| Abstract|| |
To investigate the effect of cool dialysis on hemodynamic parameters and serum nitric oxide levels in diabetic patients, we studied 20 old (mean age 63.3 ± 7.5) chronic hemodialysis diabetics who were dialyzed twice, once using cool and once using standard (37 o C) temperature dialysate solution. During the study, all the dialysis conditions were maintained the same except cooling the dialysate from 37 o C to 35°C. Hemodynamic parameters including SBP, DBP, and HR were measured hourly. Oral temperature was measured before and after dialysis. Serum urea and nitric oxide metabolites were determined before and after hemodialysis. Systolic, diastolic, and mean arterial pressure decreased significantly during standard temperature compared to cool dialysis. Maximum decrease of systolic, diastolic, and mean arterial pressure was observed during the third hour of dialysis and the magnitude of decrease was 18, 17, and 14 percent for standard temperature and 6, 1, and 4 percent for cool dialysis, respectively. Heart rate did not differ significantly between the two study groups. Compared to the pre dialysis levels of serum nitric oxide metabolites, the post dialysis levels decreased significantly with cool and standard temperature dialysate (59 ± 5 vs. 37 ± 4, and 63 ± 7 vs. 41 ± 5, µmol/L respectively, P< 0.01). Cool dialysis could decrease episodes of hypotension and stabilized hemodynamic parameters in diabetic patients. Probably other mechanisms than increased serum nitric oxide levels may be involved in hemodialysis hypotension in this group of patients.
Keywords: Cool dialysis, Diabetes, Hemodialysis, Hemodynamic parameters, Nitric oxide
|How to cite this article:|
Ghasemi A, Shafiee M, Rowghani K. Stabilizing Effects of Cool Dialysate Temperature on Hemodynamic Parameters in Diabetic Patients Undergoing Hemodialysis. Saudi J Kidney Dis Transpl 2008;19:378-83
|How to cite this URL:|
Ghasemi A, Shafiee M, Rowghani K. Stabilizing Effects of Cool Dialysate Temperature on Hemodynamic Parameters in Diabetic Patients Undergoing Hemodialysis. Saudi J Kidney Dis Transpl [serial online] 2008 [cited 2019 Aug 17];19:378-83. Available from: http://www.sjkdt.org/text.asp?2008/19/3/378/40496
| Introduction|| |
Hypotension is the most common acute complication of hemodialysis (HD).  Cool temperature dialysate is used for amelioration of symptomatic hypotension during HD.  Because this method is simple and cost effective, it has increased popularity in HD centers.  However, not all patients benefit from the cool dialysis,  and some HD complications such as cramps seem to be more frequent with cool (35 o C) than standard (37 o C) temperature dialysate. 
Although cool dialysate is used to stabilize blood pressure during HD, some reports found that decreasing dialysate temperature had no beneficial effect on mean arterial pressure in patients with stable blood pressure.  Without appropriate selection of patients for cool dialysis may result in effect not better than placebo.  Groups including women, patients over 55 years of age, patients with low body surface area, and patients with cardiovascular disease appear to benefit most from cool dialysis. 
Based on our knowledge, there is no report that exclusively investigated the effect of cool dialysis on diabetic HD patients who usually are at increased risk for hypotension during HD.  Over the years, the percentage of dialyzed diabetic patients increased tremendously.  Therefore, preventing hypotension episodes during HD may be beneficial in this group of patients.  In addition, previous studies have found that accumulation of nitric oxide is one of the major causes of hypotension during HD. 
The aim of our present study is to determine the effect of cool dialysate temperature (i.e., 35°C) compared to standard dialysate (i.e., 37°C) on the hemodynamic stability in diabetic patients. We also measured serum nitric oxide metabolites pre and post dialysis to determine the role of nitric oxide in HD hypotension.
| Patients and Methods|| |
We studied in a crossover design 20 (10 men and 10 women) old (63.3 ± 7.5 years) diabetic patients who were receiving 4hour maintenance HD three times a week for a mean duration of 28 ± 4 months at the dialysis center of Shaheed Beheshti University of Medical Sciences. Informed consent was obtained from all patients, and the protocol was approved by the ethical committee of the university.
Each patient was dialyzed twice, once with standard temperature and once with cool dialysate. During the study, all the dialysis conditions were maintained the same except cooling the dialysate from 37 o C to 35°C. All patients were dialyzed using R5 capillary dialyzers and acetate dialysate produced by Behvarzan Pharmaceutical Company, Tehran, Iran (Na + 135, K+ 2, Ca 2+ 2.5, Mg 2+ 1.0, acetate 35, and Cl - 105.5 meq/L) at a flow rate of 250 ml/min. Systolic and diastolic blood pressures (SBP & DBP) and heart rate (HR) were measured every hour during dialysis. Mean arterial pressure (MAP) was computed as the diastolic blood pressure plus one third of the pulse pressure. Hypotension episode was defined as SBP less than 90 mm Hg, or a 25 % decrease from basal levels if baseline SBP was 90-100 mmHg. 
Oral temperature was measured before and immediately after dialysis. Serum urea concentration was measured pre and post dialysis by a commercial Kit (Man Co. Tehran, Iran). The equilibrated Kt/V(Kt/Veq) was determined using equation 1 as previously reported.  Kt/Veq = (1-0.47/t) ×Kt/ Vsp + 0.02. The single pool Kt/V(Kt/Vsp) was calculated as: Kt/Vsp = -Ln (R-0.008 × t) + (4-3.5 × R) × UF/W , where R = urea post/urea pre; UF = ultrafiltration volume in Kg; T = treatment time in h; and W = body weight in kg. Urea reduction rate (URR), was calculated by formula: urea pre-urea post/urea pre × 100%.
Total nitrite and nitrate (NOx) levels measured spectrophotometrically as previously reported by Miranda et al.  The principle of this assay is the reduction of nitrate by vanadium (III) combined with detection by the acidic Griess reaction. The sensitivity of this method is 0.5 µmol/L and is useful in a variety of fluids including serum.
| Statistical Analysis|| |
Data were reported as mean ± SE ( standard error). Statistical analysis was performed by SPSS program (Version 11.5). Paired sample t-test or two-way mixed betweenwithin analysis of variance (ANOVA) were used to compare NOx levels and hemodynamic changes, respectively. McNemar test was used for comparison of hypotension episodes during cool and standard temperature dialysis.
| Results|| |
[Table - 1] reveals that the parameters of Kt/ Veq, ultrafiltration, urea reduction rate, and predialysis temperature were not significantly different between the study groups. Post dialysis temperature was significantly less in the cool dialysis than the standard temperature dialysis group as predicted (P<0.01). Patients dialyzed with cool dialysate experienced significantly fewer episodes of hypotension than those dialyzed with standard temperature dialysate, 15.8% and 57.9%, respectively (P<0.05). Except for heart rate (HR), all other hemodynamic parameters including systolic, diastolic, and mean arterial pressures were significantly less in standard temperature compared to cool dialysis, (P<0.05). Maximum decrease in SBP, DBP, and MAP occurred at the third hour of dialysis and were 18, 17, and 14 % for standard temperature and 6, 1, and 4 % for cool dialysis, [Figure - 1].
Measurement of nitric oxide metabolites before and after dialysis revealed that in both standard temperature and cool dialysis conditions serum NOx levels decreased significantly after dialysis (63 ± 7 vs. 41 ± 5 and 59 ± 5 vs.37 ± 4 µmol/L for standard temperature and cool dialysis respectively, P < 0.01). There was no significant difference between post dialysis NOx levels in both dialysis temperatures, [Figure - 2].
| Discussion|| |
In this study we found that cool dialysis compared to standard temperature dialysis had beneficial effects for diabetic patients and caused more stability in hemodynamic parameters during HD without decrease in the HD efficiency. Although not restricted to diabetic patients this finding is in line with other reports that lowering the dialysis temperature decrease the number of hypotensive episodes in HD patients and has no effect on dialysis efficiency. , However, It should be mentioned that in this study, Kt/Veq ratio observed in both situations was close to 1.0, which was less than the minimum standard level of 1.2 reported by others.  The percentages of hypotensive episodes were relatively high in our study (57.9% and 15.8 % in standard temperature and cool dialysis, respectively). Prevalence between 20-50% of symptomatic hypotension in HD was reported elsewhere.  Patients with subnormal body temperatures gain the maximum benefit from cool dialysis and euthermic patients need not be exposed to 35°C dialysis as it may not have beneficial effect and may be unnecessarily uncomfortable.  Although we did not select patients based on predialysis body temperature, subsequent analysis showed that non of the subjects had predialysis subnormal body temperature (i.e., < 36°C).
Nitric oxide is considered as a mediator of hypothermic dialysis  and accumulation of nitric oxide is reported as a cause of dialysis hypotension. , In this study, serum NOx levels decreased significantly after dialysis in both standard temperature and cool dialysis but there was no significant difference between both groups, which is compatible with findings of Beerenhout et al,  who found higher production of NOx in diabetic patients on standard temperature dialysis than on cool dialysis. The effect of cool temperature dialysis on nitric oxide production in diabetic patients needs more investigation. Nitrate is a normal constituent of human urine.  Renal clearance of nitrate is 20 ml/min which reflects substantial tubular reabsorption.  Nitrate accumulates in serum of patients between HD sessions and decreased serum levels after HD is due to its clearance with dialysis. Chronic renal failure is a state of NOx deficiency, but its plasma levels in these patients are higher than normal subjects. 
In conclusion, the results of this study suggest the use of simple and low cost method such as decreasing dialysate temperature to prevent dialysis hypotension in diabetic patients and demonstrate that probably other mechanisms than increased nitric oxide production may be responsible for dialysis hypotension in diabetic patients.
| Acknowledgements|| |
This study was supported by a grant from Prevention of Metabolic Disorders Research Center, Research Institute for Endocrine Sciences, and 15 Khordad Hospital, Shaheed Beheshti University of Medical Sciences, Tehran, Iran. We would like to thank Mrs. M. Padyab for statistical helps.
| References|| |
|1.||Bregman H, Daugirdas J, Ing T. Complications during hemodialysis. In: Daugirdas J, Blake P, Ing T (eds). Handbook of dialysis. Lippincott Williams & Wilkins, USA: 2001;148-68. |
|2.||Marcen R, Quereda C, Orofino L, et al. Hemodialysis with low-temperature dialysate: A long-term experience. Nephron 1988;49 (1):29-32. |
|3.||Maggiore Q. Isothermic dialysis for hypotension-prone patients. Semin Dial 2002; 15(3):187-90. |
|4.||Ayoub A, Finlayson M. Effect of cool temperature dialysate on the quality and patients perception of haemodialysis. Nephrol Dial Transplant 2004;19(1):190-4. |
|5.||Marcen R, Orofino L, Quereda C, Pascual J, Ortuno J. Effects of cool dialysate in dialysis-related symptoms. Nephron 1990; 54(4):356-7. |
|6.||Orofino L, Marcen R, Quereda C, et al. Epidemiology of symptomatic hypotension in hemodialysis: Is cool dialysate beneficial for all patients? Am J Nephrol 1990;10(3): 177-80. |
|7.||Cruz DN, Mahnensmith RL, Brickel HM, Perazella MA. Midodrine and cool dialysate are effective therapies for symptommatic intradialytic hypotension. Am J Kidney Dis 1999;33(5):920-6. |
|8.||Franssen CF, Dasselaar JJ, Sytsma P, Burgerhof JG, de Jong PE, Huisman RM. Automatic feedback control of relative blood volume changes during hemodialysis improves blood pressure stability during and after dialysis. Hemodial Int 2005;9(4): 383-92. |
|9.||Dheenan S, Henrich WL. Preventing dialysis hypotension: A comparison of usual protective maneuvers. Kidney Int 2001;59 (3):1175-81. |
|10.||Miranda KM, Espey MG, Wink DA. A rapid, simple spectrophotometric method for simultaneous detection of nitrate and nitrite. Nitric Oxide 2001;5(1):62-71. |
|11.||Yu AW, Ing TS, Zabaneh RI, Daugirdas JT. Effect of dialysate temperature on central hemodynamics and urea kinetics. Kidney Int 1995;48(1):237-43. |
|12.||Fine A, Penner B. The protective effect of cool dialysate is dependent on patients' predialysis temperature. Am J Kidney Dis 1996;28(2):262-5. |
|13.||Jamil KM, Yokoyama K, Takemoto F, Hara S, Yamada A. Low temperature hemodialysis prevents hypotensive episodes by reducing nitric oxide synthesis. Nephron 2000;84(3):284-6. |
|14.||Yokokawa K, Mankus R, Saklayen MG, et al. Increased nitric oxide production in patients with hypotension during hemodialysis. Ann Intern Med 1995;123(1):35-7. |
|15.||Beerenhout CH, Noris M, Kooman JP, et al. Nitric oxide synthetic capacity in relation to dialysate temperature. Blood Purif 2004;22(2):203-9. |
|16.||Green LC, Wagner DA, Glogowski J, Skipper PL, Wishnok JS, Tannenbaum SR. Analysis of nitrate, nitrite and (15N) nitrate in biological fluids. Anal Biochem 1982; 126(1):131-8. |
|17.||Wennmalm A, Benthin G, Edlund A, et al. Metabolism and excretion of nitric oxide in humans: An experimental and clinical study. Circ Res 1993;73(6):1121-7. |
|18.||Blum M, Yachnin T, Wollman Y, et al. Low nitric oxide production in patients with chronic renal failure. Nephron 1998; 79(3):265-8. |
Research Institute for Endocrine Sciences, Shaheed Beheshti University of Medical Sciences, P.O. Box 19395-4763 Tehran
[Figure - 1], [Figure - 2]
[Table - 1]