Polypharmacy in Traumatic Brain Injury

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The issue of polypharmacy is often overlooked in patients with significant traumatic brain injury (TBI). In the acute setting—which includes the emergency department, critical care unit, and hospital floor—attention is appropriately fixed on survival and medical stabilization. To that end, interventions range from neurosurgical to pharmacological. In a typical severe TBI scenario, it is not unusual for a patient to undergo multiple surgical procedures (eg, craniotomy/craniectomy, ventricular drains, various orthopedic procedures to address polytrauma, tracheostomy, gastrostomy tube placement).

The science behind the acute management of TBI is evolving, and any intervention that improves survival and reduces long-term morbidity is worthwhile. But as patients recover, many of the pharmacological interventions become counterproductive and should be discontinued. TBI is increasingly recognized as a chronic disease with chronic impairments. Therefore, the majority of care for the patient with TBI occurs post hospital. This care is often highly fragmented and many opportunities to reduce medications and avoid polypharmacy and comorbidity can be missed.

Many categories of medication frequently used in patients with TBI can contribute to polypharmacy. Some medications sedate and cloud the sensorium, potentially limiting recovery. This group includes antipsychotics, anxiolytics, antiepileptics, and opiates. Another group includes preventive medications, whether for deep venous thrombosis (DVT) and pulmonary embolism (PE), seizures, or headaches. Yet another group might be referred to as convenience medication; for example, as-needed antiemetics. There are also medications directed at specific and frequent associated conditions such as syndrome of inappropriate antidiuretic hormone secretion (SIADH), cerebral salt wasting, autonomic dysfunction, neurogenic bowel/bladder, and so on. This article will attempt to address each medication briefly. What is important for clinical practitioners to know is that every successive evaluation is an opportunity to reexamine the medication list for necessity.

Some of the most problematic contributors to polypharmacy are the most common: sedating medications. Antipsychotics, typically used in acute settings to manage behavioral complications of TBI, or in rare cases actual psychosis, are generally detrimental to TBI recovery in the long term, unless the patient is diagnosed with psychosis. Similarly, benzodiazepines are generally detrimental unless used for very specific and time-limited purposes such as obtaining diagnostics, performing procedures, and the like. In addition, like opiates, the addictive potential of these medications in a patient with TBI and associated impulsivity is high. Opiate medications are unfortunately frequently necessary in patients with TBI, at least temporarily, as there is frequently associated polytrauma. These medications carry known and varied risks as mentioned, including addictive potential. Awareness of the individual risks of each of these medications, as well as the cumulative effects of polypharmacy involving multiple agents, is paramount. Recovery from TBI is already difficult for a patient combating impaired sensation due to impairments in vision, proprioception, balance, spatial awareness, language, vertigo, and so on. Unnecessary sedation from medication does not improve the process.

Antiepileptic medication is frequently initiated prophylactically during acute care for any patient who has a TBI with intracranial bleeding, and continued use is appropriate for patients who do experience seizure disorder post TBI. However, in patients without a history of seizure post TBI, guidelines suggest that this is not recommended beyond 7 days.¹ Many antiepileptics have significant drug-drug interactions, pharmacokinetic impact, and other adverse effects. Older antiepileptics such as carbamazepine, oxcarbazepine, phenytoin, and phenobarbital have significant effects on cytochrome P450 enzymes. This leads to pharmacokinetic effects and risk for changes in serum drug levels. Valproic acid can similarly affect circulating drug levels through other mechanisms. Newer antiepileptics have less dramatic effect on serum drug levels but many remain hepatically metabolized, and therefore drug levels should be monitored and dosage adjusted. Fortunately, levetiracetam, considered a first-line agent by many for management of epilepsy post TBI, does not frequently alter the serum level of other drugs in clinical practice. In addition to seizure prophylaxis or management, some of these medications are also commonly used for various other purposes in the TBI population, including headache prevention (eg, topiramate), behavioral intervention (eg, lamotrigine, valproic acid), or neurogenic pain management (eg, gabapentin, pregabalin). These can be effective and beneficial, but as patients improve clinically over time, ongoing use should be addressed.

Many patients with TBI suffer from immobility as a consequence, whether transiently or long term. In either instance, acute immobility confers risk for DVT/PE, which some patients do experience during their illness.² Patients are commonly discharged on prophylaxis for treatment of DVT/PE. This may be with either heparin, low molecular weight heparin, warfarin, or one of the novel anticoagulants. All these medications carry their own adverse effect profiles, and many have significant polypharmacy risks due to drug-drug interactions and pharmacokinetic impacts. In cases where a patient’s mobility improves, prophylaxis should be discontinued appropriately. Other individuals with anticipated long-term immobility still do not benefit from prophylaxis indefinitely, because the risk for DVT/PE in this context wanes over time. Appropriate guidelines related to the duration of treatment for DVT or PE should be adhered to, with medication discontinued when appropriate.³

TBI is also frequently associated with other secondary complications. Disorders of homeostasis such as the SIADH or cerebral salt wasting can result in the addition of fluid restriction or the use of salt tabs and/or fludrocortisone. It is not uncommon for this condition to remain unresolved at the time of discharge from the hospital. However, most often this condition will resolve over time with recovery, and these interventions can then be discontinued.

Various other medications, used during acute care to manage hypertension, hyperglycemia, nausea/vertigo, and so on, are frequently prescribed at the time of discharge. With patient improvement, these can also unnecessarily contribute to polypharmacy. This list is exhaustive, but the primary objective here is to highlight the beneficial role of a care provider paying close attention during each visit to the medication list and the ongoing indications (or lack thereof).

Finally, as patients proceed through the recovery process, still other medications can be added. Antidepressants, headache prevention or abortive medications, antiepileptics, and many others may be clinically indicated, some even permanently. However, in all cases, vigilance on behalf of all treatment providers as to the polypharmacy concerns remains vital.

Dr Ashley is a neurologist and chief medical officer for the Centre for Neuro Skills.

References

1. Carney N, Totten AM, O’Reilly C, et al. Guidelines for the management of severe traumatic brain injury, fourth edition. Neurosurgery. 2017;80(1):6-15.

2. Mohseni S, Talving P, Lam L, et al. Venous thromboembolic events in isolated severe traumatic brain injury. J Emerg Trauma Shock. 2012;5(1):11-15.

3. Ortel TL, Neumann I, Ageno W, et al. American Society of Hematology 2020 guidelines for management of venous thromboembolism: treatment of deep vein thrombosis and pulmonary embolism. Blood Adv. 2020;4(19):4693-4738.

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