Polypharmacy and adverse outcomes after hip fracture surgery

Hip fracture in the elderly, following the trend in population aging in developed countries, is a common cause of hospital admission [1‐4]. The mean age of typical patients with acute hip fracture is high, over 80 years [5], which implies multiple comorbidities combined with polypharmacy [5‐7]. It is estimated that patients who suffer hip fracture take, on average, six different medications, which have been identified as an independent risk factor for falls in the elderly [8, 9]. Moreover, two thirds of these patients take drugs that raise the fall risk [9]. In recent years, there has been a growing interest in optimizing pharmacological treatment in the elderly by introduction of systematic medication surveys [10, 11], but their effects on post-discharge complications are not universally agreed [12, 13]. In parallel, relatively little is known how polypharmacy and treatment with specific drug classes impact readmission rate and short-term mortality after hip fracture surgery. Accordingly, the aim of this study was to explore the potential association of discharge medications with the postoperative readmission and death rate.

Table 1 shows intervention group characteristics including supine blood pressure, plasma concentrations of sodium, potassium, creatinine, and hemoglobin recorded upon admission, and the routine reassessment of the same clinical parameters on the 3rd day after hip fracture surgery. Women were overrepresented (n = 196, 72.1%), and the mean age was 82.0 ± 9.0 years, range from 53 to 100 years.

In this study, we have shown that the number of medications upon discharge is predictive of readmission but not death within six months after acute hip fracture surgery. Further, patients treated with antiosteoporotic agents, SSRI, and eye drops have increased overall risk of readmission, whereas use of vitamin K antagonists, thiazides, and tramadol is associated with increased risk of readmission due to fall injury. Finally, increased mortality may be indicated by a sole opioid use at discharge.

The medication reviews performed in our cohort revealed a considerable number of pharmacological issues that received attention and were resolved, if found appropriate.

Zermansky et al. [17] found consultations with a clinical pharmacist to be effective in care home residents, a study population with mainly the same characteristics as a group with hip fractures. From a practical point of view, this concept worked well in our study; the pharmacist started by interviewing the patient and scrutinized different data sources to complete the medication list. A form was filled in, structuring the review, and the result was presented to the internal medicine consultant who decided by consensus, which changes would be suitable and safe.

Notable was that a new trauma or fall injury were the most common reasons for new contact with the hospital. Prevention of falls, better information regarding the hip fracture, and improvement of rehabilitation seem wise, together with improvement in primary care.

Relationships between discharge medications and post-discharge complications deserve specific comments. The use of eye drops was the strongest single predictor of readmission including new trauma. We suggest that the visual impairment is the decisive factor underlying fall injury, and that this group, although not large in number, should receive more specific care, for instance, through adjustments made in their home environment. Another possible explanation of this observation is induction of bradyarrhythmia by beta-blocking component of eye drops; however, there was no significant interaction between eye drops and beta-blockers.

The association between antiosteoporotic drugs and readmissions due to a new fall injury is more obvious as the elderly with osteoporosis have double the risk of falling compared with those without osteoporosis, not only due to osteoporosis but also due to other shared risk factors such as weight loss, small muscle mass, low muscle strength, low physical exercise levels, and limited mobility [18]. Moreover, low BMI is a factor associated with higher prevalence of orthostatic hypotension [19]. The use of SSRI was particularly predictive of readmissions due to infectious disease. Of these, the two most frequent causes are urinary infection and pneumonia. SSRIs have been reported to cause urinary retention [20] and negatively influence renal and respiratory function in the post-operative period [21]. Moreover, SSRIs are associated with increased risk of falls and confusion as possible contributory factors [22]. The role of VKA in the elevated risk of readmission after fall injury can be explained by medical vigilance when dealing with patients who demonstrate higher probability of occult bleeding, and thus require prompt diagnosis including radiology, laboratory assessment, and extended observation. A fourfold increased risk of readmission due to a new fall injury was associated with thiazides, and not other types of antihypertensive drugs, is remarkable. However, regardless of antihypertensive effect, thiazide diuretics may also be involved in intravascular volume reduction and electrolytic disorders, all of which contribute to the increased risk of falls [23]. These results question the use of thiazide diuretics in elderly and frail patients and suggest the use of other types of antihypertensive drugs, or simply discontinuation of treatment. In parallel, our results question the prolonged use of tramadol in the post-discharge period, as this pharmacological agent, routinely used for the post-operative pain alleviation, was associated with almost threefold increased risk of a new trauma, most probably due to confusion, which is a well-known complication related to this drug [24]. Finally, patients treated, on discharge, with morphine only demonstrated the highest mortality, whereas those taking paracetamol demonstrated lower mortality. This observation is logical as it reflects the overall status of patient. In general, chronic and severe pain, which requires permanent opioid treatment, indicates advanced disease with poor prognosis, whereas the use of weak analgesics indicates a more benign disease course.

The reason that patients had in general more medications upon discharge than admission despite the medication optimization is related to the need for post-operative pain reduction (analgesics) as well as thrombosis prophylaxis (LMWH), both of which are routinely started at hospital and continued at discharge.

The total number of medications and use of specific drug classes are associated with increase readmission risk after acute hip fracture surgery in older patients. Medication reviews and withdrawal or modification of drugs may be justified in post-operative period as several drug-related problems were identified. Further studies, including randomized controlled trials on medication optimization, are needed.