Beers AGS 2019 criteria in very old hospitalized patients

SUMMARY

OBJECTIVE

To define the rates and types of potentially inappropriate medications (PIMs) for older adults according to the Beers AGS 2019 criteria in oldest-old patients (aged ≥80 years) hospitalized in an Internal Medicine ward.

METHODS

A retrospective analysis of prescriptions from medical records of oldest-old patients hospitalized in an Internal Medicine Teaching-Hospital ward using the Beers AGS 2019 criteria was performed. Data was also collected for gender, mean age, days of hospitalization, presence of feeding tube, delirium, and polypharmacy (≥5 drugs/day). The drugs listed in Table 2 of the Beers criteria were considered PIMs.

RESULTS

The series comprised 39 very old patients (22 men, 17 women), with a mean age of 86.3±4.7 years and hospitalization of 22.8±21.3 days. All patients were admitted via the Emergency Room. Feeding tube placement and polypharmacy occurred in 84.6% of cases and delirium in 71.8%. The prescription of a total of 16 drugs considered PIM was detected by the Beers AGS 2019 criteria (mean 1.8 ± 1.0 PIM per patient). Main prescribed PIMs were Metoclopramide “if necessary” [IN] (41.0% of cases), Omeprazole (38.5%), Regular Insulin [IN] (23.1%), Haloperidol [IN] (18.0%), Quetiapine and Amiodarone (10% each).

CONCLUSION

In the present series of oldest-old hospitalized patients, significant rates of PIM were found, especially for drugs prescribed as “If Necessary”, thereby increasing the risk of side-effects to that of the common polypharmacy in this age group.

Aged, 80 and over; Pharmaceutical preparations; Inpatients; Potentially inappropriate medication list

RESUMO

OBJETIVO

Definir percentual e tipos de medicamentos potencialmente inapropriados para idosos (MPII) pelos critérios de Beers AGS 2019 em longevos (idade ≥80 anos) hospitalizados em enfermaria de clínica médica.

MÉTODO

Análise retrospectiva das prescrições de prontuários de longevos internados em enfermaria de clínica médica de hospital terciário pelos critérios de Beers AGS 2019. Outros dados coletados: gênero, idade média, dias de hospitalização, presença de sonda de alimentação, delirium, polifarmácia (≥5 fármacos/dia). Consideraram-se como MPII os fármacos listados na Tabela 2 do referido critério.

RESULTADOS

Trinta e nove longevos (22 homens, 17 mulheres), idade média 86,3±4,7 anos e 22,8±21,3 dias de hospitalização. A presente casuística foi integralmente admitida pelo pronto-socorro, ocorrendo sonda de alimentação e polifarmácia em 84,6% dos casos e delirium em 71,8%. Detectou-se a prescrição de 16 fármacos considerados MPII pelos critérios de Beers AGS 2019 (média de 1,8±1,0 MPII por paciente). Principais MPII prescritos: metoclopramida, se necessário [SN] (41,0% dos casos), omeprazol (38,5%), insulina regular [SN] (23,1%), haloperidol [SN] (18,0%), quetiapina e amiodarona (10% cada).

CONCLUSÃO

Na presente casuística, longevos hospitalizados apresentaram percentuais significativos de MPII, notadamente em fármacos indicados como “se necessário”, o que aumenta o risco de efeitos colaterais ao fato comum de polifarmácia nessa faixa etária.

Idoso de 80 anos ou mais; Preparações farmacêuticas; Pacientes internados; Lista de medicamentos potencialmente inapropriados

INTRODUCTION

The natural process of aging - accompanied or not by the changes resulting from diseases of higher prevalence among the elderly - represents a potential for interference on the pharmacokinetics and pharmacodynamics of the human body with a significant number of medications. This relationship is often observed in clinical practice, given the high percentage of patients in this age group who simultaneously and chronically take several medications¹ .

Thus, it is easy to observe the medications that have a greater potential to harm than to benefit elderly patients. Defined as potentially inappropriate medications (PIM), these drugs resulted in the development of multiple lists and criteria with the purpose of guiding their use by patients of more advanced ages³ . The Beers criteria - now in its sixth edition - are the most commonly used and worldwide renowned list of PIM⁵ . Its previous editions served as a reference to a significant number of national studies, particularly for the Brazilian Consensus on Potentially Inappropriate Medications for the Elderly (2016)⁶ .

It is estimated that hospitalized elderly individuals take five or more medications simultaneously - defined as polypharmacy -, and one or more PIM may be present in percentages that deserve the attention of healthcare professionals⁷ . It is estimated that the so-called “iatrogenic triad” - polypharmacy, drug interactions, and PIM - occurs in approximately one-third of elderly individuals who take medications⁹ .

Considering the fact that very old individuals - age greater than or equal to 80 years - are exposed to situations of fragility and reduction of functional capacity, the analysis of PIM during hospitalizations is worthy of attention and the motivation for the present study¹⁰ .

The goal of this study is to define the percentages and types of potentially inappropriate medications (PIM) for the elderly based on the Beers criteria AGS 2019⁵ in the patients of very old age ( ≥80 years) hospitalized in the internal medicine ward of a tertiary hospital.

METHODS

A retrospective analysis of prescriptions from the medical records of very old patients hospitalized in the internal medicine ward of a tertiary hospital from 01/01/2018 to 27/10/2018, based on the Beers criteria AGS 2019. We considered as PIM the medications listed in Table 2 of these criteria⁵ . We adapted that table for the medications approved for use in Brasil by the Brazilian Health Regulatory Agency (Anvisa), according to data on their website on 23 July 2019¹² ( Table 1 of this study).

TABLE 2
MEDICATIONS CONSIDERED POTENTIALLY INAPPROPRIATE FOR THE ELDERLY BASED ON THE BEERS CRITERIA AGS 20195 AND OBSERVED IN PRESCRIPTIONS OF VERY OLD PATIENTS HOSPITALIZED IN THE INTERNAL MEDICINE WARD OF A TERTIARY HOSPITAL (70 MEDICATIONS/39 USERS).

Potentially inappropriate medications for the elderly	Women		Men		Total number of users	Percentage of users
	Age (years)		Age (years)
	80 to 89	90 or +	80 to 89	90 or +
Amiodarone	-	-	4	-	4	10.0
Atropine*	-	-	1	1	2	5.0
Clonazepam	1	-	-	-	1	2.6
Diazepam	-	-	1	-	1	2.6
Digoxin	-	-	1	-	1	2.6
Doxazosin	-	-	2	-	2	5.0
HaloperidolIN	-	2	3#	2#	7	18.0
InsulinIN	4	-	4	1	9	23.1
Methyldopa	1	-	-	-	1	2.6
MetoclopramideIN	5	1	7+	3+	16	41.0
Mineral oil	-	-	3	-	3	7.7
Omeprazole	4’	2’	6”	3”	15	38.5
Quetiapine	1	-	1	2	4	10.0
Risperidone	-	-	2	-	2	5.0
Tramadol	1	-	-	-	1	2.6
Zolpidem	-	-	1	-	1	2.6

• * = Eye drops, ^Sn = If necessary, ^#p=0.0240, p=0.0322, p=0.0251, p=0.0249
• The sum of the percentages is greater than 100.0% since in this sample there are very old individuals who took more than one potentially inappropriate medication.

TABLE 1
BEERS CRITERIA 2019 AGS® FOR POTENTIALLY INAPPROPRIATE MEDICATIONS FOR THE ELDERLY 5 . MEDICATIONS LICENSED FOR USE IN BRASIL 12 .

Therapeutic Class
Central alpha-agonists Clonidine (for first-line treatment of hypertension) Guanabenz Guanfacine Methyldopa Reserpine (>0.1 mg/day)	Antidepressants Amitriptyline Amoxapine Clomipramine Desipramine Doxepin (>6 mg/day) Imipramine Nortriptyline Paroxetine Protriptyline Trimipramine	First-Generation Antihistamines Brompheniramine Carbinoxamine Chlorpheniramine Clemastine Cyproheptadine Dexbrompheniramine Dexchlorpheniramine Dimenhydrinate Diphenhydramine (oral) Doxylamine Hydroxyzine Meclizine Pyrilamine or Mepyramine Promethazine Triprolidine	Antiparkinsonian Drugs Benzatropine (oral) Trihexyphenidyl	Barbiturates Amobarbital Butabarbital Butalbital Mephobarbital Pentobarbital Phenobarbital Secobarbital	Genitourinary drugs Desmopressin	Hormones Androgens Methyltestosterone Testosterone Other hormones Thyroid extract Estrogen with or without progesterone Growth hormone Megestrol	Other Anxiolytics Meprobamate
Peripheral Alpha-1 blockers for hypertension treatment Doxazosin Prazosin Terazosin	Antispasmodics Atropine (excludes ophthalmic use) Belladonna alkaloids Chlordiazepoxide-clidinium Dicyclomine Homatropine (excludes ophthalmic use) Hyoscyamine Methscopolamine Propantheline Scopolamine	Non-steroidal anti-inflammatory drugs Acetylsalicylic acid (>325 mg/day) Mefenamic acid Ketoprofen Ketorolac (including parenteral) Diclofenac Diflunisal Etodolac Fenoprofen Ibuprofen Indomethacin Meclofenamate Meloxicam Nabumetone Naproxen Piroxicam Sulindac Tolmetin	Antipsychotics First generation (conventional) and Second generation (atypical)	BenzodiazepinesShort or intermediate action Alprazolam Estazolam Lorazepam Oxazepam Temazepam Triazolam Prolonged Action Chlordiazepoxide (alone or associated to amitriptyline or clidinium) Clonazepam Clorazepate Diazepam Flurazepam Quazepam	Nonbenzodiazepine hypnotics(Z-drugs) Eszopiclone Zaleplon Zolpidem	Muscle Relaxants Carisoprodol Chlorzoxazone Cyclobenzaprine Methocarbamol Orphenadrine	Other cardiovascular action drugs Amiodarone Disopyramide Dronedarone Digoxin (as first-line treatment for atrial fibrillation or heart failure) Nifedipine
Antibiotics Nitrofurantoin			Antithrombotic drugs Dipyridamole (oral, short-term)	Gastrointestinal tract Metoclopramide Mineral oil (oral) Proton-pump inhibitor	Hypoglycemic DrugsSulfonylureas of prolonged action Chlorpropamide Glimepiride Glyburide or Glibenclamide Short or fast-acting insulins (in a scheme according to capillary glycemia)	Opioids Meperidine	Vasodilators of dubious efficacy Ergoloid mesylates Isoxsuprine

Other data collected: (1) gender, (2) mean age and standard deviation (3) days of hospitalization (mean and standard deviation), (4) presence of feeding tube (nasoenteral, nasogastric, or gastrostomy) based on the presence of medications with a contraindication for this route¹³ , (5) delirium (based on the Portuguese version of the Confusion Assessment Method ¹⁴ ) justified due to the usual prescription of psychotropic drugs¹⁵ , (6) polypharmacy (use of five or more medications/day⁷ ).

Statistical analysis of the data was based on the presence or absence of a certain PIM regarding gender and age groups (80 to 89 years and equal to or greater than 90 years). We used Fisher’s exact test with an alpha value of 0.05.

After being submitting the study to the Human Research Ethics Committee (CEP) of the institution to which the authors are part of and considering that the present study does not involve humans, the Committee considered there was no need to issue an opinion for it.

RESULTS

During the period of this study (300 days), 39 very old patients (22 men and 17 women) with a mean age of 86.3±4.7 years (80 to 98 years) were hospitalized in the internal medicine ward (approximate one hospitalization per week). The present sample was composed entirely of admissions from the emergency room, with an average of 22.8±21.3 days (3 to 129 days) of hospitalization. There as a need for oxygen supply and/or polypharmacy in 84.6% of cases and a diagnosis of delirium in 71.8%.

We detected the prescription of 16 drugs considered PIM based on the Beers criteria AGS 2019⁵ ( Table 2 of this study) - an average of 1.8±1.0 PIM per patient - (70 PIM/39 patients with extremes of 0 and 4 PIM). Main prescribed PIM ( Figure 1 ): (1) metoclopramide, if necessary [IN] (41.0% of cases), (2) omeprazole (38.5%), (3) regular insulin [IN] (23.1%), (4) haloperidol [IN] (18.0%), (5 and 6) quetiapine and amiodarone (10% each). The final sum resulted in 70 PIM/39 patients.

FIGURE 1
MAIN MEDICATIONS CONSIDERED POTENTIALLY INAPPROPRIATE FOR THE ELDERLY BASED ON THE BEERS CRITERIA AGS 20195 AND OBSERVED IN PRESCRIPTIONS OF VERY OLD PATIENTS HOSPITALIZED IN THE INTERNAL MEDICINE WARD OF A TERTIARY HOSPITAL (70 MEDICATIONS/39 USERS).

We found statistically significant relationships between the absence or non-use of haloperidol, metoclopramide, and omeprazole in very old men grouped by age (80 to 89 years, 90 years or more). The statistical significance of haloperidol was based on the absence of use, and that of metoclopramide and omeprazole on their higher use by nonagenarians. Omeprazole was also statistically significant among elderly women, with a tendency to non-prescription for octogenarians.

DISCUSSION

The rapid process of population aging in Brasil and, consequently, the increase in hospitalizations in this age group deserves special attention from healthcare professionals¹⁶ .

Very old patients are noteworthy for the occurrence of three or more conditions - chronic-degenerative and concomitant - 66.0% more frequently than among quinquagenarians¹⁷ . When there is an acute event and/or the decompensation of previous diseases, the risk of hospitalization in very old patients reaches 13.6% in 12 months, in contrast to 8.9% for those aged between 50 and 59 years¹⁸ . Both situations - multimorbidities and hospitalizations - lead to the simultaneous and progressive use of five or more medications daily in approximately 20.0% of elderly patients¹⁹ . This therapeutic process presents a risk for adverse reactions to medications in percentages above 60.0% of hospitalized patients and to the use of PIMs³ .

Considering the above, it is recommended that the concept of PIM - which present a higher chance of adverse events than benefits - become part of clinical practice in the care for patients of this age group. The prescription of medications must be considered a potentially iatrogenic and lethal act, especially when there is evidence and/or alternatives of other medicines with equal or better effectiveness and that are safer for the pharmacological treatment of the patient under evaluation³ .

Very old patients often become prone to the so-called “iatrogenic triad” - polypharmacy, PIM, and drug interactions - a situation that can be prevented and in which criteria such as the Beers allow health professionals to take appropriate therapeutic decisions³ - ⁵ , ⁹ .

The fact that PIMs (haloperidol, insulin, and metoclopramide) are listed as “prescribed if necessary” does not minimize their potentially inappropriate indication to very old patients. It is inferred that the application of insulin with capillary blood glucose monitoring and the indication for metoclopramide for occasional vomiting incurs the false impression that episodic use does not lead to side effects and/or drug interactions. When talking about PIM, the frequency with which “if necessary” medications are used to be noted, since - depending on the clinical condition - their use can become daily and not episodic⁵ . The same circumstance was observed in the indication of haloperidol for very old patients with conditions of delirium and/or severe cognitive dysfunction since there is a risk that doses administered without a criterion of maximum value might exceed the dose of 5 mg/24 hours¹⁵ . Thus, the standard from the place of origin of the present sample, which adds up the total doses and their milligrams, is justified to reduce the risk of adverse reactions to these medications.

Another routine in the infirmary dynamics, on which this study is based, refers to medications and feeding tubes. The indication for nutrition via alternative routes is common among the elderly - notably among very old ones - who are hospitalized. However, not all medications are able to fully accomplish their function via these routes. The Beers criteria do not comment on this aspect of the medicines analyzed in this series - digoxin, haloperidol, omeprazole, and tramadol -, which have non-crushable presentations or that precipitate with an enteral diet⁵ . This constitutes, thus, a curious situation, in which the PIM not only is contraindicated due to a greater probability of adverse events but also for the possibility of not being absorbed in this route of administration. The association of such details is worthy of mention due to the false sense of correct prescription to very old patients with overlapping iatrogenesis, i.e., from the medication (PIM) and the procedure (feeding tubes)²¹ .

The prescription of omeprazole in over one-third of very old patients justifies two comments. The medication was long considered a low hazard for the elderly, and the Beers criteria included it as a PIM just in its last two updates (2015 and 2019)⁵ . This was due to reports on adverse events during its chronic use (for more than eight weeks daily), especially among patients in this age group²³ . Omeprazole is currently related to falls and fractures, Clostidium difficile infections, community-acquired pneumonia, vitamin B12 deficiency, dementia, injury, and kidney disease²³ . The second comment, which is also a relevant factor, relates to reports that approximately 63.0% of users of this proton-pump inhibitor do not exhibit gastrointestinal symptoms, diagnosis of diseases of the digestive system, and/or the simultaneous use of other medications with the potential for gastrointestinal lesions²³ . It is recommended that, prior to the prescription of a proton-pump inhibitor, a careful evaluation of medications in use be conducted to define the therapeutic purpose of each of them. By doing this, it is possible to have a simple and low-cost mechanism that can reduce the indices of polypharmacy among the elderly - notably very old ones -, creating a culture of de-prescription, something that is being developed at the hospital of origin of the present sample²⁴ .

It is inferred that the presence of psychotropic drugs - clonazepam, diazepam, haloperidol, risperidone, quetiapine, and zolpidem - is this sample is due to the high percentage of cases of acute mental confusion, ( delirium ). It is important to note that the number of users of this pharmacological group is smaller than the percentage of patients with delirium in this study. This discrepancy is justified by the hospital protocol for early detection of acute confusional states on the site that originated sample, which enables the use of non-pharmacological measures and a reduction in prescriptions of psychotropic drugs¹⁵ .

The present sample - of convenience - does not allow the full generalization of the results but exposes a concrete need for the rational systematization of prescriptions for elderly patients, especially very old ones. There are tools available for that, with emphasis on PIM lists, particularly the Beers criteria⁵ .

CONCLUSION

Very old patients hospitalized and evaluated in this study based on the Beers criteria AGS 2019 showed a significant percentage of PIM, in particular, those indicated as “if necessary”. This increases the risk of side effects due to the high frequency of polypharmacy in this age group and indicates the need for the systematization of therapeutic care in very old patients.

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Publication Dates

• Publication in this collection
  24 Aug 2020
• Date of issue
  July 2020

History

• Received
  14 Jan 2020
• Accepted
  19 Jan 2020