Drug Dosing in Patients with Renal Insufficiency in a Hospital Setting using Electronic Prescribing and Automated Reporting of Estimated Glomerular Filtration Rate

Drug Dosing in Patients with Renal Insufficiency in a HospitalSetting using Electronic Prescribing and Automated Reporting of

Estimated Glomerular Filtration RateAnita L. Nielsen1, Daniel P. Henriksen2, Christianna Marinakis3, Annemarie Hellebek4, Henrik Birn5,6, Mads Nybo7, Jens Søndergaard8,

Anita Nymark1 and Court Pedersen1

1Department of Infectious Diseases, Odense University Hospital, Odense, Denmark, 2Department of Emergency Medicine, Odense UniversityHospital, Odense, Denmark, 3Dansk Lægemiddel Information, Copenhagen, Denmark, 4Department of Patient Safety, Capital Region of Denmark,

University of Copenhagen, Copenhagen, Denmark, 5Department of Nephrology, Aarhus University Hospital Skejby, Aarhus, Denmark,6Department of Biomedicine, University of Aarhus, Aarhus, Denmark, 7Department of Biochemistry and Pharmacology, Odense University

Hospital, Odense, Denmark and 8Research Unit of General Practice, University of Southern Denmark, Odense, Denmark

(Received 1 August 2013; Accepted 16 December 2013)

Abstract: In patients with impaired renal function, drug dose adjustment is often required. Non-adherence to clinical prescribingrecommendations may result in severe adverse events. In previous studies, the prevalence rate of non-adherence to recommendeddosing has been reported to be 19–67%. Using the clinical support system Renbase� as reference, we investigated the use anddosing of drugs in patients with impaired renal function in a university hospital setting using electronic prescription and auto-matic reporting of estimated glomerular filtration rate (eGFR). In all, 232 patients with an eGFR in the range of 10–49 ml/min./1.73 m2 were included. We identified 436 episodes with administration of renal risk drugs (prescribed to 183 patients): 410drugs required dose adjustment according to the eGFR and 26 should be avoided. In total, the use or dosing of 66 (15%) of the436 renal risk drugs was not in agreement with recommendations in Renbase�. This reflects less disagreement with expert guide-lines than reported previously, indicating a possible beneficial effect of electronic prescribing and reporting of eGFR. However,we also found that disagreement to some extent reflected inappropriate drug use. We conclude that despite implementation ofelectronic prescribing and automated reporting of eGFR, patients with renal insufficiency may still be exposed to inappropriatedrug use, with potential increased risk of adverse effects. Initiatives to reduce medication errors such as the use of electronicdecision support systems should be explored.

Medication errors are common causes of severe adverseevents that lead to hospital admission, prolongation of hospi-talization, severe adverse events and in some cases even death[1]. Patients with renal insufficiency are at risk of inappropri-ate drug dosing as many drugs and/or their metabolites areeliminated through the kidneys, implying a need for doseadjustment or drug discontinuation.Many studies have investigated drug use in patients with

reduced renal function [2–8]. The majority of these studieswere conducted in hospital settings. In a review of data pub-lished from 1966 to 2002, Long et al. [5] concluded that theprevalence of non-adherence to renal dosing guidelines in hos-pitals varied between 19% and 67%. More recent studies haveshown similar rates. In a Norwegian study that included 201subjects, each patient was treated with an average of six renalrisk drugs [4]. Forty-nine (25%) were prescribed drugs thatshould be avoided according to guidelines, and in 124 (62%)patients, there were other problems associated with the use ofrenal risk drugs, mostly incorrect dosing. Two studies investi-gated drug dosing at hospital discharge and showed that pre-scribed doses deviated significantly from guidelines in 40%and 52% of patients with renal insufficiency [2,3].

The introduction of automated reporting of estimated glomer-ular filtration rate (eGFR) provides prescribers with a rapid andmore informative estimate of GFR than do plasma creatinine lev-els. Although controversies exist regarding the use of estimatedcreatinine clearance or eGFR for drug dosing, the automatedreporting of eGFR may be expected to improve adherence toguidelines regarding drug dosing in renal disease [9].Thus, we investigated the prescription of drugs among hospi-

talized patients with impaired renal function in the setting ofelectronic prescription and automatically reported eGFR. Wefurthermore investigated the extent of agreement between expertdosing guidelines and the actual drug use and drug dosing.

Material and Methods

Study design. We conducted an observational study comprising adultpatients hospitalized at Odense University Hospital in the period from16 November 2011 to 31 December 2011. The study included allinpatients on 16 November 2011 and those who were admitted duringthe study period. The inclusion criteria were (i) age at least 18 years,(ii) an eGFR between 10 and 49 ml/min./1.73 m2 and (iii) at least onedrug administration recorded in the hospital electronic medical recordwithin 24–48 hr after the index eGFR measurement. Patients withinconsistencies in the medication records or admission to the intensivecare unit were excluded.Patients were identified from the laboratory database. Each patient

could only enter the study once.

Author for correspondence: Court Pedersen, Department of InfectiousDiseases Q, Odense University Hospital, 5000 Odense C, Denmark(fax: +45 66117418, e-mail: [email protected]).

© 2013 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society)

Basic & Clinical Pharmacology & Toxicology, 2014, 114, 407–413 Doi: 10.1111/bcpt.12185

Plasma creatinine was measured at the Department of Clinical Bio-chemistry and Pharmacology on an Architect instrument (Abbott,Wiesbaden, Germany) using an enzymatic colorimetric method withend-up reaction. The measurement range was 8.8–3536 lM. Qualitycontrol was assured with internal (SERO, Norway) and external (Ring-versuch, Germany) control programmes. CV for inter- and intra-assayvariation was <3.6%. The eGFR was automatically reported togetherwith the results of the plasma creatinine measurement. After identifica-tion of eligible patients (fig. 1), information on drug administration onthe day of eGFR measurement and for the following 5 days wascollected from the electronic medical records. Drugs prescribed ‘asneeded’ or p.r.n. were not included in the analysis.The hospital did not have a common policy concerning pharmacist

drug chart reviews. One department (emergency medicine) conducteddrug review five times weekly (Monday–Friday) during the study per-iod, and two departments each had drug reviews conducted two timesduring the inclusion period.

Definitions.

Renal function. The eGFR was calculated using the four-variableModification of Diet in Renal Disease (MDRD) equation without

correction for race, as recommended by the Danish Society ofNephrology [10,11]. A valid eGFR requires that the GFR is relativelystable, and in the present study, we defined an unstable GFR as agreater than 20% change in eGFR within 3 days after the index testdate. Renal insufficiency was classified by eGFR into moderate(49–30 ml/min./1.73 m2) or severe (29–10 ml/min./1.73 m2) inaccordance with the European Medicines Agency (EMA) [12].

Renal risk drugs and disagreement with Renbase� recommenda-

tion. Renbase� is an online clinical decision support systemdeveloped by independent clinical experts and is available tohealthcare professionals through the Terveysportti health portal [13].Renbase� offers drug-specific information for the different stages ofrenal impairment to aid in the selection of appropriate drugs anddosages. Searches are performed either by generic drug name, ATCcode or trade name. The drug is assigned one of the four action codesfor each stage of renal impairment: (i) no need for adjustment ofdosage or dose interval; (ii) the information is missing or it has beenevaluated on the basis of the pharmacokinetic characteristics of thedrug; (iii) adjustment of dosage or dose interval is recommended; and(iv) the drug should not be used. Renbase� recommendations maydiffer slightly from those of the drug summary of product

All with eGFR 10-49 ml/min/1.73 m2

386 patients

Excluded 154 patients

26 from the intensive care unit 24 from one department of surgery 2 transferred to another hospital within 24 hours 50 discharged within 24 hours 9 with inconsistencies in registration 13 other reasons 30 without drug administration

Included 232 patients

Administration of renal risk drugs 183 patients

No administration of renal risk drugs 49 patients

Severe renal insufficiency 90 patients

Moderate renal insufficiency 93 patients

Fig. 1. Patient inclusion. Flow chart showing inclusion and exclusion of patients and the number of patients with administration of renal risk drugsin relation to the degree of renal insufficiency (moderate or severe).


408 ANITA L. NIELSEN ET AL.

characteristics (SPCs) and from the online drug information portal,promedicin.dk [14]. Promedicin.dk is widely used by Danishphysicians for drug reference, and the information is peer-reviewed.Promedicin.dk does include dosing guidelines for most drugs in regardto patients with renal insufficiency. We used Renbase� as referencebecause in contrast to promedicin.dk, it has all data available in auser-friendly database format.Renal risk drugs were defined as drugs that, according to Renbase�,

should be either avoided or dose-adjusted according to the GFR. Twoclinical pharmacists collected information on the use of all renal riskdrugs and their dosing. Disagreement with recommendations wasdefined as a 24-hr cumulative dose (24–48 hr after index eGFR) loweror higher than recommended by Renbase�. Renbase� often recom-mends proportional dose reduction based on the dose used in patientswith normal renal function. As we had no knowledge of drug indica-tion, we used the maximal dose in patients with normal renal functionas reference for estimating disagreement in dosing. If disagreementwas identified, we examined whether there were any additional eGFRreports before or within the 24- to 48-hr period. If, based on any neweGFR, the dosing was in accordance with recommendations by Ren-base�, our evaluation of the dosing was reassigned as an agreement.If drug dosing was found to be in disagreement with Renbase�, it

was also investigated whether there was disagreement with promedi-cin.dk guidelines.

Statistical analysis. Results from descriptive analyses were reportedas medians or proportions. The Shapiro–Wilks test was used to testfor normality. Differences between groups of patients were testedusing the Mann–Whitney U-test for continuous variables, and a chi-squared test and Fisher’s exact test were used for categorical variables.All tests were two-tailed, and a p value <0.05 was considered to bestatistically significant. The data were analysed with Stata� (version12.1; Stata Corp., College Station, TX, USA).

Ethics and data safety. All data were handled anonymously inaccordance with the permission obtained from the Danish DataProtection Agency through Region Syddanmark (2008-58-0035). Theuse of data from medical records was approved by the DanishNational Board of Health (7-604-04-/258/KWH).

Results

Patient characteristics.In total, 386 consecutive patients with an eGFR 10–49 ml/min. were screened for eligibility. Among these, 154 wereexcluded due to reasons shown in fig. 1. The most commonreasons were discharge within 24 hr, no drug administrationin the 24- to 48-hr time window and being in the intensivecare unit. One surgical department used the medication admin-istration system in a different way than other departments, andwe therefore had to exclude all patients from this department.The remaining 232 patients were included in the study. Mostpatients were from the departments of emergency medicine,nephrology and cardiology, with each site representingapproximately 14% of patients. There were no differencesbetween those included and those excluded with respect toage (p = 0.96), sex (p = 0.65) or severity of renal impairment(p = 0.32).Baseline characteristics according to the degree of renal

insufficiency are shown in table 1. There were no significantdifferences in median age, but relatively more male and

younger people (18–44 years of age) among patients withsevere renal impairment.

Renal risk drugs.A total of 1633 drugs were administered: 867 drugs inpatients with moderate renal insufficiency and 766 drugs inpatients with severe renal insufficiency (table 2). Of 436 renalrisk drugs, 180 and 256 were administered to the moderateand severe renal insufficiency group, respectively.According to Renbase�, 410 of those drugs should be dose-

reduced, and 26 should be avoided in renal insufficiency(table 2). Sixty-three patients received one renal risk drug, 48patients received two renal risk drugs, 37 patients receivedthree renal risk drugs and 35 patients received a minimum offour.In 183 of the 232 included patients, at least one renal risk

drug was administered within the 24- to 48-hr period after theindex eGFR measurement. Of the 183 patients who receivedrenal risk drugs, 90 had severe renal impairment (eGFR of10–29 ml/min./1.73 m2) and 93 had moderate renal impair-ment (eGFR of 30–49 ml/min./1.73 m2; fig. 1).

Disagreement in dosing.In total, there was disagreement between actual dosing andRenbase� recommendations for 66 (15%) of 436 24-hr drugdosing episodes, 22 of 180 (12%) in the group with moderaterenal impairment and 44 of 257 (17%) in the group withsevere renal impairment (p = 0.17). Overall, 53 (23%) of the232 patients received at least one drug with which there was adosing disagreement. The frequency of disagreement did notchange significantly if the evaluation was performed usingpromedicin.dk guidelines instead of Renbase� guidelines asreference (results not shown).All drugs associated with disagreement are shown in

table 3. In the group with eGFR 30–49 ml/min./1.73 m2, therewere many cases with disagreements of little clinical impor-tance, but there were also cases likely to be of clinical impor-tance. One patient received a high dose of metformin. Ninepatients received magnesium oxide as a laxative, whichaccording to Renbase guidelines should be avoided due to therisk of hypermagnesemia. In the group with eGFR 10–29 ml/min./1.73 m2, there were a higher number of disagreements.The most common drugs involved were simvastatin (13patients), magnesium oxide [7], spironolactone [4], ramipril[4] and bendroflumethiazide with potassium chloride [3]. Thia-zide diuretics are not recommended for use in severe renalinsufficiency because they are likely to have no beneficialeffect and may have side effects. ACE inhibitors such as ram-ipril are often used in patients with renal insufficiency.According to Renbase�, the maximum dose of ramipril shouldnot exceed 5 mg daily in renal failure because 60% of ramip-ril and its active metabolite are excreted in the urine. OtherACE inhibitors may be safer alternatives. There are also alter-natives to simvastatin (atorvastatin or fluvastatin) in patientswith severe renal disease. One patient received methenamine


DRUG DOSING IN RENAL INSUFFICIENCY 409

and another valganciclovir in doses recommended for patientswith normal renal function.Significantly more renal risk drugs were administered to

patients with dose disagreement compared with patients with-out disagreements (median number of drugs per patient: 3(IQR 2-4) versus 1 (IQR 1-2), p < 0.001). There were no dif-ferences in the age distribution (p = 0.069), sex (p = 0.105)or severity of renal insufficiency (p = 0.061) when comparingthe groups with or without dose disagreement.Among 53 patients with medication disagreement, the eGFR

was stable in 24 (45%), a > 20% change was observed in 15(28%), and in 14 (26%), the stability of the eGFR could notbe evaluated because there were no eGFR measurementsbeyond day 2 after the index eGFR measurement.Administration of drugs initially identified as drugs with

dosing disagreements was monitored for 5 days after the indexdate. On day 4, the number of drug dose disagreements haddeclined by 26, in five patients because renal function hadimproved and in 21 because drugs had been dose modified ordiscontinued. On day 5, the number of disagreements haddeclined by 31. We did not monitor or evaluate drug therapyinitiated after the initial 24- to 48-hr period.

Discussion

We found that renal risk drugs were commonly used in hospi-talized patients with moderate-to-severe renal disease and that

in a significant number of cases, dose adjustments or drug dis-continuation was not performed in accordance with expertguidelines.Almost 15% of drug administration was not in agreement

with recommendations, and 26 drug administration involveddrugs that should be avoided according to guidelines. Animportant question is whether such disagreement reflects medi-cation errors or a relevant deviation from guidelines based onthe clinical evaluation of the prescribing physician. Dosingguidelines will guide dosing in the average patient and do notincorporate possible relevant differences in ethnicity, age,body-weight, body mass index, comorbidity, treatment indica-tion or disease severity. Our data indicate that drug dose dis-agreements, at least in some cases, reflect inappropriate drugdosing or drug use with a possible risk of adverse events. Thiswas apparent in cases where drugs such as methenamine andvalganciclovir were given in high doses to patients with severerenal insufficiency (table 3). Other drugs commonly used indisagreement with guidelines were thiazide diuretics, the ACEinhibitor ramipril, simvastatin and magnesium oxide.Overall, 23% of the study participants received at least one

drug that was not dosed in agreement with guidelines. Thisfigure is generally lower than previously reported [2–8], butdirect comparison is difficult because studies have involveddifferent populations, different inclusion criteria or definitionof renal risk drugs, different dosing guidelines and differencesin the reporting of renal function. Furthermore, the prescrip-tion pattern and recommendations may change over time. Inprevious studies, non-steroid anti-inflammatory drugs (NSAID)were commonly used and frequently associated with inappro-priate dosing in patients with renal insufficiency. In our study,NSAID was prescribed to only a few patients. Also, the useof electronic prescribing and direct reporting of eGFR mayhave reduced medication errors over time [15–17]. Althoughwe observed fewer cases of medication errors compared withthe previous studies, there were still patients receiving drugsor dosing associated with a significant risk of adverse effects.

Table 1.Baseline characteristics of 232 included patients. Results are shown according to the degree of renal insufficiency (estimated glomerular filtrationrate(eGFR), ml/min./1.73 m2).

All patients (n = 232) eGFR 30–49 (n = 128) eGFR 10–29 (n = 104) p value (eGFR 30–49 versus eGFR 10–29)

CharacteristicsAge, median (range) 76 (18–97) 78 (19–97) 75 (18–95) p = 0.151

Age groups, no. of patients (%)18–44 14 (6.0) 3 (2.3) 11 (10.6) p = 0.032

45–54 12 (5.2) 4 (3.1) 8 (7.7)55–64 22 (9.5) 16 (12.5) 6 (5.8)65–74 56 (24.1) 30 (23.4) 26 (25.0)75–84 85 (36.6) 51 (39.8) 34 (32.7)85+ 43 (18.5) 24 (18.8) 19 (18.3)Gender, no. of patients (%)Female 107 (46.1) 68 (53.1) 39 (37.5) p = 0.023

Male 125 (53.9) 60 (46.9) 65 (62.5)

1Wilcoxon–Mann–Whitney test.2Fisher’s exact test.3Chi-square test.

Table 2.Drug administration in relation to estimated glomerular filtration rate(eGFR; ml/min./1.73 m2). Number of patients is shown in roundbrackets.

All eGFR 30–49 eGFR 10–29

All drugs 1633 (232) 867 (128) 766 (104)Renal risk drugs 436 (183) 180 (93) 256 (90)Should be dose-adjustedby GFR

410 (180) 171 (92) 239 (88)

Should be avoided 26 (26) 9 (9) 17 (17)



Table3.

Observeddisagreements

betweenactual

used

dosing

andRenbase

�recommendatio

nsin

patientswith

estim

ated

glom

erular

filtrationrate

(eGFR

)(a)30–49ml/m

in./1

.73m

2and(b)10

–29ml/m

in./

1.73

m2 .

ATCcode

Drug

Num

berof

patients

24-hr

dosing,mg

Recom

mendedmaxim

aldo

sein

patients

with

GFR

>90

ml/m

in./1

.73m

2 ,mg

Renbase

recommendatio

nin

patientswith

GFR

30–49ml/m

in./1

.73m

2

(a)

A02

AA04

Magnesium

oxide

910

00–200

0Laxatives

containing

magnesium

shou

ldbe

avoided

A10BA02

Metform

in1

2000

3000

Reducedose

50–75%

B01AX05

Fond

aparinux

12

2.5

2.5

Reducedo

seto

1.5mgdaily

C09AA05

Ram

ipril

210

10Maxim

aldo

se5mgdaily

G04

BD09

Trospium

chloride

160

60Reducedo

se25

%M03BX01

Baclofen

140

100

Reducedo

se75

%M05BA08

Zoledronicacid

21

44

GFR

40–49ml:3.3mg

N02AX02

Tramadol

2400

400

Reducedose

25%

N06AX11

Mirtazapine

145

45Reducedose

25%

R05DA04

Cod

eine

115

020

0Reducedo

se50

%R06AE07

Cetirizine

110

10Reducedo

se50

%

ATCcode

Drug

Num

berof

patients

24-hr

dosing,mg

Recom

mendedmaxim

aldo

sein

patients

with

GFR

>90

ml/m

in./1

.73m

2 ,mg

Renbase

recommendatio

nin

patientswith

GFR

10–29ml/m

in./1

.73m

2

(b)

A02

AA04

Magnesium

oxide

750

0–10

00Laxatives

containing

magnesium

shou

ldbe

avoided

A03

FA01

Metoclopram

ide2

140

60Reducedo

se50

%A10BB12

Glim

epiride

12

Avoid

C03AB01

Bendroflumethiazidewith

potassium

chloride

22.5/573

Avoid

C03AB01

Bendroflumethiazidewith

potassium

chloride

11.25/573

Avoid

C03DA01

Spiron

olactone

250

Avo

idC03DA01

Spiron

olactone

220

0Avo

idC07AB03

Atenolol

110

010

0Reducedo

se50–75%

C09AA05

Ram

ipril

410

10Maxim

aldo

se5mgdaily

C09DA01

Losartanwith

hydrochlorothiazide

110

0/25

100/50

Reducedo

seof

hydrochlorothiazidewith

75%

C10AA01

Simvastatin

1340

40(80)

Reducedose

50–75%

,do

sagesabov

e10

mg/dayshou

ldbe

implem

entedcautiously

G04BD07

Tolterodine

tartrate

14

4Reducedose

50%

J01X

A01

Vancomycin

21

1000

2000

150–50

0mgdaily

J01X

X05

Methenamine

120

00Avo

idJ05A

B14

Valganciclovir

118

0018

0050

%of

standard

dose

every48

hrN02AA59

Paracetamol

with

codeine

13000/180

Avoid

theuseof

codeine

N06AX11

Mirtazapine

230

45Reducedose

50%

R06AE07

Cetirizine

110

10Reducedose

50%

R06AX13

Loratadine

110

10Reducedose

50%

1 Sub

cutaneou

sly.

2 Intravenously.



There were also cases where the use of an alternative drugmay have been more appropriate.Patients with severe renal insufficiency were prescribed

more renal risk drugs than patients with moderate renal insuf-ficiency, probably because there are more drugs defined asrenal risk drugs in patients in whom renal function is severelyreduced. We also observed that the number of drug dose dis-agreements declined during 5 days of follow-up. This findingmay be biased by the fact that we did not register new pre-scriptions with administration initiated after the 24- to 48-hrtarget period.Disagreement in dosing was defined according to Renbase�,

but we found similar results when comparing with recommen-dations by the Danish drug information and medication-guid-ing website ‘promedicin.dk’.When defining dose disagreement, we used the maximum

recommended dose in patients with normal renal function asthe basis for the calculation of the maximum dose in patientswith impaired renal function. This may have caused underesti-mation of the prevalence of dose disagreements. We did notevaluate whether patients actually had adverse effects or not.Thus, any inference as to the severity of the disagreements isdifficult. Such evaluation would require prospective collectionof detailed clinical information, which was beyond the scopeof this study because we focused on the adherence to recom-mendations rather than on the consequences of non-adherence.Other limitations include the observation that at least 28%

of the patients revealed significant changes in plasma creati-nine concentrations within the observation period. This maylead to both over- and underestimation of the true GFR[10,11,17]. The intention of our study was, however, not toevaluate the utility of eGFR to estimate renal function, but toevaluate physicians’ use of and adherence to dosing guide-lines. Finally, we may have underestimated the rate of dosingerrors because we did not include p.r.n. prescriptions in ourevaluation. We cannot exclude that p.r.n. prescriptions in somecases may have added to the 24-hr dosing of some drugs, butwe do not believe that this had any major impact on ourresults as cumulative 24-hr dosing is often relatively low forp.r.n. prescriptions, and p.r.n. prescriptions often involve anal-gesics such as morphine and paracetamol, which were notconsidered renal risk drugs according to our definition.The strengths of our study include the well-characterized

study population, the fact that we evaluated only medicationsthat were actually administered and that we examined adminis-trations within a well-defined 24-hr time period, allowing theprescribing physician to make subsequent drug changes inresponse to the eGFR.Despite limitations, our study suggests that even with elec-

tronic prescriptions and automatic reporting of eGFR, drugprescriptions in patients with moderate and severe renal insuf-ficiency could be optimized. There are several possible inter-ventions that may be applied for this. Drug chart review bypharmacists may have a positive effect on medication use andcosts, but it has no proven effect on mortality or hospital read-mission [18,19]. It is expensive, and a recent Cochrane reviewconcludes that cost-effectiveness of the intervention has not

been established [20]. In our study population, there was avery limited use of drug chart reviews, and most were per-formed at the department of emergency medicine. In a previ-ous report, it was found that 26% of patients admitted to thedepartment of emergency medicine had drug chart reviewsperformed by pharmacists [21]. We do not know the results ofdrug chart reviews during the study period, but the impact onour results was probably small as the majority of patients werenot admitted at departments having pharmacy drug chartreviews. Clinical decision support systems are alternatives todrug chart reviews, and many have been evaluated in con-trolled clinical trials. It has been documented that the systemsin general reduce medication errors and improve patient safety[22–27], in most cases by 20–50%. In the study by Chertowet al. [22], the proportion of prescriptions with an appropriatedose and frequency increased from 30% to 51% after a renalfunction-specific dosing decision support system was imple-mented. In a French study, electronic decision support did notresult in a significant decrease in inappropriate prescription[28]. A barrier to improved prescription may be physiciannon-adherence to decision support alerts. If decision supportsystems are used, it is important to implement systems thathave a minimum of nuisance alerts, work well with the elec-tronic medical record and prescription system, have a broaduser acceptance and have interruptive alerts [29].In conclusion, we have shown that disagreements between

actual used dosing and dosing as defined by expert recommen-dation are common in patients with moderate-to-severe renalfailure, even in a setting with electronic drug prescription andautomatic reporting of eGFR, and that disagreement to someextent reflects medication errors.

AcknowledgementsThe study was supported by grants from TrygFonden

(7-11-0586) and Odense University Hospital. We will alsothank Kari Laine for providing free access to Renbase� in thestudy period.

References

1 Binzer K, Hellebek A. 3,520 medication errors evaluated to assessthe potential for IT-based decision support. Stud Health TechnolInform 2011;166:31–7.

2 van Dijk EA, Drabbe NR, Kruijtbosch M, De Smet PA. Drug doseadjustments according to renal function at hospital discharge. AnnPharmacother 2006;40:1254–60.

3 Markota NP, Markota I, Tomic M, Zelenika A. Inappropriate drugdosage adjustments in patients with renal impairment. J Nephrol2009;22:497–501.

4 Blix HS, Viktil KK, Moger TA, Reikvam A. Use of renal riskdrugs in hospitalized patients with impaired renal function-anunderestimated problem? Nephrol Dial Transplant 2006;21:3164–71.

5 Long CL, Raebel MA, Price DW, Magid DJ. Compliance withdosing guidelines in patients with chronic kidney disease. AnnPharmacother 2004;38:853–8.

6 Hug BL, Witkowski DJ, Sox CM, Keohane CA, Seger DL, YoonC et al. Occurrence of adverse, often preventable, events in com-munity hospitals involving nephrotoxic drugs or those excreted bythe kidney. Kidney Int 2009;76:1192–8.



7 Wessell AM, Litvin C, Jenkins RG, Nietert PJ, Nemeth LS, Orn-stein SM. Medication prescribing and monitoring errors in primarycare: a report from the Practice Partner research Network. Qual SafHealth Care 2010;19:1–5.

8 Papaioannou A, Clarke JA, Campbell G, Bedard M. Assessment ofadherence to renal dosing guidelines in long-term facilities. J AmGer Soc 2000;48:1470–3.

9 Hudson JQ, Nyman HA. Use of estimated glomerular filtration ratefor drug dosing in the chronic kidney disease patient. Curr OpinNephrol Hypertens 2011;20:482–91.

10 Levey AS, Coresh J, Greene T, Stevens LA, Zhang YL, Hendrik-sen S et al. Using standardized serum creatinine values in themodification of diet in renal disease study equation for estimatingglomerular filtration rate. Ann Intern Med 2006;145:247–54.

11 Metoder til vurdering af nyrefunktion og proteinuri, Dansk Selskabfor Klinisk Biokemi og Dansk Nefrologisk Selskab, Juni 2009.http://www.nephrology.dk/Publikationer/5-Metoder_til_vurder-ing_af_nyrefunktion_og_proteinuri20090618_____DEF.pdf (lastaccessed on 6 January 2014).

12 Note for guidance on the evaluation of the pharmacokinetics ofmedicinal products in patients with impaired renal function. Com-mittee for Medicinal Products for Human use (CHMP). EMEA, 23June 2004.

13 Wuorela M, Kuitunen T, Helen-Salmivaara A. Database to supportdecision-making concerning pharmacotherapy of patients with renalfailure (translation). Finnish Medical Journal 2010;65:3047–9.

14 http://www.promedicin.dk (last accessed on 6 January 2014).15 Ammenwerth E, Schnell-Inderst P, Machan C, Siebert U. The

effect of electronic prescribing on medication errors and adverseevents: a systemic review. J Am Med Inform Assoc 2008;15:585–600.

16 Hemmelgarn BR, Zhang J, Manns BJ, James MT, Quinn RR, Ra-vani P et al. Nephrology visits and health care resource use beforeand after reporting estimated glomerular filtration rate. JAMA2010;303:1151–8.

17 Stevens LA, Padala S, Levey AS. Advances in glomerular filtra-tion rate-estimating equations. Cur Opin Nephrol Hypertens2010;19:298–307.

18 Hassan Y, Al-Ramahi RJ, Aziz NA, Ghazali R. Impact of a renaldrug dosing service on dose adjustment in hospitalized patients

with chronic kidney disease. Ann Pharmacother 2009;43:1598–605.

19 Graabæk T, Kjeldsen LJ. Medication reviews by pharmacists athospitals lead to improved patient outcomes: a systemic review.Basic Clin Pharmacol Toxicol 2013;6:359–73.

20 Christensen M, Lundh A. Medication review in hospitalizedpatients to reduce morbidity and mortality. Cochrane Database SystRev 2013;(2):CD008986.

21 Grønkjær LS, Jensen ML, Madsen H, Hallas J. Vellykket implem-entering af farmaceutisk intervention p�a Akut Modtage Afdeling.Ugeskr Laeger 2011;173:1353–5.

22 Chertow GM, Lee J, Kuperman GJ, Burdick E, Horsky J, SegerDL et al. Guided medication dosing for inpatients with renal insuf-ficiency. JAMA 2001;286:2839–44.

23 Helmons PJ, Grouls RJ, Roos AN, Bindels AJ, Wessels-Basten SJ,Ackerman EW et al. Using a clinical decision support system todetermine the quality of antimicrobial dosing in intensive carepatients with renal insufficiency. Qual Saf Health Care2010;19:22–6.

24 Roberts GW, Farmer CJ, Cheney PC, Govis SM, Belcher TW,Walsh SA et al. Clinical decision support implemented with aca-demic detailing improves prescribing of key renally cleared drugsin the hospital setting. J Am Med Inform Assoc 2010;17:308–12.

25 Seidling HM, Schmitt SP, Bruckner T, Kaltschmidt J, PruszydioMG, Senger C et al. Patient-specific electronic decision supportreduces prescription of excessive doses. Qual Saf Health Care2010;19:e15.

26 McCoy AB, Waitman LR, Gadd CS, Danciu I, Smith JP, LewisJB et al. A computerized provider order entry intervention formedication safety during acute kidney injury: a quality improve-ment report. Am J Kidney Dis 2010;56:832–41.

27 Tawadrous D, Shariff SZ, Haynes RB, Iansavichus AV, Jain AK,Garg AX. Use of decision support systems for kidney-related drugprescribing: a systemic review. Am J Kidney Dis 2011;58:903–14.

28 Sellier E, Colombet I, Sabatier B, Breton G, Nies J, Zapletal Eet al. Effect of alerts for drug dosage adjustment in inpatients withrenal insufficiency. J Am Med Inform Assoc 2009;16:203–10.

29 Galanter WL, Moja J, Lambert BL. Using computerized providerorder entry and clinical decision support to improve prescribing inpatients with decreased GFR. Am J Kidney Dis 2010;56:809–12.



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Drug Dosing in Patients with Renal Insufficiency in a Hospital Setting using Electronic Prescribing and Automated Reporting of Estimated Glomerular Filtration Rate