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Marry T. Vuong, PharmD, BCPPS, Neurology Clinical Pharmacy Specialist, Nicklaus Children’s Hospital; Miami, Florida

Introduction

Rates of chronic conditions in pediatric patients are steadily increasing and the medications used to treat these conditions are also showing a proportional increase. Pediatric neurocritical care patients may experience polypharmacy resulting from the management of multiple co-morbidities, organ dysfunction and drug-drug interactions (DDI). In fact, the incidence of DDI in the critically ill can be as high as 58%.¹ Polypharmacy is defined as the practice of administering or using multiple medications concurrently for the treatment of one or more medical disorders. While pediatric neurocritical care patients often require multiple medications, polypharmacy can have negative consequences including increased pill burden, adverse drug reactions (ADRs), DDI, costs (to the patient and institution), resource utilization, and mortality. Polypharmacy can also lead to problems with medication scheduling since there is greater risk of missed or late doses and issues with administration when medications are incompatible with each other. These issues do not stop in the inpatient setting and often continue after patients are discharged. As a result, polypharmacy leads to decreased efficacy and adherence at home.² 

Rappaport et. al evaluated a medication reconciliation program in a pediatric health system and found that out of 2.7 million clinic visits, 22% of patients were taking 3 to 6 medications and 11% were taking more than 7 medications. After each clinic visit, there was a 29% increase in medications prescribed.³ Subsequently, these patients may be admitted to the ICU where more medications may be started, leading to more polypharmacy. As patients transition from the clinic to the inpatient setting, there is strong evidence to support the involvement of pharmacists as members of the health care team for pediatric patients in diverse settings and at all levels of acuity, ranging from the pediatric intensive care unit (ICU) to ambulatory care clinics. A clinical pharmacist can optimize a patient’s medication regimen by reconciling medications during the transition into and out of the neurocritical care unit, ultimately improving efficacy by optimizing administration route and dose schedules and  enhanceg patient safety by identifying, managing, and preventing ADRs and DDIs, and increasing cost savings by eliminating unnecessary medications.⁴ 

Polypharmacy Consult Service

At our free-standing, 309-bed children’s hospital, we have piloted an informal polypharmacy consult service for medical teams to consult a clinical pharmacist who will optimize medication regimens for complex patients. Clinical pharmacy consults are necessary when providers need assistance with patients in areas of the hospital that do not have dedicated clinical pharmacists. Consults are not limited to just ICU patients, as many clinicians place consults for polypharmacy during the transition from ICU to the general pediatrics floor and then for the transition home.

This program is gaining traction and pending formalization. On average, we receive about 20-30 consults annually. The majority of patients have neurological, psychological, and gastrointestinal comorbidities. Consults are placed electronically or verbally to the main pharmacy/rounding clinical pharmacy specialist. Our team of 7 clinical pharmacy specialists respond to the polypharmacy consults by collecting a detailed medication history, performing medication reconciliation, assessing DDIs, rescheduling medications, and providing the family with a medication administration calendar, when appropriate. After assessing the medication profile and formulating recommendations, the clinical pharmacist writes a formal note in the electronic health record or provides verbal recommendations to the team.

For more complex patients, our team also provides unique patient hand off documents with important notes that should be handed off between nurses, residents, and attending physicians. The hand off document typically consists of special notes such as compatibility, administration instructions, complex seizure rescue plans, medication administration via feeding tubes, and carbohydrate limits. The consulted pharmacist will interview the parents, residents, and nurses to compile pertinent information to ensure proper handoff between shifts. This handoff document is typed, laminated and updated with new changes, as indicated. The consulted clinical pharmacy specialist usually keeps the document and is consulted with every admission. That individual will continue to follow and update until discharge. Through these services, we have streamlined medication regimens with the intent of improving the quality of life for our patients and caregivers. 

Case #1

Case #1 is a 19-year-old female with a past medical history including myasthenia gravis (MG), chronic migraines, intestinal pseudo-obstruction, gastroesophageal reflux disease, asthma, sleep apnea, and anemia who was admitted to our neurocritical care unit with the chief complaints of constipation, migraines, abdominal pain, and weakness. Her home medication regimen upon admission is listed in figure #1. Upon initial assessment, 11 pertinent DDIs existed and may have contributed to ongoing issues related to her chronic illnesses. For example, loratadine, scopolamine, amitriptyline, hydroxyzine, and diphenhydramine could decrease the efficacy of pyridostigmine and may have contributed to her weakness. Additionally, erythromycin, magnesium, and prochlorperazine may exacerbate symptoms of MG and may have also contributed.

The patient failed almost all possible options to treat her constipation including polyethylene glycol, bisacodyl, lactulose, senna, lubiprostone, docusate, prucalopride, and linaclotide. Of note, loratadine, scopolamine, amitriptyline, hydroxyzine, and diphenhydramine are all anticholinergic agents, which may have contributed to her constipation. After trial and error, her constipation improved with senna, prucalopride, and subcutaneous octreotide. 

Ubiquinone and riboflavin were ineffective for treating her migraines and increased her pill burden. As most abortive and prophylactic migraine medications (propranolol, botulinum toxin, magnesium, prochlorperazine, and gabapentin) should be avoided in MG, our polypharmacy consult service recommended valproic acid, which improved her migraine pain. For her abdominal pain, our service recommended nortriptyline and pregabalin. All agents helped decrease her pain scores from a 7/10 to a 3/10. 

After careful collaboration with the primary team, our service helped reconcile her DDIs, streamline her medication regimen and optimize the dosages. Upon discharge, our service reduced her home medications and DDIs (Figure 1). She reported an overall improvement of all symptoms.

Figure 1.

BID = twice daily; GT = gastric tube; INH = inhaled; PO = by mouth; QAM = every morning; QPM=every evening; QHS = nightly; Q12hr=every 12 hours; Q24hr; every 24 hours; Q6hr = every 6 hours; Q8hr = every 8 hours; Q72hr = every 72 hours; SQ = subcutaneously

 Case #2

Case #2 is a 13-year-old boy with history of intractable focal epilepsy and autism who was admitted due to increased seizure frequency. His home medications are listed in Figure 2 and consisted of 8 medications that created 14 DDIs. After initial assessment of his medication profile, there was concern about the reduced efficacy of risperidone, levothyroxine, prednisone and topiramate. Carbamazepine and phenytoin were drugs of concern as both medications induce the metabolism of CYP3A4, leading to reduced efficacy with many of his home medications. We met with the primary neurology team and worked together to wean the patient off carbamazepine and phenytoin and optimize the clobazam. Thyroid function tests (TFTs) were checked and were within normal limits despite the DDI, thus levothyroxine was discontinued. Prednisone was previously started as an anti-inflammatory by his primary care physician. Since it was deemed not medically necessary, the team tapered it off. Although phenobarbital is a CYP3A4 inducer, it was continued as it is not as potent an inducer as carbamazepine and phenytoin. The patient was discharged on 4 medications. He did not have any further seizures and his mother was satisfied with the simplified administration schedule.

Figure 2.

GT = gastric tube; Q12hr = every 12 hours; Q24hr = every 24 hours 

Conclusion

Neurocritical care patients benefit from a clinical pharmacist’s review of medications during admission, transitions of care or as needed to potentially decrease polypharmacy, ADRs, and DDIs. Benefits include decreased costs (both patient and institution), decreased waste, optimized medication regimens, and increased adherence.

At our institution, our neurocritical care patients may be admitted to or transferred to other units (some without a dedicated clinical pharmacist), thus warranting the need for our polypharmacy consult service. In addition, the polypharmacy consults help our team provide these types of clinical pharmacy services during the nights, weekends, and holidays when the dedicated clinical pharmacist for the floor is not available. We do not have a dedicated neurocritical care pharmacist, but instead a neurology/neurosurgery and a pediatric ICU pharmacist. These consults help both pharmacists work together to take care of their neurocritical care patients as they are transferred throughout different units in the hospital. A clinical pharmacist is a valuable asset for all care teams and may help improve a patient’s quality of life by assessing for polypharmacy. 

References

1. Fitzmaurice, M. G., Wong, A., Akerberg, H., Avramovska, S., Smithburger, P. L., Buckley, M. S., & Kane-Gill, S. L. (2019). Evaluation of potential drug–drug interactions in adults in the intensive care unit: a systematic review and meta-analysis. Drug safety, 42(9), 1035-1044.
2. Horace, Alexis E., and Fahamina Ahmed. Polypharmacy in pediatric patients and opportunities for pharmacists’ involvement. Integrated pharmacy research & practice 2015 Aug 21; 4:113–26. PMID:  
3. Rappaport, D. I., Collins, B., Koster, A., Mercado, A., Greenspan, J., Lawless, S. & Sharif, I. Implementing medication reconciliation in outpatient pediatrics. Pediatrics, 2011 11 Dec; 128(6), e1600-e1607. PMID:
4. Krupicka MI, Bratton SL, Sonnenthal K, et al. Impact of a pediatric clinical pharmacist in the pediatric intensive care unit. Crit Care Med. 2002, Apri;30:919–921. PMID:

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