Critically ill ICU patients typically receive a greater number of medications than patients in other care areas, and a high number of these drugs are given intravenously. A 2008 study reported that ICU nurses administer an average of 13 medications per patient per day, and seven of these were through the intravenous (IV) route.¹ While all patients are vulnerable to IV medication errors, ICU patients are at particular risk, not only due to the high number of medications received, but also due to the need for frequent titration, dose manipulation, and the medications’ narrow therapeutic indexes. While the volume of use opens the door to the possibility of error, so does the ICU working environment—which is oftentimes rife with interruptions, making proper oversight challenging. Because these severely ill patients are at the highest risk for error and adverse drug events, and their underlying illnesses reduce their resiliency and ability to compensate for complications, it is vital that health care providers manage and mitigate these risks by creating an ICU safety culture, using both standardization of processes and new technology, to ensure IV medications are administered safely and correctly.

Managing the Complexities of the ICU
The IV drug administration process is complex, and is estimated to require dozens of steps from preparation to completed drug administration and documentation. The greater the number of steps in drug administration, the higher the possibility for error. Routine medication administration is a frequent source of errors, whether due to the high volume and repetitive nature (eg, potassium supplementation) or inherent high risk. 

Other factors of the ICU environment specifically contribute to the risk for medication error, including interruptions due to emergencies, sometimes difficult working conditions due to stress or complexity, and the larger number of interventions needed to care for these critically ill patients. Drugs that are commonly used in the ICU—sedatives, antimicrobial agents, vasopressors, and anticoagulants—contribute to a higher proportion of errors than other medications and simultaneously these errors are associated with greater patient harm, including death, if not managed with care. The narrow therapeutic range of many agents in these categories and the volume of routine use are the most likely contributors to the high-risk potential.

Techniques to Ensure Standardization
When medications are prepared outside of the pharmacy there may be inconsistency in the final concentration. Safety has been improved by USP <797> standards, which have diminished the number of nurse-prepared solutions. Simple methods to minimize this source of error include the use of standardized concentrations, availability of detailed mixing instructions, and standardized labeling methods to ensure clarity of information. Pre-printed labels that indicate the drug name, concentration, date and time mixed, and which nurse prepared the drug are preferable to handwritten labels; an additional layer of safety is added through labeling the tubing as well.² Patient assessment is more efficient at shift change when all of this information is complete.

Other methods, such as use of pre-mixed IV products, can diminish the likelihood of product variability. However, for products that are prepared in the pharmacy or by nursing, standards are needed to diminish variability in the final product. Techniques to reconstitute drugs and transfer the contents to the infusion bag influence the final concentration. If the drug volume contributes significantly (eg, more than 20%) to the final volume, it may be appropriate to remove a corresponding volume from the bag prior to drug transfer. After a standard has been determined, methods should be clearly presented to staff (using recipe cards or other reference sources) so that they are practiced consistently from one technician or nurse to the next.

Weight-based dose calculation is another opportunity for standardization. Critically ill patients often have an estimated weight on admission to the emergency department, an actual weight on admission, and then daily weights throughout their stay. Septic shock patients typically receive several liters of fluid for initial therapy, and ultimately 5 to 10 liters of additional fluid for resuscitation, which affects their daily weight. While there is little data to indicate the “correct” weight, standardization is needed, and medication doses should not be recalculated daily based on shift in weight as this introduces a high risk of miscalculation and error. 

Our facility, Indiana University Health Methodist Hospital, decided to use the actual weight taken at admission as the standard weight throughout the hospital stay. However, if the weight declines by more than 20%, a new standard weight is established and changes in drug doses and infusion rates are ordered. The benefit of weight standardization is that all doses are calculated and pumps are programmed consistently, weight settings do not need to change, and variation in practice is minimized. As with most explicit policies, a few exceptions must be created; for example, drotrecogin alfa (activated) is dosed based on the weight at the time of initiation. The pump then must allow an exception that is specific for one agent, but still allow other drugs to be dosed with the standard weight.

Standardizing all aspects of IV drug therapy—concentrations, dosing units, weight for dosing calculation, preparation, and labeling—are important prerequisites for successful use of advanced technology, such as smart infusion pumps. Pharmacists should initiate and lead these standardization initiatives in conjunction with nurses and other patient-care colleagues.

Preparing for Smart Pump Implementation
Linking the standard IV solution concentrations with a smart pump library provides safeguards beyond those realized from standardization alone. The synchronization of processes from preparation to administration makes detection of error more likely, as deviations from usual practices may be more evident. It is especially valuable to describe the intended therapeutic use of the drug during ordering, which will improve the likelihood of error detection and prevention. For example, vasopressin may be dosed differently for shock due to sepsis (0.03 unit/minute) than for variceal hemorrhage (up to 0.8 unit/minute). Smart pumps may include settings for both therapeutic scenarios, but may use very different dosing limits. If this information is available at the time of order entry, solution preparation, and pump programming, optimal and efficient IV drug therapy is more likely to occur.

Smart pumps can further improve safety by standardizing the dosing units and calculating the rate in these dosing units, as well as mL/hr, eliminating the risk of calculation error. A bolus dose may be programmed to infuse over a period of time that is appropriate for the agent. Pre-defined limits for the bolus dose, infusion dose and rate, and concentration contribute to safe use of infusion therapy. 

Amiodarone is an example of a drug with complex dosing phases that can contribute to medication errors. A bolus dose of 150 mg is given over 10 minutes, followed by an infusion at 1 mg/min for treatment of ventricular arrhythmias. After 18 hours, the dose is typically lowered to 0.5 mg/min. Pump programming must consider all three phases and further accommodate repeat bolus doses of 150 mg during the infusion if there are recurrent arrhythmia events. However, amiodarone also may be given as a 5 to 7 mg/kg loading dose over 30 to 60 minutes, followed by an infusion of up to 1.25 mg/min for atrial arrhythmias. Pump settings must allow for both regimens.

The Institute for Safe Medication Practices’ (ISMP) Summit on Intravenous Medication Errors in 2008 produced a list of the features that make an ideal smart pump. The key features of the ideal pump are listed in Table 1 and include recommendations for scrolling response, dosing limits for bolus doses and infusion, reporting capabilities, and hardware features that improve efficiency and safety.³ To assist with the planning and implementation of new infusion devices, ISMP also has provided guidelines for safe implementation and use of smart infusion pumps (www.ismp.org/tools/guidelines/smartpumps/printerversion.pdf).

Continuous Drug Library Management
Over time the drug libraries within infusion pumps will need revision to accommodate new drug entities or  changes in drug use. This pattern has been exacerbated as of late, as numerous shortages of common ICU drugs have required clinicians to find alternatives to preferred agents. A clear example is the shortage of norepinephrine, which led to an increase in phenylephrine use. We have found that some patients require much higher doses of phenylephrine than anticipated to achieve the desired response—sometimes more than 200 mcg/min, and pumps that lack the proper dosing limits can complicate the medication-use process, impede patient care, and increase the risk of errors.

New Technology TrainingDeployment of new technology should be accompanied by policy statements that describe its proper use and documentation standards. Failure of staff members to use technology properly should initially trigger re-education efforts, but persistent failure to use safety technology or disregard for proper policies may necessitate corrective action. Unfortunately, regulations alone do not prevent errors⎯—we cannot mandate safety, it must be part of our culture or philosophy of practice. When our facility first started using smart pumps, failure to use the safety features led to reminders—by other pharmacists on the team, by peers at shift change, and by the tele-ICU nurses when they made electronic rounds and reviewed pump settings. Constant reinforcement of the desired behavior—not intermittent penalties—is the most useful way to model appropriate behavior for staff, and has led to near universal adoption of pump safety procedures at our facility. Nurses then feel comfortable pointing out where the pump process may be inadequate to meet their needs, helping improve nursing satisfaction and quality of care for future patients.

A simple safety feature can be incorporated into the infusion pump process by requiring an independent double-check be completed, wherein a second nurse verifies the order, pump setup, and connections to the patient, prior to initiation of therapy. However, in a busy ICU, this can mean interrupting the workflow of another nurse, potentially creating error elsewhere. If another nurse is not immediately available, this second sign-off may be deferred, allowing an error to persist until the second check, or it may be documented without actual performance. To solve this staffing issue the nursing personnel in our tele-ICU perform the independent double-check remotely and then document the action, thus improving safety and minimizing interruptions in patient care.

Developing a Collaborative Safety Team
Significant preparation is needed to ensure optimal use of smart pumps. A multiprofessional committee of nurses, pharmacists, and physicians should be assembled to define the standard concentration(s) that will be allowed, the dosing units, and the upper and lower dosing limits for the infusion and bolus doses. Periodic review of the adequacy of these parameters should be performed as a quality-control measure. For example, the dosing limits of heparin in units/hr are very broad. Our soft-maximum dose (established as a safety checkpoint to avert a potentially incorrect entry) was triggered more frequently than seemed optimal, and so the number was raised slightly. A high-dose heparin option also was needed in the library to address heparin-resistant patients or obese patients who exceeded the usual maximum dose in the initial heparin profile.

Creating an ICU Culture of Safety
Clinicians in the ICU must adapt to challenges and confront limitations to continually provide quality patient care. Unfortunately, employing these spontaneous alternative methods may bypass safety systems, although we have learned through experience that this behavior may signal that the systems have been improperly designed to achieve the stated goal. By creating and maintaining an environment where clinicians are encouraged to express concerns, seek transparent solutions to existing problems, and participate in the design of new programs, there will be a lower error rate. 

We created a culture of safety where practitioners report actual errors and near-miss errors either verbally or electronically. Inability to program a pump for a drug infusion led to a change in labeling procedures by pharmacy. Our online reporting and systematic review process allows trends to be noted more readily, but any mechanism to ensure communication of concerns is important. We acknowledge and thank the reporter, and when possible communicate the resultant changes so practitioners recognize that their concerns produce results.  

The success of this culture of safety can be assessed with the use of surveys that evaluate practitioner attitudes and willingness to report concerns. Leadership’s focus on safety is also an important component of this culture. Directors and other hospital leaders should be sure to model behaviors they want staff to embody. Also, the use of a critical incident reporting system and a willingness to report potential problems is associated with a lower risk of error in general, and especially when using IV medications in the ICU. The reporting system should be accessible and easy to understand, so all staff know how to report unsafe practices and potential sources of error.

When the safety team prioritizes error recognition and reporting, there is improved planning for methods to prevent medication errors. Groups with a safety focus learn from prior events, and apply information from a near miss to prevent future errors. When the team is focused and demonstrates a readiness for change and improvement, new processes and equipment are integrated more readily and safely. Modeling the proper behaviors and rewarding participants for recognition and reporting creates an enduring culture of safety. 

Conclusion
From medication prescribing, to drug administration, to documentation, IV drug therapy is a complex process. There are many potential sources of error involved, and the risk is compounded in busy ICUs during treatment of patients with complex, serious illness. A systematic evaluation of the risks, open discussion of the error events that are detected and averted, and a culture that supports and promotes safe medication use are needed. A multiprofessional committee should develop and institute safe medication processes, whether a facility is deploying high-technology tools or standardizing workflow. Pharmacists must assume responsibility for leading the initiatives to improve safe and effective medication use for ICU patients. 

References

1. Moss J, Berner E, Bothe O, Rymarchuk I. Intravenous medication administration in intensive care: opportunities for technological solutions. AMIA Annu Symp Proc. 2008;495-499.2. Porat N, Bitan Y, Shefi D, et al. Use of color-coded labels for intravenous high-risk medications and lines to improve patient safety. Qual Saf Health Care 2009; 18:505-509.3. Proceedings from the ISMP Summit on the Use of Smart Infusion Pumps: Guidelines for Safe Implementation and Use. Institute for Safe Medication Practices; Horsham, PA: 2009. 

Judith Jacobi, PharmD, FCCM, FCCP, BCPS, is part of the multiprofessional ICU team as a critical care pharmacy specialist for the adult critical care and neurocritical care units at Indiana University Health Methodist Hospital and is a board certified pharmacotherapy specialist. Dr. Jacobi is program director of an ASHP-accredited critical care pharmacy residency and has trained 17 residents, along with numerous doctor of pharmacy students, as affiliate assistant faculty for Purdue University and Butler University. She trained as a pharmacist at Purdue University, received her doctor of pharmacy degree from the University of Minnesota, and was one of the first critical care pharmacy residents trained at The Ohio State University. 

The Special Case of Heparin