce the education and supervise patient administration of the drug. Education includes pump function, battery checks, and medication preparation, including priming the tubing and syringe changes, site assessment for infection, and how to change sites. Patients and their caregivers need to know the drug?s effects and side effects, signs and symptoms of underdosing and overdosing, and when to call the home health nurse. Patients are instructed to not stop treprostinil infusion. Finally, teaching must include emergency management and contacts (Eells, 2004).
Conclusion
The challenges encountered with treprostinil therapy for treating PAH led to the creation of a multidisciplinary quality improvement task force. Treprostinil infusion pumps were purchased by the hospital to provide safe back up. The comprehensive protocol and flow chart were created to serve as guidelines for safe drug administration. The task force also addressed staff and patient education, pump alarm issues, and order entry requirement to reduce errors. The collaborative efforts of staff, administration, pharmacy, biomedical engineering, medicine, and the home health agency allowed the task force to achieve its goal of creating a safe medication administration process.
Table 1.
Nomenclature and Classification of Pulmonary Hypertension
PAH
IPAH
FPAH
Collagen vascular disease
Congenital systemic to pulmonary shunts
Portal hypertension
HIV infection
Drugs and toxins
Other
Associated with significant venous or capillary involvement
Pulmonary veno-occlusive disease
Pulmonary capillary hemangiomatosis
Pulmonary Venous Hypertension
Left-sided atrial or ventricular heart disease
Left-sided valvular heart disease
Pulmonary Hypertension Associated with Hypoxemia
COPD
Interstitial lung disease Sleep-disordered breathing
Alveolar hypoventilation disorders
Chronic exposure to high altitude
PH Due to Chronic Thrombotic and/or Embolic Disease
Thromboembolic obstruction of proximal pulmonary arteries
Thromboembolic obstruction of distal pulmonary arteries
Pulmonary embolism (tumor, parasites, foreign material)
Miscellaneous (sarcoidosis, histiocytosis X, lymphangiomatosis, compression of pulmonary vessels)
PAH = pulmonary arterial hypertension; IPAH = idiopathic pulmonary arterial hypertension; FPAH = familial pulmonary arterial hypertension; HIV = human immunodeficiency syndrome; COPD = chronic obstructive pulmonary disease
Adapted from Rubin, 2004, with permission.
Table 2.
New York Heart Association Functional Classification and World Health Organization Classification of Functional Status
A. New York Heart Association Functional Classification
Class 1: No symptoms with ordinary physical activity
Class 2: Symptoms with ordinary activity. Slight limitation of activity
Class 3: Symptoms with less than ordinary activity. Marked limitation of activity
Class 4: Symptoms with any activity or even at rest
B. World Health Organization Functional Assessment Classification
Class I: Patients with pulmonary hypertension but without resulting limitation of physical activity. Ordinary physical activity does not cause undue dyspnea or fatigue, chest pain, or syncope.
Class II: Patients with pulmonary hypertension resulting in slight limitation of physical activity. They are comfortable at rest. Ordinary physical activity causes undue dyspnea or fatigue, chest pain, or syncope.
Class III: Patients with pulmonary hypertension resulting in marked limitation of physical activity. They are comfortable at rest. Less than ordinary activity causes undue dyspnea or fatigue, chest pain, or near syncope.
Class IV: Patients with pulmonary hypertension with inability to carry out any physical activity without symptoms. These patients manifest signs of right-heart failure. Dyspnea and/or fatigue may even be present at rest. Discomfort is increased by any physical activity.
Adapted from Rubin, 2004, with permission.
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Agnes Roncesvalles, BSN, RN, is a Senior Nurse Recruiter, University Medical Center, Tucson, AZ.
Fu Wen Lee, MSN, RN, is a Clinical Leader, Telemetry Unit, University Medical Center, Tucson, AZ.
James Camamo, Pharm D, is a Pharmacist, Department of Pharmacy Services, University Medical Center, Tucson, AZ.
Gail Priestley, MS, CNS, APRN,BC, CCRN, is a Clinical Nurse Specialist, Medical Intensive Care Unit, University Medical Center, Tucson, AZ.
Acknowledgment: The authors would like to thank Dr. Steven Knoper, Kristy Thompson, David Moore, Laurel Hizer, Yvonne Huckleberry, and Deon Walker (Accredo Therapeutics) for their assistance in this project.
Copyright Anthony J. Jannetti, Inc. Apr 2008
(c) 2008 Medsurg Nursing. Provided by ProQuest Information and Learning. All rights Reserved.
Source: Medsurg Nursing
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