Download Prevalence pattern and outcome of hypertensive

PREVALENCE PATTERN AND OUTCOME OF HYPERTENSIVE
EMERGENCIES AMONG ADULT MEDICAL PATIENTS ADMITTED TO
BUGANDO MEDICAL CENTRE
BY
GRAHAME MTUI (MD)
A DISSERTATION TO BE SUBMITTED IN PARTIAL FULFILMENT FOR
REQUIREMENT OF THE AWARD OF MASTERS OF MEDICINE (INTERNAL
MEDICINE) OF CATHOLIC UNIVERSITY OF HEALTH AND ALLIED
SCIENCES–BUGANDO, MWANZA TANZANIA
2014
CERTIFICATION
The undersigned certify that they have ready and hereby recommend acceptance for
examination by Catholic University of Health and Allied Sciences (CUHAS) a
dissertation entitled: Prevalence pattern and outcome of hypertensive emergencies
among adult medical patients admitted to Bugando Medical Centre.
__________________________________
__________________
Prof. Johannes B Kataraihya MD, MMED (Internal Medicine)
Date
Associate Professor
Catholic University of Health and Allied sciences
__________________________________
___________________
Dr. Robert N Peck MD, MMED (Internal Medicine)
Senior Lecturer
Catholic University of Health and Allied Sciences
i
Date
DECLARATION & COPYRIGHT
I, Grahame Geofrey Mtui, hereby declare that this dissertation is my own original
work and that it has not been presented and will not be presented to any other
university for a similar or any other degree award.
Signature______________________
Date__________________________
“This dissertation is a copyright material protected under the Berne Convention, the
copyright Act of 1999 and other international and national enactments, on that behalf,
on intellectual property. It may not be reproduced by any means, in full or in part,
except for short extracts in fair dealing, for research or private study, critical scholarly
review or discourse with acknowledgement, without the written permission of the
Director of Graduate studies, on behalf of both the author and the “Catholic
University of Health and Allied Studies (CUHAS)”
ii
TABLE OF CONTENTS
CERTIFICATION ..................................................................................................................i
DECLARATION & COPYRIGHT ....................................................................................... ii
TABLE OF CONTENTS..................................................................................................... iii
LIST OF FIGURES .............................................................................................................. vi
LIST OF TABLES ..............................................................................................................vii
ACKNOWLEDGEMENTS ............................................................................................... viii
OPERATIONAL DEFINITIONS ......................................................................................... ix
ABBREVIATIONS .............................................................................................................. xi
ABSTRACT ...................................................................................................................... xiii
CHAPTER 1: INTRODUCTION .......................................................................................... 1
1.1 BACKGROUND ......................................................................................................... 1
1.2 STATEMENT OF THE PROBLEM AND RATIONALE ............................................ 4
1.3 RESEARCH QUESTION ............................................................................................ 4
1.4 HYPOTHESIS ............................................................................................................. 4
1.5 STUDY OBJECTIVES ................................................................................................ 5
1.5.1 Broad Objective: .................................................................................................... 5
1.5.2 Specific objectives: ................................................................................................ 5
CHAPTER 2: LITERATURE REVIEW ................................................................................ 6
2.1 Prevalence of hypertension and hypertensive emergencies ........................................... 6
iii
2.2 Factors associated with hypertensive emergencies ........................................................ 9
2.3 Outcome of hypertensive emergencies........................................................................ 10
CHAPTER 3: METHODOLOGY........................................................................................ 13
3.1 STUDY AREA .......................................................................................................... 13
3.2 STUDY DESIGN ....................................................................................................... 13
3.3 STUDY POPULATION ............................................................................................. 13
3.3.1 Inclusion Criteria ................................................................................................. 13
3.3.2 Exclusion criteria: ................................................................................................ 13
3.4 SAMPLE SIZE .......................................................................................................... 14
3.5 DATA COLLECTION ............................................................................................... 14
3.6 DATA PROCESSING AND ANALYSIS: ................................................................. 16
3.7 ETHICAL CONSIDERATION .................................................................................. 17
CHAPTER 4: RESULTS ..................................................................................................... 18
4.1 Enrolment .................................................................................................................. 18
4.2 Baseline socio-demographic and clinical characteristics ............................................. 19
4.3 Prevalence of hypertensive emergencies ..................................................................... 19
4.4 Outcomes ................................................................................................................... 21
4.5 Factors associated with hypertensive emergencies ...................................................... 22
4.6 Predictors of in-hospital fatality rates ......................................................................... 26
4.7 Predictors of 3 months fatality rates ............................................................................ 29
CHAPTER 5: DISCUSSION ............................................................................................... 32
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5.1 Prevalence of hypertension and hypertensive emergencies ......................................... 32
5.2 Patterns of hypertensive emergencies ......................................................................... 34
5.3 Factors associated with hypertensive emergencies ...................................................... 35
5.4 Fatality ....................................................................................................................... 37
5.5 Predictors of in-hospital and 3-months fatality............................................................ 38
CHAPTER SIX ................................................................................................................... 40
6.1 CONCLUSION .......................................................................................................... 40
6.2 LIMITATIONS .......................................................................................................... 41
6.3 RECOMENDATIONS ............................................................................................... 42
REFERENCES .................................................................................................................... 43
APPENDICES ..................................................................................................................... 46
APPENDIX 1: QUESTIONNAIRE ................................................................................. 46
APPENDIX 2: INFORMED CONSENT – ENGLISH VERSION .................................... 56
APPENDIX 3: INFORMED CONSENT – KISWAHILI VERSION ................................ 58
APPENDIX 4: ETHICAL CLEARANCE CERTIFICATE .............................................. 61
v
LIST OF FIGURES
Figure 1: Overview of study enrolment .................................................................... 18
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LIST OF TABLES
Table 1: Baseline characteristics of 647 patients admitted to BMC from October 2013
until December 2013. .............................................................................................. 20
Table 2: Types of hypertensive emergencies among 82 consecutive adults admitted to
BMC with hypertensive emergency. ........................................................................ 21
Table 3: Overlap between hypertensive emergencies among 82 consecutive adults
admitted to BMC with hypertensive emergency ....................................................... 21
Table 4: In hospital, 1 month and 3 months post-discharge outcomes among 82 adults
admitted with hypertensive emergency .................................................................... 22
Table 5: Factors associated with hypertensive emergencies among 82 adults admitted
with hypertensive emergencies to BMC by Univariate Analysis .............................. 24
Table 6: Factors associated with hypertensive emergencies among 82 adults admitted
to BMC by Multivariable logistic regression. ........................................................... 26
Table 7: Baseline Predictors of in hospital mortality among 82 adults admitted to
BMC with hypertensive emergencies and followed up until discharge by univariate
logistic regression .................................................................................................... 27
Table 8: Baseline Predictors of in hospital mortality among 82 adults admitted to
BMC with hypertensive emergencies and followed up until discharge by
Multivariable logistic regression .............................................................................. 29
Table 9: Baseline Predictors of 3 month mortality among 82 adults admitted to BMC
with hypertensive emergencies and followed up until 3 months after discharge by
univariate logistic regression ................................................................................... 29
Table 10: Baseline Predictors of 3 month mortality among 82 adults admitted to
BMC with hypertensive emergencies and followed up until 3 months after discharge
by multivariable logistic regression.......................................................................... 31
vii
ACKNOWLEDGEMENTS
I wish to express my sincere gratitude to all who have made the completion of this
dissertation possible. I would like to thank very much my supervisors Prof J.
Kataraihya and Dr R. Peck for their tireless efforts in the supervision
of my work from the beginning to the end. Their guidance, comments, critiques,
support and patience have enabled the completion of this difficult job.
I would like to express my sincere gratitude to all members of the department of
Internal Medicine BMC/CUHAS, for their constructive comments, cooperation,
support and assistance in all stages of this study. Also to my colleagues especially Dr
Taibali Abderasul and Dr Missana Yango for being hand in hand from beginning of
the study to the end especially during data collection, without forgetting Ms Rim
Elchaki (Medical student from Weill Cornell) for her assistance during data entry.
I greatly appreciate the help from Ms Eugenia for processing my samples as well as
Dr Hassani (Opthalmologist) for his assistance during fundus examination.
Special thanks to my family (my lovely wife Lilian Shao, my daughter Charisma) and
my parents for being supportive throughout my research.
viii
OPERATIONAL DEFINITIONS
Hypertension: Defined by the average of two systolic blood pressures (SBP) >140
and/or diastolic blood pressures (DBP) > 90 mmHg and/or current use of
antihypertensive medications at the time of admission.
Severe Hypertension: Defined as average systolic blood pressure (SBP) >180 and or
diastolic blood pressure (DBP) ≥110 mmHg.
Hypertensive Emergency: Is severe hypertension associated with end organ damage.

Acute Kidney Injury defined as an absolute increase in serum creatinine
concentration of ≥26.4umol/L from baseline or percentage increase in serum
creatinine concentration of ≥ 50% or decreased urine output less than
0.5mls/kg/hr for more than six hours (1). In the absence of baseline creatinine
RIFLES criteria will be used which suggest back-calculating an estimated
baseline creatinine concentration using the four variable MDRD equation,
assuming a baseline GFR of 75ml/min/1.73m2 (2).

Renal dysfunction: Defined as eGFR<60ml/min/1.73m2 (calculated using
Chronic Kidney Disease – Epidemiology equation).

Acute myocardial infarction: Was defined according to the previous World
Health Organization’s criteria for acute, evolving or recent myocardial
infarction which requires combination of two of three characteristics: typical
symptoms (i.e. chest discomfort), typical rise and gradual fall of troponin or
more rapid rise and fall of CK-MB, and ECG changes indicative of ischemia
(ST segment elevation or depression) involving the development of
pathological Q-waves.
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
Hypertensive Encephalopathy: Patients who had severe hypertension and
alteration of mental status with no focal neurological deficits which resolve
after lowering the blood pressure were considered as hypertensive
encephalopathy.

Acute Pulmonary Oedema: Defined as presence of dyspnoea and bilateral
basal crackles confirmed by chest x-ray by radiologist.

Hypertensive Retinopathy: Acute onset of blurred vision with retinal
changes by fundoscopy classified into mild, moderate, and severe.
Mild - Retinal arteriolar narrowing, wall thickening or opacification, and
arteriovenous nicking (nipping).
Moderate - Hemorrhages, either flame or dot-shaped, cotton-wool spots, hard
exudates, and microaneurysms.
Severe - Some or all of the above, as well as papilledema.

Hypertensive Stroke: severe hypertension with sudden onset of neurological
deficits and confirmed by CT scan of the brain whether ischemic, hemorrhagic
or both.
x
ABBREVIATIONS
BMC.................................................Bugando Medical Centre
BMI..................................................Body Mass Index
BP.....................................................Blood Pressure
CKD.................................................Chronic kidney disease
CT scan.............................................Computed Tomography Scan
CUHAS............................................Catholic University of Health and Allied Sciences
CVS..................................................Cardiovascular System
CXR..................................................Chest X-ray
DBP..................................................Diastolic Blood Pressure
ECG..................................................Electrocardiography
eGFR .................................................Estimated glomerular filtration rate
GCS...................................................Glasgow Coma Scale
GFR...................................................Glomerular filtration rate
HF......................................................Heart Failure
HIV...................................................Human Immunodeficiency Virus
HTN...................................................Hypertension
ICU...................................................Intensive Care Unit
JNC...................................................Joint National Committee
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KDOQI............................................ Kidney Disease Outcome Quality Initiative
LOC...................................................Loss of Consciousness
LVH..................................................Left Ventricular Hypertrophy
MAP..................................................Mean Arterial Blood Pressure
MDRD..............................................Modification of Diet in Renal Disease
SBP...................................................Systolic Blood Pressure
SSA...................................................Sub Saharan Africa
STEMI...............................................ST Elevation Myocardial infarction
USA...................................................United States of America
WHO..................................................World Health Organisation
xii
ABSTRACT
Background: Hypertension is increasingly common in sub-Saharan Africa (SSA) and
hypertensive emergencies are among the medical emergencies that cause morbidity
and mortality among hypertensive patients. In Tanzania, the prevalence of
hypertension is high with low levels of detection, treatment and control. Data
regarding the types of hypertensive emergencies, associated factors and outcomes are
lacking.
Objectives: To determine prevalence, patterns, predictors and outcome of
hypertensive emergencies among adult patients admitted to Bugando Medical Centre
(BMC).
Methodology: This was an analytical cross-sectional study with a prospective followup to determine the outcomes conducted on all adult patients admitted in medical
wards as well as in adult intensive care unit (AICU) between October and December
2013. These patients were interviewed using a modified WHO STEPS questionnaire
and screened for signs and symptoms of hypertensive emergencies. Patients with
severe hypertension underwent fundoscopy, chest x-ray, 12 lead electrocardiogram,
and serum creatinine. Brain CT scan was requested in those with stroke/altered mental
status and an echocardiogram for those with heart failure or acute myocardial
infarction. These patients were then followed up until discharge and three months
thereafter.
Results: A total of 647 patients were enrolled into the study with a median age of 45
years [32-61.5] and females were 48.2%. Eighty-two patients (12.7%) met the criteria
for hypertensive emergency, the majority (85.4%) had more than one emergency and
the commonest type was hypertensive retinopathy (62.2%). Hypertensive emergency
xiii
was significantly associated with female gender and age above 45 years. During
hospitalisation 30% of patients with hypertensive emergencies died, and by three
months more than 50% were dead. Hypertensive emergency with impaired renal
function was found a statistically significant predictor of fatality both in hospital and
at three months.
Conclusion: Hypertensive emergency is one among the common causes of admission
in medical wards of BMC associated with high fatality. Associated factors include
female gender and age above 45 years. Hypertensive emergency with impaired renal
function was significantly associated with both in hospital and three months case
fatality rates.
xiv
CHAPTER 1: INTRODUCTION
1.1 BACKGROUND
Hypertension is an established risk factor for cardiovascular, cerebrovascular, and
renal disease (3). Acute elevations in blood pressure (BP) can result in acute endorgan damage with significant morbidity and mortality. Prompt recognition,
evaluation, and appropriate treatment of these conditions are crucial to prevent
permanent end organ damage.
Worldwide, hypertension is still an important public challenge and its prevention,
detection, treatment and control should receive high priority (4). However in subSaharan Africa (SSA) most countries are still battling with infectious diseases such as
Human Immunodeficiency Virus (HIV), malaria, and tuberculosis, and most
governments in the region have limited resources and health budgets. An increasing
burden of hypertension in this region is therefore likely to be of grave consequence.
Treatment and control rates are likely to be even lower than the dismal rates in Europe
and North America. In Tanzania, the prevalence of hypertension is also high with low
levels of detection, treatment and control (5,6). Recent analysis of data from Bugando
Medical Centre (BMC) indicate that hypertension related diseases were the number
one cause of death, admission and hospital days in patients over the age of 50 years,
accounting for 28.9% of deaths, 28.5% of admissions and 27.8% of hospital stay in
this age group and that hypertensive emergencies were the most common reason for
admissions among persons with hypertension (7).
1
Hypertensive emergency is a situation in which uncontrolled hypertension is
associated with acute end-organ damage such as hypertensive encephalopathy,
retinopathy, dissecting aortic aneurysm, ischemic heart disease, acute pulmonary
oedema, and acute kidney injury. Most commonly hypertensive emergencies occur in
the setting of severe elevations in BP, such as diastolic BP (DBP) ≥ 130 mmHg. Most
patients presenting with hypertensive emergency have chronic hypertension, although
the disorder can present in previously normotensive individuals. Hypertensive
emergencies most commonly occur due to poor treatment, noncompliance with or
withdrawal from prescribed antihypertensive agents as well as acute accelerated
hypertension in a patient with existing primary as well as secondary hypertension.
However in Africa, adverse socio-economic status, obesity, cigarette smoking and
poor compliance to antihypertensive agents have been associated with poor BP
control hence complications (8).
The presentation of hypertensive emergencies depends on the organs involved. For
hypertensive encephalopathy, patients may present with headache, nausea and
vomiting, visual disturbances, confusion, rarely focal or generalised weakness etc. If
not adequately treated cerebral haemorrhage or stroke, coma and death occur, but with
proper treatment it can be completely reversible. Hypertension has profound effects
on various parts of the eyes. Classically, elevated blood pressure results in a series of
retinal microvascular changes called hypertensive retinopathy, comprised of
generalized and focal retinal arteriolar narrowing, arteriovenous nicking, (more
closely related to aging than to BP), retinal haemorrhages, microaneurysms and, in
severe cases, optic disc and macular oedema. Fundoscopy is a useful tool in
recognising these changes. The cardiovascular system is affected as increased cardiac
2
workload leading to cardiac failure; this is accompanied by left ventricular
hypertrophy, congestive heart failure (with impaired or preserved left ventricular
ejection fraction), myocardial ischemia, and/or myocardial infarction. The renal
system is impaired when high BP leads to arteriosclerosis, fibrinoid necrosis, and an
overall impairment of renal protective auto regulatory mechanisms. This may
manifest as worsening renal functions or decreased urine output.
Morbidity and mortality depend on the extent of end organ damage on presentation
and degree to which blood pressure is controlled subsequently. Therefore treatment of
these emergencies requires immediate, accurate diagnosis and therapy to interrupt
ongoing or prevent impending target-organ damage. Delay in initiating effective
therapy or too rapid reduction of BP can produce severe complications involving
these target organs. It is recommended to use short acting intravenous antihypertensive agents, with a goal to reduce mean arterial pressure (MAP) by 20-25%
over four to six hours (9).
3
1.2 STATEMENT OF THE PROBLEM AND RATIONALE
Hypertension is increasingly common in SSA. In a recent study at Bugando,
hypertension-related conditions were 2nd only to HIV as a cause of admission, death
and hospital days among adult medical inpatients. Hypertensive emergency was the
most common hypertension-related condition but the types of hypertensive
emergencies and the out-of-hospital outcomes could not be determined from this
study (7). Data regarding the types of hypertensive emergencies seen in sub-Saharan
Africa, the presenting features and the outcomes are lacking. The prevalence and
clinical picture and outcome of hypertensive emergencies in East Africa have not
been clearly described. Data on these patterns are important for improving clinicians’
awareness. Addressing the risk factors to the community will also improve awareness,
overall morbidity and mortality among these patients will be improved. Therefore
there is an essential need to conduct an epidemiological profile on the prevalence,
predictors, and outcome of hypertensive emergencies in Tanzania.
1.3 RESEARCH QUESTION
What are the prevalence, patterns, associated factors and outcome of hypertensive
emergencies among adult patients admitted in BMC?
1.4 HYPOTHESIS
We hypothesized that 10% adult admissions to BMC meet criteria for hypertensive
emergency and most common hypertensive emergencies are pulmonary oedema and
encephalopathy but hypertensive renal dysfunction is commonly undiagnosed. We
also hypothesized that adherence to anti-hypertensives at 3 months after discharge is
less or equal to 25%.
4
1.5 STUDY OBJECTIVES
1.5.1 Broad Objective:
To determine prevalence, pattern, associated factors and outcome of hypertensive
emergencies among adult patients admitted to BMC.
1.5.2 Specific objectives:
1. To determine the prevalence of hypertensive emergencies among adults
admitted to the medical wards of BMC.
2. To determine the pattern of hypertensive emergencies (i.e. types of
emergencies) among adults admitted to BMC.
3. To determine factors associated with hypertensive emergencies among adults
admitted to BMC.
4. To determine the case fatality rates both in-hospital and after 3 months among
hypertensive patients admitted to BMC
5. To determine the predictors for fatality among patients with hypertensive
emergencies admitted to BMC.
5
CHAPTER 2: LITERATURE REVIEW
2.1 Prevalence of hypertension and hypertensive emergencies
More than quarter of the world’s adult population had hypertension in 2000 and this
proportion will increase to 29% (1.56 billion) by 2025 (4). According to the seventh
joint national committee for hypertension, JNC VII (3), hypertension is the most
common primary diagnosis in USA affecting almost 25% of the people. About 30%
are unaware they have hypertension, and control rate is still below 50%.
Hypertension is also considered a major public health problem in SSA with low levels
of detection, treatment and control (5,10). A study done among civil servants in Accra
Ghana involving seven ministries showed the prevalence of hypertension to be 30.2 %
and BP control to below 140/90 mmHg was only 11.4%. This study also showed
47.5% of hypertensive patients had target organ damage associated with high SBP
and DBP. Hypertensive retinopathy accounted for 70% of the target organ damage
with 1% having grade 3 retinopathy, and none had grade 4 retinopathy. In addition,
13.4% of the participants had albuminuria (30-300 mg/d) (11).
Hypertensive emergency is one of the most common complications of hypertension
worldwide. A retrospective study done in Brazil to assess the prevalence of
hypertensive crisis among adult patients attending emergency unit of the universityaffiliated hospital showed the proportion of hypertensive emergencies among
hypertensive crisis as high as 39.6%. Most cases of hypertensive emergencies
corresponded to cerebrovascular lesions (58%), with ischemic stroke being the
6
commonest, followed by hemorrhagic stroke, and subarachnoid haemorrhage. Thirtyeight percent corresponded to cardiovascular complications, including acute
pulmonary edema, followed by acute myocardial infarction. Diabetes, present in more
than 26% of patients with hypertensive emergency was found to be a statistically
significant risk factor for the development of hypertensive emergencies (12).
A study done in Iran showed that among hypertensive patients, 39.9% had
hypertensive retinopathy (women 45.6%, men 33%). Among these patients 42.4%,
20%, 2.4% had retinopathy grade 1, 2, and 3 respectively. Prevalence rate of
retinopathy in patients suffering from severe hypertension was 84.6%. Most common
ophthalmic findings were arteriovenous narrowing 35.5%, arteriovenous nicking
17.12%, and cotton wool spots 9% (13).
However in a large multicentre study done in Italy on hospital admissions for
hypertensive crisis in the emergency departments showed a prevalence of
hypertensive crisis of 1,546/333,407 (0.46%) and 391/1,546 (25.3% ) of them had
hypertensive emergencies. Among patients with hypertensive emergencies, 121
(30.9%) had acute pulmonary edema, 86 (22.0%) had stroke, including 60 ischemic
strokes and 26 hemorrhagic strokes, 70 (17.9%) had myocardial infarction, 31 (7.9%)
had acute aortic dissection, 23 (5.9%) had acute renal failure and 19 (4.9%) had
hypertensive encephalopathy. Two patients had both acute pulmonary edema and
stroke (14).
Another multicentric study on cardiovascular emergencies in SSA by Bertrand E et al
involving more than 600 patients demonstrated that severe hypertension (32.2%) was
7
the commonest presentation followed by heart failure (27.5%) and stroke (20.3%).
The most common emergency resulting in death included was stroke 31.9% (15).
In another study done in Nigeria among hypertensive patients, only 14.2% had self
reported hypertension and of these only 18.6% had been on medication in the past
three months. Of these only 27.3% had controlled BP (16). In the same study 43%
had evidence of target organ damage whereby hypertensive retinopathy accounted for
2.2% and the commonest retinopathy was grade 1 (40.2%), followed by grade 2
(37.6%) (16). Microalbuminuria was found in 12.3%, and gross proteinuria in 15.2%.
In spite of the low levels of angina and myocardial infarction, ischemic changes and
evidence of old infarcts were found in the ECGs of 12.3% of the population studied
(16).
In Sudan, a prevalence of hypertension of 7.5% has been reported. A study by
Hussain et al in Sudan showed that among patients with hypertension, only 46.0% had
both SBP and DBP controlled to below 140/90 mmHg. Analysis of end organ damage
showed that 63.6% could be considered as being at Stage 1 of the WHO classification,
i.e., they did not exhibit any type of target organ involvement. On the other hand,
11.1% had Stage 2 involvement in the form of albuminuria, elevated plasma
creatinine (1.2 to 2 mg/dl), LVH and retinal vessel narrowing.
Moreover, WHO Stage 3 target organ damage was detected in 25.3% with angina
pectoris occurring at a frequency of 9.6% while myocardial infarction and renal
failure were each seen in 1.5% of patients. Severe retinopathy (haemorrhages or
exudates with or without papilloedema) occurred in only 3.5% of all patients and 14%
of those with Stage 3 target organ damage (8).
8
An observational study done in Angola on characteristics of 123 patients aged 45 or
under hospitalized for hypertensive emergencies showed a prevalence of hypertensive
emergency of 4.3% and the most frequent forms of presentations were hypertensive
encephalopathy and hemorrhagic stroke consisting of 9.8% and 82.1% respectively
(17).
Furthermore a study done on hypertensive emergencies at the University Hospital
Centre in Brazzaville, Congo showed a prevalence of 4% among hypertensive
patients. The disease underlying hypertensive emergency was stroke (50%), heart
failure (26.3%), hypertensive encephalopathy (14.4%), malignant hypertension
(11.8%) and renal failure in 13.1% (18).
2.2 Factors associated with hypertensive emergencies
A study done in USA showed that less effective control of systolic blood pressure on
an out-patient basis is an independent risk factor for hypertensive crisis leading to
emergency department presentation. It was not known whether the poor control was
due to non-adherence, inadequate response to specific antihypertensive medication or
both (19). In another study done in USA in outpatients clinics, old age, multi drug
regimens, lack of knowledge by the patients of their target SBP and report of
hypertension medication side effects were the independent predictors of poor control
of hypertension (20).
Furthermore non-adherence with antihypertensive medications, which adversely
affects the adequate control of hypertension, lack of a primary care physician, and the
lack of insurance, have all been shown to be risk factors for hypertensive crisis (21).
9
Another study done in Switzerland on risk factors for promoting hypertensive crisis
identified several potential risk factors including female gender, higher grades of
obesity, the presence of hypertension or coronary heart disease, the presence of
somatoform disorders, a high number of antihypertensive drugs and non adherence to
medication (22).
Very few studies have been done to determine associated factors or predictors of
hypertensive emergency among adults in SSA. A study done in South Africa on
determinants of target organ damage in black hypertensive patients attending primary
health care services found renal impairment in 26%, LVH in 35% and ischemic ECG
patterns in 49% of participants. Uncontrolled hypertension and older age were most
often associated with target organ damage (23). Another study at the University
Hospital Centre in Congo showed the predictors of hypertensive emergencies being
obesity, history of hypertension and low socioeconomic status (18).
2.3 Outcome of hypertensive emergencies
In general, the outcomes of hypertensive emergency are poor although most of this
data comes from high or middle-income countries. In United Kingdom it was shown
that renal function continues to deteriorate in some patients with malignant
hypertension despite a good degree of control of their blood pressures having been
achieved at follow up (24). In Thailand, a study on hypertensive emergencies among
patients admitted to the medical wards of Siriraj Hospital in 2003 showed
hypertensive emergencies are usually found in patients with a history of hypertension
and diabetes mellitus or kidney failure and the average hospital stay was 9.8 days and
in hospital mortality was 15% (25). A study done in Mexico City, on about 9000
patients with hypertensive crisis who are admitted to a coronary care unit showed
10
overall mortality rate for patients with hypertensive crisis in the unit to be 3.7%.
Among patients with hypertensive emergencies, 4.6% died and mortality among
hypertensive urgency cases was 0.8% (26).
Furthermore a study on practice pattern, outcomes and end-organ dysfunction for
patients with acute severe hypertension in USA revealed hospital mortality of 6.9%
with aggregate 90-day mortality rate of 11%, and 59% had acute/worsening end-organ
dysfunction during hospitalisation. The 90-day readmission rate was 37% of which
one quarter was due to recurrent acute severe hypertension (27).
Nevertheless, another observational cross sectional study done in the United States to
describe the frequency of rehospitalisation for patients with acute severe hypertension
found 90-day readmission rate was 35% (354/1,009) of patients discharged home
alive, and 41% (144/354) were readmitted more than once. Also 18 (1.9%) patients
were dead at 90 days (28).
Very few studies have been done regarding the outcomes of hypertensive emergency
in Africa. A five-year review of hypertensive related admissions into the medical
wards of the University of Nigeria Teaching Hospital showed a case fatality of 42.6%.
Forty five percent of deaths occurred during acute hypertensive crises such as cerebral
vascular accidents, hypertensive encephalopathy, and acute renal failure (29). In our
own data from BMC on hypertensive related admissions, hypertensive emergency
contributed to17.5% of all hypertensive related deaths (7).
Patients with hypertensive emergencies require immediate reduction of BP (within 46 hours) to prevent and/or arrest progressing end organ damage and to prevent death.
This may be best achieved in intensive care unit (ICU) with the use of short acting,
titrable intravenous ant-hypertensive agents such as esmolol (9). Limitations in ICU
11
beds and intravenous anti-hypertensive drug supplies may lead to delayed reduction in
BP. In a study done in Congo the length of treatment of a hypertensive emergency
averaged 14.7 hrs (range from 5 to 48hrs) (18).
From Angolan study by Garcia GM et al on hypertensive emergency among patients
of 45 years or under admitted to one of the hospitals, the in hospital mortality was
31/123 (25.2%), hemorrhagic stroke being the most common cause of death and old
age was a significant predictor of mortality with p=0.03(17).
Another study by Mayer et al on clinical practice, complications, and mortality in
neurological patients with acute severe hypertension attending emergency department
found that neurologic emergencies account for approximately 30% of hospitalized
patients with severe acute hypertension, and the majority of those who die. It also
showed mortality at 90 days was substantially higher in neurologic than in nonneurologic patients (24% vs. 6%, p<.0001). In a multivariable analysis, neurologic
patients who died experienced lower minimal blood pressure values (median 103/45
vs. 118/55 mm Hg, p<.0001) and were less likely to experience recurrent
hypertension requiring intravenous treatment (29% vs. 51%, p=.0001) than those who
survived. Mortality was also associated with an increased frequency of neurologic
deterioration (32% vs. 10%, p<.0001) (30).
Furthermore European registry for Studying the Treatment of Acute hyperTension
(Euro-STAT) in patients with acute hypertension among adult patients treated with
intravenous antihypertensive therapy while in the emergency department found that
treatment was associated with hypotension in almost 10% of patients. Overall 30-day
mortality was 4%, and new or worsening end-organ damage occurred in 19% of
patients (31).
12
CHAPTER 3: METHODOLOGY
3.1 STUDY AREA
The study was conducted on the male and female medical wards and adult ICU
(AICU) of the Bugando Medical Centre (BMC), with a total bed capacity of 170.
BMC is a tertiary consultant and teaching hospital located in Mwanza. The city is
located on the southern shores of Lake Victoria in the northwest part of The United
Republic of Tanzania. The hospital is a referral centre for seven neighbouring regions
Mara, Kagera, Shinyanga, Kigoma, Tabora Simiyu and Geita.
3.2 STUDY DESIGN
This was analytical cross-sectional study with a prospective component to determine
the outcomes.
3.3 STUDY POPULATION
All adults admitted in Bugando medical wards or Adult ICU during the study period
were eligible for enrolment.
3.3.1 Inclusion Criteria
i.
Age above 18 yrs
ii.
Informed consent by patient or the next of kin (in case patient has altered
mental status)
3.3.2 Exclusion criteria:
i.
Patients who died before screening were not included in the study.
13
3.4 SAMPLE SIZE
The sample size was calculated using Leslie Kish formula (1965):
N= Z2 P ( 1 – P)
d2
Where N = sample size
Z = score for 95% Confidence Interval which is 1.96
P = prevalence of hypertensive emergency in previous study (5.8%) (7).
d = tolerable error set at 5%.
N = 84 which was the minimum number of patients to be enrolled. However in order
to increase the power of the study for detecting predictors we enrolled all consecutive
admissions for three months and reached a sample size of 647 patients.
3.5 DATA COLLECTION
In this study, all adult medical inpatients were interviewed within 12 hours of
admission in order to determine eligibility. We measured BP on all enrolled adults
admitted to medical wards of BMC at the time of admission. BP was measured in the
sitting position (for very sick patients who could not sit we raised the head of the bed
to 45 degrees) by use of a mercury sphygmomanometer with appropriate cuff size
after resting for five minutes. BP was measured three times beginning in the right arm
and then the left arm and then in the arm that had a higher blood pressure as according
to standard guidelines with time interval of 5 minutes between each measurement.
14
The average of the first two readings was taken as patient’s BP. Patients who met the
inclusion criteria underwent an interview after obtaining the informed consent through
a structured questionnaire (modified WHO STEPS questionnaire for non
communicable disease) including history taking, physical examination, and laboratory
investigations.
All patients with hypertension were screened for symptoms and signs of hypertensive
emergencies (i.e. hypertensive encephalopathy, stroke, acute pulmonary oedema,
acute myocardial infarction, acute renal dysfunction or acute retinopathy). They also
underwent fundoscopy (confirmed by opthalmologist), CXR (read by radiologist), 12
lead ECG, and serum creatinine. Brain CT scan was requested in patients with
symptoms or signs of encephalopathy or stroke to confirm and rule out other
intracranial complications and an echocardiogram was requested in all patients with
symptoms or signs of heart failure or myocardial infarction.
Body weight to the nearest 0.5kg was measured without shoes and in light clothes
using DETECTOR scale (WEB CITY, U.S.A) as well as height to the nearest 0.5
centimetres was measured and then BMI was then calculated in kg/m2. Venopunctures
were performed for all patients to check for serum creatinine level using the COBAS
automated Integra 400 Plus analyzer, after cleansing the skin with 70% alcohol to
remove contaminating microorganisms. Renal dysfunction was then defined as
eGFR<60ml/min/1.73m2 (calculated using CKD – EPI equation) and is classified
according to the standard KDOQI CKD classification, which is as follows: Stage 0 risk of renal damage but eGFR>90ml/ml/1.73m2 ; Stage 1 - renal damage but
eGFR>90ml/min/1.73m2 ; Stage 2 - renal damage + eGFR = 60-89ml/min/1.73m2 ;
Stage 3 - renal damage + eGFR = 30-59ml/min/1.73m2 ; Stage 4 - renal damage +
eGFR = 15-29ml/min/1.73m2 ; and Stage 5 - renal damage + eGFR<15ml/min/1.73m2.
15
A 12 lead electrocardiography was also done using a Torino Italy made Bobcare, EPG
6 View ECG model page writer by trained nurse officer and interpretation was done
by the investigator with assistance of experienced physician. Any doubt was cleared
by an experienced cardiologist. In addition all investigation results and clinical
evaluation were documented in the patient’s files.
All patients who had hypertensive emergency were then followed until discharge and
then to 3 months thereafter at the medical outpatient clinic. For those who did not
return to the BMC clinic after 3 months, a phone call was made to the patient or the
next of kin in order to determine survival/mortality, compliance to
medications/follow-up and whether readmission had occurred. All results were
provided to the respective clinicians who decided about management of patients
according to BMC protocol as soon as they were available.
3.6 DATA PROCESSING AND ANALYSIS:
Data were double entered into Microsoft Excel and cleaned. Analysis was perfomed
using STATA Version 13 (San Antonio, Texas). Results were described using
proportions (%) for categorical data and means or median for continuous variables
according to distribution. Categorical variables were compared using Chi - Square or
Fisher’s Exact Test while continuous variables were compared using t-Test or Rank
Sum Test. P values < 0.05 were considered significant. Predictors with significant pvalue by univariate analysis were included in the multivariate analysis which was
perfomed using logistic regression. For predictors, odds ratio is reported with 95%
confidence intervals.
16
The primary outcome in this study (dependent variable) was the prevalence of
hypertensive emergencies while secondary outcomes were the pattern of hypertensive
emergencies seen, the predictors of hypertensive emergency and case fatality rates
both in-hospital and after three months among patients with hypertensive
emergencies. Independent variables that were investigated include age, gender, work
status, education level, history of hypertension, kidney disease and level of BP, also
obesity, compliance to ant-hypertensive agents, smoking, alcohol, HIV status and
socio-economic status.
3.7 ETHICAL CONSIDERATION
Permission to conduct this study was granted by the Joint Research and Publication
Committee of CUHAS / BMC certificate No. CREC/057/2013. Patients were only
involved after both verbal and written consent. This project was supported by grants
from Tanzanian Ministry of Health and Social welfare.
17
CHAPTER 4: RESULTS
4.1 Enrolment
A total of 682 patients were admitted during the study period. Seventeen (2.5%) died
before screening. Twelve (1.8%) patients were not eligible as they were less than 18
years of age. Therefore 665 patients were eligible. However, 6 (0.9%) were not
willing to participate in the study. Of the remaining 647 enrolled in the study: 91
(14.1%) patients had severe hypertension and 82 (12.7%) had hypertensive
emergencies. These patients were followed up until discharge and three months after
discharge as presented in Figure 1 below:
Figure 1: Overview of study enrolment
682 PATIENTS ADMITTED
DURING STUDY PERIOD
17 DIED BEFORE SCREENING
665 SCREENED
682
12 PATIENTS < 18YRS (1.8%)
6 CONSENT REFUSALS
647 INCLUDED IN THE STUDY
82 (12.7%)
565 (87.3%)
HYPERTENSIVE EMERGENCY
OTHER CONDITIONS
18
4.2 Baseline socio-demographic and clinical characteristics
Of 647 patients enrolled in our study, the median age was 45 years [32-61.5] and 312
(48.2%) were females. The majority of patients 643 (99.7%) were of African origin
and 305 (47.7%) had a primary level of education. The majority of patients were
farmers (peasants) 301 (46.8%).
Out of enrolled patients 163 (25.4%) reported history of hypertension and only 76/163
(46.6%) were on treatment for hypertension two weeks prior to admission. Of the
patients enrolled, 110 patients (17%) had loss of consciousness, 68 (10.5%) had
impaired vision, 163 (25.2%) had headache, 90 (13.9%) had chest pain and 214
(33.1%) had shortness of breath within 24 hrs prior to admission. Furthermore 215
(33.2%) of our cohort had hypertension at the time of admission. The median current
body mass index was 22.6 [20.3 to 25.3] kg/m2, whereby the majority had a normal
BMI and 10.7% (69 patients) were obese. One hundred seventeen patients (18.5%)
were known HIV positive while 5.1% were diagnosed HIV positive during admission.
More details are provided in Table 1 below.
4.3 Prevalence of hypertensive emergencies
Out of 647 patients, 91 (14.1%) had severe hypertension and 82 (12.7%) met criteria
for hypertensive emergency. A majority of these patients 70/82 (85.4%) had more
than one emergency. The most common forms of emergencies seen in this study were
hypertensive retinopathy 51 (62.2%) followed by hypertensive encephalopathy
41(50%) and the least common was hypertensive stroke 18 (22%) as illustrated in
Tables 2 and 3 below.
All patients who presented with severe hypertension with acute blurred vision (within
24 hours of admission) underwent fundoscopy where- by 11/51 (21.6%) had mild
19
retinopathy, 22/51 (43.1%) moderate retinopathy and 18/51 (35.3%) had severe
retinopathy.
Table 1: Baseline characteristics of 647 patients admitted to BMC from October 2013
until December 2013.
Characteristic
Female
Age in years
Ethnicity *
African
Other
Education *
Incomplete primary
Complete primary
Complete secondary University
Work status *
Government or business
Self employed
Farmer
Water source *
Tap water
Lake or pond water
Electricity *
Toilet *
Modern flush toilet
Pit latrine
Smoker *
Never
Previous Smoker
Current Smoker
Alcohol*
Never
Prior to last month
In last month or current
History of HTN *
History of kidney disease *
History of HF *
History of diabetes*
Urine output *
Increased
Normal
Decreased
BMI *
Underweight BMI <18.5
Normal BMI>=18.5 & BMI <25
Overweight BMI>=25 & BMI<30
Obese BMI>30
Hypertension
HIV rapid test
Not done/refused
Known
New positive
New negative
NOTE: *some data missing
Number (%) or Median [IQR]
312 (48.2%)
45 [32-61.5]
643 (99.7%)
2 (0.3%)
238 (37.0%)
305 (47.4%)
100 (15.6%)
153 (23.8%)
189 (29.4%)
301 (46.8%)
290 (45.2%)
352 (54.8%)
258 (40%)
247 (38.3%)
398 (61.7%)
520 (80.6%)
90 (14.0%)
35 (5.4%)
404 (62.4%)
190 (29.4%)
53 (8.2%)
163 (25.4%)
28 (4.3%)
81 (12.6%)
48 (7.5%)
13 (2.0%)
552 (85.7%)
79 (12.3%)
22.6 [20.3-25.3]
83 (12.9%)
390 (60.6%)
102 (15.8%)
69 (10.7%)
215 (33.2%)
25 (3.9%)
117(18.1%)
32 (5.0%)
473 (73.1%)
20
Table 2: Types of hypertensive emergencies among 82 consecutive adults admitted to
BMC with hypertensive emergency.
Pattern
Hypertensive retinopathy
Hypertensive encephalopathy
Pulmonary edema
Impaired renal function
Ischemic heart disease
Hypertensive stroke
Frequency (%)
51(62.2)
41(50.0)
39(47.6)
37(45.1)
20 (24.4)
18 (22.0)
Table 3: Overlap between hypertensive emergencies among 82 consecutive adults
admitted to BMC with hypertensive emergency
Type or Pattern
Multiple Hypertensive emergencies
Hypertensive retinopathy alone
Hypertensive Encephalopathy alone
Hypertensive stroke alone
Impaired renal function alone
Hypertensive pulmonary edema alone
Hypertensive Ischemic heart disease
alone
TOTAL
Frequency (%)
70 (85.4)
5 (6.1)
3 (3.7)
1 (1.2)
1 (1.2)
1 (1.2)
1 (1.2)
82 (100)
4.4 Outcomes
Of 82 patients with hypertensive emergency, the average length of hospital stay was 6
[3-9] days and 25/82 (30.5%) died during admission. At one month post discharge, 6
(7.3%) patients were lost to follow up. A total of 37/76 (48.7%) of the patients still in
follow-up had died. Among the living patients still in follow up, 5/39 (12.8%) had
been readmitted to the hospital, 28/39 (71.8%) were attending clinic and medication
use was 39/39 (100%). At three months, 40/76 (52.6%) had died. Among the living
patients, 4/36 (11.1%) were readmitted, clinic follow up was 29/36 (80.6%) and
medication use was (33/36) 91.7% as shown in Table 4 below.
21
Table 4: In hospital, 1 month and 3 months post-discharge outcomes among 82 adults
admitted with hypertensive emergency
Outcome
Number (%) or Median [IQR]
In-hospital case fatality rate
Duration of Hospital Stay
One month outcome:
1 month case fatality rate
1 month medication use
1 month clinic follow up
1 month readmission rate
Three month outcomes
3 month case fatality rate
3 month medication use
3 month clinic follow up
3 month readmission rate
Loss to follow up
NB:* = some data missing
25/82 (30.5%)
6 [3-9]
37/76 (48.7%) *
39/39 (100%)
28/39 (71.8%)
5/39 (12.8%)
40/76 (52.6%)
33/36 (91.7%)
29/36 (80.6%)
4/36 (11.1%)
6/57 (10.5%)
4.5 Factors associated with hypertensive emergencies
Factors significantly associated positively with hypertensive emergencies by
univariate analysis include female gender (OR 2.03, 95% CI 1.26-3.28, p= 0.004), age
(OR 1.04, 95% CI 1.03-1.05, p= <0.001), use of alcohol prior to last month before
admission (OR 1.98, 95% CI 1.21-3.25, p= 0.007), prior history of hypertension (OR
15.29, 95% CI 8.76-26.67, p= <0.001), electricity at home (OR 1.69, 95% CI 1.062.69, p= 0.028), history of diabetes mellitus (OR 2.88, 95% CI 1.45-5.72, p= 0.002),
history of loss of consciousness (OR 6.05, 95% CI 3.66-9.99, p= <0.001), impaired
vision (OR 15.73, 95% CI 8.89-27.83, p= <0.001), headache (OR 7.33, 95% CI 4.4512.08, p= <0.001), and chest pain 24 hours prior to admission (OR 2.32, 95% CI 1.324.07, p= 0.003). The following were negatively associated with hypertensive
emergency: self-employment (OR 0.51, 95% CI 0.27-0.96, p= 0.037), primary level
of education (OR 0.54, 95% CI 0.32-0.9, p= 0.017) and use of pit latrine at home (OR
0.49, 95% CI 0.31-0.78, p= 0.003). Clinical characteristics positively associated with
22
hypertensive emergency were displaced apex beat (OR 5.96, 95% CI 3.61-9.84, p=
<0.001), presence of crepitations on the lung bases (OR 1.66, 95% CI 1.01-2.73, p=
0.045), heart failure by Framingham criteria (OR 1.86, 95%CI 1.12-3.08, p= 0.02),
renal dysfunction (OR 2.18, 95% CI 1.36-3.50, p= 0.001), and obesity (OR 3.47, 95%
CI 1.83-6.56, p= <0.001) but positive HIV status (OR 0.23, 95% CI 0.97-0.53,
p=0.001) had negative association as illustrated in table 5 below.
23
Table 5: Factors associated with hypertensive emergencies among 82 adults
admitted with hypertensive emergencies to BMC by Univariate Analysis
Predictors
Hypertensive
Number (%) or Median Emergencies
(IQR)
(N=82)
Hypertensive
without
emergency
(N=215)
109 (50.7)
59 [48-68]
23 (10.7)
24 (11.2)
39 (18.1)
49 (22.8)
80 (37.2)
Odds ratio
[95% CI]
p-value
2.03[1.26-3.28]
1.04[1.03-1.05]
1
1.88[0.67-5.34]
5.23[2.05-13.33]
6.63[2.68-16.40]
8.13[3.48-19.01]
0.004
<0.001
1.36[0.8-2.31]
0.51[0.27-0.96]
1
0.26
0.037
39(47.6)
29(35.4)
14(17.1)
*
41 (50.6)
40 (49.4)
42 (51.2)
62(28.8)
56(26.1)
97(45.12)
*
90(42.3)
89(41.8)
34(16.0)
*
119 (55.9)
94 (44.1)
110 (51.2)*
44 (53.7)
38 (46.3)
Female
Age(years)
<35 years
35-44.9
45-54.9
55-64.9
>65 years
Work status
Professional
Self-employed
Farmer
Education
Incomplete primary
Complete primary
Complete secondary
Water source
Tap water
Lake or pond water
Electricity
Toilet
Modern flush toilet
Pit latrine
Smoking
Never
Previous
Current
Alcohol
Never
Prior last month
Current /in last month
BP measured by
health professional
History of HTN
52 (63.4)
61 [51-69]
7 (8.5)
8 (9.8)
15 (18.3)
19 (23.2)
33 (40.2)
History of kidney
disease
History of HF
Treatment of HTN
Treatment of HF
Treatment HTN last 2
weeks
History of diabetes
Urine output
Increased
Normal
27(32.9)
14(17.1)
41(50)
0.23
0.001
<0.001
<0.001
1
0.54[0.32-0.9]
0.83[0.43-1.61]
0.017
0.58
1
0.78[0.49-1.24]
1.69[1.06-2.69]
0.29
0.028
111 (51.6)
104 (48.4)
1
0.49[0.31-0.78]
0.003
69 (84.2)
6 (7.3)
7 (8.5)
165 (76.7)
35 (16.3)
15 (7.0)
1
0.47[0.20-1.11]
1.63[0.69-3.89]
0.09
0.27
40(48.8)
34(41.5)
8(9.8)
64 (78.1)
105(48.8)
89(41.4)
21(9.8)
164 (76.3)
1
1.98[1.21-3.25]
1.62[0.71-3.67]
4.30[2.48-7.44]
0.007
0.25
<0.001
63 (76.8)
147 (68.4)
15.29[8.76-26.67]
<0.001
5 (6.1)
17 (7.9)
1.52[0.56-4.13]
0.41
12 (14.8)*
60 (73.2)
8 (9.8)
27 (32.9)
50 (23.4)*
135 (62.8)
44 (20.6)*
78 (36.3)
1.25[0.64-2.42]
15.34[8.94-26.32]
0.89[0.41-1.93]
4.93[2.86-8.48]
0.52
<0.001
0.76
<0.001
13(16.1)*
38(17.8)*
*
5(2.4)
172(80.8)
2.88[1.45-5.72]
0.002
1.32[0.29-6.07]
1
0.73
2(2.4)
67(81.7)
24
Decreased
LOC in past 24hrs
Impaired vision 24hrs
Headache past24hr
Chest pain past 24h
Shortness of breath
past 24h
Orthopnea past 24
hours
PND past 24 hours
Displaced apex
Crepitations
Bilateral edema
Elevated JVP
Murmur
Framingham criteria
met
Renal dysfunction
BMI
Underweight
Normal
Overweight
Obese
Waist circumference
Hip circumference
WHR
SBP1
DBP1
Anti-hypertensive
started in ED
Pulse rate
GCS
Oxygen saturation
RBG
HIV rapid test
Not done
Positive
Negative
13(15.9)
38(46.9)*
38(46.9)*
52(64.2)*
20(24.7)*
34(42)*
36(16.9)
67(31.3)*
54(25.2)*
97(45.3)*
37(17.3)*
90(42.1)
1.43[0.75-2.7)
6.05[3.66-9.99]
15.73[8.89-27.83]
7.33[4.45-12.08]
2.32[1.32-4.07]
1.55[0.96-2.49]
0.28
<0.001
<0.001
<0.001
0.003
0.07
25(30.5)
70(32.6)
1.58[0.95-2.63]
0.08
19(23.2)
56(68.3)
28(34.2)
18(22.2)*
10(12.2)
12(14.8)*
27(32.9)
59(27.4)
129(60.0)
74(34.6)*
62(29.1)*
30(14.0)*
32(15.1)*
69(32.1)
1.30[0.75-2.27]
5.96[3.61-9.84]
1.66[1.01-2.73]
0.94[0.54-1.65]
1.43[0.69-2.93]
1.29[0.66-2.50]
1.86[1.12-3.08]
0.35
<0.001
0.045
0.84
0.34
0.46
0.02
37(45.1)
2.18[1.36-3.50]
0.001
4(4.9)
36(43.9)
24(29.3)
18(22)
90[81.5-100]
99.5[90-108]
0.92[0.89-0.95]
190[175-211]
115[110-127]
64(78)
85(39.5)
*
8(3.8)
105(49.3)
50(23.5)
50(23.5)
89[80-100]
97[86-106]
0.91[0.89-0.94]
160[140-190]
100[90-115]
95(44.2)
0.5[0.17-1.44]
1
3.03[1.71-5.36]
3.47[1.83-6.56]
1.06[1.04-1.07]
1.06[1.04-1.08]
5.37[0.34-84.03]
1.08[1.06-1.09]
1.13[1.11-1.16]
42.10[22.95-77.23]
0.20
92.5[80-105]
15[11-15]
93.5[88-96]
7.3[6.2-9.4]
90[80-100]
15[15-15]
95[92-96]
6.9[5.7-9.4]
1[0.99-1.01]
0.77[0.7-0.85]
0.96[0.94-0.98
1.03[0.99-1.07]
0.84
<0.001
0.001
0.17
2(2.4)
6(7.3)
74(90.2)
4(1.9)
15(7.0)
196(91.2)
0.47[0.11-2.03]
0.23[0.97-0.53]
1
0.31
0.001
<0.001
<0.001
<0.001
<0.001
0.23
<0.001
<0.001
<0.001
All variables significantly associated with hypertensive emergencies in the
univariable analysis were included in multivariate analysis except the clinical
characteristics that are results of hypertension like displaced apex beat, impaired
vision, chest pain, loss of consciousness and headache. By multivariable analysis, the
only factors significant associated with hypertensive emergency are presented in table
6 below.
25
Table 6: Factors associated with hypertensive emergencies among 82 adults admitted
to BMC by Multivariable logistic regression.
Predictors
Female gender
Age
Oxygen saturation
Odds ratio[95% CI]
2.17[1.18-4.00]
1.02[1.01-1.04]
0.97[0.94-0.997]
p-value
0.012
0.008
0.031
4.6 Predictors of in-hospital fatality rates
By univariate analysis, among adults with hypertensive emergency, in hospital case
fatality rate was significantly positively associated with current use of alcohol (OR 5,
95% CI 1.01-24.77, p=0.049), loss of consciousness within 24 hrs prior to admission
(OR 6.2, 95% CI 2.11-18.1, p=0.001), renal dysfunction (OR 3.05, 95% CI 1.15-8.10,
p=0.026), hypertensive encephalopathy (OR 6.86, 95% CI 2.24-20.97, p=0.001),
hypertensive stroke (OR 7.85, 95% CI 2.48-24.87, p=<0.001), and hypertensive
emergency with impaired renal function (OR 3.05, 95% CI 1.15-8.10, p=0.03).
Predictors that were negatively associated with fatality by univariable analysis were
history of hypertension (OR 0.28, 95% CI 0.10-0.82, p=0.02), chest pain within 24
hours prior to admission (OR 0.18, 95% CI 0.39-0.86, p=0.032), Glasgow Coma
Score (OR 0.65, 95% CI 0.52-0.81, p=<0.001), and hypertensive emergency with
ischemic heart disease (OR 0.19, 95% CI 0.04-0.89, p=0.04) as illustrated in Table 7
below.
26
Table 7: Baseline Predictors of in hospital fatality rates among 82 adults admitted to
BMC with hypertensive emergencies and followed up until discharge by univariate
logistic regression
Predictors
Number (%) or Median
(IQR)
Female
Age (years)
Work status
Professional
Self-employed
Farmer
Education
Incomplete primary
Complete primary
Complete secondary
Water source
Tap water
Lake or pond
Electricity
Toilet
Modern flush
Pit latrine
Smoking
Never
Previous
Current
Alcohol
Never
Prior last month
Current /in last month
BP measured by health
professional
History of HTN
History of kidney
disease
History of HF
Treatment of HTN
RX HTN last 2weeks
History of diabetes
Urine output
Increased
Normal
Decreased
LOC in past 24h
Impaired vision past 24
hours
Headache past 24hrs
Chest pain past 24hr
Shortness of breath
past 24h
Died during
hospitalization
(N=25)
13(52)
59.6[25-83]
Alive during
hospitalization
(N=57)
39(68.42)
58.1[26-89]
Odds ratio
[95%CI]
p-value
0.5[0.19-1.31]
1.01[0.98-1.04]
0.16
0.67
9(36)
6(24)
10(40)
18(31.6)
8(14)
31(54.4)
1.55[0.53-4.53]
2.33[0.65-8.33]
1
0.42
0.20
13(52)
7(28)
5(20)
26(45.6)
22(38.6)
9(15.8)
1
0.64[0.22-1.87]
1.11[0.31-3.99]
0.412
0.872
12(48)
13(52)
14(56)
29(51.8)
27(48.2)
28(49.1)
1
1.16[0.45-2.99]
1.32[0.51-3.39]
0.75
0.567
14(56)
11(44)
30(52.6)
27(47.4)
1
0.87[0.34-2.25]
0.778
20(80)
2(8)
3(12)
49(86)
4(7)
4(7)
1
1.23[0.21-7.23]
1.84[0.38-8.96]
0.82
0.45
10(40)
10(40)
5(20)
16(64)
30(52.6)
24(42.1)
3(5.3)
48(84.2)
1
1.25[0.45-3.49]
5[1.01-24.77]
0.33[0.11-0.98]
0.67
0.049
0.047
15(60)
1(4)
48(84.2)
4(7)
0.28[0.10-0.82]
0.55[0.59-5.21]
0.02
0.60
4(16)
15(60)
5(20)
2(8.3)
8(14.3)*
45(79)
22(38.6)
11(19.3)
1.14[0.31-4.22]
0.4[0.14-1.11]
0.40[0.13-1.21]
0.38[0.78-1.86]
0.84
0.08
0.11
0.23
0(0)
23(92)
2(8)
19(76)
14(56)
2(3.5)
44(77.2)
11(19.3)
19(33.9)*
24(42.9)
1
0.35[0.71-1.70]
6.2[2.11-18.01]
1.7[0.66-4.39]
0.19
0.001
0.28
19(76)
2(8)
8(32)
33(58.9)
18(32.1)
26(46.4)
2.21[0.76-6.38]
0.18[0.39-0.86]
0.54[0.20-1.46]
0.14
0.032
0.23
27
Orthopnea past 24hrs
Crepitations
Bilateral edema
Elevated JVP
Framingham
criteria
met
Renal dysfunction
BMI
Underweight
Normal
Overweight
Obese
Waist circumference
Hip circumferen
WHR
SBP1
DBP1
Anti-hypertensive
started in ED
Pulse rate
GCS
Oxygen saturation
RBG
HIV rapid test
Not done
Positive
Negative
HT Encephalopathy
HT stroke
HT retinopathy
HT impaired renal
function
HT Pulmonary Edema
HT Ischemic Heart
Disease
NB: *= data missing
5(20)
8(32)
3(12)
2(8)
5(20)
20(35.1)
20(35.1)
15(26.8)*
8(14)
22(38.6)
0.46[0.15-1.42]
0.87[0.32-2.37]
0.37[0.97-1.43]
0.53[0.10-2.71]
0.40[0.13-1.21]
0.18
0.79
0.15
0.45
0.11
16(64)
21(36.8)
3.05[1.15-8.10]
0.026
1(4)
13(52)
7(28)
4(16)
87.5[65-107]
94.6[70-114]
0.93[0.86-1.23]
198[100-259]
119[70-169]
18(72)
3(5.3)
23(40.4)
17(29.8)
14(24.6)
90.4[35-121]
99.7[63-152]
0.90[0.44-1.09]
191[140-278]
117[70-177]
46(80.7)
0.59[0.56-6.27]
1
0.73[0.24-2.22]
0.51[0.14-1.86]
0.99]0.95-1.02]
0.97[0.94-1.01]
56[0.06-53447]
1.01[0.99-1.02]
1.01[0.98-1.03]
0.61[0.21-1.83]
0.66
95[56-130]
11[3-15]
56[55-98]
8[4.8-18.2]
91[56-140]
14[8-15]
91.6[30-99]
8.6[4.4-23.1]
1.01[0.99-1.04]
0.65[0.52-0.81]
0.96[0.92-1.01]
0.98[0.86-1.12]
0.41
<0.001
0.08
0.77
0(0)
2(8)
23(92)
20(80)
12(48)
18(72)
16(64)
2(3.5)
4(7)
51(89.5)
21(36.8)
6(10.5)
33(57.9)
21(36.8)
1.11[0.19-6.49]
1
6.86[2.24-20.97]
7.85[2.48-24.87]
1.87[0.67-5.18]
3.05[1.15-8.10]
0.91
11(44)
2(8)
28(49.1)
18(31.6)
0.814[0.32-2.09]
0.19[0.04-0.89]
0.67
0.04
0.58
0.31
0.41
0.129
0.25
0.32
0.69
0.38
0.001
<0.001
0.23
0.03
By multivariate analysis all variables significantly associated with in hospital fatality
in the univariable analysis were included and only significant associations are
presented in table 8 below. Renal dysfunction was not included due to collinearity
with “HTN Emergency with impaired renal function”, chest pain was not included
due to collinearity with “HTN Emergency with Ischemic Heart Disease” and both
GCS and loss of consciousness were not included due to collinearity with “HTN
Emergency with Encephalopathy.”
28
Table 8: Baseline Predictors of in hospital fatality rates among 82 adults admitted to BMC
with hypertensive emergencies and followed up until discharge by Multivariable logistic
regression
Predictors
Hypertensive Emergency with
impaired renal function
Hypertensive stroke
Odds ratio [95% CI]
27.53[3.74-202.91]
p-value
0.001
31.17[3.73-260.77]
0.002
4.7 Predictors of 3 months fatality rates
The following predictors were significantly positively associated with 3-months
fatality rates by univariate logistic regression: loss of consciousness past 24 hours
prior to admission (OR 2.83, 1.11-7.23), hypertensive encephalopathy (OR 2.62, CI
1.04–6.62) and hypertensive emergency with impaired renal function (OR 4.33, CI
1.64-11.44). Negative predictors were: Glasgow Coma Score (OR 0.76, 0.61-0.94)
and oxygen saturation (OR 0.92, 0.85-0.99), as shown in the table 9 below:
Table 9: Baseline Predictors of 3 months fatality rates among 82 adults admitted to
BMC with hypertensive emergencies and followed up until 3 months after discharge
by univariate logistic regression
Predictors
Number (%)
or
Median (IQR)
Female
Age(years)
Work status
Professional
Self-employed
Farmer
Education
Incomplete primary
Complete primary
Complete secondary
Water source
Tap water
Lake or pond
Electricity
Toilet
Modern flush
Pit latrine
Smoking
Never
Previous
Death by
3months
(N=40)
24(60)
58.2[25-83]
Alive by
3months
(N=36)
22(61.1)
58.6[35-89]
Odds ratio [95%
CI]
p-value
0.95[0.38-2.40]
0.998[0.97-1.03]
0.92
0.91
15(37.5)
6(15)
19(47.5)
11(30.6)
8(22.2)
17(47.2)
1.22[0.44-3.37]
0.67[0.19-2.33
1
0.70
0.53
22(55)
11(27.5)
7(17.5)
13(36.1)
17(47.2)
6(16.7)
1
0.38[0.14-1.06]
0.69[0.19-2.50]
0.07
0.57
19(48.7)*
20(51.3)*
24(60)
20(55.6)
16(44.4)
18(50)
1
1.32[0.53-3.27]
1.5[0.60-3.72]
0.55
0.38
23(57.5)
17(42.5)
20(55.6)
16(44.4)
1
0.92[0.37-2.29]
0.86
34(85)
3(7.5)
29(80.6)
3(8.3)
1
0.85[0.16-4.55]
0.85
29
Current
Alcohol
Never
Prior last month
Current /last month
History of HTN
History of kidney
disease
History of HF
Treatment of HTN
Treatment of HTN
last 2week
History of diabetes
Urine output
Increased
Normal
Decreased
LOC past 24hrs
Impaired vision past
24 hours
Headache past 24h
Chest pain past
24hrs
Shortness of breath
past 24 hrs
Crepitations
Framingham criteria
met
Renal dysfunction
BMI
Underweight
Normal
Overweight
Obese
Waist circumferen
Hip circumferen
WHR
SBP1
DBP1
Pulse rate
GCS
Oxygen saturation
RBG
HIV rapid test
Not
Positive
Negative
HT Encephalopathy
HT stroke
HT retinopathy
HT impaired renal
function
Pulmonary Edema
Hypertensive IHD
3(7.5)
4(11.1)
0.64[0.13-3.10]
0.58
19(47.5)
15(37.5)
6(15)
27(67.5)
2(5)
17(47.2)
18(50)
1(2.8)
31(86.1)
3(8.3)
1
0.75[0.29-1.92]
5.37[0.59-49.2]
0.33[0.11-1.06]
0.58[0.09-3.68]
0.54
0.14
0.06
0.56
7(17.5)
26(65)
11(27.5)
5(14.3)*
29(80.6)
14(38.9)
1.27[0.364.44]
0.45[0.16-1.28]
0.60[0.23-1.56]
0.71
0.13
0.29
5(12.8)*
7(19.4)
0.61[0.17-2.13]
0.44
1(2.5)
34(85)
5(12.5)
24(61.5)*
18(46.2)*
1(2.78)
29(80.6)
6(16.7)
13(36.1)
18(50)
0.85[0.05-14.25]
1
0.71[0.20-2.57]
2.83[1.11-7.23]
0.86[0.45-2.12]
0.91
27(69.2)*
6(15.4)*
22(61.1)
12(33.3)
1.43[0.55-3.72]
0.36[0.12-1.11]
0.46
0.08
19(47.5)
11(31.4)*
1.97[0.77-5.08]
0.16
16(40)
15(37.5)
8(22.2)
9(25)
2.33[0.85-6.40]
1.8[0.67-4.84]
0.10
0.24
25(62.5)
10(27.8)
4.33[1.64-11.44]
0.003
3(7.5)
19(47.5)
9(22.5)
9(22.5)
87.5[35-121]
96.7[63-152]
0.91[0.44-1.23]
196.4[100-259]
118.7[70-170]
93.2[56-140]
12.3[3-15]*
87[30-98]
8.1[4.8-18.2]
0(0)
15(41.7)
13(36.1)
8(22.2)
92.2[68-114]*
100.4[[70-120]
0.92[0.72-1.09]*
192[140-278]
117.9[70-177]
91.8[63-140]
14.2[10-15]
93[56-99]
9.2[4.4-23.1]*
1
0.55[0.18-1.62]
0.89[0.28-2.86]
0.98[0.94-1.01]
0.98[0.95-1.01]
0.21[0.001-51.96]
1.005[0.99-1.02]
1.002[0.99-1.02]
1.004[0.98-1.03]
0.76[0.61-0.94]
0.92[0.85-0.99]
0.93[0.82-1.05]
0.28
0.84
0.17
0.25
0.58
0.53
0.88
0.74
0.01
0.03
0.23
0(0)
3(7.5)
37(92.5)
25(62.5)
12(30)
23(57.5)
25(62.5)
1(2.8)
3(8.3)
32(88.9)
14(38.9)
6(16.7)
24(66.7)
10(27.8)
0.86[1.16-4.59]
1
2.62[1.04-6.62]
2.14[0.71-6.48]
0.68[0.27-1.72]
4.33[1.64-11.44]
0.87
22(55)
6(15)
13(36.1)
12(33.3)
2.16[0.86-5.44]
0.35[0.12-1.07]
0.101
0.07
30
0.60
0.03
0.74
0.04
0.18
0.41
0.003
NB: *=one data missing
By multivariate analysis all variables significantly associated with 3 months fatality
rates in the univariable analysis were included + age & sex and only significant
associations are presented. However renal dysfunction and GCS/LOC were omitted
due to collinearity with the variables for “HTN Emergency with impaired renal
function” and “HTN Emergency with Encephalopathy” respectively. Hypertensive
emergency with impaired renal function was a positive predictor (OR 6.40, 2.0619.84) as well as hypertensive encephalopathy (OR 4.42, 1.41-13.84) as in table 10
below.
Table 10: Baseline Predictors of 3 months fatality rates among 82 adults admitted to BMC with
hypertensive emergencies and followed up until 3 months after discharge by multivariable logistic
regression
Predictors
Odds ratio[95% CI]
p-value
Hypertensive Emergency with 6.40 [2.06-19.84]
impaired renal function
0.001
4.42 [1.41-13.84]
0.011
Hypertensive encephalopathy
31
CHAPTER 5: DISCUSSION
This study was conducted to determine the prevalence, patterns, and factors
associated with hypertensive emergencies as well as predictors of fatality among
hypertensive patients admitted to BMC. To the best of our knowledge this is the first
study to be done in Tanzania whereby these patients were followed up until three
months post discharge to determine survival/fatality rates, readmission rates, whether
patients were still using medications and whether they were being followed up at the
clinics. We found that hypertensive emergency was one among the causes of
admission in medical wards. A majority of patients had hypertensive retinopathy.
Hypertensive emergency was significantly associated with age gender and oxygen
saturation. Thirty percent of patients with hypertensive emergencies died during
hospitalization and at three months post discharge more than 50% had died with
hypertensive encephalopathy and hypertensive kidney disease being significant
predictors.
5.1 Prevalence of hypertension and hypertensive emergencies
In this study a total of 647 patients were enrolled whereby 163 (25.4%) reported
history of hypertension and 145 (88.9%) were prescribed and used medication at
some point in their life but only 76/163 (46.6%) of these were on treatment for
hypertension for the past two weeks prior to admission. However 215 (33.2%) were
then found to be hypertensive by average BP measurements and/or being on
medication. Furthermore 68 /480 (14.2%) had no history of hypertension but were
found to be hypertensive by average BPs. This prevalence is higher compared to the
prevalence of hypertension in USA based on publication of many hypertension
32
observational studies and clinical trials reported by the JNC7 where the prevalence
was 25% (3). This increase supports the fact that hypertension is increasing in SSA.
Also this reported prevalence is higher compared to study done in Nigeria among
hypertensive patients whereby only 14.2% had self reported hypertension and of these
only 18.6% had been on medication in the past three months (16). Also prevalence of
hypertension from our study (33.2%) is higher as compared to a previous 3 year
prospective study at BMC on all patients admitted to medical wards to determine the
contribution of hypertension to death, admissions, and hospital days which reported a
prevalence of hypertension of 14.6% (7). The lower prevalence in the BMC study is
due to the fact that the diagnosis recorded was the primary diagnosis that indicated the
reason for admission and possibly missed other patients who had hypertension as a
secondary diagnosis.
In our study also 91 (14.1%) had severe hypertension. This prevalence is higher
compared to a multicentre study done in Italy on adults admitted to the emergency
departments where the prevalence was 0.46% (14). We got the higher percentages due
to the fact that majority of hypertensive patients (more than 50%) were not on
medication and the increased number of hypertensive cases contributes to the increase
in hypertensive crisis.
The prevalence of hypertensive emergencies in our study is 12.7%. This prevalence is
higher than a study done on hypertensive emergencies at the University Hospital
Centre in Brazzaville Congo which showed a prevalence of 4% which is likely lower
because of the retrospective nature of their study (18). Also our prevalence is higher
than in a study done in Angola where the prevalence of hypertensive emergency was
4.3% but this was done only in patients under 45 years of age (17). Furthermore this
prevalence is higher compared to the previous 3- year prospective study in BMC
33
among patients admitted in the medical ward which found the prevalence of
hypertensive emergency of 5.8% (7). Also poor compliance as more than 50% of
hypertensive patients were not on medication contributed to increased prevalence in
our study.
5.2 Patterns of hypertensive emergencies
Majority of patients 70 (85.4%) with hypertensive emergencies in our study had
multiple hypertensive emergencies. The most common forms were hypertensive
retinopathy (62%), hypertensive encephalopathy (50%), acute pulmonary oedema
(47.6%) and hypertensive kidney disease (45.1%). The least common form was
hypertensive stroke (22%). Twenty seven patients were suspected to have stroke and
severe hypertension however only 18/27 (66.7%) were confirmed by CT scan. Of
note, all those suspected to have stroke that had confirmatory CT scans did actually
have strokes.
Hypertensive retinopathy being the commonest pattern could be due to possibility that
these patients had retinopathies even before they had severe hypertension. This is
similar to a study done in Accra Ghana which showed hypertensive retinopathy to
account for 70% of the target organ damage (11). Also in Iran, 39.9% of hypertensive
patients had hypertensive retinopathy and among these patients 42.4%, 20%, 2.35%
had retinopathy grade 1, 2, and 3 respectively (13). However in our study moderate
(grade 2) retinopathy was the commonest presentation.
Moreover hypertensive encephalopathy was the second most common emergency
type (50%) higher than in 14% in Congo (18) and 4.9% in Italy (14).
34
In our study acute pulmonary oedema accounted for 47.6% of emergencies higher
than in other studies as most of the patients had also heart failure contributing to
pulmonary oedema. But in the Italian study, 121 (30.9%) had acute pulmonary edema,
and two patients only had both acute pulmonary edema and stroke (14) but in our
study most patients (85%) had multiple emergencies. In Brazil also acute pulmonary
oedema was one of the most common hypertensive emergencies (12).
Hypertensive kidney diseases were previously undiagnosed because of limited
facilities in our setting. Our study has shown 45% of patients with severe
hypertension had renal dysfunction, higher than in Congo where renal failure was
found in 13.1% of patients with severe hypertension (18), and also higher than in Italy
where 23 (5.9%) had acute renal failure (14).
Also hypertensive stroke in our study was lower compared to other studies as some
patients failed to undergo CT scan for confirmation. In Congo study the most
common diseases underlying hypertensive emergency was stroke, 50% (18) while in
Italian study stroke accounted for 22% (14).
5.3 Factors associated with hypertensive emergencies
Female gender 52 (63.4%) was found to have two fold increase in odds for
developing hypertensive emergencies by univariable logistic regression (OR 2.03,
95% CI 1.26-3.28, p=0.004) and by multivariate analysis (OR 2.17, 95% CI 1.184.00, p=0.012). These findings are similar to a study previously done in Switzerland
whereby female gender was one of the risk factors for promoting hypertensive crisis
(22). This support the epidemiological high prevalence of hypertension in women
than in men therefore higher chances of complications. Also we had more
hypertensive females than men suggesting women’s tendency to seek medical care
35
than men in our setting. However our results are different from the Italian study where
patients with hypertensive emergencies had higher risk of being men (OR 1.34, 95%
CI 1.06–1.70) than in women suggesting men’s lower compliance to screening and
treatment of hypertension (14).
Also in this analysis an increase in age above 45 years was found to be significant risk
of hypertensive emergencies (OR 1.04 95% CI 1.03-1.05, p=<0.004) as shown in
univariate analysis as well as in multivariate analysis (OR 1.02, 95% CI 1.01-1.04,
p=0.008). These findings are similar to studies done in USA where old age was one of
the independent predictors of poorly controlled hypertension (20). There were also
similar findings in a South African study, in which old age was most commonly
associated with target organ damage among black hypertensive patients attending
primary health care services (23). Also low oxygen saturation was significantly
associated with hypertensive emergency both in univariable and multivariable models.
Low oxygen saturation was due to pulmonary oedema seen in patients who had heart
failure.
Furthermore our study showed history of diabetes mellitus was a significant predictor
of hypertensive emergencies (OR 2.88, 95% CI 1.45-5.72, p=0.002), in univariable
analysis, although it was not found to be significant in multivariate model. This is
similar to a study done in Brazil in which diabetes mellitus was found in 20% of
patients and was found to be statistically significant factor for development of
hypertensive emergencies (12). Also a study in Ghana showed that the participants
diagnosed with diabetes had increased odds of developing target organ damage
compared to those with no diagnosis of diabetes. This was however not statistically
significant (11).
36
Moreover obesity is associated with an almost 4 fold increase in risk of hypertensive
emergencies (OR 3.47, 95% CI 1.83-6.56), p=<0.001 but was not significant in
multivariate analysis. This is the same as in Switzerland (22) as well as in the Congo
study (18) where obesity is a significant predictor of hypertensive emergency.
Our study also found high socio-economic status is significantly associated with
hypertensive emergencies by univariable analysis but not in multivariable model
where patients with electricity had more than two times the odds of having
hypertensive emergency while use of pit latrine used by majority with low income
and poverty was protective for hypertensive emergencies. This can be explained by
the current adoption of western cultures including diet changes, smoking, obesity, as
well as life changes associated with urbanisation which are all associated with
cardiovascular complications. However a study by Ellenga et al in Congo showed low
socio-economic status was significantly associated with hypertensive emergencies
(18).
5.4 Fatality
Fatalities due to hypertensive emergencies in SSA are generally unacceptably high, in
our study 25 (30.5%) patients with hypertensive emergencies died during
hospitalisation. This fatality rate is almost similar to Angolan study by Garcia GM et
al where the in hospital fatality rate was 25.2% though their population was under 45
years of age (17). But the fatality rate is very high compared to a previous study done
in USA among patients with acute severe hypertension where the hospital fatality
was 6.9% (27). The higher fatality in our study was due to the fact that majority of our
patients were admitted when very sick with multiple emergencies at presentation
compared to patients in the USA and other high income countries. For the same
reason by three-months post discharge in our study 40 (52.6%) patients died. This
37
fatality rate is very high compared to that in USA where three month fatality rate was
11% (27). Another study done in Thailand on hypertensive emergencies showed the
in hospital fatality as high as 15% (25), while in Mexico city 4.6% of patients with
hypertensive emergencies admitted to coronary care unit died (26). The fatality rates
may also be lower due to better care of these patients in developed countries
compared to our Tanzanian hospital. Furthermore in our study 3 month readmission
rate was 11.1% which is lower compared to a study done in USA where the 90-day
readmission rate was 37% (27). The reason for lower readmission rates could be due
to lower number of patients on follow up in our study because the majority died.
A prior 3-year prospective study in BMC among patients admitted in the medical
ward showed that hypertension contributed to 33.9% of non-communicable disease
deaths and 15.3% of all deaths. Hypertensive emergencies contributed to 17.5% of all
deaths where 55/314 patients died during hospitalisation (7). Diagnostic facilities are
lacking in our hospital such as cardiac biomarkers and consistent CT scan availability.
We should improve on diagnostic facilities for early diagnosis and early management
of these hypertensive emergencies to reduce fatality rates.
5.5 Predictors of in-hospital and 3-months fatality rates
Very few studies were done on predictors of in-hospital fatality among patients with
hypertensive emergencies. In our study, hypertensive emergency with impaired renal
function was found to be a significant predictor of in hospital fatality in both
univariable (OR 3.05, 95% CI 1.15-8.10), p=0.03 and multivariable models (OR
27.53, 95% CI 3.74-202.91), p=0.001. This is due to inconsistence presence of
diagnostics for kidney diseases as well as lack of advanced management of kidney
disease like dialysis or renal replacement therapy in our settings. Therefore early
detection and treatment of kidney diseases are warranted.
38
Hypertensive stroke was also found to be a statistically significant predictor of inhospital fatality during hospitalisation by univariable and multivariable models with
OR 7.85 and OR 31.17 respectively. Majority of strokes can be prevented by life style
modification and tight BP management.
Furthermore very few data in Africa exist on predictors of 3-months fatality for
hypertensive emergencies. Hypertensive encephalopathy was a significant positive
predictor of 3 months fatality (OR 2.62, CI 1.04–6.62), p=0.04 by univariable analysis
as well as by multivariable analysis (OR 4.42[1.41-13.84], p=0.01. This is similar to a
study done on neurological patients with acute severe hypertension attending
emergency department or ICU where fatality at 90 days was statistically significantly
higher in neurological than in non neurological patients and was associated with high
frequency of neurological deterioration (30).
Hypertensive emergency with impaired renal function was also a predictor of fatality
rates (OR 6.40, CI 2.06-19.84), p= 0.001 by multivariate logistic regression. This was
initially underestimated in our setting; therefore emphasis should be put on kidney
diseases in terms of diagnostics and research.
39
CHAPTER SIX
6.1 CONCLUSION

Hypertensive emergency is one among common causes of admission among
patients admitted to BMC medical wards and is associated with high fatality
rates, 30% in hospital and 52% at three months post discharge.

The most common forms of hypertensive emergency include retinopathy,
encephalopathy, pulmonary oedema and impaired renal function.

Factors commonly associated with hypertensive emergency include female
gender, as well as age above 45 years.

Predictors of in-hospital fatality rate among patients with hypertensive
emergencies include hypertensive stroke and hypertensive emergency with
impaired renal function which are both associated with a 30 times increased
odds of death.

Predictors of 3-months fatality rate among patients with hypertensive
emergencies include hypertensive emergency with impaired renal function and
hypertensive encephalopathy associated with 6 and 4 times increased odds of
deaths respectively.
40
6.2 LIMITATIONS
This was a single centre study involving a referral hospital population therefore
results may not be generalised to other health facilities or to the general population.
Some confirmatory investigations such as CT scan were not possible in all cases as
well as cardiac biomarkers could not be done due to expenses.
It was difficult in some of the cases to know whether end organ damages in this study
were from the currently severely elevated blood pressure, old previous lesion or a
result of some other chronic diseases.
41
6.3 RECOMENDATIONS

All patients should be educated on importance of consistence use of
medication on discharge so as to reduce the case fatality rate post discharge,
which is unacceptably high (more than 50% at three months).

In order to reduce fatality rates among patients with hypertensive emergencies,
screening for kidney disease as early as possible seems essential.

There is a need of educating the community on importance of lifestyle
modification such as dietary modification and exercise so as to reduce the
risks of hypertension, also to have habit of checking their blood pressures for
early detection and treatment so as to avoid the complications of hypertension
which are fatal.

Further research with larger sample size and longer duration is needed on
factors associated with fatality rates especially post discharge.
42
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Monthly Journal of the Association of Physicians. 2011 Mar;104(3):237–43.
2.
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21;289(19):2560–72.
4.
Kearney PM, Whelton M, Reynolds K, Muntner P, Whelton PK, He J. Global
burden of hypertension: analysis of worldwide data. Lancet.
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Edwards R, Unwin N, Mugusi F, Whiting D, Rashid S, Kissima J, et al.
Hypertension prevalence and care in an urban and rural area of Tanzania.
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6.
Dewhurst MJ, Dewhurst F, Gray WK, Chaote P, Orega GP, Walker RW. The
high prevalence of hypertension in rural-dwelling Tanzanian older adults and
the disparity between detection, treatment and control: a rule of sixths? Journal
of Human Hypertension. Nature Publishing Group; 2012 Dec 13;27(6):374–80.
7.
Peck RN, Green E, Mtabaji J, Majinge C, Smart LR, Downs JA, et al.
Hypertension-related diseases as a common cause of hospital mortality in
Tanzania: a 3-year prospective study. Journal of Hypertension. 2013 Jun 17;1.
8.
Hussain AA, Elzubier AG, Ahmed ME. Target organ involvement in
hypertensive patients in Eastern Sudan. Journal of Human Hypertension. 1999
Jan;13(1):9–12.
9.
Varon J, Marik PE. Clinical review: the management of hypertensive crises.
Critical Care. 2003 Oct;7(5):374–84.
10.
Cappuccio FP, Micah FB, Emmett L, Kerry SM, Antwi S, Martin-Peprah R, et
al. Prevalence, detection, management, and control of hypertension in Ashanti,
West Africa. Hypertension. 2004 May;43(5):1017–22.
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11.
Addo J, Smeeth L, Leon DA. Hypertensive target organ damage in Ghanaian
civil servants with hypertension. PloS One. 2009 Jan;4(8):e6672.
12.
Martin JFV, Higashiama E, Garcia E, Luizon MR, Cipullo JP. Hypertensive
crisis profile. Prevalence and clinical presentation. Arquivos Brasileiros de
Cardiologia. 2004 Aug;83(2):131–6; 125–30.
13.
Besharati MR, Rastegar A, Shoja MR, Maybodi ME. Prevalence of retinopathy
in hypertensive patients. Saudi Medical Journal. 2006 Nov;27(11):1725–8.
14.
Pinna G, Pascale C, Fornengo P, Arras S, Piras C, Panzarasa P, et al. Hospital
admissions for hypertensive crisis in the emergency departments: a large
multicenter Italian study. PloS One. 2014 Jan;9(4):e93542.
15.
Bertrand E, Muna WFT, Diouf SM, Ekra A, Kane A, Kingue S, et al.
[Cardiovascular emergencies in Subsaharan Africa]. Archives des maladies du
coeur et des vaisseaux. 2006 Dec;99(12):1159–65.
16.
Oladapo OO, Salako L, Sadiq L, Shoyinka K, Adedapo K, Falase a O. Targetorgan damage and cardiovascular complications in hypertensive Nigerian
Yoruba adults: a cross-sectional study. Cardiovascular Journal of Africa. 2012
Aug;23(7):379–84.
17.
García GM, Miúdo V, Manuel Lopes C da GA, Vassuelela Gomes J.
Characterization of patients aged 45 or under admitted with hypertensive
emergencies in the Hospital do Prenda. Revista portuguesa de cardiologia :
orgão oficial da Sociedade Portuguesa de Cardiologia = Portuguese Journal of
Cardiology : an official journal of the Portuguese Society of Cardiology. 2014
Jan;33(1):19–25.
18.
Ellenga MBF, Gombet TR, Mahoungou GKC, Otiobanda GF, Ossou NPM,
Ikama MS, et al. [Hypertensive emergencies at the University Hospital Center
in Brazzaville, Congo]. Médecine Tropicale : revue du Corps de santé colonial.
2011 Feb;71(1):97–8.
19.
Tisdale JE, Huang MB, Borzak S. Risk factors for hypertensive crisis:
importance of out-patient blood pressure control. Family Practice. 2004
Aug;21(4):420–4.
20.
Knight EL, Bohn RL, Wang PS, Glynn RJ, Mogun H, Avorn J. Predictors of
uncontrolled hypertension in ambulatory patients. Hypertension. 2001 Oct
1;38(4):809–14.
21.
Shea S, Misra D, Ehrlich MH, Field L, Francis CK. Predisposing factors for
severe, uncontrolled hypertension in an inner-city minority population. The
New England Journal of Medicine. 1992 Sep 10;327(11):776–81.
22.
Saguner AM, Dür S, Perrig M, Schiemann U, Stuck AE, Bürgi U, et al. Risk
factors promoting hypertensive crises: evidence from a longitudinal study.
American Journal of Hypertension. 2010 Jul;23(7):775–80.
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23.
Peer N, Steyn K, Dennison CR, Levitt NS, Nyo MTL, Nel JH, et al.
Determinants of target organ damage in black hypertensive patients attending
primary health care services in Cape Town: the Hi-Hi study. American Journal
of Hypertension. 2008 Aug;21(8):896–902.
24.
Lip GY, Beevers M, Beevers DG. Does renal function improve after diagnosis
of malignant phase hypertension? Journal of Hypertension. 1997
Nov;15(11):1309–15.
25.
Roubsanthisuk W, Wongsurin U, Buranakitjaroen P. Hypertensive emergencies
remain a clinical problem and are associated with high mortality. Journal of the
Medical Association of Thailand = Chotmaihet thangphaet. 2010 Jan;93 Suppl
1:S54–61.
26.
González Pacheco H, Morales Victorino N, Núñez Urquiza JP, Altamirano
Castillo A, Juárez Herrera U, Arias Mendoza A, et al. Patients with
hypertensive crises who are admitted to a coronary care unit: clinical
characteristics and outcomes. Journal of Clinical Hypertension. 2013
Mar;15(3):210–4.
27.
Katz JN, Gore JM, Amin A, Anderson F a, Dasta JF, Ferguson JJ, et al.
Practice patterns, outcomes, and end-organ dysfunction for patients with acute
severe hypertension: the Studying the Treatment of Acute hyperTension
(STAT) registry. American Heart Journal. Mosby, Inc.; 2009 Oct;158(4):599–
606.e1.
28.
Gore JM, Peterson E, Amin A, Anderson FA, Dasta JF, Levy PD, et al.
Predictors of 90-day readmission among patients with acute severe
hypertension. The cross-sectional observational Studying the Treatment of
Acute hyperTension (STAT) study. American Heart Journal. 2010
Sep;160(3):521–527.e1.
29.
Arodiwe EB, Ike SO, Nwokediuko SC. Case fatality among hypertensionrelated admissions in Enugu, Nigeria. Nigerian Journal of Clinical Practice.
2009 Jun;12(2):153–6.
30.
Mayer SA, Kurtz P, Wyman A, Sung GY, Multz AS, Varon J, et al. Clinical
practices, complications, and mortality in neurological patients with acute
severe hypertension: the Studying the Treatment of Acute hyperTension
registry. Critical Care Medicine. 2011 Oct;39(10):2330–6.
31.
Vuylsteke A, Vincent J, De La Garanderie DP, Anderson FA, Emery L,
Wyman A, et al. Characteristics, practice patterns, and outcomes in patients
with acute hypertension: European registry for Studying the Treatment of
Acute hyperTension (Euro-STAT). Critical Care. BioMed Central Ltd; 2011
Jan;15(6):R271.
45
APPENDICES
APPENDIX 1: QUESTIONNAIRE
Thank you for participating in our study. I will read each question loud and wait for
your response. For some questions I will also read loud some answers from which
you can choose. Please take as long as you need to remember or think about your
answer. If a question is unclear, please say, I will repeat and explain it. Please
remember all your answers will be kept confidential and this questionnaire does not
have your name on it.
First, I would like to ask you some questions about yourself and socio-economic
status
Q
Code
Questions and Filters
Coding Categories
01
INITIAL
Write interviewer’s Initials
Interviewer initials
02
DATE
Write date of interview
|__|__| |__|__|__| |__|__|__|__|
N
Day
03
|__|__|__|
Month
INTID
Enrolment ID number
|__|__|__|
INTNU
BMC number
|__|__|__|__|__|__|__|__|
46
Year
Q
Code
Questions and Filters
Coding Categories
PHONE
Contact phone number(s)
|__|__|__|__|__|__|__|__|__|patient
N
05
|__|__|__|__|__|__|__|__|__|__|N/kin
|__|__|__|__|__|__|__|__|__|__|N/kin
or close relative/neighbour
06
SEX
Sex
Male
1
Female
2
07
AGE
Age
08
ETHN
What is your ethnic background? African 1
09
EDLEV
|__|__|__| Years
Asian
2
others
3
What is the highest level of Non or incomplete primary school
formal
education
you
have
1
Complete primary school
2
Secondary school
3
University/ college
4
completed?
47
Q
Code
Questions and Filters
Coding Categories
EMPL
Which of the following best Government or Business employee
N
10
describes your main work status
1
Self employee (Petty trader)
2
Farmer (Peasant)
3
in the past 12 months?
What is the source of water you Tape water
are using?
11
12
ELEC
Lake/pond water
TOILET
2
Do you have Electricity inside YES
your home?
13
1
1
NO
2
What type of toilet do you use at Modern flash toilet
home?
Pit latrine
1
2
Now I am going to ask you some question about various health behaviors. This
includes things like smoking, drinking alcohol etc
QN
Code
Question and filters
Coding categories
14
TOB1
Have you ever smoked cigarettes, cigar or Yes 1
48
QN
Code
Question and filters
Coding categories
pipes?
No
Years |__|__|
2 ( skip to Qn 17)
15
TOB2
Duration of smoking
16
TOB4
On average, how many cigarettes do you Cigarettes └─┴─┘
smoke each day?
17
ALC1
Have you ever consumed an alcoholic Yes 1
drink
such
as
beer,
wine,
spirits,
No
2 (skip to QN 22)
fermented cider or local made?
18
ALC2
Before you became hypertensive, how
many occasions did you have at least one
└─┴─┘
alcoholic drink?
19
ALC3
In that time above, when you drank
alcohol, on average, how many standard
drinks └─┴─┘
alcoholic drinks did you have during one
drinking occasion? Duration?
20
ALC4
During the past 30 days, on how many
occasions did you have at least one
49
duration(yrs) └─┴─┘
QN
21
Code
ALC5
Question and filters
Coding categories
alcoholic drink?
└─┴─┘
Duration of alcohol use
Years └─┴─┘
HISTORY
OF
RAISED
BLOOD
PRESSURE
22
HBP1
Have you ever had your blood pressure Yes
measured by a doctor or other health
1
No
2
worker?
23
HBP2
Have you ever been told by a doctor or Yes
other health worker that you have raised
1
No
2
blood pressure or hypertension?
24
HTDR1
Have you ever been prescribed any drugs YES
for hypertension?
25
HTDR2
NO
In the past 2 weeks, have you taken drugs Yes
(medication) for hypertension?
26
HTTH
No
Have you ever seen a traditional healer for Yes
50
1
2
1
2
1
QN
Code
27
Question and filters
Coding categories
raised blood pressure or hypertension?
No
2
HBTHE Are you currently taking any herbal or Yes
traditional remedy for your raised blood
1
No
2
pressure?
28
HXDM
Have you ever been told by a doctor or Yes
other health worker that you have raised
1
No
2
blood sugar or diabetes?
SECTION4. PHYSICAL MEASUREMENTS
QN
Code
Question
Response
29
HEIGH
Height
Centimetres (cm)
30
Weight
WEIGH
Kilograms (kg)
└─┴─┴
─┘. └─┘
└─┴─┴
31
PREG
32
33
WC
HC
Yes
1
No
2
in Centimetres (cm)
└─┴─┴
For women: Are you pregnant?
Waist circumference
in Centimetres (cm)
Hip circumference
51
─┘.└─┘
└─┴─┴─┘
QN
Code
Question
Response
Reading 1
Systolic mmHg└─┴─┴─┘
BP on the Right arm
Diastolic mmHg└─┴─┴─┘
Reading 2
Systolic mmHg└─┴─┴─┘
BP on the left arm
Diastolic mmHg └─┴─┴─┘
Reading 3
Systolic mmHg└─┴─┴─┘
BP on the arm with higher BP
Diastolic mmHg└─┴─┴─┘
HR
Heart rate (beats per minute)
Reading └─┴─┴─┘
RBG
Random blood glucose
mmol/L┴─┴─┘.└─┘
SCRT1
Serum creatinine on admission
34
BP1
35
BP2
36
BP3
37
38
39
(ummol/L)└─┴─┴─┘.└─┘
40
(ummol/L)└─┴─┴─┘.└─┘ 1
SCRT3
Serum creatinine at 3month
Not done
41
Urine output in the first 24 in
UROUT the hospital
|__|__|__|__| mls
52
2
FOR THE PAST 24HRS IS
THERE A HISTORY OF?
42
RUOP
1
NO
2
YES
1
NO
2
YES
1
NO
2
YES
1
NO
2
YES
1
NO
2
Chest pain?
47
SOB
YES
Headache?
46
CHSTP
2
Impaired vision?
45
HDZ
NO
Loss of consciousness?
44
IMPVIS
1
Decreased urine output?
43
LOC
YES
Shortness of breathing?
48
GCS
Glasgow Coma Score.
┴─┴─┘
S02
SO2
(%)└─┴─┴─┘
49
50
DSAB
YES
1
NO
2
Displaced apex beat
51
CREPS
Crepitations in both lung bases YES
1
on examination.
2
NO
53
52
CXR
Normal
1
Pulmonary oedema
2
Cardiomegally
3
CXR findings
Normal Other............................4
1
53
STEMI Others...................2
4
ECG findings
Non-specific STdepression 3
ECG
54
Non-specific TWIs
4
LVH (cornel criteria)
5
Fundoscopy findings (to be
FUNDO confirmed by opthalmologist)
55
CTSCN
CT scan findings( if done)
56
ECHO
ECHO findings
54
Normal
1
Mild retinopathy
2
Moderate retinopathy
3
Normal
CT scan
Severe
retinopathy
14
Hemorrhagic stroke
2
Ischaemic stroke
3
Mixed stroke
4
Diffuse cerebral edema
5
SWMA
1 lesions
Space occupying
6
Thrombus
2
LVH
3
HHD
4
57
┴─┴─┘ days
DURTN Duration of hospital stay
58
IHOUT
Died
1
Alive
2
Died
1
In hospital Outcome
59
3MOUT 3 months outcome
Follow
Alive up mortality DIED/ALIVE
2
60
Clinic visit last 3 month?
ALIVE
If alive
Y/N
Readmission in last 3month Y / N
Still on medication?
55
Y/N
APPENDIX 2: INFORMED CONSENT – ENGLISH VERSION
You are invited to participate in a study on hypertensive emergencies. We are
studying the prevalence, pattern, predictors and outcome of hypertensive emergencies
among patients admitted at our hospital, Bugando medical centre. Participation is
strictly voluntary and unwillingness to participate in this study will not affect your
treatment in one way or another. If you are willing to participate, you need to sign this
form indicating your willingness. You may withdraw from the study at any time and
such a decision will be respected, and will not affect your treatment.
Participants will undergo an interview, a physical examination, a urine test, a blood
test, ECG, and CXR. Other investigations will depend on the condition of the patients.
The blood test may involve some pain at the time of drawing the blood sample but
overall, there is no physical harm expected from participation. To minimize risk of
microbial infections, the needle site will be sterilized. When the results of the research
are published or discussed in conferences or used in any form, no information will be
included that would reveal your identity.
Participants will benefit from this study by knowing their status and if they have any
hypertensive related complications they will receive treatment according to Tanzanian
guidelines.
In case of any questions regarding this study, please contact:
Dr. GRAHAME MTUI, principal Investigator, Catholic University of health and
allied sciences, Dept of Internal Medicine: P.O.Box 1464, Mwanza. Tel: +255-754936350.
56
Or in any case of any information about your rights as a study participant, please
contact;
Prof. Kongolla, Director, Research and Publications Committee, Catholic University
of health and allied sciences. P.O.Box 1464, Mwanza.
I have understood the above information. I understand that my participation is
voluntary and that I am free to withdraw at any time, without giving any reason,
without my medical care or legal rights being affected.
____________________
_______________
Signature of Patient / Next of Kin
Date
57
APPENDIX 3: INFORMED CONSENT – KISWAHILI VERSION
Ninafanya utafiti miongoni mwa watu wenye ugonjwa wa msukumo mkubwa wa
damu. Utafiti huu unafanyika kwa wagonjwa wote wanaolazwa kwenye idara ya tiba
katika hospitali ya rufaa ya Bugando Mwanza.
Watakaokubali kushiriki itawapasa kusaini fomu kuonyesha kukubali kwao. Aidha,
tutawahoji maswali kadhaa, kuwapima na kuchukua mkojo pamoja na damu kwa ajili
ya utafiti huu.
Faida utakayopata katika utafiti huu ni kujua kiwango chako cha msukumo wa damu
na kama kuna madhara yanayotokana na kuwa na msukumo mkubwa wa damu
mwilini mwako mfano matatizo kwenye ubongo, macho, mapafu moyo pamoja na
kwenye figo. Utapatiwa matibabu ya madhara hayo kilingana na mwongozo wa nchi
yetu. Mbali na faida, utasikia maumivu kidogo kwa kuchomwa sindano wakati wa
kuchukua damu kwa ajili ya vipimo.
Taarifa zote utakazotupatia zitakuwa siri na zitatumika tu kwa ajili ya kuboresha
huduma na utabibu kwa wagonjwa. Ushiriki wako ni wa hiari kabisa, aidha unayo
haki ya kujitoa katika utafiti huu wakati wowote ule utakapojisikia kufanya hivyo.
Uamuzi wako kushiriki ama kutoshiriki hautaathiri hata kidogo haki yako ya kupata
huduma na tiba kama mgonjwa mwingine yeyote yule.
Iwapo utakuwa na swali lolote kuhusu utafiti huu au kama umedhurika, unaweza
kuwasiliana na Dr. GRAHAME MTUI mtafiti mkuu; Chuo Kikuu Cha Sayansi za
Afya na Tiba Bugando; Idara ya Tiba; SLP 1464, Mwanza. Simu: +255-754-936350
58
Au endapo utakuwa na swali lolote kuhusu haki zako kama mshiriki katikia utafiti
huu wasiliana na:
Prof Kongola; Mkurugenzi wa Kamati ya Tafiti na Matoleo Chuoni, Chuo Kikuu Cha
Afya na Tiba Bugando, SLP: 1464, Mwanza.
Nitafurahi kama utakubali kushiriki katika utafiti huu.
MTAFITI
Mimi ____________________________ nathibitisha kuelewa maelezo
yaliyoandikwa hapo juu na kuridhika na maelezo niliyopewa kwa maswali yangu
yote. Nami, kwa hiari yangu mwenyewe, bila kushurutishwa na mtu, ninakubali
kushiriki kwenye utafiti huu.
Mgonjwa/Msindikizaji:______________
Tarehe:________________
59
60
APPENDIX 4: ETHICAL CLEARANCE CERTIFICATE
61