No. of Pages 6
The Egyptian Journal of Critical Care Medicine (2014) xxx, xxx-xxx
The Egyptian College of Critical Care Physicians The Egyptian Journal of Critical Care Medicine
http://ees.elsevier.com/ejccm www.sciencedirect.com
ORIGINAL ARTICLE
Assessment of hypotension during dialysis as a manifestation of myocardial ischemia in patients with chronic renal failure
Randa Aly Soliman a *, Mohamed Fawzy a, Hussein Kandil b, Alia Abd el Fattah a
a The Critical Care Department, Cairo university, Egypt b The Critical Department in the National Liver Institute, Egypt
Received 4 September 2013; revised 3 May 2014; accepted 15 May 2014
KEYWORDS
Intradialytic hypotension (IDH);
With chronic renal failure (CRF);
Myocardial perfusion; Imaging (MPI)
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 sequestration 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 relationship 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 session was standardized in all patients. Intradialytic blood pressure was monitored and hypotension was classified as mild (SBP > 100mmHg), 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 output, 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 contraindications 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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EJCCM 25 9 June 2014 ARTICLE IN PRESS No. of Pages 6
2 R.A. Soliman et al.
moderate or severe hypotension. Among the first group, only two patients (10%) were found to have myocardial ischemia, while in the latter group, seven patients (70%) had myocardial ischemia that is mostly moderate (p = 0.002). Stress induced LV dysfunction was also significantly prevalent in patients with moderate or severe intradialytic hypotension as opposed to the other group (p = 0.002) LVED.
Conclusions: Patients with CKD and regular hemodialysis who experience moderate or severe intradialytic hypotension have significantly higher prevalence of myocardial ischemia and stress induced myocardial dysfunction, than those who experience no or mild intradialytic hypotension.
© 2014 Production and hosting by Elsevier B.V. on behalf of The Egyptian College of Critical Care
Physicians.
1. Introduction
Intradialytic hypotension (IDH) remains to be a major complication of hemodialysis. It occurs in nearly 25% of dialysis sessions [1] and often requires aggressive resuscitative measures and sometimes premature termination of hemodialysis. It is also a significant independent factor affecting mortality in hemodialysis patients [2].
Despite the advances of machines with ultrafiltration control devices, modifying dialysate composition, temperature control, correction of nutritional deficiencies and treatment of anemia with erythropoietin therapy, many patients still have episodes of intradialytic hypotension. Among other factors, the major pathophysiology of these episodes is the removal of large volume of blood water and solutes over a short period of time, overwhelming normal compensatory mechanisms, which include plasma refilling and reduction of venous capacity (due to reduction of pressure transmission to veins).
In some patients, a seemingly paradoxical and inappropriate reduction of sympathetic tone may occur, causing reduction of arteriolar resistance, decreased transmission of pressure to veins with corresponding increase in venous capacity. Increased sequestration of blood in veins under conditions of hypovolemia reduces cardiac filling, cardiac output and ultimately blood pressure. Hypotensive episodes during hemodial-ysis in patients with end stage renal disease in the absence of inadequate maintenance of the plasma volume, pre-existence of cardiovascular disease, or autonomic nervous system dysfunction are accompanied by increased plasma concentrations of the end-products of nitric oxide metabolism (above the expected levels, based on the reduction of urea [3]).
In this controlled prospective study, patients with chronic renal failure and intradialytic hypotension episodes were thoroughly investigated, to evaluate the relationship between hypotension and myocardial ischemia after controlling other possible causes.
2. Patients and methods
This prospective study was conducted in King Fahd Hemodialysis unit in Kasr Al-Aini hospital, Hemodialysis Unit in Al-Zahraa hospital and Critical Care Medicine Department in Kasr Al-Aini hospital over the time period from February 2010 to June 2011. All patients included in the study provided informed written consent. The study includes 30 patients with chronic renal failure who receive regular hemodialysis sessions. Twenty patients developed hypotension during hemodialysis session, and the remaining 10 patients did not develop hypo-
Table 1 Baseline characteristics of the study group (n = 30).
Parameter Value [N (%) or mean ± SD]
Age (years) 44 ± 13
Weight (Kg) 66 ± 10
Male 12 (40)
Clinical
Smokers 7 (23)
Hypertension 12 (40)
History of chest pain 6 (20)
Family history of IHD 9 (30)
Autonomic neuropathy 9 (30)
AV fistula 23 (77)
Duration of hemodialysis (years) 3.7 ± 2.1
ECG and ECHO
Arrhythmia in ECG 4(13)
LVH in ECG 6 (20)
RWMA 5(17)
LVEDD (mm) 49.7 ± 5.4
LVESD (mm) 32.4 ± 4
EF (%) 62.3 ± 7.6
Grades of Albuminuria*
( + ) 6 (20)
(++) 7 (23)
(+ + +) 2(7)
Urine specific gravity 1009 ± 2.1
Hb (g/dL) 10.5 ± 0.73
Hct (%) 32.6 ± 2.9
TLC (103 cells/cmm) 6.1 ± 2.1
FBS (mg/dL) 70.2 ± 11.2
PPBS (mg/dL) 123.5 ± 15.2
HB A1C (mg/dL) 5 ± 0.59
Serum Triglycerides (mg/dL) 109.7 ± 43
Serum Cholesterol (mg/dL) 151 ± 60
Serum Urea (mg/dL) 129.8 ± 29.7
Serum Creatinine (mg/dL) 7.9 ± 2.1
GFR (ml/min/1.73 m2) 11 ± 4.2
Serum Sodium (mEq/L) 138 ± 5.8
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 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 A1C, hemoglobin A1C; GFR, glomerular
filtration rate.
* Done only for the 15 patients who were not anuric.
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Q1 Assessment of hypotension during dialysis as a manifestation of myocardial ischemia 3
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).
78 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 36 0C. 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].
Patients who required vasopressors were unstable and 116
accordingly were excluded from this study. 117
2.3. After dialysis 118
Within 2-5 h after dialysis, patients had both trans-thoracic 119
echocardiography and MPI. The echo was done using an 120
ATL machine HDI 5000 with the patient lying in the left lat- 121
eral decubitus using a 3.5 MHZ probe. MPI was done at the 122
nuclear laboratory of the critical care medicine department, 123
Kasr Al-Aini hospital, Cairo University utilizing the ''freeze 124
imaging protocol''. The set of SPECT images was acquired 125
using a triple head Siemens gamma camera with high resolu- 126
tion collimators (model Symbia E). Pharmacological stress 127
testing using Dipyridamole was done as most patients with 128
CKD could not achieve target HR during treadmill stress test- 129
ing due to marked physical limitations. 130
Patients were instructed to fast for at least 6-8 h, stop the- 131
ophylline medications for at least 24 h and not to have any caf- 132
feinated drinks or beverages for at least 24 h prior to the study. 133
Dipyridamole 0.56 mg/kg was diluted with 40 cc normal saline 134
and infused over 4 min. 2 min later, 20-25 mCi Tc-99 m Sestam- 135
ibi were injected intravenously through a wide bore cannula fol- 136
lowed by saline flush. Patients were monitored for at least 5 min 137
or till vital signs returned to baseline. Ambulant patients were 138
asked to walk for 4 min after Dipyridamole infusion. 139
Twenty projections were acquired (30 s for each frame) at 140
120 degree arc and total acquisition time of 12 min. SPECT 141
images were processed using the back-projection technique to 142
get trans-axial images then short axis, vertical long axis and 143
horizontal long axis cuts. The twenty-segment scoring system 144
was applied to estimate the Myocardium At Risk (MAR), 145
and the severity of perfusion defect was assessed for each seg- 146
ment using a ''0-4'' scoring system with ''0'' indicating normal 147
perfusion and ''4'' indicating no photon activity. The sum of 148
these scores is the Summed Stress Score (SSS). 149
Seventy two hours later, patients were re-injected with 20- 150
30 mCi Tc-99 m Sestamibi intravenously to acquire the second 151
set of SPECT images at rest, and to estimate the left ventricu- 152
lar ejection fraction (EF) utilizing the Gated SPECT tech- 153
nique. The severity of perfusion defects of MAR in this set 154
of SPECT images is assessed similarly and the sum of these 155
scores is the Summed Rest Score (SRS). 156
R.A. Soliman et al.
Table 2 Comparison of demographic, clinical, laboratory and MPI data between the 2 study groups.
Parameter Group A (n = 20) Group B (n = 10)
Age (years) 43.5 (33-54) 47.5 (28-58) 0.63
Weight (Kg) 65.5 (56-73) 67 (58-77) 0.81
Male 9(45) 3 (30) 0.69
Clinical
Smokers 5 (25) 2 (20) 1.0
Hypertension 7 (35) 5 (50) 0.69
Family history of IHD 5 (25) 4 (20) 0.43
Autonomic neuropathy 4 (20) 5 (50) 0.115
AV fistula 16 (80) 7 (70) 0.66
Duration of hemodialysis (years) 4 (3-6) 2.5 (1-4) 0.1
ECG and ECHO
Arrhythmia in ECG 1 (5) 3 (30) 0.095
LVH in ECG 3 (15) 3 (30) 0.37
RWMA 2(10) 3 (30) 0.30
LVEDD (mm) 52 (46.5-55) 44.5 (44-51) 0.046
LVESD (mm) 32 (30-35) 31.5 (28-34) 0.63
EF (%) 63 (56-70) 59.5 (56-62) 0.19
Grades of Albuminuria* n = 8 n = 7
( + ) 5/8 (62.5) 1/7 (14.3) 0.092
(++) 3/8 (37.5) 4/7 (57.1)
(+ + +) 0/8 2/7 (28.6)
Urine specific gravity 1010 (1008-1010) 1009 (1005-1010) 0.12
Hb (g/dL) 10.4 (9.8-10.9) 10.5 (10.3-11.3) 0.15
Hct (%) 31.9 (30.3-35) 33 (32.3-37) 0.098
TLC (103 cells/cmm) 5.4 (4.8-7.6) 5.2 (4-8) 0.74
FBS (mg/dL) 71 (60-80) 69 (62-76) 0.88
PPBS (mg/dL) 123 (116-131) 119 (108-134) 0.58
HB A1C (mg/dL) 4.9 (4.6-5.5) 4.8 (4.3-5.5) 0.42
Serum Triglycerides (mg/dL) 90.5 (80-117) 97 (75-170) 0.75
Serum Cholesterol (mg/dL) 135 (113-165) 117 (109-247) 0.55
Serum Urea (mg/dL) 138 (101-151) 121 (106-144) 0.4
Serum Creatinine (mg/dL) 8.4 (6.3-9.7) 7.7 (6.5-9) 0.63
GFR (ml/min/1.73 m2) 10.2 (7.9-12.4) 9.5 (8.9-12.6) 0.55
Serum Sodium (mEq/L) 138.5 (133-144) 138.5 (133-142) 1.0
Serum Potassium (mEq/L) 5.2 (4.7-5.5) 5.3 (5-6.1) 0.094
Ischemia (total count) 2(10) 7 (70) 0.002
Mild ischemia 1/1 (50) 1/7 (14.3) 0.417
Moderate ischemia 1/1 (50) 6/7 (85.7)
Scar 0 2 (20) 0.103
Stress induced LV dysfunction 2(10) 7 (70) 0.002
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 A1C, hemoglobin A1C; GFR, glomerular filtration rate.
* Done only for the 15 patients who were not anuric.
157 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).
Categorical variables are described as frequency (n) and 165
percentage (%). Quantitative variables are described as 166
mean ± standard deviation (SD) whenever parametric. Non- 167
parametric quantitative variables are described as median 168
and interquartile range (IQR). Bivariate analysis of categorical 169
variables was done using Chi-square test with Yates Continu- 170
ity correction for 2 x 2 tables. Whenever cell frequency is <5, 171
Fisher's Exact test is used. 172
Comparison of two groups of quantitative variables was 173
done using Independent-Samples Student's t test for paramet- 174
ric data, and Mann-Whitney test for non-parametric data. 175
EJCCM 25 9 June 2014 ARTICLE IN PRESS No. of Pages 6
Q1 Assessment of hypotension during dialysis as a manifestation of myocardial ischemia 5
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).
176 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 in Table 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
52mm, IQR 46.5-55) than in Group B (44.5 mm, 44-50.75) 191
(p = 0.046) (Fig. 3). 192
4. Discussion 193
Intradialytic hypotension (IDH) is a major complication of 194
hemodialysis. Two to four liters of fluid needs to be removed 195
during a regular session, equivalent to 40-80% of the blood 196
volume. It is therefore not surprising that hypotension occurs 197
so often. Although many factors - patient or treatment related 198
- play a role, a reduction of blood volume is crucial in its path- 199
ogenesis [1]. 200
Hypotension is one of the clinical presentations of CVD in 201
patients with CKD [7]. There are a number of possible expla- 202
nations for the independent association of reduced GFR and 203
CVD outcomes. First, a reduced GFR may be associated with 204
an increased level of nontraditional CVD risk factors that fre- 205
6 R.A. Soliman et al.
206 quently are not assessed in many studies. Second, reduced
207 GFR may be a marker of undiagnosed vascular disease or
208 alternatively a marker of the severity of diagnosed vascular
209 disease, especially in high or highest risk populations. Third,
210 reduced GFR may have had more severe hypertension or dysl-
211 ipidemia and therefore have suffered more vascular damage
212 secondary to hypertension or dyslipidemia. Fourth, recent
213 studies have suggested that subjects with reduced GFR are less
214 likely to receive medications or therapies such as angiotensin
215 converting enzyme inhibitors, B-blockers, aspirin, platelet
216 inhibitors, thrombolytics, or percutaneous intervention than
217 patients with preserved GFR. Perhaps as important was the
218 fact that in the same studies, patients with reduced GFR
219 who did receive the above interventions obtained similar ben-
220 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].
In conclusion, we found that patients with CKD and regu- 267
lar hemodialysis who experience moderate or severe intradia- 268
lytic hypotension have significantly higher prevalence of 269
myocardial ischemia and stress induced myocardial dysfunc- 270
tion, than those who experience no or mild intradialytic 271
hypotension. 272
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