Publication/Presentation Date

7-25-2014

Abstract

Observed Behavioral Effects when Medically Treating Type B Aortic Dissections

Jordan Williams, James Wu, M.D.

July 21, 2014

Abstract

This study sought to identify possible behavioral effects from treatment of Type B aortic dissections with antihypertensive medications. A retrospective study of 104 patient records and charts was performed searching for eleven different behavioral effects compiled from listed side effects of five different classes of antihypertensive medications. This resulted in 57 patients with observed behavioral effects, and 47 patients with no observed behavioral effects. The median age of the patient population was 68 ± 16 years. Of the 57 patients with observed behavioral effects, the most frequent symptom seen was anxiety and restlessness. Although it was not possible in this study to prove an exact cause and effect relationship between the antihypertensive medications and the behavioral effects, this study is still significant. The pattern of behavioral symptoms identified in this study, as well as the lack of statistically sound research in this area, create a need for further randomized controlled studies in order to possibly improve patient outcomes by identifying other aspects of needed treatment.

Introduction

A Stanford Type B aortic dissection is an event where the wall of the descending aorta tears, diverting blood from the true lumen, into a newly created false lumen (Kouchoukos, Blackstone, Hanley, & Kirklin, 2013). Over time this can lead to an aortic aneurysm, and possibly even a rupture of the aorta. Type B dissections are further classified as complicated and uncomplicated. Complicated dissections are those that involve spinal cord, renal and/or visceral ischemia, as well as aortic rupture (Moulakakis , et al., 2014), while uncomplicated dissections involve none of the aforementioned events. Complicated dissections usually require surgical intervention, by an endovascular stent graft or open surgical repair.

The accepted treatment of uncomplicated Type B aortic dissections continues to be medical treatment utilizing antihypertensive medications. There are many types of antihypertensive medications used in treatments today, including anti-adrenergic (including alpha and beta blockers), diuretics, calcium channel blockers, angiotensin converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARB), and drugs that are formed from combinations of all these types (Medications for Treating Hypertension, 2009). With the exception of the diuretics, all of the drugs described act on specific neurological pathways, for example ARB drugs block the angiotensin II receptor, thereby inhibiting angiotensin II from causing an increase in blood pressure.

Due to the fact that these drugs act to decrease blood pressure, changes in the patient’s perfusion may occur, especially if the patient was hypertensive before being diagnosed with the dissection. This change in perfusion then may result in a change in behavior, as the patient’s brain tissue is not receiving and exchanging the same amount of material over time as before. Because most of the prescribed antihypertensive medications act on neurological pathways, the drugs may also cause behavioral effects simply due to their mechanism of action. Patients may describe feeling, “dizzy” or “lightheaded”, among other symptoms, and in some cases may begin acting restlessly or even violently.

A literature review utilizing the key words “type B dissection”, “behavioral effects” and “medical treatment” revealed no studies done on the behavioral effects of treating Type B aortic dissections with antihypertensive medications. Furthermore this search revealed that there were no studies performed that compared the behavioral effects of different classes of antihypertensive medications being used to treat Type B aortic dissections (Chan, Lai, & Wright , 2014). A literature search using the key words “antihypertensive medication” and “behavioral effects” did result in articles published in the 1980’s and 1990’s, on the behavioral effects of various hypertensive medications. Most of these studies focused on the behavioral effects of one class of antihypertensive medication (Bird, Blizard, & Mann, 1990; Blumenthal , et al., 1988; Callender, Hodsman, Hutcheson, Lever, & Robertson, 1983; Conant , et al., 1989; McAnish & Cruickshank, 1990). However as one summary article stated, while these articles generally found no negative impacts on behavior, most of the articles utilized a patient sample of less than 20. (Muldoon, Manuck, Shapiro, & Waldstein, 1991). Therefore due to this finding, and the lack of research on the behavioral effects of treating type B aortic dissections medically, there is a need for further studies involving antihypertensive medications and their behavioral effects, especially when used to treat Type B aortic dissections.

The purpose of this study was to observe possible behavioral consequences of treating Type B aortic dissections medically, in order to determine the frequency of these behavioral consequences, and thus stimulate interest in further research involving randomized controlled trials.

Methods

This study was a retrospective study initially involving 244 patients selected from the hospital database. Patients were sorted based off of the following inclusion criteria: (1) Patient had to have Type B aortic dissection (versus Type A), (2) Patient had to be treated medically versus surgically, and (3) Patient could not have any history of behavioral disorders (stroke, dementia, etc.) before being treated for their Type B dissection. Of the 244 initial patients, 109 were found to present with type B aortic dissections. Of these 109, 104 patients were treated medically and did not have any major behavioral disorders prior to hospital treatment.

These patients’ medical records were then examined to determine if any behavioral changes after administration of antihypertensive medications could be observed. These changes were entered into a database, using the following selection options: anxiousness/restlessness, depression, disorientation, dizziness/lightheadedness, fatigue, hallucinations, headache, nausea, none found, "shakes", slurred/garbled speech and syncope. These categories were selected from common side effects listed for the major classes of antihypertensive medications found on Harvard Medical School’s health publication site (Medications for Treating Hypertension, 2009). If a new behavioral category, not seen in prior patients was discovered while reviewing the patients’ charts, this was added to the category set as well. Behavioral effects for each patient were only recorded if they didn’t present with those symptoms prior to hospitalization. For example, if a patient had a history of fatigue and then experienced fatigue, nausea, and dizziness while being treated, then only nausea and dizziness were recorded. A histogram was then constructed to show the relative frequency of the behavioral effects observed, along with a pie chart that compared the number of patients with behavioral effects found to the number of patients that had not observed behavioral effects.

Results

Table 1 Summary of Patient Demographics

Total Patients with Medically Treated Type B Aortic Dissection

104

Number with Behavioral Effects

57

Number of Males

67

Number of Females

37

Date Range

2004-2014 (10 Years)

Age Range

21-94 (73 years)

Median Age

68 ± 16 years

Number of Deaths

10

Figure 1 This figure displays the frequency of a given behavioral effect seen in the study population

Figure 2 This figure depicts the relative amount of patients in which behavioral effects found, and patients in which no effects were found

These results show that the patients in this study were mostly in their upper 60’s. From the histogram (Figure 1), it can be seen that of the behavioral effects observed, anxiousness/restless had the highest frequency. However it can also be observed that 45% of the patients did not present with any behavioral effects (Figure 2). It is also interesting to note that no events of depression or syncope were observed in the patient population (Figure 1).

Conclusion

This study revealed that while almost half of the patients observed did not present with any behavioral effects, the other half presented most frequently with “anxiousness/restlessness”. These results are interesting because the fact that half of the patients did not present with any behavioral effects, seems to possibly concur with the findings of the studies performed twenty years prior on hypertensive medications, which either found no negative effect on behavior or possibly found a positive effect. However as stated before, these studies are advanced in age, utilized very small sample sizes, and were note done on patients being treated for type B dissections. Therefore their results could be unduly biased.

For the patients that did respond to the antihypertensive medications with some form of behavioral effect, the fact that the top three frequencies of behavioral effect were anxiety and restlessness, along with nausea and fatigue, could indicate areas where patients would need more medication or other treatment. Even though this study utilized a cohort of 104 patients, it was still performed at one location, and thus results could still be skewed based on the patient population surrounding the hospital. Also because this study was retrospective in nature, exact cause and effect cannot necessarily be proven between the antihypertensive medication and the behavioral effects.

Based on these findings, randomized controlled trials need to be performed in order to better understand the effects of hypertensive medications on behavior in hypertensive only patients. These results can then be used to study effects that may or may not present themselves in treating Type B aortic dissections medically. In conclusion, this and other studies could greatly enhance the treatment of people with Type B aortic dissections, by identifying critical needs of the patient that might currently be ignored.

References

Bird, A., Blizard , R., & Mann, A. (1990). Treating hypertension in the older person: an evaluation of the association of blood pressure level and its reduction in cognitive performance. Journal of Hypertension, 147-52. Retrieved from http://www.druglib.com/abstract/bi/bird-as_j-hypertens_19900200.html

Blumenthal , J., Madden, D., Krantz, D., Light, K., McKee, D., Ekelund, L., & Simon, J. (1988). Short-term behavioral effects of beta-adrenergic medications in men with mild hypertension. Clinical Pharmacology and Therapeutics, 429-35. Retrieved from http://www.ncbi.nlm.gov/pubmed/3356086

Callender, J., Hodsman, G., Hutcheson, M., Lever, A., & Robertson, J. (1983). Mood Changes during captopril therapy for hypertension. A double-blind pilot study. Hypertension, 90-93. Retrieved from http://hyper.ahajournals.org/content/5/5_Pt_2/III90.short

Chan, K. K., Lai, P., & Wright , J. M. (2014). First-line beta-blockers versus other anithypertensive medications for chronic type B aortic dissection. Cochrane Database of Systematic Reviews . doi:DOI: 10.1002/14651858.CD010426.pub2

Conant , J., Engler , R., Janowsky, D., Maisel, A., Gilpin, E., & LeWinter, M. (1989). Central Nervous System side effects of beta-adrenergic blocking agents with high and low lipid solubility . Journal of Cardiovascular Pharmacology , 656-661. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/2471005

Kouchoukos, N., Blackstone, E., Hanley, F., & Kirklin, J. (2013). Kirklin/Barratt-Boyes Cardiac Surgery, 2 Vol Set. Elsevier Health Sciences. Retrieved 2014

McAnish , J., & Cruickshank, J. (1990). Beta-Blockers and Central Nervous System Side Effects. Pharmacology and Therapeutics , 163-197. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/1969642

Medications for Treating Hypertension. (2009, August). Harvard Women's Health Watch. Retrieved from http://www.health.harvard.edu/newsletters/Harvard_Womens_Health_Watch/2009/August/Medications-for-treating-hypertension

Moulakakis , K., Mylonas , S., Dalainas, I., Kakisis, J., Kotsis, T., & Liapis, C. (2014). Management of complicated and uncomplicated acute type B dissection. A systematic review and meta-analysis. Annals of Cardiothoracic Surgery, 234-246. Retrieved from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4052408/

Muldoon, M. F., Manuck, S. B., Shapiro, A. P., & Waldstein, S. R. (1991). Neurobehavioral effects of antihypertensive medications. Journal of Hypertension, 549-559. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/1679451

Comments

Jordan Williams, Rensselaer Polytechnic Institute.

Mentor: James Wu

Department(s)

Department of Surgery, Department of Surgery Faculty, Research Scholars, Research Scholars - Posters

Document Type

Poster

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