INTERNATIONAL JOURNAL of BIOMEDICAL SCIENCE ORIGINAL ARTICLE Polypharmacy and Anticholinergic Burden in Hospitalised Older Patients - A Cross Sectional Audit Joanna Ulley 1, Sakila Sickander 2, Ahmed H. Abdelhafiz 2 1 Department of Elderly Medicine, Rotherham General Hospital, Moorgate road, Rotherham S60 2UD, UK; 2 Department of Old Age Psychiatry, Rotherham Doncaster and South Humber NHS Foundation Trust, Woodfield House, Tickhill Road Site, Weston Rd, Doncaster DN4 8QN, UK ABSTRACT Objectives: To investigate the impact of hospital admission on polypharmacy and anticholinergic burden and explore doctors awareness of cognitive side effects of anticholinergics use. Methods: A cross sectional retrospective audit of older patients admitted to a care of elderly ward over three months. We have collected patients demographic data, number of medications and anticholinergic burden scale on admission compared to on discharge and investigated doctors knowledge about polypharmacy by answering a questionnaire. Results: 100 patients were included. Mean number of medications and anticholinergic burden were significantly higher on discharge compared to admission (9.43 v.8.27, p<0.001 and 1.50 v. 1.30, p<0.01, re4spectively). Seven doctors (25%) had no knowledge of any anticholinergic medications at all. Only 16 (57%) doctors were aware of the negative impact of this class of medications on cognitive function and 22 (79%) doctors felt not at all confident in identifying or reducing anticholinergic prescriptions for inpatients. Conclusion: Hospitalisation results in a significant increase in polypharmacy and anticholinergic burden in older people and doctors knowledge of the cognitive risks associated with anticholinergic medications in older people is poor. (Int J Biomed Sci 2018; 14 (1): 36-40) Keywords: Older people; polypharmacy; anticholinergic burden INTRODUCTION Corresponding author: Dr. Joanna Ulley, Specialty Registrar in Geriatric and Stroke Medicine, Department of Elderly Medicine, Rotherham General Hospital, Moorgate road, Rotherham, S60 2UD, UK. E-mail: Joanna.ulley@nhs.net. Received August 30, 2018; Accepted September 10, 2018 Copyright: 2018 Joanna Ulley et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.5/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. The UK population is ageing. In 2016, there was an estimated 285 older people (>65 years) for every 1000 younger people (16-64 years) and this ratio is projected to increase (1). Ageing is associated with multiple comorbidities that lead to polypharmacy and the use of inappropriate medications (2). Polypharmacy is associated with increased risk of falls, delirium, hospital admissions and increased mortality (3). One specific group of medications commonly used in older people is the anticholinergics. In the UK in 2010, an estimated 24% of older people were taking at least one drug in this class (4). This class of medications is associated with peripheral side effects such as dry mouth, urinary retention and palpitations and central 36
side effects such as delirium and cognitive decline. Older people are particularly susceptible to the side effects of these medications due to the high prevalence of polypharmacy in old age and the age-related changes in pharmacokinetics and pharmacodymamics (5). AIM To investigate whether hospital admission results in a reduction in polypharmacy particularly the use of anticholinergics and explores whether hospital doctors are aware of the potentially negative impact of anticholinergics use. METHODS Design A cross-sectional retrospective data analysis. Setting Acute care of the elderly ward (28 beds) which admits older patients ( 75 years) in a District General Hospital in the United Kingdom. Study sample The population comprised all elderly patients admitted to the acute medical ward over a three months period (March-June 2017) regardless of the admission diagnosis. Data collection a. Electronic Patient Records (EPR) was used to extract demographic data for each patient including age, gender and number of co-morbidities. b. The total regular medications and the number of anticholinergic medications on discharge were compared to those on admission for each patient. We calculated the anticholinergic burden (ACB) using the scale developed by the Ageing Brain Centre (6) and compared the ACB on discharge with that on admission. c. The indications for any anticholinergic medications added on discharge were extracted from the medical record for each patient. This was compared with the STOPP/ START criteria to check the appropriateness of each prescription (7). d. Doctors views regarding the prescription of anticholinergic medications in old age were explored using the following 5 questions: 1. Can you identify any anticholinergics side effects listed in this table? (Table 4) 2. Can you list as many anticholinergic medications that you know? 3. Older patients ( 75y old) are more susceptible to anticholinergic side effects, true or false? 4. Are you aware of any ACB scale? 5. How confident do you feel in identifying and reducing the ACB for susceptible patients and what are the reasons for your answer? Outcome measured a. The impact of hospital admission on polypharmacy and the ACB. b. The doctors knowledge and confidence in reducing ACB in older people. Statistical analysis Continuous data are presented as means and standard deviations (SD) and categorical data as frequencies and percentages. We used paired t-test for data comparison. The statistical software package Stata version 14, Stata- Corp, Texas, USA was used for the analysis. RESULTS During the study period, 100 patients were discharged and their baseline characteristics are summarised in Table 1. Almost half (48%) of patients had dementia diagnosis Table 1. Baseline Characteristics Total number of patients 100 Mean (SD) age, years 82.7 (8.33) Gender, female (%) 71% Mean (SD) number of co-morbidities 4.52 (2.01) Main co-morbidities (prevalence) Cardiovascular disease 58% Hypertension 53% Dementia 48% Respiratory disease 28% Depression 28% Diabetes mellitus 15% Mean (SD) length of hospital stay (days) 14.8 (14.1) Reason for admission: Falls 27% Delirium 19% Short of breath 12% Other 42% www.ijbs.org Int J Biomed Sci Vol. 14 No. 1 September 2018 37
on admission. Delirium or fall was the presenting complaint in 46% of patients. The mean number of medications was significantly higher on discharge compared with admission (9.43 v.8.27, p<0.001). Similarly the mean ACB was significantly higher on discharge (1.50 v. 1.30, p<0.01, Table 2). Fifty-three patients had an increase in ACB during the course of their admission. Of these, thirty-one patients had a justifiable indication for an additional anticholinergic use in line with the STOPP/START criteria (7). The remaining 22 patients could have avoided the increase by either withdrawal of or the use of an alternative treatment. (Table 3) Doctors views regarding the reasons for the ACB stasis or increase during admission are summarised in Table 4. A total of 28 doctors (4 senior doctors, 5 middle grades, and 19 junior doctors) answered a questionnaire regarding the use of anticholinergic medications in older people. Seven doctors (25%) had no knowledge of any anticholinergic medications at all. Of those that could, oxybutynin was the most commonly cited example of this category. All doctors knew that older people are more susceptible to the peripheral nervous system side effects of anticholinergics. However, only 57% of doctors were aware of the negative impact of this class of medications on cognitive function. Twenty two (79%) doctors felt not at all confident in identifying or reducing anticholinergic prescriptions for inpatients. The most commonly cited reason for this was Lack of awareness of anticholinergic risk. DISCUSSION This study demonstrated that a hospital admission resulted in an increase, rather than a decrease in the overall medication burden. This is likely to be due to the fact that patients are admitted with an additional illness which may require further medications. It has been previously reported that average number of all medications has significantly increased from 2.89 on hospital admission to 3.75, p<0.0001 on discharge (8). Other studies showed similar results (9, 11). In our study, a significant proportion (46%) of acute presentations to hospital was due to either a fall or altered mental state. A study of community-dwelling older people exploring the link between exposure to anticholinergic or sedative medications and performance on physical and cognitive functioning demonstrated a clear Table 3. Anticholinergic medications inappropriately used in 22 patients according to STOPP/START criteria (7) Medication group Incontinence medications Number of patients Fesoterodine 2 Solifenacin 1 Trospium 1 Tolterodine 1 Oxybutynin 1 Tricyclic Antidepressant Amitriptyline 4 Beta-Blockers Atenolol 3 Vitamin K antagonists Warfarin 2 Analgesia Codeine 1 Nefopam 1 Carbamazapine 1 Antihistamine Other Hydroxyzine 1 Chlorpromazine 1 Loperamide 1 Furosemide 1 Total 22 Table 2. Comparison between admission and discharge medications per patient Admission Discharge Difference (95% CI) Mean (SD) total number of medications 8.27(4.80) 9.43(5.10) 1.26 (1.63 to 2.37), p<0.001 Mean (SD) ACB 1.30 (1.6) 1.50 (1.62) 0.2 (0.05 to 0.3), p=0.010 CI, Confidence interval; ACB, Anticholinergic burden. 38
Table 4. Doctors awareness of anticholinergic burden survey (28 doctors) Can you list as many anticholinergic medications that you know? Can you identify any anticholinergics side effects? (doctors were shown 9 side effects) Awareness of nervous system side effects Peripheral symptoms Central symptoms (delirium) Are you aware of any ACB scale? How confident do you feel in identifying and reducing the ACB for susceptible patients? Reason for lack of confidence : 21 (75%) doctors had knowledge of anticholinergics. 7 (25%) doctors had no knowledge of any anticholinergics. 15 doctors (54%) identified 6/9 side effects. 13 doctors (46%) identified <6/9 side effects. 28 (100%) doctors. 16 (57%) doctors Lack of awareness of ACB. 14 (64%)* Lack of knowledge of which drugs are anticholinergics. 6 (27%) Risk of patient losing benefit of anticholinergic medication. 6 (27%) Unwilling to alter a colleague s prescription. 2 (9%) *Some doctors gave more than one answer. 19 (68%) doctors not aware. 9 (32%) doctors aware. 22 (79%) doctors are not confident. 6 (21%) doctors are confident. association between dose burden and functional decline (12). This has led to the emergence of the concept of drug burden index that quantifies the dose and the frequency of these high risk medications and provides a useful evidence-based tool for assessing the potential harms of these medications in older people (12). We have focused on the ACB due to the particular risk posed by these medications on older people and its association with cognitive decline. It might therefore be expected that for older patients admitted to hospital, the opportunity to rationalise or reduce the ACB would be undertaken. A larger scale study set out to identify risk factors that increase the patient s chance of being prescribed such medications found that poor mobility, urinary incontinence, depression and Parkinson s disease were among the most important risk factors that lead to anticholinergic medications use (13). A similar study examined the impact of a hospital admission on the drug burden index concluded that drug management of older patients during hospital stay may increase the exposure to such medications (14). With this in mind, we examined our data relating to the anticholinergic use specifically in order to investigate whether the changes were clinically justifiable or not. If there was a questionable use of the anticholinergic medication, in line with the STOPP/START criteria (7), the prescription was deemed avoidable or inappropriate. Using these criteria, we found that for 22 of the 53 patients taking anticholinergic drugs on admission, the indication for treatment was not clear, or an alternative medication could be found. With regards to the doctors survey, our study has demonstrated that hospital doctors have a significant lack of awareness regarding the existence of ACB tool and lack of knowledge regarding the associated cognitive decline risks in older age group. A recent study has reported lack of knowledge among different health care professionals, particularly general practitioners (15). STRENGTHS AND LIMITATIONS In this case the retrospective analysis, rather than prospective, was advantageous as doctors may reduce their anticholinergic prescribing if they were aware of data collection in a prospective design. This study also provides information about doctors views in particular junior doctors knowledge and understanding of the hazards of prescribing in this age group, an area which is less well covered in the literature. One limitation is that the questionnaires were provided for medical staff only; more information may have been gleaned from a greater number of participants i.e. nurse practitioners and pharmacists. Another is the small number of patients that was limited to one ward. www.ijbs.org Int J Biomed Sci Vol. 14 No. 1 September 2018 39
CONCLUSION Hospitalisation of older people appears to increase polypharmacy and ACB scale. Reasons for this increase remain unclear but are likely to include failure by hospital doctors, especially the juniors, to recognise and address the risks associated with anticholinergic prescribing. Further research to investigate whether raising awareness amongst frontline medical staff would positively impact on the treatment burden in older people is warranted. KEY POINTS Hospitalisation results in a significant increase in anticholinergic burden amongst older people. Doctors awareness of the cognitive risks associated with anticholinergic medications in older people is lacking. REFERENCES 1. Overview of the UK population: July 2017 Office for National Statistics (accessed September 2018). 2. Ramhade S, Chakarborty A, Shrivastava A, et al. A Survey on Polypharmacy and Use of Inappropriate Medications. Toxicol Int. 2012; 19: 68-73. 3. Fried TR, O Leary J, Towle V, et al. Health outcomes associated with polypharmacy in community-dwelling older adults: a systematic review. J. Am. Geriatr. Soc. 2014; 62: 2261-2272. 4. Sumukadas D, McMurdo ME, Mangoni AA, et al. Temporal trends in anticholinergic medication prescription in older people: repeated cross-sectional analysis of population prescribing data. Age Ageing. 2014; 43: 515-521. 5. Boustani M, Campbell N, Munger S, Maidment I, et al. Impact of anticholinergics on the aging brain: a review and practical application. Aging Health. 2008; 4: 311-320. 6. Indiana University-Center for Aging Research-Aging Brain Program 2012 Update (accessed September 2018). 7. Gallagher P, Ryan C, Byrne S, et al. STOPP (Screening Tool of Older Person s Prescriptions) and START (Screening Tool to Alert doctors to Right Treatment). Consensus validation. 2008; 46: 72-83. 8. Beers MH, Dang J, Hasegawa J, et al. Influence of hospitalization on drug therapy in the elderly. J. Am. Geriatr. Soc. 1989; 37: 679-683. 9. Betteridge TM, Frampton CM, Jardine DL. Polypharmacy--we make it worse! A cross-sectional study from an acute admissions unit. Intern. Med. J. 2012; 42: 208-211. 10. Gutiérrez-Valencia M, Izquierdo M, Malafarina V, et al. Impact of hospitalization in an acute geriatric unit on polypharmacy and potentially inappropriate prescriptions: A retrospective study. Geriatr. Gerontol. Int. 2017; 17: 2354-2360. 11. Frankenthal D, Lerman Y, Lerman Y. The impact of hospitalization on potentially inappropriate prescribing in an acute medical geriatric division. Int. J. Clin. Pharm. 2015; 37: 60-67. 12. Hilmer SN, Mager DE, Simonsick EM, et al. A Drug Burden Index to Define the Functional Burden of Medications in Older People. Arch. Intern. Med. 2007; 167: 781-787. 13. Wawruch M, Macugova A, Kostkova L, et al. The use of medications with anticholinergic properties and risk factors for their use in hospitalised elderly patients. Pharmacoepidemiol Drug Saf. 2012; 21: 170-176. 14. Dauphinot V, Faure R, Bourguignon L, et al. Factors associated with changes in exposure to anticholinergic and sedative medications in elderly hospitalised patients: a multicentre longtidinal study. Eur. J. Neurol. 2017; 24: 483-490. 15. Araklitis G, Thiagamoorthy G, Hunter J, et al. Anticholinergic prescription: are healthcare professionals the real burden? Int. Urogynecol J. 2017; 28: 1249-1256. 40