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Hypertension and Emergency Department Visits
by Patients with Head and Neck Cancer
Marcelo Sandoval1, Srinivas R Banala1, Maria Teresa Cruz Carreras1, Demis N Lipe1, Sai Ching J Yeung1, Ehab Y Hanna2, Knox H Todd1,2, Kumar Alagappan1 and Cielito C Reyes Gibby1,3*
1Department of Emergency Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, USA
2Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, USA
3Department of Biostatistics, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, USA
Submission: March 19, 2020; Published: March 30, 2020
*Corresponding author: Cielito C Reyes-Gibby, Associate Professor, Department of Emergency Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1468, Houston, Texas 77030, USA
How to cite this article:Marcelo S, Srinivas R B, Maria T C C, Demis N L, Sai Ching J Y, et al. Hypertension and Emergency Department Visits by Patients with
Head and Neck Cancer. J Cardiol & Cardiovasc Ther. 2020; 16(1): 555929. DOI: 10.19080/JOCCT.2020.15.555929
Background: The Emergency Department (ED) is the safety net for unanticipated or undertreated health needs. Patients with cancer have been reported to be substantial users of ED resources, to be of higher acuity than others, and to have a longer length of stay. Patients with head and neck cancer live longer than patients with other types of cancer. Therefore, we assessed the extent to which epidemiological, behavioral, and clinical factors collected prior to treatment were associated with eventual ED visits in patients with head and neck cancer.
Methods: Questionnaires were administered at baseline, prior to cancer treatment. ED data were abstracted for up to 5 years follow up period from initial diagnosis and treatment of patients newly diagnosed with squamous cell carcinoma of the head and neck (HNSCC).
Results: Our sample comprised 969 patients. The earliest ED visit occurred within 1 week of diagnosis. As many as 513 patients had ≥1 ED visit and the mean time to first ED visit was 27 weeks (SD=2.3 weeks). The most frequent chief complaints were: pain (n=181; 35.3% [abdominal pain=16.3%, chest pain=7.5%]); fever (n=107; 20.9%); nausea/vomiting (n=64; 12.5%); weakness/fatigue (n=45; 8.8%). Multivariate logistic regression indicated that hypertension (OR=1.43, 95% CI=1.02–2.03; P=0.039), T-stage (OR=2.05, 95% CI=1.45–2.92; P<0.0001), and N-stage (OR=1.47, 95% CI=1.17–1.86; P<0.001) were significantly associated with ED visits.
Conclusion: To our knowledge, our study is the first to find a specific association between hypertension and ED visits in patients with HNSCC. Further research is needed to investigate possible reasons for the association between comorbidities such as hypertension and the need for emergent care, as well as to determine whether aggressive management of comborbid conditions during and after cancer therapy might reduce the likelihood of ED visits.
Keywords: Squamous cell carcinoma of the head and neck; Emergency; Pain; Depressed mood; Fatigue; Hypertension
Emergency departments (EDs) are becoming important primary sites for the care of cancer-related complications. Patients with cancer have been reported to be substantial users of ED resources, to be of higher acuity than others, and to have a longer length of stay . ED visits can result in hospitalizations and increased costs of care, cause breaks in ongoing cancer treatment, and negatively affect quality of life and overall survival [2-5]. ED visits are an important indicator of the quality of healthcare received by cancer patients.
Standard cancer therapies, including chemotherapy, radiotherapy, and surgery, can produce numerous short-term and long-term treatment-related adverse effects that may require emergency care . Further, the malignant process and its progression can exacerbate common preexisting conditions . Prompt diagnosis and appropriate treatment of these emergencies is essential to help restore a patient’s condition  and, possibly, to circumvent a life-threatening situation. The aging of the population, existing comorbidities, and the development of new therapeutic drugs and treatment strategies for malignant
disorders increase the complexity of managing patients with
cancer when they present to the ED. Understanding risk factors for
eventual ED visits on the basis of baseline indicators-for example,
preexisting comorbidities-could promote better management for
these patients during cancer treatment and could help them avoid
subsequent utilization of emergency care services.
In this study, we assessed the extent to which clinical, behavioral,
and epidemiological factors reported before commencement of
cancer treatment were independent risk factors for eventual ED
visits. Our sample was a group of treatment-naïve patients with
newly diagnosed squamous cell carcinoma of the head and neck
(HNSCC), which includes cancers of the pharynx, larynx, and
oral cavity  who presented for treatment at a tertiary cancer
center. We selected this population because patients with HNSCC
receive intense outpatient radiation and chemotherapy and may
undergo surgical interventions (resection, tracheostomy, feeding
gastrostomy) ; they also tend to live longer than patients with
other types of cancer . Treatment side effects, debilitating
functional impairment, and complex psychosocial issues may
develop for weeks to years after diagnosis and may necessitate
visits to the ED.
Although health outcomes in patients with HNSCC are known
to vary by extent of disease, little is known about prognostic
factors for ED visits. To our knowledge, this is the first study to
include a comprehensive assessment of potential risk factors
(clinical, epidemiological, and behavioral factors) for ED visits in
this population. This is an important aspect of efforts to integrate
the ED into the spectrum of care of cancer survivors .
Study Setting and Population: The study population
included all patients with newly diagnosed HNSCC who were
initially treated in the Head & Neck Center of a tertiary cancer
center between 2006 and 2009. Follow-up data were available for
up to 5 years.
Ethical Approval: This study was conducted according to a
clinical research protocol approved by our Institutional Review
Board. All procedures adhered to its guidelines and regulations, in
accordance with the Declaration of Helsinki Ethical Principles for
Medical Research Involving Human Subjects and with US Health
Insurance Portability and Accountability Act regulations.
The primary binary outcome variable was at least one ED visit
(yes/no). The descriptive analyses included additional outcome
variables such as chief complaints at the time of ED presentation,
time to first ED visit, and frequency of ED visits during the followup
period. Patients were followed for up to 5 years or until death.
All independent variables were collected at the time of
registration in the Head & Neck Center (baseline), prior to
cancer treatment. The questionnaire was developed by an
interdisciplinary team of scientists representing the areas of
epidemiology, medical oncology, behavioral science among others.
The overarching goal was to understand the epidemiology of the
different types of cancers and the underlying factors associated
with, and risk factors for, cancer, cancer progression, and survival
outcomes. Many questionnaire items were considered, but the
committee was very cognizant of patient burden, and the final
set of questions was decided through consensus . Clinical data
including stage of disease were abstracted from patients’ charts.
Epidemiological factors: Epidemiological variables included
age at the time of cancer diagnosis, sex, and self-reported race/
ethnicity (non-Hispanic white, non-Hispanic black, or Hispanic).
We excluded patients from other race categories due to small
sample size. Patient-reported comorbidities included heart
disease, stroke, hypertension, diabetes, and lung disease.
Clinical factors: Cancer-related variables included TNM
(T=primary tumor size, extent, or depth of penetration; N=lymph
node involvement; M=presence of metastasis) staging.
Behavioral factors: Behavioral variables included smoking
and alcohol consumption. Smoking was categorized as never
smoker, former smoker, or current smoker. Alcohol intake was
classified as never, social, moderate, or heavy. We defined heavy
alcohol use as ≥4 drinks per day, irrespective of sex, and moderate
alcohol use as >14 drinks per week for males and >7 drinks per
week for females, but in either case <4 drinks per day .
Patient-Reported Outcomes: Symptoms assessed at
baseline (pretreatment) included pain, depressed mood, and
fatigue--the most common side effects of cancer and its treatment
[9,11-13]. Baseline pain was assessed with two questions: “Have
you experienced pain in the last week?” (yes/no) and “Circle the
number that best describes the pain you are having” (rated on an
11-point numeric scale, with 0=no pain and 10=pain as bad as you
can imagine). The 0–10 scale is a recommended standard for pain
assessment in clinical studies of pain . We used the National
Comprehensive Cancer Network’s cutoff score of ≥7 on the 0–10
scale to indicate severe pain .
Two items from the SF-12, a validated, widely used measure
of quality of life in patients with cancer [16-19], were used to
assess depressed mood (“During the past 4 weeks, have you felt
downhearted and blue?”) and fatigue (“During the past 4 weeks,
did you have a lot of energy?”). These items were rated on a
6-point Likert scale; patients responding “most of the time” or “all
of the time” were considered to have severe depressed mood or
fatigue, respectively .
Emergency Department Data: Our institution’s ED has 43
beds and is staffed 24 hours a day, 7 days a week. Information on
all patients who visit the ED is collected in a database maintained
by the Department of Emergency Medicine. Initiated in 2006, the
database includes demographic information, type of cancer, and
primary and secondary presenting symptoms (chief complaints).
We reviewed ED data for up to 5 years from diagnosis and
treatment for each patient
Descriptive statistics were used to summarize patient
characteristics. Patients were coded as “0” if they had no ED visits
and “1” if they had at least one ED visit. Follow-up time was defined
as time from diagnosis to first ED visit (for those who presented to
the ED at least once), or to the date of abstraction (for individuals
with no ED visits) or death (for individuals who died during the
follow-up period but did not present to the ED).
Univariate and multivariate logistic regression analyses were
used to estimate the strength of association with ED visits for
the variables. Factors found to be significant (P<0.20) in the
univariate analysis were included in the multivariate model; a
P value of 0.20 was used because the traditional value (P<0.05)
often does not identify variables shown to be important in the
literature . Further variable selection in the multivariate
model was conducted using backward elimination. To obtain
the most parsimonious model, only variables with P values
<0.05 were included in the final model. All statistical analyses
were performed using SPSS software (SPSS Inc., Chicago, IL). All
statistical tests were 2-sided.
A total of 969 patients with HNSCC comprised our sample;
of these, 274 had cancer of the pharynx, 176 had cancer of the
larynx, and 519 had cancer of the oral cavity. The mean age for the
total sample was 59±11 years, and most of the patients were men
Selected patient characteristics are shown in Table 1. The
most commonly reported comorbid conditions at baseline were
hypertension (45.9%; 445/969), followed by heart disease
(20.1%; 195/969) and diabetes (14.4%; 140/969). Approximately
one in four participants were current smokers (22.8%; 220/967)
or heavy drinkers (22.5%; 201/894). At baseline, severe pain
(rated ≥7 on the 0-10 scale) was reported by 17.4% of patients
(169/969); 8.4% (75/889) reported depressed mood and 30.2%
(263/871) reported severe levels of fatigue.
We found that 513 (53%) of the patients visited the ED at least
once after cancer treatment during the follow-up period. The
most frequent chief complaints at the first ED visit were: pain
(n=181; 35.3% [abdominal pain=16.3%, chest pain=7.5%]); fever
(n=107; 20.9%); nausea/vomiting (n=64; 12.5%); weakness/
fatigue (n=45; 8.8%); bleeding (n=35; 6.8%); shortness of breath
(n=30; 5.8%); and change in mental status (n=13; 2.5%).
The mean and median number of ED visits for the entire sample
were 1.5 visits (SD=2.3 visits) and 1 visit (range, 0–16 visits),
respectively. The first ED visit occurred during the first week after
diagnosis and presentation to the cancer center. The mean time to first ED visit for the entire sample was 27 weeks (SD=2.3 weeks).
Table 1 shows that ED visit varied significantly by comorbidities
(heart disease, lung disease, hypertension), smoking status, age,
baseline symptom severity (pain, fatigue, depressed mood) and
disease stage (TNM).
Table 2 shows the results of the univariate and multivariate
analyses. Univariate analysis revealed the following significant
factors for ED visits: extent of disease, as evidenced by T, N, and
M staging as separate variables; certain clinical comorbidities,
including heart disease, lung disease, and hypertension; and
smoking. Patients with severe levels of pain, depressed mood,
or fatigue at baseline were also more likely to visit the ED than
were patients who did not report having severe levels of these
In multivariate analyses, we assessed the extent to which
factors from the univariate model influenced ED visits, adjusting
for time to first ED visit. The multivariate models indicated that
hypertension (OR=1.43, 95% CI=1.02–2.03; P=0.039) , T-stage
(OR=2.05, 95% CI=1.45-2.92; P<0.0001), and N-stage (OR=1.47,
95% CI=1.17–1.86; P<0.001) were significant factors for ED visits.
There are more than 14 million cancer survivors in the United
States and, of these, as many as 5 million are still within 5 years
of their primary diagnosis . Although advances in cancer
treatment have led to increases in survival, the early and late
toxicities of cancer treatment can be debilitating enough to require
medical care [3,23,24] and a visit to the ED. Preexisting comorbid
conditions, such as hypertension, can not only predispose a patient
to ED utilization earlier during cancer treatment, but can also
put the patient at risk for worsening of disease. Because cancer
treatment is often provided on an outpatient basis, understanding
factors that are associated with ED presentation within the cancer
population has clinical significance.
In our sample, hypertension as a pretreatment comorbidity
was one of only two significant risk factors for ED visits in
both univariate and multivariate analysis (the other being TN
status). However, little is known about the association between
hypertension, cancer, and ED visits, even though hypertension is
the most common comorbidity seen in patients with malignant
conditions . Hypertension is a well-established risk factor
for chemotherapy-induced cardiotoxicity ; moreover, certain
chemotherapeutic agents, such as the vascular signaling pathway
inhibitors, are known to cause hypertension and can potentially
worsen preexisting disease. These drugs inhibit angiogenesis and
play a key role in cancer-targeted therapy. Surgery or radiation
therapy that involves the head or neck can lead to baroreflex
failure and to associated difficult-to-treat labile hypertension and
hypertensive crisis . Poorly controlled hypertension can cause
severe symptoms that influence cancer management, thereby
potentially increasing the number of ED visits .
Assessment of comorbid hypertension at baseline, prior to
initiation of cancer treatment, has been recommended by the panel
of Investigational Drug Steering Committee of the US National
Cancer Institute , as a way to minimize the risk of end-organ
damage, enable continuation of cancer therapy, and prevent other
complications. Therefore, patients with preexisting hypertension
presenting to the ED with newly diagnosed cancer should be
assessed for end-organ damage, worsening hypertension, and
cardiotoxicity. In our study of treatment-naïve patients, 7.5% of
patients presented to the ED with chest pain and an additional
8.3% presented with shortness of breath or altered mentation.
Those patients presenting with hypertension and not currently
on cancer treatment should be carefully assessed, and treatment
of their hypertension should be considered.
Patients with HNSCC may also be especially prone to
dehydration because of reduced oral intake resulting from
dysphagia, the severity of which depends on the size and location
of the lesion. Thus, awareness on the use of antihypertensive
medications, especially diuretics is important since these
medications can worsen dehydration and can induce hypotension
in a dehydrated patient.
Baseline disease stage (T stage and N stage) was the other
important factor influencing the probability of an ED visit. This
is expected, as patients with advanced disease often present
with symptoms indicative of disease progression; further, the
symptoms experienced by patients with advanced disease are of
increased severity, which can make emergency care necessary
Pain and fever were two of the most frequent primary chief
complaints reported by our sample of HNSCC patients at the
time of ED presentation, a finding that is consistent with results
from other studies. For example, in 2015, Tang et al.  used
nationwide population-based data to investigate the chief reasons
for ED visits made by HNSCC patients in Taiwan. The study
revealed that pain was one of three principal complaints, alongside
respiratory distress and gastrointestinal issues, for ED visits in
that patient population. Tsai et al.  also found that pain was
the most common reason that patients with cancer visit the ED.
This finding was corroborated in a study conducted at a tertiary
care center in Brazil by Kraft Rovere et al. , who reported that
the pain was the most common complaint of patients with head
and neck cancer, who comprised 9% of all emergency visits by
cancer patients. We found that most of the patients with HNCSS in
our sample who presented to the ED with pain had abdominal or
chest pain, similar to the findings by Tsai et al. .
Fever is not unusual in patients with cancer, who have
weakened immune systems that make them prone to infection.
In our study, we did not distinguish those who came to the ED
with neutropenic fever from those who did not. Nonetheless,
neutropenia is a concern for many of the HNSCC patients who come
to the ED with fever. A study by Vidal et al.  noted that infection
is the principal cause of about two-thirds of cases of fever with
prolonged neutropenia seen in patients with cancer. Infectious
Diseases Society of America 2010 guidelines  for treating
neutropenic fever state that all patients should be treated with
broad-spectrum antibiotics within 2 hours of presentation. Stable,
well-appearing patients with a solid tumor may be discharged
with oral antibiotics and close follow-up on an outpatient basis;
conversely, unstable or ill-appearing patients with solid tumors
and all patients with liquid tumors (leukemia, lymphoma)
require immediate hospital admission when neutropenic fever is
present. require hospitalization. Patients who have had stem cell
transplants are considered immunosuppressed and should be
treated much like neutropenic patients.
Our study had limitations. We did not include type of cancer
treatment as a covariate. However, treatment is driven by extent of
disease and is therefore associated with tumor stage, which was assessed in this study (hence, high multicollinearity). The study
was also limited to patients with HNSCC at one tertiary cancer
center; it is possible that additional visits were made to EDs other
than ours. Finally, only very few patients of Asian/Pacific Islander
or American Indian/Alaska Native racial origin were available for
recruitment, limiting the generalizability of our findings. Thus,
additional studies are needed to validate our findings.
The ED is the safety net for unanticipated or undertreated health
needs. To our knowledge, our study is the first to find a specific
association between hypertension and ED visits in patients with
HNSCC. Further research is needed to investigate possible reasons
for the association between comorbidities such as hypertension
and the need for emergent care, as well as to determine whether
aggressive management of comborbid conditions during and after
cancer therapy might reduce the likelihood of ED visits.
The authors acknowledge Jeanie F. Woodruff, BS, ELS,
for editorial assistance and Valda D. Page, MPH, BS, for data
Funding: This work was supported by the National Institute
of Dental and Craniofacial Research of the National Institutes of
Health (NIH) [grant number R01 DE022891; PI: Cielito C. Reyes-
Gibby]; the National Cancer Institute of the NIH [grant number
P30 CA016672, MD Anderson Cancer Center Support Grant;
PI: Peter Pisters), and the MD Anderson Program in Oncologic
Emergency Medicine [PI: Cielito C. Reyes-Gibby]. The NIH had
no role in the conduct or reporting of the study; the content of
this report is solely the responsibility of the authors and does not
necessarily represent the official views of the NIH.
Author’ Contributions: SRB, S-CJY, KHT, and CCR: study
concept and design. SRB: acquisition of data/chart review; SRB,
S-CJY, and CCR: analysis and interpretation of data; MS, SRB,
MTCC, S-CJY, and CCR: drafting of the manuscript; MS, MTCC, DNL,
S-CJY, EYH, KHT, KA, and CCR: critical revision of the manuscript
for important intellectual content; S-CJY and CCR: statistical
expertise; KHT and CCR: obtained funding; EYH, KHT, KA:
administrative, technical, or material support; KHT and KA: study
supervision. CCR takes responsibility for the paper as a whole.
Competing Interests: MS reports no conflicts of interest.
SRB reports no conflicts of interest. MTCC reports no conflicts of
interest. S-CJY reports research funding from DepoMed, Newark,
CA and Bristol-Myers Squibb (ARISTA-USA program). EYH reports
no conflicts of interest. KHT reports no conflicts of interest. KA
reports no conflicts of interest. CCR reports no conflicts of interest.
Patrick DL, Ferketich SL, Frame PS, et al. (2004) National Institutes of Health State-of-the-Science Conference Statement: symptom management in cancer: pain, depression, and fatigue, July 15-17, 2002. J Natl Cancer Inst Monogr 32: 9-16.
Vidal M, Ferrer A, Serrano S, Tobeña M, Pajares I, et al. (2009) Fever in cancer patients as a cause of attendance in emergency room. American Society of Clinical Oncology 45th Annual Meeting, Orlando FL, May 29-Jun 2, J Clin Oncol, 2009.