Pharmacist-to-dose is a novel method to provide clinical decision support via pharmacist-managed drug therapy within CPOE systems. This service has been well received at our institution. During 2007, there were over 3,000 electronic requests for pharmacists to assist with medication management, for which pharmacists have documented an estimated 1,500 hours providing clinical pharmacy consultations. Most requests were for vancomycin and aminoglycosides, which are the focus of this investigation. Pharmacists completed requests for initial dosing of vancomycin and aminoglycosides for treatment of suspected pneumonia within a median of 29 minutes, meeting the predetermined departmental goal. There was however significant variability in the time pharmacists needed to complete the consultations, indicating a need for better understanding of the established urgency for this type of consultation, which is expected from any in-house consultant. 9
This time required for providing drug protocol management for a single patient is similar to a previous report. 10
Of greater significance was the finding that total time to pharmacy verification was longer for medication orders for vancomycin and aminoglycosides in the study group (37 vs. 20 min, p = 0.028). This difference was somewhat expected given the differing steps in medication turn-around between the two groups, which is described in . The study group accurately captures each step in the process of medication turn-around beginning with initial prescribing when the request for pharmacist-to-dose is submitted and ending with medication administration. On the other hand, in the control group, we were unable to measure each step of medication turn-around because it is difficult to account for the time taken for a provider to determine and order patient-specific dosing and subsequent therapeutic drug monitoring, when indicated. We have labeled this step, time to provider order entry. Without this unmeasured step, the fair comparison of total time to pharmacy verification between groups is not possible. Therefore, the time to pharmacist order entry was selected as the primary endpoint in order to assess time taken for a clinical pharmacist to provide a consultation. Future studies examining time to provider order entry for medications with narrow therapeutic windows and effects on medication safety are warranted.
Delays in the administration of vancomycin and aminoglycosides approaching three hours to treat patients with pneumonia were noted in both the study and control groups. The difference found in the control group of shorter overall medication turn-around time of 47 minutes was not statistically significant but may be clinically significant in certain cases. To assess the clinical impact of pharmacist-to-dose, the study also examined medication turn-around time for any first antibiotic dose, or time to first antibiotic dose (TFAD), which is an important quality indicator. Frequently, the patients studied also received broad-spectrum antibiotic therapy (e.g., an antipseudomonal β-lactam) in addition to vancomycin and an aminoglycoside. These were often administered before the study medication and may have contributed to delays in the administration of the study antibiotics, although it was not shown to be a predictor of delayed turn-around time in the multivariate analysis. Data for TFAD were similar in both groups, with most patients receiving a first antibiotic dose within approximately two hours.
There are limitations to TFAD measurement and utilization. Data for TFAD have not been clearly defined regarding time to which first antibiotic dose is most important (e.g., which class of antimicrobial should be preferentially administered). However, the importance of prompt and appropriate antibiotic administration in the treatment of serious infections is well documented. 11,12
For patients infected with multidrug resistant organisms (MDROs), such as methicillin-resistant Staphylococcus aureus (MRSA) or Pseudomonas aeruginosa
, prompt administration of vancomycin or an aminoglycoside, respectively, is critical and highlights the importance of minimizing delays in medication turn-around time for first antibiotic doses of these agents. The observed delay of 47 minutes for turn-around times of vancomycin and aminoglycosides would likely be clinically significant in the case of infection with MRSA and MDR Pseudomonas aeruginosa
. The TFAD occurred within about two hours in this study but its interpretation is limited by the absence of microbiological data to determine when the first dose of the most appropriate antimicrobial was administered.
Thus, TFAD, must be better defined. Time to first appropriate antibiotic doses (TFAAD), in the cases of serious nosocomial infections, may be a better measure where appropriateness is defined based on likely pathogens, institutional susceptibility profiles, and the selected antimicrobial agents and doses. 6
Further, for empiric antimicrobial therapy, by definition, 13
the causative pathogen is unknown at the time when antibiotic therapy is initiated. Computerized decision support may be used to accurately predict an infecting pathogen. 14
However, until this or other methods are adopted, it remains difficult to predict a pathogen and it is therefore crucial to promptly administer first doses of all antibiotics. We reported wide ranges of delays in medication turn-around times with first antibiotic orders and in the multivariate analysis, both the number of first antibiotic orders and the sequence in which they were ordered predicted turn-around time. In some cases patients did not receive a first dose of an ordered antibiotic until greater than 12 hours after electronic order entry! In response to these findings, the institutional Pharmacy & Therapeutics Committee mandated that every order entered via pharmacist-to-dose request be a STAT order, to appropriately alert medical, pharmacy, and nursing staff of the urgency needed when involved in medication ordering, distribution, and administration of first antibiotic orders for empiric therapy. Additionally, institutional-wide education and computerized order sets and protocols may be useful to decrease time to first antibiotic doses and improve appropriateness of antimicrobial regimens. 15,16
Careful consideration must be given by providers to address the balance needed for empiric antimicrobial therapy that is prompt, adequately dosed, and safe. When the need for promptness is paramount, consultation could be deferred to providing recommendations for subsequent doses and monitoring. Standardized first doses of antimicrobials could be ordered for initial doses as part of an order set or bundle along with a pharmacist-to-dose request to assist with doses to follow and therapeutic drug monitoring as indicated. Additionally, using automated medication dispensing machines may facilitate expedited medication turn-around. Standardized dosing of empiric antimicrobial therapy may be an option but further studies are needed to assess its safety, efficacy, and effects on medication turn-around time.
Another drawback of TFAD is lack of a standardized initial time point. Previous studies measuring TFAD used different initial time points for community-acquired infections (e.g., measured time from emergency department arrival to administration) 17
and hospital-acquired infections (e.g., time from clinical evidence of infection to administration). 11,12
The absence of an initial time of onset of clinical evidence of nosocomial pneumonia is a limitation of our study. Without this time point, the time taken for pharmacist review and time elapsed for patients to receive first doses of vancomycin, aminoglycoside, or other antibiotics is difficult to assess although the reported delays remain clinically important.
Multivariate analyses were performed to identify significant predictors for total time to pharmacy verification and turn-around times for vancomycin or aminoglycosides. The presence of renal dysfunction was found to be a predictor of greater total time to pharmacy verification but not for greater turn-around time. Ideally, the clinical pharmacist responsible for the care of a patient (e.g., rounding with the patient care service) with more complicated medication needs (e.g., renal dysfunction) would provide this consultation. However, after business hours, clinical pharmacists may be unavailable and in these situations, the on-call pharmacy resident is frequently consulted, in a similar fashion as the house officer cross-cover model. 5
This is yet another added step in the process, which may explain the delay in pharmacist order entry noted for patients with renal dysfunction. However, PTD is a means to ensure medication safety () in this patient population who is at risk for adverse effects of aminoglycosides and vancomycin. Attention must be given by the consulting pharmacist to balance a patient's needs for prompt therapy with necessary dosage adjustments of initial doses to prevent adverse events. 6,18
Despite noted delays, the finding of 29 minutes for pharmacists to provide vancomycin and aminoglycoside protocol management consultations is on par with national averages. 10
The time of day (e.g., office hours v. overnight) antibiotics are ordered also may affect TFAD. 19
Specifically, antibiotics ordered during night-time hours may reach patients more quickly. However, this finding was not supported in the analysis of orders for vancomycin and aminoglycosides. We observed fewer new medication orders for antibiotics overnight; order entry during 3rd
shift accounted for 17% of antibiotics ordered. Fewer orders for antibiotics and other medications may allow for faster time to antibiotic administration. Increased awareness of daytime delays may lead to quality improvements focused on antibiotic administration during this time interval. Additionally, the use of automated medication dispensing machines, although not significant in this study, may expedite medication administration. Using this mode of decentralized, nursing unit-based medication delivery has demonstrated reductions in medication turn-around, medication errors, and cost savings, 20
and should be further explored in the setting of severe nosocomial infections.
Medications that have the greatest potential to be incorrectly dosed should be the target of advanced efforts to provide medication-related clinical decision support. 21
This investigation documented provider utilization of a computerized request for clinical pharmacist consultation to dose medications. Providers most frequently requested assistance dosing medications that may cause adverse events in the absence of therapeutic drug monitoring. The most frequently requested medicines for PTD consultation were tobramycin, gentamicin, vancomycin, phenytoin and fosphenytoin, and enoxaparin. In effect, medications at higher risk for causing adverse events were identified by provider utilization of pharmacist-assisted dosing guidance. Implementation of advanced clinical decision support for dosing guidance with high-risk medicines may lead to realization of improvements in medication safety and reduction in medication-related costs. 4
Indeed, fewer medication errors for vancomycin and aminoglycoside orders were reported in the study group, although this investigation was not designed to detect a difference in medication safety. Errors were identified by providers when they discontinued an initial order for vancomycin or aminoglycosides and re-entered the order for a different dosage or interval. Since determining the initial dose of vancomycin or aminoglycosides may require more consideration and the calculation of weight-based dosing, it is not surprising that multivariate analysis identified order re-entry as a predictor of greater time for verification of medication orders. We did not, however, measure clinical outcomes to assess the quality of consultations provided via pharmacist-managed drug therapy. Previous studies have noted reductions in hearing loss, renal dysfunction, drug costs, hospital length of stay, and mortality associated with institutional use of vancomycin and aminoglycoside pharmacist-provided drug protocol management. 4
Individualized initial dosing of vancomycin and aminoglycosides and subsequent therapeutic drug monitoring are likely the root of observed benefits for collaborative services. The PTD was designed to provide patient-specific dosing. It appears pharmacists provided more individualized dosing than their provider counterparts reflected by more precise weight-based vancomycin dosing and more frequent height and weight entry in the study group, which are necessary for accurate calculation of vancomycin and aminoglycoside dosing ().
Clinical decision support for computerized request for pharmacist assistance with medication dosing may be most appropriately used in academic medical centers. The presence of continuously offered clinical pharmacy services is essential to implementing dosing decision support such as PTD, which is heavily dependent on readily available clinical pharmacists to assist providers. Other dosing support tools targeting high-risk medications and vulnerable patient populations that are less dependent on accessible personnel have been described 22,23
and may be more practical for some CPOE systems. Institutions seeking to implement services similar to PTD should be advised to consider the economics and ergonomics associated with advanced dosing guidance support services. 24
Additionally, basic medication-related CDS should be implemented before advanced methods to ensure support for clinical workflow. 1,21
The role of the clinical pharmacist in the health care team involved in using CPOE systems has not been well established. Pharmacist participation in patient care rounds has demonstrated reductions in adverse events, medication errors, hospital length of stay, and medication-related costs. 25–27
An editorial in the Journal has suggested that computer-aided pharmacist order entry (CphOE) may offer an opportunity for expansion of pharmacists' responsibilities beyond traditional distributional roles. 28
Pharmacists may be best suited to perform computerized order entries for medications to provide an additional step for pharmacist review and to allow providers to focus more on patient care responsibilities. This investigation further supports CphOE by documenting the timely provision of medication-related clinical decision support by implementing computerized requests for pharmacist-managed drug therapy.