8 aThe Critical Care Department, Cairo university, Egypt 9 Q3 bThe Critical Department in the National Liver Institute, Egypt 10 Received 4 September 2013; revised 3 May 2014; accepted 1
Trang 18 aThe Critical Care Department, Cairo university, Egypt
9 Q3 bThe Critical Department in the National Liver Institute, Egypt
10 Received 4 September 2013; revised 3 May 2014; accepted 15 May 2014
11
14
15 Intradialytic hypotension
17 With chronic renal failure
19 Myocardial perfusion;
Abstract Introduction: Intradialytic hypotension (IDH) remains to be a major complication of hemodialysis occurring in nearly 25% of dialysis sessions It is a significant independent factor affecting mortality in hemodialysis patients Autonomic nervous system dysfunction, blood seques-tration in the setting of hypovolemia, cardiovascular diseases and increased plasma level of end products of nitric oxide metabolism are possible causes In this controlled prospective study we examined patients with chronic renal failure and intradialytic hypotension to evaluate the relation-ship between this hypotension and myocardial ischemia after controlling other possible causes Materials and methods: Thirty patients with chronic renal failure who are on regular dialysis were enrolled Before dialysis, patients were subjected to history taking and clinical examination Echocardiography and several lab tests were done Glomerular filtration rate (GFR) was calculated using Cockcroft’s and Gault formula Autonomic dysfunction was also assessed The dialysis ses-sion was standardized in all patients Intradialytic blood pressure was monitored and hypotenses-sion was classified as mild (SBP > 100 mmHg), moderate (SBP 80–100) or severe (SBP < 80) After dialysis, myocardial ischemia was assessed using stress myocardial perfusion imaging (MPI) (Phar-macologic stress testing using Dipyridamole) and is further classified as mild, moderate or severe ischemia Patients with sepsis, hemoglobin level less than 9 g/dL, diabetes mellitus, low cardiac out-put, coronary artery disease, significant valvular lesion or body weight below the dry weight of the patient were excluded from the study Bronchial asthma, emphysema and severe COPD are contra-indications to Dipyridamole and thus were also excluded from the study
Results: Twenty patients had no or mild intradialytic hypotension whereas ten patients had
* Corresponding author Address: 20 Abou Hazem st., Madkour,
Haram, Giza, Egypt Tel.: +20 1222402018.
E-mail address: randaalysoliman@hotmail.com (R.A Soliman).
Peer review under responsibility of The Egyptian College of Critical
Care Physicians.
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Trang 234 Intradialytic hypotension (IDH) remains to be a major
compli-35 cation of hemodialysis It occurs in nearly 25% of dialysis
ses-36 sions[1]and often requires aggressive resuscitative measures
37 and sometimes premature termination of hemodialysis It is
38 also a significant independent factor affecting mortality in
39 hemodialysis patients[2]
40 Despite the advances of machines with ultrafiltration
con-41 trol devices, modifying dialysate composition, temperature
42 control, correction of nutritional deficiencies and treatment
43 of anemia with erythropoietin therapy, many patients still have
44 episodes of intradialytic hypotension Among other factors,
45 the major pathophysiology of these episodes is the removal
46 of large volume of blood water and solutes over a short period
47 of time, overwhelming normal compensatory mechanisms,
48 which include plasma refilling and reduction of venous
capac-49 ity (due to reduction of pressure transmission to veins)
50 In some patients, a seemingly paradoxical and
inappropri-51 ate reduction of sympathetic tone may occur, causing
reduc-52 tion of arteriolar resistance, decreased transmission of
53 pressure to veins with corresponding increase in venous
capac-54 ity Increased sequestration of blood in veins under conditions
55 of hypovolemia reduces cardiac filling, cardiac output and
ulti-56 mately blood pressure Hypotensive episodes during
hemodial-57 ysis in patients with end stage renal disease in the absence of
58 inadequate maintenance of the plasma volume, pre-existence
59 of cardiovascular disease, or autonomic nervous system
dys-60 function are accompanied by increased plasma concentrations
61 of the end-products of nitric oxide metabolism (above the
62 expected levels, based on the reduction of urea[3])
63 In this controlled prospective study, patients with chronic
64 renal failure and intradialytic hypotension episodes were
thor-65 oughly investigated, to evaluate the relationship between
hypo-66 tension and myocardial ischemia after controlling other
67 possible causes
68 2 Patients and methods
69 This prospective study was conducted in King Fahd
Hemodi-70 alysis unit in Kasr Aini hospital, Hemodialysis Unit in
Al-71 Zahraa hospital and Critical Care Medicine Department in
72 Kasr Al-Aini hospital over the time period from February
73 2010 to June 2011 All patients included in the study provided
74 informed written consent The study includes 30 patients with
75 chronic renal failure who receive regular hemodialysis sessions
76 Twenty patients developed hypotension during hemodialysis
77 session, and the remaining 10 patients did not develop
hypo-Table 1 Baseline characteristics of the study group (n = 30)
Clinical
Duration of hemodialysis (years) 3.7 ± 2.1 ECG and ECHO
Grades of Albuminuria *
Urine specific gravity* 1009 ± 2.1 Labs
Serum Triglycerides (mg/dL) 109.7 ± 43 Serum Cholesterol (mg/dL) 151 ± 60
Serum Creatinine (mg/dL) 7.9 ± 2.1
Serum Potassium (mEq/L) 5.2 ± 0.63 IHD, ischemic heart disease; LVH, left ventricular hypertrophy; RWMA, regional wall motion abnormalities; LVEDD, left ven-tricle end-diastolic diameter; LVESD, left venven-tricle end-systolic diameter; EF, ejection fraction Hb, hemoglobin; Hct, hematocrit; TLC, total leukocytic count; FBS, fasting blood sugar; PPBS, post prandial blood sugar; HB A 1C , hemoglobin A 1C ; GFR, glomerular filtration rate.
* Done only for the 15 patients who were not anuric.
Trang 378 tension during the sessions Myocardial ischemia was assessed
79 in all patients using stress myocardial perfusion imaging (MPI)
80 (Pharmacologic stress testing using Dipyridamole)
81 Patients with sepsis, hemoglobin level less than 9 g/dL,
82 diabetes mellitus, low cardiac output, acute coronary
83 syndrome, significant valvular lesion or body weight below
84 the dry weight of the patient were excluded from the study
85 Bronchial Asthma, emphysema and severe COPD are
86 contraindications to Dipyridamole and thus were also
87 excluded from the study
88 2.1 Before dialysis
89 All eligible patients were subjected to full history taking and
90 clinical examination Serum Urea and Creatinine were
mea-91 sured Glomerular filtration rate (GFR) was calculated using
92 Cockcroft’s and Gault equation Autonomic dysfunction was
93 assessed using at least 2 of the following tests; blood pressure
94 (BP) response to standing, BP response to sustained handgrip,
95 Heart Rate (HR) response to standing, HR response to deep
96 breathing and HR response to valsalva Positive result of
97 any test indicates autonomic dysfunction[4]
98 2.2 During dialysis
99 Dialysis was done via AV fistula (23 patients) or dialysis
cath-100 eter (7 patients), using Fresenius 4008B, Nipro machine with
101 ultrafiltration volume control and polysulfone, Fresenius F6
102 filters Temperature of dialysate was kept at 36C Blood
103 pump was kept between 250 and 350 ml/min except during
104 the hypotensive episodes during which the blood pump was
105 decreased to only 200 ml/min and not less to insure adequate
106 dialysis session Dialysate flow was 500 ml/min All dialysis
107 sessions lasted around 4 h
108 BP is recorded using standard sphygmomanometer every
109 30 min in supine position Each time the mean of 3
measure-110 ments is recorded Intradialytic hypotension is defined as a
111 symptomatic decrease of more than 30 mmHg in systolic blood
112 pressure or as an absolute systolic blood pressure under
113 90 mmHg[5] Hypotension is further classified as mild
(Sys-114 tolic Blood Pressure (SBP) > 100 mmHg), moderate (SBP
115 80–100 mmHg) and Severe (SBP < 80 mmHg)[6]
116
Patients who required vasopressors were unstable and
117
accordingly were excluded from this study
118
2.3 After dialysis
119
Within 2–5 h after dialysis, patients had both trans-thoracic
120
echocardiography and MPI The echo was done using an
121
ATL machine HDI 5000 with the patient lying in the left
lat-122
eral decubitus using a 3.5 MHZ probe MPI was done at the
123
nuclear laboratory of the critical care medicine department,
124
Kasr Al-Aini hospital, Cairo University utilizing the ‘‘freeze
125
imaging protocol’’ The set of SPECT images was acquired
126
using a triple head Siemens gamma camera with high
resolu-127
tion collimators (model Symbia E) Pharmacological stress
128
testing using Dipyridamole was done as most patients with
129
CKD could not achieve target HR during treadmill stress
test-130
ing due to marked physical limitations
131
Patients were instructed to fast for at least 6–8 h, stop
the-132
ophylline medications for at least 24 h and not to have any
caf-133
feinated drinks or beverages for at least 24 h prior to the study
134
Dipyridamole 0.56 mg/kg was diluted with 40 cc normal saline
135
and infused over 4 min 2 min later, 20–25 mCi Tc-99 m
Sestam-136
ibi were injected intravenously through a wide bore cannula
fol-137
lowed by saline flush Patients were monitored for at least 5 min
138
or till vital signs returned to baseline Ambulant patients were
139
asked to walk for 4 min after Dipyridamole infusion
140
Twenty projections were acquired (30 s for each frame) at
141
120 degree arc and total acquisition time of 12 min SPECT
142
images were processed using the back-projection technique to
143
get trans-axial images then short axis, vertical long axis and
144
horizontal long axis cuts The twenty-segment scoring system
145
was applied to estimate the Myocardium At Risk (MAR),
146
and the severity of perfusion defect was assessed for each
seg-147
ment using a ‘‘0–4’’ scoring system with ‘‘0’’ indicating normal
148
perfusion and ‘‘4’’ indicating no photon activity The sum of
149
these scores is the Summed Stress Score (SSS)
150
Seventy two hours later, patients were re-injected with 20–
151
30 mCi Tc-99 m Sestamibi intravenously to acquire the second
152
set of SPECT images at rest, and to estimate the left
ventricu-153
lar ejection fraction (EF) utilizing the Gated SPECT
tech-154
nique The severity of perfusion defects of MAR in this set
155
of SPECT images is assessed similarly and the sum of these
156
scores is the Summed Rest Score (SRS)
Figure 1 Myocardial ischemia diagnosed by MPI in patients with moderate or severe intradialytic hypotension, in comparison to those with no or mild hypotension (p = 0.002)
Trang 4157 The difference between SSS and SRS is the Summed
Differ-158 ence Score (SDS) It is classified as follows; 0–4 indicates no
159 ischemia, 5–8 mild ischemia, 9–12 moderate ischemia and
160 more than 12 is severe ischemia
161 2.4 Statistical methods
162 Statistical analysis was done using Statistical Package for
163 Social Sciences (SPSS) software, release 16.0.0 for Windows
164 (SPSS Inc., Chicago, Illinois)
165
Categorical variables are described as frequency (n) and
166
percentage (%) Quantitative variables are described as
167
mean ± standard deviation (SD) whenever parametric
Non-168
parametric quantitative variables are described as median
169
and interquartile range (IQR) Bivariate analysis of categorical
170
variables was done using Chi-square test with Yates
Continu-171
ity correction for 2· 2 tables Whenever cell frequency is <5,
172
Fisher’s Exact test is used
173
Comparison of two groups of quantitative variables was
174
done using Independent-Samples Student’s t test for
paramet-175
ric data, and Mann–Whitney test for non-parametric data
Labs
MPI
Data are displayed as n (%) or median (inter-quartile range).
IHD, ischemic heart disease; LVH, left ventricular hypertrophy; RWMA, regional wall motion abnormalities; LVEDD, left ventricle end-diastolic diameter; LVESD, left ventricle end-systolic diameter; EF, ejection fraction; Hb, hemoglobin; Hct, hematocrit; TLC, total leukocytic count; FBS, fasting blood sugar; PPBS, post prandial blood sugar; HB A 1C , hemoglobin A 1C ; GFR, glomerular filtration rate.
* Done only for the 15 patients who were not anuric.
Trang 5176 In all cases, the 2-sided significance was always taken as p
177 value p value <0.05 is considered statistically significant
178 3 Results
179 Thirty patients were included in this study Their baseline
180 characteristics are listed inTable 1
181 We found that 70% (7/10) of patients who had moderate or
182 severe hypotension (Group B) had myocardial ischemia on
183 MPI, in comparison to 10% (2/20) of patients who experienced
184 no or mild intradialytic hypotension (Group A); a difference
185 that is statistically significant (p = 0.002) (Fig 1)
186 Several other variables were compared across both study
187 groups (Table 2) It is to be noted that patients of Group B
188 were more likely to have stress induced LV dysfunction on
189 MPI (7/10, 70%) than patients of Group A (2/20, 10%)
190 (p = 0.002) (Fig 2) LVED was wider in Group A (Median
191
52 mm, IQR 46.5–55) than in Group B (44.5 mm, 44–50.75)
192
(p = 0.046) (Fig 3)
193
4 Discussion
194
Intradialytic hypotension (IDH) is a major complication of
195
hemodialysis Two to four liters of fluid needs to be removed
196
during a regular session, equivalent to 40–80% of the blood
197
volume It is therefore not surprising that hypotension occurs
198
so often Although many factors – patient or treatment related
199
– play a role, a reduction of blood volume is crucial in its
path-200
ogenesis[1]
201
Hypotension is one of the clinical presentations of CVD in
202
patients with CKD[7] There are a number of possible
expla-203
nations for the independent association of reduced GFR and
204
CVD outcomes First, a reduced GFR may be associated with
205
an increased level of nontraditional CVD risk factors that
fre-Figure 2 Stress induced LV dysfunction diagnosed by MPI in patients with moderate or severe intradialytic hypotension in comparison
to those with no or mild hypotension (p = 0.002)
Figure 3 Left ventricular end-diastolic diameter in patients with moderate or severe intradialytic hypotension (44.5 mm [44–51]) in comparison to those with no or mild intradialytic hypotension (52 mm [46.5–55]) (p = 0.046)
Trang 6220 efit as patients with preserved GFR Finally, decreased GFR
221 itself may be a risk factor for progression of ventricular
remod-222 eling and cardiac dysfunction[7]
223 Different studies stated that, during hemodialysis, patients
224 are particularly susceptible to myocardial ischemia for number
225 of reasons including: LV hypertrophy[8], intradialytic
hypo-226 tension and instability[9], high prevalence of decreased
coro-227 nary flow reserve even in the absence of coronary vessel
228 stenosis[10,11]
229 Hakeem et al.[12]reported that in patients with CKD 40%
230 of perfusion scans were abnormal (SSS P 4) with 20% mild
231 defects and 20% moderated to severe defects
232 Q4 In line with Hakeem’s result, we found that patients who
233 experience moderate or severe intradialytic hypotension have
234 significantly higher prevalence of myocardial ischemia (70%,
235 7/10), in comparison to those who have no or mild
intradialyt-236 ic hypotension (10%, 2/20) (p = 0.002)
237 Paoletti et al.[13]stated that there is growing evidence that
238 patients with CKD have unrecognized LV dysfunction, both
239 systolic and diastolic They also pointed at the importance of
240 LV dysfunction (LV ejection fraction <40%) as a predictor
241 of cardiac death in patients with CKD
242 We similarly found that CKD patients who develop
moder-243 ate or severe intradialytic hypotension, have significantly
244 higher prevalence of stress induced LV dysfunction (70%, 7/
245 10) than those who have no or mild hypotensive episodes
246 (10%, 2/20) (p = 0.002)
247 Deterioration of renal function in CKD may lead to
dysli-248 pidemia or accumulation of uremic toxins, which can stimulate
249 oxidative stress and inflammation, which in turn contributes to
250 endothelial dysfunction and progression of atherosclerosis
251 [14] Renal failure causes changes in plasma components and
252 endothelial structure and function that favor vascular injury,
253 which may play a role as a trigger for inflammatory response
254 Dyslipidemia associated with CKD contributes to the
inflam-255 matory response in renal failure[15] However, in our study
256 we found that levels of serum cholesterol and triglycerides were
257 not significantly different between the two study groups, a
258 finding probably attributed to the small number of the study
259 group and the relatively low economic standard of those
260 patients
261 Patients with CKD also have a high prevalence of
arterio-262 sclerosis and remodeling of large arteries Remodeling may
263 be due to either pressure overload – which is distinguished
264 by wall hypertrophy and an increased wall-to-lumen ratio –
265 or flow overload, which is characterized by a proportional
266 increase in arterial diameter and wall thickness[16]
279
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