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Saudi Journal of Kidney Diseases and Transplantation
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ORIGINAL ARTICLE  
Year : 2021  |  Volume : 32  |  Issue : 1  |  Page : 111-117
The Impact of Role of Pharmacists in Renal Dosage Adjustment Program on Renal Drug Dosing Errors: A Quasi-Experimental Study


Department of Pharmaceutical Care, King Abdullah International Medical Research Center, King Saud Bin Abdulaziz University for Health Sciences, Ministry of the National Guard - Health Affairs, Jeddah, Saudi Arabia

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Date of Web Publication16-Jun-2021
 

   Abstract 


Studies have reported high prevalence of inappropriate dosing in patients with renal impairment, which was significantly reduced with pharmacists’ interventions. The objective of this study was to assess the proportions of renal drug dosing errors following the implementation of pharmacists-led renal drug dosing adjustment program. This was a quasi-experimental study conducted at the King Abdul Aziz Medical City, a tertiary teaching hospital, Jeddah, Saudi Arabia. The study comprised of 3 phases. The pre-phase and post-phase evaluated drug orders for dosing appropriateness. During the intervention phase, a renal drug dosing adjustment program was implemented, which included educational sessions on dosing in renal insufficiency and a renal drug dosing guidance. The primary outcome was to assess the change in the proportions of dosing errors following the intervention. In the pre-phase, inappropriate dosing was noted in 20.1% (70/348) of orders that required dosing adjustment. Among the total dosing errors, 44.2% (31/70) were further corrected, and pharmacists have documented intervention in 48.3% (15/31) of the corrected orders. In the post-phase, inappropriate dosing was noted in 21.9% (76/346) of orders that required dosing adjustment. Among the total dosing errors, 39.4% (30/76) were further corrected, and pharmacists have documented intervention in 66.6% (20/30) of the corrected orders. There was no statistically significant difference in inappropriate drug dosing between pre-phase and post-phase with a P = 0.56. The intervention was not associated with significant reduction in renal dosing errors, although pharmacist involvement in the corrected orders orders increased after the implementation of the intervention. This may indicate the need to integrate renal dosing guidance into the hospital prescribing system to optimize drug dosing in renal patients.

How to cite this article:
Alqurashi BY, Elsamadisi PS, Aseeri MA, Ismail SE. The Impact of Role of Pharmacists in Renal Dosage Adjustment Program on Renal Drug Dosing Errors: A Quasi-Experimental Study. Saudi J Kidney Dis Transpl 2021;32:111-7

How to cite this URL:
Alqurashi BY, Elsamadisi PS, Aseeri MA, Ismail SE. The Impact of Role of Pharmacists in Renal Dosage Adjustment Program on Renal Drug Dosing Errors: A Quasi-Experimental Study. Saudi J Kidney Dis Transpl [serial online] 2021 [cited 2021 Jul 31];32:111-7. Available from: https://www.sjkdt.org/text.asp?2021/32/1/111/318512



   Introduction Top


Renal drug dosing errors is a common problem in patients with renal impairment that can lead to adverse effects, hospital admission, or extending hospitalization time.[1] Studies have reported high prevalence of inappropriate dosing in hospitalized patients with renal impairment ranging from 15% to 58.2%.[2],[3],[4],[5],[6],[7],[8],[9],[10],[11] Given the pharmacokinetic changes that occur in this population, dosing of prescribed drugs has to be carefully evaluated.[12] A study conducted by Drenth-van Maanen et al reported that 71.4% of inappropriately doses medications had the potential to cause moderate to severe harm.[13]

Several strategies have been studied to reduce renal dosing errors to improve patient care and reduce the incidence of adverse events.[6],[8],[14],[15],[16],[17] These strategies include: the implementation of a clinical decision support system (CDSS), implementation of estimated glomerular filtration rate (eGFR) or creatinine clearance (CrCl) alert system, presence of clinical pharmacists, and development of renal dosage guidelines for pharmacists’ use.

The proportion of renal dosing errors in not known in our hospital. The large divergence of the prevalence of renal dosing errors reported in studies necessitates the evaluation of each institution’s practice and apply methods to reduce renal dosing errors. Aiming to optimize therapeutic efficacy and minimize adverse events, we conducted a study to assess the change in proportions of renal drug dosing errors following the implementation of pharmacists’ led renal drug dosage adjustment program.


   Subjects and Methods Top


Study design and sampling

This study was quasi-experimental with two different cohorts of patients before and after the intervention conducted at King Abdul Aziz Medical City, a tertiary teaching hospital, Jeddah, Saudi Arabia. The study was conducted from September 2016 to April 2017. The study was granted approval of Institutional Review Board of King Abdullah International Medical Research Center.

We identified our cohort through a convenience, systematic sampling, for prescribing orders three days every two weeks until the sample size was achieved. We aimed to capture various prescribing patterns and difference among pharmacists during various shifts with our sampling strategy.

Inclusion criteria

Patients were included if they were adults over the age of 18 years, hospitalized in a medical or surgical ward, and had chronic kidney disease (CKD) with a CrCl <60 mL/min including those with end-stage renal disease patients on regular hemodialysis(HD) and acute kidney injury (AKI). The CrCl was calculated using the Cockcroft-Gault (CG) equation.[18] AKI was defined per the Acute Kidney Injury Network’s criteria as “an increase in serum creatinine ≥0.3 mg/dL (≥26.5 μmol/L) or 50% form baseline within 48 hours”.[19],[20] Medication orders for patients were excluded if they were STAT orders and/or did not require renal dosing adjustment.

Intervention

In the intervention phase, educational sessions were provided to inpatient pharmacists. The sessions included methods for estimation of renal function, proper equations to be used for dosing adjustment, dosing in special populations, dosing principles in AKI and CKD using practical cases. Pharmacists were encouraged to communicate with the clinical pharmacists covering the ward if there is any doubt regarding dose adjustment in patients with AKI. Additionally, using multiple drug references (Micromedex, LexiComp, and manufacturers’ labeling), a dosing guidance tool was developed which included all formulary agents that require renal dosage adjustment. The guidance tool was made available and was easily accessible to staff pharmacists. This tool undergoes regular update based on the above-mentioned references’ suggestions if appropriate.

Outcomes

The primary outcome was assessing the change in the proportions of renal dosing errors following the implementation of pharmacists’ led renal drug dosing adjustment program.

Secondary outcomes included identifying the most common pharmacological classes of drugs associated with renal dosing errors, the frequency of pharmacist interventions, and comparing proportions of renal drug dosing errors among various stages of CKD. Pharmacological classes were classified into four distinct categories: antimicrobial agents, cardiovascular agents, neurological agents, and other agents.

Assessment of outcomes

During the pre-phase, orders were screened for eligibility and evaluated for renal dosing appropriateness.

Similarly, in the post-phase, all orders were screened and eligible drug orders were evaluated for renal dosing appropriateness. The selection of drug orders in this phase was at randomly chosen time without a prior knowledge of pharmacists.

In both phases, pharmacy practice resident evaluated the appropriateness of drug dosing in patients with CKD based on the developed tool. However, for patients with AKI, two clinical pharmacists reviewed the appropriateness of the orders independently.

Sample size

It was estimated that a total of 344 orders requiring renal drug dosing adjustment in each of study phase would provide a 90% power to detect a 50% difference based on prevalence of renal drug dosing errors of 15% with an alpha value of 0.05.[1]


   Statistical Analysis Top


Descriptive statistics (mean ± Standard deviation, median, interquartile range and proportions) were used for the baseline characteristics as well as for the primary and secondary outcomes, as deemed necessary. Probability test for proportions and t-test was used to detect differences in proportions and mean differences for continuous normally distributed variables, respectively. Logistic regression was used to compare the odds of inappropriate drug dosing among various stages of CKD in each phase. Intra-class correlation coefficient was used to assess the reliability between the two clinical pharmacists who assessed the appropriateness of orders in AKI. All data analysis was performed using Microsoft Excel 2016 and STAT14 software (StataCorp LP, College Station, TX, USA).


   Results Top


Pharmacy practice resident provided educational sessions to 45/47 (95.7%) of pharmacists for renal drug dosing and the use of dosing guidance tool.

A total of 274 patients were included, 134 in the pre-phase and 140 in the post-phase. The baseline characteristics are provided in [Table 1]. CKD patients were higher in pre-phase (81.3%) compared to post-phase (67.8%).
Table 1: Baseline characteristic of study participants.

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Pre-phase prescribing orders required renal dosing adjustment were identified in 348 out of 1372 orders screened. Majority of the orders were for CKD patients compared to AKI. Post-phase prescribing orders required renal dosing adjustment were identified in 346 orders of 1400 orders screened. Orders for CKD was double that of AKI. [Table 2] represents the proportions of renal dosing errors in each of the study phases.
Table 2: Renal drug dosing in the pre-phase and post-phase.

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[Table 3] represents the distribution of renal dosing errors among different stages of renal impairment in each of the study phases. High dosing errors were reported in HD patients [41.1% (21/51)] and 30.7% (16/51) in the pre-phase and post-phases, respectively.
Table 3: Percentage of renal drug dosing errors among different creatinine clearance categories in pre-phase and post-phase.

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[Figure 1] demonstrates the percentage of renal dosing errors among different pharmacological classes in each of the study phase. The majority of renal dosing errors were noted with anti-microbial agents in both phases.
Figure 1: Percentage of inappropriate renal dosing among different pharmacological classes in the pre-phase and post-phase.

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For AKI orders, the average measure of intra-class correlation coefficient was 0.84 with a 95% Confidence interval (0.71–0.89), P <0.001, indicating a very good reliability between clinical pharmacists who assessed AKI orders.


   Discussion Top


Our results are contrary to other studies that reported significant improvement in dosing errors after applying certain interventions. Although the intervention was not associated with a significant reduction in dosing errors, pharmacists’ contribution to correct inappropriately dosed drugs increased from 48.3% in the pre-phase to 66.6% in the post-phase. These percentages reflect only the documented correction that was implemented by the pharmacist after the physician agreement. In some orders, the pharmacist may contact the physician and the correction performed by the physician in the system or the physician might disagree with the pharmacist’s recommendation. In such cases, the therapeutic intervention will not be documented in the system which underestimates the overall interventions by pharmacists.

In contrast to our findings, several studies evaluating methods to improve the practice in renal drug dosing showed statistically significant benefits. However, they have different setting of intervention. For example, a study conducted by Roberts et al, showed an improvement in the prescribing of some renally eliminated medications after the implementation of a CDSS along with automatic calculation of the eGFR.[14] Additionally, a systematic review summarized studies that assessed the effectiveness of CDSS in regard to drug prescribing in renal impairment, the review reported an improvement in physicians’ prescribing after the implementation of CDSS.[21] Another study conducted by Falconnier et al, demonstrated that the presence of a clinical pharmacist providing education to the physicians as well as recommending dosage adjustments resulted in a significantly greater frequency of renal drug dosing adjustment compared to that of the control group (81% vs. 33%; P <0.001).[15] Díaz et al noted an increase in the frequency of appropriate dosing (65% to 86%; P <0.001) following the implementation of an eGFR alert system along with the development of renal dosage guidelines for staff pharmacists’ use.[16] Consistently, Ghazali et al demonstrated a significant decrease in the percentage of errors (53% to 27.5%; P <0.001) following the development of a renal dosing guideline for utilization by the clinical pharmacists.[6] In contrast, Sellier et al and Oppenheim et al showed no significant change of inappropriate prescribing of certain drugs before and after the integration of the alert system for renal patients.[8],[17]

The majority of inappropriately dosed drugs were reported with antimicrobial agents and this was consistent in both phases. This should alert clinical pharmacists and infectious disease practitioners to find strategies to optimize antimicrobial dosing to improve patients’ outcome and decrease adverse events.

In our study, inappropriate dosing was high among HD and AKI patients. This raises the concern regarding the attitude and awareness of physicians and pharmacists about dosing in these populations, necessitating special care and follow-up to be provided to these patients.

Limitations to our study include: first, we have not assessed pharmacists’ adherence to the dosing guidance provided which will negatively affect the results. Second, we were not able to retrieve pharmacists’ unaccepted recommendations and this may underestimate pharmacists’ work.

Our study has several strengths. First, we included AKI orders and we had a high degree of reliability between our raters for the assessment of CrCl to decide on appropriateness of dosing in AKI orders. Second, we implemented renal dosing program and assessed prescribing errors before and after the intervention. Finally, our study was not limited to certain pharmacological classes since we included all drugs that need renal dosing adjustment.

Further researches are needed to assess the effectiveness of the integration of reported CrCl and eGFR, and drug dosing tool into the hospital system to reduce prescribing errors and to evaluate the effect of the intervention on patients’ clinical outcomes. Notably, assessing the effect of the intervention on cost reduction is an area of controversy which is worth evaluating in further studies.[6],[10],[22]


   Acknowledgement Top


We acknowledge Abrar Alsubhi, clinical pharmacist, for assistance with assessing AKI orders that helped us to peruse the study

Conflict of interest: None declared.



 
   References Top

1.
Nielsen AL, Henriksen DP, Marinakis C, et al. Drug dosing in patients with renal insufficiency in a hospital setting using electronic prescribing and automated reporting of estimated glomerular filtration rate. Basic Clin Pharmacol Toxicol 2014;114:407-13.  Back to cited text no. 1
    
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Getachew H, Tadesse Y, Shibeshi W. Drug dosage adjustment in hospitalized patients with renal impairment at TikurAnbessa Specialized Hospital, Addis Ababa, Ethiopia. BMC Nephrol 2015;16:158.  Back to cited text no. 3
    
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Hassan Y, Al-Ramahi RJ, Aziz NA, Ghazali R. Impact of a renal drug dosing service on dose adjustment in hospitalized patients with chronic kidney disease. Ann Pharmacother 2009;43:1598-605.  Back to cited text no. 6
    
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Sellier E, Colombet I, Sabatier B, et al. Effect of alerts for drug dosage adjustment in inpatients with renal insufficiency. J Am Med Inform Assoc 2009;16:203-10.  Back to cited text no. 8
    
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Salomon L, Deray G, Jaudon MC, et al. Medication misuse in hospitalized patients with renal impairment. Int J Qual Health Care 2003;15:331-5.  Back to cited text no. 9
    
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Chertow GM, Lee J, Kuperman GJ, et al. Guided medication dosing for inpatients with renal insufficiency. JAMA 2001;286:2839-44.  Back to cited text no. 10
    
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Saleem A, Masood I. Pattern and predictors of medication dosing errors in chronic kidney disease patients in Pakistan: A single center retrospective analysis. PLoS One 2016;11:e0158677.  Back to cited text no. 11
    
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Drenth-van Maanen AC, van Marum RJ, Jansen PA, Zwart JE, van Solinge WW, Egberts TC. Adherence with dosing guideline in patients with impaired renal function at hospital discharge. PLoS One 2015;10:e0128237.  Back to cited text no. 12
    
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Matzke GR, Aronoff GR, Atkinson AJ Jr., et al. Drug dosing consideration in patients with acute and chronic kidney disease-a clinical update from kidney disease: Improving global outcomes (KDIGO). Kidney Int 2011;80:1122-37.  Back to cited text no. 13
    
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Roberts GW, Farmer CJ, Cheney PC, et al. Clinical decision support implemented with academic detailing improves prescribing of key renally cleared drugs in the hospital setting. J Am Med Inform Assoc 2010;17:308-12.  Back to cited text no. 14
    
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Falconnier AD, Haefeli WE, Schoenenberger RA, Surber C, Martin-Facklam M. Drug dosage in patients with renal failure optimized by immediate concurrent feedback. J Gen Intern Med 2001;16:369-75.  Back to cited text no. 15
    
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Such Díaz A, Saez de la Fuente J, Esteva L, et al. Drug prescribing in patients with renal impairment optimized by a computer-based, semi-automated system. Int J Clin Pharm 2013; 35:1170-7.  Back to cited text no. 16
    
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Oppenheim MI, Vidal C, Velasco FT, et al. Impact of a computerized alert during physician order entry on medication dosing in patients with renal impairment. Proc AMIA Symp 2002;577-81.  Back to cited text no. 17
    
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Joannidis M, Metnitz B, Bauer P, et al. Acute kidney injury in critically ill patients classified by AKIN versus RIFLE using the SAPS 3 database. Intensive Care Med 2009;35:1692-702.  Back to cited text no. 20
    
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Tawadrous D, Shariff SZ, Haynes RB, Iansavichus AV, Jain AK, Garg AX. Use of clinical decision support systems for kidney-related drug prescribing: A systematic review. Am J Kidney Dis 2011;58:903-14.  Back to cited text no. 21
    
22.
Preston SL, Briceland LL, Lomaestro BM, Lesar TS, Bailie GR, Drusano GL. Dosing adjustment of 10 antimicrobials for patients with renal impairment. Ann Pharmacother 1995;29:1202-7.  Back to cited text no. 22
    

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Correspondence Address:
Bashaer Y Alqurashi
Department of Pharmaceutical Care, King Abdul Aziz Medical City, National Guard Health Affairs, P. O. Box 9515, Jeddah 21423, Mail Code 6255, Jeddah
Saudi Arabia
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DOI: 10.4103/1319-2442.318512

PMID: 34145120

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